Biochemical, histological and behavioural aspects of visual function during early development of rainbow trout

USGS Publications Warehouse

Carvalho, Paulo S. M.; Noltie, Douglas B.; Tillitt, D.E.

2004-01-01

Retinal structure and concentration of retinoids involved in phototransduction changed during early development of rainbow trout Oncorhynchus mykiss, correlating with improvements in visual function. A test chamber was used to evaluate the presence of optokinetic or optomotor responses and to assess the functionality of the integrated cellular, physiological and biochemical components of the visual system. The results indicated that in rainbow trout optomotor responses start at 10 days post-hatch, and demonstrated for the first time that increases in acuity, sensitivity to low light as well as in motion detection abilities occur from this stage until exogenous feeding starts. The structure of retinal cells such as cone ellipsoids increased in length as photopic visual acuity improved, and rod densities increased concurrently with improvements in scotopic thresholds (2.2 log10 units). An increase in the concentrations of the chromophore all-trans-retinal correlated with improvements of all behavioural measures of visual function during the same developmental phase. ?? 2004 The Fisheries Society of the British Isles.

Visual Search in the Detection of Retinal Injury: A Feasibility Study

DTIC Science & Technology

2013-04-01

D, Heyes A. et al. Mobility of people with retinitis pigmentosa as a function of vision and psychological variables. Optometry and Vision Science...AFRL-RH-FS-TR-2013-0019 Visual Search in the Detection of Retinal Injury: A Feasibility Study Thomas Kuyk TASC, Inc. Lei Liu The...Detection of Retinal Injury: A Feasibility Study" 2013 0019 LEON N. McLIN, JR., DR-III, DAF Work Unit Manager 711 HPW/ RHDO POLHAMUS.GARR ETT.D

Visual BOLD Response in Late Blind Subjects with Argus II Retinal Prosthesis

PubMed Central

Castaldi, E.; Cicchini, G. M.; Cinelli, L.; Rizzo, S.; Morrone, M. C.

2016-01-01

Retinal prosthesis technologies require that the visual system downstream of the retinal circuitry be capable of transmitting and elaborating visual signals. We studied the capability of plastic remodeling in late blind subjects implanted with the Argus II Retinal Prosthesis with psychophysics and functional MRI (fMRI). After surgery, six out of seven retinitis pigmentosa (RP) blind subjects were able to detect high-contrast stimuli using the prosthetic implant. However, direction discrimination to contrast modulated stimuli remained at chance level in all of them. No subject showed any improvement of contrast sensitivity in either eye when not using the Argus II. Before the implant, the Blood Oxygenation Level Dependent (BOLD) activity in V1 and the lateral geniculate nucleus (LGN) was very weak or absent. Surprisingly, after prolonged use of Argus II, BOLD responses to visual input were enhanced. This is, to our knowledge, the first study tracking the neural changes of visual areas in patients after retinal implant, revealing a capacity to respond to restored visual input even after years of deprivation. PMID:27780207

Correlation between fundus autofluorescence and central visual function in chronic central serous chorioretinopathy.

PubMed

Eandi, Chiara M; Piccolino, Felice Cardillo; Alovisi, Camilla; Tridico, Federico; Giacomello, Daniela; Grignolo, Federico M

2015-04-01

To find possible correlations between the morphologic macular changes revealed by fundus autofluorescence (FAF) and the functional parameters such as visual acuity and retinal sensitivity in patients with chronic central serous chorioretinopathy (CSC). Prospective, cross-sectional study. Forty-six eyes (39 consecutive patients) with chronic CSC were studied with FAF and microperimetry (MP). Retinal sensitivity value maps were exactly superimposed over FAF images. The following microperimetric parameters were applied: central 10-degree visual field, 4-2-1 strategy, 61 stimulation spots, white monochromatic background, stimulation time 200 ms, stimulation spot size Goldmann III. A possible relationship between MP and FAF was investigated. Mean best-corrected visual acuity (BCVA) was 20/32 (median 20/25, range 20/20-20/200). BCVA was significantly correlated with FAF findings (Mann-Whitney test; P < .0001). A positive concordance between FAF and MP evaluation was also found (total concordance of 0.720 with a kappa of Cohen of 0.456). The hypo-autofluorescent areas showed decreased retinal sensitivity, while adjacent areas of increased FAF could be associated to both normal and decreased retinal sensitivity. Absolute scotoma, defined as 0 dB retinal sensitivity, corresponded with absence of autofluorescence. Altered FAF in chronic CSC patients has a functional correlation quantified by microperimetry. This study confirms the impact of FAF changes on retinal sensitivity and their value to reflect the functional impairment in chronic CSC. Copyright © 2015 Elsevier Inc. All rights reserved.

Hydrogen postconditioning promotes survival of rat retinal ganglion cells against ischemia/reperfusion injury through the PI3K/Akt pathway.

PubMed

Wu, Jiangchun; Wang, Ruobing; Yang, Dianxu; Tang, Wenbin; Chen, Zeli; Sun, Qinglei; Liu, Lin; Zang, Rongyu

2018-01-22

Retinal ischemia/reperfusion injury (IRI) plays a crucial role in the pathophysiology of various ocular diseases. Our previous study have shown that postconditioning with inhaled hydrogen (H 2 ) (HPC) can protect retinal ganglion cells (RGCs) in a rat model of retinal IRI. Our further study aims to investigate potential mechanisms underlying HPC-induced protection. Retinal IRI was performed on the right eyes of rats and was followed by inhalation of 67% H 2 mixed with 33% oxygen immediately after ischemia for 1 h daily for one week. RGC density was counted using haematoxylin and eosin (HE) staining, retrograde labelling with cholera toxin beta (CTB) and TUNEL staining, respectively. Visual function was assessed using flash visual evoked potentials (FVEP) and pupillary light reflex (PLR). The phosphorylated Akt was analysed by RT-PCR and western blot. The results showed that administration of HPC significantly inhibited the apoptosis of RGCs and protected the visual function. Simultaneously, HPC treatment markedly increased the phosphorylations of Akt. Blockade of PI3K activity by inhibitors (LY294002) dramatically abolished its anti-apoptotic effect and lowered both visual function and Akt phosphorylation levels. Taken together, our results demonstrate that HPC appears to confer neuroprotection against retinal IRI via the PI3K/Akt pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Estimation of prognosis and prevalence of retinitis pigmentosa and Usher syndrome in Norway.

PubMed

Grøndahl, J

1987-04-01

Retinitis pigmentosa was diagnosed in 101 persons from 53 families. The prognosis for visual function was most favourable for the autosomal dominant group (38 patients from 8 families). The autosomal recessive group (40 patients from 25 families) and the 19 solitary cases were very heterogeneous, with prognosis ranging from favourable to very bad. There was a higher intrafamiliar correlation in the autosomal recessive than in the autosomal dominant group. In 28 patients from 18 families with Usher syndrome, almost all had good visual function until 30 years of age, and few had useful visual function after the age of 50. The age when the patients were registered varied between the different genetic types of retinitis pigmentosa, reflecting differences in prognosis. Therefore, ascertainment probability and prevalence were calculated for each genetic group separately. The prevalence of retinitis pigmentosa in Norway, all genetic groups included, was calculated to be 1/4440, the autosomal dominant type of the disease being the most frequent. The prevalence of Usher syndrome was calculated to be 3.6/100,000. Both retinitis pigmentosa and Usher syndrome were more prevalent in Laps.

Assessment of Central Visual Function in Patients with Retinitis Pigmentosa.

PubMed

Fujiwara, Kohta; Ikeda, Yasuhiro; Murakami, Yusuke; Tachibana, Takashi; Funatsu, Jun; Koyanagi, Yoshito; Nakatake, Shunji; Yoshida, Noriko; Nakao, Shintaro; Hisatomi, Toshio; Yoshida, Shigeo; Yoshitomi, Takeshi; Ishibashi, Tatsuro; Sonoda, Koh-Hei

2018-05-23

In order to clarify the disease progression in retinitis pigmentosa (RP) and its related factors, reliable data on the changes in central visual function in RP are needed. In this longitudinal study, we examined 118 patients who were diagnosed with typical RP. Visual acuity (VA), visual field using a Humphrey Field Analyzer with the central 10-2 SITA-Standard program, and optical coherence tomography measurements were obtained. The slopes, which were derived from serial values of mean deviation (MD), macular sensitivity (MS), or foveal sensitivity (FS) obtained for each eye by a linear mixed model, were used for analysis. MS and FS were calculated as the average retinal sensitivity of 12 and 4 central points respectively. There were statistically significant interactions of times with levels of the central subfield thickness (CST) on the slopes of MS and FS. Compared to the eyes without macular complications, the eyes with macular complications had steeper MD, MS and FS slopes, and this interaction was no significant, but marginal trend for the MS or FS slope (P = 0.10, 0.05, respectively). The central retinal sensitivity (i.e., MS and FS) slopes calculated were effective indices of the progression of central visual function in RP.

Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement.

PubMed

Cideciyan, Artur V; Jacobson, Samuel G; Beltran, William A; Sumaroka, Alexander; Swider, Malgorzata; Iwabe, Simone; Roman, Alejandro J; Olivares, Melani B; Schwartz, Sharon B; Komáromy, András M; Hauswirth, William W; Aguirre, Gustavo D

2013-02-05

Leber congenital amaurosis (LCA) associated with retinal pigment epithelium-specific protein 65 kDa (RPE65) mutations is a severe hereditary blindness resulting from both dysfunction and degeneration of photoreceptors. Clinical trials with gene augmentation therapy have shown partial reversal of the dysfunction, but the effects on the degeneration are not known. We evaluated the consequences of gene therapy on retinal degeneration in patients with RPE65-LCA and its canine model. In untreated RPE65-LCA patients, there was dysfunction and degeneration of photoreceptors, even at the earliest ages. Examined serially over years, the outer photoreceptor nuclear layer showed progressive thinning. Treated RPE65-LCA showed substantial visual improvement in the short term and no detectable decline from this new level over the long term. However, retinal degeneration continued to progress unabated. In RPE65-mutant dogs, the first one-quarter of their lifespan showed only dysfunction, and there was normal outer photoreceptor nuclear layer thickness retina-wide. Dogs treated during the earlier dysfunction-only stage showed improved visual function and dramatic protection of treated photoreceptors from degeneration when measured 5-11 y later. Dogs treated later during the combined dysfunction and degeneration stage also showed visual function improvement, but photoreceptor loss continued unabated, the same as in human RPE65-LCA. The results suggest that, in RPE65 disease treatment, protection from visual function deterioration cannot be assumed to imply protection from degeneration. The effects of gene augmentation therapy are complex and suggest a need for a combinatorial strategy in RPE65-LCA to not only improve function in the short term but also slow retinal degeneration in the long term.

Clinical characteristics of children with severe visual impairment but favorable retinal structural outcomes from the Early Treatment for Retinopathy of Prematurity (ETROP) study.

PubMed

Siatkowski, R Michael; Good, William V; Summers, C Gail; Quinn, Graham E; Tung, Betty

2013-04-01

To describe visual function and associated characteristics at the 6-year examination in children enrolled in the Early Treatment for Retinopathy of Prematurity Study who had unfavorable visual outcomes despite favorable structural outcomes in one or both eyes. The clinical examination records of children completing the 6-year follow-up examination were retrospectively reviewed. Eligible subjects were those with visual acuity of ≤20/200 in each eye (where recordable) and a normal fundus or straightening of the temporal retinal vessels with or without macular ectopia in at least one eye. Data regarding visual function, retinal structure, presence of nystagmus, optic atrophy, optic disk cupping, seizures/shunts, and Functional Independence Measure for Children (ie, WeeFIM: pediatric functional independence measure) developmental test scores were reviewed. Of 342 participants who completed the 6-year examination, 39 (11%) met inclusion criteria. Of these, 29 (74%) had normal retinal structure, 18 (46%) had optic atrophy, and 3 (8%) had increased cupping of the optic disk in at least one eye. Latent and/or manifest nystagmus occurred in 30 children (77%). The presence of nystagmus was not related to the presence of optic atrophy. Of the 39 children, 28 (72%) had a below-normal WeeFIM score. In 25 participants (7%) completing the 6-year examination, cortical visual impairment was considered the primary cause of visual loss. The remainder likely had components of both anterior and posterior visual pathway disease. Clinical synthesis of ocular anatomy and visual and neurologic function is required to determine the etiology of poor vision in these children. Copyright © 2013 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

All-optical recording and stimulation of retinal neurons in vivo in retinal degeneration mice

PubMed Central

Strazzeri, Jennifer M.; Williams, David R.; Merigan, William H.

2018-01-01

Here we demonstrate the application of a method that could accelerate the development of novel therapies by allowing direct and repeatable visualization of cellular function in the living eye, to study loss of vision in animal models of retinal disease, as well as evaluate the time course of retinal function following therapeutic intervention. We use high-resolution adaptive optics scanning light ophthalmoscopy to image fluorescence from the calcium sensor GCaMP6s. In mice with photoreceptor degeneration (rd10), we measured restored visual responses in ganglion cell layer neurons expressing the red-shifted channelrhodopsin ChrimsonR over a six-week period following significant loss of visual responses. Combining a fluorescent calcium sensor, a channelrhodopsin, and adaptive optics enables all-optical stimulation and recording of retinal neurons in the living eye. Because the retina is an accessible portal to the central nervous system, our method also provides a novel non-invasive method of dissecting neuronal processing in the brain. PMID:29596518

Omega-3 polyunsaturated fatty acids preserve retinal function in type 2 diabetic mice.

PubMed

Sapieha, P; Chen, J; Stahl, A; Seaward, M R; Favazza, T L; Juan, A M; Hatton, C J; Joyal, J-S; Krah, N M; Dennison, R J; Tang, J; Kern, T S; Akula, J D; Smith, L E H

2012-07-23

Diabetic retinopathy (DR) is associated with hyperglycemia-driven microvascular pathology and neuronal compromise in the retina. However, DR is also linked to dyslipidemia. As omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) are protective in proliferative retinopathy, we investigated the capacity of ω-3PUFAs to preserve retinal function in a mouse model of type 2 diabetes mellitus (T2DM). Male leptin-receptor-deficient (db/db) mice were maintained for 22 weeks (4 weeks-26 weeks of life) on calorically and compositionally matched diets, except for 2% enrichment in either ω-3 or ω-6PUFAs. Visual function was assessed at 9, 14 and 26 weeks by electroretinography. Retinal capillary and neuronal integrity, as well as glucose challenge responses, were assessed on each diet. The ω-3PUFA diet significantly preserved retinal function in the mouse model of T2DM to levels similar to those observed in nondiabetic control mice on normal chow. Conversely, retinal function gradually deteriorated in db/db mice on a ω-6PUFA-rich diet. There was also an enhanced ability of ω-3PUFA-fed mice to respond to glucose challenge. The protection of visual function appeared to be independent of cytoprotective or anti-inflammatory effects of ω-3PUFAs. This study identifies beneficial effects of dietary ω-3PUFAs on visual function in T2DM. The data are consistent with dyslipidemia negatively impacting retinal function. As ω-3PUFA lipid dietary interventions are readily available, safe and inexpensive, increasing ω-3PUFA intake in diabetic patients may slow the progression of vision loss in T2DM.

Probing the functional impact of sub-retinal prosthesis

PubMed Central

Roux, Sébastien; Matonti, Frédéric; Dupont, Florent; Hoffart, Louis; Takerkart, Sylvain; Picaud, Serge; Pham, Pascale; Chavane, Frédéric

2016-01-01

Retinal prostheses are promising tools for recovering visual functions in blind patients but, unfortunately, with still poor gains in visual acuity. Improving their resolution is thus a key challenge that warrants understanding its origin through appropriate animal models. Here, we provide a systematic comparison between visual and prosthetic activations of the rat primary visual cortex (V1). We established a precise V1 mapping as a functional benchmark to demonstrate that sub-retinal implants activate V1 at the appropriate position, scalable to a wide range of visual luminance, but with an aspect-ratio and an extent much larger than expected. Such distorted activation profile can be accounted for by the existence of two sources of diffusion, passive diffusion and activation of ganglion cells’ axons en passant. Reverse-engineered electrical pulses based on impedance spectroscopy is the only solution we tested that decreases the extent and aspect-ratio, providing a promising solution for clinical applications. DOI: http://dx.doi.org/10.7554/eLife.12687.001 PMID:27549126

Structural and functional changes associated with normal and abnormal fundus autofluorescence in patients with retinitis pigmentosa.

PubMed

Greenstein, Vivienne C; Duncker, Tobias; Holopigian, Karen; Carr, Ronald E; Greenberg, Jonathan P; Tsang, Stephen H; Hood, Donald C

2012-02-01

To analyze the structure and visual function of regions bordering the hyperautofluorescent ring/arcs in retinitis pigmentosa. Twenty-one retinitis pigmentosa patients (21 eyes) with rings/arcs and 21 normal individuals (21 eyes) were studied. Visual sensitivity in the central 10° was measured with microperimetry. Retinal structure was evaluated with spectral-domain optical coherence tomography. The distance from the fovea to disruption/loss of the inner outer segment (IS/OS) junction and thicknesses of the total receptor plus retinal pigment epithelial complex and outer segment plus retinal pigment epithelial complex layers were measured. Results were compared with measurements of the distance from the fovea to the inner and outer borders of the ring/arc seen on fundus autofluorescence. Disruption/loss of the inner outer segment junction occurred closer to the inner border of the ring/arc and it was closer to the fovea in eight eyes. For 19 eyes, outer segment plus and receptor plus RPE complex thicknesses were significantly decreased at locations closer to the fovea than the appearance of the inner border of hyperautofluorescence. Mean visual sensitivity was decreased inside, across, and outside the ring/arc by 3.5 ± 3.8, 8.9 ± 4.8, and 17.0 ± 2.4 dB, respectively. Structural and functional changes can occur inside the hyperfluorescent ring/arc in retinitis pigmentosa.

A cascade model of information processing and encoding for retinal prosthesis.

PubMed

Pei, Zhi-Jun; Gao, Guan-Xin; Hao, Bo; Qiao, Qing-Li; Ai, Hui-Jian

2016-04-01

Retinal prosthesis offers a potential treatment for individuals suffering from photoreceptor degeneration diseases. Establishing biological retinal models and simulating how the biological retina convert incoming light signal into spike trains that can be properly decoded by the brain is a key issue. Some retinal models have been presented, ranking from structural models inspired by the layered architecture to functional models originated from a set of specific physiological phenomena. However, Most of these focus on stimulus image compression, edge detection and reconstruction, but do not generate spike trains corresponding to visual image. In this study, based on state-of-the-art retinal physiological mechanism, including effective visual information extraction, static nonlinear rectification of biological systems and neurons Poisson coding, a cascade model of the retina including the out plexiform layer for information processing and the inner plexiform layer for information encoding was brought forward, which integrates both anatomic connections and functional computations of retina. Using MATLAB software, spike trains corresponding to stimulus image were numerically computed by four steps: linear spatiotemporal filtering, static nonlinear rectification, radial sampling and then Poisson spike generation. The simulated results suggested that such a cascade model could recreate visual information processing and encoding functionalities of the retina, which is helpful in developing artificial retina for the retinally blind.

Ocular toxoplasmosis and retinal detachment: five case reports.

PubMed

Kianersi, F; Naderi Beni, A; Ghanbari, H; Fazel, F

2012-10-01

Ocular toxoplasmosis is a potentially blinding cause of posterior uveitis. Retinal detachment is rare complication of ocular toxoplasmosis. To report the clinical course and prognosis of retinal breaks and detachments occurring in patients with ocular toxoplasmosis. This study was a retrospective, non-comparative case series of five patients with ocular toxoplasmosis who had consulted us with retinal detachment. All of the participants had retinal detachment after severe and treatment resistant toxoplasmic retinochoroiditis, leaving one of them with decreased visual acuity to light perception in spite of treatment and final visual acuity was 20/100 or better in four patients. The functional prognosis for the patients with retinal detachment was poor. Careful retinal examination in ocular toxoplasmosis is warranted, especially in patients with severe intraocular inflammation.

Randomized controlled trial of electro-stimulation therapies to modulate retinal blood flow and visual function in retinitis pigmentosa.

PubMed

Bittner, Ava K; Seger, Kenneth; Salveson, Rachel; Kayser, Samantha; Morrison, Natalia; Vargas, Patricia; Mendelsohn, Deborah; Han, Jorge; Bi, Hua; Dagnelie, Gislin; Benavente, Alexandra; Ramella-Roman, Jessica

2018-05-01

We examined changes in visual function and ocular and retinal blood flow (RBF) among retinitis pigmentosa (RP) participants in a randomized controlled trial of electro-stimulation therapies. Twenty-one RP participants were randomized (1:1:1) to transcorneal electrical stimulation (TES) at 6 weekly half-hour sessions, electro-acupuncture or inactive laser acupuncture (sham control) at 10 half-hour sessions over 2 weeks. Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA), quick contrast sensitivity function, Goldmann visual fields, AdaptDx scotopic sensitivity, spectral flow and colour Doppler imaging of the central retinal artery (CRA), and RBF in macular capillaries were measured twice pre-treatment, after 2 TES sessions, within a week and a month after intervention completion. We measured a significant improvement in retrobulbar CRA mean flow velocity for both the TES (p = 0.038) and electro-acupuncture groups (p = 0.001) on average after 2 weeks of treatment when compared to sham controls. Transcorneal electrical simulation (TES) and electro-acupuncture subjects had significant 55% and 34% greater increases, respectively, in RBF in the macular vessels when compared to sham controls (p < 0.001; p = 0.008) within a week of completing six TES sessions or a month after electro-acupuncture. There was a significant difference in the proportion of eyes that had improved visual function when comparing the three intervention groups (p = 0.038): four of seven TES subjects (57%), two of seven electro-acupuncture subjects (29%) and none of the seven control subjects (0%) had a significant visual improvement outside of typical test-retest variability at two consecutive post-treatment visits. Increased blood flow following electro-stimulation therapies is an objective, physiological change that occurred in addition to visual function improvements in some RP patients. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Retinal Information Processing for Minimum Laser Lesion Detection and Cumulative Damage

DTIC Science & Technology

1992-09-17

TAL3Unaqr~orJ:ccd [] J ,;--Wicic tion --------------... MYRON....... . ................... ... ....... ...........................MYRON L. WOLBARSHT B D ist...possible beneficial visual function of the small retinal image movements. B . Visual System Models Prior models of visual system information processing have...against standard secondary sources whose calibrations can be traced to the National Bureau of Standards. B . Electrophysiological Techniques Extracellular

Reading ability and retinal sensitivity after surgery for macular hole and macular pucker.

PubMed

Cappello, Ezio; Virgili, Gianni; Tollot, Luigina; Del Borrello, Michele; Menchini, Ugo; Zemella, Marco

2009-09-01

To assess whether reading ability and microperimetry improve as demonstrated for visual acuity after surgery for macular hole and macular pucker. Fifty-nine consecutive patients underwent pars plana vitrectomy for macular pucker (n = 41) or full-thickness macular holes (n = 18). Functional assessment was made at 3, 6, and 12 months after surgery and included far visual acuity (Early Treatment Diabetic Retinopathy Study charts), retinal sensitivity using the microperimeter (MP1, Nidek Technologies, Padova, Italy), and reading ability (MNRead charts). An improvement was recorded both for macular holes and puckers not only for visual acuity, but also for reading acuity and mean central retinal sensitivity (P < 0.01 for the overall comparisons between baseline and follow-up values). Maximum reading speed was already good at baseline both for puckers and holes overall, and a significant mean improvement was recorded only in patients with macular hole at 6 and 12 months (P < 0.01). Although eyes with macular holes had worse baseline visual function compared with puckers (P < 0.01 for all measures of visual function except for reading speed), they recovered to similar levels thanks to greater improvement (P < 0.05 for the difference in improvement during follow-up between puckers and holes for all measures of visual function). No differences were found among indocyanine green or trypan blue staining compared with no staining for internal limiting membrane removal based on all outcome measures (P > 0.05 for the overall difference of visual function improvement during follow-up). The improvement found for visual acuity after vitrectomy for macular hole and pucker also regards retinal sensitivity and reading ability for up to 12 months. This is reassuring concerning the benefits for the patients, and this shows that visual acuity is a valid functional measure for investigating the efficacy of macular surgery.

Omega-3 polyunsaturated fatty acids preserve retinal function in type 2 diabetic mice

PubMed Central

Sapieha, P; Chen, J; Stahl, A; Seaward, M R; Favazza, T L; Juan, A M; Hatton, C J; Joyal, J-S; Krah, N M; Dennison, R J; Tang, J; Kern, T S; Akula, J D; Smith, L E H

2012-01-01

Objective: Diabetic retinopathy (DR) is associated with hyperglycemia-driven microvascular pathology and neuronal compromise in the retina. However, DR is also linked to dyslipidemia. As omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) are protective in proliferative retinopathy, we investigated the capacity of ω-3PUFAs to preserve retinal function in a mouse model of type 2 diabetes mellitus (T2DM). Design: Male leptin-receptor-deficient (db/db) mice were maintained for 22 weeks (4 weeks–26 weeks of life) on calorically and compositionally matched diets, except for 2% enrichment in either ω-3 or ω-6PUFAs. Visual function was assessed at 9, 14 and 26 weeks by electroretinography. Retinal capillary and neuronal integrity, as well as glucose challenge responses, were assessed on each diet. Results: The ω-3PUFA diet significantly preserved retinal function in the mouse model of T2DM to levels similar to those observed in nondiabetic control mice on normal chow. Conversely, retinal function gradually deteriorated in db/db mice on a ω-6PUFA-rich diet. There was also an enhanced ability of ω-3PUFA-fed mice to respond to glucose challenge. The protection of visual function appeared to be independent of cytoprotective or anti-inflammatory effects of ω-3PUFAs. Conclusion: This study identifies beneficial effects of dietary ω-3PUFAs on visual function in T2DM. The data are consistent with dyslipidemia negatively impacting retinal function. As ω-3PUFA lipid dietary interventions are readily available, safe and inexpensive, increasing ω-3PUFA intake in diabetic patients may slow the progression of vision loss in T2DM. PMID:23448719

Slow Feature Analysis on Retinal Waves Leads to V1 Complex Cells

PubMed Central

Dähne, Sven; Wilbert, Niko; Wiskott, Laurenz

2014-01-01

The developing visual system of many mammalian species is partially structured and organized even before the onset of vision. Spontaneous neural activity, which spreads in waves across the retina, has been suggested to play a major role in these prenatal structuring processes. Recently, it has been shown that when employing an efficient coding strategy, such as sparse coding, these retinal activity patterns lead to basis functions that resemble optimal stimuli of simple cells in primary visual cortex (V1). Here we present the results of applying a coding strategy that optimizes for temporal slowness, namely Slow Feature Analysis (SFA), to a biologically plausible model of retinal waves. Previously, SFA has been successfully applied to model parts of the visual system, most notably in reproducing a rich set of complex-cell features by training SFA with quasi-natural image sequences. In the present work, we obtain SFA units that share a number of properties with cortical complex-cells by training on simulated retinal waves. The emergence of two distinct properties of the SFA units (phase invariance and orientation tuning) is thoroughly investigated via control experiments and mathematical analysis of the input-output functions found by SFA. The results support the idea that retinal waves share relevant temporal and spatial properties with natural visual input. Hence, retinal waves seem suitable training stimuli to learn invariances and thereby shape the developing early visual system such that it is best prepared for coding input from the natural world. PMID:24810948

Increasing Spontaneous Retinal Activity before Eye Opening Accelerates the Development of Geniculate Receptive Fields

PubMed Central

Davis, Zachary W.; Chapman, Barbara

2015-01-01

Visually evoked activity is necessary for the normal development of the visual system. However, little is known about the capacity for patterned spontaneous activity to drive the maturation of receptive fields before visual experience. Retinal waves provide instructive retinotopic information for the anatomical organization of the visual thalamus. To determine whether retinal waves also drive the maturation of functional responses, we increased the frequency of retinal waves pharmacologically in the ferret (Mustela putorius furo) during a period of retinogeniculate development before eye opening. The development of geniculate receptive fields after receiving these increased neural activities was measured using single-unit electrophysiology. We found that increased retinal waves accelerate the developmental reduction of geniculate receptive field sizes. This reduction is due to a decrease in receptive field center size rather than an increase in inhibitory surround strength. This work reveals an instructive role for patterned spontaneous activity in guiding the functional development of neural circuits. SIGNIFICANCE STATEMENT Patterned spontaneous neural activity that occurs during development is known to be necessary for the proper formation of neural circuits. However, it is unknown whether the spontaneous activity alone is sufficient to drive the maturation of the functional properties of neurons. Our work demonstrates for the first time an acceleration in the maturation of neural function as a consequence of driving patterned spontaneous activity during development. This work has implications for our understanding of how neural circuits can be modified actively to improve function prematurely or to recover from injury with guided interventions of patterned neural activity. PMID:26511250

Concentric retinitis pigmentosa: clinicopathologic correlations.

PubMed

Milam, A H; De Castro, E B; Smith, J E; Tang, W X; John, S K; Gorin, M B; Stone, E M; Aguirre, G D; Jacobson, S G

2001-10-01

Progressive concentric (centripetal) loss of vision is one pattern of visual field loss in retinitis pigmentosa. This study provides the first clinicopathologic correlations for this form of retinitis pigmentosa. A family with autosomal dominant concentric retinitis pigmentosa was examined clinically and with visual function tests. A post-mortem eye of an affected 94 year old family member was processed for histopathology and immunocytochemistry with retinal cell specific antibodies. Unrelated simplex/multiplex patients with concentric retinitis pigmentosa were also examined. Affected family members of the eye donor and patients from the other families had prominent peripheral pigmentary retinopathy with more normal appearing central retina, good visual acuity, concentric field loss, normal or near normal rod and cone sensitivity within the preserved visual field, and reduced rod and cone electroretinograms. The eye donor, at age 90, had good acuity and function in a central island. Grossly, the central region of the donor retina appeared thinned but otherwise normal, while the far periphery contained heavy bone spicule pigment. Microscopically the central retina showed photoreceptor outer segment shortening and some photoreceptor cell loss. The mid periphery had a sharp line of demarcation where more central photoreceptors were near normal except for very short outer segments and peripheral photoreceptors were absent. Rods and cones showed abrupt loss of outer segments and cell death at this interface. It is concluded that concentric retinitis pigmentosa is a rare but recognizable phenotype with slowly progressive photoreceptor death from the far periphery toward the central retina. The disease is retina-wide but shows regional variation in severity of degeneration; photoreceptor death is severe in the peripheral retina with an abrupt edge between viable and degenerate photoreceptors. Peripheral to central gradients of unknown retinal molecule(s) may be defective or modify photoreceptor degeneration in concentric retinitis pigmentosa.

Electronic approaches to restoration of sight

NASA Astrophysics Data System (ADS)

Goetz, G. A.; Palanker, D. V.

2016-09-01

Retinal prostheses are a promising means for restoring sight to patients blinded by the gradual atrophy of photoreceptors due to retinal degeneration. They are designed to reintroduce information into the visual system by electrically stimulating surviving neurons in the retina. This review outlines the concepts and technologies behind two major approaches to retinal prosthetics: epiretinal and subretinal. We describe how the visual system responds to electrical stimulation. We highlight major differences between direct encoding of the retinal output with epiretinal stimulation, and network-mediated response with subretinal stimulation. We summarize results of pre-clinical evaluation of prosthetic visual functions in- and ex vivo, as well as the outcomes of current clinical trials of various retinal implants. We also briefly review alternative, non-electronic, approaches to restoration of sight to the blind, and conclude by suggesting some perspectives for future advancement in the field.

Electronic Approaches to Restoration of Sight

PubMed Central

Goetz, G A; Palanker, D V

2016-01-01

Retinal prostheses are a promising means for restoring sight to patients blinded by the gradual atrophy of photoreceptors due to retinal degeneration. They are designed to reintroduce information into the visual system by electrically stimulating surviving neurons in the retina. This review outlines the concepts and technologies behind two major approaches to retinal prosthetics: epiretinal and subretinal. We describe how the visual system responds to electrical stimulation. We highlight major differences between direct encoding of the retinal output with epiretinal stimulation, and network-mediated response with subretinal stimulation. We summarize results of pre-clinical evaluation of prosthetic visual functions in- and ex-vivo, as well as the outcomes of current clinical trials of various retinal implants. We also briefly review alternative, non-electronic, approaches to restoration of sight to the blind, and conclude by suggesting some perspectives for future advancement in the field. PMID:27502748

Modulation of GSK-3 provides cellular and functional neuroprotection in the rd10 mouse model of retinitis pigmentosa.

PubMed

Sánchez-Cruz, Alonso; Villarejo-Zori, Beatriz; Marchena, Miguel; Zaldivar-Díez, Josefa; Palomo, Valle; Gil, Carmen; Lizasoain, Ignacio; de la Villa, Pedro; Martínez, Ana; de la Rosa, Enrique J; Hernández-Sánchez, Catalina

2018-04-16

Retinitis pigmentosa (RP) is a group of hereditary retinal neurodegenerative conditions characterized by primary dysfunction and death of photoreceptor cells, resulting in visual loss and, eventually, blindness. To date, no effective therapies have been transferred to clinic. Given the diverse genetic etiology of RP, targeting common cellular and molecular retinal alterations has emerged as a potential therapeutic strategy. Using the Pde6b rd10/rd10 mouse model of RP, we investigated the effects of daily intraperitoneal administration of VP3.15, a small-molecule heterocyclic GSK-3 inhibitor. Gene expression was analyzed by quantitative PCR and protein expression and phosphorylation by Western blot. Photoreceptor preservation was evaluated by histological analysis and visual function was assessed by electroretinography. In rd10 retinas, increased expression of pro-inflammatory markers and reactive gliosis coincided with the early stages of retinal degeneration. Compared with wild-type controls, GSK-3β expression (mRNA and protein) remained unchanged during the retinal degeneration period. However, levels of GSK-3β Ser9 and its regulator Akt Ser473 were increased in rd10 versus wild-type retinas. In vivo administration of VP3.15 reduced photoreceptor cell loss and preserved visual function. This neuroprotective effect was accompanied by a decrease in the expression of neuroinflammatory markers. These results provide proof of concept of the therapeutic potential of VP3.15 for the treatment of retinal neurodegenerative conditions in general, and RP in particular.

Retinal Image Quality During Accommodation

PubMed Central

López-Gil, N.; Martin, J.; Liu, T.; Bradley, A.; Díaz-Muñoz, D.; Thibos, L.

2013-01-01

Purpose We asked if retinal image quality is maximum during accommodation, or sub-optimal due to accommodative error, when subjects perform an acuity task. Methods Subjects viewed a monochromatic (552nm), high-contrast letter target placed at various viewing distances. Wavefront aberrations of the accommodating eye were measured near the endpoint of an acuity staircase paradigm. Refractive state, defined as the optimum target vergence for maximising retinal image quality, was computed by through-focus wavefront analysis to find the power of the virtual correcting lens that maximizes visual Strehl ratio. Results Despite changes in ocular aberrations and pupil size during binocular viewing, retinal image quality and visual acuity typically remain high for all target vergences. When accommodative errors lead to sub-optimal retinal image quality, acuity and measured image quality both decline. However, the effect of accommodation errors of on visual acuity are mitigated by pupillary constriction associated with accommodation and binocular convergence and also to binocular summation of dissimilar retinal image blur. Under monocular viewing conditions some subjects displayed significant accommodative lag that reduced visual performance, an effect that was exacerbated by pharmacological dilation of the pupil. Conclusions Spurious measurement of accommodative error can be avoided when the image quality metric used to determine refractive state is compatible with the focusing criteria used by the visual system to control accommodation. Real focusing errors of the accommodating eye do not necessarily produce a reliably measurable loss of image quality or clinically significant loss of visual performance, probably because of increased depth-of-focus due to pupil constriction. When retinal image quality is close to maximum achievable (given the eye’s higher-order aberrations), acuity is also near maximum. A combination of accommodative lag, reduced image quality, and reduced visual function may be a useful sign for diagnosing functionally-significant accommodative errors indicating the need for therapeutic intervention. PMID:23786386

Retinal image quality during accommodation.

PubMed

López-Gil, Norberto; Martin, Jesson; Liu, Tao; Bradley, Arthur; Díaz-Muñoz, David; Thibos, Larry N

2013-07-01

We asked if retinal image quality is maximum during accommodation, or sub-optimal due to accommodative error, when subjects perform an acuity task. Subjects viewed a monochromatic (552 nm), high-contrast letter target placed at various viewing distances. Wavefront aberrations of the accommodating eye were measured near the endpoint of an acuity staircase paradigm. Refractive state, defined as the optimum target vergence for maximising retinal image quality, was computed by through-focus wavefront analysis to find the power of the virtual correcting lens that maximizes visual Strehl ratio. Despite changes in ocular aberrations and pupil size during binocular viewing, retinal image quality and visual acuity typically remain high for all target vergences. When accommodative errors lead to sub-optimal retinal image quality, acuity and measured image quality both decline. However, the effect of accommodation errors of on visual acuity are mitigated by pupillary constriction associated with accommodation and binocular convergence and also to binocular summation of dissimilar retinal image blur. Under monocular viewing conditions some subjects displayed significant accommodative lag that reduced visual performance, an effect that was exacerbated by pharmacological dilation of the pupil. Spurious measurement of accommodative error can be avoided when the image quality metric used to determine refractive state is compatible with the focusing criteria used by the visual system to control accommodation. Real focusing errors of the accommodating eye do not necessarily produce a reliably measurable loss of image quality or clinically significant loss of visual performance, probably because of increased depth-of-focus due to pupil constriction. When retinal image quality is close to maximum achievable (given the eye's higher-order aberrations), acuity is also near maximum. A combination of accommodative lag, reduced image quality, and reduced visual function may be a useful sign for diagnosing functionally-significant accommodative errors indicating the need for therapeutic intervention. © 2013 The Authors Ophthalmic & Physiological Optics © 2013 The College of Optometrists.

Pharmacologic Activation of Wnt Signaling by Lithium Normalizes Retinal Vasculature in a Murine Model of Familial Exudative Vitreoretinopathy.

PubMed

Wang, Zhongxiao; Liu, Chi-Hsiu; Sun, Ye; Gong, Yan; Favazza, Tara L; Morss, Peyton C; Saba, Nicholas J; Fredrick, Thomas W; He, Xi; Akula, James D; Chen, Jing

2016-10-01

Familial exudative vitreoretinopathy (FEVR) is characterized by delayed retinal vascular development, which promotes hypoxia-induced pathologic vessels. In severe cases FEVR may lead to retinal detachment and visual impairment. Genetic studies linked FEVR with mutations in Wnt signaling ligand or receptors, including low-density lipoprotein receptor-related protein 5 (LRP5) gene. Here, we investigated ocular pathologies in a Lrp5 knockout (Lrp5(-/-)) mouse model of FEVR and explored whether treatment with a pharmacologic Wnt activator lithium could bypass the genetic defects, thereby protecting against eye pathologies. Lrp5(-/-) mice displayed significantly delayed retinal vascular development, absence of deep layer retinal vessels, leading to increased levels of vascular endothelial growth factor and subsequent pathologic glomeruloid vessels, as well as decreased inner retinal visual function. Lithium treatment in Lrp5(-/-) mice significantly restored the delayed development of retinal vasculature and the intralaminar capillary networks, suppressed formation of pathologic glomeruloid structures, and promoted hyaloid vessel regression. Moreover, lithium treatment partially rescued inner-retinal visual function and increased retinal thickness. These protective effects of lithium were largely mediated through restoration of canonical Wnt signaling in Lrp5(-/-) retina. Lithium treatment also substantially increased vascular tubular formation in LRP5-deficient endothelial cells. These findings suggest that pharmacologic activation of Wnt signaling may help treat ocular pathologies in FEVR and potentially other defective Wnt signaling-related diseases. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Relationship between Structural and Functional Assessment of the Visual System in Mildly Disabled Relapsing-Remitting Multiple Sclerosis Patients

PubMed Central

Huseyinoglu, Nergiz; Ekinci, Metin; Ozben, Serkan; Buyukuysal, Cagatay

2014-01-01

Abstract Studies that explored the anterior visual pathway in the patients with multiple sclerosis (MS) have demonstrated contradictory results about the correlation between structural and functional status of optic nerve and retina. We aimed to investigate the functional and structural findings in our cohort of mildly disabled relapsing-remitting MS patients. A total of 134 eyes (80 eyes of the patients with MS and 54 eyes of the control group) were investigated. Eyes of MS patients were divided into two groups—as eyes with history of optic neuritis (ON group) and without history of optic neuritis (NON group). Ophthalmological investigation including visual evoked potentials, standard automated perimetry, and optical coherence tomography were performed for all participants. Retinal and macular thicknesses were significantly decreased in ON and NON groups compared with controls. Also, visual evoked potential latencies and visual field loss were worse in the both MS groups compared with control group. We did not find any correlation between visual evoked potentials and retinal or macular thickness values but visual field parameters were correlated between retinal and macular layer loss in the NON group. According to our results and some previous studies, although both functional and structural changes were detected in patients with MS, functional status markers do not always show parallelism (or synchrony) with structural changes, especially in eyes with history of optic neuritis. PMID:27928266

A system verification platform for high-density epiretinal prostheses.

PubMed

Chen, Kuanfu; Lo, Yi-Kai; Yang, Zhi; Weiland, James D; Humayun, Mark S; Liu, Wentai

2013-06-01

Retinal prostheses have restored light perception to people worldwide who have poor or no vision as a consequence of retinal degeneration. To advance the quality of visual stimulation for retinal implant recipients, a higher number of stimulation channels is expected in the next generation retinal prostheses, which poses a great challenge to system design and verification. This paper presents a system verification platform dedicated to the development of retinal prostheses. The system includes primary processing, dual-band power and data telemetry, a high-density stimulator array, and two methods for output verification. End-to-end system validation and individual functional block characterization can be achieved with this platform through visual inspection and software analysis. Custom-built software running on the computers also provides a good way for testing new features before they are realized by the ICs. Real-time visual feedbacks through the video displays make it easy to monitor and debug the system. The characterization of the wireless telemetry and the demonstration of the visual display are reported in this paper using a 256-channel retinal prosthetic IC as an example.

[Tanning lamp radiation-induced photochemical retinal damage].

PubMed

Volkov, V V; Kharitonova, N N; Mal'tsev, D S

2014-01-01

On the basis of original clinical research a rare case of bilateral retinal damage due to tanning lamp radiation exposure is presented. Along with significant decrease of visual acuity and light sensitivity of central visual field as well as color vision impairment, bilateral macular dystrophy was found during an ophthalmoscopy and confirmed by optical coherent tomography and fluorescent angiography. Intensive retinoprotective, vascular, and antioxidant therapy was effective and led to functional improvement and stabilization of the pathologic process associated with photochemical retinal damage. A brief review of literature compares mechanisms of retinal damage by either short or long-wave near visible radiation.

A fully organic retinal prosthesis restores vision in a rat model of degenerative blindness

NASA Astrophysics Data System (ADS)

Maya-Vetencourt, José Fernando; Ghezzi, Diego; Antognazza, Maria Rosa; Colombo, Elisabetta; Mete, Maurizio; Feyen, Paul; Desii, Andrea; Buschiazzo, Ambra; di Paolo, Mattia; di Marco, Stefano; Ticconi, Flavia; Emionite, Laura; Shmal, Dmytro; Marini, Cecilia; Donelli, Ilaria; Freddi, Giuliano; Maccarone, Rita; Bisti, Silvia; Sambuceti, Gianmario; Pertile, Grazia; Lanzani, Guglielmo; Benfenati, Fabio

2017-06-01

The degeneration of photoreceptors in the retina is one of the major causes of adult blindness in humans. Unfortunately, no effective clinical treatments exist for the majority of retinal degenerative disorders. Here we report on the fabrication and functional validation of a fully organic prosthesis for long-term in vivo subretinal implantation in the eye of Royal College of Surgeons rats, a widely recognized model of retinitis pigmentosa. Electrophysiological and behavioural analyses reveal a prosthesis-dependent recovery of light sensitivity and visual acuity that persists up to 6-10 months after surgery. The rescue of the visual function is accompanied by an increase in the basal metabolic activity of the primary visual cortex, as demonstrated by positron emission tomography imaging. Our results highlight the possibility of developing a new generation of fully organic, highly biocompatible and functionally autonomous photovoltaic prostheses for subretinal implants to treat degenerative blindness.

A fully organic retinal prosthesis restores vision in a rat model of degenerative blindness

PubMed Central

Antognazza, Maria Rosa; Colombo, Elisabetta; Mete, Maurizio; Feyen, Paul; Desii, Andrea; Buschiazzo, Ambra; Di Paolo, Mattia; Di Marco, Stefano; Ticconi, Flavia; Emionite, Laura; Shmal, Dmytro; Marini, Cecilia; Donelli, Ilaria; Freddi, Giuliano; Maccarone, Rita; Bisti, Silvia; Sambuceti, Gianmario; Pertile, Grazia; Lanzani, Guglielmo; Benfenati, Fabio

2017-01-01

The degeneration of photoreceptors in the retina is one of the major causes of adult blindness in humans. Unfortunately, no effective clinical treatments exist for the majority of retinal degenerative disorders. Here we report on the fabrication and functional validation of a fully organic prosthesis for long-term in vivo subretinal implantation in the eye of Royal College of Surgeons rats, a widely recognized model of Retinitis pigmentosa. Electrophysiological and behavioral analyses reveal a prosthesis-dependent recovery of light-sensitivity and visual acuity that persists up to 6-10 months after surgery. The rescue of the visual function is accompanied by an increase in the basal metabolic activity of the primary visual cortex, as demonstrated by positron emission tomography imaging. Our results highlight the possibility of developing a new generation of fully organic, highly biocompatible and functionally autonomous photovoltaic prostheses for subretinal implants to treat degenerative blindness. PMID:28250420

Perifoveal function in patients with North Carolina macular dystrophy: the importance of accounting for fixation locus.

PubMed

Seiple, William; Szlyk, Janet P; Paliga, Jennifer; Rabb, Maurice F

2006-04-01

To quantify the extent of visual function losses in patients with North Carolina Macular Dystrophy (NCMD) and to demonstrate the importance of accounting for eccentric fixation when making comparisons with normal data. Five patients with NCMD who were from a single family were examined. Multifocal electroretinograms (mfERGs) and psychophysical assessments of acuity and luminance visual field sensitivities were measured throughout the central retina. Comparisons of responses from equivalent retinal areas were accomplished by shifting normal templates to be centered at the locus of fixation for each patient. Losses of psychophysically measured visual function in patients with NCMD extend to areas adjacent to the locations of visible lesions. The multifocal ERG amplitude was reduced only within the area of visible lesion. Multifocal ERG implicit times were delayed throughout the entire central retinal area assessed. ERG timing is a sensitive assay of retinal function, and our results indicate that NCMD has a widespread effect at the level of the mid and outer retina. The findings also demonstrated that it is necessary to account for fixation locus and to ensure that equivalent retinal areas are compared when testing patients with macular disease who have eccentric fixation.

High-Resolution Opto-Electronic Retinal Prosthesis: Physical Limitations and Design

NASA Astrophysics Data System (ADS)

Palanker, D.; Vankov, A.; Huie, P.; Butterwick, A.; Chan, I.; Marmor, M. F.; Blumenkranz, M. S.

Electrical stimulation of the retina can produce visual percepts in blind patients suffering from macular degeneration and retinitis pigmentosa (RP). However, current retinal implants provide very low resolution (just a few electrodes), whereas many more pixels would be required for a functional restoration of sight.

Evaluation of patient suitability for a retinal prosthesis using structural and functional tests of inner retinal integrity

NASA Astrophysics Data System (ADS)

Huang, Qiuhen; Chowdhury, Vivek; Coroneo, Minas Theodore

2009-06-01

The purpose of this study was to assess inner retinal structure and function in patients with retinitis pigmentosa (RP) using optical coherence tomography (OCT) imaging of the retina, and electrical stimulation of the retina with a contact lens electrode. OCT images of 17 RP patients were acquired at the macula and at four quadrants of the peripheral retina in both eyes. Analysis was made of the residual inner retinal thickness and nerve fibre layer thickness in RP patients, and this was compared to normal controls. Eight of these patients further underwent contact lens electrical stimulation of one eye and thresholds for phosphene perception were obtained. OCT imaging showed a significant amount of inner retinal preservation in the peripheral retina and the macula of RP patients despite severe visual acuity and visual field loss. Phosphene thresholds were obtained across the range of pulse durations tested but were much higher than those obtained in normal controls. Phosphene thresholds in RP patients moderately correlated with inner retinal thicknesses as measured by OCT. Preservation of inner retinal structure in patients with RP and the responsiveness of these eyes to electrical stimulation suggest adequate inner retinal preservation for a retinal prosthesis to be successful.

Cone Photoreceptor Abnormalities Correlate with Vision Loss in Patients with Stargardt Disease

PubMed Central

Chen, Yingming; Ratnam, Kavitha; Sundquist, Sanna M.; Lujan, Brandon; Ayyagari, Radha; Gudiseva, V. Harini; Roorda, Austin

2011-01-01

Purpose. To study the relationship between macular cone structure, fundus autofluorescence (AF), and visual function in patients with Stargardt disease (STGD). Methods. High-resolution images of the macula were obtained with adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography in 12 patients with STGD and 27 age-matched healthy subjects. Measures of retinal structure and AF were correlated with visual function, including best-corrected visual acuity, color vision, kinetic and static perimetry, fundus-guided microperimetry, and full-field electroretinography. Mutation analysis of the ABCA4 gene was completed in all patients. Results. Patients were 15 to 55 years old, and visual acuity ranged from 20/25–20/320. Central scotomas were present in all patients, although the fovea was spared in three patients. The earliest cone spacing abnormalities were observed in regions of homogeneous AF, normal visual function, and normal outer retinal structure. Outer retinal structure and AF were most normal near the optic disc. Longitudinal studies showed progressive increases in AF followed by reduced AF associated with losses of visual sensitivity, outer retinal layers, and cones. At least one disease-causing mutation in the ABCA4 gene was identified in 11 of 12 patients studied; 1 of 12 patients showed no disease-causing ABCA4 mutations. Conclusions. AOSLO imaging demonstrated abnormal cone spacing in regions of abnormal fundus AF and reduced visual function. These findings provide support for a model of disease progression in which lipofuscin accumulation results in homogeneously increased AF with cone spacing abnormalities, followed by heterogeneously increased AF with cone loss, then reduced AF with cone and RPE cell death. (ClinicalTrials.gov number, NCT00254605.) PMID:21296825

The use of microperimetry in assessing visual function in age-related macular degeneration.

PubMed

Cassels, Nicola K; Wild, John M; Margrain, Tom H; Chong, Victor; Acton, Jennifer H

Microperimetry is a novel technique for assessing visual function that appears particularly suitable for age-related macular degeneration (AMD). Compared with standard automated perimetry, microperimetry offers several unique features. It simultaneously images the fundus, incorporates an eye-tracking system to correct the stimulus location for fixation loss, and identifies any preferred retinal loci. We identified 52 articles that met the inclusion criteria for a systematic review of microperimetry in the assessment of visual function in AMD. We discuss microperimetry and AMD in relation to disease severity, structural imaging outcomes, other measures of visual function, and evaluation of the efficacy of surgical and/or medical therapies in clinical trials. The evidence for the use of microperimetry in the functional assessment of AMD is encouraging. Disruptions of the ellipsoid zone band and retinal pigment epithelium are clearly associated with reduced differential light sensitivity despite the maintenance of good visual acuity. Reduced differential light sensitivity is also associated with outer segment thinning and retinal pigment epithelium thickening in early AMD and with both a thickening and a thinning of the whole retina in choroidal neovascularization. Microperimetry, however, lacks the robust diffuse and focal loss age-corrected probability analyses associated with standard automated perimetry, and the technique is currently limited by this omission. Copyright © 2017 Elsevier Inc. All rights reserved.

A Fine-Scale Functional Logic to Convergence from Retina to Thalamus.

PubMed

Liang, Liang; Fratzl, Alex; Goldey, Glenn; Ramesh, Rohan N; Sugden, Arthur U; Morgan, Josh L; Chen, Chinfei; Andermann, Mark L

2018-05-31

Numerous well-defined classes of retinal ganglion cells innervate the thalamus to guide image-forming vision, yet the rules governing their convergence and divergence remain unknown. Using two-photon calcium imaging in awake mouse thalamus, we observed a functional arrangement of retinal ganglion cell axonal boutons in which coarse-scale retinotopic ordering gives way to fine-scale organization based on shared preferences for other visual features. Specifically, at the ∼6 μm scale, clusters of boutons from different axons often showed similar preferences for either one or multiple features, including axis and direction of motion, spatial frequency, and changes in luminance. Conversely, individual axons could "de-multiplex" information channels by participating in multiple, functionally distinct bouton clusters. Finally, ultrastructural analyses demonstrated that retinal axonal boutons in a local cluster often target the same dendritic domain. These data suggest that functionally specific convergence and divergence of retinal axons may impart diverse, robust, and often novel feature selectivity to visual thalamus. Copyright © 2018 Elsevier Inc. All rights reserved.

Design of a high-resolution optoelectronic retinal prosthesis.

PubMed

Palanker, Daniel; Vankov, Alexander; Huie, Phil; Baccus, Stephen

2005-03-01

It has been demonstrated that electrical stimulation of the retina can produce visual percepts in blind patients suffering from macular degeneration and retinitis pigmentosa. However, current retinal implants provide very low resolution (just a few electrodes), whereas at least several thousand pixels would be required for functional restoration of sight. This paper presents the design of an optoelectronic retinal prosthetic system with a stimulating pixel density of up to 2500 pix mm(-2) (corresponding geometrically to a maximum visual acuity of 20/80). Requirements on proximity of neural cells to the stimulation electrodes are described as a function of the desired resolution. Two basic geometries of sub-retinal implants providing required proximity are presented: perforated membranes and protruding electrode arrays. To provide for natural eye scanning of the scene, rather than scanning with a head-mounted camera, the system operates similar to 'virtual reality' devices. An image from a video camera is projected by a goggle-mounted collimated infrared LED-LCD display onto the retina, activating an array of powered photodiodes in the retinal implant. The goggles are transparent to visible light, thus allowing for the simultaneous use of remaining natural vision along with prosthetic stimulation. Optical delivery of visual information to the implant allows for real-time image processing adjustable to retinal architecture, as well as flexible control of image processing algorithms and stimulation parameters.

Design of a high-resolution optoelectronic retinal prosthesis

NASA Astrophysics Data System (ADS)

Palanker, Daniel; Vankov, Alexander; Huie, Phil; Baccus, Stephen

2005-03-01

It has been demonstrated that electrical stimulation of the retina can produce visual percepts in blind patients suffering from macular degeneration and retinitis pigmentosa. However, current retinal implants provide very low resolution (just a few electrodes), whereas at least several thousand pixels would be required for functional restoration of sight. This paper presents the design of an optoelectronic retinal prosthetic system with a stimulating pixel density of up to 2500 pix mm-2 (corresponding geometrically to a maximum visual acuity of 20/80). Requirements on proximity of neural cells to the stimulation electrodes are described as a function of the desired resolution. Two basic geometries of sub-retinal implants providing required proximity are presented: perforated membranes and protruding electrode arrays. To provide for natural eye scanning of the scene, rather than scanning with a head-mounted camera, the system operates similar to 'virtual reality' devices. An image from a video camera is projected by a goggle-mounted collimated infrared LED-LCD display onto the retina, activating an array of powered photodiodes in the retinal implant. The goggles are transparent to visible light, thus allowing for the simultaneous use of remaining natural vision along with prosthetic stimulation. Optical delivery of visual information to the implant allows for real-time image processing adjustable to retinal architecture, as well as flexible control of image processing algorithms and stimulation parameters.

Analysis of retinal function using chromatic pupillography in retinitis pigmentosa and the relationship to electrically evoked phosphene thresholds.

PubMed

Kelbsch, Carina; Maeda, Fumiatsu; Lisowska, Jolanta; Lisowski, Lukasz; Strasser, Torsten; Stingl, Krunoslav; Wilhelm, Barbara; Wilhelm, Helmut; Peters, Tobias

2017-06-01

To analyse pupil responses to specific chromatic stimuli in patients with advanced retinitis pigmentosa (RP) to ascertain whether chromatic pupillography can be used as an objective marker for residual retinal function. To examine correlations between parameters of the pupil response and the perception threshold of electrically evoked phosphenes. Chromatic pupillography was performed in 40 patients with advanced RP (visual acuity < 0.02 or visual field ≤5°, non-recordable ERGs) and 40 age-matched healthy subjects. Pupil responses to full-field red (605 nm) and blue (420 nm) stimuli of 28 lx corneal illumination were recorded and analysed for two stimulus durations (1 and 4 seconds). The perception threshold of phosphenes to transcorneal electrostimulation was ascertained and correlated to the pupil responses and visual acuity. Patients with RP showed significantly reduced pupil responses to red and blue stimuli compared with the controls. With red stimuli, pupillary escape could be observed; blue stimuli resulted in a well-preserved postillumination pupil response. Phosphene thresholds were significantly increased in patients with RP and correlated with the parameters of the pupil response if all subjects were considered. Within the RP group alone, this relationship was less pronounced and statistically not significant. Chromatic pupillography demonstrated a significant decrease in outer retinal photoreceptor responses but a persisting and disinhibited intrinsic photosensitive retinal ganglion cell function in advanced RP. These phenomena may be useful as an objective marker for the efficacy of any interventional treatment for hereditary retinal diseases as well as for the selection of suitable patients for an electronic retinal implant. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Orientation-Selective Retinal Circuits in Vertebrates

PubMed Central

Antinucci, Paride; Hindges, Robert

2018-01-01

Visual information is already processed in the retina before it is transmitted to higher visual centers in the brain. This includes the extraction of salient features from visual scenes, such as motion directionality or contrast, through neurons belonging to distinct neural circuits. Some retinal neurons are tuned to the orientation of elongated visual stimuli. Such ‘orientation-selective’ neurons are present in the retinae of most, if not all, vertebrate species analyzed to date, with species-specific differences in frequency and degree of tuning. In some cases, orientation-selective neurons have very stereotyped functional and morphological properties suggesting that they represent distinct cell types. In this review, we describe the retinal cell types underlying orientation selectivity found in various vertebrate species, and highlight their commonalities and differences. In addition, we discuss recent studies that revealed the cellular, synaptic and circuit mechanisms at the basis of retinal orientation selectivity. Finally, we outline the significance of these findings in shaping our current understanding of how this fundamental neural computation is implemented in the visual systems of vertebrates. PMID:29467629

Orientation-Selective Retinal Circuits in Vertebrates.

PubMed

Antinucci, Paride; Hindges, Robert

2018-01-01

Visual information is already processed in the retina before it is transmitted to higher visual centers in the brain. This includes the extraction of salient features from visual scenes, such as motion directionality or contrast, through neurons belonging to distinct neural circuits. Some retinal neurons are tuned to the orientation of elongated visual stimuli. Such 'orientation-selective' neurons are present in the retinae of most, if not all, vertebrate species analyzed to date, with species-specific differences in frequency and degree of tuning. In some cases, orientation-selective neurons have very stereotyped functional and morphological properties suggesting that they represent distinct cell types. In this review, we describe the retinal cell types underlying orientation selectivity found in various vertebrate species, and highlight their commonalities and differences. In addition, we discuss recent studies that revealed the cellular, synaptic and circuit mechanisms at the basis of retinal orientation selectivity. Finally, we outline the significance of these findings in shaping our current understanding of how this fundamental neural computation is implemented in the visual systems of vertebrates.

Visual Functions of the Thalamus

PubMed Central

Usrey, W. Martin; Alitto, Henry J.

2017-01-01

The thalamus is the heavily interconnected partner of the neocortex. All areas of the neocortex receive afferent input from and send efferent projections to specific thalamic nuclei. Through these connections, the thalamus serves to provide the cortex with sensory input, and to facilitate interareal cortical communication and motor and cognitive functions. In the visual system, the lateral geniculate nucleus (LGN) of the dorsal thalamus is the gateway through which visual information reaches the cerebral cortex. Visual processing in the LGN includes spatial and temporal influences on visual signals that serve to adjust response gain, transform the temporal structure of retinal activity patterns, and increase the signal-to-noise ratio of the retinal signal while preserving its basic content. This review examines recent advances in our understanding of LGN function and circuit organization and places these findings in a historical context. PMID:28217740

Postconditioning with inhaled hydrogen promotes survival of retinal ganglion cells in a rat model of retinal ischemia/reperfusion injury.

PubMed

Wang, Ruobing; Wu, Jiangchun; Chen, Zeli; Xia, Fangzhou; Sun, Qinglei; Liu, Lin

2016-02-01

Retinal ischemia/reperfusion (I/R) injury plays a crucial role in the pathophysiology of various ocular diseases. Intraperitoneal injection or ocular instillation with hydrogen (H2)-rich saline was recently shown to be neuroprotective in the retina due to its anti-oxidative and anti-inflammatory effects. Our study aims to explore whether postconditioning with inhaled H2 can protect retinal ganglion cells (RGCs) in a rat model of retinal I/R injury. Retinal I/R injury was performed on the right eyes of rats and was followed by inhalation of 67% H2 mixed with 33% oxygen immediately after ischemia for 1h daily for one week. RGC density was counted using haematoxylin and eosin (HE) staining and retrograde labeling with cholera toxin beta (CTB). Visual function was assessed using flash visual evoked potentials (FVEP) and pupillary light reflex (PLR). Potential biomarkers of retinal oxidative stress and inflammatory responses were measured, including the expression of 4-Hydroxynonenalv (4-HNE), interleukin-1 beta (IL1-β) and tumor necrosis factor alpha (TNF-α). HE and CTB tracing showed that the survival rate of RGCs in the H2-treated group was significantly higher than the rate in the I/R group. Rats with H2 inhalation showed better visual function in assessments of FVEP and PLR. Moreover, H2 treatment significantly decreased the number of 4-HNE-stained cells in the ganglion cell layer and inhibited the retinal overexpression of IL1-β and TNF-α that was induced by retinal I/R injury. Our results demonstrate that postconditioning with inhaled high-dose H2 appears to confer neuroprotection against retinal I/R injury via anti-oxidative, anti-inflammatory and anti-apoptosis pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

Radial optic neurotomy for ischaemic central vein occlusion

PubMed Central

Martínez-Jardón, C S; Meza-de Regil, A; Dalma-Weiszhausz, J; Leizaola-Fernández, C; Morales-Cantón, V; Guerrero-Naranjo, J L; Quiroz-Mercado, H

2005-01-01

Background/aims: Ischaemic central retinal vein occlusion (CRVO) accounts for 20–50% of all CRVO. No treatment has been proved to be effective. The efficacy of radial optic neurotomy (RON) was evaluated in eyes with ischaemic CRVO. Methods: 10 patients with ischaemic CRVO underwent RON. After pars plana vitrectomy, a microvitreoretinal blade was used to incise the scleral ring, cribriform plate, and adjacent sclera at the nasal edge of the optic disc. Best corrected visual acuity (BCVA), intraocular pressure (IOP), fluorescein angiography (FA), multifocal electroretinography (mfERG), and optical coherence tomography (OCT) were measured preoperatively and at 1, 3, and 6 months postoperatively. Results: No visual improvement was noted in the eyes that underwent RON. FA and mfERG showed no increase in retinal perfusion or retinal function postoperatively. Mean macular central thickness changed from 841 (SD 170) μm preoperatively to 162 (SD 34) μm at the sixth postoperative month. One patient had retinal central artery perforation intraoperatively. One patient developed neovascular glaucoma. Conclusion: RON in ischaemic CRVO did not improve visual function (by mfERG) or visual acuity although macular thickness did improve. This technique may be associated with potential risks. Randomised studies are needed to corroborate these results. PMID:15834084

Features and functions of nonlinear spatial integration by retinal ganglion cells.

PubMed

Gollisch, Tim

2013-11-01

Ganglion cells in the vertebrate retina integrate visual information over their receptive fields. They do so by pooling presynaptic excitatory inputs from typically many bipolar cells, which themselves collect inputs from several photoreceptors. In addition, inhibitory interactions mediated by horizontal cells and amacrine cells modulate the structure of the receptive field. In many models, this spatial integration is assumed to occur in a linear fashion. Yet, it has long been known that spatial integration by retinal ganglion cells also incurs nonlinear phenomena. Moreover, several recent examples have shown that nonlinear spatial integration is tightly connected to specific visual functions performed by different types of retinal ganglion cells. This work discusses these advances in understanding the role of nonlinear spatial integration and reviews recent efforts to quantitatively study the nature and mechanisms underlying spatial nonlinearities. These new insights point towards a critical role of nonlinearities within ganglion cell receptive fields for capturing responses of the cells to natural and behaviorally relevant visual stimuli. In the long run, nonlinear phenomena of spatial integration may also prove important for implementing the actual neural code of retinal neurons when designing visual prostheses for the eye. Copyright © 2012 Elsevier Ltd. All rights reserved.

Visual Cortical Function in Very Low Birth Weight Infants without Retinal or Cerebral Pathology

PubMed Central

Hou, Chuan; Norcia, Anthony M.; Madan, Ashima; Tith, Solina; Agarwal, Rashi

2011-01-01

Purpose. Preterm infants are at high risk of visual and neural developmental deficits. However, the development of visual cortical function in preterm infants with no retinal or neurologic morbidity has not been well defined. To determine whether premature birth itself alters visual cortical function, swept parameter visual evoked potential (sVEP) responses of healthy preterm infants were compared with those of term infants. Methods. Fifty-two term infants and 58 very low birth weight (VLBW) infants without significant retinopathy of prematurity or neurologic morbidities were enrolled. Recruited VLBW infants were between 26 and 33 weeks of gestational age, with birth weights of less than 1500 g. Spatial frequency, contrast, and vernier offset sweep VEP tuning functions were measured at 5 to 7 months' corrected age. Acuity and contrast thresholds were derived by extrapolating the tuning functions to 0 amplitude. These thresholds and suprathreshold response amplitudes were compared between groups. Results. Preterm infants showed increased thresholds (indicating decreased sensitivity to visual stimuli) and reductions in amplitudes for all three measures. These changes in cortical responsiveness were larger in the <30 weeks ' gestational age subgroup than in the ≥30 weeks' gestational age subgroup. Conclusions. Preterm infants with VLBW had measurable and significant changes in cortical responsiveness that were correlated with gestational age. These results suggest that premature birth in the absence of identifiable retinal or neurologic abnormalities has a significant effect on visual cortical sensitivity at 5 to 7 months' of corrected age and that gestational age is an important factor in visual development. PMID:22025567

Daily visual stimulation in the critical period enhances multiple aspects of vision through BDNF-mediated pathways in the mouse retina

PubMed Central

Mui, Amanda M.; Yang, Victoria; Aung, Moe H.; Fu, Jieming; Adekunle, Adewumi N.; Prall, Brian C.; Sidhu, Curran S.; Park, Han na; Boatright, Jeffrey H.; Iuvone, P. Michael

2018-01-01

Visual experience during the critical period modulates visual development such that deprivation causes visual impairments while stimulation induces enhancements. This study aimed to determine whether visual stimulation in the form of daily optomotor response (OMR) testing during the mouse critical period (1) improves aspects of visual function, (2) involves retinal mechanisms and (3) is mediated by brain derived neurotrophic factor (BDNF) and dopamine (DA) signaling pathways. We tested spatial frequency thresholds in C57BL/6J mice daily from postnatal days 16 to 23 (P16 to P23) using OMR testing. Daily OMR-treated mice were compared to littermate controls that were placed in the OMR chamber without moving gratings. Contrast sensitivity thresholds, electroretinograms (ERGs), visual evoked potentials, and pattern ERGs were acquired at P21. To determine the role of BDNF signaling, a TrkB receptor antagonist (ANA-12) was systemically injected 2 hours prior to OMR testing in another cohort of mice. BDNF immunohistochemistry was performed on retina and brain sections. Retinal DA levels were measured using high-performance liquid chromatography. Daily OMR testing enhanced spatial frequency thresholds and contrast sensitivity compared to controls. OMR-treated mice also had improved rod-driven ERG oscillatory potential response times, greater BDNF immunoreactivity in the retinal ganglion cell layer, and increased retinal DA content compared to controls. VEPs and pattern ERGs were unchanged. Systemic delivery of ANA-12 attenuated OMR-induced visual enhancements. Daily OMR testing during the critical period leads to general visual function improvements accompanied by increased DA and BDNF in the retina, with this process being requisitely mediated by TrkB activation. These results suggest that novel combination therapies involving visual stimulation and using both behavioral and molecular approaches may benefit degenerative retinal diseases or amblyopia. PMID:29408880

Ocular dynamics and visual tracking performance after Q-switched laser exposure

NASA Astrophysics Data System (ADS)

Zwick, Harry; Stuck, Bruce E.; Lund, David J.; Nawim, Maqsood

2001-05-01

In previous investigations of q-switched laser retinal exposure in awake task oriented non-human primates (NHPs), the threshold for retinal damage occurred well below that of the threshold for permanent visual function loss. Visual function measures used in these studies involved measures of visual acuity and contrast sensitivity. In the present study, we examine the same relationship for q-switched laser exposure using a visual performance task, where task dependency involves more parafoveal than foveal retina. NHPs were trained on a visual pursuit motor tracking performance task that required maintaining a small HeNe laser spot (0.3 degrees) centered in a slowly moving (0.5deg/sec) annulus. When NHPs reliably produced visual target tracking efficiencies > 80%, single q-switched laser exposures (7 nsec) were made coaxially with the line of sight of the moving target. An infrared camera imaged the pupil during exposure to obtain the pupillary response to the laser flash. Retinal images were obtained with a scanning laser ophthalmoscope 3 days post exposure under ketamine and nembutol anesthesia. Q-switched visible laser exposures at twice the damage threshold produced small (about 50mm) retinal lesions temporal to the fovea; deficits in NHP visual pursuit tracking were transient, demonstrating full recovery to baseline within a single tracking session. Post exposure analysis of the pupillary response demonstrated that the exposure flash entered the pupil, followed by 90 msec refractory period and than a 12 % pupillary contraction within 1.5 sec from the onset of laser exposure. At 6 times the morphological threshold damage level for 532 nm q-switched exposure, longer term losses in NHP pursuit tracking performance were observed. In summary, q-switched laser exposure appears to have a higher threshold for permanent visual performance loss than the corresponding threshold to produce retinal threshold injury. Mechanisms of neural plasticity within the retina and at higher visual brain centers may mediat

Ophthalmological assessment of cannabis-induced persisting perception disorder: is there a direct retinal effect?

PubMed

Zobor, Ditta; Strasser, Torsten; Zobor, Gergely; Schober, Franziska; Messias, Andre; Strauss, Olaf; Batra, Anil; Zrenner, Eberhart

2015-04-01

Cannabis is a psychotomimetic agent that induces impairment of sensory perception. We present detailed clinical and electrophysiological data of patients with hallucinogen persisting perception disorder (HPPD) after marijuana consumption. A HPPD patient and four heavy cannabis smokers with no visual disturbances (controls) underwent complete ophthalmological examination including psychophysical tests (visual acuity, color vision, visual field, and dark adaptation) and detailed electrophysiological examinations, including extended Ganzfeld ERG, multifocal ERG, and electrooculography (EOG). Furthermore, electrically evoked phosphene thresholds (EPTs) were measured to further evaluate retinal function. Ophthalmological and most electrophysiological examinations were within normal limits for the HPPD patient and for all control subjects. Interestingly, EOG results of the HPPD patient showed a slightly reduced fast oscillation ratio, diminished standing potentials of the slow oscillations, and a light peak within normal range resulting in higher Arden ratios. The EPTs of the patient were reduced, in particular for pulses with long durations (50 ms) causing visual sensations even at lowest possible currents of the neurostimulator. The control subjects did not reveal such alterations. Our findings suggest a direct effect of cannabinoids on the retina and retinal pigment epithelium function, which may be involved in disturbances of the visual function experienced after drug consumption. The observations presented here may contribute to the elucidation of the detailed mechanism. Furthermore, EOG and EPT measurements may be useful tools to demonstrate long-term retinal alterations in cannabis-induced HPPD in patients.

Long-Term Effect of Gene Therapy on Leber’s Congenital Amaurosis

PubMed Central

Bainbridge, J.W.B.; Mehat, M.S.; Sundaram, V.; Robbie, S.J.; Barker, S.E.; Ripamonti, C.; Georgiadis, A.; Mowat, F.M.; Beattie, S.G.; Gardner, P.J.; Feathers, K.L.; Luong, V.A.; Yzer, S.; Balaggan, K.; Viswanathan, A.; de Ravel, T.J.L.; Casteels, I.; Holder, G.E.; Tyler, N.; Fitzke, F.W.; Weleber, R.G.; Nardini, M.; Moore, A.T.; Thompson, D.A.; Petersen-Jones, S.M.; Michaelides, M.; van den Born, L.I.; Stockman, A.; Smith, A.J.; Rubin, G.; Ali, R.R.

2015-01-01

BACKGROUND Mutations in RPE65 cause Leber’s congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited. METHODS We performed a phase 1–2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, and measured visual function over the course of 3 years. Four participants were administered a lower dose of the vector, and 8 were administered a higher dose. In a parallel study in dogs, we investigated the relationship among vector dose, visual function, and electroretinography (ERG) findings. RESULTS Improvements in retinal sensitivity were evident, to varying extents, in six participants for up to 3 years, peaking at 6 to 12 months after treatment and then declining. No associated improvement in retinal function was detected by means of ERG. Three participants had intraocular inflammation, and two had clinically significant deterioration of visual acuity. The reduction in central retinal thickness varied among participants. In dogs, RPE65 gene therapy with the same vector at lower doses improved vision-guided behavior, but only higher doses resulted in improvements in retinal function that were detectable with the use of ERG. CONCLUSIONS Gene therapy with rAAV2/2 RPE65 vector improved retinal sensitivity, albeit modestly and temporarily. Comparison with the results obtained in the dog model indicates that there is a species difference in the amount of RPE65 required to drive the visual cycle and that the demand for RPE65 in affected persons was not met to the extent required for a durable, robust effect. (Funded by the National Institute for Health Research and others; ClinicalTrials.gov number, NCT00643747.) PMID:25938638

Recovery from retinal lesions: molecular plasticity mechanisms in visual cortex far beyond the deprived zone.

PubMed

Hu, Tjing-Tjing; Van den Bergh, Gert; Thorrez, Lieven; Heylen, Kevin; Eysel, Ulf T; Arckens, Lutgarde

2011-12-01

In cats with central retinal lesions, deprivation of the lesion projection zone (LPZ) in primary visual cortex (area 17) induces remapping of the cortical topography. Recovery of visually driven cortical activity in the LPZ involves distinct changes in protein expression. Recent observations, about molecular activity changes throughout area 17, challenge the view that its remote nondeprived parts would not be involved in this recovery process. We here investigated the dynamics of the protein expression pattern of remote nondeprived area 17 triggered by central retinal lesions to explore to what extent far peripheral area 17 would contribute to the topographic map reorganization inside the visual cortex. Using functional proteomics, we identified 40 proteins specifically differentially expressed between far peripheral area 17 of control and experimental animals 14 days to 8 months postlesion. Our results demonstrate that far peripheral area 17 is implicated in the functional adaptation to the visual deprivation, involving a meshwork of interacting proteins, operating in diverse pathways. In particular, endocytosis/exocytosis processes appeared to be essential via their intimate correlation with long-term potentiation and neurite outgrowth mechanisms.

ATP-binding cassette transporter ABCA4 and chemical isomerization protect photoreceptor cells from the toxic accumulation of excess 11-cis-retinal.

PubMed

Quazi, Faraz; Molday, Robert S

2014-04-01

The visual cycle is a series of enzyme-catalyzed reactions which converts all-trans-retinal to 11-cis-retinal for the regeneration of visual pigments in rod and cone photoreceptor cells. Although essential for vision, 11-cis-retinal like all-trans-retinal is highly toxic due to its highly reactive aldehyde group and has to be detoxified by either reduction to retinol or sequestration within retinal-binding proteins. Previous studies have focused on the role of the ATP-binding cassette transporter ABCA4 associated with Stargardt macular degeneration and retinol dehydrogenases (RDH) in the clearance of all-trans-retinal from photoreceptors following photoexcitation. How rod and cone cells prevent the accumulation of 11-cis-retinal in photoreceptor disk membranes in excess of what is required for visual pigment regeneration is not known. Here we show that ABCA4 can transport N-11-cis-retinylidene-phosphatidylethanolamine (PE), the Schiff-base conjugate of 11-cis-retinal and PE, from the lumen to the cytoplasmic leaflet of disk membranes. This transport function together with chemical isomerization to its all-trans isomer and reduction to all-trans-retinol by RDH can prevent the accumulation of excess 11-cis-retinal and its Schiff-base conjugate and the formation of toxic bisretinoid compounds as found in ABCA4-deficient mice and individuals with Stargardt macular degeneration. This segment of the visual cycle in which excess 11-cis-retinal is converted to all-trans-retinol provides a rationale for the unusually high content of PE and its long-chain unsaturated docosahexaenoyl group in photoreceptor membranes and adds insight into the molecular mechanisms responsible for Stargardt macular degeneration.

Retinal stimulation strategies to restore vision: Fundamentals and systems.

PubMed

Yue, Lan; Weiland, James D; Roska, Botond; Humayun, Mark S

2016-07-01

Retinal degeneration, a leading cause of blindness worldwide, is primarily characterized by the dysfunctional/degenerated photoreceptors that impair the ability of the retina to detect light. Our group and others have shown that bioelectronic retinal implants restore useful visual input to those who have been blind for decades. This unprecedented approach of restoring sight demonstrates that patients can adapt to new visual input, and thereby opens up opportunities to not only improve this technology but also develop alternative retinal stimulation approaches. These future improvements or new technologies could have the potential of selectively stimulating specific cell classes in the inner retina, leading to improved visual resolution and color vision. In this review we will detail the progress of bioelectronic retinal implants and future devices in this genre as well as discuss other technologies such as optogenetics, chemical photoswitches, and ultrasound stimulation. We will discuss the principles, biological aspects, technology development, current status, clinical outcomes/prospects, and challenges for each approach. The review will cover functional imaging documented cortical responses to retinal stimulation in blind patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Functional and Morphological Correlations before and after Video-Documented 23-Gauge Pars Plana Vitrectomy with Membrane and ILM Peeling in Patients with Macular Pucker.

PubMed

Mayer, Wolfgang J; Fazekas, Clara; Schumann, Ricarda; Wolf, Armin; Compera, Denise; Kampik, Anselm; Haritoglou, Christos

2015-01-01

Purpose. To assess functional and morphological alterations following video-documented surgery for epiretinal membranes. Methods. Forty-two patients underwent video-documented 23-gauge vitrectomy with peeling of epiretinal (ERM) and inner limiting membrane (ILM). Patient assessment was performed before and 3 and 6 months including best corrected visual acuity (BCVA), slit lamp biomicroscopy, SD-OCT, and central 2° and 18° microperimetry. In addition, all video-documented areas of peeling on the retinal surface were evaluated postoperatively using an additional focal 2° microperimetry. Retinal sensitivity and BCVA were correlated with morphological changes (EZ and ELM) in the foveal region and in regions of membrane peeling. Results. Overall, BCVA increased from 0.6 (±0.2) to 0.2 (±0.2) logMAR after 6 months with an increase in retinal sensitivity (17.9 ± 2.7 dB to 26.8 ± 3.1 dB, p < 0.01). We observed a significant correlation between the integrity of the EZ but not of the ELM and the retinal sensitivity, overall and in peeling areas (p < 0.05). However, no significant correlation between alterations in the area of peeling and overall retinal sensitivity regarding visual acuity gain could be observed after 6 months (p > 0.05). In contrast, overall postoperative retinal sensitivity was significantly decreased in patients with a visual acuity gain lower than 2 lines (p < 0.05) correlating with EZ defects seen in OCT. Conclusions. Mechanical trauma of epiretinal membrane and ILM peeling due to the use of intraocular forceps may affect the outer retinal structure. Nevertheless, these changes seem to have no significant impact on postoperative functional outcome.

Memory as Perception of the Past: Compressed Time inMind and Brain.

PubMed

Howard, Marc W

2018-02-01

In the visual system retinal space is compressed such that acuity decreases further from the fovea. Different forms of memory may rely on a compressed representation of time, manifested as decreased accuracy for events that happened further in the past. Neurophysiologically, "time cells" show receptive fields in time. Analogous to the compression of visual space, time cells show less acuity for events further in the past. Behavioral evidence suggests memory can be accessed by scanning a compressed temporal representation, analogous to visual search. This suggests a common computational language for visual attention and memory retrieval. In this view, time functions like a scaffolding that organizes memories in much the same way that retinal space functions like a scaffolding for visual perception. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nanowire arrays restore vision in blind mice.

PubMed

Tang, Jing; Qin, Nan; Chong, Yan; Diao, Yupu; Yiliguma; Wang, Zhexuan; Xue, Tian; Jiang, Min; Zhang, Jiayi; Zheng, Gengfeng

2018-03-06

The restoration of light response with complex spatiotemporal features in retinal degenerative diseases towards retinal prosthesis has proven to be a considerable challenge over the past decades. Herein, inspired by the structure and function of photoreceptors in retinas, we develop artificial photoreceptors based on gold nanoparticle-decorated titania nanowire arrays, for restoration of visual responses in the blind mice with degenerated photoreceptors. Green, blue and near UV light responses in the retinal ganglion cells (RGCs) are restored with a spatial resolution better than 100 µm. ON responses in RGCs are blocked by glutamatergic antagonists, suggesting functional preservation of the remaining retinal circuits. Moreover, neurons in the primary visual cortex respond to light after subretinal implant of nanowire arrays. Improvement in pupillary light reflex suggests the behavioral recovery of light sensitivity. Our study will shed light on the development of a new generation of optoelectronic toolkits for subretinal prosthetic devices.

Noninvasive multi–photon fluorescence microscopy resolves retinol and retinal–condensation products in mouse eyes

PubMed Central

Palczewska, Grazyna; Maeda, Tadao; Imanishi, Yoshikazu; Sun, Wenyu; Chen, Yu; Williams, David R.; Piston, David; Maeda, Akiko; Palczewski, Krzysztof

2010-01-01

Multi–photon excitation fluorescence microscopy (MPM) can image certain molecular processes in vivo. In the eye, fluorescent retinyl esters in sub–cellular structures called retinosomes mediate regeneration of the visual chromophore, 11–cis–retinal, by the visual cycle. But harmful fluorescent condensation products were also identified previously. We report that in wild type mice, excitation with λ ~730 nm identified retinosomes in the retinal pigment epithelium, whereas excitation with λ ~910 nm revealed at least one additional retinal fluorophore. The latter fluorescence was absent in eyes of genetically modified mice lacking a functional visual cycle, but accentuated in eyes of older WT mice and mice with defective clearance of all–trans–retinal, an intermediate in the visual cycle. MPM, a noninvasive imaging modality that facilitates concurrent monitoring of retinosomes along with potentially harmful products in aging eyes, has the potential to detect early molecular changes due to age–related macular degeneration and other defects in retinoid metabolism. PMID:21076393

Visual field defects and retinal nerve fiber imaging in patients with obstructive sleep apnea syndrome and in healthy controls.

PubMed

Casas, Paula; Ascaso, Francisco J; Vicente, Eugenio; Tejero-Garcés, Gloria; Adiego, María I; Cristóbal, José A

2018-03-02

To assess the retinal sensitivity in obstructive sleep apnea hypopnea syndrome (OSAHS) patients evaluated with standard automated perimetry (SAP). And to correlate the functional SAP results with structural parameters obtained with optical coherence tomography (OCT). This prospective, observational, case-control study consisted of 63 eyes of 63 OSAHS patients (mean age 51.7 ± 12.7 years, best corrected visual acuity ≥20/25, refractive error less than three spherical or two cylindrical diopters, and intraocular pressure < 21 mmHg) who were enrolled and compared with 38 eyes of 38 age-matched controls. Peripapillary retinal nerve fiber layer (RNFL) thickness was measured by Stratus OCT and SAP sensitivities and indices were explored with Humphrey Field Analyzer perimeter. Correlations between functional and structural parameters were calculated, as well as the relationship between ophthalmologic and systemic indices in OSAHS patients. OSAHS patients showed a significant reduction of the sensitivity for superior visual field division (p = 0.034, t-student test). When dividing the OSAHS group in accordance with the severity of the disease, nasal peripapillary RNFL thickness was significantly lower in severe OSAHS than that in controls and mild-moderate cases (p = 0.031 and p = 0.016 respectively, Mann-Whitney U test). There were no differences between groups for SAP parameters. We found no correlation between structural and functional variables. The central visual field sensitivity of the SAP revealed a poor Pearson correlation with the apnea-hipopnea index (0.284, p = 0.024). Retinal sensitivity show minor differences between healthy subjects and OSAHS. Functional deterioration in OSAHS patients is not easy to demonstrate with visual field examination.

Retinal specializations and visual ecology in an animal with an extremely elaborate pupil shape: The Little skate Leucoraja (Raja) erinacea Mitchell, 1825.

PubMed

Jinson, S Terrell; Liebich, Jan; Senft, Stephen L; Mäthger, Lydia M

2018-05-14

Investigating retinal specializations offers insights into eye functionality. Using retinal wholemount techniques, we investigated the distribution of retinal ganglion cells in the Little skate Leucoraja erinacea by (1) dye-backfilling into the optic nerve prior to retinal wholemounting; (2) Nissl-staining of retinal wholemounts. Retinas were examined for regional specializations (higher numbers) of ganglion cells that would indicate higher visual acuity in those areas. Total ganglion cell number were low compared to other elasmobranchs (backfilled: average 49,713 total ganglion cells, average peak cell density 1,315 ganglion cells mm -2 ; Nissl-stained: average 47,791 total ganglion cells, average peak cell density 1,319 ganglion cells mm -2 ). Ganglion cells fit into three size categories: small (5-20µm); medium (20-30µm); large: (≥ 30µm), and they were not homogeneously distributed across the retina. There was a dorsally located horizontal visual streak with increased ganglion cell density; additionally, there were approximately 3 local maxima in ganglion cell distribution (potential areae centrales) within this streak in which densities were highest. Using computerized tomography (CT) and micro-CT, geometrical dimensions of the eye were obtained. Combined with ganglion cell distributions, spatial resolving power was determined to be between 1.21 to 1.37 cycles per degree. Additionally, photoreceptor sizes across different retinal areas varied; photoreceptors were longest within the horizontal visual streak. Variations in the locations of retinal specializations appear to be related to the animal's anatomy: shape of the head and eyes, position of eyes, location of tapetum, and shape of pupil, as well as the visual demands associated with lifestyle and habitat type. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Integration of spectral domain optical coherence tomography with microperimetry generates unique datasets for the simultaneous identification of visual function and retinal structure in ophthalmological applications

NASA Astrophysics Data System (ADS)

Koulen, Peter; Gallimore, Gary; Vincent, Ryan D.; Sabates, Nelson R.; Sabates, Felix N.

2011-06-01

Conventional perimeters are used routinely in various eye disease states to evaluate the central visual field and to quantitatively map sensitivity. However, standard automated perimetry proves difficult for retina and specifically macular disease due to the need for central and steady fixation. Advances in instrumentation have led to microperimetry, which incorporates eye tracking for placement of macular sensitivity values onto an image of the macular fundus thus enabling a precise functional and anatomical mapping of the central visual field. Functional sensitivity of the retina can be compared with the observed structural parameters that are acquired with high-resolution spectral domain optical coherence tomography and by integration of scanning laser ophthalmoscope-driven imaging. Findings of the present study generate a basis for age-matched comparison of sensitivity values in patients with macular pathology. Microperimetry registered with detailed structural data performed before and after intervention treatments provides valuable information about macular function, disease progression and treatment success. This approach also allows for the detection of disease or treatment related changes in retinal sensitivity when visual acuity is not affected and can drive the decision making process in choosing different treatment regimens and guiding visual rehabilitation. This has immediate relevance for applications in central retinal vein occlusion, central serous choroidopathy, age-related macular degeneration, familial macular dystrophy and several other forms of retina related visual disability.

The Argus(®) II Retinal Prosthesis System.

PubMed

Luo, Yvonne Hsu-Lin; da Cruz, Lyndon

2016-01-01

The Argus(®) II Retinal Prosthesis System (Second Sight Medical Products) is the first prosthetic vision device to obtain regulatory approval in both Europe and the USA. As such it has entered the commercial market as a treatment for patients with profound vision loss from end-stage outer retinal disease, predominantly retinitis pigmentosa. To date, over 100 devices have been implanted worldwide, representing the largest group of patients currently treated with visual prostheses. The system works by direct stimulation of the relatively preserved inner retina via epiretinal microelectrodes, thereby replacing the function of the degenerated photoreceptors. Visual information from a glasses-mounted video camera is converted to a pixelated image by an external processor, before being transmitted to the microelectrode array at the macula. Elicited retinal responses are then relayed via the normal optic nerve to the cortex for interpretation. We reviewed the animal and human studies that led to the development of the Argus(®) II device. A sufficiently robust safety profile was demonstrated in the phase I/II clinical trial of 30 patients. Improvement of function in terms of orientation and mobility, target localisation, shape and object recognition, and reading of letters and short unrehearsed words have also been shown. There remains a wide variability in the functional outcomes amongst the patients and the factors contributing to these performance differences are still unclear. Future developments in terms of both software and hardware aimed at improving visual function have been proposed. Further experience in clinical outcomes is being acquired due to increasing implantation. Copyright © 2015. Published by Elsevier Ltd.

Sector retinitis pigmentosa.

PubMed

Van Woerkom, Craig; Ferrucci, Steven

2005-05-01

Retinitis pigmentosa (RP) is one of the most common hereditary retinal dystrophies and causes of visual impairment affecting all age groups. The reported incidence varies, but is considered to be between 1 in 3,000 to 1 in 7,000. Sector retinitis pigmentosa is an atypical form of RP that is characterized by regionalized areas of bone spicule pigmentation, usually in the inferior quadrants of the retina. A 57-year-old Hispanic man with a history of previously diagnosed retinitis pigmentosa came to the clinic with a longstanding symptom of decreased vision at night. Bone spicule pigmentation was found in the nasal and inferior quadrants in each eye. He demonstrated superior and temporal visual-field loss corresponding to the areas of the affected retina. Clinical measurements of visual-field loss, best-corrected visual acuity, and ophthalmoscopic appearance have remained stable during the five years the patient has been followed. Sector retinitis pigmentosa is an atypical form of RP that is characterized by bilateral pigmentary retinopathy, usually isolated to the inferior quadrants. The remainder of the retina appears clinically normal, although studies have found functional abnormalities in these areas as well. Sector RP is generally considered a stationary to slowly progressive disease, with subnormal electro-retinogram findings and visual-field defects corresponding to the involved retinal sectors. Management of RP is very difficult because there are no proven methods of treatment. Studies have shown 15,000 IU of vitamin A palmitate per day may slow the progression, though this result is controversial. Low vision rehabilitation, long wavelength pass filters, and pedigree counseling remain the mainstay of management.

Treatment of dry age-related macular degeneration with dobesilate

PubMed Central

Cuevas, P; Outeiriño, L A; Angulo, J; Giménez-Gallego, G

2012-01-01

The authors present anatomical and functional evidences of dry age-macular degeneration improvement, after intravitreal treatment with dobesilate. Main outcomes measures were normalisation of retinal structure and function, assessed by optical coherence tomography, fundus-monitored microperimetry, electrophysiology and visual acuity. The effect might be related to the normalisation of the outer retinal architecture. PMID:22729337

Blind source separation in retinal videos

NASA Astrophysics Data System (ADS)

Barriga, Eduardo S.; Truitt, Paul W.; Pattichis, Marios S.; Tüso, Dan; Kwon, Young H.; Kardon, Randy H.; Soliz, Peter

2003-05-01

An optical imaging device of retina function (OID-RF) has been developed to measure changes in blood oxygen saturation due to neural activity resulting from visual stimulation of the photoreceptors in the human retina. The video data that are collected represent a mixture of the functional signal in response to the retinal activation and other signals from undetermined physiological activity. Measured changes in reflectance in response to the visual stimulus are on the order of 0.1% to 1.0% of the total reflected intensity level which makes the functional signal difficult to detect by standard methods since it is masked by the other signals that are present. In this paper, we apply principal component analysis (PCA), blind source separation (BSS), using Extended Spatial Decorrelation (ESD) and independent component analysis (ICA) using the Fast-ICA algorithm to extract the functional signal from the retinal videos. The results revealed that the functional signal in a stimulated retina can be detected through the application of some of these techniques.

New GABA modulators protect photoreceptor cells from light-induced degeneration in mouse models.

PubMed

Schur, Rebecca M; Gao, Songqi; Yu, Guanping; Chen, Yu; Maeda, Akiko; Palczewski, Krzysztof; Lu, Zheng-Rong

2018-01-24

No clinically approved therapies are currently available that prevent the onset of photoreceptor death in retinal degeneration. Signaling between retinal neurons is regulated by the release and uptake of neurotransmitters, wherein GABA is the main inhibitory neurotransmitter. In this work, novel 3-chloropropiophenone derivatives and the clinical anticonvulsants tiagabine and vigabatrin were tested to modulate GABA signaling and protect against light-induced retinal degeneration. Abca4 -/- Rdh8 -/- mice, an accelerated model of retinal degeneration, were exposed to intense light after prophylactic injections of one of these compounds. Imaging and functional assessments of the retina indicated that these compounds successfully protected photoreceptor cells from degeneration to maintain a full-visual-field response. Furthermore, these compounds demonstrated a strong safety profile in wild-type mice and did not compromise visual function or damage the retina, despite repeated administration. These results indicate that modulating inhibitory GABA signaling can offer prophylactic protection against light-induced retinal degeneration.-Schur, R. M., Gao, S., Yu, G., Chen, Y., Maeda, A., Palczewski, K., Lu, Z.-R. New GABA modulators protect photoreceptor cells from light-induced degeneration in mouse models.

Visual evoked potential measurement of contrast sensitivity in a case of retinal laser injury reveals visual function loss despite normal acuity

NASA Astrophysics Data System (ADS)

Glickman, Randolph D.; Harrison, Joseph M.; Zwick, Harry; Longbotham, Harold G.; Ballentine, Charles S.; Pierce, Bennie

1996-04-01

Although visual function following retinal laser injuries has traditionally been assessed by measuring visual acuity, this measure only indicates the highest spatial frequency resolvable under high-contrast viewing conditions. Another visual psychophysical parameter is contrast sensitivity (CS), which measures the minimum contrast required for detection of targets over a range of spatial frequencies, and may evaluate visual mechanisms that do not directly subserve acuity. We used the visual evoked potential (VEP) to measure CS in a population of normal subjects and in patients with ophthalmic conditions affecting retinal function, including one patient with a laser injury in the macula. In this patient, the acuity had recovered from

[Clinical electro-ophthalmology at the Max Planck Institute of the Frankfurt University Ophthalmology Clinic 1970-1991].

PubMed

Lorenz, R; Baier, M; Eckl, G; Raile, A

1996-07-01

The survey shows the frequency and distribution of diseases evaluated by electroophthalmological methods. Patients with retinal diseases (51.2%) and those with diseases of the optic nerve (21.8%) were examined most frequently. In a high percentage these investigations lead to a clinically useful assessment: described as confirmation or exclusion of a clinical diagnosis, as establishing a possible differential diagnosis or clearing up formerly unknown aspects of a disease. In cases of hereditary retinal disorders only 11% remained unclear, with presumed optic neuritis only 6%. The importance of electroophthalmological investigations is there ability to assess functional deficits in the visual system especially in somehow more rare retinal and centrally located disorders, functional deficits of unknown origins or in general diseases including the visual system.

Spatiotemporal characteristics of retinal response to network-mediated photovoltaic stimulation.

PubMed

Ho, Elton; Smith, Richard; Goetz, Georges; Lei, Xin; Galambos, Ludwig; Kamins, Theodore I; Harris, James; Mathieson, Keith; Palanker, Daniel; Sher, Alexander

2018-02-01

Subretinal prostheses aim at restoring sight to patients blinded by photoreceptor degeneration using electrical activation of the surviving inner retinal neurons. Today, such implants deliver visual information with low-frequency stimulation, resulting in discontinuous visual percepts. We measured retinal responses to complex visual stimuli delivered at video rate via a photovoltaic subretinal implant and by visible light. Using a multielectrode array to record from retinal ganglion cells (RGCs) in the healthy and degenerated rat retina ex vivo, we estimated their spatiotemporal properties from the spike-triggered average responses to photovoltaic binary white noise stimulus with 70-μm pixel size at 20-Hz frame rate. The average photovoltaic receptive field size was 194 ± 3 μm (mean ± SE), similar to that of visual responses (221 ± 4 μm), but response latency was significantly shorter with photovoltaic stimulation. Both visual and photovoltaic receptive fields had an opposing center-surround structure. In the healthy retina, ON RGCs had photovoltaic OFF responses, and vice versa. This reversal is consistent with depolarization of photoreceptors by electrical pulses, as opposed to their hyperpolarization under increasing light, although alternative mechanisms cannot be excluded. In degenerate retina, both ON and OFF photovoltaic responses were observed, but in the absence of visual responses, it is not clear what functional RGC types they correspond to. Degenerate retina maintained the antagonistic center-surround organization of receptive fields. These fast and spatially localized network-mediated ON and OFF responses to subretinal stimulation via photovoltaic pixels with local return electrodes raise confidence in the possibility of providing more functional prosthetic vision. NEW & NOTEWORTHY Retinal prostheses currently in clinical use have struggled to deliver visual information at naturalistic frequencies, resulting in discontinuous percepts. We demonstrate modulation of the retinal ganglion cells (RGC) activity using complex spatiotemporal stimuli delivered via subretinal photovoltaic implant at 20 Hz in healthy and in degenerate retina. RGCs exhibit fast and localized ON and OFF network-mediated responses, with antagonistic center-surround organization of their receptive fields.

The evolution of the centrifugal visual system of vertebrates. A cladistic analysis and new hypotheses.

PubMed

Repérant, J; Médina, M; Ward, R; Miceli, D; Kenigfest, N B; Rio, J P; Vesselkin, N P

2007-01-01

In a recent review of the available data concerning the centrifugal visual system (CVS) of vertebrates [Repérant, J., Ward, R., Miceli, D., Rio, J.P., Médina, M., Kenigfest, N.B., Vesselkin, N.P., 2006. The centrifugal visual system of vertebrates: a comparative analysis of its functional anatomical organization, Brain Res. Rev. 52, 1-57], we have shown that this feature of the visual system is not a particularity of birds, but is a permanent component of the vertebrate central nervous system which nevertheless shows considerable morphological and functional variation from one taxonomic group to another. Given these findings, the primary objective of the present article is an attempt to specify the evolutionary significance of this phylogenetic diversity. We begin by drawing up an inventory of this variation under several headings: the intracerebral location of the retinopetal neurons; the mode of intra-retinal arborizations of the centrifugal fibres and the nature of their targets; their neurochemical properties; and the afferent supplies of these neurons. We subsequently discuss these variations, particularly that of the intracerebral location of the retinopetal neurons during development and in adult forms, using the neuromeric terminology and in the framework of cladistic analysis, and seek to interpret them in a phylogenetic context. From this analysis, it becomes evident that the CVS is not a homogeneous entity formed by neurons with a common embryological origin, but rather a collection of at least eight distinct subsystems arising in very different regions of the neuraxis. These are the olfacto-retinal, dorsal thalamo-retinal, ventral thalamo-retinal, pretecto-retinal, tecto-retinal, tegmento-mesencephalo-retinal, dorsal isthmo-retinal and ventral isthmo-retinal systems. The olfacto-retinal system, which is probably absent in Agnatha, appears to be a pleisiomorphic characteristic of all Gnathostomata, while on the other hand the tegmento-mesencephalo-retinal system appears to be present only in Agnatha. Our cladistic analysis also shows that the remaining six subsystems are polyphyletic in origin and have arisen independently on several occasions in different radiations of Gnathostoma. In conclusion, we suggest that, in the course of the palaeontological history of vertebrates, these different retinopetal pathways have been selected on the basis of widely different environmental pressures which remain to be identified.

Retinal phenotypic characterization of patients with ABCA4 retinopathydue to the homozygous p.Ala1773Val mutation

PubMed Central

López-Rubio, Salvador; Chacon-Camacho, Oscar F.; Matsui, Rodrigo; Guadarrama-Vallejo, Dalia; Astiazarán, Mirena C.

2018-01-01

Purpose To describe the retinal clinical features of a group of Mexican patients with Stargardt disease carrying the uncommon p.Ala1773Val founder mutation in ABCA4. Methods Ten patients carrying the p.Ala1773Val mutation, nine of them homozygously, were included. Visual function studies included best-corrected visual acuity, electroretinography, Goldmann kinetic visual fields, and full-field electroretinography (ERG). In addition, imaging studies, such as optical coherence tomography (OCT), short-wave autofluorescence imaging, and quantitative analyses of hypofluorescence, were performed in each patient. Results Best-corrected visual acuities ranged from 20/200 to 4/200. The median age of the patients at diagnosis was 23.3 years. The majority of the patients had photophobia and nyctalopia, and were classified as Fishman stage 4 (widespread choriocapillaris atrophy, resorption of flecks, and greatly reduced ERG amplitudes). An atypical retinal pigmentation pattern was observed in the patients, and the majority showed cone-rod dystrophy on full-field ERG. In vivo retinal microstructure assessment with OCT demonstrated central retinal thinning, variable loss of photoreceptors, and three different patterns of structural retinal degeneration. Two dissimilar patterns of abnormal autofluorescence were observed. No apparent age-related differences in the pattern of retinal degeneration were observed. Conclusions The results indicate that this particular mutation in ABCA4 is associated with a severe retinal phenotype and thus, could be classified as null. Careful phenotyping of patients carrying specific mutations in ABCA4 is essential to enhance our understanding of disease expression linked to particular mutations and the resulting genotype–phenotype correlations. PMID:29422768

Methane attenuates retinal ischemia/reperfusion injury via anti-oxidative and anti-apoptotic pathways.

PubMed

Liu, Lin; Sun, Qinglei; Wang, Ruobing; Chen, Zeli; Wu, Jiangchun; Xia, Fangzhou; Fan, Xian-Qun

2016-09-01

Retinal ischemia/reperfusion injury (IRI) may cause incurable visual impairment due to neural regeneration limits. Methane was shown to exert a protective effect against IRI in many organs. This study aims to explore the possible protective effects of methane-rich saline against retinal IRI in rat. Retinal IRI was performed on the right eyes of male Sprague-Dawley rats, which were immediately injected intraperitoneally with methane-saturated saline (25ml/kg). At one week after surgery, the number of retinal ganglion cells (RGCs), total retinal thickness, visual function were measured by hematoxylin and eosin staining, FluoroGold anterograde labeling and flash visual evoked potentials. The levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), 4-Hydroxy-2-nonenal (4-HNE), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), caspase-3, caspase-9, B cell lymphoma/leukemia-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in retinas were assessed by immunofluorescence staining, enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. As expected, methane treatment significantly improved the retinal IRI-induced RGC loss, total retinal layer thinning and visual dysfunction. Moreover, methane treatment significantly reduced the levels of oxidative stress biomarkers (8-OHdG, 4-HNE, MDA) and increased the antioxidant enzyme activities (SOD, CAT, GPx) in the retinas with IRI. Meanwhile, methane treatment significantly increased the anti-apoptotic gene (Bcl-2) expression and decreased the pro-apoptotic gene (Bax) expression, accompanied by the suppression of caspase-3 and caspase-9 activity. Thus, these data demonstrated that methane can exert a neuroprotective role against retinal IRI through anti-oxidative and anti-apoptotic pathways. Copyright © 2016. Published by Elsevier B.V.

The effects of retinal abnormalities on the multifocal visual evoked potential.

PubMed

Chen, John Y; Hood, Donald C; Odel, Jeffrey G; Behrens, Myles M

2006-10-01

To examine the effects on the amplitude and latency of the multifocal visual evoked potential (mfVEP) in retinal diseases associated with depressed multifocal electroretinograms (mfERG). Static automated perimetry (SAP), mfERGs, and mfVEPs were obtained from 15 individuals seen by neuro-ophthalmologists and diagnosed with retinal disease based on funduscopic examination, visual field, and mfERG. Optic neuropathy was ruled out in all cases. Diagnoses included autoimmune retinopathy (n = 3), branch retinal arterial occlusion (n = 3), branch retinal vein occlusion (n = 1), vitamin A deficiency (n = 1), digoxin/age-related macular degeneration (n = 1), multiple evanescent white dot syndrome (n = 1), and nonspecific retinal disease (n = 5). Patients were selected from a larger group based on abnormal mfERG amplitudes covering a diameter of 20 degrees or greater. Fourteen (93%) of 15 patients showed significant mfVEP delays, as determined by either mean latency or the probability of a cluster of delayed local responses. Thirteen of 15 patients had normal mfVEP amplitudes in regions corresponding to markedly reduced or nonrecordable mfERG responses. These findings can be mimicked in normal individuals by viewing the display through a neutral-density filter. Retinal diseases can result in mfVEPs of relatively normal amplitudes, often with delays, in regions showing decreased mfERG responses and visual field sensitivity loss. Consequently, a retinal problem can be missed, or dismissed as functional, if a diagnosis is based on an mfVEP of normal or near-normal amplitude. Further, in patients with marked mfVEP delays, a retinal problem could be confused with optic neuritis, especially in a patient with a normal appearing fundus.

Arterial spin labeling fMRI measurements of decreased blood flow in primary visual cortex correlates with decreased visual function in human glaucoma.

PubMed

Duncan, Robert O; Sample, Pamela A; Bowd, Christopher; Weinreb, Robert N; Zangwill, Linda M

2012-05-01

Altered metabolic activity has been identified as a potential contributing factor to the neurodegeneration associated with primary open angle glaucoma (POAG). Consequently, we sought to determine whether there is a relationship between the loss of visual function in human glaucoma and resting blood perfusion within primary visual cortex (V1). Arterial spin labeling (ASL) functional magnetic resonance imaging (fMRI) was conducted in 10 participants with POAG. Resting cerebral blood flow (CBF) was measured from dorsal and ventral V1. Behavioral measurements of visual function were obtained using standard automated perimetry (SAP), short-wavelength automated perimetry (SWAP), and frequency-doubling technology perimetry (FDT). Measurements of CBF were compared to differences in visual function for the superior and inferior hemifield. Differences in CBF between ventral and dorsal V1 were correlated with differences in visual function for the superior versus inferior visual field. A statistical bootstrapping analysis indicated that the observed correlations between fMRI responses and measurements of visual function for SAP (r=0.49), SWAP (r=0.63), and FDT (r=0.43) were statistically significant (all p<0.05). Resting blood perfusion in human V1 is correlated with the loss of visual function in POAG. Altered CBF may be a contributing factor to glaucomatous optic neuropathy, or it may be an indication of post-retinal glaucomatous neurodegeneration caused by damage to the retinal ganglion cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

Update on visual function and choroidal-retinal thickness alterations in Parkinson's disease.

PubMed

Obis, J; Satue, M; Alarcia, R; Pablo, L E; Garcia-Martin, E

2018-05-01

Parkinson's disease (PD) is a neurodegenerative process that affects 7.5 million people around the world. Since 2004, several studies have demonstrated changes in various retinal layers in PD using optical coherence tomography (OCT). However, there are some discrepancies in the results of those studies. Some of them have correlated retinal thickness with the severity or duration of the disease, demonstrating that OCT measurements may be an innocuous and easy biomarker for PD progression. Other studies have demonstrated visual dysfunctions since early phases of the disease. Lastly, the most recent studies that use Swept Source OCT technology, have found choroidal thickness increase in PD patients and provide new information related to the retinal degenerative process in this disease. The aim of this paper is to review the literature on OCT and PD, in order to determine the altered retinal and choroidal parameters in PD and their possible clinical usefulness, and also the visual dysfunctions with higher impact in these patients. Copyright © 2018 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Normal central retinal function and structure preserved in retinitis pigmentosa.

PubMed

Jacobson, Samuel G; Roman, Alejandro J; Aleman, Tomas S; Sumaroka, Alexander; Herrera, Waldo; Windsor, Elizabeth A M; Atkinson, Lori A; Schwartz, Sharon B; Steinberg, Janet D; Cideciyan, Artur V

2010-02-01

To determine whether normal function and structure, as recently found in forms of Usher syndrome, also occur in a population of patients with nonsyndromic retinitis pigmentosa (RP). Patients with simplex, multiplex, or autosomal recessive RP (n = 238; ages 9-82 years) were studied with static chromatic perimetry. A subset was evaluated with optical coherence tomography (OCT). Co-localized visual sensitivity and photoreceptor nuclear layer thickness were measured across the central retina to establish the relationship of function and structure. Comparisons were made to patients with Usher syndrome (n = 83, ages 10-69 years). Cross-sectional psychophysical data identified patients with RP who had normal rod- and cone-mediated function in the central retina. There were two other patterns with greater dysfunction, and longitudinal data confirmed that progression can occur from normal rod and cone function to cone-only central islands. The retinal extent of normal laminar architecture by OCT corresponded to the extent of normal visual function in patients with RP. Central retinal preservation of normal function and structure did not show a relationship with age or retained peripheral function. Usher syndrome results were like those in nonsyndromic RP. Regional disease variation is a well-known finding in RP. Unexpected was the observation that patients with presumed recessive RP can have regions with functionally and structurally normal retina. Such patients will require special consideration in future clinical trials of either focal or systemic treatment. Whether there is a common molecular mechanism shared by forms of RP with normal regions of retina warrants further study.

Retinal nerve fiber layer thickness measured with optical coherence tomography is related to visual function in glaucomatous eyes.

PubMed

El Beltagi, Tarek A; Bowd, Christopher; Boden, Catherine; Amini, Payam; Sample, Pamela A; Zangwill, Linda M; Weinreb, Robert N

2003-11-01

To determine the relationship between areas of glaucomatous retinal nerve fiber layer thinning identified by optical coherence tomography and areas of decreased visual field sensitivity identified by standard automated perimetry in glaucomatous eyes. Retrospective observational case series. Forty-three patients with glaucomatous optic neuropathy identified by optic disc stereo photographs and standard automated perimetry mean deviations >-8 dB were included. Participants were imaged with optical coherence tomography within 6 months of reliable standard automated perimetry testing. The location and number of optical coherence tomography clock hour retinal nerve fiber layer thickness measures outside normal limits were compared with the location and number of standard automated perimetry visual field zones outside normal limits. Further, the relationship between the deviation from normal optical coherence tomography-measured retinal nerve fiber layer thickness at each clock hour and the average pattern deviation in each visual field zone was examined by using linear regression (R(2)). The retinal nerve fiber layer areas most frequently outside normal limits were the inferior and inferior temporal regions. The least sensitive visual field zones were in the superior hemifield. Linear regression results (R(2)) showed that deviation from the normal retinal nerve fiber layer thickness at optical coherence tomography clock hour positions 6 o'clock, 7 o'clock, and 8 o'clock (inferior and inferior temporal) was best correlated with standard automated perimetry pattern deviation in visual field zones corresponding to the superior arcuate and nasal step regions (R(2) range, 0.34-0.57). These associations were much stronger than those between clock hour position 6 o'clock and the visual field zone corresponding to the inferior nasal step region (R(2) = 0.01). Localized retinal nerve fiber layer thinning, measured by optical coherence tomography, is topographically related to decreased localized standard automated perimetry sensitivity in glaucoma patients.

Molecular medicine in ophthalmic care.

PubMed

Richer, Stuart; Stiles, William; Thomas, Carla

2009-12-01

Lipofuscin is the most consistent and phylogenically constant morphologic marker of cellular aging. Autofluorescence of the A2E fluorophore within retinal pigment epithelial (RPE) lipofuscin affords the opportunity for noninvasive evaluation of age- and disease-related pathophysiological changes in the human retina. It is being used in National Eye Institute/Age-Related Eye Disease Study II to evaluate age-related macular degeneration (AMD) geographic atrophy expansion. Experiments show lipofuscin can be reversed in cell culture and animal models in heart, brain, spinal cord, and retinal tissues, using an array of antioxidants and iron chelators. An 80-year-old man with a gastric resection presented with complaints of unremitting night driving difficulty despite treatment with lutein and omega III fatty acids. Notable parafoveal deposition of retinal lipofuscin by 50 degrees fundus auto-fluorescence (580 nm excitation/660 barrier filters) and concurrent abnormalities in non-Snellen measures of visual function-Contrast Sensitivity Function, 6.5 degrees large field tritan threshold, 10 degrees threshold visual fields, and deficits in the National Institutes of Health/National Eye Institute Visual Function Questionnaire (VFQ) 25 subjective night driving/mental health subscale questionnaire were obtained. The patient was placed on an over-the-counter daily oral polyphenolic mixture containing resveratrol and re-evaluated 5 months later. The data reveal improvements in all measures of visual function, subjective improvement in vision and mental functioning on the VFQ 25, and visible clearing of RPE lipofuscin. To our knowledge, we believe this to be the first reported human clinical case of lipofuscin reversal in the human eye correlated with measured clinical and subjective improvement in visual and mental function after nutraceutical intervention.

Optimization of neural retinal visual motor strategies in recovery of visual acuity following acute laser-induced macula injury

NASA Astrophysics Data System (ADS)

Zwick, Harry; Ness, James W.; Loveday, J.; Molchany, Jerome W.; Stuck, Bruce E.

1997-05-01

Laser induced damage to the retina may produce immediate and serious loss in visual acuity as well as subsequent recovery of visual acuity over a 1 to 6 month post exposure period. While acuity may recover, full utilization of the foveal region may not return. In one patient, a superior/temporal preferred retinal location (PRL) was apparent, while a second patient demonstrated significant foveal involvement and contrast sensitivity more reflective of foveal than parafoveal involvement. These conditions of injury wee simulated by using an artificial scotoma technique which optically stabilized a 5 degree opacity in the center of the visual field. The transmission of spatially degraded target information in the scotoma was 0 percent, 5 percent and 95 percent. Contrast sensitivity for the 0 percent and 5 percent transmission scotoma showed broad spatial frequency suppression as opposed to a bipartite contrast sensitivity function with a narrow sensitivity loss at 3 cycles/degree for the 95 percent transmission scotoma. A PRL shift to superior temporal retina with a concomitant change in accommodation was noted as target resolution became more demanding. These findings suggest that restoration of visual acuity in human laser accidents may depend upon the functionality of complex retinal and cortical adaptive mechanisms.

Visual Field Defects and Retinal Ganglion Cell Losses in Human Glaucoma Patients

PubMed Central

Harwerth, Ronald S.; Quigley, Harry A.

2007-01-01

Objective The depth of visual field defects are correlated with retinal ganglion cell densities in experimental glaucoma. This study was to determine whether a similar structure-function relationship holds for human glaucoma. Methods The study was based on retinal ganglion cell densities and visual thresholds of patients with documented glaucoma (Kerrigan-Baumrind, et al.) The data were analyzed by a model that predicted ganglion cell densities from standard clinical perimetry, which were then compared to histologic cell counts. Results The model, without free parameters, produced accurate and relatively precise quantification of ganglion cell densities associated with visual field defects. For 437 sets of data, the unity correlation for predicted vs. measured cell densities had a coefficient of determination of 0.39. The mean absolute deviation of the predicted vs. measured values was 2.59 dB, the mean and SD of the distribution of residual errors of prediction was -0.26 ± 3.22 dB. Conclusions Visual field defects by standard clinical perimetry are proportional to neural losses caused by glaucoma. Clinical Relevance The evidence for quantitative structure-function relationships provides a scientific basis of interpreting glaucomatous neuropathy from visual thresholds and supports the application of standard perimetry to establish the stage of the disease. PMID:16769839

Photochemical restoration of visual responses in blind mice

PubMed Central

Polosukhina, Aleksandra; Litt, Jeffrey; Tochitsky, Ivan; Nemargut, Joseph; Sychev, Yivgeny; De Kouchkovsky, Ivan; Huang, Tracy; Borges, Katharine; Trauner, Dirk; Van Gelder, Russell N.; Kramer, Richard H.

2012-01-01

Summary Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are degenerative blinding diseases caused by the death of rods and cones, leaving the remainder of the visual system intact but largely unable to respond to light. Here we show that, AAQ, a synthetic small molecule photoswitch, can restore light sensitivity to the retina and behavioral responses in vivo in mouse models of RP without exogenous gene delivery. Brief application of AAQ bestows prolonged light sensitivity on multiple types of retinal neurons, resulting in synaptically amplified responses and center-surround antagonism in arrays of retinal ganglion cells (RGCs). Intraocular injection of AAQ restores the pupillary light reflex and locomotory light avoidance responses in mice lacking retinal photoreceptors, indicating reconstitution of light signaling to brain circuits. AAQ and related photoswitch molecules present a new drug strategy for restoring retinal function in degenerative blinding diseases. PMID:22841312

Endogenous and Synthetic Cannabinoids as Therapeutics in Retinal Disease.

PubMed

Kokona, Despina; Georgiou, Panagiota-Christina; Kounenidakis, Mihalis; Kiagiadaki, Foteini; Thermos, Kyriaki

2016-01-01

The functional significance of cannabinoids in ocular physiology and disease has been reported some decades ago. In the early 1970s, subjects who smoked Cannabis sativa developed lower intraocular pressure (IOP). This led to the isolation of phytocannabinoids from this plant and the study of their therapeutic effects in glaucoma. The main treatment of this disease to date involves the administration of drugs mediating either the decrease of aqueous humour synthesis or the increase of its outflow and thus reduces IOP. However, the reduction of IOP is not sufficient to prevent visual field loss. Retinal diseases, such as glaucoma and diabetic retinopathy, have been defined as neurodegenerative diseases and characterized by ischemia-induced excitotoxicity and loss of retinal neurons. Therefore, new therapeutic strategies must be applied in order to target retinal cell death, reduction of visual acuity, and blindness. The aim of the present review is to address the neuroprotective and therapeutic potential of cannabinoids in retinal disease.

Relationship between macular pigment and visual function in subjects with early age-related macular degeneration.

PubMed

Akuffo, Kwadwo Owusu; Nolan, John M; Peto, Tunde; Stack, Jim; Leung, Irene; Corcoran, Laura; Beatty, Stephen

2017-02-01

To investigate the relationship between macular pigment (MP) and visual function in subjects with early age-related macular degeneration (AMD). 121 subjects with early AMD enrolled as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787) were assessed using a range of psychophysical measures of visual function, including best corrected visual acuity (BCVA), letter contrast sensitivity (CS), mesopic and photopic CS, mesopic and photopic glare disability (GD), photostress recovery time (PRT), reading performance and subjective visual function, using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). MP was measured using customised heterochromatic flicker photometry. Letter CS, mesopic and photopic CS, photopic GD and mean reading speed were each significantly (p<0.05) associated with MP across a range of retinal eccentricities, and these statistically significant relationships persisted after controlling for age, sex and cataract grade. BCVA, NEI VFQ-25 score, PRT and mesopic GD were unrelated to MP after controlling for age, sex and cataract grade (p>0.05, for all). MP relates positively to many measures of visual function in unsupplemented subjects with early AMD. The CREST trial will investigate whether enrichment of MP influences visual function among those afflicted with this condition. ISRCTN13894787. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Endoscopic device for functional imaging of the retina

NASA Astrophysics Data System (ADS)

Barriga, Simon; Lohani, Sweyta; Martell, Bret; Soliz, Peter; Ts'o, Dan

2011-03-01

Non-invasive imaging of retinal function based on the recording of spatially distributed reflectance changes evoked by visual stimuli has to-date been performed primarily using modified commercial fundus cameras. We have constructed a prototype retinal functional imager, using a commercial endoscope (Storz) for the frontend optics, and a low-cost back-end that includes the needed dichroic beam splitter to separate the stimulus path from the imaging path. This device has been tested to demonstrate its performance for the delivery of adequate near infrared (NIR) illumination, intensity of the visual stimulus and reflectance return in the imaging path. The current device was found to be capable of imaging reflectance changes of 0.1%, similar to that observable using the modified commercial fundus camera approach. The visual stimulus (a 505nm spot of 0.5secs) was used with an interrogation illumination of 780nm, and a sequence of imaged captured. At each pixel, the imaged signal was subtracted and normalized by the baseline reflectance, so that the measurement was ΔR/R. The typical retinal activity signal observed had a ΔR/R of 0.3-1.0%. The noise levels were measured when no stimulus was applied and found to vary between +/- 0.05%. Functional imaging has been suggested as a means to provide objective information on retina function that may be a preclinical indicator of ocular diseases, such as age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy. The endoscopic approach promises to yield a significantly more economical retinal functional imaging device that would be clinically important.

Effects of Retinal Morphology on Contrast Sensitivity and Reading Ability in Neovascular Age-Related Macular Degeneration

PubMed Central

Keane, Pearse A.; Patel, Praveen J.; Ouyang, Yanling; Chen, Fred K.; Ikeji, Felicia; Walsh, Alexander C.; Tufail, Adnan

2010-01-01

Purpose. To investigate the effect of changes in retinal morphology on contrast sensitivity and reading ability in patients with neovascular age-related macular degeneration (AMD) in the Avastin (bevacizumab; Genentech, South San Francisco, CA) for choroidal neovascularization (ABC) Trial. Methods. Contrast sensitivity obtained with Pelli-Robson charts, reading ability assessed with Minnesota Reading charts, and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) obtained by protocol refraction, were recorded. Raw Stratus optical coherence tomography (OCT; Carl Zeiss Meditec, Inc., Dublin, CA) images were analyzed with the publicly available software OCTOR, which allows precise delineation of any retinal compartment of interest. Thickness and volume were calculated for neurosensory retina, subretinal fluid (SRF), subretinal tissue, and pigment epithelium detachment, and the resulting measurements were correlated with each visual function parameter. Results. One hundred twenty-two patients with newly diagnosed neovascular AMD and enrolled in the ABC Trial, were evaluated. Increased subretinal tissue volume correlated with decreased contrast sensitivity (Pearson's correlation coefficient, r = −0.4944, P = 0.001). A modest correlation was detected between SRF volume and contrast sensitivity (r = −0.2562, P = 0.004). Increased retinal thickness at the foveal center also correlated with decreased visual function (ETDRS VA: r = −0.4530, P < 0.001). Conclusions. The strongest correlation detected between the functional parameters assessed and any of the OCT-derived morphologic parameters was that between decreased contrast sensitivity and increased subretinal tissue. In the future, assessment of contrast sensitivity and reading ability, in combination with quantitative subanalysis of retinal compartments, may lead to the identification of parameters relevant to functional improvement and ultimate prognosis in patients with newly diagnosed neovascular AMD (www.controlled-trials.com number, ISRCTN83325075). PMID:20554607

Correspondence between retinotopic cortical mapping and conventional functional and morphological assessment of retinal disease.

PubMed

Ritter, Markus; Hummer, Allan; Ledolter, Anna A; Holder, Graham E; Windischberger, Christian; Schmidt-Erfurth, Ursula M

2018-04-26

The present study describes retinotopic mapping of the primary visual cortex using functional MRI (fMRI) in patients with retinal disease. It addresses the relationship between fMRI data and data obtained by conventional assessment including microperimetry (MP) and structural imaging. Initial testing involved eight patients with central retinal disease (Stargardt disease, STGD) and eight with peripheral retinal disease (retinitis pigmentosa, RP), who were examined using fMRI and MP (Nidek MP-1). All had a secure clinical diagnosis supported by electrophysiological data. fMRI used population-receptive field (pRF) mapping to provide retinotopic data that were then compared with the results of MP, optical coherence tomography and fundus autofluorescence imaging. Full analysis, following assessment of fMRI data reliability criteria, was performed in five patients with STGD and seven patients with RP; unstable fixation was responsible for unreliable pRF measurements in three patients excluded from final analysis. The macular regions in patients with STGD with central visual field defects and outer retinal atrophy (ORA) at the macula correlated well with pRF coverage maps showing reduced density of activated voxels at the occipital pole. Patients with RP exhibited peripheral ORA and concentric visual field defects both on MP and pRF mapping. Anterior V1 voxels, corresponding to peripheral regions, showed no significant activation. Correspondence between MP and pRF mapping was quantified by calculating the simple matching coefficient. Retinotopic maps acquired by fMRI provide a valuable adjunct in the assessment of retinal dysfunction. The addition of microperimetric data to pRF maps allowed better assessment of macular function than MP alone. Unlike MP, pRF mapping provides objective data independent of psychophysical perception from the patient. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Retinal microvascular network alterations: potential biomarkers of cerebrovascular and neural diseases.

PubMed

Cabrera DeBuc, Delia; Somfai, Gabor Mark; Koller, Akos

2017-02-01

Increasing evidence suggests that the conditions of retinal microvessels are indicators to a variety of cerebrovascular, neurodegenerative, psychiatric, and developmental diseases. Thus noninvasive visualization of the human retinal microcirculation offers an exceptional opportunity for the investigation of not only the retinal but also cerebral microvasculature. In this review, we show how the conditions of the retinal microvessels could be used to assess the conditions of brain microvessels because the microvascular network of the retina and brain share, in many aspects, standard features in development, morphology, function, and pathophysiology. Recent techniques and imaging modalities, such as optical coherence tomography (OCT), allow more precise visualization of various layers of the retina and its microcirculation, providing a "microscope" to brain microvessels. We also review the potential role of retinal microvessels in the risk identification of cerebrovascular and neurodegenerative diseases. The association between vision problems and cerebrovascular and neurodegenerative diseases, as well as the possible role of retinal microvascular imaging biomarkers in cerebrovascular and neurodegenerative screening, their potentials, and limitations, are also discussed. Copyright © 2017 the American Physiological Society.

Low aqueous solubility of 11-cis-retinal limits the rate of pigment formation and dark adaptation in salamander rods.

PubMed

Frederiksen, Rikard; Boyer, Nicholas P; Nickle, Benjamin; Chakrabarti, Kalyan S; Koutalos, Yiannis; Crouch, Rosalie K; Oprian, Daniel; Cornwall, M Carter

2012-06-01

We report experiments designed to test the hypothesis that the aqueous solubility of 11-cis-retinoids plays a significant role in the rate of visual pigment regeneration. Therefore, we have compared the aqueous solubility and the partition coefficients in photoreceptor membranes of native 11-cis-retinal and an analogue retinoid, 11-cis 4-OH retinal, which has a significantly higher solubility in aqueous medium. We have then correlated these parameters with the rates of pigment regeneration and sensitivity recovery that are observed when bleached intact salamander rod photoreceptors are treated with physiological solutions containing these retinoids. We report the following results: (a) 11-cis 4-OH retinal is more soluble in aqueous buffer than 11-cis-retinal. (b) Both 11-cis-retinal and 11-cis 4-OH retinal have extremely high partition coefficients in photoreceptor membranes, though the partition coefficient of 11-cis-retinal is roughly 50-fold greater than that of 11-cis 4-OH retinal. (c) Intact bleached isolated rods treated with solutions containing equimolar amounts of 11-cis-retinal or 11-cis 4-OH retinal form functional visual pigments that promote full recovery of dark current, sensitivity, and response kinetics. However, rods treated with 11-cis 4-OH retinal regenerated on average fivefold faster than rods treated with 11-cis-retinal. (d) Pigment regeneration from recombinant and wild-type opsin in solution is slower when treated with 11-cis 4-OH retinal than with 11-cis-retinal. Based on these observations, we propose a model in which aqueous solubility of cis-retinoids within the photoreceptor cytosol can place a limit on the rate of visual pigment regeneration in vertebrate photoreceptors. We conclude that the cytosolic gap between the plasma membrane and the disk membranes presents a bottleneck for retinoid flux that results in slowed pigment regeneration and dark adaptation in rod photoreceptors.

Disease course in patients with autosomal recessive retinitis pigmentosa due to the USH2A gene.

PubMed

Sandberg, Michael A; Rosner, Bernard; Weigel-DiFranco, Carol; McGee, Terri L; Dryja, Thaddeus P; Berson, Eliot L

2008-12-01

To estimate the mean rates of ocular function loss in patients with autosomal recessive retinitis pigmentosa due to USH2A mutations. In 125 patients with USH2A mutations, longitudinal regression was used to estimate mean rates of change in Snellen visual acuity, Goldmann visual field area (V4e white test light), and 30-Hz (cone) full-field electroretinogram amplitude. These rates were compared with those of previously studied cohorts with dominant retinitis pigmentosa due to RHO mutations and with X-linked retinitis pigmentosa due to RPGR mutations. Rates of change in patients with the Cys759Phe mutation, the USH2A mutation associated with nonsyndromic disease, were compared with rates of change in patients with the Glu767fs mutation, the most common USH2A mutation associated with Usher syndrome type II (i.e., retinitis pigmentosa and hearing loss). Mean annual exponential rates of decline for the USH2A patients were 2.6% for visual acuity, 7.0% for visual field area, and 13.2% for electroretinogram amplitude. The rate of acuity loss fell between the corresponding rates for the RHO and RPGR patients, whereas the rates for field and ERG amplitude loss were faster than those for the RHO and RPGR patients. No significant differences were found for patients with the Cys759Phe mutation versus patients with the Glu767fs mutation. On average, USH2A patients lose visual acuity faster than RHO patients and slower than RPGR patients. USH2A patients lose visual field and cone electroretinogram amplitude faster than patients with RHO or RPGR mutations. Patients with a nonsyndromic USH2A mutation have the same retinal disease course as patients with syndromic USH2A disease.

Structural and Functional Changes Associated with Normal and Abnormal Fundus Autofluorescence in Patients with Retinitis Pigmentosa

PubMed Central

Greenstein, Vivienne C.; Duncker, Tobias; Holopigian, Karen; Carr, Ronald E.; Greenberg, Jonathan; Tsang, Stephen H.; Hood, Donald C.

2013-01-01

Purpose To analyze the structure and visual function of regions bordering the hyperautofluorescent ring/arcs in retinitis pigmentosa (RP). Methods Twenty -one RP patients (21 eyes) with rings/arcs and 21 normals (21 eyes) were studied. Visual sensitivity in the central 10° was measured with microperimetry. Retinal structure was evaluated with spectral domain optical coherence tomography (SD-OCT). The distance from the fovea to disruption/loss of the inner outer segment (IS/OS) junction and thicknesses of the total receptor plus retinal pigment epithelial (RPE) complex (R+), and outer segment plus RPE complex (OS+) layers were measured. Results were compared to measurements of the distance from the fovea to the inner and outer borders of the ring/arc seen on fundus autofluorescence (FAF). Results Disruption/loss of the IS/OS junction occurred closer to the inner border of the ring/arc and it was closer to the fovea in 8 eyes. For 19 eyes, OS+ and R+ thicknesses were significantly decreased at locations closer to the fovea than the appearance of the inner border of hyperautofluorescence. Mean visual sensitivity was decreased inside, across and outside the ring/arc by 3.5 ± 3.8, 8.9 ± 4.8 and 17.0±2.4 dB respectively. Conclusions Structural and functional changes can occur inside the hyperfluorescent ring/arc in RP. PMID:21909055

Resveratrol Based Oral Nutritional Supplement Produces Long-Term Beneficial Effects on Structure and Visual Function in Human Patients

PubMed Central

Richer, Stuart; Patel, Shana; Sockanathan, Shivani; Ulanski, Lawrence J.; Miller, Luke; Podella, Carla

2014-01-01

Background: Longevinex® (L/RV) is a low dose hormetic over-the-counter (OTC) oral resveratrol (RV) based matrix of red wine solids, vitamin D3 and inositol hexaphosphate (IP6) with established bioavailability, safety, and short-term efficacy against the earliest signs of human atherosclerosis, murine cardiac reperfusion injury, clinical retinal neovascularization, and stem cell survival. We previously reported our short-term findings for dry and wet age-related macular degeneration (AMD) patients. Today we report long term (two to three year) clinical efficacy. Methods: We treated three patients including a patient with an AMD treatment resistant variant (polypoidal retinal vasculature disease). We evaluated two clinical measures of ocular structure (fundus autofluorescent imaging and spectral domain optical coherence extended depth choroidal imaging) and qualitatively appraised changes in macular pigment volume. We further evaluated three clinical measures of visual function (Snellen visual acuity, contrast sensitivity, and glare recovery to a cone photo-stress stimulus). Results: We observed broad bilateral improvements in ocular structure and function over a long time period, opposite to what might be expected due to aging and the natural progression of the patient’s pathophysiology. No side effects were observed. Conclusions: These three cases demonstrate that application of epigenetics has long-term efficacy against AMD retinal disease, when the retinal specialist has exhausted other therapeutic modalities. PMID:25329968

Resveratrol based oral nutritional supplement produces long-term beneficial effects on structure and visual function in human patients.

PubMed

Richer, Stuart; Patel, Shana; Sockanathan, Shivani; Ulanski, Lawrence J; Miller, Luke; Podella, Carla

2014-10-17

Longevinex® (L/RV) is a low dose hormetic over-the-counter (OTC) oral resveratrol (RV) based matrix of red wine solids, vitamin D3 and inositol hexaphosphate (IP6) with established bioavailability, safety, and short-term efficacy against the earliest signs of human atherosclerosis, murine cardiac reperfusion injury, clinical retinal neovascularization, and stem cell survival. We previously reported our short-term findings for dry and wet age-related macular degeneration (AMD) patients. Today we report long term (two to three year) clinical efficacy. We treated three patients including a patient with an AMD treatment resistant variant (polypoidal retinal vasculature disease). We evaluated two clinical measures of ocular structure (fundus autofluorescent imaging and spectral domain optical coherence extended depth choroidal imaging) and qualitatively appraised changes in macular pigment volume. We further evaluated three clinical measures of visual function (Snellen visual acuity, contrast sensitivity, and glare recovery to a cone photo-stress stimulus). We observed broad bilateral improvements in ocular structure and function over a long time period, opposite to what might be expected due to aging and the natural progression of the patient's pathophysiology. No side effects were observed. These three cases demonstrate that application of epigenetics has long-term efficacy against AMD retinal disease, when the retinal specialist has exhausted other therapeutic modalities.

Transplantation of reprogrammed embryonic stem cells improves visual function in a mouse model for retinitis pigmentosa.

PubMed

Wang, Nan-Kai; Tosi, Joaquin; Kasanuki, Jennifer Mie; Chou, Chai Lin; Kong, Jian; Parmalee, Nancy; Wert, Katherine J; Allikmets, Rando; Lai, Chi-Chun; Chien, Chung-Liang; Nagasaki, Takayuki; Lin, Chyuan-Sheng; Tsang, Stephen H

2010-04-27

To study whether C57BL/6J-Tyr/J (C2J) mouse embryonic stem (ES) cells can differentiate into retinal pigment epithelial (RPE) cells in vitro and then restore retinal function in a model for retinitis pigmentosa: Rpe65/Rpe65 C57BL6 mice. Yellow fluorescent protein (YFP)-labeled C2J ES cells were induced to differentiate into RPE-like structures on PA6 feeders. RPE-specific markers are expressed from differentiated cells in vitro. After differentiation, ES cell-derived RPE-like cells were transplanted into the subretinal space of postnatal day 5 Rpe65/Rpe65 mice. Live imaging of YFP-labeled C2J ES cells demonstrated survival of the graft. Electroretinograms (ERGs) were performed on transplanted mice to evaluate the functional outcome of transplantation. RPE-like cells derived from ES cells sequentially express multiple RPE-specific markers. After transplantation, YFP-labeled cells can be tracked with live imaging for as long as 7 months. Although more than half of the mice were complicated with retinal detachments or tumor development, one fourth of the mice showed increased electroretinogram responses in the transplanted eyes. Rpe65/Rpe65 mice transplanted with RPE-like cells showed significant visual recovery during a 7-month period, whereas those injected with saline, PA6 feeders, or undifferentiated ES cells showed no rescue. ES cells can differentiate, morphologically, and functionally, into RPE-like cells. Based on these findings, differentiated ES cells have the potential for the development of new therapeutic approaches for RPE-specific diseases such as certain forms of retinitis pigmentosa and macular degeneration. Nevertheless, stringent control of retinal detachment and teratoma development will be necessary before initiation of treatment trials.

Unilateral retinitis pigmentosa sine pigmento.

PubMed Central

Pearlman, J T; Saxton, J; Hoffman, G

1976-01-01

A patient presented with unilateral findings of night blindness shown by impaired rod function and dark adaptation, constricted visual fields with good central acuity, a barely recordable electro-retinographic b-wave, and a unilaterally impaired electro-oculogram. There were none of the pigmentary changes usually associated with retinitis pigmentosa. The unaffected right eye was normal in all respects. Therefore the case is most probably one of unilateral retinitis pigmentosa sine pigmento. Images PMID:952804

Unilateral retinitis pigmentosa sine pigmento.

PubMed

Pearlman, J T; Saxton, J; Hoffman, G

1976-05-01

A patient presented with unilateral findings of night blindness shown by impaired rod function and dark adaptation, constricted visual fields with good central acuity, a barely recordable electro-retinographic b-wave, and a unilaterally impaired electro-oculogram. There were none of the pigmentary changes usually associated with retinitis pigmentosa. The unaffected right eye was normal in all respects. Therefore the case is most probably one of unilateral retinitis pigmentosa sine pigmento.

Regenerating reptile retinas: a comparative approach to restoring retinal ganglion cell function.

PubMed

Williams, D L

2017-02-01

Transection or damage to the mammalian optic nerve generally results in loss of retinal ganglion cells by apoptosis. This cell death is seen less in fish or amphibians where retinal ganglion cell survival and axon regeneration leads to recovery of sight. Reptiles lie somewhere in the middle of this spectrum of nerve regeneration, and different species have been reported to have a significant variation in their retinal ganglion cell regenerative capacity. The ornate dragon lizard Ctenophoris ornatus exhibits a profound capacity for regeneration, whereas the Tenerife wall lizard Gallotia galloti has a more variable response to optic nerve damage. Some individuals regain visual activity such as the pupillomotor responses, whereas in others axons fail to regenerate sufficiently. Even in Ctenophoris, although the retinal ganglion cell axons regenerate adequately enough to synapse in the tectum, they do not make long-term topographic connections allowing recovery of complex visually motivated behaviour. The question then centres on where these intraspecies differences originate. Is it variation in the innate ability of retinal ganglion cells from different species to regenerate with functional validity? Or is it variances between different species in the substrate within which the nerves regenerate, the extracellular environment of the damaged nerve or the supporting cells surrounding the regenerating axons? Investigations of retinal ganglion cell regeneration between different species of lower vertebrates in vivo may shed light on these questions. Or perhaps more interesting are in vitro studies comparing axon regeneration of retinal ganglion cells from various species placed on differing substrates.

Retinal thinning is uniquely associated with medial temporal lobe atrophy in neurologically normal older adults

PubMed Central

Casaletto, Kaitlin B.; Ward, Michael E.; Baker, Nicholas S.; Bettcher, Brianne M.; Gelfand, Jeffrey M.; Li, Yaqiao; Chen, Robert; Dutt, Shubir; Miller, Bruce; Kramer, Joel H.; Green, Ari J.

2017-01-01

Given the converging pathologic and epidemiologic data indicating a relationship between retinal integrity and neurodegeneration, including Alzheimer’s disease (AD), we aimed to determine if retinal structure correlates with medial temporal lobe (MTL) structure and function in neurologically normal older adults. Spectral-domain optical coherence tomography, verbal and visual memory testing, and 3T-magnetic resonance imaging of the brain were performed in 79 neurologically normal adults enrolled in a healthy aging cohort study. Retinal nerve fiber thinning and reduced total macular and macular ganglion cell volumes were each associated with smaller MTL volumes (ps < 0.04). Notably, these markers of retinal structure were not associated with primary motor cortex or basal ganglia volumes (regions relatively unaffected in AD) (ps > 0.70), or frontal, precuneus, or temporoparietal volumes (regions affected in later AD Braak staging ps > 0.20). Retinal structure was not significantly associated with verbal or visual memory consolidation performances (ps > 0.14). Retinal structure was associated with MTL volumes, but not memory performances, in otherwise neurologically normal older adults. Given that MTL atrophy is a neuropathological hallmark of AD, retinal integrity may be an early marker of ongoing AD-related brain health. PMID:28068565

Progress toward the maintenance and repair of degenerating retinal circuitry.

PubMed

Vugler, Anthony A

2010-01-01

Retinal diseases such as age-related macular degeneration and retinitis pigmentosa remain major causes of severe vision loss in humans. Clinical trials for treatment of retinal degenerations are underway and advancements in our understanding of retinal biology in health/disease have implications for novel therapies. A review of retinal biology is used to inform a discussion of current strategies to maintain/repair neural circuitry in age-related macular degeneration, retinitis pigmentosa, and Type 2 Leber congenital amaurosis. In age-related macular degeneration/retinitis pigmentosa, a progressive loss of rods/cones results in corruption of bipolar cell circuitry, although retinal output neurons/photoreceptive melanopsin cells survive. Visual function can be stabilized/enhanced after treatment in age-related macular degeneration, but in advanced degenerations, reorganization of retinal circuitry may preclude attempts to restore cone function. In Type 2 Leber congenital amaurosis, useful vision can be restored by gene therapy where central cones survive. Remarkable progress has been made in restoring vision to rodents using light-responsive ion channels inserted into bipolar cells/retinal ganglion cells. Advances in genetic, cellular, and prosthetic therapies show varying degrees of promise for treating retinal degenerations. While functional benefits can be obtained after early therapeutic interventions, efforts should be made to minimize circuitry changes as soon as possible after rod/cone loss. Advances in retinal anatomy/physiology and genetic technologies should allow refinement of future reparative strategies.

Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A treatment

USDA-ARS?s Scientific Manuscript database

We sought to determine whether lutein supplementation will slow visual function decline in patients with retinitis pigmentosa receiving vitamin A. DESIGN: Randomized, controlled, double-masked trial of 225 nonsmoking patients, aged 18 to 60 years, evaluated over a 4-year interval. Patients received ...

Retinal Structure Measurements as Inclusion Criteria for Stem Cell-Based Therapies of Retinal Degenerations.

PubMed

Jacobson, Samuel G; Matsui, Rodrigo; Sumaroka, Alexander; Cideciyan, Artur V

2016-04-01

We reviewed and illustrated the most optimal retinal structural measurements to make in stem cell clinical trials. Optical coherence tomography (OCT) and autofluorescence (AF) imaging were used to evaluate patients with severe visual loss from nonsyndromic and syndromic retinitis pigmentosa (RP), ABCA4-Stargardt disease, and nonneovascular age-related macular degeneration (AMD). Outer nuclear layer (ONL), rod outer segment (ROS) layer, inner retina, ganglion cell layer (GCL), and nerve fiber layer (NFL) thicknesses were quantified. All patients had severely reduced visual acuities. Retinitis pigmentosa patients had limited visual fields; maculopathy patients had central scotomas with retained peripheral function. For the forms of RP illustrated, there was detectable albeit severely reduced ONL across the scanned retina, and normal or hyperthick GCL and NFL. Maculopathy patients had no measurable ONL centrally; it became detectable with eccentricity. Some maculopathy patients showed unexpected GCL losses. Autofluorescence imaging illustrated central losses of RPE integrity. A hypothetical scheme to relate patient data with different phases of retinal remodeling in animal models of retinal degeneration was presented. Stem cell science is advancing, but it is not too early to open the discussion of criteria for patient selection and monitoring. Available clinical tools, such as OCT and AF imaging, can provide inclusion/exclusion criteria and robust objective outcomes. Accepting that early trials may not lead to miraculous cures, we should be prepared to know why-scientifically and clinically-so we can improve subsequent trials. We also must determine if retinal remodeling is an impediment to efficacy.

Patterned Video Sensors For Low Vision

NASA Technical Reports Server (NTRS)

Juday, Richard D.

1996-01-01

Miniature video cameras containing photoreceptors arranged in prescribed non-Cartesian patterns to compensate partly for some visual defects proposed. Cameras, accompanied by (and possibly integrated with) miniature head-mounted video display units restore some visual function in humans whose visual fields reduced by defects like retinitis pigmentosa.

Design of a High-resolution Optoelectronic Retinal Prosthesis

NASA Astrophysics Data System (ADS)

Palanker, Daniel

2005-03-01

It has been demonstrated that electrical stimulation of the retina can produce visual percepts in blind patients suffering from macular degeneration and retinitis pigmentosa. So far retinal implants have had just a few electrodes, whereas at least several thousand pixels would be required for any functional restoration of sight. We will discuss physical limitations on the number of stimulating electrodes and on delivery of information and power to the retinal implant. Using a model of extracellular stimulation we derive the threshold values of current and voltage as a function of electrode size and distance to the target cell. Electrolysis, tissue heating, and cross-talk between neighboring electrodes depend critically on separation between electrodes and cells, thus strongly limiting the pixels size and spacing. Minimal pixel density required for 20/80 visual acuity (2500 pixels/mm2, pixel size 20 um) cannot be achieved unless the target neurons are within 7 um of the electrodes. At a separation of 50 um, the density drops to 44 pixels/mm2, and at 100 um it is further reduced to 10 pixels/mm2. We will present designs of subretinal implants that provide close proximity of electrodes to cells using migration of retinal cells to target areas. Two basic implant geometries will be described: perforated membranes and protruding electrode arrays. In addition, we will discuss delivery of information to the implant that allows for natural eye scanning of the scene, rather than scanning with a head-mounted camera. It operates similarly to ``virtual reality'' imaging devices where an image from a video camera is projected by a goggle-mounted collimated infrared LED-LCD display onto the retina, activating an array of powered photodiodes in the retinal implant. Optical delivery of visual information to the implant allows for flexible control of the image processing algorithms and stimulation parameters. In summary, we will describe solutions to some of the major problems facing the realization of a functional retinal implant: high pixel density, proximity of electrodes to target cells, natural eye scanning capability, and real-time image processing adjustable to retinal architecture.

Retinitis and optic neuritis in a child with chickenpox: case report and review of literature.

PubMed

Tappeiner, Christoph; Aebi, Christoph; Garweg, Justus G

2010-12-01

In immunocompetent individuals, necrotizing retinopathy is a rare complication of chickenpox. Herein, we report on a 3-year-old immunocompetent boy who developed retinitis and optic neuritis 3 days after the onset of chickenpox and compare the findings to published cases. Since macula and optic nerve were affected, visual acuity remained poor. An early diagnosis and treatment of ocular manifestations in chickenpox is imperative for the preservation of a residual visual function and prevention of blinding secondary complications.

Characteristics of moving visual scenes influencing spatial orientation

NASA Technical Reports Server (NTRS)

Held, R.; Bauer, J.; Dichgans, J.

1975-01-01

A visual display rotating in a frontal plane induces effects equivalent to a change in the apparent direction of gravity. Magnitude of visual tilt was measured as a function of time from onset of rotation, velocity of rotation, and area and retinal location of the stimulating field. The mejor part of the tilt occurs within 30 sec from onset of stimulation. It increases with angular velocity, but independently of area and location of field, up to about 30 to 40 deg of rotation per sec and then levels off. Tilt increases with field size but the effect of thin ring-fields increases with retinal eccentricity. The interaction of visual and nonvisual determinants of the induced effects is discussed.

Visual outcomes in children in Malawi following retinopathy of severe malaria

PubMed Central

Beare, N A V; Southern, C; Kayira, K; Taylor, T E; Harding, S P

2004-01-01

Aim: To investigate whether retinal changes in children with severe malaria affect visual acuity 1 month after systemic recovery. Methods: All children with severe malaria admitted to a research ward in Malawi during one malaria season were examined by direct and indirect ophthalmoscopy. Visual acuity was tested in those attending follow up by Cardiff cards, Sheridan-Gardiner single letters, or Snellen chart. Results: 96 (68%) children attended follow up, of whom 83 (86%) had visual acuity measured. Cardiff cards were used in 47 (57%) children, and Sheridan-Gardiner letters or Snellen chart in 29 (35%). There was no significant difference in the mean logMAR visual acuity between groups with or without macular whitening (0.14 versus 0.16, p = 0.55). There was no trend for worse visual acuity with increasing severity of macular whitening (p = 0.52) including patients in whom the fovea was involved (p = 0.32). Six (4.2%) children had cortical blindness after cerebral malaria, and all six had other neurological sequelae. Ophthalmoscopy during the acute illness revealed no abnormalities in four of these children. Conclusion: Retinal changes in severe malaria, in particular macular whitening, do not appear to affect visual acuity at 1 month. This supports the hypothesis that retinal whitening is due to reversible intracellular oedema in response to relative hypoxia, caused by sequestered erythrocytes infected by Plasmodium falciparum. Impaired visual functioning after cerebral malaria is not attributable to retinal changes and appears to be a cortical phenomenon. PMID:14977760

Visual outcomes in children in Malawi following retinopathy of severe malaria.

PubMed

Beare, N A V; Southern, C; Kayira, K; Taylor, T E; Harding, S P

2004-03-01

To investigate whether retinal changes in children with severe malaria affect visual acuity 1 month after systemic recovery. All children with severe malaria admitted to a research ward in Malawi during one malaria season were examined by direct and indirect ophthalmoscopy. Visual acuity was tested in those attending follow up by Cardiff cards, Sheridan-Gardiner single letters, or Snellen chart. 96 (68%) children attended follow up, of whom 83 (86%) had visual acuity measured. Cardiff cards were used in 47 (57%) children, and Sheridan-Gardiner letters or Snellen chart in 29 (35%). There was no significant difference in the mean logMAR visual acuity between groups with or without macular whitening (0.14 versus 0.16, p = 0.55). There was no trend for worse visual acuity with increasing severity of macular whitening (p = 0.52) including patients in whom the fovea was involved (p = 0.32). Six (4.2%) children had cortical blindness after cerebral malaria, and all six had other neurological sequelae. Ophthalmoscopy during the acute illness revealed no abnormalities in four of these children. Retinal changes in severe malaria, in particular macular whitening, do not appear to affect visual acuity at 1 month. This supports the hypothesis that retinal whitening is due to reversible intracellular oedema in response to relative hypoxia, caused by sequestered erythrocytes infected by Plasmodium falciparum. Impaired visual functioning after cerebral malaria is not attributable to retinal changes and appears to be a cortical phenomenon.

[Posterior vitrectomy with gas endotamponade and retinal laser therapy in treatment of patients with macular complications of the optic disc pit].

PubMed

Cywiński, Adam; Kałużny, Jakub; Ferda, Daniela; Piwońska-Lobermajer, Anna

2015-01-01

Retrospective evaluation of functional and anatomical treatment outcomes in patients with macular cornplications of optic disc pit. 9 patients (eyes) underwent central posterior vitrectomy in conjunction with posterior vitreous detachment, retinal laser therapy to the optic disc pit area and endotamponade with expansile gas. It was followed by the patient's forced positioning (recommended for a few days especially at night), which ended the treatment protocol. Improved anatomical relationships, accompanied by functional improvement were achieved in each reported case. The resolution of macular lesions was slow, lasting even for several months. Too long delay in performing the surgery (over 5 months since the onset of visual impairment) was associated with the development of retinal complications, mainly macular hole formation, most likely caused by the long-term ischemia. The central posterior vitrectomy combined with posterior vitreous detachment, laser therapy, andd expansile gas tamponade offers good outcomes in patients with retinal complications of optic disc pit. Surgery performed shortly after the onset of visual dysfunction gives the best functional outcomes. Restoration of normal anatomical relationships is a long-term process. In some cases, though, these abnormalities may not resolve completely.

Relationship between photoreceptor outer segment length and visual acuity in diabetic macular edema.

PubMed

Forooghian, Farzin; Stetson, Paul F; Meyer, Scott A; Chew, Emily Y; Wong, Wai T; Cukras, Catherine; Meyerle, Catherine B; Ferris, Frederick L

2010-01-01

The purpose of this study was to quantify photoreceptor outer segment (PROS) length in 27 consecutive patients (30 eyes) with diabetic macular edema using spectral domain optical coherence tomography and to describe the correlation between PROS length and visual acuity. Three spectral domain-optical coherence tomography scans were performed on all eyes during each session using Cirrus HD-OCT. A prototype algorithm was developed for quantitative assessment of PROS length. Retinal thicknesses and PROS lengths were calculated for 3 parameters: macular grid (6 x 6 mm), central subfield (1 mm), and center foveal point (0.33 mm). Intrasession repeatability was assessed using coefficient of variation and intraclass correlation coefficient. The association between retinal thickness and PROS length with visual acuity was assessed using linear regression and Pearson correlation analyses. The main outcome measures include intrasession repeatability of macular parameters and correlation of these parameters with visual acuity. Mean retinal thickness and PROS length were 298 mum to 381 microm and 30 microm to 32 mum, respectively, for macular parameters assessed in this study. Coefficient of variation values were 0.75% to 4.13% for retinal thickness and 1.97% to 14.01% for PROS length. Intraclass correlation coefficient values were 0.96 to 0.99 and 0.73 to 0.98 for retinal thickness and PROS length, respectively. Slopes from linear regression analyses assessing the association of retinal thickness and visual acuity were not significantly different from 0 (P > 0.20), whereas the slopes of PROS length and visual acuity were significantly different from 0 (P < 0.0005). Correlation coefficients for macular thickness and visual acuity ranged from 0.13 to 0.22, whereas coefficients for PROS length and visual acuity ranged from -0.61 to -0.81. Photoreceptor outer segment length can be quantitatively assessed using Cirrus HD-OCT. Although the intrasession repeatability of PROS measurements was less than that of macular thickness measurements, the stronger correlation of PROS length with visual acuity suggests that the PROS measures may be more directly related to visual function. Photoreceptor outer segment length may be a useful physiologic outcome measure, both clinically and as a direct assessment of treatment effects.

Plasticity Beyond V1: Reinforcement of Motion Perception upon Binocular Central Retinal Lesions in Adulthood.

PubMed

Burnat, Kalina; Hu, Tjing-Tjing; Kossut, Małgorzata; Eysel, Ulf T; Arckens, Lutgarde

2017-09-13

Induction of a central retinal lesion in both eyes of adult mammals is a model for macular degeneration and leads to retinotopic map reorganization in the primary visual cortex (V1). Here we characterized the spatiotemporal dynamics of molecular activity levels in the central and peripheral representation of five higher-order visual areas, V2/18, V3/19, V4/21a,V5/PMLS, area 7, and V1/17, in adult cats with central 10° retinal lesions (both sexes), by means of real-time PCR for the neuronal activity reporter gene zif268. The lesions elicited a similar, permanent reduction in activity in the center of the lesion projection zone of area V1/17, V2/18, V3/19, and V4/21a, but not in the motion-driven V5/PMLS, which instead displayed an increase in molecular activity at 3 months postlesion, independent of visual field coordinates. Also area 7 only displayed decreased activity in its LPZ in the first weeks postlesion and increased activities in its periphery from 1 month onward. Therefore we examined the impact of central vision loss on motion perception using random dot kinematograms to test the capacity for form from motion detection based on direction and velocity cues. We revealed that the central retinal lesions either do not impair motion detection or even result in better performance, specifically when motion discrimination was based on velocity discrimination. In conclusion, we propose that central retinal damage leads to enhanced peripheral vision by sensitizing the visual system for motion processing relying on feedback from V5/PMLS and area 7. SIGNIFICANCE STATEMENT Central retinal lesions, a model for macular degeneration, result in functional reorganization of the primary visual cortex. Examining the level of cortical reactivation with the molecular activity marker zif268 revealed reorganization in visual areas outside V1. Retinotopic lesion projection zones typically display an initial depression in zif268 expression, followed by partial recovery with postlesion time. Only the motion-sensitive area V5/PMLS shows no decrease, and even a significant activity increase at 3 months post-retinal lesion. Behavioral tests of motion perception found no impairment and even better sensitivity to higher random dot stimulus velocities. We demonstrate that the loss of central vision induces functional mobilization of motion-sensitive visual cortex, resulting in enhanced perception of moving stimuli. Copyright © 2017 the authors 0270-6474/17/378989-11$15.00/0.

Retinitis pigmentosa and allied conditions today: a paradigm of translational research

PubMed Central

2010-01-01

Monogenic human retinal dystrophies are a group of disorders characterized by progressive loss of photoreceptor cells leading to visual handicap. Retinitis pigmentosa is a type of retinal dystrophy where degeneration of rod photoreceptors occurs at the early stages. At present, there are no available effective therapies to maintain or improve vision in patients affected with retinitis pigmentosa, but post-genomic studies are allowing the development of potential therapeutic approaches. This review summarizes current knowledge on genes that have been identified to be responsible for retinitis pigmentosa, the involvement of these genes in the different forms of the disorder, the role of the proteins encoded by these genes in retinal function, the utility of genotyping, and current efforts to develop novel therapies. PMID:20519033

Predictors of vision impairment in Multiple Sclerosis.

PubMed

Sanchez-Dalmau, Bernardo; Martinez-Lapiscina, Elena H; Pulido-Valdeolivas, Irene; Zubizarreta, Irati; Llufriu, Sara; Blanco, Yolanda; Sola-Valls, Nuria; Sepulveda, Maria; Guerrero, Ana; Alba, Salut; Andorra, Magi; Camos, Anna; Sanchez-Vela, Laura; Alfonso, Veronica; Saiz, Albert; Villoslada, Pablo

2018-01-01

Visual impairment significantly alters the quality of life of people with Multiple Sclerosis (MS). The objective of this study was to identify predictors (independent variables) of visual outcomes, and to define their relationship with neurological disability and retinal atrophy when assessed by optical coherence tomography (OCT). We performed a cross-sectional analysis of 119 consecutive patients with MS, assessing vision using high contrast visual acuity (LogMar), 2.5% and 1.25% low contrast visual acuity (Sloan charts), and color vision (Hardy-Rand-Rittler plates). Quality of vision is a patient reported outcome based on an individual's unique perception of his or her vision and was assessed with the Visual Functioning Questionnaire-25 (VFQ-25) with the 10 neuro-ophthalmologic items. MS disability was assessed using the expanded disability status scale (EDSS), the MS functional composite (MSFC) and the brief repetitive battery-neuropsychology (BRB-N). Retinal atrophy was assessed using spectral domain OCT, measuring the thickness of the peripapillar retinal nerve fiber layer (pRNFL) and the volume of the ganglion cell plus inner plexiform layer (GCIPL). The vision of patients with MS was impaired, particularly in eyes with prior optic neuritis. Retinal atrophy (pRNFL and GCIPL) was closely associated with impaired low contrast vision and color vision, whereas the volume of the GCIPL showed a trend (p = 0.092) to be associated with quality of vision. Multiple regression analysis revealed that EDSS was an explanatory variable for high contrast vision after stepwise analysis, GCIPL volume for low contrast vision, and GCIPL volume and EDSS for color vision. The explanatory variables for quality of vision were high contrast vision and color vision. In summary, quality of vision in MS depends on the impairment of high contrast visual acuity and color vision due to the disease.

Objective visual assessment of antiangiogenic treatment for wet age-related macular degeneration.

PubMed

Baseler, Heidi A; Gouws, André; Crossland, Michael D; Leung, Carmen; Tufail, Adnan; Rubin, Gary S; Morland, Antony B

2011-10-01

To assess cortical responses in patients undergoing antiangiogenic treatment for wet age-related macular degeneration (AMD) using functional magnetic resonance imaging (fMRI) as an objective, fixation-independent measure of topographic visual function. A patient with bilateral neovascular AMD was scanned using fMRI before and at regular intervals while undergoing treatment with intravitreal antiangiogenic injections (ranibizumab). Blood oxygenation level-dependent signals were measured in the brain while the patient viewed a stimulus consisting of a full-field flickering (6 Hz) white light alternating with a uniform gray background (18 s on and 18 s off). Topographic distribution and magnitude of activation in visual cortex were compared longitudinally throughout the treatment period (<1 year) and with control patients not currently undergoing treatment. Clinical behavioral tests were also administered, including visual acuity, microperimetry, and reading skills. The area of visual cortex activated increased significantly after the first treatment to include more posterior cortex that normally receives inputs from lesioned parts of the retina. Subsequent treatments yielded no significant further increase in activation area. Behavioral measures all generally showed an improvement with treatment but did not always parallel one another. The untreated control patient showed a consistent lack of significant response in the cortex representing retinal lesions. Retinal treatments may not only improve vision but also result in a concomitant improvement in fixation stability. Current clinical behavioral measures (e.g., acuity and perimetry) are largely dependent on fixation stability and therefore cannot separate improvements of visual function from fixation improvements. fMRI, which provides an objective and sensitive measure of visual function independent of fixation, reveals a significant increase in visual cortical responses in patients with wet AMD after treatment with antiangiogenic injections. Despite recent evidence that visual cortex degenerates subsequent to retinal lesions, our results indicate that it can remain responsive as its inputs are restored.

Pineal Photoreceptor Cells Are Required for Maintaining the Circadian Rhythms of Behavioral Visual Sensitivity in Zebrafish

PubMed Central

Li, Xinle; Montgomery, Jake; Cheng, Wesley; Noh, Jung Hyun; Hyde, David R.; Li, Lei

2012-01-01

In non-mammalian vertebrates, the pineal gland functions as the central pacemaker that regulates the circadian rhythms of animal behavior and physiology. We generated a transgenic zebrafish line [Tg(Gnat2:gal4-VP16/UAS:nfsB-mCherry)] in which the E. coli nitroreductase is expressed in pineal photoreceptor cells. In developing embryos and young adults, the transgene is expressed in both retinal and pineal photoreceptor cells. During aging, the expression of the transgene in retinal photoreceptor cells gradually diminishes. By 8 months of age, the Gnat2 promoter-driven nitroreductase is no longer expressed in retinal photoreceptor cells, but its expression in pineal photoreceptor cells persists. This provides a tool for selective ablation of pineal photoreceptor cells, i.e., by treatments with metronidazole. In the absence of pineal photoreceptor cells, the behavioral visual sensitivity of the fish remains unchanged; however, the circadian rhythms of rod and cone sensitivity are diminished. Brief light exposures restore the circadian rhythms of behavioral visual sensitivity. Together, the data suggest that retinal photoreceptor cells respond to environmental cues and are capable of entraining the circadian rhythms of visual sensitivity; however, they are insufficient for maintaining the rhythms. Cellular signals from the pineal photoreceptor cells may be required for maintaining the circadian rhythms of visual sensitivity. PMID:22815753

LRRTM1 underlies synaptic convergence in visual thalamus

PubMed Central

Monavarfeshani, Aboozar; Stanton, Gail; Van Name, Jonathan; Su, Kaiwen; Mills, William A; Swilling, Kenya; Kerr, Alicia; Huebschman, Natalie A; Su, Jianmin

2018-01-01

It has long been thought that the mammalian visual system is organized into parallel pathways, with incoming visual signals being parsed in the retina based on feature (e.g. color, contrast and motion) and then transmitted to the brain in unmixed, feature-specific channels. To faithfully convey feature-specific information from retina to cortex, thalamic relay cells must receive inputs from only a small number of functionally similar retinal ganglion cells. However, recent studies challenged this by revealing substantial levels of retinal convergence onto relay cells. Here, we sought to identify mechanisms responsible for the assembly of such convergence. Using an unbiased transcriptomics approach and targeted mutant mice, we discovered a critical role for the synaptic adhesion molecule Leucine Rich Repeat Transmembrane Neuronal 1 (LRRTM1) in the emergence of retinothalamic convergence. Importantly, LRRTM1 mutant mice display impairment in visual behaviors, suggesting a functional role of retinothalamic convergence in vision. PMID:29424692

Vision related quality of life in patients with type 2 diabetes in the EUROCONDOR trial.

PubMed

Trento, Marina; Durando, Olga; Lavecchia, Sonia; Charrier, Lorena; Cavallo, Franco; Costa, Miguel Angelo; Hernández, Cristina; Simó, Rafael; Porta, Massimo

2017-07-01

To evaluate vision related quality of life in the patients enrolled in The European Consortium for the Early Treatment of Diabetic Retinopathy, a clinical trial on prevention of diabetic retinopathy. Four-hundred-forty-nine patients, 153 women, with type 2 Diabetes and no or mild diabetic retinopathy were enrolled in a 2-year multicenter randomized controlled trial. The 25-item National Eye Institute Visual Functioning Questionnaire was used to explore 12 subscales of vision related quality of life. The patients were 62.8 ± 6.7 years old and had 11.1 ± 5.6 years known disease duration. Diabetic retinopathy was absent in 193 (43.0 %) and mild in 256 (57.0 %). Patients without diabetic retinopathy were older, had shorter diabetes duration and used less insulin and glucose-lowering agents but did not differ by gender, best corrected visual acuity or any subscale, except vision specific mental health and vision specific role difficulties. Patients with reduced retinal thickness at the ganglion cell layer (n = 36) did not differ for diabetic retinopathy but were older, had lower best corrected visual acuity and worse scores for ocular pain, color vision and peripheral vision. On multivariable analysis, worse scores for general vision remained associated with reduced retinal thickness, diabetes duration and best corrected visual acuity, and scores for visual specific mental health with diabetic retinopathy and lower best corrected visual acuity. Visual specific role difficulties were only associated with reduced best corrected visual acuity. Scores for driving decreased among females, with worsening of Hemoglobin A1c and best corrected visual acuity. Color vision depended only on reduced retinal thickness, and peripheral vision on both reduced thickness and best corrected visual acuity. The National Eye Institute Visual Functioning Questionnaire could detect subtle changes in patients' perception of visual function, despite absent/minimal diabetic retinopathy.

[Internal limiting membrane peeling as prophylaxis of epimacular membrane formation in eyes undergoing vitrectomy for rhegmatogenous retinal detachement].

PubMed

Hejsek, L; Dusová, J; Stepanov, A; Rozsíval, P

2014-06-01

Rhegmatogenous retinal detachment is a serious condition that can significantly impair visual function, even after a successful surgery. One of the complications that can significantly impair visual acuity in the postoperative period is a development of the epimacular membrane (ERM). The aim of this work is to monitor the effect of peeling of the internal limiting membrane (ILM) in the macula at the anatomical and functional results in the postoperative period, especially with regard to the development of ERM. Prospective study of 21 eyes, which underwent peeling of ILM during pars plana vitrectomy for rhegmatogenous retinal detachment (on detached macula). The ILM peeling was done without using decalin during this procedure. We tested best corrected visual acuity (BCVA) and followed fundus biomicroscopic findings. Proliferative vitreoretinopathy (PVR) was evaluated according to the recommendations of the Retina Society Terminology Committee. To exclude the development of ERM in the macula optical coherence tomography (OCT) was performed at the end of the 18-month follow-up period. In total, the results of 21 eyes of 21 patients who underwent PPV for rhegmatogenous retinal detachment were evaluated. In all of them was during PPV performed ILM peeling on detached macula, these are followed prospectively. ILM peeling without using decalin was sufficient in all eyes. All eyes with ILM peeling did not develop ERM at the end of the follow-up period. ILM peeling during PPV for rhegmatogenous retinal detachment reduces the risk of developing secondary ERM.

Visual cycle modulation in neurovascular retinopathy.

PubMed

Akula, James D; Hansen, Ronald M; Tzekov, Radouil; Favazza, Tara L; Vyhovsky, Tanya C; Benador, Ilan Y; Mocko, Julie A; McGee, David; Kubota, Ryo; Fulton, Anne B

2010-08-01

Rats with oxygen-induced retinopathy (OIR) model the pediatric retinal disease retinopathy of prematurity (ROP). Recent findings in OIR rats imply a causal role for the rods in the ROP disease process, although only experimental manipulation of rod function can establish this role conclusively. Accordingly, a visual cycle modulator (VCM) - with no known direct effect on retinal vasculature - was administered to "50/10 model" OIR Sprague-Dawley rats to test the hypotheses that it would 1) alter rod function and 2) consequently alter vascular outcome. Four litters of pups (N=46) were studied. For two weeks, beginning on postnatal day (P) 7, the first and fourth litters were administered 6 mg kg(-1) N-retinylacetamide (the VCM) intraperitoneally; the second and third litters received vehicle (DMSO) alone. Following a longitudinal design, retinal function was assessed by electroretinography (ERG) and the status of the retinal vessels was monitored using computerized fundus photograph analysis. Rod photoreceptor and post-receptor response amplitudes were significantly higher in VCM-treated than in vehicle-treated rats; deactivation of phototransduction was also significantly more rapid. Notably, the arterioles of VCM-treated rats showed significantly greater recovery from OIR. Presuming that the VCM did not directly affect the retinal vessels, a causal role for the neural retina - particularly the rod photoreceptors - in OIR was confirmed. There was no evidence of negative alteration of photoreceptor function consequent to VCM treatment. This finding implicates the rods as a possible therapeutic target in neurovascular diseases such as ROP. Copyright 2010 Elsevier Ltd. All rights reserved.

Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases

PubMed Central

Jones, Melissa K.; Lu, Bin; Girman, Sergey; Wang, Shaomei

2017-01-01

Cell-based therapeutics offer diverse options for treating retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). AMD is characterized by both genetic and environmental risks factors, whereas RP is mainly a monogenic disorder. Though treatments exist for some patients with neovascular AMD, a majority of retinal degenerative patients have no effective therapeutics, thus indicating a need for universal therapies to target diverse patient populations. Two main cell-based mechanistic approaches are being tested in clinical trials. Replacement therapies utilize cell-derived retinal pigment epithelial (RPE) cells to supplant lost or defective host RPE cells. These cells are similar in morphology and function to native RPE cells and can potentially supplant the responsibilities of RPE in vivo. Preservation therapies utilize supportive cells to aid in visual function and photoreceptor preservation partially by neurotrophic mechanisms. The goal of preservation strategies is to halt or slow the progression of disease and maintain remaining visual function. A number of clinical trials are testing the safety of replacement and preservation cell therapies in patients; however, measures of efficacy will need to be further evaluated. In addition, a number of prevailing concerns with regards to the immune-related response, longevity, and functionality of the grafted cells will need to be addressed in future trials. This review will summarize the current status of cell-based preclinical and clinical studies with a focus on replacement and preservation strategies and the obstacles that remain regarding these types of treatments. PMID:28111323

Synthetic 9-cis-beta-carotene inhibits photoreceptor degeneration in cultures of eye cups from rpe65rd12 mouse model of retinoid cycle defect.

PubMed

Sher, Ifat; Tzameret, Adi; Peri-Chen, Sara; Edelshtain, Victoria; Ioffe, Michael; Sayer, Alon; Buzhansky, Ludmila; Gazit, Ehud; Rotenstreich, Ygal

2018-04-17

The retinoid cycle enzymes regenerate the visual chromophore 11-cis retinal to enable vision. Mutations in the genes encoding the proteins of the retinoid cycle are the leading cause for recessively inherited retinal dystrophies such as retinitis pigmentosa, Leber congenital amaurosis, congenital cone-rod dystrophy and fundus albipunctatus. Currently there is no treatment for these blinding diseases. In previous studies we demonstrated that oral treatment with the 9-cis-β-carotene rich Dunaliella Bardawil algae powder significantly improved visual and retinal functions in patients with retinitis pigmentosa and fundus albipunctatus. Here we developed a convenient and economical synthetic route for biologically active 9-cis-β-carotene from inexpensive building materials and demonstrated that the molecule is stable for at least one month. Synthetic 9-cis-β-carotene rescued cone photoreceptors from degeneration in eye cup cultures of mice with a retinoid cycle genetic defect. This study suggests that synthetic 9-cis-β-carotene may serve as an effective treatment for retinal dystrophies involving the retinoid cycle.

Connecting Research on Retinitis Pigmentosa to the Practice of Orientation and Mobility.

ERIC Educational Resources Information Center

Geruschat, Duane R.; Turano, Kathleen A.

2002-01-01

Retinitis pigmentosa (RP) causes restriction of the visual field, progressive vision loss, and night blindness. This article presents an overview of the most common problems in orientation and mobility (O&M) for individuals with RP, appropriate interventions, vision science discoveries related to RP, and the impact of RP on functional visual…

Endogenous and Synthetic Cannabinoids as Therapeutics in Retinal Disease

PubMed Central

Kokona, Despina; Georgiou, Panagiota-Christina; Kounenidakis, Mihalis; Kiagiadaki, Foteini; Thermos, Kyriaki

2016-01-01

The functional significance of cannabinoids in ocular physiology and disease has been reported some decades ago. In the early 1970s, subjects who smoked Cannabis sativa developed lower intraocular pressure (IOP). This led to the isolation of phytocannabinoids from this plant and the study of their therapeutic effects in glaucoma. The main treatment of this disease to date involves the administration of drugs mediating either the decrease of aqueous humour synthesis or the increase of its outflow and thus reduces IOP. However, the reduction of IOP is not sufficient to prevent visual field loss. Retinal diseases, such as glaucoma and diabetic retinopathy, have been defined as neurodegenerative diseases and characterized by ischemia-induced excitotoxicity and loss of retinal neurons. Therefore, new therapeutic strategies must be applied in order to target retinal cell death, reduction of visual acuity, and blindness. The aim of the present review is to address the neuroprotective and therapeutic potential of cannabinoids in retinal disease. PMID:26881135

a Review of Retinal Prosthesis Approaches

NASA Astrophysics Data System (ADS)

Kien, Tran Trung; Maul, Tomas; Bargiela, Andrzej

Age-related macular degeneration and retinitis pigmentosa are two of the most common diseases that cause degeneration in the outer retina, which can lead to several visual impairments up to blindness. Vision restoration is an important goal for which several different research approaches are currently being pursued. We are concerned with restoration via retinal prosthetic devices. Prostheses can be implemented intraocularly and extraocularly, which leads to different categories of devices. Cortical Prostheses and Optic Nerve Prostheses are examples of extraocular solutions while Epiretinal Prostheses and Subretinal Prostheses are examples of intraocular solutions. Some of the prostheses that are successfully implanted and tested in animals as well as humans can restore basic visual functions but still have limitations. This paper will give an overview of the current state of art of Retinal Prostheses and compare the advantages and limitations of each type. The purpose of this review is thus to summarize the current technologies and approaches used in developing Retinal Prostheses and therefore to lay a foundation for future designs and research directions.

Torsional ARC Effectively Expands the Visual Field in Hemianopia

PubMed Central

Satgunam, PremNandhini; Peli, Eli

2012-01-01

Purpose Exotropia in congenital homonymous hemianopia has been reported to provide field expansion that is more useful when accompanied with harmonios anomalous retinal correspondence (HARC). Torsional strabismus with HARC provides a similar functional advantage. In a subject with hemianopia demonstrating a field expansion consistent with torsion we documented torsional strabismus and torsional HARC. Methods Monocular visual fields under binocular fixation conditions were plotted using a custom dichoptic visual field perimeter (DVF). The DVF was also modified to measure perceived visual directions under dissociated and associated conditions across the central 50° diameter field. The field expansion and retinal correspondence of a subject with torsional strabismus (along with exotropia and right hypertropia) with congenital homonymous hemianopia was compared to that of another exotropic subject with acquired homonymous hemianopia without torsion and to a control subject with minimal phoria. Torsional rotations of the eyes were calculated from fundus photographs and perimetry. Results Torsional ARC documented in the subject with congenital homonymous hemianopia provided a functional binocular field expansion up to 18°. Normal retinal correspondence was mapped for the full 50° visual field in the control subject and for the seeing field of the acquired homonymous hemianopia subject, limiting the functional field expansion benefit. Conclusions Torsional strabismus with ARC, when occurring with homonymous hemianopia provides useful field expansion in the lower and upper fields. Dichoptic perimetry permits documentation of ocular alignment (lateral, vertical and torsional) and perceived visual direction under binocular and monocular viewing conditions. Evaluating patients with congenital or early strabismus for HARC is useful when considering surgical correction, particularly in the presence of congenital homonymous hemianopia. PMID:22885782

Highly efficient retinal metabolism in cones

PubMed Central

Miyazono, Sadaharu; Shimauchi-Matsukawa, Yoshie; Tachibanaki, Shuji; Kawamura, Satoru

2008-01-01

After bleaching of visual pigment in vertebrate photoreceptors, all-trans retinal is reduced to all-trans retinol by retinol dehydrogenases (RDHs). We investigated this reaction in purified carp rods and cones, and we found that the reducing activity toward all-trans retinal in the outer segment (OS) of cones is >30 times higher than that of rods. The high activity of RDHs was attributed to high content of RDH8 in cones. In the inner segment (IS) in both rods and cones, RDH8L2 and RDH13 were found to be the major enzymes among RDH family proteins. We further found a previously undescribed and effective pathway to convert 11-cis retinol to 11-cis retinal in cones: this oxidative conversion did not require NADP+ and instead was coupled with reduction of all-trans retinal to all-trans retinol. The activity was >50 times effective than the oxidizing activity of RDHs that require NADP+. These highly effective reactions of removal of all-trans retinal by RDH8 and production of 11-cis retinal by the coupling reaction are probably the underlying mechanisms that ensure effective visual pigment regeneration in cones that function under much brighter light conditions than rods. PMID:18836074

Peripheral Refraction, Peripheral Eye Length, and Retinal Shape in Myopia.

PubMed

Verkicharla, Pavan K; Suheimat, Marwan; Schmid, Katrina L; Atchison, David A

2016-09-01

To investigate how peripheral refraction and peripheral eye length are related to retinal shape. Relative peripheral refraction (RPR) and relative peripheral eye length (RPEL) were determined in 36 young adults (M +0.75D to -5.25D) along horizontal and vertical visual field meridians out to ±35° and ±30°, respectively. Retinal shape was determined in terms of vertex radius of curvature Rv, asphericity Q, and equivalent radius of curvature REq using a partial coherence interferometry method involving peripheral eye lengths and model eye raytracing. Second-order polynomial fits were applied to RPR and RPEL as functions of visual field position. Linear regressions were determined for the fits' second order coefficients and for retinal shape estimates as functions of central spherical refraction. Linear regressions investigated relationships of RPR and RPEL with retinal shape estimates. Peripheral refraction, peripheral eye lengths, and retinal shapes were significantly affected by meridian and refraction. More positive (hyperopic) relative peripheral refraction, more negative RPELs, and steeper retinas were found along the horizontal than along the vertical meridian and in myopes than in emmetropes. RPR and RPEL, as represented by their second-order fit coefficients, correlated significantly with retinal shape represented by REq. Effects of meridian and refraction on RPR and RPEL patterns are consistent with effects on retinal shape. Patterns derived from one of these predict the others: more positive (hyperopic) RPR predicts more negative RPEL and steeper retinas, more negative RPEL predicts more positive relative peripheral refraction and steeper retinas, and steeper retinas derived from peripheral eye lengths predict more positive RPR.

Retinal Adaptation Abnormalities in Primary Open-Angle Glaucoma

PubMed Central

Dul, Mitchell; Ennis, Robert; Radner, Shira; Lee, Barry; Zaidi, Qasim

2015-01-01

Purpose. Dynamic color and brightness adaptation are crucial for visual functioning. The effects of glaucoma on retinal ganglion cells (RGCs) could compromise these functions. We have previously used slow dynamic changes of light at moderate intensities to measure the speed and magnitude of subtractive adaptation in RGCs. We used the same procedure to test if RGC abnormalities cause slower and weaker adaptation for patients with glaucoma when compared to age-similar controls. We assessed adaptation deficits in specific classes of RGCs by testing along the three cardinal color axes that isolate konio, parvo, and magno RGCs. Methods. For one eye each of 10 primary open-angle glaucoma patients and their age-similar controls, we measured the speed and magnitude of adapting to 1/32 Hz color modulations along the three cardinal axes, at central fixation and 8° superior, inferior, nasal, and temporal to fixation. Results. In all 15 comparisons (5 locations × 3 color axes), average adaptation was slower and weaker for glaucoma patients than for controls. Adaptation developed slower at central targets than at 8° eccentricities for controls, but not for patients. Adaptation speed and magnitude differed between affected and control eyes even at retinal locations showing no visual field loss with clinical perimetry. Conclusions. Neural adaptation is weaker in glaucoma patients for all three classes of RGCs. Since adaptation abnormalities are manifested even at retinal locations not exhibiting a visual field loss, this novel form of assessment may offer a functional insight into glaucoma and an early diagnosis tool. PMID:25613950

Spatial resolution, contrast sensitivity, and sensitivity to defocus of chicken retinal ganglion cells in vitro.

PubMed

Diedrich, Erich; Schaeffel, Frank

2009-11-01

The chicken has been extensively studied as an animal model for myopia because its eye growth is tightly controlled by visual experience. It has been found that the retina controls the axial eye growth rates depending on the amount and the sign of defocus imposed in the projected image. Glucagonergic amacrine cells were discovered that appear to encode for the sign of imposed defocus. It is not clear whether the downstream neurons, the retinal ganglion cells, still have access to this information-and whether it ultimately reaches the brain. We have analyzed the spike rates of chicken retinal ganglion cells in vitro using a microelectrode array. For this purpose, we initially defined spatial resolution and contrast sensitivity in vitro. Two classes of chicken retinal ganglions were found, depending on the linearity of their responses with increasing contrast. Responses generally declined with increasing defocus of the visual stimulus. These responses were well predicted by the modulation transfer function for a diffraction-limited defocused optical system, the first Bessel function. Thus, the studied retinal ganglion cells did not distinguish between a loss of contrast at a given spatial frequency due to reduced contrast of the stimulus pattern or because the pattern was presented out of focus. Furthermore, there was no indication that the retinal ganglion cells responded differently to defocus of either sign, at least for the cells that were recorded in this study.

The fundus photo has met its match: optical coherence tomography and adaptive optics ophthalmoscopy are here to stay

PubMed Central

Morgan, Jessica I. W.

2016-01-01

Purpose Over the past 25 years, optical coherence tomography (OCT) and adaptive optics (AO) ophthalmoscopy have revolutionised our ability to non-invasively observe the living retina. The purpose of this review is to highlight the techniques and human clinical applications of recent advances in OCT and adaptive optics scanning laser/light ophthalmoscopy (AOSLO) ophthalmic imaging. Recent findings Optical coherence tomography retinal and optic nerve head (ONH) imaging technology allows high resolution in the axial direction resulting in cross-sectional visualisation of retinal and ONH lamination. Complementary AO ophthalmoscopy gives high resolution in the transverse direction resulting in en face visualisation of retinal cell mosaics. Innovative detection schemes applied to OCT and AOSLO technologies (such as spectral domain OCT, OCT angiography, confocal and non-confocal AOSLO, fluorescence, and AO-OCT) have enabled high contrast between retinal and ONH structures in three dimensions and have allowed in vivo retinal imaging to approach that of histological quality. In addition, both OCT and AOSLO have shown the capability to detect retinal reflectance changes in response to visual stimuli, paving the way for future studies to investigate objective biomarkers of visual function at the cellular level. Increasingly, these imaging techniques are being applied to clinical studies of the normal and diseased visual system. Summary Optical coherence tomography and AOSLO technologies are capable of elucidating the structure and function of the retina and ONH noninvasively with unprecedented resolution and contrast. The techniques have proven their worth in both basic science and clinical applications and each will continue to be utilised in future studies for many years to come. PMID:27112222

The Pattern of Visual Fixation Eccentricity and Instability in Optic Neuropathy and Its Spatial Relationship to Retinal Ganglion Cell Layer Thickness.

PubMed

Mallery, Robert M; Poolman, Pieter; Thurtell, Matthew J; Wang, Jui-Kai; Garvin, Mona K; Ledolter, Johannes; Kardon, Randy H

2016-07-01

The purpose of this study was to assess whether clinically useful measures of fixation instability and eccentricity can be derived from retinal tracking data obtained during optical coherence tomography (OCT) in patients with optic neuropathy (ON) and to develop a method for relating fixation to the retinal ganglion cell complex (GCC) thickness. Twenty-nine patients with ON underwent macular volume OCT with 30 seconds of confocal scanning laser ophthalmoscope (cSLO)-based eye tracking during fixation. Kernel density estimation quantified fixation instability and fixation eccentricity from the distribution of fixation points on the retina. Preferred ganglion cell layer loci (PGCL) and their relationship to the GCC thickness map were derived, accounting for radial displacement of retinal ganglion cell soma from their corresponding cones. Fixation instability was increased in ON eyes (0.21 deg2) compared with normal eyes (0.06982 deg2; P < 0.001), and fixation eccentricity was increased in ON eyes (0.48°) compared with normal eyes (0.24°; P = 0.03). Fixation instability and eccentricity each correlated moderately with logMAR acuity and were highly predictive of central visual field loss. Twenty-six of 35 ON eyes had PGCL skewed toward local maxima of the GCC thickness map. Patients with bilateral dense central scotomas had PGCL in homonymous retinal locations with respect to the fovea. Fixation instability and eccentricity measures obtained during cSLO-OCT assess the function of perifoveal retinal elements and predict central visual field loss in patients with ON. A model relating fixation to the GCC thickness map offers a method to assess the structure-function relationship between fixation and areas of preserved GCC in patients with ON.

The Pattern of Visual Fixation Eccentricity and Instability in Optic Neuropathy and Its Spatial Relationship to Retinal Ganglion Cell Layer Thickness

PubMed Central

M. Mallery, Robert; Poolman, Pieter; J. Thurtell, Matthew; Wang, Jui-Kai; K. Garvin, Mona; Ledolter, Johannes; Kardon, Randy H.

2016-01-01

Purpose The purpose of this study was to assess whether clinically useful measures of fixation instability and eccentricity can be derived from retinal tracking data obtained during optical coherence tomography (OCT) in patients with optic neuropathy (ON) and to develop a method for relating fixation to the retinal ganglion cell complex (GCC) thickness. Methods Twenty-nine patients with ON underwent macular volume OCT with 30 seconds of confocal scanning laser ophthalmoscope (cSLO)-based eye tracking during fixation. Kernel density estimation quantified fixation instability and fixation eccentricity from the distribution of fixation points on the retina. Preferred ganglion cell layer loci (PGCL) and their relationship to the GCC thickness map were derived, accounting for radial displacement of retinal ganglion cell soma from their corresponding cones. Results Fixation instability was increased in ON eyes (0.21 deg2) compared with normal eyes (0.06982 deg2; P < 0.001), and fixation eccentricity was increased in ON eyes (0.48°) compared with normal eyes (0.24°; P = 0.03). Fixation instability and eccentricity each correlated moderately with logMAR acuity and were highly predictive of central visual field loss. Twenty-six of 35 ON eyes had PGCL skewed toward local maxima of the GCC thickness map. Patients with bilateral dense central scotomas had PGCL in homonymous retinal locations with respect to the fovea. Conclusions Fixation instability and eccentricity measures obtained during cSLO-OCT assess the function of perifoveal retinal elements and predict central visual field loss in patients with ON. A model relating fixation to the GCC thickness map offers a method to assess the structure–function relationship between fixation and areas of preserved GCC in patients with ON. PMID:27409502

The fundus photo has met its match: optical coherence tomography and adaptive optics ophthalmoscopy are here to stay.

PubMed

Morgan, Jessica I W

2016-05-01

Over the past 25 years, optical coherence tomography (OCT) and adaptive optics (AO) ophthalmoscopy have revolutionised our ability to non-invasively observe the living retina. The purpose of this review is to highlight the techniques and human clinical applications of recent advances in OCT and adaptive optics scanning laser/light ophthalmoscopy (AOSLO) ophthalmic imaging. Optical coherence tomography retinal and optic nerve head (ONH) imaging technology allows high resolution in the axial direction resulting in cross-sectional visualisation of retinal and ONH lamination. Complementary AO ophthalmoscopy gives high resolution in the transverse direction resulting in en face visualisation of retinal cell mosaics. Innovative detection schemes applied to OCT and AOSLO technologies (such as spectral domain OCT, OCT angiography, confocal and non-confocal AOSLO, fluorescence, and AO-OCT) have enabled high contrast between retinal and ONH structures in three dimensions and have allowed in vivo retinal imaging to approach that of histological quality. In addition, both OCT and AOSLO have shown the capability to detect retinal reflectance changes in response to visual stimuli, paving the way for future studies to investigate objective biomarkers of visual function at the cellular level. Increasingly, these imaging techniques are being applied to clinical studies of the normal and diseased visual system. Optical coherence tomography and AOSLO technologies are capable of elucidating the structure and function of the retina and ONH noninvasively with unprecedented resolution and contrast. The techniques have proven their worth in both basic science and clinical applications and each will continue to be utilised in future studies for many years to come. © 2016 The Authors Ophthalmic & Physiological Optics © 2016 The College of Optometrists.

Disease expression in Usher syndrome caused by VLGR1 gene mutation (USH2C) and comparison with USH2A phenotype.

PubMed

Schwartz, Sharon B; Aleman, Tomas S; Cideciyan, Artur V; Windsor, Elizabeth A M; Sumaroka, Alexander; Roman, Alejandro J; Rane, Tej; Smilko, Elaine E; Bennett, Jean; Stone, Edwin M; Kimberling, William J; Liu, Xue-Zhong; Jacobson, Samuel G

2005-02-01

To investigate the retinal disease expression in USH2C, the subtype of Usher syndrome type 2 recently shown to be caused by mutation in the VLGR1 gene, and compare results with those from USH2A, a more common cause of Usher syndrome. Three siblings with USH2C and 14 patients with USH2A were studied. Visual function was measured by kinetic perimetry, static chromatic perimetry, and electroretinography (ERG). Central retinal microstructure was studied with optical coherence tomography (OCT). The siblings with VLGR1 mutation showed abnormal photoreceptor-mediated function in all retinal regions, and there was greater rod than cone dysfunction. USH2A had a wider spectrum of disease expression and included patients with normal function in some retinal regions. When abnormalities were detected, there was more rod than cone dysfunction. Retinal microstructure in both USH2C and USH2A shared the abnormality of loss of outer nuclear layer thickness. Central retinal structure in both genotypes was complicated by cystic macular lesions. A coincidental finding in an USH2C patient was that oral intake of antihistamines was associated with temporary resolution of the macular cystic change. USH2C and USH2A manifest photoreceptor disease with rod- and cone-mediated visual losses and thinning of the outer nuclear layer. An orderly progression through disease stages was estimated from cross-sectional and limited longitudinal data. Intrafamilial and interfamilial variation in retinal severity in USH2A, however, suggests that genetic or nongenetic modifiers may be involved in the disease expression.

Water maze performance of aged Sprague-Dawley rats in relation to retinal morphologic measures.

PubMed

Spencer, R L; O'Steen, W K; McEwen, B S

1995-06-01

The spatial learning ability of aged male and female Sprague-Dawley rats was assessed using the Morris water maze. To determine the influence of age-related visual deficits on performance levels, retinal morphologic measures were correlated with water maze performance for each rat. Rats were first trained on the water maze task at 21 months of age and were retrained 3 or 4 times at 6-week intervals. After the last training session the rats were killed and their eyes were removed for histopathologic and morphometric evaluation of the retinas. There was a large degree of retinal degeneration in all of the aged Sprague-Dawley rats with an average decrease in the thickness of the retinal outer nuclear layer (photoreceptor nuclei containing layer) of 85% in old males and 95% in old females. Some rats, however, had less degeneration of the retinas than others, and the degree of retinal degeneration was strongly related to performance levels on the water maze task. Among the aged rats in this study with the least retinal degeneration, there was little evidence for a subset of rats that were unable, with extensive training, to learn a platform position. Of the 41 rats with the least retinal degeneration (out of a total of 81), only one was a clear non-learner on the water maze task, whereas, of the 27 rats with the most retinal degeneration, 20 were non-learners. These results illustrate the potentially serious confounding effects of deteriorating visual ability on attempts to assess cognitive functioning of aged albino rats on tasks requiring utilization of visual cues.

A second visual rhodopsin gene, rh1-2, is expressed in zebrafish photoreceptors and found in other ray-finned fishes.

PubMed

Morrow, James M; Lazic, Savo; Dixon Fox, Monica; Kuo, Claire; Schott, Ryan K; de A Gutierrez, Eduardo; Santini, Francesco; Tropepe, Vincent; Chang, Belinda S W

2017-01-15

Rhodopsin (rh1) is the visual pigment expressed in rod photoreceptors of vertebrates that is responsible for initiating the critical first step of dim-light vision. Rhodopsin is usually a single copy gene; however, we previously discovered a novel rhodopsin-like gene expressed in the zebrafish retina, rh1-2, which we identified as a functional photosensitive pigment that binds 11-cis retinal and activates in response to light. Here, we localized expression of rh1-2 in the zebrafish retina to a subset of peripheral photoreceptor cells, which indicates a partially overlapping expression pattern with rh1 We also expressed, purified and characterized Rh1-2, including investigation of the stability of the biologically active intermediate. Using fluorescence spectroscopy, we found the half-life of the rate of retinal release of Rh1-2 following photoactivation to be more similar to that of the visual pigment rhodopsin than to the non-visual pigment exo-rhodopsin (exorh), which releases retinal around 5 times faster. Phylogenetic and molecular evolutionary analyses show that rh1-2 has ancient origins within teleost fishes, is under similar selective pressure to rh1, and likely experienced a burst of positive selection following its duplication and divergence from rh1 These findings indicate that rh1-2 is another functional visual rhodopsin gene, which contradicts the prevailing notion that visual rhodopsin is primarily found as a single copy gene within ray-finned fishes. The reasons for retention of this duplicate gene, as well as possible functional consequences for the visual system, are discussed. © 2017. Published by The Company of Biologists Ltd.

Evidence for the Detection of Subclinical Retinal Involvement in Systemic Lupus Erythematosus and Sjögren Syndrome: A Potential Association with Therapies.

PubMed

Conigliaro, Paola; Triggianese, Paola; Draghessi, Gianluca; Canofari, Claudia; Aloe, Gianluca; Chimenti, Maria Sole; Valeri, Claudia; Nucci, Carlo; Perricone, Roberto; Cesareo, Massimo

2018-06-14

Retinal involvement in systemic lupus erythematosus (SLE) and Sjögren syndrome (SS) may be subclinical and thus underdiagnosed. We aimed at evaluating morphological and functional visual abnormalities in a cohort of SLE and SS patients in the absence of an overt clinical visual impairment. We also investigated potential associations between retinal disorders and disease activity, organ involvement, and treatment with steroid and/or hydroxychloroquine. The study comprised 42 SLE and 36 primary SS patients and 76 healthy controls (HC). Ophthalmological examination, standard automated perimetry, spectral-domain optical coherence tomography, and fundus perimetry were performed. Retinal thickness of the posterior pole was not different between SLE and HC groups, but it was reduced in the SS group compared with both the HC and the SLE group. In SLE and SS patients, mean defect and pattern standard deviation by standard automated perimetry were higher than in HC. Visual field index values were lower in both SLE and SS patients than in HC. SLE patients with nephritis displayed increased mean defect and pattern standard deviation and reduced visual field index values compared to patients without nephritis. In SLE and SS patients, fundus perimetry differential sensitivity was reduced, and mean defect values were higher than in HC. Disturbances in fundus perimetry in the SLE group were more prevalent in steroid-naïve patients and in SS patients who received a cumulative hydroxychloroquine dose > 1,000 g. Functional eye impairment was demonstrated in SLE patients, possibly associated with kidney involvement. In SLE, corticosteroids might exert a protective role. Morphological alterations and functional impairment were detected in SS patients, which may be linked to hydroxychloroquine toxicity. © 2018 S. Karger AG, Basel.

Structure and function of embryonic rat retinal sheet transplants.

PubMed

Peng, Qing; Thomas, Biju B; Aramant, Robert B; Chen, Zhenhai; Sadda, Srinivas R; Seiler, Magdalene J

2007-09-01

To evaluate retinal sheet transplants in S334ter-line-3 retinal degenerate rats by comparing visual responses recorded electrophysiologically with morphology based on light and electron microscopy. S334ter-line-3 retinal degenerate rats (n = 7) received retinal sheet transplants between postnatal days 28 and 31. The donor tissue was derived from transgenic embryonic day 19 (E19) rat retinae expressing human placental alkaline phosphatase (hPAP). Fresh retinal sheets were gently transplanted into the subretinal space of the left eye with the help of a custom-made implantation tool. Selected rats (n = 5) were subjected to electrophysiologic evaluation of visual responses from the superior colliculus about 84-121 days after surgery. Transplanted eyes were processed for light microscopy (LM) and electron microscopy (EM) evaluations. All the transplanted rats that were evaluated for visual responses in the brain showed responses to very low light stimulation (-3.42 to -2.8 log cd/m(2)) of the eye in a small area of the superior colliculus corresponding with the placement of the transplant in the host retina. Histologic evaluation showed that most of the transplants contained well-laminated areas with correct polarity in the subretinal space. Inside the transplant areas, rosettes of photoreceptors with inner and outer segments were found. In the laminated areas, the outer segments of photoreceptors were facing the host retinal pigment epithelium (RPE). Immunohistochemical evaluation of hPAP donor cells revealed areas with specific staining of the transplants in the subretinal space. Electron microscopic evaluation showed a glial demarcation membrane between the host and the transplant, however, processes originating from the transplant were observed inside the host retina. Sheets of E19 rat retina transplanted into the subretinal space of S334ter-line-3 rats survived without immune rejection and continued to show visual function when tested after 3 months. Well-developed photoreceptors and many synapse types were seen within the transplants. hPAP staining showed a certain degree of integration between the host retina and the transplant suggesting that transplanted photoreceptors contributed to the restored light sensitivity.

Therapeutic Potential of Co-enzyme Q10 in Retinal Diseases.

PubMed

Zhang, Xun; Tohari, Ali Mohammad; Marcheggiani, Fabio; Zhou, Xinzhi; Reilly, James; Tiano, Luca; Shu, Xinhua

2017-01-01

Coenzyme Q10 (CoQ10) plays a critical role in mitochondrial oxidative phosphorylation by serving as an electron carrier in the respiratory electron transport chain. CoQ10 also functions as a lipid-soluble antioxidant by protecting lipids, proteins and DNA damaged by oxidative stress. CoQ10 deficiency has been associated with a number of human diseases in which CoQ10 supplementation therapy has been effective in slowing or reversing pathological changes. Oxidative stress is a major contributory factor in the process of retinal degeneration. The related literature was reviewed through searching PubMed using keywords: CoQ10, CoQ10 and oxidative stress, CoQ10 and retinal degeneration. The functions of CoQ10 were summarized and its use in the treatment of age-related macular degeneration and glaucoma highlighted. The therapeutic potential of CoQ10 for other retinal diseases was also discussed. CoQ10 has been applied in different types of neurodegeneration. CoQ10 is detectable in retina and declines with ageing. Early studies showed treatment of CoQ10 improved visual function in patients with age-related macular degeneration. In glaucomatous models, CoQ10 exposure protected ganglion cell death from environmental stress; in glaucoma patients, CoQ10 treatment demonstrated beneficial effects on function of inner retina and enhancement of visual cortical response. Since oxidative stress also plays a critical role in the pathogenesis of diabetic retinopathy and retinitis pigmentosa, CoQ10 is a therapeutic target for both conditions. A wide range of evidence supports a role of CoQ10 in retinal diseases through inhibiting production of reactive oxygen species and protecting neuroretinal cells from oxidative damage. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

RNCR3 knockdown inhibits diabetes mellitus-induced retinal reactive gliosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Chang; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing

Retinal reactive gliosis is an important pathological feature of diabetic retinopathy. Identifying the underlying mechanisms causing reactive gliosis will be important for developing new therapeutic strategies for treating diabetic retinopathy. Herein, we show that long noncoding RNA-RNCR3 knockdown significantly inhibits retinal reactive gliosis. RNCR3 knockdown leads to a marked reduction in the release of several cytokines. RNCR3 knockdown alleviates diabetes mellitus-induced retinal neurodegeneration, as shown by less apoptotic retinal cells and ameliorative visual function. RNCR3 knockdown could also decrease Müller glial cell viability and proliferation, and reduce the expression of glial reactivity-related genes including GFAP and vimentin in vitro. Collectively, thismore » study shows that RNCR3 knockdown may be a promising strategy for the prevention of diabetes mellitus-induced retinal neurodegeneration. - Highlights: • RNCR3 knockdown inhibits retinal reactive gliosis. • RNCR3 knockdown causes a significant change in cytokine profile. • RNCR3 knockdown alleviates diabetes mellitus-induced retinal neurodegeneration. • RNCR3 knockdown affects Müller glial cell function in vitro.« less

Analysis of the chicken retina with an adaptive optics multiphoton microscope.

PubMed

Bueno, Juan M; Giakoumaki, Anastasia; Gualda, Emilio J; Schaeffel, Frank; Artal, Pablo

2011-06-01

The structure and organization of the chicken retina has been investigated with an adaptive optics multiphoton imaging microscope in a backward configuration. Non-stained flat-mounted retinal tissues were imaged at different depths, from the retinal nerve fiber layer to the outer segment, by detecting the intrinsic nonlinear fluorescent signal. From the stacks of images corresponding to the different retinal layers, volume renderings of the entire retina were reconstructed. The density of photoreceptors and ganglion cells layer were directly estimated from the images as a function of the retinal eccentricity. The maximum anatomical resolving power at different retinal eccentricities was also calculated. This technique could be used for a better characterization of retinal alterations during myopia development, and may be useful for visualization of retinal pathologies and intoxication during pharmacological studies.

Retinal ganglion cells in diabetes

PubMed Central

Kern, Timothy S; Barber, Alistair J

2008-01-01

Diabetic retinopathy has long been recognized as a vascular disease that develops in most patients, and it was believed that the visual dysfunction that develops in some diabetics was due to the vascular lesions used to characterize the disease. It is becoming increasingly clear that neuronal cells of the retina also are affected by diabetes, resulting in dysfunction and even degeneration of some neuronal cells. Retinal ganglion cells (RGCs) are the best studied of the retinal neurons with respect to the effect of diabetes. Although investigations are providing new information about RGCs in diabetes, including therapies to inhibit the neurodegeneration, critical information about the function, anatomy and response properties of these cells is yet needed to understand the relationship between RGC changes and visual dysfunction in diabetes. PMID:18565995

Restoration of visual function by expression of a light-gated mammalian ion channel in retinal ganglion cells or ON-bipolar cells

PubMed Central

Gaub, Benjamin M.; Berry, Michael H.; Holt, Amy E.; Reiner, Andreas; Kienzler, Michael A.; Dolgova, Natalia; Nikonov, Sergei; Aguirre, Gustavo D.; Beltran, William A.; Flannery, John G.; Isacoff, Ehud Y.

2014-01-01

Most inherited forms of blindness are caused by mutations that lead to photoreceptor cell death but spare second- and third-order retinal neurons. Expression of the light-gated excitatory mammalian ion channel light-gated ionotropic glutamate receptor (LiGluR) in retinal ganglion cells (RGCs) of the retina degeneration (rd1) mouse model of blindness was previously shown to restore some visual functions when stimulated by UV light. Here, we report restored retinal function in visible light in rodent and canine models of blindness through the use of a second-generation photoswitch for LiGluR, maleimide-azobenzene-glutamate 0 with peak efficiency at 460 nm (MAG0460). In the blind rd1 mouse, multielectrode array recordings of retinal explants revealed robust and uniform light-evoked firing when LiGluR-MAG0460 was targeted to RGCs and robust but diverse activity patterns in RGCs when LiGluR-MAG0460 was targeted to ON-bipolar cells (ON-BCs). LiGluR-MAG0460 in either RGCs or ON-BCs of the rd1 mouse reinstated innate light-avoidance behavior and enabled mice to distinguish between different temporal patterns of light in an associative learning task. In the rod-cone dystrophy dog model of blindness, LiGluR-MAG0460 in RGCs restored robust light responses to retinal explants and intravitreal delivery of LiGluR and MAG0460 was well tolerated in vivo. The results in both large and small animal models of photoreceptor degeneration provide a path to clinical translation. PMID:25489083

Probing how initial retinal configuration controls photochemical dynamics in retinal proteins

NASA Astrophysics Data System (ADS)

Wand, A.; Rozin, R.; Eliash, T.; Friedman, N.; Jung, K. H.; Sheves, M.; Ruhman, S.

2013-03-01

The effects of the initial retinal configuration and the active isomerization coordinate on the photochemistry of retinal proteins (RPs) are assessed by comparing photochemical dynamics of two stable retinal ground state configurations (all-trans,15-anti vs. 13-cis,15-syn), within two RPs: Bacteriorhodopsin (BR) and Anabaena Sensory Rhodopsin (ASR). Hyperspectral pump-probe spectroscopy shows that photochemistry starting from 13-cis retinal in both proteins is 3-10 times faster than when started in the all-trans state, suggesting that the hastening is ubiquitous to microbial RPs, regardless of their different biological functions and origin. This may also relate to the known disparity of photochemical rates between microbial RPs and visual pigments. Importance and possible underlying mechanisms are discussed as well.

COMPARISON OF VISUAL PROGNOSIS AND CLINICAL FEATURES OF CYTOMEGALOVIRUS RETINITIS IN HIV AND NON-HIV PATIENTS.

PubMed

Kim, Dong Yoon; Jo, Jaehyuck; Joe, Soo Geun; Kim, June-Gone; Yoon, Young Hee; Lee, Joo Yong

2017-02-01

To compare the visual prognosis and clinical features of cytomegalovirus (CMV) retinitis between HIV and non-HIV patients. Retrospective cross-sectional study on patients diagnosed with CMV retinitis. Depending on the presence of HIV infection, best-corrected visual acuity (VA) and clinical feature of CMV retinitis were analyzed. The clinical characteristics associated with poor visual prognosis after antiviral treatment were also identified. A total of 78 eyes (58 patients) with CMV retinitis were included in this study: 21 eyes and 57 eyes in HIV and non-HIV patients, respectively. Best-corrected VA was not significantly different between HIV and non-HIV patients. The rate of foveal involvement, retinal detachment, involved zone, and mortality did not significantly differ between the two groups. Visual acuity after antiviral treatment was significantly worse (pretreatment logarithm of the minimal angle of resolution best-corrected VA, 0.54 ± 0.67 [Snellen VA, 20/63]; posttreatment logarithm of the minimal angle of resolution best-corrected VA, 0.77 ± 0.94 [Snellen VA, 20/125]; P = 0.014). Poor visual prognosis was significantly associated with Zone 1 involvement, retinal detachment, and a poor general condition. The overall visual prognosis and the clinical features of CMV retinitis do not differ between HIV and non-HIV patients. The visual prognosis of CMV retinitis still remains quite poor despite advancements in antiviral treatment. This poor prognosis after antiviral treatment is associated with retinal detachment during follow-up, Zone 1 involvement, and the poor general condition of the patient.

Retinal detachment and retinal holes in retinitis pigmentosa sine pigmento.

PubMed

Csaky, K; Olk, R J; Mahl, C F; Bloom, S M

1991-01-01

Retinal detachment and retinal holes in two family members with retinitis pigmentosa sine pigmento are reported. We believe these are the first such cases reported in the literature. We describe the presenting symptoms and management, including cryotherapy, scleral buckling procedure, and sulfur hexafluoride injection (SF6), resulting in stable visual acuity in one case and retinal reattachment and improved visual acuity in the other case.

Methane rescues retinal ganglion cells and limits retinal mitochondrial dysfunction following optic nerve crush.

PubMed

Wang, Ruobing; Sun, Qinglei; Xia, Fangzhou; Chen, Zeli; Wu, Jiangchun; Zhang, Yuelu; Xu, Jiajun; Liu, Lin

2017-06-01

Secondary degeneration is a common event in traumatic central nervous system disorders, which involves neuronal apoptosis and mitochondrial dysfunction. Exogenous methane exerts the therapeutic effects in many organ injury. Our study aims to investigate the potential neuroprotection of methane in a rat model of optic nerve crush (ONC). Adult male Sprague-Dawley rats were subjected to ONC and administrated intraperitoneally with methane-saturated or normal saline (10 ml/kg) once per day for one week after ONC. The retinal ganglion cells (RGCs) density was assessed by hematoxylin and eosin staining and Fluoro-Gold retrogradely labeling. Visual function was evaluated by flash visual evoked potentials (FVEP). The retinal apoptosis was measured by terminal-deoxy-transferase-mediated dUTP nick end labeling (TUNEL) assay and the expression of apoptosis-related factors, such as phosphorylated Bcl-2-associated death promoter (pBAD), phosphorylated glycogen synthase kinase-3β (pGSK-3β), Bcl-2 associated X protein (Bax) and Bcl-2 extra large (Bcl-xL). Retinal mitochondrial function was assessed by the mRNA expressions of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM), the mitochondrial DNA (mtDNA) copy number, citrate synthase activity and ATP content. Methane treatment significantly improved the RGC loss and visual dysfunction following ONC. As expected, methane also remarkably inhibited the retinal neural apoptosis, such as the fewer TUNEL-positive cells in ganglion cell layer, accompanied by the up-regulations of anti-apoptotic factors (pGSK-3β, pBAD, Bcl-xL) and the down-regulation of pro-apoptotic factor (Bax). Furthermore, methane treatment suppressed up-regulations of critical mitochondrial components (PGC-1α, NRF1 and TFAM) mRNA and mtDNA copy number, as well as improved the reduction of functional mitochondria markers, including citrate synthase activity and ATP content, in retinas with ONC. Taken together, methane treatment promotes RGC survival and limits retinal mitochondrial dysfunction against ONC insult. Methane can be a potential neuroprotective agent for traumatic and glaucomatous neurodegeneration. Copyright © 2017. Published by Elsevier Ltd.

The Self-Concept of Spanish Young Adults with Retinitis Pigmentosa

ERIC Educational Resources Information Center

Lopez-Justicia, Maria Dolores; Cordoba, Inmaculada Nieto

2006-01-01

Retinitis pigmentosa (RP) is a degenerative disease of the retina that causes the severe impairment of visual functioning similar to low vision, leading, in many cases, to blindness. Because the construct of self-concept plays a key role in personality, this study was designed to measure self-concept in a group of young adults with RP. The…

Structural, functional and blood perfusion changes in the rat retina associated with elevated intraocular pressure, measured simultaneously with a combined OCT+ERG system

PubMed Central

Tan, Bingyao; MacLellan, Benjamin; Mason, Erik

2018-01-01

Acute elevation of intraocular pressure (IOP) to ischemic and non-ischemic levels can cause temporary or permanent changes in the retinal morphology, function and blood flow/blood perfusion. Previously, such changes in the retina were assessed separately with different methods in clinical studies and animal models. In this study, we used a combined OCT+ ERG system in combination with Doppler OCT and OCT angiography (OCTA) imaging protocols, in order to evaluate simultaneously and correlate changes in the retinal morphology, the retinal functional response to visual stimulation, and the retinal blood flow/blood perfusion, associated with IOP elevation to ischemic and non-ischemic levels in rats. Results from this study suggest that the inner retina responds faster to IOP elevation to levels greater than 30 mmHg with significant reduction of the total retinal blood flow (TRBF), decrease of the capillaries’ perfusion and reduction of the ON bipolar cells contribution to the ERG traces. Furthermore, this study showed that ischemic levels of IOP elevation cause an additional significant decrease in the ERG photoreceptor response in the posterior retina. Thirty minutes after IOP normalization, retinal morphology, blood flow and blood perfusion recovered to baseline values, while retinal function did not recover completely. PMID:29509807

Relating retinal nerve fiber thickness to behavioral sensitivity in patients with glaucoma: application of a linear model.

PubMed

Hood, Donald C

2007-05-01

Glaucoma causes damage to the retinal ganglion cells and their axons, and this damage can be detected with both structural and functional tests. The purpose of this study was to better understand the relationship between a structural measure of retinal nerve fiber layer (RNFL) and the most common functional test, behavioral sensitivity with static automated perimetry (SAP). First, a linear model, previously shown to describe the relationship between local visual evoked potentials and SAP sensitivity, was modified to predict the change in RNFL as measured by optical coherence tomography. Second, previous work by others was shown to be consistent with this model.

Network and Atomistic Simulations Unveil the Structural Determinants of Mutations Linked to Retinal Diseases

PubMed Central

Mariani, Simona; Dell'Orco, Daniele; Felline, Angelo; Raimondi, Francesco; Fanelli, Francesca

2013-01-01

A number of incurable retinal diseases causing vision impairments derive from alterations in visual phototransduction. Unraveling the structural determinants of even monogenic retinal diseases would require network-centered approaches combined with atomistic simulations. The transducin G38D mutant associated with the Nougaret Congenital Night Blindness (NCNB) was thoroughly investigated by both mathematical modeling of visual phototransduction and atomistic simulations on the major targets of the mutational effect. Mathematical modeling, in line with electrophysiological recordings, indicates reduction of phosphodiesterase 6 (PDE) recognition and activation as the main determinants of the pathological phenotype. Sub-microsecond molecular dynamics (MD) simulations coupled with Functional Mode Analysis improve the resolution of information, showing that such impairment is likely due to disruption of the PDEγ binding cavity in transducin. Protein Structure Network analyses additionally suggest that the observed slight reduction of theRGS9-catalyzed GTPase activity of transducin depends on perturbed communication between RGS9 and GTP binding site. These findings provide insights into the structural fundamentals of abnormal functioning of visual phototransduction caused by a missense mutation in one component of the signaling network. This combination of network-centered modeling with atomistic simulations represents a paradigm for future studies aimed at thoroughly deciphering the structural determinants of genetic retinal diseases. Analogous approaches are suitable to unveil the mechanism of information transfer in any signaling network either in physiological or pathological conditions. PMID:24009494

Tractional retinal detachment in Usher syndrome type II.

PubMed

Rani, Alka; Pal, Nikhil; Azad, Raj Vardhan; Sharma, Yog Raj; Chandra, Parijat; Vikram Singh, Deependra

2005-08-01

Retinal detachment is a rare complication in patients with retinitis pigmentosa. A case is reported of tractional retinal detachment in a patient with retinitis pigmentosa and sensorineural hearing loss, which was diagnosed as Usher syndrome type II. Because of the poor visual prognosis, the patient refused surgery in that eye. Tractional retinal detachment should be added to the differential diagnoses of visual loss in patients with retinitis pigmentosa.

Possible sources of neuroprotection following subretinal silicon chip implantation in RCS rats

NASA Astrophysics Data System (ADS)

Pardue, Machelle T.; Phillips, Michael J.; Yin, Hang; Fernandes, Alcides; Cheng, Yian; Chow, Alan Y.; Ball, Sherry L.

2005-03-01

Current retinal prosthetics are designed to stimulate existing neural circuits in diseased retinas to create a visual signal. However, implantation of retinal prosthetics may create a neurotrophic environment that also leads to improvements in visual function. Possible sources of increased neuroprotective effects on the retina may arise from electrical activity generated by the prosthetic, mechanical injury due to surgical implantation, and/or presence of a chronic foreign body. This study evaluates these three neuroprotective sources by implanting Royal College of Surgeons (RCS) rats, a model of retinitis pigmentosa, with a subretinal implant at an early stage of photoreceptor degeneration. Treatment groups included rats implanted with active and inactive devices, as well as sham-operated. These groups were compared to unoperated controls. Evaluation of retinal function throughout an 18 week post-implantation period demonstrated transient functional improvements in eyes implanted with an inactive device at 6, 12 and 14 weeks post-implantation. However, the number of photoreceptors located directly over or around the implant or sham incision was significantly increased in eyes implanted with an active or inactive device or sham-operated. These results indicate that in the RCS rat localized neuroprotection of photoreceptors from mechanical injury or a chronic foreign body may provide similar results to subretinal electrical stimulation at the current output evaluated here.

Factors associated with visual acuity in patients with cystoid macular oedema and Retinitis Pigmentosa.

PubMed

Liew, Gerald; Moore, Anthony T; Bradley, Patrick D; Webster, Andrew R; Michaelides, Michel

2018-06-01

Retinitis pigmentosa is the most common inherited retinal dystrophy. The factors associated with visual acuity in patients with other retinal diseases are well known, but are poorly understood in patients with retinitis pigmentosa. This knowledge is useful for prognosis and to support secondary endpoints in clinical trials. We conducted a cross-sectional study of consecutive patients recruited from the inherited retinal disease service from January 2012 to December 2012. Central macular thickness (CMT) was measured using spectral domain optical coherence tomography. Data were available for 81 patients and 162 eyes. After multivariable analyses, older age, earlier age of onset of symptoms, and thicker CMT were associated with lower visual acuity. Gender and inheritance pattern were not associated with visual acuity. Each decade older age, younger age of onset, and thicker CMT was associated with 0.12, 0.10, and 0.11 worse logarithm of the minimal angle of resolution units of visual acuity, respectively (p < 0.05 for all). Age, age of onset, and CMT are associated with visual acuity and important factors to measure in studies of retinitis pigmentosa.

Vision Function in HIV-infected Individuals without Retinitis; Report of the Studies of Ocular Complications of AIDS Research Group

PubMed Central

Freeman, William R.; Van Natta, Mark L.; Jabs, Douglas; Sample, Pamela A.; Sadun, Alfredo A.; Thorne, Jennifer; Shah, Kayur H.; Holland, Gary N.

2008-01-01

Purpose To evaluate the prevalence and risk factors for vision loss in patients with clinical or immunologic AIDS without infectious retinitis. Design A prospective multicentered cohort study of patients with AIDS. Methods 1,351 patients (2,671 eyes) at 19 clinical trials centers diagnosed with AIDS but without major ocular complications of HIV. Standardized measurements of visual acuity, automated perimetry, and contrast sensitivity were analyzed and correlated with measurements of patients’ health and medical data relating to HIV infection. We evaluated correlations between vision function testing and HIV-related risk factors and medical testing. Results There were significant (p<0.05) associations between measures of decreasing vision function and indices of increasing disease severity including Karnofsky score and hemoglobin. A significant relationship was seen between low contrast sensitivity and decreasing levels of CD4+ T-cell count. Three percent of eyes had a visual acuity worse than 20/40 Snellen equivalents, which was significantly associated with a history of opportunistic infections and low Karnofsky score. When compared to external groups with normal vision, 39% of eyes had abnormal mean deviation on automated perimetry, 33% had abnormal pattern standard deviation, and 12% of eyes had low contrast sensitivity. Conclusions This study confirms that visual dysfunction is common in patients with AIDS but without retinitis. The most prevalent visual dysfunction is loss of visual field; nearly 40% of patients have some abnormal visual field. There is an association between general disease severity and less access to care and vision loss. The pathophysiology of this vision loss is unknown but is consistent with retinovascular disease or optic nerve disease. PMID:18191094

Relationship between Scanning Laser Polarimetry with Enhanced Corneal Compensation and with Variable Corneal Compensation

PubMed Central

Kim, Kyung Hoon; Choi, Jaewan; Lee, Chang Hwan; Cho, Beom-Jin; Kook, Michael S.

2008-01-01

Purpose To evaluate the structure-function relationships between retinal sensitivity measured by Humphrey visual field analyzer (HVFA) and the retinal nerve fiber layer (RNFL) thickness measured by scanning laser polarimetry (SLP) with variable corneal compensation (VCC) and enhanced corneal compensation (ECC) in glaucomatous and healthy eyes. Methods Fifty-three eyes with an atypical birefringence pattern (ABP) based on SLP-VCC (28 glaucomatous eyes and 25 normal healthy eyes) were enrolled in this cross-sectional study. RNFL thickness was measured by both VCC and ECC techniques, and the visual field was examined by HVFA with 24-2 full-threshold program. The relationships between RNFL measurements in superior and inferior sectors and corresponding retinal mean sensitivity were sought globally and regionally with linear regression analysis in each group. Coefficients of the determination were calculated and compared between VCC and ECC techniques. Results In eyes with ABP, R2 values for the association between SLP parameters and retinal sensitivity were 0.06-0.16 with VCC, whereas they were 0.21-0.48 with ECC. The association of RNFL thickness with retinal sensitivity was significantly better with ECC than with VCC in 5 out of 8 regression models between SLP parameters and HVF parameters (P<0.05). Conclusions The strength of the structure-function association was higher with ECC than with VCC in eyes with ABP, which suggests that the ECC algorithm is a better approach for evaluating the structure-function relationship in eyes with ABP. PMID:18323701

Photoreceptor Cells With Profound Structural Deficits Can Support Useful Vision in Mice

PubMed Central

Thompson, Stewart; Blodi, Frederick R.; Lee, Swan; Welder, Chris R.; Mullins, Robert F.; Tucker, Budd A.; Stasheff, Steven F.; Stone, Edwin M.

2014-01-01

Purpose. In animal models of degenerative photoreceptor disease, there has been some success in restoring photoreception by transplanting stem cell–derived photoreceptor cells into the subretinal space. However, only a small proportion of transplanted cells develop extended outer segments, considered critical for photoreceptor cell function. The purpose of this study was to determine whether photoreceptor cells that lack a fully formed outer segment could usefully contribute to vision. Methods. Retinal and visual function was tested in wild-type and Rds mice at 90 days of age (RdsP90). Photoreceptor cells of mice homozygous for the Rds mutation in peripherin 2 never develop a fully formed outer segment. The electroretinogram and multielectrode recording of retinal ganglion cells were used to test retinal responses to light. Three distinct visual behaviors were used to assess visual capabilities: the optokinetic tracking response, the discrimination-based visual water task, and a measure of the effect of vision on wheel running. Results. RdsP90 mice had reduced but measurable electroretinogram responses to light, and exhibited light-evoked responses in multiple types of retinal ganglion cells, the output neurons of the retina. In optokinetic and discrimination-based tests, acuity was measurable but reduced, most notably when contrast was decreased. The wheel running test showed that RdsP90 mice needed 3 log units brighter luminance than wild type to support useful vision (10 cd/m2). Conclusions. Photoreceptors that lack fully formed outer segments can support useful vision. This challenges the idea that normal cellular structure needs to be completely reproduced for transplanted cells to contribute to useful vision. PMID:24569582

Intravitreal triamcinolone acetonide injections in the treatment of retinal vein occlusions.

PubMed

Roth, Daniel B; Cukras, Catherine; Radhakrishnan, Ravi; Feuer, William J; Yarian, David L; Green, Stuart N; Wheatley, Harold M; Prenner, Jonathan

2008-01-01

To report the visual acuity response after intravitreal triamcinolone injection in patients with macular edema due to retinal vein occlusions. Retrospective nonrandomized interventional series of 172 consecutive patients with macular edema due to retinal vein occlusions who were treated with intravitreal triamcinolone acetonide injection. Patients underwent Snellen visual acuity testing and ophthalmoscopic examination at baseline and 1, 3, 6, and 12 months after intravitreal triamcinolone acetonide injection. All subtypes of retinal vein occlusions showed significant improvements in mean visual acuity 1 month after injection. This improvement in visual acuity was maintained over the 12-month period for all but the central retinal vein occlusion group. Seventy-one (41.3%) of the 172 patients received more than one intravitreal triamcinolone injection for unresolved or recurrent macular edema. This study demonstrates a benefit associated with intravitreal triamcinolone acetonide injection for retinal vein occlusions that was maintained by patients with branch retinal vein occlusions and hemiretinal vein occlusions over a 12-month period. Visual acuity improvement was not maintained in patients with central retinal vein occlusions with this course of treatment.

Causal evidence for retina dependent and independent visual motion computations in mouse cortex

PubMed Central

Hillier, Daniel; Fiscella, Michele; Drinnenberg, Antonia; Trenholm, Stuart; Rompani, Santiago B.; Raics, Zoltan; Katona, Gergely; Juettner, Josephine; Hierlemann, Andreas; Rozsa, Balazs; Roska, Botond

2017-01-01

How neuronal computations in the sensory periphery contribute to computations in the cortex is not well understood. We examined this question in the context of visual-motion processing in the retina and primary visual cortex (V1) of mice. We disrupted retinal direction selectivity – either exclusively along the horizontal axis using FRMD7 mutants or along all directions by ablating starburst amacrine cells – and monitored neuronal activity in layer 2/3 of V1 during stimulation with visual motion. In control mice, we found an overrepresentation of cortical cells preferring posterior visual motion, the dominant motion direction an animal experiences when it moves forward. In mice with disrupted retinal direction selectivity, the overrepresentation of posterior-motion-preferring cortical cells disappeared, and their response at higher stimulus speeds was reduced. This work reveals the existence of two functionally distinct, sensory-periphery-dependent and -independent computations of visual motion in the cortex. PMID:28530661

[Methods for estimating personal costs of disease using retinal diseases as an example].

PubMed

Porz, G; Scholl, H P N; Holz, F G; Finger, R P

2010-03-01

Age-related macular degeneration (AMD) and other retinal diseases, such as diabetic retinopathy (DRP) and hereditary retinal dystrophy can not only lead to a loss of visual function but also to a higher psychological and financial burden for the affected persons. Against this background a quantification of personal cost and vision-related quality of life was performed. A total of 66 patients (mean age 69 years, SD 13 years) with clinically confirmed diagnoses of AMD, DRP or retinal dystrophy were interviewed regarding costs for medicines, aids and equipment, support in everyday life and social benefits. Vision-related quality of life was recorded using the Impact of Vision Impairment profile (IVI). The average total annual cost was 751 per patient, out of which the largest amount was cost of support in everyday life (506). Costs as well as dependence on other persons or social services increased with decreasing visual acuity (p=0.013). Vision-related quality of life decreased with increasing visual disability especially in the IVI subscales mobility and independence as well as reading and accessing information (p=0.002). Prevention or delay of visual disability and blindness caused by AMD or other retinal diseases and thus ensuring independence is not only relevant from a medical perspective but also from a health economic perspective. Against the background of a relative shortage of resources, costs should be reduced regardless of whether they are personal or societal costs.

Analysis of the chicken retina with an adaptive optics multiphoton microscope

PubMed Central

Bueno, Juan M.; Giakoumaki, Anastasia; Gualda, Emilio J.; Schaeffel, Frank; Artal, Pablo

2011-01-01

The structure and organization of the chicken retina has been investigated with an adaptive optics multiphoton imaging microscope in a backward configuration. Non-stained flat-mounted retinal tissues were imaged at different depths, from the retinal nerve fiber layer to the outer segment, by detecting the intrinsic nonlinear fluorescent signal. From the stacks of images corresponding to the different retinal layers, volume renderings of the entire retina were reconstructed. The density of photoreceptors and ganglion cells layer were directly estimated from the images as a function of the retinal eccentricity. The maximum anatomical resolving power at different retinal eccentricities was also calculated. This technique could be used for a better characterization of retinal alterations during myopia development, and may be useful for visualization of retinal pathologies and intoxication during pharmacological studies. PMID:21698025

Protective effect of basic fibroblast growth factor on retinal injury induced by argon laser photocoagulation

NASA Astrophysics Data System (ADS)

Chen, P.; Zhang, C. P.; San, Q.; Wang, C. Z.; Yang, Z. F.; Kang, H. X.; Qian, H. W.

2010-12-01

Laser photocoagulation treatment is often complicated by a side effect of visual impairment, which is caused by the unavoidable laser-induced retinal destruction. At present no specific is found to cure this retinopathy. The aim of this study was to observe the neuroprotective effect of bFGF on laser-induced retinal injury. Chinchilla rabbits were divided into three groups and argon laser lesions were created in the retinas. Then bFGF or dexamethasone, a widely used ophthalmic preparation, or saline was given severally by retrobulbar injection. The retinal lesions were evaluated histologically and morphometrically, and visual function was examined by ERG. The results showed that bFGF administration better preserved morphology of retinal photoreceptors and significantly diminished the area of the lesions. Furthermore, bFGF promoted the restoration of the ERG b-wave amplitude. In rabbits treated with dexamethasone, however, the lesions showed almost no ameliorative changes. This is the first study to investigate the potential role of bFGF as a remedial agent in laser photocoagulation treatment. These findings suggest that bFGF has significant neuroprotective properties in the retina and this type of neuroprotection may be of clinical significance in reducing iatrogenic laser-induced retinal injuries in humans.

Retrospective, controlled observational case study of patients with central retinal vein occlusion and initially low visual acuity treated with an intravitreal dexamethasone implant.

PubMed

Winterhalter, Sibylle; Vom Brocke, Gerrit Alexander; Pilger, Daniel; Eckert, Annabelle; Schlomberg, Juliane; Rübsam, Anne; Klamann, Matthias Karl; Gundlach, Enken; Dietrich-Ntoukas, Tina; Joussen, Antonia Maria

2016-10-27

Patients with initially low visual acuity were excluded from the therapy approval studies for retinal vein occlusion. But up to 28 % of patients presenting with central retinal vein occlusion have a baseline BCVA of less than 34 ETDRS letters (0.1). The purpose of our study was to assess visual acuity and central retinal thickness in patients suffering from central retinal vein occlusion and low visual acuity (<0.1) in comparison to patients with visual acuity (≥0.1) treated with Dexamethasone implant 0.7 mg for macular edema. Retrospective, controlled observational case study of 30 eyes with macular edema secondary to central retinal vein occlusion, which were treated with a dexamethasone implantation. Visual acuity, central retinal thickness and intraocular pressure were measured monthly. Analyses were performed separately for eyes with visual acuity <0.1 and ≥0.1. Two months post intervention, visual acuity improved only marginally from 0.05 to 0.07 (1 month; p = 0,065) and to 0.08 (2 months; p = 0,2) in patients with low visual acuity as compared to patients with visual acuity ≥0.1 with an improvement from 0.33 to 0.47 (1 month; p = 0,005) and to 0.49 (2 months; p = 0,003). The central retinal thickness, however, was reduced in both groups, falling from 694 to 344 μm (1 month; p = 0.003,) to 361 μm (2 months; p = 0,002) and to 415 μm (3 months; p = 0,004) in the low visual acuity group and from 634 to 315 μm (1 month; p < 0,001) and to 343 μm (2 months; p = 0,001) in the visual acuity group ≥0.1. Absence of visual acuity improvement was related to macular ischemia. In patients with central retinal vein occlusion and initially low visual acuity, a dexamethasone implantation can lead to an important reduction of central retinal thickness but may be of limited use to increase visual acuity.

Clinical Features of Pregnancy-associated Retinal and Choroidal Diseases Causing Acute Visual Disturbance.

PubMed

Park, Young Joo; Park, Kyu Hyung; Woo, Se Joon

2017-08-01

To report clinical features of patients with retinal and choroidal diseases presenting with acute visual disturbance during pregnancy. In this retrospective case series, patients who developed acute visual loss during pregnancy (including puerperium) and visited a tertiary hospital from July 2007 to June 2015, were recruited by searching electronic medical records. Patients were categorized according to the cause of visual loss. Clinical features and required diagnostic modalities were analyzed in the retinal and choroidal disease group. Acute visual loss occurred in 147 patients; 49 (38.9%) were classified into the retinal and choroidal group. The diagnoses included central serous chorioretinopathy (22.4%), hypertensive retinopathy with or without pre-eclampsia (22.4%), retinal tear with or without retinal detachment (18.4%), diabetic retinopathy progression (10.2%), Vogt-Koyanagi-Harada disease (4.1%), retinal artery occlusion (4.1%), multiple evanescent white dot syndrome (4.1%), and others (14.3%). Visual symptoms first appeared at gestational age 25.9 ± 10.3 weeks. The initial best-corrected visual acuity (BCVA) was 0.27 ± 0.39 logarithm of the minimum angle of resolution (logMAR); the final BCVA after delivery improved to 0.13 ± 0.35 logMAR. Serious visual deterioration (BCVA worth than 20 / 200) developed in two patients. Differential diagnoses were established with characteristic fundus and spectral-domain optical coherence tomography findings in all cases. In pregnant women with acute visual loss, retinal and choroidal diseases are common and could be vision threatening. Physicians should be aware of pregnancy-associated retinal and choroidal diseases and their clinical features. The differential diagnosis can be established with non-invasive techniques. © 2017 The Korean Ophthalmological Society

Retinal adaptation abnormalities in primary open-angle glaucoma.

PubMed

Dul, Mitchell; Ennis, Robert; Radner, Shira; Lee, Barry; Zaidi, Qasim

2015-01-22

Dynamic color and brightness adaptation are crucial for visual functioning. The effects of glaucoma on retinal ganglion cells (RGCs) could compromise these functions. We have previously used slow dynamic changes of light at moderate intensities to measure the speed and magnitude of subtractive adaptation in RGCs. We used the same procedure to test if RGC abnormalities cause slower and weaker adaptation for patients with glaucoma when compared to age-similar controls. We assessed adaptation deficits in specific classes of RGCs by testing along the three cardinal color axes that isolate konio, parvo, and magno RGCs. For one eye each of 10 primary open-angle glaucoma patients and their age-similar controls, we measured the speed and magnitude of adapting to 1/32 Hz color modulations along the three cardinal axes, at central fixation and 8° superior, inferior, nasal, and temporal to fixation. In all 15 comparisons (5 locations × 3 color axes), average adaptation was slower and weaker for glaucoma patients than for controls. Adaptation developed slower at central targets than at 8° eccentricities for controls, but not for patients. Adaptation speed and magnitude differed between affected and control eyes even at retinal locations showing no visual field loss with clinical perimetry. Neural adaptation is weaker in glaucoma patients for all three classes of RGCs. Since adaptation abnormalities are manifested even at retinal locations not exhibiting a visual field loss, this novel form of assessment may offer a functional insight into glaucoma and an early diagnosis tool. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

[Visual acuity in anti-VEGF therapy for AMD : Can specific characteristics in the SD-OCT help?

PubMed

Book, B; Ziegler, M; Heimes, B; Gutfleisch, M; Spital, G; Pauleikhoff, D; Lommatzsch, A

2017-01-01

The efficacy of anti-VEGF therapy in exudative AMD has been established in several large clinical trials using a fixed injection regimen as well as a SD-OCT-based PRN regimen. In these studies, after the first three injections, an increase of the mean visual acuity was observed, which could be stabilized with constant treatment for up to 24 months. However, the specific course of the visual acuity is very different between individuals. The aim of the present study was to correlate specific initial SD-OCT parameters with the course of visual acuity in order to characterize factors that may be important for the individual visual prognosis. In a prospective case study, the visual course and SD-OCT changes of 156 patients with minimum follow-up of 12 months (mean 80.1 months) were analysed. Visual acuity (LogMar) was investigated at regular intervals and correlated with specific SD-OCT parameters (foveal thickness, height of sub-retinal fluid or presence of associated PED, presence of intra-retinal cysts, length of IS/OS break, choroidal thickness). The initial increase in visual acuity could be stabilized over time. This effect was associated with a decrease in foveal retinal thickness, which also persisted over time. While sub-retinal fluid, presence of PED, and choroidal thickness showed no prognostic relevance for the change in visual acuity, the presence of more advanced central retinal thickness, of intra-retinal cysts or a longer break in the IS/OS junction were associated with a less favourable development of visual acuity. In the present study, the presence of more advanced central retinal thickness, of intra-retinal cysts or a larger IS/OS break correlated significantly with a worse visual prognosis. These might be clinical signs for more extensive pre-existing intra-retinal changes. Further analysis and new diagnostic tools may prove this and may result in specific additive neuroprotective or regenerative therapeutic approaches in exudative AMD.

Luminescence- and nanoparticle-mediated increase of light absorption by photoreceptor cells: Converting UV light to visible light.

PubMed

Li, Lei; Sahi, Sunil K; Peng, Mingying; Lee, Eric B; Ma, Lun; Wojtowicz, Jennifer L; Malin, John H; Chen, Wei

2016-02-10

We developed new optic devices - singly-doped luminescence glasses and nanoparticle-coated lenses that convert UV light to visible light - for improvement of visual system functions. Tb(3+) or Eu(3+) singly-doped borate glasses or CdS-quantum dot (CdS-QD) coated lenses efficiently convert UV light to 542 nm or 613 nm wavelength narrow-band green or red light, or wide-spectrum white light, and thereby provide extra visible light to the eye. In zebrafish (wild-type larvae and adult control animals, retinal degeneration mutants, and light-induced photoreceptor cell degeneration models), the use of Tb(3+) or Eu(3+) doped luminescence glass or CdS-QD coated glass lenses provide additional visible light to the rod and cone photoreceptor cells, and thereby improve the visual system functions. The data provide proof-of-concept for the future development of optic devices for improvement of visual system functions in patients who suffer from photoreceptor cell degeneration or related retinal diseases.

Visual Prognosis in USH2A-Associated Retinitis Pigmentosa Is Worse for Patients with Usher Syndrome Type IIa Than for Those with Nonsyndromic Retinitis Pigmentosa.

PubMed

Pierrache, Laurence H M; Hartel, Bas P; van Wijk, Erwin; Meester-Smoor, Magda A; Cremers, Frans P M; de Baere, Elfride; de Zaeytijd, Julie; van Schooneveld, Mary J; Cremers, Cor W R J; Dagnelie, Gislin; Hoyng, Carel B; Bergen, Arthur A; Leroy, Bart P; Pennings, Ronald J E; van den Born, L Ingeborgh; Klaver, Caroline C W

2016-05-01

USH2A mutations are an important cause of retinitis pigmentosa (RP) with or without congenital sensorineural hearing impairment. We studied genotype-phenotype correlations and compared visual prognosis in Usher syndrome type IIa and nonsyndromic RP. Clinic-based, longitudinal, multicenter study. Consecutive patients with Usher syndrome type IIa (n = 152) and nonsyndromic RP (n = 73) resulting from USH2A mutations from ophthalmogenetic clinics in the Netherlands and Belgium. Data on clinical characteristics, visual acuity, visual field measurements, retinal imaging, and electrophysiologic features were extracted from medical charts over a mean follow-up of 9 years. Cumulative lifetime risks of low vision and blindness were estimated using Kaplan-Meier survival analysis. Low vision and blindness. Participant groups had similar distributions of gender (48% vs. 45% males in Usher syndrome type IIa vs. nonsydromic RP; P = 0.8), ethnicity (97% vs. 99% European; P = 0.3), and median follow-up time (6.5 years vs. 3 years; P = 0.3). Usher syndrome type IIa patients demonstrated symptoms at a younger age (median age, 15 years vs. 25 years; P < 0.001), were diagnosed earlier (median age, 26 years vs. 36.5 years; P < 0.001), and became visually impaired 13 years earlier (median age, 41 years vs. 54 years; P < 0.001) based on VF and 18 years earlier based on VA (median age, 54 years vs. 72 years; P < 0.001) than nonsyndromic RP patients. The presence of 2 truncating mutations in USH2A was associated mostly with the syndromic phenotype, whereas other combinations were present in both groups. We found novel variants in Usher syndrome type IIa (25%) and nonsyndromic RP (19%): 29 missense mutations, 10 indels, 14 nonsense mutations, 9 frameshift mutations, and 5 splice-site mutations. Most patients with USH2A-associated RP have severe visual impairment by age 50. However, those with Usher syndrome type IIa have an earlier decline of visual function and a higher cumulative risk of visual impairment than those without nonsyndromic RP. Complete loss of function of the USH2A protein predisposes to Usher syndrome type IIa, but remnant protein function can lead to RP with or without hearing loss. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Environmental Enrichment Extends Photoreceptor Survival and Visual Function in a Mouse Model of Retinitis Pigmentosa

PubMed Central

Barone, Ilaria; Novelli, Elena; Piano, Ilaria; Gargini, Claudia; Strettoi, Enrica

2012-01-01

Slow, progressive rod degeneration followed by cone death leading to blindness is the pathological signature of all forms of human retinitis pigmentosa (RP). Therapeutic schemes based on intraocular delivery of neuroprotective agents prolong the lifetime of photoreceptors and have reached the stage of clinical trial. The success of these approaches depends upon optimization of chronic supply and appropriate combination of factors. Environmental enrichment (EE), a novel neuroprotective strategy based on enhanced motor, sensory and social stimulation, has already been shown to exert beneficial effects in animal models of various disorders of the CNS, including Alzheimer and Huntington disease. Here we report the results of prolonged exposure of rd10 mice, a mutant strain undergoing progressive photoreceptor degeneration mimicking human RP, to such an enriched environment from birth. By means of microscopy of retinal tissue, electrophysiological recordings, visual behaviour assessment and molecular analysis, we show that EE considerably preserves retinal morphology and physiology as well as visual perception over time in rd10 mutant mice. We find that protective effects of EE are accompanied by increased expression of retinal mRNAs for CNTF and mTOR, both factors known as instrumental to photoreceptor survival. Compared to other rescue approaches used in similar animal models, EE is highly effective, minimally invasive and results into a long-lasting retinal protection. These results open novel perspectives of research pointing to environmental strategies as useful tools to extend photoreceptor survival. PMID:23209820

Effects of nicergoline on the retinal and cortical electrophysiological responses in glaucoma patients: a preliminary open study.

PubMed

Parisi, V; Colacino, G; Milazzo, G; Scuderi, A C; Manni, G

1999-09-01

The retinal dysfunction and the delayed visual cortex responses shown by patients affected by glaucoma can be objectively assessed by Pattern Electroretinogram (PERG) and Visual Evoked Potentials (VEP) recordings. The present study aims to evaluate the effects of nicergoline on the retinal function and on the visual cortical responses in glaucoma patients. Sixty patients (mean age 44.6+/-3.7) with open angle glaucoma were enrolled. The patients were divided into two groups: NG Group, where 30 patients were treated with nicergoline (Cebran((R)), 2 cps day) for 30 days; and CG Group, where 30 patients were not treated. Simultaneous recordings of PERG and VEP were performed in NG patients at the baseline, at 30 days after treatment with nicergoline (day 30), and at 45 days from the end of the treatment (day 75). PERG and VEP were recorded in CG patients at the baseline and after 30 and 75 days. The visual stimulus for recording PERGs and VEPs was a checkerboard whose elements subtended a visual arc of 60' and 15' with a 70% contrast, and alternated at a frequency of 2 Hz. At the baseline none of the electrophysiological parameters observed in NG Group patients differed (P>0.05) from those of CG Group patients. At days 30 and 75, in CG Group patients the values of the PERG and VEP parameters were unmodified (P>0.05) with respect to the baseline. In NG Group patients, the 30-day treatment period with nicergoline induced a significant (P<0.01) improvement of the PERG and VEP parameters. At day 75 all the electrophysiological parameters of NG Group did not differ significantly (P>0.05) from those at the baseline. Treatment with nicergoline induces an improvement of the retinal function and of the visual cortical responses in patients affected by glaucoma. This effect disappears within 45 days after the suspension of the treatment. Copyright 1999 Academic Press.

The human visual cortex responds to gene therapy–mediated recovery of retinal function

PubMed Central

Ashtari, Manzar; Cyckowski, Laura L.; Monroe, Justin F.; Marshall, Kathleen A.; Chung, Daniel C.; Auricchio, Alberto; Simonelli, Francesca; Leroy, Bart P.; Maguire, Albert M.; Shindler, Kenneth S.; Bennett, Jean

2011-01-01

Leber congenital amaurosis (LCA) is a rare degenerative eye disease, linked to mutations in at least 14 genes. A recent gene therapy trial in patients with LCA2, who have mutations in RPE65, demonstrated that subretinal injection of an adeno-associated virus (AAV) carrying the normal cDNA of that gene (AAV2-hRPE65v2) could markedly improve vision. However, it remains unclear how the visual cortex responds to recovery of retinal function after prolonged sensory deprivation. Here, 3 of the gene therapy trial subjects, treated at ages 8, 9, and 35 years, underwent functional MRI within 2 years of unilateral injection of AAV2-hRPE65v2. All subjects showed increased cortical activation in response to high- and medium-contrast stimuli after exposure to the treated compared with the untreated eye. Furthermore, we observed a correlation between the visual field maps and the distribution of cortical activations for the treated eyes. These data suggest that despite severe and long-term visual impairment, treated LCA2 patients have intact and responsive visual pathways. In addition, these data suggest that gene therapy resulted in not only sustained and improved visual ability, but also enhanced contrast sensitivity. PMID:21606598

MEMS-based system and image processing strategy for epiretinal prosthesis.

PubMed

Xia, Peng; Hu, Jie; Qi, Jin; Gu, Chaochen; Peng, Yinghong

2015-01-01

Retinal prostheses have the potential to restore some level of visual function to the patients suffering from retinal degeneration. In this paper, an epiretinal approach with active stimulation devices is presented. The MEMS-based processing system consists of an external micro-camera, an information processor, an implanted electrical stimulator and a microelectrode array. The image processing strategy combining image clustering and enhancement techniques was proposed and evaluated by psychophysical experiments. The results indicated that the image processing strategy improved the visual performance compared with direct merging pixels to low resolution. The image processing methods assist epiretinal prosthesis for vision restoration.

Retinal Structures and Visual Cortex Activity are Impaired Prior to Clinical Vision Loss in Glaucoma.

PubMed

Murphy, Matthew C; Conner, Ian P; Teng, Cindy Y; Lawrence, Jesse D; Safiullah, Zaid; Wang, Bo; Bilonick, Richard A; Kim, Seong-Gi; Wollstein, Gadi; Schuman, Joel S; Chan, Kevin C

2016-08-11

Glaucoma is the second leading cause of blindness worldwide and its pathogenesis remains unclear. In this study, we measured the structure, metabolism and function of the visual system by optical coherence tomography and multi-modal magnetic resonance imaging in healthy subjects and glaucoma patients with different degrees of vision loss. We found that inner retinal layer thinning, optic nerve cupping and reduced visual cortex activity occurred before patients showed visual field impairment. The primary visual cortex also exhibited more severe functional deficits than higher-order visual brain areas in glaucoma. Within the visual cortex, choline metabolism was perturbed along with increasing disease severity in the eye, optic radiation and visual field. In summary, this study showed evidence that glaucoma deterioration is already present in the eye and the brain before substantial vision loss can be detected clinically using current testing methods. In addition, cortical cholinergic abnormalities are involved during trans-neuronal degeneration and can be detected non-invasively in glaucoma. The current results can be of impact for identifying early glaucoma mechanisms, detecting and monitoring pathophysiological events and eye-brain-behavior relationships, and guiding vision preservation strategies in the visual system, which may help reduce the burden of this irreversible but preventable neurodegenerative disease.

Retinal Structures and Visual Cortex Activity are Impaired Prior to Clinical Vision Loss in Glaucoma

PubMed Central

Murphy, Matthew C.; Conner, Ian P.; Teng, Cindy Y.; Lawrence, Jesse D.; Safiullah, Zaid; Wang, Bo; Bilonick, Richard A.; Kim, Seong-Gi; Wollstein, Gadi; Schuman, Joel S.; Chan, Kevin C.

2016-01-01

Glaucoma is the second leading cause of blindness worldwide and its pathogenesis remains unclear. In this study, we measured the structure, metabolism and function of the visual system by optical coherence tomography and multi-modal magnetic resonance imaging in healthy subjects and glaucoma patients with different degrees of vision loss. We found that inner retinal layer thinning, optic nerve cupping and reduced visual cortex activity occurred before patients showed visual field impairment. The primary visual cortex also exhibited more severe functional deficits than higher-order visual brain areas in glaucoma. Within the visual cortex, choline metabolism was perturbed along with increasing disease severity in the eye, optic radiation and visual field. In summary, this study showed evidence that glaucoma deterioration is already present in the eye and the brain before substantial vision loss can be detected clinically using current testing methods. In addition, cortical cholinergic abnormalities are involved during trans-neuronal degeneration and can be detected non-invasively in glaucoma. The current results can be of impact for identifying early glaucoma mechanisms, detecting and monitoring pathophysiological events and eye-brain-behavior relationships, and guiding vision preservation strategies in the visual system, which may help reduce the burden of this irreversible but preventable neurodegenerative disease. PMID:27510406

Human Blue Cone Opsin Regeneration Involves Secondary Retinal Binding with Analog Specificity.

PubMed

Srinivasan, Sundaramoorthy; Fernández-Sampedro, Miguel A; Morillo, Margarita; Ramon, Eva; Jiménez-Rosés, Mireia; Cordomí, Arnau; Garriga, Pere

2018-03-27

Human color vision is mediated by the red, green, and blue cone visual pigments. Cone opsins are G-protein-coupled receptors consisting of an opsin apoprotein covalently linked to the 11-cis-retinal chromophore. All visual pigments share a common evolutionary origin, and red and green cone opsins exhibit a higher homology, whereas blue cone opsin shows more resemblance to the dim light receptor rhodopsin. Here we show that chromophore regeneration in photoactivated blue cone opsin exhibits intermediate transient conformations and a secondary retinoid binding event with slower binding kinetics. We also detected a fine-tuning of the conformational change in the photoactivated blue cone opsin binding site that alters the retinal isomer binding specificity. Furthermore, the molecular models of active and inactive blue cone opsins show specific molecular interactions in the retinal binding site that are not present in other opsins. These findings highlight the differential conformational versatility of human cone opsin pigments in the chromophore regeneration process, particularly compared to rhodopsin, and point to relevant functional, unexpected roles other than spectral tuning for the cone visual pigments. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

New animal models to study the role of tyrosinase in normal retinal development.

PubMed

Lavado, Alfonso; Montoliu, Lluis

2006-01-01

Albino animals display a hypopigmented phenotype associated with several visual abnormalities, including rod photoreceptor cell deficits, abnormal patterns of connections between the eye and the brain and a general underdevelopment of central retina. Oculocutaneous albinism type I, a common form of albinism, is caused by mutations in the tyrosinase gene. In mice, the albino phenotype can be corrected by functional tyrosinase transgenes. Tyrosinase transgenic animals not only show normal pigmentation but the correction of all visual abnormalities associated with albinism, confirming a role of tyrosinase, a key enzyme in melanin biosynthesis, in normal retinal development. Here, we will discuss recent work carried out with new tyrosinase transgenic mouse models, to further analyse the role of tyrosinase in retinal development. We will first report a transgenic model with inducible tyrosinase expression that has been used to address the regulated activation of this gene and its associated effects on the development of the visual system. Second, we will comment on an interesting yeast artificial chromosome (YAC)-tyrosinase transgene, lacking important regulatory elements, that has highlighted the significance of local interactions between the retinal pigment epithelium (RPE) and developing neural retina.

Combination treatment of pediatric coats' disease: a bicenter study in Taiwan.

PubMed

Lin, Chun-Ju; Chen, San-Ni; Hwang, Jiunn-Feng; Yang, Chung-May

2013-01-01

To present the clinical outcome of different combination treatment modalities in pediatric Coats' disease in two Taiwan medical centers. A retrospective review of clinical records was done of pediatric patients with Coats' disease treated at National Taiwan University Hospital and Changhua Christian Hospital. Data regarding the age at the time of diagnosis, initial presentation, methods of treatment, visual and anatomic results, and complications were recorded. Changes in vision and retinal status with the different methods of treatment were specifically evaluated. From 2005 through 2011, 10 eyes of 9 patients were treated under the diagnosis of Coats' disease. The clinical manifestations varied from localized vascular abnormalities with subretinal fluid and hard exudates to extensive detachment with massive exudates and retinal hemorrhage. The main treatment modalities include argon laser photocoagulation, micropulse laser, and cryotherapy. The adjunctive therapies included intravitreal triamcinolone, bevacizumab, and ranibizumab. The mean follow-up was 40.50 ± 20.52 months (range: 14 to 72 months). Best corrected visual acuity at last follow-up was light perception to 1.0 (20/20 Snellen). Anatomic improvement was achieved in 9 eyes (90%). Visual improvement was noted in 7 eyes (70%), visual stabilization in 2 eyes (20%), and visual deterioration in 1 eye (10%). Vitreous fibrosis evolving into tractional retinal detachment occurred in 1 patient receiving cryotherapy combined with intravitreal bevacizumab injections. No enucleation was ultimately necessary. Pediatric Coats' disease varies greatly in severity. Carefully selected treatment modalities can improve most eyes with different conditions. Intravitreal anti-vascular endothelial growth factor agents may act as useful adjuncts to improve anatomic and functional outcome. Cryotherapy combined with the intravitreal bevacizumab injection in severe cases of exudative retinal detachment may carry the risk of vitreoretinal traction and tractional retinal detachment.

Retinal Wave Patterns Are Governed by Mutual Excitation among Starburst Amacrine Cells and Drive the Refinement and Maintenance of Visual Circuits

PubMed Central

Xu, Hong-Ping; Burbridge, Timothy J.; Ye, Meijun; Chen, Minggang; Ge, Xinxin; Zhou, Z. Jimmy

2016-01-01

Retinal waves are correlated bursts of spontaneous activity whose spatiotemporal patterns are critical for early activity-dependent circuit elaboration and refinement in the mammalian visual system. Three separate developmental wave epochs or stages have been described, but the mechanism(s) of pattern generation of each and their distinct roles in visual circuit development remain incompletely understood. We used neuroanatomical, in vitro and in vivo electrophysiological, and optical imaging techniques in genetically manipulated mice to examine the mechanisms of wave initiation and propagation and the role of wave patterns in visual circuit development. Through deletion of β2 subunits of nicotinic acetylcholine receptors (β2-nAChRs) selectively from starburst amacrine cells (SACs), we show that mutual excitation among SACs is critical for Stage II (cholinergic) retinal wave propagation, supporting models of wave initiation and pattern generation from within a single retinal cell type. We also demonstrate that β2-nAChRs in SACs, and normal wave patterns, are necessary for eye-specific segregation. Finally, we show that Stage III (glutamatergic) retinal waves are not themselves necessary for normal eye-specific segregation, but elimination of both Stage II and Stage III retinal waves dramatically disrupts eye-specific segregation. This suggests that persistent Stage II retinal waves can adequately compensate for Stage III retinal wave loss during the development and refinement of eye-specific segregation. These experiments confirm key features of the “recurrent network” model for retinal wave propagation and clarify the roles of Stage II and Stage III retinal wave patterns in visual circuit development. SIGNIFICANCE STATEMENT Spontaneous activity drives early mammalian circuit development, but the initiation and patterning of activity vary across development and among modalities. Cholinergic “retinal waves” are initiated in starburst amacrine cells and propagate to retinal ganglion cells and higher-order visual areas, but the mechanism responsible for creating their unique and critical activity pattern is incompletely understood. We demonstrate that cholinergic wave patterns are dictated by recurrent connectivity within starburst amacrine cells, and retinal ganglion cells act as “readouts” of patterned activity. We also show that eye-specific segregation occurs normally without glutamatergic waves, but elimination of both cholinergic and glutamatergic waves completely disrupts visual circuit development. These results suggest that each retinal wave pattern during development is optimized for concurrently refining multiple visual circuits. PMID:27030771

Moderate perinatal thyroid hormone insufficiency alters visual system function in adult rats.

PubMed

Boyes, William K; Degn, Laura; George, Barbara Jane; Gilbert, Mary E

2018-04-21

Thyroid hormone (TH) is critical for many aspects of neurodevelopment and can be disrupted by a variety of environmental contaminants. Sensory systems, including audition and vision are vulnerable to TH insufficiencies, but little data are available on visual system development at less than severe levels of TH deprivation. The goal of the current experiments was to explore dose-response relations between graded levels of TH insufficiency during development and the visual function of adult offspring. Pregnant Long Evans rats received 0 or 3 ppm (Experiment 1), or 0, 1, 2, or 3 ppm (Experiment 2) of propylthiouracil (PTU), an inhibitor of thyroid hormone synthesis, in drinking water from gestation day (GD) 6 to postnatal day (PN) 21. Treatment with PTU caused dose-related reductions of serum T4, with recovery on termination of exposure, and euthyroidism by the time of visual function testing. Tests of retinal (electroretinograms; ERGs) and visual cortex (visual evoked potentials; VEPs) function were assessed in adult offspring. Dark-adapted ERG a-waves, reflecting rod photoreceptors, were increased in amplitude by PTU. Light-adapted green flicker ERGs, reflecting M-cone photoreceptors, were reduced by PTU exposure. UV-flicker ERGs, reflecting S-cones, were not altered. Pattern-elicited VEPs were significantly reduced by 2 and 3 ppm PTU across a range of stimulus contrast values. The slope of VEP amplitude-log contrast functions was reduced by PTU, suggesting impaired visual contrast gain. Visual contrast gain primarily reflects function of visual cortex, and is responsible for adjusting sensitivity of perceptual mechanisms in response to changing visual scenes. The results indicate that moderate levels of pre-and post-natal TH insufficiency led to alterations in visual function of adult rats, including both retinal and visual cortex sites of dysfunction. Copyright © 2018. Published by Elsevier B.V.

Comparative prospective study of rhegmatogenous retinal detachments in phakic or pseudophakic patients with high myopia.

PubMed

Bernheim, Diane; Rouberol, Frederic; Palombi, Karine; Albrieux, Magali; Romanet, Jean-Paul; Chiquet, Christophe

2013-01-01

To compare the anatomical and functional results of primary rhegmatogenous retinal detachment in highly myopic phakic or pseudophakic eyes. This prospective 2-center study included 191 consecutive eyes (151 phakic and 40 pseudophakic eyes) from a prospective cohort of 835 patients (IRB #5891, between 2004 and 2008). Baseline and follow-up data were systematically recorded at presentation, 1 month, and 6 months or more after surgery. On final examination, two groups were considered based on the need for one or more surgeries to achieve retinal reapplication. End points were primary reattachment rate at the 6-month visit, final anatomical success rate, postoperative visual acuity, and intraoperative and postoperative complications. Pseudophakic eyes differed from phakic eyes in age (60.8 ± 10.4 vs. 49.9 ± 12.3, P < 0.001), smaller pupil dilation (8.0 ± 1.5 vs. 8.5 ± 1.2 mm, P = 0.02), fewer retinal tears seen preoperatively (1.5 ± 1.6 vs. 2.2 ± 2.2, P = 0.06), more frequent use of pars plana vitrectomy (80% vs. 28.5%, P < 0.001), and higher single reattachment rate (92.5% vs. 80.7%). Visual acuity was greater than or equal to 20/40 in 54% of cases with single retinal detachment surgery and 44% of cases with multiple surgeries. Multiple logistic regression analysis showed that only 3 independent variables were significantly predictive of good final visual acuity (20/40): initial visual acuity (<20/400, odds ratio = 0.19; 95% confidence interval, 0.07-0.51; P = 0.002), axial length (odds ratio = 0.57; 95% confidence interval, 0.44-0.75, P < 0.001), and pars plana vitrectomy (odds ratio = 0.33; 95% confidence interval, 0.15-0.71, P = 0.004). This prospective study showed similar baseline retinal detachment characteristics of high myopic phakic or pseudophakic eyes, suggesting that high myopia was the main pathogenic factor in both groups. Although high myopic eye presents anatomical characteristics that could favor surgical morbidity, these recent prospective data show that high myopic eyes exhibit functional and anatomical prognosis close to that described in emmetropic eyes.

Macular function and morphological features in juvenile Stargardt disease: Longitudinal study

PubMed Central

Testa, Francesco; Melillo, Paolo; Iorio, Valentina Di; Orrico, Ada; Attanasio, Marcella; Rossi, Settimio; Simonelli, Francesca

2014-01-01

Purpose to evaluate disease progression in a cohort of patients with clinical and genetic diagnosis of Stargardt disease. Design longitudinal cohort study. Subjects 56 selected patients with a clinical and molecular diagnosis of Stargardt disease, an early age of onset and a median follow-up length of two years. Methods patients underwent routine examination including full-field electroretinography, microperimetry and optical coherence tomography. Main Outcome Measures best corrected visual acuity, mean retinal sensitivity, fixation stability, preferred retinal locus, inner-outer segment (IS/OS) junction loss, atrophic lesion area. Results 56 patients with a mean age of disease onset of 15.3 years (range: 3 - 28 years), a mean disease length of 12.1 years and a mean age at baseline of 27.4 years were analyzed. The median best corrected visual acuity was 20/200 in both eyes. Optical coherence tomography parameters (IS/OS alteration and retinal pigment epithelium lesion area) were obtained in 49 patients because signal quality was poor in the remaining 7 patients. Optical coherence tomography revealed a mean retinal pigment epithelium lesion area of 2.6 mm2, preserved foveal IS/OS in 4.1% of patients, loss of foveal IS/OS in 59.2%, and extensive loss of macular IS/OS in 36.7%. Microperimetric findings showed a reduced macular sensitivity (mean 10 dB) and an unstable fixation in half of the patient cohort. The longitudinal analysis showed a significant progressive reduction of best corrected visual acuity and macular sensitivity (at an estimated rate of 0.04 decimals and 1.19 dB per year, respectively) associated with a significant enlargement of retinal pigment epithelium lesion area (0.282 mm2 per year). No significant changes in ophthalmoscopic findings and electroretinographic responses were detected. Conclusions this study highlights the importance of microperimetry and optical coherence tomography in monitoring Stargardt patients. In fact, quantifying the decline of visual functionality and detecting morphological macular changes proves useful to evaluate disease progression over a short-term follow-up and should be taken into account for the design of future gene therapy clinical trials to treat retinal dystrophy. PMID:25097154

[Topographic mapping of retinal function with a scanning laser ophthalmoscope and multifocal electroretinography using short M-sequences].

PubMed

Rudolph, G; Bechmann, M; Berninger, T; Kutschbach, E; Held, U; Tornow, R P; Kalpadakis, P; Zol'nikova, I V; Shamshinova, A M

2001-01-01

A new method of multifocal electroretinography making use of scanning laser ophthalmoscope with a wavelength of 630 nm (SLO-m-ERG), evoking short spatial visual stimuli on the retina, is proposed. Algorithm of presenting the visual stimuli and analysis of distribution of local electroretinograms on the surface of the retina is based on short m-sequences. Mathematical cross correlation analysis shows a three-dimensional distribution of bioelectrical activity of the retina in the central visual field. In normal subjects the cone bioelectrical activity is the maximum in the macular area (corresponding to the density of cone distribution) and absent in the blind spot. The method detects the slightest pathological changes in the retina under control of the site of stimulation and ophthalmoscopic picture of the fundus oculi. The site of the pathological process correlates with the topography of changes in bioelectrical activity of the examined retinal area in diseases of the macular area and pigmented retinitis detectable by ophthalmoscopy.

Adaptive optics retinal imaging: emerging clinical applications.

PubMed

Godara, Pooja; Dubis, Adam M; Roorda, Austin; Duncan, Jacque L; Carroll, Joseph

2010-12-01

The human retina is a uniquely accessible tissue. Tools like scanning laser ophthalmoscopy and spectral domain-optical coherence tomography provide clinicians with remarkably clear pictures of the living retina. Although the anterior optics of the eye permit such non-invasive visualization of the retina and associated pathology, the same optics induce significant aberrations that obviate cellular-resolution imaging in most cases. Adaptive optics (AO) imaging systems use active optical elements to compensate for aberrations in the optical path between the object and the camera. When applied to the human eye, AO allows direct visualization of individual rod and cone photoreceptor cells, retinal pigment epithelium cells, and white blood cells. AO imaging has changed the way vision scientists and ophthalmologists see the retina, helping to clarify our understanding of retinal structure, function, and the etiology of various retinal pathologies. Here, we review some of the advances that were made possible with AO imaging of the human retina and discuss applications and future prospects for clinical imaging.

The Active Side of Stereopsis: Fixation Strategy and Adaptation to Natural Environments.

PubMed

Gibaldi, Agostino; Canessa, Andrea; Sabatini, Silvio P

2017-03-20

Depth perception in near viewing strongly relies on the interpretation of binocular retinal disparity to obtain stereopsis. Statistical regularities of retinal disparities have been claimed to greatly impact on the neural mechanisms that underlie binocular vision, both to facilitate perceptual decisions and to reduce computational load. In this paper, we designed a novel and unconventional approach in order to assess the role of fixation strategy in conditioning the statistics of retinal disparity. We integrated accurate realistic three-dimensional models of natural scenes with binocular eye movement recording, to obtain accurate ground-truth statistics of retinal disparity experienced by a subject in near viewing. Our results evidence how the organization of human binocular visual system is finely adapted to the disparity statistics characterizing actual fixations, thus revealing a novel role of the active fixation strategy over the binocular visual functionality. This suggests an ecological explanation for the intrinsic preference of stereopsis for a close central object surrounded by a far background, as an early binocular aspect of the figure-ground segregation process.

Gene replacement therapy for retinal CNG channelopathies.

PubMed

Schön, Christian; Biel, Martin; Michalakis, Stylianos

2013-10-01

Visual phototransduction relies on the function of cyclic nucleotide-gated channels in the rod and cone photoreceptor outer segment plasma membranes. The role of these ion channels is to translate light-triggered changes in the second messenger cyclic guanosine 3'-5'-monophosphate levels into an electrical signal that is further processed within the retinal network and then sent to higher visual centers. Rod and cone photoreceptors express distinct CNG channels. The rod photoreceptor CNG channel is composed of one CNGB1 and three CNGA1 subunits, whereas the cone channel is formed by one CNGB3 and three CNGA3 subunits. Mutations in any of these channel subunits result in severe and currently untreatable retinal degenerative diseases like retinitis pigmentosa or achromatopsia. In this review, we provide an overview of the human diseases and relevant animal models of CNG channelopathies. Furthermore, we summarize recent results from preclinical gene therapy studies using adeno-associated viral vectors and discuss the efficacy and translational potential of these gene therapeutic approaches.

Cyclic reconstruction of 4D retinal blood flow with pulse synchronization

NASA Astrophysics Data System (ADS)

Schmoll, Tilman; Lasser, Theo; Leitgeb, Rainer A.

2009-02-01

Doppler OCT systems allow nowadays to visualize quantitative and qualitative angiographic maps of retinal tissue. We equipped the instrument with a pulse oximeter and recorded the pulse synchronously with the resonant Doppler flow data. Recombination of tomograms according to the heart beat cycles yields full volumes for each cycle instant. We believe such multi-dimensional functional information and the ability to monitor dynamic processes over time to open exciting perspectives that ultimately contribute to a better understanding of retinal physiology and patho-physiology in-vivo.

A visual pathway links brain structures active during magnetic compass orientation in migratory birds.

PubMed

Heyers, Dominik; Manns, Martina; Luksch, Harald; Güntürkün, Onur; Mouritsen, Henrik

2007-09-26

The magnetic compass of migratory birds has been suggested to be light-dependent. Retinal cryptochrome-expressing neurons and a forebrain region, "Cluster N", show high neuronal activity when night-migratory songbirds perform magnetic compass orientation. By combining neuronal tracing with behavioral experiments leading to sensory-driven gene expression of the neuronal activity marker ZENK during magnetic compass orientation, we demonstrate a functional neuronal connection between the retinal neurons and Cluster N via the visual thalamus. Thus, the two areas of the central nervous system being most active during magnetic compass orientation are part of an ascending visual processing stream, the thalamofugal pathway. Furthermore, Cluster N seems to be a specialized part of the visual wulst. These findings strongly support the hypothesis that migratory birds use their visual system to perceive the reference compass direction of the geomagnetic field and that migratory birds "see" the reference compass direction provided by the geomagnetic field.

Deafferented Adult Rod Bipolar Cells Create New Synapses with Photoreceptors to Restore Vision

PubMed Central

Hovhannisyan, Anahit; Kung, Jennifer; Lee, Seungjun; Lee, Dae Yeong; Huie, Philip; Dalal, Roopa; Palanker, Daniel

2017-01-01

Upon degeneration of photoreceptors in the adult retina, interneurons, including bipolar cells, exhibit a plastic response leading to their aberrant rewiring. Photoreceptor reintroduction has been suggested as a potential approach to sight restoration, but the ability of deafferented bipolar cells to establish functional synapses with photoreceptors is poorly understood. Here we use photocoagulation to selectively destroy photoreceptors in adult rabbits while preserving the inner retina. We find that rods and cones shift into the ablation zone over several weeks, reducing the blind spot at scotopic and photopic luminances. During recovery, rod and cone bipolar cells exhibit markedly different responses to deafferentation. Rod bipolar cells extend their dendrites to form new synapses with healthy photoreceptors outside the lesion, thereby restoring visual function in the deafferented retina. Secretagogin-positive cone bipolar cells did not exhibit such obvious dendritic restructuring. These findings are encouraging to the idea of photoreceptor reintroduction for vision restoration in patients blinded by retinal degeneration. At the same time, they draw attention to the postsynaptic side of photoreceptor reintroduction; various bipolar cell types, representing different visual pathways, vary in their response to the photoreceptor loss and in their consequent dendritic restructuring. SIGNIFICANCE STATEMENT Loss of photoreceptors during retinal degeneration results in permanent visual impairment. Strategies for vision restoration based on the reintroduction of photoreceptors inherently rely on the ability of the remaining retinal neurons to correctly synapse with new photoreceptors. We show that deafferented bipolar cells in the adult mammalian retina can reconnect to rods and cones and restore retinal sensitivity at scotopic and photopic luminances. Rod bipolar cells extend their dendrites to form new synapses with healthy rod photoreceptors. These findings support the idea that bipolar cells might be able to synapse with reintroduced photoreceptors, thereby restoring vision in patients blinded by retinal degeneration. PMID:28373392

Photovoltaic restoration of sight in rodents with retinal degeneration (Conference Presentation)

NASA Astrophysics Data System (ADS)

Palanker, Daniel V.

2017-02-01

To restore vision in patients who lost their photoreceptors due to retinal degeneration, we developed a photovoltaic subretinal prosthesis which converts light into pulsed electric current, stimulating the nearby inner retinal neurons. Visual information is projected onto the retina by video goggles using pulsed near-infrared ( 900nm) light. This design avoids the use of bulky electronics and wiring, thereby greatly reducing the surgical complexity. Optical activation of the photovoltaic pixels allows scaling the implants to thousands of electrodes, and multiple modules can be tiled under the retina to expand the visual field. We found that similarly to normal vision, retinal response to prosthetic stimulation exhibits flicker fusion at high frequencies (>20Hz), adaptation to static images, and non-linear summation of subunits in the receptive fields. Photovoltaic arrays with 70um pixels restored visual acuity up to a single pixel pitch, which is only two times lower than natural acuity in rats. If these results translate to human retina, such implants could restore visual acuity up to 20/250. With eye scanning and perceptual learning, human patients might even cross the 20/200 threshold of legal blindness. In collaboration with Pixium Vision, we are preparing this system (PRIMA) for a clinical trial. To further improve visual acuity, we are developing smaller pixels - down to 40um, and on 3-D interface to improve proximity to the target neurons. Scalability, ease of implantation and tiling of these wireless modules to cover a large visual field, combined with high resolution opens the door to highly functional restoration of sight.

Visual Prostheses: The Enabling Technology to Give Sight to the Blind

PubMed Central

Maghami, Mohammad Hossein; Sodagar, Amir Masoud; Lashay, Alireza; Riazi-Esfahani, Hamid; Riazi-Esfahani, Mohammad

2014-01-01

Millions of patients are either slowly losing their vision or are already blind due to retinal degenerative diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) or because of accidents or injuries. Employment of artificial means to treat extreme vision impairment has come closer to reality during the past few decades. Currently, many research groups work towards effective solutions to restore a rudimentary sense of vision to the blind. Aside from the efforts being put on replacing damaged parts of the retina by engineered living tissues or microfabricated photoreceptor arrays, implantable electronic microsystems, referred to as visual prostheses, are also sought as promising solutions to restore vision. From a functional point of view, visual prostheses receive image information from the outside world and deliver them to the natural visual system, enabling the subject to receive a meaningful perception of the image. This paper provides an overview of technical design aspects and clinical test results of visual prostheses, highlights past and recent progress in realizing chronic high-resolution visual implants as well as some technical challenges confronted when trying to enhance the functional quality of such devices. PMID:25709777

Rapid recovery from the effects of early monocular deprivation is enabled by temporary inactivation of the retinas.

PubMed

Fong, Ming-Fai; Mitchell, Donald E; Duffy, Kevin R; Bear, Mark F

2016-12-06

A half-century of research on the consequences of monocular deprivation (MD) in animals has revealed a great deal about the pathophysiology of amblyopia. MD initiates synaptic changes in the visual cortex that reduce acuity and binocular vision by causing neurons to lose responsiveness to the deprived eye. However, much less is known about how deprivation-induced synaptic modifications can be reversed to restore normal visual function. One theoretically motivated hypothesis is that a period of inactivity can reduce the threshold for synaptic potentiation such that subsequent visual experience promotes synaptic strengthening and increased responsiveness in the visual cortex. Here we have reduced this idea to practice in two species. In young mice, we show that the otherwise stable loss of cortical responsiveness caused by MD is reversed when binocular visual experience follows temporary anesthetic inactivation of the retinas. In 3-mo-old kittens, we show that a severe impairment of visual acuity is also fully reversed by binocular experience following treatment and, further, that prolonged retinal inactivation alone can erase anatomical consequences of MD. We conclude that temporary retinal inactivation represents a highly efficacious means to promote recovery of function.

ACUTE ZONAL OCCULT OUTER RETINOPATHY: Structural and Functional Analysis Across the Transition Zone Between Healthy and Diseased Retina.

PubMed

Duncker, Tobias; Lee, Winston; Jiang, Fan; Ramachandran, Rithambara; Hood, Donald C; Tsang, Stephen H; Sparrow, Janet R; Greenstein, Vivienne C

2018-01-01

To assess structure and function across the transition zone (TZ) between relatively healthy and diseased retina in acute zonal occult outer retinopathy. Six patients (6 eyes; age 22-71 years) with acute zonal occult outer retinopathy were studied. Spectral-domain optical coherence tomography, fundus autofluorescence, near-infrared reflectance, color fundus photography, and fundus perimetry were performed and images were registered to each other. The retinal layers of the spectral-domain optical coherence tomography scans were segmented and the thicknesses of two outer retinal layers, that is, the total receptor and outer segment plus layers, and the retinal nerve fiber layer were measured. All eyes showed a TZ on multimodal imaging. On spectral-domain optical coherence tomography, the TZ was in the nasal retina at varying distances from the fovea. For all eyes, it was associated with loss of the ellipsoid zone band, significant thinning of the two outer retinal layers, and in three eyes with thickening of the retinal nerve fiber layer. On fundus autofluorescence, all eyes had a clearly demarcated peripapillary area of abnormal fundus autofluorescence delimited by a border of high autofluorescence; the latter was associated with loss of the ellipsoid zone band and with a change from relatively normal to markedly decreased or nonrecordable visual sensitivity on fundus perimetry. The results of multimodal imaging clarified the TZ in acute zonal occult outer retinopathy. The TZ was outlined by a distinct high autofluorescence border that correlated with loss of the ellipsoid zone band on spectral-domain optical coherence tomography. However, in fundus areas that seemed healthy on fundus autofluorescence, thinning of the outer retinal layers and thickening of the retinal nerve fiber layer were observed near the TZ. The TZ was also characterized by a decrease in visual sensitivity.

Visual Acuity is Related to Parafoveal Retinal Thickness in Patients with Retinitis Pigmentosa and Macular Cysts

PubMed Central

Brockhurst, Robert J.; Gaudio, Alexander R.; Berson, Eliot L.

2008-01-01

Purpose To quantify the prevalence and effect on visual acuity of macular cysts in a large cohort of patients with retinitis pigmentosa. Methods In 316 patients with typical forms of retinitis pigmentosa, we measured visual acuities with Early Treatment Diabetic Retinopathy Study (ETDRS) charts, detected macular cysts with optical coherence tomography (OCT), and quantified retinal thicknesses by OCT. We used the FREQ, LOGISTIC, and GENMOD procedures of SAS to evaluate possible risk factors for cyst prevalence and the MIXED procedure to quantify the relationships of visual acuity to retinal thickness measured at different locations within the macula. Results We found macular cysts in 28% of the patients, 40% of whom had cysts in only one eye. Macular cysts were seen most often in patients with dominant disease and not at all in patients with X-linked disease (p = 0.006). In eyes with macular cysts, multiple regression analysis revealed that visual acuity was inversely and independently related to retinal thickness at the foveal center (p = 0.038) and within a ring spanning an eccentricity of 5° to 10° from the foveal center (p = 0.004). Conclusions Macular cysts are a common occurrence in retinitis pigmentosa, especially among patients with dominantly-inherited disease. Visual acuity is influenced by edema in the parafovea, as well as in the fovea. PMID:18552390

Retinal abnormalities in β-thalassemia major

PubMed Central

Bhoiwala, Devang L.; Dunaief, Joshua L.

2015-01-01

Patients with beta (β)-thalassemia (β-TM: thalassemia major, β-TI: thalassemia intermedia) have a variety of complications that may affect all organs, including the eye. Ocular abnormalities include retinal pigment epithelium degeneration, angioid streaks, venous tortuosity, night blindness, visual field defects, decreased visual acuity, color vision abnormalities, and acute visual loss. Patients with β-TM are transfusion dependent and require iron chelation therapy (ICT) in order to survive. Retinal degeneration may result from either retinal iron accumulation from transfusion-induced iron overload or retinal toxicity induced by ICT. Some who were never treated with ICT exhibited retinopathy, and others receiving ICT had chelator-induced retinopathy. We will focus on retinal abnormalities present in individuals with β-TM viewed in light of new findings on the mechanisms and manifestations of retinal iron toxicity. PMID:26325202

Psychological and Educational Recommendations for Working with Young People with Retinitis Pigmentosa

ERIC Educational Resources Information Center

Chacón-López, Helena; López-Justicia, Maria D.; Vervloed, Mathijs P. J.

2014-01-01

This article reviews the consequences of Retinitis Pigmentosa, a retinal degenerative disease with progressive reduction of the visual field, visual acuity, contrast sensitivity, and night blindness. Retinitis Pigmentosa is addressed from both a psychological and an educational standpoint, focusing on the impact on learning, emotional well-being,…

Artificial vision: needs, functioning, and testing of a retinal electronic prosthesis.

PubMed

Chader, Gerald J; Weiland, James; Humayun, Mark S

2009-01-01

Hundreds of thousands around the world have poor vision or no vision at all due to inherited retinal degenerations (RDs) like retinitis pigmentosa (RP). Similarly, millions suffer from vision loss due to age-related macular degeneration (AMD). In both of these allied diseases, the primary target for pathology is the retinal photoreceptor cells that dysfunction and die. Secondary neurons though are relatively spared. To replace photoreceptor cell function, an electronic prosthetic device can be used such that retinal secondary neurons receive a signal that simulates an external visual image. The composite device has a miniature video camera mounted on the patient's eyeglasses, which captures images and passes them to a microprocessor that converts the data to an electronic signal. This signal, in turn, is transmitted to an array of electrodes placed on the retinal surface, which transmits the patterned signal to the remaining viable secondary neurons. These neurons (ganglion, bipolar cells, etc.) begin processing the signal and pass it down the optic nerve to the brain for final integration into a visual image. Many groups in different countries have different versions of the device, including brain implants and retinal implants, the latter having epiretinal or subretinal placement. The device furthest along in development is an epiretinal implant sponsored by Second Sight Medical Products (SSMP). Their first-generation device had 16 electrodes with human testing in a Phase 1 clinical trial beginning in 2002. The second-generation device has 60+ electrodes and is currently in Phase 2/3 clinical trial. Increased numbers of electrodes are planned for future versions of the device. Testing of the device's efficacy is a challenge since patients admitted into the trial have little or no vision. Thus, methods must be developed that accurately and reproducibly record small improvements in visual function after implantation. Standard tests such as visual acuity, visual field, electroretinography, or even contrast sensitivity may not adequately capture some aspects of improvement that relate to a better quality of life (QOL). Because of this, some tests are now relying more on "real-world functional capacity" that better assesses possible improvement in aspects of everyday living. Thus, a new battery of tests have been suggested that include (1) standard psychophysical testing, (2) performance in tasks that are used in real-life situations such as object discrimination, mobility, etc., and (3) well-crafted questionnaires that assess the patient's own feelings as to the usefulness of the device. In the Phase 1 trial of the SSMP 16-electrode device, six subjects with severe RP were implanted with ongoing, continuing testing since then. First, it was evident that even limited sight restoration is a slow, learning process that takes months for improvement to become evident. However, light perception was restored in all six patients. Moreover, all subjects ultimately saw discrete phosphenes and could perform simple visual spatial and motion tasks. As mentioned above, a Phase 2/3 trial is now ongoing with a 60+ device. A 250+ device is on the drawing board, and one with over 1000 electrodes is being planned. Each has the possibility of significantly improving a patient's vision and QOL, being smaller and safer in design and lasting for the lifetime of the patient. From theoretical modeling, it is estimated that a device with approximately 1000 electrodes could give good functional vision, i.e., face recognition and reading ability. This could be a reality within 5-10 years from now. In summary, no treatments are currently available for severely affected patients with RP and dry AMD. An electrical prosthetic device appears to offer hope in replacing the function of degenerating or dead photoreceptor neurons. Devices with new, sophisticated designs and increasing numbers of electrodes could allow for long-term restoration of functional sight in patients with improvement in object recognition, mobility, independent living, and general QOL.

Adaptive Optics Microperimetry and OCT Images Show Preserved Function and Recovery of Cone Visibility in Macular Telangiectasia Type 2 Retinal Lesions

PubMed Central

Wang, Qinyun; Tuten, William S.; Lujan, Brandon J.; Holland, Jennifer; Bernstein, Paul S.; Schwartz, Steven D.; Duncan, Jacque L.; Roorda, Austin

2015-01-01

Purpose. To evaluate visual function and disease progression in the retinal structural abnormalities of three patients from two unrelated families with macular telangiectasia (MacTel) type 2. Methods. Adaptive optics scanning laser ophthalmoscopy (AOSLO) and AOSLO microperimetry (AOMP) were used to evaluate the structure and function of macular cones in three eyes with MacTel type 2. Cone spacing was estimated using histogram analysis of intercone distances, and registered spectral-domain optical coherence tomography (SD-OCT) scans were used to evaluate retinal anatomy. AOMP was used to assess visual sensitivity in and around areas of apparent cone loss. Results. Although overall lesion surface area increased, some initially affected regions subsequently showed clear, contiguous, and normally spaced cone mosaics with recovered photoreceptor inner/outer segment (IS/OS) reflectivity (two of two eyes). The AOMP test sites fell within three categories: normal-appearing cones (N), dimly reflecting cones (D), and RPE cell mosaics (R). At N sites, AOMP threshold values (arbitrary units [au]) increased with increasing eccentricity (slope = 0.054 au/degree, r2 = 0.77). The N thresholds ranged from 0.04 to 0.27 au, D thresholds from 0.04 to 0.33 au, and R thresholds from 0.14 to 1.00 au. There was measurable visual sensitivity everywhere except areas without intact external limiting membrane (ELM) and with diffuse scattering in the IS/OS and posterior tips of the outer segments (PTOS) regions on OCT. Conclusions. Visual sensitivity and recovery of cone visibility in areas of apparent focal cone loss suggests that MacTel type 2 lesions with a preserved ELM may contain functioning cones with abnormal scattering and/or waveguiding characteristics. (ClinicalTrials.gov number, NCT00254605.) PMID:25587056

Autologous neurosensory retinal free patch transplantation for persistent full-thickness macular hole.

PubMed

De Giacinto, Chiara; D'Aloisio, Rossella; Cirigliano, Gabriella; Pastore, Marco Rocco; Tognetto, Daniele

2018-03-27

To evaluate anatomical and functional outcomes after autologous neurosensory retinal free patch (ANRFP) transplantation for persistent idiopathic full-thickness macular hole (iFTMH). A 65-year-old woman with persistent macular hole in her right eye after previous 27-gauge pars plana vitrectomy with internal limiting membrane peeling and long-acting gas tamponade underwent ANRFP transplantation. Before surgery, best corrected visual acuity in her right eye was 20/800. Optical coherence tomography (OCT) showed a 715-micron-diameter FTMH. To treat the persistent FTMH, a small autologous neurosensory retinal patch was transplanted and placed inside the macular hole under perfluorocarbon liquids (PFCL). PFCL-air exchange was performed, and long-acting gas tamponade was carried out. Clinical features of the macular area, visual acuity (VA), fundus autofluorescence, microperimetry and OCT were recorded during the 10-month follow-up. The macular hole appeared successfully closed with retinal patch stable and well plugged into the hole during the whole follow-up. VA improved to 20/100 and microperimetry revealed an increase in mean retinal sensitivity from 14.7 dB at 1 month to 15.6 dB at 10 months postoperatively. OCT showed a well-distinguishable retinal patch into the hole 1 month after surgery and a completely integrated retinal patch between the retinal layers 10 months postoperatively. No intra- and postoperative complications were noticed. ANRFP transplantation may represent an innovative technique for persistent iFTMH treatment.

Structural analysis of retinal photoreceptor ellipsoid zone and postreceptor retinal layer associated with visual acuity in patients with retinitis pigmentosa by ganglion cell analysis combined with OCT imaging

PubMed Central

Liu, Guodong; Li, Hui; Liu, Xiaoqiang; Xu, Ding; Wang, Fang

2016-01-01

Abstract The aim of this study was to examine changes in photoreceptor ellipsoid zone (EZ) and postreceptor retinal layer in retinitis pigmentosa (RP) patients by ganglion cell analysis (GCA) combined with optical coherence tomography (OCT) imaging to evaluate the structure–function relationships between retinal layer changes and best corrected visual acuity (BCVA). Sixty-eight eyes of 35 patients with RP and 65 eyes of 35 normal controls were analyzed in the study. The average length of EZ was 911.1 ± 208.8 μm in RP patients, which was shortened with the progression of the disease on the OCT images. The average ganglion cell–inner plexiform layer thickness (GCIPLT) was 54.7 ± 18.9 μm in RP patients, while in normal controls it was 85.6 ± 6.8 μm. The GCIPLT in all quarters became significantly thinner along with outer retinal thinning. There was a significantly positive correlation between BCVA and EZ (r = −0.7622, P < 0.001) and GCIPLT (r = −0.452, P < 0.001). Therefore, we assess the retinal layer changes from a new perspective in RP patients, which suggests that EZ and GCIPLT obtained by GCA combined with OCT imaging are the direct and valid indicators to diagnosis and predict the pathological process of RP. PMID:28033301

Toward high-resolution optoelectronic retinal prosthesis

NASA Astrophysics Data System (ADS)

Palanker, Daniel; Huie, Philip; Vankov, Alexander; Asher, Alon; Baccus, Steven

2005-04-01

It has been already demonstrated that electrical stimulation of retina can produce visual percepts in blind patients suffering from macular degeneration and retinitis pigmentosa. Current retinal implants provide very low resolution (just a few electrodes), while several thousand pixels are required for functional restoration of sight. We present a design of the optoelectronic retinal prosthetic system that can activate a retinal stimulating array with pixel density up to 2,500 pix/mm2 (geometrically corresponding to a visual acuity of 20/80), and allows for natural eye scanning rather than scanning with a head-mounted camera. The system operates similarly to "virtual reality" imaging devices used in military and medical applications. An image from a video camera is projected by a goggle-mounted infrared LED-LCD display onto the retina, activating an array of powered photodiodes in the retinal implant. Such a system provides a broad field of vision by allowing for natural eye scanning. The goggles are transparent to visible light, thus allowing for simultaneous utilization of remaining natural vision along with prosthetic stimulation. Optical control of the implant allows for simple adjustment of image processing algorithms and for learning. A major prerequisite for high resolution stimulation is the proximity of neural cells to the stimulation sites. This can be achieved with sub-retinal implants constructed in a manner that directs migration of retinal cells to target areas. Two basic implant geometries are described: perforated membranes and protruding electrode arrays. Possibility of the tactile neural stimulation is also examined.

Serial imaging and structure-function correlates of high-density rings of fundus autofluorescence in retinitis pigmentosa.

PubMed

Robson, Anthony G; Tufail, Adnan; Fitzke, Fred; Bird, Alan C; Moore, Anthony T; Holder, Graham E; Webster, Andrew R

2011-09-01

To document the evolution and functional and structural significance of parafoveal rings of high-density fundus autofluorescence (AF) in patients with retinitis pigmentosa and preserved visual acuity. Fifty-two patients with nonsyndromic retinitis pigmentosa or Usher syndrome, who had a parafoveal ring of high-density AF and a visual acuity of 20/30 or better, were ascertained. All had international standard full-field electroretinography and pattern electroretinography. Autofluorescence imaging was repeated in 30 patients after periods of up to 9.3 years. Of the 52 patients, 35 underwent optical coherence tomography. Progressive constriction of the ring was detected in 17 patients. Ring radius reduced by up to 40% at a mean rate of between 0.8% and 15.8% per year. In 1 patient, a small ring was replaced by irregular AF; visual acuity deteriorated over the same period. There was a high correspondence between the lateral extent of the preserved optical coherence tomography inner segment/outer segment band and the diameter of the ring along the same optical coherence tomographic scan plane (slope, 0.9; r = 0.97; P < 0.005; n = 35) and between preserved inner segment/outer segment lamina and the pattern electroretinography P50 measure of macular function (R = 0.72; P < 0.005; n = 34). Rings of increased AF surround areas of preserved outer retina and preserved photopic function. Serial fundus AF may provide prognostic indicators for preservation of central acuity and potentially assist in the identification and evaluation of patients suitable for treatment aimed at preservation of remaining function.

Retinal Wave Patterns Are Governed by Mutual Excitation among Starburst Amacrine Cells and Drive the Refinement and Maintenance of Visual Circuits.

PubMed

Xu, Hong-Ping; Burbridge, Timothy J; Ye, Meijun; Chen, Minggang; Ge, Xinxin; Zhou, Z Jimmy; Crair, Michael C

2016-03-30

Retinal waves are correlated bursts of spontaneous activity whose spatiotemporal patterns are critical for early activity-dependent circuit elaboration and refinement in the mammalian visual system. Three separate developmental wave epochs or stages have been described, but the mechanism(s) of pattern generation of each and their distinct roles in visual circuit development remain incompletely understood. We used neuroanatomical,in vitroandin vivoelectrophysiological, and optical imaging techniques in genetically manipulated mice to examine the mechanisms of wave initiation and propagation and the role of wave patterns in visual circuit development. Through deletion of β2 subunits of nicotinic acetylcholine receptors (β2-nAChRs) selectively from starburst amacrine cells (SACs), we show that mutual excitation among SACs is critical for Stage II (cholinergic) retinal wave propagation, supporting models of wave initiation and pattern generation from within a single retinal cell type. We also demonstrate that β2-nAChRs in SACs, and normal wave patterns, are necessary for eye-specific segregation. Finally, we show that Stage III (glutamatergic) retinal waves are not themselves necessary for normal eye-specific segregation, but elimination of both Stage II and Stage III retinal waves dramatically disrupts eye-specific segregation. This suggests that persistent Stage II retinal waves can adequately compensate for Stage III retinal wave loss during the development and refinement of eye-specific segregation. These experiments confirm key features of the "recurrent network" model for retinal wave propagation and clarify the roles of Stage II and Stage III retinal wave patterns in visual circuit development. Spontaneous activity drives early mammalian circuit development, but the initiation and patterning of activity vary across development and among modalities. Cholinergic "retinal waves" are initiated in starburst amacrine cells and propagate to retinal ganglion cells and higher-order visual areas, but the mechanism responsible for creating their unique and critical activity pattern is incompletely understood. We demonstrate that cholinergic wave patterns are dictated by recurrent connectivity within starburst amacrine cells, and retinal ganglion cells act as "readouts" of patterned activity. We also show that eye-specific segregation occurs normally without glutamatergic waves, but elimination of both cholinergic and glutamatergic waves completely disrupts visual circuit development. These results suggest that each retinal wave pattern during development is optimized for concurrently refining multiple visual circuits. Copyright © 2016 the authors 0270-6474/16/363872-16$15.00/0.

Visual Function Changes after Laser Exposure.

DTIC Science & Technology

1984-04-01

degeneration induced by prolonged exposure to flourescent light. Using the ERG as a criterion response Noell et al (5) showed that the damage action...without photoreceptors. Exp Neurol 1972;34:446-454 15. Bennett 11H, Dyer RF, Dunn JD. Light-induced retinal degeneration : effect upon light-dark...20. Lemmon V, Anderson VV. Behavioral effects of retinal degeneration . Exp Neurol 1979;63:35-49 21. Wright A, Sperling HG. Psychophysical biochemical

Assessing the spatial relationship between fixation and foveal specializations.

PubMed

Wilk, Melissa A; Dubis, Adam M; Cooper, Robert F; Summerfelt, Phyllis; Dubra, Alfredo; Carroll, Joseph

2017-03-01

Increased cone photoreceptor density, an avascular zone (FAZ), and the displacement of inner retinal neurons to form a pit are distinct features of the human fovea. As the fovea provides the majority of our vision, appreciating how these anatomical specializations are related is important for understanding foveal development, normal visual function, and retinal disease. Here we evaluated the relationship between these specializations and their location relative to the preferred retinal locus of fixation (PRL). We measured foveal pit volume, FAZ area, peak cone density, and location of the PRL in 22 subjects with normal vision using optical coherence tomography and adaptive optics scanning light ophthalmoscopy. Foveal pit volume was positively correlated with FAZ area; however, peak cone density was not correlated with pit volume. In addition, there was no systematic offset of the location of any of these specializations relative to PRL, and there was no correlation between the magnitude of the offset from PRL and the corresponding foveal specialization measurements (pit volume, FAZ area, peak cone density). The standard deviation of our PRL measurements was consistent with previous measurements of fixational stability. These data provide insight into the sequence of events during foveal development and may have implications for visual function and retinal disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Macular function and morphology in acute retinal pigment epithelitis.

PubMed

Gundogan, Fatih C; Diner, Oktay; Tas, Ahmet; Ilhan, Abdullah; Yolcu, Umit

2014-12-01

A 20-year-old man applied with vision loss in the left eye. Right eye examination was unremarkable. Best-corrected visual acuity (BCVA) in the left eye was 20/200. Fundus examination revealed a few yellow spots within a round-shaped macular lesion. Autofluorescence imaging showed hyperautofluorescence in the lesion. Central amplitudes in multifocal electroretinogram (mfERG) were depressed. The patient reported a rhinopharyngitis 7-10 days before the visual loss. The patient was diagnosed as acute retinal pigment epithelitis. BCVA improved gradually up to 20/20 in 4 weeks. mfERG amplitudes returned to normal. A slight pigmentary distortion was the only residual fundus finding.

Stroboscopic Goggles as a Countermeasure for Dynamic Visual Acuity and Landing Sickness in Crewmembers Returning from Long-Duration Spaceflight

NASA Technical Reports Server (NTRS)

Rosenberg, M. J. F.; Kreutzberg, G. A.; Peters, B. T.; Reschke, M. F.

2017-01-01

Long-term exposure to microgravity causes sensorimotor adaptations that result in functional deficits upon returning to a gravitational environment. At landing, the vestibular system and the central nervous system, responsible for coordinating head and eye movements via the vestibulo-occular reflex (VOR), are adapted to microgravity and must re-adapt to the Earth's gravitational environment. This re-adaptation causes decrements in gaze control and dynamic visual acuity, with astronauts reporting oscillopsia and blurred vision. These effects are caused by retinal slip, or the inability to keep an image focused on their retina, which is thought to drive motion sickness symptoms experienced upon landing. Retinal slip can be estimated by dynamic visual acuity (DVA); visual acuity while in motion. Peters et al. (2011) find that DVA is worsened in astronauts by an average of 0.75 eye-chart lines one day after landing. Previously, the use of stroboscopic goggles has shown to be effective in minimizing motion sickness symptoms due to retinal slip (Reschke et al. 2007). In this study, we simulated the decrement in DVA caused by sensorimotor re-adaptation by using minifying lenses and then testing the efficacy of stroboscopic goggles in preventing retinal slip and improving DVA. Dynamic visual acuity is assessed using an oscillating chair developed in the Neuroscience Laboratory at JSC. This chair is motor-driven and oscillates vertically at 2 Hz with a vertical displacement of +/- 2 cm to simulate the vertical translations that occur while walking. As the subject is being oscillated, they are asked to discern the direction of Landolt-C optotypes of varying sizes and record their direction using a gamepad. The visual acuity thresholds are determined using an algorithm that alters the size of the optotype based on the previous responses of the subject using a forced-choice best parameter estimation that is able to rapidly converge on the threshold value. Visual acuity thresholds were determined both for static (seated) and dynamic (oscillating) conditions. Dynamic visual acuity is defined as the difference between the dynamic and static conditions. We found that healthy subjects (n=20) have a significantly impaired DVA while wearing the minifying lenses, demonstrating that the VOR is in an adaptive state and retinal slip is occurring. When subjects' acuity was tested wearing the stroboscopic goggles with the minifying lenses, there was no significant difference in their DVA compared to their baseline DVA. This suggests that stroboscopic goggles are preventing retinal slip and would function as an efficient countermeasure for VOR adaptations and thus help mitigate landing sickness symptoms experienced by long-duration crewmembers. These goggles might also be used to counter blurred vision (caused by retinal slip) experienced by crewmembers during launch where the vehicle vibrations are greatest. The stroboscopic effect could be built into a section of their head mounted displays on the visor of their helmets to be used in these high vibration situation if a mission critical task is necessary.

A Novel Role for the Immunoproteasome in Retinal Function

PubMed Central

Hussong, Stacy A.; Roehrich, Heidi; Kapphahn, Rebecca J.; Maldonado, Marcela; Pardue, Machelle T.

2011-01-01

Purpose. The immunoproteasome is a proteasome subtype with a well-characterized role in the immune system. The presence of high immunoproteasome concentrations in the photoreceptors and synaptic regions of the immune-privileged retina implies a role in visual transmission. In this study, immunoproteasome knockout (KO) mice lacking either one (lmp7−/−, L7) or two (lmp7−/−/mecl-1−/−, L7M1) catalytic subunits of the immunoproteasome were used to test the hypothesis that it is essential for the maintenance of normal retinal function. Methods. Wild-type (WT) and immunoproteasome KO mice lacking either one (L7) or two (L7M1) catalytic subunits of the immunoproteasome were studied to determine the importance of the immunoproteasome in maintaining normal retinal function and morphology. Changes in retinal morphology were assessed in mice 2 to 24 months of age. Retinal function was measured with electroretinography (ERG), and relative content of select retinal proteins was assessed by immunoblot analysis. Results. Retinal morphometry showed no major abnormalities in age-matched WT or KO mice. No significant difference was observed in the levels of proteins involved in vision transmission. ERGs from KO mice exhibited an approximate 25% decrease in amplitude of the dark- and light-adapted b-waves and faster dark-adapted b-wave implicit times. Conclusions. Immunoproteasome deficiency causes defects in bipolar cell response. These results support a previously unrecognized role for the immunoproteasome in vision transmission. PMID:20881299

Melanopsin-based brightness discrimination in mice and humans.

PubMed

Brown, Timothy M; Tsujimura, Sei-Ichi; Allen, Annette E; Wynne, Jonathan; Bedford, Robert; Vickery, Graham; Vugler, Anthony; Lucas, Robert J

2012-06-19

Photoreception in the mammalian retina is not restricted to rods and cones but extends to a small number of intrinsically photoreceptive retinal ganglion cells (ipRGCs), expressing the photopigment melanopsin. ipRGCs are known to support various accessory visual functions including circadian photoentrainment and pupillary reflexes. However, despite anatomical and physiological evidence that they contribute to the thalamocortical visual projection, no aspect of visual discrimination has been shown to rely upon ipRGCs. Based on their currently known roles, we hypothesized that ipRGCs may contribute to distinguishing brightness. This percept is related to an object's luminance-a photometric measure of light intensity relevant for cone photoreceptors. However, the perceived brightness of different sources is not always predicted by their respective luminance. Here, we used parallel behavioral and electrophysiological experiments to first show that melanopsin contributes to brightness discrimination in both retinally degenerate and fully sighted mice. We continued to use comparable paradigms in psychophysical experiments to provide evidence for a similar role in healthy human subjects. These data represent the first direct evidence that an aspect of visual discrimination in normally sighted subjects can be supported by inner retinal photoreceptors. Copyright © 2012 Elsevier Ltd. All rights reserved.

Hypothalamic Projections to the Optic Tectum in Larval Zebrafish

PubMed Central

Heap, Lucy A.; Vanwalleghem, Gilles C.; Thompson, Andrew W.; Favre-Bulle, Itia; Rubinsztein-Dunlop, Halina; Scott, Ethan K.

2018-01-01

The optic tectum of larval zebrafish is an important model for understanding visual processing in vertebrates. The tectum has been traditionally viewed as dominantly visual, with a majority of studies focusing on the processes by which tectal circuits receive and process retinally-derived visual information. Recently, a handful of studies have shown a much more complex role for the optic tectum in larval zebrafish, and anatomical and functional data from these studies suggest that this role extends beyond the visual system, and beyond the processing of exclusively retinal inputs. Consistent with this evolving view of the tectum, we have used a Gal4 enhancer trap line to identify direct projections from rostral hypothalamus (RH) to the tectal neuropil of larval zebrafish. These projections ramify within the deepest laminae of the tectal neuropil, the stratum album centrale (SAC)/stratum griseum periventriculare (SPV), and also innervate strata distinct from those innervated by retinal projections. Using optogenetic stimulation of the hypothalamic projection neurons paired with calcium imaging in the tectum, we find rebound firing in tectal neurons consistent with hypothalamic inhibitory input. Our results suggest that tectal processing in larval zebrafish is modulated by hypothalamic inhibitory inputs to the deep tectal neuropil. PMID:29403362

Preferred retinal locus in macular disease: characteristics and clinical implications.

PubMed

Greenstein, Vivienne C; Santos, Rodrigo A V; Tsang, Stephen H; Smith, R Theodore; Barile, Gaetano R; Seiple, William

2008-10-01

To investigate the location and fixation stability of preferred retinal locations (PRLs) in patients with macular disease, and the relationship among areas of abnormal fundus autofluorescence, the PRL and visual sensitivity. Fifteen patients (15 eyes) were studied. Seven had Stargardt disease, 1 bull's eye maculopathy, 5 age-related macular degeneration, 1 Best disease, and 1 pattern dystrophy. All tested eyes had areas of abnormal fundus autofluorescence. The PRL was evaluated with fundus photography and the Nidek microperimeter. Visual field sensitivity was measured with the Nidek microperimeter. Of the 15 eyes, 4 had foveal and 11 had eccentric fixation. Eccentric PRLs were above the atrophic lesion and their stability did not depend on the degree of eccentricity from the fovea. Visual sensitivity was markedly decreased in locations corresponding to hypofluorescent areas. Sensitivity was not decreased in hyperfluorescent areas corresponding to flecks but was decreased if hyperfluorescence was in the form of dense annuli. Eccentric PRLs were in the superior retina in regions of normal fundus autofluorescence. Fixation stability was not correlated with the degree of eccentricity from the fovea. To assess the outcomes of treatment trials it is important to use methods that relate retinal morphology to visual function.

Hypothalamic Projections to the Optic Tectum in Larval Zebrafish.

PubMed

Heap, Lucy A; Vanwalleghem, Gilles C; Thompson, Andrew W; Favre-Bulle, Itia; Rubinsztein-Dunlop, Halina; Scott, Ethan K

2017-01-01

The optic tectum of larval zebrafish is an important model for understanding visual processing in vertebrates. The tectum has been traditionally viewed as dominantly visual, with a majority of studies focusing on the processes by which tectal circuits receive and process retinally-derived visual information. Recently, a handful of studies have shown a much more complex role for the optic tectum in larval zebrafish, and anatomical and functional data from these studies suggest that this role extends beyond the visual system, and beyond the processing of exclusively retinal inputs. Consistent with this evolving view of the tectum, we have used a Gal4 enhancer trap line to identify direct projections from rostral hypothalamus (RH) to the tectal neuropil of larval zebrafish. These projections ramify within the deepest laminae of the tectal neuropil, the stratum album centrale (SAC)/stratum griseum periventriculare (SPV), and also innervate strata distinct from those innervated by retinal projections. Using optogenetic stimulation of the hypothalamic projection neurons paired with calcium imaging in the tectum, we find rebound firing in tectal neurons consistent with hypothalamic inhibitory input. Our results suggest that tectal processing in larval zebrafish is modulated by hypothalamic inhibitory inputs to the deep tectal neuropil.

Conditional Ablation of Retinol Dehydrogenase 10 in the Retinal Pigmented Epithelium Causes Delayed Dark Adaption in Mice*

PubMed Central

Sahu, Bhubanananda; Sun, Wenyu; Perusek, Lindsay; Parmar, Vipulkumar; Le, Yun-Zheng; Griswold, Michael D.; Palczewski, Krzysztof; Maeda, Akiko

2015-01-01

Regeneration of the visual chromophore, 11-cis-retinal, is a crucial step in the visual cycle required to sustain vision. This cycle consists of sequential biochemical reactions that occur in photoreceptor cells and the retinal pigmented epithelium (RPE). Oxidation of 11-cis-retinol to 11-cis-retinal is accomplished by a family of enzymes termed 11-cis-retinol dehydrogenases, including RDH5 and RDH11. Double deletion of Rdh5 and Rdh11 does not limit the production of 11-cis-retinal in mice. Here we describe a third retinol dehydrogenase in the RPE, RDH10, which can produce 11-cis-retinal. Mice with a conditional knock-out of Rdh10 in RPE cells (Rdh10 cKO) displayed delayed 11-cis-retinal regeneration and dark adaption after bright light illumination. Retinal function measured by electroretinogram after light exposure was also delayed in Rdh10 cKO mice as compared with controls. Double deletion of Rdh5 and Rdh10 (cDKO) in mice caused elevated 11/13-cis-retinyl ester content also seen in Rdh5−/−Rdh11−/− mice as compared with Rdh5−/− mice. Normal retinal morphology was observed in 6-month-old Rdh10 cKO and cDKO mice, suggesting that loss of Rdh10 in the RPE does not negatively affect the health of the retina. Compensatory expression of other retinol dehydrogenases was observed in both Rdh5−/− and Rdh10 cKO mice. These results indicate that RDH10 acts in cooperation with other RDH isoforms to produce the 11-cis-retinal chromophore needed for vision. PMID:26391396

A paradigm shift in imaging biomarkers in neovascular age-related macular degeneration.

PubMed

Schmidt-Erfurth, Ursula; Waldstein, Sebastian M

2016-01-01

Neovascular age-related macular degeneration (AMD) has undergone substantial break-throughs in diagnostic as well as therapeutic respect, with optical coherence tomography (OCT) allowing to identify disease morphology in great detail, and intravitreal anti-vascular endothelial growth factor therapy providing unprecedented benefit. However, these two paths have yet not been combined in an optimal way, real-world outcomes are inferior to expectations, and disease management is largely inefficient in the real-world setting. This dilemma can be solved by identification of valid biomarkers relevant for visual function, disease activity and prognosis, which can provide solid guidance for therapeutic management on an individual level as well as on the population base. Qualitative and quantitative morphological features obtained by advanced OCT provide novel insight into exudative and degenerative stages of neovascular AMD. However, conclusions from structure/function correlations evolve differently from previous paradigms. While central retinal thickness was used as biomarker for guiding retreatment management in clinical trials and practice, fluid localization in different compartments offers superior prognostic value: Intraretinal cystoid fluid has a negative impact on visual acuity and is considered as degenerative when persisting through the initial therapeutic interval. Subretinal fluid is associated with superior visual benefit and a lower rate of progression towards geographic atrophy. Detachment of the retinal pigment epithelium was identified as most pathognomonic biomarker, often irresponsive to therapy and responsible for visual decline during a pro-re-nata regimen. Alterations of neurosensory tissue are usually associated with irreversible loss of functional elements and a negative prognosis. Novel OCT technologies offer crucial insight into corresponding changes at the level of the photoreceptor--retinal pigment epithelial--choriocapillary unit, identifying the biological limits of therapeutic interventions. To optimally benefit from high-resolution multi-modal imaging, an integrated analysis of all functional and structural features is required involving reliable automated algorithms and computational data analyses. Using innovative analysis methods, retinal biomarkers can be used to provide efficient personalized therapy for the individual patient, predictive disease- and population-based models for large-scale management and identifying promising targets for the development of novel therapeutic strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Eye Development in Sepia officinalis Embryo: What the Uncommon Gene Expression Profiles Tell Us about Eye Evolution.

PubMed

Imarazene, Boudjema; Andouche, Aude; Bassaglia, Yann; Lopez, Pascal-Jean; Bonnaud-Ponticelli, Laure

2017-01-01

In metazoans, there is a remarkable diversity of photosensitive structures; their shapes, physiology, optical properties, and development are different. To approach the evolution of photosensitive structures and visual function, cephalopods are particularly interesting organisms due to their most highly centralized nervous system and their camerular eyes which constitute a convergence with those of vertebrates. The eye morphogenesis in numerous metazoans is controlled mainly by a conserved Retinal Determination Gene Network (RDGN) including pax, six, eya , and dac playing also key developmental roles in non-retinal structures and tissues of vertebrates and Drosophila . Here we have identified and explored the role of Sof-dac, Sof-six1/2, Sof-eya in eye morphogenesis, and nervous structures controlling the visual function in Sepia officinalis . We compare that with the already shown expressions in eye development of Sof-otx and Sof-pax genes. Rhodopsin is the pigment responsible for light sensitivity in metazoan, which correlate to correlate visual function and eye development. We studied Sof-rhodopsin expression during retina differentiation. By in situ hybridization, we show that (1) all of the RDGN genes, including Sof-pax6 , are expressed in the eye area during the early developmental stages but they are not expressed in the retina, unlike Sof-otx , which could have a role in retina differentiation; (2) Sof-rhodopsin is expressed in the retina just before vision gets functional, from stage 23 to hatching. Our results evidence a role of Sof-six1/2, Sof-eya , and Sof-dac in eye development. However, the gene network involved in the retinal photoreceptor differentiation remains to be determined. Moreover, for the first time, Sof-rhodopsin expression is shown in the embryonic retina of cuttlefish suggesting the evolutionary conservation of the role of rhodopsin in visual phototransduction within metazoans. These findings are correlated with the physiological and behavioral observations suggesting that S. officinalis is able to react to light stimuli from stage 25 of organogenesis on, as soon as the first retinal pigments appear.

Eye Development in Sepia officinalis Embryo: What the Uncommon Gene Expression Profiles Tell Us about Eye Evolution

PubMed Central

Imarazene, Boudjema; Andouche, Aude; Bassaglia, Yann; Lopez, Pascal-Jean; Bonnaud-Ponticelli, Laure

2017-01-01

In metazoans, there is a remarkable diversity of photosensitive structures; their shapes, physiology, optical properties, and development are different. To approach the evolution of photosensitive structures and visual function, cephalopods are particularly interesting organisms due to their most highly centralized nervous system and their camerular eyes which constitute a convergence with those of vertebrates. The eye morphogenesis in numerous metazoans is controlled mainly by a conserved Retinal Determination Gene Network (RDGN) including pax, six, eya, and dac playing also key developmental roles in non-retinal structures and tissues of vertebrates and Drosophila. Here we have identified and explored the role of Sof-dac, Sof-six1/2, Sof-eya in eye morphogenesis, and nervous structures controlling the visual function in Sepia officinalis. We compare that with the already shown expressions in eye development of Sof-otx and Sof-pax genes. Rhodopsin is the pigment responsible for light sensitivity in metazoan, which correlate to correlate visual function and eye development. We studied Sof-rhodopsin expression during retina differentiation. By in situ hybridization, we show that (1) all of the RDGN genes, including Sof-pax6, are expressed in the eye area during the early developmental stages but they are not expressed in the retina, unlike Sof-otx, which could have a role in retina differentiation; (2) Sof-rhodopsin is expressed in the retina just before vision gets functional, from stage 23 to hatching. Our results evidence a role of Sof-six1/2, Sof-eya, and Sof-dac in eye development. However, the gene network involved in the retinal photoreceptor differentiation remains to be determined. Moreover, for the first time, Sof-rhodopsin expression is shown in the embryonic retina of cuttlefish suggesting the evolutionary conservation of the role of rhodopsin in visual phototransduction within metazoans. These findings are correlated with the physiological and behavioral observations suggesting that S. officinalis is able to react to light stimuli from stage 25 of organogenesis on, as soon as the first retinal pigments appear. PMID:28883798

Subthreshold and micropulse diode laser photocoagulation.

PubMed

Dorin, Giorgio

2003-09-01

Retinal laser photocoagulation is a proven, effective treatment for various retinal disorders. Common clinical protocols use intra-operatively visible endpoints that cause iatrogenic chorioretinal damage. For this reason, laser therapy is normally limited to levels of disease severity for which the benefit-to-risk ratio justifies its application. The use of 810 nm diode lasers in the MicroPulse mode offers the surgeon the possibility to minimize iatrogenic retinal damage. A less destructive laser therapy with a more favorable benefit-to-risk ratio could justify treatment earlier in the course of the disease, allowing for stabilization or improvement of less compromised visual functions.

The Effect of Cone Opsin Mutations on Retinal Structure and the Integrity of the Photoreceptor Mosaic

PubMed Central

Carroll, Joseph; Dubra, Alfredo; Gardner, Jessica C.; Mizrahi-Meissonnier, Liliana; Cooper, Robert F.; Dubis, Adam M.; Nordgren, Rick; Genead, Mohamed; Connor, Thomas B.; Stepien, Kimberly E.; Sharon, Dror; Hunt, David M.; Banin, Eyal; Hardcastle, Alison J.; Moore, Anthony T.; Williams, David R.; Fishman, Gerald; Neitz, Jay; Neitz, Maureen; Michaelides, Michel

2012-01-01

Purpose. To evaluate retinal structure and photoreceptor mosaic integrity in subjects with OPN1LW and OPN1MW mutations. Methods. Eleven subjects were recruited, eight of whom have been previously described. Cone and rod density was measured using images of the photoreceptor mosaic obtained from an adaptive optics scanning light ophthalmoscope (AOSLO). Total retinal thickness, inner retinal thickness, and outer nuclear layer plus Henle fiber layer (ONL+HFL) thickness were measured using cross-sectional spectral-domain optical coherence tomography (SD-OCT) images. Molecular genetic analyses were performed to characterize the OPN1LW/OPN1MW gene array. Results. While disruptions in retinal lamination and cone mosaic structure were observed in all subjects, genotype-specific differences were also observed. For example, subjects with “L/M interchange” mutations resulting from intermixing of ancestral OPN1LW and OPN1MW genes had significant residual cone structure in the parafovea (∼25% of normal), despite widespread retinal disruption that included a large foveal lesion and thinning of the parafoveal inner retina. These subjects also reported a later-onset, progressive loss of visual function. In contrast, subjects with the C203R missense mutation presented with congenital blue cone monochromacy, with retinal lamination defects being restricted to the ONL+HFL and the degree of residual cone structure (8% of normal) being consistent with that expected for the S-cone submosaic. Conclusions. The photoreceptor phenotype associated with OPN1LW and OPN1MW mutations is highly variable. These findings have implications for the potential restoration of visual function in subjects with opsin mutations. Our study highlights the importance of high-resolution phenotyping to characterize cellular structure in inherited retinal disease; such information will be critical for selecting patients most likely to respond to therapeutic intervention and for establishing a baseline for evaluating treatment efficacy. PMID:23139274

Ocular Changes in TgF344-AD Rat Model of Alzheimer's Disease

PubMed Central

Tsai, Yuchun; Lu, Bin; Ljubimov, Alexander V.; Girman, Sergey; Ross-Cisneros, Fred N.; Sadun, Alfredo A.; Svendsen, Clive N.; Cohen, Robert M.; Wang, Shaomei

2014-01-01

Purpose. Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive decline in learning, memory, and executive functions. In addition to cognitive and behavioral deficits, vision disturbances have been reported in early stage of AD, well before the diagnosis is clearly established. To further investigate ocular abnormalities, a novel AD transgenic rat model was analyzed. Methods. Transgenic (Tg) rats (TgF344-AD) heterozygous for human mutant APPswe/PS1ΔE9 and age-matched wild type (WT) rats, as well as 20 human postmortem retinal samples from both AD and healthy donors were used. Visual function in the rodent was analyzed using the optokinetic response. Immunohistochemistry on retinal and brain sections was used to detect various markers including amyloid-β (Aβ) plaques. Results. As expected, Aβ plaques were detected in the hippocampus, cortex, and retina of Tg rats. Plaque-like structures were also found in two AD human whole-mount retinas. The choroidal thickness was significantly reduced in both Tg rat and in AD human eyes when compared with age-matched controls. Tg rat eyes also showed hypertrophic retinal pigment epithelial cells, inflammatory cells, and upregulation of complement factor C3. Although visual acuity was lower in Tg than in WT rats, there was no significant difference in the retinal ganglion cell number and retinal vasculature. Conclusions. Further studies are needed to elucidate the significance and mechanisms of this pathological change and luminance threshold recording from the superior colliculus. PMID:24398104

Retinal pigment epithelial detachments and tears, and progressive retinal degeneration in light chain deposition disease.

PubMed

Spielberg, Leigh H; Heckenlively, John R; Leys, Anita M

2013-05-01

Light-chain deposition disease (LCDD) is a rare condition characterised by deposition of monoclonal immunoglobulin light chains (LCs) in tissues, resulting in varying degrees of organ dysfunction. This study reports the characteristic clinical ocular findings seen in advanced LCDD upon development of ocular fundus changes. This is the first report to describe this entity in vivo in a series of patients. A case series of ocular fundus changes in three patients with kidney biopsy-proven LCDD. All patients underwent best corrected visual acuity (BCVA) exam, perimetry, colour fundus photography and fluorescein angiography; two patients underwent indocyanine green angiography, optical coherence tomography, ultrasound and electroretinography; and one patient underwent fundus autofluorescence. Three patients, 53-60 years old at initial presentation, were studied. All three presented with night blindness, poor dark adaptation, metamorphopsia and visual loss. Examination revealed serous and serohaemorrhagic detachments, multiple retinal pigment epithelial (RPE) tears, diffuse RPE degeneration and progressive fibrotic changes. Neither choroidal neovascularisation nor other vascular abnormalities were present. Final best corrected visual acuity (BCVA) ranged from 20/40 to 20/300. Progressive LC deposition in the fundus seems to damage RPE pump function with flow disturbance between choroid and retina. This pathogenesis can explain the evolution to RPE detachments and subsequent rips and progressive retinal malfunction.

Dependence of chromatic responses in V1 on visual field eccentricity and spatial frequency: an fMRI study.

PubMed

D'Souza, Dany V; Auer, Tibor; Frahm, Jens; Strasburger, Hans; Lee, Barry B

2016-03-01

Psychophysical sensitivity to red-green chromatic modulation decreases with visual eccentricity, compared to sensitivity to luminance modulation, even after appropriate stimulus scaling. This is likely to occur at a central, rather than a retinal, site. Blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to stimuli designed to separately stimulate different afferent channels' [red-green, luminance, and short-wavelength (S)-cone] circular gratings were recorded as a function of visual eccentricity (±10  deg) and spatial frequency (SF) in human primary visual cortex (V1) and further visual areas (V2v, V3v). In V1, the SF tuning of BOLD fMRI responses became coarser with eccentricity. For red-green and luminance gratings, similar SF tuning curves were found at all eccentricities. The pattern for S-cone modulation differed, with SF tuning changing more slowly with eccentricity than for the other two modalities. This may be due to the different retinal distribution with eccentricity of this receptor type. A similar pattern held in V2v and V3v. This would suggest that transformation or spatial filtering of the chromatic (red-green) signal occurs beyond these areas.

Contrast visual acuity in patients with retinitis pigmentosa assessed by a contrast sensitivity tester.

PubMed

Oishi, Maho; Nakamura, Hajime; Hangai, Masanori; Oishi, Akio; Otani, Atsushi; Yoshimura, Nagahisa

2012-01-01

To assess contrast visual acuity (CVA) in patients with retinitis pigmentosa (RP) and compare the result with standard visual acuity (VA), retinal thickness, status of inner segment/outer segment junction, and central visual field. Thirty-nine eyes of 39 patients with RP and 39 eyes of 39 healthy individuals were studied. To see the difference in CVA between RP patients and normal controls, only subjects with standard VA of 1.0 (20/20) or better were included. This was a cross-sectional study. CVA in various light conditions was measured with CAT-2000 and was compared between patients and controls. CVA of patients was further analyzed for association with other parameters including foveal retinal thickness, outer nuclear layer thickness, the status of inner segment/outer segment junction measured with optical coherence tomography (OCT), and visual field mean deviation (MD) measured with Humphrey field analyzer 10-2 program. CVA impairment was evident in RP patients compared to controls (P < 0.01, in all measurement conditions). Multivariate analysis showed association of logarithm of the minimum angle of resolution (logMAR) with CVAs in several conditions. None of the OCT measurements was associated with CVA. When patients were divided into three groups based on MD, the most advanced group (MD worse than or equal to -20 dB) showed impairment of mesopic CVA (P < 0.05, under mesopic condition of 100% without glare, with glare, and 25% without glare). CVA impairment was confirmed in RP patients, especially in advanced cases. CVA measured with CAT-2000 may be a useful tool for assessing foveal function in RP patients.

The functional performance of the Argus II retinal prosthesis

PubMed Central

Stronks, H Christiaan; Dagnelie, Gislin

2014-01-01

Summary Visual prostheses are devices to treat profound vision loss by stimulating secondary nerve cells anywhere along the visual pathway, typically with electrical pulses. The Argus® II implant, developed by Second Sight Medical Products (SSMP, Sylmar, CA, USA), targets the retina and features 60 electrodes that electrically stimulate the surviving retinal neurons. Of the approximately 20 research groups that are actively developing visual prostheses, SSMP has the longest track record. The Argus II was the first visual prosthesis to become commercially available: It received the CE mark in Europe in 2011 and FDA approval was granted in early 2013 for humanitarian use in the USA. Meanwhile, the Argus II safety/benefit study has been extended for research purposes, and is ongoing. In this review we will discuss the performance of the Argus II in restoring sight to the blind, and we will shed light on its expected developments in the coming years. PMID:24308734

[A case of MEWDS. "The multiple evanescent white-dot syndrome"].

PubMed

Lefrançois, A; Hamard, H; Corbe, C; Schmitt, A; Badelon, I; Vidal, A

1989-01-01

A young white man developed acute bilateral visual loss with no previous general illness. Ophthalmoscopic examination showed multiple small yellow-white lesions scattered throughout the posterior poles and mild periphery fundus. There was also fine granularity of two foveal areas and one optic disc margin was blurred. Fluorescein angiography showed early hyperfluorescence of the lesions and late staining of the retinal pigment epithelium. Electrophysiologic abnormalities were transient, asymmetric, more marked in photopic than in scotopic. The origin could be in retinal bipolar cells. These lesions regressed, with return of normal visual function within several weeks. These clinical findings are different from others acute inflammatory diseases primarily involving retinal pigment epithelium and photoreceptors. This aspect is usually described as "multiple evanescent white dot syndrome". The etiology of this syndrome remains unknown with no evidence of systemic disease. A history of flulike illness is rare.

Melanopsin-expressing retinal ganglion-cell photoreceptors: cellular diversity and role in pattern vision

PubMed Central

Ecker, Jennifer L.; Dumitrescu, Olivia N.; Wong, Kwoon Y.; Alam, Nazia M.; Chen, Shih-Kuo; LeGates, Tara; Renna, Jordan M.; Prusky, Glen T.; Berson, David M.; Hattar, Samer

2010-01-01

Using the photopigment melanopsin, intrinsically photosensitive retinal ganglion cells (ipRGCs) respond directly to light to drive circadian clock resetting and pupillary constriction. We now report that ipRGCs are more abundant and diverse than previously appreciated, project more widely within the brain, and can support spatial visual perception. A Cre-based melanopsin reporter mouse line revealed at least five subtypes of ipRGCs with distinct morphological and physiological characteristics. Collectively, these cells project beyond the known brain targets of ipRGCs to heavily innervate the superior colliculus and dorsal lateral geniculate nucleus, retinotopically-organized nuclei mediating object localization and discrimination. Mice lacking classical rod-cone photoreception, and thus entirely dependent on melanopsin for light detection, were able to discriminate grating stimuli from equiluminant gray, and had measurable visual acuity. Thus, non-classical retinal photoreception occurs within diverse cell types, and influences circuits and functions encompassing luminance as well as spatial information. PMID:20624591

Modeling a space-variant cortical representation for apparent motion.

PubMed

Wurbs, Jeremy; Mingolla, Ennio; Yazdanbakhsh, Arash

2013-08-06

Receptive field sizes of neurons in early primate visual areas increase with eccentricity, as does temporal processing speed. The fovea is evidently specialized for slow, fine movements while the periphery is suited for fast, coarse movements. In either the fovea or periphery discrete flashes can produce motion percepts. Grossberg and Rudd (1989) used traveling Gaussian activity profiles to model long-range apparent motion percepts. We propose a neural model constrained by physiological data to explain how signals from retinal ganglion cells to V1 affect the perception of motion as a function of eccentricity. Our model incorporates cortical magnification, receptive field overlap and scatter, and spatial and temporal response characteristics of retinal ganglion cells for cortical processing of motion. Consistent with the finding of Baker and Braddick (1985), in our model the maximum flash distance that is perceived as an apparent motion (Dmax) increases linearly as a function of eccentricity. Baker and Braddick (1985) made qualitative predictions about the functional significance of both stimulus and visual system parameters that constrain motion perception, such as an increase in the range of detectable motions as a function of eccentricity and the likely role of higher visual processes in determining Dmax. We generate corresponding quantitative predictions for those functional dependencies for individual aspects of motion processing. Simulation results indicate that the early visual pathway can explain the qualitative linear increase of Dmax data without reliance on extrastriate areas, but that those higher visual areas may serve as a modulatory influence on the exact Dmax increase.

Purtscher's retinopathy associated with acute pancreatitis.

PubMed

Hamp, Ania M; Chu, Edward; Slagle, William S; Hamp, Robert C; Joy, Jeffrey T; Morris, Robert W

2014-02-01

Purtscher's retinopathy is a rare condition that is associated with complement-activating systemic diseases such as acute pancreatitis. After pancreatic injury or inflammation, proteases such as trypsin activate the complement system and can potentially cause coagulation and leukoembolization of retinal precapillary arterioles. Specifically, intermediate-sized emboli are sufficiently small enough to pass through larger arteries yet large enough to remain lodged in precapillary arterioles and cause the clinical appearance of Purtscher's retinopathy. This pathology may present with optic nerve edema, impaired visual acuity, visual field loss, as well as retinal findings such as cotton-wool spots, retinal hemorrhage, artery attenuation, venous dilation, and Purtscher flecken. A 57-year-old white man presented with an acute onset of visual field scotomas and decreased visual acuity 1 week after being hospitalized for acute pancreatitis. The retinal examination revealed multiple regions of discrete retinal whitening surrounding the disk, extending through the macula bilaterally, as well as bilateral optic nerve hemorrhages. The patient identified paracentral bilateral visual field defects on Amsler Grid testing, which was confirmed with subsequent Humphrey visual field analysis. Although the patient presented with an atypical underlying etiology, he exhibited classic retinal findings for Purtscher's retinopathy. After 2 months, best corrected visual acuity improved and the retinal whitening was nearly resolved; however, bilateral paracentral visual field defects remained. Purtscher's retinopathy has a distinctive clinical presentation and is typically associated with thoracic trauma but may be a sequela of nontraumatic systemic disease such as acute pancreatitis. Patients diagnosed with acute pancreatitis should have an eye examination to rule out Purtscher's retinopathy. Although visual improvement is possible, patients should be educated that there may be permanent ocular sequelae.

Iron, zinc, and copper in retinal physiology and disease.

PubMed

Ugarte, Marta; Osborne, Neville N; Brown, Laurence A; Bishop, Paul N

2013-01-01

The essential trace metals iron, zinc, and copper play important roles both in retinal physiology and disease. They are involved in various retinal functions such as phototransduction, the visual cycle, and the process of neurotransmission, being tightly bound to proteins and other molecules to regulate their structure and/or function or as unbound free metal ions. Elevated levels of "free" or loosely bound metal ions can exert toxic effects, and in order to maintain homeostatic levels to protect retinal cells from their toxicity, appropriate mechanisms exist such as metal transporters, chaperones, and the presence of certain storage molecules that tightly bind metals to form nontoxic products. The pathways to maintain homeostatic levels of metals are closely interlinked, with various metabolic pathways directly and/or indirectly affecting their concentrations, compartmentalization, and oxidation/reduction states. Retinal deficiency or excess of these metals can result from systemic depletion and/or overload or from mutations in genes involved in maintaining retinal metal homeostasis, and this is associated with retinal dysfunction and pathology. Iron accumulation in the retina, a characteristic of aging, may be involved in the pathogenesis of retinal diseases such as age-related macular degeneration (AMD). Zinc deficiency is associated with poor dark adaptation. Zinc levels in the human retina and RPE decrease with age in AMD. Copper deficiency is associated with optic neuropathy, but retinal function is maintained. The changes in iron and zinc homeostasis in AMD have led to the speculation that iron chelation and/or zinc supplements may help in its treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

Test-Retest Intervisit Variability of Functional and Structural Parameters in X-Linked Retinoschisis.

PubMed

Jeffrey, Brett G; Cukras, Catherine A; Vitale, Susan; Turriff, Amy; Bowles, Kristin; Sieving, Paul A

2014-09-01

To examine the variability of four outcome measures that could be used to address safety and efficacy in therapeutic trials with X-linked juvenile retinoschisis. Seven men with confirmed mutations in the RS1 gene were evaluated over four visits spanning 6 months. Assessments included visual acuity, full-field electroretinograms (ERG), microperimetric macular sensitivity, and retinal thickness measured by optical coherence tomography (OCT). Eyes were separated into Better or Worse Eye groups based on acuity at baseline. Repeatability coefficients were calculated for each parameter and jackknife resampling used to derive 95% confidence intervals (CIs). The threshold for statistically significant change in visual acuity ranged from three to eight letters. For ERG a-wave, an amplitude reduction greater than 56% would be considered significant. For other parameters, variabilities were lower in the Worse Eye group, likely a result of floor effects due to collapse of the schisis pockets and/or retinal atrophy. The criteria for significant change (Better/Worse Eye) for three important parameters were: ERG b/a-wave ratio (0.44/0.23), point wise sensitivity (10.4/7.0 dB), and central retinal thickness (31%/18%). The 95% CI range for visual acuity, ERG, retinal sensitivity, and central retinal thickness relative to baseline are described for this cohort of participants with X-linked juvenile retinoschisis (XLRS). A quantitative understanding of the variability of outcome measures is vital to establishing the safety and efficacy limits for therapeutic trials of XLRS patients.

Five-year safety and performance results from the Argus II Retinal Prosthesis System clinical trial

PubMed Central

da Cruz, Lyndon; Dorn, Jessy D.; Humayun, Mark S.; Dagnelie, Gislin; Handa, James; Barale, Pierre-Olivier; Sahel, José-Alain; Stanga, Paulo E.; Hafezi, Farhad; Safran, Avinoam B.; Salzmann, Joel; Santos, Arturo; Birch, David; Spencer, Rand; Cideciyan, Artur V.; de Juan, Eugene; Duncan, Jacque L.; Eliott, Dean; Fawzi, Amani; Olmos de Koo, Lisa C.; Ho, Allen C.; Brown, Gary; Haller, Julia; Regillo, Carl; Del Priore, Lucian V.; Arditi, Aries; Greenberg, Robert J.

2016-01-01

Purpose The Argus® II Retinal Prosthesis System (Second Sight Medical Products, Inc., Sylmar, CA) was developed to restore some vision to patients blind from retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception due to end-stage RP. Design The study is a prospective, multicenter, single-arm, clinical trial. Within-patient controls included the non-implanted fellow eye and patients' native residual vision compared to their vision when using the System. Subjects There were 30 subjects in 10 centers in the U.S. and Europe. Methods The worse-seeing eye of blind patients was implanted with the Argus II System. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. Main Outcome Measures The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by three computer-based, objective tests. Secondary measures included functional vision performance on objectively-scored real-world tasks. Results Twenty-four out of 30 patients remained implanted with functioning Argus II Systems at 5 years post-implant. Only one additional serious adverse event was experienced since the 3-year time point. Patients performed significantly better with the System ON than OFF on all visual function tests and functional vision tasks. Conclusions The five-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada. PMID:27453256

Five-Year Safety and Performance Results from the Argus II Retinal Prosthesis System Clinical Trial.

PubMed

da Cruz, Lyndon; Dorn, Jessy D; Humayun, Mark S; Dagnelie, Gislin; Handa, James; Barale, Pierre-Olivier; Sahel, José-Alain; Stanga, Paulo E; Hafezi, Farhad; Safran, Avinoam B; Salzmann, Joel; Santos, Arturo; Birch, David; Spencer, Rand; Cideciyan, Artur V; de Juan, Eugene; Duncan, Jacque L; Eliott, Dean; Fawzi, Amani; Olmos de Koo, Lisa C; Ho, Allen C; Brown, Gary; Haller, Julia; Regillo, Carl; Del Priore, Lucian V; Arditi, Aries; Greenberg, Robert J

2016-10-01

The Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) was developed to restore some vision to patients blind as a result of retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception resulting from end-stage RP. Prospective, multicenter, single-arm clinical trial. Within-patient controls included the nonimplanted fellow eye and patients' native residual vision compared with their vision with the Argus II. Thirty participants in 10 centers in the United States and Europe. The worse-seeing eye of blind patients was implanted with the Argus II. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Secondary measures included functional vision performance on objectively scored real-world tasks. Twenty-four of 30 patients remained implanted with functioning Argus II Systems at 5 years after implantation. Only 1 additional serious adverse event was experienced after the 3-year time point. Patients performed significantly better with the Argus II on than off on all visual function tests and functional vision tasks. The 5-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind as a result of RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Recessive NRL mutations in patients with clumped pigmentary retinal degeneration and relative preservation of blue cone function.

PubMed

Nishiguchi, Koji M; Friedman, James S; Sandberg, Michael A; Swaroop, Anand; Berson, Eliot L; Dryja, Thaddeus P

2004-12-21

Mice lacking the transcription factor Nrl have no rod photoreceptors and an increased number of short-wavelength-sensitive cones. Missense mutations in NRL are associated with autosomal dominant retinitis pigmentosa; however, the phenotype associated with the loss of NRL function in humans has not been reported. We identified two siblings who carried two allelic mutations: a predicted null allele (L75fs) and a missense mutation (L160P) altering a highly conserved residue in the domain involved in DNA-binding-site recognition. In vitro luciferase reporter assays demonstrated that the NRL-L160P mutant had severely reduced transcriptional activity compared with the WT NRL protein, consistent with a severe loss of function. The affected patients had night blindness since early childhood, consistent with a severe reduction in rod function. Color vision was normal, suggesting the presence of all cone color types; nevertheless, a comparison of central visual fields evaluated with white-on-white and blue-on-yellow light stimuli was consistent with a relatively enhanced function of short-wavelength-sensitive cones in the macula. The fundi had signs of retinal degeneration (such as vascular attenuation) and clusters of large, clumped, pigment deposits in the peripheral fundus at the level of the retinal pigment epithelium (clumped pigmentary retinal degeneration). Our report presents an unusual clinical phenotype in humans with loss-of-function mutations in NRL.

Pharmacological and rAAV Gene Therapy Rescue of Visual Functions in a Blind Mouse Model of Leber Congenital Amaurosis

PubMed Central

Batten, Matthew L; Imanishi, Yoshikazu; Tu, Daniel C; Doan, Thuy; Zhu, Li; Pang, Jijing; Glushakova, Lyudmila; Moise, Alexander R; Baehr, Wolfgang; Van Gelder, Russell N.; Hauswirth, William W; Rieke, Fred; Palczewski, Krzysztof

2005-01-01

Background Leber congenital amaurosis (LCA), a heterogeneous early-onset retinal dystrophy, accounts for ~15% of inherited congenital blindness. One cause of LCA is loss of the enzyme lecithin:retinol acyl transferase (LRAT), which is required for regeneration of the visual photopigment in the retina. Methods and Findings An animal model of LCA, the Lrat −/− mouse, recapitulates clinical features of the human disease. Here, we report that two interventions—intraocular gene therapy and oral pharmacologic treatment with novel retinoid compounds—each restore retinal function to Lrat −/− mice. Gene therapy using intraocular injection of recombinant adeno-associated virus carrying the Lrat gene successfully restored electroretinographic responses to ~50% of wild-type levels (p < 0.05 versus wild-type and knockout controls), and pupillary light responses (PLRs) of Lrat −/− mice increased ~2.5 log units (p < 0.05). Pharmacological intervention with orally administered pro-drugs 9-cis-retinyl acetate and 9-cis-retinyl succinate (which chemically bypass the LRAT-catalyzed step in chromophore regeneration) also caused long-lasting restoration of retinal function in LRAT-deficient mice and increased ERG response from ~5% of wild-type levels in Lrat −/− mice to ~50% of wild-type levels in treated Lrat −/− mice (p < 0.05 versus wild-type and knockout controls). The interventions produced markedly increased levels of visual pigment from undetectable levels to 600 pmoles per eye in retinoid treated mice, and ~1,000-fold improvements in PLR and electroretinogram sensitivity. The techniques were complementary when combined. Conclusion Intraocular gene therapy and pharmacologic bypass provide highly effective and complementary means for restoring retinal function in this animal model of human hereditary blindness. These complementary methods offer hope of developing treatment to restore vision in humans with certain forms of hereditary congenital blindness. PMID:16250670

Retinal abnormalities in β-thalassemia major.

PubMed

Bhoiwala, Devang L; Dunaief, Joshua L

2016-01-01

Patients with beta (β)-thalassemia (β-TM: β-thalassemia major, β-TI: β-thalassemia intermedia) have a variety of complications that may affect all organs, including the eye. Ocular abnormalities include retinal pigment epithelial degeneration, angioid streaks, venous tortuosity, night blindness, visual field defects, decreased visual acuity, color vision abnormalities, and acute visual loss. Patients with β-thalassemia major are transfusion dependent and require iron chelation therapy to survive. Retinal degeneration may result from either retinal iron accumulation from transfusion-induced iron overload or retinal toxicity induced by iron chelation therapy. Some who were never treated with iron chelation therapy exhibited retinopathy, and others receiving iron chelation therapy had chelator-induced retinopathy. We will focus on retinal abnormalities present in individuals with β-thalassemia major viewed in light of new findings on the mechanisms and manifestations of retinal iron toxicity. Copyright © 2016 Elsevier Inc. All rights reserved.

Retinal Detachment Associated With Basketball-Related Eye Trauma.

PubMed

Lee, Tsung-Han; Chen, Yi-Hao; Kuo, Hsi-Kung; Chen, Yung-Jen; Chen, Chih-Hsin; Lee, Jong-Jer; Wu, Pei-Chang

2017-08-01

Basketball is a popular sport involving significant body contact, which may frequently result in ocular trauma. The aim of this study was to evaluate the characteristics and visual outcomes of retinal detachment associated with basketball-related injury. Retrospective, interventional case series. We reviewed the course of patients who sustained traumatic retinal detachment from basketball-related ocular trauma between 2003 and 2015. Thirteen patients were evaluated for basketball-related traumatic retinal detachment. Twelve (92%) were male and 1 (8%) female, with an average age of 18.2 years. The majority (9 of 13, 70%) of patients had moderate-to-high myopia, and none were using protective eyewear when they sustained the eye trauma. Rhegmatogenous retinal detachment was observed in all eyes. The preoperative mean visual acuity was 20/625 (range, hand motions to 20/20). Initial surgery using scleral buckling alone was performed in most (8 of 13, 62%) of the patients. Retinal reattachment was achieved in 10 (76%) eyes after the first operation and in 12 (92%) at the end of the intervention. The mean follow-up was 3.9 years (range, 4 months to 12 years). The visual acuity during last follow-up was 20/231 (range, light perception to 20/20). In the multivariable analysis, initial visual acuity was an independent factor affecting the final visual outcome (P = .006). Retinal detachment associated with basketball-related injury may cause severe visual loss. In the current study, all retinal detachments were of rhegmatogenous type and commonly occurred in young individuals with myopia. Initial visual acuity was associated with the prognosis. Risk awareness for early detection and intervention are important in these traumas. Copyright © 2017 Elsevier Inc. All rights reserved.

Developing Extracellular Matrix Technology to Treat Retinal or Optic Nerve Injury

PubMed Central

van der Merwe, Yolandi

2015-01-01

Abstract Adult mammalian CNS neurons often degenerate after injury, leading to lost neurologic functions. In the visual system, retinal or optic nerve injury often leads to retinal ganglion cell axon degeneration and irreversible vision loss. CNS axon degeneration is increasingly linked to the innate immune response to injury, which leads to tissue-destructive inflammation and scarring. Extracellular matrix (ECM) technology can reduce inflammation, while increasing functional tissue remodeling, over scarring, in various tissues and organs, including the peripheral nervous system. However, applying ECM technology to CNS injuries has been limited and virtually unstudied in the visual system. Here we discuss advances in deriving fetal CNS-specific ECMs, like fetal porcine brain, retina, and optic nerve, and fetal non-CNS-specific ECMs, like fetal urinary bladder, and the potential for using tissue-specific ECMs to treat retinal or optic nerve injuries in two platforms. The first platform is an ECM hydrogel that can be administered as a retrobulbar, periocular, or even intraocular injection. The second platform is an ECM hydrogel and polymer “biohybrid” sheet that can be readily shaped and wrapped around a nerve. Both platforms can be tuned mechanically and biochemically to deliver factors like neurotrophins, immunotherapeutics, or stem cells. Since clinical CNS therapies often use general anti-inflammatory agents, which can reduce tissue-destructive inflammation but also suppress tissue-reparative immune system functions, tissue-specific, ECM-based devices may fill an important need by providing naturally derived, biocompatible, and highly translatable platforms that can modulate the innate immune response to promote a positive functional outcome. PMID:26478910

Pigmentary retinopathy associated with the mitochondrial DNA 3243 point mutation.

PubMed

Sue, C M; Mitchell, P; Crimmins, D S; Moshegov, C; Byrne, E; Morris, J G

1997-10-01

Fourteen patients from four unrelated families were studied to determine the prevalence of retinal pigmentary abnormalities associated with the MELAS A to G 3243 point mutation. Neurologic and ophthalmic examinations, retinal photography, pattern shift visual evoked potentials, and electroretinography were performed in all patients. Eight of the 14 patients had retinal pigmentary abnormalities characterized by symmetric areas of depigmentation involving predominantly the posterior pole and midperipheral retina. None of the patients had optic atrophy and only one patient with pigmentary retinal abnormalities had impaired visual acuity. None of the diabetic subjects (n = 6) had signs of diabetic retinopathy. Fluorescein angiography demonstrated mottled hyper- and hypofluorescent areas indicating multiple window defects in the retinal pigmentary epithelium. Visual evoked potentials showed delayed P100 responses in four of the eight patients with retinal pigmentary abnormalities. We conclude that there is a high prevalence of retinal pigmentary abnormalities in patients with MELAS A to G 3243 point mutation. These abnormalities are usually asymptomatic and best detected by retinal photography.

Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats.

PubMed

Lund, Raymond D; Wang, Shaomei; Klimanskaya, Irina; Holmes, Toby; Ramos-Kelsey, Rebeca; Lu, Bin; Girman, Sergej; Bischoff, N; Sauvé, Yves; Lanza, Robert

2006-01-01

Embryonic stem cells promise to provide a well-characterized and reproducible source of replacement tissue for human clinical studies. An early potential application of this technology is the use of retinal pigment epithelium (RPE) for the treatment of retinal degenerative diseases such as macular degeneration. Here we show the reproducible generation of RPE (67 passageable cultures established from 18 different hES cell lines); batches of RPE derived from NIH-approved hES cells (H9) were tested and shown capable of extensive photoreceptor rescue in an animal model of retinal disease, the Royal College of Surgeons (RCS) rat, in which photoreceptor loss is caused by a defect in the adjacent retinal pigment epithelium. Improvement in visual performance was 100% over untreated controls (spatial acuity was approximately 70% that of normal nondystrophic rats) without evidence of untoward pathology. The use of somatic cell nuclear transfer (SCNT) and/or the creation of banks of reduced complexity human leucocyte antigen (HLA) hES-RPE lines could minimize or eliminate the need for immunosuppressive drugs and/or immunomodulatory protocols.

Correspondence between visual and electrical input filters of ON and OFF mouse retinal ganglion cells

NASA Astrophysics Data System (ADS)

Sekhar, S.; Jalligampala, A.; Zrenner, E.; Rathbun, D. L.

2017-08-01

Objective. Over the past two decades retinal prostheses have made major strides in restoring functional vision to patients blinded by diseases such as retinitis pigmentosa. Presently, implants use single pulses to activate the retina. Though this stimulation paradigm has proved beneficial to patients, an unresolved problem is the inability to selectively stimulate the on and off visual pathways. To this end our goal was to test, using white noise, voltage-controlled, cathodic, monophasic pulse stimulation, whether different retinal ganglion cell (RGC) types in the wild type retina have different electrical input filters. This is an important precursor to addressing pathway-selective stimulation. Approach. Using full-field visual flash and electrical and visual Gaussian noise stimulation, combined with the technique of spike-triggered averaging (STA), we calculate the electrical and visual input filters for different types of RGCs (classified as on, off or on-off based on their response to the flash stimuli). Main results. Examining the STAs, we found that the spiking activity of on cells during electrical stimulation correlates with a decrease in the voltage magnitude preceding a spike, while the spiking activity of off cells correlates with an increase in the voltage preceding a spike. No electrical preference was found for on-off cells. Comparing STAs of wild type and rd10 mice revealed narrower electrical STA deflections with shorter latencies in rd10. Significance. This study is the first comparison of visual cell types and their corresponding temporal electrical input filters in the retina. The altered input filters in degenerated rd10 retinas are consistent with photoreceptor stimulation underlying visual type-specific electrical STA shapes in wild type retina. It is therefore conceivable that existing implants could target partially degenerated photoreceptors that have only lost their outer segments, but not somas, to selectively activate the on and off visual pathways.

Fundus autofluorescence and retinal structure as determined by spectral domain optical coherence tomography, and retinal function in retinitis pigmentosa.

PubMed

Iriyama, Aya; Yanagi, Yasuo

2012-03-01

To investigate the association between fundus autofluorescence (FAF) and retinal structure and function in retinitis pigmentosa (RP). For image acquisition, HRA2 (Heidelberg Engineering) and 3D-OCT1000 (Topcon Corp.) were used. Based on FAF examination, 88 eyes of 44 RP patients were categorized into three types. The area within the hyperautofluorescent ring and the area of preserved retinal autofluorescence with FAF was calculated. The association between the pattern of FAF and the residual area of the junction between the inner and outer segments of the photoreceptors (IS/OS line), and the relationship between the area within hyperautofluorescent ring, the area of preserved retinal autofluorescence and the mean deviation (MD) of static perimetry were assessed. Twenty-four eyes were with preserved retinal autofluorescence without hyperautofluorescent ring, 54 eyes were with hyperautofluorescent ring and ten eyes were with abnormal foveal autofluorescence both in the fovea and the periphery of the 30° scan. In the first type, the IS/OS line was clearly detected. In the second type, the residual area of the partially distinct IS/OS line corresponded with the area within hyperautofluorescent ring with significant correlation between the area within hyperautofluorescent ring and the MD (R(2) = 0.705, p < 0.001); however, there was no correlation between the area of preserved retinal autofluorescence and the MD, or between the area of preserved retinal autofluorescence and the area within hyperautofluorescent ring. In the third type, the IS/OS line was completely absent. The residual IS/OS line can be found in the area inside the hyperautofluorescent ring and correlates with residual visual function.

Multiparametric optical coherence tomography imaging of the inner retinal hemodynamic response to visual stimulation

NASA Astrophysics Data System (ADS)

Radhakrishnan, Harsha; Srinivasan, Vivek J.

2013-08-01

The hemodynamic response to neuronal activation is a well-studied phenomenon in the brain, due to the prevalence of functional magnetic resonance imaging. The retina represents an optically accessible platform for studying lamina-specific neurovascular coupling in the central nervous system; however, due to methodological limitations, this has been challenging to date. We demonstrate techniques for the imaging of visual stimulus-evoked hyperemia in the rat inner retina using Doppler optical coherence tomography (OCT) and OCT angiography. Volumetric imaging with three-dimensional motion correction, en face flow calculation, and normalization of dynamic signal to static signal are techniques that reduce spurious changes caused by motion. We anticipate that OCT imaging of retinal functional hyperemia may yield viable biomarkers in diseases, such as diabetic retinopathy, where the neurovascular unit may be impaired.

Delineation of the vitreous and posterior hyaloid using bromophenol blue.

PubMed

Haritoglou, Christos; Strauss, Rupert; Priglinger, Siegfried G; Kreutzer, Thomas; Kampik, Anselm

2008-02-01

To describe visualization of the vitreous and the posterior hyaloid membrane using bromophenol blue during vitrectomy for macular hole and retinal detachment. Six patients with macular holes and four with retinal detachments were included in the study. Before and after surgery, complete clinical examination, including funduscopy and measurements of best-corrected visual acuity and intraocular pressure, was performed. Additional functional tests, such as fluorescein angiography, optical coherence tomography (Stratus OCT; Carl Zeiss Meditec, Jena, Germany, Germany), Goldmann perimetry, and multifocal electroretinography as well as photography of the posterior pole, were performed for macular hole patients. Bromophenol blue was used in concentrations of 0.2%. During macular hole surgery, the dye was injected into the air-filled globe, while during surgery for retinal detachment, the globe was partially filled with perfluorocarbon before dye injection after induction of a posterior vitreous detachment to stain the vitreous peripherally. Bromophenol blue provided sufficient staining of the attached posterior hyaloid membrane and vitreous remnants in the periphery. This was especially helpful for patients in whom a posterior vitreous detachment could not be induced mechanically by suction using the vitrectomy probe alone, as seen in three of six interventions for a macular hole in this series. In addition, staining of the vitreous or vitreous remnants in the periphery and at the vitreous base was seen in all patients and helped to completely remove the vitreous in a controlled fashion. After macular hole surgery, increase of visual acuity from 20/100 (mean) to 20/40 was seen during follow-up up to 6 months. In one case, the hole persisted and required a second operation. Finally, closure of the hole was achieved in all patients. After retinal detachment surgery, reattachment was achieved in all cases. No dye-related adverse events were seen during follow-up as shown by the functional tests (visual acuity measurement, electroretinography, and perimetry) applied. Delineation of the vitreous and the posterior hyaloid using bromophenol blue staining greatly facilitates vitreoretinal procedures. Bromophenol blue appeared to be a very helpful and safe tool to visualize the posterior hyaloid membrane in macular hole surgery and assured its complete separation from the retinal surface. The dye also helped to remove vitreous at the vitreous base during retinal detachment surgery. Therefore, bromophenol blue appears as a very good alternative to triamcinolone, which has been used for this purpose, because the dye has no pharmacological properties and no side effects are likely to occur such as cataract formation and increase in intraocular pressure. Further studies including larger numbers of patients are mandatory.

Following the ontogeny of retinal waves: pan-retinal recordings of population dynamics in the neonatal mouse

PubMed Central

Maccione, Alessandro; Hennig, Matthias H; Gandolfo, Mauro; Muthmann, Oliver; van Coppenhagen, James; Eglen, Stephen J; Berdondini, Luca; Sernagor, Evelyne

2014-01-01

The immature retina generates spontaneous waves of spiking activity that sweep across the ganglion cell layer during a limited period of development before the onset of visual experience. The spatiotemporal patterns encoded in the waves are believed to be instructive for the wiring of functional connections throughout the visual system. However, the ontogeny of retinal waves is still poorly documented as a result of the relatively low resolution of conventional recording techniques. Here, we characterize the spatiotemporal features of mouse retinal waves from birth until eye opening in unprecedented detail using a large-scale, dense, 4096-channel multielectrode array that allowed us to record from the entire neonatal retina at near cellular resolution. We found that early cholinergic waves propagate with random trajectories over large areas with low ganglion cell recruitment. They become slower, smaller and denser when GABAA signalling matures, as occurs beyond postnatal day (P) 7. Glutamatergic influences dominate from P10, coinciding with profound changes in activity dynamics. At this time, waves cease to be random and begin to show repetitive trajectories confined to a few localized hotspots. These hotspots gradually tile the retina with time, and disappear after eye opening. Our observations demonstrate that retinal waves undergo major spatiotemporal changes during ontogeny. Our results support the hypotheses that cholinergic waves guide the refinement of retinal targets and that glutamatergic waves may also support the wiring of retinal receptive fields. PMID:24366261

Successful arrest of photoreceptor and vision loss expands the therapeutic window of retinal gene therapy to later stages of disease

PubMed Central

Beltran, William A.; Cideciyan, Artur V.; Iwabe, Simone; Swider, Malgorzata; Kosyk, Mychajlo S.; McDaid, Kendra; Martynyuk, Inna; Ying, Gui-Shuang; Shaffer, James; Deng, Wen-Tao; Boye, Sanford L.; Lewin, Alfred S.; Hauswirth, William W.; Jacobson, Samuel G.; Aguirre, Gustavo D.

2015-01-01

Inherited retinal degenerations cause progressive loss of photoreceptor neurons with eventual blindness. Corrective or neuroprotective gene therapies under development could be delivered at a predegeneration stage to prevent the onset of disease, as well as at intermediate-degeneration stages to slow the rate of progression. Most preclinical gene therapy successes to date have been as predegeneration interventions. In many animal models, as well as in human studies, to date, retinal gene therapy administered well after the onset of degeneration was not able to modify the rate of progression even when successfully reversing dysfunction. We evaluated consequences of gene therapy delivered at intermediate stages of disease in a canine model of X-linked retinitis pigmentosa (XLRP) caused by a mutation in the Retinitis Pigmentosa GTPase Regulator (RPGR) gene. Spatiotemporal natural history of disease was defined and therapeutic dose selected based on predegeneration results. Then interventions were timed at earlier and later phases of intermediate-stage disease, and photoreceptor degeneration monitored with noninvasive imaging, electrophysiological function, and visual behavior for more than 2 y. All parameters showed substantial and significant arrest of the progressive time course of disease with treatment, which resulted in long-term improved retinal function and visual behavior compared with control eyes. Histology confirmed that the human RPGR transgene was stably expressed in photoreceptors and associated with improved structural preservation of rods, cones, and ON bipolar cells together with correction of opsin mislocalization. These findings in a clinically relevant large animal model demonstrate the long-term efficacy of RPGR gene augmentation and substantially broaden the therapeutic window for intervention in patients with RPGR-XLRP. PMID:26460017

Resting-State Retinotopic Organization in the Absence of Retinal Input and Visual Experience

PubMed Central

Binda, Paola; Benson, Noah C.; Bridge, Holly; Watkins, Kate E.

2015-01-01

Early visual areas have neuronal receptive fields that form a sampling mosaic of visual space, resulting in a series of retinotopic maps in which the same region of space is represented in multiple visual areas. It is not clear to what extent the development and maintenance of this retinotopic organization in humans depend on retinal waves and/or visual experience. We examined the corticocortical receptive field organization of resting-state BOLD data in normally sighted, early blind, and anophthalmic (in which both eyes fail to develop) individuals and found that resting-state correlations between V1 and V2/V3 were retinotopically organized for all subject groups. These results show that the gross retinotopic pattern of resting-state connectivity across V1-V3 requires neither retinal waves nor visual experience to develop and persist into adulthood. SIGNIFICANCE STATEMENT Evidence from resting-state BOLD data suggests that the connections between early visual areas develop and are maintained even in the absence of retinal waves and visual experience. PMID:26354906

Proinsulin slows retinal degeneration and vision loss in the P23H rat model of retinitis pigmentosa.

PubMed

Fernández-Sánchez, Laura; Lax, Pedro; Isiegas, Carolina; Ayuso, Eduard; Ruiz, José M; de la Villa, Pedro; Bosch, Fatima; de la Rosa, Enrique J; Cuenca, Nicolás

2012-12-01

Proinsulin has been characterized as a neuroprotective molecule. In this work we assess the therapeutic potential of proinsulin on photoreceptor degeneration, synaptic connectivity, and functional activity of the retina in the transgenic P23H rat, an animal model of autosomal dominant retinitis pigmentosa (RP). P23H homozygous rats received an intramuscular injection of an adeno-associated viral vector serotype 1 (AAV1) expressing human proinsulin (hPi+) or AAV1-null vector (hPi-) at P20. Levels of hPi in serum were determined by enzyme-linked immunosorbent assay (ELISA), and visual function was evaluated by electroretinographic (ERG) recording at P30, P60, P90, and P120. Preservation of retinal structure was assessed by immunohistochemistry at P120. Human proinsulin was detected in serum from rats injected with hPi+ at all times tested, with average hPi levels ranging from 1.1 nM (P30) to 1.4 nM (P120). ERG recordings showed an amelioration of vision loss in hPi+ animals. The scotopic b-waves were significantly higher in hPi+ animals than in control rats at P90 and P120. This attenuation of visual deterioration correlated with a delay in photoreceptor degeneration and the preservation of retinal cytoarchitecture. hPi+ animals had 48.7% more photoreceptors than control animals. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were preserved in hPi+ P23H rats. Furthermore, in hPi+ rat retinas the number of rod bipolar cell bodies was greater than in control rats. Our data demonstrate that hPi expression preserves cone and rod structure and function, together with their contacts with postsynaptic neurons, in the P23H rat. These data strongly support the further development of proinsulin-based therapy to counteract retinitis pigmentosa.

The use of bevacizumab in a multilevel retinal hemorrhage secondary to retinal macroaneurysm: a 39-month follow-up case report

PubMed Central

Tsakpinis, Dimitrios; Nasr, Mayssa B; Tranos, Paris; Krassas, Nikos; Giannopoulos, Theodoros; Symeonidis, Chrysanthos; Dimitrakos, Stavros A; Konstas, Anastasios GP

2011-01-01

Purpose The evaluation of long-term visual outcome after the use of bevacizumab for the management of multilevel hemorrhage due to retinal arterial macroaneurysm (MA). Case report A 71-year-old hypertensive female presented with sudden reduction of visual acuity in her left eye (OS). Fundoscopy revealed an arterial macroaneurysm with preretinal and subretinal hemorrhage in the eye. Due to significant macular involvement, the patient received two intravitreal injections of bevacizumab within 2 months. Results Significant visual and anatomical recovery was observed 2 months later, which was confirmed by fluorescein angiography. At the end of a follow-up period (39 months) visual acuity and visual field were at normal levels. Conclusion Retinal MA is a relatively rare condition. Anti-vascular endothelial growth factor therapy appears a safe and effective treatment option for selected symptomatic individuals that may offer faster visual rehabilitation. Herein we report, for the first time, a 39-month follow-up of a retinal MA treated with anti-vascular endothelial growth factor therapy. PMID:22069349

Ganglion cell-inner plexiform layer and retinal nerve fibre layer changes within the macula in retinitis pigmentosa: a spectral domain optical coherence tomography study.

PubMed

Yoon, Chang Ki; Yu, Hyeong Gon

2018-03-01

To investigate how macular ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fibre layer (RNFL) thicknesses within the macula change with retinitis pigmentosa (RP) severity. Spectral domain optical coherence tomography (SD-OCT) was used to examine 177 patients with RP and 177 normal controls. An optical coherence tomography (OCT) line scan was used to grade RP severity. Retinitis pigmentosa (RP) was categorized as more advanced if there was no identifiable inner segment ellipsoid (ISe) band (NISE) and as less advanced if an ISe band could be identified and peripheral loss of ISe was apparent (IISE). Ganglion cell-inner plexiform layer (GCIPL) and RNFL thicknesses were manually measured on OCT images and analysed. Pearson's correlation analyses were used to examine correlations between GCIPL thickness, RNFL thickness, visual acuity (VA) and visual field extent in patients and controls. Ganglion cell-inner plexiform layer (GCIPL) was significantly thicker in IISE than in control eyes (p < 0.001), but significantly thinner in NISE than in IISE eyes (p < 0.001) in both horizontal and vertical OCT scans. Retinal nerve fibre layer (RNFL) was significantly thicker in eyes with IISE and NISE than in control eyes in both horizontal and vertical meridians (all p < 0.001). Ganglion cell-inner plexiform layer (GCIPL) thickness showed a weak positive correlation with vision, and RNFL thickness showed a weak negative correlation with vision and visual field extent. Based on these results, the inner retina, including the GCIPL and RNFL, maintains its gross integrity longer than the photoreceptor layer in RP. Additionally, thickening of the inner retina may have some functional implications in patients with RP. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Retrobulbar optic neuritis and rhegmatogenous retinal detachment in a fourteen-year-old girl with retinitis pigmentosa sine pigmento.

PubMed

Hatta, M; Hayasaka, S; Kato, T; Kadoi, C

2000-01-01

A 14-year-old girl complained of a sudden decrease in right visual acuity. The patient had night blindness, a mottled retina but no pigments, extinguished scotopic electroretinographic response, central scotoma in the right eye and rhegmatogenous retinal detachment. She had initially received laser photocoagulation around the retinal tear and then corticosteroid therapy, cryoretinopexy and segmental buckling. Her right visual acuity increased to 1.0. The association of retinitis pigmentosa sine pigmento, retrobulbar optic neuritis and rhegmatogenous retinal detachment, as demonstrated in our patient, may be uncommon. Copyright 2000 S. Karger AG, Basel

X‐linked retinoschisis: an update

PubMed Central

Sikkink, Stephen K; Biswas, Susmito; Parry, Neil R A; Stanga, Paulo E; Trump, Dorothy

2007-01-01

X‐linked retinoschisis is the leading cause of macular degeneration in males and leads to splitting within the inner retinal layers leading to visual deterioration. Many missense and protein truncating mutations have now been identified in the causative retinoschisis gene (RS1) which encodes a 224 amino acid secreting retinal protein, retinoschisin. Retinoschisin octamerises is implicated in cell–cell interactions and cell adhesion perhaps by interacting with β2 laminin. Mutations cause loss of retinoschisin function by one of the three mechanisms: by interfering with protein secretion, by preventing its octamerisation or by reducing function in the secreted octamerised protein. The development of retinoschisis mouse models have provided a model system that closely resembles the human disease. Recent reports of RS1 gene transfer to these models and the sustained restoration of some retinal function and morphology suggest gene replacement may be a possible future therapy for patients. PMID:17172462

Emergence of binocular functional properties in a monocular neural circuit

PubMed Central

Ramdya, Pavan; Engert, Florian

2010-01-01

Sensory circuits frequently integrate converging inputs while maintaining precise functional relationships between them. For example, in mammals with stereopsis, neurons at the first stages of binocular visual processing show a close alignment of receptive-field properties for each eye. Still, basic questions about the global wiring mechanisms that enable this functional alignment remain unanswered, including whether the addition of a second retinal input to an otherwise monocular neural circuit is sufficient for the emergence of these binocular properties. We addressed this question by inducing a de novo binocular retinal projection to the larval zebrafish optic tectum and examining recipient neuronal populations using in vivo two-photon calcium imaging. Notably, neurons in rewired tecta were predominantly binocular and showed matching direction selectivity for each eye. We found that a model based on local inhibitory circuitry that computes direction selectivity using the topographic structure of both retinal inputs can account for the emergence of this binocular feature. PMID:19160507

Clinical application of optical coherence tomography in combination with functional diagnostics: advantages and limitations for diagnosis and assessment of therapy outcome in central serous chorioretinopathy.

PubMed

Schliesser, Joshua A; Gallimore, Gary; Kunjukunju, Nancy; Sabates, Nelson R; Koulen, Peter; Sabates, Felix N

2014-01-01

While identifying functional and structural parameters of the retina in central serous chorioretinopathy (CSCR) patients, this study investigated how an optical coherence tomography (OCT)-based diagnosis can be significantly supplemented with functional diagnostic tools and to what degree the determination of disease severity and therapy outcome can benefit from diagnostics complementary to OCT. CSCR patients were evaluated prospectively with microperimetry (MP) and spectral domain optical coherence tomography (SD-OCT) to determine retinal sensitivity function and retinal thickness as outcome measures along with measures of visual acuity (VA). Patients received clinical care that involved focal laser photocoagulation or pharmacotherapy targeting inflammation and neovascularization. Correlation of clinical parameters with a focus on functional parameters, VA, and mean retinal sensitivity, as well as on the structural parameter mean retinal thickness, showed that functional measures were similar in diagnostic power. A moderate correlation was found between OCT data and the standard functional assessment of VA; however, a strong correlation between OCT and MP data showed that diagnostic measures cannot always be used interchangeably, but that complementary use is of higher clinical value. The study indicates that integrating SD-OCT with MP provides a more complete diagnosis with high clinical relevance for complex, difficult to quantify diseases such as CSCR.

Observation of Human Retinal Remodeling in Octogenarians with a Resveratrol Based Nutritional Supplement

PubMed Central

Richer, Stuart; Stiles, William; Ulanski, Lawrence; Carroll, Donn; Podella, Carla

2013-01-01

Purpose: Rare spontaneous remissions from age-related macular degeneration (AMD) suggest the human retina has large regenerative capacity, even in advanced age. We present examples of robust improvement of retinal structure and function using an OTC oral resveratrol (RV) based nutritional supplement called Longevinex® or L/RV (circa 2004, Resveratrol Partners, LLC, Las Vegas, NV, USA). RV, a polyphenolic phytoalexin caloric-restriction mimic, induces hormesis at low doses with widespread beneficial effects on systemic health. RV alone inhibits neovascularization in the murine retina. Thus far, published evidence includes L/RV mitigation of experimentally induced murine cardiovascular reperfusion injury, amelioration of human atherosclerosis serum biomarkers in a human Japanese randomized placebo controlled trial, modulation of micro RNA 20b and 539 that control hypoxia-inducing-factor (HIF-1) and vascular endothelial growth factor (VEGF) genes in the murine heart (RV inhibited micro RNA20b 189-fold, L/RV 1366-fold). Little is known about the effects of L/RV on human ocular pathology. Methods: Absent FDA IRB approval, but with permission from our Chief of Staff and medical center IRB, L/RV is reserved for AMD patients, on a case-by-case compassionate care basis. Patients include those who progress on AREDS II type supplements, refuse intra-vitreal anti-VEGF injections or fail to respond to Lucentis®, Avastin® or Eylea®. Patients are clinically followed traditionally as well as with multi-spectral retinal imaging, visual acuity, contrast sensitivity, cone glare recovery and macular visual fields. Three cases are presented. Results: Observed dramatic short-term anti-VEGF type effect including anatomic restoration of retinal structure with a suggestion of improvement in choroidal blood flow by near IR multispectral imaging. The visual function improvement mirrors the effect seen anatomically. The effect is bilateral with the added benefit of better RPE function. Effects have lasted for one year or longer when taken daily, at which point one patient required initiation of anti-VEGF agents. Unanticipated systemic benefits were observed. Conclusions: Preliminary observations support previous publications in animals and humans. Restoration of structure and visual function in octogenarians with daily oral consumption of L/RV is documented. Applications include failure on AREDS II supplements, refusing or failing conventional anti-VEGF therapy, adjunct therapy to improve RPE function, and compassionate use in medically underserved or economically depressed third-world countries. PMID:23736827

Retinitis Pigmentosa Sine Pigmento Mimicking a Chiasm Disease.

PubMed

Pellegrini, Francesco; Prosdocimo, Giovanni; Romano, Francesco; Interlandi, Emanuela

2017-08-01

A 75-year-old woman presented to her ophthalmologist complaining of visual loss for several years. The ophthalmic examination was remarkable for a bitemporal visual field defect. Magnetic resonance imaging (MRI) scan of the brain was normal without evidence of chiasm compression. Neuro-ophthalmic examination was consistent with a retinal rather than a chiasmal disease. Retinal multimodal imaging helped in the correct diagnosis of retinitis pigmentosa, later confirmed by genetic testing.

2,3,7,8-TCDD effects on visual structure and function in swim-up rainbow trout

USGS Publications Warehouse

Carvalho, Paulo S. M.

2004-01-01

An understanding of mechanisms of contaminant effects across levels of biological organization is essential in ecotoxicology if we are to generate predictive models for population-level effects. We applied a suite of biochemical, histological, and behavioral end points related to visual structure and function and foraging behavior to evaluate effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on swim-up rainbow trout. We detected a dose-dependent decrease in densities of retinal ganglion cells (RGC), key retinal neurons that link the eye with the brain. These changes resulted in corresponding deficits in visual/motor function including reductions in visual acuity and in scotopic and photopic thresholds due to TCDD. The loss of RGCs suggests an increase in convergence of synapses from photoreceptors to RGCs as a cellular mechanism for the visual deficits. Dose-dependent increases in immunohistochemical detection of CYP1A protein in the vasculature of the brain and eye choroid was proportional with decreased ganglion cell densities in the retina. TCDD-induced AHR-regulated effects on these tissues might be involved in the detected decrease in ganglion cell densities. Prey capture rate decreased after TCDD exposure only at the highest treatment groups evaluated. Collectively, these results show that TCDD causes biochemical and structural changes in the eye and brain of rainbow trout that are associated with behavioral deficits leading to decreased individual fitness.

Preservation of visual cortical function following retinal pigment epithelium transplantation in the RCS rat using optical imaging techniques.

PubMed

Gias, Carlos; Jones, Myles; Keegan, David; Adamson, Peter; Greenwood, John; Lund, Ray; Martindale, John; Johnston, David; Berwick, Jason; Mayhew, John; Coffey, Peter

2007-04-01

The aim of this study was to determine the extent of cortical functional preservation following retinal pigment epithelium (RPE) transplantation in the Royal College of Surgeons (RCS) rat using single-wavelength optical imaging and spectroscopy. The cortical responses to visual stimulation in transplanted rats at 6 months post-transplantation were compared with those from age-matched untreated dystrophic and non-dystrophic rats. Our results show that cortical responses were evoked in non-dystrophic rats to both luminance changes and pattern stimulation, whereas no response was found in untreated dystrophic animals to any of the visual stimuli tested. In contrast, a cortical response was elicited in most of the transplanted rats to luminance changes and in many of those a response was also evoked to pattern stimulation. Although the transplanted rats did not respond to high spatial frequency information we found evidence of preservation in the cortical processing of luminance changes and low spatial frequency stimulation. Anatomical sections of transplanted rat retinas confirmed the capacity of RPE transplantation to rescue photoreceptors. Good correlation was found between photoreceptor survival and the extent of cortical function preservation determined with optical imaging techniques. This study determined the efficacy of RPE transplantation to preserve visual cortical processing and established optical imaging as a powerful technique for its assessment.

Early light deprivation effects on human cone-driven retinal function.

PubMed

Esposito Veneruso, Paolo; Ziccardi, Lucia; Magli, Giulia; Parisi, Vincenzo; Falsini, Benedetto; Magli, Adriano

2017-03-01

To assess whether the early light deprivation induced by congenital cataract may influence the cone-driven retinal function in humans. Forty-one patients affected by congenital cataract (CC) who had undergone uncomplicated cataract extraction surgery and intraocular lens implant, and 14 healthy subjects (HS) were enrolled. All patients underwent complete ophthalmological and orthoptic evaluations and best-corrected visual acuity (BCVA) measurement; light-adapted full-field electroretinograms (ERG) and photopic negative responses (PhNR) were recorded to obtain a reliable measurement of the outer/inner retinal function and of the retinal ganglion cells' function respectively. Mean values of light-adapted ERG a- and b-wave and PhNR amplitude of CC eyes were significantly reduced and photopic ERG b-wave implicit time mean values were significantly delayed when compared to HS ones. When studying photopic ERG mean amplitudes at 5 ms, significant differences were found when comparing CC and control eyes. In CC eyes, statistically significant correlations were found between a- and b- wave amplitudes and PhNR amplitudes. No significant correlations were found between ERG parameters and BCVA, as well as between the age of CC patients at surgery and the time elapsed from lens extraction. No significant differences were found when functional parameters of bilateral and unilateral congenital cataract (uCC) eyes were compared, however uCC eyes showed significant differences when compared with contralateral healthy eyes. We found a significant impairment of cone-driven retinal responses in patients with a history of congenital cataract. These changes might result from the long-lasting effects of early light deprivation on the cone retinal pathways. Our findings support the relevance of retinal involvement in deficits induced by early light deprivation. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Representation of the visual field in the primary visual area of the marmoset monkey: magnification factors, point-image size, and proportionality to retinal ganglion cell density.

PubMed

Chaplin, Tristan A; Yu, Hsin-Hao; Rosa, Marcello G P

2013-04-01

The primary visual area (V1) forms a systematic map of the visual field, in which adjacent cell clusters represent adjacent points of visual space. A precise quantification of this map is key to understanding the anatomical relationships between neurons located in different stations of the visual pathway, as well as the neural bases of visual performance in different regions of the visual field. We used computational methods to quantify the visual topography of V1 in the marmoset (Callithrix jacchus), a small diurnal monkey. The receptive fields of neurons throughout V1 were mapped in two anesthetized animals using electrophysiological recordings. Following histological reconstruction, precise 3D reconstructions of the V1 surface and recording sites were generated. We found that the areal magnification factor (M(A) ) decreases with eccentricity following a function that has the same slope as that observed in larger diurnal primates, including macaque, squirrel, and capuchin monkeys, and humans. However, there was no systematic relationship between M(A) and polar angle. Despite individual variation in the shape of V1, the relationship between M(A) and eccentricity was preserved across cases. Comparison between V1 and the retinal ganglion cell density demonstrated preferential magnification of central space in the cortex. The size of the cortical compartment activated by a punctiform stimulus decreased from the foveal representation towards the peripheral representation. Nonetheless, the relationship between the receptive field sizes of V1 cells and the density of ganglion cells suggested that each V1 cell receives information from a similar number of retinal neurons, throughout the visual field. Copyright © 2012 Wiley Periodicals, Inc.

Visual field defects after missile injuries to the geniculo-striate pathway in man.

NASA Technical Reports Server (NTRS)

Koerner, F.; Teuber, H.-L.

1973-01-01

The main objective of the survey reported was a quantitative comparison of different visual functions at identical retinal points of individual patients. The possibility to develop objective forms of visual-field testing was also explored, taking into account reports by Frydrychowicz and Harms (1940) and Harms (1951). These investigators had insisted that pupillary responses to light are depressed in areas of homonymous scotomata. The shapes of homonymous visual field defects are discussed together with questions regarding the association and dissociation of symptoms.

Deafferented Adult Rod Bipolar Cells Create New Synapses with Photoreceptors to Restore Vision.

PubMed

Beier, Corinne; Hovhannisyan, Anahit; Weiser, Sydney; Kung, Jennifer; Lee, Seungjun; Lee, Dae Yeong; Huie, Philip; Dalal, Roopa; Palanker, Daniel; Sher, Alexander

2017-04-26

Upon degeneration of photoreceptors in the adult retina, interneurons, including bipolar cells, exhibit a plastic response leading to their aberrant rewiring. Photoreceptor reintroduction has been suggested as a potential approach to sight restoration, but the ability of deafferented bipolar cells to establish functional synapses with photoreceptors is poorly understood. Here we use photocoagulation to selectively destroy photoreceptors in adult rabbits while preserving the inner retina. We find that rods and cones shift into the ablation zone over several weeks, reducing the blind spot at scotopic and photopic luminances. During recovery, rod and cone bipolar cells exhibit markedly different responses to deafferentation. Rod bipolar cells extend their dendrites to form new synapses with healthy photoreceptors outside the lesion, thereby restoring visual function in the deafferented retina. Secretagogin-positive cone bipolar cells did not exhibit such obvious dendritic restructuring. These findings are encouraging to the idea of photoreceptor reintroduction for vision restoration in patients blinded by retinal degeneration. At the same time, they draw attention to the postsynaptic side of photoreceptor reintroduction; various bipolar cell types, representing different visual pathways, vary in their response to the photoreceptor loss and in their consequent dendritic restructuring. SIGNIFICANCE STATEMENT Loss of photoreceptors during retinal degeneration results in permanent visual impairment. Strategies for vision restoration based on the reintroduction of photoreceptors inherently rely on the ability of the remaining retinal neurons to correctly synapse with new photoreceptors. We show that deafferented bipolar cells in the adult mammalian retina can reconnect to rods and cones and restore retinal sensitivity at scotopic and photopic luminances. Rod bipolar cells extend their dendrites to form new synapses with healthy rod photoreceptors. These findings support the idea that bipolar cells might be able to synapse with reintroduced photoreceptors, thereby restoring vision in patients blinded by retinal degeneration. Copyright © 2017 the authors 0270-6474/17/374635-10$15.00/0.

Management of inadvertent needle penetration resulting in subretinal triamcinolone acetonide and retinal detachment.

PubMed

Tran, Kimberly D; Crane, Ashley M; Flynn, Harry W

2018-06-01

To report management of inadvertent needle penetration during subtenons triamcinolone acetonide administration resulting in retinal detachment. A 71-year-old female with history of diabetes, hypothyroidism, and mild myopia underwent subtenons triamcinolone acetonide (TA) injection in the right eye for nodular scleritis. There was unexpected patient movement concurrent with the injection resulting in needle penetration, subretinal and intravitreal injection of TA, superotemporal retinal break, and macula-involving retinal detachment. The patient underwent partial subretinal TA removal, successful retinal detachment repair, and recovered 20/25 visual acuity. In spite of prominent subretinal TA and retinal detachment, successful repair of retinal detachment and recovery of good visual acuity is possible.

Colour vision in ADHD: part 1--testing the retinal dopaminergic hypothesis.

PubMed

Kim, Soyeon; Al-Haj, Mohamed; Chen, Samantha; Fuller, Stuart; Jain, Umesh; Carrasco, Marisa; Tannock, Rosemary

2014-10-24

To test the retinal dopaminergic hypothesis, which posits deficient blue color perception in ADHD, resulting from hypofunctioning CNS and retinal dopamine, to which blue cones are exquisitely sensitive. Also, purported sex differences in red color perception were explored. 30 young adults diagnosed with ADHD and 30 healthy young adults, matched on age and gender, performed a psychophysical task to measure blue and red color saturation and contrast discrimination ability. Visual function measures, such as the Visual Activities Questionnaire (VAQ) and Farnsworth-Munsell 100 hue test (FMT), were also administered. Females with ADHD were less accurate in discriminating blue and red color saturation relative to controls but did not differ in contrast sensitivity. Female control participants were better at discriminating red saturation than males, but no sex difference was present within the ADHD group. Poorer discrimination of red as well as blue color saturation in the female ADHD group may be partly attributable to a hypo-dopaminergic state in the retina, given that color perception (blue-yellow and red-green) is based on input from S-cones (short wavelength cone system) early in the visual pathway. The origin of female superiority in red perception may be rooted in sex-specific functional specialization in hunter-gather societies. The absence of this sexual dimorphism for red colour perception in ADHD females warrants further investigation.

Effects of heavy ions on visual function and electrophysiology of rodents: the ALTEA-MICE project

NASA Technical Reports Server (NTRS)

Sannita, W. G.; Acquaviva, M.; Ball, S. L.; Belli, F.; Bisti, S.; Bidoli, V.; Carozzo, S.; Casolino, M.; Cucinotta, F.; De Pascale, M. P.;

Assessment of Human Visual Performance with a Swept Evoked Potential Technique

DTIC Science & Technology

1984-07-01

obtained in naive patients. Retinitis pigmentosa patients with < 20/50 vision have shown contrast sensitivity losses at the higher spatial frequencies...X and Y visual subsystems The new visual duplicity. Th« observation that cat retinal ganglion cells can be divided into those which sum luminous...bias in retinal ganglion cells (cat: Levick & Thibos, 1980; monkey: DeMonasterio, 1978). The bias is weak. In cat, when the stimulus orientation was

A Computerized System for Measuring Detection Sensitivity over the Visual Field,

DTIC Science & Technology

1986-06-01

variety of conditions can act to degrade this basic configuration of detection capability; e.g., pathology, such as glaucoma and retinitis pigmentosa ...the central line of sight involving the retinal fovea is clearly the locus of greatest visual resolution under photopic viewing conditions, the...Skills. 1974; 41:467-474. 6. Kobrick JL, Appleton S. Effects of hypoxia on visual performance and retinal vascular state. J. Appl. Physiol. 1971; 31:357

Bilateral nanophthalmos and pigmentary retinal dystrophy--an unusual syndrome.

PubMed

Proença, Helena; Castanheira-Dinis, A; Monteiro-Grillo, M

2006-09-01

To report the clinical picture of the rare association of nanophthalmos and pigmentary retinal dystrophy and its cataract surgery outcome. We report a case of a 60-year-old female who presented with bilateral slowly progressive visual loss. The patient presented with bilateral light perception visual acuity, exotropia, brunescent cataract hindering fundus examination and hypodontia. Ultrasonography revealed bilateral nanophthalmos. A visual-evoked potential was also performed preoperatively. Cataract surgery with +40D IOL implantation was uneventful. Postoperative fundus examination revealed pigmentary retinal dystrophy, confirmed by electrophysiologic tests. Glycosaminoglycan urinary excretion was normal. Congenital bilateral nanophthalmos may rarely be associated with pigmentary retinal dystrophy. We suggest thorough preoperative evaluation in nanophthalmic eyes for the exclusion of significant features concerning visual prognosis.

Subchronic Toluene Exposure alters Retinal Function in Long Evans Rats: Experimental Evidence Supporting Observations from Studies of Exposed Humans.

EPA Science Inventory

Studies of humans chronically exposed to volatile organic solvents commonly report impaired visual functions, including low contrast sensitivity and reduced color discrimination. These reports have been controversial, however, in part due to a lack of confirmation from controlled...

IFESS 2005 Special Session 5 Artifical Vision. Final progress report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weiland, James D.

A special session on visual prostheses was held during the Annual Meeting of the International Functional Electrical Stimulation Society (IFESS), in Montreal, Canada, July 5-9, 2005. IFESS is a meeting that typically attracts researchers in implantable nerve stimulators, functional electrical stimulation, and rehabilitation. All of these areas have significant overlap with the retinal prosthesis, but these areas have decades of research behind them. The special session provided a forum for researchers with vast experience in nerve stimulation to interact with leading research in retinal and cortical visual prostheses. The grant paid for the travel and conference costs of the presentersmore » in the session. The session was chaired by James Weiland (the PI on this grant). The session co-chair was Phil Troyk, Ph.D., from the Illinois Institute of Technology. The Department of Energy was acknowledged at the start of the session as the sponsor. The following talks were delivered: Clinical Trial of a Prototype Retinal Prosthesis James Weiland, Ph.D. Doheny Eye Institute, Los Angeles, California The U.S. Department of Energy's Artificial Sight Program Elias Greenbaum, Ph.D. Oak Ridge National Laboratory, Oak Ridge, Tennessee A 16-Channel stimulator ASIC for use in an intracortical visual prosthesis Phillip R. Troyk, Ph.D. Illinois Institute of Technology, Chicago, Illinois Two approaches to the Optic Nerve Visual Prosthesis Jean Delbeke, M.D. University Cath de Louvain, Louvain, Belgium Design and Implementation of High Power Efficiency Modules for a Cortical Visual Stimulator Mohammad Sawan, Ph.D. Ecole Polytechnique de Montreal, Montreal, Canada Remaining funds from the grant were used to support Dr. Weiland's travel to the Association for Research in Vision and Ophthalmology in May 2006, with DOE approval, where several projects, supported by the DOE artificial retina program, were presented.« less

EOG as a monitor of desferrioxamine retinal toxicity.

PubMed

Hidajat, Rudy R; McLay, Jan L; Goode, David H; Spearing, Ruth L

2004-11-01

Iron overload caused by blood transfusion-dependent anaemia usually results in lethal cardiac toxicity unless treated by iron-chelation therapy. Chelation therapy with desferrioxamine (DFO) is well established and widely used to remove excess iron. Unfortunately, visual disorders have been recorded after DFO infusion. In this investigation, a 61-year-old Caucasian female received DFO for her autoimmune haemolytic anaemia. Prior to starting with the DFO treatment, her baseline ophthalmic screening and electrooculogram (EOG) were completely normal. Two years later she noticed a grey scotoma in her right eye. Visual acuity in this eye was reduced from 6/5 to 6/9 and funduscopy revealed evidence of non-specific mottling of the retinal pigment epithelium of both retinae. The EOG was flat (106%) in the right eye and subnormal in the left (155%). The lower limit of our EOG Arden Ratio for normal subjects is 180%. After her DFO treatment was stopped, her right visual acuity returned to 6/5, her field tests showed progressive improvement bilaterally and the EOG went back to the normal range. While waiting for splenectomy, the patient was restarted on a lower dose of DFO and EOG measurements were carried out every two (or three) weeks to monitor for DFO toxicity. The EOG varied during this period indicating some deterioration of function in the retinal pigment epithelium. However, normalisation of the EOG values (right = 217%, left = 217%) occurred after splenectomy and cessation of DFO therapy. Her visual function was normal and her visual acuity 6/4 bilateral when she was discharged from our outpatient clinic. On reviewing her history it was apparent that the EOG was the most sensitive indicator of DFO toxicity.

A novel platform for minimally invasive delivery of cellular therapy as a thin layer across the subretina for treatment of retinal degeneration

NASA Astrophysics Data System (ADS)

Rotenstreich, Ygal; Tzameret, Adi; Kalish, Sapir E.; Belkin, Michael; Meir, Amilia; Treves, Avraham J.; Nagler, Arnon; Sher, Ifat

2015-03-01

Incurable retinal degenerations affect millions worldwide. Stem cell transplantation rescued visual functions in animal models of retinal degeneration. In those studies cells were transplanted in subretinal "blebs", limited number of cells could be injected and photoreceptor rescue was restricted to areas in proximity to the injection sites. We developed a minimally-invasive surgical platform for drug and cell delivery in a thin layer across the subretina and extravascular spaces of the choroid. The novel system is comprised of a syringe with a blunt-tipped needle and an adjustable separator. Human bone marrow mesenchymal stem cells (hBM-MSCs) were transplanted in eyes of RCS rats and NZW rabbits through a longitudinal triangular scleral incision. No immunosuppressants were used. Retinal function was determined by electroretinogram analysis and retinal structure was determined by histological analysis and OCT. Transplanted cells were identified as a thin layer across the subretina and extravascular spaces of the choroid. In RCS rats, cell transplantation delayed photoreceptor degeneration across the entire retina and significantly enhanced retinal functions. No retinal detachment or choroidal hemorrhages were observed in rabbits following transplantation. This novel platform opens a new avenue for drug and cell delivery, placing the transplanted cells in close proximity to the damaged RPE and retina as a thin layer, across the subretina and thereby slowing down cell death and photoreceptor degeneration, without retinal detachment or choroidal hemorrhage. This new transplantation system may increase the therapeutic effect of other cell-based therapies and therapeutic agents. This study is expected to directly lead to phase I/II clinical trials for autologous hBM-MSCs transplantation in retinal degeneration patients.

Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration.

PubMed

Mehat, Manjit S; Sundaram, Venki; Ripamonti, Caterina; Robson, Anthony G; Smith, Alexander J; Borooah, Shyamanga; Robinson, Martha; Rosenthal, Adam N; Innes, William; Weleber, Richard G; Lee, Richard W J; Crossland, Michael; Rubin, Gary S; Dhillon, Baljean; Steel, David H W; Anglade, Eddy; Lanza, Robert P; Ali, Robin R; Michaelides, Michel; Bainbridge, James W B

2018-06-05

Transplantation of human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells offers the potential for benefit in macular degeneration. Previous trials have reported improved visual acuity (VA), but lacked detailed analysis of retinal structure and function in the treated area. Phase 1/2 open-label dose-escalation trial to evaluate safety and potential efficacy (clinicaltrials.gov identifier, NCT01469832). Twelve participants with advanced Stargardt disease (STGD1), the most common cause of macular degeneration in children and young adults. Subretinal transplantation of up to 200 000 hESC-derived RPE cells with systemic immunosuppressive therapy for 13 weeks. The primary end points were the safety and tolerability of hESC-derived RPE cell administration. We also investigated evidence of the survival of transplanted cells and measured retinal structure and function using microperimetry and spectral-domain OCT. Focal areas of subretinal hyperpigmentation developed in all participants in a dose-dependent manner in the recipient retina and persisted after withdrawal of systemic immunosuppression. We found no evidence of uncontrolled proliferation or inflammatory responses. Borderline improvements in best-corrected VA in 4 participants either were unsustained or were matched by a similar improvement in the untreated contralateral eye. Microperimetry demonstrated no evidence of benefit at 12 months in the 12 participants. In one instance at the highest dose, localized retinal thinning and reduced sensitivity in the area of hyperpigmentation suggested the potential for harm. Participant-reported quality of life using the 25-item National Eye Institute Visual Function Questionnaire indicated no significant change. Subretinal hyperpigmentation is consistent with the survival of viable transplanted hESC-derived RPE cells, but may reflect released pigment in their absence. The findings demonstrate the value of detailed analysis of spatial correlation of retinal structure and function in determining with appropriate sensitivity the impact of cell transplantation and suggest that intervention in early stage of disease should be approached with caution. Given the slow rate of progressive degeneration at this advanced stage of disease, any protection against further deterioration may be evident only after a more extended period of observation. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Eccentric correction for off-axis vision in central visual field loss.

PubMed

Gustafsson, Jörgen; Unsbo, Peter

2003-07-01

Subjects with absolute central visual field loss use eccentric fixation and magnifying devices to utilize their residual vision. This preliminary study investigated the importance of an accurate eccentric correction of off-axis refractive errors to optimize the residual visual function for these subjects. Photorefraction using the PowerRefractor instrument was used to evaluate the ametropia in eccentric fixation angles. Methods were adapted for measuring visual acuity outside the macula using filtered optotypes from high-pass resolution perimetry. Optical corrections were implemented, and the visual function of subjects with central visual field loss was measured with and without eccentric correction. Of the seven cases reported, five experienced an improvement in visual function in their preferred retinal locus with eccentric refraction. The main result was that optical correction for better image quality on the peripheral retina is important for the vision of subjects with central visual field loss, objectively as well as subjectively.

Restoration of vision in blind individuals using bionic devices: a review with a focus on cortical visual prostheses.

PubMed

Lewis, Philip M; Ackland, Helen M; Lowery, Arthur J; Rosenfeld, Jeffrey V

2015-01-21

The field of neurobionics offers hope to patients with sensory and motor impairment. Blindness is a common cause of major sensory loss, with an estimated 39 million people worldwide suffering from total blindness in 2010. Potential treatment options include bionic devices employing electrical stimulation of the visual pathways. Retinal stimulation can restore limited visual perception to patients with retinitis pigmentosa, however loss of retinal ganglion cells precludes this approach. The optic nerve, lateral geniculate nucleus and visual cortex provide alternative stimulation targets, with several research groups actively pursuing a cortically-based device capable of driving several hundred stimulating electrodes. While great progress has been made since the earliest works of Brindley and Dobelle in the 1960s and 1970s, significant clinical, surgical, psychophysical, neurophysiological, and engineering challenges remain to be overcome before a commercially-available cortical implant will be realized. Selection of candidate implant recipients will require assessment of their general, psychological and mental health, and likely responses to visual cortex stimulation. Implant functionality, longevity and safety may be enhanced by careful electrode insertion, optimization of electrical stimulation parameters and modification of immune responses to minimize or prevent the host response to the implanted electrodes. Psychophysical assessment will include mapping the positions of potentially several hundred phosphenes, which may require repetition if electrode performance deteriorates over time. Therefore, techniques for rapid psychophysical assessment are required, as are methods for objectively assessing the quality of life improvements obtained from the implant. These measures must take into account individual differences in image processing, phosphene distribution and rehabilitation programs that may be required to optimize implant functionality. In this review, we detail these and other challenges facing developers of cortical visual prostheses in addition to briefly outlining the epidemiology of blindness, and the history of cortical electrical stimulation in the context of visual prosthetics. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Diosmin alleviates retinal edema by protecting the blood-retinal barrier and reducing retinal vascular permeability during ischemia/reperfusion injury.

PubMed

Tong, Nianting; Zhang, Zhenzhen; Zhang, Wei; Qiu, Yating; Gong, Yuanyuan; Yin, Lili; Qiu, Qinghua; Wu, Xingwei

2013-01-01

Retinal swelling, leading to irreversible visual impairment, is an important early complication in retinal ischemia/reperfusion (I/R) injury. Diosmin, a naturally occurring flavonoid glycoside, has been shown to have antioxidative and anti-inflammatory effects against I/R injury. The present study was performed to evaluate the retinal microvascular protective effect of diosmin in a model of I/R injury. Unilateral retinal I/R was induced by increasing intraocular pressure to 110 mm Hg for 60 min followed by reperfusion. Diosmin (100 mg/kg) or vehicle solution was administered intragastrically 30 min before the onset of ischemia and then daily after I/R injury until the animals were sacrificed. Rats were evaluated for retinal functional injury by electroretinogram (ERG) just before sacrifice. Retinas were harvested for HE staining, immunohistochemistry assay, ELISA, and western blotting analysis. Evans blue (EB) extravasation was determined to assess blood-retinal barrier (BRB) disruption and the structure of tight junctions (TJ) was examined by transmission electron microscopy. Diosmin significantly ameliorated the reduction of b-wave, a-wave, and b/a ratio in ERG, alleviated retinal edema, protected the TJ structure, and reduced EB extravasation. All of these effects of diosmin were associated with increased zonular occluden-1 (ZO-1) and occludin protein expression and decreased VEGF/PEDF ratio. Maintenance of TJ integrity and reduced permeability of capillaries as well as improvements in retinal edema were observed with diosmin treatment, which may contribute to preservation of retinal function. This protective effect of diosmin may be at least partly attributed to its ability to regulate the VEGF/PEDF ratio.

Focal damage to macaque photoreceptors produces persistent visual loss

PubMed Central

Strazzeri, Jennifer M.; Hunter, Jennifer J.; Masella, Benjamin D.; Yin, Lu; Fischer, William S.; DiLoreto, David A.; Libby, Richard T.; Williams, David R.; Merigan, William H.

2014-01-01

Insertion of light-gated channels into inner retina neurons restores neural light responses, light evoked potentials, visual optomotor responses and visually-guided maze behavior in mice blinded by retinal degeneration. This method of vision restoration bypasses damaged outer retina, providing stimulation directly to retinal ganglion cells in inner retina. The approach is similar to that of electronic visual protheses, but may offer some advantages, such as avoidance of complex surgery and direct targeting of many thousands of neurons. However, the promise of this technique for restoring human vision remains uncertain because rodent animal models, in which it has been largely developed, are not ideal for evaluating visual perception. On the other hand, psychophysical vision studies in macaque can be used to evaluate different approaches to vision restoration in humans. Furthermore, it has not been possible to test vision restoration in macaques, the optimal model for human-like vision, because there has been no macaque model of outer retina degeneration. In this study, we describe development of a macaque model of photoreceptor degeneration that can in future studies be used to test restoration of perception by visual prostheses. Our results show that perceptual deficits caused by focal light damage are restricted to locations at which photoreceptors are damaged, that optical coherence tomography (OCT) can be used to track such lesions, and that adaptive optics retinal imaging, which we recently used for in vivo recording of ganglion cell function, can be used in future studies to examine these lesions. PMID:24316158

Retinitis Pigmentosa Sine Pigmento Mimicking a Chiasm Disease

PubMed Central

Pellegrini, Francesco; Prosdocimo, Giovanni; Romano, Francesco; Interlandi, Emanuela

2017-01-01

ABSTRACT A 75-year-old woman presented to her ophthalmologist complaining of visual loss for several years. The ophthalmic examination was remarkable for a bitemporal visual field defect. Magnetic resonance imaging (MRI) scan of the brain was normal without evidence of chiasm compression. Neuro-ophthalmic examination was consistent with a retinal rather than a chiasmal disease. Retinal multimodal imaging helped in the correct diagnosis of retinitis pigmentosa, later confirmed by genetic testing. PMID:29344059

Retinal Origin of Direction Selectivity in the Superior Colliculus

PubMed Central

Shi, Xuefeng; Barchini, Jad; Ledesma, Hector Acaron; Koren, David; Jin, Yanjiao; Liu, Xiaorong; Wei, Wei; Cang, Jianhua

2017-01-01

Detecting visual features in the environment such as motion direction is crucial for survival. The circuit mechanisms that give rise to direction selectivity in a major visual center, the superior colliculus (SC), are entirely unknown. Here, we optogenetically isolate the retinal inputs that individual direction-selective SC neurons receive and find that they are already selective as a result of precisely converging inputs from similarly-tuned retinal ganglion cells. The direction selective retinal input is linearly amplified by the intracollicular circuits without changing its preferred direction or level of selectivity. Finally, using 2-photon calcium imaging, we show that SC direction selectivity is dramatically reduced in transgenic mice that have decreased retinal selectivity. Together, our studies demonstrate a retinal origin of direction selectivity in the SC, and reveal a central visual deficit as a consequence of altered feature selectivity in the retina. PMID:28192394

Visual Circuit Development Requires Patterned Activity Mediated by Retinal Acetylcholine Receptors

PubMed Central

Burbridge, Timothy J.; Xu, Hong-Ping; Ackman, James B.; Ge, Xinxin; Zhang, Yueyi; Ye, Mei-Jun; Zhou, Z. Jimmy; Xu, Jian; Contractor, Anis; Crair, Michael C.

2014-01-01

SUMMARY The elaboration of nascent synaptic connections into highly ordered neural circuits is an integral feature of the developing vertebrate nervous system. In sensory systems, patterned spontaneous activity before the onset of sensation is thought to influence this process, but this conclusion remains controversial largely due to the inherent difficulty recording neural activity in early development. Here, we describe novel genetic and pharmacological manipulations of spontaneous retinal activity, assayed in vivo, that demonstrate a causal link between retinal waves and visual circuit refinement. We also report a de-coupling of downstream activity in retinorecipient regions of the developing brain after retinal wave disruption. Significantly, we show that the spatiotemporal characteristics of retinal waves affect the development of specific visual circuits. These results conclusively establish retinal waves as necessary and instructive for circuit refinement in the developing nervous system and reveal how neural circuits adjust to altered patterns of activity prior to experience. PMID:25466916

Retinal pigment epithelial detachments and tears, and progressive retinal degeneration in light chain deposition disease

PubMed Central

Spielberg, Leigh H; Heckenlively, John R; Leys, Anita M

2013-01-01

Background/purpose Light-chain deposition disease (LCDD) is a rare condition characterised by deposition of monoclonal immunoglobulin light chains (LCs) in tissues, resulting in varying degrees of organ dysfunction. This study reports the characteristic clinical ocular findings seen in advanced LCDD upon development of ocular fundus changes. This is the first report to describe this entity in vivo in a series of patients. Methods A case series of ocular fundus changes in three patients with kidney biopsy-proven LCDD. All patients underwent best corrected visual acuity (BCVA) exam, perimetry, colour fundus photography and fluorescein angiography; two patients underwent indocyanine green angiography, optical coherence tomography, ultrasound and electroretinography; and one patient underwent fundus autofluorescence. Results Three patients, 53–60 years old at initial presentation, were studied. All three presented with night blindness, poor dark adaptation, metamorphopsia and visual loss. Examination revealed serous and serohaemorrhagic detachments, multiple retinal pigment epithelial (RPE) tears, diffuse RPE degeneration and progressive fibrotic changes. Neither choroidal neovascularisation nor other vascular abnormalities were present. Final best corrected visual acuity (BCVA) ranged from 20/40 to 20/300. Conclusions Progressive LC deposition in the fundus seems to damage RPE pump function with flow disturbance between choroid and retina. This pathogenesis can explain the evolution to RPE detachments and subsequent rips and progressive retinal malfunction. PMID:23385633

Long-term results from an epiretinal prosthesis to restore sight to the blind

PubMed Central

Ho, Allen C.; Humayun, Mark S.; Dorn, Jessy D.; da Cruz, Lyndon; Dagnelie, Gislin; Handa, James; Barale, Pierre-Olivier; Sahel, José-Alain; Stanga, Paulo E.; Hafezi, Farhad; Safran, Avinoam B.; Salzmann, Joel; Santos, Arturo; Birch, David; Spencer, Rand; Cideciyan, Artur V.; de Juan, Eugene; Duncan, Jacque L.; Eliott, Dean; Fawzi, Amani; Olmos de Koo, Lisa C.; Brown, Gary C.; Haller, Julia A.; Regillo, Carl D.; Del Priore, Lucian V.; Arditi, Aries; Geruschat, Duane R.; Greenberg, Robert J.

2015-01-01

Purpose Retinitis Pigmentosa (RP) is a group of inherited retinal degenerations leading to blindness due to photoreceptor loss. A rare disease, it affects about 100,000 people in the United States. There is no cure and no approved medical therapy to slow or reverse RP. The purpose of this clinical trial was to evaluate the safety, reliability, and benefit of the Argus® II Retinal Prosthesis System (Second Sight Medical Products, Inc., Sylmar, CA) in restoring some visual function to subjects completely blind from RP. Herein, we report clinical trial results at 1 and 3 years post-implant. Design The study is a multicenter, single-arm, prospective clinical trial. Subjects There were 30 subjects in 10 centers in the U.S. and Europe. Subjects served as their own controls – i.e., implanted eye vs. fellow eye, and System ON vs. System OFF (native residual vision). Methods The Argus II System was implanted on and in a single eye (typically the worse-seeing eye) of blind subjects. Subjects wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. Main Outcome Measures The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by three computer-based, objective tests. Results Twenty-nine out of 30 subjects remained implanted with functioning Argus II Systems at 3 years post-implant. Eleven subjects experienced a total of 23 serious device- or surgery-related adverse events. All were treated with standard ophthalmic care. As a group, subjects performed significantly better with the System ON than OFF on all visual function tests and functional vision assessments. Conclusions The three-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. Earlier results from this trial were used to gain approval of the Argus II by the FDA and a CE Mark in Europe. The Argus II System is the first and only retinal implant to have both approvals. PMID:26162233

Retinal Spectral Domain Optical Coherence Tomography in Early Atrophic Age-Related Macular Degeneration (AMD) and a New Metric for Objective Evaluation of the Efficacy of Ocular Nutrition

PubMed Central

Richer, Stuart; Cho, Jane; Stiles, William; Levin, Marc; Wrobel, James S.; Sinai, Michael; Thomas, Carla

2012-01-01

Purpose: A challenge in ocular preventive medicine is identification of patients with early pathological retinal damage that might benefit from nutritional intervention. The purpose of this study is to evaluate retinal thinning (RT) in early atrophic age-related macular degeneration (AMD) against visual function data from the Zeaxanthin and Visual Function (ZVF) randomized double masked placebo controlled clinical trial (FDA IND #78973). Methods: Retrospective, observational case series of medical center veterans with minimal visible AMD retinopathy (AREDS Report #18 simplified grading 1.4/4.0 bilateral retinopathy). Foveal and extra-foveal four quadrant SDOCT RT measurements were evaluated in n = 54 clinical and ZVF AMD patients. RT by age was determined and compared to the OptoVue SD OCT normative database. RT by quadrant in a subset of n = 29 ZVF patients was correlated with contrast sensitivity and parafoveal blue cone increment thresholds. Results: Foveal RT in AMD patients and non-AMD patients was preserved with age. Extrafoveal regions, however, showed significant slope differences between AMD patients and non-AMD patients, with the superior and nasal quadrants most vulnerable to retinal thinning (sup quad: −5.5 μm/decade thinning vs. Non-AMD: −1.1 μm/decade, P < 0.02; nasal quad: −5.0 μm/decade thinning vs. Non-AMD: −1.0 μm/decade, P < 0.04). Two measures of extrafoveal visual deterioration were correlated: A significant inverse correlation between % RT and contrast sensitivity (r = −0.33, P = 0.01, 2 Tailed Paired T) and an elevated extrafoveal increment blue cone threshold (r = +0.34, P = 0.01, 2 Tailed T). Additional SD OCT RT data for the non-AMD oldest age group (ages 82–91) is needed to fully substantiate the model. Conclusion: A simple new SD OCT clinical metric called “% extra-foveal RT” correlates well with functional visual loss in early AMD patients having minimal visible retinopathy. This metric can be used to follow the effect of repleting ocular nutrients, such as zinc, antioxidants, carotenoids, n-3 essential fats , resveratrol and vitamin D. PMID:23363992

Retinal Layer Abnormalities as Biomarkers of Schizophrenia.

PubMed

Samani, Niraj N; Proudlock, Frank A; Siram, Vasantha; Suraweera, Chathurie; Hutchinson, Claire; Nelson, Christopher P; Al-Uzri, Mohammed; Gottlob, Irene

2018-06-06

Schizophrenia is associated with several brain deficits, as well as visual processing deficits, but clinically useful biomarkers are elusive. We hypothesized that retinal layer changes, noninvasively visualized using spectral-domain optical coherence tomography (SD-OCT), may represent a possible "window" to these abnormalities. A Leica EnvisuTM SD-OCT device was used to obtain high-resolution central foveal B-scans in both eyes of 35 patients with schizophrenia and 50 demographically matched controls. Manual retinal layer segmentation was performed to acquire individual and combined layer thickness measurements in 3 macular regions. Contrast sensitivity was measured at 3 spatial frequencies in a subgroup of each cohort. Differences were compared using adjusted linear models and significantly different layer measures in patients underwent Spearman Rank correlations with contrast sensitivity, quantified symptoms severity, disease duration, and antipsychotic medication dose. Total retinal and photoreceptor complex thickness was reduced in all regions in patients (P < .0001). Segmentation revealed consistent thinning of the outer nuclear layer (P < .001) and inner segment layer (P < .05), as well as a pattern of parafoveal ganglion cell changes. Low spatial frequency contrast sensitivity was reduced in patients (P = .002) and correlated with temporal parafoveal ganglion cell complex thinning (R = .48, P = .01). Negative symptom severity was inversely correlated with foveal photoreceptor complex thickness (R = -.54, P = .001) and outer nuclear layer thickness (R = -.47, P = .005). Our novel findings demonstrate considerable retinal layer abnormalities in schizophrenia that are related to clinical features and visual function. With time, SD-OCT could provide easily-measurable biomarkers to facilitate clinical assessment and further our understanding of the disease.

Imaging light responses of foveal ganglion cells in the living macaque eye.

PubMed

Yin, Lu; Masella, Benjamin; Dalkara, Deniz; Zhang, Jie; Flannery, John G; Schaffer, David V; Williams, David R; Merigan, William H

2014-05-07

The fovea dominates primate vision, and its anatomy and perceptual abilities are well studied, but its physiology has been little explored because of limitations of current physiological methods. In this study, we adapted a novel in vivo imaging method, originally developed in mouse retina, to explore foveal physiology in the macaque, which permits the repeated imaging of the functional response of many retinal ganglion cells (RGCs) simultaneously. A genetically encoded calcium indicator, G-CaMP5, was inserted into foveal RGCs, followed by calcium imaging of the displacement of foveal RGCs from their receptive fields, and their intensity-response functions. The spatial offset of foveal RGCs from their cone inputs makes this method especially appropriate for fovea by permitting imaging of RGC responses without excessive light adaptation of cones. This new method will permit the tracking of visual development, progression of retinal disease, or therapeutic interventions, such as insertion of visual prostheses.

The Role of mf-ERG in the Diagnosis and Treatment of Age-Related Macular Degeneration: Electrophysiological Features of AMD.

PubMed

Moschos, Marilita M; Nitoda, Eirini

2018-01-01

Age-related macular cegeneration (AMD) is the leading cause of visual dysfunction worldwide, affecting 9-25% of individuals between 65 and 75 years old. We have reviewed the published articles investigating the role of multifocal electroretinogram (mf-ERG) in the diagnosis and treatment of AMD. Visual evoked potentials have revealed decreased amplitudes and higher latencies in patients with AMD, while the degeneration of photoreceptors and abnormalities of retinal pigment epithelium can be identified by electro-oculogram recordings. Moreover, ERG can detect the functional abnormalities observed in AMD and evaluate each therapeutic approach. The record of local electrophysiological responses coming from different retinal areas can be accurately performed by mfERG. The accuracy of mfERG in detecting the degeneration of photoreceptors, as well the disturbances of macular function, could be useful both in the early diagnosis of AMD and the assessment of treatment efficacy.

Comparison between the Correlations of Retinal Nerve Fiber Layer Thickness Measured by Spectral Domain Optical Coherence Tomography and Visual Field Defects in Standard Automated White-on-White Perimetry versus Pulsar Perimetry.

PubMed

Alnawaiseh, Maged; Hömberg, Lisann; Eter, Nicole; Prokosch, Verena

2017-01-01

To compare the structure-function relationships between retinal nerve fiber layer thickness (RNFLT) and visual field defects measured either by standard automated perimetry (SAP) or by Pulsar perimetry (PP). 263 eyes of 143 patients were prospectively included. Depending on the RNFLT, patients were assigned to the glaucoma group (group A: RNFL score 3-6) or the control group (group B: RNFL score 0-2). Structure-function relationships between RNFLT and mean sensitivity (MS) measured by SAP and PP were analyzed. Throughout the entire group, the MS assessed by PP and SAP correlated significantly with RNFLT in all sectors. In the glaucoma group, there was no significant difference between the correlations RNFL-SAP and RNFL-PP, whereas a significant difference was found in the control group. In the control group, the correlation between structure and function based on the PP data was significantly stronger than that based on SAP.

The Effects of Dietary Carotenoid Supplementation and Retinal Carotenoid Accumulation on Vision-Mediated Foraging in the House Finch

PubMed Central

Toomey, Matthew B.; McGraw, Kevin J.

2011-01-01

Background For many bird species, vision is the primary sensory modality used to locate and assess food items. The health and spectral sensitivities of the avian visual system are influenced by diet-derived carotenoid pigments that accumulate in the retina. Among wild House Finches (Carpodacus mexicanus), we have found that retinal carotenoid accumulation varies significantly among individuals and is related to dietary carotenoid intake. If diet-induced changes in retinal carotenoid accumulation alter spectral sensitivity, then they have the potential to affect visually mediated foraging performance. Methodology/Principal Findings In two experiments, we measured foraging performance of house finches with dietarily manipulated retinal carotenoid levels. We tested each bird's ability to extract visually contrasting food items from a matrix of inedible distracters under high-contrast (full) and dimmer low-contrast (red-filtered) lighting conditions. In experiment one, zeaxanthin-supplemented birds had significantly increased retinal carotenoid levels, but declined in foraging performance in the high-contrast condition relative to astaxanthin-supplemented birds that showed no change in retinal carotenoid accumulation. In experiments one and two combined, we found that retinal carotenoid concentrations predicted relative foraging performance in the low- vs. high-contrast light conditions in a curvilinear pattern. Performance was positively correlated with retinal carotenoid accumulation among birds with low to medium levels of accumulation (∼0.5–1.5 µg/retina), but declined among birds with very high levels (>2.0 µg/retina). Conclusion/Significance Our results suggest that carotenoid-mediated spectral filtering enhances color discrimination, but that this improvement is traded off against a reduction in sensitivity that can compromise visual discrimination. Thus, retinal carotenoid levels may be optimized to meet the visual demands of specific behavioral tasks and light environments. PMID:21747917

Functional Architecture of the Retina: Development and Disease

PubMed Central

Hoon, Mrinalini; Okawa, Haruhisa; Santina, Luca Della; Wong, Rachel O.L.

2014-01-01

Structure and function are highly correlated in the vertebrate retina, a sensory tissue that is organized into cell layers with microcircuits working in parallel and together to encode visual information. All vertebrate retinas share a fundamental plan, comprising five major neuronal cell classes with cell body distributions and connectivity arranged in stereotypic patterns. Conserved features in retinal design have enabled detailed analysis and comparisons of structure, connectivity and function across species. Each species, however, can adopt structural and/or functional retinal specializations, implementing variations to the basic design in order to satisfy unique requirements in visual function. Recent advances in molecular tools, imaging and electrophysiological approaches have greatly facilitated identification of the cellular and molecular mechanisms that establish the fundamental organization of the retina and the specializations of its microcircuits during development. Here, we review advances in our understanding of how these mechanisms act to shape structure and function at the single cell level, to coordinate the assembly of cell populations, and to define their specific circuitry. We also highlight how structure is rearranged and function is disrupted in disease, and discuss current approaches to re-establish the intricate functional architecture of the retina. PMID:24984227

Functional architecture of the retina: development and disease.

PubMed

Hoon, Mrinalini; Okawa, Haruhisa; Della Santina, Luca; Wong, Rachel O L

2014-09-01

Structure and function are highly correlated in the vertebrate retina, a sensory tissue that is organized into cell layers with microcircuits working in parallel and together to encode visual information. All vertebrate retinas share a fundamental plan, comprising five major neuronal cell classes with cell body distributions and connectivity arranged in stereotypic patterns. Conserved features in retinal design have enabled detailed analysis and comparisons of structure, connectivity and function across species. Each species, however, can adopt structural and/or functional retinal specializations, implementing variations to the basic design in order to satisfy unique requirements in visual function. Recent advances in molecular tools, imaging and electrophysiological approaches have greatly facilitated identification of the cellular and molecular mechanisms that establish the fundamental organization of the retina and the specializations of its microcircuits during development. Here, we review advances in our understanding of how these mechanisms act to shape structure and function at the single cell level, to coordinate the assembly of cell populations, and to define their specific circuitry. We also highlight how structure is rearranged and function is disrupted in disease, and discuss current approaches to re-establish the intricate functional architecture of the retina. Copyright © 2014 Elsevier Ltd. All rights reserved.

Normal Visual Acuity and Electrophysiological Contrast Gain in Adults with High-Functioning Autism Spectrum Disorder.

PubMed

Tebartz van Elst, Ludger; Bach, Michael; Blessing, Julia; Riedel, Andreas; Bubl, Emanuel

2015-01-01

A common neurodevelopmental disorder, autism spectrum disorder (ASD), is defined by specific patterns in social perception, social competence, communication, highly circumscribed interests, and a strong subjective need for behavioral routines. Furthermore, distinctive features of visual perception, such as markedly reduced eye contact and a tendency to focus more on small, visual items than on holistic perception, have long been recognized as typical ASD characteristics. Recent debate in the scientific community discusses whether the physiology of low-level visual perception might explain such higher visual abnormalities. While reports of this enhanced, "eagle-like" visual acuity contained methodological errors and could not be substantiated, several authors have reported alterations in even earlier stages of visual processing, such as contrast perception and motion perception at the occipital cortex level. Therefore, in this project, we have investigated the electrophysiology of very early visual processing by analyzing the pattern electroretinogram-based contrast gain, the background noise amplitude, and the psychophysical visual acuities of participants with high-functioning ASD and controls with equal education. Based on earlier findings, we hypothesized that alterations in early vision would be present in ASD participants. This study included 33 individuals with ASD (11 female) and 33 control individuals (12 female). The groups were matched in terms of age, gender, and education level. We found no evidence of altered electrophysiological retinal contrast processing or psychophysical measured visual acuities. There appears to be no evidence for abnormalities in retinal visual processing in ASD patients, at least with respect to contrast detection.

Plasticity of the human visual system after retinal gene therapy in patients with Leber’s congenital amaurosis

PubMed Central

Ashtari, Manzar; Zhang, Hui; Cook, Philip A.; Cyckowski, Laura L.; Shindler, Kenneth S.; Marshall, Kathleen A.; Aravand, Puya; Vossough, Arastoo; Gee, James C.; Maguire, Albert M.; Baker, Chris I.; Bennett, Jean

2015-01-01

Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber’s congenital amaurosis (LCA), who regained vision through gene therapy. Using non-invasive multimodal neuroimaging methods, we demonstrated that reversing blindness with gene therapy promoted long-term structural plasticity in the visual pathways emanating from the treated retina of LCA patients. The data revealed improvements and normalization along the visual fibers corresponding to the site of retinal injection of the gene therapy vector carrying the therapeutic gene in the treated eye compared to the visual pathway for the untreated eye of LCA patients. After gene therapy, the primary visual pathways (for example, geniculostriate fibers) in the treated retina were similar to those of sighted control subjects, whereas the primary visual pathways of the untreated retina continued to deteriorate. Our results suggest that visual experience, enhanced by gene therapy, may be responsible for the reorganization and maturation of synaptic connectivity in the visual pathways of the treated eye in LCA patients. The interactions between the eye and the brain enabled improved and sustained long-term visual function in patients with LCA after gene therapy. PMID:26180100

Inner neural retina loss in central retinal artery occlusion.

PubMed

Ikeda, Fumiko; Kishi, Shoji

2010-09-01

To report morphologic retinal changes and visual outcomes in acute and chronic central retinal artery occlusion (CRAO). We reviewed ten eyes of ten patients with CRAO (age, 65.3 ± 10.2 years) and measured retinal thicknesses at the central fovea and the perifovea using optical coherence tomography (OCT) over 8 ± 4 months. During the acute phase (within 10 days), the mean inner retinal thicknesses were 148% and 139% of normal values at 1 mm nasal and temporal to the fovea. They decreased to 22% and 11% of normal inner retinal thickness during the chronic phase (3 months or later). The retinal thickness at the perifovea decreased linearly until 3 months but was stable during the chronic phase. In contrast, the foveal thickness increased slightly in the acute phase but was equivalent to the normal level during the chronic phase. As a result of inner retinal atrophy, the foveal pit was shallow during the chronic phase. The final visual acuity was correlated positively with retinal thickness at the perifovea during the chronic CRAO phase. OCT showed that inner retinal necrosis with early swelling and late atrophy occurred in CRAO. The fovea and outer retina appeared to be excluded from ischemic change. The residual inner retina at the perifovea determined the final visual outcomes.

Humans do not have direct access to retinal flow during walking

PubMed Central

Souman, Jan L.; Freeman, Tom C.A.; Eikmeier, Verena; Ernst, Marc O.

2013-01-01

Perceived visual speed has been reported to be reduced during walking. This reduction has been attributed to a partial subtraction of walking speed from visual speed (Durgin & Gigone, 2007; Durgin, Gigone, & Scott, 2005). We tested whether observers still have access to the retinal flow before subtraction takes place. Observers performed a 2IFC visual speed discrimination task while walking on a treadmill. In one condition, walking speed was identical in the two intervals, while in a second condition walking speed differed between intervals. If observers have access to the retinal flow before subtraction, any changes in walking speed across intervals should not affect their ability to discriminate retinal flow speed. Contrary to this “direct-access hypothesis”, we found that observers were worse at discrimination when walking speed differed between intervals. The results therefore suggest that observers do not have access to retinal flow before subtraction. We also found that the amount of subtraction depended on the visual speed presented, suggesting that the interaction between the processing of visual input and of self-motion is more complex than previously proposed. PMID:20884509

Early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model.

PubMed

Dietrich, Michael; Helling, Niklas; Hilla, Alexander; Heskamp, Annemarie; Issberner, Andrea; Hildebrandt, Thomas; Kohne, Zippora; Küry, Patrick; Berndt, Carsten; Aktas, Orhan; Fischer, Dietmar; Hartung, Hans-Peter; Albrecht, Philipp

2018-03-07

In multiple sclerosis (MS), neurodegeneration is the main reason for chronic disability. Alpha-lipoic acid (LA) is a naturally occurring antioxidant which has recently been demonstrated to reduce the rate of brain atrophy in progressive MS. However, it remains uncertain if it is also beneficial in the early, more inflammatory-driven phases. As clinical studies are costly and time consuming, optic neuritis (ON) is often used for investigating neuroprotective or regenerative therapeutics. We aimed to investigate the prospect for success of a clinical ON trial using an experimental autoimmune encephalomyelitis-optic neuritis (EAE-ON) model with visual system readouts adaptable to a clinical ON trial. Using an in vitro cell culture model for endogenous oxidative stress, we compared the neuroprotective capacity of racemic LA with the R/S-enantiomers and its reduced form. In vivo, we analyzed retinal neurodegeneration using optical coherence tomography (OCT) and the visual function by optokinetic response (OKR) in MOG 35-55 -induced EAE-ON in C57BL/6J mice. Ganglion cell counts, inflammation, and demyelination were assessed by immunohistological staining of retinae and optic nerves. All forms of LA provided equal neuroprotective capacities in vitro. In EAE-ON, prophylactic LA therapy attenuated the clinical EAE score and prevented the thinning of the inner retinal layer while therapeutic treatment was not protective on visual outcomes. A prophylactic LA treatment is necessary to protect from visual loss and retinal thinning in EAE-ON, suggesting that a clinical ON trial starting therapy after the onset of symptoms may not be successful.

Light-Emitting Diode (LED) therapy improves occipital cortex damage by decreasing apoptosis and increasing BDNF-expressing cells in methanol-induced toxicity in rats.

PubMed

Ghanbari, Amir; Ghareghani, Majid; Zibara, Kazem; Delaviz, Hamdallah; Ebadi, Elham; Jahantab, Mohammad Hossein

2017-05-01

Methanol-induced retinal toxicity, frequently associated with elevated free radicals and cell edema, is characterized by progressive retinal ganglion cell (RGC) death and vision loss. Previous studies investigated the effect of photomodulation on RGCs, but not the visual cortex. In this study, the effect of 670nm Light-Emitting Diode (LED) therapy on RGCs and visual cortex recovery was investigated in a seven-day methanol-induced retinal toxicity protocol in rats. Methanol administration showed a reduction in the number of RGCs, loss of neurons (neuronal nuclear antigen, NeuN+), activation of glial fibrillary acidic protein (GFAP+) expressing cells, suppression of brain-derived neurotrophic factor (BDNF+) positive cells, increase in apoptosis (caspase 3+) and enhancement of nitric oxide (NO) release in serum and brain. On the other hand, LED therapy significantly reduced RGC death, in comparison to the methanol group. In addition, the number of BDNF positive cells was significantly higher in the visual cortex of LED-treated group, in comparison to methanol-intoxicated and control groups. Moreover, LED therapy caused a significant decrease in cell death (caspase 3+ cells) and a significant reduction in the NO levels, both in serum and brain tissue, in comparison to methanol-intoxicated rats. Overall, LED therapy demonstrated a number of beneficial effects in decreasing oxidative stress and in functional recovery of RGCs and visual cortex. Our data suggest that LED therapy could be a potential condidate as a non-invasive approach for treatment of retinal damage, which needs further clinicl studies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Mutations in C8ORF37 cause Bardet Biedl syndrome (BBS21)

PubMed Central

Heon, Elise; Kim, Gunhee; Qin, Sophie; Garrison, Janelle E.; Tavares, Erika; Vincent, Ajoy; Nuangchamnong, Nina; Scott, C. Anthony; Slusarski, Diane C.; Sheffield, Val C.

2016-01-01

Bardet Biedl syndrome (BBS) is a multisystem genetically heterogeneous ciliopathy that most commonly leads to obesity, photoreceptor degeneration, digit anomalies, genito-urinary abnormalities, as well as cognitive impairment with autism, among other features. Sequencing of a DNA sample from a 17-year-old female affected with BBS did not identify any mutation in the known BBS genes. Whole-genome sequencing identified a novel loss-of-function disease-causing homozygous mutation (K102*) in C8ORF37, a gene coding for a cilia protein. The proband was overweight (body mass index 29.1) with a slowly progressive rod-cone dystrophy, a mild learning difficulty, high myopia, three limb post-axial polydactyly, horseshoe kidney, abnormally positioned uterus and elevated liver enzymes. Mutations in C8ORF37 were previously associated with severe autosomal recessive retinal dystrophies (retinitis pigmentosa RP64 and cone-rod dystrophy CORD16) but not BBS. To elucidate the functional role of C8ORF37 in a vertebrate system, we performed gene knockdown in Danio rerio and assessed the cardinal features of BBS and visual function. Knockdown of c8orf37 resulted in impaired visual behavior and BBS-related phenotypes, specifically, defects in the formation of Kupffer’s vesicle and delays in retrograde transport. Specificity of these phenotypes to BBS knockdown was shown with rescue experiments. Over-expression of human missense mutations in zebrafish also resulted in impaired visual behavior and BBS-related phenotypes. This is the first functional validation and association of C8ORF37 mutations with the BBS phenotype, which identifies BBS21. The zebrafish studies hereby show that C8ORF37 variants underlie clinically diagnosed BBS-related phenotypes as well as isolated retinal degeneration. PMID:27008867

Rapid Recovery of Visual Function Associated with Blue Cone Ablation in Zebrafish

PubMed Central

Hagerman, Gordon F.; Noel, Nicole C. L.; Cao, Sylvia Y.; DuVal, Michèle G.; Oel, A. Phillip; Allison, W. Ted

2016-01-01

Hurdles in the treatment of retinal degeneration include managing the functional rewiring of surviving photoreceptors and integration of any newly added cells into the remaining second-order retinal neurons. Zebrafish are the premier genetic model for such questions, and we present two new transgenic lines allowing us to contrast vision loss and recovery following conditional ablation of specific cone types: UV or blue cones. The ablation of each cone type proved to be thorough (killing 80% of cells in each intended cone class), specific, and cell-autonomous. We assessed the loss and recovery of vision in larvae via the optomotor behavioural response (OMR). This visually mediated behaviour decreased to about 5% or 20% of control levels following ablation of UV or blue cones, respectively (P<0.05). We further assessed ocular photoreception by measuring the effects of UV light on body pigmentation, and observed that photoreceptor deficits and recovery occurred (p<0.01) with a timeline coincident to the OMR results. This corroborated and extended previous conclusions that UV cones are required photoreceptors for modulating body pigmentation, addressing assumptions that were unavoidable in previous experiments. Functional vision recovery following UV cone ablation was robust, as measured by both assays, returning to control levels within four days. In contrast, robust functional recovery following blue cone ablation was unexpectedly rapid, returning to normal levels within 24 hours after ablation. Ablation of cones led to increased proliferation in the retina, though the rapid recovery of vision following blue cone ablation was demonstrated to not be mediated by blue cone regeneration. Thus rapid visual recovery occurs following ablation of some, but not all, cone subtypes, suggesting an opportunity to contrast and dissect the sources and mechanisms of outer retinal recovery during cone photoreceptor death and regeneration. PMID:27893779

Diagnostic Power of Macular Retinal Thickness Analysis and Structure-Function Relationship in Glaucoma Diagnosis Using SPECTRALIS OCT.

PubMed

Rolle, Teresa; Manerba, Linda; Lanzafame, Pietro; Grignolo, Federico M

2016-05-01

To evaluate the diagnostic power of the Posterior Pole Asymmetry Analysis (PPAA) from the SPECTRALIS OCT in glaucoma diagnosis and to define the correlation between the visual field sensitivity (VFS) and macular retinal thickness (MRT). 90 consecutive open-angle glaucoma patients and 23 healthy subjects were enrolled. All subjects underwent Visual Field test (Humphrey Field Analyzer, central 24-2 SITA-Standard) and SD-OCT volume scans (SPECTRALIS, Posterior Pole Asymmetry Analysis). The areas under the Receiving Operating Characteristic curve (AROC) were calculated to assess discriminating power for glaucoma, at first considering total MRT values and hemisphere MRT value and then quadrant MRT values from 16 square cells in a 8 x 8 posterior pole retinal thickness map that were averaged for a mean retinal thickness value. Structure function correlation was performed for total values, hemisphere values and for each quadrant compared to the matching central test points of the VF. The AROCs ranged from 0.70 to 0.82 (p < 0.0001), with no significant differences between each other. The highest AROC observed was in inferior nasal quadrant. The VFS showed a strong correlation only with the corresponding MRT value s for quadrant analysis: Superior Temporal (r = 0.33, p = 0.0013), Superior Nasal (r = 0.43, p < 0.0001), Inferior Temporal (r = 0.57, p < 0.0001) and Inferior Nasal (r = 0.55, p < 0.0001). the quadrant analysis showed statistically significant structure-function correlations and may provide additional data for the diagnostic performance of SPECTRALIS OCT.

Autophagy in the eye: Development, degeneration, and aging.

PubMed

Boya, Patricia; Esteban-Martínez, Lorena; Serrano-Puebla, Ana; Gómez-Sintes, Raquel; Villarejo-Zori, Beatriz

2016-11-01

Autophagy is a catabolic pathway that promotes the degradation and recycling of cellular components. Proteins, lipids, and even whole organelles are engulfed in autophagosomes and delivered to the lysosome for elimination. In response to stress, autophagy mediates the degradation of cell components, which are recycled to generate the nutrients and building blocks required to sustain cellular homeostasis. Moreover, it plays an important role in cellular quality control, particularly in neurons, in which the total burden of altered proteins and damaged organelles cannot be reduced by redistribution to daughter cells through cell division. Research has only begun to examine the role of autophagy in the visual system. The retina, a light-sensitive tissue, detects and transmits electrical impulses through the optic nerve to the visual cortex in the brain. Both the retina and the eye are exposed to a variety of environmental insults and stressors, including genetic mutations and age-associated alterations that impair their function. Here, we review the main studies that have sought to explain autophagy's importance in visual function. We describe the role of autophagy in retinal development and cell differentiation, and discuss the implications of autophagy dysregulation both in physiological aging and in important diseases such as age-associated macular degeneration and glaucoma. We also address the putative role of autophagy in promoting photoreceptor survival and discuss how selective autophagy could provide alternative means of protecting retinal cells. The findings reviewed here underscore the important role of autophagy in maintaining proper retinal function and highlight novel therapeutic approaches for blindness and other diseases of the eye. Copyright © 2016 Elsevier Ltd. All rights reserved.

Optical devices in highly myopic eyes with low vision: a prospective study.

PubMed

Scassa, C; Cupo, G; Bruno, M; Iervolino, R; Capozzi, S; Tempesta, C; Giusti, C

2012-01-01

To compare, in relation to the cause of visual impairment, the possibility of rehabilitation, the corrective systems already in use and the finally prescribed optical devices in highly myopic patients with low vision. Some considerations about the rehabilitation of these subjects, especially in relation to their different pathologies, have also been made. 25 highly myopic subjects were enrolled. We evaluated both visual acuity and retinal sensitivity by Scanning Laser Ophthalmoscope (SLO) microperimetry. 20 patients (80%) were rehabilitated by means of monocular optical devices while five patients (20%) were rehabilitated binocularly. We found a good correlation between visual acuity and retinal sensitivity only when the macular pathology did not induce large areas of chorioretinal atrophy that cause lack of stabilization of the preferential retinal locus. In fact, the best results in reading and performing daily visual tasks were obtained by maximizing the residual vision in patients with retinal sensitivity greater than 10 dB. A well circumscribed area of absolute scotoma with a defined new retinal fixation locus could be considered as a positive predictive factor for the final rehabilitation process. A more careful evaluation of visual acuity, retinal sensitivity and preferential fixation locus is necessary in order to prescribe the best optical devices to patients with low vision, thus reducing the impact of the disability on their daily life.

Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays.

PubMed

Light, Jacob G; Fransen, James W; Adekunle, Adewumi N; Adkins, Alice; Pangeni, Gobinda; Loudin, James; Mathieson, Keith; Palanker, Daniel V; McCall, Maureen A; Pardue, Machelle T

2014-11-01

Photovoltaic arrays (PVA) implanted into the subretinal space of patients with retinitis pigmentosa (RP) are designed to electrically stimulate the remaining inner retinal circuitry in response to incident light, thereby recreating a visual signal when photoreceptor function declines or is lost. Preservation of inner retinal circuitry is critical to the fidelity of this transmitted signal to ganglion cells and beyond to higher visual targets. Post-implantation loss of retinal interneurons or excessive glial scarring could diminish and/or eliminate PVA-evoked signal transmission. As such, assessing the morphology of the inner retina in RP animal models with subretinal PVAs is an important step in defining biocompatibility and predicting success of signal transmission. In this study, we used immunohistochemical methods to qualitatively and quantitatively compare inner retinal morphology after the implantation of a PVA in two RP models: the Royal College of Surgeons (RCS) or transgenic S334ter-line 3 (S334ter-3) rhodopsin mutant rat. Two PVA designs were compared. In the RCS rat, we implanted devices in the subretinal space at 4 weeks of age and histologically examined them at 8 weeks of age and found inner retinal morphology preservation with both PVA devices. In the S334ter-3 rat, we implanted devices at 6-12 weeks of age and again, inner retinal morphology was generally preserved with either PVA design 16-26 weeks post-implantation. Specifically, the length of rod bipolar cells and numbers of cholinergic amacrine cells were maintained along with their characteristic inner plexiform lamination patterns. Throughout the implanted retinas we found nonspecific glial reaction, but none showed additional glial scarring at the implant site. Our results indicate that subretinally implanted PVAs are well-tolerated in rodent RP models and that the inner retinal circuitry is preserved, consistent with our published results showing implant-evoked signal transmission. Published by Elsevier Ltd.

Cytomegalovirus retinitis associated with acquired immunodeficiency syndrome.

PubMed

Geng, Shuang; Ye, Jun-jie; Zhao, Jia-liang; Li, Tai-sheng; Han, Yang

2011-04-01

Cytomegalovirus (CMV) retinitis is the most severe intraocular complication that results in total retinal destruction and loss of visual acuity in patients with acquired immunodeficiency syndrome (AIDS). This study aimed to investigate the fundus characteristics, systemic manifestations and therapeutic outcomes of CMV retinitis associated with AIDS. It was a retrospective case series. CMV retinitis was present in 39 eyes (25 patients). Best corrected visual acuities, anterior segment, fundus features, fundus fluorescence angiography (FFA) and CD4(+) T-lymphocyte counts of the patients with CMV retinitis associated with AIDS were analyzed. Intravitreal injections of ganciclovir (400 µg) were performed in 4 eyes (2 patients). Retinal vasculitis, dense, full-thickness, yellow-white lesions along vascular distribution with irregular granules at the border, and hemorrhage on the retinal surface were present in 28 eyes. The vitreous was clear or mildly opaque. Late stage of the retinopathy was demonstrated in 8 eyes characterized as atrophic retina, sclerotic and attenuated vessels, retinal pigment epithelium (RPE) atrophy, and optic nerve atrophy. Retinal detachment was found in 3 eyes. The average CD4(+) T-lymphocyte count in peripheral blood of the patients with CMV retinitis was (30.6 ± 25.3) × 10(6)/L (range, (0 - 85) × 10(6)/L). After intravitreal injections of ganciclovir, visual acuity was improved and fundus lesions regressed. CMV retinitis is the most severe and the most common intraocular complication in patients with AIDS. For the patients with yellow-white retinal lesions, hemorrhage and retinal vasculitis without clear cause, human immunodeficiency virus (HIV) serology should be performed. Routine eye examination is also indicated in HIV positive patients.

Targeting neuronal gap junctions in mouse retina offers neuroprotection in glaucoma

PubMed Central

Kumar, Sandeep; Ramakrishnan, Hariharasubramanian; Roy, Kaushambi; Viswanathan, Suresh; Bloomfield, Stewart A.

2017-01-01

The progressive death of retinal ganglion cells and resulting visual deficits are hallmarks of glaucoma, but the underlying mechanisms remain unclear. In many neurodegenerative diseases, cell death induced by primary insult is followed by a wave of secondary loss. Gap junctions (GJs), intercellular channels composed of subunit connexins, can play a major role in secondary cell death by forming conduits through which toxic molecules from dying cells pass to and injure coupled neighbors. Here we have shown that pharmacological blockade of GJs or genetic ablation of connexin 36 (Cx36) subunits, which are highly expressed by retinal neurons, markedly reduced loss of neurons and optic nerve axons in a mouse model of glaucoma. Further, functional parameters that are negatively affected in glaucoma, including the electroretinogram, visual evoked potential, visual spatial acuity, and contrast sensitivity, were maintained at control levels when Cx36 was ablated. Neuronal GJs may thus represent potential therapeutic targets to prevent the progressive neurodegeneration and visual impairment associated with glaucoma. PMID:28604388

Eyecup scope—optical recordings of light stimulus-evoked fluorescence signals in the retina

PubMed Central

Hausselt, Susanne E.; Breuninger, Tobias; Castell, Xavier; Denk, Winfried; Margolis, David J.; Detwiler, Peter B.

2009-01-01

Dendritic signals play an essential role in processing visual information in the retina. To study them in neurites too small for electrical recording, we developed an instrument that combines a multi-photon (MP) microscope with a through-the-objective high-resolution visual stimulator. An upright microscope was designed that uses the objective lens for both MP imaging and delivery of visual stimuli to functionally intact retinal explants or eyecup preparations. The stimulator consists of a miniature liquid-crystal-on-silicon display coupled into the optical path of an infrared-excitation laser-scanning microscope. A pair of custom-made dichroic filters allows light from the excitation laser and three spectral bands (‘colors’) from the stimulator to reach the retina, leaving two intermediate bands for fluorescence imaging. Special optics allow displacement of the stimulator focus relative to the imaging focus. Spatially resolved changes in calcium-indicator fluorescence in response to visual stimuli were recorded in dendrites of different types of mammalian retinal neurons. PMID:19023590

Intrinsically photosensitive retinal ganglion cells.

PubMed

Do, Michael Tri Hoang; Yau, King-Wai

2010-10-01

Life on earth is subject to alternating cycles of day and night imposed by the rotation of the earth. Consequently, living things have evolved photodetective systems to synchronize their physiology and behavior with the external light-dark cycle. This form of photodetection is unlike the familiar "image vision," in that the basic information is light or darkness over time, independent of spatial patterns. "Nonimage" vision is probably far more ancient than image vision and is widespread in living species. For mammals, it has long been assumed that the photoreceptors for nonimage vision are also the textbook rods and cones. However, recent years have witnessed the discovery of a small population of retinal ganglion cells in the mammalian eye that express a unique visual pigment called melanopsin. These ganglion cells are intrinsically photosensitive and drive a variety of nonimage visual functions. In addition to being photoreceptors themselves, they also constitute the major conduit for rod and cone signals to the brain for nonimage visual functions such as circadian photoentrainment and the pupillary light reflex. Here we review what is known about these novel mammalian photoreceptors.

Eye Velocity Gain Fields in MSTd During Optokinetic Stimulation

PubMed Central

Brostek, Lukas; Büttner, Ulrich; Mustari, Michael J.; Glasauer, Stefan

2015-01-01

Lesion studies argue for an involvement of cortical area dorsal medial superior temporal area (MSTd) in the control of optokinetic response (OKR) eye movements to planar visual stimulation. Neural recordings during OKR suggested that MSTd neurons directly encode stimulus velocity. On the other hand, studies using radial visual flow together with voluntary smooth pursuit eye movements showed that visual motion responses were modulated by eye movement-related signals. Here, we investigated neural responses in MSTd during continuous optokinetic stimulation using an information-theoretic approach for characterizing neural tuning with high resolution. We show that the majority of MSTd neurons exhibit gain-field-like tuning functions rather than directly encoding one variable. Neural responses showed a large diversity of tuning to combinations of retinal and extraretinal input. Eye velocity-related activity was observed prior to the actual eye movements, reflecting an efference copy. The observed tuning functions resembled those emerging in a network model trained to perform summation of 2 population-coded signals. Together, our findings support the hypothesis that MSTd implements the visuomotor transformation from retinal to head-centered stimulus velocity signals for the control of OKR. PMID:24557636

Fyn kinase genetic ablation causes structural abnormalities in mature retina and defective Müller cell function.

PubMed

Chavez-Solano, Marbella; Ibarra-Sanchez, Alfredo; Treviño, Mario; Gonzalez-Espinosa, Claudia; Lamas, Monica

2016-04-01

Fyn kinase is widely expressed in neuronal and glial cells of the brain, where it exerts multiple functional roles that affect fundamental physiological processes. The aim of our study was to investigate the, so far unknown, functional role of Fyn in the retina. We report that Fyn is expressed, in vivo, in a subpopulation of Müller glia. We used a mouse model of Fyn genetic ablation and Müller-enriched primary cultures to demonstrate that Fyn deficiency induces morphological alterations in the mature retina, a reduction in the thickness of the outer and inner nuclear layers and alterations in postnatal Müller cell physiology. These include shortening of Müller cell processes, a decrease in cell proliferation, inactivation of the Akt signal transduction pathway, a reduced number of focal adhesions points and decreased adhesion of these cells to the ECM. As abnormalities in Müller cell physiology have been previously associated to a compromised retinal function we evaluated behavioral responses to visual stimulation. Our results associate Fyn deficiency with impaired visual optokinetic responses under scotopic and photopic light conditions. Our study reveals novel roles for Fyn kinase in retinal morphology and Müller cell physiology and suggests that Fyn is required for optimal visual processing. Copyright © 2016 Elsevier Inc. All rights reserved.

Cytomegalovirus retinitis and HIV: Case reviews from KwaZulu-Natal Province, South Africa.

PubMed

Hassan-Moosa, R; Chinappa, T; Jeena, L; Visser, L; Naidoo, K

2017-09-22

Retinal cytomegalovirus (CMV) infection is a common opportunistic infection and remains a significant contributor to visual loss in patients with AIDS. We highlight the poor outcomes of CMV retinitis in three HIV-infected patients who were initiated on antiretroviral therapy (ART). We conducted a retrospective chart review of advanced stage HIV-infected patients with known CMV retinitis.Case 1. A 37-year-old man, with a CD4+ cell count of 35 cells/µL, presented for ART initiation with a 5-month history of visual loss in his left eye. Fundoscopy showed left eye CMV retinitis and right eye HIV retinopathy. ART and 5 months of weekly intravitreal ganciclovir injections (left eye) were commenced. Six-month outcomes included virological suppression, and visual acuity in the right eye of 6/6 and in the left eye of 3/60.Case 2. A 31-year-old woman, with a CD4+ cell count of 39 cells/µL and on tuberculosis therapy, presented for ART initiation. She presented with a 2-month history of decreased visual acuity. Fundoscopy showed bilateral CMV retinitis, which was more pronounced in the left eye. ART and 8 months of intravitreal ganciclovir injections were commenced. Six-month outcomes included virological suppression and visual acuity in the right eye of 6/9, and in the left eye of 6/24.Case 3. A 29-year-old woman, with a CD4+ cell count of 24 cells/µL, who was on tuberculosis therapy and ART, complained of blurred vision at her 2-month ART follow-up visit. Fundoscopy showed bilateral retinal detachment secondary to CMV retinitis. While silicone oil tamponade and subsequent retinectomy successfully repaired the right eye, extensive damage rendered the left eye irreparable. Six-month outcomes included virological suppression, with 6/120 visual acuity in the right eye and complete blindness in the left eye. CMV retinitis causes debilitating, permanent sequelae, which is preventable by ART initiation at higher CD4+ cell counts. Despite achieving virological suppression, vision could not be completely restored in these patients, irrespective of the severity of CMV retinitis.

The Impact of Supplemental Antioxidants on Visual Function in Nonadvanced Age-Related Macular Degeneration: A Head-to-Head Randomized Clinical Trial.

PubMed

Akuffo, Kwadwo Owusu; Beatty, Stephen; Peto, Tunde; Stack, Jim; Stringham, Jim; Kelly, David; Leung, Irene; Corcoran, Laura; Nolan, John M

2017-10-01

The purpose of this study was to evaluate the impact of supplemental macular carotenoids (including versus not including meso-zeaxanthin) in combination with coantioxidants on visual function in patients with nonadvanced age-related macular degeneration. In this study, 121 participants were randomly assigned to group 1 (Age-Related Eye Disease Study 2 formulation with a low dose [25 mg] of zinc and an addition of 10 mg meso-zeaxanthin; n = 60) or group 2 (Age-Related Eye Disease Study 2 formulation with a low dose [25 mg] of zinc; n = 61). Visual function was assessed using best-corrected visual acuity, contrast sensitivity (CS), glare disability, retinal straylight, photostress recovery time, reading performance, and the National Eye Institute Visual Function Questionnaire-25. Macular pigment was measured using customized heterochromatic flicker photometry. There was a statistically significant improvement in the primary outcome measure (letter CS at 6 cycles per degree [6 cpd]) over time (P = 0.013), and this observed improvement was statistically comparable between interventions (P = 0.881). Statistically significant improvements in several secondary outcome visual function measures (letter CS at 1.2 and 2.4 cpd; mesopic and photopic CS at all spatial frequencies; mesopic glare disability at 1.5, 3, and 6 cpd; photopic glare disability at 1.5, 3, 6, and 12 cpd; photostress recovery time; retinal straylight; mean and maximum reading speed) were also observed over time (P < 0.05, for all), and were statistically comparable between interventions (P > 0.05, for all). Statistically significant increases in macular pigment at all eccentricities were observed over time (P < 0.0005, for all), and the degree of augmentation was statistically comparable between interventions (P > 0.05). Antioxidant supplementation in patients with nonadvanced age-related macular degeneration results in significant increases in macular pigment and improvements in CS and other measures of visual function. (Clinical trial, http://www.isrctn.com/ISRCTN13894787).

Visual Aids and Eye Protection for the Aviator

DTIC Science & Technology

1976-10-01

pigmentosa patients. Retinitis pigmen- toss robs you of your night vision very quickly. You still can see centrally and in the daytime but very little at...AND VISUAL AIDS by D.H.Brennan CI INTEGRATION OF AVIATOR’S EYE PROTECTION AND VISUAL AIDS by G.TChisum and P.E.Morway C2 PROTECTION FROM RETINAL BURNS...ensure that infra red wavelengths outside the visible band (MOO-1400 nm) are also attenuated to avoid any possibility of retinal burns. Short ultra

Estimates of underwater and aerial visual acuity in the European beaver Castor fiber L. based on morphological data.

PubMed

Mass, A M; Supin, A Ya

2017-03-01

The eye optics and topographic distribution of ganglion cells were studied using whole mount preparations from European beaver Castor fiber L. The beaver eye optics provides emmetropia in air and hypermetropia in water. The optometrical measurements predict retinal resolution of the beaver eye around 17' in air and 9' in water. In air, retinal resolution corresponds to the real visual acuity, whereas in water, visual acuity is below the retinal resolution because of the non-precise focusing.

Image analysis for microelectronic retinal prosthesis.

PubMed

Hallum, L E; Cloherty, S L; Lovell, N H

2008-01-01

By way of extracellular, stimulating electrodes, a microelectronic retinal prosthesis aims to render discrete, luminous spots-so-called phosphenes-in the visual field, thereby providing a phosphene image (PI) as a rudimentary remediation of profound blindness. As part thereof, a digital camera, or some other photosensitive array, captures frames, frames are analyzed, and phosphenes are actuated accordingly by way of modulated charge injections. Here, we present a method that allows the assessment of image analysis schemes for integration with a prosthetic device, that is, the means of converting the captured image (high resolution) to modulated charge injections (low resolution). We use the mutual-information function to quantify the amount of information conveyed to the PI observer (device implantee), while accounting for the statistics of visual stimuli. We demonstrate an effective scheme involving overlapping, Gaussian kernels, and discuss extensions of the method to account for shortterm visual memory in observers, and their perceptual errors of omission and commission.

Mixing of Chromatic and Luminance Retinal Signals in Primate Area V1

PubMed Central

Li, Xiaobing; Chen, Yao; Lashgari, Reza; Bereshpolova, Yulia; Swadlow, Harvey A.; Lee, Barry B.; Alonso, Jose Manuel

2015-01-01

Vision emerges from activation of chromatic and achromatic retinal channels whose interaction in visual cortex is still poorly understood. To investigate this interaction, we recorded neuronal activity from retinal ganglion cells and V1 cortical cells in macaques and measured their visual responses to grating stimuli that had either luminance contrast (luminance grating), chromatic contrast (chromatic grating), or a combination of the two (compound grating). As with parvocellular or koniocellular retinal ganglion cells, some V1 cells responded mostly to the chromatic contrast of the compound grating. As with magnocellular retinal ganglion cells, other V1 cells responded mostly to the luminance contrast and generated a frequency-doubled response to equiluminant chromatic gratings. Unlike magnocellular and parvocellular retinal ganglion cells, V1 cells formed a unimodal distribution for luminance/color preference with a 2- to 4-fold bias toward luminance. V1 cells associated with positive local field potentials in deep layers showed the strongest combined responses to color and luminance and, as a population, V1 cells encoded a diverse combination of luminance/color edges that matched edge distributions of natural scenes. Taken together, these results suggest that the primary visual cortex combines magnocellular and parvocellular retinal inputs to increase cortical receptive field diversity and to optimize visual processing of our natural environment. PMID:24464943

COMPARISON OF RETINAL PATHOLOGY VISUALIZATION IN MULTISPECTRAL SCANNING LASER IMAGING.

PubMed

Meshi, Amit; Lin, Tiezhu; Dans, Kunny; Chen, Kevin C; Amador, Manuel; Hasenstab, Kyle; Muftuoglu, Ilkay Kilic; Nudleman, Eric; Chao, Daniel; Bartsch, Dirk-Uwe; Freeman, William R

2018-03-16

To compare retinal pathology visualization in multispectral scanning laser ophthalmoscope imaging between the Spectralis and Optos devices. This retrospective cross-sectional study included 42 eyes from 30 patients with age-related macular degeneration (19 eyes), diabetic retinopathy (10 eyes), and epiretinal membrane (13 eyes). All patients underwent retinal imaging with a color fundus camera (broad-spectrum white light), the Spectralis HRA-2 system (3-color monochromatic lasers), and the Optos P200 system (2-color monochromatic lasers). The Optos image was cropped to a similar size as the Spectralis image. Seven masked graders marked retinal pathologies in each image within a 5 × 5 grid that included the macula. The average area with detected retinal pathology in all eyes was larger in the Spectralis images compared with Optos images (32.4% larger, P < 0.0001), mainly because of better visualization of epiretinal membrane and retinal hemorrhage. The average detection rate of age-related macular degeneration and diabetic retinopathy pathologies was similar across the three modalities, whereas epiretinal membrane detection rate was significantly higher in the Spectralis images. Spectralis tricolor multispectral scanning laser ophthalmoscope imaging had higher rate of pathology detection primarily because of better epiretinal membrane and retinal hemorrhage visualization compared with Optos bicolor multispectral scanning laser ophthalmoscope imaging.

Retinal Prosthesis System for Advanced Retinitis Pigmentosa: A Health Technology Assessment Update

PubMed Central

Lee, Christine; Tu, Hong Anh; Wells, David; Holubowich, Corinne

2017-01-01

Background Retinitis pigmentosa is a group of inherited disorders characterized by the degeneration of the photoreceptors in the retina, resulting in progressive vision loss. The Argus II system is designed to restore partial functional vision in patients with profound vision loss from advanced retinitis pigmentosa. At present, it is the only treatment option approved by Health Canada for this patient population. In June 2016, Health Quality Ontario published a health technology assessment of the Argus II retinal prosthesis system for patients with advanced retinitis pigmentosa. Based on that assessment, the Ontario Health Technology Advisory Committee recommended against publicly funding the Argus II system for this population. It also recommended that Health Quality Ontario re-evaluate the evidence in 1 year. The objective of this report was to examine new evidence published since the 2016 health technology assessment. Methods We completed a health technology assessment, which included an evaluation of clinical benefits and harms, value for money, and patient preferences related to the Argus II system. We performed a systematic literature search for studies published since the 2016 Argus II health technology assessment. We developed a Markov decision-analytic model to assess the cost-effectiveness of the Argus II system compared with standard care, and we calculated incremental cost-effectiveness ratios over a 20-year time horizon. We also conducted a five-year budget impact analysis. Finally, we interviewed people with retinitis pigmentosa about their lived experience with vision loss, and with the Argus II system. Results Four publications from one multicentre international study were included in the clinical review. Patients showed significant improvements in visual function and functional outcomes with the Argus II system, and these outcomes were sustained up to a 5-year follow-up (moderate quality of evidence). The safety profile was generally acceptable. In the base case economic analysis, the Argus II system was cost-effective compared with standard care if the willingness to pay was more than $97,429 per quality-adjusted life-year. We estimated that funding the Argus II system would cost the province $0.71 to $0.78 million per year over 5 years, assuming 4 implants per year. People with lived experience spoke about the challenges of retinitis pigmentosa, including the gradual but persistent progression of the disease; its impact on their quality of life and their families; and the accessibility challenges they faced. Those who used the Argus II system spoke about its positive impact on their quality of life. Conclusions Based on evidence of moderate quality, the Argus II retinal prosthesis system improved visual function, real-life functional outcomes, and quality of life in patients with advanced retinitis pigmentosa. The Argus II system is expensive, but the cost to publicly fund it would be low, because of the small number of eligible patients. The Argus II system can only enable perception of light/dark and shapes/objects, but these advancements represent important gains for people with retinitis pigmentosa in terms of mobility and quality of life. PMID:29201260

Visual dysfunction in Parkinson’s disease

PubMed Central

Weil, Rimona S.; Schrag, Anette E.; Warren, Jason D.; Crutch, Sebastian J.; Lees, Andrew J.; Morris, Huw R.

2016-01-01

Patients with Parkinson’s disease have a number of specific visual disturbances. These include changes in colour vision and contrast sensitivity and difficulties with complex visual tasks such as mental rotation and emotion recognition. We review changes in visual function at each stage of visual processing from retinal deficits, including contrast sensitivity and colour vision deficits to higher cortical processing impairments such as object and motion processing and neglect. We consider changes in visual function in patients with common Parkinson’s disease-associated genetic mutations including GBA and LRRK2. We discuss the association between visual deficits and clinical features of Parkinson’s disease such as rapid eye movement sleep behavioural disorder and the postural instability and gait disorder phenotype. We review the link between abnormal visual function and visual hallucinations, considering current models for mechanisms of visual hallucinations. Finally, we discuss the role of visuo-perceptual testing as a biomarker of disease and predictor of dementia in Parkinson’s disease. PMID:27412389

Correlation between aqueous flare and residual visual field area in retinitis pigmentosa.

PubMed

Nishiguchi, Koji M; Yokoyama, Yu; Kunikata, Hiroshi; Abe, Toshiaki; Nakazawa, Toru

2018-06-01

To investigate the relationship between aqueous flare, visual function and macular structures in retinitis pigmentosa (RP). Clinical data from 123 patients with RP (227 eyes), 35 patients with macular dystrophy (68 eyes) and 148 controls (148 eyes) were analysed. The differences in aqueous flare between clinical entities and the correlation between aqueous flare (measured with a laser flare cell meter) versus visual acuity, visual field area (Goldmann perimetry) and macular thickness (optical coherence tomography) in patients with RP were determined. Influence of selected clinical data on flare was assessed using linear mixed-effects model. Aqueous flare was higher in patients with RP than patients with macular dystrophy or controls (p=7.49×E-13). Aqueous flare was correlated with visual field area (R=-0.379, p=3.72×E-9), but not with visual acuity (R=0.083, p=0.215). Macular thickness (R=0.234, p=3.74×E-4), but not foveal thickness (R=0.122, p=0.067), was positively correlated with flare. Flare was not affected by the presence of macular complications. All these associations were maintained when the right and the left eyes were assessed separately. Analysis by linear mixed-effects model revealed that age (p=8.58×E-5), visual field area (p=8.01×E-7) and average macular thickness (p=0.037) were correlated with flare. Aqueous flare and visual field area were correlated in patients with RP. Aqueous flare may reflect the degree of overall retinal degeneration more closely than the local foveal impairment. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Applications of Optical Coherence Tomography in Pediatric Clinical Neuroscience

PubMed Central

Avery, Robert A.; Rajjoub, Raneem D.; Trimboli-Heidler, Carmelina; Waldman, Amy T.

2015-01-01

For nearly two centuries, the ophthalmoscope has permitted examination of the retina and optic nerve—the only axons directly visualized by the physician. The retinal ganglion cells project their axons, which travel along the innermost retina to form the optic nerve, marking the beginning of the anterior visual pathway. Both the structure and function of the visual pathway are essential components of the neurologic examination as it can be involved in numerous acquired, congenital and genetic central nervous system conditions. The development of optical coherence tomography now permits the pediatric neuroscientist to visualize and quantify the optic nerve and retinal layers with unprecedented resolution. As optical coherence tomography becomes more accessible and integrated into research and clinical care, the pediatric neuroscientist may have the opportunity to utilize and/or interpret results from this device. This review describes the basic technical features of optical coherence tomography and highlights its potential clinical and research applications in pediatric clinical neuroscience including optic nerve swelling, optic neuritis, tumors of the visual pathway, vigabatrin toxicity, nystagmus, and neurodegenerative conditions. PMID:25803824

Applications of optical coherence tomography in pediatric clinical neuroscience.

PubMed

Avery, Robert A; Rajjoub, Raneem D; Trimboli-Heidler, Carmelina; Waldman, Amy T

2015-04-01

For nearly two centuries, the ophthalmoscope has permitted examination of the retina and optic nerve-the only axons directly visualized by the physician. The retinal ganglion cells project their axons, which travel along the innermost retina to form the optic nerve, marking the beginning of the anterior visual pathway. Both the structure and function of the visual pathway are essential components of the neurologic examination as it can be involved in numerous acquired, congenital and genetic central nervous system conditions. The development of optical coherence tomography now permits the pediatric neuroscientist to visualize and quantify the optic nerve and retinal layers with unprecedented resolution. As optical coherence tomography becomes more accessible and integrated into research and clinical care, the pediatric neuroscientist may have the opportunity to utilize and/or interpret results from this device. This review describes the basic technical features of optical coherence tomography and highlights its potential clinical and research applications in pediatric clinical neuroscience including optic nerve swelling, optic neuritis, tumors of the visual pathway, vigabatrin toxicity, nystagmus, and neurodegenerative conditions. Georg Thieme Verlag KG Stuttgart · New York.

Long-term Outcomes of Cytomegalovirus Retinitis in the Era of Modern Antiretroviral Therapy; Results from a United States Cohort

PubMed Central

Jabs, Douglas A.; Ahuja, Alka; Van Natta, Mark L.; Lyon, Alice T.; Yeh, Steven; Danis, Ronald

2015-01-01

Objectives To describe the long-term outcomes of patients with cytomegalovirus (CMV) retinitis and the acquired immunodeficiency syndrome (AIDS)in the modern era of combination antiretroviral therapy. Design Prospective, observational, cohort study Participants Patients with AIDS and CMV retinitis Testing Immune recovery, defined as a CD4+ T cell count>100 cells/μL for ≥ 3 months. Main outcome measures Mortality, visual impairment (visual acuity worse than 20/40) and blindness (visual acuity 20/200 or worse) on logarithmic visual acuity charts, loss of visual field on quantitative Goldmann perimetry. Results Patients without immune recovery had a mortality of 44.4/100 person years (PY), and a median survival of 13.5 months after the diagnosis of CMV retinitis, whereas those with immune recovery had a mortality of 2.7/100 PY (P<0.001), and an estimated median survival of 27.0 years after the diagnosis of CMV retinitis. The rates of bilateral visual impairment and blindness were 0.9/100 PY and 0.4/100 PY, respectively, and were similar between those with and without immune recovery. Among those with immune recovery, the rate of visual field loss was ~1% of the normal field/year, whereas among those without immune recovery it was ~7% of the normal field/year. Conclusions Among persons with CMV retinitis and AIDS, if there is immune recovery, long-term survival is likely, whereas if there is no immune recovery, the mortality rate is substantial. Although higher than the rates seen in the non-HIV-infected population, the rates of bilateral visual impairment and blindness are low, especially when compared to rates seen in the era before modern antiretroviral therapy. PMID:25892019

Long-term Outcomes of Cytomegalovirus Retinitis in the Era of Modern Antiretroviral Therapy: Results from a United States Cohort.

PubMed

Jabs, Douglas A; Ahuja, Alka; Van Natta, Mark L; Lyon, Alice T; Yeh, Steven; Danis, Ronald

2015-07-01

To describe the long-term outcomes of patients with cytomegalovirus (CMV) retinitis and AIDS in the modern era of combination antiretroviral therapy. Prospective, observational cohort study. Patients with AIDS and CMV retinitis. Immune recovery, defined as a CD4+ T-cell count >100 cells/μl for ≥3 months. Mortality, visual impairment (visual acuity <20/40), and blindness (visual acuity ≤20/200) on logarithmic visual acuity charts and loss of visual field on quantitative Goldmann perimetry. Patients without immune recovery had a mortality of 44.4/100 person-years (PYs) and a median survival of 13.5 months after the diagnosis of CMV retinitis, whereas those with immune recovery had a mortality of 2.7/100 PYs (P < 0.001) and an estimated median survival of 27.0 years after the diagnosis of CMV retinitis. The rates of bilateral visual impairment and blindness were 0.9 and 0.4/100 PYs, respectively, and were similar between those with and without immune recovery. Among those with immune recovery, the rate of visual field loss was approximately 1% of the normal field per year, whereas among those without immune recovery it was approximately 7% of the normal field per year. Among persons with CMV retinitis and AIDS, if there is immune recovery, long-term survival is likely, whereas if there is no immune recovery, the mortality rate is substantial. Although higher than the rates in the population not infected by human immunodeficiency virus, the rates of bilateral visual impairment and blindness are low, especially when compared with rates in the era before modern antiretroviral therapy. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Association of Vitamin A Supplementation With Disease Course in Children With Retinitis Pigmentosa.

PubMed

Berson, Eliot L; Weigel-DiFranco, Carol; Rosner, Bernard; Gaudio, Alexander R; Sandberg, Michael A

2018-05-01

While oral vitamin A supplementation is considered to potentially slow loss of retinal function in adults with retinitis pigmentosa and normal liver function, little data from children with this disease are available. To compare disease courses in children with retinitis pigmentosa taking or not taking vitamin A supplementation. Retrospective, nonrandomized comparison of vitamin A and control cohorts followed up for a mean of 4 to 5 years by the Electroretinography Service of the Massachusetts Eye and Ear Infirmary. The study included children with different genetic types of typical retinitis pigmentosa: 55 taking vitamin A and 25 not taking vitamin A. The dates for patient evaluations ranged from June 1976 to July 2016, and the data analysis occurred in October 2016. Age-adjusted dose of oral vitamin A palmitate (≤15 000 IU/d). Mean exponential rates of change of full-field cone electroretinogram amplitude to 30-Hz flashes estimated by repeated-measures longitudinal regression without and with adjusting for potential confounders. Of the 55 children in the vitamin A cohort, 38 (69%) were male; the mean [SD] age was 9.1 [1.9] years; and 48 (87%) were white , 6 (11%) were Asian, and 1 (2%) was black. Of the 25 members of the control cohort, 19 (76%) were male; the mean [SD] age was 9.2 [1.7] years; and 25 (100%) were white. The estimated mean rates of change with the unadjusted model were -0.0713 loge unit/y (-6.9% per year) for the vitamin A cohort and -0.1419 loge unit per year (-13.2% per year) for the control cohort (difference, 0.0706 loge unit per year; 95% CI for the difference, 0.0149-0.1263 loge unit per year; P = .01). The adjusted model confirmed a slower mean rate of decline in the vitamin A cohort (difference, 0.0771 loge-unit per year; 95% CI for the difference, 0.0191-0.1350 loge-unit per year; P = .009). With respect to ocular safety, the mean exponential rates of change of visual field area and visual acuity and the incidences of falling to a visual field diameter of 20° or less or a visual acuity of 20/200 or less in at least 1 eye did not differ by cohort. A vitamin A palmitate supplement was associated with a slower loss of cone electroretinogram amplitude in children with retinitis pigmentosa. Although the relatively small-sample, retrospective, nonrandomized design does not allow a test of causation and is subject to possible biases, these findings support consideration of an age-adjusted dose of vitamin A in the management of most children with the common forms of retinitis pigmentosa.

Müller glia: Stem cells for generation and regeneration of retinal neurons in teleost fish

PubMed Central

Lenkowski, Jenny R.; Raymond, Pamela A.

2014-01-01

Adult zebrafish generate new neurons in the brain and retina throughout life. Growth-related neurogenesis allows a vigorous regenerative response to damage, and fish can regenerate retinal neurons, including photoreceptors, and restore functional vision following photic, chemical, or mechanical destruction of the retina. Müller glial cells in fish function as radial-glial-like neural stem cells. During adult growth, Müller glial nuclei undergo sporadic, asymmetric, self-renewing mitotic divisions in the inner nuclear layer to generate a rod progenitor that migrates along the radial fiber of the Müller glia into the outer nuclear layer, proliferates, and differentiates exclusively into rod photoreceptors. When retinal neurons are destroyed, Müller glia in the immediate vicinity of the damage partially and transiently dedifferentiate, re-express retinal progenitor and stem cell markers, re-enter the cell cycle, undergo interkinetic nuclear migration (characteristic of neuroepithelial cells), and divide once in an asymmetric, self-renewing division to generate a retinal progenitor. This daughter cell proliferates rapidly to form a compact neurogenic cluster surrounding the Müller glia; these multipotent retinal progenitors then migrate along the radial fiber to the appropriate lamina to replace missing retinal neurons. Some aspects of the injury-response in fish Müller glia resemble gliosis as observed in mammals, and mammalian Müller glia exhibit some neurogenic properties, indicative of a latent ability to regenerate retinal neurons. Understanding the specific properties of fish Müller glia that facilitate their robust capacity to generate retinal neurons will inform and inspire new clinical approaches for treating blindness and visual loss with regenerative medicine. PMID:24412518

Novel VCP modulators mitigate major pathologies of rd10, a mouse model of retinitis pigmentosa

PubMed Central

Ikeda, Hanako Ohashi; Sasaoka, Norio; Koike, Masaaki; Nakano, Noriko; Muraoka, Yuki; Toda, Yoshinobu; Fuchigami, Tomohiro; Shudo, Toshiyuki; Iwata, Ayana; Hori, Seiji; Yoshimura, Nagahisa; Kakizuka, Akira

2014-01-01

Neuroprotection may prevent or forestall the progression of incurable eye diseases, such as retinitis pigmentosa, one of the major causes of adult blindness. Decreased cellular ATP levels may contribute to the pathology of this eye disease and other neurodegenerative diseases. Here we describe small compounds (Kyoto University Substances, KUSs) that were developed to inhibit the ATPase activity of VCP (valosin-containing protein), the most abundant soluble ATPase in the cell. Surprisingly, KUSs did not significantly impair reported cellular functions of VCP but nonetheless suppressed the VCP-dependent decrease of cellular ATP levels. Moreover, KUSs, as well as exogenous ATP or ATP-producing compounds, e.g. methylpyruvate, suppressed endoplasmic reticulum stress, and demonstrably protected various types of cultured cells from death, including several types of retinal neuronal cells. We then examined their in vivo efficacies in rd10, a mouse model of retinitis pigmentosa. KUSs prevented photoreceptor cell death and preserved visual function. These results reveal an unexpected, crucial role of ATP consumption by VCP in determining cell fate in this pathological context, and point to a promising new neuroprotective strategy for currently incurable retinitis pigmentosa. PMID:25096051

Effect of microgravity on several visual functions during STS shuttle missions

NASA Technical Reports Server (NTRS)

Oneal, Melvin R.; Task, H. Lee; Genco, Louis V.

1992-01-01

Changes in the acuity of astronaut vision during flight are discussed. Parameters such as critical flicker vision, stereopsis to 10 seconds of arc, visual acuity in small steps to 20/7.7, cyclophoria, lateral and vertical phoria and retinal rivalry were tested using a visual function tester. Twenty-three Space Transportation System (STS) astronauts participated in the experiments. Their vision was assessed twice before launch and after landing, and three to four times while on-orbit and landing. No significant differences during space flight were observed for any of the visual parameters tested. In some cases, slight changes in acuity and stereopsis were observed with a subsequent return to normal vision after flight.

Reading Visual Braille with a Retinal Prosthesis

PubMed Central

Lauritzen, Thomas Z.; Harris, Jordan; Mohand-Said, Saddek; Sahel, Jose A.; Dorn, Jessy D.; McClure, Kelly; Greenberg, Robert J.

2012-01-01

Retinal prostheses, which restore partial vision to patients blinded by outer retinal degeneration, are currently in clinical trial. The Argus II retinal prosthesis system was recently awarded CE approval for commercial use in Europe. While retinal prosthesis users have achieved remarkable visual improvement to the point of reading letters and short sentences, the reading process is still fairly cumbersome. This study investigates the possibility of using an epiretinal prosthesis to stimulate visual braille as a sensory substitution for reading written letters and words. The Argus II retinal prosthesis system, used in this study, includes a 10 × 6 electrode array implanted epiretinally, a tiny video camera mounted on a pair of glasses, and a wearable computer that processes the video and determines the stimulation current of each electrode in real time. In the braille reading system, individual letters are created by a subset of dots from a 3 by 2 array of six dots. For the visual braille experiment, a grid of six electrodes was chosen out of the 10 × 6 Argus II array. Groups of these electrodes were then directly stimulated (bypassing the camera) to create visual percepts of individual braille letters. Experiments were performed in a single subject. Single letters were stimulated in an alternative forced choice (AFC) paradigm, and short 2–4-letter words were stimulated (one letter at a time) in an open-choice reading paradigm. The subject correctly identified 89% of single letters, 80% of 2-letter, 60% of 3-letter, and 70% of 4-letter words. This work suggests that text can successfully be stimulated and read as visual braille in retinal prosthesis patients. PMID:23189036

Reading visual braille with a retinal prosthesis.

PubMed

Lauritzen, Thomas Z; Harris, Jordan; Mohand-Said, Saddek; Sahel, Jose A; Dorn, Jessy D; McClure, Kelly; Greenberg, Robert J

2012-01-01

Retinal prostheses, which restore partial vision to patients blinded by outer retinal degeneration, are currently in clinical trial. The Argus II retinal prosthesis system was recently awarded CE approval for commercial use in Europe. While retinal prosthesis users have achieved remarkable visual improvement to the point of reading letters and short sentences, the reading process is still fairly cumbersome. This study investigates the possibility of using an epiretinal prosthesis to stimulate visual braille as a sensory substitution for reading written letters and words. The Argus II retinal prosthesis system, used in this study, includes a 10 × 6 electrode array implanted epiretinally, a tiny video camera mounted on a pair of glasses, and a wearable computer that processes the video and determines the stimulation current of each electrode in real time. In the braille reading system, individual letters are created by a subset of dots from a 3 by 2 array of six dots. For the visual braille experiment, a grid of six electrodes was chosen out of the 10 × 6 Argus II array. Groups of these electrodes were then directly stimulated (bypassing the camera) to create visual percepts of individual braille letters. Experiments were performed in a single subject. Single letters were stimulated in an alternative forced choice (AFC) paradigm, and short 2-4-letter words were stimulated (one letter at a time) in an open-choice reading paradigm. The subject correctly identified 89% of single letters, 80% of 2-letter, 60% of 3-letter, and 70% of 4-letter words. This work suggests that text can successfully be stimulated and read as visual braille in retinal prosthesis patients.

Intraocular and extraocular cameras for retinal prostheses: Effects of foveation by means of visual prosthesis simulation

NASA Astrophysics Data System (ADS)

McIntosh, Benjamin Patrick

Blindness due to Age-Related Macular Degeneration and Retinitis Pigmentosa is unfortunately both widespread and largely incurable. Advances in visual prostheses that can restore functional vision in those afflicted by these diseases have evolved rapidly from new areas of research in ophthalmology and biomedical engineering. This thesis is focused on further advancing the state-of-the-art of both visual prostheses and implantable biomedical devices. A novel real-time system with a high performance head-mounted display is described that enables enhanced realistic simulation of intraocular retinal prostheses. A set of visual psychophysics experiments is presented using the visual prosthesis simulator that quantify, in several ways, the benefit of foveation afforded by an eye-pointed camera (such as an eye-tracked extraocular camera or an implantable intraocular camera) as compared with a head-pointed camera. A visual search experiment demonstrates a significant improvement in the time to locate a target on a screen when using an eye-pointed camera. A reach and grasp experiment demonstrates a 20% to 70% improvement in time to grasp an object when using an eye-pointed camera, with the improvement maximized when the percept is blurred. A navigation and mobility experiment shows a 10% faster walking speed and a 50% better ability to avoid obstacles when using an eye-pointed camera. Improvements to implantable biomedical devices are also described, including the design and testing of VLSI-integrable positive mobile ion contamination sensors and humidity sensors that can validate the hermeticity of biomedical device packages encapsulated by hermetic coatings, and can provide early warning of leaks or contamination that may jeopardize the implant. The positive mobile ion contamination sensors are shown to be sensitive to externally applied contamination. A model is proposed to describe sensitivity as a function of device geometry, and verified experimentally. Guidelines are provided on the use of spare CMOS oxide and metal layers to maximize the hermeticity of an implantable microchip. In addition, results are presented on the design and testing of small form factor, very low power, integrated CMOS clock generation circuits that are stable enough to drive commercial image sensor arrays, and therefore can be incorporated in an intraocular camera for retinal prostheses.

Normal aging affects movement execution but not visual motion working memory and decision-making delay during cue-dependent memory-based smooth-pursuit.

PubMed

Fukushima, Kikuro; Barnes, Graham R; Ito, Norie; Olley, Peter M; Warabi, Tateo

2014-07-01

Aging affects virtually all functions including sensory/motor and cognitive activities. While retinal image motion is the primary input for smooth-pursuit, its efficiency/accuracy depends on cognitive processes. Elderly subjects exhibit gain decrease during initial and steady-state pursuit, but reports on latencies are conflicting. Using a cue-dependent memory-based smooth-pursuit task, we identified important extra-retinal mechanisms for initial pursuit in young adults including cue information priming and extra-retinal drive components (Ito et al. in Exp Brain Res 229:23-35, 2013). We examined aging effects on parameters for smooth-pursuit using the same tasks. Elderly subjects were tested during three task conditions as previously described: memory-based pursuit, simple ramp-pursuit just to follow motion of a single spot, and popping-out of the correct spot during memory-based pursuit to enhance retinal image motion. Simple ramp-pursuit was used as a task that did not require visual motion working memory. To clarify aging effects, we then compared the results with the previous young subject data. During memory-based pursuit, elderly subjects exhibited normal working memory of cue information. Most movement-parameters including pursuit latencies differed significantly between memory-based pursuit and simple ramp-pursuit and also between young and elderly subjects. Popping-out of the correct spot motion was ineffective for enhancing initial pursuit in elderly subjects. However, the latency difference between memory-based pursuit and simple ramp-pursuit in individual subjects, which includes decision-making delay in the memory task, was similar between the two groups. Our results suggest that smooth-pursuit latencies depend on task conditions and that, although the extra-retinal mechanisms were functional for initial pursuit in elderly subjects, they were less effective.

Retinal sensitivity and choroidal thickness in high myopia.

PubMed

Zaben, Ahmad; Zapata, Miguel Á; Garcia-Arumi, Jose

2015-03-01

To estimate the association between choroidal thickness in the macular area and retinal sensitivity in eyes with high myopia. This investigation was a transversal study of patients with high myopia, all of whom had their retinal sensitivity measured with macular integrity assessment microperimetry. The choroidal thicknesses in the macular area were then measured by optical coherence tomography, and statistical correlations between their functionality and the anatomical structuralism, as assessed by both types of measurements, were analyzed. Ninety-six eyes from 77 patients with high myopia were studied. The patients had a mean age ± standard deviation of 38.9 ± 13.2 years, with spherical equivalent values ranging from -6.00 diopter to -20.00 diopter (8.74 ± 2.73 diopter). The mean central choroidal thickness was 159.00 ± 50.57. The mean choroidal thickness was directly correlated with sensitivity (r = 0.306; P = 0.004) and visual acuity but indirectly correlated with the spherical equivalent values and patient age. The mean sensitivity was not significantly correlated with the macular foveal thickness (r = -0.174; P = 0.101) or with the overall macular thickness (r = 0.103; P = 0.334); furthermore, the mean sensitivity was significantly correlated with visual acuity (r = 0.431; P < 0.001) and the spherical equivalent values (r = -0.306; P = 0.003). Retinal sensitivity in highly myopic eyes is directly correlated with choroidal thickness and does not seem to be associated with retinal thickness. Thus, in patients with high myopia, accurate measurements of choroidal thickness may provide more accurate information about this pathologic condition because choroidal thickness correlates to a greater degree with the functional parameters, patient age, and spherical equivalent values.

Ocular changes in TgF344-AD rat model of Alzheimer's disease.

PubMed

Tsai, Yuchun; Lu, Bin; Ljubimov, Alexander V; Girman, Sergey; Ross-Cisneros, Fred N; Sadun, Alfredo A; Svendsen, Clive N; Cohen, Robert M; Wang, Shaomei

2014-01-29

Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive decline in learning, memory, and executive functions. In addition to cognitive and behavioral deficits, vision disturbances have been reported in early stage of AD, well before the diagnosis is clearly established. To further investigate ocular abnormalities, a novel AD transgenic rat model was analyzed. Transgenic (Tg) rats (TgF344-AD) heterozygous for human mutant APPswe/PS1ΔE9 and age-matched wild type (WT) rats, as well as 20 human postmortem retinal samples from both AD and healthy donors were used. Visual function in the rodent was analyzed using the optokinetic response and luminance threshold recording from the superior colliculus. Immunohistochemistry on retinal and brain sections was used to detect various markers including amyloid-β (Aβ) plaques. As expected, Aβ plaques were detected in the hippocampus, cortex, and retina of Tg rats. Plaque-like structures were also found in two AD human whole-mount retinas. The choroidal thickness was significantly reduced in both Tg rat and in AD human eyes when compared with age-matched controls. Tg rat eyes also showed hypertrophic retinal pigment epithelial cells, inflammatory cells, and upregulation of complement factor C3. Although visual acuity was lower in Tg than in WT rats, there was no significant difference in the retinal ganglion cell number and retinal vasculature. In this study, we observed pathological changes in the choroid and in RPE cells in the TgF344-AD rat model; choroidal thinning was observed further in human AD retina. Along with Ab deposition, the inflammatory response was manifested by microglial recruitment and complement activation. Further studies are needed to elucidate the significance and mechanisms of these pathological changes [corrected].

Receptive Field Vectors of Genetically-Identified Retinal Ganglion Cells Reveal Cell-Type-Dependent Visual Functions

PubMed Central

Katz, Matthew L.; Viney, Tim J.; Nikolic, Konstantin

2016-01-01

Sensory stimuli are encoded by diverse kinds of neurons but the identities of the recorded neurons that are studied are often unknown. We explored in detail the firing patterns of eight previously defined genetically-identified retinal ganglion cell (RGC) types from a single transgenic mouse line. We first introduce a new technique of deriving receptive field vectors (RFVs) which utilises a modified form of mutual information (“Quadratic Mutual Information”). We analysed the firing patterns of RGCs during presentation of short duration (~10 second) complex visual scenes (natural movies). We probed the high dimensional space formed by the visual input for a much smaller dimensional subspace of RFVs that give the most information about the response of each cell. The new technique is very efficient and fast and the derivation of novel types of RFVs formed by the natural scene visual input was possible even with limited numbers of spikes per cell. This approach enabled us to estimate the 'visual memory' of each cell type and the corresponding receptive field area by calculating Mutual Information as a function of the number of frames and radius. Finally, we made predictions of biologically relevant functions based on the RFVs of each cell type. RGC class analysis was complemented with results for the cells’ response to simple visual input in the form of black and white spot stimulation, and their classification on several key physiological metrics. Thus RFVs lead to predictions of biological roles based on limited data and facilitate analysis of sensory-evoked spiking data from defined cell types. PMID:26845435

Visual acuity at 10 years in Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) study eyes: effect of retinal residua of retinopathy of prematurity.

PubMed

Dobson, Velma; Quinn, Graham E; Summers, C Gail; Hardy, Robert J; Tung, Betty

2006-02-01

To describe recognition (letter) acuity at age 10 years in eyes with and without retinal residua of retinopathy of prematurity (ROP). Presence and severity of ROP residua were documented by a study ophthalmologist. Masked testers measured monocular recognition visual acuity (Early Treatment of Diabetic Retinopathy Study) when the children were 10 years old. Two hundred forty-seven of 255 surviving Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) randomized trial patients participated. A reference group of 102 of 104 Philadelphia-based CRYO-ROP study participants who did not develop ROP was also tested. More severe retinal residua were associated with worse visual acuity, regardless of whether retinal ablation was performed to treat the severe acute-phase ROP. However, within each ROP residua category, there was a wide range of visual acuity results. This is the first report of the relation between visual acuity (Early Treatment of Diabetic Retinopathy Study charts) and structural abnormalities related to ROP in a large group of eyes that developed threshold ROP in the perinatal period. Visual deficits are greater in eyes with more severe retinal residua than in eyes with mild or no residua. However, severity of ROP residua does not predict the visual acuity of an individual eye because within a single residua category, acuity may range from near normal to blind.

An analysis of observer-rated functional vision in patients implanted with the Argus II Retinal Prosthesis System at three years.

PubMed

Geruschat, Duane R; Richards, Thomas P; Arditi, Aries; da Cruz, Lyndon; Dagnelie, Gislin; Dorn, Jessy D; Duncan, Jacque L; Ho, Allen C; Olmos de Koo, Lisa C; Sahel, José-Alain; Stanga, Paulo E; Thumann, Gabriele; Wang, Vizhong; Greenberg, Robert J

2016-05-01

The purpose of this analysis was to compare observer-rated tasks in patients implanted with the Argus II Retinal Prosthesis System, when the device is ON versus OFF. The Functional Low-Vision Observer Rated Assessment (FLORA) instrument was administered to 26 blind patients implanted with the Argus II Retinal Prosthesis System at a mean follow-up of 36 months. FLORA is a multi-component instrument that consists in part of observer-rated assessment of 35 tasks completed with the device ON versus OFF. The ease with which a patient completes a task is scored using a four-point scale, ranging from easy (score of 1) to impossible (score of 4). The tasks are evaluated individually and organised into four discrete domains, including 'Visual orientation', 'Visual mobility', 'Daily life and 'Interaction with others'. Twenty-six patients completed each of the 35 tasks. Overall, 24 out of 35 tasks (69 per cent) were statistically significantly easier to achieve with the device ON versus OFF. In each of the four domains, patients' performances were significantly better (p < 0.05) with the device ON versus OFF, ranging from 19 to 38 per cent improvement. Patients with an Argus II Retinal Prosthesis implanted for 18 to 44 months (mean 36 months), demonstrated significantly improved completion of vision-related tasks with the device ON versus OFF. © 2016 The Authors Clinical and Experimental Optometry published by John Wiley & Sons Australia, Ltd on behalf of Optometry Australia.

An analysis of observer‐rated functional vision in patients implanted with the Argus II Retinal Prosthesis System at three years

PubMed Central

Richards, Thomas P; Arditi, Aries; da Cruz, Lyndon; Dagnelie, Gislin; Dorn, Jessy D; Duncan, Jacque L; Ho, Allen C; Olmos de Koo, Lisa C; Sahel, José‐Alain; Stanga, Paulo E; Thumann, Gabriele; Wang, Vizhong; Greenberg, Robert J

2016-01-01

Abstract Objective The purpose of this analysis was to compare observer‐rated tasks in patients implanted with the Argus II Retinal Prosthesis System, when the device is ON versus OFF. Methods The Functional Low‐Vision Observer Rated Assessment (FLORA) instrument was administered to 26 blind patients implanted with the Argus II Retinal Prosthesis System at a mean follow‐up of 36 months. FLORA is a multi‐component instrument that consists in part of observer‐rated assessment of 35 tasks completed with the device ON versus OFF. The ease with which a patient completes a task is scored using a four‐point scale, ranging from easy (score of 1) to impossible (score of 4). The tasks are evaluated individually and organised into four discrete domains, including ‘Visual orientation’, ‘Visual mobility’, ‘Daily life and ‘Interaction with others’. Results Twenty‐six patients completed each of the 35 tasks. Overall, 24 out of 35 tasks (69 per cent) were statistically significantly easier to achieve with the device ON versus OFF. In each of the four domains, patients’ performances were significantly better (p < 0.05) with the device ON versus OFF, ranging from 19 to 38 per cent improvement. Conclusion Patients with an Argus II Retinal Prosthesis implanted for 18 to 44 months (mean 36 months), demonstrated significantly improved completion of vision‐related tasks with the device ON versus OFF. PMID:26804484

Postoperative Recovery of Visual Function after Macula-Off Rhegmatogenous Retinal Detachment

PubMed Central

van de Put, Mathijs A. J.; Croonen, Danna; Nolte, Ilja M.; Japing, Wouter J.; Hooymans, Johanna M. M.; Los, Leonoor I.

2014-01-01

Purpose To determine which factors affect the recovery of visual function in macula off rhegmatogenous retinal detachment (RRD). Methods In a prospective study of forty-five patients with a primary macula-off RRD of 24 hours to 6 weeks duration, the height of the macular detachment was determined by ultrasonography. At 12 months postoperatively, best corrected visual acuity (BCVA), contrast acuity, and color confusion indexes (CCI) were obtained. Results Macular detachment was present for 2–32 (median 7) days before repair. A shorter duration of macular detachment was correlated with a better CCI saturé (p = 0.0026) and lower LogMAR BCVA (better Snellen visual acuity)(p = 0.012). Also, a smaller height of macular detachment was correlated with a lower LogMAR BCVA (p = 0.0034). A younger age and lower pre-operative LogMAR BCVA at presentation were both correlated with better postoperative contrast acuity in the total group (age: p = 1.7×10−4 and pre-operative LogMAR BCVA: p = 0.0034). Conclusion Functional recovery after macula-off RRD is affected by the duration and the height of the macular detachment. Recovery of contrast acuity is also affected by age and BCVA at presentation. Meeting presentation ARVO annual meeting 2013, May 7, Seattle, Washington, United States of America. Trial registration: trialregister.nl NTR839 PMID:24927502

Nonsyndromic Retinitis Pigmentosa in the Ashkenazi Jewish Population: Genetic and Clinical Aspects.

PubMed

Kimchi, Adva; Khateb, Samer; Wen, Rong; Guan, Ziqiang; Obolensky, Alexey; Beryozkin, Avigail; Kurtzman, Shoshi; Blumenfeld, Anat; Pras, Eran; Jacobson, Samuel G; Ben-Yosef, Tamar; Newman, Hadas; Sharon, Dror; Banin, Eyal

2018-05-01

To analyze the genetic and clinical findings in retinitis pigmentosa (RP) patients of Ashkenazi Jewish (AJ) descent, aiming to identify genotype-phenotype correlations. Cohort study. Retinitis pigmentosa patients from 230 families of AJ origin. Sanger sequencing was performed to detect specific founder mutations known to be prevalent in the AJ population. Ophthalmologic analysis included a comprehensive clinical examination, visual acuity (VA), visual fields, electroretinography, color vision testing, and retinal imaging by OCT, pseudocolor, and autofluorescence fundus photography. Inheritance pattern and causative mutation; retinal function as assessed by VA, visual fields, and electroretinography results; and retinal structural changes observed on clinical funduscopy as well as by pseudocolor, autofluorescence, and OCT imaging. The causative mutation was identified in 37% of families. The most prevalent RP-causing mutations are the Alu insertion (c.1297_8ins353, p.K433Rins31*) in the male germ cell-associated kinase (MAK) gene (39% of families with a known genetic cause for RP) and c.124A>G, p.K42E in dehydrodolichol diphosphate synthase (DHDDS) (33%). Additionally, disease-causing mutations were identified in 11 other genes. Analysis of clinical parameters of patients with mutations in the 2 most common RP-causing genes revealed that MAK patients had better VA and visual fields at relatively older ages in comparison with DHDDS patients. Funduscopic findings of DHDDS patients matched those of MAK patients who were 20 to 30 years older. Patients with DHDDS mutations were referred for electrophysiologic evaluation at earlier ages, and their cone responses became nondetectable at a much younger age than MAK patients. Our AJ cohort of RP patients is the largest reported to date and showed a substantial difference in the genetic causes of RP compared with cohorts of other populations, mainly a high rate of autosomal recessive inheritance and a unique composition of causative genes. The most common RP-causing genes in our cohort, MAK and DHDDS, were not described as major causative genes in other populations. The clinical data show that in general, patients with biallelic MAK mutations had a later age of onset and a milder retinal phenotype compared with patients with biallelic DHDDS mutations. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Clinical Features of Newly Diagnosed Cytomegalovirus Retinitis in Northern Thailand

PubMed Central

Ausayakhun, Somsanguan; Keenan, Jeremy D; Ausayakhun, Sakarin; Jirawison, Choeng; Khouri, Claire M; Skalet, Alison H; Heiden, David; Holland, Gary N; Margolis, Todd P

2011-01-01

Purpose To characterize the clinical manifestations of cytomegalovirus (CMV) retinitis in northern Thailand. Design Prospective, observational cross-sectional study. Methods We recorded characteristics of 52 consecutive patients newly diagnosed with CMV retinitis at a tertiary university-based medical center in northern Thailand. Indirect ophthalmoscopy by experienced ophthalmologists was supplemented with fundus photography to determine the proportion of eyes with various clinical features of CMV retinitis. Results Of the 52 patients with CMV retinitis, 55.8% were female. All were HIV-positive. The vast majority (90.4%) had started antiretroviral therapy. CMV retinitis was bilateral in 46.2% of patients. Bilateral visual acuity worse than 20/60 was observed in 23.1% of patients. Of 76 eyes with CMV retinitis, 61.8% had zone I disease and 21.6% had lesions involving the fovea. Lesions larger than 25% of the retinal area were observed in 57.5% of affected eyes. CMV retinitis lesions commonly had marked or severe border opacity (47.4% of eyes). Vitreous haze was often present (46.1% of eyes). Visual impairment was more common in eyes with larger retinitis lesions. Retinitis lesion size, used as a proxy for duration of disease, was associated with fulminant appearance (OR 1.24 [1.01 – 1.51]), and marked or severe border opacity (OR 1.36 [1.11 – 1.67]). Based on lesion size, retinitis preceded antiretroviral treatment in each patient. Conclusions Patients presenting to a tertiary medical center in northern Thailand have advanced CMV retinitis, possibly due to delayed diagnosis. Earlier screening and treatment of CMV retinitis may limit progression of disease and prevent visual impairment in this population. PMID:22265148

The efficacy of fluid-gas exchange for the treatment of postvitrectomy retinal detachment.

PubMed

Jang, Ji Hye; Kim, Yu Cheol; Kim, Kwang Soo

2009-12-01

This study was designed to evaluate the efficacy of fluid-gas exchange for the treatment of postvitrectomy retinal detachment. We retrospectively reviewed the records of 33 consecutive patients (35 eyes) who underwent fluid-gas exchange treatment for postvitrectomy retinal detachment using the two-needle pars plana approach technique. The retinal reattachment rate was 80.0% after complete intravitreal gas disappearance following the fluid-gas exchange; the overall success rate was 65.7%. Visual acuity was improved or stable in 80.0% of cases; a two-line or greater vision improvement or a best-corrected visual acuity of 0.4 or better occurred in 62.9% of cases. The success rates for superior retinal detachments and posterior pole retinal detachments were 76.5% and 85.7%, respectively. Fluid-gas exchange represents a simple and cost-effective alternative outpatient procedure for retinal reattachment without reoperation for the treatment of superior and posterior pole retinal detachments.

Light and the laboratory mouse.

PubMed

Peirson, Stuart N; Brown, Laurence A; Pothecary, Carina A; Benson, Lindsay A; Fisk, Angus S

2018-04-15

Light exerts widespread effects on physiology and behaviour. As well as the widely-appreciated role of light in vision, light also plays a critical role in many non-visual responses, including regulating circadian rhythms, sleep, pupil constriction, heart rate, hormone release and learning and memory. In mammals, responses to light are all mediated via retinal photoreceptors, including the classical rods and cones involved in vision as well as the recently identified melanopsin-expressing photoreceptive retinal ganglion cells (pRGCs). Understanding the effects of light on the laboratory mouse therefore depends upon an appreciation of the physiology of these retinal photoreceptors, including their differing sens itivities to absolute light levels and wavelengths. The signals from these photoreceptors are often integrated, with different responses involving distinct retinal projections, making generalisations challenging. Furthermore, many commonly used laboratory mouse strains carry mutations that affect visual or non-visual physiology, ranging from inherited retinal degeneration to genetic differences in sleep and circadian rhythms. Here we provide an overview of the visual and non-visual systems before discussing practical considerations for the use of light for researchers and animal facility staff working with laboratory mice. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Pseudo-Fovea Formation After Gene Therapy for RPE65-LCA

PubMed Central

Cideciyan, Artur V.; Aguirre, Geoffrey K.; Jacobson, Samuel G.; Butt, Omar H.; Schwartz, Sharon B.; Swider, Malgorzata; Roman, Alejandro J.; Sadigh, Sam; Hauswirth, William W.

2015-01-01

Purpose. The purpose of this study was to evaluate fixation location and oculomotor characteristics of 15 patients with Leber congenital amaurosis (LCA) caused by RPE65 mutations (RPE65-LCA) who underwent retinal gene therapy. Methods. Eye movements were quantified under infrared imaging of the retina while the subject fixated on a stationary target. In a subset of patients, letter recognition under retinal imaging was performed. Cortical responses to visual stimulation were measured using functional magnetic resonance imaging (fMRI) in two patients before and after therapy. Results. All patients were able to fixate on a 1° diameter visible target in the dark. The preferred retinal locus of fixation was either at the anatomical fovea or at an extrafoveal locus. There were a wide range of oculomotor abnormalities. Natural history showed little change in oculomotor abnormalities if target illuminance was increased to maintain target visibility as the disease progressed. Eleven of 15 study eyes treated with gene therapy showed no differences from baseline fixation locations or instability over an average of follow-up of 3.5 years. Four of 15 eyes developed new pseudo-foveas in the treated retinal regions 9 to 12 months after therapy that persisted for up to 6 years; patients used their pseudo-foveas for letter identification. fMRI studies demonstrated that preservation of light sensitivity was restricted to the cortical projection zone of the pseudo-foveas. Conclusions. The slow emergence of pseudo-foveas many months after the initial increases in light sensitivity points to a substantial plasticity of the adult visual system and a complex interaction between it and the progression of underlying retinal disease. The visual significance of pseudo-foveas suggests careful consideration of treatment zones for future gene therapy trials. (ClinicalTrials.gov number, NCT00481546.) PMID:25537204

The mapping of the visual field onto the dorso-lateral tectum of the pigeon (Columba livia) and its relations with retinal specializations.

PubMed

Letelier, Juan-Carlos; Marin, Gonzalo; Sentis, Elisa; Tenreiro, Andrea; Fredes, Felipe; Mpodozis, Jorge

2004-01-30

Most of the physiological studies of the pigeon retino-tectal visual pathway have investigated the accessible tectum, a small dorso-lateral tectal section that can be easily accessed by a simple craniotomy. However, at present we lack a detailed study of the topographical arrangement between the visual field, the retina and the accessible tectum. In particular, it is not known which section of the visual field is mapped onto the accessible tectum, and which of the specialized retinal areas mediates this projection. Here we determined, using local field potential (LFP) recordings and reverse retinoscopy, the shape, size and position in the visual space of the portion of the visual field mapped onto the accessible tectum (called here the accessible visual field, or AVF). Using this data and the mapping of Nalbach et al. [Vis. Res. 30 (4) (1990) 529], the retinal area corresponding to the AVF was determined. Such retinal area was also directly delimited by means of retrograde transport of DiI. The results indicate that the AVF is a triangular perifoveal zone encompassing only 15% of total visual field. The retinal region corresponding to the AVF has the shape of an elongated triangle that runs parallel to the visual equator and contains the fovea, the tip of the pecten, a perifoveal region of the yellow field and a small crescent of the red field. In agreement with this anatomical heterogeneity, visual evoked potentials measured in different parts of the accessible tectum present steep variations in shape and size. These results are helpful to better design and interpret anatomical and physiological experiments involving the pigeon's visual system.

Virally delivered Channelrhodopsin-2 Safely and Effectively Restores Visual Function in Multiple Mouse Models of Blindness

PubMed Central

Doroudchi, M Mehdi; Greenberg, Kenneth P; Liu, Jianwen; Silka, Kimberly A; Boyden, Edward S; Lockridge, Jennifer A; Arman, A Cyrus; Janani, Ramesh; Boye, Shannon E; Boye, Sanford L; Gordon, Gabriel M; Matteo, Benjamin C; Sampath, Alapakkam P; Hauswirth, William W; Horsager, Alan

2011-01-01

Previous work established retinal expression of channelrhodopsin-2 (ChR2), an algal cation channel gated by light, restored physiological and behavioral visual responses in otherwise blind rd1 mice. However, a viable ChR2-based human therapy must meet several key criteria: (i) ChR2 expression must be targeted, robust, and long-term, (ii) ChR2 must provide long-term and continuous therapeutic efficacy, and (iii) both viral vector delivery and ChR2 expression must be safe. Here, we demonstrate the development of a clinically relevant therapy for late stage retinal degeneration using ChR2. We achieved specific and stable expression of ChR2 in ON bipolar cells using a recombinant adeno-associated viral vector (rAAV) packaged in a tyrosine-mutated capsid. Targeted expression led to ChR2-driven electrophysiological ON responses in postsynaptic retinal ganglion cells and significant improvement in visually guided behavior for multiple models of blindness up to 10 months postinjection. Light levels to elicit visually guided behavioral responses were within the physiological range of cone photoreceptors. Finally, chronic ChR2 expression was nontoxic, with transgene biodistribution limited to the eye. No measurable immune or inflammatory response was observed following intraocular vector administration. Together, these data indicate that virally delivered ChR2 can provide a viable and efficacious clinical therapy for photoreceptor disease-related blindness. PMID:21505421

Closed-Loop Efficient Searching of Optimal Electrical Stimulation Parameters for Preferential Excitation of Retinal Ganglion Cells

PubMed Central

Guo, Tianruo; Yang, Chih Yu; Tsai, David; Muralidharan, Madhuvanthi; Suaning, Gregg J.; Morley, John W.; Dokos, Socrates; Lovell, Nigel H.

2018-01-01

The ability for visual prostheses to preferentially activate functionally-distinct retinal ganglion cells (RGCs) is important for improving visual perception. This study investigates the use of high frequency stimulation (HFS) to elicit RGC activation, using a closed-loop algorithm to search for optimal stimulation parameters for preferential ON and OFF RGC activation, resembling natural physiological neural encoding in response to visual stimuli. We evaluated the performance of a wide range of electrical stimulation amplitudes and frequencies on RGC responses in vitro using murine retinal preparations. It was possible to preferentially excite either ON or OFF RGCs by adjusting amplitudes and frequencies in HFS. ON RGCs can be preferentially activated at relatively higher stimulation amplitudes (>150 μA) and frequencies (2–6.25 kHz) while OFF RGCs are activated by lower stimulation amplitudes (40–90 μA) across all tested frequencies (1–6.25 kHz). These stimuli also showed great promise in eliciting RGC responses that parallel natural RGC encoding: ON RGCs exhibited an increase in spiking activity during electrical stimulation while OFF RGCs exhibited decreased spiking activity, given the same stimulation amplitude. In conjunction with the in vitro studies, in silico simulations indicated that optimal HFS parameters could be rapidly identified in practice, whilst sampling spiking activity of relevant neuronal subtypes. This closed-loop approach represents a step forward in modulating stimulation parameters to achieve appropriate neural encoding in retinal prostheses, advancing control over RGC subtypes activated by electrical stimulation. PMID:29615857

Retinal ganglion cell projections to the hamster suprachiasmatic nucleus, intergeniculate leaflet, and visual midbrain: bifurcation and melanopsin immunoreactivity

NASA Technical Reports Server (NTRS)

Morin, Lawrence P.; Blanchard, Jane H.; Provencio, Ignacio

2003-01-01

The circadian clock in the suprachiasmatic nucleus (SCN) receives direct retinal input via the retinohypothalamic tract (RHT), and the retinal ganglion cells contributing to this projection may be specialized with respect to direct regulation of the circadian clock. However, some ganglion cells forming the RHT bifurcate, sending axon collaterals to the intergeniculate leaflet (IGL) through which light has secondary access to the circadian clock. The present studies provide a more extensive examination of ganglion cell bifurcation and evaluate whether ganglion cells projecting to several subcortical visual nuclei contain melanopsin, a putative ganglion cell photopigment. The results showed that retinal ganglion cells projecting to the SCN send collaterals to the IGL, olivary pretectal nucleus, and superior colliculus, among other places. Melanopsin-immunoreactive (IR) ganglion cells are present in the hamster retina, and some of these cells project to the SCN, IGL, olivary pretectal nucleus, or superior colliculus. Triple-label analysis showed that melanopsin-IR cells bifurcate and project bilaterally to each SCN, but not to the other visual nuclei evaluated. The melanopsin-IR cells have photoreceptive characteristics optimal for circadian rhythm regulation. However, the presence of moderately widespread bifurcation among ganglion cells projecting to the SCN, and projection by melanopsin-IR cells to locations distinct from the SCN and without known rhythm function, suggest that this ganglion cell type is generalized, rather than specialized, with respect to the conveyance of photic information to the brain. Copyright 2003 Wiley-Liss, Inc.

A Rare Complication After Septoplasty: Visual Loss Due to Right Retinal Artery Spasm.

PubMed

Günay, Celal; Altin, Gökhan; Kersin, Burak; Odabaşi, Mahmut

2018-03-01

Septoplasty is a commonly used procedure for correcting septal cartilage deformities. Hemorrhage, abscesses, scaling, adhesions, and scar tissue are often seen after the operation of the septoplasty, but temporary or permanent visual loss due to local anesthetic use has been reported very rarely in the literature. The authors also aimed to present a female patient with retinal artery spasm in the right eye after septoplasty in this article. A 27-year-old female patient was admitted to the authors' clinic with long-standing nasal obstruction and postnasal drip. There was no feature in her history and also no sign other than nasal septal deviation on physical examination. The patient was informed about the operation and the operation was planned. Emergency eye consultation was requested after the patient said that the right eye of the patient had never seen in the postoperative wake-up hall. Examination by an ophthalmologist; mild exotropia and total loss of vision in the right eye (including loss of light reflex) was detected. The light reaction in the affected eye was negative and indirect reaction was positive. After enlargement of the pupil, fundus examination revealed that the right posterior pole region (inside of the macula and vessel arches) was pale and no central retinal artery pulsation was observed. The patient was diagnosed with central retinal artery occlusion and emergency intervention was performed. The right eye massage, paracentesis, and hyperbaric oxygen therapy returned to the patient's visual function.

Cell surgery and growth factors in dry age-related macular degeneration: visual prognosis and morphological study

PubMed Central

Limoli, Paolo Giuseppe; Limoli, Celeste; Vingolo, Enzo Maria; Scalinci, Sergio Zaccaria; Nebbioso, Marcella

2016-01-01

Background The aim of this research was to study the overall restoration effect on residual retinal cells through surgically grafted autologous cells onto the surrounding tissue, choroid and retina in order to produce a constant secretion of growth factors (GFs) in dry age-related macular degeneration (AMD) patients. Results 6 months after surgery, several values were statistically significant in the group with higher RTA. Also patient compliance analysis (PCA) in relation to functional change perception appeared to be very good. Methods Thirty-six eyes of 25 patients (range 64-84 years of age) affected by dry AMD were included in study, and divided in two groups by spectral domain-optical coherence tomography (SD-OCT): group A with retinal thickness average (RTA) less than 250 microns (μm) and group B with RTA equal to or more than 250 μm. Adipocytes, adipose-derived stem cells from the stromal-vascular fraction, and platelets from platelet-rich plasma were implanted in the suprachoroidal space. Particularly, the following parameters were evaluated: best corrected visual acuity (BCVA) for far and near distance, retinal thickness maps, scotopic and photopic electroretinogram (ERG), and microperimetry (MY). All statistical analyses were performed with STATA 14.0 (Collage Station, Texas, USA). Conclusions The available set of GFs allowed biological retinal neuroenhancement. After 6 months it improved visual performance (VP), but the increase was better if RTA recorded by OCT was higher, probably in relation to the presence of areas with greater cellularity. PMID:27391437

Cell surgery and growth factors in dry age-related macular degeneration: visual prognosis and morphological study.

PubMed

Limoli, Paolo Giuseppe; Limoli, Celeste; Vingolo, Enzo Maria; Scalinci, Sergio Zaccaria; Nebbioso, Marcella

2016-07-26

The aim of this research was to study the overall restoration effect on residual retinal cells through surgically grafted autologous cells onto the surrounding tissue, choroid and retina in order to produce a constant secretion of growth factors (GFs) in dry age-related macular degeneration (AMD) patients. 6 months after surgery, several values were statistically significant in the group with higher RTA. Also patient compliance analysis (PCA) in relation to functional change perception appeared to be very good. Thirty-six eyes of 25 patients (range 64-84 years of age) affected by dry AMD were included in study, and divided in two groups by spectral domain-optical coherence tomography (SD-OCT): group A with retinal thickness average (RTA) less than 250 microns (µm) and group B with RTA equal to or more than 250 µm. Adipocytes, adipose-derived stem cells from the stromal-vascular fraction, and platelets from platelet-rich plasma were implanted in the suprachoroidal space. Particularly, the following parameters were evaluated: best corrected visual acuity (BCVA) for far and near distance, retinal thickness maps, scotopic and photopic electroretinogram (ERG), and microperimetry (MY). All statistical analyses were performed with STATA 14.0 (Collage Station, Texas, USA). The available set of GFs allowed biological retinal neuroenhancement. After 6 months it improved visual performance (VP), but the increase was better if RTA recorded by OCT was higher, probably in relation to the presence of areas with greater cellularity.

Suppression of Melatonin Secretion in Totally Visually Blind People by Ocular Exposure to White Light: Clinical Characteristics.

PubMed

Hull, Joseph T; Czeisler, Charles A; Lockley, Steven W

2018-04-03

Although most totally visually blind individuals exhibit nonentrained circadian rhythms due to an inability of light to entrain the circadian pacemaker, a small proportion retain photic circadian entrainment, melatonin suppression, and other nonimage-forming responses to light. It is thought that these responses to light persist because of the survival of melanospin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs), which project primarily to the circadian pacemaker and are functionally distinct from the rod and cone photoreceptors that mediate vision. We aimed to assess the integrity of nonimage-forming photoreception in totally visually blind patients with a range of ocular disorders. Within-subject, dark-controlled design. A total of 18 totally visually blind individuals (7 females; mean age ± standard deviation = 49.8±11.0 years) with various causes of blindness, including 3 bilaterally enucleated controls. Melatonin concentrations were compared during exposure to a 6.5-hour bright white light (∼7000 lux) with melatonin concentrations measured 24 hours earlier at the corresponding clock times under dim-light (4 lux) conditions. Area under the curve (AUC) for melatonin concentration. Melatonin concentrations were significantly suppressed (defined as ≥33% suppression) during the bright-light condition compared with the dim-light condition in 5 of 15 participants with eyes (retinitis pigmentosa, n = 2; retinopathy of prematurity [ROP], n = 2; bilateral retinal detachments, n = 1). Melatonin concentrations remained unchanged in response to light in the remaining 10 participants with eyes (ROP, n = 3; optic neuritis/neuropathy, n = 2; retinopathy unknown, n = 2; congenital glaucoma, n = 1; congenital rubella syndrome, n = 1; measles retinopathy, n = 1) and in all 3 bilaterally enucleated participants. These data confirm that light-induced suppression of melatonin remains functionally intact in a minority of totally visually blind individuals with eyes. None of the bilaterally enucleated individuals or those with phthisis bulbi was responsive to light; of the remainder, half were responsive to light. Although inner retinal damage is associated with a high likelihood that nonimage-forming photoreception is absent, the impact of outer retinal damage is more ambiguous, and therefore the assessment of the presence, attenuation, or absence of nonimage-forming light responses in totally blind patients requires careful individual confirmation and cannot simply be assumed from the type of blindness. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Patterns of peripheral retinal and central macula ischemia in diabetic retinopathy as evaluated by ultra-widefield fluorescein angiography.

PubMed

Sim, Dawn A; Keane, Pearse A; Rajendram, Ranjan; Karampelas, Michael; Selvam, Senthil; Powner, Michael B; Fruttiger, Marcus; Tufail, Adnan; Egan, Catherine A

2014-07-01

To investigate the association between peripheral and central ischemia in diabetic retinopathy. Retrospective, cross-sectional. Consecutive ultra-widefield fluorescein angiography images were collected from patients with diabetes over a 12-month period. Parameters quantified include the foveal avascular zone (FAZ) area, peripheral ischemic index, peripheral leakage index, and central retinal thickness measurements, as well as visual acuity. The peripheral ischemia or leakage index was calculated as the area of capillary nonperfusion or leakage, expressed as a percentage of the total retinal area. Forty-seven eyes of 47 patients were included. A moderate correlation was observed between the peripheral ischemia index and FAZ area (r = 0.49, P = .0001). A moderate correlation was also observed between the peripheral leakage index and FAZ area, but only in eyes that were laser naïve (r = 0.44, P = .02). A thinner retina was observed in eyes with macular ischemia (217 ± 81.8 μm vs 272 ± 36.0 μm) (P = .02), but not peripheral ischemia (258 ± 76.3 μm vs 276 ± 68.0 μm) (P = .24). The relationships between different patterns of peripheral and central macular pathology and visual acuity were evaluated in a step-wise multivariable regression model, and the variables that remained independently associated were age (r = 0.33, P = .03), FAZ area (r = 0.45, P = .02), and central retinal thickness (r = 0.38, P = .01), (R(2)-adjusted = 0.36). Ultra-widefield fluorescein angiography provides an insight into the relationships between diabetic vascular complications in the retinal periphery and central macula. Although we observed relationships between ischemia and vascular leakage in the macula and periphery, it was only macular ischemia and retinal thinning that was independently associated with a reduced visual function. Copyright © 2014 Elsevier Inc. All rights reserved.

Reperfusion of occluded branch retinal arteries by transluminal Nd:YAG laser embolysis combined with intravenous thrombolysis of urokinase

PubMed Central

Chai, Fang; Du, Shanshuang; Zhao, Xiquan

2017-01-01

Purpose: To report successful treatment with transluminal Nd:YAG laser embolysis (TYE) combined with urokinase thrombolysis for reperfusion of occluded branch retinal arteries with visible emboli. Methods: A total of 34 eyes from 34 patients with acute, severe vision loss secondary to a branch retinal artery occlusion with visible emboli and retinal whitening were examined. Each patient was administered TYE therapy, which focused on the embolus, using an ocular contact lens; a 0.3–0.9 mJ laser pulse was delivered directly and gradually according to the reaction. Fundus photographs and fundus fluorescein angiography (FFA) were obtained before and immediately after the laser treatment. All patients received urokinase thrombolysis therapy drops intravenously for 5 days at 10–20 u/d. The follow-up period ranged from 6 to 14 months after therapy. The morphological characteristics of FFA associated with obstruction recovery of arterial fluorescence filling and visual function were analyzed. Results: After TYE therapy, FFA examinations showed that the retinal artery and its branches exhibited completely restored blood flow without obstruction in 13 eyes, accounting for 38.2% of the cases. The blood flow was mostly recovered in 11 eyes (32.4% of patients). FFA examinations following the combined intravenous urokinase thrombolysis therapy showed that the retinal artery and its branches exhibited completely restored blood flow after obstruction in 16 eyes (47.1% of patients). The blood flow was mostly recovered in 15 eyes (44.1% of patients). Conclusion: TYE combined with urokinase thrombolysis is effective for reperfusion of occluded branch retinal arteries and improving visual recovery in patients with visible emboli. PMID:29162667

Mixing of Chromatic and Luminance Retinal Signals in Primate Area V1.

PubMed

Li, Xiaobing; Chen, Yao; Lashgari, Reza; Bereshpolova, Yulia; Swadlow, Harvey A; Lee, Barry B; Alonso, Jose Manuel

2015-07-01

Vision emerges from activation of chromatic and achromatic retinal channels whose interaction in visual cortex is still poorly understood. To investigate this interaction, we recorded neuronal activity from retinal ganglion cells and V1 cortical cells in macaques and measured their visual responses to grating stimuli that had either luminance contrast (luminance grating), chromatic contrast (chromatic grating), or a combination of the two (compound grating). As with parvocellular or koniocellular retinal ganglion cells, some V1 cells responded mostly to the chromatic contrast of the compound grating. As with magnocellular retinal ganglion cells, other V1 cells responded mostly to the luminance contrast and generated a frequency-doubled response to equiluminant chromatic gratings. Unlike magnocellular and parvocellular retinal ganglion cells, V1 cells formed a unimodal distribution for luminance/color preference with a 2- to 4-fold bias toward luminance. V1 cells associated with positive local field potentials in deep layers showed the strongest combined responses to color and luminance and, as a population, V1 cells encoded a diverse combination of luminance/color edges that matched edge distributions of natural scenes. Taken together, these results suggest that the primary visual cortex combines magnocellular and parvocellular retinal inputs to increase cortical receptive field diversity and to optimize visual processing of our natural environment. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

High ocular CMV copies and mismatched receipts may predict poor visual prognosis in CMV retinitis patients following allogeneic haematopoietic stem cell transplantation.

PubMed

Zhang, Yuehong; Ruan, Xiangcai; Yang, Weizhong; Li, Ling; Xian, Zhuanhua; Feng, Qiting; Mo, Wenjian

2017-11-29

To summarize the clinical characteristics and potential factors affecting the visual outcomes in patients with cytomegalovirus retinitis following allogeneic haematopoietic stem cell transplantation (HSCT). This retrospective study enrolled 12 patients (19 eyes) with cytomegalovirus retinitis after HSCT at Guangzhou First People's Hospital in China between January 2013 and December 2014. Demographic and clinical characteristics, ocular manifestations and visual outcomes were evaluated by reviewing medical records at the Departments of Hematology and Ophthalmology. All patients were followed up at least 6 months after stopping antiviral therapy. The visual outcome was defined as improvement, stabilization and deterioration. The subjects were composed of 7 human leucocyte antigen-matched and 5 mismatched receipts. All patients received combined systemic and intravitreous antiviral therapy. Eleven eyes gained improved or stabilized visual acuity, while 8 eyes suffered deterioration. Eyes with cytomegalovirus load less than 1 × 10 4 copies/ml in vitreous accounted for higher rate in eyes with good visual prognosis than those with cytomegalovirus copies above 1 × 10 4 copies/ml (52.63% vs 5.26%, P < 0.001). Human leucocyte antigen-matched receipts gained better visual prognosis than those mismatched ones (47.37% vs10.53%, P < 0.05). The virus types, cytomegalovirus peak in the blood, involved retinal zone and size had no influence on the visual outcomes (all P > 0.05). High ocular cytomegalovirus copies and mismatched receipts may be potential adverse factors affecting visual outcomes in cytomegalovirus retinitis patients following allogeneic HSCT.

Anatomical and functional outcomes of retinectomies in retinal detachments complicated by proliferative vitreoretinopathy.

PubMed

Adhi, Mohammad Idrees; Siyal, Nisar; Aziz, Sumbul

2017-01-01

To study anatomical and functional outcomes of retinectomies in rhegmatogenous retinal detachments complicated by proliferative vitreoretinopathy. This is a retrospective interventional consecutive case series of eyes with rhegmatogenous retinal detachments complicated by advanced proliferative vitreoretinopathy and managed by relaxing retinectomy over a period of seventeen years. Three-port pars plana vitrectomy included core vitrectomy and removal of all epi-retinal membranes. On failure to flatten, retina was cut and excised. Basal vitrectomy and removal of anterior flap of retina then followed. Silicone oil was used as temponade in majority of cases. The dependent variables were anatomical and functional outcomes. The statistical analysis was performed on SPSS 21. Series included 370 eyes of 337 patients. Mean follow up was 39 months. Scleral explant was used in 90(24.39%) cases. Two hundred and nine (56.49%) eyes were operated with trans conjunctival sutureless vitrectomy technique. Procedure was bilateral in 33 patients (09.79%). Retina attached in 311(84.05%) eyes after initial surgery. Final re-attachment after one or more surgeries was achieved in 344(92.97%) eyes. Two hundred and eleven (57.02%) cases achieved visual acuity of 6/60 or better. Relaxing retinectomies have good and encouraging anatomical and functional outcomes. This surgery can be effectively carried out with trans conjunctival sutureless vitrectomy technique.

Pattern of retinal morphological and functional decay in a light-inducible, rhodopsin mutant mouse.

PubMed

Gargini, Claudia; Novelli, Elena; Piano, Ilaria; Biagioni, Martina; Strettoi, Enrica

2017-07-18

Hallmarks of Retinitis Pigmentosa (RP), a family of genetic diseases, are a typical rod-cone-degeneration with initial night blindness and loss of peripheral vision, followed by decreased daylight sight and progressive visual acuity loss up to legal blindness. Great heterogeneity in nature and function of mutated genes, variety of mutations for each of them, variability in phenotypic appearance and transmission modality contribute to make RP a still incurable disease. Translational research relies on appropriate animal models mimicking the genetic and phenotypic diversity of the human pathology. Here, we provide a systematic, morphological and functional analysis of Rho Tvrm4 /Rho + rhodopsin mutant mice, originally described in 2010 and portraying several features of common forms of autosomal dominant RP caused by gain-of-function mutations. These mice undergo photoreceptor degeneration only when exposed briefly to strong, white light and allow controlled timing of induction of rod and cone death, which therefore can be elicited in adult animals, as observed in human RP. The option to control severity and retinal extent of the phenotype by regulating intensity and duration of the inducing light opens possibilities to exploit this model for multiple experimental purposes. Altogether, the unique features of this mutant make it an excellent resource for retinal degeneration research.

Assessment of Safety and Functional Efficacy of Stem Cell-Based Therapeutic Approaches Using Retinal Degenerative Animal Models

PubMed Central

Lin, Tai-Chi; Zhu, Danhong; Hinton, David R.; Clegg, Dennis O.; Humayun, Mark S.

2017-01-01

Dysfunction and death of retinal pigment epithelium (RPE) and or photoreceptors can lead to irreversible vision loss. The eye represents an ideal microenvironment for stem cell-based therapy. It is considered an “immune privileged” site, and the number of cells needed for therapy is relatively low for the area of focused vision (macula). Further, surgical placement of stem cell-derived grafts (RPE, retinal progenitors, and photoreceptor precursors) into the vitreous cavity or subretinal space has been well established. For preclinical tests, assessments of stem cell-derived graft survival and functionality are conducted in animal models by various noninvasive approaches and imaging modalities. In vivo experiments conducted in animal models based on replacing photoreceptors and/or RPE cells have shown survival and functionality of the transplanted cells, rescue of the host retina, and improvement of visual function. Based on the positive results obtained from these animal experiments, human clinical trials are being initiated. Despite such progress in stem cell research, ethical, regulatory, safety, and technical difficulties still remain a challenge for the transformation of this technique into a standard clinical approach. In this review, the current status of preclinical safety and efficacy studies for retinal cell replacement therapies conducted in animal models will be discussed. PMID:28928775

Plasticity of the human visual system after retinal gene therapy in patients with Leber's congenital amaurosis.

PubMed

Ashtari, Manzar; Zhang, Hui; Cook, Philip A; Cyckowski, Laura L; Shindler, Kenneth S; Marshall, Kathleen A; Aravand, Puya; Vossough, Arastoo; Gee, James C; Maguire, Albert M; Baker, Chris I; Bennett, Jean

2015-07-15

Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber's congenital amaurosis (LCA), who regained vision through gene therapy. Using non-invasive multimodal neuroimaging methods, we demonstrated that reversing blindness with gene therapy promoted long-term structural plasticity in the visual pathways emanating from the treated retina of LCA patients. The data revealed improvements and normalization along the visual fibers corresponding to the site of retinal injection of the gene therapy vector carrying the therapeutic gene in the treated eye compared to the visual pathway for the untreated eye of LCA patients. After gene therapy, the primary visual pathways (for example, geniculostriate fibers) in the treated retina were similar to those of sighted control subjects, whereas the primary visual pathways of the untreated retina continued to deteriorate. Our results suggest that visual experience, enhanced by gene therapy, may be responsible for the reorganization and maturation of synaptic connectivity in the visual pathways of the treated eye in LCA patients. The interactions between the eye and the brain enabled improved and sustained long-term visual function in patients with LCA after gene therapy. Copyright © 2015, American Association for the Advancement of Science.

Targeting of Drosophila Rhodopsin Requires Helix 8 but Not the Distal C-Terminus

PubMed Central

Kock, Ines; Bulgakova, Natalia A.; Knust, Elisabeth; Sinning, Irmgard; Panneels, Valérie

2009-01-01

Background The fundamental role of the light receptor rhodopsin in visual function and photoreceptor cell development has been widely studied. Proper trafficking of rhodopsin to the photoreceptor membrane is of great importance. In human, mutations in rhodopsin involving its intracellular mislocalization, are the most frequent cause of autosomal dominant Retinitis Pigmentosa, a degenerative retinal pathology characterized by progressive blindness. Drosophila is widely used as an animal model in visual and retinal degeneration research. So far, little is known about the requirements for proper rhodopsin targeting in Drosophila. Methodology/Principal Findings Different truncated fly-rhodopsin Rh1 variants were expressed in the eyes of Drosophila and their localization was analyzed in vivo or by immunofluorescence. A mutant lacking the last 23 amino acids was found to properly localize in the rhabdomeres, the light-sensing organelle of the photoreceptor cells. This constitutes a major difference to trafficking in vertebrates, which involves a conserved QVxPA motif at the very C-terminus. Further truncations of Rh1 indicated that proper localization requires the last amino acid residues of a region called helix 8 following directly the last transmembrane domain. Interestingly, the very C-terminus of invertebrate visual rhodopsins is extremely variable but helix 8 shows conserved amino acid residues that are not conserved in vertebrate homologs. Conclusions/Significance Despite impressive similarities in the folding and photoactivation of vertebrate and invertebrate visual rhodopsins, a striking difference exists between mammalian and fly rhodopsins in their requirements for proper targeting. Most importantly, the distal part of helix 8 plays a central role in invertebrates. Since the last amino acid residues of helix 8 are dispensable for rhodopsin folding and function, we propose that this domain participates in the recognition of targeting factors involved in transport to the rhabdomeres. PMID:19572012

Selective loss of orientation column maps in visual cortex during brief elevation of intraocular pressure.

PubMed

Chen, Xin; Sun, Chao; Huang, Luoxiu; Shou, Tiande

2003-01-01

To compare the orientation column maps elicited by different spatial frequency gratings in cortical area 17 of cats before and during brief elevation of intraocular pressure (IOP). IOP was elevated by injecting saline into the anterior chamber of a cat's eye through a syringe needle. The IOP was elevated enough to cause a retinal perfusion pressure (arterial pressure minus IOP) of approximately 30 mm Hg during a brief elevation of IOP. The visual stimulus gratings were varied in spatial frequency, whereas other parameters were kept constant. The orientation column maps of the cortical area 17 were monocularly elicited by drifting gratings of different spatial frequencies and revealed by a brain intrinsic signal optical imaging system. These maps were compared before and during short-term elevation of IOP. The response amplitude of the orientation maps in area 17 decreased during a brief elevation of IOP. This decrease was dependent on the retinal perfusion pressure but not on the absolute IOP. The location of the most visible maps was spatial-frequency dependent. The blurring or loss of the pattern of the orientation maps was most severe when high-spatial-frequency gratings were used and appeared most significantly on the posterior part of the exposed cortex while IOP was elevated. However, the basic patterns of the maps remained unchanged. Changes in cortical signal were not due to changes in the optics of the eye with elevation of IOP. A stable normal IOP is essential for maintaining normal visual cortical functions. During a brief and high elevation of IOP, the cortical processing of high-spatial-frequency visual information was diminished because of a selectively functional decline of the retinogeniculocortical X pathway by a mechanism of retinal circulation origin.

Visual pattern recognition based on spatio-temporal patterns of retinal ganglion cells’ activities

PubMed Central

Jing, Wei; Liu, Wen-Zhong; Gong, Xin-Wei; Gong, Hai-Qing

2010-01-01

Neural information is processed based on integrated activities of relevant neurons. Concerted population activity is one of the important ways for retinal ganglion cells to efficiently organize and process visual information. In the present study, the spike activities of bullfrog retinal ganglion cells in response to three different visual patterns (checker-board, vertical gratings and horizontal gratings) were recorded using multi-electrode arrays. A measurement of subsequence distribution discrepancy (MSDD) was applied to identify the spatio-temporal patterns of retinal ganglion cells’ activities in response to different stimulation patterns. The results show that the population activity patterns were different in response to different stimulation patterns, such difference in activity pattern was consistently detectable even when visual adaptation occurred during repeated experimental trials. Therefore, the stimulus pattern can be reliably discriminated according to the spatio-temporal pattern of the neuronal activities calculated using the MSDD algorithm. PMID:21886670

Synaptology of physiologically identified ganglion cells in the cat retina: a comparison of retinal X- and Y-cells.

PubMed

Weber, A J; Stanford, L R

1994-05-15

It has long been known that a number of functionally different types of ganglion cells exist in the cat retina, and that each responds differently to visual stimulation. To determine whether the characteristic response properties of different retinal ganglion cell types might reflect differences in the number and distribution of their bipolar and amacrine cell inputs, we compared the percentages and distributions of the synaptic inputs from bipolar and amacrine cells to the entire dendritic arbors of physiologically characterized retinal X- and Y-cells. Sixty-two percent of the synaptic input to the Y-cell was from amacrine cell terminals, while the X-cells received approximately equal amounts of input from amacrine and bipolar cells. We found no significant difference in the distributions of bipolar or amacrine cell inputs to X- and Y-cells, or ON-center and OFF-center cells, either as a function of dendritic branch order or distance from the origin of the dendritic arbor. While, on the basis of these data, we cannot exclude the possibility that the difference in the proportion of bipolar and amacrine cell input contributes to the functional differences between X- and Y-cells, the magnitude of this difference, and the similarity in the distributions of the input from the two afferent cell types, suggest that mechanisms other than a simple predominance of input from amacrine or bipolar cells underlie the differences in their response properties. More likely, perhaps, is that the specific response features of X- and Y-cells originate in differences in the visual responses of the bipolar and amacrine cells that provide their input, or in the complex synaptic arrangements found among amacrine and bipolar cell terminals and the dendrites of specific types of retinal ganglion cells.

In vivo cellular-resolution retinal imaging in infants and children using an ultracompact handheld probe

NASA Astrophysics Data System (ADS)

Larocca, Francesco; Nankivil, Derek; Dubose, Theodore; Toth, Cynthia A.; Farsiu, Sina; Izatt, Joseph A.

2016-09-01

Enabled by adaptive optics, retinal photoreceptor cell imaging is changing our understanding of retinal structure and function, as well as the pathogenesis of numerous ocular diseases. To date, use of this technology has been limited to cooperative adult subjects due to the size, weight and inconvenience of the equipment, thus excluding study of retinal maturation during human development. Here, we report the design and operation of a handheld probe that can perform both scanning laser ophthalmoscopy and optical coherence tomography of the parafoveal photoreceptor structure in infants and children without the need for adaptive optics. The probe, featuring a compact optical design weighing only 94 g, was able to quantify packing densities of parafoveal cone photoreceptors and visualize cross-sectional photoreceptor substructure in children with ages ranging from 14 months to 12 years. The probe will benefit paediatric research by improving the understanding of retinal development, maldevelopment and early onset of disease during human growth.

Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease.

PubMed

Beck, Susanne C; Feng, Yuxi; Sothilingam, Vithiyanjali; Garcia Garrido, Marina; Tanimoto, Naoyuki; Acar, Niyazi; Shan, Shenliang; Seebauer, Britta; Berger, Wolfgang; Hammes, Hans-Peter; Seeliger, Mathias W

2017-01-01

Loss of Norrin signalling due to mutations in the Norrie disease pseudoglioma gene causes severe vascular defects in the retina, leading to visual impairment and ultimately blindness. While the emphasis of experimental work so far was on the developmental period, we focus here on disease mechanisms that induce progression into severe adult disease. The goal of this study was the comprehensive analysis of the long-term effects of the absence of Norrin on vascular homeostasis and retinal function. In a mouse model of Norrie disease retinal vascular morphology and integrity were studied by means of in vivo angiography; the vascular constituents were assessed in detailed histological analyses using quantitative retinal morphometry. Finally, electroretinographic analyses were performed to assess the retinal function in adult Norrin deficient animals. We could show that the primary developmental defects not only persisted but developed into further vascular abnormalities and microangiopathies. In particular, the overall vessel homeostasis, the vascular integrity, and also the cellular constituents of the vascular wall were affected in the adult Norrin deficient retina. Moreover, functional analyses indicated to persistent hypoxia in the neural retina which was suggested as one of the major driving forces of disease progression. In summary, our data provide evidence that the key to adult Norrie disease are ongoing vascular modifications, driven by the persistent hypoxic conditions, which are ineffective to compensate for the primary Norrin-dependent defects.

Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease

PubMed Central

Sothilingam, Vithiyanjali; Garcia Garrido, Marina; Tanimoto, Naoyuki; Acar, Niyazi; Shan, Shenliang; Seebauer, Britta; Berger, Wolfgang; Hammes, Hans-Peter; Seeliger, Mathias W.

2017-01-01

Loss of Norrin signalling due to mutations in the Norrie disease pseudoglioma gene causes severe vascular defects in the retina, leading to visual impairment and ultimately blindness. While the emphasis of experimental work so far was on the developmental period, we focus here on disease mechanisms that induce progression into severe adult disease. The goal of this study was the comprehensive analysis of the long-term effects of the absence of Norrin on vascular homeostasis and retinal function. In a mouse model of Norrie disease retinal vascular morphology and integrity were studied by means of in vivo angiography; the vascular constituents were assessed in detailed histological analyses using quantitative retinal morphometry. Finally, electroretinographic analyses were performed to assess the retinal function in adult Norrin deficient animals. We could show that the primary developmental defects not only persisted but developed into further vascular abnormalities and microangiopathies. In particular, the overall vessel homeostasis, the vascular integrity, and also the cellular constituents of the vascular wall were affected in the adult Norrin deficient retina. Moreover, functional analyses indicated to persistent hypoxia in the neural retina which was suggested as one of the major driving forces of disease progression. In summary, our data provide evidence that the key to adult Norrie disease are ongoing vascular modifications, driven by the persistent hypoxic conditions, which are ineffective to compensate for the primary Norrin-dependent defects. PMID:28575130

Dysflective cones: Visual function and cone reflectivity in long-term follow-up of acute bilateral foveolitis.

PubMed

Tu, Joanna H; Foote, Katharina G; Lujan, Brandon J; Ratnam, Kavitha; Qin, Jia; Gorin, Michael B; Cunningham, Emmett T; Tuten, William S; Duncan, Jacque L; Roorda, Austin

2017-09-01

Confocal adaptive optics scanning laser ophthalmoscope (AOSLO) images provide a sensitive measure of cone structure. However, the relationship between structural findings of diminished cone reflectivity and visual function is unclear. We used fundus-referenced testing to evaluate visual function in regions of apparent cone loss identified using confocal AOSLO images. A patient diagnosed with acute bilateral foveolitis had spectral-domain optical coherence tomography (SD-OCT) (Spectralis HRA + OCT system [Heidelberg Engineering, Vista, CA, USA]) images indicating focal loss of the inner segment-outer segment junction band with an intact, but hyper-reflective, external limiting membrane. Five years after symptom onset, visual acuity had improved from 20/80 to 20/25, but the retinal appearance remained unchanged compared to 3 months after symptoms began. We performed structural assessments using SD-OCT, directional OCT (non-standard use of a prototype on loan from Carl Zeiss Meditec) and AOSLO (custom-built system). We also administered fundus-referenced functional tests in the region of apparent cone loss, including analysis of preferred retinal locus (PRL), AOSLO acuity, and microperimetry with tracking SLO (TSLO) (prototype system). To determine AOSLO-corrected visual acuity, the scanning laser was modulated with a tumbling E consistent with 20/30 visual acuity. Visual sensitivity was assessed in and around the lesion using TSLO microperimetry. Complete eye examination, including standard measures of best-corrected visual acuity, visual field tests, color fundus photos, and fundus auto-fluorescence were also performed. Despite a lack of visible cone profiles in the foveal lesion, fundus-referenced vision testing demonstrated visual function within the lesion consistent with cone function. The PRL was within the lesion of apparent cone loss at the fovea. AOSLO visual acuity tests were abnormal, but measurable: for trials in which the stimulus remained completely within the lesion, the subject got 48% correct, compared to 78% correct when the stimulus was outside the lesion. TSLO microperimetry revealed reduced, but detectible, sensitivity thresholds within the lesion. Fundus-referenced visual testing proved useful to identify functional cones despite apparent photoreceptor loss identified using AOSLO and SD-OCT. While AOSLO and SD-OCT appear to be sensitive for the detection of abnormal or absent photoreceptors, changes in photoreceptors that are identified with these imaging tools do not correlate completely with visual function in every patient. Fundus-referenced vision testing is a useful tool to indicate the presence of cones that may be amenable to recovery or response to experimental therapies despite not being visible on confocal AOSLO or SD-OCT images.

FBG-based sensorized light pipe for robotic intraocular illumination facilitates bimanual retinal microsurgery.

PubMed

Horise, Yuki; He, Xingchi; Gehlbach, Peter; Taylor, Russell; Iordachita, Iulian

2015-01-01

In retinal surgery, microsurgical instruments such as micro forceps, scissors and picks are inserted through the eye wall via sclerotomies. A handheld intraocular light source is typically used to visualize the tools during the procedure. Retinal surgery requires precise and stable tool maneuvers as the surgical targets are micro scale, fragile and critical to function. Retinal surgeons typically control an active surgical tool with one hand and an illumination source with the other. In this paper, we present a "smart" light pipe that enables true bimanual surgery via utilization of an active, robot-assisted source of targeted illumination. The novel sensorized smart light pipe measures the contact force between the sclerotomy and its own shaft, thereby accommodating the motion of the patient's eye. Forces at the point of contact with the sclera are detected by fiber Bragg grating (FBG) sensors on the light pipe. Our calibration and validation results demonstrate reliable measurement of the contact force as well as location of the sclerotomy. Preliminary experiments have been conducted to functionally evaluate robotic intraocular illumination.

Computer-controlled impalement of cells in retinal wholemounts visualized by infrared CCD imaging on an inverted microscope.

PubMed

Reitsamer, H; Groiss, H P; Franz, M; Pflug, R

2000-01-31

We present a computer-guided microelectrode positioning system that is routinely used in our laboratory for intracellular electrophysiology and functional staining of retinal neurons. Wholemount preparations of isolated retina are kept in a superfusion chamber on the stage of an inverted microscope. Cells and layers of the retina are visualized by Nomarski interference contrast using infrared light in combination with a CCD camera system. After five-point calibration has been performed the electrode can be guided to any point inside the calibrated volume without moving the retina. Electrode deviations from target cells can be corrected by the software further improving the precision of this system. The good visibility of cells avoids prelabeling with fluorescent dyes and makes it possible to work under completely dark adapted conditions.

The potential of the second sight system bionic eye implant for partial sight restoration.

PubMed

Luo, Yvonne Hsu-Lin; Fukushige, Eka; Da Cruz, Lyndon

2016-07-01

Second Sight System bionic eye implant, a commercially available visual prosthesis developed by Second Sight Medical Products, has been implanted in over 125 patients with outer retinal dystrophies such as retinitis pigmentosa. The system has gained regulatory approval in both the USA and Europe, and aims to restore vision by electrical stimulation of the nerve cells of the inner retina. In this review, we present the safety profile of this implant from the international clinical trial and discuss the nature and levels of improvement in visual function achieved by patients implanted with the system. Expert commentary: Future developments for the system will be explored following the discussion of the current usefulness of the device, its limitation as and the areas in which further development is necessary.

Multifocal and full-field electroretinogram changes associated with color-vision loss in mercury vapor exposure.

PubMed

Ventura, Dora F; Costa, Marcelo T V; Costa, Marcelo F; Berezovsky, Adriana; Salomão, Solange R; Simões, Ana Luíza; Lago, Marcos; Pereira, Luiz H M Canto; Faria, Marcília A M; De Souza, John M; Silveira, Luiz Carlos L

2004-01-01

We evaluated the color vision of mercury-contaminated patients and investigated possible retinal origins of losses using electroretinography. Participants were retired workers from a fluorescent lamp industry diagnosed with mercury contamination (n = 43) and age-matched controls (n = 21). Color discrimination was assessed with the Cambridge Colour Test (CCT). Retinal function was evaluated by using the ISCEV protocol for full-field electroretinography (full-field ERG), as well as by means of multifocal electroretinography (mfERG). Color-vision losses assessed by the CCT consisted of higher color-discrimination thresholds along the protan, deutan, and tritan axes and significantly larger discrimination ellipses in mercury-exposed patients compared to controls. Full-field ERG amplitudes from patients were smaller than those of the controls for the scotopic response b-wave, maximum response, sum of oscillatory potentials (OPs), 30-Hz flicker response, and light-adapted cone response. OP amplitudes measured in patients were smaller than those of controls for O2 and O3. Multifocal ERGs recorded from ten randomly selected patients showed smaller N1-P1 amplitudes and longer latencies throughout the 25-deg central field. Full-field ERGs showed that scotopic, photopic, peripheral, and midperipheral retinal functions were affected, and the mfERGs indicated that central retinal function was also significantly depressed. To our knowledge, this is the first demonstration of retinal involvement in visual losses caused by mercury toxicity.

Phospholipase D1 modulates protein kinase C-epsilon in retinal pigment epithelium cells during inflammatory response.

PubMed

Tenconi, Paula E; Giusto, Norma M; Salvador, Gabriela A; Mateos, Melina V

2016-12-01

Inflammation is a key factor in the pathogenesis of several retinal diseases. In view of the essential role of the retinal pigment epithelium in visual function, elucidating the molecular mechanisms elicited by inflammation in this tissue could provide new insights for the treatment of retinal diseases. The aim of the present work was to study protein kinase C signaling and its modulation by phospholipases D in ARPE-19 cells exposed to lipopolysaccharide. This bacterial endotoxin induced protein kinase C-α/βII phosphorylation and protein kinase-ε translocation to the plasma membrane in ARPE-19 cells. Pre-incubation with selective phospholipase D inhibitors demonstrated that protein kinase C-α phosphorylation depends on phospholipase D1 and 2 while protein kinase C-ε activation depends only on phospholipase D1. The inhibition of α and β protein kinase C isoforms with Go 6976 did not modify the reduced mitochondrial function induced by lipopolysaccharide. On the contrary, the inhibition of protein kinase C-α, β and ε with Ro 31-8220 potentiated the decrease in mitochondrial function. Moreover, inhibition of protein kinase C-ε reduced Bcl-2 expression and Akt activation and increased Caspase-3 cleavage in cells treated or not with lipopolysaccharide. Our results demonstrate that through protein kinase C-ε regulation, phospholipase D1 protects retinal pigment epithelium cells from lipopolysaccharide-induced damage. Copyright © 2016 Elsevier Ltd. All rights reserved.

Incomplete cortical reorganization in macular degeneration.

PubMed

Liu, Tingting; Cheung, Sing-Hang; Schuchard, Ronald A; Glielmi, Christopher B; Hu, Xiaoping; He, Sheng; Legge, Gordon E

2010-12-01

Activity in regions of the visual cortex corresponding to central scotomas in subjects with macular degeneration (MD) is considered evidence for functional reorganization in the brain. Three unresolved issues related to cortical activity in subjects with MD were addressed: Is the cortical response to stimuli presented to the preferred retinal locus (PRL) different from other retinal loci at the same eccentricity? What effect does the role of age of onset and etiology of MD have on cortical responses? How do functional responses in an MD subject's visual cortex vary for task and stimulus conditions? Eight MD subjects-four with age-related onset (AMD) and four with juvenile onset (JMD)-and two age-matched normal vision controls, participated in three testing conditions while undergoing functional magnetic resonance imaging (fMRI). First, subjects viewed a small stimulus presented at the PRL compared with a non-PRL control location to investigate the role of the PRL. Second, they viewed a full-field flickering checkerboard compared with a small stimulus in the original fovea to investigate brain activation with passive viewing. Third, they performed a one-back task with scene images to investigate brain activation with active viewing. A small stimulus at the PRL generated more extensive cortical activation than at a non-PRL location, but neither yielded activation in the foveal cortical projection. Both passive and active viewing of full-field stimuli left a silent zone at the posterior pole of the occipital cortex, implying a lack of complete cortical reorganization. The silent zone was smaller in the task requiring active viewing compared with the task requiring passive viewing, especially in JMD subjects. The PRL for MD subjects has more extensive cortical representation than a retinal region with matched eccentricity. There is evidence for incomplete functional reorganization of early visual cortex in both JMD and AMD. Functional reorganization is more prominent in JMD. Feedback signals, possibly associated with attention, play an important role in the reorganization.

Incomplete Cortical Reorganization in Macular Degeneration

PubMed Central

Cheung, Sing-Hang; Schuchard, Ronald A.; Glielmi, Christopher B.; Hu, Xiaoping; He, Sheng; Legge, Gordon E.

2010-01-01

Purpose. Activity in regions of the visual cortex corresponding to central scotomas in subjects with macular degeneration (MD) is considered evidence for functional reorganization in the brain. Three unresolved issues related to cortical activity in subjects with MD were addressed: Is the cortical response to stimuli presented to the preferred retinal locus (PRL) different from other retinal loci at the same eccentricity? What effect does the role of age of onset and etiology of MD have on cortical responses? How do functional responses in an MD subject's visual cortex vary for task and stimulus conditions? Methods. Eight MD subjects—four with age-related onset (AMD) and four with juvenile onset (JMD)—and two age-matched normal vision controls, participated in three testing conditions while undergoing functional magnetic resonance imaging (fMRI). First, subjects viewed a small stimulus presented at the PRL compared with a non-PRL control location to investigate the role of the PRL. Second, they viewed a full-field flickering checkerboard compared with a small stimulus in the original fovea to investigate brain activation with passive viewing. Third, they performed a one-back task with scene images to investigate brain activation with active viewing. Results. A small stimulus at the PRL generated more extensive cortical activation than at a non-PRL location, but neither yielded activation in the foveal cortical projection. Both passive and active viewing of full-field stimuli left a silent zone at the posterior pole of the occipital cortex, implying a lack of complete cortical reorganization. The silent zone was smaller in the task requiring active viewing compared with the task requiring passive viewing, especially in JMD subjects. Conclusions. The PRL for MD subjects has more extensive cortical representation than a retinal region with matched eccentricity. There is evidence for incomplete functional reorganization of early visual cortex in both JMD and AMD. Functional reorganization is more prominent in JMD. Feedback signals, possibly associated with attention, play an important role in the reorganization. PMID:20631240

Targeted Ablation of the Pde6h Gene in Mice Reveals Cross-species Differences in Cone and Rod Phototransduction Protein Isoform Inventory*

PubMed Central

Brennenstuhl, Christina; Tanimoto, Naoyuki; Burkard, Markus; Wagner, Rebecca; Bolz, Sylvia; Trifunovic, Dragana; Kabagema-Bilan, Clement; Paquet-Durand, Francois; Beck, Susanne C.; Huber, Gesine; Seeliger, Mathias W.; Ruth, Peter; Wissinger, Bernd; Lukowski, Robert

2015-01-01

Phosphodiesterase-6 (PDE6) is a multisubunit enzyme that plays a key role in the visual transduction cascade in rod and cone photoreceptors. Each type of photoreceptor utilizes discrete catalytic and inhibitory PDE6 subunits to fulfill its physiological tasks, i.e. the degradation of cyclic guanosine-3′,5′-monophosphate at specifically tuned rates and kinetics. Recently, the human PDE6H gene was identified as a novel locus for autosomal recessive (incomplete) color blindness. However, the three different classes of cones were not affected to the same extent. Short wave cone function was more preserved than middle and long wave cone function indicating that some basic regulation of the PDE6 multisubunit enzyme was maintained albeit by a unknown mechanism. To study normal and disease-related functions of cone Pde6h in vivo, we generated Pde6h knock-out (Pde6h−/−) mice. Expression of PDE6H in murine eyes was restricted to both outer segments and synaptic terminals of short and long/middle cone photoreceptors, whereas Pde6h−/− retinae remained PDE6H-negative. Combined in vivo assessment of retinal morphology with histomorphological analyses revealed a normal overall integrity of the retinal organization and an unaltered distribution of the different cone photoreceptor subtypes upon Pde6h ablation. In contrast to human patients, our electroretinographic examinations of Pde6h−/− mice suggest no defects in cone/rod-driven retinal signaling and therefore preserved visual functions. To this end, we were able to demonstrate the presence of rod PDE6G in cones indicating functional substitution of PDE6. The disparities between human and murine phenotypes caused by mutant Pde6h/PDE6H suggest species-to-species differences in the vulnerability of biochemical and neurosensory pathways of the visual signal transduction system. PMID:25739440

A Computational Framework for Realistic Retina Modeling.

PubMed

Martínez-Cañada, Pablo; Morillas, Christian; Pino, Begoña; Ros, Eduardo; Pelayo, Francisco

2016-11-01

Computational simulations of the retina have led to valuable insights about the biophysics of its neuronal activity and processing principles. A great number of retina models have been proposed to reproduce the behavioral diversity of the different visual processing pathways. While many of these models share common computational stages, previous efforts have been more focused on fitting specific retina functions rather than generalizing them beyond a particular model. Here, we define a set of computational retinal microcircuits that can be used as basic building blocks for the modeling of different retina mechanisms. To validate the hypothesis that similar processing structures may be repeatedly found in different retina functions, we implemented a series of retina models simply by combining these computational retinal microcircuits. Accuracy of the retina models for capturing neural behavior was assessed by fitting published electrophysiological recordings that characterize some of the best-known phenomena observed in the retina: adaptation to the mean light intensity and temporal contrast, and differential motion sensitivity. The retinal microcircuits are part of a new software platform for efficient computational retina modeling from single-cell to large-scale levels. It includes an interface with spiking neural networks that allows simulation of the spiking response of ganglion cells and integration with models of higher visual areas.

Identifying a Clinically Meaningful Threshold for Change in Uveitic Macular Edema Evaluated by Optical Coherence Tomography

PubMed Central

Sugar, Elizabeth A.; Jabs, Douglas A.; Altaweel, Michael M.; Lightman, Sue; Acharya, Nisha; Vitale, Albert T.; Thorne, Jennifer E.

2011-01-01

Purpose To identify a clinically meaningful threshold for change in retinal thickness measured by optical coherence tomography (OCT) for patients with uveitic macular edema, using correlation with change in visual acuity. Design Cross-sectional and longitudinal study. Methods 128 eyes (101 individuals) with macular edema enrolled in the Multicenter Uveitis Steroid Treatment (MUST) trial. At enrollment and after six months of follow-up, retinal thickness was measured at the central subfield with time domain OCT and visual acuity was measured with logarithmic (ETDRS) visual acuity charts. Participants were classified as having macular edema if the retinal thickness was ≥260μm. Results A threshold for change in retinal center subfield thickness of 20% balanced the percentage of false positives and negatives for predicting greater than 10-letter change in visual acuity with sensitivity of 77% and a specificity of 75%. The results were similar for greater than 5 or 15 or greater letter changes. Those with a 20% or greater reduction in retinal thickness had a mean 11.0 letter improvement (95% CI: 7.7 to 14.3) as compared to a -0.4 letter change (95% CI: -4.1 to 3.3) in visual acuity for those without a 20% reduction (p < 0.01). Conclusions In addition to being above the level of measurement uncertainty, a 20% change in retinal thickness in patients with macular edema appears to be optimal for clinically important changes in visual acuity and may be considered as an outcome for clinical trials of treatments for uveitic macular edema. PMID:21861971

Comparative analysis of cytomegalovirus retinitis and microvascular retinopathy in patients with acquired immunodeficiency syndrome

PubMed Central

Chen, Chao; Guo, Chun-Gang; Meng, Li; Yu, Jing; Xie, Lian-Yong; Dong, Hong-Wei; Wei, Wen-Bin

2017-01-01

AIM To compare the clinical manifestation of cytomegalovirus (CMV) retinitis and microvascular retinopathy (MVR) in patients with acquired immunodeficiency syndrome (AIDS) in China. METHODS A total of 93 consecutive patients with AIDS, including 41 cases of CMV retinitis and 52 cases of MVR were retrospectively reviewed. Highly active antiretroviral therapy (HAART) status was recorded. HIV and CMV immunoassay were also tested. CD4+ T-lymphocyte count and blood CMV-DNA test were performed in all patients. Aqueous humor CMV-DNA test was completed in 39 patients. Ophthalmological examinations including best corrected visual acuity (BCVA, by International Standard Vision Chart), intraocular pressure (IOP), slit-lamp biomicroscopy, indirect ophthalmoscopy were performed. RESULTS In MVR group, the anterior segment examination was normal in all patients with a mean BCVA of 0.93±0.13. Blood CMV-DNA was 0 (0, 269 000) and 42 patients (80.77%) did not receive HAART. In CMV retinitis group, 13 patients (31.71%) had anterior segment abnormality. The mean BCVA was 0.64±0.35 and blood CMV-DNA was 3470 (0, 1 450 000). Nineteen patients (46.34%) had not received HAART. MVR group and CMV retinitis group the positive rates of aqueous CMV-DNA were 0 and 50%, respectively. Two patients with MVR progressed to CMV retinitis during the follow-up period. CONCLUSION In comparison of CMV, patients with MVR have relatively mild visual function impairment. Careful ophthalmological examination and close follow-up are mandatory, especially for patients who have systemic complications, positive CMV-DNA test and without received HAART. PMID:28944199

QLT091001, a 9-cis-Retinal Analog, Is Well-Tolerated by Retinas of Mice with Impaired Visual Cycles

PubMed Central

Maeda, Tadao; Dong, Zhiqian; Jin, Hui; Sawada, Osamu; Gao, Songqi; Utkhede, Deepank; Monk, Wendy; Palczewska, Grazyna; Palczewski, Krzysztof

2013-01-01

Purpose. Investigate whether retinas of mice with impaired retinal cycles exposed to light or kept in the dark tolerate prolonged high-dose administration of QLT091001, which contains as an active ingredient, the 9-cis-retinal precursor, 9-cis-retinyl acetate. Methods. Four- to six-week-old Lrat−/− and Rpe65−/− mice (n = 126) as well as crossbred Gnat1−/− mice lacking rod phototransduction (n = 110) were gavaged weekly for 6 months with 50 mg/kg QLT091001, either after being kept in the dark or after light bleaching for 30 min/wk followed by maintenance in a 12-hour light ≤ 10 lux)/12-hour dark cycle. Retinal health was monitored by spectral-domain optical coherent tomography (SD-OCT) and scanning laser ophthalmoscopy (SLO) every other month and histological, biochemical, and visual functional analyses were performed at the end of the experiment. Two-photon microscopy (TPM) was used to observe retinoid-containing retinosome structures in the RPE. Results. Retinal thickness and morphology examined by SD-OCT were well maintained in all strains treated with QLT091001. No significant increases of fundus autofluorescence were detected by SLO imaging of any strain. Accumulation of all-trans-retinyl esters varied with genetic background, types of administered compounds and lighting conditions but retinal health was not compromised. TPM imaging clearly revealed maintenance of retinosomes in the RPE of all mouse strains tested. Conclusions. Retinas of Lrat−/−, Rpe65−/−, and crossbred Gnat1−/− mice tolerated prolonged high-dose QLT091001 treatment well. PMID:23249702

STRUCTURAL AND FUNCTIONAL CHARACTERIZATION OF BENIGN FLECK RETINA USING MULTIMODAL IMAGING.

PubMed

Neriyanuri, Srividya; Rao, Chetan; Raman, Rajiv

2017-01-01

To report structural and functional features in a case series of benign fleck retina using multimodal imaging. Four cases with benign fleck retina underwent complete ophthalmic examination that included detailed history, visual acuity, and refractive error testing, FM-100 hue test, dilated fundus evaluation, full field electroretinogram, fundus photography with autofluorescence, fundus fluorescein angiography, and swept-source optical coherence tomography. Age group of the cases ranged from 19 years to 35 years (3 males and 1 female). Parental consanguinity was reported in two cases. All of them were visually asymptomatic with best-corrected visual acuity of 20/20 (moderate astigmatism) in both the eyes. Low color discrimination was seen in two cases. Fundus photography showed pisciform flecks which were compactly placed on posterior pole and were discrete, diverging towards periphery. Lesions were seen as smaller dots within 1500 microns from fovea and were hyperfluorescent on autofluorescence. Palisading retinal pigment epithelium defects were seen in posterior pole on fundus fluorescein angiography imaging; irregular hyper fluorescence was also noted. One case had reduced cone responses on full field electroretinogram; the other three cases had normal electroretinogram. On optical coherence tomography, level of lesions varied from retinal pigment epithelium, inner segment to outer segment extending till external limiting membrane. Functional and structural deficits in benign fleck retina were picked up using multimodal imaging.

Retinal complications after aqueous shunt surgical procedures for glaucoma.

PubMed

Law, S K; Kalenak, J W; Connor, T B; Pulido, J S; Han, D P; Mieler, W F

1996-12-01

To assess retinal complications and to identify risk factors for retinal complications following aqueous shunt procedures. Records of 38 consecutive aqueous shunt procedures that were performed on 36 patients at the Eye Institute of the Medical College of Wisconsin, Milwaukee, from June 1993 to March 1995 (minimum follow-up, 6 months) were reviewed. The mean +/- SD follow-up was 11.4 +/- 5.2 months (median, 10.5 months). Twelve patients (32%) had the following retinal complications: 4 serous choroidal effusions (10%) that required drainage, 3 suprachoroidal hemorrhages (8%), 2 vitreous hemorrhages (5%), 1 rhegmatogenous retinal detachment (3%), 1 endophthalmitis (3%), and 1 scleral buckling extrusion (3%). Surgical procedures for retinal complications were required in 8 (67%) of these 12 patients. Visual acuity decreased 2 lines or more in 9 (75%) of these 12 patients. The median onset of a postoperative retinal complication was 12.5 days, with 10 patients (83%) experiencing complications within 35 days. Serous choroidal effusions developed in 10 other patients (26%), and these effusions resolved spontaneously. Visual acuity decreased 2 lines or more in 2 (20%) of these additional 10 patients. Patients who experienced serious retinal complications were significantly older, had a higher rate of hypertension, and postoperative ocular hypotony. Serious retinal complications were distributed evenly among patients with Krupin valves with discs and Molteno and Baerveldt devices. Experience with the Ahmed glaucoma valve implant was limited. Aqueous shunt procedures may be associated with significant retinal complications and subsequent visual loss.

Tickling the retina: integration of subthreshold electrical pulses can activate retinal neurons

NASA Astrophysics Data System (ADS)

Sekhar, S.; Jalligampala, A.; Zrenner, E.; Rathbun, D. L.

2016-08-01

Objective. The field of retinal prosthetics has made major progress over the last decade, restoring visual percepts to people suffering from retinitis pigmentosa. The stimulation pulses used by present implants are suprathreshold, meaning individual pulses are designed to activate the retina. In this paper we explore subthreshold pulse sequences as an alternate stimulation paradigm. Subthreshold pulses have the potential to address important open problems such as fading of visual percepts when patients are stimulated at moderate pulse repetition rates and the difficulty in preferentially stimulating different retinal pathways. Approach. As a first step in addressing these issues we used Gaussian white noise electrical stimulation combined with spike-triggered averaging to interrogate whether a subthreshold sequence of pulses can be used to activate the mouse retina. Main results. We demonstrate that the retinal network can integrate multiple subthreshold electrical stimuli under an experimental paradigm immediately relevant to retinal prostheses. Furthermore, these characteristic stimulus sequences varied in their shape and integration window length across the population of retinal ganglion cells. Significance. Because the subthreshold sequences activate the retina at stimulation rates that would typically induce strong fading (25 Hz), such retinal ‘tickling’ has the potential to minimize the fading problem. Furthermore, the diversity found across the cell population in characteristic pulse sequences suggests that these sequences could be used to selectively address the different retinal pathways (e.g. ON versus OFF). Both of these outcomes may significantly improve visual perception in retinal implant patients.

Retinal Tissue Thickness is Reduced in Diabetic Peripheral Neuropathy.

PubMed

Srinivasan, Sangeetha; Pritchard, Nicola; Vagenas, Dimitrios; Edwards, Katie; Sampson, Geoff P; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

2016-10-01

To investigate the relationship between diabetic peripheral neuropathy (DPN) and retinal tissue thickness. Full retinal thickness in the central retinal, parafoveal, and perifoveal zones and thickness of the ganglion cell complex and retinal nerve fiber layer (RNFL) were assessed in 193 individuals (84 with type 1 diabetes, 67 with type 2 diabetes, and 42 healthy controls) using spectral domain optical coherence tomography. Among those with diabetes, 44 had neuropathy defined using a modified neuropathy disability score recorded on a 0-10 scale. Multiple regression analysis was performed to investigate the relationship between diabetic neuropathy and retinal tissue thickness, adjusted for the presence of diabetic retinopathy (DR), age, sex, duration of diabetes, and HbA 1c levels. In individuals with diabetes, perifoveal thickness was inversely related to the severity of neuropathy (p < 0.05), when adjusted for age, sex, duration of diabetes, and HbA 1c levels. DR was associated with reduced thickness in parafovea (p < 0.01). The RNFL was thinner in individuals with greater degrees of neuropathy (p < 0.04). DPN is associated with structural compromise involving several retinal layers. This compromise may represent a threat to visual integrity and therefore warrants examination of functional correlates.

[Bilateral spontaneously reattached rhegmatogenous retinal detachment. Case report and differential diagnosis with pigmentary retinopathies].

PubMed

García-Guzmán, Jorge Guillermo; Franco-Yáñez, Yasmín; Lima-Gómez, Virgilio

2014-01-01

A dark pigmentation of the ocular fundus presents in degenerative diseases such as retinitis pigmentosa; this disease must be distinguished from others whose evolution is not progressive, in order to estimate the functional prognosis of the patient. To analyze the features which distinguish spontaneously reattached retinal detachment from other causes of ocular fundus pigmentation, in order to be able to identify it even in bilateral cases. A case of a female with chronic visual loss is presented, who was referred for evaluation with the diagnosis of a pigmented retinopathy. Clinical exploration discarded causes as retinitis pigmentosa, retinal inflammatory diseases or trauma. Based on the clinical features, on the topography of pigmentation and in the information provided by electroretinography, a bilateral spontaneous reattachment of rhegmatogenous retinal detachment was diagnosed made. Clinical features of this entity are discussed, as well as the diagnostic approach to distinguish it from other pigment retinopathies. Clinical features of spontaneously reattached retinal detachment allow the explorer to distinguish it from other causes of bilateral pigmentation, despite presenting bilaterally. Since the prognosis of the attached retina is better than that of a degenerative disease, the correct diagnosis makes rehabilitation easier.

Activity-dependent disruption of intersublaminar spaces and ABAKAN expression does not impact functional on and off organization in the ferret retinogeniculate system

PubMed Central

2011-01-01

In the adult visual system, functionally distinct retinal ganglion cells (RGCs) within each eye project to discrete targets in the brain. In the ferret, RGCs encoding light increments or decrements project to independent On and Off sublaminae within each eye-specific layer of the dorsal lateral geniculate nucleus (dLGN). Here we report a manipulation of retinal circuitry that alters RGC action potential firing patterns during development and eliminates the anatomical markers of segregated On and Off sublaminae in the LGN, including the intersublaminar spaces and the expression of a glial-associated inhibitory molecule, ABAKAN, normally separating On and Off leaflets. Despite the absence of anatomically defined On and Off sublaminae, electrophysiological recordings in the dLGN reveal that On and Off dLGN cells are segregated normally. These data demonstrate a dissociation between normal anatomical sublamination and segregation of function in the dLGN and call into question a purported role for ABAKAN boundaries in the developing visual system. PMID:21401945

Comparison between the Correlations of Retinal Nerve Fiber Layer Thickness Measured by Spectral Domain Optical Coherence Tomography and Visual Field Defects in Standard Automated White-on-White Perimetry versus Pulsar Perimetry

PubMed Central

Hömberg, Lisann; Eter, Nicole

2017-01-01

Purpose To compare the structure-function relationships between retinal nerve fiber layer thickness (RNFLT) and visual field defects measured either by standard automated perimetry (SAP) or by Pulsar perimetry (PP). Materials and Methods 263 eyes of 143 patients were prospectively included. Depending on the RNFLT, patients were assigned to the glaucoma group (group A: RNFL score 3–6) or the control group (group B: RNFL score 0–2). Structure-function relationships between RNFLT and mean sensitivity (MS) measured by SAP and PP were analyzed. Results Throughout the entire group, the MS assessed by PP and SAP correlated significantly with RNFLT in all sectors. In the glaucoma group, there was no significant difference between the correlations RNFL-SAP and RNFL-PP, whereas a significant difference was found in the control group. Conclusions In the control group, the correlation between structure and function based on the PP data was significantly stronger than that based on SAP. PMID:29119021

Visual Function in Carriers of X-linked Retinitis Pigmentosa

PubMed Central

Comander, Jason; Weigel-DiFranco, Carol; Sandberg, Michael A.; Berson, Eliot L.

2015-01-01

Purpose To determine the frequency and severity of visual function loss in female carriers of X-linked retinitis pigmentosa (XLRP). Design Case series. Participants XLRP carriers with cross-sectional data (n = 242) and longitudinal data (n = 34, median follow-up: 16 years, follow-up range: 3–37 years). Half of the carriers were from RPGR- or RP2-genotyped families. Methods Retrospective medical records review. Main Outcome Measures Visual acuities, visual field areas, final dark adaptation thresholds, and full-field ERGs to 0.5 Hz and 30 Hz flashes. Results In genotyped families, 40% of carriers showed a baseline abnormality on at least one of the three psychophysical tests. There was a wide range of function among carriers; for example 3 of 121 (2%) of genotyped carriers were legally blind due to poor visual acuity, some as young as 35 years of age. Visual fields were less affected than visual acuity. In all carriers, the average ERG amplitude to 30 Hz flashes was about 50% of normal, and the average exponential rate of amplitude loss over time was half that of XLRP males (3.7%/year vs 7.4%/year, respectively). Among obligate carriers with affected fathers and/or sons, 53 of 55 (96%) had abnormal baseline ERGs. Some carriers who initially had completely normal fundi in both eyes went on to develop moderately decreased vision, though not legal blindness. Among carriers with RPGR mutations, those with mutations in ORF15, compared to those in exons 1–14, had worse final dark adaptation thresholds and lower 0.5 Hz and 30 Hz ERG amplitudes. Conclusions Most carriers of XLRP had mildly or moderately reduced visual function but rarely became legally blind. In most cases, obligate carriers could be identified by ERG testing. Carriers of RPGR ORF15 mutations tended to have worse visual function than carriers of RPGR exon 1–14 mutations. Since XLRP carrier ERG amplitudes and decay rates over time were on average half of those of affected males, these observations were consistent with the Lyon hypothesis of random X-inactivation. PMID:26143542

Visual acuity loss and OCT changes as initial signs of leukaemia

PubMed Central

Ortiz, Jose M; Ruiz-Moreno, Jose M; Pozo-Martos, Paola; Montero, Javier A

2010-01-01

AIM To report two cases where decreased visual acuity was the first symptom of leukaemia and optical coherence tomography (OCT) allowed identification and localization of the retinal lesions. METHODS Retrospective, interventional, case reports. RESULTS One case of lymphoblastic acute leukaemia and chronic lymphoid leukaemia were diagnosed following decreased visual acuity. OCT showed macular serous detachment in the first case. The second case presented hypo fluorescent retinal infiltrates which appeared as hyper reflective lesions by OCT. Retinal changes disappeared and visual acuity was recovered following complete remission of the neoplasm. CONCLUSION OCT is a valuable, non invasive diagnostic tool permitting detection, localization and follow-up of ocular dissemination of neoplasms. PMID:22553573

Retinitis Pigmentosa.

ERIC Educational Resources Information Center

Carr, Ronald E.

1979-01-01

The author describes the etiology of retinitis pigmentosa, a visual dysfunction which results from progressive loss of the retinal photoreceptors. Sections address signs and symptoms, ancillary findings, heredity, clinical diagnosis, therapy, and research. (SBH)

Retina and Omega-3

PubMed Central

Querques, Giuseppe; Forte, Raimondo; Souied, Eric H.

2011-01-01

Over the last decade, several epidemiological studies based on food frequency questionnaires suggest that omega-3 polyunsaturated fatty acids could have a protective role in reducing the onset and progression of retinal diseases. The retina has a high concentration of omega-3, particularly DHA, which optimizes fluidity of photoreceptor membranes, retinal integrity, and visual function. Furthermore, many studies demonstrated that DHA has a protective, for example antiapoptotic, role in the retina. From a nutritional point of view, it is known that western populations, particularly aged individuals, have a higher than optimal omega-6/omega-3 ratio and should enrich their diet with more fish consumption or have DHA supplementation. This paper underscores the potential beneficial effect of omega-3 fatty acids on retinal diseases. PMID:22175009

Mesenchymal stromal cell-mediated neuroprotection and functional preservation of retinal ganglion cells in a rodent model of glaucoma.

PubMed

Mead, Ben; Hill, Lisa J; Blanch, Richard J; Ward, Kelly; Logan, Ann; Berry, Martin; Leadbeater, Wendy; Scheven, Ben A

2016-04-01

Glaucoma is a leading cause of irreversible blindness involving loss of retinal ganglion cells (RGC). Mesenchymal stromal cells (MSC) have shown promise as a paracrine-mediated therapy for compromised neurons. It is, however, unknown whether dental pulp stem cells (DPSC) are effective as a cellular therapy in glaucoma and how their hypothesized influence compares with other more widely researched MSC sources. The present study aimed to compare the efficacy of adipose-derived stem cells, bone marrow-derived MSC (BMSC) and DPSC in preventing the loss of RGC and visual function when transplanted into the vitreous of glaucomatous rodent eyes. Thirty-five days after raised intraocular pressure (IOP) and intravitreal stem cell transplantation, Brn3a(+) RGC numbers, retinal nerve fibre layer thickness (RNFL) and RGC function were evaluated by immunohistochemistry, optical coherence tomography and electroretinography, respectively. Control glaucomatous eyes that were sham-treated with heat-killed DPSC had a significant loss of RGC numbers, RNFL thickness and function compared with intact eyes. BMSC and, to a greater extent, DPSC provided significant protection from RGC loss and RNFL thinning and preserved RGC function. The study supports the use of DPSC as a neuroprotective cellular therapy in retinal degenerative disease such as glaucoma. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

The Specificity of Colored Lenses as Visual Aids in Retinal Disease.

ERIC Educational Resources Information Center

Gawande, A.; And Others

1992-01-01

This study of the effects of lenses of different colors on the visual abilities and comfort of 20 patients with retinal disease found that, in home trials, the critical issue was density more than color. Office tests of visual acuity and contrast sensitivity with colored lenses did not predict subjective benefit. (Author/JDD)

Neuronal Organization of Deep Brain Opsin Photoreceptors in Adult Teleosts

PubMed Central

Hang, Chong Yee; Kitahashi, Takashi; Parhar, Ishwar S.

2016-01-01

Biological impacts of light beyond vision, i.e., non-visual functions of light, signify the need to better understand light detection (or photoreception) systems in vertebrates. Photopigments, which comprise light-absorbing chromophores bound to a variety of G-protein coupled receptor opsins, are responsible for visual and non-visual photoreception. Non-visual opsin photopigments in the retina of mammals and extra-retinal tissues of non-mammals play an important role in non-image-forming functions of light, e.g., biological rhythms and seasonal reproduction. This review highlights the role of opsin photoreceptors in the deep brain, which could involve conserved neurochemical systems that control different time- and light-dependent physiologies in in non-mammalian vertebrates including teleost fish. PMID:27199680

How aquatic water-beetle larvae with small chambered eyes overcome challenges of hunting under water.

PubMed

Stowasser, Annette; Buschbeck, Elke K

2014-11-01

A particularly unusual visual system exists in the visually guided aquatic predator, the Sunburst Diving Beetle, Thermonectus marmoratus (Coleoptera: Dytiscidae). The question arises: how does this peculiar visual system function? A series of experiments suggests that their principal eyes (E1 and E2) are highly specialized for hunting. These eyes are tubular and have relatively long focal lengths leading to high image magnification. Their retinae are linear, and are divided into distinct green-sensitive distal and UV and polarization-sensitive proximal portions. Each distal retina, moreover, has many tiers of photoreceptors with rhabdomeres the long axis of which are peculiarly oriented perpendicular to the light path. Based on detailed optical investigations, the lenses of these eyes are bifocal and project focused images onto specific retinal tiers. Behavioral experiments suggest that these larvae approach prey within their eyes' near-fields, and that they can correctly gauge prey distances even when conventional distance-vision mechanisms are unavailable. In the near-field of these eyes object distance determines which of the many retinal layers receive the best-focused images. This retinal organization could facilitate an unusual distance-vision mechanism. We here summarize past findings and discuss how these eyes allow Thermonectus larvae to be such successful predators.

Partial results after treatment of diabetic macular edema with Bevacizumab

PubMed Central

Marius, Giurgică; Dorin, Chiseliță; Doina, Dimofte

2015-01-01

Purpose: To present the morphological and functional results after treating diabetic macular edema with Bevacizumab. Patient and method: It is a prospective trial which includes 15 patients with diabetic macular edema (proved by OCT and fluorescein angiography examination). The inclusion criteria are: central retinal thickness over 250 µm, visual acuity of the studied eye between 0.1 and 0.5, absence of a previous treatment. We excluded patients with macular edema caused by other ethiology or with any other macular disease. Every patient was treated with 3 intravitreal injections with Bevacizumab at every 6 weeks; we analyzed the results after 4 months. Results: The mean visual acuity improved from 0.33 ± 0.06 at baseline to 0.49 ± 0.13 at 4 months (or from 31±3.9 ETDRS letters to 39±5.67 letters). The central retinal thickness decreased from 457 ± 174 µm to 338 ± 139 µm. There was also an improvement of retinal sensibility on the microperimetry map. Conclusions: The treatment of diabetic macular edema produced an increase of visual acuity and a decrease of macular thickness after the first 3 injections with Avastin, but it is necessary to monitor the patients to detect the rebound of the edema and to initiate retreatment. PMID:29450315

Partial results after treatment of diabetic macular edema with Bevacizumab.

PubMed

Marius, Giurgică; Dorin, Chiseliță; Doina, Dimofte

2015-01-01

Purpose: To present the morphological and functional results after treating diabetic macular edema with Bevacizumab. Patient and method: It is a prospective trial which includes 15 patients with diabetic macular edema (proved by OCT and fluorescein angiography examination). The inclusion criteria are: central retinal thickness over 250 µm, visual acuity of the studied eye between 0.1 and 0.5, absence of a previous treatment. We excluded patients with macular edema caused by other ethiology or with any other macular disease. Every patient was treated with 3 intravitreal injections with Bevacizumab at every 6 weeks; we analyzed the results after 4 months. Results: The mean visual acuity improved from 0.33 ± 0.06 at baseline to 0.49 ± 0.13 at 4 months (or from 31±3.9 ETDRS letters to 39±5.67 letters). The central retinal thickness decreased from 457 ± 174 µm to 338 ± 139 µm. There was also an improvement of retinal sensibility on the microperimetry map. Conclusions: The treatment of diabetic macular edema produced an increase of visual acuity and a decrease of macular thickness after the first 3 injections with Avastin, but it is necessary to monitor the patients to detect the rebound of the edema and to initiate retreatment.

Interaction of aberrations, diffraction, and quantal fluctuations determine the impact of pupil size on visual quality.

PubMed

Xu, Renfeng; Wang, Huachun; Thibos, Larry N; Bradley, Arthur

2017-04-01

Our purpose is to develop a computational approach that jointly assesses the impact of stimulus luminance and pupil size on visual quality. We compared traditional optical measures of image quality and those that incorporate the impact of retinal illuminance dependent neural contrast sensitivity. Visually weighted image quality was calculated for a presbyopic model eye with representative levels of chromatic and monochromatic aberrations as pupil diameter was varied from 7 to 1 mm, stimulus luminance varied from 2000 to 0.1  cd/m², and defocus varied from 0 to -2 diopters. The model included the effects of quantal fluctuations on neural contrast sensitivity. We tested the model's predictions for five cycles per degree gratings by measuring contrast sensitivity at 5  cyc/deg. Unlike the traditional Strehl ratio and the visually weighted area under the modulation transfer function, the visual Strehl ratio derived from the optical transfer function was able to capture the combined impact of optics and quantal noise on visual quality. In a well-focused eye, provided retinal illuminance is held constant as pupil size varies, visual image quality scales approximately as the square root of illuminance because of quantum fluctuations, but optimum pupil size is essentially independent of retinal illuminance and quantum fluctuations. Conversely, when stimulus luminance is held constant (and therefore illuminance varies with pupil size), optimum pupil size increases as luminance decreases, thereby compensating partially for increased quantum fluctuations. However, in the presence of -1 and -2 diopters of defocus and at high photopic levels where Weber's law operates, optical aberrations and diffraction dominate image quality and pupil optimization. Similar behavior was observed in human observers viewing sinusoidal gratings. Optimum pupil size increases as stimulus luminance drops for the well-focused eye, and the benefits of small pupils for improving defocused image quality remain throughout the photopic and mesopic ranges. However, restricting pupils to <2  mm will cause significant reductions in the best focus vision at low photopic and mesopic luminances.

Multifocal retinitis in New Zealand sheep dogs.

PubMed

Hughes, P L; Dubielzig, R R; Kazacos, K R

1987-01-01

Thirty-nine percent of 1,448 working sheep dogs were affected with varying degrees of multifocal retinal disease on ophthalmoscopic examination. Lesions consisted of localized areas of hyperreflexia in the tapetal fundus, often associated with hyperpigmentation. Severely affected animals had widespread hyperreflexia with retinal vascular attenuation. Only 6% of 125 New Zealand dogs raised in urban environment were similarly affected. Both eyes of 70 dogs from New Zealand were examined histologically. Forty-seven of 70 dogs had ocular inflammatory disease. Ten other dogs had noninflammatory eye disease, and 13 dogs had normal eyes. Histologically, eyes with inflammatory disease were divided into three categories: Dogs 3 years of age or less with active inflammatory disease of the retina, uvea, and vitreous. Four dogs in this group had migrating nematode larvae identified morphologically as genus Toxocara. Diffuse retinitis and retinal atrophy in conjunction with localized retinal necrosis and choroidal fibrosis. Dogs in this category were severely, clinically affected. Chronic, low-grade retinitis with variable retinal atrophy. Most dogs in this category were over 3 years of age, and many were visually functional. The existence of a definable spectrum of morphological changes associated with inflammation, suggests that Toxocara sp. ocular larva migrans may be the cause of a highly prevalent, potentially blinding syndrome of working sheep dogs in New Zealand.

Vitrectomy for floaters: prospective efficacy analyses and retrospective safety profile.

PubMed

Sebag, Jerry; Yee, Kenneth M P; Wa, Christianne A; Huang, Laura C; Sadun, Alfredo A

2014-06-01

Floaters impact vision but the mechanism is unknown. We hypothesize that floaters reduce contrast sensitivity function, which can be normalized by vitrectomy, and that minimally invasive vitrectomy will have lower incidences of retinal tears (reported at 30%) and cataracts (50-76%). Seventy-six eyes (34 phakic) with floaters were evaluated in 2 separate studies. Floater etiologies were primarily posterior vitreous detachment in 61 of 76 eyes (80%) and myopic vitreopathy in 24 of 76 eyes (32%). Minimally invasive 25G vitrectomy was performed without posterior vitreous detachment induction, leaving anterior vitreous, and using nonhollow probes for cannula extraction. Efficacy was studied prospectively (up to 9 months) in 16 floater cases with Freiburg Acuity Contrast Testing (Weber index [%W] reproducibility = 92.1%) and the National Eye Institute Visual Function Questionnaire. Safety was separately evaluated in 60 other cases followed up on an average of 17.5 months (range, 3-51 months). Floater eyes had 67% contrast sensitivity function attenuation (4.0 ± 2.3 %W; control subjects = 2.4 ± 0.9 %W, P < 0.013). After vitrectomy, contrast sensitivity function normalized in each case at 1 week (2.0 ± 1.4 %W, P < 0.01) and remained normal at 1 month (2.0 ± 1.0 %W, P < 0.003) and 3 months to 9 months (2.2 ± 1.5 %W, P < 0.018). Visual Function Questionnaire was 28.3% lower in floater patients (73.2 ± 15.6, N = 16) than in age-matched control subjects (93.9 ± 8.0, N = 12, P < 0.001), and postoperatively improved by 29.2% (P < 0.001). In the safety study of 60 floater cases treated with vitrectomy, none developed retinal breaks, infection, or glaucoma after a mean follow-up of 17.5 months. Only 8 of 34 cases (23.5%) required cataract surgery (none younger than 53 years) at an average of 15 months postvitrectomy. Floaters lower contrast sensitivity function, which normalizes after vitrectomy. Visual Function Questionnaire quantified improvement in satisfaction. Not inducing posterior vitreous detachment reduced retinal tear incidence from 30% to 0% (P < 0.007). Postvitrectomy cataract incidence was reduced from 50% to 23.5% (P < 0.02). This approach thus seems effective and safe in alleviating the visual dysfunction induced by floaters.

ACUTE RETINAL ARTERIAL OCCLUSIVE DISORDERS

PubMed Central

Hayreh, Sohan Singh

2011-01-01

The initial section deals with basic sciences; among the various topics briefly discussed are the anatomical features of ophthalmic, central retinal and cilioretinal arteries which may play a role in acute retinal arterial ischemic disorders. Crucial information required in the management of central retinal artery occlusion (CRAO) is the length of time the retina can survive following that. An experimental study shows that CRAO for 97 minutes produces no detectable permanent retinal damage but there is a progressive ischemic damage thereafter, and by 4 hours the retina has suffered irreversible damage. In the clinical section, I discuss at length various controversies on acute retinal arterial ischemic disorders. Classification of acute retinal arterial ischemic disorders These are of 4 types: CRAO, branch retinal artery occlusion (BRAO), cotton wools spots and amaurosis fugax. Both CRAO and BRAO further comprise multiple clinical entities. Contrary to the universal belief, pathogenetically, clinically and for management, CRAO is not one clinical entity but 4 distinct clinical entities – non-arteritic CRAO, non-arteritic CRAO with cilioretinal artery sparing, arteritic CRAO associated with giant cell arteritis (GCA) and transient non-arteritic CRAO. Similarly, BRAO comprises permanent BRAO, transient BRAO and cilioretinal artery occlusion (CLRAO), and the latter further consists of 3 distinct clinical entities - non-arteritic CLRAO alone, non-arteritic CLRAO associated with central retinal vein occlusion and arteritic CLRAO associated with GCA. Understanding these classifications is essential to comprehend fully various aspects of these disorders. Central retinal artery occlusion The pathogeneses, clinical features and management of the various types of CRAO are discussed in detail. Contrary to the prevalent belief, spontaneous improvement in both visual acuity and visual fields does occur, mainly during the first 7 days. The incidence of spontaneous visual acuity improvement during the first 7 days differs significantly (p<0.001) among the 4 types of CRAO; among them, in eyes with initial visual acuity of counting finger or worse, visual acuity improved, remained stable or deteriorated in nonarteritic CRAO in 22%, 66% and 12% respectively; in nonarteritic CRAO with cilioretinal artery sparing in 67%, 33% and none respectively; and in transient nonarteritic CRAO in 82%, 18% and none respectively. Arteritic CRAO shows no change. Recent studies have shown that administration of local intra-arterial thrombolytic agent not only has no beneficial effect but also can be harmful. Prevalent multiple misconceptions on CRAO are discussed. Branch retinal artery occlusion Pathogeneses, clinical features and management of various types of BRAO are discussed at length. The natural history of visual acuity outcome shows a final visual acuity of 20/40 or better in 89% of permanent BRAO cases, 100% of transient BRAO and 100% of nonarteritic CLRAO alone. Cotton wools spots These are common, non-specific acute focal retinal ischemic lesions, seen in many retinopathies. Their pathogenesis and clinical features are discussed in detail. Amaurosis fugax Its pathogenesis, clinical features and management are described. PMID:21620994

Acute painless monocular visual loss due to central retinal artery occlusion in a patient with Churg-Strauss vasculitis.

PubMed

Skrapari, Ioanna; Kagkelari, Eleftheria; Charitatos, Evangelos; Pantelidaki, Catherine; Gounaris, Theodoros; Sioula, Evagelia

2008-01-01

Ocular involvement in Churg-Strauss syndrome (CSS) is infrequent. We describe a case of a 50-year-old woman, with blood eosinophilia, involvement of the respiratory tract, skin, and peripheral nervous system, fulfilling the American College of Rheumatology criteria for CSS, who presented with left foot drop followed by left acute painless visual loss. Central retinal artery occlusion was diagnosed by fundoscopic findings (retinal whitening with a cherry-red spot). CSS was confirmed by sural nerve biopsy. Despite treatment with high-dose corticosteroids, cyclophosphamide, and anticoagulant therapy, visual acuity was not substantially improved. Acute blindness in CSS has been rarely described. Even more rarely, central retinal artery occlusion has been found to be the underlying cause of this infrequent clinical manifestation in CSS.

Braille alexia during visual hallucination in a blind man with selective calcarine atrophy.

PubMed

Maeda, Kengo; Yasuda, Hitoshi; Haneda, Masakazu; Kashiwagi, Atsunori

2003-04-01

The case of a 56-year-old man who has been blind for 25 years due to retinal degeneration is herein described. The patient complained of elementary visual hallucination, during which it was difficult for him to read Braille. Brain magnetic resonance imaging showed marked atrophy of the bilateral striate cortex. Visual hallucination as a release phenomenon of the primary visual cortex has never been reported to cause alexia for Braille. The present case supports the results of recent functional imaging studies of the recruitment of striate and prestriate cortex for Braille reading.

Transient Retinal Dysfunctions after Acute Cannabis Use.

PubMed

Schwitzer, Thomas; Robert, Matthieu P; Giersch, Anne; Angioi-Duprez, Karine; Ingster-Moati, Isabelle; Pon-Monnier, Amandine; Schwan, Raymund; Laprevote, Vincent

2016-01-01

Although cannabis is very widespread worldwide, the impact of cannabis on visual function remains poorly understood. This is partly due to numerous difficulties met in developing clinical studies in cannabis users. Here, we report the first documented case of neuroretinal dysfunction after acute cannabis smoking. This observation was favored by the need of an annual ophthalmic evaluation in the context of a chloroquine intake for a systemic lupus erythematosus in a 47-year-old heavy cannabis user. A complete ophthalmic evaluation including visual acuity tests, intraocular pressure, fundoscopic examination, automated 10° central visual field, full-field electroretinogram (ERG) and multifocal ERG was performed twice - 30 min and 5 h after cannabis smoking. A strong decrease (up to 48%) in the a-wave amplitude of the full-field ERG was measured 30 min after cannabis smoking for all scotopic responses compared with the responses 5 h after smoking. Other tests showed reproducible results between the 2 series of measurements. This clinical case suggests that acute inhalation of cannabis affects the photoreceptors functioning. This rare situation suggests further investigations are required on the impact of cannabis on retinal processing, especially since cannabis has been incriminated in car injuries. © 2016 S. Karger AG, Basel.

Bilateral phacoemulsification and intraocular lens implantation in a great horned owl.

PubMed

Carter, Renee T; Murphy, Christopher J; Stuhr, Charles M; Diehl, Kathryn A

2007-02-15

A great horned owl of estimated age < 1 year that was captured by wildlife rehabilitators was evaluated because of suspected cataracts. Nuclear and incomplete cortical cataracts were evident in both eyes. Ocular ultrasonography revealed no evidence of retinal detachment, and electroretinography revealed normal retinal function. For visual rehabilitation, cataract surgery was planned and intraocular lens design was determined on the basis of values obtained from the schematic eye, which is a mathematical model representing a normal eye for a species. Cataract surgery and intraocular lens placement were performed in both eyes. After surgery, refraction was within -0.75 diopters in the right eye and -0.25 diopters in the left eye. Visual rehabilitation was evident on the basis of improved tracking and feeding behavior, and the owl was eventually released into the wild. In raptors with substantial visual compromise, euthanasia or placement in a teaching facility is a typical outcome because release of such a bird is unacceptable. Successful intraocular lens implantation for visual rehabilitation and successful release into the wild are achievable.

Diagnostic Utility of Ocular Symptoms and Vision for Cytomegalovirus Retinitis.

PubMed

Liu, Yingna; Chen, Alexander S; Kamphaengkham, Siripim; Leenasirimakul, Prattana; Jirawison, Choeng; Ausayakhun, Somsanguan; Margolis, Todd P; Keenan, Jeremy D

2016-01-01

Cytomegalovirus (CMV) retinitis remains a leading cause of blindness in countries with a high burden of AIDS. Although dilated fundus examinations are recommended for those with CD4 counts below 100 cells/μL, in practice only those with poor vision and/or symptoms are routinely referred for screening. Therefore, the predictive value of this common practice should be assessed. This is a prospective cross-sectional study. Patients with known HIV and a CD4 count of less than 100 cells/μL attending an HIV clinic in Chiang Mai, Thailand completed a standardized questionnaire about visual symptoms and underwent visual acuity testing and dilated fundus examination. Participants without CMV retinitis were invited for repeated examinations every 3 months until their CD4 count exceeded 100 cells/μL. Patient-level statistical analyses were conducted to calculate diagnostic test characteristics, with bootstrapping to account for correlated data. Of 103 study participants, 16 had CMV retinitis diagnosed at some point during the study. Participants with CMV retinitis were more likely to complain of visual symptoms compared to those without CMV retinitis (p = 0.01), including scotoma (p = 0.0002), itchy or watery eyes (p < 0.0001), and eye pain (p = 0.003); they were also more likely to have visual acuity worse than Counting Fingers (p = 0.0003). However, the absence of eye symptoms and the absence of poor vision did not strongly affect the probability that a patient did not have disease (negative likelihood ratio 0.56 and 0.76, respectively). Ocular symptoms and poor visual acuity were poor diagnostic indicators for the presence of CMV retinitis. Systematic screening of HIV patients with CD4 counts below 100 cells/μl should be carried out to detect disease at an early stage, when blindness can still be prevented.

Rational Tuning of Visual Cycle Modulator Pharmacodynamics

PubMed Central

Kiser, Philip D.; Zhang, Jianye; Badiee, Mohsen; Kinoshita, Junzo; Peachey, Neal S.; Tochtrop, Gregory P.

2017-01-01

Modulators of the visual cycle have been developed for treatment of various retinal disorders. These agents were designed to inhibit retinoid isomerase [retinal pigment epithelium-specific 65 kDa protein (RPE65)], the rate-limiting enzyme of the visual cycle, based on the idea that attenuation of visual pigment regeneration could reduce formation of toxic retinal conjugates. Of these agents, certain ones that contain primary amine groups can also reversibly form retinaldehyde Schiff base adducts, which contributes to their retinal protective activity. Direct inhibition of RPE65 as a therapeutic strategy is complicated by adverse effects resulting from slowed chromophore regeneration, whereas effective retinal sequestration can require high drug doses with potential off-target effects. We hypothesized that the RPE65-emixustat crystal structure could help guide the design of retinaldehyde-sequestering agents with varying degrees of RPE65 inhibitory activity. We found that addition of an isopropyl group to the central phenyl ring of emixustat and related compounds resulted in agents effectively lacking in vitro retinoid isomerase inhibitory activity, whereas substitution of the terminal 6-membered ring with branched moieties capable of stronger RPE65 interaction potentiated inhibition. The isopropyl derivative series produced discernible visual cycle suppression in vivo, albeit much less potently than compounds with a high affinity for the RPE65 active site. These agents were distributed into the retina and formed Schiff base adducts with retinaldehyde. Except for one compound [3-amino-1-(3-isopropyl-5-((2,6,6-trimethylcyclohex-1-en-1-yl)methoxy)phenyl)propan-1-ol (MB-007)], these agents conferred protection against retinal phototoxicity, suggesting that both direct RPE65 inhibition and retinal sequestration are mechanisms of potential therapeutic relevance. PMID:28476927

Changes in Retinal Microvasculature and Visual Acuity After Antivascular Endothelial Growth Factor Therapy in Retinal Vein Occlusion.

PubMed

Winegarner, Andrew; Wakabayashi, Taku; Fukushima, Yoko; Sato, Tatsuhiko; Hara-Ueno, Chikako; Busch, Caleb; Nishiyama, Issei; Shiraki, Nobuhiko; Sayanagi, Kaori; Nishida, Kentaro; Sakaguchi, Hirokazu; Nishida, Kohji

2018-06-01

To investigate the changes in the retinal microvasculature during the course of anti-VEGF therapy in eyes with macular edema due to retinal vein occlusion (RVO) and their association with visual outcomes. The vessel density (VD) and foveal avascular zone (FAZ) area in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were quantitatively measured by optical coherence tomography angiography (OCTA) in 48 consecutive eyes with RVO before and 1, 3, 6, 9, and 12 months after anti-VEGF therapy. Anti-VEGF therapy was performed either with ranibizumab or aflibercept following a pro re nata (PRN) regimen. The correlation between post-treatment best-corrected visual acuity (BCVA) and changes in the retinal microvasculature evaluated by OCTA were assessed. The BCVA improved significantly at 12 months (P < 0.001). Better BCVA at 12 months was significantly associated with a better VD in the SCP and DCP both at baseline (R2 = 0.524, P < 0.001 and R2 = 0.457, P < 0.001, respectively) and at 12 months (R2 = 0.521, P < 0.001 and R2 = 0.662, P < 0.001, respectively). Overall, both VD and FAZ did not change significantly during the 12 months. However, the progression of nonperfusion was observed in the SCP in 6 (13%) eyes and in the DCP in 10 (21%) eyes. The number of macular edema recurrence was significantly associated with a decrease in the VD (P = 0.006 [SCP] and P < 0.001 [DCP]) and less visual gain (P = 0.02) after treatment. Anti-VEGF therapy maintains retinal perfusion in most patients with RVO. Preserving retinal perfusion is crucial for better visual outcomes.

Origin and Evolution of Retinoid Isomerization Machinery in Vertebrate Visual Cycle: Hint from Jawless Vertebrates

PubMed Central

Stearn, Olivia; Li, Yan; Campos, Maria Mercedes; Gentleman, Susan; Rogozin, Igor B.; Redmond, T. Michael

2012-01-01

In order to maintain visual sensitivity at all light levels, the vertebrate eye possesses a mechanism to regenerate the visual pigment chromophore 11-cis retinal in the dark enzymatically, unlike in all other taxa, which rely on photoisomerization. This mechanism is termed the visual cycle and is localized to the retinal pigment epithelium (RPE), a support layer of the neural retina. Speculation has long revolved around whether more primitive chordates, such as tunicates and cephalochordates, anticipated this feature. The two key enzymes of the visual cycle are RPE65, the visual cycle all-trans retinyl ester isomerohydrolase, and lecithin:retinol acyltransferase (LRAT), which generates RPE65’s substrate. We hypothesized that the origin of the vertebrate visual cycle is directly connected to an ancestral carotenoid oxygenase acquiring a new retinyl ester isomerohydrolase function. Our phylogenetic analyses of the RPE65/BCMO and N1pC/P60 (LRAT) superfamilies show that neither RPE65 nor LRAT orthologs occur in tunicates (Ciona) or cephalochordates (Branchiostoma), but occur in Petromyzon marinus (Sea Lamprey), a jawless vertebrate. The closest homologs to RPE65 in Ciona and Branchiostoma lacked predicted functionally diverged residues found in all authentic RPE65s, but lamprey RPE65 contained all of them. We cloned RPE65 and LRATb cDNAs from lamprey RPE and demonstrated appropriate enzymatic activities. We show that Ciona ß-carotene monooxygenase a (BCMOa) (previously annotated as an RPE65) has carotenoid oxygenase cleavage activity but not RPE65 activity. We verified the presence of RPE65 in lamprey RPE by immunofluorescence microscopy, immunoblot and mass spectrometry. On the basis of these data we conclude that the crucial transition from the typical carotenoid double bond cleavage functionality (BCMO) to the isomerohydrolase functionality (RPE65), coupled with the origin of LRAT, occurred subsequent to divergence of the more primitive chordates (tunicates, etc.) in the last common ancestor of the jawless and jawed vertebrates. PMID:23209628

Origin and evolution of retinoid isomerization machinery in vertebrate visual cycle: hint from jawless vertebrates.

PubMed

Poliakov, Eugenia; Gubin, Alexander N; Stearn, Olivia; Li, Yan; Campos, Maria Mercedes; Gentleman, Susan; Rogozin, Igor B; Redmond, T Michael

2012-01-01

In order to maintain visual sensitivity at all light levels, the vertebrate eye possesses a mechanism to regenerate the visual pigment chromophore 11-cis retinal in the dark enzymatically, unlike in all other taxa, which rely on photoisomerization. This mechanism is termed the visual cycle and is localized to the retinal pigment epithelium (RPE), a support layer of the neural retina. Speculation has long revolved around whether more primitive chordates, such as tunicates and cephalochordates, anticipated this feature. The two key enzymes of the visual cycle are RPE65, the visual cycle all-trans retinyl ester isomerohydrolase, and lecithin:retinol acyltransferase (LRAT), which generates RPE65's substrate. We hypothesized that the origin of the vertebrate visual cycle is directly connected to an ancestral carotenoid oxygenase acquiring a new retinyl ester isomerohydrolase function. Our phylogenetic analyses of the RPE65/BCMO and N1pC/P60 (LRAT) superfamilies show that neither RPE65 nor LRAT orthologs occur in tunicates (Ciona) or cephalochordates (Branchiostoma), but occur in Petromyzon marinus (Sea Lamprey), a jawless vertebrate. The closest homologs to RPE65 in Ciona and Branchiostoma lacked predicted functionally diverged residues found in all authentic RPE65s, but lamprey RPE65 contained all of them. We cloned RPE65 and LRATb cDNAs from lamprey RPE and demonstrated appropriate enzymatic activities. We show that Ciona ß-carotene monooxygenase a (BCMOa) (previously annotated as an RPE65) has carotenoid oxygenase cleavage activity but not RPE65 activity. We verified the presence of RPE65 in lamprey RPE by immunofluorescence microscopy, immunoblot and mass spectrometry. On the basis of these data we conclude that the crucial transition from the typical carotenoid double bond cleavage functionality (BCMO) to the isomerohydrolase functionality (RPE65), coupled with the origin of LRAT, occurred subsequent to divergence of the more primitive chordates (tunicates, etc.) in the last common ancestor of the jawless and jawed vertebrates.

Surgical treatment in combined hamartoma of the retina and retinal pigment epithelium.

PubMed

Sánchez-Vicente, J L; Rueda-Rueda, T; Llerena-Manzorro, L; Molina-Socola, F E; Contreras-Díaz, M; Szewc, M; Vital-Berral, C; Alfaro-Juárez, A; Medina-Tapia, A; López-Herrero, F; González-García, L; Muñoz-Morales, A

2017-03-01

The case is presented of a 39 year-old man with a combined hamartoma of the retina and retinal pigment epithelium, who experienced progressive visual loss and worsening of metamorphopsia. The patient underwent vitrectomy and epiretinal component peeling, with improvement in visual acuity, metamorphopsia, and retinal architecture, assessed by optical coherence tomography. Selected patients with combined hamartomas of the retina and retinal pigment epithelium may benefit from surgical management. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Cancer-associated retinopathy with unusual retinal whitening.

PubMed

Lee, Joan J; Vrabec, Tamara R; Baldassano, Vincent F

2015-01-01

To describe the clinical characteristics and results of ocular and systemic testing in an atypical case of cancer-associated retinopathy. This study is a retrospective case report of a female patient. Rapidly progressive visual loss, vitritis, white, ring- and coin-shaped retinal lesions, and panretinal optical coherence tomography thinning preceded the diagnosis of poorly differentiated cervical carcinoma with neuroendocrine features consistent with small-cell carcinoma. Cancer-associated retinopathy can present with ring- and coin-shaped retinal lesions, vitritis, and panretinal thinning. The presence of intraocular inflammation and retinal and choroidal vasculopathy may herald more rapid visual demise.

The Relationship between OCT-measured Central Retinal Thickness and Visual Acuity in Diabetic Macular Edema

PubMed Central

2008-01-01

Objective To compare optical coherence tomography (OCT)-measured retinal thickness and visual acuity in eyes with diabetic macular edema (DME) both before and after macular laser photocoagulation. Design Cross-sectional and longitudinal study. Participants 210 subjects (251 eyes) with DME enrolled in a randomized clinical trial of laser techniques. Methods Retinal thickness was measured with OCT and visual acuity was measured with the electronic-ETDRS procedure. Main Outcome Measures OCT-measured center point thickness and visual acuity Results The correlation coefficients for visual acuity versus OCT center point thickness were 0.52 at baseline and 0.49, 0.36, and 0.38 at 3.5, 8, and 12 months post-laser photocoagulation. The slope of the best fit line to the baseline data was approximately 4.4 letters (95% C.I.: 3.5, 5.3) better visual acuity for every 100 microns decrease in center point thickness at baseline with no important difference at follow-up visits. Approximately one-third of the variation in visual acuity could be predicted by a linear regression model that incorporated OCT center point thickness, age, hemoglobin A1C, and severity of fluorescein leakage in the center and inner subfields. The correlation between change in visual acuity and change in OCT center point thickening 3.5 months after laser treatment was 0.44 with no important difference at the other follow-up times. A subset of eyes showed paradoxical improvements in visual acuity with increased center point thickening (7–17% at the three time points) or paradoxical worsening of visual acuity with a decrease in center point thickening (18%–26% at the three time points). Conclusions There is modest correlation between OCT-measured center point thickness and visual acuity, and modest correlation of changes in retinal thickening and visual acuity following focal laser treatment for DME. However, a wide range of visual acuity may be observed for a given degree of retinal edema and paradoxical increases in center point thickening with increases in visual acuity as well as paradoxical decreases in center point thickening with decreases in visual acuity were not uncommon. Thus, although OCT measurements of retinal thickness represent an important tool in clinical evaluation, they cannot reliably substitute as a surrogate for visual acuity at a given point in time. This study does not address whether short-term changes on OCT are predictive of long-term effects on visual acuity. PMID:17123615

Auditory and visual interactions between the superior and inferior colliculi in the ferret.

PubMed

Stitt, Iain; Galindo-Leon, Edgar; Pieper, Florian; Hollensteiner, Karl J; Engler, Gerhard; Engel, Andreas K

2015-05-01

The integration of visual and auditory spatial information is important for building an accurate perception of the external world, but the fundamental mechanisms governing such audiovisual interaction have only partially been resolved. The earliest interface between auditory and visual processing pathways is in the midbrain, where the superior (SC) and inferior colliculi (IC) are reciprocally connected in an audiovisual loop. Here, we investigate the mechanisms of audiovisual interaction in the midbrain by recording neural signals from the SC and IC simultaneously in anesthetized ferrets. Visual stimuli reliably produced band-limited phase locking of IC local field potentials (LFPs) in two distinct frequency bands: 6-10 and 15-30 Hz. These visual LFP responses co-localized with robust auditory responses that were characteristic of the IC. Imaginary coherence analysis confirmed that visual responses in the IC were not volume-conducted signals from the neighboring SC. Visual responses in the IC occurred later than retinally driven superficial SC layers and earlier than deep SC layers that receive indirect visual inputs, suggesting that retinal inputs do not drive visually evoked responses in the IC. In addition, SC and IC recording sites with overlapping visual spatial receptive fields displayed stronger functional connectivity than sites with separate receptive fields, indicating that visual spatial maps are aligned across both midbrain structures. Reciprocal coupling between the IC and SC therefore probably serves the dynamic integration of visual and auditory representations of space. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Astrocytes and Müller Cell Alterations During Retinal Degeneration in a Transgenic Rat Model of Retinitis Pigmentosa

PubMed Central

Fernández-Sánchez, Laura; Lax, Pedro; Campello, Laura; Pinilla, Isabel; Cuenca, Nicolás

2015-01-01

Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes, and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer (GCL) of P23H vs. SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina. PMID:26733810

Allogeneic Transplantation of Müller-Derived Retinal Ganglion Cells Improves Retinal Function in a Feline Model of Ganglion Cell Depletion

PubMed Central

Becker, Silke; Eastlake, Karen; Jayaram, Hari; Jones, Megan F.; Brown, Robert A.; McLellan, Gillian J.; Charteris, David G.; Khaw, Peng T.

2016-01-01

Human Müller glia with stem cell characteristics (hMGSCs) have been shown to improve retinal function upon transplantation into rat models of retinal ganglion cell (RGC) depletion. However, their translational potential may depend upon successful engraftment and improvement of retinal function in experimental models with anatomical and functional features resembling those of the human eye. We investigated the effect of allogeneic transplantation of feline Müller glia with the ability to differentiate into cells expressing RGC markers, following ablation of RGCs by N-methyl-d-aspartate (NMDA). Unlike previous observations in the rat, transplantation of hMGSC-derived RGCs into the feline vitreous formed aggregates and elicited a severe inflammatory response without improving visual function. In contrast, allogeneic transplantation of feline MGSC (fMGSC)-derived RGCs into the vitrectomized eye improved the scotopic threshold response (STR) of the electroretinogram (ERG). Despite causing functional improvement, the cells did not attach onto the retina and formed aggregates on peripheral vitreous remnants, suggesting that vitreous may constitute a barrier for cell attachment onto the retina. This was confirmed by observations that cellular scaffolds of compressed collagen and enriched preparations of fMGSC-derived RGCs facilitated cell attachment. Although cells did not migrate into the RGC layer or the optic nerve, they significantly improved the STR and the photopic negative response of the ERG, indicative of increased RGC function. These results suggest that MGSCs have a neuroprotective ability that promotes partial recovery of impaired RGC function and indicate that cell attachment onto the retina may be necessary for transplanted cells to confer neuroprotection to the retina. Significance Müller glia with stem cell characteristics are present in the adult human retina, but they do not have regenerative ability. These cells, however, have potential for development of cell therapies to treat retinal disease. Using a feline model of retinal ganglion cell (RGC) depletion, cell grafting methods to improve RGC function have been developed. Using cellular scaffolds, allogeneic transplantation of Müller glia-derived RGC promoted cell attachment onto the retina and enhanced retinal function, as judged by improvement of the photopic negative and scotopic threshold responses of the electroretinogram. The results suggest that the improvement of RGC function observed may be ascribed to the neuroprotective ability of these cells and indicate that attachment of the transplanted cells onto the retina is required to promote effective neuroprotection. PMID:26718648

A Microparticle/Hydrogel Combination Drug-Delivery System for Sustained Release of Retinoids

PubMed Central

Gao, Song-Qi; Maeda, Tadao; Okano, Kiichiro; Palczewski, Krzysztof

2012-01-01

Purpose. To design and develop a drug-delivery system containing a combination of poly(d,l-lactide-co-glycolide) (PLGA) microparticles and alginate hydrogel for sustained release of retinoids to treat retinal blinding diseases that result from an inadequate supply of retinol and generation of 11-cis-retinal. Methods. To study drug release in vivo, either the drug-loaded microparticle–hydrogel combination was injected subcutaneously or drug-loaded microparticles were injected intravitreally into Lrat−/− mice. Orally administered 9-cis-retinoids were used for comparison and drug concentrations in plasma were determined by HPLC. Electroretinography (ERG) and both chemical and histologic analyses were used to evaluate drug effects on visual function and morphology. Results. Lrat−/− mice demonstrated sustained drug release from the microparticle/hydrogel combination that lasted 4 weeks after subcutaneous injection. Drug concentrations in plasma of the control group treated with the same oral dose rose to higher levels for 6−7 hours but then dropped markedly by 24 hours. Significantly increased ERG responses and a markedly improved retinal pigmented epithelium (RPE)–rod outer segment (ROS) interface were observed after subcutaneous injection of the drug-loaded delivery combination. Intravitreal injection of just 2% of the systemic dose of drug-loaded microparticles provided comparable therapeutic efficacy. Conclusions. Sustained release of therapeutic levels of 9-cis-retinoids was achieved in Lrat−/− mice by subcutaneous injection in a microparticle/hydrogel drug-delivery system. Both subcutaneous and intravitreal injections of drug-loaded microparticles into Lrat−/− mice improved visual function and retinal structure. PMID:22918645

Learning to see again: biological constraints on cortical plasticity and the implications for sight restoration technologies

NASA Astrophysics Data System (ADS)

Beyeler, Michael; Rokem, Ariel; Boynton, Geoffrey M.; Fine, Ione

2017-10-01

The ‘bionic eye’—so long a dream of the future—is finally becoming a reality with retinal prostheses available to patients in both the US and Europe. However, clinical experience with these implants has made it apparent that the visual information provided by these devices differs substantially from normal sight. Consequently, the ability of patients to learn to make use of this abnormal retinal input plays a critical role in whether or not some functional vision is successfully regained. The goal of the present review is to summarize the vast basic science literature on developmental and adult cortical plasticity with an emphasis on how this literature might relate to the field of prosthetic vision. We begin with describing the distortion and information loss likely to be experienced by visual prosthesis users. We then define cortical plasticity and perceptual learning, and describe what is known, and what is unknown, about visual plasticity across the hierarchy of brain regions involved in visual processing, and across different stages of life. We close by discussing what is known about brain plasticity in sight restoration patients and discuss biological mechanisms that might eventually be harnessed to improve visual learning in these patients.

Long-term results of repeated anti-vascular endothelial growth factor therapy in eyes with retinal pigment epithelial tears.

PubMed

Moreira, Carlos A; Arana, Luis A; Zago, Rommel J

2013-02-01

To evaluate the long-term results of retinal pigment epithelium tears in eyes treated with repeated anti-vascular endothelial growth factor (VEGF) therapy. Five patients with retinal pigment epithelial tears (without foveal center involvement) after anti-VEGF injection were studied retrospectively. Mean follow-up time was 52 months, with measurements of visual acuity and evaluation of macular findings by angiography and optical coherence tomography during this period. All eyes had a persistent submacular neovascular membrane 30 days after the tear. An anti-VEGF drug was reinjected until the membranes stopped leaking. The mean initial visual acuity immediately after the tear was 20/160, and the mean final visual acuity was 20/60. The number of anti-VEGF reinjections varied from two to eight during the follow-up period. Long-term optical coherence tomography analysis showed reduced fluid and remodeling of the torn retinal pigment epithelium. Long-term visual results with repeated anti-VEGF therapy are not as devastating as suggested previously. Visual acuity and metamorphopsia improve with time as long as the neovascular membrane is inactive. Optical coherence tomography changes in the macular area reflect the visual acuity improvement.

Intravitreal bevacizumab injections for treatment of central retinal vein occlusion: six-month results of a prospective trial.

PubMed

Priglinger, Siegfried G; Wolf, Armin H; Kreutzer, Thomas C; Kook, Daniel; Hofer, Anja; Strauss, Rupert W; Alge, Claudia S; Kunze, Christian; Haritoglou, Christos; Kampik, Anselm

2007-10-01

To evaluate the effect of intravitreal bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) injections on visual acuity and foveal retinal thickness in patients with central retinal vein occlusion (CRVO). In this prospective, noncomparative, consecutive, interventional case series, 46 patients received repeated intravitreal injections (1.25 mg) of bevacizumab. Main outcome measures were visual acuity (Snellen and ETDRS charts) and optical coherence tomography measurements in a 6-month follow-up period. Mean visual acuity improved from 20/250 at baseline to 20/80 at the 6-month follow-up (P < 0.001). ETDRS chart findings revealed a mean letter gain +/-SD from baseline to 6 months of 13.9 +/- 14.4 letters. Mean central retinal thickness +/-SD decreased from 535 +/- 148 microm at baseline to 323 +/- 116 microm at the 6-month follow-up. Ischemic CRVO was associated with significantly lower visual acuity than nonischemic CRVO (P < 0.001). However, visual acuity gain was similar in both groups. Independent of duration of symptoms, CRVO was associated with a similar gain in visual acuity. Intravitreal injection of bevacizumab appears to be a new treatment option for patients with macular edema secondary to CRVO.

An introduction to DARC technology.

PubMed

Ahmad, Syed Shoeb

2017-01-01

Glaucoma is a multi-factorial neurodegenerative disorder. The common denominator in all types of glaucomas is retinal ganglion cell death through apoptosis. However, this cellular demise in glaucoma is detected late by structural or functional analyses. There can be a 10-year delay prior to the appearance of visual field defects and pre-perimetric glaucoma is an issue still being addressed. However, a new cutting-edge technology called detection of apoptosing retinal cells (DARC) is being developed. This technique is capable of non-invasive, real-time visualization of apoptotic changes at the cellular level. It can detect glaucomatous cell damage at a very early stage, at the moment apoptosis starts, and thus management can be initiated even prior to development of visual field changes. In future, this technique will also be able to provide conclusive evidence of the effectiveness of treatment protocol and the need for any modifications which may be required. This article aims to provide a concise review of DARC technology.

Identifying a clinically meaningful threshold for change in uveitic macular edema evaluated by optical coherence tomography.

PubMed

Sugar, Elizabeth A; Jabs, Douglas A; Altaweel, Michael M; Lightman, Sue; Acharya, Nisha; Vitale, Albert T; Thorne, Jennifer E

2011-12-01

To identify a clinically meaningful threshold for change in retinal thickness measured by optical coherence tomography for patients with uveitic macular edema using correlation with change in visual acuity. Cross-sectional and longitudinal study. One hundred twenty-eight eyes (101 individuals) with macular edema enrolled in the Multicenter Uveitis Steroid Treatment (MUST) trial. At enrollment and after 6 months of follow-up, retinal thickness was measured at the central subfield with time-domain optical coherence tomography and visual acuity was measured with logarithmic (Early Treatment Diabetic Retinopathy Study) visual acuity charts. Participants were classified as having macular edema if the retinal thickness was 260 μm or more. A threshold for change in retinal center subfield thickness of 20% balanced the percentage of false positives and false negatives for predicting more than a 10-letter change in visual acuity with a sensitivity of 77% and a specificity of 75%. The results were similar for more than 5-letter changes and for 15-letter or more changes. Those with a 20% or more reduction in retinal thickness had a mean 11.0-letter improvement (95% confidence interval, 7.7 to 14.3) as compared with a -0.4-letter change (95% confidence interval, -4.1 to 3.3) in visual acuity for those without a 20% reduction (P < .01). In addition to being above the level of measurement uncertainty, a 20% change in retinal thickness in patients with macular edema seems to be optimal for clinically important changes in visual acuity and may be considered as an outcome for clinical trials of treatments for uveitic macular edema. Copyright © 2011 Elsevier Inc. All rights reserved.

Middle Cerebral Artery, Ophthalmic Artery, and Multibranch Retinal Vessel Occlusion After Cosmetic Autologous Fat Transfer to Forehead.

PubMed

Roshandel, Danial; Soheilian, Masoud; Pakravan, Mohammad; Aghayan, Sara; Peyman, Gholam A

2015-05-01

A 65-year-old woman with left hemiparesis and sudden loss of visual acuity in her right eye presented a few hours after cosmetic injection of autologous fat to her forehead. Right eye visual acuity was no light perception. Funduscopy revealed widespread retinal whitening and multibranch retinal vessel occlusion. Fluorescein angiography showed markedly delayed choroidal and retinal filling together with occlusion of multiple branches of retinal arteries and veins. On magnetic resonance imaging of the brain, multiple lesions compatible with recent infarction were detected. The authors diagnosed multibranch retinal artery and vein occlusion in the right ophthalmic and middle cerebral arteries due to fat emboli. This case emphasizes the need to reevaluate the safety of such aesthetic procedures, particularly in the facial zone to prevent devastating complications. Copyright 2015, SLACK Incorporated.

Advanced multiphoton methods for in vitro and in vivo functional imaging of mouse retinal neurons (Conference Presentation)

NASA Astrophysics Data System (ADS)

Cohen, Noam; Schejter, Adi; Farah, Nairouz; Shoham, Shy

2016-03-01

Studying the responses of retinal ganglion cell (RGC) populations has major significance in vision research. Multiphoton imaging of optogenetic probes has recently become the leading approach for visualizing neural populations and has specific advantages for imaging retinal activity during visual stimulation, because it leads to reduced direct photoreceptor excitation. However, multiphoton retinal activity imaging is not straightforward: point-by-point scanning leads to repeated neural excitation while optical access through the rodent eye in vivo has proven highly challenging. Here, we present two enabling optical designs for multiphoton imaging of responses to visual stimuli in mouse retinas expressing calcium indicators. First, we present an imaging solution based on Scanning Line Temporal Focusing (SLITE) for rapidly imaging neuronal activity in vitro. In this design, we scan a temporally focused line rather than a point, increasing the scan speed and reducing the impact of repeated excitation, while maintaining high optical sectioning. Second, we present the first in vivo demonstration of two-photon imaging of RGC activity in the mouse retina. To obtain these cellular resolution recordings we integrated an illumination path into a correction-free imaging system designed using an optical model of the mouse eye. This system can image at multiple depths using an electronically tunable lens integrated into its optical path. The new optical designs presented here overcome a number of outstanding obstacles, allowing the study of rapid calcium- and potentially even voltage-indicator signals both in vitro and in vivo, thereby bringing us a step closer toward distributed monitoring of action potentials.

Wide-field fundus autofluorescence abnormalities and visual function in patients with cone and cone-rod dystrophies.

PubMed

Oishi, Maho; Oishi, Akio; Ogino, Ken; Makiyama, Yukiko; Gotoh, Norimoto; Kurimoto, Masafumi; Yoshimura, Nagahisa

2014-05-20

To evaluate the clinical utility of wide-field fundus autofluorescence (FAF) in patients with cone dystrophy and cone-rod dystrophy. Sixteen patients with cone dystrophy (CD) and 41 patients with cone-rod dystrophy (CRD) were recruited at one institution. The right eye of each patient was included for analysis. We obtained wide-field FAF images using a ultra-widefield retinal imaging device and measured the area of abnormal FAF. The association between the area of abnormal FAF and the results of visual acuity measurements, kinetic perimetry, and electroretinography (ERG) were investigated. The mean age of the participants was 51.4 ± 17.4 years, and the mean logarithm of the minimum angle of resolution was 1.00 ± 0.57. The area of abnormal FAF correlated with the scotoma measured by the Goldman perimetry I/4e isopter (ρ = 0.79, P < 0.001). The area also correlated with amplitudes of the rod ERG (ρ = -0.63, P < 0.001), combined ERG a-wave (ρ = -0.72, P < 0.001), combined ERG b-wave (ρ = -0.66, P < 0.001), cone ERG (ρ = -0.44, P = 0.001), and flicker ERG (ρ = -0.47, P < 0.001). The extent of abnormal FAF reflects the severity of functional impairment in patients with cone-dominant retinal dystrophies. Fundus autofluorescence measurements are useful for predicting retinal function in these patients. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Comparison of amplitude-decorrelation, speckle-variance and phase-variance OCT angiography methods for imaging the human retina and choroid

PubMed Central

Gorczynska, Iwona; Migacz, Justin V.; Zawadzki, Robert J.; Capps, Arlie G.; Werner, John S.

2016-01-01

We compared the performance of three OCT angiography (OCTA) methods: speckle variance, amplitude decorrelation and phase variance for imaging of the human retina and choroid. Two averaging methods, split spectrum and volume averaging, were compared to assess the quality of the OCTA vascular images. All data were acquired using a swept-source OCT system at 1040 nm central wavelength, operating at 100,000 A-scans/s. We performed a quantitative comparison using a contrast-to-noise (CNR) metric to assess the capability of the three methods to visualize the choriocapillaris layer. For evaluation of the static tissue noise suppression in OCTA images we proposed to calculate CNR between the photoreceptor/RPE complex and the choriocapillaris layer. Finally, we demonstrated that implementation of intensity-based OCT imaging and OCT angiography methods allows for visualization of retinal and choroidal vascular layers known from anatomic studies in retinal preparations. OCT projection imaging of data flattened to selected retinal layers was implemented to visualize retinal and choroidal vasculature. User guided vessel tracing was applied to segment the retinal vasculature. The results were visualized in a form of a skeletonized 3D model. PMID:27231598

Inferior retinal light exposure is more effective than superior retinal exposure in suppressing melatonin in humans

NASA Technical Reports Server (NTRS)

Glickman, Gena; Hanifin, John P.; Rollag, Mark D.; Wang, Jenny; Cooper, Howard; Brainard, George C.

2003-01-01

Illumination of different areas of the human retina elicits differences in acute light-induced suppression of melatonin. The aim of this study was to compare changes in plasma melatonin levels when light exposures of equal illuminance and equal photon dose were administered to superior, inferior, and full retinal fields. Nine healthy subjects participated in the study. Plexiglass eye shields were modified to permit selective exposure of the superior and inferior halves of the retinas of each subject. The Humphrey Visual Field Analyzer was used both to confirm intact full visual fields and to quantify exposure of upper and lower visual fields. On study nights, eyes were dilated, and subjects were exposed to patternless white light for 90 min between 0200 and 0330 under five conditions: (1) full retinal exposure at 200 lux, (2) full retinal exposure at 100 lux, (3) inferior retinal exposure at 200 lux, (4) superior retinal exposure at 200 lux, and (5) a dark-exposed control. Plasma melatonin levels were determined by radioimmunoassay. ANOVA demonstrated a significant effect of exposure condition (F = 5.91, p < 0.005). Post hoc Fisher PLSD tests showed significant (p < 0.05) melatonin suppression of both full retinal exposures as well as the inferior retinal exposure; however, superior retinal exposure was significantly less effective in suppressing melatonin. Furthermore, suppression with superior retinal exposure was not significantly different from that of the dark control condition. The results indicate that the inferior retina contributes more to the light-induced suppression of melatonin than the superior retina at the photon dosages tested in this study. Findings suggest a greater sensitivity or denser distribution of photoreceptors in the inferior retina are involved in light detection for the retinohypothalamic tract of humans.

Analysis by NASA's VESGEN Software of Retinal Blood Vessels Before and After 70-Day Bed Rest: A Retrospective Study

NASA Technical Reports Server (NTRS)

Raghunandan, Sneha; Vyas, Ruchi J.; Vizzeri, Gianmarco; Taibbi, Giovanni; Zanello, Susana B.; Ploutz-Snyder, Robert; Parsons-Wingerter, Patricia A.

2016-01-01

Significant risks for visual impairment associated with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions. Impairments include decreased near visual acuity, posterior globe flattening, choroidal folds, optic disc edema and cotton wool spots. We hypothesize that microgravity-induced fluid shifts result in pathological changes within the retinal blood vessels that precede development of visual and other ocular impairments. Potential contributions of retinal vascular remodeling to VIIP etiology are therefore being investigated by NASAs innovative VESsel GENeration Analysis (VESGEN) software for two studies: (1) head-down tilt in human subjects before and after 70 days of bed rest, and (2) U.S. crew members before and after ISS missions. VESGEN analysis in previous research supported by the US National Institutes of Health identified surprising new opportunities to regenerate retinal vessels during early-stage, potentially reversible progression of the visually impairing and blinding disease, diabetic retinopathy.

Use of placental extract for the treatment of myopic and senile chorio-retinal dystrophies.

PubMed

Girotto, G; Malinverni, W

1982-01-01

After an examination of the literature, the authors evaluate the activity of placenta extract in 34 subjects suffering from chorio-retinal dystrophy of different types (myopic and senile) and of different degrees of anatomo-functional alteration. The parameters used for this study were visual acuity, the luminous sense, the visual field and the electrophysiological activity of the retina. The aqueous solution was administered by intramuscular route at a daily dose of 3 ml (equivalent to 1,80 g of fresh organ) during 20 days; the parameters were tested before and at the end of the treatment. The results obtained during this study show that the parameters were improved, in different degrees, by the administration of the placenta extract. This is clearly demonstrated by the significant improvement in the luminous sense.

OPTICAL COHERENCE TOMOGRAPHY BASELINE PREDICTORS FOR INITIAL BEST-CORRECTED VISUAL ACUITY RESPONSE TO INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT IN EYES WITH DIABETIC MACULAR EDEMA: The CHARTRES Study.

PubMed

Santos, Ana R; Costa, Miguel Â; Schwartz, Christian; Alves, Dalila; Figueira, João; Silva, Rufino; Cunha-Vaz, Jose G

2018-06-01

To identify baseline optical coherence tomography morphologic characteristics predicting the visual response to anti-vascular endothelial growth factor therapy in diabetic macular edema. Sixty-seven patients with diabetic macular edema completed a prospective, observational study (NCT01947881-CHARTRES). All patients received monthly intravitreal injections of Lucentis for 3 months followed by PRN treatment and underwent best-corrected visual acuity measurements and spectral domain optical coherence tomography at Baseline, Months 1, 2, 3, and 6. Visual treatment response was characterized as good (≥10 letters), moderate (5-10 letters), and poor (<5 or letters loss). Spectral domain optical coherence tomography images were graded before and after treatment by a certified Reading Center. One month after loading dose, 26 patients (38.80%) were identified as good responders, 19 (28.35%) as Moderate and 22 (32.83%) as poor responders. There were no significant best-corrected visual acuity and central retinal thickness differences at baseline (P = 0.176; P = 0.573, respectively). Ellipsoid zone disruption and disorganization of retinal inner layers were good predictors for treatment response, representing a significant risk for poor visual recovery to anti-vascular endothelial growth factor therapy (odds ratio = 10.96; P < 0.001 for ellipsoid zone disruption and odds ratio = 7.05; P = 0.034 for disorganization of retinal inner layers). Damage of ellipsoid zone, higher values of disorganization of retinal inner layers, and central retinal thickness decrease are good predictors of best-corrected visual acuity response to anti-vascular endothelial growth factor therapy.

Relationship among visual field, blood flow, and neural structure measurements in glaucoma.

PubMed

Hwang, John C; Konduru, Ranjith; Zhang, Xinbo; Tan, Ou; Francis, Brian A; Varma, Rohit; Sehi, Mitra; Greenfield, David S; Sadda, Srinivas R; Huang, David

2012-05-17

To determine the relationship among visual field, neural structural, and blood flow measurements in glaucoma. Case-control study. Forty-seven eyes of 42 patients with perimetric glaucoma were age-matched with 27 normal eyes of 27 patients. All patients underwent Doppler Fourier-domain optical coherence tomography to measure retinal blood flow and standard glaucoma evaluation with visual field testing and quantitative structural imaging. Linear regression analysis was performed to analyze the relationship among visual field, blood flow, and structure, after all variables were converted to logarithmic decibel scale. Retinal blood flow was reduced in glaucoma eyes compared to normal eyes (P < 0.001). Visual field loss was correlated with both reduced retinal blood flow and structural loss of rim area and retinal nerve fiber layer (RNFL). There was no correlation or paradoxical correlation between blood flow and structure. Multivariate regression analysis revealed that reduced blood flow and structural loss are independent predictors of visual field loss. Each dB decrease in blood flow was associated with at least 1.62 dB loss in mean deviation (P ≤ 0.001), whereas each dB decrease in rim area and RNFL was associated with 1.15 dB and 2.56 dB loss in mean deviation, respectively (P ≤ 0.03). There is a close link between reduced retinal blood flow and visual field loss in glaucoma that is largely independent of structural loss. Further studies are needed to elucidate the causes of the vascular dysfunction and potential avenues for therapeutic intervention. Blood flow measurement may be useful as an independent assessment of glaucoma severity.

Getting signals into the brain: visual prosthetics through thalamic microstimulation.

PubMed

Pezaris, John S; Eskandar, Emad N

2009-07-01

Common causes of blindness are diseases that affect the ocular structures, such as glaucoma, retinitis pigmentosa, and macular degeneration, rendering the eyes no longer sensitive to light. The visual pathway, however, as a predominantly central structure, is largely spared in these cases. It is thus widely thought that a device-based prosthetic approach to restoration of visual function will be effective and will enjoy similar success as cochlear implants have for restoration of auditory function. In this article the authors review the potential locations for stimulation electrode placement for visual prostheses, assessing the anatomical and functional advantages and disadvantages of each. Of particular interest to the neurosurgical community is placement of deep brain stimulating electrodes in thalamic structures that has shown substantial promise in an animal model. The theory of operation of visual prostheses is discussed, along with a review of the current state of knowledge. Finally, the visual prosthesis is proposed as a model for a general high-fidelity machine-brain interface.

Retinopathy of prematurity: inflammation, choroidal degeneration, and novel promising therapeutic strategies.

PubMed

Rivera, José Carlos; Holm, Mari; Austeng, Dordi; Morken, Tora Sund; Zhou, Tianwei Ellen; Beaudry-Richard, Alexandra; Sierra, Estefania Marin; Dammann, Olaf; Chemtob, Sylvain

2017-08-22

Retinopathy of prematurity (ROP) is an important cause of childhood blindness globally, and the incidence is rising. The disease is characterized by initial arrested retinal vascularization followed by neovascularization and ensuing retinal detachment causing permanent visual loss. Although neovascularization can be effectively treated via retinal laser ablation, it is unknown which children are at risk of entering this vision-threatening phase of the disease. Laser ablation may itself induce visual field deficits, and there is therefore a need to identify targets for novel and less destructive treatments of ROP. Inflammation is considered a key contributor to the pathogenesis of ROP. A large proportion of preterm infants with ROP will have residual visual loss linked to loss of photoreceptor (PR) and the integrity of the retinal pigment epithelium (RPE) in the macular region. Recent studies using animal models of ROP suggest that choroidal degeneration may be associated with a loss of integrity of the outer retina, a phenomenon so far largely undescribed in ROP pathogenesis. In this review, we highlight inflammatory and neuron-derived factors related to ROP progression, as well, potential targets for new treatment strategies. We also introduce choroidal degeneration as a significant cause of residual visual loss following ROP. We propose that ROP should no longer be considered an inner retinal vasculopathy only, but also a disease of choroidal degeneration affecting both retinal pigment epithelium and photoreceptor integrity.

Relations between Cardiac and Visual Phenotypes in Diabetes: A Multivariate Approach.

PubMed

Oliveiros, Bárbara; Sanches, Mafalda; Quendera, Bruno; Graça, Bruno; Guelho, Daniela; Gomes, Leonor; Carrilho, Francisco; Caseiro-Alves, Filipe; Castelo-Branco, Miguel

2016-01-01

Cardiovascular disease and diabetes represent a major public health concern. The former is the most frequent cause of death and disability in patients with type 2 diabetes, where left ventricular dysfunction is highly prevalent. Moreover, diabetic retinopathy is becoming a dominant cause of visual impairment and blindness. The complex relation between cardiovascular disease and diabetic retinopathy as a function of ageing, obesity and hypertension remains to be clarified. Here, we investigated such relations in patients with diabetes type 2, in subjects with neither overt heart disease nor advanced proliferative diabetic retinopathy. We studied 47 patients and 50 controls, aged between 45 and 65 years, equally distributed according to gender. From the 36 measures regarding visual structure and function, and the 11 measures concerning left ventricle function, we performed data reduction to obtain eight new derived variables, seven of which related to the eye, adjusted for age, gender, body mass index and high blood pressure using both discriminant analysis (DA) and logistic regression (LR). We found moderate to strong correlation between left ventricle function and the eye constructs: minimum correlation was found for psychophysical motion thresholds (DA: 0.734; LR: 0.666), while the maximum correlation was achieved with structural volume density in the neural retina (DA: 0.786; LR: 0.788). Controlling the effect of pairwise correlated visual constructs, the parameters that were most correlated to left ventricle function were volume density in retina and thickness of the retinal nerve fiber layers (adjusted multiple R2 is 0.819 and 0.730 for DA and LR), with additional contribution of psychophysical loss in achromatic contrast discrimination. We conclude that visual structural and functional changes in type 2 diabetes are related to heart dysfunction, when the effects of clinical, demographic and associated risk factors are taken into account, revealing a genuine relation between cardiac and retinal diabetic phenotypes.

Retinal damage caused by air-fluid exchange during pars plana vitrectomy.

PubMed

Yang, Sam S; McDonald, H Richard; Everett, A I; Johnson, Robert N; Jumper, J Michael; Fu, Arthur D

2006-03-01

To report two cases of retinal damage associated with air infusion during pars plana vitrectomy. Observational case report. The authors reviewed the course of two patients who had retinal damage during par plana vitrectomy and air-fluid exchange for the treatment of macular hole and optic pit-related macular detachment, respectively. The intraoperative observations, postoperative course, and outcomes were reported. As a result of high air infusion flow during air-fluid exchange, retinal damage was created in the area contralateral to the infusion port. In Case 1, an oval area of whitening was noted on the first postoperative day. This area subsequently developed into a large retinal break associated with retinal detachment. In the second case, retinal whitening was noted intraoperatively. This region of pallor resolved quickly during the early postoperative period but resulted in a corresponding inferotemporal visual field defect. High infusion flow during air-fluid exchange in eyes undergoing vitrectomy surgery may result in significant retinal damage. This pressure-induced trauma initially causes retinal whitening that may be seen intraoperatively or during the early postoperative period. The region of damaged retina may develop a retinal break and detachment or a corresponding visual field defect.

A Promising Tool in Retina Regeneration: Current Perspectives and Challenges When Using Mesenchymal Progenitor Stem Cells in Veterinary and Human Ophthalmological Applications.

PubMed

Cislo-Pakuluk, Anna; Marycz, Krzysztof

2017-10-01

Visual impairment is a common ailment of the current world population, with more exposure to CCD screens and fluorescent lighting, approximately 285 billion people suffer from this deficiency and 13% of those are considered clinically blind. More common causes for visual impairment include age-related macular degeneration (AMD), glaucoma and diabetic retinopathy (Zhu et al. Molecular Medicine Reports, 2015; Kolb et al. 2007; Machalińska et al. Current Eye Research, 34(9),748-760, 2009) among a few. As cases of retinal and optic nerve diseases rise, it is vital to find a treatment, which has led to investigation of the therapeutic potential of various stem cells types (Bull et al. Investigative Opthalmology & Visual Science, 50(9), 4244, 2009; Bull et al. Investigative Opthalmology & Visual Science, 49(8), 3449, 2008; Yu et al. Biochemical and Biophysical Research Communications, 344(4), 1071-1079, 2006; Na et al. Graefe's Archive for Clinical and Experimental Ophthalmology, 247(4), 503-514, 2008). In previous studies, some of the stem cell variants used include human Muller SCs and bone marrow derived SCs. Some of the regenerative potential characteristics of mesenchymal progenitor stem cells (MSCs) include their multilineage differentiation potential, their immunomodulatory effects, their high proliferative activity, they can be easily cultured in vitro, and finally their potential to synthesize and secrete membrane derived vesicles rich in growth factors, mRNA and miRNA which possibly aid in regulation of tissue damage regeneration. These facts alone, explain why MSCs are so widely used in clinical trials, 350 up to date (Switonski, Reproductive Biology, 14(1), 44-50, 2014). Animal studies have demonstrated that sub-retinal transplantation of MSCs delays retinal degeneration and preserves retinal function through trophic response (Inoue et al. Experimental Eye Research, 85(2), 234-241, 2007). Umbilical cord derived MSCs (UC/MSCs) have also been shown to contain neuroprotective features of ganglion cells in rat studies (Zwart et al. Experimental Neurology, 216(2), 439-448, 2009). This review aims to present current MSC therapies in practice, as well as their retinal regeneration potential in animal models, and their innovative prospects for treatment of human retinal diseases.

Retinal prostheses: progress toward the next generation implants

PubMed Central

Ghezzi, Diego

2015-01-01

In the last decade, various clinical trials proved the capability of visual prostheses, in particular retinal implants, to restore a useful form of vision. These encouraging results promoted the emerging of several strategies for neuronal stimulation aiming at the restoration of sight. Besides the traditional approach based on electrical stimulation through metal electrodes in the different areas of the visual path (e.g., the visual cortex, the lateral geniculate nucleus, the optic nerve, and the retina), novel concepts for neuronal stimulation have been mostly exploited as building blocks of the next generation of retinal implants. This review is focused on critically discussing recent major advancements in the field of retinal stimulation with particular attention to the findings in the application of novel concepts and materials. Last, the major challenges in the field and their clinical implications will be outlined. PMID:26347602

Course of Cytomegalovirus Retinitis in the Era of Highly Active Antiretroviral Therapy: Five-year Outcomes

PubMed Central

Jabs, Douglas A.; Ahuja, Alka; Van Natta, Mark; Lyon, Alice; Srivastava, Sunil; Gangaputra, Sapna

2010-01-01

Purpose To describe the five-year outcomes of patients with cytomegalovirus (CMV) retinitis and AIDS in the era of highly active antiretroviral therapy (HAART). Design Prospective, multicenter, observational study Participants 503 patients with AIDS and CMV retinitis Methods Follow-up every 3 months with medical history, ophthalmologic examination, laboratory testing, and retinal photographs. Participants were classified as having previously-diagnosed CMV retinitis and immune recovery (CD4+ T cells >100 cells/µL), previously-diagnosed retinitis and immune compromise, and newly-diagnosed CMV retinitis (diagnosis < 45 days prior to enrollment). Main outcome measures Mortality, retinitis progression (movement of the border of a CMV lesion ≥ ½ disc diameter or occurrence of a new lesion), retinal detachment, immune recovery uveitis (IRU), and visual loss (to worse than 20/40 and to 20/200 or worse), Results Overall mortality was 9.8 deaths/100 person-years (PY). Rates varied by group at enrollment from 3.0/100 PY for those with previously-diagnosed retinitis and immune recovery to 26.1/100 PY for those with newly-diagnosed retinitis. The rate of retinitis progression was 7.0/100 PY and varied from 1.4/100 PY for those with previously-diagnosed retinitis and immune recovery to 28.0/100 PY for those with newly-diagnosed retinitis. The rate of retinal detachment was 2.3/100 eye-years (EY) and varied from 1.2/100 EY for those with previously-diagnosed retinitis and immune recovery to 4.9/100 EY for those with newly-diagnosed retinitis. The rate of IRU was 1.7/100 PY and varied from 1.3/100 PY for those with previously-diagnosed retinitis and immune recovery at enrollment to 3.6/100 PY for those with newly-diagnosed retinitis who subsequently experienced immune recovery. The rates of visual loss to worse than 20/40 and to 20/200 or worse were 7.9/100 EY and 3.4/100 EY, respectively; they varied from 6.1/100 EY and 2.7/100 EY for those with previously-diagnosed retinitis and immune recovery to 11.8/100 EY and 5.1/100 EY for those with newly-diagnosed retinitis. Although the event rates tended to decline with time, in general, at no time did they reach zero. Conclusions Despite the availability of HAART, patients with AIDS and CMV retinitis remain at increased risk for mortality, retinitis progression, complications of the retinitis, and visual loss over a 5-year period. PMID:20673591

Electroretinogram analysis of the visual response in zebrafish larvae.

PubMed

Chrispell, Jared D; Rebrik, Tatiana I; Weiss, Ellen R

2015-03-16

The electroretinogram (ERG) is a noninvasive electrophysiological method for determining retinal function. Through the placement of an electrode on the surface of the cornea, electrical activity generated in response to light can be measured and used to assess the activity of retinal cells in vivo. This manuscript describes the use of the ERG to measure visual function in zebrafish. Zebrafish have long been utilized as a model for vertebrate development due to the ease of gene suppression by morpholino oligonucleotides and pharmacological manipulation. At 5-10 dpf, only cones are functional in the larval retina. Therefore, the zebrafish, unlike other animals, is a powerful model system for the study of cone visual function in vivo. This protocol uses standard anesthesia, micromanipulation and stereomicroscopy protocols that are common in laboratories that perform zebrafish research. The outlined methods make use of standard electrophysiology equipment and a low light camera to guide the placement of the recording microelectrode onto the larval cornea. Finally, we demonstrate how a commercially available ERG stimulator/recorder originally designed for use with mice can easily be adapted for use with zebrafish. ERG of larval zebrafish provides an excellent method of assaying cone visual function in animals that have been modified by morpholino oligonucleotide injection as well as newer genome engineering techniques such as Zinc Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9, all of which have greatly increased the efficiency and efficacy of gene targeting in zebrafish. In addition, we take advantage of the ability of pharmacological agents to penetrate zebrafish larvae to evaluate the molecular components that contribute to the photoresponse. This protocol outlines a setup that can be modified and used by researchers with various experimental goals.

A novel role for visual perspective cues in the neural computation of depth

PubMed Central

Kim, HyungGoo R.; Angelaki, Dora E.; DeAngelis, Gregory C.

2014-01-01

As we explore a scene, our eye movements add global patterns of motion to the retinal image, complicating visual motion produced by self-motion or moving objects. Conventionally, it has been assumed that extra-retinal signals, such as efference copy of smooth pursuit commands, are required to compensate for the visual consequences of eye rotations. We consider an alternative possibility: namely, that the visual system can infer eye rotations from global patterns of image motion. We visually simulated combinations of eye translation and rotation, including perspective distortions that change dynamically over time. We demonstrate that incorporating these “dynamic perspective” cues allows the visual system to generate selectivity for depth sign from motion parallax in macaque area MT, a computation that was previously thought to require extra-retinal signals regarding eye velocity. Our findings suggest novel neural mechanisms that analyze global patterns of visual motion to perform computations that require knowledge of eye rotations. PMID:25436667

21 CFR 886.1630 - AC-powered photostimulator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false AC-powered photostimulator. 886.1630 Section 886.1630 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... allows measurement of retinal or visual function by perceptual or electrical methods (e.g., stroboscope...

Sensitivity of Retinal Ganglion Cell Photoreceptors in Traumatic Brain Injury Patients with Photophobia

DTIC Science & Technology

2015-11-01

This work should also stimulate future investigations into therapeutic interventions that restore ipRGC function as a potential therapy for...visual acuity, refractive error, cover test, and optic nerve cup -to-disk (C/D) ratio values are means (SEM). These values were compared using Mann

Multimodal adaptive optics for depth-enhanced high-resolution ophthalmic imaging

NASA Astrophysics Data System (ADS)

Hammer, Daniel X.; Mujat, Mircea; Iftimia, Nicusor V.; Lue, Niyom; Ferguson, R. Daniel

2010-02-01

We developed a multimodal adaptive optics (AO) retinal imager for diagnosis of retinal diseases, including glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinitis pigmentosa (RP). The development represents the first ever high performance AO system constructed that combines AO-corrected scanning laser ophthalmoscopy (SLO) and swept source Fourier domain optical coherence tomography (SSOCT) imaging modes in a single compact clinical prototype platform. The SSOCT channel operates at a wavelength of 1 μm for increased penetration and visualization of the choriocapillaris and choroid, sites of major disease activity for DR and wet AMD. The system is designed to operate on a broad clinical population with a dual deformable mirror (DM) configuration that allows simultaneous low- and high-order aberration correction. The system also includes a wide field line scanning ophthalmoscope (LSO) for initial screening, target identification, and global orientation; an integrated retinal tracker (RT) to stabilize the SLO, OCT, and LSO imaging fields in the presence of rotational eye motion; and a high-resolution LCD-based fixation target for presentation to the subject of stimuli and other visual cues. The system was tested in a limited number of human subjects without retinal disease for performance optimization and validation. The system was able to resolve and quantify cone photoreceptors across the macula to within ~0.5 deg (~100-150 μm) of the fovea, image and delineate ten retinal layers, and penetrate to resolve targets deep into the choroid. In addition to instrument hardware development, analysis algorithms were developed for efficient information extraction from clinical imaging sessions, with functionality including automated image registration, photoreceptor counting, strip and montage stitching, and segmentation. The system provides clinicians and researchers with high-resolution, high performance adaptive optics imaging to help guide therapies, develop new drugs, and improve patient outcomes.

Visual Space and Object Space in the Cerebral Cortex of Retinal Disease Patients

PubMed Central

Spileers, Werner; Wagemans, Johan; Op de Beeck, Hans P.

2014-01-01

The lower areas of the hierarchically organized visual cortex are strongly retinotopically organized, with strong responses to specific retinotopic stimuli, and no response to other stimuli outside these preferred regions. Higher areas in the ventral occipitotemporal cortex show a weak eccentricity bias, and are mainly sensitive for object category (e.g., faces versus buildings). This study investigated how the mapping of eccentricity and category sensitivity using functional magnetic resonance imaging is affected by a retinal lesion in two very different low vision patients: a patient with a large central scotoma, affecting central input to the retina (juvenile macular degeneration), and a patient where input to the peripheral retina is lost (retinitis pigmentosa). From the retinal degeneration, we can predict specific losses of retinotopic activation. These predictions were confirmed when comparing stimulus activations with a no-stimulus fixation baseline. At the same time, however, seemingly contradictory patterns of activation, unexpected given the retinal degeneration, were observed when different stimulus conditions were directly compared. These unexpected activations were due to position-specific deactivations, indicating the importance of investigating absolute activation (relative to a no-stimulus baseline) rather than relative activation (comparing different stimulus conditions). Data from two controls, with simulated scotomas that matched the lesions in the two patients also showed that retinotopic mapping results could be explained by a combination of activations at the stimulated locations and deactivations at unstimulated locations. Category sensitivity was preserved in the two patients. In sum, when we take into account the full pattern of activations and deactivations elicited in retinotopic cortex and throughout the ventral object vision pathway in low vision patients, the pattern of (de)activation is consistent with the retinal loss. PMID:24505449

Step-By-Step Instructions for Retina Recordings with Perforated Multi Electrode Arrays

PubMed Central

Idrees, Saad; Mutter, Marion; Benkner, Boris; Münch, Thomas A.

2014-01-01

Multi-electrode arrays are a state-of-the-art tool in electrophysiology, also in retina research. The output cells of the retina, the retinal ganglion cells, form a monolayer in many species and are well accessible due to their proximity to the inner retinal surface. This structure has allowed the use of multi-electrode arrays for high-throughput, parallel recordings of retinal responses to presented visual stimuli, and has led to significant new insights into retinal organization and function. However, using conventional arrays where electrodes are embedded into a glass or ceramic plate can be associated with three main problems: (1) low signal-to-noise ratio due to poor contact between electrodes and tissue, especially in the case of strongly curved retinas from small animals, e.g. rodents; (2) insufficient oxygen and nutrient supply to cells located on the bottom of the recording chamber; and (3) displacement of the tissue during recordings. Perforated multi-electrode arrays (pMEAs) have been found to alleviate all three issues in brain slice recordings. Over the last years, we have been using such perforated arrays to study light evoked activity in the retinas of various species including mouse, pig, and human. In this article, we provide detailed step-by-step instructions for the use of perforated MEAs to record visual responses from the retina, including spike recordings from retinal ganglion cells and in vitro electroretinograms (ERG). In addition, we provide in-depth technical and methodological troubleshooting information, and show example recordings of good quality as well as examples for the various problems which might be encountered. While our description is based on the specific equipment we use in our own lab, it may also prove useful when establishing retinal MEA recordings with other equipment. PMID:25165854

Advances in Retinal Prosthetic Research: A Systematic Review of Engineering and Clinical Characteristics of Current Prosthetic Initiatives.

PubMed

Cheng, Derrick L; Greenberg, Paul B; Borton, David A

2017-03-01

To date, reviews of retinal prostheses have focused primarily on devices undergoing human trials in the Western Hemisphere and fail to capture significant advances in materials and engineering research in countries such as Japan and Korea, as well as projects in early stages of development. To address these gaps, this systematic review examines worldwide advances in retinal prosthetic research, evaluates engineering characteristics and clinical progress of contemporary device initiatives, and identifies potential directions for future research in the field of retinal prosthetics. A literature search using PubMed, Google Scholar, and IEEExplore was conducted following the PRISMA Guidelines for Systematic Review. Inclusion criteria were peer-reviewed papers demonstrating progress in human or animal trials and papers discussing the prosthetic engineering design. For each initiative, a description of the device, its engineering considerations, and recent clinical results were provided. Ten prosthetic initiatives met our inclusion criteria and were organized by stimulation location. Of these initiatives, four have recently completed human trials, three are undergoing multi- or single-center human trials, and three are undergoing preclinical animal testing. Only the Argus II (FDA 2013, CE 2011) has obtained FDA approval for use in the United States; the Alpha-IMS (CE 2013) has achieved the highest visual acuity using a Landolt-C test to date and is the only device presently undergoing a multicenter clinical trial. Several distinct approaches to retinal stimulation have been successful in eliciting visual precepts in animals and/or humans. However, many clinical needs are still not met and engineering challenges must be addressed before a retinal prosthesis with the capability to fully and safely restore functional vision can be realized.

Thinner retinal layers are associated with changes in the visual pathway: A population-based study.

PubMed

Mutlu, Unal; Ikram, Mohammad K; Roshchupkin, Gennady V; Bonnemaijer, Pieter W M; Colijn, Johanna M; Vingerling, Johannes R; Niessen, Wiro J; Ikram, Mohammad A; Klaver, Caroline C W; Vernooij, Meike W

2018-06-23

Increasing evidence shows that thinner retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL), assessed on optical coherence tomography (OCT), are reflecting global brain atrophy. Yet, little is known on the relation of these layers with specific brain regions. Using voxel-based analysis, we aimed to unravel specific brain regions associated with these retinal layers. We included 2,235 persons (mean age: 67.3 years, 55% women) from the Rotterdam Study (2007-2012) who had gradable retinal OCT images and brain magnetic resonance imaging (MRI) scans, including diffusion tensor (DT) imaging. Thicknesses of peripapillary RNFL and perimacular GCL were measured using an automated segmentation algorithm. Voxel-based morphometry protocols were applied to process DT-MRI data. We investigated the association between retinal layer thickness with voxel-wise gray matter density and white matter microstructure by performing linear regression models. We found that thinner RNFL and GCL were associated with lower gray matter density in the visual cortex, and with lower fractional anisotropy and higher mean diffusivity in white matter tracts that are part of the optic radiation. Furthermore, thinner GCL was associated with lower gray matter density of the thalamus. Thinner RNFL and GCL are associated with gray and white matter changes in the visual pathway suggesting that retinal thinning on OCT may be specifically associated with changes in the visual pathway rather than with changes in the global brain. These findings may serve as a basis for understanding visual symptoms in elderly patients, patients with Alzheimer's disease, or patients with posterior cortical atrophy. © 2018 Wiley Periodicals, Inc.

Retinal Laminar Architecture in Human Retinitis Pigmentosa Caused by Rhodopsin Gene Mutations

PubMed Central

Aleman, Tomas S.; Cideciyan, Artur V.; Sumaroka, Alexander; Windsor, Elizabeth A. M.; Herrera, Waldo; White, D. Alan; Kaushal, Shalesh; Naidu, Anjani; Roman, Alejandro J.; Schwartz, Sharon B.; Stone, Edwin M.; Jacobson, Samuel G.

2008-01-01

Purpose. To determine the underlying retinal micropathology in subclasses of autosomal dominant retinitis pigmentosa (ADRP) caused by rhodopsin (RHO) mutations. Methods. Patients with RHO-ADRP (n = 17, ages 6–73 years), representing class A (R135W and P347L) and class B (P23H, T58R, and G106R) functional phenotypes, were studied with optical coherence tomography (OCT), and colocalized visual thresholds were determined by dark- and light-adapted chromatic perimetry. Autofluorescence imaging was performed with near-infrared light. Retinal histology in hT17M-rhodopsin mice was compared with the human results. Results. Class A patients had only cone-mediated vision. The outer nuclear layer (ONL) thinned with eccentricity and was not detectable within 3 to 4 mm of the fovea. Scotomatous extracentral retina showed loss of ONL, thickening of the inner retina, and demelanization of RPE. Class B patients had superior–inferior asymmetry in function and structure. The superior retina could have normal rod and cone vision, normal lamination (including ONL) and autofluorescence of the RPE melanin; laminopathy was found in the scotomas. With Fourier-domain-OCT, there was apparent inner nuclear layer (INL) thickening in regions with ONL thinning. Retinal regions without ONL had a thick hyporeflective layer that was continuous with the INL from neighboring regions with normal lamination. Transgenic mice had many of the laminar abnormalities found in patients. Conclusions. Retinal laminar abnormalities were present in both classes of RHO-ADRP and were related to the severity of colocalized vision loss. The results in human class B and the transgenic mice support the following disease sequence: ONL diminution with INL thickening; amalgamation of residual ONL with the thickened INL; and progressive retinal remodeling with eventual thinning. PMID:18385078

The Rat With Oxygen-Induced Retinopathy Is Myopic With Low Retinal Dopamine

PubMed Central

Zhang, Nan; Favazza, Tara L.; Baglieri, Anna Maria; Benador, Ilan Y.; Noonan, Emily R.; Fulton, Anne B.; Hansen, Ronald M.; Iuvone, P. Michael; Akula, James D.

2013-01-01

Purpose. Dopamine (DA) is a neurotransmitter implicated both in modulating neural retinal signals and in eye growth. Therefore, it may participate in the pathogenesis of the most common clinical sequelae of retinopathy of prematurity (ROP), visual dysfunction and myopia. Paradoxically, in ROP myopia the eye is usually small. The eye of the rat with oxygen-induced retinopathy (OIR) is characterized by retinal dysfunction and short axial length. There have been several investigations of the early maturation of DA in rat retina, but little at older ages, and not in the OIR rat. Therefore, DA, retinal function, and refractive state were investigated in the OIR rat. Methods. In one set of rats, the development of dopaminergic (DAergic) networks was evaluated in retinal cross-sections from rats aged 14 to 120 days using antibodies against tyrosine hydroxylase (TH, the rate-limiting enzyme in the biosynthesis of DA). In another set of rats, retinoscopy was used to evaluate spherical equivalent (SE), electoretinography (ERG) was used to evaluate retinal function, and high-pressure liquid chromatography (HPLC) was used to evaluate retinal contents of DA, its precursor levodopamine (DOPA), and its primary metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). Results. The normally rapid postnatal ramification of DAergic neurons was disrupted in OIR rats. Retinoscopy revealed that OIR rats were relatively myopic. In the same eyes, ERG confirmed retinal dysfunction in OIR. HPLC of those eyes' retinae confirmed low DA. Regression analysis indicated that DA metabolism (evaluated by the ratio of DOPAC to DA) was an important additional predictor of myopia beyond OIR. Conclusions. The OIR rat is the first known animal model of myopia in which the eye is smaller than normal. Dopamine may modulate, or fail to modulate, neural activity in the OIR eye, and thus contribute to this peculiar myopia. PMID:24168993

The rat with oxygen-induced retinopathy is myopic with low retinal dopamine.

PubMed

Zhang, Nan; Favazza, Tara L; Baglieri, Anna Maria; Benador, Ilan Y; Noonan, Emily R; Fulton, Anne B; Hansen, Ronald M; Iuvone, P Michael; Akula, James D

2013-12-19

Dopamine (DA) is a neurotransmitter implicated both in modulating neural retinal signals and in eye growth. Therefore, it may participate in the pathogenesis of the most common clinical sequelae of retinopathy of prematurity (ROP), visual dysfunction and myopia. Paradoxically, in ROP myopia the eye is usually small. The eye of the rat with oxygen-induced retinopathy (OIR) is characterized by retinal dysfunction and short axial length. There have been several investigations of the early maturation of DA in rat retina, but little at older ages, and not in the OIR rat. Therefore, DA, retinal function, and refractive state were investigated in the OIR rat. In one set of rats, the development of dopaminergic (DAergic) networks was evaluated in retinal cross-sections from rats aged 14 to 120 days using antibodies against tyrosine hydroxylase (TH, the rate-limiting enzyme in the biosynthesis of DA). In another set of rats, retinoscopy was used to evaluate spherical equivalent (SE), electoretinography (ERG) was used to evaluate retinal function, and high-pressure liquid chromatography (HPLC) was used to evaluate retinal contents of DA, its precursor levodopamine (DOPA), and its primary metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). The normally rapid postnatal ramification of DAergic neurons was disrupted in OIR rats. Retinoscopy revealed that OIR rats were relatively myopic. In the same eyes, ERG confirmed retinal dysfunction in OIR. HPLC of those eyes' retinae confirmed low DA. Regression analysis indicated that DA metabolism (evaluated by the ratio of DOPAC to DA) was an important additional predictor of myopia beyond OIR. The OIR rat is the first known animal model of myopia in which the eye is smaller than normal. Dopamine may modulate, or fail to modulate, neural activity in the OIR eye, and thus contribute to this peculiar myopia.

Wide-field fundus autofluorescence imaging to evaluate retinal function in patients with retinitis pigmentosa.

PubMed

Ogura, Shuntaro; Yasukawa, Tsutomu; Kato, Aki; Usui, Hideaki; Hirano, Yoshio; Yoshida, Munenori; Ogura, Yuichiro

2014-11-01

To study the correlation between the visual fields (VF) and wide-field fundus autofluorescence (FAF) in patients with retinitis pigmentosa (RP). Retrospective, observational, consecutive case series. Twenty-four eyes of 12 patients diagnosed with RP were enrolled. The VFs measured by Goldmann perimetry and wide-field FAF images were compared for each eye. The relationship between the areas of hypoautofluorescence on the wide-field FAF images and scotoma on Goldmann perimetry were evaluated. The VF and FAF images in the central 60 degrees were trimmed and superimposed to calculate the percentage agreement between the hypoautofluorescence and the scotomas and between the isoautofluorescence and hyperautofluorescence and the remaining VFs. The areas of hypoautofluorescence on the FAF images were correlated significantly (R = 0.86, P < .001) with the areas of the VF defects on Goldmann perimetry. The mean percentage agreement between the hypoautofluorescence and the scotomas was 91.0% ± 7.7% and that of the isoautofluorescence and hyperautofluorescence with the remaining VFs was 84.5% ± 7.4%. The areas of geographic hypoautofluorescence with or without hyperautofluorescent bands reflected the VF defects, while nummular or mottled hypoautofluorescence without VF defects was seen in 7 eyes. These results suggested that wide-field FAF imaging is useful to evaluate the remaining retinal function in patients with RP. Abnormal fundus autofluorescence precedes loss of retinal function and is helpful for monitoring disease progression. Copyright © 2014 Elsevier Inc. All rights reserved.

Retinotopic Distribution of Structural and Functional Damages following Bright Light Exposure of Juvenile Rats

PubMed Central

Polosa, Anna; Liu, Wenwen; Lachapelle, Pierre

2016-01-01

In the present study, we aimed at better understanding the short (acute) and long term (chronic) degenerative processes characterizing the juvenile rat model of light-induced retinopathy. Electroretinograms, visual evoked potentials (VEP), retinal histology and western blots were obtained from juvenile albino Sprague-Dawley rats at preselected postnatal ages (from P30 to P400) following exposure to 10,000 lux from P14 to P28. Our results show that while immediately following the cessation of exposure, photoreceptor degeneration was concentrated within a well delineated area of the superior retina (i.e. the photoreceptor hole), with time, this hole continued to expand to form an almost photoreceptor-free region covering most of superior-inferior axis. By the end of the first year of life, only few photoreceptors remained in the far periphery of the superior hemiretina. Interestingly, despite a significant impairment of the outer retinal function, the retinal output (VEP) was maintained in the early phase of this retinopathy. Our findings thus suggest that postnatal exposure to a bright luminous environment triggers a degenerative process that continues to impair the retinal structure and function (mostly at the photoreceptor level) long after the cessation of the exposure regimen (more than 1 year documented herein). Given the slow degenerative process triggered following postnatal bright light exposure, we believe that our model represents an attractive alternative (to other more genetic models) to study the pathophysiology of photoreceptor-induced retinal degeneration as well as therapeutic strategies to counteract it. PMID:26784954

[Ocular toxocariasis--case report].

PubMed

Moraru, Andreea; Panfil, Madălina; Totolici, Geanina; Brănişteanu, Daniel; Costin, Dănut; Schmitzer, Speranţa

2014-01-01

Ocular Toxocariasis is a parasitosis caused by Toxocara catis/canis larvae localized in the eye. The most frequent clinical manifestations are the central retinal granuloma, peripheral retinal granuloma and chronic endophthalmitis. Secondary complications due to the presence of parasite in the posterior segment of the eye may have significant consequences on visual function. We present the case of a 23 years old patient, admitted for progressive decrease of the right eye BCVA during the last 6 months. After performing clinical examination and serological tests we established the diagnosis of ocular Toxocariasis. The patient presented a particular form of the disease consisting in the presence of both a central retinal granuloma and a peripheral one. We performed 23G pars plana vitrectomy and membrane peeling. VA improved as soon as the first month after surgery.

An Automated System for Comprehensive Assessment of Visual Field Sensitivity.

DTIC Science & Technology

1985-04-01

act to degrade this basic configuration; e.g., pathology, such as glaucoma and retinitis pigmentosa ; environmental extremes, such as hypoxia...and B. Appleton. 1971. Effects of hypoxia on visual performance and retinal vascular state. Journal of Applied Physiology. 31: 357蘺. Kobrick, J. L

Anatomical Analysis of the Retinal Specializations to a Crypto-Benthic, Micro-Predatory Lifestyle in the Mediterranean Triplefin Blenny Tripterygion delaisi

PubMed Central

Fritsch, Roland; Collin, Shaun P.; Michiels, Nico K.

2017-01-01

The environment and lifestyle of a species are known to exert selective pressure on the visual system, often demonstrating a tight link between visual morphology and ecology. Many studies have predicted the visual requirements of a species by examining the anatomical features of the eye. However, among the vast number of studies on visual specializations in aquatic animals, only a few have focused on small benthic fishes that occupy a heterogeneous and spatially complex visual environment. This study investigates the general retinal anatomy including the topography of both the photoreceptor and ganglion cell populations and estimates the spatial resolving power (SRP) of the eye of the Mediterranean triplefin Tripterygion delaisi. Retinal wholemounts were prepared to systematically and quantitatively analyze photoreceptor and retinal ganglion cell (RGC) densities using design-based stereology. To further examine the retinal structure, we also used magnetic resonance imaging (MRI) and histological examination of retinal cross sections. Observations of the triplefin’s eyes revealed them to be highly mobile, allowing them to view the surroundings without body movements. A rostral aphakic gap and the elliptical shape of the eye extend its visual field rostrally and allow for a rostro-caudal accommodatory axis, enabling this species to focus on prey at close range. Single and twin cones dominate the retina and are consistently arranged in one of two regular patterns, which may enhance motion detection and color vision. The retina features a prominent, dorso-temporal, convexiclivate fovea with an average density of 104,400 double and 30,800 single cones per mm2, and 81,000 RGCs per mm2. Based on photoreceptor spacing, SRP was calculated to be between 6.7 and 9.0 cycles per degree. Location and resolving power of the fovea would benefit the detection and identification of small prey in the lower frontal region of the visual field. PMID:29311852

Anatomical Analysis of the Retinal Specializations to a Crypto-Benthic, Micro-Predatory Lifestyle in the Mediterranean Triplefin Blenny Tripterygion delaisi.

PubMed

Fritsch, Roland; Collin, Shaun P; Michiels, Nico K

2017-01-01

The environment and lifestyle of a species are known to exert selective pressure on the visual system, often demonstrating a tight link between visual morphology and ecology. Many studies have predicted the visual requirements of a species by examining the anatomical features of the eye. However, among the vast number of studies on visual specializations in aquatic animals, only a few have focused on small benthic fishes that occupy a heterogeneous and spatially complex visual environment. This study investigates the general retinal anatomy including the topography of both the photoreceptor and ganglion cell populations and estimates the spatial resolving power (SRP) of the eye of the Mediterranean triplefin Tripterygion delaisi . Retinal wholemounts were prepared to systematically and quantitatively analyze photoreceptor and retinal ganglion cell (RGC) densities using design-based stereology. To further examine the retinal structure, we also used magnetic resonance imaging (MRI) and histological examination of retinal cross sections. Observations of the triplefin's eyes revealed them to be highly mobile, allowing them to view the surroundings without body movements. A rostral aphakic gap and the elliptical shape of the eye extend its visual field rostrally and allow for a rostro-caudal accommodatory axis, enabling this species to focus on prey at close range. Single and twin cones dominate the retina and are consistently arranged in one of two regular patterns, which may enhance motion detection and color vision. The retina features a prominent, dorso-temporal, convexiclivate fovea with an average density of 104,400 double and 30,800 single cones per mm 2 , and 81,000 RGCs per mm 2 . Based on photoreceptor spacing, SRP was calculated to be between 6.7 and 9.0 cycles per degree. Location and resolving power of the fovea would benefit the detection and identification of small prey in the lower frontal region of the visual field.

The Glenn A. Fry Award Lecture 2012: Plasticity of the visual system following central vision loss.

PubMed

Chung, Susana T L

2013-06-01

Following the onset of central vision loss, most patients develop an eccentric retinal location outside the affected macular region, the preferred retinal locus (PRL), as their new reference for visual tasks. The first goal of this article is to present behavioral evidence showing the presence of experience-dependent plasticity in people with central vision loss. The evidence includes the presence of oculomotor re-referencing of fixational saccades to the PRL; the characteristics of the shape of the crowding zone (spatial region within which the presence of other objects affects the recognition of a target) at the PRL are more "foveal-like" instead of resembling those of the normal periphery; and the change in the shape of the crowding zone at a para-PRL location that includes a component referenced to the PRL. These findings suggest that there is a shift in the referencing locus of the oculomotor and the sensory visual system from the fovea to the PRL for people with central vision loss, implying that the visual system for these individuals is still plastic and can be modified through experiences. The second goal of the article is to demonstrate the feasibility of applying perceptual learning, which capitalizes on the presence of plasticity, as a tool to improve functional vision for people with central vision loss. Our finding that visual function could improve with perceptual learning presents an exciting possibility for the development of an alternative rehabilitative strategy for people with central vision loss.

Improved Visualization of Glaucomatous Retinal Damage Using High-speed Ultrahigh-Resolution Optical Coherence Tomography

PubMed Central

Mumcuoglu, Tarkan; Wollstein, Gadi; Wojtkowski, Maciej; Kagemann, Larry; Ishikawa, Hiroshi; Gabriele, Michelle L.; Srinivasan, Vivek; Fujimoto, James G.; Duker, Jay S.; Schuman, Joel S.

2009-01-01

Purpose To test if improving optical coherence tomography (OCT) resolution and scanning speed improves the visualization of glaucomatous structural changes as compared with conventional OCT. Design Prospective observational case series. Participants Healthy and glaucomatous subjects in various stages of disease. Methods Subjects were scanned at a single visit with commercially available OCT (StratusOCT) and high-speed ultrahigh-resolution (hsUHR) OCT. The prototype hsUHR OCT had an axial resolution of 3.4 μm (3 times higher than StratusOCT), with an A-scan rate of 24 000 hertz (60 times faster than StratusOCT). The fast scanning rate allowed the acquisition of novel scanning patterns such as raster scanning, which provided dense coverage of the retina and optic nerve head. Main Outcome Measures Discrimination of retinal tissue layers and detailed visualization of retinal structures. Results High-speed UHR OCT provided a marked improvement in tissue visualization as compared with StratusOCT. This allowed the identification of numerous retinal layers, including the ganglion cell layer, which is specifically prone to glaucomatous damage. Fast scanning and the enhanced A-scan registration properties of hsUHR OCT provided maps of the macula and optic nerve head with unprecedented detail, including en face OCT fundus images and retinal nerve fiber layer thickness maps. Conclusion High-speed UHR OCT improves visualization of the tissues relevant to the detection and management of glaucoma. PMID:17884170

Insights into the pathogenesis of dominant retinitis pigmentosa associated with a D477G mutation in RPE65.

PubMed

Choi, Elliot H; Suh, Susie; Sander, Christopher L; Hernandez, Christian J Ortiz; Bulman, Elizabeth R; Khadka, Nimesh; Dong, Zhiqian; Shi, Wuxian; Palczewski, Krzysztof; Kiser, Philip D

2018-04-12

RPE65 is the essential trans-cis isomerase of the classical retinoid (visual) cycle. Mutations in RPE65 give rise to severe retinal dystrophies, most of which are associated with loss of protein function and recessive inheritance. The only known exception is a c.1430G>A (D477G) mutation that gives rise to dominant retinitis pigmentosa with delayed onset and choroidal and macular involvement. Position 477 is distant from functionally critical regions of RPE65. Hence, the mechanism of D477G pathogenicity remains unclear, although protein misfolding and aggregation mechanisms have been suggested. We characterized a D477G knock-in mouse model which exhibited mild age-dependent changes in retinal structure and function. Immunoblot analysis of protein extracts from the eyes of the knock-in mice demonstrated the presence of ubiquitinated RPE65 and reduced RPE65 expression. We observed an accumulation of retinyl esters in the knock-in mice as well as a delay in rhodopsin regeneration kinetics and diminished electroretinography responses, indicative of RPE65 functional impairment induced by the D477G mutation in vivo. However, a cell line expressing D477G RPE65 revealed protein expression levels, cellular localization, and retinoid isomerase activity comparable to cells expressing wild-type protein. Structural analysis of an RPE65 chimera suggested that the D477G mutation does not perturb protein folding or tertiary structure. Instead, the mutation generates an aggregation-prone surface that could induce cellular toxicity through abnormal complex formation as suggested by crystal packing analysis. These results indicate that a toxic gain-of-function induced by the D477G RPE65 substitution may play a role in the pathogenesis of this form of dominant retinitis pigmentosa.

Retinal image restoration by means of blind deconvolution

NASA Astrophysics Data System (ADS)

Marrugo, Andrés G.; Šorel, Michal; Šroubek, Filip; Millán, María S.

2011-11-01

Retinal imaging plays a key role in the diagnosis and management of ophthalmologic disorders, such as diabetic retinopathy, glaucoma, and age-related macular degeneration. Because of the acquisition process, retinal images often suffer from blurring and uneven illumination. This problem may seriously affect disease diagnosis and progression assessment. Here we present a method for color retinal image restoration by means of multichannel blind deconvolution. The method is applied to a pair of retinal images acquired within a lapse of time, ranging from several minutes to months. It consists of a series of preprocessing steps to adjust the images so they comply with the considered degradation model, followed by the estimation of the point-spread function and, ultimately, image deconvolution. The preprocessing is mainly composed of image registration, uneven illumination compensation, and segmentation of areas with structural changes. In addition, we have developed a procedure for the detection and visualization of structural changes. This enables the identification of subtle developments in the retina not caused by variation in illumination or blur. The method was tested on synthetic and real images. Encouraging experimental results show that the method is capable of significant restoration of degraded retinal images.

Contribution to the theory of photopic vision: Retinal phenomena

NASA Technical Reports Server (NTRS)

Calvet, H.

1979-01-01

Principles of thermodynamics are applied to the study of the ultramicroscopic anatomy of the inner eye. Concepts introduced and discussed include: the retina as a three-dimensional sensor, light signals as coherent beams in relation to the dimensions of retinal pigments, pigment effects topographed by the conjugated antennas effect, visualizing lights, the autotropic function of hemoglobin and some cytochromes, and reversible structural arrangements during photopic adaptation. A paleoecological diagram is presented which traces the evolution of scotopic vision (primitive system) to photopic vision (secondary system) through the emergence of structures sensitive to the intensity, temperature, and wavelengths of the visible range.

Gene therapy for inherited retinal degenerations: initial successes and future challenges

NASA Astrophysics Data System (ADS)

Gupta, Priya R.; Huckfeldt, Rachel M.

2017-10-01

Inherited retinal degenerations are a clinically and genetically heterogeneous group of conditions that have historically shared an untreatable course. In recent years, however, a wide range of therapeutic strategies have demonstrated efficacy in preclinical studies and entered clinical trials with a common goal of improving visual function for patients affected with these conditions. Gene therapy offers a particularly elegant and precise opportunity to target the causative genetic mutations underlying these monogenic diseases. The present review will provide an overview of gene therapy with particular emphasis on key clinical results to date and challenges for the future.

Rapid Retinal Release from a Cone Visual Pigment Following Photoactivation*

PubMed Central

Chen, Min-Hsuan; Kuemmel, Colleen; Birge, Robert R.; Knox, Barry E.

2012-01-01

As part of the visual cycle, the retinal chromophore in both rod and cone visual pigments undergoes reversible Schiff base hydrolysis and dissociation following photobleaching. We characterized light-activated retinal release from a short-wavelength sensitive cone pigment (VCOP) in 0.1% dodecyl maltoside using fluorescence spectroscopy. The half-time (t1/2) of retinal release from VCOP was 7.1 s, 250-fold faster than rhodopsin. VCOP exhibited pH-dependent release kinetics, with the t1/2 decreasing from 23 s to 4 s with pH 4.1 to 8, respectively. However, the Arrhenius activation energy (Ea) for VCOP derived from kinetic measurements between 4° and 20°C was 17.4 kcal/mol, similar to 18.5 kcal/mol for rhodopsin. There was a small kinetic isotope (D2O) effect in VCOP, but less than that observed in rhodopsin. Mutation of the primary Schiff base counterion (VCOPD108A) produced a pigment with an unprotonated chromophore (⌊max = 360 nm) and dramatically slowed (t1/2 ~ 6.8 min) light-dependent retinal release. Using homology modeling, a VCOP mutant with two substitutions (S85D/ D108A) was designed to move the counterion one alpha helical turn into the transmembrane region from the native position. This double mutant had a UV-visible absorption spectrum consistent with a protonated Schiff base (⌊max = 420 nm). Moreover, VCOPS85D/D108A mutant had retinal release kinetics (t1/2 = 7 s) and Ea (18 kcal/mol) similar to the native pigment exhibiting no pH-dependence. By contrast, the single mutant VCOPS85D had a ~3-fold decrease in retinal release rate compared to the native pigment. Photoactivated VCOPD108A had kinetics comparable to a rhodopsin counterion mutant, RhoE113Q, both requiring hydroxylamine to fully release retinal. These results demonstrate that the primary counterion of cone visual pigments is necessary for efficient Schiff base hydrolysis. We discuss how the large differences in retinal release rates between rod and cone visual pigments arise, not from inherent differences in the rate of Schiff base hydrolysis, but rather from differences in the non-covalent binding properties of the retinal chromophore to the protein. PMID:22217337

Mapping by VESGEN of Blood Vessels in the Retinas of ISS Crew Members and Bed Rest Subjects for Increased Understanding of VIIP

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, P. A.; Vizzeri, G.; Tabbi, G.; Zanello, S. B.; Ploutz-Snyder, R.

2014-01-01

Research by NASA has established that significant risks for visual impairment in association with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions. Impairments include decreased near visual acuity, posterior globe flattening, choroidal folds, optic disc edema, and cotton wool spots. Much remains to be learned about the etiology of VIIP before effective countermeasures can be developed. Contributions of retinal vascular remodeling to the etiology of VIIP have not yet been investigated, primarily due to the current lack of ophthalmic tools for precisely measuring progressive pathophysiological remodeling of the retinal microvasculature. Although ophthalmic science and clinical practice are now highly sophisticated at detecting indirect, secondary signs of vascular remodeling such as cotton wool spots that arise during the progression of retinal vascular diseases, methods for quantifying direct, primary vascular changes are not yet established. To help develop insightful analysis of retinal vascular remodeling for aerospace medicine, we will map and quantify by our innovative VESsel GENeration Analysis (VESGEN) software the remodeling status of retinal blood vessels in crew members before and after ISS missions, and in healthy human subjects before and after head-down tilt bed rest. For this proof-of-concept study, we hypothesize that pathophysiological remodeling of retinal blood vessels occurs in coordination with microgravity-induced fluid shifts prior to development of visual impairments. VESGEN analysis in previous research supported by the US National Institutes of Health identified surprising new opportunities to regenerate retinal vessels during early-stage progression of the visually impairing, potentially blinding disease, diabetic retinopathy.

ULTRAHIGH SPEED SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF RETINAL AND CHORIOCAPILLARIS ALTERATIONS IN DIABETIC PATIENTS WITH AND WITHOUT RETINOPATHY.

PubMed

Choi, WooJhon; Waheed, Nadia K; Moult, Eric M; Adhi, Mehreen; Lee, ByungKun; De Carlo, Talisa; Jayaraman, Vijaysekhar; Baumal, Caroline R; Duker, Jay S; Fujimoto, James G

2017-01-01

To investigate the utility of ultrahigh speed, swept source optical coherence tomography angiography in visualizing retinal microvascular and choriocapillaris (CC) changes in diabetic patients. The study was prospective and cross-sectional. A 1,050 nm wavelength, 400 kHz A-scan rate swept source optical coherence tomography prototype was used to perform volumetric optical coherence tomography angiography of the retinal and CC vasculatures in diabetic patients and normal subjects. Sixty-three eyes from 32 normal subjects, 9 eyes from 7 patients with proliferative diabetic retinopathy, 29 eyes from 16 patients with nonproliferative diabetic retinopathy, and 51 eyes from 28 diabetic patients without retinopathy were imaged. Retinal and CC microvascular abnormalities were observed in all stages of diabetic retinopathy. In nonproliferative diabetic retinopathy and proliferative diabetic retinopathy, optical coherence tomography angiography visualized a variety of vascular abnormalities, including clustered capillaries, dilated capillary segments, tortuous capillaries, regions of capillary dropout, reduced capillary density, abnormal capillary loops, and foveal avascular zone enlargement. In proliferative diabetic retinopathy, retinal neovascularization above the inner limiting membrane was visualized. Regions of CC flow impairment in patients with proliferative diabetic retinopathy and nonproliferative diabetic retinopathy were also observed. In 18 of the 51 of eyes from diabetic patients without retinopathy, retinal mircrovascular abnormalities were observed and CC flow impairment was found in 24 of the 51 diabetic eyes without retinopathy. The ability of optical coherence tomography angiography to visualize retinal and CC microvascular abnormalities suggests it may be a useful tool for understanding pathogenesis, evaluating treatment response, and earlier detection of vascular abnormalities in patients with diabetes.

Rapid Onset of Retinal Toxicity From High-Dose Hydroxychloroquine Given for Cancer Therapy.

PubMed

Leung, Loh-Shan B; Neal, Joel W; Wakelee, Heather A; Sequist, Lecia V; Marmor, Michael F

2015-10-01

To report rapid onset of retinal toxicity in a series of patients followed on high-dose (1000 mg daily) hydroxychloroquine during an oncologic clinical trial studying hydroxychloroquine with erlotinib for non-small cell lung cancer. Retrospective observational case series. Ophthalmic surveillance was performed on patients in a multicenter clinical trial testing high-dose (1000 mg daily) hydroxychloroquine for advanced non-small cell lung cancer. The US Food & Drug Administration-recommended screening protocol included only visual acuity testing, dilated fundus examination, Amsler grid testing, and color vision testing. In patients seen at Stanford, additional sensitive screening procedures were added at the discretion of the retinal physician: high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, Humphrey visual field (HVF) testing, and multifocal electroretinography (mfERG). Out of the 7 patients having exposure of at least 6 months, 2 developed retinal toxicity (at 11 and 17 months of exposure). Damage was identified by OCT imaging, mfERG testing, and, in 1 case, visual field testing. Fundus autofluorescence imaging remained normal. Neither patient had symptomatic visual acuity loss. These cases show that high doses of hydroxychloroquine can initiate the development of retinal toxicity within 1-2 years. Although synergy with erlotinib is theoretically possible, there are no prior reports of erlotinib-associated retinal toxicity despite over a decade of use in oncology. These results also suggest that sensitive retinal screening tests should be added to ongoing and future clinical trials involving high-dose hydroxychloroquine to improve safety monitoring and preservation of vision. Published by Elsevier Inc.

Study of Retinal Nerve Fibre Layer Thickness and Visual Contrast Sensitivity in HIV Positive Individuals.

PubMed

Paul, Rudrajit; Ghosh, Asim K; Nag, Adwaita; Biswas, Shyamapada; Naiya, Britisundar; Mondal, Jayati

2017-06-01

Measurement of Retinal Nerve Fibre Layer Thickness (RNFLT) by Optical Coherence Tomography (OCT) is a sensitive, non invasive and cheap method of detecting early retinal changes in a variety of diseases. In HIV infection, RNFLT is altered and this may have effect on other visual functions like Contrast Sensitivity (CS) and visual acuity. Such ocular pathology can affect the daily life and profession (especially driving) of HIV infected individuals. However, studies on this topic in HIV infected population are rare from India. To study RNFLT, CS and their correlation in a sample of HIV positive Indian population. The present cross-sectional study was done in a tertiary care medical college hospital of Eastern India between May 2016 and September 2016. We did this study on HIV positive subjects with no clinically apparent ocular infection or other pathology. In this study, we have measured the RNFLT using the HRA-OCT Spectralis machine. The CS was tested using a smartphone version of the Pellie-Robson chart. CD4 count, visual acuity and colour vision were also tested. The data was analysed using SPSS version 20.0 for any correlation between these parameters. Pearson coefficient was used for continuous data and Spearman rank correlation was used for categorical data. A p-value <0.05 was considered significant. We had 17 patients, that is 34 eyes. RNFLT loss was found in 21% of the eyes and borderline thinning was found in a further 26%. Predominantly, the temporal quadrant was involved. The mean of log CS was 1.33±0.38. Taking 1.5 as the cut-off value for normalcy, 47% of the eyes tested showed decreased CS. Log CS showed significant correlation with RNFLT of the temporal quadrant only (r=0.37; 95% C.I. 0.041 to 0.631; p=0.02). Temporal RNFLT also showed statistical correlation with the CD4 count. The low CS was also significantly correlated with low visual acuity (r=0.5). In HIV infected persons, subtle ocular changes may occur and this may affect visual functions quite early. Hence, a comprehensive eye check-up should include parameters like CS and OCT.

An optimized content-aware image retargeting method: toward expanding the perceived visual field of the high-density retinal prosthesis recipients

NASA Astrophysics Data System (ADS)

Li, Heng; Zeng, Yajie; Lu, Zhuofan; Cao, Xiaofei; Su, Xiaofan; Sui, Xiaohong; Wang, Jing; Chai, Xinyu

2018-04-01

Objective. Retinal prosthesis devices have shown great value in restoring some sight for individuals with profoundly impaired vision, but the visual acuity and visual field provided by prostheses greatly limit recipients’ visual experience. In this paper, we employ computer vision approaches to seek to expand the perceptible visual field in patients implanted potentially with a high-density retinal prosthesis while maintaining visual acuity as much as possible. Approach. We propose an optimized content-aware image retargeting method, by introducing salient object detection based on color and intensity-difference contrast, aiming to remap important information of a scene into a small visual field and preserve their original scale as much as possible. It may improve prosthetic recipients’ perceived visual field and aid in performing some visual tasks (e.g. object detection and object recognition). To verify our method, psychophysical experiments, detecting object number and recognizing objects, are conducted under simulated prosthetic vision. As control, we use three other image retargeting techniques, including Cropping, Scaling, and seam-assisted shrinkability. Main results. Results show that our method outperforms in preserving more key features and has significantly higher recognition accuracy in comparison with other three image retargeting methods under the condition of small visual field and low-resolution. Significance. The proposed method is beneficial to expand the perceived visual field of prosthesis recipients and improve their object detection and recognition performance. It suggests that our method may provide an effective option for image processing module in future high-density retinal implants.

Massive Bilateral Serous Retinal Detachment in a Case of Hypertensive Chorioretinopathy

PubMed Central

Villalba-Pinto, Luis; Hernández-Ortega, M. Ángeles; de los Mozos, F. Javier Lavid; Pascual-Camps, Isabel; Dolz-Marco, Rosa; Arevalo, J. Fernando; Gallego-Pinazo, Roberto

2014-01-01

Introduction Systemic high blood pressure is related to a variety of retinal manifestations. We present an atypical case of hypertensive chorioretinopathy with massive bilateral serous retinal detachment. Case Report A 26-year-old male with a genitourinary malformation and secondary grade IV chronic kidney failure as well as high blood pressure complained of acute vision loss. Dilated fundus examination evidenced a bilateral serous retinal detachment with macular involvement. The patient was unresponsive to oral antihypertensive therapy and dialysis treatment. The serous retinal detachment progressively decreased after the restoration of dialysis and antihypertensive therapy. The final visual acuity was 0.50 in both eyes. Discussion In cases of serous macular detachment, it is mandatory to rule out different systemic and ocular diseases. The presence of uncontrolled high blood pressure may produce aggressive bilateral retinal changes, thus hypertension must be under early and strict control in order to improve the visual outcomes. PMID:25120474

[Spinocerebellar ataxia type 2 associated to pigmentary retinitis].

PubMed

Jiménez-Caballero, Pedro Enrique; Serviá, Mónica

2010-07-01

Ocular disorders are useful in the characterisation of the different types of spinocerebellar ataxias (SCA); pigmentary retinitis is an alteration that is specifically associated to SCA type 7 and is characterised by night blindness, sensitivity to glare and progressive narrowing of the visual field. A 34-year-old woman with clinical symptoms of progressive ataxia and visual impairment secondary to pigmentary retinitis. The patient had a personal history with an autosomal dominant pattern of a similar disorder in her father and paternal grandmother. In the genetic study she presented a triplet expansion in the SCA type 2 gene. CONCLUSIONS; Although pigmentary retinitis belongs to the SCA type 7 phenotype, our patient presented this retinal disorder, as in other cases of SCA type 2. A genetic study for SCA type 2 must therefore be conducted in patients with a degenerative ataxic clinical picture and who present evidence of pigmentary retinitis.

Application of stem cell-derived retinal pigmented epithelium in retinal degenerative diseases: present and future.

PubMed

Luo, Mingyue; Chen, Youxin

2018-01-01

As a constituent of blood-retinal barrier and retinal outer segment (ROS) scavenger, retinal pigmented epithelium (RPE) is fundamental to normal function of retina. Malfunctioning of RPE contributes to the onset and advance of retinal degenerative diseases. Up to date, RPE replacement therapy is the only possible method to completely reverse retinal degeneration. Transplantation of human RPE stem cell-derived RPE (hRPESC-RPE) has shown some good results in animal models. With promising results in terms of safety and visual improvement, human embryonic stem cell-derived RPE (hESC-RPE) can be expected in clinical settings in the near future. Despite twists and turns, induced pluripotent stem cell-derived RPE (iPSC-RPE) is now being intensely investigated to overcome genetic and epigenetic instability. By far, only one patient has received iPSC-RPE transplant, which is a hallmark of iPSC technology development. During follow-up, no major complications such as immunogenicity or tumorigenesis have been observed. Future trials should keep focusing on the safety of stem cell-derived RPE (SC-RPE) especially in long period, and better understanding of the nature of stem cell and the molecular events in the process to generate SC-RPE is necessary to the prosperity of SC-RPE clinical application.

Filling in the retinal image

NASA Technical Reports Server (NTRS)

Larimer, James; Piantanida, Thomas

1990-01-01

The optics of the eye form an image on a surface at the back of the eyeball called the retina. The retina contains the photoreceptors that sample the image and convert it into a neural signal. The spacing of the photoreceptors in the retina is not uniform and varies with retinal locus. The central retinal field, called the macula, is densely packed with photoreceptors. The packing density falls off rapidly as a function of retinal eccentricity with respect to the macular region and there are regions in which there are no photoreceptors at all. The retinal regions without photoreceptors are called blind spots or scotomas. The neural transformations which convert retinal image signals into percepts fills in the gaps and regularizes the inhomogeneities of the retinal photoreceptor sampling mosaic. The filling-in mechamism plays an important role in understanding visual performance. The filling-in mechanism is not well understood. A systematic collaborative research program at the Ames Research Center and SRI in Menlo Park, California, was designed to explore this mechanism. It was shown that the perceived fields which are in fact different from the image on the retina due to filling-in, control some aspects of performance and not others. Researchers have linked these mechanisms to putative mechanisms of color coding and color constancy.

Dimerization deficiency of enigmatic retinitis pigmentosa-linked rhodopsin mutants

PubMed Central

Ploier, Birgit; Caro, Lydia N.; Morizumi, Takefumi; Pandey, Kalpana; Pearring, Jillian N.; Goren, Michael A.; Finnemann, Silvia C.; Graumann, Johannes; Arshavsky, Vadim Y.; Dittman, Jeremy S.; Ernst, Oliver P.; Menon, Anant K.

2016-01-01

Retinitis pigmentosa (RP) is a blinding disease often associated with mutations in rhodopsin, a light-sensing G protein-coupled receptor and phospholipid scramblase. Most RP-associated mutations affect rhodopsin's activity or transport to disc membranes. Intriguingly, some mutations produce apparently normal rhodopsins that nevertheless cause disease. Here we show that three such enigmatic mutations—F45L, V209M and F220C—yield fully functional visual pigments that bind the 11-cis retinal chromophore, activate the G protein transducin, traffic to the light-sensitive photoreceptor compartment and scramble phospholipids. However, tests of scramblase activity show that unlike wild-type rhodopsin that functionally reconstitutes into liposomes as dimers or multimers, F45L, V209M and F220C rhodopsins behave as monomers. This result was confirmed in pull-down experiments. Our data suggest that the photoreceptor pathology associated with expression of these enigmatic RP-associated pigments arises from their unexpected inability to dimerize via transmembrane helices 1 and 5. PMID:27694816

Safety and Efficacy of Gene Transfer for Leber’s Congenital Amaurosis

PubMed Central

Maguire, Albert M.; Simonelli, Francesca; Pierce, Eric A.; Pugh, Edward N.; Mingozzi, Federico; Bennicelli, Jeannette; Banfi, Sandro; Marshall, Kathleen A.; Testa, Francesco; Surace, Enrico M.; Rossi, Settimio; Lyubarsky, Arkady; Arruda, Valder R.; Konkle, Barbara; Stone, Edwin; Sun, Junwei; Jacobs, Jonathan; Dell’Osso, Lou; Hertle, Richard; Ma, Jian-xing; Redmond, T. Michael; Zhu, Xiaosong; Hauck, Bernd; Zelenaia, Olga; Shindler, Kenneth S.; Maguire, Maureen G.; Wright, J. Fraser; Volpe, Nicholas J.; McDonnell, Jennifer Wellman; Auricchio, Alberto; High, Katherine A.; Bennett, Jean

2010-01-01

SUMMARY Leber’s congenital amaurosis (LCA) is a group of inherited blinding diseases with onset during childhood. One form of the disease, LCA2, is caused by mutations in the retinal pigment epithelium–specific 65-kDa protein gene (RPE65). We investigated the safety of subretinal delivery of a recombinant adeno-associated virus (AAV) carrying RPE65 complementary DNA (cDNA) (ClinicalTrials.gov number, NCT00516477). Three patients with LCA2 had an acceptable local and systemic adverse-event profile after delivery of AAV2.hRPE65v2. Each patient had a modest improvement in measures of retinal function on subjective tests of visual acuity. In one patient, an asymptomatic macular hole developed, and although the occurrence was considered to be an adverse event, the patient had some return of retinal function. Although the follow-up was very short and normal vision was not achieved, this study provides the basis for further gene therapy studies in patients with LCA. PMID:18441370

Dimerization deficiency of enigmatic retinitis pigmentosa-linked rhodopsin mutants

NASA Astrophysics Data System (ADS)

Ploier, Birgit; Caro, Lydia N.; Morizumi, Takefumi; Pandey, Kalpana; Pearring, Jillian N.; Goren, Michael A.; Finnemann, Silvia C.; Graumann, Johannes; Arshavsky, Vadim Y.; Dittman, Jeremy S.; Ernst, Oliver P.; Menon, Anant K.

2016-10-01

Retinitis pigmentosa (RP) is a blinding disease often associated with mutations in rhodopsin, a light-sensing G protein-coupled receptor and phospholipid scramblase. Most RP-associated mutations affect rhodopsin's activity or transport to disc membranes. Intriguingly, some mutations produce apparently normal rhodopsins that nevertheless cause disease. Here we show that three such enigmatic mutations--F45L, V209M and F220C--yield fully functional visual pigments that bind the 11-cis retinal chromophore, activate the G protein transducin, traffic to the light-sensitive photoreceptor compartment and scramble phospholipids. However, tests of scramblase activity show that unlike wild-type rhodopsin that functionally reconstitutes into liposomes as dimers or multimers, F45L, V209M and F220C rhodopsins behave as monomers. This result was confirmed in pull-down experiments. Our data suggest that the photoreceptor pathology associated with expression of these enigmatic RP-associated pigments arises from their unexpected inability to dimerize via transmembrane helices 1 and 5.

Monte Carlo investigation on quantifying the retinal pigment epithelium melanin concentration by photoacoustic ophthalmoscopy.

PubMed

Shu, Xiao; Liu, Wenzhong; Zhang, Hao F

2015-10-01

The retinal pigment epithelium (RPE) melanin plays an important role in maintaining normal visual functions. A decrease in the RPE melanin concentration with aging is believed to be associated with several blinding diseases, including age-related macular degeneration. Quantifying the RPE melanin noninvasively is therefore important in evaluating the retinal health and aging conditions. Photoacoustic ophthalmoscopy (PAOM), as an optical absorption-based imaging technology, can potentially be applied to measure variations in the RPE melanin if the relationship between the detected photoacoustic (PA) signal amplitudes and the RPE melanin concentrations can be established. In this work, we tested the feasibility of using PA signals from retinal blood vessels as references to measure RPE melanin variation using Monte Carlo (MC) simulation. The influences from PAOM axial resolution, the depth and diameter of the retinal blood vessel, and the RPE thickness were examined. We proposed a calibration scheme by relating detected PA signals to the RPE melanin concentrations, and we found that the scheme is robust to these tested parameters. This study suggests that PAOM has the capability of quantitatively measuring the RPE melanin in vivo.

Monte Carlo investigation on quantifying the retinal pigment epithelium melanin concentration by photoacoustic ophthalmoscopy

NASA Astrophysics Data System (ADS)

Shu, Xiao; Liu, Wenzhong; Zhang, Hao F.

2015-10-01

The retinal pigment epithelium (RPE) melanin plays an important role in maintaining normal visual functions. A decrease in the RPE melanin concentration with aging is believed to be associated with several blinding diseases, including age-related macular degeneration. Quantifying the RPE melanin noninvasively is therefore important in evaluating the retinal health and aging conditions. Photoacoustic ophthalmoscopy (PAOM), as an optical absorption-based imaging technology, can potentially be applied to measure variations in the RPE melanin if the relationship between the detected photoacoustic (PA) signal amplitudes and the RPE melanin concentrations can be established. In this work, we tested the feasibility of using PA signals from retinal blood vessels as references to measure RPE melanin variation using Monte Carlo (MC) simulation. The influences from PAOM axial resolution, the depth and diameter of the retinal blood vessel, and the RPE thickness were examined. We proposed a calibration scheme by relating detected PA signals to the RPE melanin concentrations, and we found that the scheme is robust to these tested parameters. This study suggests that PAOM has the capability of quantitatively measuring the RPE melanin in vivo.

Psychophysical and perceptual performance in a simulated-scotoma model of human eye injury

NASA Astrophysics Data System (ADS)

Brandeis, R.; Egoz, I.; Peri, D.; Sapiens, N.; Turetz, J.

2008-02-01

Macular scotomas, affecting visual functioning, characterize many eye and neurological diseases like AMD, diabetes mellitus, multiple sclerosis, and macular hole. In this work, foveal visual field defects were modeled, and their effects were evaluated on spatial contrast sensitivity and a task of stimulus detection and aiming. The modeled occluding scotomas, of different size, were superimposed on the stimuli presented on the computer display, and were stabilized on the retina using a mono Purkinje Eye-Tracker. Spatial contrast sensitivity was evaluated using square-wave grating stimuli, whose contrast thresholds were measured using the method of constant stimuli with "catch trials". The detection task consisted of a triple conjunctive visual search display of: size (in visual angle), contrast and background (simple, low-level features vs. complex, high-level features). Search/aiming accuracy as well as R.T. measures used for performance evaluation. Artificially generated scotomas suppressed spatial contrast sensitivity in a size dependent manner, similar to previous studies. Deprivation effect was dependent on spatial frequency, consistent with retinal inhomogeneity models. Stimulus detection time was slowed in complex background search situation more than in simple background. Detection speed was dependent on scotoma size and size of stimulus. In contrast, visually guided aiming was more sensitive to scotoma effect in simple background search situation than in complex background. Both stimulus aiming R.T. and accuracy (precision targeting) were impaired, as a function of scotoma size and size of stimulus. The data can be explained by models distinguishing between saliency-based, parallel and serial search processes, guiding visual attention, which are supported by underlying retinal as well as neural mechanisms.

Effect of EPI-743 on the clinical course of the mitochondrial disease Leber hereditary optic neuropathy.

PubMed

Sadun, Alfredo A; Chicani, Carlos Filipe; Ross-Cisneros, Fred N; Barboni, Piero; Thoolen, Martin; Shrader, William D; Kubis, Kenneth; Carelli, Valerio; Miller, Guy

2012-03-01

To evaluate the safety and efficacy of a new therapeutic agent, EPI-743, in Leber hereditary optic neuropathy (LHON) using standard clinical, anatomic, and functional visual outcome measures. Open-label clinical trial. University medical center. Patients  Five patients with genetically confirmed LHON with acute loss of vision were consecutively enrolled and treated with the experimental therapeutic agent EPI-743 within 90 days of conversion. Intervention  During the course of the study, 5 consecutive patients received EPI-743, by mouth, 3 times daily (100-400 mg per dose). Treatment effect was assessed by serial measurements of anatomic and functional visual indices over 6 to 18 months, including Snellen visual acuity, retinal nerve fiber layer thickness measured by optical coherence tomography, Humphrey visual fields (mean decibels and area with 1-log unit depression), and color vision. Treatment effect in this clinical proof of principle study was assessed by comparison of the prospective open-label treatment group with historical controls. Of 5 subjects treated with EPI-743, 4 demonstrated arrest of disease progression and reversal of visual loss. Two patients exhibited a total recovery of visual acuity. No drug-related adverse events were recorded. In a small open-label trial, EPI-743 arrested disease progression and reversed vision loss in all but 1 of the 5 consecutively treated patients with LHON. Given the known natural history of acute and rapid progression of LHON resulting in chronic and persistent bilateral blindness, these data suggest that the previously described irreversible priming to retinal ganglion cell loss may be reversed.

Ultra-wide-field autofluorescence imaging in non-traumatic rhegmatogenous retinal detachment

PubMed Central

Witmer, M T; Cho, M; Favarone, G; Paul Chan, R V; D'Amico, D J; Kiss, S

2012-01-01

Purpose Rhegmatogenous retinal detachment (RRD) affects the function of the retina before and after surgical repair. We investigated ultra-wide-field autofluorescence (UAF) abnormalities in patients with acute RRD to improve our understanding of the functional changes in the retina before and after surgery. Methods In this retrospective study, we present the UAF imaging findings of 16 patients with acute, non-traumatic RRD. Imaging was obtained with the Optos 200 Tx (Optos) in 14 eyes preoperatively and in 12 eyes postoperatively. Twelve eyes had RRDs that involved the macula (group A), whereas four eyes had macula-sparing RRDs (group B). Results All patients (100%) with bullous retinal detachments demonstrated hypofluorescence over the area of retinal detachment. A hyperfluorescent leading edge (HLE) to the retinal detachment was observed preoperatively in 100% of eyes in group A and 75% of eyes in group B. Preoperative UAF through the fovea of group A eyes was normal (30%), hypofluorescent (50%) or hyperfluorescent (20%). In all patients with a HLE preoperatively, the HLE resolved by the 1-month postoperative visit. A residual line of demarcation remained in 8 of the 12 eyes (67%). In group A eyes, postoperative granular autofluorescent changes were present in four of the nine (44%) eyes, and were associated with worse preoperative (P=0.04) and postoperative (P=0.09) visual acuity. Conclusion UAF imaging reveals abnormalities in RRDs that allow excellent demarcation of the extent of the retinal detachment and assist in preoperative characterization of the detachment and postoperative counselling. PMID:22722489

Profound re-organization of cell surface proteome in equine retinal pigment epithelial cells in response to in vitro culturing.

PubMed

Szober, Christoph M; Hauck, Stefanie M; Euler, Kerstin N; Fröhlich, Kristina J H; Alge-Priglinger, Claudia; Ueffing, Marius; Deeg, Cornelia A

2012-10-31

The purpose of this study was to characterize the cell surface proteome of native compared to cultured equine retinal pigment epithelium (RPE) cells. The RPE plays an essential role in visual function and represents the outer blood-retinal barrier. We are investigating immunopathomechanisms of equine recurrent uveitis, an autoimmune inflammatory disease in horses leading to breakdown of the outer blood-retinal barrier and influx of autoreactive T-cells into affected horses' vitrei. Cell surface proteins of native and cultured RPE cells from eye-healthy horses were captured by biotinylation, analyzed by high resolution mass spectrometry coupled to liquid chromatography (LC MS/MS), and the most interesting candidates were validated by PCR, immunoblotting and immunocytochemistry. A total of 112 proteins were identified, of which 84% were cell surface membrane proteins. Twenty-three of these proteins were concurrently expressed by both cell states, 28 proteins exclusively by native RPE cells. Among the latter were two RPE markers with highly specialized RPE functions: cellular retinaldehyde-binding protein (CRALBP) and retinal pigment epithelium-specific protein 65kDa (RPE65). Furthermore, 61 proteins were only expressed by cultured RPE cells and absent in native cells. As we believe that initiating events, leading to the breakdown of the outer blood-retinal barrier, take place at the cell surface of RPE cells as a particularly exposed barrier structure, this differential characterization of cell surface proteomes of native and cultured equine RPE cells is a prerequisite for future studies.

Ablation of the Proapoptotic Genes Chop or Ask1 Does Not Prevent or Delay Loss of Visual Function in a P23H Transgenic Mouse Model of Retinitis Pigmentosa

PubMed Central

Adekeye, Adeseye; Haeri, Mohammad; Solessio, Eduardo; Knox, Barry E.

2014-01-01

The P23H mutation in rhodopsin (RhoP23H) is a prevalent cause of autosomal dominant retinitis pigmentosa. We examined the role of the ER stress proteins, Chop and Ask1, in regulating the death of rod photoreceptors in a mouse line harboring the RhoP23H rhodopsin transgene (GHL+). We used knockout mice models to determine whether Chop and Ask1 regulate rod survival or retinal degeneration. Electrophysiological recordings showed similar retinal responses and sensitivities for GHL+, GHL+/Chop−/− and GHL+/Ask1−/− animals between 4–28 weeks, by which time all three mouse lines exhibited severe loss of retinal function. Histologically, ablation of Chop and Ask1 did not rescue photoreceptor loss in young animals. However, in older mice, a regional protective effect was observed in the central retina of GHL+/Chop−/− and GHL+/Ask1−/−, a region that was severely degenerated in GHL+ mice. Our results show that in the presence of the RhoP23H transgene, the rate of decline in retinal sensitivity is similar in Chop or Ask1 ablated and wild-type retinas, suggesting that these proteins do not play a major role during the acute phase of photoreceptor loss in GHL+ mice. Instead they may be involved in regulating secondary pathological responses such as inflammation that are upregulated during later stages of disease progression. PMID:24523853

Visual System Neural Responses to Laser Exposure from Local Q-Switched Pulses and Extended Source CW Speckle Patterns.

DTIC Science & Technology

1985-09-30

layers of the retina as seen in retinitis pigmentosa (Wolbarsht & Landers, 1980; Stefansson et al, 1981 a). Those are all long-term effects with a delay...block numoer) FIELD GROUP SUB-GROUP retinal damage center-surround 20 05 laser injury cat retina 20 06 visual perception N02 anesthesia 19. ABSTRACT...Continue on reverse if necessary and identify by block number) The reports of retinal damage from exposure to short pulse laser energy without any

Reduced-illuminance autofluorescence imaging in ABCA4-associated retinal degenerations

NASA Astrophysics Data System (ADS)

Cideciyan, Artur V.; Swider, Malgorzata; Aleman, Tomas S.; Roman, Marisa I.; Sumaroka, Alexander; Schwartz, Sharon B.; Stone, Edwin M.; Jacobson, Samuel G.

2007-05-01

The health of the retinal pigment epithelium (RPE) can be estimated with autofluorescence (AF) imaging of lipofuscin, which accumulates as a byproduct of retinal exposure to light. Lipofuscin may be toxic to the RPE, and its toxicity may be enhanced by short-wavelength (SW) illumination. The high-intensity and SW excitation light used in conventional AF imaging could, at least in principle, increase the rate of lipofuscin accumulation and/or increase its toxicity. We considered two reduced-illuminance AF imaging (RAFI) methods as alternatives to conventional AF imaging. RAFI methods use either near-infrared (NIR) light or reduced-radiance SW illumination for excitation of fluorophores. We quantified the distribution of RAFI signals in relation to retinal structure and function in patients with the prototypical lipofuscin accumulation disease caused by mutations in ABCA4. There was evidence for two subclinical stages of macular ABCA4 disease involving hyperautofluorescence of both SW- and NIR-RAFI with and without associated loss of visual function. Use of RAFI methods and microperimetry in future clinical trials involving lipofuscinopathies should allow quantification of subclinical disease expression and progression without subjecting the diseased retina/RPE to undue light exposure.

In vivo biocompatibility of a new cyanine dye for ILM peeling.

PubMed

Thaler, S; Haritoglou, C; Schuettauf, F; Choragiewicz, T; May, C A; Gekeler, F; Fischer, M D; Langhals, H; Schatz, A

2015-03-01

To investigate the biocompatibility of the new cyanine dye: 3,3'-Di-(4-sulfobutyl)-1,1,1',1'-tetramethyl-di-1H-benz[e]indocarbocyanine (DSS) as a vital dye for intraocular application in an in vivo rat model and to evaluate the effects of this dye on retinal structure and function. DSS at a concentration of 0.5% was applied via intravitreal injections to adult Brown Norway rats with BSS serving as a control. Retinal toxicity was assessed 7 days later by means of retinal ganglion cell (RGC) counts, light microscopy, optical coherence tomography (OCT), and electroretinography (ERG). No significant decrease in RGC numbers was observed. No structural changes of the central retina were observed either in vivo (OCT) or under light microscopy. ERGs detected a temporary reduction of retinal function 7 days after injection; this was no longer evident 14 days after injection. DSS showed good biocompatibility in a well-established experimental in vivo setting and may be usable for intraocular surgery as an alternative to other cyanine dyes. In contrast to indocyanine green, it additionally offers fluorescence in the visual spectrum. Further studies with other animal models are needed before translation into clinical application.