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Sample records for myopic choroidal neovascular

  1. Multimodal imaging and diagnosis of myopic choroidal neovascularization in Caucasians

    PubMed Central

    Milani, Paolo; Massacesi, Amedeo; Moschini, Stefania; Setaccioli, Marco; Bulone, Ennio; Tremolada, Gemma; Ciaccia, Stefano; Mantovani, Elena; Morale, Daniela; Bergamini, Fulvio

    2016-01-01

    Purpose To investigate myopic choroidal neovascularization (mCNV) by fluorescein angiography (FA), spectral-domain optical coherence tomography (SD-OCT), near-infrared (NIR) reflectance, and autofluorescence (AF). Methods This retrospective study included 65 eyes of 62 Caucasian patients with a mean age of 66.72 years (95% confidence interval [CI] 63–70 years) and a mean refraction of −9.72 diopters (95% CI −8.74 to −10.70 diopters). Results Most of the mCNV cases were foveal-juxtafoveal (60/65, 92.3%), with thickening of the corresponding retina (62/65, 95.3%) and leakage on FA (44/65, 67.6%). No retinal fluid was detectable in 32 (49.2%) eyes and there was no hemorrhage in 25 (38.4%) eyes. Papillary chorioretinal atrophy was evident in 58 (89.2%), a shadowing effect in 48 (73.8%), and an epiretinal membrane in 38 (58.4%) eyes. If an area of macular chorioretinal atrophy was present, mCNV frequently developed adjacent to it and was hyperfluorescent rather than with leakage (P⩽0.001). In eyes with edema or hemorrhage, hyper-reflective foci were more frequent (P⩽0.005). NIR and AF features were indeterminable in 19 (29.2%) and 27 (41.5%) eyes, respectively. The predominant feature was black or grayish on NIR (34/65, 52.3%) and patchy (hypo- and hyperfluorescence was observed) on AF (25/65, 38.4%). FA and SD-OCT correctly detected mCNV in 49 (75.3%) and 48 (73.8%) eyes, respectively, whereas NIR and AF exhibited limited diagnostic sensitivity. Doubtful diagnosis was associated with hyperfluorescent mCNV (P⩽0.001), absence of retinal fluid and epiretinal membrane (P⩽0.05), and presence of macular chorioretinal atrophy (P⩽0.01). Conclusion Tomographic, angiographic, AF, and NIR features of mCNV are described in this study. Combination of SD-OCT and FA is recommendable for diagnosis. PMID:27672306

  2. Evaluation of 10 AMD Associated Polymorphisms as a Cause of Choroidal Neovascularization in Highly Myopic Eyes

    PubMed Central

    Anter, Jaouad; Bezunartea, Jaione; Hernandez-Sanchez, Maria; García-García, Laura; Alonso, Elena; Ruiz-Moreno, Jose María; Araiz-Iribarren, Javier; Fernandez-Robredo, Patricia; García-Layana, Alfredo

    2016-01-01

    Choroidal neovascularization (CNV) commonly occurs in age related macular degeneration and pathological myopia patients. In this study we conducted a case-control prospective study including 431 participants. The aim of this study was to determine the potential association between 10 single nucleotide polymorphisms (SNPs) located in 4 different genetic regions (CFI, COL8A1, LIPC, and APOE), and choroidal neovascularization in age-related macular degeneration and the development of choroidal neovascularization in highly myopic eyes of a Caucasian population. Univariate and multivariate logistic regression analysis adjusted for age, sex and hypertension was performed for each allele, genotype and haplotype frequency analysis. We found that in the univariate analysis that both single-nucleotide polymorphisms in COL8A1 gene (rs13095226 and rs669676) together with age, sex and hypertension were significantly associated with myopic CNV development in Spanish patients (p<0.05). After correcting for multiple testing none of the polymorphisms studied remained significantly associated with myopic CNV (p>0.05); however, analysis of the axial length between genotypes of rs13095226 revealed an important influence of COL8A1 in the development of CNV in high myopia. Furthermore we conducted a meta-analysis of COL8A1, CFI and LIPC genes SNPs (rs669676, rs10033900 and rs10468017) and found that only rs669676 of these SNPs were associated with high myopia neovascularization. PMID:27643879

  3. Lack of polypoidal lesions in patients with myopic choroidal neovascularization as evaluated by indocyanine green angiography.

    PubMed

    Kang, Hae Min; Koh, Hyoung Jun

    2014-02-01

    To investigate the prevalence of polypoidal choroidal vasculopathy (PCV) in patients with myopic choroidal neovascularization (CNV) using indocyanine green angiography (ICGA). Retrospective cross-sectional study. A total of 297 eyes (255 patients) who presented with treatment-naive myopic CNV between January 2005 and December 2011 at Yonsei University Medical Center in Seoul, South Korea, were reviewed. Fluorescein angiography (FA) images obtained from the patients were analyzed to detect CNV presence and classify disease type. ICGA images were reviewed to detect polypoidal lesions. The main outcome measure was the prevalence of polypoidal lesions in patients with myopic CNV. All 297 eyes with myopic CNV were type 2 CNV, and mean age at diagnosis was 47.32 ± 14.69 years. The mean refractive error was -11.95 ± 5.88 diopters, and the mean axial length was 29.39 ± 2.02 mm in the affected eyes. Among the myopic CNV eyes, 141 eyes (118 patients) were older than 50 years of age (mean 60.48 ± 7.34 years). No eyes with myopic CNV showed polypoidal lesions on ICGA at initial presentation. After treatments for myopic CNV, 243 eyes (206 patients) completed at least 12 months of follow-up, and 86 eyes (35.4%) showed at least one recurrence of CNV during follow-up. The follow-up imaging studies, FA, and ICGA, showed no polypoidal lesions associated with recurred myopic CNV. ICGA analysis demonstrated no polypoidal component in myopic eyes with CNV. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Indocyanine Green Angiographic Features of Myopic Subfoveal Choroidal Neovascularization as a Prognostic Factor after Photodynamic Therapy

    PubMed Central

    Byeon, Suk Ho; Kwon, Oh Woong; Lee, Sung Chul; Kim, Sung Soo

    2006-01-01

    Purpose To determine the influence of clinical features and Indocyanine green (ICG) angiographic features on the visual outcome of patients with myopic sub-foveal choroidal neovascularization (CNV) who received photodynamic therapy (PDT). Methods Thirty-six consecutive patients (39 eyes) with myopic CNV who were followed up for more than one year after PDT were enrolled in this study. Clinical features included age, gender, refractive error, great linear dimension, and subretinal hemorrhage. ICG features included the lesion size, lacquer cracks, hypofluorescence surrounding the CNV (dark rim), peripapillary atrophy size, and visible prominent choroidal veins under the macula. Linear regression analysis was performed using the change in visual acuity (ΔlogMAR) as the dependent variable and the above factors as independent variables. Results At one-year follow-up after PDT, a younger age (p=0.002) and the presence of a dark rim (p=0.002) were significantly correlated with an improvement of visual acuity (decrement in logMAR) after PDT. Other factors had no significant influence on changes in visual acuity. Conclusions Younger patients and patients with a dark rim on ICG angiography had a higher chance of visual improvement after PDT in myopic CNV. PMID:16768186

  5. Long-term remission of myopic choroidal neovascular membrane after treatment with ranibizumab: a case report

    PubMed Central

    2009-01-01

    Introduction Myopia has become a big public health problem in certain parts of the world. Sight-threatening complications like choroidal neovascularisation membranes occur in up to 10% of pathological myopia, and natural history studies show a trend towards progressive visual loss. There are long-term financial and quality-of-life implications in this group of patients, and treatment strategies should aim for long-term preservation of vision. Case presentation A 56-year-old Caucasian woman presented with a best-corrected visual acuity of 6/6-1 in her right eye and 6/24 in her left. Fundal examination revealed pathological myopia in both eyes and an elevated lesion associated with pre-retinal haemorrhage in the left macula. Ocular coherence tomography and fundus fluorescein angiogram confirmed a subfoveal classic choroidal neovascularisation membrane. The patient decided to proceed with intravitreal ranibizumab (0.5 mg) therapy. One month after treatment, best-corrected visual acuity improved to 6/12 in her left eye, with complete resolution subretinal fluid on ocular coherence tomography. After three months, best-corrected visual acuity further improved to 6/9, which was maintained up to 16 months post-treatment. Conclusion We suggest intravitreal ranibizumab as an alternative treatment for long-term remission of myopic choroidal neovascular membrane. It also suggests that myopic choroidal neovascularisation membranes may require fewer treatments to achieve sustained remission. Furthermore, this could serve as a feasible long-term management option if used in conjunction with ocular coherence tomography. PMID:19946560

  6. Analysis of Scleral Feeder Vessel in Myopic Choroidal Neovascularization Using Optical Coherence Tomography Angiography

    PubMed Central

    Louzada, Ricardo Noguera; Ferrara, Daniela; Novais, Eduardo Amorim; Moult, Eric; Cole, Emily; Lane, Mark; Fujimoto, James; Duker, Jay S.; Baumal, Caroline R.

    2017-01-01

    To describe the appearance of a scleral-derived feeder vessel in a highly myopic eye with secondary choroidal neovascularization (CNV) as visualized on both en face high-speed swept-source (SS) optical coherence tomography angiography (OCTA) prototype, and a commercially available spectral-domain (SD) OCTA, with the corresponding en face and cross-sectional structural OCT images. In this case report, a 60-year-old white male presented with high myopia and secondary CNV in the right eye, previously treated with anti-vascular endothelial growth factor, and was imaged on both SD-OCT and SS-OCT. The neovascular complex could be visualized on both devices. Structural en face SS-OCT images demonstrated a large choroidalscleral feeder vessel that was not visualized with SD-OCT. The authors concluded that structural en face SS-OCT better visualizes scleral feeder vessel compared to SD-OCT due to the longer wavelength (~1,050 nm) with increased choroidal penetration and decreased sensitivity roll-off in the SS-OCT system. PMID:27759864

  7. Management of Myopic Choroidal Neovascularization: Focus on Anti-VEGF Therapy.

    PubMed

    Teo, Kelvin Yi Chong; Ng, Wei Yan; Lee, Shu Yen; Cheung, Chui Ming Gemmy

    2016-07-01

    Myopic choroidal neovascularization (mCNV) is the second most common form of CNV after age-related macular degeneration (AMD). It is a sight-threatening complication of pathologic myopia (PM) and often affects patients in their working years causing significant impact on quality of life. Previous therapies such as photodynamic therapy with verteporfin have shown limited success. Due to the similarities in pathogenesis of mCNV and AMD CNV, anti-vascular endothelial growth factor therapy (anti-VEGF), which has so far been the mainstay of treatment for AMD CNV, has been shown to be effective in the treatment of mCNV and has become the first-line treatment of choice. This article aims to examine briefly the epidemiology and pathophysiology of mCNV, as well as review the evidence for efficacy, safety, and clinical use of anti-VEGF treatment for mCNV.

  8. Forty-two-month outcome of intravitreal bevacizumab in myopic choroidal neovascularization.

    PubMed

    Traversi, Claudio; Nuti, Elisabetta; Marigliani, Davide; Cevenini, Gabriele; Balestrazzi, Angelo; Martone, Gianluca; Caporossi, Tomaso; Tosi, Gian Marco

    2015-04-01

    To evaluate the long-term efficacy of bevacizumab in the treatment of choroidal neovascularization (CNV) secondary to pathological myopia. In this retrospective single-center non-comparative study the medical records of 29 eyes from 29 patients with naïve CNV secondary to high myopia and at least 42 months of follow up were reviewed. All eyes received a loading dose of one intravitreal injection per month for two consecutive months and were retreated on an as-needed basis during the course of follow up. The main outcome measures were post-treatment ETDRS best-corrected visual acuity (BCVA) and visual stabilization over time. Stepwise linear regression analysis was performed to identify prognostic factors for visual acuity gain and final visual acuity outcome at 42 months. At 42 months of follow-up bevacizumab was associated with the maintenance of significant benefits in visual acuity compared to baseline. No adverse ocular or systemic effects from treatment were encountered. No statistically significant correlations were found between BCVA change and any of the quantitative variables. However, when final BCVA was taken as a dependent variable and CNV size and pre-treatment VA were included as predictors, a bivariate model was identified by stepwise regression which gave a 75 % of explained variance. Bevacizumab treatment was found to be efficacious in the treatment of myopic CNV, resulting in stable gains in visual acuity lasting at least 42 months, without any adverse ocular or general events. Myopic CNV size was identified as a significant prognostic factor.

  9. Long-term functional and morphologic retinal changes after ranibizumab and photodynamic therapy in myopic choroidal neovascularization.

    PubMed

    Parravano, Mariacristina; Ricci, Federico; Oddone, Francesco; Missiroli, Filippo; De Felici, Cecilia; Varano, Monica

    2014-10-01

    To assess and compare the long-term functional and anatomical outcomes in eyes with myopic choroidal neovascularization (CNV) treated with intravitreal injections of ranibizumab or with photodynamic therapy (PDT). Eighty-five eyes of 85 consecutive patients with myopic CNV and treated with either PDT (43/85) or ranibizumab 0.5 mg (42/85) and at least 24 months of follow-up were collected. Data from the best-corrected visual acuity, optical coherence tomography, and fluorescein angiography were compared between the groups. Differences in the regression pattern of myopic CNV and the rate of chorioretinal atrophy development were also compared between the groups. The effect of treatment over time on best-corrected visual acuity and the central retinal thickness was significantly greater in the ranibizumab group (P = 0.0012 and P < 0.0002, respectively), with eyes treated with ranibizumab showing a significant central retinal thickness decrease since the first visit and maintained until 24 months. The proportion of patients showing a complete closure of CNV was similar between the groups (93% [39 of 42 eyes in the ranibizumab group] vs. 88% [38 of 43 eyes in the PDT group], P = 0.48). Both treatments were associated with an increase of chorioretinal atrophy size, which was greater in the PDT-treated eyes (P = 0.016). Ranibizumab therapy showed a greater long-term efficacy compared with PDT in myopic CNV eyes, with a fewer proportion of eyes developing an increase of lesion and chorioretinal atrophy size.

  10. Treatment Satisfaction and Well-Being in Patients with Myopic Choroidal Neovascularization Treated with Ranibizumab in the REPAIR Study

    PubMed Central

    Amoaku, Winfried M.; Gale, Richard P.; Lotery, Andrew J.; Menon, Geeta; Sivaprasad, Sobha; Petrillo, Jennifer; Quinn, Jennifer

    2015-01-01

    The Ranibizumab for the Treatment of Choroidal Neovascularisation (CNV) Secondary to Pathological Myopia (PM): an Individualized Regimen (REPAIR) trial was a prospective study exploring the efficacy and safety of intravitreal ranibizumab 0.5 mg using an individualized treatment regimen over 12 months. The current study investigated the impact of treatment with ranibizumab as needed (pro re nata [PRN]) on individuals with myopic choroidal neovascularization (mCNV) in the REPAIR study, using patient-reported outcome measures (PROMs) for treatment satisfaction and well-being. This study included 65 adults with mCNV and a best-corrected visual acuity (BCVA) letter score of 24–78 in the study eye. Patients completed the Macular Disease Treatment Satisfaction Questionnaire (MacTSQ) at months 1, 6 and 12, and the 12-item Well-Being Questionnaire (W-BQ12) at baseline and months 1, 6 and 12. Subgroup analyses investigated the relationship between PROM scores and treatment in the better- or worse-seeing eye (BSE/WSE), number of injections received, baseline BCVA, BCVA improvement and age. Pearson correlations between change in BCVA, MacTSQ scores and W-BQ12 scores were calculated. The main outcome measures were treatment satisfaction measured with the MacTSQ (score 0–72) and well-being measured with the W-BQ12 (score 0–36). Treatment satisfaction significantly increased over the study period (p = 0.0001). Mean MacTSQ scores increased by 9.7 and 10.0 in patients treated in their WSE and BSE, respectively. Treatment satisfaction was highest in individuals receiving only one injection at month 1; however, by month 12, scores were similar across injection subgroups. Patients aged 68 years or older had the highest MacTSQ scores. Well-being scores also significantly increased over the study period (p = 0.03). Mean W-BQ12 scores increased by 1.7 in patients treated in their WSE and by 2.1 in patients treated in their BSE. Individuals aged 40 years or younger had the greatest

  11. Comparison of visual prognoses between natural course of simple hemorrhage and choroidal neovascularization treated with intravitreal bevacizumab in highly myopic eyes: a 1-year follow-up.

    PubMed

    Goto, So; Sayanagi, Kaori; Ikuno, Yasushi; Jo, Yukari; Gomi, Fumi; Nishida, Kohji

    2015-03-01

    To compare the long-term outcomes of simple hemorrhage (SH) without any treatments and myopic choroidal neovascularization (mCNV) treated with intravitreal bevacizumab in highly myopic eyes. Twenty eyes (17 patients) with SH and 28 eyes (27 patients) with mCNV were included. We retrospectively evaluated the refractive error, axial length, age, best-corrected visual acuity, and the integrity of photoreceptor inner segment/outer segment junction and compared the two groups. The mean patient age was 41.6 ± 11.2 years, the mean refractive error -12.7 ± 3.57 diopters, and the mean axial length was 29.64 ± 1.42 mm. Patients in the SH group were significantly (P < 0.001) younger than those in the mCNV group (34.8 vs. 46.5 years, respectively). There were no significant differences in other parameters between the groups. Compared with baseline, the best-corrected visual acuity improved significantly (P < 0.01) at 12 months in both groups. The change in vision at 12 months in the SH group was significantly (P < 0.05) better than that in the mCNV group, although there were no significant differences at 3 months or 6 months. The final integrity of photoreceptor inner segment/outer segment junction was significantly associated with the final best-corrected visual acuity (P < 0.05). Eyes with SH had a more favorable visual prognosis compared with eyes with mCNV treated with intravitreal bevacizumab. The differential diagnosis of these pathologies is important.

  12. Treatment of choroidal neovascularization in high myopia.

    PubMed

    Montero, Javier A; Ruiz-Moreno, Jose M

    2010-05-01

    High myopia affects approximately 2% of general population, and is a major cause of legal blindness in many developed countries. Choroidal neovascularization (CNV) is the most common vision-threatening complication of high myopia. Different therapeutic approaches have been attempted such as thermal laser photocoagulation, surgery and photodynamic therapy with verteporfin (PDT). The visual outcome of these therapies has been reported to be better than the natural history of the condition. However, the limited visual acuity improvement after PDT monotherapy and the appearance of subretinal fibrosis and chorioretinal atrophy prompted the association of other therapies. In the past few years a tremendous advance in the knowledge of the mechanisms underling CNV secondary to high myopia and age related macular degeneration has been achieved, leading to new therapeutic targets and novel drugs and combined therapies. These new therapeutic weapons have been designed to achieve a selective shut down of choroidal new vessels. Recent reviews have been published on the natural history and therapies for myopic CNV. Ohno-Matsui reported on the natural history of the condition as well as the outcome of laser photocoagulation, surgical extraction of CNV, foveal translocation and photodynamic therapy on myopic CNV in the short-term. Soubrane et al reviewed the new advances on surgery, laser photocoagulation and PDT, considering some of the potential effects of triamcinolone, pegaptanib and ranibizumab in CNV secondary to age related macular degeneration (AMD). Novack et al reported on the pharmacological therapy of CNV in AMD. The aim of this review is to summarize the recent advances in myopic CNV pathophysiology and the new therapeutic targets and drugs that are changing the clinical management of myopic CNV.

  13. [Intravitreal ranibizumab therapy for choroidal neovascularization secondary to pathological myopia].

    PubMed

    Lukács, Regina; Sándor, Gábor; Resch, Miklós; Szabó, Antal; Barcsay, György; Ecsedy, Mónika; Szepessy, Zsuzsanna; Nagy, Zoltán Zsolt; Papp, András

    2017-04-01

    Pathological myopia is one of the leading causes of vision loss worldwide, especially among young people of working age. Choroidal neovascularization is one of the most important cause of visual impairment in pathological myopia. To evaluate the efficacy of intravitreal ranibizumab for the treatment of myopic choroidal neovascularization. In this retrospective analysis 14 eyes of 14 patients (mean age: 61 ± 17 years) with myopic choroidal neovascularization were treated with intravitreal ranibizumab as needed. Best-corrected visual acuity, thickness of choroidal neovascularization lesion and the number of injections were assessed. The mean visual acuity changed from 55.8 ± 19.3 letters to 64.8 + 15.5 at 12 months (p = 0.0414), and 62.6 ± 16.3 during follow-up time (p = 0.2896). Mean follow-up time was 19.7 ± 23.9 months, average number of injections was 2.8 ± 2.1. Visual acuity declined in four patients despite the treatment. Intravitreal ranibizumab is an effective therapy in pathological myopia. Some patients experience deterioration of visual acuity despite of treatment. Orv. Hetil., 2017, 158(15), 579-586.

  14. Choroidal neovascularization in a child with traumatic choroidal rupture: clinical and ultrastructural findings.

    PubMed

    Abri, Adele; Binder, Susanne; Pavelka, Margit; Tittl, Michael; Neumüller, Josef

    2006-07-01

    Choroidal neovascularization in children is uncommon and mostly associated with inflammation, infectious diseases or trauma. The clinical and histological findings of a choroidal neovascular membrane that developed in a 9-year-old boy after traumatic choroidal rupture are reported.

  15. Perspectives of choroidal neovascularization therapy.

    PubMed

    Caputo, M; Zirpoli, H; Di Benedetto, R; De Nadai, K; Tecce, M F

    2011-02-01

    Vision loss secondary to Choroidal Neovascularization (CNV) is becoming a major disease condition in developed world. CNV is typically secondary to Age-related Macular Degeneration (AMD) and these conditions are major, and also substantially increasing, causes of blindness among aged people. Several therapeutic options are currently available to treat CNV with variable efficacy on disease progress. Among existing treatments there are laser photocoagulation, photodynamic therapies, local corticosteroids and, more recently, the use of anti-angiogenic factors. Although by these treatments very effective results are obtained and their further improvement is still possible, it is also reasonable and necessary to look for more successful and definitive alternatives. The research in this direction is already very active and it can be expected that applications of the more recent molecular technologies will bring important advances also for CNV. These will likely regard the use of gene therapy and of new target specific factors. Gene therapies methodologies are rapidly becoming closer to current clinical use and, since the eye is a particularly favourable organ for drug delivery, their ocular use is probably going to be among the first successful applications of these techniques. In addition to its specific technology, gene therapy requires the knowledge of specific genes to be modulated to adequately affect pathogenesis and progression of the disease in which has to be applied. This will also be true for the use of novel target specific drugs such as antibodies and other molecules able to affect cellular factors and pathways also related to disease development. For this reason, a major direction of future CNV therapies will be the identification of specific gene, gene products, metabolic pathways and metabolites related to the disease. This information, in addition to be suitable for gene and target specific therapies, will also allow the development of new procedures to

  16. Inflammatory choroidal neovascular membrane after healed tuberculous choroidal granuloma

    PubMed Central

    Lodhi, Sikander A. K.; Saifuddin, Khadija; Devulapally, Santhosh

    2017-01-01

    Objective: To present a case of choroidal granuloma masquerading as intraocular tumor that healed on anti-tuberculous treatment but led to the development of inflammatory choroidal neovascular membrane (CNVM). Method: A 42-year-old female patient with past history of hysterectomy presented with diminution of vision in the right eye. Fundus examination in the right eye showed a yellowish white choroidal mass with associated bullous retinal detachment superotemporal to fovea. Left eye fundus was normal. Fundus flourescein angiography showed early and late hyperflourescence with late pooling in serous detachments. Complete systemic evaluation did not yield a clue to diagnosis. Positron emission tomography scan (PET scan) showed enlarged lymph nodes in cervical, mediastinal and peritoneal regions. Lymph node biopsy showed caseating granulomas. Results: The granuloma subsided and a scar formed 5 months after starting anti-tuberculous treatment with improvement in vision. Six months later, the vision deteriorated again with the development of a choroidal neovascular membrane (CNVM) at the margin of the scar. The CNVM resolved and all the signs of activity subsided after giving intravitreal antivascular endothelial growth factor (anti-VEGF) injections. Conclusions: Making a diagnosis of tuberculous granuloma in a case of choroidal mass lesion is a challenge. PET scan helps in identifying metabolically active lymph nodes appropriate for biopsy. Healed scars of tuberculous choroid lesions should be followed closely to detect the development of CNVM. PMID:28293535

  17. Focal choroidal excavaction associated with idiopathic choroidal neovascularization.

    PubMed

    Sánchez-Vicente, J L; Rueda-Rueda, T; Martínez-Borrego, A C; Moruno-Rodríguez, A; Molina-Socola, F E; Contreras-Díaz, M; Medina-Tapia, A; Muñoz-Morales, A; López-Herrero, F

    2017-06-02

    The case is presented of a 45 year-old man with a focal choroidal excavation associated with choroidal neovascularisation not included in the area of excavation. Clinical features were analysed using retinography, fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography. The patient was treated with 3 intravitreal injections of bevacizumab, with a good response. Focal choroidal excavation can be associated with choroidal neovascularization not included in the area of excavation. Multimodal imaging provides a complete description of clinical features, before and after treatment. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. CHOROIDAL NEOVASCULARIZATION SECONDARY TO ALEXANDRITE LASER EXPOSURE.

    PubMed

    Wang, Rui; Wykoff, Charles C; Christie, Lynsey; Croft, Daniel E; Major, James C; Fish, Richard H; Brown, David M

    2016-01-01

    To report macular photic trauma after accidental occupational exposure to a 750-nm Alexandrite laser and management of secondary choroidal neovascularization. Institutional review board-approved retrospective case report. A 30-year-old woman presented with immediate vision loss in her left eye after direct inadvertent exposure to a single discharge from an occupational 750-nm Alexandrite laser used for laser hair removal. Baseline Snellen visual acuity was 20/40 in the involved left eye. One week after the initial exposure, the patient experienced subjective visual decline to 20/50, was treated with oral prednisone, and then developed a subretinal hemorrhage (SRH) in the setting of choroidal neovascularization 2 weeks later, or 3 weeks after initial trauma. The patient subsequently received 5 intravitreal ranibizumab injections over 25 weeks with resolution of the SRH. Final visual acuity was 20/50. The present case documents development and management of subretinal hemorrhage associated with choroidal neovascularization following macular photic trauma after accidental occupational to a 750-nm Alexandrite laser.

  19. CCR3 and choroidal neovascularization.

    PubMed

    Li, Yiwen; Huang, Deqiang; Xia, Xin; Wang, Zhengying; Luo, Lingyu; Wen, Rong

    2011-02-15

    Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly in industrialized countries. The "wet" AMD, characterized by the development of choroidal neovacularization (CNV), could result in rapid and severe loss of central vision. The critical role of vascular endothelial growth factor A (VEGF-A) in CNV development has been established and VEGF-A neutralization has become the standard care for wet AMD. Recently, CCR3 was reported to play an important role in CNV development and that CCR3 targeting was reported to be superior to VEGF-A targeting in CNV suppression. We investigated the role of CCR3 in CNV development using the Matrigel induced CNV and found that in both rats and mice, CNV was well-developed in the control eyes as well as in eyes treated with CCR3 antagonist SB328437 or CCR3 neutralizing antibodies. No statistically significant difference in CNV areas was found between the control and SB328437 or CCR3-ab treated eyes. Immunostaining showed no specific expression of CCR3 in or near CNV. In contrast, both VEGF-A neutralizing antibodies and rapamycin significantly suppressed CNV. These results indicate that CCR3 plays no significant role in CNV development and question the therapeutic approach of CCR3 targeting to suppress CNV. On the other hand, our data support the therapeutic strategies of VEGF-A and mTOR (mammalian target of rapamycin) targeting for CNV.

  20. Risk of choroidal neovascularization among the uveitides

    PubMed Central

    Baxter, Sally L.; Pistilli, Maxwell; Pujari, Siddharth S.; Liesegang, Teresa L.; Suhler, Eric B.; Thorne, Jennifer E.; Foster, C. Stephen; Jabs, Douglas A.; Levy-Clarke, Grace A.; Nussenblatt, Robert B.; Rosenbaum, James T.; Kempen, John H.

    2013-01-01

    Purpose To evaluate the risk, risk factors, and visual impact of choroidal neovascularization (CNV) in uveitis cases. Design Retrospective cohort study Methods Standardized medical record review at five tertiary centers. Results Among 15,137 uveitic eyes (8,868 patients), CNV was rare in the cases of anterior or intermediate uveitis. Among the 4,041 eyes (2,307 patients) with posterior or panuveitis, 81 (2.0%) presented with CNV. Risk factors included posterior uveitis in general and specific uveitis syndromes affecting the outer retina/retinal pigment epithelium (RPE)/choroid interface. Among the 2,364 eyes (1,357 patients) with posterior or panuveitis and free of CNV at the time of cohort entry, the cumulative two-year incidence of CNV was 2.7% (95% confidence interval (95%CI): 1.8-3.5%). Risk factors for incident CNV included currently active inflammation (adjusted HR [aHR] 2.13, 95%CI: 1.26-3.60), preretinal neovascularization (aHR 3.19, 95%CI: 1.30-7.80), and prior diagnosis of CNV in the contralateral eye (aHR 5.79, 95%CI: 2.77-12.09). Among specific syndromes, the incidence was greater in Vogt-Koyanagi-Harada Syndrome (aHR 3.37, 95%CI: 1.52-7.46), and punctate inner choroiditis (aHR 8.67, 95%CI: 2.83-26.54). Incident CNV was associated with two lines’ loss of visual acuity (+0.19 logMAR units, 95%CI: 0.079–0.29) from the preceding visit. Conclusions CNV is an uncommon complication of uveitis associated with visual impairment, which more commonly occurs in forms affecting the outer retina/RPE/choroid interface, during periods of inflammatory activity, in association with preretinal neovascularization, and in second eyes of patients with unilateral CNV. Because CNV is treatable, a systematic approach to early detection in high-risk patients may be appropriate. PMID:23795984

  1. Beals-Hecht syndrome and choroidal neovascularization.

    PubMed

    Gallego-Pinazo, Roberto; López-Lizcano, Ruth; Millán, José María; Arevalo, J Fernando; Mullor, J Luis; Díaz-Llopis, Manuel

    2010-08-09

    To describe a case of choroidal neovascularization (CNV) in a female diagnosed with Beals-Hecht syndrome. A retrospective, interventional case is described in a 26-year-old female complaining of metamorphopsia and visual loss in her left eye (counting fingers). The fluorescein angiogram and the optical coherence tomography supported the diagnosis of CNV. Intravitreal ranibizumab was administered. After the third intravitreal ranibizumab, her visual acuity improved to 0.8 and the morphology of the macular area was restored. To our knowledge this is the first report of CNV in Beals-Hecht syndrome treated with ranibizumab. Self-monitoring by periodically performing Amsler grid test is strongly recommended in these patients in order to achieve an early diagnosis of eventual CNV and avoid visual acuity loss.

  2. Vascular endothelial growth factor inhibitor use and treatment approach for choroidal neovascularization secondary to pathologic myopia.

    PubMed

    Pakzad-Vaezi, Kaivon; Mehta, Hemal; Mammo, Zaid; Tufail, Adnan

    2016-07-01

    Myopic choroidal neovascularization (CNV) is the most common cause of CNV in those under 50 years of age. It is a significant cause of visual loss in those with pathologic myopia. The current standard of care involves therapy with intravitreal inhibitors of vascular endothelial growth factor (VEGF). The epidemiology of myopia, high myopia, pathologic myopia, and myopic CNV is reviewed, along with a brief discussion of historical treatments. The pharmacology of the three most commonly used anti-VEGF agents is discussed, with an emphasis on the licensed drugs, ranibizumab and aflibercept. A comprehensive clinical approach to diagnosis and treatment of myopic CNV is presented. The current standard of care for myopic CNV is intravitreal inhibition of VEGF, with ranibizumab and aflibercept licensed for intraocular use. The diagnosis, OCT features of disease activity and retreatment algorithm for myopic CNV is different from wet age-related macular degeneration. In the long-term, myopic CNV may be associated with gradual, irreversible visual loss due to progressive chorioretinal atrophy, for which there is currently no treatment.

  3. Diagnostic Challenges in Inflammatory Choroidal Neovascular Membranes.

    PubMed

    Bansal, Reema; Bansal, Pooja; Gupta, Amod; Gupta, Vishali; Dogra, Mangat R; Singh, Ramandeep; Katoch, Deeksha

    2017-08-01

    To describe the clinical presentations of inflammatory choroidal neovascular membranes (CNVMs) and factors leading to their delayed diagnosis. Retrospective analysis of chart records and digital images of 60 patients (73 eyes) with inflammatory CNVM (January 1998 to December 2013) to obtain demographic and clinical details, particularly the time of the first documentation of inflammatory CNVM by the uveitis specialist, time of its actual appearance on digital images, and the earliest clinical indicators of a CNVM. In total, 14 (19.2%) eyes had a delayed diagnosis of inflammatory CNVMs, of which five developed significant visual loss. The earliest clinical indicators of CNVM that were overlooked initially due to their subtle appearance, included a tiny subretinal hemorrhage (five eyes), peripapillary halo/fluid/scar (eight eyes), and a subfoveal scar (one eye). The causes of uveitis in these eyes included Vogt-Koyanagi-Harada disease (five eyes, 35.7%), tubercular uveitis (five eyes, 35.7%), idiopathic (three eyes, 21.4%), and sympathetic ophthalmia (one eye, 7.1%). Presence of significant background fundus scarring, sunset glow fundus, visually significant cataract, poorly dilating pupil, media haze due to vitritis, cystoid macular edema, and multiple chorioretinal scars in these eyes probably predisposed to delayed detection of an underlying CNVM. A high index of suspicion and comparison of serial fundus photographs to identify the earliest clues of inflammatory CNVMs are important to prevent diagnostic delays and poorer outcomes.

  4. Optical Coherence Tomography Angiography Study of Choroidal Neovascularization Associated With Focal Choroidal Excavation.

    PubMed

    Chawla, Rohan; Mittal, Kanhaiya; Vohra, Rajpal

    2016-10-01

    The authors report the use of optical coherence tomography angiography (OCTA) (DRI OCT Triton; Topcon, Tokyo, Japan) to localize, characterize, and confirm the presence of a choroidal neovascular membrane in a patient of focal choroidal excavation (FCE) with recent-onset metamorphopsia and visual blurring. En face OCTA images just above the level of the retinal pigment epithelium-Bruch's membrane complex typically showed the presence of a glomerulus-like neovascular network with an adjacent dark area suggestive of a Type 2 choroidal neovascularization (CNV). OCTA was found to be a very useful, noninvasive, and quick imaging modality to detect secondary CNV formation in a case of FCE. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:969-971.].

  5. The relationship between scleral staphyloma and choroidal thinning in highly myopic eyes: The Beijing Eye Study.

    PubMed

    Zhou, Ling Xiao; Shao, Lei; Xu, Liang; Wei, Wen Bin; Wang, Ya Xing; You, Qi Sheng

    2017-08-29

    Based on the Beijing Eye Study 2011, a detailed ophthalmic examination was performed including spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging for measurement of subfoveal choroidal thickness (SFCT) and relative height of posterior scleral staphyloma. OCT images were obtained in 103 highly myopic eyes (≤-6.00 diopters) and 227 normal eyes. The mean SFCT in highly myopic eyes was 110.6 ± 85.2 μm (range, 3 to 395 μm). The SFCT of high myopia without posterior scleral staphyloma(55 eyes) was 157.79 ± 85.18 μm, which was significantly greater than that (54.94 ± 49.96 μm) of high myopia with posterior scleral staphyloma (48 eyes) (P < 0.001). In multivariate analysis, posterior scleral staphyloma was the most important factor of choroidal thinning in high myopia (F = 22.63; P < 0.001), then age (F = 19.14; P < 0.001), axial length (F = 17.37; P < 0.001) and gender (F = 17.31; P < 0.001). The SFCT in highly myopic eyes is very thin and undergoes further thinning with increasing age and axial length (refractive error). Posterior staphyloma formation was a key factor in choroidal thinning in highly myopic eyes and to be a good indicator for risk management of choroidal thinning. Abnormalities of the choroid may play a role in the pathogenesis of myopic degeneration.

  6. Optical coherence tomography angiography in pediatric choroidal neovascularization

    PubMed Central

    Veronese, Chiara; Maiolo, Chiara; Huang, David; Jia, Yali; Armstrong, Grayson W.; Morara, Mariachiara; Ciardella, Antonio P.

    2016-01-01

    Purpose To report two cases of pediatric choroidal neovascularization (CNV) and the associated neo-vascular and retinal findings identified on Optical Coherence Tomography Angiography (OCTA) imaging. Methods A 14-year-old boy with handheld laser-induced maculopathy-related CNV and a 13-year-old boy with idiopathic CNV were evaluated with visual acuity testing, slit-lamp exam, fundus photography, fluorescein angiography, indocyanine green angiography, spectral domain optical coherence tomography, and OCTA. Results Macular CNV were identified in both pediatric patients using OCTA imaging. The first case demonstrated a classic pediatric type II CNV with a “tree-like” pattern and a single vessel in-growth site, while the second case demonstrated a type I CNV with a “glomerular” pattern. Conclusion Distinct choroidal neovascular patterns were visualized in these two cases of pediatric CNV when compared to adult subtypes. OCTA is a noninvasive imaging modality capable of evaluating and characterizing pediatric CNV and their associated vascular patterns. PMID:27990495

  7. Attenuation of Choroidal Neovascularization by β2-Adrenergic Receptor Antagonism

    PubMed Central

    Lavine, Jeremy A.; Sang, Yanzhi; Wang, Shoujian; Ip, Michael S.; Sheibani, Nader

    2013-01-01

    Objectives To determine if β-adrenergic blockade inhibits choroidal neovascularization (CNV) in a mouse model of laser-induced CNV, and to investigate the mechanism by which β-adrenoreceptor antagonism blunts CNV. Methods The impact of β-adrenoreceptor blockade on CNV was determined using the laser-induced CNV model. Briefly, mice were subjected to laser burns, inducing CNV, and treated with daily intraperitoneal injections of propranolol. Neovascularization was measured on choroidal-sclera flat mounts using intercellular adhesion molecule-2 immunofluorescence staining. The impact of β-adrenergic receptor signaling on expression of vascular endothelial growth factor (VEGF) was investigated using primary mouse choroidal endothelial cells (ChEC) and retinal pigment epithelial (RPE) cells. These cells were incubated with β-adrenoreceptor agonists and/or antagonists, and assayed for VEGF mRNA and protein levels. Results Propranolol-treated mice demonstrated a 50% reduction in laser-induced CNV. Norepinephrine treatment stimulated VEGF mRNA expression and protein secretion in both ChEC and RPE cells. This effect was blocked by β2-adrenoreceptor antagonism and mimicked by β2-adrenergic receptor agonists. Conclusions and Clinical Relevance β-Adrenergic blockade attenuated CNV. β2-Adrenergic receptors regulated VEGF expression in ChEC and RPE cells. Antagonists of β-adrenergic receptors are safe and well tolerated in patients with glaucoma and cardiovascular disease. Thus, blockade of β-adrenoreceptors may provide a new avenue to inhibit VEGF expression in CNV. PMID:23303344

  8. OCT Angiography Identification of Choroidal Neovascularization Secondary to Acute Zonal Occult Outer Retinopathy.

    PubMed

    Levison, Ashleigh L; Baynes, Kimberly; Lowder, Careen Y; Srivastava, Sunil K

    2016-01-01

    A 74-year-old female with acute zonal occult outer retinopathy presented with a new lesion suspicious for choroidal neovascularization (CNV) in her right eye. Optical coherence tomography angiography (OCTA) confirmed the presence of CNV. OCTA is a new imaging technique that may help guide diagnosis and management of choroidal neovascular membranes in uveitic diseases.

  9. Choroidal neovascularization in pathologic myopia: intravitreal ranibizumab versus bevacizumab--a randomized controlled trial.

    PubMed

    Gharbiya, Magda; Giustolisi, Rosalia; Allievi, Francesca; Fantozzi, Nicoletta; Mazzeo, Luigi; Scavella, Vittorio; Gabrieli, Corrado Balacco

    2010-03-01

    To compare the short-term efficacy and safety of intravitreal ranibizumab versus bevacizumab in treating myopic choroidal neovascularization (CNV). Prospective, comparative, randomized, interventional study. Thirty-two eyes from 32 patients with myopic CNV were consecutively enrolled and randomly treated, in a 1:1 ratio, with intravitreal ranibizumab (0.5 mg) or bevacizumab (1.25 mg) as needed, after the first injection. ETDRS best-corrected visual acuity (BCVA), foveal center thickness (FCT) on optical coherence tomography (OCT), and fluorescein angiographic findings were examined before and after treatment. Patients were followed up for 6 months. No statistically significant difference in the BCVA improvement, as well as in the FCT reduction, was found between groups during follow-up (P value at 1, 3, 6 months > .05). Complete resolution of fluorescein leakage was observed in all 16 bevacizumab-treated eyes and in 15 out of 16 (93.7%) ranibizumab-treated eyes. No ocular or systemic adverse effects from treatment were encountered. This randomized clinical study cannot determine a statistically significant difference in anti-VEGF treatment effect between ranibizumab and bevacizumab for the treatment of CNV secondary to pathologic myopia. A larger study is required to determine the relative efficacy and duration of action of these drugs. (c) 2010 Elsevier Inc. All rights reserved.

  10. Improved assessment of laser-induced choroidal neovascularization

    PubMed Central

    Toma, Hassanain S.; Barnett, Joshua M.; Penn, John S.; Kim, Stephen J.

    2011-01-01

    The primary objective of this study was to develop and evaluate new methods of analyzing laser-induced choroidal neovascularization (CNV), in order to make recommendations for improving the reporting of experimental CNV in the literature. Six laser burns of sufficient power to rupture Bruch's membrane were concentrically placed in each eye of 18 adult Norway rats. Eyes received intravitreal injections of either triamcinolone acetonide, ketorolac, or balanced salt solution (BSS). Fluorescein angiography (FA) was performed 2 and 3 weeks after injection, followed by choroidal flat mount preparation. Vascular leakage on FAs and vascular budding on choroidal mounts were quantified by measuring either the cross-sectional area of each CNV lesion contained within the best-fitting polygon using Adobe Photoshop (Lasso Technique or Quick Selection Technique), or the area of bright pixels within a lesion using Image-Pro Plus. On choroidal mounts, the Lasso Technique and Image-Pro Plus detected a significant difference in lesion size between either ketorolac or triamcinolone when compared to BSS, while the Quick Selection Technique did not (Lasso Technique, 0.78 and 0.64; Image-Pro Plus, 0.77 and 0.65). On FA, the Lasso Technique and Quick Selection Technique detected a significant difference in lesion size between either ketorolac or triamcinolone when compared to BSS, while Image-Pro Plus did not (Lasso Tool, 0.81 and 0.54; Quick Selection Tool, 0.76 and 0.57). Choroidal mounts and FA are both valuable for imaging experimental CNV. Adobe Photoshop and Image-Pro Plus are both able to detect subtle differences in CNV lesion size, when images are not manipulated. The combination of choroidal mounts and FA provides a more comprehensive assessment of CNV anatomy and physiology. PMID:20553963

  11. Improved assessment of laser-induced choroidal neovascularization.

    PubMed

    Toma, Hassanain S; Barnett, Joshua M; Penn, John S; Kim, Stephen J

    2010-12-01

    The primary objective of this study was to develop and evaluate new methods of analyzing laser-induced choroidal neovascularization (CNV), in order to make recommendations for improving the reporting of experimental CNV in the literature. Six laser burns of sufficient power to rupture Bruch's membrane were concentrically placed in each eye of 18 adult Norway rats. Eyes received intravitreal injections of either triamcinolone acetonide, ketorolac, or balanced salt solution (BSS). Fluorescein angiography (FA) was performed 2 and 3 weeks after injection, followed by choroidal flat mount preparation. Vascular leakage on FAs and vascular budding on choroidal mounts were quantified by measuring either the cross-sectional area of each CNV lesion contained within the best-fitting polygon using Adobe Photoshop (Lasso Technique or Quick Selection Technique), or the area of bright pixels within a lesion using Image-Pro Plus. On choroidal mounts, the Lasso Technique and Image-Pro Plus detected a significant difference in lesion size between either ketorolac or triamcinolone when compared to BSS, while the Quick Selection Technique did not (Lasso Technique, 0.78 and 0.64; Image-Pro Plus, 0.77 and 0.65). On FA, the Lasso Technique and Quick Selection Technique detected a significant difference in lesion size between either ketorolac or triamcinolone when compared to BSS, while Image-Pro Plus did not (Lasso Tool, 0.81 and 0.54; Quick Selection Tool, 0.76 and 0.57). Choroidal mounts and FA are both valuable for imaging experimental CNV. Adobe Photoshop and Image-Pro Plus are both able to detect subtle differences in CNV lesion size, when images are not manipulated. The combination of choroidal mounts and FA provides a more comprehensive assessment of CNV anatomy and physiology.

  12. A Mouse Model for Laser-induced Choroidal Neovascularization.

    PubMed

    Shah, Ronil S; Soetikno, Brian T; Lajko, Michelle; Fawzi, Amani A

    2015-12-27

    The mouse laser-induced choroidal neovascularization (CNV) model has been a crucial mainstay model for neovascular age-related macular degeneration (AMD) research. By administering targeted laser injury to the RPE and Bruch's membrane, the procedure induces angiogenesis, modeling the hallmark pathology observed in neovascular AMD. First developed in non-human primates, the laser-induced CNV model has come to be implemented into many other species, the most recent of which being the mouse. Mouse experiments are advantageously more cost-effective, experiments can be executed on a much faster timeline, and they allow the use of various transgenic models. The miniature size of the mouse eye, however, poses a particular challenge when performing the procedure. Manipulation of the eye to visualize the retina requires practice of fine dexterity skills as well as simultaneous hand-eye-foot coordination to operate the laser. However, once mastered, the model can be applied to study many aspects of neovascular AMD such as molecular mechanisms, the effect of genetic manipulations, and drug treatment effects. The laser-induced CNV model, though useful, is not a perfect model of the disease. The wild-type mouse eye is otherwise healthy, and the chorio-retinal environment does not mimic the pathologic changes in human AMD. Furthermore, injury-induced angiogenesis does not reflect the same pathways as angiogenesis occurring in an age-related and chronic disease state as in AMD. Despite its shortcomings, the laser-induced CNV model is one of the best methods currently available to study the debilitating pathology of neovascular AMD. Its implementation has led to a deeper understanding of the pathogenesis of AMD, as well as contributing to the development of many of the AMD therapies currently available.

  13. Choroid thickness measurement with RTVue optical coherence tomography in emmetropic eyes, mildly myopic eyes, and highly myopic eyes.

    PubMed

    Coscas, Gabriel; Zhou, Qienyuan; Coscas, Florence; Zucchiatti, Ilaria; Rispoli, Marco; Uzzan, Joel; De Benedetto, Umberto; Savastano, Maria C; Soules, Kelly; Goldenberg, Dafna; Loewenstein, Anat; Lumbroso, Bruno

    2012-01-01

    To evaluate choroid thickness (CT) with RTVue spectral domain optical coherence tomography (SD-OCT) and the effect of age and myopia in eyes without posterior complications.
 In this multicenter cross-sectional study, all enrolled patients were over age 18 and divided them in 3 groups based on refraction: emmetropia (+1 D to -1 D), mild myopia (-1 D to -6 D), and high myopia (-6 D to -20 D) groups. Horizontal scans through the fovea were acquired with RTVue OCT (Optovue Inc., Fremont, California, USA). Choroid thickness was measured at 500 µm intervals up to 1,500 µm temporal and nasal to the fovea by 2 graders. Mean CT was calculated based on the average of the 7 locations. Statistical analysis was performed to evaluate CT at each location, the effects of age and myopia, and grader agreement. 
 A total 85 eyes of 85 subjects (30 emmetropic, 24 myopic, and 31 high myopic) were enrolled. Excellent grader agreement was observed with an intraclass correlation coefficient (ICC) >0.97. The mean CT was 248.2±78.5 (µm) for emmetropia (age = 58±18), 247.0±85.4 (µm) for myopia (age = 45±20), and 131.5±70.9 (µm) for high myopia (age = 54±13). The mean CT was not significantly different between emmetropia and myopia groups, which were significantly thicker than high myopia group. The overall slope of age-related change for the mean CT was -1.95 µm/y and the effect of age differed among the groups. Choroid thickness can be measured from RTVue OCT images with good reproducibility. Age and high myopia appear to negatively affect CT. The age effect may vary with refraction groups.

  14. RAGE Regulates Immune Cell Infiltration and Angiogenesis in Choroidal Neovascularization

    PubMed Central

    McVicar, Carmel; Ward, Michael; Colhoun, Liza; Quinn, Michael; Bierhaus, Angelika; Xu, Heping; Stitt, Alan W.

    2014-01-01

    Purpose RAGE regulates pro-inflammatory responses in diverse cells and tissues. This study has investigated if RAGE plays a role in immune cell mobilization and choroidal neovascular pathology that is associated with the neovascular form of age-related macular degeneration (nvAMD). Methods RAGE null (RAGE−/−) mice and age-matched wild type (WT) control mice underwent laser photocoagulation to generate choroidal neovascularization (CNV) lesions which were then analyzed for morphology, S100B immunoreactivity and inflammatory cell infiltration. The chemotactic ability of bone marrow derived macrophages (BMDMs) towards S100B was investigated. Results RAGE expression was significantly increased in the retina during CNV of WT mice (p<0.001). RAGE−/− mice exhibited significantly reduced CNV lesion size when compared to WT controls (p<0.05). S100B mRNA was upregulated in the lasered WT retina but not RAGE−/− retina and S100B immunoreactivity was present within CNV lesions although levels were less when RAGE−/− mice were compared to WT controls. Activated microglia in lesions were considerably less abundant in RAGE−/− mice when compared to WT counterparts (p<0.001). A dose dependent chemotactic migration was observed in BMDMs from WT mice (p<0.05–0.01) but this was not apparent in cells isolated from RAGE−/− mice. Conclusions RAGE-S100B interactions appear to play an important role in CNV lesion formation by regulating pro-inflammatory and angiogenic responses. This study highlights the role of RAGE in inflammation-mediated outer retinal pathology. PMID:24586862

  15. A Simple Optical Coherence Tomography Quantification Method for Choroidal Neovascularization

    PubMed Central

    Sulaiman, Rania S.; Quigley, Judith; Qi, Xiaoping; O'Hare, Michael N.; Grant, Maria B.; Boulton, Michael E.

    2015-01-01

    Abstract Purpose: Therapeutic efficacy is routinely assessed by measurement of lesion size using flatmounted choroids and confocal microscopy in the laser-induced choroidal neovascularization (L-CNV) rodent model. We investigated whether optical coherence tomography (OCT) quantification, using an ellipsoid volume measurement, was comparable to standard ex vivo evaluation methods for this model and whether this approach could be used to monitor treatment-related lesion changes. Methods: Bruch's membrane was ruptured by argon laser in the dilated eyes of C57BL/6J mice, followed by intravitreal injections of anti-VEGF164 or vehicle, or no injection. In vivo OCT images were acquired using Micron III or InVivoVue systems at 7, 10, and/or 14 days post-laser and neovascular lesion volume was calculated as an ellipsoid. Subsequently, lesion volume was compared to that calculated from confocal Z-stack images of agglutinin-stained choroidal flatmounts. Results: Ellipsoid volume measurement of orthogonal 2-dimensional OCT images obtained from different imaging systems correlated with ex vivo lesion volumes for L-CNV (Spearman's ρ=0.82, 0.75, and 0.82 at days 7, 10, and 14, respectively). Ellipsoid volume calculation allowed temporal monitoring and evaluation of CNV lesions in response to antivascular endothelial growth factor treatment. Conclusions: Ellipsoid volume measurements allow rapid, quantitative use of OCT for the assessment of CNV lesions in vivo. This novel method can be used with different OCT imaging systems with sensitivity to distinguish between treatment conditions. It may serve as a useful adjunct to the standard ex vivo confocal quantification, to assess therapeutic efficacy in preclinical models of CNV, and in models of other ocular diseases. PMID:26060878

  16. Suppression of Experimental Choroidal Neovascularization by Curcumin in Mice

    PubMed Central

    Xie, Ping; Zhang, WeiWei; Yuan, Songtao; Chen, Zhiqiang; Yang, Qin; Yuan, DongQing; Wang, Feng; Liu, QingHuai

    2012-01-01

    Purpose To investigate the effects of curcumin on the development of experimental choroidal neovascularization (CNV) with underlying cellular and molecular mechanisms. Methods C57BL/6N mice were pretreated with intraperitoneal injections of curcumin daily for 3 days prior to laser-induced CNV, and the drug treatments were continued until the end of the study. The CNV area was analyzed by fluorescein-labeled dextran angiography of retinal pigment epithelium (RPE)-choroid flat mounts on day 7 and 14, and CNV leakage was evaluated by fluorescein angiography (FA) on day 14 after laser photocoagulation. The infiltration of F4/80 positive macrophages and GR-1 positive granulocytes were evaluated by immunohistochemistry on RPE-choroid flat mounts on day 3. Their expression in RPE-choroid complex was quantified by real-time PCR (F4/80) and Western blotting (GR-1) on day 3. RPE-choroid levels of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 were examined by ELISA on day 3. Double immunostaining of F4/80 and VEGF was performed on cryo-sections of CNV lesions on day 3. The expression of nuclear factor (NF)-κB and hypoxia-inducible factor (HIF)−1α in the RPE-choroid was determined by Western blotting. Results Curcumin-treated mice had significantly less CNV area (P<0.05) and CNV leakage (P<0.001) than vehicle-treated mice. Curcumin treatment led to significant inhibition of F4/80 positive macrophages (P<0.05) and GR-1 positive granulocytes infiltration (P<0.05). VEGF mainly expressed in F4/80 positive macrophages in laser injury sites, which was suppressed by curcumin treatment (P<0.01). Curcumin inhibited the RPE-choroid levels of TNF-α (P<0.05), MCP-1 (P<0.05) and ICAM-1 (P<0.05), and suppressed the activation of NF-κB in nuclear extracts (P<0.05) and the activation of HIF−1α (P<0.05). Conclusion Curcumin treatment led to the suppression of CNV development

  17. Geographic mapping of choroidal thickness in myopic eyes using 1050-nm spectral domain optical coherence tomography.

    PubMed

    Zhang, Qinqin; Neitz, Maureen; Neitz, Jay; Wang, Ruikang K

    2015-07-01

    To provide a geographical map of choroidal thickness (CT) around the macular region among subjects with low, moderate and high myopia. 20 myopic subjects (n = 40 eyes) without other identified pathologies participated in this study: 20 eyes of ≤ 3 diopters (D) (low myopic), 10 eyes between -3 and -6D (moderate myopic), and 10 eyes of ≥ 6D (high myopic). The mean age of subjects was 30.2 years (± 7.6 years; range, 24 to 46 years). A 1050 nm spectral-domain optical coherence tomography (SD-OCT) system, operating at 120 kHz imaging rate, was used in this study to simultaneously capture 3D anatomical images of the choroid and measure intraocular length (IOL) in the subject. The 3D OCT images of the choroid were segmented into superior, inferior, nasal and temporal quadrants, from which the CT was measured, representing radial distance between the outer retinal pigment epithelium (RPE) layer and inner scleral border. Measurements were made within concentric regions centered at fovea centralis, extended to 5 mm away from fovea at 1 mm intervals in the nasal and temporal directions. The measured IOL was the distance from the anterior cornea surface to the RPE in alignment along the optical axis of the eye. Statistical analysis was performed to evaluate CT at each geographic region and observe the relationship between CT and the degree of myopia. For low myopic eyes, the IOL was measured at 24.619 ± 0.016 mm. The CT (273.85 ± 49.01 µm) was greatest under fovea as is in the case of healthy eyes. Peripheral to the fovea, the mean CT decreased rapidly along the nasal direction, reaching a minimum of 180.65 ± 58.25 µm at 5 mm away from the fovea. There was less of a change in thickness from the fovea in the temporal direction reaching a minimum of 234.25 ± 42.27 µm. In contrast to the low myopic eyes, for moderate and high myopic eyes, CTs were thickest in temporal region (where CT = 194.94 ± 27.28 and 163 ± 34.89 µm, respectively). Like the low myopic eyes

  18. Influence of macular choroidal thickness on visual function in highly myopic eyes.

    PubMed

    Parravano, Mariacristina; Oddone, Francesco; Giorno, Paola; Cacciamani, Andrea; Abbate, Rosa; Caminiti, Giulia; Peiretti, Enrico; Varano, Monica

    2014-01-01

    To explore the retinal and choroidal thicknesses (RT, CT), as measured using enhanced depth imaging (EDI) optical coherence tomography (OCT, Spectralis) in highly myopic eyes and its relationship with visual function. Prospective, case-control, noninterventional clinical study. CT was measured by EDI-OCT in highly myopic eyes (≥6 dpt) without any macular diseases and age-matched control eyes. A complete ophthalmological examination, visual acuity assessment and MP1 microperimetry were obtained. 38 myopic (15 M/23 F, mean age 51 ± 8.9 years) and 21 control eyes (5 M/16 F, mean age 50 ± 5.4 years) were included. The myopic mean refractive error was -13.3 ± 4.9 dpt and axial length 29.2 ± 2.2 mm. The mean best-corrected visual acuity (BCVA) was lower in highly myopic than in control eyes (77.3 ± 9.25 vs. 84.8 ± 0.6 letters, p = 0.0001, respectively) as was the mean retinal sensitivity (MRS; 16.32 ± 2.6 vs. 19.9 ± 0.2 dB, p < 0.0001). While RT was similar between groups (291.5 ± 24.2 vs. 283.6 ± 13.9 µm, p = 0.06, respectively), subfoveal CT was thinner in highly myopic compared to control eyes (114.3 ± 78.5 vs. 272.6 ± 110.2 µm, p < 0.0001). A significant relationship was found between subfoveal CT and MRS (R(2) = 0.22; p = 0.003) and BCVA (R(2) = 0.13; p = 0.027). Macular function is reduced in highly myopic eyes without any visible macular diseases compared to controls, and a significant proportion of the macular function variability seems to be related to a reduced CT. © 2014 S. Karger AG, Basel.

  19. [Choroidal neovascularization secondary to angioid streaks: A familial case report].

    PubMed

    Benitez-Herreros, J; Camara-Gonzalez, C; Lopez-Guajardo, L; Beckford-Torngren, C; Pareja-Esteban, J

    2014-05-01

    We report a familial case of 2 brothers that suffered choroidal neovascularization (CNV) secondary to angioid streaks. They were both treated with a monthly intravitreal injection of ranibizumab (Lucentis(®)) for 3 months. Visual acuity was stabilized and fluorescein angiography revealed complete resolution of CNV. Neither recurrent CNV lesion nor new hemorrhages were reported during the follow-up period. The use of intravitreal ranibizumab for the treatment of CNV in patients with angioid streaks has shown favorable results. However, further studies with a longer follow-up and larger number of patients are necessary to more precisely determine the results of this therapy. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  20. Dramatic Inhibition of Retinal and Choroidal Neovascularization by Oral Administration of a Kinase Inhibitor

    PubMed Central

    Seo, Man Seong; Kwak, Nohoon; Ozaki, Hiroaki; Yamada, Haruhiko; Okamoto, Naoyuki; Yamada, Eri; Fabbro, Doriano; Hofmann, Francesco; Wood, Jeanette M.; Campochiaro, Peter A.

    1999-01-01

    The most common cause of new blindness in young patients is retinal neovascularization, and in the elderly is choroidal neovascularization. Therefore, there has been a great deal of attention focused on the development of new treatments for these disease processes. Previous studies have demonstrated partial inhibition of retinal neovascularization in animal models using antagonists of vascular endothelial growth factor or other signaling molecules implicated in the angiogenesis cascade. These studies have indicated potential for drug treatment, but have left many questions unanswered. Is it possible to completely inhibit retinal neovascularization using drug treatment with a mode of administration that is feasible to use in patients? Do agents that inhibit retinal neovascularization have any effect on choroidal neovascularization? In this study, we demonstrate complete inhibition of retinal neovascularization in mice with oxygen-induced ischemic retinopathy by oral administration of a partially selective kinase inhibitor that blocks several members of the protein kinase C family, along with vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinases. The drug also blocks normal vascularization of the retina during development but has no identifiable adverse effects on mature retinal vessels. In addition, the kinase inhibitor causes dramatic inhibition of choroidal neovascularization in a laser-induced murine model. These data provide proof of concept that pharmacological treatment is a viable approach for therapy of both retinal and choroidal neovascularization. PMID:10362799

  1. An Angiogenic Role for Adrenomedullin in Choroidal Neovascularization

    PubMed Central

    Sakimoto, Susumu; Kidoya, Hiroyasu; Kamei, Motohiro; Naito, Hisamichi; Yamakawa, Daishi; Sakaguchi, Hirokazu; Wakabayashi, Taku; Nishida, Kohji; Takakura, Nobuyuki

    2013-01-01

    Purpose Adrenomedullin (ADM) has been shown to take part in physiological and pathological angiogenesis. The purpose of this study was to investigate whether ADM signaling is involved in choroidal neovascularization (CNV) using a mouse model. Methods and Results CNV was induced by laser photocoagulation in 8-week-old C57BL/6 mice. ADM mRNA expression significantly increased following treatment, peaking 4 days thereafter. The expression of ADM receptor (ADM-R) components (CRLR, RAMP2 and RAMP 3) was higher in CD31+CD45− endothelial cells (ECs) than CD31−CD45− non-ECs. Inflammatory stimulation upregulated the expression of ADM not only in cell lines but also in cells in primary cultures of the choroid/retinal pigment epithelium complex. Supernatants from TNFα-treated macrophage cell lines potentiated the proliferation of ECs and this was partially suppressed by an ADM antagonist, ADM (22–52). Intravitreous injection of ADM (22–52) or ADM neutralizing monoclonal antibody (mAb) after laser treatment significantly reduced the size of CNV compared with vehicle-treated controls (p<0.01). Conclusions ADM signaling is involved in laser-induced CNV formation, because both an ADM antagonist and ADM mAb significantly inhibited it. Suppression of ADM signaling might be a valuable alternative treatment for CNV associated with age-related macular degeneration. PMID:23520487

  2. Attenuation of Choroidal Neovascularization by Histone Deacetylase Inhibitor

    PubMed Central

    Chan, Nymph; He, Shikun; Spee, Christine K.; Ishikawa, Keijiro; Hinton, David R.

    2015-01-01

    Choroidal neovascularization (CNV) is a blinding complication of age-related macular degeneration that manifests as the growth of immature choroidal blood vessels through Bruch’s membrane, where they can leak fluid or hemorrhage under the retina. Here, we demonstrate that the histone deacetylase inhibitor (HDACi) trichostatin A (TSA) can down-regulate the pro-angiogenic hypoxia-inducible factor-1α and vascular endothelial growth factor (VEGF), and up-regulate the anti-angiogenic and neuro-protective pigment epithelium derived factor in human retinal pigment epithelial (RPE) cells. Most strikingly, TSA markedly down-regulates the expression of VEGF receptor-2 in human vascular endothelial cells and, thus, can knock down pro-angiogenic cell signaling. Additionally, TSA suppresses CNV-associated wound healing response and RPE epithelial-mesenchymal transdifferentiation. In the laser-induced model of CNV using C57Bl/6 mice, systemic administration of TSA significantly reduces fluorescein leakage and the size of CNV lesions at post—laser days 7 and 14 as well as the immunohistochemical expression of VEGF, VEGFR2, and smooth muscle actin in CNV lesions at post-laser day 7. This report suggests that TSA, and possibly HDACi’s in general, should be further evaluated for their therapeutic potential for the treatment of CNV. PMID:25807249

  3. Segmentation of choroidal neovascularization in fundus fluorescein angiograms.

    PubMed

    Abdelmoula, Walid M; Shah, Syed M; Fahmy, Ahmed S

    2013-05-01

    Choroidal neovascularization (CNV) is a common manifestation of age-related macular degeneration (AMD). It is characterized by the growth of abnormal blood vessels in the choroidal layer causing blurring and deterioration of the vision. In late stages, these abnormal vessels can rupture the retinal layers causing complete loss of vision at the affected regions. Determining the CNV size and type in fluorescein angiograms is required for proper treatment and prognosis of the disease. Computer-aided methods for CNV segmentation is needed not only to reduce the burden of manual segmentation but also to reduce inter- and intraobserver variability. In this paper, we present a framework for segmenting CNV lesions based on parametric modeling of the intensity variation in fundus fluorescein angiograms. First, a novel model is proposed to describe the temporal intensity variation at each pixel in image sequences acquired by fluorescein angiography. The set of model parameters at each pixel are used to segment the image into regions of homogeneous parameters. Preliminary results on datasets from 21 patients with Wet-AMD show the potential of the method to segment CNV lesions in close agreement with the manual segmentation.

  4. Inhibitory role of adiponectin peptide I on rat choroidal neovascularization

    PubMed Central

    Lyzogubov, Valeriy V.; Tytarenko, Ruslana G.; Bora, Nalini S.; Bora, Puran S.

    2013-01-01

    Age-related macular degeneration (AMD) is a leading cause of central blindness in elderly population. Wet type of AMD is characterized by extensive growth of new vessels. One of the effective strategies to treat wet AMD is to limit the choroidal neovascularization (CNV). We studied effect of adiponectin peptide I (APNpI) on new vessel growth in laser-induced rat model of wet AMD and on rat choroidal endothelial cell (CEC) culture. CNV size and vessel density was investigated by microscopy. Immunohistochemical staining (IHC) for Von Willebrand Factor (vWF), APN, APN receptors 1 (AdipoR1), 2 (AdipoR2), VEGF, VEGF receptor 2 (VEGF-R2), proliferating cell nuclear antigen (PCNA) was performed in CNV area. The mRNA expression of VEGF and VEGF-R2 in RPE-choroid was investigated by RT-PCR and real-time PCR. APNpI inhibited area of CNV by 4 fold, number of vWF positive vessels by 99% and area of subretinal tissue by 40%. The expression of VEGF and VEGF-R2 at mRNA and protein levels were decreased after APNpI treatment in vivo. Proliferative index (PCNA) was 5 fold less in laser spots of APNpI treated rats compared to controls. In conclusion, APNpI inhibited formation of new vessels in rat model of CNV by decreasing VEGF, VEGF-R2 expression and cell proliferation. Thus, APNpI may have potential therapeutic use for AMD treatment since it significantly inhibited CNV. PMID:22633972

  5. Spontaneous Regression of Choroidal Neovascularization in a Patient with Pattern Dystrophy

    PubMed Central

    Goleni, Flamur; Livir-Rallatos, Gerasimos; Livir-Rallatos, Charalampos; Zafirakis, Panagiotis; Allen Fishman, Gerald

    2016-01-01

    Purpose. To present a case of a patient with pattern dystrophy (PD) associated choroidal neovascularization (CNV) that resolved spontaneously without treatment. Methods. A 69-year-old male patient was referred to our unit, for evaluation of a recent visual loss (metamorphopsias) in his left eye. Fundus examination, fundus autofluorescence imaging, and fluorescein angiography showed a choroidal neovascular membrane in his left eye. Since visual acuity was satisfactory the patient elected observation. Clinical examination and OCT testing were repeated at 6 and 12 months after presentation. Results. Visual acuity remained stable at the level of 0.9 (baseline BCVA) during the follow-up period (12 months). Repeat OCT testing showed complete spontaneous regression of the choroidal neovascular membrane without evidence of intra- or subretinal fluid in both follow-up visits. Conclusions. Spontaneous regression of choroidal neovascularization can occur in patients with retinal dystrophies and associated choroidal neovascular membranes. The decision to treat or observe these patients relies strongly on the presenting visual acuity, since, in isolated instances, spontaneous resolution of choroidal neovascularization may occur. PMID:27847664

  6. Intravitreal aflibercept for the treatment of choroidal neovascularization associated with pathologic myopia: a pilot study

    PubMed Central

    Korol, Andrii R; Zadorozhnyy, Oleg S; Naumenko, Volodymyr O; Kustryn, Taras B; Pasyechnikova, Nataliya V

    2016-01-01

    Purpose To determine the efficacy of intravitreal aflibercept injections for the treatment of patients with choroidal neovascularization (CNV) associated with pathologic myopia. Methods In this uncontrolled, prospective cohort study, 31 eyes of 30 consecutive patients affected by CNV associated with pathologic myopia were treated with intravitreal aflibercept (2 mg) as needed following two initial monthly doses and observed over a 12-month follow-up period. The primary endpoint was change in best-corrected visual acuity (BCVA) at month 12, while central retinal thickness (CRT) on optical coherence tomography (OCT), neovascularization activity on fluorescein angiography, the number of aflibercept injections administered, and safety were examined as secondary endpoints. Results Patients received a mean of 2.6 intravitreal aflibercept injections over the 12-month study period. Compared with baseline, BCVA improved significantly at all time points (P<0.05). Mean (standard deviation [SD]) decimal BCVA was 0.2 (0.1) at baseline and 0.35 (0.16) at month 12. The greatest improvement in BCVA was seen within the first 2 months (P=0.01). Mean (SD) CRT on OCT decreased from 285 (62) µm at baseline to 227 (42) µm (P=0.01) at month 12. There was a continuous decrease in mean CRT on OCT over time. No cases of endophthalmitis, uveitis, stroke, or retinal detachment were noted. No patient demonstrated an intraocular pressure >20 mmHg during any study visit. Conclusion The 12-month results of intravitreal aflibercept for myopic CNV using an as-needed regimen were positive, showing benefits in visual and anatomic outcomes and an acceptable tolerability profile. PMID:27853350

  7. Ketorolac inhibits choroidal neovascularization by suppression of retinal VEGF

    PubMed Central

    Kim, Stephen J.; Toma, Hassanain S.; Barnett, Joshua M.; Penn, John S.

    2011-01-01

    We assessed the effect of topical ketorolac on laser-induced choroidal neovascularization (CNV), measured retinal PGE2 and VEGF levels after laser treatment, and determined the effect of ketorolac on PGE2 and VEGF production. Six laser burns were placed in eyes of rats which then received topical ketorolac 0.4% or artificial tears four times daily until sacrifice. Fluorescein angiography (FA) was performed at 2 and 3 weeks and retinal pigment epithelium-choroid-sclera flat mounts were prepared. The retina and vitreous were isolated at 1, 3, 5, 7, and 14 days after laser treatment and tested for VEGF and PGE2. Additional animals were lasered and treated with topical ketorolac or artificial tears and tested at 3 and 7 days for retinal and vitreous VEGF and PGE2. Ketorolac reduced CNV on FA by 27% at 2 weeks (P < 0.001) and 25% at 3 weeks (P < 0.001). Baseline retina and vitreous PGE2 levels were 29.4 μg/g and 16.5 μg/g respectively, and reached 51.2 μg/g and 26.9 μg/g respectively, 24 h after laser treatment (P < 0.05). Retinal VEGF level was 781 pg/g 24 h after laser treatment and reached 931 pg/g by 7 days (P < 0.01). Ketorolac reduced retinal PGE2 by 35% at 3 days (P < 0.05) and 29% at 7 days (P < 0.001) and retinal VEGF by 31% at 3 days (P = 0.10) and 19% at 7 days (P < 0.001). Topical ketorolac inhibited CNV and suppressed retinal PGE2 and VEGF production. PMID:20659449

  8. Effect of pitavastatin on experimental choroidal neovascularization in rats.

    PubMed

    Sagara, Nina; Kawaji, Takahiro; Takano, Akiomi; Inomata, Yasuya; Inatani, Masaru; Fukushima, Mikiko; Tanihara, Hidenobu

    2007-06-01

    The association between the use of statins and age-related macular degeneration (AMD), a leading cause of blindness, has been evaluated in many clinical studies; however, the results have been contradictory. We evaluated the effect of pitavastatin administration on laser-induced experimental choroidal neovascularization (CNV) in rats. Brown Norway rats received pitavastatin (1.0mg/kg per day) for 1day prior to laser-induced CNV and continued to receive the drug for 14days. Fluorescein angiograms were graded by masked observers. CNV area and thickness were assessed by fluorescein isothiocyanate-labeled dextran angiography and histology, respectively. Vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (Ccl-2; also known as MCP-1), and intercellular adhesion molecule-1 (ICAM-1) mRNA levels were measured using reverse-transcription polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR. Pitavastatin-treated rats had significantly less fluorescence leakage compared with the vehicle-treated rats estimated by CNV score using fluorescein angiography. Both the area and the thickness of CNV in pitavastatin-treated rats were significantly reduced compared with the vehicle-treated rats. Gene expression of VEGF, Ccl-2, and ICAM-1 were significantly decreased by pitavastatin administration in experimental CNV. Thus, we demonstrated that the therapeutic dose of pitavastatin for human hypocholesterolemia effectively suppressed experimental CNV in rats. The use of pitavastatin may be helpful in preventing CNV development in AMD patients.

  9. Change in choroidal thickness and the relationship with accommodation following myopic excimer laser surgery.

    PubMed

    Li, M; Cheng, H; Yuan, Y; Wang, J; Chen, Q; Me, R; Ke, B

    2016-07-01

    PurposeTo investigate early changes in choroidal thickness (CT) and the relationship with accommodation after myopic excimer laser surgery.MethodsWe enrolled the right eye of 70 patients with myopia and without other ophthalmic or systemic diseases who were suitable for myopic excimer laser surgery. The CT was measured at the fovea and at distances of 0.5 and 2.5 mm for the following: nasal; temporal; superior; and inferior to the fovea preoperatively and at 1 month postoperatively. Other data collected included demographic information (age, sex, and refractive error), the amplitude of accommodation (AA), intraocular pressure, axial length, corneal thickness, and surgical parameters. The data were analyzed with a paired Student's t-test, stepwise linear regression, and correlation analysis.ResultsThe CT was significantly thicker postoperatively compared with the preoperative CT. The AA significantly decreased postoperatively. The change in the AA was the most significant factor associated with the change in the CT at the fovea. Except for 2.5 mm inferior to the fovea, the increase in the CT at other locations was positively correlated with the decrease in the AA.ConclusionsThe CT increased following myopic excimer laser surgery and the change was most obvious when accompanied by a decrease in the AA early after the surgery.

  10. Idiopathic polypoidal choroidal vasculopathy in Thai patients with clinical and angiographic choroidal neovascularization

    PubMed Central

    Bhoomibunchoo, Chavakij; Yospaiboon, Yosanan; Thoongsuwan, Somanus; Rojanaporn, Duangnate; Watanachai, Nawat; Jirarattanasopa, Pichai; Wongcumchang, Nattapon; Amphornphruet, Atchara; Vongkulsiri, Sritatath; Arayangkoon, Eakkachai

    2017-01-01

    Objective This study aimed to study the prevalence and characteristics of idiopathic polypoidal choroidal vasculopathy (IPCV) in Thai patients with clinical and angiographic choroidal neovascularization (CNV). Patients and methods A consecutive case study of 140 patients presenting with CNV was conducted in nine large referral eye centers throughout Thailand. The demographic data, fundus photographs, fundus fluorescein angiography and indocyanine green angiography of the patients were analyzed. Results Of 129 patients with clinical and angiographic CNV, IPCV was diagnosed in 100 patients (77.52%), idiopathic CNVs in 16 patients (12.40%) and age-related macular degeneration (AMD) in 12 patients (9.30%). Of the 107 eyes with IPCV, 90 eyes (84.11%) had both branching venous networks (BVNs) and polypoidal lesions. Most IPCV patients (93%) had unilateral involvement and were at a younger age than AMD patients. In all, 79 eyes (73.83%) had lesions found in the macular area, 14 eyes (13.08%) in the temporal to vascular arcades, ten eyes (9.35%) in the peripapillary area and four eyes (3.74%) in both macular and peripapillary areas. The clinical manifestations of IPCV at presentation were categorized into two patterns. There were 95 eyes (88.79%) of a hemorrhagic pattern and 12 eyes (11.21%) of an exudative pattern. Conclusion IPCV is the most common macular disease in Thai patients with CNV. Most IPCVs have both BVNs and polypoidal lesions located in the macular area and present with a hemorrhagic pattern. PMID:28223776

  11. Choroidal thickness profiles in myopic eyes of young adults in the Correction of Myopia Evaluation Trial cohort

    PubMed Central

    Harb, Elise; Hyman, Leslie; Gwiazda, Jane; Marsh-Tootle, Wendy; Zhang, Qinghua; Hou, Wei; Norton, Thomas T; Weise, Katherine; Dirkes, Keri; Zangwill, Linda M

    2015-01-01

    Purpose To examine the relationship of choroidal thickness with axial length (AL) and myopia in young adult eyes in the ethnically diverse Correction of Myopia Evaluation Trial (COMET) cohort. Design Cross-sectional, multi-center, study Methods In addition to measures of myopia by cycloplegic autorefraction and AL by A-scan ultrasonography, participants underwent optical coherence tomography imaging of the choroid (RTVue) in both eyes at their last visit (14 years after baseline). Using digital calipers, two independent readers measured choroidal thickness in the right eye (left eye if poor quality; n=37) at seven locations: fovea and 750, 1500, 2250μm nasal (N) and temporal (T) to the fovea. Results Choroidal thickness measurements were available from 294/346 (85%) of imaged participants (mean age: 24.3±1.4 years; 44.9% male) with mean myopia of -5.3±2.0D and mean AL of 25.5±1.0mm. Overall, choroidal thickness varied by location (p<0.0001) and was thickest at the fovea (273.8±70.9 μm) and thinnest nasally (N2250,191.5±69.3 μm). Multivariable analyses showed significantly thinner choroids in eyes with more myopia and longer AL at all locations except T2250 (p≤0.001) and presence of peri-papillary crescent at all locations except T1500 and T2250 (p≤0.0001). Choroidal thickness varied by ethnicity at N2250 (p<0.0001), with Asians having the thinnest and African Americans the thickest choroids. Conclusion Choroids are thinner in longer, more myopic young adult eyes. The thinning was most prominent nasally and in eyes with a crescent. In the furthest nasal location, ethnicity was associated with choroidal thickness. The findings suggest that choroidal thickness should be evaluated, especially in the nasal regions where myopic degenerations are most commonly seen clinically. PMID:25896460

  12. Choroidal Thickness Profiles in Myopic Eyes of Young Adults in the Correction of Myopia Evaluation Trial Cohort.

    PubMed

    Harb, Elise; Hyman, Leslie; Gwiazda, Jane; Marsh-Tootle, Wendy; Zhang, Qinghua; Hou, Wei; Norton, Thomas T; Weise, Katherine; Dirkes, Keri; Zangwill, Linda M

    2015-07-01

    To examine the relationship of choroidal thickness with axial length (AL) and myopia in young adult eyes in the ethnically diverse Correction of Myopia Evaluation Trial (COMET) cohort. Cross-sectional, multicenter study. In addition to measures of myopia by cycloplegic autorefraction and AL by A-scan ultrasonography, participants underwent optical coherence tomography imaging of the choroid in both eyes at their last visit (14 years after baseline). Using digital calipers, 2 independent readers measured choroidal thickness in the right eye (left eye if poor quality; n = 37) at 7 locations: fovea and 750, 1500, and 2250 μm nasal (N) and temporal (T) to the fovea. Choroidal thickness measurements were available from 294 of 346 (85%) imaged participants (mean age: 24.3 ± 1.4 years; 44.9% male) with mean myopia of -5.3 ± 2.0 diopters and mean AL of 25.5 ± 1.0 mm. Overall, choroidal thickness varied by location (P < .0001) and was thickest at the fovea (273.8 ± 70.9 μm) and thinnest nasally (N2250, 191.5 ± 69.3 μm). Multivariable analyses showed significantly thinner choroids in eyes with more myopia and longer AL at all locations except T2250 (P ≤ .001) and presence of peripapillary crescent at all locations except T1500 and T2250 (P ≤ .0001). Choroidal thickness varied by ethnicity at N2250 (P < .0001), with Asians having the thinnest and African Americans the thickest choroids. Choroids are thinner in longer, more myopic young adult eyes. The thinning was most prominent nasally and in eyes with a crescent. In the furthest nasal location, ethnicity was associated with choroidal thickness. The findings suggest that choroidal thickness should be evaluated, especially in the nasal regions where myopic degenerations are most commonly seen clinically. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Objective Area Measurement Technique for Choroidal Neovascularization from Fluorescein Angiography

    PubMed Central

    Guthrie, Micah J.; Osswald, Christian R.; Valio, Nicole L.; Mieler, William F.; Kang-Mieler, Jennifer J.

    2014-01-01

    The purpose of this study was to develop a non-biased method of quantitatively measuring choroidal neovascularization (CNV) areas based on late-phase fluorescein angiography (FA) images. Experimental CNV was induced in Long Evans rats by laser disruption of the Bruch’s membrane. FA was performed weekly for 5 weeks. Multi-Otsu thresholding (MOT) was used to quantify CNV in late-phase FA images from both experimental rodent CNV and wet age-related macular degeneration patients (wAMD). Images were automatically thresholded into three levels based on the image histogram, with the highest level containing CNV. To determine the technique’s ability to quantify CNV areas, rats were given either triamcinolone acetonide or dexamethasone sodium phosphate to treat CNV and compared to untreated rats. The rat CNV lesion areas measured from 5-week histology sections from each treatment group were compared to areas measured from the corresponding FA images. MOT was able to detect statistical decreases in rodent CNV area in the treatment groups versus control from weeks 3 through 5. The ratio of CNV area measured from histology to area measured from FA images was not statistically different between groups. Finally, to determine the usefulness of MOT on pathological morphologies of CNV, MOT was performed on late-phase FA images from patients with classic and diffuse CNV. The technique was able to segment classical CNV in wAMD patients, but performed poorly with diffuse CNV. MOT provides a robust, objective, and quantifiable area measurement of CNV lesion area in both experimentally-induced and pathological CNV. The results indicate that MOT could be a useful research tool in helping evaluate the effects of therapeutics on CNV growth. PMID:24316422

  14. Modifying Choroidal Neovascularization Development with a Nutritional Supplement in Mice

    PubMed Central

    Ivanescu, Alina Adriana; Fernández-Robredo, Patricia; Heras-Mulero, Henar; Sádaba-Echarri, Luis Manuel; García-García, Laura; Fernández-García, Vanessa; Moreno-Orduna, Maite; Redondo-Exposito, Aitor; Recalde, Sergio; García-Layana, Alfredo

    2015-01-01

    We examined the effect of nutritional supplements (modified Age Related Eye Disease Study (AREDS)-II formulation containing vitamins, minerals, lutein, resveratrol, and omega-3 fatty acids) on choroidal neovascularization (CNV). Supplements were administered alone and combined with intravitreal anti-VEGF in an early-CNV (diode laser-induced) murine model. Sixty mice were evenly divided into group V (oral vehicle, intravitreal saline), group S (oral supplement, intravitreal saline), group V + aVEGF (oral vehicle, intravitreal anti-VEGF), and group S + aVEGF (oral supplement, intravitreal anti-VEGF). Vehicle and nutritional supplements were administered daily for 38 days beginning 10 days before laser. Intravitreal injections were administered 48 h after laser. Fluorescein angiography (FA) and flat-mount CD31 staining evaluated leakage and CNV lesion area. Expression of VEGF, MMP-2 and MMP-9 activity, and NLRP3 were evaluated with RT-PCR, zymography, and western-blot. Leakage, CNV size, VEGF gene and protein expression were lower in groups V + aVEGF, S + aVEGF, and S than in V (all p < 0.05). Additionally, MMP-9 gene expression differed between groups S + aVEGF and V (p < 0.05) and MMP-9 activity was lower in S + aVEGF than in V and S (both p < 0.01). Levels of MMP-2 and NLRP3 were not significantly different between groups. Nutritional supplements either alone or combined with anti-VEGF may mitigate CNV development and inhibit retinal disease involving VEGF overexpression and CNV. PMID:26153682

  15. Chorioretinal Coloboma Complications: Retinal Detachment and Choroidal Neovascular Membrane

    PubMed Central

    Hussain, Rehan M.; Abbey, Ashkan M.; Shah, Ankoor R.; Drenser, Kimberly A.; Trese, Michael T.; Capone, Antonio

    2017-01-01

    Purpose: To report the chorioretinal coloboma, and its association with increased risk of retinal detachment (RD) and choroidal neovascularization (CNV). Methods: This retrospective case series included eyes with chorioretinal coloboma diagnosed between 1995 and 2014 with a focus on RD and CNV as related complications. Cases of CNV were managed with laser photocoagulation or intravitreal injection of bevacizumab. For eyes with CNV, therapeutic success was defined as resolution of the subretinal hemorrhage on fundus examination and resolution of the subretinal and intraretinal fluid on optical coherence tomography (OCT). For eyes with RD, anatomic success following surgical intervention was defined as attachment of the retina at the last follow-up visit. Results: Fifty-one eyes of 31 patients with chorioretinal coloboma were identified for review. Bilateral chorioretinal coloboma was present in 64.5% of subjects. RD developed in 15 eyes (29.4%). Among 15 eyes with RD, 4 eyes (27%) had retinal breaks identified within the coloboma, 5 eyes (33%) had retinal breaks outside the coloboma, 2 eyes (13%) showed retinal breaks both inside and outside the coloboma, and in 4 eyes (27%) the causative retinal break was not localized. The overall rate of anatomic success after RD repair was 85.7%. CNV developed in 7 eyes (13.7%) and was located along the margin of the coloboma in all cases. CNV was bilateral in 2 of the 5 affected individuals (40%). Conclusion: RD and CNV were present in a high percentage of eyes with chorioretinal coloboma in these series. The frequent finding of retinal breaks outside the coloboma bed suggests that vitreoretinal interface abnormalities may play a role in development of RD in these eyes. PMID:28299000

  16. Intravitreal bevacizumab treatment for choroidal neovascularization in pathologic myopia: 12-month results.

    PubMed

    Gharbiya, Magda; Allievi, Francesca; Mazzeo, Luigi; Gabrieli, Corrado Balacco

    2009-01-01

    To evaluate the short-term efficacy and safety of intravitreal bevacizumab for the treatment of myopic choroidal neovascularization (CNV). Prospective, nonrandomized, interventional case series. Twenty eyes from 20 patients with CNV secondary to pathologic myopia participated in this prospective nonrandomized interventional case series. All patients were scheduled for three monthly intravitreal bevacizumab 1.25 mg injections. Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), foveal center thickness (FCT) on optical coherence tomography (OCT), and fluorescein angiographic findings were examined before and after treatment. Patients were followed up for 12 months. The mean BCVA (+/- standard deviation [SD]) at baseline was 24.8 (+/- 11.86) letters (Snellen equivalent: 20/80). At 12 months after treatment, the mean BCVA (+/- SD) improved significantly (P = .000001) to 43 (+/- 12.38) letters (Snellen equivalent: 20/35). At 12 month follow-up, BCVA improved 10 letters or more in 18 (90%) out of 20 treated eyes and improved 15 letters or more in 14 (70%) out of 20 treated eyes. No treated eyes experienced a worsening of BCVA from baseline. The mean FCT (+/- SD) at baseline was 223 (+/- 47.43) microns. At 12 months after treatment, the mean FCT (+/- SD) reduced to 206 (+/- 50.87) microns. This reduction in FCT after treatment was not statistically significant (P = .11). At 12 months follow-up, absence of fluorescein leakage from the CNV was demonstrated in 19 (95%) out of 20 treated eyes and persistent leakage in one eye (5%). None of the 19 eyes that had CNV closure experienced recurrence at 12-month follow-up. No ocular or systemic adverse effects from treatment were encountered. These results of intravitreal bevacizumab in myopic CNV are very promising with no apparent short-term safety concerns. At 12 months, treated eyes had a significant improvement in visual acuity (VA). OCT findings, as well, showed a trend consistent with the

  17. Choroidal thickness variation in highly myopic eyes during the water drinking test.

    PubMed

    Germano, Renato Antunes Schiave; Hatanaka, Marcelo; Susanna, Remo

    2016-01-01

    To evaluate variations in choroidal thickness (CT) during the water drinking test (WDT) in emmetropic eyes (EE) and highly myopic eyes (ME) using spectral-domain optical coherence tomography (SD-OCT). Clinical trial performed at a tertiary care hospital comprising 30 randomly selected eyes. The WDT and SD-OCT macular scans were performed 10 and 45 min after water ingestion in 15 myopic and 15 EE of 15 healthy patients in each group. Primary study outcomes were average macular CT measured by SD-OCT and intraocular pressure (IOP) during the WDT. The mean spherical equivalent refraction was 0.15 ± 0.24 D in emmetropic and -7.1 ± 1.75 D in ME (p<0.001). No statistical differences between EE and ME were observed during the WDT response. EE had higher CT compared with ME at the fovea (361.4 ± 55.4 vs 257.9 ± 95.3; p<0.001), 3 mm nasal to the fovea (158.0 ± 71.8 vs 122.5 ± 54.5; p =0.047), and 3 mm temporally to the fovea (310.6 ± 52.4 vs 247.6 ± 90.1; p=0.05). Regarding CT variation, significant differences in foveal CT at 10 min after water ingestion were observed in both EE and ME, with no statistically significant difference observed between groups. A moderate correlation between IOP peak during the WDT and CT was demonstrated in ME (r=0.52; p=0.04). No statistically significant differences in CT variation during the WDT were observed between EE and ME, indicating similar behavior of the choroidal bed during the WDT in both groups. Further, CT was thinner in highly ME, with CT variation unable to explain elevations in IOP observed during the WDT.

  18. Bone marrow transplantation transfers age-related susceptibility to neovascular remodeling in murine laser-induced choroidal neovascularization.

    PubMed

    Espinosa-Heidmann, Diego G; Malek, Goldis; Mettu, Priyatham S; Caicedo, Alejandro; Saloupis, Peter; Gach, Sarah; Dunnon, Askia K; Hu, Peng; Spiga, Maria-Grazia; Cousins, Scott W

    2013-11-13

    Neovascular remodeling (NVR), the progression of small capillaries into large-caliber arterioles with perivascular fibrosis, represents a major therapeutic challenge in neovascular age-related macular degeneration (AMD). Neovascular remodeling occurs after laser-induced choroidal neovascularization (CNV) in aged but not young mice. Additionally, bone marrow-derived cells, including macrophages, endothelial precursor cells, and mesenchymal precursor cells, contribute to CNV severity. In this study, we investigated the impact of aged bone marrow transplantation (BMT) on the degree of fibrosis, size, and vascular morphology of CNV lesions in a mouse model of laser-induced CNV. Young (2 months) and old (16 months) mice were transplanted with green fluorescent protein (GFP)-labeled bone marrow isolated from either young or old donors. Laser CNV was induced 1 month following transplant, and eyes were analyzed via choroidal flat mounts and immunohistochemistry 1 month postlaser. The identity of cells infiltrating CNV lesions was determined using specific markers for the labeled transplanted cells (GFP+), macrophages (F4/80+), perivascular mesenchymal-derived cells (smooth muscle actin, SMA+), and endothelial cells (CD31+). Bone marrow transplantation from aged mice transferred susceptibility to NVR into young recipients. Inversely, transplantation of young marrow into old mice prevented NVR, preserving small size and minimal fibrosis. Mice with NVR demonstrated a greater relative contribution of marrow-derived SMA+ perivascular mesenchymal cells as compared to other cells. Our findings indicate that the status of bone marrow is an important determining factor of neovascular severity. Furthermore, we find that perivascular mesenchymal cells, rather than endothelial cells, derived from aged bone marrow may contribute to increased CNV severity in this murine model of experimental neovascularization.

  19. Bone Marrow Transplantation Transfers Age-Related Susceptibility to Neovascular Remodeling in Murine Laser-Induced Choroidal Neovascularization

    PubMed Central

    Espinosa-Heidmann, Diego G.; Malek, Goldis; Mettu, Priyatham S.; Caicedo, Alejandro; Saloupis, Peter; Gach, Sarah; Dunnon, Askia K.; Hu, Peng; Spiga, Maria-Grazia; Cousins, Scott W.

    2013-01-01

    Purpose. Neovascular remodeling (NVR), the progression of small capillaries into large-caliber arterioles with perivascular fibrosis, represents a major therapeutic challenge in neovascular age-related macular degeneration (AMD). Neovascular remodeling occurs after laser-induced choroidal neovascularization (CNV) in aged but not young mice. Additionally, bone marrow–derived cells, including macrophages, endothelial precursor cells, and mesenchymal precursor cells, contribute to CNV severity. In this study, we investigated the impact of aged bone marrow transplantation (BMT) on the degree of fibrosis, size, and vascular morphology of CNV lesions in a mouse model of laser-induced CNV. Methods. Young (2 months) and old (16 months) mice were transplanted with green fluorescent protein (GFP)-labeled bone marrow isolated from either young or old donors. Laser CNV was induced 1 month following transplant, and eyes were analyzed via choroidal flat mounts and immunohistochemistry 1 month postlaser. The identity of cells infiltrating CNV lesions was determined using specific markers for the labeled transplanted cells (GFP+), macrophages (F4/80+), perivascular mesenchymal-derived cells (smooth muscle actin, SMA+), and endothelial cells (CD31+). Results. Bone marrow transplantation from aged mice transferred susceptibility to NVR into young recipients. Inversely, transplantation of young marrow into old mice prevented NVR, preserving small size and minimal fibrosis. Mice with NVR demonstrated a greater relative contribution of marrow-derived SMA+ perivascular mesenchymal cells as compared to other cells. Conclusions. Our findings indicate that the status of bone marrow is an important determining factor of neovascular severity. Furthermore, we find that perivascular mesenchymal cells, rather than endothelial cells, derived from aged bone marrow may contribute to increased CNV severity in this murine model of experimental neovascularization. PMID:24135751

  20. Bevacizumab in choroidal neovascularization secondary to Indian tick typhus: A rare case report

    PubMed Central

    Ijeri, Raghavendra; Beladiya, Gautam; Bhomaj, Sharad

    2016-01-01

    Tick typhus causes hemorrhagic lesions over the skin. Retina also shows hemorrhages and exudates. Many cases have been reported in western literature about this condition. To our best of knowledge, this is the first case report of tick typhus in India which was also associated with inflammatory choroidal neovascularization. PMID:27905346

  1. VEGF-Production by CCR2-Dependent Macrophages Contributes to Laser-Induced Choroidal Neovascularization

    PubMed Central

    Krause, Torsten A.; Alex, Anne F.; Engel, Daniel R.; Kurts, Christian; Eter, Nicole

    2014-01-01

    Age-related macular degeneration (AMD) is the most prevalent cause of blindness in the elderly, and its exsudative subtype critically depends on local production of vascular endothelial growth factor A (VEGF). Mononuclear phagocytes, such as macrophages and microglia cells, can produce VEGF. Their precursors, for example monocytes, can be recruited to sites of inflammation by the chemokine receptor CCR2, and this has been proposed to be important in AMD. To investigate the role of macrophages and CCR2 in AMD, we studied intracellular VEGF content in a laser-induced murine model of choroidal neovascularisation. To this end, we established a technique to quantify the VEGF content in cell subsets from the laser-treated retina and choroid separately. 3 days after laser, macrophage numbers and their VEGF content were substantially elevated in the choroid. Macrophage accumulation was CCR2-dependent, indicating recruitment from the circulation. In the retina, microglia cells were the main VEGF+ phagocyte type. A greater proportion of microglia cells contained VEGF after laser, and this was CCR2-independent. On day 6, VEGF-expressing macrophage numbers had already declined, whereas numbers of VEGF+ microglia cells remained increased. Other sources of VEGF detectable by flow cytometry included in dendritic cells and endothelial cells in both retina and choroid, and Müller cells/astrocytes in the retina. However, their VEGF content was not increased after laser. When we analyzed flatmounts of laser-treated eyes, CCR2-deficient mice showed reduced neovascular areas after 2 weeks, but this difference was not evident 3 weeks after laser. In summary, CCR2-dependent influx of macrophages causes a transient VEGF increase in the choroid. However, macrophages augmented choroidal neovascularization only initially, presumably because VEGF production by CCR2-independent eye cells prevailed at later time points. These findings identify macrophages as a relevant source of VEGF in laser

  2. VEGF-production by CCR2-dependent macrophages contributes to laser-induced choroidal neovascularization.

    PubMed

    Krause, Torsten A; Alex, Anne F; Engel, Daniel R; Kurts, Christian; Eter, Nicole

    2014-01-01

    Age-related macular degeneration (AMD) is the most prevalent cause of blindness in the elderly, and its exsudative subtype critically depends on local production of vascular endothelial growth factor A (VEGF). Mononuclear phagocytes, such as macrophages and microglia cells, can produce VEGF. Their precursors, for example monocytes, can be recruited to sites of inflammation by the chemokine receptor CCR2, and this has been proposed to be important in AMD. To investigate the role of macrophages and CCR2 in AMD, we studied intracellular VEGF content in a laser-induced murine model of choroidal neovascularisation. To this end, we established a technique to quantify the VEGF content in cell subsets from the laser-treated retina and choroid separately. 3 days after laser, macrophage numbers and their VEGF content were substantially elevated in the choroid. Macrophage accumulation was CCR2-dependent, indicating recruitment from the circulation. In the retina, microglia cells were the main VEGF+ phagocyte type. A greater proportion of microglia cells contained VEGF after laser, and this was CCR2-independent. On day 6, VEGF-expressing macrophage numbers had already declined, whereas numbers of VEGF+ microglia cells remained increased. Other sources of VEGF detectable by flow cytometry included in dendritic cells and endothelial cells in both retina and choroid, and Müller cells/astrocytes in the retina. However, their VEGF content was not increased after laser. When we analyzed flatmounts of laser-treated eyes, CCR2-deficient mice showed reduced neovascular areas after 2 weeks, but this difference was not evident 3 weeks after laser. In summary, CCR2-dependent influx of macrophages causes a transient VEGF increase in the choroid. However, macrophages augmented choroidal neovascularization only initially, presumably because VEGF production by CCR2-independent eye cells prevailed at later time points. These findings identify macrophages as a relevant source of VEGF in laser

  3. Idiopathic Multifocal Choroiditis

    PubMed Central

    Tavallali, Ali; Yannuzzi, Lawrence A.

    2016-01-01

    Idiopathic multifocal choroiditis (MFC) and/or punctate inner choroidopathy (PIC) describe a chronic progressive bilateral inflammatory chorioretinopathy that predominantly affect healthy myopic white women with no known associated systemic or ocular diseases. The principal sites of involvement are the retinal pigment epithelium (RPE) and outer retinal spaces; the choroid is not affected during the active phase of the disease. Idiopathic MFC with atrophy is a recently described variant. Although there is no generally accepted standard treatment, anti-inflammatory and anti-VEGF (vascular endothelial growth factor) agents are necessary in the acute stage to control the inflammation and choroidal neovascularization (CNV). PMID:27994812

  4. Visible-Light Optical Coherence Tomography Angiography for Monitoring Laser-Induced Choroidal Neovascularization in Mice

    PubMed Central

    Shah, Ronil S.; Soetikno, Brian T.; Yi, Ji; Liu, Wenzhong; Skondra, Dimitra; Zhang, Hao F.; Fawzi, Amani A.

    2016-01-01

    Purpose This study sought to determine the earliest time-point at which evidence of choroidal neovascularization (CNV) could be detected with visible-light optical coherence tomography angiography (vis-OCTA) in a mouse model of laser-induced CNV. Methods Visible light-OCTA was used to study laser-induced CNV at different time-points after laser injury to monitor CNV development and measure CNV lesion size. Measurements obtained from vis-OCTA angiograms were compared with histopathologic measurements from isolectin-stained choroidal flatmounts. Results Choroidal neovascularization area measurements between the vis-OCTA system and isolectin-stained choroidal flatmounts were significantly different in area for days 2 to 4 postlaser injury, and were not significantly different in area for days 5, 7, and 14. Choroidal neovascularization area measurements taken from the stained flatmounts were larger than their vis-OCTA counterparts for all time-points. Both modalities showed a similar trend of CNV size increasing from the day of laser injury until a peak of day 7 postlaser injury and subsequently decreasing by day 14. Conclusions The earliest vis-OCTA can detect the presence of aberrant vessels in a mouse laser-induced CNV model is 5 days after laser injury. Visible light-OCTA was able to visualize the maximum of the CNV network 7 days postlaser injury, in accordance with choroidal flatmount immunostaining. Visible light-OCTA is a reliable tool in both detecting the presence of CNV development, as well as accurately determining the size of the lesion in a mouse laser-induced CNV model. PMID:27409510

  5. Choroidal neovascularization secondary to ocular penetration during retrobulbar anesthesia and its treatment

    PubMed Central

    Dikci, Seyhan; Yılmaz, Turgut; Gök, Zarife Ekici; Demirel, Soner; Genç, Oğuzhan

    2017-01-01

    Retrobulbar anesthesia is still used before ocular surgery; however, it has various complications including ocular penetration. The penetration/perforation of the globe can cause complications such as endophthalmitis, retinal detachment, and scotoma. Choroidal neovascularization (CNV) is rarely seen, following choroidal rupture in penetrating eye injuries. Here, we present a patient who underwent a pars plana vitrectomy for vitreous hemorrhage secondary to ocular penetration during a retrobulbar injection for cataract surgery. This patient later developed CNV at the penetration site during follow-up. Physicians should remember that CNV can occur as an unusual late complication of ocular penetration during retrobulbar anesthesia.

  6. Comparison of 2D reconstructions of surgically excised subfoveal choroidal neovascularization with fluorescein angiographic features: SST report No. 15.

    PubMed

    2006-02-01

    To compare topographic features of surgically excised subfoveal choroidal neovascularization with preoperative and postoperative fluorescein angiographic features from Submacular Surgery Trials (SST) patients, and to compare histological and angiographic features with preoperative and postoperative visual acuities (VAs). Patients enrolled in the SST Groups N, B, and H trials between October 1999 and September 2001 and assigned to the surgery arm had surgically removed choroidal neovascularization sent to the SST Pathology Center. Grossly intact specimens were sectioned serially for 2-dimensional reconstruction and were assigned to growth pattern groups based on topographic mapping of the location of cellular components relative to the retinal pigment epithelium (RPE): sub-RPE, subretinal, combined, or indeterminate. These features were compared with preoperative fluorescein angiographic features. The histological choroidal neovascularization growth pattern was compared with preoperative VAs. Two-dimensional reconstructions of surgically excised choroidal neovascularization could not be matched point for point to fluorescein angiographic features. Among the 52 specimens selected, the growth pattern could be determined by 2-dimensional reconstruction in 34 instances (65%), including 28 (80%) of 35 Group N specimens, 2 (40%) of 5 Group B specimens, and 4 (33%) of 12 Group H specimens. Among the choroidal neovascularization growth patterns that could be determined from specimens submitted, the majority of Group N specimens were combined, and the majority of Group H specimens were subretinal. In most instances for Group B specimens, the growth pattern was indeterminate. The postoperative abnormalities on fluorescein angiography were generally larger than measurements of excised specimens. The subretinal growth pattern was associated with the smallest decrease in 3-month postoperative average VA. Among the 52 specimens from the SST with adequate tissue to try to evaluate

  7. Anti-VEGF therapy in a silicone oil-filled myopic eye with choroidal neovascularisation

    PubMed Central

    Chhablani, Jay; Narayanan, Raja

    2015-01-01

    A 33-year-old man presented with vision loss in his right eye due to rhegmatogenous retinal detachment, for which he underwent pars plana vitrectomy with silicone oil injection. Three months later, the patient presented with sudden vision loss. On examination, his visual acuity was 20/200 with presence of subretinal haemorrhage with attached retina and silicone oil in situ. Fluorescein angiography confirmed the diagnosis of choroidal neovascularisation (CNV). The patient underwent intravitreal ranibizumab injection (0.5 mg per 0.05 mL). He subsequently underwent oil removal along with intravitreal bevacizumab injection (1.25 mg per 0.05 mL). The CNV completely regressed. At 7 years follow-up, the patient's best corrected visual acuity was 20/50 with attached retina and macular scar due to regressed CNV. His other eye was within normal limits throughout the follow-up period. This unique case demonstrates the successful outcome of intravitreal ranibizumab injection in a silicone oil-filled eye with myopic CNV. PMID:25870215

  8. Characteristics of choroidal neovascularization in the complications of age-related macular degeneration prevention trial.

    PubMed

    Maguire, Maureen G; Alexander, Judith; Fine, Stuart L

    2008-09-01

    To describe the characteristics of incident choroidal neovascularization (CNV) in observed and treated eyes in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). Cross-sectional descriptive study within a multicenter, randomized clinical trial. Patients who developed CNV during CAPT follow-up. Inclusion criteria for CAPT specified bilateral large drusen (>or=10 drusen at least 125 micro), visual acuity >or=20/40 in each eye, and age >or=50. Exclusion criteria included CNV and geographic atrophy >1 Macular Photocoagulation Study (MPS) disc area or within 500 micro of the foveal center. One eye of each person was selected randomly for low-intensity laser treatment and the contralateral eye was observed. Fluorescein angiography was performed at baseline, annually for >or=5 years, and whenever there were symptoms of CNV. Trained readers at the CAPT Photograph Reading Center assessed color stereo photographs and angiogram negatives to identify CNV. Choroidal neovascularization was classified by type (predominantly classic CNV, minimally classic CNV, occult only CNV, or scar), location, and area. Visual acuity was measured by certified examiners. Symmetry of characteristics between eyes of bilaterally affected patients was examined. Choroidal neovascularization developed in 282 eyes of 225 patients. At the time of detection, 192 (68%) of the lesions were occult only, 153 (54%) were subfoveal, and 157 (56%) were or=20/40 in 123 (69%) of 179 eyes with visual acuity measured at the time of detection. Choroidal neovascularization developed in both eyes in 57 patients (25%) during CAPT follow-up. Lesions in eyes of bilaterally affected patients were no more similar to each other than affected eyes in 2 different patients. When patients are monitored closely, many CNV lesions can be detected outside of the fovea and when they are relatively small. Early detection may lead to improved long-term visual acuity.

  9. Impact of Valsalva maneuver on central choroid, central macula, and disk fiber layer thickness among high myopic and hyperopic patients.

    PubMed

    Kurultay-Ersan, Isil; Emre, Sinan

    2017-05-11

    To evaluate the alterations in mean central choroidal, central macular, and disk retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) during Valsalva maneuver among patients with high refractive errors. A total of 60 high myopic (≥-6.0 D) and 50 high hyperopic (≥ + 3.0 D) eyes of 58 patients aged 19-65 years with visual acuity of 20/20 and without any ophthalmologic or systemic diseases were evaluated by OCT before and after the Valsalva maneuver. The choroidal thickness was measured with enhanced depth imaging OCT method. Central macular thickness, disk RNFL thickness, and axial length were also assessed. Mean choroidal thickness increased significantly from 275.0 ± 27.2 μm at rest to 279.8 ± 31.6 μm after Valsalva maneuver in high myopic patients, and from 308.2 ± 27.3 μm to 313.6 ± 28.5 μm in high hyperopic patients (p<0.01 for each). A significant negative correlation of the choroidal thickness was noted with axial length (r = -0.509, p<0.01) and age (r = -0.224, p = 0.01) in the overall study population. Mean central macular thickness was 242.9 ± 44.4 μm and 254.0 ± 22.8 μm, while mean disk RNFL thickness was 81.6 ± 12.4 μm and 98.4 ± 13.3 μm in high myopic and hyperopic patients, respectively. Valsalva maneuver was not associated with significant change in central macular or disk RNFL thickness. Significant association of Valsalva maneuver with an increase in choroidal thickness was noted among patients with high degree of myopia and hyperopia. Our findings emphasize the likelihood of increase in choroidal volume due to venous distension to be responsible for the increase observed in choroidal thickness after Valsalva maneuver.

  10. Anti-angiogenic effect of KR-31831 on corneal and choroidal neovascularization in rat models.

    PubMed

    Kim, In-Tae; Park, Hae-Young Lopilly; Choi, Jun-Sub; Joo, Choun-Ki

    2012-05-31

    We attempt to determine the effect and mechanism of KR-31831 in rat models of corneal neovascularization and choroidal neovascularization (CNV). Corneal neovascularization was induced by silver nitrate cauterization. Balanced salt solution (for control), KR-31831 (0.1 mg/mL), and bevacizumab (10 mg/mL) were applied topically with or without subsequent subconjunctival injection (10 μL). The degree of corneal neovascularization was compared among treatments. The effects of intravitreal (0.1 and 0.3 mg/mL) and intraperitoneal (25 mg/kg) of KR-31831, and intravitreal injection of bevacizumab (2.5 mg/mL) were compared in a laser-induced CNV model. FITC-dextran was used to observe the choroid vessels and to evaluate vessel leakage by fluorescence intensity. In the silver nitrate cauterized rat, topical KR-31831 (P = 0.008) or bevacizumab (P = 0.008) reduced effectively the area of corneal neovascularization compared to control on day 14. This was reduced further by additional subconjunctival injection of KR-31831 (P = 0.024) and bevacizumab (P = 0.016). After KR-31831 application, vascular endothelial growth factor (VEGF) receptor 2 and matrix metalloproteinase (MMP)-2 expression was decreased in the cornea. In the CNV model, intravitreal (0.3 mg/mL) and intraperitoneal KR-31831 inhibited significantly the CNV area (P = 0.008 and P = 0.008, respectively) and fluorescence leakage (P = 0.008 and P = 0.032, respectively). This effect was more significant compared to intravitreal bevacizumab in terms of the CNV area (P = 0.032 and P = 0.008, respectively) and fluorescence leakage (P = 0.016 and P = 0.008, respectively). The anti-angiogenic effect of KR-31831 was comparable in the cornea and more effective in the choroid compared to that of bevacizumab, and it may exert its effect by VEGF signaling and MMP-2.

  11. The Application of OCTA in Assessment of Anti-VEGF Therapy for Idiopathic Choroidal Neovascularization

    PubMed Central

    Sun, Zihan; Dai, Hong

    2016-01-01

    Purpose. To assess the morphology of idiopathic choroidal neovascularization (ICNV) by optical coherence tomography angiography (OCTA) and determine the therapeutic effects of intravitreal antivascular endothelial growth factor (anti-VEGF). Method. Patients with naive ICNV were assessed by spectral domain optical coherence tomography (SD-OCT) and OCTA in this observational study. The timing of observation was before treatment, 1 day after treatment with intravitreal anti-VEGF injection, and 1 month after the treatment. The central retina thickness (CRT) on SD-OCT, selected CNV area, and flow area on OCTA were measured. Results. A total of 17 eyes from 17 patients with ICNV were included in this study. OCTA showed visible irregular choroidal neovascularization with “tree-in-bud” form on outer retinal layer. After treatment, as well as in the 1-day follow-up, CNV decreased in size from the periphery, and the vessel density was reduced. As shown on OCTA, the selected CNV area and flow area were significantly reduced compared to pretreatment. The rate of CNV vessel area changes was higher on OCTA than the changes in CRT on SD-OCT at 1-day and 1-month follow-up. Conclusion. Intravitreal injection of anti-VEGF is effective for idiopathic choroidal neovascularization, and the treatment outcomes are observable after 1 day. OCTA provides a useful approach for monitoring and evaluating the treatment of intravitreal anti-VEGF for CNV. PMID:27471600

  12. Fluorocoxib A enables targeted detection of cyclooxygenase-2 in laser-induced choroidal neovascularization

    NASA Astrophysics Data System (ADS)

    Uddin, Md. Jashim; Moore, Chauca E.; Crews, Brenda C.; Daniel, Cristina K.; Ghebreselasie, Kebreab; McIntyre, J. Oliver; Marnett, Lawrence J.; Jayagopal, Ashwath

    2016-09-01

    Ocular angiogenesis is a blinding complication of age-related macular degeneration and other retinal vascular diseases. Clinical imaging approaches to detect inflammation prior to the onset of neovascularization in these diseases may enable early detection and timely therapeutic intervention. We demonstrate the feasibility of a previously developed cyclooxygenase-2 (COX-2) targeted molecular imaging probe, fluorocoxib A, for imaging retinal inflammation in a mouse model of laser-induced choroidal neovascularization. This imaging probe exhibited focal accumulation within laser-induced neovascular lesions, with minimal detection in proximal healthy tissue. The selectivity of the probe for COX-2 was validated in vitro and by in vivo retinal imaging with nontargeted 5-carboxy-X-rhodamine dye, and by blockade of the COX-2 active site with nonfluorescent celecoxib prior to injection of fluorocoxib A. Fluorocoxib A can be utilized for imaging COX-2 expression in vivo for further validation as an imaging biomarker in retinal diseases.

  13. Cytochrome P450 monooxygenase lipid metabolites are significant second messengers in the resolution of choroidal neovascularization.

    PubMed

    Hasegawa, Eiichi; Inafuku, Saori; Mulki, Lama; Okunuki, Yoko; Yanai, Ryoji; Smith, Kaylee E; Kim, Clifford B; Klokman, Garrett; Bielenberg, Diane R; Puli, Narender; Falck, John R; Husain, Deeba; Miller, Joan W; Edin, Matthew L; Zeldin, Darryl C; Lee, Kin Sing Stephen; Hammock, Bruce D; Schunck, Wolf-Hagen; Connor, Kip M

    2017-09-05

    Age-related macular degeneration (AMD) is the most common cause of blindness for individuals age 50 and above in the developed world. Abnormal growth of choroidal blood vessels, or choroidal neovascularization (CNV), is a hallmark of the neovascular (wet) form of advanced AMD and leads to significant vision loss. A growing body of evidence supports a strong link between neovascular disease and inflammation. Metabolites of long-chain polyunsaturated fatty acids derived from the cytochrome P450 (CYP) monooxygenase pathway serve as vital second messengers that regulate a number of hormones and growth factors involved in inflammation and vascular function. Using transgenic mice with altered CYP lipid biosynthetic pathways in a mouse model of laser-induced CNV, we characterized the role of these lipid metabolites in regulating neovascular disease. We discovered that the CYP-derived lipid metabolites epoxydocosapentaenoic acids (EDPs) and epoxyeicosatetraenoic acids (EEQs) are vital in dampening CNV severity. Specifically, overexpression of the monooxygenase CYP2C8 or genetic ablation or inhibition of the soluble epoxide hydrolase (sEH) enzyme led to increased levels of EDP and EEQ with attenuated CNV development. In contrast, when we promoted the degradation of these CYP-derived metabolites by transgenic overexpression of sEH, the protective effect against CNV was lost. We found that these molecules work in part through their ability to regulate the expression of key leukocyte adhesion molecules, on both leukocytes and endothelial cells, thereby mediating leukocyte recruitment. These results suggest that CYP lipid signaling molecules and their regulators are potential therapeutic targets in neovascular diseases.

  14. CD200R signaling inhibits pro-angiogenic gene expression by macrophages and suppresses choroidal neovascularization

    PubMed Central

    Horie, Shintaro; Robbie, Scott J.; Liu, Jian; Wu, Wei-Kang; Ali, Robin R.; Bainbridge, James W.; Nicholson, Lindsay B.; Mochizuki, Manabu; Dick, Andrew D.; Copland, David A.

    2013-01-01

    Macrophages are rapidly conditioned by cognate and soluble signals to acquire phenotypes that deliver specific functions during inflammation, wound healing and angiogenesis. Whether inhibitory CD200R signaling regulates pro-angiogenic macrophage phenotypes with the potential to suppress ocular neovascularization is unknown. CD200R-deficient bone marrow derived macrophages (BMMΦ) were used to demonstrate that macrophages lacking this inhibitory receptor exhibit enhanced levels of Vegfa, Arg-1 and Il-1β when stimulated with PGE2 or RPE-conditioned (PGE2-enriched) media. Endothelial tube formation in HUVECs was increased when co-cultured with PGE2-conditioned CD200R−/− BMMΦ, and laser-induced choroidal neovascularization was enhanced in CD200R-deficient mice. In corroboration, signaling through CD200R results in the down-regulation of BMMΦ angiogenic and pro-inflammatory phenotypes. Translational potential of this pathway was investigated in the laser-induced model of choroidal neovascularization. Local delivery of a CD200R agonist mAb to target myeloid infiltrate alters macrophage phenotype and inhibits pro-angiogenic gene expression, which suppresses pathological angiogenesis and CNV development. PMID:24170042

  15. Retinal and choroidal neovascularization in a transgenic mouse model of sickle cell disease.

    PubMed Central

    Lutty, G. A.; McLeod, D. S.; Pachnis, A.; Costantini, F.; Fabry, M. E.; Nagel, R. L.

    1994-01-01

    A complication of sickle cell disease is proliferative retinopathy. We investigated the eyes from a transgenic mouse model of sickle cell disease (alpha H beta S[beta MDD] type) to determine if pathological changes occurred in their retinas and choroids. One retina from each animal was processed by flat-embedding adenosine diphosphatase-reacted retinas in glycol methacrylate. The fellow eye from each animal was embedded whole in glycol methacrylate for histopathological analysis of all ocular structures. Retinal vascular occlusions resulted in nonperfused areas of retina and arterio-venous anastomoses. Intra- and extraretinal neovascularization was observed adjacent to nonperfused areas. Retinal pigmented lesions were formed by the migration of retinal pigment epithelial cells into sensory retina, often ensheathing choroidal neovascularization. The incidence of this bilateral chorioretinopathy was 30% in animals older than 15 months of age. The ocular histopathological changes we observed in the mouse model mimicked many aspects of human proliferative sickle cell retinopathy. Furthermore, this is the first genetically derived animal model for chorio-retinal neovascularization. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7519831

  16. Lymphocytic Microparticles Modulate Angiogenic Properties of Macrophages in Laser-induced Choroidal Neovascularization

    PubMed Central

    Tahiri, Houda; Omri, Samy; Yang, Chun; Duhamel, François; Samarani, Suzanne; Ahmad, Ali; Vezina, Mark; Bussières, Martin; Vaucher, Elvire; Sapieha, Przemyslaw; Hickson, Gilles; Hammamji, Karim; Lapointe, Réjean; Rodier, Francis; Tremblay, Sophie; Royal, Isabelle; Cailhier, Jean-François; Chemtob, Sylvain; Hardy, Pierre

    2016-01-01

    Pathological choroidal neovascularization (CNV) is the common cause of vision loss in patients with age-related macular degeneration (AMD). Macrophages possess potential angiogenic function in CNV. We have demonstrated that human T lymphocyte-derived microparticles (LMPs) exert a potent antiangiogenic effect in several pathological neovascularization models. In this study, we investigated the alteration of proangiogenic properties of macrophages by LMPs treatment in vitro and in vivo models. LMPs regulated the expression of several angiogenesis-related factors in macrophages and consequently stimulated their antiangiogenic effects evidenced by the suppression of the proliferation of human retinal endothelial cells in co-culture experiments. The involvement of CD36 receptor in LMPs uptake by macrophages was demonstrated by in vitro assays and by immunostaining of choroidal flat mounts. In addition, ex vivo experiments showed that CD36 mediates the antiangiogenic effect of LMPs in murine and human choroidal explants. Furthermore, intravitreal injection of LMPs in the mouse model of laser-induced CNV significantly suppressed CNV in CD36 dependent manner. The results of this study suggested an ability of LMPs to alter the gene expression pattern of angiogenesis-related factors in macrophages, which provide important information for a new therapeutic approach for efficiently interfering with both vascular and extravascular components of CNV. PMID:27874077

  17. Lymphocytic Microparticles Modulate Angiogenic Properties of Macrophages in Laser-induced Choroidal Neovascularization.

    PubMed

    Tahiri, Houda; Omri, Samy; Yang, Chun; Duhamel, François; Samarani, Suzanne; Ahmad, Ali; Vezina, Mark; Bussières, Martin; Vaucher, Elvire; Sapieha, Przemyslaw; Hickson, Gilles; Hammamji, Karim; Lapointe, Réjean; Rodier, Francis; Tremblay, Sophie; Royal, Isabelle; Cailhier, Jean-François; Chemtob, Sylvain; Hardy, Pierre

    2016-11-22

    Pathological choroidal neovascularization (CNV) is the common cause of vision loss in patients with age-related macular degeneration (AMD). Macrophages possess potential angiogenic function in CNV. We have demonstrated that human T lymphocyte-derived microparticles (LMPs) exert a potent antiangiogenic effect in several pathological neovascularization models. In this study, we investigated the alteration of proangiogenic properties of macrophages by LMPs treatment in vitro and in vivo models. LMPs regulated the expression of several angiogenesis-related factors in macrophages and consequently stimulated their antiangiogenic effects evidenced by the suppression of the proliferation of human retinal endothelial cells in co-culture experiments. The involvement of CD36 receptor in LMPs uptake by macrophages was demonstrated by in vitro assays and by immunostaining of choroidal flat mounts. In addition, ex vivo experiments showed that CD36 mediates the antiangiogenic effect of LMPs in murine and human choroidal explants. Furthermore, intravitreal injection of LMPs in the mouse model of laser-induced CNV significantly suppressed CNV in CD36 dependent manner. The results of this study suggested an ability of LMPs to alter the gene expression pattern of angiogenesis-related factors in macrophages, which provide important information for a new therapeutic approach for efficiently interfering with both vascular and extravascular components of CNV.

  18. Diagnostic evaluation of type 2 (classic) choroidal neovascularization: optical coherence tomography, indocyanine green angiography, and fluorescein angiography.

    PubMed

    Sulzbacher, Florian; Kiss, Christopher; Munk, Marion; Deak, Gabor; Sacu, Stefan; Schmidt-Erfurth, Ursula

    2011-11-01

    To evaluate the diagnostic characteristics of type 2 (classic) choroidal neovascularizations secondary to age-related macular degeneration using spectral domain-optical coherence tomography (SD OCT), indocyanine green angiography (ICGA), and fluorescein angiography (FA). Observational case series. Institutional. Thirteen treatment-naïve eyes with type 2 choroidal neovascularization without an occult component. Greatest horizontal dimension, based on the anatomic features of the neovascular complex by SD OCT (Spectralis; Heidelberg Engineering), ICGA, and FA; retinal leakage area in late-phase FA and ICGA; and the area of retinal edema in SD OCT. For direct comparison, ICGA and FA images were overlaid manually on infrared plus SD OCT images using VirtualDub and Paint.NET software. Greatest horizontal dimension was measured using Image J software (National Institutes of Health). The mean greatest horizontal dimension of the neovascular complex and the retinal leakage area consistently were smaller on ICGA compared with the area of retinal edema on SD OCT. According to FA, the greatest horizontal dimension of early, well-demarcated hyperfluorescence was significantly smaller than the neovascular complex on SD OCT. In addition, the greatest horizontal dimension of the retinal leakage area in late-phase FA consistently was smaller than the area of retinal edema on SD OCT. In classic choroidal neovascularization, ICGA and FA seem to underestimate the extension of the neovascular complex and the associated retinal pathologic features compared with SD OCT imaging. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration

    PubMed Central

    Jia, Yali; Bailey, Steven T.; Wilson, David J.; Tan, Ou; Klein, Michael L.; Flaxel, Christina J.; Potsaid, Benjamin; Liu, Jonathan J.; Lu, Chen D.; Kraus, Martin F.; Fujimoto, James G.; Huang, David

    2014-01-01

    Purpose To detect and quantify choroidal neovascularization (CNV) in age-related macular degeneration (AMD) patients using optical coherence tomography (OCT) angiography. Design Observational, cross-sectional study. Participants Five normal subjects and five neovascular AMD patients were included. Methods Five eyes with neovascular AMD and five normal age-matched controls were scanned by a high-speed (100,000 A-scans/sec) 1050 nm wavelength swept-source OCT. The macular angiography scan covered a 3×3 mm area and comprised 200×200×8 A-scans acquired in 3.5 sec. Flow was detected using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Motion artifacts were removed by three dimensional (3D) orthogonal registration and merging of 4 scans. The 3D angiography was segmented into 3 layers: inner retina (to show retinal vasculature), outer retina (to identify CNV), and choroid. En face maximum projection was used to obtain 2D angiograms from the 3 layers. CNV area and flow index were computed from the en face OCT angiogram of the outer retinal layer. Flow (decorrelation) and structural data were combined in composite color angiograms for both en face and cross-sectional views. Main Outcome Measurements CNV angiogram, CNV area, and CNV flow index. Results En face OCT angiograms of CNVs showed sizes and locations that were confirmed by fluorescein angiography. OCT angiography provided more distinct vascular network patterns that were less obscured by subretinal hemorrhage. The en face angiograms also showed areas of reduced choroidal flow adjacent to the CNV in all cases and significantly reduced retinal flow in one case. Cross-sectional angiograms were used to visualize CNV location relative to the retinal pigment epithelium and Bruch’s layer and classify type I and type II CNV. A feeder vessel could be identified in one case. Higher flow indexes were associated with larger CNV and type II CNV. Conclusions OCT angiography provides depth

  20. Aryl hydrocarbon receptor knock-out exacerbates choroidal neovascularization via multiple pathogenic pathways

    PubMed Central

    Choudhary, Mayur; Kazmin, Dmitri; Hu, Peng; Thomas, Russell S; McDonnell, Donald P; Malek, Goldis

    2015-01-01

    The aryl hydrocarbon receptor (AhR) is a heterodimeric transcriptional regulator with pleiotropic functions in xenobiotic metabolism and detoxification, vascular development and cancer. Herein, we report a previously undescribed role for the AhR signalling pathway in the pathogenesis of the wet, neovascular subtype of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly in the Western world. Comparative analysis of gene expression profiles of aged AhR−/− and wild-type (wt) mice, using high-throughput RNA sequencing, revealed differential modulation of genes belonging to several AMD-related pathogenic pathways, including inflammation, angiogenesis and extracellular matrix regulation. To investigate AhR regulation of these pathways in wet AMD, we experimentally induced choroidal neovascular lesions in AhR−/− mice and found that they measured significantly larger in area and volume compared to age-matched wt mice. Furthermore, these lesions displayed a higher number of ionized calcium-binding adaptor molecule 1-positive (Iba1+) microglial cells and a greater amount of collagen type IV deposition, events also seen in human wet AMD pathology specimens. Consistent with our in vivo observations, AhR knock-down was sufficient to increase choroidal endothelial cell migration and tube formation in vitro. Moreover, AhR knock-down caused an increase in collagen type IV production and secretion in both retinal pigment epithelial (RPE) and choroidal endothelial cell cultures, increased expression of angiogenic and inflammatory molecules, including vascular endothelial growth factor A (VEGFA) and chemokine (C–C motif) ligand 2 (CCL2) in RPE cells, and increased expression of secreted phosphoprotein 1 (SPP1) and transforming growth factor-β1 (TGFβ1) in choroidal endothelial cells. Collectively, our findings identify AhR as a regulator of multiple pathogenic pathways in experimentally induced choroidal neovascularization, findings that

  1. Aryl hydrocarbon receptor knock-out exacerbates choroidal neovascularization via multiple pathogenic pathways.

    PubMed

    Choudhary, Mayur; Kazmin, Dmitri; Hu, Peng; Thomas, Russell S; McDonnell, Donald P; Malek, Goldis

    2015-01-01

    The aryl hydrocarbon receptor (AhR) is a heterodimeric transcriptional regulator with pleiotropic functions in xenobiotic metabolism and detoxification, vascular development and cancer. Herein, we report a previously undescribed role for the AhR signalling pathway in the pathogenesis of the wet, neovascular subtype of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly in the Western world. Comparative analysis of gene expression profiles of aged AhR(-/-) and wild-type (wt) mice, using high-throughput RNA sequencing, revealed differential modulation of genes belonging to several AMD-related pathogenic pathways, including inflammation, angiogenesis and extracellular matrix regulation. To investigate AhR regulation of these pathways in wet AMD, we experimentally induced choroidal neovascular lesions in AhR(-/-) mice and found that they measured significantly larger in area and volume compared to age-matched wt mice. Furthermore, these lesions displayed a higher number of ionized calcium-binding adaptor molecule 1-positive (Iba1(+) ) microglial cells and a greater amount of collagen type IV deposition, events also seen in human wet AMD pathology specimens. Consistent with our in vivo observations, AhR knock-down was sufficient to increase choroidal endothelial cell migration and tube formation in vitro. Moreover, AhR knock-down caused an increase in collagen type IV production and secretion in both retinal pigment epithelial (RPE) and choroidal endothelial cell cultures, increased expression of angiogenic and inflammatory molecules, including vascular endothelial growth factor A (VEGFA) and chemokine (C-C motif) ligand 2 (CCL2) in RPE cells, and increased expression of secreted phosphoprotein 1 (SPP1) and transforming growth factor-β1 (TGFβ1) in choroidal endothelial cells. Collectively, our findings identify AhR as a regulator of multiple pathogenic pathways in experimentally induced choroidal neovascularization, findings that

  2. Role of Intravitreal Antivascular Endothelial Growth Factor Injections for Choroidal Neovascularization due to Choroidal Osteoma

    PubMed Central

    Mansour, Ahmad M.; Al Kahtani, Eman; Zegarra, Hernando; Anand, Rajiv; Ahmadieh, Hamid; Sisk, Robert A.; Mirza, Salman; Tuncer, Samuray; Navea Tejerina, Amparo; Mataix, Jorge; Ascaso, Francisco J.; Pulido, Jose S.; Guthoff, Rainer; Goebel, Winfried; Roh, Young Jung; Banker, Alay S.; Gentile, Ronald C.; Martinez, Isabel Alonso; Morris, Rodney; Panday, Neeraj; Min, Park Jung; Mercé, Emilie; Lai, Timothy Y. Y.; Massoud, Vicky; Ghazi, Nicola G.

    2014-01-01

    We treated 26 eyes of 25 young patients having a mean age of 30 years with intravitreal vascular endothelial growth factor (VEGF) inhibitor for choroidal new vessel (CNV) formation overlying choroidal osteoma over a mean follow-up of 26 months. Mean number of injections was 2.4 at 6 months, 3.2 at 12 months, and 5.5 at 24 months. CNV was subfoveal in 14 eyes, juxtafoveal in 5, extrafoveal in 5, and peripapillary in 2. By paired comparison, mean decrease from baseline was 119.7 microns at 6 months (n = 15; P = 0.001), 105.3 microns at 1 year (n = 10; P = 0.03), and 157.6 microns at 2 years (n = 7; P = 0.08). BCVA improved by 3.3 lines at 6 months after therapy (n = 26; P < 0.001), 2.8 lines (n = 20; P = 0.01) at 1 year, and 3.1 lines (n = 13; P = 0.049) at 2 years. We conclude that intravitreal anti-VEGF injections improve vision in majority of eyes with CNV from choroidal osteoma. PMID:25147732

  3. Role of Intravitreal Antivascular Endothelial Growth Factor Injections for Choroidal Neovascularization due to Choroidal Osteoma.

    PubMed

    Mansour, Ahmad M; Arevalo, J Fernando; Al Kahtani, Eman; Zegarra, Hernando; Abboud, Emad; Anand, Rajiv; Ahmadieh, Hamid; Sisk, Robert A; Mirza, Salman; Tuncer, Samuray; Navea Tejerina, Amparo; Mataix, Jorge; Ascaso, Francisco J; Pulido, Jose S; Guthoff, Rainer; Goebel, Winfried; Roh, Young Jung; Banker, Alay S; Gentile, Ronald C; Martinez, Isabel Alonso; Morris, Rodney; Panday, Neeraj; Min, Park Jung; Mercé, Emilie; Lai, Timothy Y Y; Massoud, Vicky; Ghazi, Nicola G

    2014-01-01

    We treated 26 eyes of 25 young patients having a mean age of 30 years with intravitreal vascular endothelial growth factor (VEGF) inhibitor for choroidal new vessel (CNV) formation overlying choroidal osteoma over a mean follow-up of 26 months. Mean number of injections was 2.4 at 6 months, 3.2 at 12 months, and 5.5 at 24 months. CNV was subfoveal in 14 eyes, juxtafoveal in 5, extrafoveal in 5, and peripapillary in 2. By paired comparison, mean decrease from baseline was 119.7 microns at 6 months (n = 15; P = 0.001), 105.3 microns at 1 year (n = 10; P = 0.03), and 157.6 microns at 2 years (n = 7; P = 0.08). BCVA improved by 3.3 lines at 6 months after therapy (n = 26; P < 0.001), 2.8 lines (n = 20; P = 0.01) at 1 year, and 3.1 lines (n = 13; P = 0.049) at 2 years. We conclude that intravitreal anti-VEGF injections improve vision in majority of eyes with CNV from choroidal osteoma.

  4. Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization.

    PubMed

    Cousins, Scott W; Espinosa-Heidmann, Diego G; Miller, Daniel M; Pereira-Simon, Simone; Hernandez, Eleut P; Chien, Hsin; Meier-Jewett, Courtney; Dix, Richard D

    2012-01-01

    The neovascular (wet) form of age-related macular degeneration (AMD) leads to vision loss due to choroidal neovascularization (CNV). Since macrophages are important in CNV development, and cytomegalovirus (CMV)-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV), laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF), an outcome that requires active virus replication.

  5. MFGE8 Does Not Influence Chorio-Retinal Homeostasis or Choroidal Neovascularization in vivo

    PubMed Central

    Raoul, William; Poupel, Lucie; Tregouet, David-Alexandre; Lavalette, Sophie; Camelo, Serge; Keller, Nicole; Krumeich, Sophie; Calippe, Bertrand; Guillonneau, Xavier; Behar-Cohen, Francine; Cohen, Salomon-Yves; Baatz, Holger; Combadière, Christophe; Théry, Clotilde; Sennlaub, Florian

    2012-01-01

    Purpose Milk fat globule-epidermal growth factor-factor VIII (MFGE8) is necessary for diurnal outer segment phagocytosis and promotes VEGF-dependent neovascularization. The prevalence of two single nucleotide polymorphisms (SNP) in MFGE8 was studied in two exsudative or “wet” Age-related Macular Degeneration (AMD) groups and two corresponding control groups. We studied the effect of MFGE8 deficiency on retinal homeostasis with age and on choroidal neovascularization (CNV) in mice. Methods The distribution of the SNP (rs4945 and rs1878326) of MFGE8 was analyzed in two groups of patients with “wet” AMD and their age-matched controls from Germany and France. MFGE8-expressing cells were identified in Mfge8+/− mice expressing ß-galactosidase. Aged Mfge8+/− and Mfge8−/− mice were studied by funduscopy, histology, electron microscopy, scanning electron microscopy of vascular corrosion casts of the choroid, and after laser-induced CNV. Results rs1878326 was associated with AMD in the French and German group. The Mfge8 promoter is highly active in photoreceptors but not in retinal pigment epithelium cells. Mfge8−/− mice did not differ from controls in terms of fundus appearance, photoreceptor cell layers, choroidal architecture or laser-induced CNV. In contrast, the Bruch's membrane (BM) was slightly but significantly thicker in Mfge8−/− mice as compared to controls. Conclusions Despite a reproducible minor increase of rs1878326 in AMD patients and a very modest increase in BM in Mfge8−/− mice, our data suggests that MFGE8 dysfunction does not play a critical role in the pathogenesis of AMD. PMID:22438901

  6. Influence of Choroidal Neovascularization and Biodegradable Polymeric Particle Size on Transscleral Sustained Delivery of Triamcinolone Acetonide

    PubMed Central

    Kadam, Rajendra S.; Tyagi, Puneet; Edelhauser, Henry F.; Kompella, Uday B.

    2012-01-01

    Purpose One objective of this study was to determine whether polymeric nanoparticles and/or microparticles sustain transscleral choroidal and retinal delivery of triamcinolone acetonide (TA) for two months in therapeutically effective concentrations after single periocular administration. Another objective of this study was to assess the influence of choroidal neovascularization on transscleral delivery of TA. Methods Polymeric nano- and micro-particles of TA were prepared by o/w emulsion- solvent evaporation method using poly-L-lactide (PLA). Particles were characterized for drug loading, size, surface morphology, and the in vitro drug release profile. Choroidal neovascularization (CNV) was induced in brown Norway (BN) rats using a 532 nm diode argon laser and the CNV induction was assessed using fluorescein angiography. In vivo delivery was assessed in control and CNV induced rats at 2 months after periocular injection of TA loaded nano- or micro-particle suspension, or plain TA suspension in PBS (pH7.4). Ocular tissue levels of TA were estimated using LC-MS/MS following liquid-liquid extraction of drug from tissue samples. Nile red loaded microparticles entrapped in periocular tissue at the end of the study were visualized using scanning electron microscopy and confocal microscopy. Inhibitory effect of TA on VEGF secretion was evaluated in ARPE-19 cells. Results Triamcinolone acetonide-PLA nano- (551 nm) and micro-particles (2090 nm), with 14.7 and 29.5 % drug loading, respectively, sustained in vitro TA release for about 45 and 120 days. After subconjunctival injection, microparticles were able to sustain the delivery in all intraocular tissues for 2 months; whereas no drug levels were detected for TA loaded nanoparticles and plain suspension of TA. Intraocular delivery of TA from microparticles was higher in CNV induced rats when compared to control rats. Significant amount of microparticles remained in periocular tissue at 2 months after injection, and

  7. A Proinflammatory Function of Toll-Like Receptor 2 in the Retinal Pigment Epithelium as a Novel Target for Reducing Choroidal Neovascularization in Age-Related Macular Degeneration.

    PubMed

    Feng, Lili; Ju, Meihua; Lee, Kei Ying V; Mackey, Ashley; Evangelista, Mariasilvia; Iwata, Daiju; Adamson, Peter; Lashkari, Kameran; Foxton, Richard; Shima, David; Ng, Yin Shan

    2017-10-01

    Current treatments for choroidal neovascularization, a major cause of blindness for patients with age-related macular degeneration, treat symptoms but not the underlying causes of the disease. Inflammation has been strongly implicated in the pathogenesis of choroidal neovascularization. We examined the inflammatory role of Toll-like receptor 2 (TLR2) in age-related macular degeneration. TLR2 was robustly expressed by the retinal pigment epithelium in mouse and human eyes, both normal and with macular degeneration/choroidal neovascularization. Nuclear localization of NF-κB, a major downstream target of TLR2 signaling, was detected in the retinal pigment epithelium of human eyes, particularly in eyes with advanced stages of age-related macular degeneration. TLR2 antagonism effectively suppressed initiation and growth of spontaneous choroidal neovascularization in a mouse model, and the combination of anti-TLR2 and antivascular endothelial growth factor receptor 2 yielded an additive therapeutic effect on both area and number of spontaneous choroidal neovascularization lesions. Finally, in primary human fetal retinal pigment epithelium cells, ligand binding to TLR2 induced robust expression of proinflammatory cytokines, and end products of lipid oxidation had a synergistic effect on TLR2 activation. Our data illustrate a functional role for TLR2 in the pathogenesis of choroidal neovascularization, likely by promoting inflammation of the retinal pigment epithelium, and validate TLR2 as a novel therapeutic target for reducing choroidal neovascularization. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  8. Intermediate uveitis complicated by choroidal granuloma following subretinal neovascular membrane: case reports.

    PubMed

    Garcia, Carlos Alexandre de Amorim; Segundo, Paulo de Souza; Garcia Filho, Carlos Alexandre de Amorim; Garcia, Ana Cláudia Medeiros de Amorim

    2008-01-01

    Choroidal neovascularization is a very rare complication in intermediate uveitis. A 27-year-old female patient diagnosed with intermediate uveitis two years ago. She presented with 20/200 visual acuity, snowballs, snowbanks, and macular cystoid edema in the right eye observed by fluorescein and optical coherence tomography (OCT). Photocoagulation was performed in the inferior peripheral retina in both eyes. The patient refused to undergo the prescribed clinical treatment. She returned twelve months later presenting with count fingers visual acuity, dry retina and subretinal macular pigmented granuloma observed on OCT. A 15-year-old female patient with decreased visual acuity of 20/400 in the right eye for eight days. She presented with bilateral vasculitis and papilitis, in the right eye, hemorrhage and extramacular subretinal neovascular membrane were observed on fluorescein and OCT. She was treated with 40 mg prednisone and intravitreous injection of 1.25 mg bevacizumab. Five months later she presented with 20/50 visual acuity, and extramacular granuloma observed on OCT. The formation of subretinal granuloma in intermediate uveitis is a possibility when complicated by subretinal neovascular membrane.

  9. Topical Antiangiogenic SRPK1 Inhibitors Reduce Choroidal Neovascularization in Rodent Models of Exudative AMD

    PubMed Central

    Gammons, Melissa V.; Fedorov, Oleg; Ivison, David; Du, Chunyun; Clark, Tamsyn; Hopkins, Claire; Hagiwara, Masatoshi; Dick, Andrew D.; Cox, Russell; Harper, Steven J.; Hancox, Jules C.; Knapp, Stefan; Bates, David O.

    2013-01-01

    Purpose. Exudative AMD (wet AMD) is treated by monthly injection into the eye of anti-VEGF proteins. VEGF is alternatively spliced to produce numerous isoforms that differ in angiogenic activity. Serine-rich protein kinase-1 (SRPK1) has been identified as a regulator of pro-angiogenic VEGF splicing by phosphorylating serine-rich splicing factor-1 (SRSF1), which binds to VEGF pre-mRNA. We tested the hypothesis that topical (eye drop) SRPK1-selective inhibitors could be generated that reduce pro-angiogenic isoforms, and prevent choroidal neovascularization in vivo. Methods. Novel inhibitors were tested for SRPK inhibition in vitro, pro-angiogenic VEGF production in RPE cells by PCR and ELISA, and for inhibition of choroidal neovascularisation in mice and rats. Results. A novel disubstituted furan inhibitor was selective for the SRPK family of kinases and reduced expression of pro-angiogenic but not antiangiogenic VEGF isoforms. This inhibitor and previously identified SRPK inhibitors significantly reduced choroidal neovascularisation in vivo. Topical administration of SRPK inhibitors dose-dependently blocked CNV with an EC50 of 9 μM. Conclusions. These results indicate that novel SRPK1 selective inhibitors could be a potentially novel topical (eye drop) therapeutic for wet AMD. PMID:23887803

  10. 3D choroid neovascularization growth prediction based on reaction-diffusion model

    NASA Astrophysics Data System (ADS)

    Zhu, Shuxia; Chen, Xinjian; Shi, Fei; Xiang, Dehui; Zhu, Weifang; Chen, Haoyu

    2016-03-01

    Choroid neovascularization (CNV) is a kind of pathology from the choroid and CNV-related disease is one important cause of vision loss. It is desirable to predict the CNV growth rate so that appropriate treatment can be planned. In this paper, we seek to find a method to predict the growth of CNV based on 3D longitudinal Optical Coherence Tomography (OCT) images. A reaction-diffusion model is proposed for prediction. The method consists of four phases: pre-processing, meshing, CNV growth modeling and prediction. We not only apply the reaction-diffusion model to the disease region, but also take the surrounding tissues into consideration including outer retinal layer, inner retinal layer and choroid layer. The diffusion in these tissues is considered as isotropic. The finite-element-method (FEM) is used to solve the partial differential equations (PDE) in the diffusion model. The curve of CNV growth with treatment are fitted and then we can predict the CNV status in a future time point. The preliminary results demonstrated that our proposed method is accurate and the validity and feasibility of our model is obvious.

  11. Lipopolysaccharide Promotes Choroidal Neovascularization by Up-Regulation of CXCR4 and CXCR7 Expression in Choroid Endothelial Cell

    PubMed Central

    Feng, Yi-fan; Guo, Hua; Yuan, Fei; Shen, Min-qian

    2015-01-01

    Stromal cell-derived factor-1 (SDF-1) has been confirmed to participate in the formation of choroidal neovascularization (CNV) via its two receptors: CXC chemokine receptors 4 (CXCR4) and CXCR7. Previous studies have indicated that the activation of Toll-like receptors (TLRs) by lipopolysaccharide (LPS) might elevate CXCR4 and/or CXCR7 expression in tumor cells, enhancing the response to SDF-1 to promote invasion and cell dissemination. However, the impact of LPS on the CXCR4 and CXCR7 expression in endothelial cells and subsequent pathological angiogenesis formation remains to be elucidated. The present study shows that LPS enhanced the CXCR4 and CXCR7 expression via activation of the TLR4 pathway in choroid-retinal endothelial (RF/6A) cells. In addition, the transcriptional regulation of CXCR4 and CXCR7 by LPS was found to be mediated by phosphorylation of the extracellular signal-related kinase (ERK) 1/2 and activation of nuclear factor kappa B (NF-κB) signaling pathways, which were blocked by ERK- or NF-κB-specific inhibitors. Furthermore, the increased CXCR4 and CXCR7 expression resulted in increased SDF-1-induced RF/6A cells proliferation, migration and tube formation. In vivo, LPS-treated rat had significantly higher mRNA levels of CXCR4 and CXCR7 expression and lager laser-induced CNV area than vehicle-treated rat. SDF-1 blockade with a neutralizing antibody attenuated the progression of CNV in LPS-treated rat after a single intravitreal injection. Altogether, these results demonstrated that LPS might influence CNV formation by enhancing CXCR7 and CXCR7 expression in endothelial cells, possibly providing a new perspective for the treatment of CNV-associated diseases. PMID:26288180

  12. Identification of Chlamydia pneumoniae within human choroidal neovascular membranes secondary to age-related macular degeneration.

    PubMed

    Kalayoglu, Murat V; Bula, Deisy; Arroyo, Jorge; Gragoudas, Evangelos S; D'Amico, Donald; Miller, Joan W

    2005-11-01

    Age-related macular degeneration (AMD) is a leading cause of blindness in the United States, and increasing evidence suggests that it is an inflammatory disease. The prokaryotic obligate intracellular pathogen Chlamydia pneumoniae is emerging as a novel risk factor in cardiovascular disease, and recent sero-epidemiological data suggest that C. pneumoniae infection is also associated with AMD. In this study, we examined choroidal neovascular membrane (CNV) tissue from patients with neovascular AMD for the presence of C. pneumoniae and determined whether the pathogen can dysregulate the function of key cell types in ways that can cause neovascular AMD. Nine CNV removed from patients with neovascular AMD were examined for the presence of C. pneumoniae by immunohistochemistry (IHC) and polymerase chain reaction (PCR); in addition, we performed PCR on nine non-AMD eyes, and IHC on five non-AMD CNV, seven non-AMD eyes, and one internal limiting membrane specimen. Finally, human monocyte-derived macrophages and retinal pigment epithelial (RPE) cells were exposed to C. pneumoniae and assayed in vitro for the production of pro-angiogenic immunomodulators (VEGF, IL-8, and MCP-1). C. pneumoniae was detected in four of nine AMD CNV by IHC and two of nine AMD CNV by PCR, induced VEGF production by human macrophages, and increased production of IL-8 and MCP-1 by RPE cells. In contrast, none of the 22 non-AMD specimens showed evidence for C. pneumoniae. These data indicate that a pathogen capable of inducing chronic inflammation and pro-angiogenic cytokines can be detected in some AMD CNV, and suggest that infection may contribute to the pathogenesis of AMD.

  13. Type 1 Choroidal Neovascularization Lesion Size: Indocyanine Green Angiography Versus Optical Coherence Tomography Angiography.

    PubMed

    Costanzo, Eliana; Miere, Alexandra; Querques, Giuseppe; Capuano, Vittorio; Jung, Camille; Souied, Eric H

    2016-07-01

    To evaluate the size of type 1 choroidal neovascularization (CNV) in neovascular AMD by optical coherence tomography angiography (OCTA) and to compare with indocyanine green angiography (ICGA). Patients diagnosed type 1 CNV underwent multimodal imaging by fluorescein angiography (FA), ICGA, spectral-domain (SD)-OCT, and OCTA. Lesion size was measured both on OCTA at the choriocapillaris level with "select area" and "vessel area" functions, incorporated in AngioVue software and on ICGA at intermediate and late phases, by two masked independent readers. Nineteen eyes of 17 patients (mean age 80.6 ± 8.36) were included in the analysis. Mean visual acuity was 0.2 logMAR. All OCTA revealed a high flow neovascular network in the choriocapillaris segmentation. On OCTA, interclass correlation between readers 1 and 2 was 0.96 (95% confidence interval [CI] 0.94-0.99) for select area and 0.97 (95% CI 0.96-0.99) for vessel area. The difference between lesion size in OCTA versus ICGA was detected in all eyes and it was statistically significant for both readers (P < 0.05). Optical coherence tomography angiography provides both quantitative and qualitative information on type 1 CNV and appears as a new reproducible way to evaluate CNV area and vessels area. Type 1 CNV lesion size in the choriocapillaris segmentation of OCTA and ICGA intermediate and late phases revealed that the OCTA size is significantly smaller than the ICGA size. This supports the idea that OCTA could be considered for evaluation of the neovascular lesion and for evaluation of therapeutic responses.

  14. Neuroprotectin D1 Attenuates Laser-induced Choroidal Neovascularization in Mouse

    PubMed Central

    Sheets, Kristopher G.; Zhou, Yongdong; Ertel, Monica K.; Knott, Eric J.; Regan, Cornelius E.; Elison, Jasmine R.; Gordon, William C.; Gjorstrup, Per

    2010-01-01

    Purpose To examine the effects of neuroprotectin D1 (NPD1), a stereospecific derivative of docosahexaenoic acid, on choroidal neovascularization (CNV) in a laser-induced mouse model. Specifically, this was assessed by clinically grading laser-induced lesions, measuring leakage area, and volumetrically quantifying vascular endothelial cell proliferation. Methods C57Bl/6 mice were treated with vehicle control or NPD1, and choroidal neovascularization was induced by laser rupture of Bruch's membrane; treatment was administered throughout the first week of recovery. One and two weeks after CNV induction, fundus fluorescein angiography was performed. Angiograms were clinically graded to assess leakage severity, while leakage area was measured by image analysis of angiograms. Proliferation of vascular endothelial cells was evaluated volumetrically by three-dimensional laser confocal immunofluorescent microscopy of cytoskeletal, nuclear, and endothelial cell markers. Results At seven days after CNV induction, NPD1-treated mice had 60% fewer clinically relevant lesions than controls, dropping to 80% fewer by 14 days. NPD1 mice exhibited 25% smaller leakage area than controls at 7 days and 44% smaller area at 14 days. Volumetric immunofluorescence revealed 46% less vascular endothelial cell volume in 7-day NPD1-treated mice than in 7-day controls, and by 14 days NPD1 treatment was 68% lower than controls. Furthermore, comparison of 7- and 14-day volumes of NPD1-treated mice revealed a 50% reduction at 14 days. Conclusions NPD1 significantly inhibits choroidal neovascularization. There are at least two possible mechanisms that could explain the neuroprotective action of NPD1. Ultimately, nuclear factor-κB could be inhibited with a reduction in cyclooxygenase-2 (COX-2) to reduce vascular endothelial growth factor (VEGF) expression, and/or activation of the resolution phase of the inflammatory response/survival pathways could be upregulated. Moreover, NPD1 continues to be

  15. Rap1 GTPase Activation and Barrier Enhancement in RPE Inhibits Choroidal Neovascularization In Vivo

    PubMed Central

    McCloskey, Manabu; Wang, Haibo; Quilliam, Lawrence A.; Chrzanowska-Wodnicka, Magdalena; Hartnett, M. Elizabeth

    2013-01-01

    Loss of barrier integrity precedes the development of pathologies such as metastasis, inflammatory disorders, and blood-retinal barrier breakdown present in neovascular age-related macular degeneration. Rap1 GTPase is involved in regulating both endothelial and epithelial cell junctions; the specific role of Rap1A vs. Rap1B isoforms is less clear. Compromise of retinal pigment epithelium barrier function is a contributing factor to the development of AMD. We utilized shRNA of Rap1 isoforms in cultured human retinal pigment epithelial cells, along with knockout mouse models to test the role of Rap1 on promoting RPE barrier properties, with emphasis on the dynamic junctional regulation that is triggered when the adhesion between cells is challenged. In vitro, Rap1A shRNA reduced steady-state barrier integrity, whereas Rap1B shRNA affected dynamic junctional responses. In a laser-induced choroidal neovascularization (CNV) model of macular degeneration, Rap1b−/− mice exhibited larger CNV volumes compared to wild-type or Rap1a−/−. In vivo, intravitreal injection of a cAMP analog (8CPT-2′-O-Me-cAMP) that is a known Rap1 activator significantly reduced laser-induced CNV volume, which correlated with the inhibition of CEC transmigration across 8CPT-2′O-Me-cAMP-treated RPE monolayers in vitro. Rap1 activation by 8CPT-2′-O-Me-cAMP treatment increased recruitment of junctional proteins and F-actin to cell-cell contacts, increasing both the linearity of junctions in vitro and in cells surrounding laser-induced lesions in vivo. We conclude that in vitro, Rap1A may be important for steady state barrier integrity, while Rap1B is involved more in dynamic junctional responses such as resistance to junctional disassembly induced by EGTA and reassembly of cell junctions following disruption. Furthermore, activation of Rap1 in vivo inhibited development of choroidal neovascular lesions in a laser-injury model. Our data suggest that targeting Rap1 isoforms in vivo with 8

  16. Retinal Inhibition of CCR3 Induces Retinal Cell Death in a Murine Model of Choroidal Neovascularization

    PubMed Central

    Wang, Haibo; Han, Xiaokun; Gambhir, Deeksha; Becker, Silke; Kunz, Eric; Liu, Angelina Jingtong; Hartnett, M. Elizabeth

    2016-01-01

    Inhibition of chemokine C-C motif receptor 3 (CCR3) signaling has been considered as treatment for neovascular age-related macular degeneration (AMD). However, CCR3 is expressed in neural retina from aged human donor eyes. Therefore, broad CCR3 inhibition may be harmful to the retina. We assessed the effects of CCR3 inhibition on retina and choroidal endothelial cells (CECs) that develop into choroidal neovascularization (CNV). In adult murine eyes, CCR3 colocalized with glutamine-synthetase labeled Műller cells. In a murine laser-induced CNV model, CCR3 immunolocalized not only to lectin-stained cells in CNV lesions but also to the retina. Compared to non-lasered controls, CCR3 mRNA was significantly increased in laser-treated retina. An intravitreal injection of a CCR3 inhibitor (CCR3i) significantly reduced CNV compared to DMSO or PBS controls. Both CCR3i and a neutralizing antibody to CCR3 increased TUNEL+ retinal cells overlying CNV, compared to controls. There was no difference in cleaved caspase-3 in laser-induced CNV lesions or in overlying retina between CCR3i- or control-treated eyes. Following CCR3i, apoptotic inducible factor (AIF) was significantly increased and anti-apoptotic factor BCL2 decreased in the retina; there were no differences in retinal vascular endothelial growth factor (VEGF). In cultured human Műller cells exposed to eotaxin (CCL11) and VEGF, CCR3i significantly increased TUNEL+ cells and AIF but decreased BCL2 and brain derived neurotrophic factor, without affecting caspase-3 activity or VEGF. CCR3i significantly decreased AIF in RPE/choroids and immunostaining of phosphorylated VEGF receptor 2 (p-VEGFR2) in CNV with a trend toward reduced VEGF. In cultured CECs treated with CCL11 and/or VEGF, CCR3i decreased p-VEGFR2 and increased BCL2 without increasing TUNEL+ cells and AIF. These findings suggest that inhibition of retinal CCR3 causes retinal cell death and that targeted inhibition of CCR3 in CECs may be a safer if CCR3 inhibition

  17. Retinal Inhibition of CCR3 Induces Retinal Cell Death in a Murine Model of Choroidal Neovascularization.

    PubMed

    Wang, Haibo; Han, Xiaokun; Gambhir, Deeksha; Becker, Silke; Kunz, Eric; Liu, Angelina Jingtong; Hartnett, M Elizabeth

    2016-01-01

    Inhibition of chemokine C-C motif receptor 3 (CCR3) signaling has been considered as treatment for neovascular age-related macular degeneration (AMD). However, CCR3 is expressed in neural retina from aged human donor eyes. Therefore, broad CCR3 inhibition may be harmful to the retina. We assessed the effects of CCR3 inhibition on retina and choroidal endothelial cells (CECs) that develop into choroidal neovascularization (CNV). In adult murine eyes, CCR3 colocalized with glutamine-synthetase labeled Műller cells. In a murine laser-induced CNV model, CCR3 immunolocalized not only to lectin-stained cells in CNV lesions but also to the retina. Compared to non-lasered controls, CCR3 mRNA was significantly increased in laser-treated retina. An intravitreal injection of a CCR3 inhibitor (CCR3i) significantly reduced CNV compared to DMSO or PBS controls. Both CCR3i and a neutralizing antibody to CCR3 increased TUNEL+ retinal cells overlying CNV, compared to controls. There was no difference in cleaved caspase-3 in laser-induced CNV lesions or in overlying retina between CCR3i- or control-treated eyes. Following CCR3i, apoptotic inducible factor (AIF) was significantly increased and anti-apoptotic factor BCL2 decreased in the retina; there were no differences in retinal vascular endothelial growth factor (VEGF). In cultured human Műller cells exposed to eotaxin (CCL11) and VEGF, CCR3i significantly increased TUNEL+ cells and AIF but decreased BCL2 and brain derived neurotrophic factor, without affecting caspase-3 activity or VEGF. CCR3i significantly decreased AIF in RPE/choroids and immunostaining of phosphorylated VEGF receptor 2 (p-VEGFR2) in CNV with a trend toward reduced VEGF. In cultured CECs treated with CCL11 and/or VEGF, CCR3i decreased p-VEGFR2 and increased BCL2 without increasing TUNEL+ cells and AIF. These findings suggest that inhibition of retinal CCR3 causes retinal cell death and that targeted inhibition of CCR3 in CECs may be a safer if CCR3 inhibition

  18. Thy-1 Regulates VEGF-Mediated Choroidal Endothelial Cell Activation and Migration: Implications in Neovascular Age-Related Macular Degeneration

    PubMed Central

    Wang, Haibo; Han, Xiaokun; Kunz, Eric; Hartnett, M. Elizabeth

    2016-01-01

    Purpose This study addresses the hypothesis that age-related stresses upregulate Thy-1 in choroidal endothelial cells (CECs) and contribute to CEC activation and migration, processes important in choroidal neovascularization (CNV). Methods Measurements were made of Thy-1 protein (Western blot) in CECs and Thy-1 mRNA (real time quantitative PCR) in CECs treated with VEGF, CCL11, or PBS or in RPE/choroids from young or old donors or lasered or nonlasered mice. Immunolabeled Thy-1 in ocular sections was compared from young versus old human donor eyes or those with or without neovascular AMD or from lasered versus nonlasered mice. Choroidal endothelial cells transfected with Thy-1 or control siRNA or pretreated with Thy-1 blocking peptide or control were stimulated with VEGF or 7-ketocholesterol (7-KC). Choroidal endothelial cell migration, proliferation, cytoskeletal stress fibers, Rac1 activation, and phosphorylated VEGF receptor 2 (VEGFR2), integrin β3, and Src were measured. Statistics were performed using ANOVA. Results Thy-1 was expressed in retinal ganglion cells and in vascular endothelial-cadherin–labeled choroid and localized to human or mouse laser-induced CNV lesions. Thy-1 protein and mRNA were significantly increased in CECs treated with VEGF or CCL11 and in RPE/choroids from aged versus young donor eyes or from lasered mice versus nonlasered controls. Knockdown or inhibition of Thy-1 in CECs significantly reduced VEGF-induced CEC migration and proliferation, stress fiber formation and VEGFR2, Src, integrin β3 and Rac1 activation, and 7-KC–induced Rac1 and Src activation. Conclusions Thy-1 in CECs regulates VEGF-induced CEC activation and migration and links extracellular 7-KC to intracellular signaling. Future studies elucidating Thy-1 mechanisms in neovascular AMD are warranted. PMID:27768790

  19. Geographic Atrophy and Choroidal Neovascularization in the Same Eye: A Review.

    PubMed

    Kaszubski, Patrick; Ben Ami, Tal; Saade, Celine; Smith, R Theodore

    2016-01-01

    Geographic atrophy (GA) and choroidal neovascularization (CNV), the two late forms of age-related macular degeneration, are generally considered two distinct entities. However, GA and CNV can occur simultaneously in the same eye, with GA usually occurring first. The prevalence of this combined entity is higher in histological studies than in clinical studies. No distinct systemic or genetic risk characteristics are associated with the combined GA/CNV entity, although on clinical examination and retinal imaging it can feature drusen or subretinal drusenoid deposits. GA and CNV may exist within the spectrum of a single disease, or they may be two very different diseases. Therapy with antivascular endothelial growth factor (anti-VEGF) is often successful for CNV, but some evidence suggests increased rates of GA development in eyes treated with anti-VEGF. In this article, we review the current literature regarding the epidemiology, clinical presentation, and treatment options for patients with the combined GA/CNV entity.

  20. Nonrigid registration of 3D longitudinal optical coherence tomography volumes with choroidal neovascularization

    NASA Astrophysics Data System (ADS)

    Wei, Qiangding; Shi, Fei; Zhu, Weifang; Xiang, Dehui; Chen, Haoyu; Chen, Xinjian

    2017-02-01

    In this paper, we propose a 3D registration method for retinal optical coherence tomography (OCT) volumes. The proposed method consists of five main steps: First, a projection image of the 3D OCT scan is created. Second, the vessel enhancement filter is applied on the projection image to detect vessel shadow. Third, landmark points are extracted based on both vessel positions and layer information. Fourth, the coherent point drift method is used to align retinal OCT volumes. Finally, a nonrigid B-spline-based registration method is applied to find the optimal transform to match the data. We applied this registration method on 15 3D OCT scans of patients with Choroidal Neovascularization (CNV). The Dice coefficients (DSC) between layers are greatly improved after applying the nonrigid registration.

  1. Combined choroidal neovascularization and hypopituitarism in a patient with homozygous mutation in methylenetetrahydrofolate reductase gene

    PubMed Central

    Aydogdu, Aydogan; Haymana, Cem; Baskoy, Kamil; Durukan, Ali H.; Ozgur, Gokhan; Azal, Omer

    2014-01-01

    We report a case of choroidal neovascularization (CNV) secondary to methylenetetrahydrofolate reductase (MTHFR) gene mutation in a 20-year-old male patient with hypopituitarism. Treatment with three consecutive injections of intravitreal ranibizumab (anti-vascular endothelial growth factor) resulted in significant improvement of the patient's vision and the appearance of the macula. A search of the literature produced no previously reported case of MTHFR gene mutation associated both CNV and possibly hypopituitarism. With hormone replacement therapy of hypopituitarism, acetyl salicylic acid 100 mg/day also was started. The patient was clinically stable both for CNV and other thromboembolic disorders over a 6-month follow-up and also 1-year follow-up period. PMID:24672570

  2. Drusen complement components C3a and C5a promote choroidal neovascularization

    PubMed Central

    Nozaki, Miho; Raisler, Brian J.; Sakurai, Eiji; Sarma, J. Vidya; Barnum, Scott R.; Lambris, John D.; Chen, Yali; Zhang, Kang; Ambati, Balamurali K.; Baffi, Judit Z.; Ambati, Jayakrishna

    2006-01-01

    Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in industrialized nations, affecting 30–50 million people worldwide. The earliest clinical hallmark of AMD is the presence of drusen, extracellular deposits that accumulate beneath the retinal pigmented epithelium. Although drusen nearly always precede and increase the risk of choroidal neovascularization (CNV), the late vision-threatening stage of AMD, it is unknown whether drusen contribute to the development of CNV. Both in patients with AMD and in a recently described mouse model of AMD, early subretinal pigmented epithelium deposition of complement components C3 and C5 occurs, suggesting a contributing role for these inflammatory proteins in the development of AMD. Here we provide evidence that bioactive fragments of these complement components (C3a and C5a) are present in drusen of patients with AMD, and that C3a and C5a induce VEGF expression in vitro and in vivo. Further, we demonstrate that C3a and C5a are generated early in the course of laser-induced CNV, an accelerated model of neovascular AMD driven by VEGF and recruitment of leukocytes into the choroid. We also show that genetic ablation of receptors for C3a or C5a reduces VEGF expression, leukocyte recruitment, and CNV formation after laser injury, and that antibody-mediated neutralization of C3a or C5a or pharmacological blockade of their receptors also reduces CNV. Collectively, these findings establish a mechanistic basis for the clinical observation that drusen predispose to CNV, revealing a role for immunological phenomena in angiogenesis and providing therapeutic targets for AMD. PMID:16452172

  3. Bilateral midperipheral large drusen and retinal pigment epithelial detachments associated with multifocal areas of choroidal neovascularization: a histopathologic study.

    PubMed

    Tabandeh, Homayoun; Dubovy, Sander; Green, W Richard

    2006-01-01

    The ocular histopathologic features of a patient with bilateral multiple midperipheral areas of choroidal vascularization, large drusen, and detachments of the retinal pigment epithelium (RPE) are presented. The eyes were obtained at autopsy and fixed in 4% buffered formaldehyde. Serial sections through the macula area and inferior segments were prepared. Light as well as electron microscopy was performed. Microscopic examination disclosed numerous large drusen measuring up to 200 micro m in height and 280 micro m in diameter and areas of serous RPE detachments in the midperiphery of both eyes. Some of the large drusen had choroidal vascularization. Areas of sub-RPE neovascularization that measured up to 6.5 mm in diameter were present in the midperiphery of both eyes. The choroidal origin for neovascularization was evident in 10 areas. A 1-mm area of hemorrhagic detachment of the RPE contiguous with choroidal neovascularization (CNV) was present in the immediate postequatorial area temporally in the left eye. No drusen, basal deposit, or CNV was present in the macular area. Multifocal midperipheral RPE detachments and CNV can occur in the absence of significant age-related macular disease.

  4. Bilateral choroidal neovascularization associated with optic nerve head drusen treated by antivascular endothelial growth factor therapy

    PubMed Central

    Delas, Barbara; Almudí, Lorena; Carreras, Anabel; Asaad, Mouafk

    2012-01-01

    Objective To report a good clinical outcome in a patient with bilateral choroidal neovascularization (CNV) associated with optic nerve head drusen (ONHD) treated with intravitreal ranibizumab injection. Methods A 12-year-old girl was referred for loss of right eye vision detected in a routine check-up. Best-corrected visual acuity (BCVA) was hand movements in the right eye and 0.9 in the left eye. Funduscopy revealed the presence of superficial and buried bilateral ONHD, which was confirmed by ultrasonography and computed tomography, and the study was completed with perimetry. The presence of bilateral CNV, active in the right eye, was observed and subsequently confirmed using fluorescein angiography and optical coherence tomography. Results Treatment with two consecutive injections of intravitreal ranibizumab resulted in inactivation of the neovascular membrane with subretinal fluid reabsorption and improved right eye BCVA. After 12 months’ follow-up, this was 20/60 and stable. Conclusion Although there are no published studies of safety in children, antiangiogenic therapy for CNV secondary to ONHD may be useful and safe. A search of the literature produced only one previously reported case of ONHD-associated CNV treated with antivascular endothelial growth factor alone. PMID:22368440

  5. Gut microbiota influences pathological angiogenesis in obesity-driven choroidal neovascularization.

    PubMed

    Andriessen, Elisabeth Mma; Wilson, Ariel M; Mawambo, Gaelle; Dejda, Agnieszka; Miloudi, Khalil; Sennlaub, Florian; Sapieha, Przemyslaw

    2016-12-01

    Age-related macular degeneration in its neovascular form (NV AMD) is the leading cause of vision loss among adults above the age of 60. Epidemiological data suggest that in men, overall abdominal obesity is the second most important environmental risk factor after smoking for progression to late-stage NV AMD To date, the mechanisms that underscore this observation remain ill-defined. Given the impact of high-fat diets on gut microbiota, we investigated whether commensal microbes influence the evolution of AMD Using mouse models of NV AMD, microbiotal transplants, and other paradigms that modify the gut microbiome, we uncoupled weight gain from confounding factors and demonstrate that high-fat diets exacerbate choroidal neovascularization (CNV) by altering gut microbiota. Gut dysbiosis leads to heightened intestinal permeability and chronic low-grade inflammation characteristic of inflammaging with elevated production of IL-6, IL-1β, TNF-α, and VEGF-A that ultimately aggravate pathological angiogenesis. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  6. Inhibition of Choroidal Neovascularization by Intravenous Injection of Adenoviral Vectors Expressing Secretable Endostatin

    PubMed Central

    Mori, Keisuke; Ando, Akira; Gehlbach, Peter; Nesbitt, David; Takahashi, Kyoichi; Goldsteen, Donna; Penn, Michael; Chen, Cheauyan T.; Mori, Keiko; Melia, Michele; Phipps, Sandrina; Moffat, Diana; Brazzell, Kim; Liau, Gene; Dixon, Katharine H.; Campochiaro, Peter A.

    2001-01-01

    Endostatin is a cleavage product of collagen XVIII that inhibits tumor angiogenesis and growth. Interferon α2a blocks tumor angiogenesis and causes regression of hemangiomas, but has no effect on choroidal neovascularization (CNV). Therefore, inhibitors of tumor angiogenesis do not necessarily inhibit ocular neovascularization. In this study, we used an intravenous injection of adenoviral vectors containing a sig-mEndo transgene consisting of murine immunoglobulin κ-chain leader sequence coupled to sequence coding for murine endostatin to investigate the effect of high serum levels of endostatin on CNV in mice. Mice injected with a construct in which sig-mEndo expression was driven by the Rous sarcoma virus promoter had moderately high serum levels of endostatin and significantly smaller CNV lesions at sites of laser-induced rupture of Bruch’s membrane than mice injected with null vector. Mice injected with a construct in which sig-mEndo was driven by the simian cytomegalovirus promoter had ∼10-fold higher endostatin serum levels and had nearly complete prevention of CNV. There was a strong inverse correlation between endostatin serum level and area of CNV. This study provides proof of principle that gene therapy to increase levels of endostatin can prevent the development of CNV and may provide a new treatment for the leading cause of severe loss of vision in patients with age-related macular degeneration. PMID:11438478

  7. The Anti-angiogenic Effect of Chlorogenic Acid on Choroidal Neovascularization

    PubMed Central

    Kim, Cinoo; Yu, Hyeong Gon

    2010-01-01

    Purpose To evaluate the inhibitory effect of chlorogenic acid on laser-induced choroidal neovascularization (CNV) in a rat model. Methods Intraperitoneal injection of chlorogenic acid (10 mg/kg) was inititated one day prior to laser photocoagulation and continued for eight days. Eyes were removed 14 days after laser photocoagulation. Fluorescein angiography was employed at seven and 14 days to assess the CNV lesions, and histological examination was performed. Quantification of CNV size and leakage were performed both in histological sections and fluorescein angiography in order to compare the inhibitory effects of chlorogenic acid on CNV with the results of the control. Results Histological analysis showed no significant difference in CNV size between the treated and control groups. However, CNV leakage on fluorescein angiography had significantly decreased in the chlorogenic acid-treated group at 14 days after laser photocoagulation compared with that of the control group. In addition, CNV size on fluorescein angiography had significantly decreased in the treated group at seven and 14 days. Conclusions These results suggest that chlorogenic acid has anti-angiogenic effects on CNV and may be useful as an inhibitor in the treatment or prevention of neovascular age-related macular degeneration. PMID:20532143

  8. Block copolymers encapsulated poly (aryl benzyl ether) dendrimer silicon (IV) phthalocyanine for in vivo and in vitro photodynamic efficacy of choroidal neovascularization

    NASA Astrophysics Data System (ADS)

    Wang, Xiongwei; Chen, Kuizhi; Huang, Zheng; Peng, Yiru

    2015-03-01

    A novel series of poly (aryl benzyl ether) dendrimer silicon phthalocyanines loaded block copolymers ethoxypoly(ethylene glycol)-poly (lactic-co-glycolic acid) (MPEG-PLGA)were formed. The time-dependent intracellular uptake of nanoparticles in HUVECs cells increased as they were incorporated into nanoparticles. With its highly effective selective accumulation on choroidal neovascularization(CNV). This treatment resulted in a efficacious choroidal neovascularization (CNV) occlusion with minimal unfavorable phototoxicity.

  9. Preferential Hyperacuity Perimeter (PreView PHP) for detecting choroidal neovascularization study.

    PubMed

    Alster, Yair; Bressler, Neil M; Bressler, Susan B; Brimacombe, Judith A; Crompton, R Michael; Duh, Yi-Jing; Gabel, Veit-Peter; Heier, Jeffrey S; Ip, Michael S; Loewenstein, Anat; Packo, Kirk H; Stur, Michael; Toaff, Techiya

    2005-10-01

    To assess the ability of the Preferential Hyperacuity Perimeter (PreView PHP; Carl Zeiss Meditec, Dublin, CA) to detect recent-onset choroidal neovascularization (CNV) resulting from age-related macular degeneration (AMD) and to differentiate it from an intermediate stage of AMD. Prospective, comparative, concurrent, nonrandomized, multicenter study. Eligible participants' study eyes had a corrected visual acuity of 20/160 or better and either untreated CNV from AMD diagnosed within the last 60 days or an intermediate stage of AMD. After obtaining consent, visual acuity with habitual correction, masked PHP testing, stereoscopic color fundus photography, and fluorescein angiography were performed. Photographs and angiograms were evaluated by graders masked to diagnosis and PHP results. The reading center's diagnosis determined if the patient was categorized as having intermediate AMD or neovascular AMD. A successful study outcome was defined a priori as a sensitivity of at least 80% and a specificity of at least 80%. Of 185 patients who gave consent to be enrolled, 11 (6%) had PHP results judged to be unreliable. An additional 52 were not included because they did not meet all eligibility criteria. Of the remaining 122 patients, 57 had an intermediate stage of AMD and 65 had neovascular AMD. The sensitivity to detect newly diagnosed CNV using PHP testing was 82% (95% confidence interval [CI], 70%-90%). The specificity to differentiate newly diagnosed CNV from the intermediate stage of AMD using PHP testing was 88% (95% CI, 76%-95%). Preferential Hyperacuity Perimeter testing can detect recent-onset CNV resulting from AMD and can differentiate it from an intermediate stage of AMD with high sensitivity and specificity. These data suggest that monitoring with PHP should detect most cases of CNV of recent onset with few false-positive results at a stage when treatment usually would be beneficial. Thus, this monitoring should be considered in the management of the

  10. Complement Regulatory Protein CD46 Protects against Choroidal Neovascularization in Mice

    PubMed Central

    Lyzogubov, Valeriy; Wu, Xiaobo; Jha, Purushottam; Tytarenko, Ruslana; Triebwasser, Michael; Kolar, Grant; Bertram, Paula; Bora, Puran S.; Atkinson, John P.; Bora, Nalini S.

    2015-01-01

    Dysregulation of the complement system is increasingly recognized as a contributing factor in age-related macular degeneration. Although the complement regulator CD46 is expressed ubiquitously in humans, in mouse it was previously thought to be expressed only on spermatozoa. We detected CD46 mRNA and protein in the posterior ocular segment (neuronal retina, retinal pigment epithelium, and choroid) of wild-type (WT) C57BL/6J mice. Cd46−/− knockout mice exhibited increased levels of the membrane attack complex and of vascular endothelial growth factor (VEGF) in the retina and choroid. The Cd46−/− mice were also more susceptible to laser-induced choroidal neovascularization (CNV). In Cd46−/− mice, 19% of laser spots were positive for CNV at day 2 after treatment, but no positive spots were detected in WT mice. At day 3, 42% of laser spots were positive in Cd46−/− mice, but only 11% in WT mice. A fully developed CNV complex was noted in both Cd46−/− and WT mice at day 7; however, lesion size was significantly (P < 0.05) increased in Cd46−/− mice. Our findings provide evidence for expression of CD46 in the mouse eye and a role for CD46 in protection against laser-induced CNV. We propose that the Cd46−/− mouse has a greater susceptibility to experimental CNV because of insufficient complement inhibition, which leads to increased membrane attack complex deposition and VEGF expression. PMID:25019227

  11. Inhibition of choroidal neovascularization by lentivirus-mediated PEDF gene transfer in rats

    PubMed Central

    Yu, Ya-Jie; Mo, Bin; Liu, Lu; Yue, Yan-Kun; Yue, Chang-Li; Liu, Wu

    2016-01-01

    AIM To evaluate the effects of lentivirus-mediated pigment epithelium-derived factor (PEDF) gene transfer performed in treatment of rats with established choroidal neovascularization (CNV), and investigates the mechanism by which PEDF inhibits CNV in rats. METHODS Brown Norway (BN) rats (n=204) were induced by exposure to a laser, and then randomly assigned to 3 groups: no treatment; treatments with intravitreal injection of lentivirus-PEDF-green fluorescent protein (GFP) or lentivirus-control GFP (free fluorescent protein). Following induction and treatment, the CNV tissue was assessed for form, size and vessel leakage by fluorescein fundus angiography (FFA), optical coherence tomography (OCT), histopathology, and examination of choroidal flat mounts. VEGF, Flk-1, and PEDF expression were evaluated by real-time polymerase chain reaction (PCR) and Western blot. RESULTS A stable laser-induced rat model of CNV was successfully established, and used to demonstrate lentivirus-mediated PEDG gene transfer by intravitreal injection. Expression of green fluorescence labelled PEDF was observed in the retina up to 28d after injection. An intravitreal injection of lentivirus-PEDF-GFP at 7d led to a significant reduction in the size, thickness and area of CNV showed by FFA, OCT and choroidal flat mounts. PEDF was up-regulated while VEGF and Flk-1 were down-regulated in the lentivirus-PEDF-GFP group. The differences in VEGF and Flk-1 expression in the control and lentivirus-PEDF groups at 7, 14, 21 and 28d after laser induction were all statistically significant. CONCLUSION Lentivirus-mediated PEDF gene transfer is effective for use in treatment of laser-induced CNV, and PEDF exerts its therapeutic effects by inhibiting expression of VEGF and Flk-1. PMID:27588264

  12. Enhanced depth imaging optical coherence tomography of choroidal osteoma with secondary neovascular membranes: report of two cases.

    PubMed

    Mello, Patrícia Correa de; Berensztejn, Patricia; Brasil, Oswaldo Ferreira Moura

    2016-01-01

    We report enhanced depth imaging optical coherence tomography (EDI-OCT) features based on clinical and imaging data from two newly diagnosed cases of choroidal osteoma presenting with recent visual loss secondary to choroidal neovascular membranes. The features described in the two cases, compression of the choriocapillaris and disorganization of the medium and large vessel layers, are consistent with those of previous reports. We noticed a sponge-like pattern previously reported, but it was subtle. Both lesions had multiple intralesional layers and a typical intrinsic transparency with visibility of the sclerochoroidal junction.

  13. Relapse of choroidal neovascularization in Bietti's crystalline retinopathy following anti-vascular endothelial growth factor therapy: A case report

    PubMed Central

    HUA, RUI; CHEN, KANG; HU, YUEDONG; WANG, XINLING; CHEN, LEI

    2015-01-01

    Choroidal neovascularization secondary to retinitis pigmentosa is rarely observed in clinical practice. The present study describes a case of atypical retinitis pigmentosa, crystalline retinal pigmentary degeneration, complicated by choroidal neovascularization (CNV) in a 26-year-old man presenting with blurred vision in the right eye. Heidelberg multimodality imaging was performed to achieve a confirmed diagnosis. Bevacizumab was injected once intravitreally. The 3-month follow-up included visualization of the lesion's regression with spectral domain optical coherence tomography (SD-OCT). However, at 3 months after the injection, the CNV reoccurred. To the best of our knowledge, this is the first time that a case of CNV secondary to retinitis pigmentosa, in which the diagnosis was confirmed via multimodality imaging and the therapeutic efficacy was evaluated by SD-OCT, has been reported in China. PMID:26640540

  14. Incident choroidal neovascularization in fellow eyes of patients with unilateral subfoveal choroidal neovascularization secondary to age-related macular degeneration: SST report No. 20 from the Submacular Surgery Trials Research Group.

    PubMed

    Solomon, Sharon D; Jefferys, Joan L; Hawkins, Barbara S; Bressler, Neil M

    2007-10-01

    To describe incident choroidal neovascular lesions in fellow eyes of participants in the Submacular Surgery Trials who had age-related macular degeneration (AMD). Review of baseline fluorescein angiograms confirmed the absence of neovascular AMD in fellow eyes of 364 participants at risk. Subjects were eligible for a minimum of 2 years of follow-up with angiograms of eyes at risk reevaluated to estimate incidence rates of choroidal neovascularization (CNV) and to characterize these lesions. Incidence of CNV during follow-up, characteristics of the incident lesion (composition, size, and location), and visual acuity at the time of incidence. Incident lesions were confirmed in 98 fellow eyes of participants, yielding 2- and 4-year cumulative incidence rates of 22% and 37%. Incident lesions were predominantly CNV in 87 fellow eyes (90%), extrafoveal in 29 fellow eyes (30%), and juxtafoveal in 9 fellow eyes (9%). Occult without classic CNV lesions were found in 64 eyes (67%), minimally classic CNV and predominantly classic CNV lesions in 12 eyes (13%) each, and predominantly blood lesions in 4 eyes (4%). Nearly two-thirds of all incident lesions were 3 disc areas or smaller in size. Median visual acuity decreased from 20/25 at baseline to 20/250 at the 4-year follow-up in fellow eyes with incident CNV. CONCLUSIONS AND APPLICATION TO CLINICAL PRACTICE: Frequent angiographic follow-up of fellow eyes at risk for CNV may lead to earlier detection and treatment of neovascular AMD and better visual acuity outcomes.

  15. Metabolic Syndrome Triggered by High-Fructose Diet Favors Choroidal Neovascularization and Impairs Retinal Light Sensitivity in the Rat

    PubMed Central

    Thierry, Magalie; Pasquis, Bruno; Acar, Niyazi; Grégoire, Stéphane; Febvret, Valérie; Buteau, Bénédicte; Gambert-Nicot, Ségolène; Bron, Alain M.; Creuzot-Garcher, Catherine P.; Bretillon, Lionel

    2014-01-01

    Diabetic retinopathy and age-related macular degeneration are the leading causes of blindness in Western populations. Although it is a matter of controversy, large-scale population-based studies have reported increased prevalence of age-related macular degeneration in patients with diabetes or diabetic retinopathy. We hypothesized that metabolic syndrome, one of the major risk factors for type 2 diabetes, would represent a favorable environment for the development of choroidal neovascularization, the main complication of age-related macular degeneration. The fructose-fed rat was used as a model for metabolic syndrome in which choroidal neovascularization was induced by laser photocoagulation. Male Brown Norway rats were fed for 1, 3, and 6 months with a standard equilibrated chow diet or a 60%-rich fructose diet (n = 24 per time point). The animals expectedly developed significant body adiposity (+17%), liver steatosis at 3 and 6 months, hyperleptinemia at 1 and 3 months (two-fold increase) and hyperinsulinemia at 3 and 6 months (up to two-fold increase), but remained normoglycemic and normolipemic. The fructose-fed animals exhibited partial loss of rod sensitivity to light stimulus and reduced amplitude of oscillatory potentials at 6 months. Fructose-fed rats developed significantly more choroidal neovascularization at 14 and 21 days post-laser photocoagulation after 1 and 3 months of diet compared to animals fed the control diet. These results were consistent with infiltration/activation of phagocytic cells and up-regulation of pro-angiogenic gene expression such as Vegf and Leptin in the retina. Our data therefore suggested that metabolic syndrome would exacerbate the development of choroidal neovascularization in our experimental model. PMID:25380250

  16. Effect of cytokeratin 17 on retinal pigment epithelium degeneration and choroidal neovascularization

    PubMed Central

    Shen, Yi; Zhuang, Pei; Xiao, Tao; Chiou, George CY

    2016-01-01

    AIM To study the effects of cytokeratin 17 (CK17) on sodium iodate (NaIO3) induced rat retinal pigment epithelium (RPE) degeneration, laser induced rat choroidal neovascularization (CNV), and oxidative stress of human retinal pigment epithelium cells (ARPE-19) and human umbilical vein endothelial cell (HUVEC). METHODS Thirty 8-week-old male Brown Norway rats were randomly divided into 3 groups, 10 rats in control group treated with solvent alone; 10 rats in NaIO3 group treated with solvent and 35 mg/kg NaIO3 injection through hypoglossal vein and 10 rats in CK17+NaIO3 group treated with 1% CK17 eye drop 3 times a day for 1wk before and 4wk after NaIO3 injection. RPE function was measured with c-wave of electroretinogram (ERG). Another 20 rats were randomly divided into 2 groups. Of them 10 rats in CK17 group were anesthetized to receive Nd:YAG laser and given 1% CK17 eye drop before same as above; 10 rats in control were received Nd:YAG and treated with solvent. The development of choroidal neovascularization (CNV) was determined by fundus fluorescein angiography (FFA) performed on 4wk after laser. Methylthiazoly tetrazolium (MTT) assay was used to study effect of CK17 on various oxidants induced injury in ARPE-19 and HUVEC in vitro. RESULTS Four weeks after NaIO3 injection, the c-wave amplitude of ERG was 0.393±0.02 V in the control group, 0.184±0.018 V in NaIO3 group and 0.3±0.01 V in CK17+NaIO3 group. There was a significant reversal of the c-wave by CK17 as compared to NaIO3 group (P<0.01). Four weeks after laser, the size of the CNV lesion was 2.57±0.27 mm2 in control group and 1.64±0.08 mm2 in CK17 group. The lesion size significantly diminished in CK17 group (P<0.01). The in vitro results showed CK17 also reversed the various oxidants induced injuries in ARPE-19 at the dose of 100 µg/mL and enhanced the injury in HUVECs at different concentrations. CONCLUSION CK17 can significantly protect RPE from NaIO3 induced degeneration in vivo and in vitro and

  17. Surgery for Hemorrhagic Choroidal Neovascular Lesions of Age-Related Macular Degeneration: Ophthalmic Findings

    PubMed Central

    2005-01-01

    Purpose To present best-corrected visual acuity (BCVA) findings and other clinical outcomes from eyes of patients enrolled in one of the Submacular Surgery Trials (SST) evaluating surgical removal versus observation of predominantly hemorrhagic subfoveal choroidal neovascularization (CNV) associated with age-related macular degeneration. Design Randomized clinical trial (SST Group B Trial). Participants Eligible patients had subfoveal choroidal neovascular lesions greater than 3.5 disk areas (8.9 mm2) composed of at least 50% blood (either blood or CNV underlying the center of the foveal avascular zone) and BCVA of 20/100 to light perception in the study eye. Intervention Patients were assigned randomly at time of enrollment to observation or surgical removal of blood and any associated CNV. Main Outcome Measure A successful outcome was defined a priori as either improvement in visual acuity (VA), no change in VA, or a decline in VA of no more than 1 line (7 letters) from baseline to the 24-month examination based on an intent-to-treat analysis. Results Of 336 patients enrolled, 168 were assigned to each treatment arm; treatment arms were balanced by baseline characteristics. Of 1501 expected examinations 3 months through 36 months after baseline, 1370 (91%) were performed. Loss of ≥2 lines (≥8 letters) of VA occurred in 56% of surgery eyes, versus 59% of observation eyes examined at 24 months. Although severe loss of VA was not the primary outcome of interest, surgery more often prevented such loss: 36% in the observation arm versus 21% in the surgery arm at the 24-month examination (χ2 P = 0.004). Of initially phakic eyes, the cumulative percentage that had undergone cataract surgery by 24 months was 44% in the surgery arm, compared with 6% in the observation arm. Twenty-seven eyes (16%) in the surgical arm, compared with 3 eyes (2%) in the observation arm, had a rhegmatogenous retinal detachment (RD). Conclusions Submacular surgery as performed in the SST

  18. Ocular Safety of Intravitreal Propranolol and Its Efficacy in Attenuation of Choroidal Neovascularization

    PubMed Central

    Nourinia, Ramin; Rezaei Kanavi, Mozhgan; Kaharkaboudi, Amir; Taghavi, Seyed Iman; Aldavood, Seyed Javid; Darjatmoko, Soesiawati R.; Wang, Shoujian; Gurel, Zafer; Lavine, Jeremy A.; Safi, Sare; Ahmadieh, Hamid; Daftarian, Narsis; Sheibani, Nader

    2015-01-01

    Purpose Determine the safe dose of intravitreal propranolol (IVP), and evaluate its inhibitory effect on laser-induced choroidal neovascularization (CNV). Methods To determine the IVP safe dose, 32 rabbits were divided into 4 groups. Three of these groups received IVP (15 μL) corresponding to 15 μg (group B), 30 μg (group C), and 60 μg (group D). The control group (A) received 15 μL saline. Safety was assessed by ocular examination, electroretinography (ERG), routine histopathologic evaluation, immunohistochemistry for glial fibrillary acidic protein (GFAP), and real-time qPCR for GFAP, VEGF, thrombospondin 1 (TSP1), and pigment epithelium-derived factor (PEDF). A similar experiment was performed in 24 mice by using a 100-fold lower amount of propranolol (0.15, 0.3, and 0.6 μg in 2 μL) based on vitreous volume. For assessment of the angioinhibitory effects of IVP, CNV was induced in 42 mice via laser burns. Mice were divided into two groups: group 1 received the safe dose of IVP (0.3 μg in 2 μL) and group 2 received saline. Neovascularization area was quantified by intercellular adhesion molecule (ICAM)-2 immunostaining of choroidal–scleral flat mounts by using ImageJ software. Results According to clinical, ERG, and histopathologic findings, 30 μg IVP was chosen as the safe dose in rabbit eyes, comparable to 0.3 μg IVP in mouse eyes. As compared to the control eyes, the development of CNV was attenuated (4.8-fold) in mice receiving 0.3 μg IVP. Conclusions Intravitreal propranolol injection up to the final dose of 30 μg in rabbits and 0.3 μg in mice was safe, and was effective in attenuation of CNV in mice. PMID:26720475

  19. Neovascular Glaucoma After Stereotactic Radiotherapy for Juxtapapillary Choroidal Melanoma: Histopathologic and Dosimetric Findings

    SciTech Connect

    Fernandes, Bruno F.; Weisbrod, Daniel; Yuecel, Yeni H.; Follwell, Matthew; Krema, Hatem; Heydarian, Mostafa; Xu Wei; Payne, David; McGowan, Hugh; Simpson, Ernest R.; Laperriere, Normand; Sahgal, Arjun

    2011-06-01

    Purpose: Enucleation after stereotactic radiotherapy (SRT) for juxtapapillary choroidal melanoma may be required because of tumor progression (TP) or the development of intractable radiation-induced neovascular glaucoma (NVG). We compare pathologic changes and dosimetric findings in those eyes enucleated secondary to NVG as opposed to TP to better understand potential mechanisms. Methods and Materials: Patients with juxtapapillary choroidal melanoma treated with SRT (70 Gy in 5 fractions, alternate days over a total of 10 days) at the Princess Margaret Hospital, Toronto, Ontario, Canada, who underwent enucleation between 1998 and 2006 were selected. We correlated dosimetric data based on the patient's original SRT treatment plan with histopathologic findings in the retina, optic nerve head, and anterior chamber. A dedicated ocular pathologist reviewed each case in a blinded fashion. Results: Ten eyes in ten patients were enucleated after SRT. Six were enucleated secondary to NVG and four secondary to because of TP. Aggressive tumor features such as invasion of the sclera and epithelioid cell type were observed predominantly in the TP group. Retinal damage was more predominant in the NVG group, as were findings of radiation-related retinal vascular changes of fibrinoid necrosis and hyalinization. No conclusive radiation-related effects were found in the anterior chamber. The maximum point dose and dose to 0.1 cc were lower for the anterior chamber as compared with the dose to the tumor, retina, and optic nerve head. The mean 0.1-cc doses to the retina were 69.4 Gy and 73.5 Gy and to the anterior chamber were 4.9 Gy and 17.3 Gy for the NVG group and tumor progression group, respectively. Conclusions: Our findings suggest that NVG is due to radiation damage to the posterior chamber of the eye rather than primary radiation damage to the anterior segment.

  20. Surgical Removal vs Observation for Subfoveal Choroidal Neovascularization, Either Associated With the Ocular Histoplasmosis Syndrome or Idiopathic

    PubMed Central

    2005-01-01

    Objective To present visual acuity findings and related outcomes from eyes of patients enrolled in a randomized trial conducted by the Submacular Surgery Trials (SST) Research Group (SST Group H Trial) to compare surgical removal vs observation of subfoveal choroidal neovascular lesions that were either idiopathic or associated with ocular histoplasmosis. Methods Eligible patients 18 years or older had subfoveal choroidal neovascularization (new or recurrent) that included a classic component on fluorescein angiography and best-corrected visual acuity of 20/50 to 20/800 in 1 eye (“study eye”). Patients were examined 3, 6, 12, and 24 months after enrollment to assess study outcomes and adverse events. Best-corrected visual acuity was measured by a masked examiner at the 24-month examination. A successful outcome was defined a priori as 24-month visual acuity better or no more than 1 line (7 letters) worse than at baseline. Results Among 225 patients enrolled (median visual acuity 20/100), 113 study eyes were assigned to observation and 112 to surgery. Forty-six percent of the eyes in the observation arm and 55% in the surgery arm had a successful outcome (success ratio, 1.18; 95% confidence interval, 0.89–1.56). Median visual acuity at the 24-month examination was 20/250 among eyes in the observation arm and 20/160 for eyes in the surgery arm. The prespecified subgroup of eyes with visual acuity worse than 20/100 at baseline (n=92) had more successes with surgery; 31 (76%) of 41 eyes in the surgery arm vs 20 (50%) of 40 eyes in the observation arm examined at 24 months (success ratio, 1.53; 95% confidence interval, 1.08–2.16). Five (4%) of 111 eyes in the surgery arm subsequently had a rhegmatogenous retinal detachment. Twenty-seven (24%) of 112 initially phakic eyes in the surgery arm (none in the observation arm) had cataract surgery during follow-up, all among patients older than 50 years. Recurrent choroidal neovascularization developed by the 24-month

  1. Melissa officinalis Extract Inhibits Laser-Induced Choroidal Neovascularization in a Rat Model

    PubMed Central

    Lee, Eun Kyoung; Kim, Young Joo; Kim, Jin Young; Song, Hyun Beom; Yu, Hyeong Gon

    2014-01-01

    Purpose This study investigated the effect of Melissa officinalis extract on laser-induced choroidal neovascularization (CNV) in a rat model. The mechanism by which M. officinalis extract acted was also investigated. Methods Experimental CNV was induced by laser photocoagulation in Brown Norway rats. An active fraction of the Melissa leaf extract was orally administered (50 or 100 mg/kg/day) beginning 3 days before laser photocoagulation and ending 14 days after laser photocoagulation. Optical coherence tomography and fluorescein angiography were performed in vivo to evaluate the thickness and leakage of CNV. Choroidal flat mount and histological analysis were conducted to observe the CNV in vitro. Vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9 expression were measured in retinal and choroidal-scleral lysates 7 days after laser injury. Moreover, the effect of M. officinalis extract on tertiary-butylhydroperoxide (t-BH)-induced VEGF secretion and mRNA levels of VEGF, MMP-2, and MMP-9 were evaluated in human retinal epithelial cells (ARPE-19) as well as in human umbilical vein endothelial cells (HUVECs). Results The CNV thickness in M. officinalis-treated rats was significantly lower than in vehicle-treated rats by histological analysis. The CNV thickness was 33.93±7.64 µm in the high-dose group (P<0.001), 44.09±12.01 µm in the low-dose group (P = 0.016), and 51.00±12.37 µm in the control group. The proportion of CNV lesions with clinically significant fluorescein leakage was 9.2% in rats treated with high-dose M. officinalis, which was significantly lower than in control rats (53.4%, P<0.001). The levels of VEGF, MMP-2, and MMP-9 were significantly lower in the high-dose group than in the control group. Meanwhile, M. officinalis extract suppressed t-BH-induced transcription of VEGF and MMP-9 in ARPE-19 cells and HUVECs. Conclusions Systemic administration of M. officinalis extract suppressed laser-induced CNV

  2. Measurements of retinal temperature increase during photodynamic therapy for choroidal neovascularization

    NASA Astrophysics Data System (ADS)

    Chen, Hongxia; Yang, Zaifu; Gu, Ying; Li, Xiaoxia; Zhao, Youquan; Zhang, Luyong; Qiu, Haixia

    2010-11-01

    To study the risk of retinal thermal injury from 532 nm laser during photodynamic therapy (PDT) for choroidal neovascularization (CNV) by measuring the retinal temperature increase of rabbit eyes. A microthermocouple technique was developed to measure retinal temperature increase during PDT in pigmented and non-pigmented rabbit eyes. The 532 nm laser exposures were performed with 100-s duration, 2-mm spot size, and retinal irradiance ranging from 400 to 1600 mW/cm2. A K-type microthermocouple was inserted through the sclerotomy and advanced until the tip reached the retina at the posterior pole. The thermocouple was connected a computer that recorded and analyzed retinal temperature data. The results showed that the retinal temperature increase during laser exposure was proportional to retinal irradiance with a particular spot diameter, exposure duration, wavelength, and fundus pigmentation. And the measured retinal temperature increases in pigmented rabbits were a little higher than those in albino rabbits under the same radiant condition. Retinal threshold irradiance required for visible lesions at laser wavelength of 532 nm with 2.0-mm spot size and 100-s duration was 1657 mW/cm2 in albino and 1003 mW/cm2 in pigmented rabbits, respectively, corresponding to retinal temperature increase of about 8 °C and 6 °C. The measured temperatures in albino and pigmented rabbit eyes were both lower than the model predictions, especially in pigmented rabbits. Therefore, further parameter modifying should be performed to obtain accuracy prediction of retinal temperature.

  3. Ocular toxocariasis: a rare presentation of a posterior pole granuloma with an associated choroidal neovascular membrane.

    PubMed

    Lampariello, D A; Primo, S A

    1999-04-01

    Ocular toxocariasis is a rare infection caused by the nematode larvae of toxocara canis, which is commonly found in dogs. Human transmission is usually via geophagia, the ingestion of food contaminated with the toxocara eggs, or contact with infected puppies, often resulting in devastating ocular and/or systemic effects. Distribution is worldwide; however, a higher incidence is demonstrated in the United States. A 17-year-old black woman sought treatment at a neighborhood health center with a report of gradual decrease in vision from her left eye over a 3-month period. Her ocular and systemic histories were unremarkable. Anterior segment evaluation revealed no signs of anterior uveitis. The posterior pole showed a 1.5 DD, round, raised, white, subretinal lesion adjacent to the fovea with an overlying serous retinal detachment and retinal hemorrhage. She was referred to a retinologist who performed both fluorescein and indocyanine green (ICG) angiographies. A serum toxocara ELISA test was also ordered. Fluorescein angiography revealed hyperfluorescence consistent with the granuloma. The ICG demonstrated an occult choroidal neovascular membrane (CNV) underlying the area of hemorrhage inferotemporal to the granuloma. This paper illustrates the case presentation and includes an extensive review of the ocular and systemic manifestations of toxocariases. A description of ICG videoangiography, therapeutic approaches, and management will also be discussed.

  4. Matrix metalloproteinases in human choroidal neovascular membranes excised following verteporfin photodynamic therapy

    PubMed Central

    Tatar, Olcay; Adam, Annemarie; Shinoda, Kei; Eckert, Tillmann; Scharioth, Gábor B; Klein, Micheal; Yoeruek, Efdal; Bartz‐Schmidt, Karl Ulrich; Grisanti, Salvatore

    2007-01-01

    Aim To evaluate expression of proangiogenic matrix metalloproteinases (MMP) 2 and 9 at distinct intervals after verteporfin photodynamic therapy (PDT) in human choroidal neovascular membranes (CNV) secondary to age‐related macular degeneration (AMD). Methods Retrospective review of an interventional case series of 49 patients who underwent removal of CNV. Twenty‐six patients were treated with PDT 3 to 383 days prior to surgery. Twenty‐three CNV without previous treatment were used as controls. CNV were stained for CD34, cytokeratin 18, endostatin, MMP‐2 and MMP‐9 by immunohistochemistry. Results CNV without previous therapy disclosed MMP‐2, MMP‐9 in RPE–Bruch's membrane, vessels and stroma in different intensities. Three days after PDT, MMP‐9 expression was significantly weaker in stroma (p = 0.0019). Endostatin was significantly reduced in vessels (p<0.001). At longer post‐PDT intervals, a significant increase of MMP‐9 in stroma (p = 0.037) and of endostatin in RPE–Bruch's membrane (p = 0.02), vessels (p = 0.005) and stroma (p<0.001) were disclosed. No significant changes in MMP‐2 expression were detected. Conclusions PDT induced an early, temporary decrease in MMP‐9 and endostatin expression. At longer intervals, MMP‐9 increase is possibly associated with the angiogenic process responsible for recurrence after PDT. MMP‐9, however, acts as a double‐edged sword by concomitant induction of endostatin, an endogenous inhibitor of angiogenesis. PMID:17475706

  5. Choroidal neovascularization induced by immunogenic alteration of the retinal pigment epithelium in dengue Fever.

    PubMed

    Veloso, Carlos Eduardo; Schmidt-Erfurth, Ursula; Nehemy, Márcio B

    2015-01-01

    To report the first case of choroidal neovascularization (CNV) secondary to dengue fever. A 54-year-old female was referred to our department with blurred vision and metamorphopsia in her left eye. Two weeks earlier, she had presented all of the classic symptoms of dengue fever including a positive serology. Her best-corrected visual acuity (BCVA) was 20/150 in the left eye. She underwent a fundus examination, fluorescein angiography (FA) and spectral domain optical coherence tomography. All findings were consistent with CNV secondary to dengue fever. FA revealed a classic CNV associated with focal retinal pigment epithelium (RPE) destruction and detachment. Three consecutive monthly injections of intravitreal ranibizumab resulted in functional and anatomical improvement for as long as 6 months with a BCVA of 20/25. However, CNV recurred 2 years later, again with an improvement after ranibizumab therapy, but with persistence of a fibrovascular RPE detachment, highlighting the pathomechanism of a classic CNV formation. Maculopathy in dengue fever may be followed by CNV as a result of the immunologic alteration of the RPE. Physicians should be aware of this manifestation to be able to initiate adequate treatment with excellent functional and anatomical results.

  6. Polypoidal choroidal vasculopathy: a common type of neovascular age-related macular degeneration in Caucasians.

    PubMed

    Yadav, Sohraab; Parry, David G; Beare, Nick A V; Pearce, Ian A

    2017-10-01

    To describe the prevalence of polypoidal choroidal vasculopathy (PCV) in a Caucasian population with neovascular age-related macular degeneration (NAMD). All patients referred to a city AMD service over a 2-year period underwent imaging including Indocyanine Green Angiography at baseline. A panel of experts confirmed the patients with NAMD and diagnosed the lesion type including PCV. The proportion of Caucasian patients with PCV was identified. Two authors independently reviewed clinical imaging and recorded data of patients with PCV on lesion characteristics. Further information including treatments received and visual acuity at different time points was analysed. A total of 492 patients were diagnosed with NAMD during the 2-year study period. Of these patients, 204 had occult lesions (41.5%). PCV was identified in 45 patients (22.1% of occult NAMD and 9.1% of all NAMD). 23 patients received anti-vascular endothelial growth factor (VEGF) monotherapy, 8 received verteporfin photodynamic therapy (PDT) monotherapy and the remaining 14 patients were managed with combined PDT and anti-VEGF treatment. The prevalence of PCV in Caucasians is higher than previously reported. Indocyanine Green Angiography should be a standard investigation for all new patients with NAMD, particularly those with occult NAMD, to avoid missing this important subset. 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/.

  7. Comparison of fluorescein angiography and optical coherence tomography for patients with choroidal neovascularization after photodynamic therapy.

    PubMed

    Eter, Nicole; Spaide, Richard F

    2005-09-01

    To investigate retinal morphology by means of fluorescein angiography (FA) and optical coherence tomography (OCT) in patients who had undergone photodynamic therapy (PDT) with verteporfin at their 3-month-interval examination. Sixty patients with predominantly classic choroidal neovascularization (CNV) secondary to age-related macular degeneration were evaluated with FA and OCT 3 months after their last PDT. FA images were evaluated in a masked fashion for staining of and leakage from the lesion and also for cystoid loculation of fluorescein in the macula. OCT was used to evaluate foveal thickness and the presence of subretinal fluid or cystoid spaces within the retina, also in a masked fashion. The median age of the 60 patients was 78 years, and the median visual acuity of the eyes examined was 20/100. The median number of previous PDT sessions was 2. Fluorescein staining was seen in 57 eyes (95%), and fluorescein leakage was seen in 50 eyes (83%). Cystoid loculation of fluorescein was seen in 21 eyes (35%). By OCT, cystoid spaces in the macula were seen in 42 patients (70%), and subretinal fluid was seen in 15 patients (25%). Leakage seen shown by FA was correlated with the OCT finding of cystoid spaces but not with the OCT finding of subretinal fluid. Some patients had leakage during FA that did not have any observable induced OCT abnormality attributable to fluid accumulation. After PDT leakage from CNV seen during FA is associated with intraretinal fluid, often seen in loculated cystoid spaces, but not with subretinal fluid.

  8. [Experimental choroidal neovascularization induced by laser in the eyes of rhesus monkeys].

    PubMed

    Zhang, Ming; Yan, Mi; Wang, Li; Zhang, Jun-jun; Liu, Bin; Meng, Dan; Du, Cai-feng

    2008-07-01

    To establish an experimental model of choroidal neovascularization (CNV) through perimacular laser treatment in the eyes of rhesus Monkey. The experimental CNV was induced by perimacular laser injury in the eyes of 8 rhesus monkeys and confirmed by a comparison before and after the laser treatment (20 d, 34 d, 48 d) with fluorescence fundus angiography (FFA) and optical coherence tomography (OCT). Classic CNV similar to human CNV appeared in 68.8% of the laser spots. Hypofluorescence in the early phase and fluorescence leakage in the late phase were detected by the FFA. High reflect light echogenic mass and retina edema were detected by the OCT. The histopathologic examinations found proliferated fiber-vasculosa membranes in the laser burnt spots. The pathological changes lasted 48 days until the monkeys were killed. The laser induced experimental CNV in rhesus monkey has a high prevalence and stability, which maintains a long period. It is an ideal experimental model for studying the pathologic mechanism of CNV and effective treatment for CNV.

  9. Detection of heat shock protein 70 in choroidal neovascular membranes secondary to age related macular degeneration

    PubMed Central

    2011-01-01

    Background Heat shock proteins are acute phase proteins that are upregulated in inflammation or following thermal stress. We analyzed the presence of the heat shock protein 70 (Hsp 70) in choroidal neovascular (CNV) membranes secondary to AMD after treatment with verteporphin photodynamic therapy (PDT) or transpupillary thermo therapy (TTT) to determine whether treatment correlated with the presence of Hsp70. Results CNV membranes were removed by pars plana vitrectomy (ppV) and subretinal extraction. The membranes were analysed by light microscopy and the presence of Hsp 70 was examined using histochemistry. HeLa Cells served as controls. Of the 14 membranes analysed 11 were Hsp70 positive and 3 negative. In the no pre-treatment group of 8 membranes 6 were Hsp70 positive and 2 negative; in the PTD group all 4 membranes were positive and in the TTT group 1 membrane was positive and 1 membrane was negative for Hsp70. Conclusion Hsp70 is present in the most CNV membranes secondary to AMD. Pre-treatment of the membrane with PTD or TTT does not appear to influence the expression of Hsp70. PMID:21477309

  10. Multiple Intravitreal Ranibizumab Injections for Persistant Choroidal Neovascularization Associated with Presumed Ocular Histoplasmosis Syndrome

    PubMed Central

    Yılmaz, Turgut; Dikci, Seyhan; Genç, Oğuzhan; Mutlu, Kayhan

    2017-01-01

    Presumed ocular histoplasmosis syndrome (POHS) is a clinical entity that is characterized by small, round, discrete, macular or mid peripheral atrophic (punched out) chorioretinal lesions (histo spots), peripapillary scarring, choroidal neovascularization (CNV), and the absence of anterior uveitis and vitritis. Diagnosis of this disorder is based upon characteristic clinical findings and a positive histoplasmin skin test or residence in an endemic region for Histoplasma capsulatum. There is no active systemic disease during diagnosis of POHS. Disciform scarring and macular CNV secondary to POHS is a well-known complication which leads to loss of visual acuity or visual disturbance. Without therapy, the visual prognosis in these patients is unfavorable. Submacular surgery, radiation, steroids, photodynamic therapy, and most recently anti-vascular endothelial growth factor therapy are current therapeutic options for this condition. We report a case with persistent CNV secondary to POHS in a middle-aged woman with moderate myopia and the clinical course of treatment with multiple intravitreal ranibizumab (Lucentis®, Novartis) injections. PMID:28405488

  11. Aflibercept: a review of its use in the treatment of choroidal neovascularization due to age-related macular degeneration

    PubMed Central

    Balaratnasingam, Chandrakumar; Dhrami-Gavazi, Elona; McCann, Jesse T; Ghadiali, Quraish; Freund, K Bailey

    2015-01-01

    Choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) is an important cause of visual morbidity globally. Modern treatment strategies for neovascular AMD achieve regression of CNV by suppressing the activity of key growth factors that mediate angiogenesis. Vascular endothelial growth factor (VEGF) has been the major target of neovascular AMD therapy for almost two decades, and there have been several intravitreally-administered agents that have enabled anatomical restitution and improvement in visual function with continual dosing. Aflibercept (EYLEA®), initially named VEGF Trap-eye, is the most recent anti-VEGF agent to be granted US Food and Drug Administration approval for the treatment of neovascular AMD. Biologic advantages of aflibercept include its greater binding affinity for VEGF, a longer intravitreal half-life relative to other anti-VEGF agents, and the capacity to antagonize growth factors other than VEGF. This paper provides an up-to-date summary of the molecular mechanisms mediating CNV. The structural, pharmacodynamic, and pharmacokinetic advantages of aflibercept are also reviewed to rationalize the utility of this agent for treating CNV. Results of landmark clinical investigations, including VIEW 1 and 2 trials, and other important studies are then summarized and used to illustrate the efficacy of aflibercept for managing treatment-naïve CNV, recalcitrant CNV, and CNV due to polypoidal choroidal vasculopathy. Safety profile, patient tolerability, and quality of life measures related to aflibercept are also provided. The evidence provided in this paper suggests aflibercept to be a promising agent that can be used to reduce the treatment burden of neovascular AMD. PMID:26719668

  12. Aflibercept: a review of its use in the treatment of choroidal neovascularization due to age-related macular degeneration.

    PubMed

    Balaratnasingam, Chandrakumar; Dhrami-Gavazi, Elona; McCann, Jesse T; Ghadiali, Quraish; Freund, K Bailey

    2015-01-01

    Choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) is an important cause of visual morbidity globally. Modern treatment strategies for neovascular AMD achieve regression of CNV by suppressing the activity of key growth factors that mediate angiogenesis. Vascular endothelial growth factor (VEGF) has been the major target of neovascular AMD therapy for almost two decades, and there have been several intravitreally-administered agents that have enabled anatomical restitution and improvement in visual function with continual dosing. Aflibercept (EYLEA(®)), initially named VEGF Trap-eye, is the most recent anti-VEGF agent to be granted US Food and Drug Administration approval for the treatment of neovascular AMD. Biologic advantages of aflibercept include its greater binding affinity for VEGF, a longer intravitreal half-life relative to other anti-VEGF agents, and the capacity to antagonize growth factors other than VEGF. This paper provides an up-to-date summary of the molecular mechanisms mediating CNV. The structural, pharmacodynamic, and pharmacokinetic advantages of aflibercept are also reviewed to rationalize the utility of this agent for treating CNV. Results of landmark clinical investigations, including VIEW 1 and 2 trials, and other important studies are then summarized and used to illustrate the efficacy of aflibercept for managing treatment-naïve CNV, recalcitrant CNV, and CNV due to polypoidal choroidal vasculopathy. Safety profile, patient tolerability, and quality of life measures related to aflibercept are also provided. The evidence provided in this paper suggests aflibercept to be a promising agent that can be used to reduce the treatment burden of neovascular AMD.

  13. Activation of Rap1 inhibits NADPH oxidase-dependent ROS generation in retinal pigment epithelium and reduces choroidal neovascularization

    PubMed Central

    Wang, Haibo; Jiang, Yanchao; Shi, Dallas; Quilliam, Lawrence A.; Chrzanowska-Wodnicka, Magdalena; Wittchen, Erika S.; Li, Dean Y.; Hartnett, M. Elizabeth

    2014-01-01

    Activation of Rap1 GTPase can improve the integrity of the barrier of the retina pigment epithelium (RPE) and reduce choroidal neovascularization (CNV). Inhibition of NADPH oxidase activation also reduces CNV. We hypothesize that Rap1 inhibits NADPH oxidase-generated ROS and thereby reduces CNV formation. Using a murine model of laser-induced CNV, we determined that reduced Rap1 activity in RPE/choroid occurred with CNV formation and that activation of Rap1 by 2′-O-Me-cAMP (8CPT)-reduced laser-induced CNV via inhibiting NADPH oxidase-generated ROS. In RPE, inhibition of Rap1 by Rap1 GTPase-activating protein (Rap1GAP) increased ROS generation, whereas activation of Rap1 by 8CPT reduced ROS by interfering with the assembly of NADPH oxidase membrane subunit p22phox with NOX4 or cytoplasmic subunit p47phox. Activation of NADPH oxidase with Rap1GAP reduced RPE barrier integrity via cadherin phosphorylation and facilitated choroidal EC migration across the RPE monolayer. Rap1GAP-induced ROS generation was inhibited by active Rap1a, but not Rap1b, and activation of Rap1a by 8CPT in Rap1b−/− mice reduced laser-induced CNV, in correlation with decreased ROS generation in RPE/choroid. These findings provide evidence that active Rap1 reduces CNV by interfering with the assembly of NADPH oxidase subunits and increasing the integrity of the RPE barrier.—Wang, H., Jiang, Y., Shi, D., Quilliam, L. A., Chrzanowska-Wodnicka, M., Wittchen, E. S., Li, D. Y., Hartnett, M. E. Activation of Rap1 inhibits NADPH oxidase-dependent ROS generation in retinal pigment epithelium and reduces choroidal neovascularization. PMID:24043260

  14. Visual function 5 years or more after macular translocation surgery for myopic choroidal neovascularisation and age-related macular degeneration

    PubMed Central

    Takeuchi, K; Kachi, S; Iwata, E; Ishikawa, K; Terasaki, H

    2012-01-01

    Purpose To evaluate the changes in the best-corrected visual acuity (BCVA) after 1 year and after ≥5 years after macular translocation for age-related macular degeneration (AMD) or myopic choroidal neovascularisation (mCNV). Methods The medical records of 61 consecutive patients who underwent macular translocation with 360° retinotomy for AMD (35 eyes) or mCNV (26 eyes) were reviewed. Overall, 40 patients, 17 mCNV and 23 AMD, were followed for at least 5 years. BCVA and area of the Goldmann visual field (VF) measured before, 12 months after surgery, and at the final visit. Results In the 23 AMD eyes followed for ≥5 years, the mean preoperative BCVA was 1.149±0.105 logMAR units, which significantly improved to 0.69±0.06 logMAR units at 1 year (P<0.001). This BCVA was maintained at 0.633±0.083 logMAR units on their final examination. In the 17 eyes with mCNV followed for ≥5 years, the mean preoperative BCVA was 1.083±0.119 logMAR units, which was significantly improved to 0.689±0.121 logMAR units at 1 year (P=0.001). This BCVA was maintained at 0.678±0.142 logMAR units on their final examination. The area of the VF was significantly decreased at 12 months and did not change significantly thereafter. Conclusions Our results show that macular translocation surgery significantly improves the BCVA and significantly decreases the VF area of eyes with mCNV or AMD after first 1 year. The BCVA and VF area do not change significantly from the values at 1 year for at least 5 years. PMID:22173070

  15. Long-term outcomes of myopic choroidal neovascularisation treated with combined ranibizumab and dexamethasone characterised by multi-modal imaging.

    PubMed

    Tan, Anna C S; Teo, Kelvin; Guan, Ong Sze; Koh, Adrian

    2016-10-01

    To characterise the long-term outcomes of myopic choroidal neovascularisation (mCNV) treated with combined ranibizumab and dexamethasone, with the use of multi-modal imaging. A retrospective study of 20 eyes with mCNV treated with intra-vitreal ranibizumab and dexamethasone on a treat-as-needed basis were followed up for a mean period of 47 months (range 19-81 months). The mean age was 55 ± 16 years, with mean refractive error of -9.0 diopters. Subfoveal mCNV was seen in 11 eyes (52 %) and the others were juxtafoveal. At the final visit, 13 patients (65 %) had improvement, while four patients (20 %) had worsening in vision. The average number of ranibizumab and dexamethasone injections required was 3 ± 1.7. There was a significant improvement in the mean visual acuity, reduction of the central retinal thickness, and an enlargement of the area of chorioretinal atrophy. The mean rate of increase in chorioretinal atrophy area was 0.05 ± 0.09 mm(2)/month. Disruption of the photoreceptor layer, fragmentation of the retinal pigment epithelium, and breaks in the Bruch's membrane with a hyper-reflective lesion causing separation of the outer retinal layers were changes associated with active mCNV seen on optical coherence tomography (OCT). Visual outcomes of mCNV treated with ranibizumab and dexamethasone on a treat-as-needed basis have favourable visual acuity outcomes. Using multi-modal imaging to monitor treatment response, chorioretinal atrophy, which may be related to visual function, should be used as an additional outcome measure to study the effect of combination treatment versus monotherapy.

  16. Intravitreal Topotecan Inhibits Laser-induced Choroidal Neovascularization in a Rat Model

    PubMed Central

    Gholipour, Mohammad Ali; Kanavi, Mozhgan Rezaei; Ahmadieh, Hamid; Aldavood, Seyed Javid; Nourinia, Ramin; Hosseini, Seyed Bagher; Daftarian, Narsis; Nashtaei, Ebrahim Mohammad; Tousi, Adib; Safi, Sare

    2015-01-01

    Purpose: A two-phase preclinical study was designed to determine the safe dose of intravitreal topotecan and its inhibitory effect on experimental choroidal neovascularization (CNV) in a rat model. Methods: In phase I, 42 rats were categorized into 6 groups, 5 of which received intravitreal topotecan injections of 0.125 μg, 0.25 μg, 0.5 μg, 0.75 μg, and 1.0 μg/5 μl, respectively; the control group received an injection of normal saline. Ophthalmic examination and electroretinography (ERG) were performed on days 7 and 28, and enucleated globes were processed for histopathology and immunostaining for glial fibrillary acidic protein. In phase II, CNV was induced via laser burns in 20 rats and the animals were divided into 2 groups. One group received topotecan and the other received normal saline intravitreally. Four weeks later, mean scores of fluorescein leakage on fluorescein angiography as well as mean CNV areas on histology sections were compared. Results: In phase I, clinical, ERG and histopathologic results were unremarkable in terms of retinal toxicity in all groups. Based on the results of phase I, a dose of 1 μg/5 μl topotecan was chosen for phase II. Leakage scores obtained from late-phase fluorescein angiography were significantly lower in topotecan-treated than control eyes (P < 0.01) four weeks after induction of CNV. Compared to control eyes, topotecan-treated eyes showed a significantly lower incidence of fibrovascular proliferation (8.7% vs. 96.2%) and significantly smaller areas of CNV (P < 0.01). Conclusion: Intravitreal injection of topotecan at a dose of 1 μg/5 μl is safe and may be a promising treatment for CNV. PMID:26730316

  17. Role of c-Cbl–Dependent Regulation of Phospholipase Cγ1 Activation in Experimental Choroidal Neovascularization

    PubMed Central

    Meyer, Rosana D.; Mehta, Manisha; Pfeifer, Walther M.; Chou, Eva; Navruzbekov, Gregory; Ahmed, Ednan; Rahimi, Nader

    2010-01-01

    Purpose. Activation of phospholipase Cγ1 (PLCγ1) by vascular endothelial growth factor receptor (VEGFR)-2 is necessary for proliferation and tube formation of endothelial cells in vitro. Previous work has demonstrated that Casitas B-lineage lymphoma (c-Cbl) promotes ubiquitination of PLCγ1 and suppression of its tyrosine phosphorylation. This study was designed to evaluate the importance of PLCγ1 and c-Cbl in experimental choroidal neovascularization (CNV). Methods. The role of PLCγ1 was studied in three models of angiogenesis: the endothelial cell culture system, the chorioallantoic membrane (CAM) assay, and the laser-induced CNV model. Endothelial cells were analyzed for the role of PLCγ1 in promoting tube formation. CAMs were incubated with pharmacologic agents that either inhibit or stimulate PLCγ1. CNV was induced in wild-type and c-Cbl–knockout mice, and the progression of CNV was evaluated by fluorescein angiography. Results. Activation of PLCγ1 was necessary for tube formation of endothelial cells. PLCγ1 stimulation increased the growth of blood vessels and conversely, PLCγ1 inhibition decreased the growth of blood vessels in the CAM model. CNV lesions in the c-Cbl–knockout mice were significantly greater in number, more confluent, and increased in size with time, compared with those in the control wild-type mice. Conclusions. The data show that PLCγ1 plays an important role in angiogenesis. Loss of c-Cbl results in enhanced CNV in the eye. The study also shows that c-Cbl plays an important role in ocular angiogenesis, suggesting that modulation of c-Cbl activity or inhibition of PLCγ1 would be a compelling target for antiangiogenesis therapy. PMID:20592236

  18. Role of c-Cbl-dependent regulation of phospholipase Cgamma1 activation in experimental choroidal neovascularization.

    PubMed

    Husain, Deeba; Meyer, Rosana D; Mehta, Manisha; Pfeifer, Walther M; Chou, Eva; Navruzbekov, Gregory; Ahmed, Ednan; Rahimi, Nader

    2010-12-01

    Activation of phospholipase Cγ1 (PLCγ1) by vascular endothelial growth factor receptor (VEGFR)-2 is necessary for proliferation and tube formation of endothelial cells in vitro. Previous work has demonstrated that Casitas B-lineage lymphoma (c-Cbl) promotes ubiquitination of PLCγ1 and suppression of its tyrosine phosphorylation. This study was designed to evaluate the importance of PLCγ1 and c-Cbl in experimental choroidal neovascularization (CNV). The role of PLCγ1 was studied in three models of angiogenesis: the endothelial cell culture system, the chorioallantoic membrane (CAM) assay, and the laser-induced CNV model. Endothelial cells were analyzed for the role of PLCγ1 in promoting tube formation. CAMs were incubated with pharmacologic agents that either inhibit or stimulate PLCγ1. CNV was induced in wild-type and c-Cbl-knockout mice, and the progression of CNV was evaluated by fluorescein angiography. Activation of PLCγ1 was necessary for tube formation of endothelial cells. PLCγ1 stimulation increased the growth of blood vessels and conversely, PLCγ1 inhibition decreased the growth of blood vessels in the CAM model. CNV lesions in the c-Cbl-knockout mice were significantly greater in number, more confluent, and increased in size with time, compared with those in the control wild-type mice. The data show that PLCγ1 plays an important role in angiogenesis. Loss of c-Cbl results in enhanced CNV in the eye. The study also shows that c-Cbl plays an important role in ocular angiogenesis, suggesting that modulation of c-Cbl activity or inhibition of PLCγ1 would be a compelling target for antiangiogenesis therapy.

  19. Modulation of choroidal neovascularization by subretinal injection of retinal pigment epithelium and polystyrene microbeads

    PubMed Central

    Schmack, Ingo; Berglin, Lennart; Nie, Xiaoyan; Wen, Jing; Kang, Shin J.; Marcus, Adam I; Yang, Hua; Lynn, Michael J.; Kapp, Judith A

    2009-01-01

    Purpose The study was conducted to create a rapidly developing and reproducible animal model of subretinal choroidal neovascularization (CNV) that allows a time-dependent evaluation of growth dynamics, histopathologic features, and cytokine expression. Methods C57BL/6 and chemoattractant leukocyte protein-2 deficient (∆Ccl-2) mice were studied. Mice received single or combined subretinal injections of cultured retinal pigment epithelium (RPE; C57BL/6-derived), polystyrene microbeads, or phosphate buffer solution (PBS). Fluorescence angiograms were performed over a period of 3 weeks. Mice were euthanized on post inoculation day 3, 7, 10, 14, or 21, and their eyes were evaluated by light, confocal, and electron microscopy. Results CNV membranes occurred in all study groups with an overall incidence of 94.3%. They extended in the subretinal space through central breaks in Bruch’s membrane. CNV lesions were characterized by dynamic changes such as initiation, active inflammatory, and involution stages. CNV thickness peaked around PI day 7 and was greater in mice that received combined injections of RPE and microbeads or RPE cells alone. Small lesions developed in the control groups (microbeads or PBS only), in ∆Ccl-2, and old C57BL/6 mice. Variable expression of cytokines and growth factors was detected within the membranes. Conclusions Our murine model represents a reliable approach inducing CNV growth by subretinal injection of either RPE cells alone or RPE cells and microbeads. The development of CNV lesions is a dynamic process that relies in part on macrophage trafficking and age. PMID:19158960

  20. Changes of choroidal neovascularization in indocyanine green angiography after intravitreal ranibizumab injection.

    PubMed

    Lee, Ji Eun; Kim, Hyun Woong; Lee, Sang Joon; Lee, Joo Eun

    2015-05-01

    To investigate vascular structural changes of choroidal neovascularization (CNV) followed by intravitreal ranibizumab injections using indocyanine green angiography. A total of 31 patients with exudative age-related macular degeneration and CNV whose structures were identifiable in indocyanine green angiography were included. Ranibizumab was injected into the vitreous cavity once a month for 3 months and then as needed for the next 3 months prospectively. Indocyanine green angiography was performed at baseline, 3, and 6 months. Early to midphase images of the indocyanine green angiography in the details of vascular structure of the CNV were discerned the best were used in the image analysis. Vascular structures of CNV were described as arteriovenular and capillary components, and structural changes were assessed. Arteriovenular components were observed in 29 eyes (94%). Regression of the capillary components was observed in most cases. Although regression of arteriovenular component was noted in 14 eyes (48%), complete resolution was not observed. The eyes were categorized into 3 groups according to CNV structural changes: the regressed (Group R, 10 eyes, 31%), the matured (Group M, 7 eyes, 23%), and the growing (Group G, 14 eyes, 45%). In Group R, there was no regrowth of CNV found at 6 months. In Group M, distinct vascular structures were observed at 3 months and persisted without apparent changes at 6 months. In Group G, growth or reperfusion of capillary components from the persisting arteriovenular components was noted at 6 months. Both capillary and arteriovenular components were regressed during monthly ranibizumab injections. However, CNV regrowth was observed in a group of patients during the as-needed treatment phase.

  1. A Pharmacodynamic Analysis of Choroidal Neovascularization in a Porcine Model Using Three Targeted Drugs

    PubMed Central

    Tran, Jeffrey; Craven, Caroline; Wabner, Kathy; Schmit, Jenn; Matter, Brock; Kompella, Uday; Grossniklaus, Hans E.; Olsen, Timothy W.

    2017-01-01

    Purpose To compare the efficacy of microneedle-delivered suprachoroidal (SC) pazopanib to intravitreal (Ivit) delivery of pazopanib, bevacizumab, or a fusion protein hI-con1 versus vehicle controls on choroidal neovascularization (CNV) growth in a pig model. Methods Forty-one pigs were injected on the day of CNV induction (hI-con1 on postinduction day 14) with either 2.5 mg Ivit bevacizumab (n = 9), 1 mg Ivit pazopanib (n = 9), 300 Ivit μg hI-con1 (n = 4), or 1 mg SC pazopanib (n = 9), vs. 10 vehicle controls (3 SC + 7 Ivit = 10). Pigs were euthanized at week 2 (11), 3 (8), 4 (11), and 8 (11), and eyes were fixed for histology. The size of the CNV was determined from histology, and CNV height was the primary outcome measure. Immunostaining for cytotoxic T-cells was performed in the hI-con1 study. Results In 39 of 41 (95%) eyes, type 2 CNV lesions were identified. One CNV lesion was lost during dissection. One animal was euthanized due to surgical complications. For mean CNV size comparisons, Ivit pazopanib had smaller mean height measurements (90 ± 20 μm) versus controls (180 ± 20 μm; P = 0.009), and Ivit pazopanib had smaller maximum CNV height (173 ± 43 μm) compared to SC pazopanib (478 ± 105 μm; P = 0.018). The mean lesion size in hI-con1–treated animals trended smaller than in controls (P = 0.11). Immunostaining did not detect cytotoxic T-cells. Conclusions Intravitreal pazopanib and to a lesser extent hI-con1 reduced the size of CNV lesions. The pig model has nearly a 100% rate of type 2 CNV induction and is a reliable preclinical model with pharmacodynamics similar to humans. PMID:28738417

  2. Functional characterization and multimodal imaging of treatment-naive "quiescent" choroidal neovascularization.

    PubMed

    Querques, Giuseppe; Srour, Mayer; Massamba, Nathalie; Georges, Anouk; Ben Moussa, Naima; Rafaeli, Omer; Souied, Eric H

    2013-10-21

    To investigate the multimodal morphological and functional characteristics of treatment-naïve "quiescent" choroidal neovascularization (CNV) secondary to AMD. Eleven patients with treatment-naïve "quiescent" CNV that consecutively presented over a 6-month period, underwent multimodal morphological and functional assessment (including indocyanine green angiography [ICGA], spectral-domain optical coherence tomography [SD-OCT], microperimetry, and preferential hyperacuity perimeter [PHP]). For the purpose of this study, asymptomatic previously untreated CNVs showing absence of intraretinal/subretinal exudation in two consecutive visits (at least 6 months apart) were defined as treatment-naïve "quiescent" CNV. Eleven eyes of 11 patients (9 females; mean age 76.5 ± 8.5 years) were included. On fluorescein angiography (FA), "quiescent" CNVs appeared as late speckled hyperfluorescent lesions lacking well-demarcated borders. Mid-late phase ICGA allowed visualizing the hyperfluorescent "quiescent" CNV network and delineating the plaque. Mean lesion area (mid-late phase ICGA) appeared larger compared with earliest previous examination performed 23.8 ± 16.0 months before (3.24 ± 2.51 mm(2) vs. 3.52 ± 2.46 mm(2), respectively; P = 0.01). SD-OCT revealed, at the site of "quiescent" CNV, an irregularly slightly elevated RPE, without hyporeflective intraretinal/subretinal fluid, showing a major axis in the horizontal plane, which was characterized by collections of moderately reflective material in the sub-RPE space and clear visualization of the hyperreflective Bruch's membrane. Hypergeometric distribution revealed a significant correlation between microperimetry and PHP with respect to locations of "affected areas" (P = 0.001). "Quiescent" CNVs are sub-RPE CNVs secondary to AMD, showing absence of intraretinal/subretinal exudation on repeated OCT. "Quiescent" CNVs enlarge over time and may contribute to local reduced retinal sensitivity and metamorphopsia.

  3. Repeatability of swept-source optical coherence tomography retinal and choroidal thickness measurements in neovascular age-related macular degeneration.

    PubMed

    Hanumunthadu, Daren; Ilginis, Tomas; Restori, Marie; Sagoo, Mandeep S; Tufail, Adnan; Balaggan, Kamaljit S; Patel, Praveen J

    2017-05-01

    The aim was to determine the intrasession repeatability of swept-source optical coherence tomography (SS-OCT)-derived retinal and choroidal thickness measurements in eyes with neovascular age-related macular degeneration (nAMD). A prospective study consisting of patients with active nAMD enrolled in the Distance of Choroid Study at Moorfields Eye Hospital, London. Patients underwent three 12×9 mm macular raster scans using the deep range imaging (DRI) OCT-1 SS-OCT (Topcon) device in a single imaging session. Retinal and choroidal thicknesses were calculated for the ETDRS macular subfields. Repeatability was calculated according to methods described by Bland and Altman. 39 eyes of 39 patients with nAMD were included with a mean (±SD) age of 73.9 (±7.2) years. The mean (±SD) retinal thickness of the central macular subfield was 225.7 μm (±12.4 μm). The repeatability this subfield, expressed as a percentage of the mean central macular subfield thickness, was 23.2%. The percentage repeatability of the other macular subfields ranged from 13.2% to 28.7%. The intrasession coefficient of repeatability of choroidal thickness of the central macular subfield was 57.2 μm with a mean choroidal thickness (±SD) of 181 μm (±15.8 μm). This study suggests that a change >23.2% of retinal thickness and 57.2 μm choroidal thickness in the central macular subfield is required to distinguish true clinical change from measurement variability when using the DRI OCT-1 device to manage patients with nAMD. 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/.

  4. Choroid, Haller's, and Sattler's Layer Thickness in Intermediate Age-Related Macular Degeneration With and Without Fellow Neovascular Eyes

    PubMed Central

    Esmaeelpour, Marieh; Ansari-Shahrezaei, Siamak; Glittenberg, Carl; Nemetz, Susanne; Kraus, Martin F.; Hornegger, Joachim; Fujimoto, James G.; Drexler, Wolfgang; Binder, Susanne

    2014-01-01

    Purpose. To analyze choroidal, Sattler's, and Haller's layer thickness maps in age-related macular degeneration (AMD) patients having eyes with bilateral large drusen and pigment changes (intermediate AMD), in patients having intermediate AMD eyes with neovascular fellow eyes (nAMD), and in healthy subjects using three-dimensional (3D) 1060-nm optical coherence tomography (OCT). Methods. Automatically generated choroidal thickness (ChT), retinal thickness, and Sattler's and Haller's layer thickness maps were statistically analyzed in 67 subjects consisting of intermediate AMD (n = 21), intermediate AMD (n = 22) with fellow nAMD eyes (n = 22), and healthy eyes (n = 24) with no age and axial eye length difference between groups of eyes (P > 0.05, ANOVA). Eyes were imaged by a prototype high-speed (60,000 A-scans/s) spectral-domain 3D 1060-nm OCT over a 36° × 36° field of view. Results. The mean ± SD (μm) subfoveal ChT for healthy subjects and for bilateral intermediate AMD, unilateral intermediate AMD, and their nAMD fellow eyes was 259 ± 95 and 222 ± 98, 149 ± 60, and 171 ± 78, respectively. Choroidal thickness maps demonstrated significant submacular thinning in unilateral intermediate AMD in comparison to healthy and bilateral intermediate AMD eyes (P < 0.001, ANOVA, post hoc P < 0.001 and P < 0.05, respectively). Sattler's and Haller's layers were thinnest in intermediate AMDs that presented with nAMD fellow eyes (Kruskal-Wallis test P < 0.01). For the choroid and its sublayers, there was no difference between the intermediate AMD eyes and their fellow nAMD eyes (paired testing, P < 0.05). Conclusions. The 3D 1060-nm OCT choroidal imaging visualized significant changes in choroidal, Sattler's, and Haller's layer thickness in relation to the progression of AMD. This may be important for understanding the choroidopathy in the pathophysiology of AMD. PMID:25052997

  5. Choroid morphometric analysis in non-neovascular age-related macular degeneration by means of optical coherence tomography angiography.

    PubMed

    Cicinelli, Maria Vittoria; Rabiolo, Alessandro; Marchese, Alessandro; de Vitis, Luigi; Carnevali, Adriano; Querques, Lea; Bandello, Francesco; Querques, Giuseppe

    2017-09-01

    To describe the vascular changes in patients affected by non-neovascular age-related macular degeneration (AMD), featuring reticular pseudodrusen (RPD), drusen, or both RPD and drusen by means of optical coherence tomography angiography (OCT-A). Cross-sectional observational case series. Patients with non-neovascular AMD presenting at the Medical Retina Service of the Department of Ophthalmology, University Vita-Salute San Raffaele in Milan were recruited. Patients underwent best-corrected visual acuity, biomicroscopy, infrared reflectance, short-wavelength fundus autofluorescence and OCT-A (AngioPlex, CIRRUS HD-OCT 5000, Carl Zeiss Meditech, Dublin, USA). Main outcome was quantification of vessel density, stromal tissue, and vascular/stromal (V/S) ratio at the choriocapillaris (CC), the Sattler and Haller's and the whole choroid layers among different groups of patients with non-neovascular AMD by means of binarised OCT-A scans. 45 eyes of 34 patients were enrolled (15 eyes of 11 patients with RPD, group 1; 15 eyes of 11 patients with drusen, group 2; 15 eyes of 12 patients with mixed phenotype, group 3). The CC, the Sattler and Haller's and the whole choroid vessel density were reduced in all groups of patients (p=0.023, p=0.007 and p=0.011 in group 1, group 2 and group 3 for the CC; p=0.021, p=0.037 and p=0.043 in group 1, group 2 and group 3 for the Sattler and Haller's density; p=0.016, p=0.002 and p<0.001 in group 1, group 2 and group 3 for the choroidal density), with significantly lower V/S ratios compared with healthy controls. Patients with non-neovascular AMD show significant choroidal vascular depletion and fibrotic replacement, suggesting a possible role in the pathogenesis and progression of the disease. 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/.

  6. Local Production of the Alternative Pathway Component Factor B Is Sufficient to Promote Laser-Induced Choroidal Neovascularization

    PubMed Central

    Schnabolk, Gloriane; Coughlin, Beth; Joseph, Kusumam; Kunchithapautham, Kannan; Bandyopadhyay, Mausumi; O'Quinn, Elizabeth C.; Nowling, Tamara; Rohrer, Bärbel

    2015-01-01

    Purpose. Complement factor B (CFB) is a required component of the alternative pathway (AP) of complement, and CFB polymorphisms are associated with age-related macular degeneration (AMD) risk. Complement factor B is made in the liver, but expression has also been detected in retina and retinal pigment epithelium (RPE)-choroid. We investigated whether production of CFB by the RPE can promote AP activation in mouse choroidal neovascularization (CNV). Methods. Transgenic mice expressing CFB under the RPE65 promoter were generated and crossed onto factor B-deficient (CFB-KO) mice. Biological activity was determined in vitro using RPE monolayers and in vivo using laser-induced CNV. Contribution of systemic CFB was investigated using CFB-KO reconstituted with CFB-sufficient serum. Results. Transgenic mice (CFB-tg) expressed CFB in RPE-choroid; no CFB was detected in serum. Cultured CFB-tg RPE monolayers secreted CFB apically and basally upon exposure to oxidative stress that was biologically active. Choroidal neovascularization sizes were comparable between wild-type and CFB-tg mice, but significantly increased when compared to lesions in CFB-KO mice. Injections of CFB-sufficient serum into CFB-KO mice resulted in partial reconstitution of systemic AP activity and significantly increased CNV size. Conclusions. Mouse RPE cells express and secrete CFB sufficient to promote RPE damage and CNV. This further supports that local complement production may regulate disease processes; however, the reconstitution experiments suggest that additional components may be sequestered from the bloodstream. Understanding the process of ocular complement production and regulation will further our understanding of the AMD disease process and the requirements of a complement-based therapeutic. PMID:25593023

  7. International photographic classification and grading system for myopic maculopathy.

    PubMed

    Ohno-Matsui, Kyoko; Kawasaki, Ryo; Jonas, Jost B; Cheung, Chui Ming Gemmy; Saw, Seang-Mei; Verhoeven, Virginie J M; Klaver, Caroline C W; Moriyama, Muka; Shinohara, Kosei; Kawasaki, Yumiko; Yamazaki, Mai; Meuer, Stacy; Ishibashi, Tatsuro; Yasuda, Miho; Yamashita, Hidetoshi; Sugano, Akira; Wang, Jie Jin; Mitchell, Paul; Wong, Tien Yin

    2015-05-01

    To develop a classification and grading system for myopic maculopathy. Development and evaluation of a classification system for myopic maculopathy based on observational case series. A comprehensive set of myopic macular lesions was defined via literature review and through consensus meetings among retinal specialists and clinician scientists. A classification of myopic maculopathy was formulated based on fundus photographs and a modified Delphi process and consensus. Inter- and intraobserver reproducibility, assessed as agreement (%) and weighted kappa values, were evaluated. One hundred retinal photographs with myopia and myopic macular lesions were selected from case series at the High Myopia Clinic of the Tokyo Medical and Dental University, Tokyo, Japan. We defined 5 categories of myopic maculopathy including "no myopic retinal degenerative lesion" (Category 0), "tessellated fundus" (Category 1), "diffuse chorioretinal atrophy" (Category 2), "patchy chorioretinal atrophy" (Category 3), and "macular atrophy" (Category 4). Three additional features to supplement these categories were defined as "plus" lesions, namely, lacquer cracks, myopic choroidal neovascularization, and Fuchs spot. Posterior staphyloma was considered as a further, important sign of myopic retinopathy. The intraobserver agreement was ≥85% and the corresponding weighted kappa statistic was ≥0.6 between observations. After a brief training session, interobserver kappa statistics reached the predefined satisfactory level (≥0.4), considered as above moderate agreement. We propose a classification system for myopic maculopathy that was found to be reproducible. Applying a uniform classification in different studies will facilitate communication and comparison of findings from clinical trials and epidemiologic studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Focal Choroidal Excavation

    PubMed Central

    Cebeci, Zafer; Bayraktar, Şerife; Oray, Merih; Kır, Nur

    2016-01-01

    Focal choroidal excavation is a choroidal pit that can be detected by optical coherence tomography. Central serous chorioretinopathy, choroidal neovascularization and polypoidal choroidal vasculopathy are pathologies associated with focal choroidal excavation. In this article, we present the follow-up and treatment outcomes of three eyes of two patients with focal choroidal excavation. PMID:28050329

  9. Focal Choroidal Excavation.

    PubMed

    Cebeci, Zafer; Bayraktar, Şerife; Oray, Merih; Kır, Nur

    2016-12-01

    Focal choroidal excavation is a choroidal pit that can be detected by optical coherence tomography. Central serous chorioretinopathy, choroidal neovascularization and polypoidal choroidal vasculopathy are pathologies associated with focal choroidal excavation. In this article, we present the follow-up and treatment outcomes of three eyes of two patients with focal choroidal excavation.

  10. Adhesion Failures Determine the Pattern of Choroidal Neovascularization in the Eye: A Computer Simulation Study

    PubMed Central

    Shirinifard, Abbas; Glazier, James Alexander; Swat, Maciej; Gens, J. Scott; Family, Fereydoon; Jiang, Yi; Grossniklaus, Hans E.

    2012-01-01

    Choroidal neovascularization (CNV) of the macular area of the retina is the major cause of severe vision loss in adults. In CNV, after choriocapillaries initially penetrate Bruch's membrane (BrM), invading vessels may regress or expand (CNV initiation). Next, during Early and Late CNV, the expanding vasculature usually spreads in one of three distinct patterns: in a layer between BrM and the retinal pigment epithelium (sub-RPE or Type 1 CNV), in a layer between the RPE and the photoreceptors (sub-retinal or Type 2 CNV) or in both loci simultaneously (combined pattern or Type 3 CNV). While most studies hypothesize that CNV primarily results from growth-factor effects or holes in BrM, our three-dimensional simulations of multi-cell model of the normal and pathological maculae recapitulate the three growth patterns, under the hypothesis that CNV results from combinations of impairment of: 1) RPE-RPE epithelial junctional adhesion, 2) Adhesion of the RPE basement membrane complex to BrM (RPE-BrM adhesion), and 3) Adhesion of the RPE to the photoreceptor outer segments (RPE-POS adhesion). Our key findings are that when an endothelial tip cell penetrates BrM: 1) RPE with normal epithelial junctions, basal attachment to BrM and apical attachment to POS resists CNV. 2) Small holes in BrM do not, by themselves, initiate CNV. 3) RPE with normal epithelial junctions and normal apical RPE-POS adhesion, but weak adhesion to BrM (e.g. due to lipid accumulation in BrM) results in Early sub-RPE CNV. 4) Normal adhesion of RBaM to BrM, but reduced apical RPE-POS or epithelial RPE-RPE adhesion (e.g. due to inflammation) results in Early sub-retinal CNV. 5) Simultaneous reduction in RPE-RPE epithelial binding and RPE-BrM adhesion results in either sub-RPE or sub-retinal CNV which often progresses to combined pattern CNV. These findings suggest that defects in adhesion dominate CNV initiation and progression. PMID:22570603

  11. Anatomic response of occult choroidal neovascularization to intravitreal ranibizumab: a study by indocyanine green angiography.

    PubMed

    Querques, Giuseppe; Tran, Thi Ha Chau; Forte, Raimondo; Querques, Lea; Bandello, Francesco; Souied, Eric H

    2012-04-01

    To investigate changes in indocyanine green angiography (ICGA) features of occult choroidal neovascularization (CNV) after intravitreal ranibizumab injections. We reviewed the charts of all consecutive patients with newly diagnosed occult CNV secondary to age-related macular degeneration (AMD) treated by intravitreal ranibizumab. In all patients, optical coherence tomography (OCT) and ICGA were performed at baseline, after 3 months and 12 months. Fifty-one eyes of 44 patients (ten males, 34 females, mean age 77.8 ± 7.3 years) were included. Mean follow-up was 20.3 ± 6.2 months. During the first 12 months, patients received 5.5 ± 2.7 intravitreal ranibizumab injections. When compared with baseline, best-corrected visual acuity (BCVA) significantly improved at the 3-month follow-up visit (60.5 ±22.0 vs 50.9 ±20.7 letters, p = 0.04), and stabilized at 12-month visit (55.7 ±18.2 letters; p = 0.05). Central macular thickness (CMT) significantly improved during follow-up (229.0 ±54.7 μm vs 281.0 ±61.3 μm at baseline, p = 0.003). An overall stabilization was observed on ICGA in both the lesion area (5.27 ± 3.9 mm(2) at baseline vs 4.60 ± 3.5 mm(2) at month 12, p = 0.4), and greatest linear dimension (GLD 2.66 ± 1.2 mm at baseline vs 2.55 ± 1.0 mm at month 12, p = 0.3). Eight eyes (15.7%) showed CNV growth on ICGA (lesion area 3.98 ± 3.2 mm2 at baseline vs 4.3 ± 2.7 mm2 at month-12, p = 0.6; GLD 2.11 ± 1.0 mm at baseline vs 2.70 ± 0.8 mm at month-12, p = 0.05). ICGA suggests that functional outcomes after intravitreal ranibizumab is related to CMT reduction rather than CNV regression.

  12. Long-term follow-up of patients with choroidal neovascularization due to angioid streaks

    PubMed Central

    Martinez-Serrano, Maria Guadalupe; Rodriguez-Reyes, Abelardo; Guerrero-Naranjo, Jose Luis; Salcedo-Villanueva, Guillermo; Fromow-Guerra, Jans; García-Aguirre, Gerardo; Morales-Canton, Virgilio; Velez-Montoya, Raul

    2017-01-01

    Background The following case series describes the long-term anatomical and functional outcome of a group of seven patients with choroidal neovascularization (CNV), secondary to angioid streaks (AS), who were treated with antiangiogenic drugs in a pro re nata (PRN) regimen. After the 4-year mark, visual acuity tends to return to pretreatment level. Treatment delays and lack of awareness and self-referral by the patients are believed to be the cause of the PRN regimen failure. Purpose To assess the long-term outcomes (>4 years) of patients with CNV due to AS treated with a PRN regimen of antiangiogenic. Methods This was a retrospective, case series, single-center study. We reviewed the electronic medical records from patients with CNV due to AS. From each record, we noted general demographic data and relevant medical history; clinical presentation, changes in best-corrected visual acuity (BCVA) over time, optical coherent tomography parameters, treatment and retreatment details, and systemic associations. Changes in BCVA and central macular thickness were assessed with a Wilcoxon two-sample test, with an alpha value of ≤0.05 for statistical significance. Results The mean follow-up time was 53.8±26.8 months. BCVA at baseline was: 1.001±0.62 logMAR; at the end of follow-up: 0.996±0.56 logMAR (P=0.9). Central macular thickness at baseline was: 360.85±173.82 μm; at the end of follow-up: 323.85±100.34 μm (P=0.6). Mean number of intravitreal angiogenic drugs: 6±4.16 injections (range 4–15). Mean time between injections was 3.8±2.7 months (range 1.9–5.8 months). Conclusion Despite initial anatomical and functional improvement, patients at the end of the follow-up had no visual improvement after a pro re nata regimen of antiangiogenic drugs. The amount of retreatments, number of recurrences, and time between intravitreal injections were similar to previous reports with shorter follow-up. PMID:28031699

  13. Smoking as a risk factor for choroidal neovascularization secondary to presumed ocular histoplasmosis syndrome.

    PubMed

    Chheda, Lena V; Ferketich, Amy K; Carroll, C Patrick; Moyer, Paul D; Kurz, Daryl E; Kurz, Paul A

    2012-02-01

    To investigate the relationship of smoking to choroidal neovascularization (CNV) secondary to presumed ocular histoplasmosis syndrome (POHS). Retrospective, case-control study. A total of 568 patients 18 to 50 years of age, 142 of whom were diagnosed with CNV secondary to POHS in a private retina practice between July 1, 2000, and August 1, 2010. Four hundred twenty-six were controls selected from a private comprehensive ophthalmology practice at the same location. A retrospective medical record review was performed for all participants. Age, gender, zip code, CNV diagnosis date, insurance status, and smoking status at CNV diagnosis date were collected first for the POHS patients. For each of these 142 patients, 3 randomly selected comprehensive clinic patients, whose visit date fell within 3 months of the corresponding POHS patient's CNV diagnosis date, served as controls. Age, gender, zip code, visit date, reason for visit, insurance type, and smoking status were recorded. Descriptive statistics were calculated for cases and controls. Logistic regression analyses were performed for both univariate and multivariate models, with CNV secondary to POHS as the main outcome variable and smoking as the main predictor variable, while adjusting for age, gender, insurance type, median household income, and education level. The mean age of patients with CNV secondary to POHS was 39.0±7.1 years, whereas that of the control patients was 35.7±9.1 years. Of the patients with CNV secondary to POHS, 47.2% were current or former smokers (42.3% current, 4.9% former). Of the control patients, 22.5% were current or former smokers (21.8% current, 0.7% former). Age, insurance type, median income, educational attainment, and smoking status were significant in the univariate models. In the final adjusted logistic regression model, only age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.07; P = 0.001), level of educational attainment by zip code (OR, 0.95; 95% CI, 0

  14. The anti-angiogenic role of discoidin domain receptor 2 (DDR2) in laser-induced choroidal neovascularization.

    PubMed

    Zhu, Tong; Zhu, Jie; Bu, Xin; Zhao, Hu; Zhang, Shuya; Chang, Yuan; Li, Rong; Yao, Libo; Wang, Yusheng; Su, Jin

    2015-02-01

    Choroidal neovascularization (CNV), an aberrant growth of blood vessels in the choroid layer of the eye, is a major cause of vision loss. In view of our recent finding that discoidin domain receptor 2 (DDR2), a collagen-binding receptor tyrosine kinase, is involved in control of vascular endothelial activity and tumor angiogenesis, the present study aims to investigate whether and how DDR2 affects the pathogenesis of CNV. We initially found that a spontaneous DDR2 mutant mouse colony (slie) exhibited enhanced amplitude of laser-induced CNV. The inhibitory role of DDR2 in CNV development was further confirmed by experiments through intravitreous injection of DDR2 small interference RNA (siRNA) or DDR2-expressing adenovirus. Quantitative real-time polymerase chain reaction (qPCR) and immunoblot analysis showed that DDR2 regulates the expression of several major pro-angiogenic factors in the laser-injured choroid as well as in retinal pigment epithelium (RPE) cells. In addition, it was demonstrated that the CNV-induced increases in the phosphorylation levels of Akt and mTOR were affected by the upregulation or downregulation of DDR2. Thus, the data from this study for the first time revealed that DDR2 negatively regulates the development of experimental CNV in vivo, which may provide a novel target for preventing human pathological ocular neovascularization. Key messages: DDR2 does not affect retinal development. DDR2 inhibits laser-induced CNV. DDR2 regulates angiogenic factor expression in CNV lesion as well as in RPE cells. DDR2 is involved in modulation of CNV-induced activation of PI3K pathway.

  15. DETECTION OF TREATMENT-NAIVE CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION BY SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

    PubMed

    Ahmed, Daniel; Stattin, Martin; Graf, Alexandra; Forster, Julia; Glittenberg, Carl; Krebs, Ilse; Ansari-Shahrezaei, Siamak

    2017-09-04

    To compare the detection rate of choroidal neovascularization (CNV) in treatment-naive neovascular age-related macular degeneration by swept source optical coherence tomography angiography (SS-OCTA, Topcon's DRI Triton) working at 1,050 nm wavelength versus fluorescence angiography. Cross-sectional analysis of 156 eyes (107 neovascular age-related macular degeneration and 49 dry AMD) in 98 patients, previously diagnosed by multimodal imaging using fluorescein (FA) and indocyanine green angiography (Heidelberg's Spectralis) in a tertiary retina center, evaluated by SS-OCTA 4.5 mm × 4.5 mm and 6 mm × 6 mm macular cubes. Main outcome measures were sensitivity and specificity of SS-OCTA in AMD. Potential factors influencing CNV detection rate were analyzed. Swept source optical coherence tomography angiography detected CNV in 81 of 107 eyes, resulting in a sensitivity of 75.7%. In 49 eyes with dry AMD, no CNV could be identified (specificity 100%). A statistical significance was calculated for nondetection of treatment-naive CNV by SS-OCTA in pigment epithelial detachment over 400 μm (P = 0.0238). Topcon's SS-OCTA was not able to detect all CNV lesions. Large pigment epithelial detachments were associated with signal loss. Fluorescence angiography still remains the gold standard, but the tested SS-OCTA device can be considered as a feasible additional diagnostic tool in AMD.

  16. Retinal pigment epithelial cell expression of active Rap 1a by scAAV2 inhibits choroidal neovascularization

    PubMed Central

    Wang, Haibo; Han, Xiaokun; Bretz, Colin A; Becker, Silke; Gambhir, Deeksha; Smith, George W; Samulski, R Jude; Wittchen, Erika S; Quilliam, Lawrence A; Chrzanowska-Wodnicka, Magdalena; Hartnett, M Elizabeth

    2016-01-01

    To test the hypothesis that increased Rap1a activity specifically in retinal pigment epithelial cells resists choroidal neovascularization (CNV), self-complementary adeno-associated virus 2 (scAAV2) with RPE65-promoter-driven GFP vectors were generated and introduced subretinally into Rap1b-deficient mice. Six-week-old mice that received subretinal control (scAAV2-Con) or constitutively active Rap1a (scAAV2-CARap1a) showed strong GFP at the 5 × 108 viral particle/µl dose 5 weeks later without altering retinal morphology or function. Compared to scAAV2-Con- or phosphate-buffered saline (PBS)-injected, eyes injected with scAAV2-CARap1a had increased Rap1 in retinal pigment epithelial (RPE)/choroidal lysates and a significant reduction in CNV volume 7 days after laser, comparable to eyes that received intravitreal anti-VEGF versus IgG control. scAAV2-CARap1a-, but not anti-VEGF-, injected eyes had increased pan-cadherin in RPE/choroids. In cultured RPE cells, increased active Rap1a inhibited TNFα-induced disassociation of junctional pan-cadherin/β-catenin complexes, increased transepithelial electrical resistance through an interaction of β-catenin with phosphorylated scaffold protein, IQGAP1, and inhibited choroidal endothelial cell (CEC) transmigration of an RPE monolayer. This evidence shows that increased Rap1a activity specifically in RPE cells is sufficient to reduce CEC transmigration and CNV and involves IQGAP1-mediated protection of RPE junctional complexes. PMID:27606349

  17. Retinal pigment epithelial cell expression of active Rap 1a by scAAV2 inhibits choroidal neovascularization.

    PubMed

    Wang, Haibo; Han, Xiaokun; Bretz, Colin A; Becker, Silke; Gambhir, Deeksha; Smith, George W; Samulski, R Jude; Wittchen, Erika S; Quilliam, Lawrence A; Chrzanowska-Wodnicka, Magdalena; Hartnett, M Elizabeth

    2016-01-01

    To test the hypothesis that increased Rap1a activity specifically in retinal pigment epithelial cells resists choroidal neovascularization (CNV), self-complementary adeno-associated virus 2 (scAAV2) with RPE65-promoter-driven GFP vectors were generated and introduced subretinally into Rap1b-deficient mice. Six-week-old mice that received subretinal control (scAAV2-Con) or constitutively active Rap1a (scAAV2-CARap1a) showed strong GFP at the 5 × 10(8) viral particle/µl dose 5 weeks later without altering retinal morphology or function. Compared to scAAV2-Con- or phosphate-buffered saline (PBS)-injected, eyes injected with scAAV2-CARap1a had increased Rap1 in retinal pigment epithelial (RPE)/choroidal lysates and a significant reduction in CNV volume 7 days after laser, comparable to eyes that received intravitreal anti-VEGF versus IgG control. scAAV2-CARap1a-, but not anti-VEGF-, injected eyes had increased pan-cadherin in RPE/choroids. In cultured RPE cells, increased active Rap1a inhibited TNFα-induced disassociation of junctional pan-cadherin/β-catenin complexes, increased transepithelial electrical resistance through an interaction of β-catenin with phosphorylated scaffold protein, IQGAP1, and inhibited choroidal endothelial cell (CEC) transmigration of an RPE monolayer. This evidence shows that increased Rap1a activity specifically in RPE cells is sufficient to reduce CEC transmigration and CNV and involves IQGAP1-mediated protection of RPE junctional complexes.

  18. Mechanism for laser-induced neovascularization in rat choroid: Accumulation of integrin α chain-positive cells and their ligands

    PubMed Central

    Nakajima, Takeshi; Hirata, Masayuki; Shearer, Thomas R.

    2014-01-01

    Purpose Inhibitors binding to integrins α5 and αv are antiangiogenic in models of choroidal neovascularization (CNV). However, a comprehensive understanding of the accumulation of integrin α isoform-positive cells, their ligands, and associations is limited. The purpose of the present study was to examine the localization of integrin α chain-positive cells and their extracellular matrix (ECM) ligands in the RPE/choroid after laser injury. Methods CNV, observed with fluorescein isothiocyanate (FITC)-labeled isolectin, was produced in Brown Norway rats with a 532 nm green laser. Localization of α5 and αv integrins and their ligands was performed with immunohistochemistry in consecutive cryosections. To test the binding specificity between the integrin α chains and ECM ligands, an in vitro cell adhesion assay was performed using retinal endothelial cells and specific antibodies. Results Angiogenesis was observed on day 7 after laser injury in choroidal flat mounts and cryosections. The number of integrin α5- and αv-positive cells markedly increased at day 3 and then gradually decreased, but was still elevated on day 14. One day after laser treatment, α integrin ligands fibronectin (FN) and vitronectin (VN) were markedly increased, and localized closely to integrins in the laser-injured regions. FN decreased on day 7, but was still retained until 14 days. In contrast, VN disappeared. Cell adhesion assays showed specific association of integrin α5 to FN, and integrin αv to VN. Conclusions Laser-induced choroidal injury increased FN and VN, followed by accumulation of integrin α5- and αv-positive cells. The interaction between integrin α chain-positive cells and their specific ligands FN and VN may be important steps leading to CNV. PMID:24959065

  19. Study on choroidal neovascularization with anti-VEGF treatment in the mouse retina using optical coherence tomography angiography (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Park, Jang Ryul; Choi, WooJhon; Kim, Jaeryung; Hong, Hye Kyong; Kim, Yongjoo; Hwang, Yoonha; Park, Sang Jun; Woo, Se Joon; Kim, Pilhan; Park, Kyu Hyung; Koh, Gou Young; Oh, Wang-Yuhl

    2017-02-01

    To understand the pathogenesis of ophthalmic disease, utilizing small animal models such as mouse is necessary because of their ease of maintenance and availability. For identifying pathophysiology and drug development of retinal diseases in mouse model, optical coherence tomography angiography (OCTA) is promising imaging modality visualizing not only microstructure but also microvasculature. In this study, we serially imaged 3D structure and angiography of laser-induced choroidal neovascularization (CNV) in the mouse retina with/without anti-VEGF treatment. Also, the volume changes of CNV and avascular region in choroid layer are measured for identifying effects of anti-VEGF. A lab-built high-speed OCTA prototype using the wavelength-swept laser centered at 1040 nm with 230 kHz A-scan rate acquired 3-D volumetric data consisted of 1024 x 1024 x 3 A-scans. The OCTA scanned 1.7 mm x 1.7 mm area around ONH. For obtaining angiography, amplitude decorrelation from 3 consecutive B-scans at each position was generated. Seven days after the laser photocoagulation at mouse retina for generation of the laser-induced CNV, intravitreal administration of Fc and VEGF-Trap was given in the therapeutic arm. The OCTA were performed at 6, 14, 21 and 35 days after laser photocoagulation. Vasculatures of inner retina, outer retina and choroid layers were separately visualized after RPE flattening and layer segmentation. To investigate therapeutic effects of anti-VEGF treatment, the relative area and volume of CNV in outer retina layer is measured. Also, total volume of avascular zone surrounding the laser injury site in choroid layer is also analyzed.

  20. Choroid, Haller's, and Sattler's layer thickness in intermediate age-related macular degeneration with and without fellow neovascular eyes.

    PubMed

    Esmaeelpour, Marieh; Ansari-Shahrezaei, Siamak; Glittenberg, Carl; Nemetz, Susanne; Kraus, Martin F; Hornegger, Joachim; Fujimoto, James G; Drexler, Wolfgang; Binder, Susanne

    2014-07-22

    To analyze choroidal, Sattler's, and Haller's layer thickness maps in age-related macular degeneration (AMD) patients having eyes with bilateral large drusen and pigment changes (intermediate AMD), in patients having intermediate AMD eyes with neovascular fellow eyes (nAMD), and in healthy subjects using three-dimensional (3D) 1060-nm optical coherence tomography (OCT). Automatically generated choroidal thickness (ChT), retinal thickness, and Sattler's and Haller's layer thickness maps were statistically analyzed in 67 subjects consisting of intermediate AMD (n = 21), intermediate AMD (n = 22) with fellow nAMD eyes (n = 22), and healthy eyes (n = 24) with no age and axial eye length difference between groups of eyes (P > 0.05, ANOVA). Eyes were imaged by a prototype high-speed (60,000 A-scans/s) spectral-domain 3D 1060-nm OCT over a 36° × 36° field of view. The mean ± SD (μm) subfoveal ChT for healthy subjects and for bilateral intermediate AMD, unilateral intermediate AMD, and their nAMD fellow eyes was 259 ± 95 and 222 ± 98, 149 ± 60, and 171 ± 78, respectively. Choroidal thickness maps demonstrated significant submacular thinning in unilateral intermediate AMD in comparison to healthy and bilateral intermediate AMD eyes (P < 0.001, ANOVA, post hoc P < 0.001 and P < 0.05, respectively). Sattler's and Haller's layers were thinnest in intermediate AMDs that presented with nAMD fellow eyes (Kruskal-Wallis test P < 0.01). For the choroid and its sublayers, there was no difference between the intermediate AMD eyes and their fellow nAMD eyes (paired testing, P < 0.05). The 3D 1060-nm OCT choroidal imaging visualized significant changes in choroidal, Sattler's, and Haller's layer thickness in relation to the progression of AMD. This may be important for understanding the choroidopathy in the pathophysiology of AMD. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  1. Optical Coherence Tomography Angiography Demonstration of Choroidal Neovascularization in Malattia Leventinese.

    PubMed

    Corbelli, Eleonora; Corvi, Federico; Carnevali, Adriano; Querques, Lea; Zucchiatti, Ilaria; Bandello, Francesco; Querques, Giuseppe

    2016-06-01

    In a case of Malattia Leventinese, optical coherence tomography angiography led to the diagnosis of type 1 neovascularization, despite absence of evidence on conventional dye-based angiography. The authors hypothesize that, at least in some cases, accumulation of subretinal fluid in Malattia Leventinese could be due to a subretinal pigment epithelium (RPE) neovascular component rather than creation of hydrophobic barrier at the RPE and Bruch's membrane. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:602-604.].

  2. Inhibition of new vessel growth in mouse model of laser-induced choroidal neovascularization by adiponectin peptide II

    PubMed Central

    Lyzogubov, Valeriy V.; Tytarenko, Ruslana G.; Thotakura, Sushma; Viswanathan, Tito; Bora, Nalini S.; Bora, Puran S.

    2012-01-01

    We have investigated the effect of adiponectin (APN) peptide II on new vessel growth in mouse model of choroidal neovascularization (CNV) or wet type age-related macular degeneration (AMD). Mice were injected intraperitoneally with APN peptide II, control peptide, or PBS on day 1–7 or day 5–14. APN, AdipoR1, PCNA, and VEGF localization was investigated using confocal microscopy, immunohistochemistry, and RT-PCR. APN peptide II decreased the relative area of FITC-dextran perfused vessels by 4-fold, PCNA expression by 3-fold, and the number of PCNA stained HUVEC and MAVEC cells by 38 and 46%, respectively. We concluded that APN peptide II inhibits CNV size on days 7 and 14 by inhibiting the proliferation of endothelial cells in vivo and in vitro. APN peptide II may have therapeutic potential to inhibit CNV or wet AMD. PMID:19422927

  3. Risk factors for neovascular glaucoma after carbon ion radiotherapy of choroidal melanoma using dose-volume histogram analysis

    SciTech Connect

    Hirasawa, Naoki . E-mail: naoki_h@nirs.go.jp; Tsuji, Hiroshi; Ishikawa, Hitoshi; Koyama-Ito, Hiroko; Kamada, Tadashi; Mizoe, Jun-Etsu; Ito, Yoshiyuki; Naganawa, Shinji; Ohnishi, Yoshitaka; Tsujii, Hirohiko

    2007-02-01

    Purpose: To determine the risk factors for neovascular glaucoma (NVG) after carbon ion radiotherapy (C-ion RT) of choroidal melanoma. Methods and Materials: A total of 55 patients with choroidal melanoma were treated between 2001 and 2005 with C-ion RT based on computed tomography treatment planning. All patients had a tumor of large size or one located close to the optic disk. Univariate and multivariate analyses were performed to identify the risk factors of NVG for the following parameters; gender, age, dose-volumes of the iris-ciliary body and the wall of eyeball, and irradiation of the optic disk (ODI). Results: Neovascular glaucoma occurred in 23 patients and the 3-year cumulative NVG rate was 42.6 {+-} 6.8% (standard error), but enucleation from NVG was performed in only three eyes. Multivariate analysis revealed that the significant risk factors for NVG were V50{sub IC} (volume irradiated {>=}50 GyE to iris-ciliary body) (p = 0.002) and ODI (p = 0.036). The 3-year NVG rate for patients with V50{sub IC} {>=}0.127 mL and those with V50{sub IC} <0.127 mL were 71.4 {+-} 8.5% and 11.5 {+-} 6.3%, respectively. The corresponding rate for the patients with and without ODI were 62.9 {+-} 10.4% and 28.4 {+-} 8.0%, respectively. Conclusion: Dose-volume histogram analysis with computed tomography indicated that V50{sub IC} and ODI were independent risk factors for NVG. An irradiation system that can reduce the dose to both the anterior segment and the optic disk might be worth adopting to investigate whether or not incidence of NVG can be decreased with it.

  4. A RANDOMIZED PILOT STUDY OF SYSTEMIC IMMUNOSUPPRESSION IN THE TREATMENT OF AGE-RELATED MACULAR DEGENERATION WITH CHOROIDAL NEOVASCULARIZATION

    PubMed Central

    Nussenblatt, Robert B.; Byrnes, Gordon; Sen, H. Nida; Yeh, Steven; Faia, Lisa; Meyerle, Catherine; Wroblewski, Keith; Li, Zhuqing; Liu, Baoying; Chew, Emily; Sherry, Patti R.; Friedman, Penelope; Ferris, Frederick

    2011-01-01

    Background Age-related macular degeneration remains the leading cause of irreversible blindness in the United States and the developed world. Intravitreal injections of anti–vascular endothelial growth factor (VEGF) medications have become standard of care for the treatment of the wet form of the disease. Recent reports have demonstrated an association with various immune factors. We aimed to investigate the effect of immunosuppressive therapy in the clinical course of the wet form of the disease. We compared anti-VEGF therapy plus one of three systemic immunosuppressive therapies versus anti-VEGF therapy alone for recurrent choroidal neovascularization associated with age-related macular degeneration. Methods This was a pilot, Phase I/II, prospective, randomized, unmasked, single-center trial. Patients with subretinal exudation secondary to recurrent choroidal neovascularization associated with age-related macular degeneration were included in the study. Patients were randomized to 1 of 3 systemic arms immunosuppressive agents (daclizumab, rapamycin, or infliximab) for 6 months plus intraocular anti-VEGF therapy if indicated, compared with a group who received only anti-VEGF therapy if indicated. Results The number of anti-VEGF injections per group, visual acuity, retinal thickness, and safety measures were assessed in all groups. Thirteen patients were randomized; comparing anti-VEGF injections before and during the study, a decrease in the number of injections from 0.73 injections per month to 0.42 for daclizumab and from 0.67 to 0.34 for sirolimus was seen, while no apparent decrease was seen for either infliximab or observation. Visual acuities were maintained in all groups. Conclusion These preliminary data suggest that some immunosuppressive agents given systemically can alter the clinical course of the wet form of the disease and support the notion that more definitive clinical trials of immune mediation of age-related macular degeneration are indicated

  5. Plasma-activated medium suppresses choroidal neovascularization in mice: a new therapeutic concept for age-related macular degeneration

    PubMed Central

    Ye, Fuxiang; Kaneko, Hiroki; Nagasaka, Yosuke; Ijima, Ryo; Nakamura, Kae; Nagaya, Masatoshi; Takayama, Kei; Kajiyama, Hiroaki; Senga, Takeshi; Tanaka, Hiromasa; Mizuno, Masaaki; Kikkawa, Fumitaka; Hori, Masaru; Terasaki, Hiroko

    2015-01-01

    Choroidal neovascularization (CNV) is the main pathogenesis of age-related macular degeneration (AMD), which leads to severe vision loss in many aged patients in most advanced country. CNV compromises vision via hemorrhage and retinal detachment on account of pathological neovascularization penetrating the retina. Plasma medicine represents the medical application of ionized gas “plasma” that is typically studied in the field of physical science. Here we examined the therapeutic ability of plasma-activated medium (PAM) to suppress CNV. The effect of PAM on vascularization was assessed on the basis of human retinal endothelial cell (HREC) tube formation. In mice, laser photocoagulation was performed to induce CNV (laser-CNV), followed by intravitreal injection of PAM. N-Acetylcysteine was used to examine the role of reactive oxygen species in PAM-induced CNV suppression. Fundus imaging, retinal histology examination, and electroretinography (ERG) were also performed to evaluate PAM-induced retinal toxicity. Interestingly, HREC tube formation and laser-CNV were both reduced by treatment with PAM. N-acetylcysteine only partly neutralized the PAM-induced reduction in laser-CNV. In addition, PAM injection had no effect on regular retinal vessels, nor did it show retinal toxicity in vivo. Our findings indicate the potential of PAM as a novel therapeutic agent for suppressing CNV. PMID:25573059

  6. Antiproliferative, Apoptotic, and Autophagic Activity of Ranibizumab, Bevacizumab, Pegaptanib, and Aflibercept on Fibroblasts: Implication for Choroidal Neovascularization

    PubMed Central

    Lytvynchuk, Lyubomyr; Sergienko, Andrii; Lavrenchuk, Galina; Petrovski, Goran

    2015-01-01

    Purpose. Choroidal neovascularization (CNV) is one of the most common complications of retinal diseases accompanied by elevated secretion of vascular endothelial growth factor (VEGF). Intravitreal anti-VEGFs (ranibizumab, bevacizumab, pegaptanib, and aflibercept) can suppress neovascularization, decrease vascular permeability and CNV size, and, thereby, improve visual function. The antiproliferative, apoptotic, and autophagic effect of anti-VEGF drugs on fibroblasts found in CNVs has not been yet explored. Methods. Concentration-dependent cellular effects of the four anti-VEGFs were examined in L929 fibroblasts over a 5-day period. The cell survival, mitotic and polykaryocytic indices, the level of apoptosis and autophagy, and the cellular growth kinetics were all assessed. Results. The anti-VEGFs could inhibit the survival, mitotic activity, and proliferation as well as increase the cellular heterogeneity, apoptosis, and autophagy of the fibroblasts in a dose-dependent manner. Cellular growth kinetics showed ranibizumab to be less aggressive, but three other anti-VEGFs showed higher antiproliferative and apoptotic activity and expressed negative cellular growth kinetics. Conclusions. The antiproliferative, apoptotic, and autophagic activity of anti-VEGFs upon fibroblasts may explain the cellular response and the etiology of CNV involution in vivo and serve as a good study model for CNV in vitro. PMID:26491557

  7. Indocyanine Green Angiography and Optical Coherence Tomography Angiography of Choroidal Neovascularization in Age-Related Macular Degeneration.

    PubMed

    Eandi, Chiara M; Ciardella, Antonio; Parravano, Mariacristina; Missiroli, Filippo; Alovisi, Camilla; Veronese, Chiara; Morara, Maria C; Grossi, Massimo; Virgili, Gianni; Ricci, Federico

    2017-07-01

    To compare the capability of indocyanine green angiography (ICGA) and optical coherence tomography angiography (OCTA) in detecting choroidal neovascularization (CNV). In this prospective study, patients with CNV detected with fluorescein angiography (FA) underwent ICGA and OCTA, spectral domain OCT (SD-OCT), and infrared or fundus color photographs. CNV lesions were outlined on ICGA and OCTA images, and the composition and size of the CNV was documented. One hundred eighty-two eyes were included. With ICGA, well-defined lesions were observed in 37.9%, partly defined in 44.5%, and undefined in 17% of eyes. On OCTA, well-defined, partly defined, and undefined vessels were observed in 53.8%, 27.5%, and 18.7% of eyes, respectively. There was a good correlation between CNV size measured with the two instruments (r = 0.84). However, OCTA underestimated CNV area by about 4.5% (slope coefficient with linear regression: 0.55, 95% confidence interval [CI]: 0.46 to 0.65; intercept: 0.27, 95% CI: -0.2 to 0.56). On ICGA, CNV composition was capillary in 28%, mature in 14.3%, and mixed (capillary and major neovascular complex) in 57.7% of eyes. Similarly, OCTA revealed capillary, mature, and mixed CNV in 28.9%, 15.9%, and 55.5% of eyes, respectively. OCTA provides the clinician the ability to perform precise structural and vascular assessment of CNV noninvasively. Our study is, to our knowledge, the largest OCTA analysis to date of CNV secondary to neovascular AMD analyzed simultaneously by ICGA and OCTA.

  8. Effect of Brimonidine on Retinal and Choroidal Neovascularization in a Mouse Model of Retinopathy of Prematurity and Laser-Treated Rats

    PubMed Central

    Kusari, Jyotirmoy; Padillo, Edwin; Zhou, Sheila X.; Bai, Yanyan; Wang, Juanjuan; Song, Zhiming; Zhu, Meili; Le, Yun-Zheng; Gil, Daniel W.

    2011-01-01

    Purpose. To determine whether chronic treatment with brimonidine (BRI) attenuates retinal vascular leakage and neovascularization in neonatal mice after exposure to high oxygen in a mouse model of retinopathy of prematurity (ROP), and choroidal neovascularization (CNV) in rats after laser treatment. Methods. Experimental CNV was induced by laser treatment in Brown Norway (BN) rats. BRI or vehicle (VEH) was administered by osmotic minipumps, and CNV formation was measured 11 days after laser treatment. Oxygen-induced retinopathy was generated in neonatal mice by exposure to 75% oxygen from postnatal day (P)7 to P12. BRI or VEH was administered by gavage, and vitreoretinal vascular endothelial growth factor (VEGF) concentrations and retinal vascular leakage, neovascularization, and vaso-obliteration were measured on P17. Experimental CNV was induced in rabbits by subretinal lipopolysaccharide/fibroblast growth factor-2 injection. Results. Systemic BRI treatment significantly attenuated laser-induced CNV formation in BN rats when initiated 3 days before or within 1 hour after laser treatment. BRI treatment initiated during exposure to high oxygen significantly attenuated vitreoretinal VEGF concentrations, retinal vascular leakage, and retinal neovascularization in P17 mice subjected to oxygen-induced retinopathy. Intravitreal treatment with BRI had no effect on CNV formation in a rabbit model of nonischemic angiogenesis. Conclusions. BRI treatment significantly attenuated vitreoretinal VEGF concentrations, retinal vascular leakage, and retinal and choroidal neovascularization in animal models of ROP and CNV. BRI may inhibit underlying event(s) of ischemia responsible for upregulation of vitreoretinal VEGF and thus reduce vascular leakage and retinal-choroidal neovascularization. PMID:21482645

  9. Surgery for Hemorrhagic Choroidal Neovascular Lesions of Age-Related Macular Degeneration: Quality-of-Life Findings

    PubMed Central

    2005-01-01

    Purpose To present and compare findings from health-related quality-of-life (HRQOL) interviews conducted with patients enrolled in the SST Group B Trial evaluating surgical removal of subfoveal choroidal neovascular lesions associated with age-related macular degeneration versus observation. Design Randomized clinical trial. Participants Eligible patients had predominantly hemorrhagic subfoveal choroidal neovascular lesions (total lesion size of >3.5 disc areas, area of blood at least 50% of the lesion area, and at least 75% of blood posterior to the equator) and best-corrected visual acuity (VA) of 20/100 to <20/1600 but at least light perception in the study eye. Three hundred thirty-six patients enrolled after baseline quality-of-life interviews, 168 assigned to each of surgery or observation. Methods Clinical and HRQOL data were collected before randomization and at 6, 12, 24, 36, and 48 months after enrollment. Baseline clinical evidence was used to stratify patients as having unilateral or bilateral neovascularization at the time of randomization. The HRQOL interviews included the National Eye Institute Visual Function Questionnaire (NEI-VFQ), the 36-item Short Form Health Survey, and the Hospital Anxiety and Depression Scale. Main Outcomes Measure Two-year change in NEI-VFQ. Results At 24 months after enrollment, overall NEI-VFQ scores had a median decrease of 1 point from baseline in the observation arm (95% confidence interval [CI]: −4 to 3 points) and no change in the surgery arm (95% CI: −3 to 3 points) (P = 0.70). Changes from baseline on NEI-VFQ subscales also were similar between treatment arms. Differences in scores by unilateral or bilateral involvement seen at baseline in each treatment arm persisted throughout follow-up for most outcomes. Planned analyses stratified by VA showed trends (P = 0.17) in favor of surgery at 24 months in the patients with baseline VA greater than 20/200 for the NEI-VFQ scale (3.5-point median increase from baseline

  10. Krypton laser photocoagulation induces retinal vascular remodeling rather than choroidal neovascularization.

    PubMed

    Behar-Cohen, F; Benezra, D; Soubrane, G; Jonet, L; Jeanny, J C

    2006-08-01

    The purpose of this study is to analyze the retina and choroid response following krypton laser photocoagulation. Ninety-two C57BL6/Sev129 and 32 C57BL/6J, 5-6-week-old mice received one single krypton (630 nm) laser lesion: 50 microm, 0.05 s, 400 mW. On the following day, every day thereafter for 1 week and every 2-3 days for the following 3 weeks, serial sections throughout the lesion were systematically collected and studied. Immunohistology using specific markers or antibodies for glial fibrillary acidic protein (GFAP) (astrocytes, glia and Muller's cells), von Willebrand (vW) (vascular endothelial cells), TUNEL (cells undergoing caspase dependent apoptosis), PCNA (proliferating cell nuclear antigen) p36, CD4 and F4/80 (infiltrating inflammatory and T cells), DAPI (cell nuclei) and routine histology were carried out. Laser confocal microscopy was also performed on flat mounts. Temporal and spatial observations of the created photocoagulation lesions demonstrate that, after a few hours, activated glial cells within the retinal path of the laser beam express GFAP. After 48 h, GFAP-positive staining was also detected within the choroid lesion center. "Movement" of this GFAP-positive expression towards the lasered choroid was preceded by a well-demarcated and localized apoptosis of the retina outer nuclear layer cells within the laser beam path. Later, death of retinal outer nuclear cells and layer thinning at this site was followed by evagination of the inner nuclear retinal layer. Funneling of the entire inner nuclear and the thinned outer nuclear layers into the choroid lesion center was accompanied by "dragging" of the retinal capillaries. Thus, from days 10 to 14 after krypton laser photocoagulation onward, well-formed blood capillaries (of retinal origin) were observed within the lesion. Only a few of the vW-positive capillary endothelial cells stained also for PCNA p36. In the choroid, dilatation of the vascular bed occurred at the vicinity of the

  11. Risk factors for choroidal neovascularization and geographic atrophy in the complications of age-related macular degeneration prevention trial.

    PubMed

    2008-09-01

    To determine risk factors for choroidal neovascularization (CNV) and of geographic atrophy (GA) in eyes with large drusen. Cohort study within a multicenter, randomized clinical trial of laser treatment for the prevention of vision loss from advanced age-related macular degeneration. One thousand fifty-two participants with 10 or more large drusen (>or=125 microm) and visual acuity of 20/40 or better in each eye. At baseline, participants provided a brief medical history. Trained readers evaluated baseline color photographs for drusen characteristics and pigmentary abnormalities. One eye of each participant was assigned to laser treatment and the contralateral eye was assigned to observation. The Complications of Age-Related Macular Degeneration Prevention Trial (CAPT) Reading Center readers identified CNV and endpoint GA from color photographs and fluorescein angiograms obtained during follow-up visits scheduled for 5 or 6 years. Estimates of relative risks (RRs) and 95% confidence intervals (CIs) were obtained from survival analyses of observed and treated eyes, considered separately and combined. Development of CNV and of endpoint GA. Choroidal neovascularization developed in 141 observed eyes and 141 treated eyes, including 57 patients affected bilaterally. Statistically significant risk factors for CNV in the multivariate model for all eyes were older age (RR, 2.81 [95% CI, 1.33-5.94] for >79 years vs. 50-59 years), cigarette smoking (RR, 1.98 [95% CI, 1.16-3.39] for current vs. never), and focal hyperpigmentation (RR, 1.84 [95% CI, 1.22-2.76] for >or=250 microm vs. none). Among eyes free of GA at baseline, endpoint GA developed in 61 observed eyes and in 58 treated eyes, including 29 patients affected bilaterally. Statistically significant risk factors for GA in the multivariate model for all eyes were older age (RR, 6.39 [95% CI, 1.64-24.9] for >79 years vs. 50-59 years), greater retinal area covered by drusen (RR, 5.10 [95% CI, 2.57-10.1] for >or=25% vs

  12. Surgery for hemorrhagic choroidal neovascular lesions of age-related macular degeneration: ophthalmic findings: SST report no. 13.

    PubMed

    Bressler, Neil M; Bressler, Susan B; Childs, Ashley L; Haller, Julia A; Hawkins, Barbara S; Lewis, Hilel; MacCumber, Mathew W; Marsh, Marta J; Redford, Maryann; Sternberg, Paul; Thomas, Matthew A; Williams, George A

    2004-11-01

    To present best-corrected visual acuity (BCVA) findings and other clinical outcomes from eyes of patients enrolled in one of the Submacular Surgery Trials (SST) evaluating surgical removal versus observation of predominantly hemorrhagic subfoveal choroidal neovascularization (CNV) associated with age-related macular degeneration. Randomized clinical trial (SST Group B Trial). Eligible patients had subfoveal choroidal neovascular lesions greater than 3.5 disk areas (8.9 mm2) composed of at least 50% blood (either blood or CNV underlying the center of the foveal avascular zone) and BCVA of 20/100 to light perception in the study eye. Patients were assigned randomly at time of enrollment to observation or surgical removal of blood and any associated CNV. A successful outcome was defined a priori as either improvement in visual acuity (VA), no change in VA, or a decline in VA of no more than 1 line (7 letters) from baseline to the 24-month examination based on an intent-to-treat analysis. Of 336 patients enrolled, 168 were assigned to each treatment arm; treatment arms were balanced by baseline characteristics. Of 1501 expected examinations 3 months through 36 months after baseline, 1370 (91%) were performed. Loss of > or =2 lines (> or =8 letters) of VA occurred in 56% of surgery eyes, versus 59% of observation eyes examined at 24 months. Although severe loss of VA was not the primary outcome of interest, surgery more often prevented such loss: 36% in the observation arm versus 21% in the surgery arm at the 24-month examination (chi2 P = 0.004). Of initially phakic eyes, the cumulative percentage that had undergone cataract surgery by 24 months was 44% in the surgery arm, compared with 6% in the observation arm. Twenty-seven eyes (16%) in the surgical arm, compared with 3 eyes (2%) in the observation arm, had a rhegmatogenous retinal detachment (RD). Submacular surgery as performed in the SST Group B Trial did not increase the chance of stable or improved VA (the

  13. Comparison Between Spectral-Domain and Swept-Source Optical Coherence Tomography Angiographic Imaging of Choroidal Neovascularization

    PubMed Central

    Miller, Andrew R.; Roisman, Luiz; Zhang, Qinqin; Zheng, Fang; Rafael de Oliveira Dias, Joao; Yehoshua, Zohar; Schaal, Karen B.; Feuer, William; Gregori, Giovanni; Chu, Zhongdi; Chen, Chieh-Li; Kubach, Sophie; An, Lin; Stetson, Paul F.; Durbin, Mary K.; Wang, Ruikang K.; Rosenfeld, Philip J.

    2017-01-01

    Purpose The purpose of this study was to compare imaging of choroidal neovascularization (CNV) using swept-source (SS) and spectral-domain (SD) optical coherence tomography angiography (OCTA). Methods Optical coherence tomography angiography was performed using a 100-kHz SS-OCT instrument and a 68-kHz SD-OCTA instrument (Carl Zeiss Meditec, Inc.). Both 3 × 3- and 6 × 6-mm2 scans were obtained on both instruments. The 3 × 3-mm2 SS-OCTA scans consisted of 300 A-scans per B-scan at 300 B-scan positions, and the SD-OCTA scans consisted of 245 A-scans at 245 B-scan positions. The 6 × 6-mm2 SS-OCTA scans consisted of 420 A-scans per B-scan at 420 B-scan positions, and the SD-OCTA scans consisted of 350 A-scans and 350 B-scan positions. B-scans were repeated four times at each position in the 3 × 3-mm2 scans and twice in the 6 × 6-mm2 scans. Choroidal neovascularization was excluded if not fully contained within the 3 × 3-mm2 scans. The same algorithm was used to detect CNV on both instruments. Two graders outlined the CNV, and the lesion areas were compared between instruments. Results Twenty-seven consecutive eyes from 23 patients were analyzed. For the 3 × 3-mm2 scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.17 and 1.01 mm2, respectively (P = 0.047). For the 6 × 6-mm2 scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.24 and 0.74 mm2 (P = 0.003). Conclusions The areas of CNV tended to be larger when imaged with SS-OCTA than with SD-OCTA, and this difference was greater for the 6 × 6-mm2 scans. PMID:28273316

  14. Novel CCR3 Antagonists Are Effective Mono- and Combination Inhibitors of Choroidal Neovascular Growth and Vascular Permeability

    PubMed Central

    Nagai, Nori; Ju, Meihua; Izumi-Nagai, Kanako; Robbie, Scott J.; Bainbridge, James W.; Gale, David C.; Pierre, Esaie; Krauss, Achim H.P.; Adamson, Peter; Shima, David T.; Ng, Yin-Shan

    2016-01-01

    Choroidal neovascularization (CNV) is a defining feature of wet age-related macular degeneration. We examined the functional role of CCR3 in the development of CNV in mice and primates. CCR3 was associated with spontaneous CNV lesions in the newly described JR5558 mice, whereas CCR3 ligands localized to CNV-associated macrophages and the retinal pigment epithelium/choroid complex. Intravitreal injection of neutralizing antibodies against vascular endothelial growth factor receptor 2, CCR3, CC chemokine ligand 11/eotaxin-1, and CC chemokine ligand 24/eotaxin-2 all reduced CNV area and lesion number in these mice. Systemic administration of the CCR3 antagonists GW766994X and GW782415X reduced spontaneous CNV in JR5558 mice and laser-induced CNV in mouse and primate models in a dose-dependent fashion. Combination treatment with antivascular endothelial growth factor receptor 2 antibody and GW766994X yielded additive reductions in CNV area and hyperpermeability in mice. Interestingly, topical GW766994X and intravitreal anti-CCR3 antibody yielded strong systemic effects, reducing CNV in the untreated, contralateral eye. Contrarily, ocular administration of GW782415X in primates failed to substantially elevate plasma drug levels or to reduce the development of grade IV CNV lesions. These findings suggest that CCR3 signaling may be an attractive therapeutic target for CNV, utilizing a pathway that is at least partly distinct from that of vascular endothelial growth factor receptor. The findings also demonstrate that systemic exposure to CCR3 antagonists may be crucial for CNV-targeted activity. PMID:26188133

  15. Topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles

    PubMed Central

    Chu, Yongchao; Chen, Ning; Yu, Huajun; Mu, Hongjie; He, Bin; Hua, Hongchen; Wang, Aiping; Sun, Kaoxiang

    2017-01-01

    A nanoparticle (NP) was developed to target choroidal neovascularization (CNV) via topical ocular administration. The NPs were prepared through conjugation of internalizing arginine-glycine-aspartic acid RGD (iRGD; Ac-CCRGDKGPDC) and transactivated transcription (TAT) (RKKRRQRRRC) peptide to polymerized ethylene glycol and lactic-co-glycolic acid. The iRGD sequence can specifically bind with integrin αvβ3, while TAT facilitates penetration through the ocular barrier. 1H nuclear magnetic resonance and high-performance liquid chromatography demonstrated that up to 80% of iRGD and TAT were conjugated to poly(ethylene glycol)– poly(lactic-co-glycolic acid). The resulting particle size was 67.0±1.7 nm, and the zeta potential of the particles was −6.63±0.43 mV. The corneal permeation of iRGD and TAT NPs increased by 5.50- and 4.56-fold compared to that of bare and iRGD-modified NPs, respectively. Cellular uptake showed that the red fluorescence intensity of iRGD and TAT NPs was highest among primary NPs and iRGD- or TAT-modified NPs. CNV was fully formed 14 days after photocoagulation in Brown Norway (BN) rats as shown by optical coherence tomography and fundus fluorescein angiography analyses. Choroidal flat mounts in BN rats showed that the red fluorescence intensity of NPs followed the order of iRGD and TAT NPs > TAT-modified NPs > iRGD-modified NPs > primary NPs. iRGD and TAT dual-modified NPs thus displayed significant targeting and penetration ability both in vitro and in vivo, indicating that it is a promising drug delivery system for managing CNV via topical ocular administration. PMID:28260884

  16. Novel CCR3 Antagonists Are Effective Mono- and Combination Inhibitors of Choroidal Neovascular Growth and Vascular Permeability.

    PubMed

    Nagai, Nori; Ju, Meihua; Izumi-Nagai, Kanako; Robbie, Scott J; Bainbridge, James W; Gale, David C; Pierre, Esaie; Krauss, Achim H P; Adamson, Peter; Shima, David T; Ng, Yin-Shan

    2015-09-01

    Choroidal neovascularization (CNV) is a defining feature of wet age-related macular degeneration. We examined the functional role of CCR3 in the development of CNV in mice and primates. CCR3 was associated with spontaneous CNV lesions in the newly described JR5558 mice, whereas CCR3 ligands localized to CNV-associated macrophages and the retinal pigment epithelium/choroid complex. Intravitreal injection of neutralizing antibodies against vascular endothelial growth factor receptor 2, CCR3, CC chemokine ligand 11/eotaxin-1, and CC chemokine ligand 24/eotaxin-2 all reduced CNV area and lesion number in these mice. Systemic administration of the CCR3 antagonists GW766994X and GW782415X reduced spontaneous CNV in JR5558 mice and laser-induced CNV in mouse and primate models in a dose-dependent fashion. Combination treatment with antivascular endothelial growth factor receptor 2 antibody and GW766994X yielded additive reductions in CNV area and hyperpermeability in mice. Interestingly, topical GW766994X and intravitreal anti-CCR3 antibody yielded strong systemic effects, reducing CNV in the untreated, contralateral eye. Contrarily, ocular administration of GW782415X in primates failed to substantially elevate plasma drug levels or to reduce the development of grade IV CNV lesions. These findings suggest that CCR3 signaling may be an attractive therapeutic target for CNV, utilizing a pathway that is at least partly distinct from that of vascular endothelial growth factor receptor. The findings also demonstrate that systemic exposure to CCR3 antagonists may be crucial for CNV-targeted activity.

  17. In vivo imaging of a new indocyanine green micelle formulation in an animal model of laser-induced choroidal neovascularization.

    PubMed

    Meyer, Johanna; Cunea, Alexander; Sonntag-Bensch, Dagmar; Welker, Pia; Licha, Kai; Holz, Frank G; Schmitz-Valckenberg, Steffen

    2014-09-04

    We investigated a novel formulation of indocyanine green (ICG/HS 15) in an animal model of laser-induced choroidal neovascularization (CNV). The ICG was formulated with the nonionic solubilizer and emulsifying agent Kolliphor HS 15 to create ICG/HS 15 to improve the chemical stability and fluorescence efficacy. In vivo imaging was performed in rats that had undergone laser photocoagulation. Retinal uptake and fluorescence intensity of ICG and ICG/HS 15 were compared following intravenous injection of 3 dosages (0.05, 0.1, and 0.15 mg/kg body weight) at 7, 14, and 21 days following laser treatment. Postmortem analysis included histology with frozen sections and flat mounts. Immediately following injection of ICG or ICG/HS 15, a strong fluorescence was visible in the retinal vasculature and at the site of laser lesions. Pixel intensity was higher for ICG/HS 15 compared to conventional ICG at 8 minutes after injection for all different injection days and dosages. Over time, a continuous decrease of the fluorescent signal was observed for up to 60 minutes to baseline level. Flow cytometry data showed an increased uptake of micellar dye of macrophages and endothelial cells. Histology revealed an accumulation of the micellar dye within the laser lesion. Micelle formulated ICG can be visualized in the retinal vasculature and laser-induced CNV in vivo and ex vivo. Micellar ICG/HS 15 showed in vivo stronger signal intensity when compared to ICG for all tested dosages. Following further investigations, ICG/HS 15 may be evaluated in patients with retinal and choroidal diseases for more refined diagnosis. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  18. Temperature distribution during ICG-dye-enhanced laser photocoagulation of feeder vessels in treatment of AMD-related choroidal neovascularization.

    PubMed

    Zhu, Liang; Banerjee, Rupak K; Salloum, Maher; Bachmann, Albert; Flower, Robert W

    2008-06-01

    Laser photocoagulation of the feeder vessels of age-related macula degeneration-related choroidal neovascularization (CNV) membranes is a compelling treatment modality, one important reason being that the treatment site is removed from the fovea in cases of sub- or juxtafoveal CNV. To enhance the energy absorption in a target feeder vessel, an indocyanine green dye bolus is injected intravenously, and the 805 nm wavelength diode laser beam is applied when the dye bolus transits the feeder vessel; this tends to reduce concomitant damage to adjacent tissue. A 3D theoretical simulation, using the Pennes bioheat equation, was performed to study the temperature distribution in the choroidal feeder vessel and its vicinity during laser photocoagulation. The results indicate that temperature elevation in the target feeder vessel increases by 20% in dye-enhanced photocoagulation, compared to just photocoagulation alone. The dye bolus not only increases the laser energy absorption in the feeder vessel but also shifts the epicenter of maximum temperature away from the sensitive sensory retina and retinal pigment epithelial layers and toward the feeder vessel. Two dominant factors in temperature elevation of the feeder vessel are location of the feeder vessel and blood flow velocity through it. Feeder vessel temperature elevation becomes smaller as distance between it and the choriocapillaris layer increases. The cooling effect of blood flow through the feeder vessel can reduce the temperature elevation by up to 21% of the maximum that could be produced. Calculations were also performed to examine the effect of the size of the laser spot. To achieve the same temperature elevation in the feeder vessel when the laser spot diameter is doubled, the laser power level has to be increased by only 60%. In addition, our results have suggested that more studies are needed to measure the constants in the Arrhenius integral for assessing thermal damage in various tissues.

  19. Topical Application of PPADS Inhibits Complement Activation and Choroidal Neovascularization in a Model of Age-Related Macular Degeneration

    PubMed Central

    Birke, Kerstin; Lipo, Erion; Birke, Marco T.; Kumar-Singh, Rajendra

    2013-01-01

    Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly. AMD patients have elevated levels of membrane attack complex (MAC) in their choroidal blood vessels and retinal pigment epithelium (RPE). MAC forms pores in cell membranes. Low levels of MAC result in an elevation of cytokine release such as vascular endothelial growth factor (VEGF) that promotes the formation of choroidal neovascularization (CNV). High levels of MAC result in cell lysis and RPE degeneration is a hallmark of advanced AMD. The current standard of care for CNV associated with wet AMD is intravitreal injection of anti-VEGF molecules every 4 to 12 weeks. Such injections have significant side effects. Recently, it has been found that membrane pore-forming proteins such as α-haemolysin can mediate their toxic effects through auto- and paracrine signaling and that complement-induced lysis is amplified through ATP release followed by P2X receptor activation. We hypothesized that attenuation of P2X receptor activation may lead to a reduction in MAC deposition and consequent formation of CNV. Hence, in this study we investigated topical application of the purinergic P2X antagonist Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) as a potential treatment for AMD. We found that 4.17 µM PPADS inhibited formation of HUVEC master junctions and master segments by 74.7%. In a human complement mediated cell lysis assay, 104 µM PPADS enabled almost complete protection of Hepa1c1c7 cells from 1% normal human serum mediated cell lysis. Daily topical application of 4.17 mM PPADS for 3 days attenuated the progression of laser induced CNV in mice by 41.8% and attenuated the deposition of MAC at the site of the laser injury by 19.7%. Our data have implications for the future treatment of AMD and potentially other ocular disorders involving CNV such as angioid streaks, choroidal rupture and high myopia. PMID:24130789

  20. TNF-α mediates choroidal neovascularization by upregulating VEGF expression in RPE through ROS-dependent β-catenin activation.

    PubMed

    Wang, Haibo; Han, Xiaokun; Wittchen, Erika S; Hartnett, M Elizabeth

    2016-01-01

    Inflammation, oxidative stress, and angiogenesis have been proposed to interact in age-related macular degeneration. It has been postulated that external stimuli that cause oxidative stress can increase production of vascular endothelial growth factor (VEGF) in retinal pigment epithelial (RPE) cells. In this study, we tested the hypothesis that the inflammatory cytokine, tumor necrosis factor alpha (TNF-α), contributed to choroidal neovascularization (CNV) by upregulating VEGF in RPE through intracellular reactive oxygen species (ROS)-dependent signaling and sought to understand the mechanisms involved. In a murine laser-induced CNV model, 7 days after laser treatment and intravitreal neutralizing mouse TNF-α antibody or isotype immunoglobulin G (IgG) control, the following measurements were made: 1) TNF-α protein and VEGF protein in RPE/choroids with western blot, 2) CNV volume in RPE/choroidal flatmounts, and 3) semiquantification of oxidized phospholipids stained with E06 antibody within CNV with immunohistochemistry (IHC). In cultured human RPE cells treated with TNF-α or PBS control, 1) ROS generation was measured using the 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence assay, and 2) NOX4 protein and VEGF protein or mRNA were measured with western blot or quantitative real-time PCR in cells pretreated with apocynin or nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) inhibitor, VAS 2870, or transfected with p22phox siRNA, and each was compared to its appropriate control. Western blots of phosphorylated p65 (p-p65), total p65 and β-actin, and quantitative real-time PCR of VEGF mRNA were measured in human RPE cells treated with TNF-α and pretreatment with the nuclear factor kappa B inhibitor, Bay 11-7082 or control. Western blots of β-catenin, VEGF, and p22phox and coimmunoprecipitation of β-catenin and T-cell transcriptional factor were performed in human RPE cells treated with TNF-α following pretreatment with

  1. TNF-α mediates choroidal neovascularization by upregulating VEGF expression in RPE through ROS-dependent β-catenin activation

    PubMed Central

    Wang, Haibo; Han, Xiaokun; Wittchen, Erika S.

    2016-01-01

    Purpose Inflammation, oxidative stress, and angiogenesis have been proposed to interact in age-related macular degeneration. It has been postulated that external stimuli that cause oxidative stress can increase production of vascular endothelial growth factor (VEGF) in retinal pigment epithelial (RPE) cells. In this study, we tested the hypothesis that the inflammatory cytokine, tumor necrosis factor alpha (TNF-α), contributed to choroidal neovascularization (CNV) by upregulating VEGF in RPE through intracellular reactive oxygen species (ROS)-dependent signaling and sought to understand the mechanisms involved. Methods In a murine laser-induced CNV model, 7 days after laser treatment and intravitreal neutralizing mouse TNF-α antibody or isotype immunoglobulin G (IgG) control, the following measurements were made: 1) TNF-α protein and VEGF protein in RPE/choroids with western blot, 2) CNV volume in RPE/choroidal flatmounts, and 3) semiquantification of oxidized phospholipids stained with E06 antibody within CNV with immunohistochemistry (IHC). In cultured human RPE cells treated with TNF-α or PBS control, 1) ROS generation was measured using the 2’,7’-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence assay, and 2) NOX4 protein and VEGF protein or mRNA were measured with western blot or quantitative real-time PCR in cells pretreated with apocynin or nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) inhibitor, VAS 2870, or transfected with p22phox siRNA, and each was compared to its appropriate control. Western blots of phosphorylated p65 (p-p65), total p65 and β-actin, and quantitative real-time PCR of VEGF mRNA were measured in human RPE cells treated with TNF-α and pretreatment with the nuclear factor kappa B inhibitor, Bay 11–7082 or control. Western blots of β-catenin, VEGF, and p22phox and coimmunoprecipitation of β-catenin and T-cell transcriptional factor were performed in human RPE cells treated with TNF-α following

  2. Intravitreal bevacizumab for subfoveal choroidal neovascularization secondary to age-related macular degeneration in an Indian population.

    PubMed

    Azad, Raj Vardhan; Khan, Mansur Ali; Chanana, Bhuvan; Azad, Shorya

    2008-01-01

    To investigate the 6-month safety profile and clinical outcomes of intravitreal bevacizumab for treating subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (AMD). We performed a prospective nonrandomized interventional study of 40 consecutive patients (40 eyes) with subfoveal CNV due to AMD. Patients underwent standard ophthalmic examination, optical coherence tomography, and fundus fluorescein angiography. All patients were administered one or more intravitreal injections of bevacizumab (1.25 mg) as primary therapy. Outcomes were also analyzed in subgroups based on lesion type (classic or occult) and lesion size (< or =3000 microm or >3000 microm). At the 6 months' follow-up, mean best-corrected visual acuity (BCVA) improved from 20/160 to 20/100 (P = 0.014), and the mean contrast sensitivity improved from 0.38 to 0.62 (P = 0.001). The mean greatest linear diameter and mean central macular thickness significantly decreased from 3.79 mm to 2.4 mm (P = 0.0001) and from 438.5 microm to 363 microm (P = 0.0001), respectively. Visual acuity gain of 15 letters or more was seen in 20% of patients, and the gain was more in the small-lesion subgroup (31.5%) than in the large-lesion subgroup (9.5%). No significant adverse effects were observed. Intravitreal bevacizumab is a safe and effective modality for treatment of CNV secondary to AMD. A significant improvement in BCVA with intravitreal bevacizumab was observed for all lesion types.

  3. Myeloid-Specific Blockade of Notch Signaling Attenuates Choroidal Neovascularization through Compromised Macrophage Infiltration and Polarization in Mice

    PubMed Central

    Dou, Guo-Rui; Li, Na; Chang, Tian-Fang; Zhang, Ping; Gao, Xiang; Yan, Xian-Chun; Liang, Liang; Han, Hua; Wang, Yu-Sheng

    2016-01-01

    Macrophages have been recognized as an important inflammatory component in choroidal neovascularization (CNV). However, it is unclear how these cells are activated and polarized, how they affect angiogenesis and what the underlining mechanisms are during CNV. Notch signaling has been implicated in macrophage activation. Previously we have shown that inducible disruption of RBP-J, the critical transcription factor of Notch signaling, in adult mice results in enhanced CNV, but it is unclear what is the role of macrophage-specific Notch signaling in the development of CNV. In the current study, by using the myeloid specific RBP-J knockout mouse model combined with the laser-induced CNV model, we show that disruption of Notch signaling in macrophages displayed attenuated CNV growth, reduced macrophage infiltration and activation, and alleviated angiogenic response after laser induction. The inhibition of CNV occurred with reduced expression of VEGF and TNF-α in infiltrating inflammatory macrophages in myeloid specific RBP-J knockout mice. These changes might result in direct inhibition of EC lumen formation, as shown in an in vitro study. Therefore, clinical intervention of Notch signaling in CNV needs to pinpoint myeloid lineage to avoid the counteractive effects of global inhibition. PMID:27339903

  4. Long-Term Results of Photodynamic Therapy for Choroidal Neovascularization in Pediatric Patients with Best Vitelliform Macular Dystrophy.

    PubMed

    Sodi, Andrea; Murro, Vittoria; Caporossi, Orsola; Passerini, Ilaria; Bacci, Giacomo Maria; Caputo, Roberto; Menchini, Ugo

    2015-06-01

    To report long-term results of photodynamic therapy (PDT) in young patients affected by Best vitelliform macular dystrophy (VMD) complicated by choroidal neovascularization (CNV). We evaluated a group of 30 VMD patients with confirmed mutations in the BEST1 gene. Five of these patients had been diagnosed with CNV when younger than 15 years of age and three of them were treated by PDT. After the treatment they were followed for an average period of 77 months (range 62-99). In all the treated eyes visual acuity was stable during the first year of follow-up and then slowly improved even some years after the treatment. The improvement in visual acuity was associated with the development of fibrous tissue in the macula. PDT was a safe procedure in our series of pediatric patients with VMD complicated by CNV. It was followed by a CNV regression and a consequent improvement in visual acuity which continued to progress even several years after the treatment.

  5. SIRT1 mediated inhibition of VEGF/VEGFR2 signaling by Resveratrol and its relevance to choroidal neovascularization

    PubMed Central

    Zhang, Huiming; He, Shikun; Spee, Christine; Ishikawa, Keijiro; Hinton, David R.

    2015-01-01

    SIRT1, a NAD+ dependent histone deacetylase, has been shown to act as a key regulator of angiogenesis. The purpose of this study was to determine the effects of resveratrol (RSV, a SIRT1 activator) on the vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway and to establish its relevance to choroidal neovascularization (CNV), a blinding complication of age-related macular degeneration. Western blot and ELISA assay showed that RSV inhibited hypoxia-inducible factor (HIF)-1α accumulation and VEGF secretion induced by cobalt chloride (CoCl2) through SIRT1 in human retinal pigment epithelial (hRPE) cells. Furthermore, RSV down-regulated VEGFR2 phosphorylation and activation induced by VEGF in endothelial cells via SIRT1. Thus, the inhibitory effect of RSV on the HIF-1α\\VEGF\\ VEGFR2 signaling axis is mediated, at least in part, through SIRT1. The results suggest that targeting SIRT1 could have therapeutic potential for the treatment of CNV. PMID:26174951

  6. The Role of Macrophage Class A Scavenger Receptors in a Laser-Induced Murine Choroidal Neovascularization Model

    PubMed Central

    Jawad, Shayma; Liu, Baoying; Li, Zhiyu; Katamay, Robert; Campos, Mercedes; Wei, Lai; Sen, H. Nida; Ling, Diamond; Martinez Estrada, Fernando; Amaral, Juan; Chan, Chi-Chao; Fariss, Robert; Gordon, Siamon; Nussenblatt, Robert B.

    2013-01-01

    Purpose. Laser-induced choroidal neovascularization (CNV) is a widely used model to mimic many features of CNV resulting from wet AMD. Macrophages have been implicated in the pathogenesis of AMD. Class A scavenger receptors, scavenger receptor-A (SR-A) and macrophage receptor with collagenous domain (MARCO), are expressed on macrophages and are associated with macrophage function. The goal of this study is to examine the role of macrophage scavenger receptors in immune cell recruitment and the formation of CNV. Methods. Laser photocoagulation was performed in wild-type and knockout mice with deletion of SR-A (SR-A−/−), MARCO (MARCO−/−), or both SR-A and MARCO double knockout (DKO). Immune cell recruitment at different time points and CNV lesions at 14 days after laser treatment were evaluated through immunostaining and confocal microscopy. Microarray analysis was performed in eyes 1 day after laser injury. Results. Wild-type eyes showed higher chemokine/receptor expression compared with knockout eyes after laser injury. Scavenger receptor deficiency markedly impaired the recruitment of neutrophils and macrophages to CNV lesions at 1- and 3-days post laser injury, respectively. Significantly reduced CNV volumes were found in the eyes from scavenger receptor knockout mice compared with wild-type mice. Conclusions. The deficiency of scavenger receptors impairs the formation of CNV and immune cell recruitment. Our findings suggest a potential role for scavenger receptors in contributing to CNV formation and inflammation in AMD. PMID:23927892

  7. Proton-beam irradiation of subfoveal choroidal neovascular membranes in presumed ocular histoplasmosis syndrome: a case report.

    PubMed

    Liem, S E; Armbruster, F C

    1998-08-01

    Presumed ocular histoplasmosis syndrome (POHS) refers to a choroidopathy that is characterized by the presence of multiple peripheral atrophic chorioretinal scars, peri-papillary atrophy, and choroidal neovascular membranes (CNVM), usually in or adjacent to the fovea. In the United States, POHS is an important cause of loss of central visual acuity in patients between the ages of 20 and 50 years. A number of treatment options for subfoveal and juxtafoveal CNVMs in POHS have been under investigation, including laser photocoagulation, surgical excision of the CNVM, and radiation therapy. A 28-year-old women was referred to our office reporting decreased depth perception and finger-counting vision in the right eye for the duration of 1 month. A diagnosis of POHS with subfoveal CNVM was made and the patient was referred for an experimental protocol of proton-beam irradiation. Four months after her initial visit, the patient returned, reporting blurry vision with a blind spot in her left eye. A subfoveal CNVM in the left eye was subsequently treated with irradiation as well. Seven months after the initial treatment, visual acuities were 20/20 in each treated eye. Although is currently an experimental procedure, proton-beam irradiation appears to be a promising treatment for subfoveal CNVM in patients with POHS.

  8. PKR promotes choroidal neovascularization via upregulating the PI3K/Akt signaling pathway in VEGF expression

    PubMed Central

    Zhu, Manhui; Liu, Xiaojuan; Wang, Shengcun; Miao, Jin; Wu, Liucheng; Yang, Xiaowei; Wang, Ying; Kang, Lihua; Li, Wendie; Cui, Chen; Sang, Aimin

    2016-01-01

    Purpose The aim of this study was to investigate the functions of dsRNA-activated protein kinase (PKR) in choroidal neovascularization (CNV) and related signaling pathways in the production of vascular endothelial growth factor (VEGF). Methods A chemical hypoxia model of in vitro RF/6A cells, a rhesus choroid-retinal endothelial cell line, was established by adding cobalt chloride (CoCl2) to the culture medium. PKR, phosphophosphatidylinositol 3-kinase (p-PI3K), phosphoprotein kinase B (p-Akt), and VEGF protein levels in RF/6A cells were detected with western blotting. PKR siRNA and the PI3K inhibitor LY294002 were used to evaluate the roles of the PKR and PI3K signaling pathways in VEGF expression with western blotting. In an ARPE-19 (RPE cell line) and RF/6A cell coculture system, proliferation, migration, and tube formation of RF/6A cells under hypoxic conditions were measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), Transwell, and Matrigel Transwell assays, respectively. In vivo CNV lesions were induced in C57BL/6J mice using laser photocoagulation. The mice were euthanized in a timely manner, and the eyecups were dissected from enucleated eyes. PKR, p-PI3K, p-Akt, and VEGF protein levels in tissues were detected with western blotting. To evaluate the leakage area, fundus fluorescein angiography and choroidal flat mount were performed on day 7 after intravitreal injection of an anti-PKR monoclonal antibody. Results The in vitro RF/6A cell chemical hypoxia model showed that PKR expression was upregulated in parallel with p-PI3K, p-Akt, and VEGF expression, peaking at 12 h. PKR siRNA downregulated PKR, p-PI3K, p-Akt, and VEGF expression. In addition, the PI3K inhibitor LY294002 greatly decreased the p-PI3K, p-Akt, and VEGF protein levels, but PKR expression was unaffected, indicating that Akt was a downstream molecule of PKR that upregulated VEGF expression. In the ARPE-19 (RPE cell line) and RF/6A cell coculture system, PKR si

  9. OCT angiography documented reperfusion of translocated autologous full thickness RPE-choroid graft for complicated neovascular age-related macular degeneration.

    PubMed

    Veckeneer, M; Augustinus, C; Feron, E; Schauwvlieghe, P-P; Ruys, J; Cosemans, I; Van Meurs, J

    2017-09-01

    PurposeThe purpose of this study is to investigate the reperfusion of translocated retinal pigment epithelium (RPE)-choroid graft in the treatment of patients with neovascular age-related macular degeneration (nAMD), using OCT angiography (OCTA), a novel non-invasive, high-resolution imaging modality.Patients and methodsEighteen eyes of 18 consecutive patients suffering from complicated nAMD underwent RPE-choroid patch graft translocation surgery using a peripheral retinotomy and flap-over technique. We analyzed functional and anatomical outcome using visual acuity, Spectral Domain OCT and OCTA.ResultsWith a mean follow-up of 11 months, out of 18 patients, 15 gained vision, 1 remained stable, and 2 lost vision. Overall, the visual acuity improved with a mean of 30 letters. Perfusion of the graft tissue was confirmed in all patients. Two patients developed signs of a recurrent neovascular membrane during follow-up. No cases of proliferative vitreoretinopathy occurred in this series.ConclusionsOCTA images show signs of perfusion in all grafts. Encouraging functional results and low risk of severe complications suggest that RPE-choroid graft translocation is a valid option in patients with complicated nAMD.

  10. Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration: twelve-month results of the DENALI study.

    PubMed

    Kaiser, Peter K; Boyer, David S; Cruess, Alan F; Slakter, Jason S; Pilz, Stefan; Weisberger, Annemarie

    2012-05-01

    To demonstrate noninferiority of ranibizumab in combination with verteporfin photodynamic therapy (PDT) versus ranibizumab monotherapy in patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). Prospective, multicenter, double-masked, randomized, phase IIIb clinical trial. Three hundred twenty-one patients randomized to receive either ranibizumab 0.5 mg monotherapy (n = 112), standard fluence (SF) verteporfin PDT combination therapy (n = 104), or reduced fluence (RF) verteporfin PDT combination therapy (n = 105). Ranibizumab was administered monthly in the monotherapy group. In both combination therapy groups, ranibizumab was initiated with 3 consecutive monthly injections, followed by retreatment as needed (pro re nata) with monthly monitoring. All patients were evaluated monthly for 12 months. Mean change in best-corrected visual acuity (BCVA) from baseline at month 12 and proportion of patients randomized to either combination therapy with a ranibizumab treatment-free interval of 3 months or longer. Two hundred eighty-six patients (89.1%) completed the 12-month study. Mean BCVA change at month 12 was +5.3 and +4.4 letters with verteporfin SF (n = 103) or verteporfin RF (n = 105) plus ranibizumab, respectively, compared with +8.1 letters with ranibizumab monotherapy (n = 110; adjusted 97.5% confidence interval [CI], (-7.90 to infinity); P = 0.0666; and 97.5% CI, (-8.51 to infinity); P = 0.1178; for combination regimens vs. monotherapy, respectively). Noninferiority of either combination regimen to monthly ranibizumab monotherapy was not demonstrated (primary end point). A ranibizumab treatment-free interval of 3 months or longer was achieved in 92.6% and 83.5% of the patients randomized to verteporfin SF or verteporfin RF groups, respectively, with a mean of 5.1 and 5.7 ranibizumab injections, respectively, and patients in the ranibizumab monotherapy arm received 10.5 injections. At month 12, mean central retinal

  11. A Sema3C Mutant Resistant to Cleavage by Furin (FR-Sema3C) Inhibits Choroidal Neovascularization

    PubMed Central

    Toledano, Shira; Lu, Huayi; Palacio, Agustina; Ziv, Keren; Kessler, Ofra; Schaal, Shlomit; Neufeld, Gera; Barak, Yoreh

    2016-01-01

    In age-related macular degeneration (AMD), abnormal sub retinal choroidal neovascularization (CNV) is a major cause of blindness. FR-sema3C is a point mutated form of semaphorin-3C that is resistant to cleavage by furin like pro-protein convertases (FPPC). We have found in previous work that FR-sema3C functions as an anti-angiogenic factor. In this study we investigated the possible use of FR-sema3C as an inhibitor of CNV. FR-sema3C inhibits VEGF as well as PDGF-BB signal transduction in endothelial cells and to less extent bFGF induced signal transduction using a mechanism that does not depend upon the binding of VEGF like the drugs that are currently the mainstay treatment for AMD. CNV was induced in eyes of C57 black mice by laser photocoagulation. Intravitreal injection of FR-Sema3C or aflibercept (VEGF-trap) was then used to inhibit CNV formation. Invading choroidal vessels were visualized a week later by injection of FITC-dextran into the circulation, followed by the measurement of the area of the invading blood vessels. Injection of 0.1 μg FR-Sema3C inhibited CNV by 55% (P<0.01) and was as effective as 5 μg aflibercept. FR-sema3C did not display any adverse effects on retinal function following its injection into eyes of healthy mice as assessed by optokinetic reflex (OKR) and Electro-retinogram (ERG) criteria. Furthermore, FR-sema3C did not induce apoptosis in the retina as determined by TUNEL nor was there any discernable structural damage to the retina as assessed by several immuno-histochemical criteria. Our results suggest that FR-sema3C could perhaps be used for the treatment of AMD, and that it may perhaps be of benefit to patients that do not respond well to current treatments relying on VEGF sequestering agents. PMID:28036336

  12. Two‐year results of surgical removal of choroidal neovascular membranes related to non‐age‐related macular degeneration

    PubMed Central

    Essex, Rohan W; Tufail, Adnan; Bunce, Catie; Aylward, G William

    2007-01-01

    Purpose To present the 2‐year outcomes of surgical removal of non‐age‐related macular degeneration (AMD)‐related choroidal neovascular membranes and to evaluate any association between visual outcome and baseline clinical factors. Methods Retrospective consecutive case series. All patients who had surgery for non‐AMD‐related choroidal neovascularisation (CNV) between November 1997 and March 2003 under the care of a single surgeon (WA) were included in the study. Baseline data including patient age, duration of subfoveal CNV, preoperative visual acuity (VA), lesion size, lesion components and aetiology were collected. The primary outcome was VA change with secondary outcomes retinal detachment, operative peripheral retinal break formation, CNV recurrence and cataract. Results A total of 52 eyes were included in the study. The aetiology of CNV was: punctate inner choridopathy 21 (40%); idiopathic 8 (15%); pathologic myopia 6 (12%); ocular histoplasmosis syndrome 1 (2%); and other 16 (31%). The mean age of patients was 41(range 14–72) years. 24‐month follow‐up was available for 41 (80%) eyes. The mean logMAR equivalent baseline acuity was 1.1 and mean lesion size 1.2 disc areas. An improvement in VA >1 Snellen line was noted in 26 (63%) eyes, whereas 10 (24%) eyes remained the same (within 1 line) and 5 (12%) lost >1 line of acuity. Improvement in VA was associated with worse baseline VA (84% for eyes with VA ⩽6/36 vs 31% for those with VA>6/36, p = 0.001). No evidence of association between 2‐year visual outcome and any other baseline factor under study was observed. Peripheral retinal breaks were noted in 5 (10%) eyes at the time of surgery, and 3 (5.8%) eyes developed postoperative retinal detachments. Persistent/recurrent CNV was noted in 17 (33%) eyes. The median time to presentation of CNV in these eyes was 27 (range 2–172) weeks. Five eyes underwent cataract surgery during the follow‐up period. The mean age of these patients

  13. Successful long-term management of choroidal neovascularization secondary to angioid streaks in a patient with pseudoxanthoma elasticum: a case report.

    PubMed

    Savastano, Maria Cristina; Minnella, Angelo Maria; Zinzanella, Gaetano; Falsini, Benedetto; Caporossi, Aldo

    2014-12-22

    We describe the long-term effectiveness and tolerability of intravitreal vascular endothelial growth factor inhibitor ranibizumab in a patient with pseudoxanthoma elasticum with bilateral macular choroidal neovascularization secondary to angioid streaks. A 54-year-old Caucasian man with history of heart disease presented with visual loss in his right eye. An examination revealed choroidal neovascularization and reduced visual acuity, while no abnormalities were seen in his left eye. He was diagnosed with angioid streaks associated with pseudoxanthoma elasticum. Off-label treatment with intravitreal bevacizumab once a month initiated in December 2007 was discontinued after 3 months due to lack of efficacy. In September 2008, the patient reported reduced visual acuity in his left eye and an examination revealed changes. Left eye treatment was initiated in October 2008 with a loading dose (three consecutive monthly intravitreal injections of ranibizumab 0.5mg/50 μL) followed by 0.5mg/50 μL followed by treatment as needed until May 2014. After 21 ranibizumab injections, an examination revealed angioid streaks and choroidal neovascularization in both eyes. His right eye showed retinal layer deterioration with outer limiting membrane and photoreceptor inner/outer segment junction involvement. His left eye had a smaller foveal scar, with other areas preserved. Visual acuity was stable in his treated left eye, but had deteriorated in his right eye. Ranibizumab treatment was well tolerated with no adverse events reported. In the present case, an as-needed regimen of ranibizumab after an initial loading dose, achieved maintenance of visual function and was well tolerated over a period of almost 6 years in a patient with pseudoxanthoma elasticum and high cardiovascular risk. As anti-vascular endothelial growth factor agents are associated with increased risk of systemic effects, particularly arterial thromboembolic events, following intravenous administration, the absence

  14. EFFICACY AND SAFETY OF RANIBIZUMAB FOR THE TREATMENT OF CHOROIDAL NEOVASCULARIZATION DUE TO UNCOMMON CAUSE: Twelve-Month Results of the MINERVA Study.

    PubMed

    Lai, Timothy Y Y; Staurenghi, Giovanni; Lanzetta, Paolo; Holz, Frank G; Melissa Liew, Shiao Hui; Desset-Brethes, Sabine; Staines, Harry; Hykin, Philip G

    2017-07-12

    To evaluate the efficacy and safety of ranibizumab 0.5 mg in adult patients with choroidal neovascularization because of an uncommon cause enrolled in the 12-month MINERVA study. In this Phase III, double-masked study, adult (≥18 years) patients (N = 178) were randomized 2:1 to receive either ranibizumab (n = 119) or sham (n = 59) at baseline and, if needed, at Month 1 and open-label individualized ranibizumab from Month 2. Best-corrected visual acuity change from baseline to Month 2 (primary endpoint) and Month 12, treatment exposure, and safety over 12 months were reported. Subgroup analysis was conducted on five predefined choroidal neovascularization etiologies (angioid streak, postinflammatory, central serous chorioretinopathy, idiopathic, and miscellaneous). Ranibizumab showed superior efficacy versus sham from baseline to Month 2 (adjusted least-squares mean best-corrected visual acuity: +9.5 vs. -0.4 letters; P < 0.001). At Month 12, the mean best-corrected visual acuity change was +11.0 letters (ranibizumab) and +9.3 letters (sham). Across the 5 subgroups, the treatment effect ranged from +5.0 to +14.6 letters. The mean number of ranibizumab injections was 5.8 (ranibizumab arm) with no new ocular or nonocular adverse events. Ranibizumab 0.5 mg resulted in clinically significant treatment effect versus sham at Month 2. Overall, ranibizumab was effective in treating choroidal neovascularization of various etiologies with no new safety findings.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  15. Shared genetic variants for polypoidal choroidal vasculopathy and typical neovascular age-related macular degeneration in East Asians.

    PubMed

    Fan, Qiao; Cheung, Chui Ming Gemmy; Chen, Li Jia; Yamashiro, Kenji; Ahn, Jeeyun; Laude, Augustinus; Mathur, Ranjana; Mun, Chan Choi; Yeo, Ian Y; Lim, Tock Han; Teo, Yik-Ying; Khor, Chiea Chuen; Park, Kyu-Hyung; Yoshimura, Nagahisa; Pang, Chi Pui; Wong, Tien Yin; Cheng, Ching-Yu

    2017-08-24

    Polypoidal choroidal vasculopathy (PCV), a subtype of age-related macular degeneration (AMD) more frequently seen in East Asians, has both common and distinct clinical manifestations with typical neovascular AMD (tAMD). We aim to examine the extent to which common genetic variants are shared between these two subtypes. We performed the meta-analysis of association in a total of 1062 PCV patients, 1157 tAMD patients and 5275 controls of East Asian descent from the Genetics of AMD in Asians Consortium at the 34 known AMD loci. A total of eight loci were significantly associated with PCV, including age-related maculopathy susceptibility 2 (ARMS2)-HtrA serine peptidase 1 (HTRA1), complement factor H (CFH), C2-CFB-SKIV2L, CETP, VEGFA, ADAMTS9-AS2 and TGFBR1 (P<5 × 10(-4)) from the single-nucleotide polymorphism-based test and COL4A3 from the gene-based tests (Pgene=2.02 × 10(-4)). PCV and tAMD are genetically highly correlated (rg=0.69, P=4.68 × 10(-3)), with AMD known loci accounting for up to 36% variation. Weaker association for PCV was observed at ARMS2-HTRA1 (Pdif=4.39 × 10(-4)) and KMT2E-SRPK2(Pdif=4.43 × 10(-3)), compared with tAMD. Variants at CFH, CETP and VEGFA exhibited different association signals in East Asians, in contrast to those in European individuals. Our data suggest a substantially shared genetic susceptibility for PCV and tAMD, while also highlight the unique associations for PCV, which is useful in understanding the pathogenesis of PCV.Journal of Human Genetics advance online publication, 24 August 2017; doi:10.1038/jhg.2017.83.

  16. Treatment-Naïve Quiescent Choroidal Neovascularization in Geographic Atrophy Secondary to Nonexudative Age-Related Macular Degeneration.

    PubMed

    Capuano, Vittorio; Miere, Alexandra; Querques, Lea; Sacconi, Riccardo; Carnevali, Adriano; Amoroso, Francesca; Bandello, Francesco; Souied, Eric H; Querques, Giuseppe

    2017-10-01

    To describe the characteristics and natural history of quiescent choroidal neovascularization (CNV) in geographic atrophy (GA) secondary to nonexudative age-related macular degeneration (AMD) through multimodal imaging. Retrospective observational case series. Patients diagnosed with quiescent CNV were analyzed in 2 high-volume referral centers. Imaging features obtained using fluorescein angiography (FA), indocyanine green angiography (ICGA), structural optical coherence tomography (OCT), and OCT angiography (OCT-A) were noted at first presentation and during the study period. Nineteen eyes of 19 patients were included. Mean (+SD) follow-up was 45.7 ± 14.7 months. Quiescent CNV appeared as an ill-defined hyperfluorescent lesion without leakage or pooling of dye in the late phase of FA. On ICGA, quiescent CNV appeared as a distinct area of hyperfluorescence (vascular network) in early to intermediate frames and as a hyperfluorescent plaque in the late frame (late plaque). OCT-A revealed a flow signal beneath the small irregular elevation of the retinal pigment epithelium at the site of the quiescent CNV visualized by structural OCT. During the study period, 5 of the 19 CNV patients developed exudation. The remainder showed specific alterations in both structural OCT and OCT-A imaging. At last follow-up, 92% of the quiescent CNV seemed to cover the area spared from atrophy. The characteristics of the quiescent CNVs were very similar to those already described for intermediate AMD, although they had several specific features in the context of GA. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Retinal injury thresholds for 532, 578, and 630 nm lasers in connection to photodynamic therapy for choroidal neovascularization.

    PubMed

    Chen, Hongxia; Yang, Zaifu; Zou, Xianbiao; Wang, Jiarui; Zhu, Jianguo; Gu, Ying

    2014-01-01

    The purpose of this study was to explore the retinal injury thresholds in rabbits and evaluate the influence of retinal pigmentation on threshold irradiance at laser wavelengths of 532, 578, and 630 nm which might be involved in hypocrellin B (HB) and hematoporphyrin monomethyl ether (HMME) photodynamic therapy (PDT) for choroidal neovascularization (CNV). The eyes of pigmented and non-pigmented rabbits were exposed to 532, 578, and 630 nm lasers coupled to a slit lamp biological microscope. The exposure duration was 100 seconds and the retinal spot size was 2 mm throughout the experiment. The minimum visible lesions were detected by funduscopy at 1 and 24 hours post exposure. Bliss probit analysis was performed to determine the ED50 thresholds, fiducial limits and probit slope. In pigmented rabbits, the 24-hour retinal threshold irradiances at 532, 578, and 630 nm were 1,003, 1,475, and 1,720 mW/cm(2) , respectively. In non-pigmented rabbits, the 24-hour threshold irradiances were 1,657, 1,865, and 15,360 mW/cm(2) , respectively. The ED50 for 24-hour observation differed very little from the ED50 for 1-hour observation. The non-pigmented rabbits required a ninefold increase in threshold irradiance at 630 nm comparing to the pigmented rabbits. This study will contribute to the knowledge base for the limits of laser irradiance in application of HB or HMME PDT for CNV. © 2013 Wiley Periodicals, Inc.

  18. [Unusual myopic fundus alteration].

    PubMed

    Münzenberg, C; Paulsen, F; Kalinski, T; Dmitriew, A; Duncker, G I W; Sel, S

    2009-07-01

    A 44-year-old female patient reported a "black dot" which had been in front of the right eye for more than 4 days and which moved together with eye movements. The optical coherence tomography (OCT) image of the right macula showed large cystic cavities and thickening within the retinal pigment epithelium (RPE) near the fovea centralis as well as small bore cystic alterations, which indicated an event in the region of the choroid. Fluorescein angiography and indocyanine green angiography excluded choroidal neovascularization (CNV). The diagnosis revealed a broad superficial choroidal blood vessel mimicking a subretinal hemorrhage.

  19. Immunotherapy for choroidal neovascularization in a laser-induced mouse model simulating exudative (wet) macular degeneration

    NASA Astrophysics Data System (ADS)

    Bora, Puran S.; Hu, Zhiwei; Tezel, Tongalp H.; Sohn, Jeong-Hyeon; Kang, Shin Goo; Cruz, Jose M. C.; Bora, Nalini S.; Garen, Alan; Kaplan, Henry J.

    2003-03-01

    Age-related macular degeneration (AMD) is the leading cause of blindness after age 55 in the industrialized world. Severe loss of central vision frequently occurs with the exudative (wet) form of AMD, as a result of the formation of a pathological choroidal neovasculature (CNV) that damages the macular region of the retina. We tested the effect of an immunotherapy procedure, which had been shown to destroy the pathological neovasculature in solid tumors, on the formation of laser-induced CNV in a mouse model simulating exudative AMD in humans. The procedure involves administering an Icon molecule that binds with high affinity and specificity to tissue factor (TF), resulting in the activation of a potent cytolytic immune response against cells expressing TF. The Icon binds selectively to TF on the vascular endothelium of a CNV in the mouse and pig models and also on the CNV of patients with exudative AMD. Here we show that the Icon dramatically reduces the frequency of CNV formation in the mouse model. After laser treatment to induce CNV formation, the mice were injected either with an adenoviral vector encoding the Icon, resulting in synthesis of the Icon by vector-infected mouse cells, or with the Icon protein. The route of injection was i.v. or intraocular. The efficacy of the Icon in preventing formation of laser-induced CNV depends on binding selectively to the CNV. Because the Icon binds selectively to the CNV in exudative AMD as well as to laser-induced CNV, the Icon might also be efficacious for treating patients with exudative AMD.

  20. The effect of triamcinolone acetonide on laser-induced choroidal neovascularization in mice using a hypoxia visualization bio-imaging probe

    PubMed Central

    Takata, Shinsuke; Masuda, Tomomi; Nakamura, Shinsuke; Kuchimaru, Takahiro; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Nagasawa, Hideko; kizaka-Kondoh, Shinae; Hara, Hideaki

    2015-01-01

    Hypoxic stress is a risk factor of ocular neovascularization. Hypoxia visualization may provide clues regarding the underlying cause of angiogenesis. Recently, we developed a hypoxia-specific probe, protein transduction domain-oxygen-dependent degradation domain-HaloTag-Rhodamine (POH-Rhodamine). In this study, we observed the localization of HIF-1α proteins by immunohistochemistry and the fluorescence of POH-Rhodamine on RPE-choroid flat mounts. Moreover, we compared the localization of POH-Rhodamine with pimonidazole which is a standard reagent for detecting hypoxia. Next, we investigated the effects of triamcinolone acetonide (TAAC) against visual function that was evaluated by recording electroretinogram (ERG) and choroidal neovascularization (CNV) development. Mice were given laser-induced CNV using a diode laser and treated with intravitreal injection of TAAC. Finally, we investigated POH-Rhodamine on CNV treated with TAAC. In this study, the fluorescence of POH-Rhodamine and HIF-1α were co-localized in laser-irradiated sites, and both the POH-Rhodamine and pimonidazole fluorescent areas were almost the same. Intravitreal injection of TAAC restored the reduced ERG b-wave but not the a-wave and decreased the mean CNV area. Furthermore, the area of the POH-Rhodamine-positive cells decreased. These findings indicate that POH-Rhodamine is useful for evaluating tissue hypoxia in a laser-induced CNV model, suggesting that TAAC suppressed CNV through tissue hypoxia improvement. PMID:25927172

  1. Incidence of Choroidal Neovascularization in the Fellow Eye in the Comparison of Age-related Macular Degeneration Treatments Trials

    PubMed Central

    Maguire, Maureen G.; Daniel, Ebenezer; Shah, Ankoor R.; Grunwald, Juan E.; Hagstrom, Stephanie A.; Avery, Robert L.; Huang, Jiayan; Martin, Revell W.; Roth, Daniel B.; Castellarin, Alessandro A.; Bakri, Sophie J.; Fine, Stuart L.; Martin, Daniel F.

    2013-01-01

    Objective To assess the influence of drug, dosing regimen, and traditional, non-traditional, and genetic risk factors on the incidence of choroidal neovascularization (CNV) in the fellow eye of patients treated for CNV with ranibizumab or bevacizumab. Design Cohort study of patients enrolled in a multicenter randomized clinical trial. Participants Patients with no CNV in the fellow eye at the time of enrollment in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Methods Eligibility criteria for the clinical trial required that study eyes have evidence on fluorescein angiography and optical coherence tomography (OCT) of CNV secondary to age-related macular degeneration (AMD) and visual acuity between 20/25 and 20/320. Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to three different regimens for dosing over a two-year period. The genotypes for four single nucleotide polymorphisms (SNPS) associated with risk of AMD were determined. Only patients without CNV in the fellow eye at baseline were considered at risk. CATT ophthalmologists examined patients every four weeks through two years and recorded treatment for CNV in the fellow eye. Main Outcome Measures Development of CNV in the fellow eye. Results Among 1185 CATT participants, 727 (61%) had no CNV in the fellow eye at enrollment. At two years, CNV had developed in 75 (20.6%) of 365 patients treated with ranibizumab and 60 (16.6%) of 362 patients treated with bevacizumab (absolute difference 4.0%, 95% confidence interval (−1.7%, 9.6%); p=0.17). The risk ratio for pro re nata (PRN) dosing relative to monthly dosing was 1.1 (95% confidence interval (0.8, 1.6)). Greater elevation of the retinal pigment epithelium and fluid in the foveal center of the study eye were associated with increased incidence of CNV in the fellow eye. Incidence was not associated with genotype on rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3

  2. Randomized trial of a home monitoring system for early detection of choroidal neovascularization home monitoring of the Eye (HOME) study.

    PubMed

    Chew, Emily Y; Clemons, Traci E; Bressler, Susan B; Elman, Michael J; Danis, Ronald P; Domalpally, Amitha; Heier, Jeffrey S; Kim, Judy E; Garfinkel, Richard

    2014-02-01

    To determine whether home monitoring with the ForeseeHome device (Notal Vision Ltd, Tel Aviv, Israel), using macular visual field testing with hyperacuity techniques and telemonitoring, results in earlier detection of age-related macular degeneration-associated choroidal neovascularization (CNV), reflected in better visual acuity, when compared with standard care. The main predictor of treatment outcome from anti-vascular endothelial growth factor (VEGF) agents is the visual acuity at the time of CNV treatment. Unmasked, controlled, randomized clinical trial. One thousand nine hundred and seventy participants 53 to 90 years of age at high risk of CNV developing were screened. Of these, 1520 participants with a mean age of 72.5 years were enrolled in the Home Monitoring of the Eye study at 44 Age-Related Eye Disease Study 2 clinical centers. In the standard care and device arms arm, investigator-specific instructions were provided for self-monitoring vision at home followed by report of new symptoms to the clinic. In the device arm, the device was provided with recommendations for daily testing. The device monitoring center received test results and reported changes to the clinical centers, which contacted participants for examination. The main outcome measure was the difference in best-corrected visual acuity scores between baseline and detection of CNV. The event was determined by investigators based on clinical examination, color fundus photography, fluorescein angiography, and optical coherence tomography findings. Masked graders at a central reading center evaluated the images using standardized protocols. Seven hundred sixty-three participants were randomized to device monitoring and 757 participants were randomized to standard care and were followed up for a mean of 1.4 years between July 2010 and April 2013. At the prespecified interim analysis, 82 participants progressed to CNV, 51 in the device arm and 31 in the standard care arm. The primary analysis

  3. Automated Quantitation of Choroidal Neovascularization: A Comparison Study Between Spectral-Domain and Swept-Source OCT Angiograms

    PubMed Central

    Zhang, Qinqin; Chen, Chieh-Li; Chu, Zhongdi; Zheng, Fang; Miller, Andrew; Roisman, Luiz; Rafael de Oliveira Dias, Joao; Yehoshua, Zohar; Schaal, Karen B.; Feuer, William; Gregori, Giovanni; Kubach, Sophie; An, Lin; Stetson, Paul F.; Durbin, Mary K.; Rosenfeld, Philip J.; Wang, Ruikang K.

    2017-01-01

    Purpose To compare the lesion sizes of choroidal neovascularization (CNV) imaged with spectral-domain (SD) and swept-source (SS) optical coherence tomography angiography (OCTA) and measured using an automated detection algorithm. Methods Patients diagnosed with CNV were imaged by SD-OCTA and SS-OCTA systems using 3 × 3-mm and 6 × 6-mm scans. The complex optical microangiography (OMAGC) algorithm was used to generate the OCTA images. Optical coherence tomography A datasets for imaging CNV were derived by segmenting from the outer retina to 8 μm below Bruch's membrane. An artifact removal algorithm was used to generate angiograms free of retinal vessel projection artifacts. An automated detection algorithm was developed to quantify the size of the CNV. Automated measurements were compared with manual measurements. Measurements from SD-OCTA and SS-OCTA instruments were compared as well. Results Twenty-seven eyes from 23 subjects diagnosed with CNV were analyzed. No significant differences were detected between manual and automatic measurements: SD-OCTA 3 × 3-mm (P = 0.61, paired t-test) and 6 × 6-mm (P = 0.09, paired t-test) scans and the SS-OCTA 3 × 3-mm (P = 0.41, paired t-test) and 6 × 6-mm (P = 0.16, paired t-test) scans. Bland-Altman analyses were performed to confirm the agreement between automatic and manual measurements. Mean lesion sizes were significantly larger for the SS-OCTA images compared with the SD-OCTA images: 3 × 3-mm scans (P = 0.011, paired sample t-test) and the 6 × 6-mm scans (P = 0.021, paired t-test). Conclusions The automated algorithm measurements of CNV were in agreement with the hand-drawn measurements. On average, automated SS-OCTA measurements were larger than SD-OCTA measurements and consistent with the results from using hand-drawn measurements. PMID:28273317

  4. Myopic defocus in the evening is more effective at inhibiting eye growth than defocus in the morning: Effects on rhythms in axial length and choroid thickness in chicks.

    PubMed

    Nickla, Debora L; Thai, Pearl; Zanzerkia Trahan, Rinita; Totonelly, Kristen

    2017-01-01

    Animal models have shown that myopic defocus is a potent inhibitor of ocular growth: brief (1-2 h) daily periods of defocus are sufficient to counter the effects of much longer periods of hyperopic defocus, or emmetropic vision. While the variables of duration and frequency have been well-documented with regard to effect, we ask whether the efficacy of the exposures might also depend on the time of day that they are given. We also ask whether there are differential effects on the rhythms in axial length or choroidal thickness. 2-week-old chickens were divided into 2 groups: (1) "2-hr lens-wear". Chicks wore monocular +10D lenses for 2 h per day for 5 days at one of 3 times of day: 5:30 a.m. (n = 11), 12 p.m. (n = 8) or 7:30 p.m. (n = 11). (2) "2-hr minus lens-removal". Chicks wore monocular -10D lenses continually for 7 days, except for a 2-hr period when lenses were removed; the removal occurred at one of 2 times: 5:30 a.m. (n = 8) or 7:30 p.m. (n = 8). Both paradigms exposed eyes to brief myopic defocus that differed in its magnitude, and in the visual experience for the rest of the day. High frequency A-scan ultrasonography was done at the start of the experiment; on the last day, it was done at 6-hr intervals, starting at noon, over 24-hr, to assess rhythm parameters. Refractive errors were measured using a Hartinger's refractometer at the end. In both paradigms, myopic defocus in the evening was significantly more effective at inhibiting eye growth than in the morning ("2-hr lens-wear": X-C: -149 vs -83 μm/5d; "2-hr lens-removal": X-C: 91 vs 245 μm/7d; post-hoc Bonferroni test, p < 0.01 for both). Data for "noon" was similar to that of "evening". In general, the refractive errors were consistent with the eye growth. In both paradigms, a 2-way ANOVA showed that "time of day" accounted for the differences between the morning versus evening groups ("2-hr lens-wear": p = 0.0161; "2-hr lens-removal": p = 0.038). In the "plus-lens" morning

  5. A reproducible and quantifiable model of choroidal neovascularization induced by VEGF A165 after subretinal adenoviral gene transfer in the rabbit

    PubMed Central

    Kreppel, Florian; Beck, Susanne; Heiduschka, Peter; Brito, Veronica; Schnichels, Sven; Kochanek, Stefan; Schraermeyer, Ulrich

    2008-01-01

    Purpose To determine the effects of the vascular endothelial growth factor (VEGF)-A165 delivered using a high capacity adenoviral vector (HC Ad.VEGF-A) on vascular growth and pathological changes in the rabbit eye. To combine different detection methods of VEGF-A165 overexpression-induced neovascularization in the rabbit. Methods HC Ad.VEGF-A165 was constructed and injected at 5x106 infectious units (iu) into the subretinal space of rabbit eyes. Two and four weeks postinjection, the development of neovascularization and the expression of HC Ad-transduced VEGF-A165 protein were followed up in vivo by scanning laser ophthalmoscopy, fluorescein and indocyanine green angiographies and ex vivo by electron microscopy and immunohistochemistry Results We observed a choroidal neovascularization (CNV) with leakage in 83% of the rabbit eyes. Our findings present clear indications that there is a significant effect on the endothelial cells of the choriocapillaris after subretinal transduction of the retinal pigment epithelium (RPE) with VEGF-A165 vector. The choroidal endothelial cells were activated, adherent junctions opened, and the fenestration was minimized, while the extracellular matrix localized between the RPE and the endothelium of the choriocapillaris was enlarged toward the lumen of the vessels, inducing a deep invagination of the endothelial cells into the vessel lumen. They also proliferated and formed pathological vessels in the subretinal space. Moreover,there was an increased expression of basic fibroblast growth factor and VEGF-A accompanied by macrophage stimulation, retinal edema, and photoreceptor loss. Conclusions This is the first model of VEGF-induced CNV in the rabbit in which the pathological events following overexpression of VEGF by RPE cells have been described in detail. Many of the features of our experimental CNV resemble those observed clinically in patients having wet age-related macular degeneration. PMID:18682809

  6. COL8A1 rs13095226 polymorphism shows no association with neovascular age-related macular degeneration or polypoidal choroidal vasculopathy in Chinese subjects.

    PubMed

    Yu, Yang; Huang, Lvzhen; Wang, Bin; Zhang, Chunfang; Bai, Yujing; Li, Xiaoxin

    2015-01-01

    Age-related macular degeneration (AMD) is the main cause of visual impairment and legal blindness in older individuals. COL8A1 rs13095226 variants have recently been implicated associated with neovascular age-related macular degeneration (nAMD) and Polypoidal Choroidal Vasculopathy (PCV) in American studies. The aim of this study was to investigate the association between the COL8A1 rs13095226 Polymorphism and neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in Chinese people. 900 Chinese subjects-300 cases with nAMD, 300 cases with PCV and 300 controls, were enrolled in a cross-sectional observational study. The diagnoses of nAMD and PCV were confirmed by Fundus photography, Fluorescence Fundus Angiography (FFA) and Indocyanine Green Angiography (ICGA). Genomic DNA was extracted from venous blood leukocytes and genotypes of rs13095226 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Differences in allele distribution between cases and controls were tested by chi-square tests, with age and gender adjusted by logistic regression analysis. The COL8A1 rs13095226 polymorphism was not statistically significantly different from the nAMD or PCV to the normal controls (P>0.05) in Chinese Population. The association remained insignificant after adjustment for age and gender differences (P>0.05). This case-control study indicated that the COL8A1 rs13095226 polymorphism is not associated with nAMD or PCV, which suggesting this gene maybe not a susceptibility gene locus for nAMD or PCV in Chinese subjects.

  7. Management of recurrent inflammatory choroidal neovascular membrane secondary to Vogt-Koyanagi-Harada syndrome, using combined intravitreal injection of bevacizumab and triamcinolone acetate

    PubMed Central

    Pai, Sivakami A; Hebri, Sudhira P; Lootah, Afra M

    2012-01-01

    The purpose of this report is to evaluate the efficacy and safety of combined intravitreal injection of bevacizumab and intravitreal triamcinolone acetonide (IVTA) for recurrent inflammatory choroidal neovascular membrane (CNVM). It was a prospective interventional study of a young female, who was a known case of Vogt-Koyanagi-Harada syndrome. She presented with an inflammatory choroidal neovascualar membrane and signs of panuveitis in the right eye. She underwent a complete ophthalmic examination. She was given intravitreal injection of bevacizumab and IVTA at different sites. There was complete regression of CNVM and ocular inflammation within a week. After six months, she had recurrence of CNVM in the same eye, which was treated similarly. There was a complete resolution of CNVM and ocular inflammation after the combination therapy and systemic steroids, until one year of follow-up. No serious systemic or ocular adverse events were noted. Combination therapy appears to be an effective and safe method in the management of recurrent inflammatory CNVM. PMID:23202396

  8. The Sustained Delivery of Resveratrol or a Defined Grape Powder Inhibits New Blood Vessel Formation in a Mouse Model of Choroidal Neovascularization

    PubMed Central

    Kanavi, Mozhgan Rezaie; Darjatmoko, Soesiawati; Wang, Shoujian; Azari, Amir A.; Farnoodian, Mitra; Kenealey, Jason D.; van Ginkel, Paul R.; Albert, Daniel M.; Sheibani, Nader; Polans, Arthur S.

    2015-01-01

    The objective of this study was to determine whether resveratrol or a defined, reconstituted grape powder can attenuate the formation of new blood vessels in a mouse model of choroidal neovascularization (CNV). To accomplish this objective, C57BL/6J mice were randomized into control or treatment groups which received either resveratrol or grape powder by daily oral gavage, resveratrol or grape powder delivered ad libitum through the drinking water, or resveratrol by slow release via implanted osmotic pumps. A laser was used to rupture Bruch’s membrane to induce CNV which was then detected in sclerochoroidal eyecups stained with antibodies against intercellular adhesion molecule-2. CNV area was measured using fluorescence microscopy and Image J software. Ad libitum delivery of both resveratrol and grape powder was shown to significantly reduce the extent of CNV by 68% and 57%, respectively. Parallel experiments conducted in vitro demonstrated that resveratrol activates p53 and inactivates Akt/protein kinase B in choroidal endothelial cells, contributing to its anti-proliferative and anti-migratory properties. In addition resveratrol was shown to inhibit the formation of endothelial cell networks, augmenting its overall anti-angiogenic effects. The non-toxic nature of resveratrol makes it an especially attractive candidate for the prevention and/or treatment of CNV. PMID:25361423

  9. Intravitreal Poly(L-lactide) Microparticles Sustain Retinal and Choroidal Delivery of TG-0054, a Hydrophilic Drug Intended for Neovascular Diseases

    PubMed Central

    Shelke, Namdev B; Kadam, Rajendra; Tyagi, Puneet; Rao, Vidhya R; Kompella, Uday B.

    2012-01-01

    While poorly soluble drugs such as corticosteroids sustain drug delivery in the vitreous humor by virtue of slow dissolution, macromolecules such as antibodies and their fragments sustain their levels due to their slow clearance. However, currently there are no approaches to sustain the delivery of well water soluble small molecule drugs in the vitreous. In this study we optimized a PLA microparticle formulation for sustained intravitreal delivery of TG-0054, a well water soluble anti-angiogenic drug that is of potential value in treating choroid neovascularization. After determining the influence of process parameters on particle size and drug loading, spherical microparticles syringeable through a 27 G needle, with a mean diameter of 7.6 μm, 10% w/w TG-0054 loading, sustained in vitro drug release for at least 6 months, and low residual organic solvent content (~ 1 ppb/mg) were prepared. Microparticles as well as drug solution were assessed for their in vivo drug delivery over 3 months following intravitreal injection in New Zealand white rabbits. Drug levels in the microparticle dosed eyes at 3 months were 43.7 ± 16.2, 243 ± 42.6, 62.8 ± 22.6 μg/g vitreous, retina, and choroid-RPE, respectively, and similar to levels at one month. Intravitreal injection of plain drug solution resulted in significantly lower amounts of drug in the dosed eye, with the levels being 0.8 ± 0.5, 2.7 ± 2.8, and 4.9± 4.2 μg/g in vitreous, retina, and choroid-RPE, respectively, at one month, with no detectable drug at three months. Although surface degradation was evident, microparticles maintained their spherical structure during the 6 months in vitro study and the 3 months in vivo study, with the vitreal particle retention at 1 and 3 months being 60% and 27%, respectively. Thus, PLA microparticles capable of sustaining retinal and choroidal delivery of TG-0054 for three to six months were developed. PMID:22888471

  10. Connecting the innate and adaptive immune responses in mouse choroidal neovascularization via the anaphylatoxin C5a and γδT-cells

    PubMed Central

    Coughlin, Beth; Schnabolk, Gloriane; Joseph, Kusumam; Raikwar, Himanshu; Kunchithapautham, Kannan; Johnson, Krista; Moore, Kristi; Wang, Yi; Rohrer, Bärbel

    2016-01-01

    Neovascular age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV). An overactive complement system is associated with AMD pathogenesis, and serum pro-inflammatory cytokines, including IL-17, are elevated in AMD patients. IL-17 is produced by complement C5a-receptor-expressing T-cells. In murine CNV, infiltrating γδT- rather than Th17-cells produce the IL-17 measurable in lesioned eyes. Here we asked whether C5a generated locally in response to CNV recruits IL-17-producing T-cells to the eye. CNV lesions were generated using laser photocoagulation and quantified by imaging; T-lymphocytes were characterized by QRT-PCR. CNV resulted in an increase in splenic IL-17-producing γδT- and Th17-cells; yet in the CNV eye, only elevated levels of γδT-cells were observed. Systemic administration of anti-C5- or anti-C5a-blocking antibodies blunted the CNV-induced production of splenic Th17- and γδT-cells, reduced CNV size and eliminated ocular γδT-cell infiltration. In ARPE-19 cell monolayers, IL-17 triggered a pro-inflammatory state; and splenocyte proliferation was elevated in response to ocular proteins. Thus, we demonstrated that CNV lesions trigger a systemic immune response, augmenting local ocular inflammation via the infiltration of IL-17-producing γδT-cells, which are presumably recruited to the eye in a C5a-dependent manner. Understanding the complexity of complement-mediated pathological mechanisms will aid in the development of an AMD treatment. PMID:27029558

  11. Change in choroidal thickness after intravitreal aflibercept in pretreated and treatment-naive eyes for neovascular age-related macular degeneration

    PubMed Central

    Mazaraki, Kyriaki; Fassnacht-Riederle, Heidi; Blum, Robert; Becker, Matthias; Michels, Stephan

    2015-01-01

    Aim Evaluation of effects of intravitreal aflibercept therapy on choroidal thickness (CT) in neovascular age-related macular degeneration. Methods Retrospective cohort study evaluating the change in CT following a loading dose of three intravitreal aflibercept injections at 4 weeks interval. Pretreated and treatment-naive eyes as well as untreated fellow eyes were evaluated at five retinal locations (subfoveal, 300 and 2500 µm nasal and temporal to the fovea) using spectral domain optical coherence tomography prior to and 4 weeks after a loading dose of three intravitreal aflibercept injections. Results A total of 84 treated eyes (61 pretreated, 23 treatment naive) and 48 fellow eyes were enrolled into the study. Treatment-naive and pretreated eyes showed a significant reduction in CT at all retinal locations. The effect was more pronounced in treatment-naive eyes. In the pretreated group, the mean reduction in CT was greatest at 2500 µm temporal to the fovea at 10.7 µm compared with 22.4 at 300 µm nasal to the fovea in the treatment-naive group. Only the fellow eyes in the treatment-naive group showed a significant CT reduction 12 weeks after initiation of therapy to the partner eye. Conclusions Aflibercept induces a reduction in CT in treatment-naive and pretreated eyes with neovascular age-related macular degeneration. There is some evidence of a systemic effect of aflibercept reflected by CT reduction in untreated fellow eyes. PMID:25877895

  12. Intravitreal anti-vascular endothelial growth factor combined with half-fluence photodynamic therapy for choroidal neovascularization in chronic central serous chorioretinopathy

    PubMed Central

    Smretschnig, E; Hagen, S; Glittenberg, C; Ristl, R; Krebs, I; Binder, S; Ansari-Shahrezaei, S

    2016-01-01

    Purpose To evaluate the results of indocyanine green angiography (ICGA)-guided verteporfin photodynamic therapy (PDT) with half-fluence rate combined with intravitreal application of anti-VEGF in treating choroidal neovascularization (CNV) in chronic central serous chorioretinopathy (CSCR). Patients and methods In this retrospective cohort study 17 consecutive patients with secondary CNV due to chronic CSCR had their diagnosis verified with fluorescein angiography (FA) and ICGA at baseline. All eyes received either intravitreal ranibizumab (IVR) or bevacizumab (IVB). On the consecutive day following the initial IVR/IVB treatment, ICGA-guided verteporfin (6 mg/m2) PDT with half-fluence rate (25 J/cm2) was performed on every patient. IVR or IVB was rescheduled on a pro re nata regimen. Main outcome measures were changes in visual acuity (VA) according to the ETDRS letter score and changes in the central foveal thickness (CFT). Results Best-corrected VA at baseline was 65.6 letters (±6.7; n=17) according to the ETDRS letter score. At 12 months, mean ETDRS letter score improved to 71.2 letters (P=0.34). CFT was 309 μm and decreased to 216 μm at month 12 control (P=0.0004). Nine eyes (52.9%) received additional treatment with IVR/IVB due to recurrence of subretinal fluid, with an overall mean number of IVR/IVB treatment of 1.8±3.6 per patient with no systemic side effects during 12 months' follow-up. Conclusions IVR or IVB combined with ICGA-guided half-fluence PDT with verteporfin is effective in treating CNV in chronic CSCR, with choroidal hyperpermeability in ICGA, resulting in stable vision and significant reduction of CFT. PMID:26965012

  13. TGF-β participates choroid neovascularization through Smad2/3-VEGF/TNF-α signaling in mice with Laser-induced wet age-related macular degeneration.

    PubMed

    Wang, Xiaolei; Ma, Wei; Han, Song; Meng, Zhaoyang; Zhao, Lu; Yin, Yi; Wang, Yanling; Li, Junfa

    2017-08-29

    Choroidal neovascularization(CNV) is the most severe complication in Age-related macular degeneration(AMD) and the most common cause of irreversible blindness in the elderly in developed world. The aim of this study was to identify the effect of transforming growth factor-β(TGF-β) and Smad2/3-VEGF/TNF-α signaling on CNV angiopoiesis, and to explore TGF-β inhibitors on the development of CNV in a CNV mouse model. Fundus fluorescein angiography(FFA) was used to evaluate the laser-induced CNV formation. The histology of CNV lesions stained with hematoxylin-eosin(HE) was obtained. The immunofluorescent staining was performed to determine TGF-β protein expression. The expressions of TGF-β, phosphorylated Smad2/3, VEGF and TNF-α were determined by using Western blot analysis. The CNV areas were analyzed by using fluorescein stain on RPE/choroid-sclera flat mounts. We found the levels of TGF-β protein expression increasingly reached the peak till 3rd week during the CNV development. The protein levels of VEGF and TNF-α also increased significantly in CNV mice, which were inhibited by a synthetic TGF-β inhibitor LY2157299 or a natural TGF-β inhibitor Decorin. The phosphorylated Smad2/3 levels increased significantly in CNV mice, but this response was profoundly suppressed by the TGF-β inhibitors. Here we have demonstrated that TGF-β/Smad signaling plays an important role in Laser-induced CNV formation through down-regulation of VEGF and TNF-α expressions, suggesting TGF-β inhibitors may provide an alternative to traditional methods in wet AMD treatment.

  14. Equine infectious anemia viral vector-mediated codelivery of endostatin and angiostatin driven by retinal pigmented epithelium-specific VMD2 promoter inhibits choroidal neovascularization.

    PubMed

    Kachi, Shu; Binley, Katie; Yokoi, Katsutoshi; Umeda, Naoyasu; Akiyama, Hideo; Muramatu, Daisuke; Iqball, Sharifah; Kan, On; Naylor, Stuart; Campochiaro, Peter A

    2009-01-01

    Equine infectious anemia virus (EIAV) is a nonprimate lentivirus that does not cause human disease. Subretinal injection into mice of a recombinant EIAV lentiviral vector in which lacZ is driven by a CMV promoter (EIAV CMV LacZ) resulted in rapid and strong expression of LacZ in retinal pigmented epithelial (RPE) cells and some other cells including ganglion cells, resulting in the presence of 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside within the optic nerve. Substitution of the RPE-specific promoter from the vitelliform macular dystrophy (VMD2) gene for the CMV promoter resulted in prolonged (at least 1 year) expression of LacZ that was restricted to RPE cells, albeit reduced 6- to 10-fold compared with the CMV promoter. Similarly, the amount of FLAG-tagged endostatin detected in eyes injected with the EIAV VMD2 Endo(FLAG) vector was similar to that seen in eyes injected with a vector that expressed both endostatin and angiostatin [EIAV VMD2 Endo(FLAG)/Angio]; expression was approximately 6-fold lower than with identical vectors in which the CMV promoter drove expression. Compared with murine eyes treated with a control EIAV vector, subretinal injection of EIAV vectors expressing murine endostatin alone or in combination with angiostatin driven by either the CMV or VMD2 promoter caused significant suppression of choroidal neovascularization (NV) at laser-induced rupture sites in Bruch's membrane. These data support proceeding toward clinical studies with EIAV-based gene therapy for choroidal NV, using the VMD2 promoter to selectively drive expression of a combination of endostatin and angiostatin in RPE cells.

  15. Stereotactic radiotherapy in neovascular age-related macular degeneration: Real-life efficacy and morphological evaluation of the outer retina-choroid complex.

    PubMed

    Ranjbar, Mahdy; Kurz, Maximilian; Holzhey, Annekatrin; Melchert, Corinna; Rades, Dirk; Grisanti, Salvatore

    2016-12-01

    Stereotactic radiotherapy (SRT) is a new approach to treat neovascular age-related macular degeneration (nAMD). The INTREPID trial suggested that SRT could reduce the frequency of regular intravitreal injections (IVIs) with antivascular endothelial growth factor drugs, which are necessary to control disease activity. However, the efficacy of SRT in nAMD and resulting morphological changes have not been validated under real-life circumstances, an issue, which we would like to address in this retrospective analysis.Patients who met the INTREPID criteria for best responders were eligible for SRT. A total of 32 eyes of 32 patients were treated. Thereafter, patients were examined monthly for 12 months and received pro re nata IVI of aflibercept or ranibizumab. Outcome measures were: mean number of injections, best-corrected visual acuity, and morphological changes of the outer retina-choroid complex as well as patient safety.Mean number of IVI decreased by almost 50% during the 12 months after SRT compared to the year before, whereas visual acuity increased by one line (logMAR). Morphological evaluation showed that most changes affect outer retinal layers.Stereotactic radiotherapy significantly reduced IVI retreatment in nAMD patients under real-life circumstances. Therefore, SRT might be the first step to stop visual loss as a result of IVI undertreatment, which is a major risk.

  16. Preliminary in vitro and in vivo assessment of a new targeted inhibitor for choroidal neovascularization in age-related macular degeneration

    PubMed Central

    Li, Wenbo; Dong, Lijie; Ma, Minwang; Hu, Bojie; Lu, Zhenyu; Liu, Xun; Liu, Juping; Li, Xiaorong

    2016-01-01

    Choroidal neovascularization (CNV) in age-related macular degeneration usually causes blindness. We established a novel targeted inhibitor for CNV in age-related macular degeneration. The inhibitor CR2-sFlt 1 comprises a CR2-targeting fragment and an anti-vascular endothelial growth factor (VEGF) domain (sFlt 1). The targeting of CR2-sFlt 1 was studied using the transwell assay in vitro and frozen sections in vivo using green fluorescent labeling. Transwell assay results showed that CR2-sFlt 1 migrated to the interface of complement activation products and was present in the retinal tissue of the CR2-sFlt 1-treated CNV mice. Treatment effects were assessed by investigating the VEGF concentration in retinal pigmented epithelial cell medium and the thickness of the CNV complex in the mice treated with CR2-sFlt 1. CR2-sFlt 1 significantly reduced the VEGF secretion from retinal pigmented epithelial cells in vitro and retarded CNV progress in a mouse model. Expression analysis of VEGF and VEGFRs after CR2-sFlt 1 intervention indicated the existence of feedback mechanisms in exogenous CR2-sFlt 1, endogenous VEGF, and VEGFR interaction. In summary, we demonstrated for the first time that using CR2-sFlt 1 could inhibit CNV with clear targeting and high selectivity. PMID:27799741

  17. Preliminary in vitro and in vivo assessment of a new targeted inhibitor for choroidal neovascularization in age-related macular degeneration.

    PubMed

    Li, Wenbo; Dong, Lijie; Ma, Minwang; Hu, Bojie; Lu, Zhenyu; Liu, Xun; Liu, Juping; Li, Xiaorong

    2016-01-01

    Choroidal neovascularization (CNV) in age-related macular degeneration usually causes blindness. We established a novel targeted inhibitor for CNV in age-related macular degeneration. The inhibitor CR2-sFlt 1 comprises a CR2-targeting fragment and an anti-vascular endothelial growth factor (VEGF) domain (sFlt 1). The targeting of CR2-sFlt 1 was studied using the transwell assay in vitro and frozen sections in vivo using green fluorescent labeling. Transwell assay results showed that CR2-sFlt 1 migrated to the interface of complement activation products and was present in the retinal tissue of the CR2-sFlt 1-treated CNV mice. Treatment effects were assessed by investigating the VEGF concentration in retinal pigmented epithelial cell medium and the thickness of the CNV complex in the mice treated with CR2-sFlt 1. CR2-sFlt 1 significantly reduced the VEGF secretion from retinal pigmented epithelial cells in vitro and retarded CNV progress in a mouse model. Expression analysis of VEGF and VEGFRs after CR2-sFlt 1 intervention indicated the existence of feedback mechanisms in exogenous CR2-sFlt 1, endogenous VEGF, and VEGFR interaction. In summary, we demonstrated for the first time that using CR2-sFlt 1 could inhibit CNV with clear targeting and high selectivity.

  18. [High myopic patients: A survey of their history, feelings, beliefs and needs].

    PubMed

    Gaucher, D; Chartier, C; Cohen, S-Y; Malecaze, F; Souied, E H; Weber, M; Leveziel, N

    2016-01-01

    High myopia (HM), which affects 0.9 to 3.1% of the population, is a major cause of vision loss. The purpose of this investigation was to study and evaluate the impact of their high myopia on the daily lives of patients and to better understand their expectations in order to better meet their needs. The survey was conducted between February 19 and March 21, 2014. To be eligible, patients had to have myopia of at least -8 diopters and be over 40 years of age, with or without myopic complications. Patients' degree of myopia was defined as the optical prescription of their worse eye. The 123 patients included were interviewed by phone using a questionnaire developed and validated by a scientific committee composed of experts and members of the patients' Association against myopic maculopathy (AMAM). The phone interview, semi-structured, lasted 20 minutes. On average, myopia was -11.7 diopters. Women accounted for 71% of the population, 89% of patients were under 65 years and were mostly professionals (65%). Over half of the subjects reported myopic complications; 5% of patients had choroidal neovascularization (CNV). Only 29% had been informed of the risk of CNV or maculopathy. HM was a handicap in sports for 64% of patients, in leisure activities for 51%, and in professional activities for more than a quarter (28%). Only 56% of HM patients reported living perfectly well with their condition. This survey is the first study on the daily life of people with HM aiming to analyze their social and emotional environment. It shows that HM has a profound impact on the daily lives of patients and may affect social life and professional activity. Most myopic patients possess incomplete or unclear information about the nature and risk of myopic complications. They expressed the desire to be better informed about their condition earlier, before the onset of complications. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  19. Changes in Fundus Autofluorescence after Anti-vascular Endothelial Growth Factor According to the Type of Choroidal Neovascularization in Age-related Macular Degeneration.

    PubMed

    Lee, Ji Young; Chung, Hyewon; Kim, Hyung Chan

    2016-02-01

    To describe the changes of fundus autofluorescence (FAF) in patients with age-related macular degeneration before and after intravitreal injection of anti-vascular endothelial growth factor according to the type of choroidal neovascularization (CNV) and to evaluate the correlation of FAF with spectral domain optical coherence tomography (SD-OCT) parameters and vision. This was a retrospective study. Twenty-one treatment-naïve patients with neovascular age-related macular degeneration were included. Study eyes were divided into two groups according to the type of CNV. Fourteen eyes were type 1 CNV and seven eyes were type 2 CNV. All eyes underwent a complete ophthalmologic examination, including an assessment of best-corrected visual acuity, SD-OCT, fluorescein angiography, and FAF imaging, before and 3 months after intravitreal anti-vascular endothelial growth factor injection. Gray scales of FAF image for CNV areas, delineated as in fluorescein angiography, were analyzed using the ImageJ program, which were adjusted by comparison with normal background areas. Correlation of changes in FAF with changes in SD-OCT parameters, including CNV thickness, photoreceptor inner and outer segment junction disruption length, external limiting membrane disruption length, central macular thickness, subretinal fluid, and intraretinal fluid were analyzed. Eyes with both type 1 and type 2 CNV showed reduced FAF before treatment. The mean gray scales (%) of type 1 and type 2 CNV were 52.20% and 42.55%, respectively. The background values were 106.72 and 96.86. After treatment, the mean gray scales (%) of type 1 CNV and type 2 CNV were changed to 57.61% (p = 0.005) and 57.93% (p = 0.008), respectively. After treatment, CNV thickness, central macular thickness, and inner and outer segment junction disruption length were decreased while FAF increased. FAF was noted to be reduced in eyes with newly diagnosed wet age-related macular degeneration, but increased after anti

  20. Gene Transfer of Prolyl Hydroxylase Domain 2 Inhibits Hypoxia-inducible Angiogenesis in a Model of Choroidal Neovascularization

    PubMed Central

    Takei, Anna; Ekström, Malena; Mammadzada, Parviz; Aronsson, Monica; Yu, Ma; Kvanta, Anders; André, Helder

    2017-01-01

    Cellular responses to hypoxia are mediated by the hypoxia-inducible factors (HIF). In normoxia, HIF-α proteins are regulated by a family of dioxygenases, through prolyl and asparagyl hydroxylation, culminating in proteasomal degradation and transcriptional inactivation. In hypoxia, the dioxygenases become inactive and allow formation of HIF transcription factor, responsible for upregulation of hypoxia genes. In ocular neoangiogenic diseases, such as neovascular age-related macular degeneration (nAMD), hypoxia seems pivotal. Here, we investigate the effects of HIF regulatory proteins on the hypoxia pathway in retinal pigment epithelium (RPE) cells, critically involved in nAMD pathogenesis. Our data indicates that, in ARPE-19 cells, prolyl hydroxylase domain (PHD)2 is the most potent negative-regulator of the HIF pathway. The negative effects of PHD2 on the hypoxia pathway were associated with decreased HIF-1α protein levels, and concomitant decrease in angiogenic factors. ARPE-19 cells stably expressing PHD2 impaired angiogenesis in vitro by wound healing, tubulogenesis, and sprouting assays, as well as in vivo by iris-induced angiogenesis. Gene transfer of PHD2 in vivo resulted in mitigation of HIF-mediated angiogenesis in a mouse model of nAMD. These results may have implications for the clinical treatment of nAMD patients, particularly regarding the use of gene therapy to negatively regulate neoangiogenesis. PMID:28186209

  1. Gene Transfer of Prolyl Hydroxylase Domain 2 Inhibits Hypoxia-inducible Angiogenesis in a Model of Choroidal Neovascularization.

    PubMed

    Takei, Anna; Ekström, Malena; Mammadzada, Parviz; Aronsson, Monica; Yu, Ma; Kvanta, Anders; André, Helder

    2017-02-10

    Cellular responses to hypoxia are mediated by the hypoxia-inducible factors (HIF). In normoxia, HIF-α proteins are regulated by a family of dioxygenases, through prolyl and asparagyl hydroxylation, culminating in proteasomal degradation and transcriptional inactivation. In hypoxia, the dioxygenases become inactive and allow formation of HIF transcription factor, responsible for upregulation of hypoxia genes. In ocular neoangiogenic diseases, such as neovascular age-related macular degeneration (nAMD), hypoxia seems pivotal. Here, we investigate the effects of HIF regulatory proteins on the hypoxia pathway in retinal pigment epithelium (RPE) cells, critically involved in nAMD pathogenesis. Our data indicates that, in ARPE-19 cells, prolyl hydroxylase domain (PHD)2 is the most potent negative-regulator of the HIF pathway. The negative effects of PHD2 on the hypoxia pathway were associated with decreased HIF-1α protein levels, and concomitant decrease in angiogenic factors. ARPE-19 cells stably expressing PHD2 impaired angiogenesis in vitro by wound healing, tubulogenesis, and sprouting assays, as well as in vivo by iris-induced angiogenesis. Gene transfer of PHD2 in vivo resulted in mitigation of HIF-mediated angiogenesis in a mouse model of nAMD. These results may have implications for the clinical treatment of nAMD patients, particularly regarding the use of gene therapy to negatively regulate neoangiogenesis.

  2. The association of age-related maculopathy susceptibility 2 polymorphisms with phenotype in typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy

    PubMed Central

    Bessho, Hiroaki; Kondo, Naoshi; Negi, Akira

    2011-01-01

    Purpose To determine the association of age-related maculopathy susceptibility 2 (ARMS2) gene polymorphisms with the phenotype of typical neovascular age-related macular degeneration (tAMD) and polypoidal choroidal vasculopathy (PCV) and the effects of photodynamic therapy (PDT). Methods The single nucleotide polymorphisms at rs10490924 (A69S) in ARMS2 of 68 tAMD and 119 PCV patients who underwent PDT were genotyped using the TaqMan assay. The baseline best corrected visual acuity (BCVA) and lesion size were compared among the three genotypes at rs10490924. A multivariate regression analysis was performed to evaluate the influence of the baseline BCVA, greatest linear dimension (GLD), and lesion phenotype (tAMD or PCV) on the association of rs10490924 with the BCVA 12 months after the first PDT. Results The mean lesion size was significantly different among the GG, GT, and TT genotypes at rs10490924 in the PCV group, although no significant differences were detected in the tAMD group. PCV patients with a G allele had significantly better vision at 3 months after the initial PDT. tAMD patients with a TT genotype had significantly poorer vision at 12 months after the first PDT. In the multivariate regression analysis, the additive model of the G allele at rs10490924 was associated with a significantly better BCVA 12 months after the first PDT in tAMD and PCV patients. Conclusions ARMS2 variants are likely associated with the phenotype and the effects of PDT in tAMD and PCV. PMID:21541271

  3. Adeno-Associated Viral Vector-Mediated mTOR Inhibition by Short Hairpin RNA Suppresses Laser-Induced Choroidal Neovascularization.

    PubMed

    Park, Tae Kwann; Lee, Si Hyung; Choi, Jun Sub; Nah, Seung Kwan; Kim, Hee Jong; Park, Ha Yan; Lee, Heuiran; Lee, Steven Hyun Seung; Park, Keerang

    2017-09-15

    Choroidal neovascularization (CNV) is the defining characteristic feature of the wet subtype of age-related macular degeneration (AMD) and may result in irreversible blindness. Based on anti-vascular endothelial growth factor (anti-VEGF), the current therapeutic approaches to CNV are fraught with difficulties, and mammalian target of rapamycin (mTOR) has recently been proposed as a possible therapeutic target, although few studies have been conducted. Here, we show that a recombinant adeno-associated virus-delivered mTOR-inhibiting short hairpin RNA (rAAV-mTOR shRNA), which blocks the activity of both mTOR complex 1 and 2, represents a promising therapeutic approach for the treatment of CNV. Eight-week-old male C57/B6 mice were treated with the short hairpin RNA (shRNA) after generating CNV lesions in the eyes via laser photocoagulation. The recombinant adeno-associated virus (rAAV) delivery vehicle was able to effectively transduce cells in the inner retina, and significantly fewer inflammatory cells and less extensive CNV were observed in the animals treated with rAAV-mTOR shRNA when compared with control- and rAAV-scrambled shRNA-treated groups. Presumably related to the reduction of CNV, increased autophagy was detected in CNV lesions treated with rAAV-mTOR shRNA, whereas significantly fewer apoptotic cells detected in the outer nuclear layer around the CNV indicate that mTOR inhibition may also have neuroprotective effects. Taken together, these results demonstrate the therapeutic potential of mTOR inhibition, resulting from rAAV-mTOR shRNA activity, in the treatment of AMD-related CNV. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Detailed functional and structural phenotype of Bietti crystalline dystrophy associated with mutations in CYP4V2 complicated by choroidal neovascularization.

    PubMed

    Fuerst, Nicole M; Serrano, Leona; Han, Grace; Morgan, Jessica I W; Maguire, Albert M; Leroy, Bart P; Kim, Benjamin J; Aleman, Tomas S

    2016-12-01

    To describe in detail the phenotype of a patient with Bietti crystalline dystrophy (BCD) complicated by choroidal neovascularization (CNV) and the response to intravitreal Bevacizumab (Avastin(®); Genentech/Roche). A 34-year-old woman with BCD and mutations in CYP4V2 (c.802-8_806del13/p.H331P:c992A>C) underwent a complete ophthalmic examination, full-field flash electroretinography (ERG), kinetic and two-color dark-adapted perimetry, and dark-adaptometry. Imaging was performed with spectral domain optical coherence tomography (SD-OCT), near infrared (NIR) and short wavelength (SW) fundus autofluorescence (FAF), and fluorescein angiography (FA). Best-corrected visual acuity (BCVA) was 20/20 and 20/60 for the right and left eye, respectively. There were corneal paralimbal crystal-like deposits. Kinetic fields were normal in the peripheral extent. Retinal crystals were most obvious on NIR-reflectance and corresponded with hyperreflectivities within the RPE on SD-OCT. There was parafoveal/perifoveal hypofluorescence on SW-FAF and NIR-FAF. Rod > cone sensitivity loss surrounded fixation and extended to ~10° of eccentricity corresponding to regions of photoreceptor outer segment-retinal pigmented epithelium (RPE) interdigitation abnormalities. The outer nuclear layer was normal in thickness. Recovery of sensitivity following a ~76% rhodopsin bleach was normal. ERGs were normal. A subretinal hemorrhage in the left eye co-localized with elevation of the RPE on SD-OCT and leakage on FA, suggestive of CNV. Three monthly intravitreal injections of Bevacizumab led to restoration of BCVA to baseline (20/25). crystals in BCD were predominantly located within the RPE. Photoreceptor outer segment and apical RPE abnormalities underlie the relatively extensive retinal dysfunction observed in relatively early-stage BCD. Intravitreal Bevacizumab was effective in treating CNV in this setting.

  5. Analysis of Fundus Shape in Highly Myopic Eyes by Using Curvature Maps Constructed from Optical Coherence Tomography

    PubMed Central

    Miyake, Masahiro; Yamashiro, Kenji; Akagi-Kurashige, Yumiko; Oishi, Akio; Tsujikawa, Akitaka; Hangai, Masanori; Yoshimura, Nagahisa

    2014-01-01

    Purpose To evaluate fundus shape in highly myopic eyes using color maps created through optical coherence tomography (OCT) image analysis. Methods We retrospectively evaluated 182 highly myopic eyes from 113 patients. After obtaining 12 lines of 9-mm radial OCT scans with the fovea at the center, the Bruch’s membrane line was plotted and its curvature was measured at 1-µm intervals in each image, which was reflected as a color topography map. For the quantitative analysis of the eye shape, mean absolute curvature and variance of curvature were calculated. Results The color maps allowed staphyloma visualization as a ring of green color at the edge and as that of orange-red color at the bottom. Analyses of mean and variance of curvature revealed that eyes with myopic choroidal neovascularization tended to have relatively flat posterior poles with smooth surfaces, while eyes with chorioretinal atrophy exhibited a steep, curved shape with an undulated surface (P<0.001). Furthermore, eyes with staphylomas and those without clearly differed in terms of mean curvature and the variance of curvature: 98.4% of eyes with staphylomas had mean curvature ≥7.8×10−5 [1/µm] and variance of curvature ≥0.26×10−8 [1/µm]. Conclusions We established a novel method to analyze posterior pole shape by using OCT images to construct curvature maps. Our quantitative analysis revealed that fundus shape is associated with myopic complications. These values were also effective in distinguishing eyes with staphylomas from those without. This tool for the quantitative evaluation of eye shape should facilitate future research of myopic complications. PMID:25259853

  6. Choroidal neovascularization analyzed on ultra-high speed swept source optical coherence tomography angiography compared to spectral domain optical coherence tomography angiography

    PubMed Central

    Novais, Eduardo A.; Adhi, Mehreen; Moult, Eric M.; Louzada, Ricardo N.; Cole, Emily D.; Husvogt, Lennart; Lee, ByungKun; Dang, Sabin; Regatieri, Caio V. S.; Witkin, André J.; Baumal, Caroline R.; Hornegger, Joachim; Jayaraman, Vijaysekhar; Fujimoto, James G; Duker, Jay S.; Waheed, Nadia K.

    2016-01-01

    Purpose To compare visualization of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) using an ultra-high speed swept-source (SS)-optical coherence tomography angiography (OCTA) prototype versus a spectral-domain (SD)-OCTA device. Design Comparative analysis of diagnostic instruments. Methods Patients were prospectively recruited to be imaged on SD-OCT and SS-OCT devices on the same day. The SD-OCT device employed is the RTVue Avanti that operates at ~840nm wavelength and 70,000 A-scans/second. The SS-OCT device used is an ultra-high speed long-wavelength prototype that operates at ~1050nm wavelength and 400,000 A-scans/second. Two observers independently measured the CNV area on OCTA en face images from the two devices using ImageJ. The non-parametric Wilcoxon signed-rank test was used to compare area measurements and p-values of <0.05 were considered statistically significant. Results Fourteen eyes from 13 patients were enrolled. The CNV in 11 eyes (78.6%) were classified as type-1, 2 eyes (14.3%) as type-2, and 1 eye (7.1%) as mixed type. Total CNV area measured using SS-OCT and SD-OCT 3mm × 3mm OCTA were 0.949 ± 1.168mm2 and 0.340 ± 0.301mm2, respectively (p=0.001). For the 6mm × 6mm OCTA the total CNV area using SS-OCT and SD-OCT were 1.218 ± 1.284mm2 and 0.604 ± 0.597mm2, respectively (p=0.0019). The field of view did not significantly affect the measured CNV area (p=0.19 and p=0.18 for SS-OCT and SD-OCT respectively). Conclusion SS-OCTA yielded significantly larger CNV areas than SD-OCTA. It is possible that SS-OCTA is better able to demarcate the full extent of CNV vasculature. PMID:26851725

  7. Intravitreal triamcinolone with transpupillary therapy for subfoveal choroidal neovascularization in age related macular degeneration. A randomized controlled pilot study [ISRCTN74123635

    PubMed Central

    Agurto-Rivera, Ricardo; Diaz-Rubio, Jose; Torres-Bernal, Luis; Macky, Tamer A; Colina-Luquez, Juner; Papa-Oliva, Gabriela; Jager, Rama D; Martinez-Jardon, Susana; Fromow-Guerra, Jans; Quiroz-Mercado, Hugo

    2005-01-01

    Background To assess the effect of intravitreal triamcinolone acetonide (iTA) as an adjunctive treatment to transpupillary therapy (TTT) for new subfoveal choroidal neovascular membranes (CNV) in age-related macular degeneration (AMD). Methods This prospective randomized controlled pilot study comprised 26 patients scheduled to receive TTT, due to either absent indications for photodynamic therapy or financial issues. Patients were assigned into; Group A (n = 14) received TTT alone and Group B (n = 12) received iTA (4 mg) followed by TTT within one week. Follow ups were at 2 weeks, and 1, 3 and 6 months for; best-corrected visual acuity (BCVA) by ETDRS chart at 4 meters, intraocular pressures (IOP), fluorescein angiography (FAG), and central foveal thickness by optical coherence tomography (OCT). Results All 26 patients completed 6 months of follow ups. The average age for both groups was 74 years. Occult CNV formed 64% and 41%; classis/predominately classic 21% and 16.6%; and minimally classic 15% and 42.4% of group A and B respectively. At baseline; the mean BCVA was 0.045 for group A and 0.04 for group B; mean CNV size was 6.15 disc diameter (DD) and 2.44 DD; mean OCT foveal thickness was 513 um and 411 um for group A and B respectively with no statistical differences (P = 0.8, 0.07, and 0.19). At six months the proportion of patients gained ≥ 1 lines was 14% and 25% (P = 0.136) and stabilization was 86% and 66% (P = 0.336); the mean size of the CNV was 5.63 DD and 2.67 DD (P = 0.162); rate of CNV closure was 64% and 83% (P = 0.275); and the mean OCT central foveal thickness was 516.36 um and 453.67 um (P = 0.341), for group A and B respectively. Conclusion The use of iTA as an adjunctive to TTT for new subfoveal CNV in AMD showed a tendency towards better functional results. However due to the small sample size of the study a statistically significant results could not be reached. PMID:16309554

  8. Photodynamic therapy for polypoidal choroidal vasculopathy secondary to choroidal nevus

    PubMed Central

    Wong, James G; Lai, Xin Jie; Sarafian, Richard Y; Wong, Hon Seng; Smith, Jeremy B

    2017-01-01

    We report a case of a Caucasian female who developed active polypoidal choroidal vasculopathy (PCV) at the edge of a stable choroidal nevus and was successfully treated with verteporfin photodynamic therapy. No active polyp was detectable on indocyanine green angiography 2 years after treatment, and good vision was maintained. Indocyanine green angiography is a useful investigation to diagnose PCV and may be underutilized. Unlike treatment of choroidal neovascularization secondary to choroidal nevus, management of PCV secondary to nevus may not require intravitreal anti-vascular endothelial growth factor therapy. Photodynamic monotherapy may be an effective treatment of secondary PCV. PMID:28243154

  9. Peripapillary subretinal neovascularization and serous macular detachment. Association with congenital optic nerve pits.

    PubMed

    Borodic, G E; Gragoudas, E S; Edward, W O; Brockhurst, R J

    1984-02-01

    Congenital anomalous disc changes were associated with acquired macular detachment and peripapillary choroidal neovascularization in two cases. The anomalous disc changes resembled optic nerve pits. In one case, the peripapillary choroidal neovascularization was treated with argon laser photocoagulation, with subsequent reattachment of the macula and considerable improvement in the visual acuity. Although the pathogenesis of macular detachment occurring with optic nerve pits is usually not disclosed by fluorescein angiography, leakage from choroidal neovascularization can occur with this congenital defect and may contribute to the formation of a neurosensory macular detachment. If found, choroidal neovascularization may represent a remedial cause for visual loss in a condition with an otherwise poor prognosis.

  10. Long-term Results of Carbon Ion Radiation Therapy for Locally Advanced or Unfavorably Located Choroidal Melanoma: Usefulness of CT-based 2-Port Orthogonal Therapy for Reducing the Incidence of Neovascular Glaucoma

    SciTech Connect

    Toyama, Shingo; Tsuji, Hiroshi; Mizoguchi, Nobutaka; Nomiya, Takuma; Kamada, Tadashi; Tokumaru, Sunao; Mizota, Atsushi; Ohnishi, Yoshitaka; Tsujii, Hirohiko

    2013-06-01

    Purpose: To determine the long-term results of carbon ion radiation therapy (C-ion RT) in patients with choroidal melanoma, and to assess the usefulness of CT-based 2-port irradiation in reducing the risk of neovascular glaucoma (NVG). Methods and Materials: Between January 2001 and February 2012, a total of 116 patients with locally advanced or unfavorably located choroidal melanoma received CT-based C-ion RT. Of these patients, 114 were followed up for more than 6 months and their data analyzed. The numbers of T3 and T2 patients (International Union Against Cancer [UICC], 5th edition) were 106 and 8, respectively. The total dose of C-ion RT varied from 60 to 85 GyE, with each dose given in 5 fractions. Since October 2005, 2-port therapy (51 patients) has been used in an attempt to reduce the risk of NVG. A dose-volume histogram analysis was also performed in 106 patients. Results: The median follow-up was 4.6 years (range, 0.5-10.6 years). The 5-year overall survival, cause-specific survival, local control, distant metastasis-free survival, and eye retention rates were 80.4% (95% confidence interval 89.0%-71.8%), 82.2% (90.6%-73.8%), 92.8% (98.5%-87.1%), 72.1% (81.9%-62.3%), and 92.8% (98.1%-87.5%), respectively. The overall 5-year NVG incidence rate was 35.9% (25.9%-45.9%) and that of 1-port group and 2-port group were 41.6% (29.3%-54.0%) and 13.9% (3.2%-24.6%) with statistically significant difference (P<.001). The dose-volume histogram analysis showed that the average irradiated volume of the iris-ciliary body was significantly lower in the non-NVG group than in the NVG group at all dose levels, and significantly lower in the 2-port group than in the 1-port group at high dose levels. Conclusions: The long-term results of C-ion RT for choroidal melanoma are satisfactory. CT-based 2-port C-ion RT can be used to reduce the high-dose irradiated volume of the iris-ciliary body and the resulting risk of NVG.

  11. Combined therapy (intravitreal bevacizumab plus verteporfin photodynamic therapy) versus intravitreal bevacizumab monotherapy for choroidal neovascularization due to age-related macular degeneration: a 1-year follow-up study

    PubMed Central

    Saviano, Sandro; Leon, Pia Easter; Mangogna, Alessandro; Tognetto, Daniele

    2016-01-01

    Purpose To assess the efficacy and safety of combined intravitreal bevacizumab and low-fluency-rate photodynamic therapy (PDT) in the treatment of choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) and to compare it with intravitreal bevacizumab monotherapy. Methods A total of 62 eyes of 62 patients with angiographic evidence of CNV were divided into 2 groups: the eyes of one group were treated with a combined therapy of 1 intravitreal bevacizumab injection (1.25 mg) and PDT within 7 days; the eyes of the other group received intravitreal bevacizumab monotherapy. Clinical evidence of complications, best-corrected visual acuity (BVCA) and fluorescein leakage were evaluated. Best-corrected visual acuity and optical coherence tomography (OCT) were tested monthly and followed for 12 months. Results In the combined group the mean BCVA increased from 0.61 logMAR before the treatment to 0.54 logMAR at 12 months’ follow-up. In the monotherapy group the mean BCVA increased from 0.65 logMAR to 0.60 logMAR at 12 months’ follow-up. There was no significant difference in visual acuity outcomes between groups (P > 0.05). In the combined group the mean number of treatments was 1.19 per patient; in the monotherapy group, 5.31 per patient (P < 0.01). Conclusions Combined therapy appears to be an effective option for CNV associated with AMD treatment allowing a significant reduction of intravitreal injections. PMID:27582675

  12. Peripapillary choroidal thickness in childhood.

    PubMed

    Read, Scott A; Alonso-Caneiro, David; Vincent, Stephen J; Collins, Michael J

    2015-06-01

    Changes in the thickness of the invivo peripapillary choroid have been documented in a range of ocular conditions in adults; however, choroidal thickness in the peripapillary region of children has not been examined in detail. This study therefore aimed to investigate the thickness of the peripapillary choroid and the overlying retinal nerve fibre layer (RNFL) in a population of normal children with a range of refractive errors. Ninety-three children (37 myopes and 56 non-myopes) aged between 11 and 16 years, had measurements of peripapillary choroidal and RNFL thickness derived from enhanced depth imaging optical coherence tomography images (EDI-OCT, Heidelberg Spectralis). The average thickness was determined in a series of five 0.25 mm width concentric annuli (each divided into 8 equal sized 45° sectors) centred on the optic nerve head boundary, accounting for individual ocular magnification factors and the disc-fovea angle. Significant variations in peripapillary choroidal thickness were found to occur with both annulus location (p < 0.001) and sector position (p < 0.001) in this population of children. The innermost annulus (closest to the edge of the optic disc) exhibited the thinnest choroid (mean 77 ± 16 μm) and the outermost annulus, the thickest choroid (191 ± 52 μm). The choroid was thinnest inferior to the optic nerve head (139 ± 38 μm) and was thickest in the superior temporal sector (157 ± 40 μm). Significant differences in the distribution of choroidal thickness were also associated with myopia, with myopic children having significantly thinner choroids in the inner and outer annuli of the nasal and temporal sectors respectively (p < 0.001). RNFL thickness also varied significantly with annulus location and sector (p < 0.001), and showed differences in thickness distribution associated with refractive error. This study establishes the normal variations in the thickness of the peripapillary choroid with radial distance and azimuthal angle

  13. [Choroidal neovascularisation in a patient with choroidal osteoma visualized by OCT angiography].

    PubMed

    Mihailovic, N; Alnawaiseh, M; Merté, R-L; Eter, N

    2016-11-04

    We present the case of a 38-year-old Asian patient who reported vision loss of her left eye since 4 weeks. The funduscopy showed a choroidal tumor in the papillomacular bundle, which could be identified as a choroidal osteoma with secondary choroidal neovascularization (CNV). OCT angiography (OCT-A) detected abnormal flow in the choriocapillaris; the osteoma showed no flow in the OCT angiogram of the choroid level. Therefore, OCT-A can be a helpful adjuvant for diagnosis of CNV secondary to choroidal osteoma.

  14. Comparative study between a spectral domain and a high-speed single-beam swept source OCTA system for identifying choroidal neovascularization in AMD.

    PubMed

    Told, R; Ginner, L; Hecht, A; Sacu, S; Leitgeb, R; Pollreisz, A; Schmidt-Erfurth, U

    2016-12-05

    This comparative study between a SD- and SS-OCTA system for visualizing neovascular patterns in AMD, also assessed the influence of cataract on OCTA imaging. 25 eyes with active CNV (AMD) were documented by FA, ICGA and SD-OCT. Two OCTA devices were used: A custom built SS-OCTA (1050 nm, 400,000 A-scans/s, 5 × 5 mm, no image segmentation); AngioVue (OptoVue, CA, USA) SD-OCTA (840 nm, 70.000 A-scans/s, 3 × 3 mm, SSADA technology). Two retina experts graded CNV types and vascular patterns. Cataract influence on OCTA image quality was reported for the superficial retinal plexus (6 eyes). The SS-OCTA prototype showed more CNV lesions compared to the SD-OCTA system (p = 0.01). Overall sensitivity of SD- and SS-OCTA systems to detect CNV lesions was.32 and.68, respectively. The SS-OCTA system was able to detect discrete lesion characteristics better than the SD-OCTA. No significant difference was found in the ability to identify CNV in treatment-naïve eyes. There was no significant influence of cataract. The SS-OCTA prototype detected CNV-associated vascular patterns more reliably than the SD-OCTA system. This is attributed to the SS-OCTA system's longer center wavelength and higher A-scan rate yielding higher definition and contrast of small neovascular structures. The SS-OCTA system used showed no advantage regarding cataract influence.

  15. Comparative study between a spectral domain and a high-speed single-beam swept source OCTA system for identifying choroidal neovascularization in AMD

    PubMed Central

    Told, R.; Ginner, L.; Hecht, A.; Sacu, S.; Leitgeb, R.; Pollreisz, A.; Schmidt-Erfurth, U.

    2016-01-01

    This comparative study between a SD- and SS-OCTA system for visualizing neovascular patterns in AMD, also assessed the influence of cataract on OCTA imaging. 25 eyes with active CNV (AMD) were documented by FA, ICGA and SD-OCT. Two OCTA devices were used: A custom built SS-OCTA (1050 nm, 400,000 A-scans/s, 5 × 5 mm, no image segmentation); AngioVue (OptoVue, CA, USA) SD-OCTA (840 nm, 70.000 A-scans/s, 3 × 3 mm, SSADA technology). Two retina experts graded CNV types and vascular patterns. Cataract influence on OCTA image quality was reported for the superficial retinal plexus (6 eyes). The SS-OCTA prototype showed more CNV lesions compared to the SD-OCTA system (p = 0.01). Overall sensitivity of SD- and SS-OCTA systems to detect CNV lesions was.32 and.68, respectively. The SS-OCTA system was able to detect discrete lesion characteristics better than the SD-OCTA. No significant difference was found in the ability to identify CNV in treatment-naïve eyes. There was no significant influence of cataract. The SS-OCTA prototype detected CNV-associated vascular patterns more reliably than the SD-OCTA system. This is attributed to the SS-OCTA system’s longer center wavelength and higher A-scan rate yielding higher definition and contrast of small neovascular structures. The SS-OCTA system used showed no advantage regarding cataract influence. PMID:27917889

  16. Comparative study between a spectral domain and a high-speed single-beam swept source OCTA system for identifying choroidal neovascularization in AMD

    NASA Astrophysics Data System (ADS)

    Told, R.; Ginner, L.; Hecht, A.; Sacu, S.; Leitgeb, R.; Pollreisz, A.; Schmidt-Erfurth, U.

    2016-12-01

    This comparative study between a SD- and SS-OCTA system for visualizing neovascular patterns in AMD, also assessed the influence of cataract on OCTA imaging. 25 eyes with active CNV (AMD) were documented by FA, ICGA and SD-OCT. Two OCTA devices were used: A custom built SS-OCTA (1050 nm, 400,000 A-scans/s, 5 × 5 mm, no image segmentation); AngioVue (OptoVue, CA, USA) SD-OCTA (840 nm, 70.000 A-scans/s, 3 × 3 mm, SSADA technology). Two retina experts graded CNV types and vascular patterns. Cataract influence on OCTA image quality was reported for the superficial retinal plexus (6 eyes). The SS-OCTA prototype showed more CNV lesions compared to the SD-OCTA system (p = 0.01). Overall sensitivity of SD- and SS-OCTA systems to detect CNV lesions was.32 and.68, respectively. The SS-OCTA system was able to detect discrete lesion characteristics better than the SD-OCTA. No significant difference was found in the ability to identify CNV in treatment-naïve eyes. There was no significant influence of cataract. The SS-OCTA prototype detected CNV-associated vascular patterns more reliably than the SD-OCTA system. This is attributed to the SS-OCTA system’s longer center wavelength and higher A-scan rate yielding higher definition and contrast of small neovascular structures. The SS-OCTA system used showed no advantage regarding cataract influence.

  17. CHOROIDAL MORPHOLOGY IN EYES WITH POLYPOIDAL CHOROIDAL VASCULOPATHY AND NORMAL OR SUBNORMAL SUBFOVEAL CHOROIDAL THICKNESS.

    PubMed

    Lee, Won Ki; Baek, Jiwon; Dansingani, Kunal K; Lee, Jae Hyung; Freund, K Bailey

    2016-12-01

    To subsegment the choroid in patients with polypoidal choroidal vasculopathy and to determine whether the ratio of choriocapillaris/Sattler layer thickness to total choroidal thickness is decreased at sites of polypoidal pathology. Retrospective, observational, cross-sectional study. A total of 320 eyes of 305 patients with polypoidal choroidal vasculopathy were studied with optical coherence tomography and dye angiography. The ratio of choriocapillaris/Sattler layer thickness to total choroidal thickness was calculated at polypoidal lesion sites in eyes with subfoveal choroidal thickness (SFCT) ≤200 μm. Mean SFCT was 267.7 ± 118.5 μm for the entire cohort. Mean SFCT was 151.2 ± 35.0 μm in eyes with SFCT ≤200 μm (n = 124, 39%). In this subgroup, dilated Haller vessels (pachyvessels) were identified under the site of neovascular ingrowth in 117 eyes (94%). Choroidal thickness in the pachyvessel zone was greater (213.3 ± 52.2 μm) than SFCT (P < 0.001) with a significantly lower choriocapillaris/Sattler layer to total thickness ratio (P < 0.001). Qualitative alterations of the retinal pigment epithelium were observed in 60 eyes (51%). Eyes with normal or subnormal SFCT exhibited extrafoveal choroidal thickening at sites of polypoidal disease. The choriocapillaris and Sattler layers were attenuated at these locations, but Haller vessels were markedly dilated. These changes were topographically associated with sites of neovascular ingrowth and support the classification of polypoidal choroidal vasculopathy as a pachychoroid disorder.

  18. [The results of intravitreal bevacizumab in high myopic subretinal neovascularisation].

    PubMed

    Branisteanu, D; Moraru, Andreea

    2013-01-01

    To asses the anatomical and functional results after intravitreal bevacizumab administration in choroidal neovascularization secondary to pathologic myopia; To asses the safety and results stability; Prospective, interventional case study of 18 eyes with choroidal neovascularization secondary to pathologic myopia treated with 1.25 mg. intravitreal bevacizumab (AVASTIN). Intravitreal injection was repeated, if needed, at 4-6 weeks until leakage stopped. In all cases fluorescein angiograms and Spectral 3D OCTs were performed. Visual acuity was measured with ETDRS optotype. Cases were followed-up at least 6 months. Statistical analysis was performed using ANOVA and Wilcoxon tests. Mean age of patients in the study was 43.86%--6.32 years (ranging 24-62 years). The mean number of intravitreal injections was 2.62%--0.53 (ranging between 1 - 4 injections). Mean visual acuity improved in all cases. An increase of more than 15 letters was noted in 44.44.% of the cases. OCT confirmed a reduced depth of lesion and also a reduced lesion volume after treatment. No major local or systemic side-effects were noted. At 6 months follow-up the choroidal neovascularization reappeared in 5 cases (27.77%) requiring additional treatment. These results confirm the efficacy and safety of intravitreal bevacizumab in controlling the choroidal neovascularization secondary to pathologic myopia. More than 40% of the cases regained at least 3 lines in ETDRS chart but a recurrence was noted in 27.77% of the cases at 6 months.

  19. Focal Choroidal Excavation in Best Vitelliform Macular Dystrophy: Case Report.

    PubMed

    Esfahani, Mohammad Riazi; Esfahani, Hamid Riazi; Mahmoudi, Alireza; Johari, Mohammad Karim; Hemati, Karim

    2015-05-01

    Focal choroidal excavation (FCE) was first reported as a choroidal posteriorly excavated zone without any scleral change. Choroidal excavation also divided into conforming and nonconforming type. Numerous reports demonstrated association between FCE and other disease such as choroidal neovascularization and central serous choroidoretinopathy. Here, we report a rare case of FCE in a patient with Best disease. The patient was diagnosed by spectoral domain optical coherence tomography (SD-OCT). To the best of our knowledge, our patient is the second report of choroidal excavation in Best vitelliform macular dystrophy.

  20. PATTERNS OF FUNDUS AUTOFLUORESCENCE DEFECTS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION SUBTYPES.

    PubMed

    Ozkok, Ahmet; Sigford, Douglas K; Tezel, Tongalp H

    2016-11-01

    To test define characteristic fundus autofluorescence patterns of different exudative age-related macular degeneration subtypes. Cross-sectional study. Fifty-two patients with choroidal neovascularization because of three different neovascular age-related macular degeneration subtypes were included in the study. Macular and peripheral fundus autofluorescence patterns of study subjects were compared in a masked fashion. Fundus autofluorescence patterns of all three neovascular age-related macular degeneration subtypes revealed similar patterns. However, peripapillary hypo-autofluorescence was more common among patients with polypoidal choroidal vasculopathy (88.2%) compared with patients with retinal angiomatous proliferation (12.5%) and patients without retinal angiomatous proliferation and polypoidal choroidal vasculopathy (21.1%) (P < 0.0001). Presence of peripapillary fundus autofluorescence defects in neovascular age-related macular degeneration maybe suggestive of polypoidal choroidal vasculopathy as a variant of neovascular age-related macular degeneration.

  1. Choroidal OCT

    NASA Astrophysics Data System (ADS)

    Esmaeelpour, Marieh; Drexler, Wolfgang

    Novel imaging devices, imaging strategies and automated image analysis with optical coherence tomography have improved our understanding of the choroid in health and pathology. Non-invasive in-vivo high resolution choroidal imaging has had its highest impact in the investigation of macular diseases such as diabetes macular edema and age-related macular degeneration. Choroidal thickness may provide a clinically feasible measure of disease stage and treatment success. It will even support disease diagnosis and phenotyping as is demonstrated in this chapter. Utilizing color coded thickness mapping of the choroid and its Sattler's and Haller's layer may further strengthen the sensitivity of the investigation findings.

  2. Swept Source OCT Angiography of Neovascular Macular Telangiectasia Type 2

    PubMed Central

    Zhang, Qinqin; Wang, Ruikang K.; Chen, Chieh-Li; Legarreta, Andrew D.; Durbin, Mary K.; An, Lin; Sharma, Utkarsh; Stetson, Paul F.; Legarreta, John E.; Roisman, Luiz; Gregori, Giovanni; Rosenfeld, Philip J.

    2015-01-01

    Objective To image subretinal neovascularization in proliferative macular telangiectasia type 2 (MacTel2) using swept source optical coherence tomography based microangiography (OMAG). Study Design Patients with MacTel2 were enrolled in a prospective, observational study known as the MacTel Project and evaluated using a high-speed 1050nm swept-source OCT (SS-OCT) prototype system. The OMAG algorithm generated en face flow images from three retinal layers, as well as the region bounded by the outer retina and Bruch’s membrane, the choriocapillaris, and the remaining choroidal vasculature. The en face OMAG images were compared to images from fluorescein angiography (FA) and indocyanine green angiography (ICGA). Results Three eyes with neovascular MacTel2 were imaged. The neovascularization was best identified from the en face OMAG images that included a layer between the outer retinal boundary and Bruch’s membrane. OMAG images identified these abnormal vessels better than FA and were comparable to the images obtained using ICGA. In all three cases, OMAG identified choroidal vessels communicating with the neovascularization, and these choroidal vessels were evident in the two cases with ICGA imaging. In one case, monthly injections of bevacizumab reduced the microvascular complexity of the neovascularization, as well as the telangiectatic changes within the retinal microvasculature. In another case, less frequent bevacizumab therapy was associated with growth of the subretinal neovascular complex. Conclusions OMAG imaging provided detailed, depth-resolved information about subretinal neovascularization in MacTel2 eyes demonstrating superiority to FA imaging and similarities to ICGA imaging for documenting the retinal microvascular changes, the size and extent of the neovascular complex, the communications between the neovascular complex and the choroidal circulation, and the response to monthly bevacizumab therapy. PMID:26457402

  3. Peripapillary crescent enlargement in highly myopic eyes evaluated by fluorescein and indocyanine green angiography

    PubMed Central

    Yasuzumi, K; Ohno-Matsui, K; Yoshida, T; Kojima, A; Shimada, N; Futagami, S; Tokoro, T; Mochizuki, M

    2003-01-01

    Aims: To evaluate angiographic features of myopic crescents using fluorescein angiography (FA) and indocyanine green angiography (IA). Methods: FA and IA angiograms of 88 highly myopic eyes (47 consecutive patients) were reviewed. The follow up period ranged from 5–28 years. Results: FA revealed two zones of the myopic crescent: a consistently hypofluorescent inner zone and an outer zone with delayed choroidal filling. IA revealed dislocation of the Zinn-Haller ring to the border between the two zones. Myopic crescent enlargement occurred in 68.1%. Only the outer zone increased significantly in most of the eyes with enlarged crescents. Conclusions: The inner zone might develop as a result of mechanical stretching, and the outer zone might be the result a secondary circulatory disturbance and mechanical stretching. PMID:12928272

  4. [Choroidal Melanoma].

    PubMed

    Coutinho, Inês; Teixeira, Tânia; Simões, Paulo César; Lopes, João Casalta; Borrego, Margarida; Fernandes, Júlia; Cabral, João; Prieto, Isabel; Proença, Rui

    2017-08-31

    Choroidal melanoma is the most common primary intraocular malignant tumor in adults. None of the different treatments available offers advantages of survival, resorting more and more to conservative treatments such as brachytherapy, which has been available in Portugal since 2013. In this article we review the clinical characteristics, risk factors, diagnosis, complementary exams and therapeutic options in choroidal melanoma.

  5. 'Shadow sign' in congenital hypertrophy of the retinal pigment epithelium of young myopic pigmented patients.

    PubMed

    Chang, M Y; McBeath, J B; McCannel, C A; McCannel, T A

    2016-01-01

    PURPOSE Congenital hypertrophy of the retinal pigment epithelium (CHRPE) may simulate choroidal melanoma in certain cases. We report unique clinical features we have observed in cases of CHRPE in young myopic pigmented patients.METHODS Patients who were referred for evaluation of a suspicious choroidal lesion and found to have a CHRPE lesion with the clinical appearance of lesion elevation and a subretinal fluid-like 'shadow sign' were included. Patient and lesion characteristics were tabulated. Available images, including fundus photography, ultrasonography, optical coherence tomography (OCT), and fluorescein angiography (FA) were reviewed.ResultsSix patients were included. The 'shadow sign' was anterior to the CHRPE lesion in all cases. The mean age of the patients was 27.3 years. The ethnicities of the patients were Chinese (n=1), Hispanic (n=3), or African-American (n=2). Five of six patients were myopic.CONCLUSIONS Although most CHRPE lesions appear flat on ophthalmoscopy, lesions in young myopic patients of pigmented ethnicities may appear elevated with a 'shadow sign' due to 'dark without pressure.' This new finding may be related to the vitreoretinal interface in young myopic pigmented patients and must be distinguished from true subretinal fluid and lesion thickness, which are often observed in choroidal melanoma.

  6. Intrachoroidal Neovascularization in Transgenic Mice Overexpressing Vascular Endothelial Growth Factor in the Retinal Pigment Epithelium

    PubMed Central

    Schwesinger, Catherine; Yee, Charles; Rohan, Richard M.; Joussen, Antonia M.; Fernandez, Antonio; Meyer, Tobias N.; Poulaki, Vassiliki; Ma, Joseph J. K.; Redmond, T. Michael; Liu, Suyan; Adamis, Anthony P.; D’Amato, Robert J.

    2001-01-01

    Choroidal neovascularization in age-related macular degeneration is a frequent and poorly treatable cause of vision loss in elderly Caucasians. This choroidal neovascularization has been associated with the expression of vascular endothelial growth factor (VEGF). In current animal models choroidal neovascularization is induced by subretinal injection of growth factors or vectors encoding growth factors such as VEGF, or by disruption of the Bruch’s membrane/retinal pigment epithelium complex with laser treatment. We wished to establish a transgenic murine model of age-related macular degeneration, in which the overexpression of VEGF by the retinal pigment epithelium induces choroidal neovascularization. A construct consisting of a tissue-specific murine retinal pigment epithelium promoter (RPE65 promoter) coupled to murine VEGF164 cDNA with a rabbit β-globin-3′ UTR was introduced into the genome of albino mice. Transgene mRNA was expressed in the retinal pigment epithelium at all ages peaking at 4 months. The expression of VEGF protein was increased in both the retinal pigment epithelium and choroid. An increase of intravascular adherent leukocytes and vessel leakage was observed. Histopathology revealed intrachoroidal neovascularization that did not penetrate through an intact Bruch’s membrane. These results support the hypothesis that additional insults to the integrity of Bruch’s membrane are required to induce growth of choroidal vessels into the subretinal space as seen in age-related macular degeneration. This model may be useful to screen for inhibitors of choroidal vessel growth. PMID:11238064

  7. Optical Defocus Rapidly Changes Choroidal Thickness in Schoolchildren

    PubMed Central

    Liu, Manli; Lee, Roger Pak Kin; Sun, Yuan; Zhang, Ting; Lam, Chuen; Liu, Quan; To, Chi Ho

    2016-01-01

    The current study aimed to examine the short-term choroidal response to optical defocus in schoolchildren. Myopic schoolchildren aged 8–16 were randomly allocated to control group (CG), myopic defocus group (MDG) and hyperopic defocus group (HDG) (n = 17 per group). Children in MDG and HDG received additional +3D and -3D lenses, respectively, to their full corrections on the right eyes. Full correction was given to their left eyes, and on both eyes in the CG. Axial length (AXL) and subfoveal choroidal thickness (SFChT) were then measured by spectral domain optical coherence tomography. Children wore their group-specific correction for 2 hours after which any existing optical defocus was removed, and subjects wore full corrections for another 2 hours. Both the AXL and SFChT were recorded hourly for 4 hours. The mean refraction of all subjects was -3.41 ± 0.37D (± SEM). SFChT thinned when exposed to hyperopic defocus for 2 hours but less thinning was observed in response to myopic defocus compared to the control group (p < 0.05, two-way ANOVA). Removal of optical defocus significantly decreased SFChT in the MDG and significantly increased SFChT in the HDG after 1 and 2 hours (mean percentage change at 2-hour; control vs. hyperopic defocus vs. myopic defocus; -0.33 ± 0.59% vs. 3.04 ± 0.60% vs. -1.34 ± 0.74%, p < 0.01). Our results showed short-term exposure to myopic defocus induced relative choroidal thickening while hyperopic defocus led to choroidal thinning in children. This rapid and reversible choroidal response may be an important clinical parameter in gauging retinal response to optical defocus in human myopia. PMID:27537606

  8. [Choroidal melanoma].

    PubMed

    Desjardins, Laurence

    2016-03-01

    Choroidal melanoma is the most common form of eye cancer in adults. Treatments enabling the tumour to be destroyed or removed while preserving the eye socket are mainly based on surgery, proton therapy and brachytherapy.

  9. Tumoral and Choroidal Vascularization

    PubMed Central

    Jost, Maud; Maillard, Catherine; Lecomte, Julie; Lambert, Vincent; Tjwa, Marc; Blaise, Pierre; Alvarez Gonzalez, Maria-Luz; Bajou, Khalid; Blacher, Silvia; Motte, Patrick; Humblet, Chantal; Defresne, Marie Paule; Thiry, Marc; Frankenne, Francis; Gothot, André; Carmeliet, Peter; Rakic, Jean-Marie; Foidart, Jean-Michel; Noël, Agnès

    2007-01-01

    An adequate balance between serine proteases and their plasminogen activator inhibitor-1 (PAI-1) is critical for pathological angiogenesis. PAI-1 deficiency in mice is associated with impaired choroidal neovascularization (CNV) and tumoral angiogenesis. In the present work, we demonstrate unexpected differences in the contribution of bone marrow (BM)-derived cells in these two processes regulated by PAI-1. PAI-1−/− mice grafted with BM-derived from wild-type mice were able to support laser-induced CNV formation but not skin carcinoma vascularization. Engraftment of irradiated wild-type mice with PAI-1−/− BM prevented CNV formation, demonstrating the crucial role of PAI-1 delivered by BM-derived cells. In contrast, the transient infiltration of tumor transplants by local PAI-1-producing host cells rather than by BM cells was sufficient to rescue tumor growth and angiogenesis in PAI-1-deficient mice. These data identify PAI-1 as a molecular determinant of a local permissive soil for tumor angiogenesis. Altogether, the present study demonstrates that different cellular mechanisms contribute to PAI-1-regulated tumoral and CNV. PAI-1 contributes to BM-dependent choroidal vascularization and to BM-independent tumor growth and angiogenesis. PMID:17717143

  10. [Macular serpiginous choroiditis complicated by macular hole].

    PubMed

    Brănişteanu, D; Moraru, Andreea

    2014-01-01

    Macular serpiginouschoroiditis is a rare variant of serpiginous choroiditis characterized by a severe recurrent inflammation of both central choroid and retinal pigment epithelium. Visual prognosis is severe due to subsequent distruction of retinal structures. Permanent central visual loss is the consequence of retinal pigment epithelium hyper or hypoplasia and/or subretinal neovascularization leading to fibrous scarring. This article reports the unusual case of rapid development of a macular hole soon after the onset of characteristic clinical features. Despite anti-inflammatory treatment and successful macular hole surgery the visual function remained significantly impaired by secondary central retinal pigment epithelium changes.

  11. The expanded spectrum of focal choroidal excavation.

    PubMed

    Margolis, Ron; Mukkamala, Sri Krishna; Jampol, Lee M; Spaide, Richard F; Ober, Michael D; Sorenson, John A; Gentile, Ronald C; Miller, Joel A; Sherman, Jerome; Freund, K Bailey

    2011-10-01

    To describe the clinical and imaging findings in patients with focal choroidal excavation. Retrospective observational case series. The medical records of 12 patients (13 eyes) with focal choroidal excavation were reviewed. Clinical histories and imaging findings (including color photography, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and enhanced depth imaging spectral-domain optical coherence tomography) were analyzed. The mean age of the patients was 45 years (range, 22-62 years). Four patients were Asian. Mean visual acuity was 20/31 (range, 20/20 to 20/100). Mean refractive error was -3.54 diopters (D) (range, 6.00 to -8.00 D). One patient had bilateral involvement. All patients manifested varying degrees of foveal pigmentary changes that were usually hypoautofluorescent on fundus autofluorescence images. Fluorescein angiographic findings varied with degree of retinal pigment epithelial alterations. Indocyanine green angiography revealed relative hypofluorescence. In 7 eyes, spectral-domain optical coherence tomography revealed outer retinal layers conforming to retinal pigment epithelial alterations within the excavation. In the other 6 eyes, spectral-domain optical coherence tomography revealed a separation between the outer retina and the retinal pigment epithelium within the excavation. In 7 eyes studied with enhanced depth imaging spectral-domain optical coherence tomography, there was no evidence of scleral ectasia. Mean choroidal thickness of the uninvolved choroid was thicker than normal at 319 μm (range, 244-439 μm). All lesions remained stable except for in 1 eye, which had findings of central serous chorioretinopathy and secondary type 2 (subretinal) neovascularization. Focal choroidal excavation is a newly described idiopathic entity in eyes having 1 or more focal areas of choroidal excavation. In some patients, there may be an association with central

  12. Longitudinal changes in choroidal thickness and eye growth in childhood.

    PubMed

    Read, Scott A; Alonso-Caneiro, David; Vincent, Stephen J; Collins, Michael J

    2015-05-01

    To examine longitudinal changes in choroidal thickness and axial length in a population of children with a range of refractive errors. One hundred and one children (41 myopes and 60 nonmyopes) aged 10 to 15 years participated in this prospective, observational longitudinal study. For each child, 6-month measures of choroidal thickness (using enhanced depth imaging optical coherence tomography) and axial ocular biometry were collected four times over an 18-month period. Linear mixed-models were used to examine the longitudinal changes in choroidal thickness and the relationship between changes in choroidal thickness and axial eye growth over the study period. A significant group mean increase in subfoveal choroidal thickness was observed over 18 months (mean increase 13 ± 22 μm, P < 0.001). Myopic children exhibited significantly thinner choroids compared with nonmyopic children (P < 0.001), although there was no significant time by refractive group interaction (P = 0.46), indicating similar changes in choroidal thickness over time in myopes and nonmyopes. However, a significant association between the change in choroidal thickness and the change in axial length over time was found (P < 0.001, β = -0.14). Children showing faster axial eye growth exhibited significantly less choroidal thickening over time compared with children showing slower axial eye growth. A significant increase in choroidal thickness occurs over an 18-month period in normal 10- to 15-year-old children. Children undergoing faster axial eye growth exhibited less thickening and, in some cases, a thinning of the choroid. These findings support a potential role for the choroid in the mechanisms regulating eye growth in childhood.

  13. Semiautomated segmentation of the choroid in spectral-domain optical coherence tomography volume scans.

    PubMed

    Hu, Zhihong; Wu, Xiaodong; Ouyang, Yanwei; Ouyang, Yanling; Sadda, Srinivas R

    2013-03-07

    Changes in the choroid, in particular its thickness, are believed to be of importance in the pathophysiology of a number of retinal diseases. The purpose of this study was to adapt the graph search algorithm to semiautomatically identify the choroidal layer in spectral-domain optical coherence tomography (SD-OCT) volume scans and compare its performance to manual delineation. A graph-based multistage segmentation approach was used to identify the choroid, defined as the layer between the outer border of the RPE band and the choroid-sclera junction. Thirty randomly chosen macular SD-OCT (1024 × 37 × 496 voxels, Heidelberg Spectralis) volumes were obtained from 20 healthy subjects and 10 subjects with non-neovascular AMD. The positions of the choroidal borders and resultant thickness were compared with consensus manual delineation performed by two graders. For consistency of the statistical analysis, the left eyes were horizontally flipped in the x-direction. The algorithm-defined position of the outer RPE border and choroid-sclera junction was consistent with the manual delineation, resulting in highly correlated choroidal thickness values with r = 0.91 to 0.93 for the healthy subjects and 0.94 for patients with non-neovascular AMD. Across all cases, the mean and absolute differences between the algorithm and manual segmentation for the outer RPE boundary was -0.74 ± 3.27 μm and 3.15 ± 3.07 μm; and for the choroid-sclera junction was -3.90 ± 15.93 μm and 21.39 ± 10.71 μm. Excellent agreement was observed between the algorithm and manual choroidal segmentation in both normal eyes and those with non-neovascular AMD. The choroid was thinner in AMD eyes. Semiautomated choroidal thickness calculation may be useful for large-scale quantitative studies of the choroid.

  14. Photodynamic therapy for treatment subretinal neovascularization

    NASA Astrophysics Data System (ADS)

    Avetisov, Sergey E.; Budzinskaja, Maria V.; Kiseleva, Tatyana N.; Balatskaya, Natalia V.; Gurova, Irina V.; Loschenov, Viktor B.; Shevchik, Sergey A.; Kuzmin, Sergey G.; Vorozhtsov, Georgy N.

    2007-07-01

    This work are devoted our experience with photodynamic therapy (PDT) with <> for patients with choroidal neovascularization (CNV). 18 patients with subfoveal CNV in age-related macular degeneration (AMD), 24 patients with subfoveal CNV in pathological myopia (PM) and 4 patients with subfoveal CNV associated with toxoplasmic retinochoroiditis were observed. CNV was 100% classic in all study patients. Standardized protocol refraction, visual acuity testing, ophthalmologic examinations, biomicroscopy, fluorescein angiography, and ultrasonography were performed before treatment and 1 month, 3 months, 6 months, and 1 year after treatment; were used to evaluate the results of photodynamic therapy with <> (0.02% solution of mixture sulfonated aluminium phtalocyanine 0.05 mg/kg, intravenously). A diode laser (<>, Inc, Moscow) was used operating in the range of 675 nm. Need for retreatment was based on fluorescein angiographic evidence of leakage at 3-month follow-up intervals. At 3, 6, 9 month 26 (56.5%) patients had significant improvement in the mean visual acuity. At the end of the 12-month minimal fluorescein leakage from choroidal neovascularization was seen in 12 (26.1%) patients and the mean visual acuity was slightly worse than 0.2 which was not statistically significant as compared with the baseline visual acuity. Patients with fluorescein leakage from CNV underwent repeated PDT with <>. 3D-mode ultrasound shown the decreasing thickness of chorioretinal complex in CNV area. Photodynamic therapy with <> can safely reduce the risk of severe vision loss in patients with predominantly classic subfoveal choroidal neovascularization secondary to AMD, PM and toxoplasmic retinochoroiditis.

  15. Correlation between neovascular lesion type and clinical characteristics of nonneovascular fellow eyes in patients with unilateral, neovascular age-related macular degeneration.

    PubMed

    Marsiglia, Marcela; Boddu, Sucharita; Chen, Christine Y; Jung, Jesse J; Mrejen, Sarah; Gallego-Pinazo, Roberto; Freund, K Bailey

    2015-05-01

    To investigate the association between the type of neovascularization (NV) and the clinical characteristics of nonneovascular fellow eyes in patients with unilateral, neovascular age-related macular degeneration. Eighty-three patients with treatment-naive, unilateral, neovascular age-related macular degeneration were retrospectively analyzed. Neovascular lesions were classified using both fluorescein angiography and optical coherence tomography as Type 1 (subretinal pigment epithelium), 2 (subretinal), 3 (intraretinal), or mixed NV. The associations between NV lesion type and baseline clinical and imaging characteristics of the fellow eye, including central geographic atrophy, noncentral geographic atrophy, pigmentary changes, soft drusen, cuticular drusen, reticular pseudodrusen, and subfoveal choroidal thickness, were examined. Subfoveal choroidal thickness was defined as thin if thickness was <120 μm. In the fellow eyes of patients with treatment-naive, unilateral, neovascular age-related macular degeneration, Type 3 NV had an increased adjusted odds ratio of reticular pseudodrusen (15.361, P < 0.001) and thin subfoveal choroidal thickness (21.537, P < 0.001) as well as a tendency toward an increased adjusted odds ratio of central geographic atrophy (4.775, P = 0.028). Fellow eyes of patients with Type 1 NV showed a decreased adjusted odds ratio of reticular pseudodrusen (0.233, P = 0.007) and thin subfoveal choroidal thickness (0.080, P = 0.005). In patients with unilateral, neovascular age-related macular degeneration, certain nonneovascular features of the fellow eye correlate with the NV lesion composition based on type, as anatomically classified utilizing both fluorescein angiography and optical coherence tomography. Patients with Type 3 NV were more likely to have reticular pseudodrusen and/or thin subfoveal choroidal thickness in the fellow eye compared with those with Type 1 NV. Patients with Type 3 NV also showed a trend toward increased central

  16. Cytochrome P450-generated metabolites derived from ω-3 fatty acids attenuate neovascularization

    PubMed Central

    Yanai, Ryoji; Mulki, Lama; Hasegawa, Eiichi; Takeuchi, Kimio; Sweigard, Harry; Suzuki, Jun; Gaissert, Philipp; Vavvas, Demetrios G.; Sonoda, Koh-Hei; Rothe, Michael; Schunck, Wolf-Hagen; Miller, Joan W.; Connor, Kip M.

    2014-01-01

    Ocular neovascularization, including age-related macular degeneration (AMD), is a primary cause of blindness in individuals of industrialized countries. With a projected increase in the prevalence of these blinding neovascular diseases, there is an urgent need for new pharmacological interventions for their treatment or prevention. Increasing evidence has implicated eicosanoid-like metabolites of long-chain polyunsaturated fatty acids (LCPUFAs) in the regulation of neovascular disease. In particular, metabolites generated by the cytochrome P450 (CYP)–epoxygenase pathway have been shown to be potent modulators of angiogenesis, making this pathway a reasonable previously unidentified target for intervention in neovascular ocular disease. Here we show that dietary supplementation with ω-3 LCPUFAs promotes regression of choroidal neovessels in a well-characterized mouse model of neovascular AMD. Leukocyte recruitment and adhesion molecule expression in choroidal neovascular lesions were down-regulated in mice fed ω-3 LCPUFAs. The serum of these mice showed increased levels of anti-inflammatory eicosanoids derived from eicosapentaenoic acid and docosahexaenoic acid. 17,18-epoxyeicosatetraenoic acid and 19,20-epoxydocosapentaenoic acid, the major CYP-generated metabolites of these primary ω-3 LCPUFAs, were identified as key lipid mediators of disease resolution. We conclude that CYP-derived bioactive lipid metabolites from ω-3 LCPUFAs are potent inhibitors of intraocular neovascular disease and show promising therapeutic potential for resolution of neovascular AMD. PMID:24979774

  17. BILATERAL ISOLATED CHOROIDAL MELANOCYTOSIS.

    PubMed

    Mason, Lauren B; Mason, John O

    2016-01-01

    To report a very rare case of bilateral isolated choroidal melanocystosis. Clinical case report and literature review. A 24-year-old asymptomatic African American woman presented with bilateral diffuse choroidal pigmentation. The diagnosis of bilateral isolated choroidal melanocytosis was made, and optical coherence tomography was remarkable for increased choroidal thickness with a normal inner and outer retina. Although extremely rare, bilateral isolated choroidal melanocytosis may occur in young patients, as well as in those who are African American. Longer follow-up of this case and those in the literature will elucidate whether these choroidal lesions enlarge or have a risk of developing uveal melanoma.

  18. Polypoidal Choroidal Vasculopathy in Asians

    PubMed Central

    Wong, Chee Wai; Wong, Tien Y.; Cheung, Chui Ming Gemmy

    2015-01-01

    Age related macular degeneration (AMD) in Asians has been suggested to differ from their Western counterparts in terms of epidemiology, pathogenesis, clinical presentation and treatment. In particular, polypoidal choroidal vasculopathy (PCV) appears to be the predominant subtype of exudative AMD in Asian populations, in contrast to choroidal neovascularization secondary to AMD (CNV-AMD) in Western populations. Epidemiological data on PCV has been largely limited to hospital-based studies and there are currently no data on the incidence of PCV. Similarities and differences in risk factor profile between PCV and CNV-AMD point to some shared pathogenic mechanisms but also differential underlying mechanisms leading to the development of each phenotype. Serum biomarkers such as CRP, homocysteine and matrix metalloproteinases suggest underlying inflammation, atherosclerosis and deranged extracellular matrix metabolism as possible pathogenic mechanisms. In addition, recent advances in genome sequencing have revealed differences in genetic determinants of each subtype. While the standard of care for CNV-AMD is anti-vascular endothelial growth factor (VEGF) therapy, photodynamic therapy (PDT) has been the mainstay of treatment for PCV, although long-term visual prognosis remains unsatisfactory. The optimal treatment for PCV requires further clarification, particularly with different types of anti-VEGF agents and possible benefits of reduced fluence PDT. PMID:26239448

  19. Choroidal Round Hyporeflectivities in Geographic Atrophy

    PubMed Central

    De Vitis, Luigi Antonio; Carnevali, Adriano; Rabiolo, Alessandro; Querques, Lea; Bandello, Francesco; Querques, Giuseppe

    2016-01-01

    Purpose In geographic atrophy (GA), choroidal vessels typically appear on structural optical coherence tomography (OCT) as hyperreflective round areas with highly reflective borders. We observed that some GA eyes show choroidal round hyporeflectivities with highly reflective borders beneath the atrophy, and futher investigated the charcteristcs by comparing structural OCT, indocyanine green angiography (ICGA) and OCT angiography (OCT-A). Methods Round hyporeflectivities were individuated from a pool of patients with GA secondary to non-neovascular age-related macular degeneration consecutively presenting between October 2015 and March 2016 at the Medical Retina & Imaging Unit of the University Vita-Salute San Raffaele. Patients underwent a complete ophthalmologic examination including ICGA, structural OCT and OCT-A. The correspondence between choroidal round hyporeflectivities beneath GA on structural OCT and ICGA and OCT-A imaging were analyzed. Results Fifty eyes of 26 consecutive patients (17 females and 9 males; mean age 76.8±6.2 years) with GA were included. Twenty-nine round hyporeflectivities have been found by OCT in choroidal layers in 21 eyes of 21 patients (42.0%; estimated prevalence of 57.7%). All 29 round hyporeflectivities showed constantly a hyperreflective border and a backscattering on structural OCT, and appeared as hypofluorescent in late phase ICGA and as dark foci with non detectable flow in the choroidal segmentation of OCT-A. Interestingly, the GA area was greater in eyes with compared to eyes without round hyporeflectivities (9.30±5.74 and 5.57±4.48mm2, respectively; p = 0.01). Conclusions Our results suggest that most round hyporeflectivities beneath GA may represent non-perfused or hypo-perfused choroidal vessels with non-detectable flow. PMID:27880806

  20. Some physiological and psychological characteristics of myopic and non-myopic young men.

    PubMed

    Pärssinen, O; Era, P; Leskinen, A L

    1985-01-01

    As a part of a research project on the health and functional capacity of men at different ages a comparison of selected physiological and psychological characteristics of myopic and non-myopic 31-35 year-old men was made. The random sample studied consisted of 31 myopic and 100 non-myopic men. It was found that the body mass index and fat content were lower among the myopic than among the non-myopic. No significant differences were found in the elastic properties of skin, in blood pressure or in haematological assays studied between the groups. With respect to physical performance it was observed that the myopic had a higher aerobic capacity whereas there were no significant differences in muscular strength between the groups. In the psychological functions the myopic had a higher level in certain tests of intelligence. In the ophthalmological examination there were no significant differences between the groups in corrected vision, in eye tension and in dark adaptation. The amplitude of accommodation was 0.6-0.9 D. wider among the myopic. The results indicated some differences in physical and psychological characteristics between myopic and non-myopic young men. The differences could mainly be explained by differences in education and in physical activity during leisure.

  1. Focal Choroidal Excavation in Retinal Dystrophies.

    PubMed

    Braimah, Imoro Zeba; Rapole, Shruthi; Dumpala, Sunila; Chhablani, Jay

    2016-08-17

    To investigate the presence of focal choroidal excavation (FCE) in patients with retinitis pigmentosa (RP), Stargardt's disease (STGD), and Best disease in the Indian population. This retrospective consecutive case series included 309 eyes of 157 patients with RP (183 eyes), STGD (93 eyes), and Best disease (33 eyes) with good-quality, enhanced-depth spectral domain optical coherence tomography scans. Comprehensive ophthalmic examination data were collected. Characteristics of FCE, including location of FCE, type (conforming and non-conforming), maximal width, and depth, were noted. FCE was found in 2 out of 33 (6%) eyes with Best disease and no FCE was found in eyes with RP or STGD. The location of the FCE was extrafoveal in both cases. The first case had non-conforming FCE while the second case had the conforming type and the FCE occurred in association with choroidal neovascularization in the second case. The first case maintained good visual acuity of 20/20 over the entire period of follow-up (14 months), while the second case had a visual acuity of 20/200 at the last follow-up (three years) due to scarred choroidal neovascular membranes. The FCE showed no change in both eyes over the entire duration of follow-up. Focal choroidal excavation was found in 6% of eyes with Best disease, which remained stable throughout follow up. Eyes with RP and STGD did not have any FCE. Further studies are required to determine the role of vitelliform material in FCE development in Best disease.

  2. MACULAR BRUCH MEMBRANE DEFECTS IN HIGHLY MYOPIC EYES: The Beijing Eye Study.

    PubMed

    You, Qi Sheng; Peng, Xiao Yan; Xu, Liang; Chen, Chang Xi; Wei, Wen Bin; Wang, YaXing; Jonas, Jost B

    2016-03-01

    To examine prevalence and associations of macular Bruch membrane defects (MBMDs) in a population-based setting. Population-based cross-sectional study. The Beijing Eye Study 2011 included 3,468 subjects who underwent a detailed ophthalmic examination including spectral domain optical coherence tomography with enhanced depth imaging of the macula. Macular Bruch membrane defects were defined as an interruption of Bruch membrane on the optical coherence tomography images in the macular region. Macular Bruch membrane defects could be detected only in highly myopic eyes (defined as refractive error of ≤-6 diopters or axial length of ≥26.5 mm) with a prevalence of 17/164 (10.4%, 95% confidence interval [CI], 5.7%-18.1%). Best-corrected visual acuity <0.05 was found in 5 (29%) of 17 eyes with MBMDs, and in 7 (41%) eyes, visual acuity was <0.3 and ≥0.05. In the MBMD region, retinal pigment epithelium and choriocapillaris were completely lost, and the deep and middle layers of the retina and the choroid were almost completely absent. In the MBMD region, mean retinal thickness was 153 ± 57 μm (mean ± SD) and choroidal thickness was 12.7 ± 28.1 μm. On the fundus photographs, MBMDs appeared as whitish areas with round borders. In multivariate regression analysis, presence of MBMD was significantly associated only with longer axial length (Odds ratio: 3.87; 95% CI, 1.64-9.14). Macular Bruch membrane defects with a prevalence of approximately 10% in highly myopic eyes are associated with a complete loss of retinal pigment epithelium and choriocapillaris, an almost complete loss of photoreceptors and choroid, and marked reduction in visual acuity. Macular Bruch membrane defects may be added to the panoply of features of myopic maculopathy.

  3. Choroidal and Retinal Thickness in Children With Different Refractive Status Measured by Swept-Source Optical Coherence Tomography.

    PubMed

    Jin, Peiyao; Zou, Haidong; Zhu, Jianfeng; Xu, Xun; Jin, Jiali; Chang, Ta Chen; Lu, Lina; Yuan, Hong; Sun, Sifei; Yan, Bo; He, Jiangnan; Wang, Mingjin; He, Xiangui

    2016-08-01

    To investigate the choroidal and retinal thickness in myopic, emmetropic, and hyperopic Chinese children by swept-source longer-wavelength optical coherence tomography. Cross-sectional study. Two-hundred and seventy-six schoolchildren aged 7-13 years underwent comprehensive ophthalmic examinations, including cycloplegic refraction, and swept-source optical coherence tomography measurements. The thickness of the choroid, retina, ganglion cell layer, and nerve fiber layer were compared among children of different refractive status. The topographic variation and factors related to the thickness of the choroid and retinal layers were analyzed. Compared to emmetropic subjects, those with myopia had a significantly thinner choroid in all regions (P < .01), and hyperopic subjects had a thicker choroid in most regions (P < .05). The myopic retinas were thinner than those of emmetropic or hyperopic subjects in the superior parafoveal and all 4 perifoveal subfields (P < .05), but no other subfields differed significantly among different refractive groups (P > .05). The axial length and refractive diopters were independently related to central foveal choroidal thickness (R(2) = 0.17, P < .01), while age and intraocular pressure were independently associated with central fovea retinal (R(2) = 0.15, P < .01) and ganglion cell layer thicknesses (R(2) = 0.10, P < .01) after adjustment for other systematic and ocular factors. Central foveal choroidal and retinal thickness were unrelated in children of different refractive status (P > .05). Choroidal thickness, but not retinal thickness, correlated closely with axial length and refractive diopters in Chinese children. Choroid thinning occurs before retina thinning early in myopic progression. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. Apelin Is Required for Non-Neovascular Remodeling in the Retina

    PubMed Central

    McKenzie, Jenny A.G.; Fruttiger, Marcus; Abraham, Sabu; Lange, Clemens A.K.; Stone, Jay; Gandhi, Pranita; Wang, Xiaomeng; Bainbridge, James; Moss, Stephen E.; Greenwood, John

    2012-01-01

    Retinal pathologies are frequently accompanied by retinal vascular responses, including the formation of new vessels by angiogenesis (neovascularization). Pathological vascular changes may also include less well characterized traits of vascular remodeling that are non-neovascular, such as vessel pruning and the emergence of dilated and tortuous vessel phenotypes (telangiectasis). The molecular mechanisms underlying neovascular growth versus non-neovascular remodeling are poorly understood. We therefore undertook to identify novel regulators of non-neovascular remodeling in the retina by using the dystrophic Royal College of Surgeons (RCS) rat and the retinal dystrophy 1 (RD1) mouse, both of which display pronounced non-neovascular remodeling. Gene expression profiling of isolated retinal vessels from these mutant rodent models and wild-type controls revealed 60 differentially expressed genes. These included the genes for apelin (Apln) and for its receptor (Aplnr), both of which were strongly up-regulated in the mutants. Crossing RD1 mice into an Apln-null background substantially reduced vascular telangiectasia. In contrast, Apln gene deletion had no effect in two models of neovascular pathology [laser-induced choroidal neovascularization and the very low density lipoprotein receptor (Vldlr)-knockout mouse]. These findings suggest that in these models apelin has minimal effect on sprouting retinal angiogenesis, but contributes significantly to pathogenic non-neovascular remodeling. PMID:22067912

  5. The choroid in glaucoma.

    PubMed

    Banitt, Michael

    2013-03-01

    Prior studies have not conclusively established a relationship between the choroid and glaucoma. The development of an enhanced imaging technique for spectral domain optical coherence tomography (SD-OCT) has allowed for measurements of choroidal thickness that are more accurate than previously possible. Therefore, the SD-OCT may be capable of documenting the changes in the choroid as they relate to glaucoma. When applied to the SD-OCT, the technique of enhanced depth imaging allows for reproducible measurements of choroidal thickness. Nine reports have been published about choroidal thickness within the macula, as measured by OCT, in eyes with glaucoma. In six publications, there was no significant difference between the macular choroidal thicknesses of patients with glaucoma compared with those without glaucoma. Additional five studies have reported on peripapillary choroidal thickness in glaucoma patients. Although three of the studies determined that the peripapillary choroid is thinner in glaucoma patients, two others failed to establish this relationship. The SD-OCT is capable of reproducibly measuring choroidal thickness in the peripapillary and macular areas. In those with glaucoma, choroidal thickness does not change within the macula. In a few subsets of glaucoma, the peripapillary choroid is thinner when compared with normals.

  6. TYPE 2 (SUBRETINAL) NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH PURE RETICULAR PSEUDODRUSEN PHENOTYPE.

    PubMed

    Naysan, Jonathan; Jung, Jesse J; Dansingani, Kunal K; Balaratnasingam, Chandrakumar; Freund, K Bailey

    2016-03-01

    To report the association of pure type 2 neovascularization (NV) in age-related macular degeneration occurring almost exclusively in patients with reticular pseudodrusen. An observational retrospective cohort study of all eyes receiving antivascular endothelial growth factor therapy for newly diagnosed neovascular age-related macular degeneration by a single practitioner over a 6-year period. Only patients with treatment-naive, pure type 2 NV who also had either pre-neovascular imaging of the study eye or imaging of a nonneovascular fellow eye available to determine baseline characteristics including drusen type and choroidal thickness were incuded. Of 694 patients treated for neovascular age-related macular degeneration, only 8 met the inclusion criteria with pure type 2 NV. Of these, 7 (88%) had exclusively reticular pseudodrusen (5 in the nonneovascular fellow eye, 2 in the study eye before developing NV). Six (75%) patients in the affected neovascular eye and 6 (75%) in the fellow nonneovascular eye had choroidal thickness <120 μm. Mean follow-up was 46 months (range, 3.0-63.3). Best-corrected vision improved from 20/89 (range, 20/30-20/796) at baseline to 20/60 (range, 20/20-20/399) at last follow-up. Pure type 2 NV is rare in age-related macular degeneration, occurring almost exclusively in patients with reticular pseudodrusen and thin choroids.

  7. Optical coherence tomography: imaging of the choroid and beyond.

    PubMed

    Mrejen, Sarah; Spaide, Richard F

    2013-01-01

    Seventy percent of the blood flow to the eye goes to the choroid, a structure that is vitally important to the function of the retina. The in vivo structure of the choroid in health and disease is incompletely visualized with traditional imaging modalities, including indocyanine green angiography, ultrasonography, and spectral domain optical coherence tomography (OCT). Use of new OCT modalities, including enhanced depth imaging OCT, image averaging, and swept-source OCT, have led to increased visualization of the choroidal anatomy. The correlation of these new anatomical findings with other imaging modalities results increases understanding of many eye diseases and recognises of new ones. The status of the choroid appears to be a crucial determinant in the pathogenesis of diseases such as age-related choroidal atrophy, myopic chorioretinal atrophy, central serous chorioretinopathy, chorioretinal inflammatory diseases, and tumors. Extension of these imaging techniques has provided insights into abnormalities of the sclera and optic nerve. Future developments will include blood flow information, 3D rendering of various ocular structures, and the ability to evaluate changes in 3D structural information over time (4D imaging). Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Lack of netrin-4 modulates pathologic neovascularization in the eye

    PubMed Central

    Kociok, Norbert; Crespo-Garcia, Sergio; Liang, Yong; Klein, Sabrina V.; Nürnberg, Christina; Reichhart, Nadine; Skosyrski, Sergej; Moritz, Eva; Maier, Anna-Karina; Brunken, William J.; Strauß, Olaf; Koch, Manuel; Joussen, Antonia M.

    2016-01-01

    Netrins are a family of matrix-binding proteins that function as guidance signals. Netrin-4 displays pathologic roles in tumorigenesis and neovascularization. To answer the question whether netrin-4 acts either pro- or anti-angiogenic, angiogenesis in the retina was assessed in Ntn-4−/− mice with oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV), mimicking hypoxia-mediated neovascularization and inflammatory mediated angiogenesis. The basement membrane protein netrin-4 was found to be localised to mature retinal blood vessels. Netrin-4, but not netrin-1 mRNA expression, increased in response to relative hypoxia and recovered to normal levels at the end of blood vessel formation. No changes in the retina were found in normoxic Ntn-4−/− mice. In OIR, Ntn-4−/− mice initially displayed larger avascular areas which recovered faster to revascularization. Ganzfeld electroretinography showed faster recovery of retinal function in Ntn-4−/− mice. Expression of netrin receptors, Unc5H2 (Unc-5 homolog B, C. elegans) and DCC (deleted in colorectal carcinoma), was found in Müller cells and astrocytes. Laser-induced neovascularization in Nnt-4−/− mice did not differ to that in the controls. Our results indicate a role for netrin-4 as an angiogenesis modulating factor in O2-dependent vascular homeostasis while being less important during normal retinal developmental angiogenesis or during inflammatory neovascularization. PMID:26732856

  9. Choroidal Thickness and Biometric Markers for the Screening of Lacquer Cracks in Patients with High Myopia

    PubMed Central

    Wang, Nan-Kai; Lai, Chi-Chun; Chou, Chai Lin; Chen, Yen-Po; Chuang, Lan-Hsin; Chao, An-Ning; Tseng, Hsiao-Jung; Chang, Chee-Jen; Wu, Wei-Chi; Chen, Kuan-Jen; Tsang, Stephen H.

    2013-01-01

    Objectives Validation of choroidal thickness and other biometrics measured by spectral domain optical coherence tomography (SD-OCT) in predicting lacquer cracks formation in highly myopic eyes. Methods Patients with a refractive error worse than −8 diopters and moderate myopic maculopathy were recruited into two groups based on the presence or absence of lacquer cracks (36 eyes without and 33 eyes with lacquer cracks). Choroidal thickness, refractive error, and axial length were measured and subjected to receiver operating characteristic curve analysis to identify the optimal cutoff values at predicting lacquer crack formation. The width of the retinal pigment epithelium (RPE), RPE to the inner segment/outer segment line, RPE to the external limiting membrane were also measured and compared to the subfoveal choroidal thickness to assess their relationships as potential markers of lacquer crack formation. Results Lacquer crack is associated with decreased choroidal thickness, lower best-corrected visual acuity, longer axial length and higher refractive errors. Choroidal thickness has the strongest association with lacquer crack formation versus axial length and refractive error. In eyes with lacquer cracks, stellate lacquer cracks are associated with thinner choroidal thickness compared to eyes with linear lacquer cracks. Subfoveal choroidal thickness less than the width of the retinal pigment epithelium to the inner segment/outer segment line is also associated with lacquer crack formation (sensitivity 78.8%, specificity 88.3%, and accuracy 81.2%). Conclusions This study suggests that choroidal thickness and other SD-OCT measurements could be employed clinically to predict the development and severity of lacquer cracks in patients with high myopia. PMID:23349728

  10. Choroidal Thickness Changes After Intravitreal Ranibizumab for Exudative Age-Related Macular Degeneration.

    PubMed

    Minnella, Angelo Maria; Federici, Matteo; Falsini, Benedetto; Barbano, Lucilla; Gambini, Gloria; Lanza, Angela; Caporossi, Aldo; Savastano, Maria Cristina

    2016-08-01

    The results regarding changes of choroidal thickness following intravitreal ranibizumab injections in the literature are controversial. Vascular endothelial growth factor A is implicated in pathogenesis of neovascular age-related macular degeneration (AMD). The suspected unchanged choroidal layer thickness after intravitreal injections of ranibizumab suggests a possible protection of the outer blood-retinal barrier in the human eye. The aim was to evaluate choroidal thickness following the first administration of the study drug ranibizumab into the eyes of naïve wet AMD patients (nAMD). In this open label, 3-month, prospective, single-center, interventional, single-arm pilot study, 20 nAMD eyes were included and underwent three consecutive monthly injections of ranibizumab (0.5 mg/0.05 ml). Vital signs (i.e., blood pressure and pulse), ophthalmic examinations, intraocular pressure, best correct visual acuity and subfoveal choroidal thickness as examined with optical coherence tomography using enhanced depth imaging (OCT-EDI) were assessed at each visit. All patients were evaluated at baseline and at 15, 30 60 and 90 days after intravitreal injection. Ten eyes with fibrotic AMD lesions were evaluated as the control group. In all eyes, the choroidal thicknesses (µm) exhibited no significant changes from the baseline visit to the visits at 15, 30, 60 and 90 days post-injection (P > 0.05). The intravitreal treatment with ranibizumab was well tolerated, and no adverse events were registered. Choroidal thickness appeared to be unmodified following the intravitreal injection of ranibizumab into nAMD eyes. Intravitreal ranibizumab injections probably elicit a pharmacologic effect only in the choroidal neovascularization and not in the choroid circulation under neovascular lesions. Clinical Trials Eudract Registration #: 2013-005091-17.

  11. THE MULTIFUNCTIONAL CHOROID

    PubMed Central

    Nickla, Debora L.; Wallman, Josh

    2010-01-01

    The choroid of the eye is primarily a vascular structure supplying the outer retina. It has several unusual features: It contains large membrane-lined lacunae, which, at least in birds, function as part of the lymphatic drainage of the eye and which can change their volume dramatically, thereby changing the thickness of the choroid as much as four-fold over a few days (much less in primates). It contains non-vascular smooth muscle cells, especially behind the fovea, the contraction of which may thin the choroid, thereby opposing the thickening caused by expansion of the lacunae. It has intrinsic choroidal neurons, also mostly behind the central retina, which may control these muscles and may modulate choroidal blood-flow as well. These neurons receive sympathetic, parasympathetic and nitrergic innervation. The choroid has several functions: Its vasculature is the major supply for the outer retina; impairment of the flow of oxygen from choroid to retina may cause Age-Related Macular Degeneration. The choroidal blood flow, which is as great as in any other organ, may also cool and warm the retina. In addition to its vascular functions, the choroid contains secretory cells, probably involved in modulation of vascularization and in growth of the sclera. Finally, the dramatic changes in choroidal thickness move the retina forward and back, bringing the photoreceptors into the plane of focus, a function demonstrated by the thinning of the choroid that occurs when the focal plane is moved back by the wearing of negative lenses, and, conversely, by the thickening that occurs when positive lenses are worn. In addition to focusing the eye, more slowly than accommodation and more quickly than emmetropization, we argue that the choroidal thickness changes also are correlated with changes in the growth of the sclera, and hence of the eye. Because transient increases in choroidal thickness are followed by a prolonged decrease in synthesis of extracellular matrix molecules and a

  12. Polypoidal choroidal vasculopathy: simultaneous indocyanine green angiography and eye-tracked spectral domain optical coherence tomography findings.

    PubMed

    Khan, Samira; Engelbert, Michael; Imamura, Yutaka; Freund, K Bailey

    2012-06-01

    To describe simultaneous scanning laser ophthalmoscope indocyanine green angiographic and eye-tracked spectral-domain optical coherence tomography findings in eyes with polypoidal choroidal vasculopathy (PCV). Eighteen eyes of 18 patients with PCV because of a variety of different diagnoses were imaged with simultaneous scanning laser ophthalmoscope indocyanine green angiography and eye-tracked spectral-domain optical coherence tomography to localize the polyps and their associated vascular structures with respect to the retinal layers. Regardless of the underlying diagnosis, simultaneous scanning laser ophthalmoscope indocyanine green angiography and eye-tracked spectral-domain optical coherence tomography imaging localized the polypoidal structures of PCV to within larger Type 1 neovascular complexes occurring within or above Bruch membrane. In 8 eyes, PCV appeared to adhere to the undersurface of an elevated retinal pigment epithelial detachment. In 1 eye, a PCV lesion was detected within the neurosensory retina having apparently eroded through the overlying retinal pigment epithelium. Simultaneous scanning laser ophthalmoscope indocyanine green angiography and eye-tracked spectral-domain optical coherence tomography demonstrate that a majority of PCV represents a variant of the Type 1 neovascular growth pattern, which can occur in a variety of different neovascularized maculopathies. Polypoidal choroidal vasculopathy lesions appear to originate from long-standing choroidal neovascularization, rather than from the choroidal vasculature itself. Given these observations, PCV would be more accurately described as a neovasculopathy rather than as a choroidal vasculopathy.

  13. Prospective evaluation of myopic keratomileusis.

    PubMed

    Swinger, C A; Barker, B A

    1984-07-01

    The initial results of a prospective evaluation of myopic keratomileusis are reported. The procedure was attempted on 42 eyes, with an average follow-up of 10 months. The average reductions of myopia were 7.05 D and 11.59 D when measured by keratometry and refraction, respectively. Regular astigmatism increased by 0.50 D on keratometry, but there was no change in the refractive cylinder. The majority of patients had some irregular astigmatism on corneoscopy. The average percent correction, based on refraction, was 94.1 +/- 24%, and the correlation coefficient was 0.43. Visual rehabilitation was rapid. No patient followed for 1 year or more had a decrease in the best-corrected acuity, and 63% of this group had an average improvement of 1.5 lines with as much as five lines. The final refraction may take up to 6 months to stabilize. Complications consisted of epithelium and debris in the interface and focal necrosis of Bowman's membrane. The technique is difficult but may have application in the visual rehabilitation of the high myope.

  14. Assessment of Optical Coherence Tomography Color Probability Codes in Myopic Glaucoma Eyes After Applying a Myopic Normative Database.

    PubMed

    Seol, Bo Ram; Kim, Dong Myung; Park, Ki Ho; Jeoung, Jin Wook

    2017-09-12

    To evaluate the optical coherence tomography (OCT) color probability codes based on a myopic normative database and to investigate whether the implementation of the myopic normative database can improve the OCT diagnostic ability in myopic glaucoma. Comparative validity study. In this study, 305 eyes (154 myopic healthy eyes and 151 myopic glaucoma eyes) were included. A myopic normative database was obtained based on myopic healthy eyes. We evaluated the agreement between OCT color probability codes after applying the built-in and myopic normative databases, respectively. Another 120 eyes (60 myopic healthy eyes and 60 myopic glaucoma eyes) were included and the diagnostic performance of OCT color codes using a myopic normative database was investigated. The mean weighted kappa (Kw) coefficients for quadrant retinal nerve fiber layer (RNFL) thickness, clock-hour RNFL thickness, and ganglion cell-inner plexiform layer (GCIPL) thickness were 0.636, 0.627, and 0.564, respectively. The myopic normative database showed a higher specificity than did the built-in normative database in quadrant RNFL thickness, clock-hour RNFL thickness, and GCIPL thickness (P < .001, P < .001, and P < .001, respectively). The receiver operating characteristic curve values increased when using the myopic normative database in quadrant RNFL thickness, clock-hour RNFL thickness, and GCIPL thickness (P = .011, P = .004, P < .001, respectively). The diagnostic ability of OCT color codes for detection of myopic glaucoma significantly improved after application of the myopic normative database. The implementation of a myopic normative database is needed to allow more precise interpretation of OCT color probability codes when used in myopic eyes. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. [Subretinal neovascular membrane in angioid streaks treated with intravitreal bevacizumab].

    PubMed

    García-López, A; González-Castaño, C

    2014-05-01

    Angioid streaks are breaks in Bruch's membrane that may be associated, among others, with pseudoxanthoma elasticum. Its most common complication is the development of subretinal neovascular membranes (SRNVM) and the decreased vision this entails. A 28 year old woman with angioid streaks and SRNVM in the left eye, who received 3 injections of intravitreal bevacizumab, with rapid improvement in vision and stability during 11 months follow up. The finding of angioid streaks led to the diagnosis of pseudoxanthoma elasticum. Intravitreal bevacizumab should be considered as an effective treatment option for choroidal neovascularization associated with angioid streaks. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  16. SEMIAUTOMATED QUANTITATIVE APPROACH TO CHARACTERIZE TREATMENT RESPONSE IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Real-World Study.

    PubMed

    Roberts, Philipp K; Nesper, Peter L; Gill, Manjot K; Fawzi, Amani A

    2017-08-01

    To perform a quantitative study of the vascular microstructure in actively treated choroidal neovascularization by optical coherence tomographic angiography. Patients undergoing individualized anti-vascular endothelial growth factor therapy of minimum 12 months duration were included in this cross-sectional observational study and imaged using optical coherence tomographic angiography. En face optical coherence tomographic angiography images were analyzed for quantitative features, such as junction density, vessel length, and lacunarity using validated software (Angiotool). Patients were divided into 2 groups depending on their individualized treatment interval: "good responders, treated less frequently than 6 weeks" versus "poor responders, treated every 6 weeks or more frequently." Nonparametric testing was used to assess differences between these groups. Twenty-five eyes of 23 consecutive patients with a median 58-month history of choroidal neovascularization, treated by median of 34 anti-vascular endothelial growth factor injections, were included in the analysis. There was no significant difference between any of the microvascular choroidal neovascularization features between the 2 groups (P > 0.05). The semiautomated vessel segmentation software provides an objective and quantitative approach for choroidal neovascularization characterization. The consistently nonsignificant outcomes between the groups may provide evidence to support the "normalization hypothesis." This would suggest that regardless of treatment interval, individualized therapy in these eyes established vessel stability.

  17. Molecular Pathogenesis of Retinal and Choroidal Vascular Diseases

    PubMed Central

    Campochiaro, Peter A.

    2015-01-01

    There are two major types of ocular neovascularization that affect the retina, retinal neovascularization (NV) and subretinal or choroidal NV. Retinal NV occurs in a group of diseases referred to as ischemic retinopathies in which damage to retinal vessels results in retinal ischemia. Most prevalent of these are diabetic retinopathy and retinal vein occlusions. Subretinal and choroidal NV occur in diseases of the outer retina and Bruch’s membrane, the most prevalent of which is age-related macular degeneration. Numerous studies in mouse models have helped to elucidate the molecular pathogenesis underlying retinal, subretinal, and choroidal NV. There is considerable overlap because the precipitating event in each is stabilization of hypoxia inducible factor-1 (HIF-1) which leads to upregulation of several hypoxia-regulated gene products, including vascular endothelial growth factor (VEGF), angiopoietin 2, vascular endothelial-protein tyrosine phosphatase (VE-PTP), and several others. Stimulation of VEGF signaling and suppression of Tie2 by angiopoietin 2 and VE-PTP are critical for sprouting of retinal, subretinal, and choroidal NV, with perturbation of Bruch’s membrane also needed for the latter. Additional HIF-1-regulated gene products cause further stimulation of the NV. It is difficult to model macular edema in animals and therefore proof-of-concept clinical trials were done and demonstrated that VEGF plays a central role and that suppression of Tie2 is also important. Neutralization of VEGF is currently the first line therapy for all of the above disease processes, but new treatments directed at some of the other molecular targets, particularly stabilization of Tie2, are likely to provide additional benefit for subretinal/choroidal NV and macular edema. In addition, the chronicity of these diseases as well as the implication of VEGF as a cause of retinal nonperfusion and progression of background diabetic retinopathy make sustained delivery approaches for

  18. Strategies for improving early detection and diagnosis of neovascular age-related macular degeneration

    PubMed Central

    Keane, Pearse A; de Salvo, Gabriella; Sim, Dawn A; Goverdhan, Srini; Agrawal, Rupesh; Tufail, Adnan

    2015-01-01

    Treatment of the neovascular form of age-related macular degeneration (AMD) has been revolutionized by the introduction of such agents as ranibizumab, bevacizumab, and aflibercept. As a result, the incidence of legal blindness occurring secondary to AMD has fallen dramatically in recent years in many countries. While these agents have undoubtedly been successful in reducing visual impairment and blindness, patients with neovascular AMD typically lose some vision over time, and often lose the ability to read, drive, or perform other important activities of daily living. Efforts are therefore under way to develop strategies that allow for earlier detection and treatment of this disease. In this review, we begin by providing an overview of the rationale for, and the benefits of, early detection and treatment of neovascular AMD. To achieve this, we begin by providing an overview of the pathophysiology and natural history of choroidal neovascularization, before reviewing the evidence from both clinical trials and “real-world” outcome studies. We continue by highlighting an area that is often overlooked: the importance of patient education and awareness for early AMD detection. We conclude the review by reviewing an array of both established and emerging technologies for early detection of choroidal neovascularization, ranging from Amsler chart testing, to hyperacuity testing, to advanced imaging techniques, such as optical coherence tomography. PMID:25733802

  19. Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization

    PubMed Central

    Liu, Chi-Hsiu; Sun, Ye; Li, Jie; Gong, Yan; Tian, Katherine T.; Evans, Lucy P.; Morss, Peyton C.; Fredrick, Thomas W.; Saba, Nicholas J.; Chen, Jing

    2015-01-01

    Pathologic ocular neovascularization commonly causes blindness. It is critical to identify the factors altered in pathologically proliferating versus normally quiescent vessels to develop effective targeted therapeutics. MicroRNAs regulate both physiological and pathological angiogenesis through modulating expression of gene targets at the posttranscriptional level. However, it is not completely understood if specific microRNAs are altered in pathologic ocular blood vessels, influencing vascular eye diseases. Here we investigated the potential role of a specific microRNA, miR-150, in regulating ocular neovascularization. We found that miR-150 was highly expressed in normal quiescent retinal blood vessels and significantly suppressed in pathologic neovessels in a mouse model of oxygen-induced proliferative retinopathy. MiR-150 substantially decreased endothelial cell function including cell proliferation, migration, and tubular formation and specifically suppressed the expression of multiple angiogenic regulators, CXCR4, DLL4, and FZD4, in endothelial cells. Intravitreal injection of miR-150 mimic significantly decreased pathologic retinal neovascularization in vivo in both wild-type and miR-150 knockout mice. Loss of miR-150 significantly promoted angiogenesis in aortic rings and choroidal explants ex vivo and laser-induced choroidal neovascularization in vivo. In conclusion, miR-150 is specifically enriched in quiescent normal vessels and functions as an endothelium-specific endogenous inhibitor of pathologic ocular neovascularization. PMID:26374840

  20. JNK inhibition reduces apoptosis and neovascularization in a murine model of age-related macular degeneration

    PubMed Central

    Du, Hongjun; Sun, Xufang; Guma, Monica; Luo, Jing; Ouyang, Hong; Zhang, Xiaohui; Zeng, Jing; Quach, John; Nguyen, Duy H.; Shaw, Peter X.; Karin, Michael; Zhang, Kang

    2013-01-01

    Age-related macular degeneration (AMD) is the leading cause of registered blindness among the elderly and affects over 30 million people worldwide. It is well established that oxidative stress, inflammation, and apoptosis play critical roles in pathogenesis of AMD. In advanced wet AMD, although, most of the severe vision loss is due to bleeding and exudation of choroidal neovascularization (CNV), and it is well known that vascular endothelial growth factor (VEGF) plays a pivotal role in the growth of the abnormal blood vessels. VEGF suppression therapy improves visual acuity in AMD patients. However, there are unresolved issues, including safety and cost. Here we show that mice lacking c-Jun N-terminal kinase 1 (JNK1) exhibit decreased inflammation, reduced CNV, lower levels of choroidal VEGF, and impaired choroidal macrophage recruitment in a murine model of wet AMD (laser-induced CNV). Interestingly, we also detected a substantial reduction in choroidal apoptosis of JNK1-deficient mice. Intravitreal injection of a pan-caspase inhibitor reduced neovascularization in the laser-induced CNV model, suggesting that apoptosis plays a role in laser-induced pathological angiogenesis. Intravitreal injection of a specific JNK inhibitor decreased choroidal VEGF expression and reduced pathological CNV. These results suggest that JNK1 plays a key role in linking oxidative stress, inflammation, macrophage recruitment apoptosis, and VEGF production in wet AMD and pharmacological JNK inhibition offers a unique and alternative avenue for prevention and treatment of AMD. PMID:23341606

  1. Choroidal volume variations with age, axial length, and sex in healthy subjects: a three-dimensional analysis

    PubMed Central

    Barteselli, Giulio; Chhablani, Jay; El-Emam, Sharif; Wang, Haiyan; Chuang, Janne; Kozak, Igor; Cheng, Lingyun; Bartsch, Dirk-Uwe; Freeman, William R.

    2012-01-01

    -dimensional topography of the choroid and to measure choroidal volume at the posterior pole using manual segmentation. Age and axial length are inversely correlated with choroidal volume, most likely leading to changes in retinal metabolic support in old and high myopic patients. Sexual differences should be considered when interpreting an EDI SD-OCT scan of the choroid. PMID:22921388

  2. THE GOAL OF VALUE-BASED MEDICINE ANALYSES: COMPARABILITY. THE CASE FOR NEOVASCULAR MACULAR DEGENERATION

    PubMed Central

    Brown, Gary C.; Brown, Melissa M.; Brown, Heidi C.; Kindermann, Sylvia; Sharma, Sanjay

    2007-01-01

    Purpose To evaluate the comparability of articles in the peer-reviewed literature assessing the (1) patient value and (2) cost-utility (cost-effectiveness) associated with interventions for neovascular age-related macular degeneration (ARMD). Methods A search was performed in the National Library of Medicine database of 16 million peer-reviewed articles using the key words cost-utility, cost-effectiveness, value, verteporfin, pegaptanib, laser photocoagulation, ranibizumab, and therapy. All articles that used an outcome of quality-adjusted life-years (QALYs) were studied in regard to (1) percent improvement in quality of life, (2) utility methodology, (3) utility respondents, (4) types of costs included (eg, direct healthcare, direct nonhealthcare, indirect), (5) cost bases (eg, Medicare, National Health Service in the United Kingdom), and (6) study cost perspective (eg, government, societal, third-party insurer). To qualify as a value-based medicine analysis, the patient value had to be measured using the outcome of the QALYs conferred by respective interventions. As with value-based medicine analyses, patient-based time tradeoff utility analysis had to be utilized, patient utility respondents were necessary, and direct medical costs were used. Results Among 21 cost-utility analyses performed on interventions for neovascular macular degeneration, 15 (71%) met value-based medicine criteria. The 6 others (29%) were not comparable owing to (1) varying utility methodology, (2) varying utility respondents, (3) differing costs utilized, (4) differing cost bases, and (5) varying study perspectives. Among value-based medicine studies, laser photocoagulation confers a 4.4% value gain (improvement in quality of life) for the treatment of classic subfoveal choroidal neovascularization. Intravitreal pegaptanib confers a 5.9% value gain (improvement in quality of life) for classic, minimally classic, and occult subfoveal choroidal neovascularization, and photodynamic therapy

  3. Vitelliform focal choroidal excavation.

    PubMed

    Or, Chris; Forooghian, Farzin

    2014-05-30

    Focal choroidal excavations (FCE) are characterized by foveal or perifoveal choroid excavations seen on optical coherence tomography (OCT). The authors report a case of FCE associated with a vitelliform lesion within the excavation. A case of FCE associated with a small vitelliform lesion has been described previously, but the larger extent of the vitelliform lesion observed in the current case has not been previously reported. This may represent a novel category of FCE, vitelliform focal choroidal excavation, in which deposition of vitelliform material is associated with its development.

  4. Structural and Biochemical Analyses of Choroidal Thickness in Human Donor Eyes

    PubMed Central

    Sohn, Elliott H.; Khanna, Aditi; Tucker, Budd A.; Abràmoff, Michael D.; Stone, Edwin M.; Mullins, Robert F.

    2014-01-01

    Purpose. The choroid plays a vital role in the health of the outer retina. While measurements of choroid using optical coherence tomography show altered thickness in aging and macular disease, detailed histopathologic and proteomic analyses are lacking. In this study we sought to evaluate biochemical differences in human donor eyes between very thin and thick choroids. Methods. One hundred forty-one eyes from 104 donors (mean age ± standard deviation, 81.5 ± 12.2) were studied. Macular sections were collected, and the distance between Bruch's membrane and the inner surface of the sclera was measured in control, early/dry age-related macular degeneration (AMD), neovascular AMD, and geographic atrophy eyes. Proteins from the RPE-choroid of eyes with thick and thin choroids were analyzed using two-dimensional electrophoresis and/or mass spectrometry. Two proteins with altered abundance were confirmed using Western blot analysis. Results. Donor eyes showed a normal distribution of thicknesses. Eyes with geographic atrophy had significantly thinner choroids than age-matched controls or early AMD eyes. Proteomic analysis showed higher levels of the serine protease SERPINA3 in thick choroids and increased levels of tissue inhibitor of metalloproteinases-3 (TIMP3) in thin choroids. Conclusions. Consistent with clinical imaging observations, geographic atrophy was associated with choroidal thinning. Biochemical data suggest an alteration in the balance between proteases and protease inhibitors in eyes that lie at the extremes of choroidal thickness. An improved understanding of the basic mechanisms associated with choroidal thinning may guide the development of new therapies for AMD. PMID:24519422

  5. Choroidal neovascularisation on optical coherence tomography angiography in punctate inner choroidopathy and multifocal choroiditis.

    PubMed

    Levison, Ashleigh L; Baynes, Kimberly M; Lowder, Careen Y; Kaiser, Peter K; Srivastava, Sunil K

    2017-05-01

    To describe the findings seen on optical coherence tomography angiography (OCTA) in patients with punctate inner choroidopathy (PIC) and multifocal choroiditis and panuveitis (MCP) complicated by choroidal neovascular membranes. This was an Institutional Review Board-approved prospective, descriptive case series. 12 patients with PIC and MCP complicated by choroidal neovascularisation (CNV) were included. Each patient underwent slit-lamp examination by a uveitis specialist followed by conventional spectral domain OCT imaging of the macula. OCTA images of the macula were then obtained. 12 patients were enrolled in the study, out of which 9 patients were followed longitudinally. CNV was identified in 11 of the 12 patients. In all patients where fluorescein angiography (FA) was inconclusive for presence of CNV, OCTA identified CNV. Various lesions on OCT suggestive of activity correlated with changes in the vascular structure of OCTA to confirm suspicion of clinical activity. In patients with PIC and MCP complicated by CNV, OCTA successfully identified underlying CNV. Given the difficulty of differentiating inflammatory lesions from early CNV on OCT and FA, OCTA may provide a valuable method of monitoring patients with posterior uveitis highly correlated with development of CNV. 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/.

  6. Progression of choroid plexus papilloma.

    PubMed

    Dhillon, Rana S; Wang, Yi Yuen; McKelvie, Penny A; O'Brien, Brendan

    2013-12-01

    Choroid plexus papillomas are rare neoplasms that arise from choroid plexus epithelium. The World Health Organization classification describes three histological grades. Grade I is choroid plexus papilloma, grade II is atypical choroid plexus papilloma and grade III is choroid plexus carcinoma. Progression between grades is rare but documented. We present two adult cases, a 53-year-old female and a 70-year-old male, who demonstrated clear interval histological progression from grade I choroid plexus papilloma to higher grades. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Neuropilin 1 Involvement in Choroidal and Retinal Neovascularisation

    PubMed Central

    Fernández-Robredo, Patricia; Sim, Dawn A.; Fruttiger, Marcus

    2017-01-01

    Purpose Inhibiting VEGF is the gold standard treatment for neovascular age-related macular degeneration (AMD). It is also effective in preventing retinal oedema and neovascularisation (NV) in diabetic retinopathy (DR) and retinal vein occlusions (RVO). Neuropilin 1 (Nrp1) is a co-receptor for VEGF and many other growth factors, and therefore a possible alternative drug target in intra ocular neovascular disease. Here we assessed choroidal and retinal NV in an inducible, endothelial specific knock out model for Nrp1. Methods Crossing Nrp1 floxed mice with Pdgfb-CreERT2 mice produced tamoxifen-inducible, endothelial specific Nrp1 knock out mice (Nrp1ΔEC) and Cre-negative, control littermates. Cre-recombinase activity was confirmed in the Ai3(RCL-EYFP) reporter strain. Animals were subjected to laser-induced CNV (532 nm) and spectral domain-optical coherence tomography (SD-OCT) was performed immediately after laser and at day 7. Fluorescein angiography (FA) evaluated leakage and postmortem lectin staining in flat mounted RPE/choroid complexes was also used to measure CNV. Furthermore, retinal neovascularisation in the oxygen induced retinopathy (OIR) model was assessed by immunohistochemistry in retinal flatmounts. Results In vivo FA, OCT and post-mortem lectin staining showed a statistically significant reduction in leakage (p<0.05), CNV volume (p<0.05) and CNV area (p<0.05) in the Nrp1ΔEC mice compared to their Cre-negative littermates. Also the OIR model showed reduced retinal NV in the mutant animals compared to wild types (p<0.001). Conclusion We have demonstrated reduced choroidal and retinal NV in animals that lack endothelial Nrp1, confirming a role of Nrp1 in those processes. Therefore, Nrp1 may be a promising drug target for neovascular diseases in the eye. PMID:28107458

  8. Increased choroidal mast cells and their degranulation in age-related macular degeneration

    PubMed Central

    Bhutto, Imran A; McLeod, D Scott; Jing, Tian; Sunness, Janet S.; Seddon, Johanna M.; Lutty, Gerard A

    2016-01-01

    Background/Aims Inflammation has been implicated in age-related macular degeneration (AMD). This study investigates the association of mast cells (MCs), a resident choroidal inflammatory cell, with pathological changes in AMD. Methods Human donor eyes included aged controls (n=10), clinically diagnosed with early AMD (n=8), geographic atrophy (GA, n=4), and exudative AMD (n=11). The choroids were excised and incubated alkaline phosphatase (APase; blood vessels) and nonspecific esterase activities (MCs). Degranulated (DG) and nondegranulated (NDG) MCs in four areas of posterior choroid (nasal, nonmacular, paramacular, and submacular) were counted in flat mounts (4∼6 fields/area). Choroids were subsequently embedded in JB-4 and sectioned for histological analyses. Results The number of MCs was significantly increased in all choroidal areas in early AMD (p=0.0006) and in paramacular area in exudative AMD (139.44±55.3 cells/mm2; p=0.0091) and GA (199.08±82.0 cells/mm2; p=0.0019) compared to the aged controls. DG MCs was also increased in paramacular (p=0.001) and submacula choroid (p=0.02) in all forms of AMD. Areas with the greatest numbers of DG MC had loss of choriocapillaris (CC). Sections revealed that the MCs were widely distributed in Sattler's and Haller's layer in the choroidal stroma in aged controls, whereas MCs were frequently found in close proximity to CC in GA and exudative AMD and in choroidal neovascularization (CNV). Conclusion Increased MC numbers and degranulation were observed in all AMD choroids. These results suggest that MC degranulation may contribute to the pathogenesis of AMD: death of CC and RPE and CNV formation. The proteolytic enzymes released from MC granules may result in thinning of AMD choroid. PMID:26931413

  9. STAT3 activation in circulating monocytes contributes to neovascular age-related macular degeneration

    PubMed Central

    Chen, Mei; Lechner, Judith; Zhao, Jiawu; Toth, Levente; Hogg, Ruth; Silvestri, Giuliana; Kissenpfennig, Adrien; Chakravarthy, Usha; Xu, Heping

    2016-01-01

    Infiltrating macrophages are critically involved in pathogenic angiogenesis such as neovascular age-related macular degeneration (nAMD). Macrophages originate from circulating monocytes and three subtypes of monocyte exist in humans: classical (CD14+CD16-), non-classical (CD14-CD16+) and intermediate (CD14+CD16+) monocytes. The aim of this study was to investigate the role of circulating monocyte in neovascular age-related macular degeneration (nAMD). Flow cytometry analysis showed that the intermediate monocytes from nAMD patients expressed higher levels of CX3CR1 and HLA-DR compared to those from controls. Monocytes from nAMD patients expressed higher levels of phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3), and produced higher amount of VEGF. In the mouse model of choroidal neovascularization (CNV), pSTAT3 expression was increased in the retina and RPE/choroid, and 49.24% of infiltrating macrophages express pSTAT3. Genetic deletion of the Suppressor of Cytokine Signalling 3 (SOCS3) in myeloid cells in the LysM-Cre+/-:SOCS3fl/fl mice resulted in spontaneous STAT3 activation and accelerated CNV formation. Inhibition of STAT3 activation using a small peptide LLL12 suppressed laser-induced CNV. Our results suggest that monocytes, in particular the intermediate subset of monocytes are activated in nAMD patients. STAT3 activation in circulating monocytes may contribute to the development of choroidal neovascularisation in AMD. PMID:27009107

  10. Girdin and its phosphorylation dynamically regulate neonatal vascular development and pathological neovascularization in the retina.

    PubMed

    Ito, Takanori; Komeima, Keiichi; Yasuma, Tetsuhiro; Enomoto, Atsushi; Asai, Naoya; Asai, Masato; Iwase, Sayoko; Takahashi, Masahide; Terasaki, Hiroko

    2013-02-01

    Vascular endothelial growth factor (VEGF) is recognized as a principal mediator of vessel growth. VEGF regulates various endothelial cellular processes, including cell migration, proliferation, and survival, through the serine threonine protein kinase Akt. The Akt substrate girdin, an actin-binding protein, is known to regulate VEGF-mediated postnatal angiogenesis. However, the role of girdin and its phosphorylation in neonatal retinal vascular development and ocular pathological neovascularization in vivo has not been elucidated. In the present study, therefore, we investigated these processes using Girdin(+/-) mice lacking one copy of the girdin gene and girdin S1416A knockin (Girdin-KI(SA/SA)) mice in which the phosphorylation site of girdin is completely disrupted. We used three mouse models of pathological ocular neovascularization: oxygen-induced retinopathy (a mouse model of ischemic retinopathies), laser-induced choroidal neovascularization, and a human VEGF transgenic mouse that overexpresses human VEGF specifically in photoreceptor cells and generates pathological neovascularization in the retina. Neonatal vascular development was delayed and pathological neovascularization was decreased in both Girdin(+/-) mice and Girdin-KI(SA/SA) mice. These results demonstrate that girdin and its phosphorylation play an important role in neonatal vascular development and in pathological neovascularization in the retina. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  11. Polymeric materials for neovascularization

    NASA Astrophysics Data System (ADS)

    DeVolder, Ross John

    Revascularization therapies have emerged as a promising strategy to treat various acute and chronic wounds, cardiovascular diseases, and tissue defects. It is common to either administer proangiogenic growth factors, such as vascular endothelial growth factor (VEGF), or transplant cells that endogenously express multiple proangiogenic factors. Additionally, these strategies utilize a wide variety of polymeric systems, including hydrogels and biodegradable plastics, to deliver proangiogenic factors in a sophisticated manner to maintain a sustained proangiogenic environment. Despite some impressive results in rebuilding vascular networks, it is still a challenging task to engineer mature and functional neovessels in target tissues, because of the increasing complexities involved with neovascularization applications. To resolve these challenges, this work aims to design a wide variety of proangiogenic biomaterial systems with tunable properties used for neovascularization therapies. This thesis describes the design of several biomaterial systems used for the delivery of proangiogenic factors in neovascularization therapies, including: an electrospun/electrosprayed biodegradable plastic patch used for directional blood vessel growth (Chapter 2), an alginate-g-pyrrole hydrogel system that biochemically stimulates cellular endogenous proangiogenic factor expression (Chapter 3), an enzyme-catalyzed alginate-g-pyrrole hydrogel system for VEGF delivery (Chapter 4), an enzyme-activated alginate-g-pyrrole hydrogel system with systematically controllable electrical and mechanical properties (Chapter 5), and an alginate-g-pyrrole hydrogel that enables the decoupled control of electrical conductivity and mechanical rigidity and is use to electrically stimulate cellular endogenous proangiogenic factor expression (Chapter 6). Overall, the biomaterial systems developed in this thesis will be broadly useful for improving the quality of a wide array of molecular and cellular based

  12. Therapeutic Effects of PPARα Agonist on Ocular Neovascularization in Models Recapitulating Neovascular Age-Related Macular Degeneration.

    PubMed

    Qiu, Fangfang; Matlock, Greg; Chen, Qian; Zhou, Kelu; Du, Yanhong; Wang, Xiang; Ma, Jian-Xing

    2017-10-01

    This study was designed to evaluate effects of fenofibric acid (Feno-FA), a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, on ocular neovascularization (NV) in models recapitulating neovascular age-related macular degeneration (AMD), and to explore whether the effects are PPARα dependent. Laser-induced choroidal NV (CNV) in rats and very low-density lipoprotein receptor knockout (Vldlr-/-) mice received daily intraperitoneal injections of Feno-FA or vehicle. Vascular leakage was examined by fundus fluorescein angiography and permeability assay using Evans blue as tracer. In CNV rats, severity of CNV was evaluated by CNV areas and CNV volume. In Vldlr-/- mice, subretinal NV (SRNV) and intraretinal NV (IRNV) were quantified in choroid flat mount and retina flat mount, respectively. Inflammatory factors were measured using Western blotting and retinal leukostasis assay. Further, Pparα-/- mice and age-matched wild-type (WT) mice were used for laser-induced CNV and treated with Feno-FA to explore the underlying mechanism. Feno-FA significantly reduced vascular leakage in CNV rats and Vldlr-/- mice, reduced CNV volume in laser-induced CNV rats, and suppressed SRNV and IRNV in Vldlr-/- mice. In addition, Feno-FA downregulated the expression of inflammatory factors, including VEGF, TNF-α, and intercellular cell adhesion molecule-1 (ICAM-1), in the eyecups of CNV rats and decreased adherent retinal leukocytes in Vldlr-/- mice. Furthermore, Pparα-/- mice developed more severe CNV compared with WT mice, and PPARα knockout abolished the beneficial effects of Feno-FA on CNV. Feno-FA has therapeutic effects on ocular NV in models recapitulating neovascular AMD through a PPARα-dependent mechanism.

  13. Effect of retinal image defocus on the thickness of the human choroid.

    PubMed

    Chiang, Samuel T-H; Phillips, John R; Backhouse, Simon

    2015-07-01

    To describe the time-course and amplitude of changes to sub-foveal choroidal thickness (SFCT) induced by imposed hyperopic and myopic retinal defocus and to compare the responses in emmetropic and myopic subjects. Twelve East Asian subjects (age: 18-34 years; six were emmetropic and six had myopia between -2.00 and -5.00 dioptres (D)) viewed a distant target (video movie at 6 m) for 60 min on two separate occasions while optical coherence tomography (OCT) images of the choroid were taken in both eyes every 5 min to monitor SFCT. On each occasion, one eye was optimally corrected for distance with a contact lens while the other eye wore a contact lens imposing either 2.00 D hyperopic or 2.00 D myopic retinal defocus. Baseline SFCT in myopic eyes (mean ± S.D.): 256 ± 42 μm was significantly less than in emmetropic eyes (423 ± 62 μm; p < 0.01) and was correlated with magnitude of myopia (-39 μm per dioptre of myopia, R(2) = 0.67: p < 0.01). Repeated measures anova (General Linear Model) analysis revealed that in both subject groups, 2.00 D of myopic defocus caused a rapid increase in SFCT in the defocussed eye (significant by 10 min, increasing to approximately 20 μm within 60 min: p < 0.01), with little change in the control eye. In contrast, 2.00 D of hyperopic defocus caused a decrease in SFCT in the experimental eye (significant by 20-35 min. SFCT decreased by approximately 20 μm within 60 min: p < 0.01) with little change in the control eye. Small but significant changes in SFCT (5-8%) were caused by retinal defocus. SFCT increased within 10 min of exposure to 2.00 D of monocular myopic defocus, but decreased more slowly in response to 2.00 D of monocular hyperopic defocus. In our relatively small sample we could detect no difference in the magnitude of changes to SFCT caused by defocus in myopic eyes compared to emmetropic eyes. © 2015 The Authors Ophthalmic & Physiological Optics © 2015 The College of Optometrists.

  14. Management of neovascular glaucoma.

    PubMed

    Ajvazi, Halil; Goranci, Ilhami; Lutaj, Pajtim

    2013-01-01

    Neovascular glaucoma is an atrophic optic neuropathy resulting from the neovascularization of the iridocorneal angle increasing the intraocular pressure. To show the incidence of NVG in comparison to the other types of glaucoma and to compare with the relevant literature data and other referent clinics. In this study were included 116 patients with NVG, of whom 75 or 64.7% male and 41 or 35.3% female, treated from January 2003 until February 2013. Visual acuity damages from NVG, were classified as big damages with 84.7% of cases and minor damages with 15.3% of cases. Cases with heavy damages were the cases with blindness, L+P+/- up to V = 0.3 and cases with slightly damages with V = 0.4-1.0. NVG caused by PDR with 52 cases or 44.8% and CRVO with 12 cases or 10.3%. We should be focused on prevention of diabetic retinopathy which requires interdisciplinary cooperation. In cases when diabetic retinopathy is present, we have to advise patients to undergo PRP as soon as possible, since it is the only way to prevent NVG and heavy consequences.

  15. Choriovitreal ingrowth of a large choroidal vessel after scatter retinal photocoagulation.

    PubMed

    Behera, Umesh C; Modi, Rohit Ramesh

    2015-01-01

    Choriovitreal ingrowth of a large choroidal vessel is a known complication of intense focal retinal laser photocoagulation. With a standard grey-white burn in panretinal photocoagulation where the power density used is low, such an invasion is rarely reported. We came across the complication in a clinical scenario where a patient with proliferative diabetic retinopathy and associated ocular ischemic syndrome developed the neovascular ingrowth after scatter retinal photocoagulation.

  16. Clinicopathologic correlation of retinal to choroidal venous collaterals of the optic nerve head.

    PubMed

    Schatz, H; Green, W R; Talamo, J H; Hoyt, W F; Johnson, R N; McDonald, H R

    1991-08-01

    An optic nerve meningioma developed in an elderly woman and was followed for 13 years until her death. The optic nerve was initially normal. Over time it became swollen and then atrophic and developed retinal venous to choroidal venous collaterals. Five hundred serial sections were prepared through the optic nerve and for approximately 1.5 mm superiorly and inferiorly to the optic nerve to trace the course of the collaterals that were seen ophthalmoscopically and angiographically in the optic nerve head. This clinicopathologic study shows clearly that the abnormal channels are, in fact, retinal venous to choroidal venous collaterals (bypass channels). Four collaterals extended around the end of Bruch's membrane at the optic nerve head. Two more collaterals extended through the retinal pigment epithelium to become continuous with a subretinal pigment epithelial neovascular membrane, the vessels of which connected with the choroidal vessels through a defect in Bruch's membrane.

  17. Thrombospondin-2 Expression During Retinal Vascular Development and Neovascularization

    PubMed Central

    Fei, Ping; Palenski, Tammy L.; Wang, Shoujian; Gurel, Zafer; Hankenson, Kurt D.; Sorenson, Christine M.

    2015-01-01

    Abstract Purpose: To determine thrombospondin-2 (TSP2) expression and its impact on postnatal retinal vascular development and retinal neovascularization. Methods: The TSP2-deficient (TSP2−/−) mice and a line of TSP2 reporter mice were used to assess the expression of TSP2 during postnatal retinal vascular development and neovascularization. The postnatal retinal vascularization was evaluated using immunostaining of wholemount retinas prepared at different postnatal days by collagen IV staining and/or TSP2 promoter driven green fluorescent protein (GFP) expression. The organization of astrocytes was evaluated by glial fibrillary acidic protein (GFAP) staining. Retinal vascular densities were determined using trypsin digestion preparation of wholemount retinas at 3- and 6-weeks of age. Retinal neovascularization was assessed during the oxygen-induced ischemic retinopathy (OIR). Choroidal neovascularization (CNV) was assessed using laser-induced CNV. Results: Using the TSP2-GFP reporter mice, we observed significant expression of TSP2 mRNA in retinas of postnatal day 5 (P5) mice, which increased by P7 and remained high up to P42. Similar results were observed in retinal wholemount preparations, and western blotting for GFP with the highest level of GFP was observed at P21. In contrast to high level of mRNA at P42, the GFP fluorescence or protein level was dramatically downregulated. The primary retinal vasculature developed at a faster rate in TSP2−/− mice compared with TSP2+/+ mice up to P5. However, the developing retinal vasculature in TSP2+/+ mice caught up with that of TSP2−/− mice after P7. No significant differences in retinal vascular density were observed at 3- or 6-weeks of age. TSP2−/− mice also exhibited a similar sensitivity to the hyperoxia-mediated vessel obliteration and similar level of neovascularization during OIR as TSP2+/+ mice. Lack of TSP2 expression minimally affected laser-induced CNV compared with TSP2+/+ mice. Conclusions

  18. Postnatal Chick Choroids Exhibit Increased Retinaldehyde Dehydrogenase Activity During Recovery From Form Deprivation Induced Myopia

    PubMed Central

    Harper, Angelica R.; Wang, Xiang; Moiseyev, Gennadiy; Ma, Jian-Xing; Summers, Jody A.

    2016-01-01

    Purpose Increases in retinaldehyde dehydrogenase 2 (RALDH2) transcript in the chick choroid suggest that RALDH2 may be responsible for increases observed in all-trans-retinoic acid (atRA) synthesis during recovery from myopic defocus. The purpose of the present study was to examine RALDH2 protein expression, RALDH activity, and distribution of RALDH2 cells in control and recovering chick ocular tissues. Methods Myopia was induced in White Leghorn chicks for 10 days, followed by up to 15 days of unrestricted vision (recovery). Expression of RALDH isoforms in chick ocular tissues was evaluated by Western blot. Catalytic activity of RALDH was measured in choroidal cytosol fractions using an in vitro atRA synthesis assay together with HPLC quantification of synthesized atRA. Distribution of RALDH2 cells throughout the choroid was evaluated by immunohistochemistry. Results RALDH2 was expressed predominately in the chick choroid (P < 0.001) and increased after 24 hours and 4 days of recovery (76%, 74%, and 165%, respectively; P < 0.05). Activity of RALDH was detected solely in the choroid and was elevated at 3 and 7 days of recovery compared to controls (70% and 48%, respectively; P < 0.05). The number of RALDH2 immunopositive cells in recovering choroids was increased at 24 hours and 4 to 15 days of recovery (P < 0.05) and were concentrated toward the RPE side compared to controls. Conclusions The results of this study suggest that RALDH2 is the major RALDH isoform in the chick choroid and is responsible for the increased RALDH activity seen during recovery. PMID:27654415

  19. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review

    PubMed Central

    Yang, Shiqi; Zhao, Jingke; Sun, Xiaodong

    2016-01-01

    As a progressive chronic disease, age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF) plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance. PMID:27330279

  20. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review.

    PubMed

    Yang, Shiqi; Zhao, Jingke; Sun, Xiaodong

    2016-01-01

    As a progressive chronic disease, age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF) plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance.

  1. Implants for draining neovascular glaucoma.

    PubMed Central

    Molteno, A C; Van Rooyen, M M; Bartholomew, R S

    1977-01-01

    The implant design, surgical technique, and pharmacological methods of controlling bleb fibrosis, used to treat neovascular glaucoma, are described, together with the results of 14 operations performed on 12 eyes. Images PMID:843508

  2. Association of focal choroidal excavation with age-related macular degeneration.

    PubMed

    Kuroda, Yoshimasa; Tsujikawa, Akitaka; Ooto, Sotaro; Yamashiro, Kenji; Oishi, Akio; Nakanishi, Hideo; Kumagai, Kyoko; Hata, Masayuki; Arichika, Shigeta; Ellabban, Abdallah A; Yoshimura, Nagahisa

    2014-09-04

    To study the prevalence, tomographic features, and clinical characteristics of focal choroidal excavation (FCE) in eyes with exudative age-related macular degeneration (AMD). We examined 243 consecutive eyes with exudative AMD with a prototype swept-source optical coherence tomography (OCT) system. Three-dimensional images of the macular area, covering 6 × 6 mm(2), were reconstructed by segmentation of the outer surface of the retinal pigment epithelium. Three-dimensional swept-source OCT revealed 15 excavations in 12 eyes (4.9%); 10 had a single excavation and 2 had multiple excavations (2 and 3 excavations, respectively). In multiaveraged scans, unusual choroidal tissue was found beneath 5 excavations, bridging the excavation with the outer choroidal boundary. Additionally, the suprachoroidal space was observed beneath 7 excavations-the outer choroidal boundary appeared to be pulled inward by this bridging tissue. In 9 excavations, color fundus photographs showed pigmentary disturbance. Fourteen excavations (93.3%) were located within or adjacent to the choroidal neovascularization area. Compared with eyes without FCE, in eyes with FCE, the mean age was significantly higher (P = 0.040) and mean visual acuity was significantly better (P = 0.014). In addition, polypoidal lesions were observed in 8 of 12 eyes with FCE, but they appeared to have a limited effect on either the rate of FCE (P = 0.44) or the clinical characteristics of the eyes. While FCE may be partially related to the choroidal neovascularization associated with exudative AMD, other factors may also influence this association. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  3. OUTER RETINAL TUBULATION: Characteristics in Patients With Neovascular Age-Related Macular Degeneration.

    PubMed

    Iaculli, Cristiana; Barone, Antonio; Scudieri, Marilisa; Giovanna Palumbo, Maria; Delle Noci, Nicola

    2015-10-01

    To assess the incidence, characteristics, best-corrected visual acuity (BCVA), central macular thickness (CMT), and retinal sensitivity correlations in patients with and without outer retinal tubulation (ORT) affected by subfoveal choroidal neovascularization due to neovascular age-related macular degeneration. Prospective case series including 78 eyes of 78 consecutive patients with subfoveal choroidal neovascularization due to neovascular age-related macular degeneration. Baseline and follow-up visits included BCVA, intraocular pressure, ophthalmoscopic examination, CMT as measured by spectral domain optical coherence tomography, and retinal sensitivity tested with fundus-related perimetry (MP-1). Fluorescent angiography was performed at baseline. At the end of the follow-up period, the mean BCVA and CMT of patients with ORT were statistically different from those without ORT (BCVA: 0.61 ± 0.13 vs. 0.37 ± 1.59, P < 0.0001; CMT: 290 ± 26.7 vs. 215.2 ± 33.5 μm; P < 0.0001). Patients with ORT showed a decreased mean retinal sensitivity compared with patients without ORT (6.31 ± 2.5 dB vs. 9.89 ± 5.43 dB; P < 0.0001). The results of this study investigating the BCVA, CMT, and retinal sensitivity detected by MP-1 between patients with and without ORT in neovascular age-related macular degeneration suggest that these parameters are statistically different in patients with ORT; this may be due to the pathogenesis of ORT formation, secondary to retinal pigment epithelial tears or photoreceptor damage. MP-1 microperimeter is a noninvasive instrument that provides useful information to better characterize the functional aspect of ORT in patients with age-related macular degeneration.

  4. Choroidal Nevi in USAF Aviators

    DTIC Science & Technology

    1990-12-01

    choroidal neovescularizs- tion. Figure 2. Distribution of choroidal nevus in the fundus. 3 None of the aviators had any defect in visual acuity, stereopsis ...I1DT IC F-1LEw COP Y USAFSAM-TP-89-1 1 CHOROIDAL NEVI IN USAF AVIATORS AD-A233 042 Daniel L. Vandivort, Second Lieutenant, USAF Thomas J. Tredici...COVERED I Dec 1990 Interim 88/06-89/06 4. TITLE AND SUBTITLE S. FUNDING NUMBERS Choroidal Nevi in USAF Aviators PE 62202F PR 7755 6. AUTHOR(S) TA 24 WU 02

  5. Choroid plexus taurine transport.

    PubMed

    Keep, R F; Xiang, J

    1996-04-09

    The putative osmoregulatory agent, taurine, is lost from the brain during hypo-osmotic stress or ischemia, but the regulatory mechanisms involved in this loss have not been fully elucidated. In this study, we have examined taurine transport by the isolated rat choroid plexus, one element of the brain-blood interface, and examined how it may be regulated as part of brain volume regulation. Choroid plexus taurine uptake was Na- and Cl-dependent with a Vmax and Km of 6.5 +/- 0.3 pmol/mg/min and 232 +/- 33 microM. The latter is substantially greater than the normal CSF taurine concentration and this may be important in removing taurine released into the CSF during parenchymal cell swelling. Taurine uptake also appears calmodulin dependent as it was reduced by 84 and 91% in the presence of 25 microM trifluoperazine and 100 microM W-7, two calmodulin inhibitors. Taurine efflux from choroid plexus was stimulated by trifluoperazine, taurine, and hypo-osmotic stress. The latter two effects were reduced by niflumic acid, suggesting that taurine and hypo-osmotic stress act on the same pathway. The stimulation of efflux by hypo-osmotic stress decreased with time, whereas the effect of external taurine was sustained. If this efflux pathway is involved in the movement of taurine from choroid plexus to blood, these results suggest that changes in extracellular taurine may be more important than the direct effect of hypo-osmolality in the long-term loss of taurine from the brain.

  6. [Retinal detachment in various myopic refractions].

    PubMed

    Alimanović-Halilović, Emina

    2009-01-01

    The basic aim of this study was to find the group of "critical" myopic refraction with the highest occurrence of retinal detachment. In the study, 180 myopic eyes were analyzed. Upon the targeted ophthalmological anamnesis, definition of the objective refraction, and indirect binocular ophthalmoscopy, we analyzed the distribution of retinal detachment and the area affected in relation to refraction. All the eyes were divided into groups according to the refraction height. Average age of our patients ranged from 48.43 to 51.60 years with SD from 13.88 to 18.45. We did not find a statistically significant difference for a certain age. The study covered 102 (56.6%) male and 78 (43.3%) female patients. The highest occurrence of retinal detachment was found in Refraction Group from 3.5 to 7.49 dsph, total 21 (11.6%). The retinal detachments usually affected 2/4 or 3/4 of the eye fundus surface respectively.

  7. Regulation of signaling events involved in the pathophysiology of neovascular AMD.

    PubMed

    Wang, Haibo; Hartnett, M Elizabeth

    2016-01-01

    Neovascular age-related macular degeneration (AMD) is a complex disease in which an individual's genetic predisposition is affected by aging and environmental stresses, which trigger signaling pathways involving inflammation, oxidation, and/or angiogenesis in the RPE cells and choroidal endothelial cells (CECs), to lead to vision loss from choroidal neovascularization. Antiangiogenic therapies have greatly improved clinical outcomes in the last decade; however, vision improves in less than half of patients treated for neovascular AMD, and treatments remain inadequate for atrophic AMD. Many studies focus on genetic predisposition or the association of outcomes in trials of human neovascular AMD but are unable to evaluate the effects between different cell types involved in AMD and the signaling events that take place to cause pathologic biologic events. This manuscript complements other reviews in that it describes what is known generally in human AMD studies and clinical trials testing methods to inhibit vascular endothelial growth factor (VEGF inhibitors) and presents pathologic signaling events that develop in two important cell types, the RPE cells and the CECs, when stimulated by stresses or placed into conditions similar to what is currently understood to occur in neovascular AMD. This manuscript complements other reviews by discussing signaling events that are activated by cell-cell or cell-matrix interactions. These considerations are particularly important when considering growth factors, such as VEGF, which are important in physiologic and pathologic processes, or GTPases that are present but active only if GTP bound. In either case, it is essential to understand the role of signaling activation to distinguish what is pathologic from what is physiologic. Particularly important is the essential role of activated Rac1 in CEC transmigration of the RPE monolayer, an important step in blindness associated with neovascular AMD. Other concepts discussed include

  8. Synthesis and Biological Evaluation of Novel Homoisoflavonoids for Retinal Neovascularization

    PubMed Central

    Lee, Hyungjun; Sulaiman, Rania S.; An, Hongchan; Magaña, Carlos; Shadmand, Mehdi; Vayl, Alexandra; Rajashekhar, Gangaraju; Kim, Eun-Yeong; Suh, Young-Ger; Lee, Kiho

    2016-01-01

    Eye diseases characterized by excessive angiogenesis such as wet age-related macular degeneration, proliferative diabetic retinopathy, and retinopathy of prematurity are major causes of blindness. Cremastranone is an anti-angiogenic, naturally occurring homoisoflavanone with efficacy in retinal and choroidal neovascularization models and antiproliferative selectivity for endothelial cells over other cell types. We undertook a cell-based structure-activity relationship study to develop more potent cremastranone analogs, with improved antiproliferative selectivity for retinal endothelial cells. Phenylalanyl-incorporated homoisoflavonoids showed improved activity and remarkable selectivity for retinal microvascular endothelial cells. A lead compound inhibited angiogenesis in vitro without inducing apoptosis, and had efficacy in the oxygen-induced retinopathy model in vivo. PMID:26035340

  9. Effects of a human VEGF antibody (Bevacizumab) on deprivation myopia and choroidal thickness in the chicken.

    PubMed

    Mathis, Ute; Ziemssen, Focke; Schaeffel, Frank

    2014-10-01

    Vascular endothelial growth factor (VEGF) is a dimeric glycoprotein which is responsible for neovascularization and fenestrations of the choriocapillaris. In neovascular maculopathies secondary to age-related degeneration (nAMD) or pathologic myopia (PM-CNV), its inhibition by humanized antibodies is currently the most successful therapy. The choroid has an important role in maintaining retinal health and its thickness declines with age and with myopia. Since choroidal thickness depends on its perfusion rate, one would expect that anti-VEGF agents can also change choroidal thickness. We have tested the hypothesis in the chicken model, using a humanized antibody, Bevacizumab, and also studied the distribution of VEGF-A in the chicken fundal layers by immunohistochemical techniques. Even though it was raised against human VEGF, Bevacizumab had several long lasting effects in the chicken eye (1) after a single unilateral intravitreal injection of 0.5 mg, it partially suppressed the development of deprivation myopia, similarly in both eyes, (2) it completely suppressed choroidal thickening that normally occurs when eyes recover from induced myopia over a time period of about 10 days, (3) it had little effect on the choroidal thickness in eyes that had normal visual experience, (4) VEGF-A was absent in sclera, but highly expressed in the walls of choroidal blood vessels and presumed nerve fiber bundles, as well as in retinal photoreceptors and cells of the inner and outer nuclear layer. One day after the injection of Bevacizumab, the immunoreactivity against VEGF-A had largely disappeared. In conclusion, Bevacizumab is similary effective in human and chicken tissue, has similar time constants (few days), has almost symmetrical effects on myopia in both eyes even after monocular application, and fully suppresses choroidal thickening that normally occurs during recovery from deprivation myopia. The mechanisms by which Bevacizumab acts on the choroidal thickness are

  10. MACULAR ATROPHY AND MACULAR MORPHOLOGY IN AFLIBERCEPT-TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

    PubMed

    Kuroda, Yoshimasa; Yamashiro, Kenji; Ooto, Sotaro; Tamura, Hiroshi; Oishi, Akio; Nakanishi, Hideo; Miyata, Manabu; Hata, Masayuki; Takahashi, Ayako; Wakazono, Tomotaka; Yoshimura, Nagahisa; Tsujikawa, Akitaka

    2017-07-04

    To investigate the incidence and predictors of macular atrophy during treatment with aflibercept for neovascular age-related macular degeneration in Japanese patients. This study included patients with treatment-naive subfoveal neovascular age-related macular degeneration treated from December 2012 through January 2015. Patients were treated with bi-monthly aflibercept injections after 3 monthly loading injections for the first year. Diagnosis of retinal pigment epithelial atrophy was made based on color fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence. Baseline characteristics and morphological features were analyzed for their association with the development of macular atrophy. This study included 123 eyes that had no baseline macular atrophy and treated with aflibercept injections for 12 months. Thirteen eyes (10.6%) developed new macular atrophy at 12 months. Logistic regression analysis showed that the presence of intraretinal fluid and thinner subfoveal choroidal thickness at baseline were associated with the development of macular atrophy after aflibercept treatment. Macular atrophy developed in about 10% of eyes with neovascular age-related macular degeneration during 12 months of treatment with a fixed regimen of aflibercept. Intraretinal fluid and subfoveal choroidal thickness seem to be predictors for development of macular atrophy after anti-vascular endothelial growth factor (VEGF) therapy.

  11. Pressureless Orbital Decompression for Myopic Proptosis.

    PubMed

    Rajak, Saul N; McGovern, Richard A; Selva, Dinesh

    2017-01-01

    Orbital decompression surgery increases the orbital volume. It has rarely been used for proptosis of the large highly myopic globe. However, external decompression surgery carries significant risks because of the large thin-walled globe. The authors report the first use of endoscopic medial wall orbital decompression surgery in this setting to obviate the risk of globe pressure.Endoscopic medial wall decompression brought about a 4 mm reduction of proptosis, correction of exotropia and elimination of retrobulbar ache providing good symmetry with the fellow eye.Endoscopic medial wall orbital decompression can be very effective for correcting the proptosis of high myopia and minimizes the risk of damage to the very large, thin-walled globe.

  12. Photochemical Thrombosis Of Retinal And Choroidal Vessels Using Rose Bengal

    NASA Astrophysics Data System (ADS)

    Lewis, Mary Lou; Winward, Kirk; Watson, Brant D.; Hernandez, Eleut

    1989-09-01

    Rose bengal is an effective photosensitizing agent which interacts with argon green light to induce photochemical thrombosis of irradiated vessels. We used focal, low energy irradiation to occlude retinal and choroidal vessels in both albino and pigmented rabbits. Immediately after intravenous injection of rose bengal at concentrations of 10 and 20 mg/kg, irradiation was performed via a slit lamp-delivered argon green laser (514.5 nm) with the aid of fundus contact lens. In 11 eyes, arteries were treated with 50-100 interrupted bursts of 75u spot size at 0.2 sec and 40-100 mW (9 choroidal vessels, serous elevation of the retina, and disc neovascularization. In eight eyes choroidal vessels were irradiated with 10-20 mW, 15-60 sec, 500u spot size (31 choroidal vessels. There was minimal damage to surrounding tissue. Control eyes in all three groups irradiated utilizing the same parameters, but without rose bengal, demonstrated no evidence of thermal injury.

  13. Enhanced visualization of choroidal vessels using ultrahigh resolution ophthalmic OCT at 1050 nm.

    PubMed

    Povazay, B; Bizheva, K; Hermann, B; Unterhuber, A; Sattmann, H; Fercher, A; Drexler, W; Schubert, C; Ahnelt, P; Mei, M; Holzwarth, R; Wadsworth, W; Knight, J; Russell, P St J

    2003-08-25

    In this article the ability of ultrahigh resolution ophthalmic optical coherence tomography (OCT) to image small choroidal blood vessels below the highly reflective and absorbing retinal pigment epithelium is demonstrated for the first time. A new light source (lambdac= 1050 nm, Deltalambda = 165 nm, Pout= 10 mW), based on a photonic crystal fiber pumped by a compact, self-starting Ti:Al2O3 laser has therefore been developed. Ex-vivo ultrahigh resolution OCT images of freshly excised pig retinas acquired with this light source demonstrate enhanced penetration into the choroid and better visualization of choroidal vessels as compared to tomograms acquired with a state-of-the art Ti:Al2O3 laser (Femtolasers Compact Pro, lc= 780 nm, Deltalambda= 160 nm, Pout= 400 mW), normally used in clinical studies for in vivo ultrahigh resolution ophthalmic OCT imaging. These results were also compared with retinal tomograms acquired with a novel, spectrally broadened fiber laser (MenloSystems, lambdac= 1350 nm, Deltalambda= 470 nm, Pout = 4 mW) permitting even greater penetration in the choroid. Due to high water absorption at longer wavelengths retinal OCT imaging at ~1300 nm may find applications in animal ophthalmic studies. Detection and follow-up of choroidal neovascularization improves early diagnosis of many retinal pathologies, e.g. age-related macular degeneration or diabetic retinopathy and can aid development of novel therapy approaches.

  14. Choroidal Structure in Children with Anisohypermetropic Amblyopia Determined by Binarization of Optical Coherence Tomographic Images.

    PubMed

    Nishi, Tomo; Ueda, Tetsuo; Mizusawa, Yuutaro; Shinomiya, Kayo; Semba, Kentaro; Mitamura, Yoshinori; Sonoda, Shozo; Uchino, Eisuke; Sakamoto, Taiji; Ogata, Nahoko

    2016-01-01

    To compare the choroidal structure of the subfoveal area in the eyes of children with anisohypermetropic amblyopia to that of the fellow eyes and to age-matched controls using a binarization method of the images obtained by enhanced depth imaging optical coherence tomography (EDI-OCT). This study was performed at Nara Medical University Hospital, Tokushima University Hospital, and Kagoshima University Hospital, Japan. Forty amblyopic eyes with anisohypermetropic amblyopia and their fellow eyes (5.9 ± 2.1 years, mean ± standard deviation), and 103 age-matched controls (6.7 ± 2.4 years) were studied. The control eyes were divided into myopic, emmetropic, and hyperopic eyes. The total choroidal area, luminal area and stromal area of the subfoveal choroid were measured by the binarization method. The luminal/stromal ratio and the axial length of the amblyopic eyes were compared to that of the control eyes. The total choroidal area in the amblyopic eyes was significantly larger than that of the fellow eyes (P = 0.005). The luminal/stromal ratio was significantly larger in the amblyopic eyes than that of the fellow eyes (P<0.001) and the control hyperopic eyes (P<0.001). There was a significant negative correlation between the luminal/stromal ratio and the axial length in the control eyes (r = -0.30, P = 0.001), but no significant correlation was found in the amblyopic eyes. The choroidal structure of the amblyopic eyes was different from that of the fellow and the control hyperopic eyes. The choroidal changes are related to amblyopia.

  15. Choroidal Structure in Children with Anisohypermetropic Amblyopia Determined by Binarization of Optical Coherence Tomographic Images

    PubMed Central

    Nishi, Tomo; Ueda, Tetsuo; Mizusawa, Yuutaro; Shinomiya, Kayo; Semba, Kentaro; Mitamura, Yoshinori; Sonoda, Shozo; Uchino, Eisuke; Sakamoto, Taiji; Ogata, Nahoko

    2016-01-01

    Purpose To compare the choroidal structure of the subfoveal area in the eyes of children with anisohypermetropic amblyopia to that of the fellow eyes and to age-matched controls using a binarization method of the images obtained by enhanced depth imaging optical coherence tomography (EDI-OCT). Methods This study was performed at Nara Medical University Hospital, Tokushima University Hospital, and Kagoshima University Hospital, Japan. Forty amblyopic eyes with anisohypermetropic amblyopia and their fellow eyes (5.9 ± 2.1 years, mean ± standard deviation), and 103 age-matched controls (6.7 ± 2.4 years) were studied. The control eyes were divided into myopic, emmetropic, and hyperopic eyes. The total choroidal area, luminal area and stromal area of the subfoveal choroid were measured by the binarization method. The luminal/stromal ratio and the axial length of the amblyopic eyes were compared to that of the control eyes. Results The total choroidal area in the amblyopic eyes was significantly larger than that of the fellow eyes (P = 0.005). The luminal/stromal ratio was significantly larger in the amblyopic eyes than that of the fellow eyes (P<0.001) and the control hyperopic eyes (P<0.001). There was a significant negative correlation between the luminal/stromal ratio and the axial length in the control eyes (r = -0.30, P = 0.001), but no significant correlation was found in the amblyopic eyes. Conclusions The choroidal structure of the amblyopic eyes was different from that of the fellow and the control hyperopic eyes. The choroidal changes are related to amblyopia. PMID:27736947

  16. Breaking barriers: insight into the pathogenesis of neovascular age-related macular degeneration

    PubMed Central

    Wang, Haibo; Wittchen, Erika S; Hartnett, M Elizabeth

    2011-01-01

    Neovascular age-related macular degeneration (AMD) is a leading cause of central visual acuity loss in a growing segment of the population, those over the age of 60 years. Treatment has improved over the last decade, with the availability of agents that inhibit the bioactivity of vascular endothelial growth factor (VEGF), but it is still limited, because of tachyphylaxis and potential risk and toxicity of anti-VEGF agents. The authors have sought to understand the mechanisms of choroidal endothelial cell (CEC) activation and transmigration of the retinal pigment epithelium (RPE) and of RPE barrier dysfunction, events preceding vision-threatening neovascular AMD. The authors developed physiologically relevant human RPE and CEC coculture and transmigration models that have been important in helping to understand causes of events in human neovascular AMD. The authors can control for interactions between these cells and can separately assess activation of signaling pathways in each cell type relevant during CEC transmigration. Using these models, it was found that VEGF, particularly the cell-associated VEGF splice variant VEGF189, accounts for about 40% of CEC transmigration across the RPE. This percentage is in the range of similar reports following clinical inhibition of VEGF in neovascular AMD. RPE VEGF189 working through CEC VEGF receptor 2 activates the small guanosine triphosphatase (GTPase) of the Rho family, Rac1, in CECs, which in turn facilitates CEC transmigration. Conversely, inhibition of Rac1 activity prevents CEC transmigration. Once activated, Rac1 aggregates with subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, resulting in the generation of reactive oxygen species. Activated NADPH oxidase increases choroidal neovascularization in animal models of laser-induced injury. Rac1 is also downstream of the eotaxin-CCR3 pathway, another pathway important in human neovascular AMD. Studies also suggest that active Ras-related protein 1

  17. Distribution and Quantification of Choroidal Macrophages in Human Eyes With Age-Related Macular Degeneration

    PubMed Central

    McLeod, D. Scott; Bhutto, Imran; Edwards, Malia M.; Silver, Rachel E.; Seddon, Johanna M.; Lutty, Gerard A.

    2016-01-01

    Purpose Increasing evidence suggests a role for macrophages in the pathogenesis of age-related macular degeneration (AMD). This study examined choroidal macrophages and their activation in postmortem eyes from subjects with and without AMD. Methods Choroids were incubated with anti-ionized calcium-binding adapter molecule 1 (anti-IBA1) to label macrophages, anti-human leukocyte antigen-antigen D-related (anti-HLA-DR) as a macrophage activation marker, and Ulex europaeus agglutinin lectin to label blood vessels. Whole mounts were imaged using confocal microscopy. IBA1- and HLA-DR–positive (activated) cells were counted in submacula, paramacula, and nonmacula, and cell volume and sphericity were determined using computer-assisted image analysis. Results In aged control eyes, the mean number of submacular IBA1+ and HLA-DR+ macrophages was 433/mm2 and 152/mm2, respectively. In early AMD eyes, there was a significant increase in IBA1+ and HLA-DR+ cells in submacula compared to those in controls (P = 0.0015 and P = 0.008, respectively). In eyes with neovascular AMD, there were significantly more HLA-DR+ cells associated with submacular choroidal neovascularization (P = 0.001). Mean cell volume was significantly lower (P ≤ 0.02), and sphericity was significantly higher (P ≤ 0.005) in all AMD groups compared to controls. Conclusions The average number of IBA1+ macrophages in submacular and paramacular choroid was significantly higher in early/intermediate AMD compared to that in aged controls. HLA-DR+ submacular macrophages were significantly increased in all stages of AMD, and they were significantly more round and smaller in size in the submacular AMD choroid, suggesting their activation. These findings support the concept that AMD is an inflammatory disease. PMID:27802514

  18. Distribution and Quantification of Choroidal Macrophages in Human Eyes With Age-Related Macular Degeneration.

    PubMed

    McLeod, D Scott; Bhutto, Imran; Edwards, Malia M; Silver, Rachel E; Seddon, Johanna M; Lutty, Gerard A

    2016-11-01

    Increasing evidence suggests a role for macrophages in the pathogenesis of age-related macular degeneration (AMD). This study examined choroidal macrophages and their activation in postmortem eyes from subjects with and without AMD. Choroids were incubated with anti-ionized calcium-binding adapter molecule 1 (anti-IBA1) to label macrophages, anti-human leukocyte antigen-antigen D-related (anti-HLA-DR) as a macrophage activation marker, and Ulex europaeus agglutinin lectin to label blood vessels. Whole mounts were imaged using confocal microscopy. IBA1- and HLA-DR-positive (activated) cells were counted in submacula, paramacula, and nonmacula, and cell volume and sphericity were determined using computer-assisted image analysis. In aged control eyes, the mean number of submacular IBA1+ and HLA-DR+ macrophages was 433/mm2 and 152/mm2, respectively. In early AMD eyes, there was a significant increase in IBA1+ and HLA-DR+ cells in submacula compared to those in controls (P = 0.0015 and P = 0.008, respectively). In eyes with neovascular AMD, there were significantly more HLA-DR+ cells associated with submacular choroidal neovascularization (P = 0.001). Mean cell volume was significantly lower (P ≤ 0.02), and sphericity was significantly higher (P ≤ 0.005) in all AMD groups compared to controls. The average number of IBA1+ macrophages in submacular and paramacular choroid was significantly higher in early/intermediate AMD compared to that in aged controls. HLA-DR+ submacular macrophages were significantly increased in all stages of AMD, and they were significantly more round and smaller in size in the submacular AMD choroid, suggesting their activation. These findings support the concept that AMD is an inflammatory disease.

  19. Delayed Patchy Choroidal Filling in the Comparison of Age-related Macular Degeneration Treatment Trials (CATT)

    PubMed Central

    Gewaily, Dina Y.; Grunwald, Juan E.; Pistilli, Maxwell; Ying, Gui-Shuang; Maguire, Maureen G.; Daniel, Ebenezer; Ostroff, Candace P.; Fine, Stuart L.

    2015-01-01

    Purpose To determine the relationship between delayed patchy choroidal filling and morphologic and functional outcomes among eyes treated with ranibizumab or bevacizumab. Design Cohort study. Methods Comparison of Age-related Macular Degeneration Treatment Trials participants were randomly assigned to ranibizumab or bevacizumab on a monthly or as needed schedule. Presence of delayed patchy choroidal filling and morphologic and functional outcomes were evaluated among eyes with gradeable fluorescein angiography at baseline (N=973) and at one year (N=860) eyes. Results Delayed filling was present in 75 (7.7%) of 973 eyes at baseline. Eyes with incident delayed filling at one year (23 (2.9%) of 798) showed a mean decrease of 1.7 letters in visual acuity, whereas eyes without incident delayed filling had a mean improvement of 8.1 letters (Δ=−9.8 [−15.8, −3.9], p<0.01). Eyes with incident delayed filling had a larger increase in mean total lesion area of choroidal neovascularization (3.00 mm2) than eyes without incident delayed filling (0.56 mm2, Δ=2.4 [0.4, 4.4], p=0.02). The proportion with incident delayed filling at one year was similar among eyes treated with ranibizumab (10 (2.4%) of 413) or bevacizumab (13 (3.3%) of 385, p=0.53) and among eyes treated monthly (12 (3.1%) of 388) or as needed (11 (2.7%) of 410, p=0.83). Conclusions Delayed patchy choroidal filling was uncommon at baseline. Although only a small percentage of eyes developed delayed filling during the first year of anti-vascular endothelial growth factor treatment, these eyes had worse visual acuity and a larger increase in total lesion area of choroidal neovascularization. PMID:24949820

  20. Intravitreal dobesilate in the treatment of choroidal neovascularisation associated with age-related macular degeneration: report of two cases

    PubMed Central

    Cuevas, Pedro; Outeiriño, Luis; Azanza, Carlos; Giménez-Gallego, Guillermo

    2012-01-01

    This case report presents the effectiveness of intravitreal administration of dobesilate, a synthetic fibroblast growth factor inhibitor, in two patients showing neovascular age-related macular degeneration of the classic, and of the occult choroidal neovascularisation types, respectively. Our study demonstrates that the treatment induces the regression of both forms of this pathology, as assessed by spectral optical coherence tomography. Improvement of the lesions was accompanied of visual acuity improvement. PMID:22948997

  1. Intravitreal dobesilate in the treatment of choroidal neovascularisation associated with age-related macular degeneration: report of two cases.

    PubMed

    Cuevas, Pedro; Outeiriño, Luis; Azanza, Carlos; Giménez-Gallego, Guillermo

    2012-09-03

    This case report presents the effectiveness of intravitreal administration of dobesilate, a synthetic fibroblast growth factor inhibitor, in two patients showing neovascular age-related macular degeneration of the classic, and of the occult choroidal neovascularisation types, respectively. Our study demonstrates that the treatment induces the regression of both forms of this pathology, as assessed by spectral optical coherence tomography. Improvement of the lesions was accompanied of visual acuity improvement.

  2. Choroidal nevus: a review of prevalence, features, genetics, risks, and outcomes.

    PubMed

    Chien, Jason L; Sioufi, Kareem; Surakiatchanukul, Thamolwan; Shields, Jerry A; Shields, Carol L

    2017-05-01

    To review the prevalence, clinical features, imaging findings, cytogenetics, and risks and outcomes of choroidal nevus. Choroidal nevus is a benign melanocytic tumor, often discovered incidentally on ophthalmic examination. This lesion is generally well circumscribed and pigmented. The prevalence of choroidal nevus in postequatorial region in United States adults (≥40 years old) is approximately 5%. Choroidal nevus is associated with higher lifetime unopposed estrogen and greater BMI. In population-based evaluation, the mean nevus basal dimension is approximately 1.25 mm. Giant nevus (basal dimension ≥10 mm) carries greater risk for malignant transformation. Imaging modalities for evaluation of choroidal nevus include ultrasonography, fundus autofluorescence, and optical coherence tomography (OCT). Fluorescein angiography is occasionally employed to detect multifocal pinpoint leaks or choroidal neovascular membrane. Recently, OCT angiography demonstrated nevus with minimal overlying macular microvascular changes compared with melanoma. Cytogenetically, GNA11 or GNAQ mutations have been documented in uveal melanoma in 83% and in some cutaneous nevus subtypes. Further mutations lead to the development of melanoma at a rate of one of 8845 cases. Risk factors for transformation of nevus into melanoma are recalled by the mnemonic 'To find small ocular melanoma using helpful hints daily' representing thickness (T) more than 2 mm, subretinal fluid (F), symptoms (S) of flashes/floaters/blurred vision, orange (O) lipofuscin pigment, margin (M) less than 3 mm from optic disk, ultrasonographic hollowness (UH), halo (H) absence, and drusen (D) absence. The presence of three or more risk factors implies more than 50% chance for transformation to melanoma within 5 years. A new, online ocular oncology reading center can help judge nevus risk. Choroidal nevus is a common intraocular lesion, found predominantly in Whites. This mass carries a small risk (<1%) for

  3. Peripapillary choroidal thickness in Chinese children using enhanced depth imaging optical coherence tomography

    PubMed Central

    Wu, Xi-Shi; Shen, Li-Jun; Chen, Ru-Ru; Lyu, Zhe

    2016-01-01

    AIM To evaluate the peripapillary choroidal thickness (PPCT) in Chinese children, and to analyze the influencing factors. METHODS PPCT was measured with enhanced depth imaging optical coherence tomography (EDI-OCT) in 70 children (53 myopes and 17 non-myopes) aged 7 to 18y, with spherical equivalent refractive errors between 0.50 and −5.87 diopters (D). Peripapillary choroidal imaging was performed using circular scans of a diameter of 3.4 mm around the optic disc. PPCT was measured by EDI-OCT in six sectors: nasal (N), superonasal (SN), superotemporal (ST), temporal (T), inferotemporal (IT) and inferonasal (IN), as well as global RNFL thickness (G). RESULTS The mean global PPCT was 165.49±33.76 µm. The temporal, inferonasal, inferotemporal PPCT were significantly thinner than the nasal, superonasal, superotemporal segments PPCT were significantly thinner in the myopic group at temporal, superotemporal and inferotemporal segments. The axial length was significantly associated with the average global (β=−0.419, P=0.014), superonasal (β=−2.009, P=0.049) and inferonasal (β= −2.000, P=0.049) PPCT. The other factors (gender, age, SE) were not significantly associated with PPCT. CONCLUSION PPCT was thinner in the myopic group at temporal, superotemporal and inferotemporal segments. The axial length was found to be negatively correlated to PPCT. We need more further studies about the relationship between PPCT and myopia. PMID:27803863

  4. The HIF-1 antagonist acriflavine: visualization in retina and suppression of ocular neovascularization.

    PubMed

    Zeng, Mingbing; Shen, Jikui; Liu, Yuanyuan; Lu, Lucy Yang; Ding, Kun; Fortmann, Seth D; Khan, Mahmood; Wang, Jiangxia; Hackett, Sean F; Semenza, Gregg L; Campochiaro, Peter A

    2017-04-01

    Acriflavine, a fluorescent drug previously used for bacterial and trypanosomal infections, reduces hypoxia-inducible factor-1 (HIF-1) and HIF-2 transcriptional activity. In mice with oxygen-induced ischemic retinopathy, intraocular or intraperitoneal injections of acriflavine caused dose-dependent suppression of retinal neovascularization (NV) and significantly reduced expression of HIF-1-responsive genes. Intraocular injection of 100 ng caused inner retina fluorescence within 1 h that was seen throughout the entire retina between 1 and 5 days, and at 7 days after injection, strongly suppressed choroidal NV at Bruch's membrane rupture sites. After suprachoroidal injection of 300 ng in rats, there was retinal fluorescence in the quadrant of the injection at 1 h that spread throughout the entire retina and choroid by 1 day, was detectable for 5 days, and dramatically reduced choroidal NV 14 days after rupture of Bruch's membrane. After topical administration of acriflavine in mice, fluorescence was seen in the retina and retinal pigmented epithelium within 5 min and was detectable for 6-12 h. Administration of 0.5% drops to the cornea twice a day significantly reduced choroidal NV in mice. Electroretinographic b-wave amplitudes were normal 7 days after intravitreous injection of 100 ng of acriflavine in mice, showed mild threshold reductions at highest stimulus intensities after injection of 250 ng, and more extensive changes after injection of 500 ng. These data provide additional evidence for an important role for HIF-1 in retinal and choroidal NV and suggest that acriflavine can target HIF-1 through a variety of modes of administration and has good potential to provide a novel therapy for retinal and choroidal vascular diseases.

  5. Choroid plexus cysts and aneuploidy.

    PubMed Central

    Peleg, D; Yankowitz, J

    1998-01-01

    The association of choroid plexus cysts with fetal aneuploidy, particularly trisomy 18, was first noted in 1986. Through the years there have been numerous reports on this subject, but no consensus has been reached with regard to chromosomal risk. In this review, we attempt to summarise published reports on second trimester choroid plexus cysts, with an emphasis on the strengths and weaknesses of each report. Based on these reports, additional malformations are a significant risk factor for aneuploidy and an indication for determination of fetal karyotype. The management of isolated choroid plexus cysts remains controversial. PMID:9678699

  6. Growing Hemorrhagic Choroidal Fissure Cyst

    PubMed Central

    Gelal, Fazıl; Gurkan, Gokhan; Feran, Hamit

    2016-01-01

    Choroidal fissure cysts are often incidentally discovered. They are usually asymptomatic. The authors report a case of growing and hemorrhagic choroidal fissure cyst which was treated surgically. A 22-year-old female presented with headache. Cranial MRI showed a left-sided choroidal fissure cyst. Follow-up MRI showed that the size of the cyst had increased gradually. Twenty months later, the patient was admitted to our emergency department with severe headache. MRI and CT showed an intracystic hematoma. Although such cysts usually have a benign course without symptoms and progression, they may rarely present with intracystic hemorrhage, enlargement of the cyst and increasing symptomatology. PMID:26962426

  7. RETICULAR PSEUDODRUSEN ARE NOT A PREDICTIVE FACTOR FOR THE 1-YEAR RESPONSE TO INTRAVITREAL RANIBIZUMAB IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

    PubMed

    Nghiem-Buffet, Sylvia; Giocanti-Auregan, Audrey; Jung, Camille; Dubois, Lise; Dourmad, Pauline; Galbadon, Lea; Fajnkuchen, Franck; Quentel, Gabriel; Cohen, Salomon Y

    2017-01-01

    To investigate reticular pseudodrusen (RPD) as a potential baseline factor predictive of a poor 1-year response to intravitreal ranibizumab in eyes with neovascular age-related macular degeneration. Retrospective, monocentric case series including 98 consecutive naive neovascular age-related macular degeneration patients. Presence of RPD was assessed by two graders based on color, blue-light, fundus autofluorescence pictures, and spectral-domain optical coherence tomography. A correlation between the presence of RPD and the visual change was investigated. Other baseline characteristics studied in a monovariate and multivariate analysis were the following: age, gender, affected side, loading dose, type of neovascularization, presence of retinal pigment epithelial detachment >250 μm, subretinal or intraretinal fluid, blood over >50% of the lesion, and subfoveal choroidal thickness. The presence of RPD was not associated with a visual change (P = 0.96), but with a thin subfoveal choroidal thickness at baseline (P < 0.0001). The monovariate analysis showed that the presence of blood at baseline was associated with visual gain (P = 0.007). The presence of RPD at baseline was not identified as a factor associated with a poor 1-year response to ranibizumab in eyes with neovascular age-related macular degeneration. Studies with a longer follow-up may be needed to assess the impact of RPD on the visual prognosis of eyes with neovascular age-related macular degeneration.

  8. Analysis of Morphological Features and Vascular Layers of Choroid in Diabetic Retinopathy Using Spectral-Domain Optical Coherence Tomography

    PubMed Central

    Adhi, Mehreen; Brewer, Erika; Waheed, Nadia K; Duker, Jay S.

    2014-01-01

    Importance Diabetic retinopathy (DR) is characterized by microaneurysms, capillary nonperfusion, and ischemia within the retina, ultimately leading to neovascularization and/or macular edema. Evidence suggests that choroidal angiopathy may coexist with retinal vascular damage. Recent advances in spectral-domain optical coherence tomography (SD-OCT) permit an efficient visualization of the choroid. Objective To analyze the morphological features and vascular layers of the choroid in patients with DR using SD-OCT. Design A cross-sectional retrospective review identified patients with DR and healthy (control) subjects who underwent 1-line raster scanning from February 1, 2010, through June 30, 2012. Patients were classified into the following 3 groups: nonproliferative DR without macular edema (9 eyes), proliferative DR without macular edema (PDR) (10 eyes), and diabetic macular edema (DME) (14 eyes). Two independent raters experienced in analyzing OCT images evaluated the morphological features and vasculature of the choroid. Setting New England Eye Center. Participants Thirty-three eyes of 33 patients with DR and 24 eyes of 24 controls. Exposure Diabetic retinopathy. Main outcome and measure Choroidal morphological features and vasculature analysis. Results The choroidoscleral interface had an irregular contour in 8 of 9 eyes with nonproliferative DR (89%), 9 of 10 eyes with PDR (90%), and 13 of 14 eyes with DME (93%) compared with 0 of 24 controls. The thickest point of the choroid was displaced from under the fovea, and focal choroidal thinning was observed in eyes with DR. Mean subfoveal choroidal thickness and mean subfoveal medium choroidal vessel layer and choriocapillaris layer thickness were significantly reduced in eyes with PDR (P < .05) and DME (P < .05) compared with controls. Conclusions and relevance Choroidal morphological features are altered in patients with moderate to severe DR. The subfoveal choroidal thickness and the subfoveal medium choroidal

  9. Analysis of morphological features and vascular layers of choroid in diabetic retinopathy using spectral-domain optical coherence tomography.

    PubMed

    Adhi, Mehreen; Brewer, Erika; Waheed, Nadia K; Duker, Jay S

    2013-10-01

    Diabetic retinopathy (DR) is characterized by microaneurysms, capillary nonperfusion, and ischemia within the retina, ultimately leading to neovascularization and/or macular edema. Evidence suggests that choroidal angiopathy may coexist with retinal vascular damage. Recent advances in spectral-domain optical coherence tomography (SD-OCT) permit an efficient visualization of the choroid. To analyze the morphological features and vascular layers of the choroid in patients with DR using SD-OCT. A cross-sectional retrospective review identified patients with DR and healthy (control) subjects who underwent 1-line raster scanning from February 1, 2010, through June 30, 2012. Patients were classified into the following 3 groups: nonproliferative DR without macular edema (9 eyes), proliferative DR without macular edema (PDR) (10 eyes), and diabetic macular edema (DME) (14 eyes). Two independent raters experienced in analyzing OCT images evaluated the morphological features and vasculature of the choroid. New England Eye Center. Thirty-three eyes of 33 patients with DR and 24 eyes of 24 controls. Diabetic retinopathy. Choroidal morphological features and vasculature analysis. The choroidoscleral interface had an irregular contour in 8 of 9 eyes with nonproliferative DR (89%), 9 of 10 eyes with PDR (90%), and 13 of 14 eyes with DME (93%) compared with 0 of 24 controls. The thickest point of the choroid was displaced from under the fovea, and focal choroidal thinning was observed in eyes with DR. Mean subfoveal choroidal thickness and mean subfoveal medium choroidal vessel layer and choriocapillaris layer thickness were significantly reduced in eyes with PDR (P < .05) and DME (P < .05) compared with controls. Choroidal morphological features are altered in patients with moderate to severe DR. The subfoveal choroidal thickness and the subfoveal medium choroidal vessel layer and choriocapillaris layer thicknesses are significantly reduced in patients with PDR and DME. To our

  10. A value-based medicine analysis of ranibizumab for the treatment of subfoveal neovascular macular degeneration.

    PubMed

    Brown, Melissa M; Brown, Gary C; Brown, Heidi C; Peet, Jonathan

    2008-06-01

    To assess the conferred value and average cost-utility (cost-effectiveness) for intravitreal ranibizumab used to treat occult/minimally classic subfoveal choroidal neovascularization associated with age-related macular degeneration (AMD). Value-based medicine cost-utility analysis. MARINA (Minimally Classic/Occult Trial of the Anti-Vascular Endothelial Growth Factor Antibody Ranibizumab in the Treatment of Neovascular AMD) Study patients utilizing published primary data. Reference case, third-party insurer perspective, cost-utility analysis using 2006 United States dollars. Conferred value in the forms of (1) quality-adjusted life-years (QALYs) and (2) percent improvement in health-related quality of life. Cost-utility is expressed in terms of dollars expended per QALY gained. All outcomes are discounted at a 3% annual rate, as recommended by the Panel on Cost-effectiveness in Health and Medicine. Data are presented for the second-eye model, first-eye model, and combined model. Twenty-two intravitreal injections of 0.5 mg of ranibizumab administered over a 2-year period confer 1.039 QALYs, or a 15.8% improvement in quality of life for the 12-year period of the second-eye model reference case of occult/minimally classic age-related subfoveal choroidal neovascularization. The reference case treatment cost is $52652, and the cost-utility for the second-eye model is $50691/QALY. The quality-of-life gain from the first-eye model is 6.4% and the cost-utility is $123887, whereas the most clinically simulating combined model yields a quality-of-life gain of 10.4% and cost-utility of $74169. By conventional standards and the most commonly used second-eye and combined models, intravitreal ranibizumab administered for occult/minimally classic subfoveal choroidal neovascularization is a cost-effective therapy. Ranibizumab treatment confers considerably greater value than other neovascular macular degeneration pharmaceutical therapies that have been studied in randomized

  11. Radiotherapy for choroidal melanoma. An 18-year experience with radon

    SciTech Connect

    Davidorf, F.H.; Pajka, J.T.; Makley, T.A. Jr.; Kartha, M.K.

    1987-03-01

    Twenty-three patients were treated with radon therapy for choroidal melanoma at the Ohio State University Hospitals, Columbus, between 1968 and 1976. We present an 18-year experience, including follow-up of at least eight years, in all those receiving therapy. Three patients (13%) died of metastatic disease. Four patients (17.4%) died of other causes. Sixteen patients (69.6%) were alive, with no signs of metastatic disease. Eight patients subsequently required enucleation due to inadequate tumor response. Of the 15 patients who demonstrated successful tumor destruction and retained their eyes, 13 (86.7%) developed substantial irradiation-induced retinopathy, including hard exudates, telangiectasias, neovascularization, microaneurysms, intraretinal and vitreous hemorrhages, secondary glaucoma, and irradiation-induced cataract. Our long-term results indicate a high incidence of both vascular complications and decreased visual acuity.

  12. Sympathetic ophthalmia complicating helium ion irradiation of a choroidal melanoma

    SciTech Connect

    Fries, P.D.; Char, D.H.; Crawford, J.B.; Waterhouse, W.

    1987-11-01

    Sympathetic ophthalmia was diagnosed 49 months after helium ion irradiation of a left choroidal melanoma. The patient maintained good vision until 18 months after therapy, when she developed neovascular glaucoma. This complication required multiple therapeutic procedures, including topical anti-inflammatory and antiglaucomatous drops, 360 degrees peripheral panretinal cryoblation, and a single 180 degrees application of inferior cyclocryotherapy over a 2 1/2-year period. Four weeks after the cyclocryotherapy, inflammation was noted in both eyes, and, one month later, enucleation of the left sympathogenic eye was performed. Serial histopathologic sections showed a full-thickness, fibrovascular, scleral scar and tantalum marker ring suture without uveal incarceration. Penetrating surgical trauma, a uveal melanoma, and multiple nonpenetrating treatments resulted in the development of sympathetic ophthalmia.

  13. SD-OCT findings in polypoidal choroidal vasculopathy.

    PubMed

    Asensio-Sánchez, V M

    2016-01-01

    To examine patients with polypoidal choroidal vasculopathy (PCV), using spectral-domain optical coherence tomography (SD-OCT) to characterise and locate the PCV lesions. A series of 15 eyes of 10 patients diagnosed with PCV were examined. All eyes were imaged with macular SD-OCT. SD-OCT cross-sectional scan findings included atypical and typical pigment epithelial detachments (PEDs). Polyps and neovascularisation were located above Bruch membrane. All 15 eyes (100%) showed sub-retinal fluid (SRF) in association with PEDs. These SD-OCT findings located the vascular lesions of PCV in the sub-retinal pigment epithelium (RPE) space, and strongly suggest that PCV is a variant of type 1 neovascularization. Copyright © 2015. Published by Elsevier España, S.L.U.

  14. Chick eyes compensate for chromatic simulations of hyperopic and myopic defocus: evidence that the eye uses longitudinal chromatic aberration to guide eye-growth.

    PubMed

    Rucker, Frances J; Wallman, Josh

    2009-07-01

    Longitudinal chromatic aberration (LCA) causes short wavelengths to be focused in front of long wavelengths. This chromatic signal is evidently used to guide ocular accommodation. We asked whether chick eyes exposed to static gratings simulating the chromatic effects of myopic or hyperopic defocus would "compensate" for the simulated defocus. We alternately exposed one eye of each chick to a sine-wave grating (5 or 2 cycle/deg) simulating myopic defocus ("MY defocus": image focused in front of retina; hence, red contrast higher than blue) and the other eye to a grating of the same spatial frequency simulating hyperopic defocus ("HY defocus": blue contrast higher than red). The chicks were placed in a drum with one eye covered with one grating, and then switched to another drum with the other grating with the other eye covered. To minimize the effects of altered eye-growth on image contrast, we studied only the earliest responses: first, we measured changes in choroidal thickness 45 min to 1 h after one 15-min episode in the drum, then we measured glycosaminoglycans (GAG) synthesis in sclera and choroid (by the incorporation of labeled sulfate in tissue culture) after a day of four 30-min episodes in the drum. The eyes compensated in the appropriate directions: The choroids of the eyes exposed to the HY simulation showed significantly more thinning (less thickening) over the course of the experiment than the choroids of the eyes exposed to the MY simulation (all groups mean:-17 microm; 5 c/d groups: -24 microm; paired t-test (one-tailed): p=0.0006). The rate of scleral GAG synthesis in the eye exposed to the HY simulation was significantly greater than in the eye exposed to the MY simulation (HY/MY ratio=1.20; one sample t-test (one-tailed): p=0.015). There was no significant interaction between the sign of the simulated defocus and either the spatial frequency or the presence of a +3 D lens used to compensate for the 33 cm distance of the drum. Although previous

  15. Chick eyes compensate for chromatic simulations of hyperopic and myopic defocus: Evidence that the eye uses longitudinal chromatic aberration to guide eye-growth

    PubMed Central

    Wallman, Josh

    2009-01-01

    Longitudinal chromatic aberration (LCA) causes short wavelengths to be focused in front of long wavelengths. This chromatic signal is evidently used to guide ocular accommodation. We asked whether chick eyes exposed to static gratings simulating the chromatic effects of myopic or hyperopic defocus would “compensate” for the simulated defocus. We alternately exposed one eye of each chick to a sine-wave grating (5 or 2 cycle/deg) simulating myopic defocus (“MY defocus”: image focused in front of retina; hence, red contrast higher than blue) and the other eye to a grating of the same spatial frequency simulating hyperopic defocus (“HY defocus”: blue contrast higher than red). The chicks were placed in a drum with one eye covered, with one grating, and then switched to another drum with the other eye covered, with the other grating. To minimize the effects of altered eye-growth on image contrast, we studied only the earliest responses: first, we measured changes in choroidal thickness 45 min to 1 hour after one 15-min episode in the drum, then we measured glycosaminoglycans (GAG) synthesis in sclera and choroid (by the incorporation of labeled sulfate in tissue culture) after a day of four 30-min episodes in the drum. The eyes compensated in the appropriate directions: The choroids of the eyes exposed to the HY simulation showed significantly more thinning (less thickening) over the course of the experiment than the choroids of the eyes exposed to the MY simulation (all groups mean: −17 μm; 5 c/d groups: −24 μm; paired t-test (one-tailed): p=0.0006). The rate of scleral GAG synthesis in the eye exposed to the HY simulation was significantly greater than in the eye exposed to the MY simulation (HY/MY ratio = 1.20; one sample t-test (one-tailed): p=0.015). There was no significant interaction between the sign of the simulated defocus and either the spatial frequency or the presence of a +3 D lens used to compensate for the 33 cm distance of the drum

  16. Xanthogranuloma of the choroid plexus

    SciTech Connect

    Pear, B.L.

    1984-08-01

    Uncommon tumefactions known as xanthogranulomas can occur throughout the body. Some appear to develop as benign or malignant neoplasms. An even less familiar xanthogranuloma occurs within the choroid plexus. Most are tiny plaques only a few millimeters in diameter. However, they can present as masses of significant size within the glomus. When large and unilateral, they are included in the differential diagnosis of choroid plexus tumors. A computed tomographic (CT) study of such a tumor is presented.

  17. [Choroidal melanoma - evolution and prognosis].

    PubMed

    Chiruţa, Daria; Stan, Cristina

    2014-01-01

    Choroidal melanoma is the most common primary intraocular malignant tumor. We present the case of a 62 year old patient who was diagnosed with intraocular tumor in his right eye, for about three years. Regarding the fact that the patient refused any kind of treatment during this period, we just had the opportunity to monitor this case. Finally, the diagnosis was choroidal melanoma, confirmed by the histopathological exam.

  18. Prevalence of myopic shifts among patients seeking cataract surgery.

    PubMed

    Iribarren, Rafael; Iribarren, Guillermo

    2013-01-01

    Modern cataract surgery by phacoemulsification is a widely accepted procedure with a rapid recovery time. The prescription of specific intraocular lens, implanted during surgery, makes it possible to anticipate whether the patient will need reading glasses after the procedure. The present study analyses a sample of cataract surgery patients to show the frequency of myopic shifts related to nuclear opacity, which can result in clear near vision before surgery. A non-selected sample of consecutive patients who underwent elective cataract surgery in a private clinic was studied retrospectively. The myopic shift in refraction was assessed by comparing the old prescription with the spectacle correction at the time of interviewing.The mean age of the 229 subjects studied was 71.5 ± 10.4 years (109, 47.6%, males). A myopic shift in refraction, defined as at least - 0.5 diopters, was present in 37.1% of subjects (95% CI: 30.8%-43.4%). The mean change in refraction in these subjects was -2.52 ± 1.52 diopters. The percentage of subjects who had developed a myopic shift was significantly greater in those who presented greater nuclear opalescence. There were also differences in the mean myopic shift by refractive group, with the emmetropes having the greatest myopic shift. In this study of patients seeking cataract surgery in a clinical setting, more than one third had myopic shifts in refraction. This must be taken into account in order that patients maintain the benefit of clear near vision after surgery.

  19. Choroidal detachment and ocular hypotony: CT evaluation

    SciTech Connect

    Mafee, M.F.; Peyman, G.A.

    1984-12-01

    The computed tomographic (CT) findings in 20 patients with hemorrhagic choroidal detachment, serous choroidal detachment and/or ocular hypotony are described. Hemorrhagic choroidal detachment appeared as an area of high attenuation that was usually localized, uniformly hyperdense, and not position-dependent. Serous choroidal detachment appeared as a convex, thick line of increased density within the vitreous cavity. Inflammatory choroidal detachment produces a diffuse intrauveal and suprachoroidal accumulation of high-density, position-dependent fluid, and uveoscleral thickening and enhancement, which in cross section resembles a ring. CT has proved valuable in localizing and differentiating serous or hemorrhagic choroidal detachment and uveoscleral infolding.

  20. Correlation between choroidal thickness and degree of myopia assessed with enhanced depth imaging optical coherence tomography.

    PubMed

    El-Shazly, Amany A; Farweez, Yousra A; ElSebaay, Marwa E; El-Zawahry, Walid M A

    2017-08-30

    To assess the choroidal thickness in different degrees of myopia using enhanced depth imaging optical coherence tomography (EDI-OCT) compared with healthy subjects. We included 240 patients with myopia and 60 emmetropes as controls. Participants underwent full ophthalmologic examination, axial length measurement, and EDI-OCT imaging of the choroid. Choroidal thickness (CT) was measured at 5 locations, including subfoveal (SFCT), 2 mm nasal, temporal, upper, and lower to fovea. Choroidal thickness was significantly lower in myopic eyes compared to controls. Regardless of the degree of myopia, nasal regions showed the lowest CT with decremental pattern with advance of myopia (low myopia 279.00 ± 24.50 µm, moderate myopia 269.58 ± 20.69 µm, high myopia 189.58 ± 25.95 µm, advanced myopia 96.75 ± 24.83 µm). Highest CT was variable according to the degree of myopia with decremental pattern with advance of myopia (low myopia in subfoveal region 354.40 ± 35.14 µm, moderate myopia in temporal region 337.87 ± 35.75 µm, high myopia in lower region 312.15 ± 38.90 µm, and advanced myopia in upper region 201.25 ± 18.27 µm). Axial length showed significant negative correlation with SFCT and CT in different studied regions. Different degrees of myopia showed thinner choroidal thickness than that of normal control eyes with decremental thinning with progress of myopia. This might be secondary to the longer axial length, which was the determining factor in some locations such as subfoveal, nasal, and upper CT.

  1. Bevacizumab inhibits proliferation of choroidal endothelial cells by regulation of the cell cycle.

    PubMed

    Rusovici, Raluca; Patel, Chirag J; Chalam, Kakarla V

    2013-01-01

    The purpose of this study was to evaluate cell cycle changes in choroidal endothelial cells treated with varying doses of bevacizumab in the presence of a range of concentrations of vascular endothelial growth factor (VEGF). Bevacizumab, a drug widely used in the treatment of neovascular age-related macular degeneration, choroidal neovascularization, and proliferative diabetic retinopathy, neutralizes all isoforms of VEGF. However, the effect of intravitreal administration of bevacizumab on the choroidal endothelial cell cycle has not been established. Monkey choroidal endothelial (RF/6A) cells were treated with VEGF 50 ng/mL and escalating doses of bevacizumab 0.1-2 mg/mL for 72 hours. Cell cycle changes in response to bevacizumab were analyzed by flow cytometry and propidium iodide staining. Cell proliferation was measured using the WST-1 assay. Morphological changes were recorded by bright field cell microscopy. Bevacizumab inhibited proliferation of choroidal endothelial cells by stabilization of the cell cycle in G0/G1 phase. Cell cycle analysis of VEGF-enriched choroidal endothelial cells revealed a predominant increase in the G2/M population (21.84%, P, 0.01) and a decrease in the G0/G1 phase population (55.08%, P, 0.01). Addition of escalating doses of bevacizumab stabilized VEGF-enriched cells in the G0/G1 phase (55.08%, 54.49%, 56.3%, and 64% [P, 0.01]) and arrested proliferation by inhibiting the G2/M phase (21.84%, 21.46%, 20.59%, 20.94%, and 16.1% [P, 0.01]). The increase in G0/G1 subpopulation in VEGF-enriched and bevacizumab-treated cells compared with VEGF-enriched cells alone was dose-dependent. Bevacizumab arrests proliferation of VEGF-enriched choroidal endothelial cells by stabilizing the cell cycle in the G0/G1 phase and inhibiting the G2/M phase in a dose-dependent fashion.

  2. Neovascularization in Left Atrial Myxoma

    PubMed Central

    Dubey, Laxman; Chaurasia, Amit Kumar

    2012-01-01

    Abstract We report a case with a left atrial mass who underwent coronary angiography to rule out coronary artery disease. Coronary angiography revealed an anomalous tortuous vascular structure originating from the left circumflex coronary artery to the left atrial tumor suggestive of neovascularization. Preoperative coronary angiography is useful for coronary artery evaluation and also provides additional information regarding the feeding vessel supplying the mass. PMID:24757609

  3. Heterotypic RPE-choroidal endothelial cell contact increases choroidal endothelial cell transmigration via PI 3-kinase and Rac1

    PubMed Central

    Peterson, Lynda J.; Wittchen, Erika S.; Geisen, Pete; Burridge, Keith; Hartnett, M. Elizabeth

    2008-01-01

    Age-related macular degeneration (AMD) is the major cause of non-preventable blindness. Severe forms of AMD involve breaching of the retinal pigment epithelial (RPE) barrier by underlying choroidal endothelial cells (CECs), followed by migration into, and subsequent neovascularization of the neurosensory retina. However, little is known about the interactions between RPE and CECs and the signaling events leading to CEC transmigration. While soluble chemotactic factors secreted from RPE can contribute to inappropriate CEC transmigration, other unidentified stimuli may play an additional role. Using a coculture model that maintains the natural structural orientation of CECs to the basal aspect of RPE, we show that “contact” with RPE and/or RPE extracellular matrix increases CEC transmigration of the RPE barrier. From a biochemical standpoint, contact between CECs and RPE results in an increase in the activity of the GTPase Rac1 within the CECs; this increase is dependent on upstream activation of PI 3-K and Akt1. To confirm a link between these signaling molecules and increased CEC transmigration, we performed transmigration assays while inhibiting both PI 3-K and Rac1 activity, and observed that both decreased CEC transmigration. We hypothesize that contact between CECs and RPE stimulates a signaling pathway involving PI 3-K, Akt1, and Rac1 that facilitates CEC transmigration across the RPE barrier, an important step in the development of neovascular AMD. PMID:17292356

  4. Diffuse villous hyperplasia of choroid plexus.

    PubMed

    Iplikcioglu, A C; Bek, S; Gökduman, C A; Bikmaz, K; Cosar, M

    2006-06-01

    Diffuse villous hyperplasia of choroid plexus (DVHCP) is a rare condition which is characterized by the presence of diffuse enlargement of the entire choroid plexus throughout the length of the choroidal fissure and overproduction of CSF. The diagnosis of diffuse villous hyperplasia of choroid plexus can be established by the MR demonstration of diffusely large, contrast enhanced choroid plexus in the cases of overproduction hydrocephalus. Although some authors recommend choroid plexus excision or coagulation, ventriculo-atrial shunt insertion is a simple and effective treatment modality in cases of diffuse villous hyperplasia of the choroid plexus. In this report we present a case of diffuse villous hyperplasia of the choroid plexus and a short review of the literature. To our knowledge, in the CT and MRI era only 5 cases of DVHCP cases have been reported.

  5. Tamponade or Filling Effect: Changes of Forces in Myopic Eyes

    PubMed Central

    Morescalchi, Francesco; Romano, Mario R.

    2014-01-01

    Myopia is the most common ocular abnormality. Its high and growing prevalence has contributed to a recent surge in surgical interest in the disorder, since retinal detachment in eyes with high myopia differs from that in emmetropic eyes or eyes with low myopia. The myopic eye, because of its specific anatomy, poses special challenges that need to be overcome to ensure the appropriate use of vitreous substitutes. However, intraocular tamponades have shown great potential for revolutionizing retinal detachment surgery and vitreomacular surgery in general in myopic eyes. We provide an updated review of the clinical use of vitreous substitutes in the myopic eye, paying particular attention to analyzing the ideal function of endotamponade agents and comparing the effects of these agents on the physical and biological properties of the eye. PMID:25101290

  6. Ocular residual astigmatism's effect on high myopic astigmatism LASIK surgery

    PubMed Central

    Teus, M A; Arruabarrena, C; Hernández-Verdejo, J L; Cañones, R; Mikropoulos, D G

    2014-01-01

    Purpose To analyze the effect of ocular residual astigmatism (ORA) on the effectiveness of LASIK for treating high myopic astigmatism. Methods This is an observational, cross-sectional study. We studied 116 consecutive myopic eyes with −3 diopters (D) or more of astigmatism that underwent LASIK surgery. The magnitude of uncorrected residual refractive astigmatism 3 months postoperatively was measured. Results The mean preoperative cylinder was −4.0±0.83 D (range, −7.5 to −3 D) and the mean preoperative ORA was 0.82±0.5 D. The mean residual refractive cylinder 3 months postoperatively was −0.78±0.83 D (range, −3 to 0 D). No correlation was found between ORA and the refractive cylinder 3 months postoperatively (P=0.6). Conclusion In eyes with high myopic astigmatism undergoing LASIK, ORA was not correlated with the residual postoperative cylinder. PMID:24971989

  7. One sister and brother with mirror image myopic anisometropia.

    PubMed

    Park, Sung Joon; Kim, Joo Yeon; Baek, Seung-Hee; Kim, Eung Suk; Kim, Ungsoo S

    2010-02-01

    We report a case of one sister and brother with mirror image myopic anisometropia. One sister and brother complained visual disturbance. The sister was 10 years 11 months old, and brother was 8 years 4 months old. Full ophthalmic examinations were performed, including slit lamp examination, intraocular pressure, keratometry, anterior chamber depth, axial length, fundus examination and the cycloplegic refraction. The cycloplegic refractive power was -15.50 dpt cyl.+4.50 dpt Ax 85 degrees (right eye), -1.00 dpt cyl.+0.50 dpt Ax 90 degrees (left eye) in the sister; -1.75 dpt cyl.+2.25 dpt Ax 90 degrees (right eye), -9.50 dpt cyl.+4.00 dpt Ax 80 degrees (left eye) in the brother. The co-occurrence of severe myopic anisometropia in a sister and brother is extremely rare. The present case suggests that severe myopic anisometropia may be related by genetic inheritance.

  8. Focal choroidal excavation associated with polypoidal choroidal vasculopathy.

    PubMed

    Say, Emil Anthony T; Jani, Pooja D; Appenzeller, Matthew F; Houghton, Odette M

    2013-01-01

    A 48-year-old woman presented with blurred vision in her right eye for 6 weeks. Visual acuity was 20/300 and 20/25 in the right and left eyes, respectively. Fundus examination showed subretinal hemorrhage in the superonasal macula in the right eye, whereas the left eye was normal. Fluorescein angiography showed blocked fluorescence from hemorrhage and a round distinct hypofluorescent spot along the inferotemporal arcade. Indocyanine green angiography revealed hyperfluorescent tubular and aneurysmal dilatations consistent with polypoidal choroidal vasculopathy in the superior macula. Spectral-domain optical coherence tomography showed retinal pigment epithelial irregularities and detachment. Scans through the round area of hypofluorescence revealed a conforming focal choroidal excavation and thinning of the underlying choriocapillaries. Because the pathogenesis of focal choroidal excavation is currently unclear, the authors propose the possibility of an acquired etiology related to loss of choriocapillaries from perfusion abnormalities as evidenced here.

  9. ω-3 and ω-6 long-chain PUFAs and their enzymatic metabolites in neovascular eye diseases.

    PubMed

    Gong, Yan; Fu, Zhongjie; Liegl, Raffael; Chen, Jing; Hellström, Ann; Smith, Lois Eh

    2017-07-01

    Neovascular eye diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration, threaten the visual health of children and adults. Current treatment options, including anti-vascular endothelial growth factor therapy and laser retinal photocoagulation, have limitations and are associated with adverse effects; therefore, the identification of additional therapies is highly desirable. Both clinical and experimental studies show that dietary ω-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFAs) reduce retinal and choroidal angiogenesis. The ω-3 LC-PUFA metabolites from 2 groups of enzymes, cyclooxygenases and lipoxygenases, inhibit [and the ω-6 (n-6) LC-PUFA metabolites promote] inflammation and angiogenesis. However, both of the ω-3 and the ω-6 lipid products of cytochrome P450 oxidase 2C promote neovascularization in both the retina and choroid, which suggests that inhibition of this pathway might be beneficial. This review summarizes our current understanding of the roles of ω-3 and ω-6 LC-PUFAs and their enzymatic metabolites in neovascular eye diseases. © 2017 American Society for Nutrition.

  10. Choroidal thickness profile in healthy Indian children.

    PubMed

    Chhablani, Jay Kumar; Deshpande, Riddhima; Sachdeva, Virender; Vidya, Sagar; Rao, P Srinivasa; Panigati, Anand; Mahat, Birendra; Pappuru, Rajeev Reddy; Pehere, Niranjan; Pathengay, Avinash

    2015-06-01

    The purpose was to study choroidal thickness and its profile based on location in healthy Indian children using enhanced depth spectral-domain-optical coherence tomography (SD-OCT). In this cross-sectional observational study 255 eyes of 136 children with no retinal or choroidal disease were consecutively scanned using enhanced depth SD-OCT. Eyes with any ocular disease or axial length (AXL) >25 mm or < 20 mm were excluded. A single observer measured choroidal thickness from the posterior edge of the retinal pigment epithelium to the choroid/sclera junction at 500-microns intervals up to 2500 microns temporal and nasal to the fovea. Generalized estimating equations were used to evaluate the correlation between choroidal thickness at various locations and age, AXL, gender and spherical equivalent (SEq). Mean age of the subjects was 11.9 ± 3.4 years (range: 5-18 years). There were 62 Females and 74 males. The mean AXL was 23.55 ± 0.74 mm. Mean subfoveal choroidal thickness was 312.1 ± 45.40 μm. Choroid was found to be thickest subfoveally, then temporally. Age, AXL and SEq showed a significant correlation with choroidal thickness, whereas gender did not affect choroidal thickness. Our study provides a valid normative database of choroidal thickness in healthy Indian children. This database could be useful for further studies evaluating choroidal changes in various chorioretinal disorders. Age and AXL are critical factors, which negatively correlated with choroidal thickness.

  11. Rapid response of retinal pigment epithelial detachments to intravitreal aflibercept in neovascular age-related macular degeneration refractory to bevacizumab and ranibizumab

    PubMed Central

    Patel, K H; Chow, C C; Rathod, R; Mieler, W F; Lim, J I; Ulanski, L J; Leiderman, Y I; Arun, V; Chau, F Y

    2013-01-01

    Purpose The aim of this study is to report the short-term efficacy of aflibercept in the treatment of neovascular age-related macular degeneration (AMD) with associated retinal pigment epithelial detachment (PED) which is refractory or develops tachyphylaxis to bevacizumab and ranibizumab. Methods The method comprised a retrospective review of the medical records of patients with neovascular AMD and associated PEDs recently treated with aflibercept and previously treated with bevacizumab and ranibizumab. Results Three eyes of three female patients of ages 49, 55, and 65 years old with large serous PEDs and subretinal fluid (SRF) associated with occult choroidal neovascularization and neovascular AMD were treated with aflibercept after intravitreal bevacizumab and/or ranibizumab failed to resolve the lesions. All had complete resolution of SRF and complete or near-complete resolution of the PEDs after aflibercept injections over a 3-month period. Visual acuity improved in all three eyes. Conclusion Intravitreal aflibercept may be an effective treatment option for serous PED in neovascular AMD patients after bevacizumab and ranibizumab have previously failed. Larger studies with longer follow-up are required to determine the role of aflibercept in treatment of PED in neovascular AMD. PMID:23558214

  12. Reduced Macular Vascular Density in Myopic Eyes

    PubMed Central

    Fan, Hua; Chen, Hao-Yu; Ma, Hong-Jie; Chang, Zheng; Yin, Hai-Quan; Ng, Danny Siu-Chun; Cheung, Carol Y; Hu, Shan; Xiang, Xiang; Tang, Shi-Bo; Li, Shuang-Nong

    2017-01-01

    Background: Morphological changes of the vasculature system in patients with myopia have been observed by Doppler ultrasound and fundus fluorescein angiography (FFA); however, these studies have limitations. Doppler ultrasound provides low-resolution images which are mainly obtained from visualized large vessels, and FFA is an invasive examination. Optic coherence tomography (OCT) angiography is a noninvasive, high-resolution measurement for vascular density. The purpose of this study was to investigate the change of vascular density in myopic eyes using OCT angiography. Methods: This cross-sectional study includes a total of 91 eyes from 47 participants including control, moderate, and high myopia that were evaluated by OCT angiography. Patients with myopia were recruited from the Refractive Department, Shenzhen Aier Eye Hospital, from August 5, 2015 to April 1, 2016. Emmetropic eyes were from healthy volunteers. The vascular density at macula and optic disc regions, ganglion cell complex (GCC) thickness, and retinal nerve fiber layer (RNFL) thickness were measured. Their relationships with axial length (AL) and refractive error were analyzed. One-way analysis of variance (ANOVA), Pearson's correlation, and generalized estimating equation were used for statistical analysis. Results: Both superficial and deep macular vascular density were highest in control (25.64% ± 3.76% and 37.12% ± 3.66%, respectively), then in moderate myopia (21.15% ± 5.33% and 35.35% ± 5.50%, respectively), and lowest in high myopia group (19.64% ± 3.87% and 32.81% ± 6.29%, respectively) (F = 13.74 and 4.57, respectively; both P < 0.001). Both superficial (β = −0.850 and 0.460, respectively) and deep (β = −0.766 and 0.396, respectively) macular vascular density were associated with AL and spherical equivalent (all P < 0.001). Superficial macular vascular density was associated with GCC thickness (β = 0.244, P = 0.040), independent of spherical equivalent. The vascular density in

  13. Retinal and choroidal expression of BMP-2 in lens-induced myopia and recovery from myopia in guinea pigs.

    PubMed

    Li, Honghui; Wu, Juan; Cui, Dongmei; Zeng, Junwen

    2016-03-01

    The present study investigated the retinal and choroidal expression of bone morphogenetic protein-2 (BMP-2) in myopia and in myopia recovery in a guinea pig model. For this investigation, two groups of guinea pigs, lens‑induced myopia and recovery from myopia, were used, and defocused myopia was induced the guinea pigs wearing ‑4.00 D lenses on the right eyes for 3 weeks, with the left eyes serving as the contralateral. In the following week, the lenses of the guinea pigs in the recovery group were removed, and the refractive power and axial length were measured. The expression of BMP‑2 in the eyeballs was observed using immunohistochemistry and analyzed using Western blot analysis. After 3 weeks, the eyes acquired relative myopia and longer axial lengths in the two groups of guinea pigs. After 1 week without lenses in the recovery group, the myopia and axial lengths regressed. Immunofluorescence staining showed that BMP‑2 was expressed in the posterior retina, RPE, choroid and sclera. The expression of BMP‑2 decreased in the myopic retina of the guinea pigs. Following the regression of myopia in the recovery group, no difference in the expression of BMP‑2 was observed between the recovered treated eyes and the contralateral eyes. The choroidal expression level of BMP‑2 in the treated eyes showed no significant changes in either group. Therefore, BMP‑2 may be involved in the development of myopia, however, it does not have a primary role in the retinal and choroidal signals regulating scleral remodeling.

  14. Effect of photodynamic therapy alone or combined with posterior subtenon triamcinolone acetonide or intravitreal bevacizumab on choroidal hypofluorescence by indocyanine green angiography.

    PubMed

    Hatta, Yoshiyuki; Ishikawa, Kohei; Nishihara, Hiroaki; Ozawa, Shinsuke; Ito, Yasuki; Terasaki, Hiroko

    2010-03-01

    Choroidal hypofluorescence has been reported beneath the photodynamic therapy (PDT) site in clinical studies. We evaluated the choroidal hypofluorescence after combined PDT with posterior subtenon injection of triamcinolone acetonide or PDT with an intravitreal injection of bevacizumab for age-related macular degeneration. Two hundred and forty-two eyes with a subfoveal choroidal neovascularization caused by age-related macular degeneration were studied. Ninety-two eyes underwent PDT alone, 90 eyes underwent PDT with sub-Tenon injection of triamcinolone acetonide, and 60 eyes underwent PDT with intravitreal injection of bevacizumab. Verteporfin-induced choroidal hypoperfusion was determined by indocyanine green angiograms. The intensity of the diffuse fluorescence within the PDT site away from the choroidal neovascularization lesion and from the normal retina just peripheral to the optic disk was measured by densitometry (Topcon IMAGEnet computer system, Topcon, Tokyo, Japan) in the indocyanine green angiogram images obtained at 10 minutes 3 months after the PDT. The ratio of the average brightness of the retina within the PDT area to that of the retina peripheral to the optic disk (irradiated/nonirradiated retinal brightness ratio) was calculated for each angiogram. The irradiated/nonirradiated retinal brightness ratio of the angiograms was 0.96 in the PDT-alone group, 0.85 in the sub-Tenon injection of triamcinolone acetonide-PDT group, and 0.89 in the intravitreal injection of bevacizumab-PDT group (Kruskal-Wallis H test, P < 0.05). The degree of choroidal hypofluorescence in the indocyanine green angiogram images 3 months after PDT in the sub-Tenon injection of triamcinolone acetonide and intravitreal injection of bevacizumab group was higher than that of PDT-alone group. Sub-Tenon injection of triamcinolone acetonide and intravitreal injection of bevacizumab can prolong the duration of the choroidal hypofluorescence after PDT.

  15. Endoplasmic Reticulum Stress in Age-Related Macular Degeneration: Trigger for Neovascularization

    PubMed Central

    Salminen, Antero; Kauppinen, Anu; Hyttinen, Juha MT; Toropainen, Elisa; Kaarniranta, Kai

    2010-01-01

    Age-related macular degeneration (AMD) can be classified into two main categories: the atrophic, dry form and the exudative, wet form. The crucial difference between dry and wet AMD is the development of choroidal neovascularization in wet AMD. One fundamental cause of the neovascularization is the increased expression of VEGF (vascular endothelial growth factor) in retinal pigment epithelial cells. Progression of AMD is linked to augmentation of cellular stress, for example, oxidative stress, proteotoxic stress, inflammation and hypoxia. All these conditions can trigger stress in endoplasmic reticulum (ER), which maintains protein quality control in cells. ER stress induces the unfolded protein response (UPR) via IRE1 (inositol-requiring protein-1), PERK (protein kinase RNA-like ER kinase) and ATF6 (activating transcription factor-6) transducers. UPR signaling is a double-edged sword, that is, it can restore cellular homeostasis as far as possible, but ultimately may lead to chronic, overwhelming stress that can cause apoptotic cell death. Interestingly, ER stress is a well-known inducer of angiogenesis in cancer. Moreover, stress conditions associated with the progress of AMD can induce the expression of VEGF. We discuss the role of ER stress in the regulation of neovascularization and the conversion of dry AMD to its wet, detrimental counterpart. PMID:20683548

  16. Combined intravitreal bevacizumab and photodynamic therapy for neovascular age-related macular degeneration.

    PubMed

    Ladewig, Markus S; Karl, Stefanie E; Hamelmann, Victoria; Helb, Hans-Martin; Scholl, Hendrik P N; Holz, Frank G; Eter, Nicole

    2008-01-01

    Our aim was to evaluate the short-term safety and efficacy of combined photodynamic therapy (PDT) with verteporfin and intravitreal bevacizumab in neovascular age-related macular degeneration (AMD). A prospective non-randomized interventional case series of 30 eyes of 30 patients with choroidal neovascularization (CNV) caused by AMD was studied. All patients were treated with PDT followed by an intravitreal injection of bevacizumab (1.5 mg) on the same day. Ophthalmic evaluations included determination of best-corrected visual acuity by using ETDRS charts. CNV lesion characteristics were determined by fluorescein angiography, and retinal morphology by optical coherence tomography. Review examinations were performed 1, 4, and 12 weeks following treatment. The median ETDRS letter scores increased by 3 letters after 4 weeks and 4.3 letters after 12 weeks. Median central retinal thickness decreased from the baseline by 145 microm (week 1), 205 microm (week 4), and 171 microm (week 12), respectively (P < 0.0001, for all comparisons). One patient experienced a transient moderate vision loss after 4 weeks post treatment. Leakage on fluorescein angiography was resolved in all patients at week 12. No significant ocular or systemic side-effects were observed. Short-term results suggest that a single PDT in combination with intravitreal bevacizumab is safe and associated with stabilization of visual acuity and decrease of intraretinal and subretinal fluid accumulation in the macula. Further evaluation of this treatment strategy for neovascular AMD appears warranted.

  17. [Neovascular glaucoma--etipathogeny and diagnosis].

    PubMed

    Călugăru, D; Călugăru, M

    2012-01-01

    Neovascular glaucoma is defined as an iris and/or anterior chamber angle neovascularization associated with increased intraocular presure. It is a secondary glaucoma most frequently determined by a severe retinal ischemia. The most common diseases responsible for the development of neovascular glaucoma are diabetic retinopathy, ischemic central retinal vein occlusion and ocular ischemic syndrome; the uncommon causes include ocular radiation, ocular tumors, uveitis and other miscellaneous conditions. Vascular endothelial growth factor is an important and probably predominant agent in the pathogenesis of both intraocular neovascularization and neovascular glaucoma. The evolution of clinical and histopathological changes from predisposing conditions to the occurrence of rubeosis iridis as well as neovacular glaucoma is divided into four grades that is prerubeotic, preglaucomatous, open-angle and angle closure glaucoma stages.

  18. Posterior scleral reinforcement combined with vitrectomy for myopic foveoschisis

    PubMed Central

    Li, Xiu-Juan; Yang, Xiao-Peng; Li, Qiu-Ming; Wang, Yu-Ying; Wang, Jing; Lyu, Xiao-Bei; Jia, Heng

    2016-01-01

    AIM To investigate the effects of posterior scleral reinforcement (PSR) combined with vitrectomy for myopic foveoschisis. METHODS Thirty-nine highly myopic eyes of 39 patients with myopic foveoschisis underwent PSR combined with vitrectomy. Best corrected visual acuity (BCVA), refraction error, and the foveal thickness by optical coherence tomography (OCT) were recorded before and after the surgery, and complications were noted. RESULTS The follow-up period was 12mo, and the main focus was on the results of the 12-month follow-up visit. The mean preoperative BCVA was 0.96±0.43 logMAR. At the final follow-up visit, the mean BCVA was 0.46±0.28 logMAR, which significantly improved compared with the preoperative one (P=0.003). The BCVA improved in 33 eyes (84.62%), and unchanged in 6 eyes (15.38%). At the end of follow-up, the mean refractive error was -15.13±2.55 D, and the improvement was significantly compared with the preoperative one (-17.53±4.51 D) (P=0.002). Twelve months after surgery, OCT showed complete resolution of the myopic foveoschisis and a reat-tachment of the fovea in 37 eyes (94.87%) and partial resolution in the remained two eyes (5.13%). The foveal thickness was obviously reduced at 12-month follow-up visit (196.45±36.35 µm) compared with the preoperative one (389.32±75.56 µm) (P=0.002). There were no serious complications during the 12mo follow-up period. CONCLUSION PSR combined with vitrectomy is a safe and effective procedure for myopic foveoschisis with both visual and anatomic improvement. PMID:26949646

  19. Stereotactic radiotherapy in neovascular age-related macular degeneration

    PubMed Central

    Ranjbar, Mahdy; Kurz, Maximilian; Holzhey, Annekatrin; Melchert, Corinna; Rades, Dirk; Grisanti, Salvatore

    2016-01-01

    Abstract Stereotactic radiotherapy (SRT) is a new approach to treat neovascular age-related macular degeneration (nAMD). The INTREPID trial suggested that SRT could reduce the frequency of regular intravitreal injections (IVIs) with antivascular endothelial growth factor drugs, which are necessary to control disease activity. However, the efficacy of SRT in nAMD and resulting morphological changes have not been validated under real-life circumstances, an issue, which we would like to address in this retrospective analysis. Patients who met the INTREPID criteria for best responders were eligible for SRT. A total of 32 eyes of 32 patients were treated. Thereafter, patients were examined monthly for 12 months and received pro re nata IVI of aflibercept or ranibizumab. Outcome measures were: mean number of injections, best-corrected visual acuity, and morphological changes of the outer retina-choroid complex as well as patient safety. Mean number of IVI decreased by almost 50% during the 12 months after SRT compared to the year before, whereas visual acuity increased by one line (logMAR). Morphological evaluation showed that most changes affect outer retinal layers. Stereotactic radiotherapy significantly reduced IVI retreatment in nAMD patients under real-life circumstances. Therefore, SRT might be the first step to stop visual loss as a result of IVI undertreatment, which is a major risk. PMID:28033280

  20. Characterization of the choroidal mast cell.

    PubMed Central

    Godfrey, W A

    1987-01-01

    The experimental studies performed on nonpigmented rat choroids and the review of the important literature covered in this thesis seem to justify the following statements: 1. Mast cells are present in the choroid in significant numbers. 2. Mast cell numbers vary considerably from one individual to another and from one location in the choroid to another. 3. The major concentration of mast cells in the uvea is in the posterior choroid. 4. The mast cells of the choroid have a preferential location along arterial vessels. 5. Choroidal mast cell population density apparently decreases with senescence. 6. Mast cell products are present in sufficient quantity to exert substantial effects on physiologic, immunologic, and inflammatory responses in the choroid. 7. Choroidal mast cell products are released with appropriate stimulation and share some properties with the connective-tissue mast cell. 8. Choroidal mast cell demonstrate enough differences to suggest that a local differentiation may be present and may represent a locally controlled modulating effect for choroidal physiologic, immunologic, and inflammatory reactions. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 FIGURE 11 FIGURE 12 FIGURE 13 FIGURE 14 FIGURE 15 FIGURE 16 FIGURE 17 PMID:3328921

  1. The Choroid and Optical Coherence Tomography

    PubMed Central

    Sezer, Taha; Altınışık, Muhammet; Koytak, İbrahim Arif; Özdemir, Mehmet Hakan

    2016-01-01

    The choroid is the most vascular tissue in the eye and it plays an important role in the pathophysiology of various common chorioretinal diseases such as central serous retinopathy, age-related macular degeneration and degenerative myopia. Quantitative assessment of the choroid has been quite challenging with traditional imaging modalities such as indocyanine green angiography and ultrasonography due to limited resolution and repeatability. With the advent of optical coherence tomography (OCT) technology, detailed visualization of the choroid in vivo is now possible. Measurements of choroidal thickness have also enabled new directions in research to study normal and pathological processes within the choroid. The aim of the present study is to review the current literature on choroidal imaging using OCT. PMID:27800255

  2. Reduction in choroidal blood flow occurs in chicks wearing goggles that induce eye growth toward myopia

    PubMed Central

    Shih, Yung-Feng; Fitzgerald, Malinda E.C.; Norton, Thomas T.; Gamlin, Paul D.R.; Hodos, William; Reiner, Anton

    2015-01-01

    Goggles that degrade the retinal image produce axial enlargement of the ocular globe and large myopic refractive errors. Many authors have assumed that visual image degradation itself leads to myopia. Hodos and co-authors have shown, however, that goggled eyes in chicks are considerably warmer than normal. Such temperature changes may either underlie or be a consequence of alterations in choroidal blood flow (CBF). Since alterations in CBF could affect eye growth, we explored the effect of monocular goggling on CBF in chicks. Plastic goggles were glued over one eye in four-day old chicks and the goggles were left in place for 12 or 14 days. Fourteen days after the goggling, CBF was measured using laser Doppler velocimetry. Three groups of chicks were studied: 1) chicks with goggles for 14 days; 2) chicks with goggles for 12 days followed by no goggles for the two days; 3) age matched non-goggled chicks. A-scan ultrasonography confirmed that the visual deprivation produced vitreous chamber elongation in the goggled eye and that the degree of elongation for the goggled eye was the same for the two goggled groups. The results were : 1) blood flow in non-goggled chicks was similar in both eyes; 2) blood flow was significantly reduced in the goggled eye in chicks wearing goggles for 14 days- 37% of control; and 3) blood flow was still significantly reduced in the goggled eye in chicks whose goggles were removed two days before measurement- 51% of control. These results show that CBF is reduced by goggles that result in myopic eye growth. These findings have implications for the mechanisms underlying myopic eye growth and for the retinopathy that often attends high myopia. PMID:8482110

  3. Five-year visual acuity outcomes and injection patterns in patients with pro-re-nata treatments for AMD, DME, RVO and myopic CNV

    PubMed Central

    Wecker, Thomas; Ehlken, Christoph; Bühler, Anima; Lange, Clemens; Agostini, Hansjürgen; Böhringer, Daniel; Stahl, Andreas

    2017-01-01

    Background Anti vascular endothelial growth factor (VEGF) therapy is an established treatment for various retinal diseases. Long-term data on injection frequencies and visual acuity (VA), however, are still rare. Methods Five-year analysis of real-life VA developments and injection patterns from 2072 patients (2577 eyes; 33 187 injections) with chronically active disease undergoing pro-re-nata treatment for age-related macular degeneration (AMD), diabetic macular oedema (DME), retinal vein occlusion (RVO) and myopic choroidal neovascularisation (CNV). Results Maximum mean VA gain in year 1 was+5.2 letters in AMD, +6.2 in DME, +10 in RVO and+7.2 in myopic CNV. Over 5 years, however, VA in patients with AMD declined. By year 5, 34% of patients with AMD had experienced VA loss of >15 letters, 56% had remained stable and 10% had gained >15 letters. Long-term VA developments in DME and RVO were more favourable with 81% of DME and 79% of patients with RVO gaining or maintaining vision at 5 years. In AMD, median injection frequency was six in year 1 and between four and five in consecutive years. In DME and RVO, median injection frequency was six in year 1 but lower compared with AMD in consecutive years. Injection frequency in DME was weakly associated with patient age (rs=0.1; p=0.03). Conclusions In AMD, the initial VA gain was not maintained long term despite higher injection numbers compared with DME, RVO and myopic CNV. The presented real-world data provide a peer-group-based estimate of VA developments and injection frequencies for counselling patients undergoing long-term anti-VEGF therapy. PMID:27215744

  4. Five-year visual acuity outcomes and injection patterns in patients with pro-re-nata treatments for AMD, DME, RVO and myopic CNV.

    PubMed

    Wecker, Thomas; Ehlken, Christoph; Bühler, Anima; Lange, Clemens; Agostini, Hansjürgen; Böhringer, Daniel; Stahl, Andreas

    2017-03-01

    Anti vascular endothelial growth factor (VEGF) therapy is an established treatment for various retinal diseases. Long-term data on injection frequencies and visual acuity (VA), however, are still rare. Five-year analysis of real-life VA developments and injection patterns from 2072 patients (2577 eyes; 33 187 injections) with chronically active disease undergoing pro-re-nata treatment for age-related macular degeneration (AMD), diabetic macular oedema (DME), retinal vein occlusion (RVO) and myopic choroidal neovascularisation (CNV). Maximum mean VA gain in year 1 was+5.2 letters in AMD, +6.2 in DME, +10 in RVO and+7.2 in myopic CNV. Over 5 years, however, VA in patients with AMD declined. By year 5, 34% of patients with AMD had experienced VA loss of >15 letters, 56% had remained stable and 10% had gained >15 letters. Long-term VA developments in DME and RVO were more favourable with 81% of DME and 79% of patients with RVO gaining or maintaining vision at 5 years. In AMD, median injection frequency was six in year 1 and between four and five in consecutive years. In DME and RVO, median injection frequency was six in year 1 but lower compared with AMD in consecutive years. Injection frequency in DME was weakly associated with patient age (rs=0.1; p=0.03). In AMD, the initial VA gain was not maintained long term despite higher injection numbers compared with DME, RVO and myopic CNV. The presented real-world data provide a peer-group-based estimate of VA developments and injection frequencies for counselling patients undergoing long-term anti-VEGF therapy. 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/.

  5. Dengue associated choroiditis: a rare entity.

    PubMed

    Yadav, Harshali Manish; Dutta Majumder, Parthopratim; Biswas, Jyotirmay

    2017-12-01

    We report a case of choroiditis during dengue fever. A 35-year-old female presented with blurring of vision during dengue fever. Her fundus examination revealed yellow deep choroidal lesions at right macula, multiple small, yellowish subretinal macular dots along papillomacular bundle, and hyperemic disc. There was a small retinal hemorrhage at temporal margin of disc. The left eye had similar small discrete lesion superonasal and inferotemporal to macula. We report a hitherto undescribed case of choroiditis in a dengue patient.

  6. Choroidal thickness profile in healthy Indian children

    PubMed Central

    Chhablani, Jay Kumar; Deshpande, Riddhima; Sachdeva, Virender; Vidya, Sagar; Rao, P Srinivasa; Panigati, Anand; Mahat, Birendra; Pappuru, Rajeev Reddy; Pehere, Niranjan; Pathengay, Avinash

    2015-01-01

    Purpose: The purpose was to study choroidal thickness and its profile based on location in healthy Indian children using enhanced depth spectral-domain-optical coherence tomography (SD-OCT). Methods: In this cross-sectional observational study 255 eyes of 136 children with no retinal or choroidal disease were consecutively scanned using enhanced depth SD-OCT. Eyes with any ocular disease or axial length (AXL) >25 mm or < 20 mm were excluded. A single observer measured choroidal thickness from the posterior edge of the retinal pigment epithelium to the choroid/sclera junction at 500-microns intervals up to 2500 microns temporal and nasal to the fovea. Generalized estimating equations were used to evaluate the correlation between choroidal thickness at various locations and age, AXL, gender and spherical equivalent (SEq). Results: Mean age of the subjects was 11.9 ± 3.4 years (range: 5–18 years). There were 62 Females and 74 males. The mean AXL was 23.55 ± 0.74 mm. Mean subfoveal choroidal thickness was 312.1 ± 45.40 μm. Choroid was found to be thickest subfoveally, then temporally. Age, AXL and SEq showed a significant correlation with choroidal thickness, whereas gender did not affect choroidal thickness. Conclusion: Our study provides a valid normative database of choroidal thickness in healthy Indian children. This database could be useful for further studies evaluating choroidal changes in various chorioretinal disorders. Age and AXL are critical factors, which negatively correlated with choroidal thickness. PMID:26265634

  7. Cooperation enhanced by moderate tolerance ranges in myopically selective interactions

    NASA Astrophysics Data System (ADS)

    Chen, Xiaojie; Wang, Long

    2009-10-01

    We present a mode of myopically selective interaction to study the evolutionary prisoner’s dilemma game in scale-free networks. Each individual has a reputation-based tolerance range and only tends to interact with the neighbors whose reputation is within its tolerance range. Moreover, its reputation is assessed in response to the interactions in the neighborhood. Interestingly, we show that moderate values of tolerance range can result in the best promotion of cooperation due to the emergence of group selection mechanism. Furthermore, we study the effects of weighting factor in the assessment rule of reputation on the evolution of cooperation. We also show how cooperation evolves in some extended situations, where an interaction stimulus payment is considered for individuals, and where the strategy and reputation of individuals can spread simultaneously. Our results may enhance the understanding of evolutionary dynamics in graph-structured populations where individuals conditionally play with their neighbors according to some myopic selection criteria.

  8. Effect of irradiation on neovascularization in rat skinfold chambers: Implications for clinical trials of low-dose radiotherapy for wet-type age-related macular degeneration

    SciTech Connect

    Hori, Katsuyoshi . E-mail: k-hori@idac.tohoku.ac.jp; Saito, Sachiko; Tamai, Makoto

    2004-12-01

    Purpose: Wet-type age-related macular degeneration is a refractory eye disease that involves choroidal neovascularization. Randomized controlled trials of low-dose radiotherapy for this disease performed in Japan showed that, at 12 months of follow-up, visual acuity was significantly well preserved and the neovascular membrane size decreased. Because understanding the effect of irradiation on new vascular networks is an important prerequisite for clinical trials, we used a rat skinfold chamber technique to investigate X-ray-induced changes in neovasculature microcirculation. Methods and materials: Neovascularization was induced in rat skinfold chambers via polyvinyl chloride resin plates. Neovessels were irradiated in a single 10-Gy dose, after which, changes in vascular density, blood velocity, tissue blood flow, and interstitial fluid pressure (IFP), were measured. Results: Vascular density, tissue blood flow, and IFP measurements in resin-induced inflammatory tissue were much higher than those measurements in normal tissue. Although overall blood velocity was low and sluggish or blood-flow stasis occurred in the neovascular network, after a single 10-Gy dose of radiation, the velocity increased, stasis improved markedly, and many dilated vessels narrowed. Thereafter, vascular density, blood flow, and IFP significantly decreased and approached normal values. Conclusion: These findings may help explain clinical results related to radiotherapy-induced changes in neovascular membranes in age-related macular degeneration. Both vascular morphology and vascular function in inflammatory tissue returned to normal, without vessel destruction, after an appropriate radiation dose.

  9. Fundus autofluorescence of choroidal nevus and melanoma

    PubMed Central

    Lavinsky, Daniel; Belfort, Rubens N; Navajas, Eduardo; Torres, Virginia; Martins, Maria Cristina; Belfort, Rubens

    2007-01-01

    Background To describe autofluorescence patterns of choroidal melanocytic lesions using the Heidelberg Retinal Angiograph 2 system (HRA2). Methods 20 patients with choroidal melanocytic lesions in the ocular fundus underwent ophthalmologic examination, fundus photography, autofluorescence and optical coherence tomography (OCT). Pathologic examination was performed on one enucleated eye with a large choroidal melanoma. Results 15 patients had choroidal nevi and 5 had malignant choroidal melanoma (1 small, 1 medium and 3 large tumours). Choroidal nevi did not show any characteristic autofluorescence pattern, although secondary retinal pigment epithelium (RPE) changes, such as drusen and pigment epithelium detachment, appeared faintly hyperautofluorescent in 2 patients. Only the small malignant choroidal melanomas had prominent orange pigmentation, although all melanomas had an intense confluent hyperautofluorescent signal over the lesions. Pathology of one large malignant melanoma revealed lipofuscin underlying RPE. Conclusion Most nevi did not have characteristic hyperautofluorescent features, but choroidal melanomas seemed to have a pattern of confluent hyperautofluorescence. Therefore, autofluorescence may be a useful non‐invasive tool to assess lipofuscin in pigmented choroidal lesions, which may contribute to the diagnosis of malignancy. This hypothesis, however, remains to be confirmed in large prospective studies. PMID:17431017

  10. Verteporfin photodynamic therapy for the treatment of choroidal haemangioma associated with Sturge-Weber syndrome.

    PubMed

    Hussain, Rumana N; Jmor, Fidan; Damato, Bertil; Heimann, Heinrich

    2016-09-01

    Choroidal haemangiomas associated with Sturge Weber syndrome most commonly affect the posterior pole and consequently result in amblyopia. Treatment is often challenging but usually unwarranted unless there is visual deterioration caused by exudative or neovascular complications. The main objective is to demonstrate the effectivity of photodynamic therapy in this context. Retrospective analysis of prospectively collected data regarding verteporfin photodynamic therapy (PDT) in the treatment of patients with choroidal haemangiomas associated with Sturge Weber syndrome. Six patients (4 male, 2 female) with a median age of 28 years (range, 23-67) had a mean tumour belly diameter of 12.2mm (range, 9-16.8). There was regression of the tumour in all cases, albeit after 3 treatments in a single case. The exudative retinal detachment resolved in 2 out of 3 patients. Visual outcome improved in 3 patients, remaining poor but stable in the other three, due to pre-existing amblyopia. PDT is an effective and safe treatment for patients with choroidal haemangioma associated with Sturge-Weber syndrome. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Airbag-Associated Severe Blunt Eye Injury Causes Choroidal Rupture and Retinal Hemorrhage: A Case Report

    PubMed Central

    Wang, Shih Hao; Lim, Chen Chee; Teng, Yu Ti

    2017-01-01

    A case of choroidal rupture caused by airbag-associated blunt eye trauma and complicated with massive subretinal hemorrhage and vitreous hemorrhage that was successfully treated with intravitreal injection of expansile gas and bevacizumab is presented. A 53-year-old man suffered from loss of vision in his right eye due to blunt eye trauma by a safety airbag after a traffic accident. On initial examination, the patient had no light perception in his right eye. Dilated ophthalmoscopy revealed massive subretinal hemorrhage with macular invasion and faint vitreous hemorrhage. We performed intravitreal injection of pure sulfur hexafluoride twice for displacement, after which visual acuity improved to 0.03. For persistent subretinal hemorrhage and suspicion of choroidal neovascularization (CNV), intravitreal bevacizumab (1.25 mg/0.05 mL) injection was administered. After 3 weeks, the visual acuity of his right eye recovered to 0.4. For early-stage choroidal rupture-induced subretinal hemorrhage and complications of suspected CNV, intravitreal injection of expandable gas and intraocular injection of antiangiogenesis drugs seem to be an effective treatment. PMID:28203191

  12. Myopic astigmatism a substitute for accommodation in pseudophakia.

    PubMed

    Huber, C

    1981-12-16

    The power of an intraocular lens can be calculated before surgery to make the eye emmetropic or ametropic. The physiological mechanism of accommodation however, cannot be restored with an inelastic lens. An increased depth of focus in the implanted eye can be predicted through optical principles alone, if the postoperative ametropia of the implanted eye is a simple myopic astigmatism. This increased depth of focus without accommodation was tested in artificial ametropia and found to be used in nature by the seal. To increase the precision of intraocular lens calculation the average change in corneal power induced at surgery is used to predict the postoperative corneal power. By controlled suture release in the postoperative phase, the amount of induced corneal astigmatism is adjusted to obtain a simple myopic astigmatism. Patients with an intraocular lens and a simple myopic astigmatism as a residual ametropia, are spectacle independent most of the time. They need their glasses only for driving or prolonged reading. The methods used to calculate the postoperative cornea, the postoperative anterior chamber depth and the intraocular lens are described with the corresponding calculator programs for the HP 41C calculator. Clinical results and measurements of the depth of focus are shown in a series of 50 successive implant cases.

  13. Ocular Biometrics of Myopic Eyes With Narrow Angles.

    PubMed

    Chong, Gabriel T; Wen, Joanne C; Su, Daniel Hsien-Wen; Stinnett, Sandra; Asrani, Sanjay

    2016-02-01

    The purpose of this study was to compare the ocular biometrics between myopic patients with and without narrow angles. Patients with a stable myopic refraction (myopia worse than -1.00 D spherical equivalent) were prospectively recruited. Angle status was assessed using gonioscopy and biometric measurements were performed using an anterior segment optical coherence tomography and an IOLMaster. A total of 29 patients (58 eyes) were enrolled with 13 patients (26 eyes) classified as having narrow angles and 16 patients (32 eyes) classified as having open angles. Baseline demographics of age, sex, and ethnicity did not differ significantly between the 2 groups. The patients with narrow angles were on average older than those with open angles but the difference did not reach statistical significance (P=0.12). The central anterior chamber depth was significantly less in the eyes with narrow angles (P=0.05). However, the average lens thickness, although greater in the eyes with narrow angles, did not reach statistical significance (P=0.10). Refractive error, axial lengths, and iris thicknesses did not differ significantly between the 2 groups (P=0.32, 0.47, 0.15). Narrow angles can occur in myopic eyes. Routine gonioscopy is therefore recommended for all patients regardless of refractive error.

  14. Spontaneous Necrosis of Choroidal Melanoma

    PubMed Central

    Thareja, Shalini; Rashid, Alia; Grossniklaus, Hans E.

    2014-01-01

    Background/Aims The purpose of this study was to examine the clinical presentations and pathological features of spontaneously necrotic choroidal melanomas. Methods The clinical and histological features of patients who underwent enucleation for uveal melanoma from 1989 to 2012 at Emory University and were found to have spontaneously necrotic choroidal melanomas were retrospectively analyzed. Results A total of 6 cases were identified. All cases had 90-100% tumor necrosis and also exhibited marked ischemic necrosis of the iris and ciliary body; 5 of 6 cases exhibited marked ischemic necrosis of the retina. The tumor consisted of melanoma ghost cells often surrounded by a zone of pigmented macrophages. Thrombi were not found in any of the cases. All of the tumors in our cases were centered around the equatorial choroid and 2 extended into the ciliary body. One of the cases exhibited a wedge-shaped infarct in a lateral aspect of the tumor. In most of the cases, microscopic areas of intact tumor cells were present in the peripheries of the tumors. Conclusions Spontaneous necrosis may occur in uveal melanoma. We believe that this occurs secondary to tumor hypoxia in the center of the tumor, followed by secondary inflammation, generalized ischemia and finally complete tumor necrosis. PMID:27175363

  15. Spectral-Domain Optical Coherence Tomography of Polypoidal Choroidal Vasculopathy Associated With Benign Choroidal Nevus.

    PubMed

    De Salvo, Gabriella; Vaz-Pereira, Sara; Sehmi, Kulwant S; Andrews, Richard M; Sagoo, Mandeep S

    2015-01-01

    Two cases of polypoidal choroidal vasculopathy (PCV) complicating benign choroidal nevus and their tomographic features at spectral-domain optical coherence tomography (SD-OCT) are reported. Two eyes with choroidal nevus and associated subretinal fluid underwent complete ophthalmological examination, SD-OCT, fundus fluorescein angiography, and indocyanine green angiography (ICGA). SD-OCT and ICGA confirmed the diagnosis of PCV in both cases. Ophthalmologists should be aware of this rare combination between choroidal nevus and PCV. If a choroidal nevus presents with subretinal fluid, this does not always herald malignant transformation, and PCV should be ruled out so that the correct treatment can be planned.

  16. Indocyanine green mediated photothrombosis for the management of predominantly classic choroidal neovascularisation caused by age related macular degeneration

    PubMed Central

    Farah, M E; Cardillo, J A; Luzardo, A C; Calucci, D; Williams, G A; Costa, R A

    2004-01-01

    Aims: To study the effectiveness of indocyanine green mediated photothrombosis in the management of predominantly classic subfoveal choroidal neovascularisation associated with age related macular degeneration. Methods: Prospective, non-comparative, interventional case series of nine patients with predominantly classic subfoveal choroidal neovascularisation secondary to age related macular degeneration who declined photocoagulation or verteporfin photodynamic therapy. Patients were submitted to one or more treatments with an intravenous injection of a small volume of high concentration indocyanine green solution followed by low irradiance, large spot 810 nm continuous laser application via a transpupillary approach. Main outcome measures were change in best corrected visual acuity and macular exudative manifestations. Results: After 12 months of follow up, the final best corrected visual acuity was the same (plus or minus two ETDRS lines) in five eyes (55%), improved more than two ETDRS lines in three eyes (33%), and worsened by more than two lines in the remaining eye. The improved vision was probably related to partial or complete restoration of the macular architecture as a result of fluid resolution, whereas the worsened vision was primarily the result of treatment failure in achieving substantial choroidal neovascular occlusion. There were no complications related to the procedure. Conclusion: Indocyanine green mediated photothrombosis may be an effective alternative treatment for predominantly classic subfoveal choroidal neovascularisation caused by age related macular degeneration. PMID:15258024

  17. Choroidal thickness changes after intravitreal ranibizumab and photodynamic therapy in recurrent polypoidal choroidal vasculopathy.

    PubMed

    Maruko, Ichiro; Iida, Tomohiro; Oyamada, Hiroshi; Sugano, Yukinori; Ojima, Akira; Sekiryu, Tetsuju

    2013-09-01

    To evaluate subfoveal choroidal thickness changes in cases with recurrent polypoidal choroidal vasculopathy (PCV) after combination therapy with intravitreal ranibizumab and photodynamic therapy (PDT). Retrospective observational case series study. We measured subfoveal choroidal thickness in PCV using optical coherence tomography (OCT) before and after PDT. In recurrent cases, the choroidal thickness was measured at the time of the recurrence. In nonrecurrent cases, choroidal thickness was measured 1 year after PDT. Combination therapy was performed in 27 eyes (27 patients). Polypoidal lesions regressed within 3 months after initial treatment in all eyes. Retreatment was needed in 10 of 27 eyes (37.0%) after more than 3 months of follow-up. In recurrent cases, subfoveal choroid decreased from 188 μm at baseline to 157 μm 3 months after PDT (P < .01); however, choroidal thickness increased to 179 μm with recurrence (P = .54 compared to baseline; average, 8.0 months). In nonrecurrent cases, subfoveal choroid decreased from 257 μm at baseline to 210 μm 3 months after PDT and 212 μm 1 year after PDT (P < .01, respectively). Subfoveal choroidal thickness in PCV at the time of recurrence returned to the baseline level after choroidal thinning as a result of PDT treatment. Choroidal thickness changes after PDT examined using OCT may reflect disease activity in PCV. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Aflibercept for neovascular age-related macular degeneration

    PubMed Central

    Sarwar, Salman; Clearfield, Elizabeth; Soliman, Mohamed Kamel; Sadiq, Mohammad Ali; Baldwin, Andrew J; Hanout, Mostafa; Agarwal, Aniruddha; Sepah, Yasir J; Do, Diana V; Nguyen, Quan Dong

    2016-01-01

    Background Central vision loss caused by age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Neovascular AMD is characterized by choroidal neovascularization (CNV). Growth of new blood vessels in patients with neovascular AMD is driven by a complex process that involves a signal protein called vascular endothelial growth factor A (VEGF-A). Anti-VEGF drugs that block this protein include ranibizumab, bevacizumab, and aflibercept. Objectives To assess and compare the effectiveness and safety of intravitreal injections of aflibercept versus ranibizumab, bevacizumab, or sham for treatment of patients with neovascular AMD. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (Issue 11, 2015), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), PubMed (1948 to November 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched December 4, 2014), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on November 30, 2015. Selection criteria We included randomized controlled trials (RCTs) in which aflibercept monotherapy was compared with ranibizumab, bevacizumab, or sham for participants with neovascular AMD who were treatment-naive. Data collection and analysis We used standard methodological procedures of The Cochrane Collaboration for screening, data abstraction, and study assessment. Two review authors

  19. Morphologic Characteristics of Choroid in the Major Choroidal Thickening Diseases, Studied by Optical Coherence Tomography

    PubMed Central

    Kang, Se Woong; Woo, Se Joon; Ryoo, Na-Kyung; Kim, Sang Jin; Han, Gyule

    2016-01-01

    We investigated morphologic features of choroid in the choroidal thickening diseases, including central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV), and Vogt-Koyanagi-Harada disease (VKH), by a novel tomographic classification system of the choroid. This cross-sectional study involved 30 patients with active CSC, 30 patients with active PCV, and 27 patients with active VKH, and 30 normal controls. Utilizing enhanced depth imaging optical coherence tomography, we classified the morphology of the choroid into five categories: 1) Standard (S), 2) Dilated outer layer and Attenuated inner layer (DA), 3) Darkened (D), 4) Marbled (M), and 5) Pauci-Vascular (PV) types. Additional tomographic characteristics of the choroid such as choroidal vascular dilation, convolution, scleral invisibility, and choroidal hyper- or hypo-thickening were identified as well. The distribution of five choroidal tomographic morphology and additional tomographic characteristics in each group were analyzed. The DA type was observed in the CSC group more frequently than in the normal control group (53.3% vs 3.3%, P < 0.001). Additional tomographic characteristics, such as choroidal vascular dilation (76.7%), and choroidal hyper-thickening (36.7%), were more prevalent in the CSC group than in the control group. The PCV group showed higher prevalence of DA type (33.3% vs. 3.3%, P = 0.006) than the control group. The VKH group showed a significantly higher frequency of the D type (63.0%), convolution (40.7%), and scleral invisibility (70.4%) than controls (0% for all three findings). In conclusion, CSC and PCV shared common morphologic characteristics of choroid, including dilated outer vascular layer and focally attenuated innermost layer. Dense hypo-reflectivity and convolution of choroid were the specific tomographic markers for acute VKH. A new tomographic classification system of choroid may provide discrimination ability and insight into major pachychoroidopathies

  20. Bietti crystalline dystrophy and choroidal neovascularisation.

    PubMed

    Gupta, B; Parvizi, S; Mohamed, M D

    2011-02-01

    Bietti crystalline dystrophy is a rare autosomal recessive condition characterised by the presence of crystals in the retina and is followed by retinal and choroidal degeneration. We present a novel finding of juxtafoveal choroidal neovascularisation in Bietti crystalline dystrophy and demonstrate a spectral domain optical coherence tomography image of this disorder.

  1. Vascular tumors of the choroid and retina

    PubMed Central

    Shanmugam, P Mahesh; Ramanjulu, Rajesh

    2015-01-01

    Vascular tumors of the retina and choroid can be seen occasionally. In the following article, the key clinical and diagnostic features of the major retinal and choroidal vascular tumors, their systemic associations, and the literature pertaining to the most currently available treatment strategies are reviewed. PMID:25827544

  2. Schistosomotic choroiditis. II. Report of first case.

    PubMed Central

    Pittella, J. E.; Oréfice, F.

    1985-01-01

    The first case of granulomatous choroiditis produced by Schistosoma mansoni with histological confirmation is reported. The patient had the hepatosplenic and cardiopulmonary forms of the disease and presented with cerebral schistosomiasis. The funduscopic aspects of the lesion and the possible pathways taken by the parasite to reach the choroid are discussed. Images PMID:3994947

  3. Vascular tumors of the choroid and retina.

    PubMed

    Shanmugam, P Mahesh; Ramanjulu, Rajesh

    2015-02-01

    Vascular tumors of the retina and choroid can be seen occasionally. In the following article, the key clinical and diagnostic features of the major retinal and choroidal vascular tumors, their systemic associations, and the literature pertaining to the most currently available treatment strategies are reviewed.

  4. Choroidal osteoma: acoustic shadowing and reduplication echoes.

    PubMed

    Abramson, D H; Servodidio, C A; Poole, T A; Budinger, K

    1996-12-01

    A 27-year-old woman had a curious choroidal mass of 12 years duration in her right eye. Interesting ultrasonic findings of a choroidal osteoma, including acoustic shadowing and reduplication echoes on A-scan and B-scan are presented. Ophthalmic nurses can assist in performing ophthalmic examinations and in reinforcing regular follow-up examinations for these patients.

  5. Indocyanine green fluorescence angiography of the choroid.

    PubMed Central

    Craandijk, A; Van Beek, C A

    1976-01-01

    Indocyanine green fluorescence (ICG) angiography of the choroid gives better visualization of the choroidal vessels than does fluorescein angiography. We found that the detachment of the pigment epithelium seems bigger on ICG than on fluorescein angiograms, and pigmented lesions are more clearly delineated. Images PMID:952809

  6. Peripapillary choroidal thickness in healthy Chinese subjects

    PubMed Central

    2013-01-01

    Background To evaluate the peripapillary choroidal thickness of a healthy Chinese population, and to determine its influencing factors. Methods A total of 76 healthy volunteers (76 eyes) without ophthalmic or systemic symptoms were enrolled. Choroidal scans (360-degree 3.4 mm diameter peripapillary circle scans) were obtained for all eyes using enhanced depth imaging spectral-domain optical coherence tomography. Choroid thickness was measured at the temporal, superotemporal, superior, superonasal, nasal, inferonasal, inferior, and inferotemporal segments. Results The average peripapillary choroidal thicknesses were 165.03 ± 40.37 μm. Inferonasal, inferior, and inferotemporal thicknesses were significantly thinner than temporal, superotemporal, superior, superonasal, nasal thicknesses (p < 0.05). No statistically significant difference was found among inferonasal, inferior, and inferotemporal thicknesses. The average peripapillary choroidal thickness decreased linearly with age (β = −1.33, 95% CI −1.98, -0.68, P < 0.001). No correlation was noted between average choroidal thickness and other factors (gender, refractive error, axial length, average retinal nerve fiber layer thickness, intraocular pressure, diastolic blood pressure, systolic blood pressure, mean blood pressure, diastolic ocular perfusion pressure, systolic ocular perfusion pressure, and mean ocular perfusion pressure). Conclusions The inferonasal, inferior, inferotemporal peripapillary choroidal thicknesses were significantly thinner than temporal, superotemporal, superior, superonasal, and nasal thicknesses. A thinner peripapillary choroid is associated with increasing age. PMID:23758729

  7. Human tears reveal insights into corneal neovascularization.

    PubMed

    Zakaria, Nadia; Van Grasdorff, Sigi; Wouters, Kristien; Rozema, Jos; Koppen, Carina; Lion, Eva; Cools, Nathalie; Berneman, Zwi; Tassignon, Marie-José

    2012-01-01

    Corneal neovascularization results from the encroachment of blood vessels from the surrounding conjunctiva onto the normally avascular cornea. The aim of this study is to identify factors in human tears that are involved in development and/or maintenance of corneal neovascularization in humans. This could allow development of diagnostic tools for monitoring corneal neovascularization and combination monoclonal antibody therapies for its treatment. In an observational case-control study we enrolled a total of 12 patients with corneal neovascularization and 10 healthy volunteers. Basal tears along with reflex tears from the inferior fornix, superior fornix and using a corneal bath were collected along with blood serum samples. From all patients, ocular surface photographs were taken. Concentrations of the pro-angiogenic cytokines interleukin (IL)-6, IL-8, Vascular Endothelial Growth Factor (VEGF), Monocyte Chemoattractant Protein 1 (MCP-1) and Fas Ligand (FasL) were determined in blood and tear samples using a flow cytometric multiplex assay. Our results show that the concentration of pro-angiogenic cytokines in human tears are significantly higher compared to their concentrations in serum, with highest levels found in basal tears. Interestingly, we could detect a significantly higher concentration of IL- 6, IL-8 and VEGF in localized corneal tears of patients with neovascularized corneas when compared to the control group. This is the first study of its kind demonstrating a significant difference of defined factors in tears from patients with neovascularized corneas as compared to healthy controls. These results provide the basis for future research using animal models to further substantiate the role of these cytokines in the establishment and maintenance of corneal neovascularization.

  8. Human Tears Reveal Insights into Corneal Neovascularization

    PubMed Central

    Wouters, Kristien; Rozema, Jos; Koppen, Carina; Lion, Eva; Cools, Nathalie; Berneman, Zwi; Tassignon, Marie-José

    2012-01-01

    Corneal neovascularization results from the encroachment of blood vessels from the surrounding conjunctiva onto the normally avascular cornea. The aim of this study is to identify factors in human tears that are involved in development and/or maintenance of corneal neovascularization in humans. This could allow development of diagnostic tools for monitoring corneal neovascularization and combination monoclonal antibody therapies for its treatment. In an observational case-control study we enrolled a total of 12 patients with corneal neovascularization and 10 healthy volunteers. Basal tears along with reflex tears from the inferior fornix, superior fornix and using a corneal bath were collected along with blood serum samples. From all patients, ocular surface photographs were taken. Concentrations of the pro-angiogenic cytokines interleukin (IL)-6, IL-8, Vascular Endothelial Growth Factor (VEGF), Monocyte Chemoattractant Protein 1 (MCP-1) and Fas Ligand (FasL) were determined in blood and tear samples using a flow cytometric multiplex assay. Our results show that the concentration of pro-angiogenic cytokines in human tears are significantly higher compared to their concentrations in serum, with highest levels found in basal tears. Interestingly, we could detect a significantly higher concentration of IL- 6, IL-8 and VEGF in localized corneal tears of patients with neovascularized corneas when compared to the control group. This is the first study of its kind demonstrating a significant difference of defined factors in tears from patients with neovascularized corneas as compared to healthy controls. These results provide the basis for future research using animal models to further substantiate the role of these cytokines in the establishment and maintenance of corneal neovascularization. PMID:22590547

  9. ICG videoangiography at very low light level of choroidal neovascularization and of central serous choroidopathy

    NASA Astrophysics Data System (ADS)

    Longobardi, Giuseppe; Ciamberlini, Claudio; Guarnieri, Vittorio; Panzardi, G.; Donati, M. C.

    1996-01-01

    ICG videoangiography has widely demonstrated its importance as an investigation method in several ocular pathologies. By means of an optoelectronic system developed by the authors, many cases of age related macular degeneration and central serous coroidopathy affecting patients of different ages have been investigated. The analysis of the eye fundus infrared-light images obtained allows the clinician to draw medical conclusions otherwise not obtainable with traditional visible-light techniques. A comprehensive survey and discussion of the most significant cases are presented.

  10. [Evaluation of antiangiogenic treatment results in choroidal neovascularization related to pathological myopia].

    PubMed

    Carvalho, Beatriz; Freitas-Costa, Paulo; Pinheiro-Costa, João; Falcão, Manuel; Carneiro, Ângela; Falcão-Reis, Fernando

    2014-01-01

    Introdução: A neovascularização coroideia associada à miopia patológica é uma das principais causas de perda de visão central e irreversível em indivíduos jovens. Os objetivos deste estudo são avaliar os resultados a longo prazo do tratamento antiangiogénico, com ranibizumab e/ou bevacizumab, na neovascularização coroideia associada à miopia patológica e caraterizar os fatores preditivos dos resultados funcionais e anatómicos obtidos.Material e Métodos: Avaliámos os resultados de 84 olhos de 81 doentes com neovascularização coroideia miópica, dos quais 84 (100%) completaram 12 meses de seguimento, 67 (79,8%) 24 meses de seguimento, 54 (64,3%) 36 meses de seguimento, 29 (34,5%) 48 meses de seguimento e 15 (16,7%) 60 meses de seguimento. Procedemos à recolha de dados relativos à melhor acuidade visual corrigida em escala ETDRS, espessura foveal na tomografia de coerência óptica e caraterísticas da angiografia fluoresceínica, inicial e após tratamento.Resultados: As melhorias na melhor acuidade visual corrigida e na espessura foveal foram significativas para todos os tempos de seguimento (p < 0,05). A média da melhor acuidade visual corrigida inicial era de 43,7 ± 20,1 letras e da espessura foveal inicial de 304,8 ± 127,9μm. As médias da melhor acuidade visual corrigida foram de 55,6 ± 18,5, 52,1 ± 22,3, 52,1 ± 22,6, 50,3 ± 23,8 e 47,8 ± 24,5 para os 12, 24, 36, 48 e 60 meses de tratamento, respetivamente. As médias das espessuras foveais foram de 209,7 ± 86,2, 190,6 ± 76,1, 174,7 ± 60,6, 189,8 ± 96,7 e 159,4 ± 73,3 para os mesmos tempos de seguimento. Apenas a melhor acuidade visual corrigida inicial foi preditiva de melhores resultados na melhor acuidade visual corrigida final (p < 0,001).Discussão/Conclusão: As injecções intravítreas de anti-VEGF em doentes com neovascularização coroideia miópica cursam com uma melhoria funcional e anatómica significativa e sustentada no tempo. Ensaios clínicos randomizados com follow-up mais extenso são necessários para comprovar a eficácia sustentada destes agentes.

  11. Analysis of the Serum Lipid Profile in Polypoidal Choroidal Vasculopathy

    PubMed Central

    Li, Miaoling; Zhang, Xiongze; Liao, Nanying; Ye, Baikang; Peng, Yuting; Ji, Yuying; Wen, Feng

    2016-01-01

    Polypoidal choroidal vasculopathy (PCV), the predominant subtype of neovascular age-related macular degeneration in the Asian population, is associated with genetic polymorphism of lipid metabolism. In this study, we performed the untargeted lipidomics approach of ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) to reveal the potential discriminating lipid profile of PCV patients in serum (21 PCV patients and 19 age-matched controls). Unsupervised principal component, supervised orthogonal partial least squares analysis, correlation analysis, and heatmap analysis were performed with the data obtained by UPLC-MS. Forty–one discriminating metabolites were identified. Receiver operating characteristic curve analysis, pathway analysis and functional analysis were performed subsequently, and platelet-activating factor (PAF) was further selected as the key indicator of the distinct lipid metabolism in PCV patients. Finally, the serum level of PAF was validated by enzyme-linked immunosorbent assay, which is significantly higher in PCV patients compared to controls (65 PCV patients and 63 age-matched controls, p < 0.0001), consistent with the UPLC-MS analysis. Our results suggested that PAF is considered as the major indicator of the distinct lipid metabolism in PCV patients. PMID:27910906

  12. Choroidal thickness in traumatic optic neuropathy.

    PubMed

    Lee, Ju-Yeun; Eo, Doo-Ri; Park, Kyung-Ah; Oh, Sei Yeul

    2017-09-22

    To examine the choroidal thickness in patients with indirect traumatic optic neuropathy (TON) Methods: Patients with unilateral traumatic optic neuropathy over a period of 4 years were included in this study. Horizontal and vertical enhanced-depth imaging (EDI) from spectral-domain optical coherence tomography (SD-OCT) scans of the fovea were obtained in patients with unilateral TON within 2 weeks of injury. The main outcome measure was the choroidal thickness at nine locations. The choroidal thickness was compared between affected and unaffected eyes in the TON group, and the mean difference in the choroidal thickness in both eyes was compared between TON and control groups. A total of 16 patients and 20 control subjects were included. The choroidal thickness at horizontal, vertical and average subfoveal, inner temporal, and outer inferior locations was significantly thicker (13-23%) in affected eyes than in unaffected fellow eyes (p = 0.042, 0.046, 0.024, 0.013, 0.018, and 0.027, respectively). The mean difference value between choroidal thickness measurements in both eyes was significantly larger in the TON group than in the control group at the horizontal, vertical and average subfoveal, inner temporal, inner nasal, inner superior, inner inferior, and outer superior locations (p = 0.001, 0.011, <0.001, 0.001, 0.033, 0.014, 0.011, and 0.014, respectively). The choroidal thickness at subfoveal locations showed no statistical difference between TON and control eyes (p > 0.05). Eyes affected by TON showed a regionally thicker choroid than unaffected fellow eye. This thick choroid might be due to impaired blood circulation and vascular remodeling of the optic nerve head and choroid. These results help to better understand the pathophysiology of TON.

  13. Gene expression signatures in tree shrew choroid in response to three myopiagenic conditions

    PubMed Central

    He, Li; Frost, Michael R.; Siegwart, John T.; Norton, Thomas T.

    2014-01-01

    We examined gene expression in tree shrew choroid in response to three different myopiagenic conditions: minus lens (ML) wear, form deprivation (FD), and continuous darkness (DK). Four groups of tree shrews (n = 7 per group) were used. Starting 24 days after normal eye opening (days of visual experience [DVE]), the ML group wore a monocular −5 D lens for 2 days. The FD group wore a monocular translucent diffuser for 2 days. The DK group experienced continuous darkness binocularly for 11 days, starting at 17 DVE. An age-matched normal group was examined at 26 DVE. Quantitative PCR was used to measure the relative (treated eye vs. control eye) differences in mRNA levels in the choroid for 77 candidate genes. Small myopic changes were observed in the treated eyes (relative to the control eyes) of the ML group (−1.0 ± 0.2 D; mean ± SEM) and FD group (−1.9 ± 0.2 D). A larger myopia developed in the DK group (−4.4 ± 1.0 D) relative to Normal eyes (both groups, mean of right and left eyes). In the ML group, 28 genes showed significant differential mRNA expression; eighteen were down-regulated. A very similar pattern occurred in the FD group; twenty-seven of the same genes were similarly regulated, along with five additional genes. Fewer expression differences in the DK group were significant compared to normal or the control eyes of the ML and FD groups, but the pattern was similar to that of the ML and FD differential expression patterns. These data suggest that, at the level of the choroid, the gene expression signatures produced by “GO” emmetropization signals are highly similar despite the different visual conditions. PMID:25072854

  14. Association Between Choroidal Thickness and Metabolic Activity on Positron Emission Tomography in Eyes With Choroidal Melanoma.

    PubMed

    Lee, Ji Hwan; Lee, Sung Chul; Cho, Arthur; Keum, Ki Chang; Suh, Yang-Gun; Lee, Christopher Seungkyu

    2015-12-01

    To investigate the relationship between subfoveal choroidal thickness and metabolic activity in eyes with choroidal melanoma. Retrospective, interventional case series. The medical records of 16 patients with unilateral choroidal melanoma who underwent ruthenium (Ru) 106 brachytherapy with adjuvant transpupillary thermotherapy and who had available pretreatment positron emission tomography-computed tomography (PET-CT) images were retrospectively reviewed. Subfoveal choroidal thickness was measured in tumor eyes and in unaffected fellow eyes using enhanced-depth imaging spectral-domain optical coherence tomography (EDI OCT). Tumor eyes were divided into 2 groups (metabolically active and inactive) based on PET-CT findings and subfoveal choroidal thickness was compared between groups. Additionally, choroidal thickness measurements were compared before and after treatment. Before treatment, mean choroidal thickness was 293.31 ± 46.80 μm in tumor eyes and 242.44 ± 65.37 μm in fellow eyes, a difference that was statistically significant (P = .003). Eyes with metabolically active tumors had a significantly thicker choroid (348.00 ± 17.32 μm) than eyes with metabolically inactive tumors (280.69 ± 42.04 μm, P = .019). In tumor eyes, mean choroidal thickness significantly decreased from pretreatment values to 253.56 ± 61.27 μm 6 months after treatment (P = .018). Eyes with choroidal melanoma had thicker choroids than unaffected fellow eyes. Increased choroidal thickness was more prominent in metabolically active tumors. Choroidal thickness significantly decreased in tumor eyes 6 months after treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Choroidal Imaging with Swept-Source Optical Coherence Tomography in Patients with Birdshot Chorioretinopathy: Choroidal Reflectivity and Thickness.

    PubMed

    Dastiridou, Anna I; Bousquet, Elodie; Kuehlewein, Laura; Tepelus, Tudor; Monnet, Dominique; Salah, Sawsen; Brezin, Antoine; Sadda, Srinivas R

    2017-08-01

    To characterize choroidal thickness and choroidal reflectivity in the eyes of patients with birdshot chorioretinopathy (BSCR). Cross-sectional observational study. Two hundred twenty BSCR patients and 59 healthy controls. Patients with BSCR and healthy controls underwent imaging of the macula in both eyes with a swept-source optical coherence tomography device (DRI-OCT1 Atlantis; Topcon). Images were exported from the device, and analysis was performed by 2 graders in the Doheny Image Reading Center using Image J software. The choroidal thickness at the foveal center was measured. In addition, the inner and outer boundaries of the choroid and retinal pigment epithelium (RPE) as well as the inner retinal surface all were segmented to allow the brightness and reflectivity of the pixels in the choroid, RPE band, and overlying vitreous to be quantified. An adjusted or normalized choroidal reflectivity, with the RPE as the bright reference standard and the vitreous as the dark reference standard, was computed using the formula: normalized choroidal reflectivity = (choroidal reflectivity-vitreous reflectivity)/RPE reflectivity. Choroidal reflectivity and choroidal thickness. Three hundred eighty-six eyes in the BSCR group and 59 eyes in the control group were included in this analysis. Higher choroidal reflectivity and lower choroidal thickness were documented in inactive BSCR patients compared with active BSCR and controls (P < 0.01). Active BSCR patients showed lower choroidal thickness compared with controls (P < 0.01). There was a negative correlation between choroidal reflectivity and choroidal thickness (r = -0.793; P < 0.001). On multiple regression analysis, choroidal thickness, age, and disease duration (all P < 0.01) all were significant predictors of choroidal reflectivity. Choroidal reflectivity and choroidal thickness changes are evident in active and inactive BSCR patients. Novel choroidal parameters such as choroidal reflectivity may warrant further

  16. Acute transient myopic shift induced by red wine: a case report.

    PubMed

    Liu, Ziyuan; Wang, Wei

    2015-01-01

    This case report described a patient presenting with unilateral transient myopic shift after consuming a lot of red wine. Ultrasound biomicroscopy detected annular shallow ciliary body detachment with supraciliary effusion, as well as a narrow chamber angle. The myopic shift was spontaneously resolved about one week after the onset without any treatment.

  17. Optical coherence tomography angiography reproducibility of lesion size measurements in neovascular age-related macular degeneration (AMD).

    PubMed

    Amoroso, Francesca; Miere, Alexandra; Semoun, Oudy; Jung, Camille; Capuano, Vittorio; Souied, Eric H

    2017-08-30

    To evaluate the reproducibility and interuser agreement of measurements of choroidal neovascularisation in optical coherence tomography angiography (OCTA). Prospective non-interventional study. Consecutive patients, presenting with neovascular age-related macular degeneration (AMD), underwent two sequential OCTA examinations (AngioVue, Optovue, Fremont, California, USA), performed by the same trained examiner. Neovascular lesion area was then measured on both examinations in the choriocapillaris automatic segmentation by two masked readers, using the semiautomated measuring software embedded in the instrument. Two measuring features were used: the first corresponding to the total manually contoured lesion area with the flow draw tool (select area) and the second to the total area of solely vessels with high flow within the lesion (vessel area). These measurements were then compared in order to assess both the reproducibility of OCTA examination and the interuser agreement with the embedded software. Forty-eight eyes of 46 patients (77.4 mean age,+/-8.2 SD, range from 62 to 95 years old, eight men, 38 women) were included in our study. Mean choroidal neovascularisation area was of 0.72+/-0.7 mm(2) for the first measurement and 0.75+/-0.76 mm(2) for the second measurement; difference between the first and the second measurement was 0.03 mm(2). Intrauser agreement was of 0.98 (CI 0.98 to 0.99) for both 'vessel area' and 'select area' features. Interuser agreement was of 0.98 (CI 0.97 to 0.99) for 'select area' and 'vessel area' features. Our data suggest that OCTA provide reproducible imaging for evaluation of the neovascular size in the setting of AMD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Influence of Near Tasks on Posture in Myopic Chinese Schoolchildren.

    PubMed

    Bao, Jinhua; Drobe, Björn; Wang, Yuwen; Chen, Ke; Seow, Eu Jin; Lu, Fan

    2015-08-01

    To investigate near-vision posture in Chinese myopic schoolchildren and compare near-vision posture during different near-vision tasks (i.e., playing video games, reading, and writing). The study investigated 120 myopic children (grades 1 through 6 and aged 6 to 13 years). An electromagnetic motion-tracking system was used for continuous measurements of the working distance and head declination of the subjects while they were playing video games or reading or writing at a desk. The reading and writing documents were adjusted by grade level (i.e., grades 1 to 2, 3 to 4, and 5 to 6). For analysis, the subjects were grouped in two refractive groups according to their median spherical equivalent refractive error (-1.50D). The myopic schoolchildren used close working distances for all tasks: 21.3 ± 5.2 cm (video games), 27.2 ± 6.4 cm (reading), and 24.9 ± 5.8 cm (writing). The mean head declinations were 63.5 ± 12.2 deg (video games), 37.1 ± 12.8 deg (reading), and 44.5 ± 14.1 deg (writing). Working distance decreased significantly across time for the reading and writing tasks (p < 0.001). Head declination increased significantly across time only for the reading task (p < 0.001). Grade level significantly influenced working distance, but the difference was not significant when working distance was adjusted by the subject's size. No differences were observed within the refractive or the accommodative lag groups in terms of the posture data (p > 0.05). Working distance was negatively correlated with head declination (r = -0.53, p < 0.001). Close working distances were observed for Chinese myopic schoolchildren. The attention dedicated to each task, the task difficulty, and the page/screen size may affect near working distance and head declination. Handheld video games were associated with the closest working distance, which may be a risk factor for myopia progression, according to previous studies.

  19. [Neovascularization in ocular tissues: mechanisms and role of proangiogenic and antiangiogenic factors].

    PubMed

    Nowak, Jerzy Z; Wiktorowska-Owczarek, Anna

    2004-01-01

    Blood vessel growth and stability are under precise control of an array of pro- and anti-angiogenic factors. Under physiological conditions, actions of particular regulatory factors, as well as their mutual interactions are harmonized and balanced. Disruption of the balance between these pro- and anti-angiogenic factors is characteristic of many vascular diseases, including those occurring within the eye. Functional dominancy of proangiogenic factors (e.g., vascular endothelial growth factor, VEGF) over antiangiogenic ones (e.g., pigment epithelium-derived growth factor, PEDF), which may occur under ischemic conditions, may initiate the process of retinal or choroidal neovascularization, representing a major threat to the eyesight. This article presents and discusses current ideas concerning molecular and cellular processes underlying aberrant growth on new blood vessels in ocular tissues, in relation to microvascular ocular complications associated mainly (but not only), with diabetes mellitus, age-related macular degeneration (AMD), and retinopathy of prematurity (ROP). This review also surveys latest achievements in the field of clinically more effective future therapeutic strategies, including gene therapy applicable to the neovascular eye diseases.

  20. BMP9/ALK1 inhibits neovascularization in mouse models of age-related macular degeneration

    PubMed Central

    Ntumba, Kalonji; Akla, Naoufal; Oh, S. Paul; Eichmann, Anne; Larrivée, Bruno

    2016-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in aging populations of industrialized countries. The drawbacks of inhibitors of vascular endothelial growth factor (VEGFs) currently used for the treatment of AMD, which include resistance and potential serious side-effects, require the identification of new therapeutic targets to modulate angiogenesis. BMP9 signaling through the endothelial Alk1 serine-threonine kinase receptor modulates the response of endothelial cells to VEGF and promotes vessel quiescence and maturation during development. Here, we show that BMP9/Alk1 signaling inhibits neovessel formation in mouse models of pathological ocular angiogenesis relevant to AMD. Activating Alk1 signaling in laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR) inhibited neovascularization and reduced the volume of vascular lesions. Alk1 signaling was also found to interfere with VEGF signaling in endothelial cells whereas BMP9 potentiated the inhibitory effects of VEGFR2 signaling blockade, both in OIR and laser-induced CNV. Together, our data show that targeting BMP9/Alk1 efficiently prevents the growth of neovessels in AMD models and introduce a new approach to improve conventional anti-VEGF therapies. PMID:27517154

  1. Cystic choroid plexus papilloma in the cavum septum pellucidum.

    PubMed

    Tuchman, Alexander; Kalhorn, Stephen P; Mikolaenko, Irina; Wisoff, Jeffrey H

    2009-12-01

    A choroid plexus papilloma is a rare CNS neoplasm arising from the neuroepithelial lining of the choroid plexus. A third ventricular location of a choroid plexus papilloma is rare compared with the more common sites in the lateral and fourth ventricles. Cystic choroid plexus papilloma represents an infrequent subtype that may present diagnostic ambiguity. The authors present a case of cystic choroid plexus papilloma within a cavum septum pellucidum that radiographically mimicked neurocysticercosis.

  2. [Cytogenetic analysis of choroidal melanoma].

    PubMed

    Filloy, A; Caminal, J M; Varela, M M; Gomà, M; Arias, L; Arruga, J

    2014-01-01

    To investigate the presence of known cytogenetic alterations of choroidal melanoma in a series of patients diagnosed and treated in our Ocular Oncology Service. A review of the present literature on this topic is also presented. Microsatellite analysis (MSA) studies on loss of heterozygosity (LOH) of chromosome 3, as well as multiplex ligation prove amplification (MLPA) on chromosomes 1, 3, 6 and 8, were performed on enucleation or local resection samples obtained from a total of 27 patients, over a 2 year period. Twenty patients showed at least one of the cytogenetic alterations looked for. A total of 11 cases were found that showed LOH of chromosome 3 (44%), 8 gains of chromosome 8 (30%), 8 gains of chromosome 6p (30%), and 7 partial or total losses of chromosome 1 (26%). This is the first study on the cytogenetics of choroidal melanoma performed in our country. The results are similar to that published in the literature. Cytogenetic analysis provides more accurate knowledge on a vital individual prognosis. It also may become a valuable tool for establishing the most adequate follow-up regimes, and the need for adjuvant therapies. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  3. Choroidal Metastases From Cutaneous Melanoma.

    PubMed

    Mercado, Carmel L; Toy, Brian C; Kistler, Henry B; Moshfeghi, Darius M

    2016-05-01

    A 92-year-old man presented with months of progressive blurry vision, worsening acutely in his right eye. He denied pain, diplopia, or photopsias. His history was significant for multiple myeloma, prostate cancer, and malignant melanoma of his right shoulder treated with local excision. He had local recurrence with hepatic metastasis of the melanoma treated with radiation and chemotherapy. On examination, his visual acuity was counting fingers in the right eye and 20/60 in the left eye. Amsler grid testing demonstrated metamorphopsia in the right eye. Fundus exam of the right and left eyes revealed multiple, elevated, pigmented choroidal lesions, with associated subretinal fluid in the right macula. This appearance is consistent with hematogenous metastasis of cutaneous malignant melanoma to the choroid and associated serous fluid-causing metamorphopsia. The patient was enrolled in a clinical trial combining plasmid IL-12 with pembrolizumab (Keytruda; Merck, Whitehouse Station, NJ). He passed away 2 months after initial presentation to our clinic. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:497.]. Copyright 2016, SLACK Incorporated.

  4. Influence of ranibizumab treatment on the extracellular matrix in patients with neovascular age-related macular degeneration

    PubMed Central

    Nita, Małgorzata; Michalska-Małecka, Katarzyna; Mazurek, Urszula; Kimsa, Małgorzata; Strzałka-Mrozik, Barbara; Grzybowski, Andrzej; Romaniuk, Dorota

    2014-01-01

    Background We know the influence of the intravitreal anti-vascular endothelial growth factor (VEGF) injections on the choroidal neovascularization in the course of exudative age-related macular degeneration (AMD). However, the influence of the ranibizumab therapy in question on the extracellular matrix (ECM) remains unknown. We aimed to estimate the influence of Lucentis intravitreal injections on the gene expression of structural components of the extracellular matrix in patients with neovascular AMD. Material/Methods Patients with subfoveal localization of neovascularization in AMD, which was clinically active and observed using optical coherence tomography, were treated with ranibizumab (0.5 mg/0.05 mL) in accordance with the PrONTO scheme. Total RNA was extracted from peripheral blood mononuclear cells, and an oligonucleotide microarray technique enabled comparison of the expression level of genes encoding collagens, elastin, and laminins in AMD patients compared to control subjects. Results After 3 intravitreal injections of ranibizumab (Lucentis), COL1A1 and COL6A1 genes showed increased expression, whereas decreased expression mainly occurred for the following genes: COL4A5, COL11A1, COL4A6, LAMB4, and LAMC2. Conclusions Anti-VEGF local therapy influences the gene expression of structural components of the ECM as measured from blood samples. The loading dose of ranibizumab for the retina changes the expression of collagen and laminin genes, but does not influence the expression of the elastin gene. PMID:24866589

  5. Retinal Pigment Epithelial Atrophy in Neovascular Age-Related Macular Degeneration After Ranibizumab Treatment.

    PubMed

    Kuroda, Yoshimasa; Yamashiro, Kenji; Tsujikawa, Akitaka; Ooto, Sotaro; Tamura, Hiroshi; Oishi, Akio; Nakanishi, Hideo; Miyake, Masahiro; Yoshikawa, Munemitsu; Yoshimura, Nagahisa

    2016-01-01

    To investigate the risk factors for development and progression of retinal pigment epithelial (RPE) atrophy during ranibizumab treatment for neovascular age-related macular degeneration (AMD) in Japanese patients. Retrospective interventional case series. This study included 195 eyes with treatment-naïve subfoveal neovascular AMD. All patients were treated with an as-needed regimen after 3 monthly ranibizumab treatments. Color fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence were evaluated for RPE atrophy diagnosis. Baseline characteristics and ARMS2 A69S and CFH I62V polymorphisms were analyzed for their association with development and progression of RPE atrophy. Ten of 195 eyes (5.1%) had RPE atrophy at baseline; 3 had typical AMD and 7 had polypoidal choroidal vasculopathy (PCV). Among 185 eyes without preexisting RPE atrophy at baseline, 7 (3.8%) developed RPE atrophy at 12 months and 10 (5.4%) during the mean follow-up of 26.7 months. The incidence of newly developed RPE atrophy was lower in PCV than in typical AMD (P = .036), while the progression of the RPE atrophy area was faster in typical AMD than in PCV (0.57 ± 0.35 and 0.31 ± 0.13 mm/year, respectively; P = .018). The ARMS2 A69S and CFH I62V polymorphisms were significantly associated with the baseline RPE atrophy (P = .014 and P = .009, respectively). The RPE atrophy developed in 5.4% of eyes with neovascular AMD during the 26.7 months of ranibizumab treatment. When compared with white individuals, RPE atrophy developed less frequently in Japanese patients, but the progression rate was similar. The subtype of AMD thus affects the development of RPE atrophy. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Cytokines in neovascular age-related macular degeneration: fundamentals of targeted combination therapy.

    PubMed

    de Oliveira Dias, João Rafael; Rodrigues, Eduardo Büchele; Maia, Mauricio; Magalhães, Octaviano; Penha, Fernando Marcondes; Farah, Michel Eid

    2011-12-01

    The neovascular form of age-related macular degeneration (AMD), called wet-AMD or choroidal neovascularisation, begins with damage to the outer retinal cells and retinal pigment epithelium (RPE), which elicits a cascade of inflammatory and angiogenic responses leading to neovascularisation under the macula. Studies showed that oxidative damage, chronic inflammation of the RPE and complement misregulation work at different steps of this disease. After established neovascularisation, several pro- and antiangiogenic agents start to play an important role. Vascular endothelial growth factors (VEGFs) are the most specific and potent regulators of angiogenesis, which are inhibited by intravitreal injections of ranibizumab, bevacizumab, VEGF Trap, pegaptanib sodium and other agents under investigation. Pigment epithelium-derived factor, on the other hand, shows neuroprotective and antiangiogenic activities. Hepatocyte growth factor (HGF) has a mitogenic effect on a wide range of epithelial and endothelial cells, and it is inhibited by an anti-HGF monoclonal antibody. Platelet-derived growth factor is a potent chemoattractant and mitogen for both fibroblasts and retinal RPE cells, which has been inhibited experimentally by VEGF Trap and human anti-platelet-derived growth factor-D monoclonal antibody. Fibroblast growth factor-2 has pleiotropic effects in different cell and organ systems, and it is blocked by anti-FGF antibodies, with a greater benefit regarding antiangiogenesis when combined treatment with anti-VEGF is performed. Tumour necrosis factor alpha is expressed in the retina and the choroid, and its blockade in choroidal neovascularisation includes the use of monoclonals such as infliximab. This paper reviews the most important cytokines involved in the pathogenesis of wet-AMD, with emphasis on potential combined therapies for disease control.

  7. Gene expression signatures in tree shrew choroid during lens-induced myopia and recovery

    PubMed Central

    He, Li; Frost, Michael R.; Siegwart, John T.; Norton, Thomas T.

    2014-01-01

    Gene expression in tree shrew choroid was examined during the development of minus-lens induced myopia (LIM, a GO condition), after completion of minus-lens compensation (a STAY condition), and early in recovery (REC) from induced myopia (a STOP condition). Five groups of tree shrews (n = 7 per group) were used. Starting 24 days after normal eye-opening (days of visual experience [DVE]), one minus-lens group wore a monocular −5 D lens for 2 days (LIM-2), another minus-lens group achieved stable lens compensation while wearing a monocular −5 D lens for 11 days (LIM-11); a recovery group also wore a −5D lens for 11 days and then received 2 days of recovery starting at 35 DVE (REC-2). Two age-matched normal groups were examined at 26 DVE and 37 DVE. Quantitative PCR was used to measure the relative differences in mRNA levels in the choroid for 77 candidate genes that were selected based on previous studies or because a whole-transcriptome analysis suggested their expression would change during myopia development or recovery. Small myopic changes were observed in the treated eyes of the LIM-2 group (−1.0 ± 0.2 D; mean ± SEM) indicating eyes were early in the process of developing LIM. The LIM-11 group exhibited complete refractive compensation (−5.1 ± 0.2 D) that was stable for five days. The REC-2 group recovered by 1.3 ± 0.3 D from full refractive compensation. Sixty genes showed significant mRNA expression differences during normal development, LIM, or REC conditions. In LIM-2 choroid (GO), 18 genes were significantly down-regulated in the treated eyes relative to the fellow control eyes and 10 genes were significantly up-regulated. In LIM-11 choroid (STAY), 10 genes were significantly down-regulated and 12 genes were significantly up-regulated. Expression patterns in GO and STAY were similar, but not identical. All genes that showed differential expression in GO and STAY were regulated in the same direction in both conditions. In REC-2 choroid (STOP

  8. Heritability of Choroidal Thickness in the Amish.

    PubMed

    Sardell, Rebecca J; Nittala, Muneeswar G; Adams, Larry D; Laux, Reneé A; Cooke Bailey, Jessica N; Fuzzell, Denise; Fuzzell, Sarada; Reinhart-Mercer, Lori; Caywood, Laura J; Horst, Violet; Mackay, Tine; Dana, Debbie; Sadda, SriniVas R; Scott, William K; Stambolian, Dwight; Haines, Jonathan L; Pericak-Vance, Margaret A

    2016-12-01

    To evaluate the heritability of choroidal thickness and its relationship to age-related macular degeneration (AMD). Cohort study. Six hundred eighty-nine individuals from Amish families with early or intermediate AMD. Ocular coherence tomography was used to quantify choroidal thickness, and fundus photography was used to classify eyes into categories using a modified Clinical Age-Related Maculopathy Staging (CARMS) system. Repeatability and heritability of choroidal thickness and its phenotypic and genetic correlations with the AMD phenotype (CARMS category) were estimated using a generalized linear mixed model (GLMM) approach that accounted for relatedness, repeated measures (left and right eyes), and the effects of age, gender, and refraction. Heritability of choroidal thickness and its phenotypic and genetic correlation with the AMD phenotype (CARMS category). Phenotypic correlation between choroidal thickness and CARMS category was moderate (Spearman's rank correlation, rs = -0.24; n = 1313 eyes) and significant (GLMM posterior mean, -4.27; 95% credible interval [CI], -7.88 to -0.79; P = 0.02) after controlling for relatedness, age, gender, and refraction. Eyes with advanced AMD had thinner choroids than eyes without AMD (posterior mean, -73.8; 95% CI, -94.7 to -54.6; P < 0.001; n = 1178 eyes). Choroidal thickness was highly repeatable within individuals (repeatability, 0.78; 95% CI, 0.68 to 0.89) and moderately heritable (heritability, 0.40; 95% CI, 0.14 to 0.51), but did not show significant genetic correlation with CARMS category, although the effect size was moderate (genetic correlation, -0.18; 95% CI, -0.49 to 0.16). Choroidal thickness also varied with age, gender, and refraction. The CARMS category showed moderate heritability (heritability, 0.49; 95% CI, 0.26 to 0.72). We quantify the heritability of choroidal thickness for the first time, highlighting a heritable, quantitative trait that is measurable in all individuals regardless of AMD

  9. Carbon-ion radiotherapy for locally advanced or unfavorably located choroidal melanoma: A Phase I/II dose-escalation study

    SciTech Connect

    Tsuji, Hiroshi . E-mail: h_tsuji@nirs.go.jp; Ishikawa, Hitoshi; Yanagi, Takeshi; Hirasawa, Naoki; Kamada, Tadashi; Mizoe, Jun-Etsu; Kanai, Tatsuaki; Tsujii, Hirohiko; Ohnishi, Yoshitaka

    2007-03-01

    Purpose: To evaluate the applicability of carbon ion beams for the treatment of choroidal melanoma with regard to normal tissue morbidity and local tumor control. Methods and Materials: Between January 2001 and February 2006, 59 patients with locally advanced or unfavorably located choroidal melanoma were enrolled in a Phase I/II clinical trial of carbon-ion radiotherapy at the National Institute of Radiologic Sciences. The primary endpoint of this study was normal tissue morbidity, and secondary endpoints were local tumor control and patient survival. Of the 59 subjects enrolled, 57 were followed >6 months and analyzed. Results: Twenty-three patients (40%) developed neovascular glaucoma, and three underwent enucleation for eye pain due to elevated intraocular pressure. Incidence of neovascular glaucoma was dependent on tumor size and site. Five patients had died at analysis, three of distant metastasis and two of concurrent disease. All but one patient, who developed marginal recurrence, were controlled locally. Six patients developed distant metastasis, five in the liver and one in the lung. Three-year overall survival, disease-free survival, and local control rates were 88.2%, 84.8%, and 97.4%, respectively. No apparent dose-response relationship was observed in either tumor control or normal tissue morbidity at the dose range applied. Conclusion: Carbon-ion radiotherapy can be applied to choroidal melanoma with an acceptable morbidity and sufficient antitumor effect, even with tumors of unfavorable size or site.

  10. Comparison of Loteprednol with Fluorometholone after Myopic Photorefractive Keratectomy

    PubMed Central

    Karimian, Farid; Faramarzi, Amir; Fekri, Sahba; Mohammad-Rabie, Hossein; Najdi, Danial; Doozandeh, Azadeh; Delfaza-Baher, Siamak; Yaseri, Mehdi

    2017-01-01

    Purpose: To compare the efficacy and side effects of loteprednol versus fluorometholone after myopic photorefractive keratectomy (PRK). Methods: One hundred and twenty four eyes of 62 patients who underwent PRK were enrolled in this study. One eye of each subject was randomized to receive loteprednol 0.5% and the fellow eye was given fluorometholone 0.1%. Patients were followed up for three months. Results: There was no significant difference in uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction, corneal haze, intraocular pressure (IOP), and ocular discomfort and redness between groups at the final visit. At 3 months postoperatively, 20/25 or better UDVA was achieved in 95% of the loteprednol group and 92% of the fluorometholone group (P > 0.05). There was neither visually significant corneal haze nor ocular hypertension (IOP rise > 10 mmHg or IOP > 21 mmHg) in any group. Conclusion: The efficacy and side effects of loteprednol 0.5% and fluorometholone 0.1% after myopic PRK are comparable. PMID:28299001

  11. Comparison of Loteprednol with Fluorometholone after Myopic Photorefractive Keratectomy.

    PubMed

    Karimian, Farid; Faramarzi, Amir; Fekri, Sahba; Mohammad-Rabie, Hossein; Najdi, Danial; Doozandeh, Azadeh; Delfaza-Baher, Siamak; Yaseri, Mehdi

    2017-01-01

    To compare the efficacy and side effects of loteprednol versus fluorometholone after myopic photorefractive keratectomy (PRK). One hundred and twenty four eyes of 62 patients who underwent PRK were enrolled in this study. One eye of each subject was randomized to receive loteprednol 0.5% and the fellow eye was given fluorometholone 0.1%. Patients were followed up for three months. There was no significant difference in uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction, corneal haze, intraocular pressure (IOP), and ocular discomfort and redness between groups at the final visit. At 3 months postoperatively, 20/25 or better UDVA was achieved in 95% of the loteprednol group and 92% of the fluorometholone group (P > 0.05). There was neither visually significant corneal haze nor ocular hypertension (IOP rise > 10 mmHg or IOP > 21 mmHg) in any group. The efficacy and side effects of loteprednol 0.5% and fluorometholone 0.1% after myopic PRK are comparable.

  12. Idiopathic Peripapillary Subretinal Neovascular Membrane in a Young Woman with Recurrence of the Lesion during Pregnancy after Treatment with Intravitreal Bevacizumab

    PubMed Central

    Al-Gharbi, Nasra; Al Abdulsalam, Omar; Al Habash, Ahmed

    2015-01-01

    We report a 27-year-old woman who was diagnosed with idiopathic peripapillary subretinal neovascular membrane (PSRNVM) in her left eye with best-corrected visual acuity (BCVA) of 20/160. She had been treated by three monthly doses of intravitreal bevacizumab (1.25 mg/0.05 ml) at 4-week intervals, which showed a favorable response. The treatment led to regression of the choroidal neovascular membrane (CNVM) with complete resorption of subretinal fluid and improvement of BCVA to 20/25. Subsequently, recurrence of the CNVM was observed during pregnancy (28 months after treatment). To the best of our knowledge, this is the first report of recurrence of idiopathic PSRNVM during pregnancy. PMID:25949086

  13. TEN-YEAR FOLLOW-UP OF EYES TREATED WITH STEREOTACTIC FRACTIONATED EXTERNAL BEAM RADIATION FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION

    PubMed Central

    TRIKHA, RUPAN; MORSE, LAWRENCE S.; ZAWADZKI, ROBERT J.; WERNER, JOHN S.; PARK, SUSANNA S.

    2012-01-01

    Purpose To determine the long-term effects of stereotactic fractionated external beam radiation on eyes treated for neovascular age-related macular degeneration. Methods A retrospective review of all eyes treated with stereotactic fractionated external beam radiation (20–40 Gy, 2-Gy fractions) between 1997 and 2000 was performed to identify eyes with ≥2-year follow-up for analysis. A subset was imaged prospectively using a high-resolution Fourier-domain optical coherence tomography. Results Among 94 eyes treated, 33 eyes (32 subjects) had ≥2-year follow-up information (mean follow-up, 6.2 years; range, 2–10 years). Final visual acuity ranged from 20/50 to no light perception. Final macular findings included central geographic atrophy (49%), disciform scar (30%), and active choroidal neovascular membrane (9%). Fourier-domain optical coherence tomography images of three eyes with geographic atrophy revealed photoreceptor layer loss within areas of geographic atrophy with intact retinal morphology in areas of radiation exposure outside geographic atrophy. Radiation retinopathy was suspected in 18% and confirmed by fluorescein angiography in 15%, ranging from mild to neovascular glaucoma/phthisis bulbi (2 eyes). Mean time from stereotactic fractionated external beam radiation to development of radiation retinopathy was 5.4 years (range, 1–10 years). Conclusion A moderate rate of delayed radiation retinopathy was noted in eyes with neovascular age-related macular degeneration treated with stereotactic fractionated external beam radiation. Geographic atrophy was a common finding. PMID:21499195

  14. Predictive role of gene polymorphisms affecting thrombin-generation pathway in variable efficacy of photodynamic therapy for neovascular age-related macular degeneration.

    PubMed

    Parmeggiani, Francesco; Gemmati, Donato; Costagliola, Ciro; Sebastiani, Adolfo; Incorvaia, Carlo

    2009-01-01

    Age-related macular degeneration (AMD) represents the leading cause of central blindness in developed countries. The majority of severe vision loss occurs in the neovascular form of AMD, generally characterized by the presence of choroidal neovascularization (CNV) beneath the fovea. Photodynamic therapy with verteporfin (PDT-V) and drugs acting against vascular endothelial growth factor are the most commonly employed treatments for AMD-related subfoveal CNV. The combined use of both these strategies is the most promising therapeutic approach towards this harmful disease. The therapeutic action of PDT-V depends to a photochemical perturbation of thrombo-coagulative processes within CNV. Predictive correlations between peculiar coagulation-balance gene polymorphisms and different levels of post-PDT-V benefit have been recently documented in Caucasian patients with neovascular AMD. Particularly, heterozygous A-allele carriers of factor V Leiden 1691 or prothrombin 20210 gene are characterized by a greater possibility to exhibit clinical benefit after PDT-V. Both mutations induce thrombophilia increasing the thrombin generation in plasma and, thus, they can consistently intensify the photothrombotic phase of the therapeutic CNV occlusion. In prospect, considering the different individual susceptibility to PDT-V, a preoperative assessment of the genotypic thrombophilic background could optimize the eligibility criteria of this intriguing treatment. This review summarizes some of the recent published patents on treatment of neovascular AMD, with a particular attention to PDT-V application in combined therapeutic modalities.

  15. [Evaluation of the arterial blood flow parameters in the eye of myopic patients].

    PubMed

    Mrugacz, Małgorzata; Bryl, Anna

    2013-04-01

    Myopia is a common refractive defect. Has a good vision from near and deterioration of vision with increasing distance. The main reason for its occurrence is too long axis of the eyeball. The consequence of elongation of the eyeball is the development of degenerative changes in the retina. Despite much research has failed to clearly identify the causes of degenerative changes in those short-sighted. The aim of the study was to evaluate the maximum and minimum speed in arterial blood vessels of the eye in people with myopia. The study included 70 patients (138 eyes), 53 women and 17 men, aged from 18 to 79 years, with myopia of -0.25 to -18.0 Dsph and length of the eyeball from 22.61 to 33.36 mm. Depending on the kind and the degree of the progress of degenerative changes, patients were divided in 4 groups: I - without degenerative changes on the fundus (n=32; K-23, M-9); II- with the short-sighted sickle (n=20; K-14, M-6); Ill - with the structure thinned down of the retina, accompanying the short-sighted sickle (n = 8; K-6, M-2); IV - with extensive choroidal-retina disappearances in the fundus (n = 10; K-7, M-3). In all individuals enrolled underwent Color Doppler ultrasound with apparatus SSA 770A Toshiba Aplio with linear probe frequency 12 MHz, judging maximum (Vmax) and minimum (Vmin) speed in the arteries of the eye: ophthalmic artery (OA), central retinal artery (CRA) and short posterior ciliary arteries (SPCA) located on the nasal and temporal side of the optic disc. The results were statistically analyzed. No statistically significant relationship between the nature of degenerative changes of the eye, and blood velocity in the OA. There was a increase in Vmax and Vmin blood in OA in Group IV, but these changes were not statistically significant. Statistically significant correlation was observed while in the CRA. With a decrease in Vmax and Vmin of blood flowing through a vessel exacerbation of retinal degeneration. Vmax and Vmin changes in the blood did

  16. Enucleation versus plaque irradiation for choroidal melanoma

    SciTech Connect

    Straatsma, B.R.; Fine, S.L.; Earle, J.D.; Hawkins, B.S.; Diener-West, M.; McLaughlin, J.A.

    1988-07-01

    The Collaborative Ocular Melanoma Study (COMS) is an international, multicenter-controlled study. The organization includes an Executive Committee, Steering Committee, 6 Central Units, 32 Clinical Centers, and a Data and Safety Monitoring Committee. Scientifically, the COMS consists of (1) a randomized trial of patients with medium choroidal melanoma treated with enucleation versus iodine-125 plaque irradiation, (2) a randomized trial of patients with large choroidal melanoma treated with enucleation versus preenucleation external beam irradiation and enucleation, and (3) a prospective observational study of patients with small choroidal melanoma to determine whether a randomized trial of treatment is appropriate. In design and conduct of the COMS, special consideration is given to biostatistics and sample size considerations, iodine-125 plaque irradiation of choroidal melanoma, and coordinated ocular melanoma research. Recruitment is in progress. However, the pool of eligible patients is limited and the COMS needs the continued support and cooperation of ophthalmologists throughout the United States and Canada.

  17. [Evaluation of the choroid in central serous chorioretinopathy].

    PubMed

    Maruko, Ichiro

    2012-11-01

    Studies using indocyanine green angiography (ICGA) revealed that the main cause of central serous chorioretionopathy (CSC) stems from choroidal abnormalities such as choroidal vascular hyperpermeability. However, there are no methods to evaluate the choroid except for either the invasive ICGA or low-resolution ultrasonography. The recently developed enhanced depth imaging optical coherence tomography (EDI-OCT) technique can visualize the choroid appropriately and noninvasively using conventional OCT. EDI-OCT showed that both the affected and unaffected eyes in CSC patients have a thickened choroid; whereas the remarkably thickened choroid in Vogt-Koyanagi-Harada disease decreases immediately after corticosteroid treatment and the eyes with high myopia show a thinner choroid. We evaluated the choroidal thickness after treatment of CSC. The subfoveal choroidal thickness in typical CSC treated with laser photocoagulation showed no changes during the follow-up. On the other hand, the subfoveal choroid in chronic CSC treated with half-dose verteporfin photodynamic therapy (PDT) showed temporary thickening after 2 days but thinned back 1 month after treatment. Both the choroidal thickness and choroidal vascular hyperpermeability in ICGA decreased after PDT, but they did not change after laser photocoagulation. These findings suggest that PDT can affect the abnormal choroid directly and works through a different mechanism from conventional laser photocoagulation. It is important to evaluate the choroid using OCT in CSC and other macular diseases.

  18. The choroid as a sclera growth regulator.

    PubMed

    Summers, Jody A

    2013-09-01

    Emmetropization is a vision dependent mechanism that attempts to minimize refractive error through coordinated growth of the cornea, lens and sclera such that the axial length matches the focal length of the eye. It is generally accepted that this visually guided eye growth is controlled via a cascade of locally generated chemical events that are initiated in the retina and ultimately cause changes in scleral extracellular matrix (ECM) remodeling which lead to changes in eye size and refraction. Of much interest, therefore, are the molecular mechanisms that underpin emmetropization and visually guided ocular growth. The choroid, a highly vascularized layer located between the retina and the sclera is uniquely situated to relay retina-derived signals to the sclera to effect changes in ECM synthesis and ocular size. Studies initiated by Josh Wallman clearly demonstrate that the choroid plays an active role in emmetropization, both by modulation of its thickness to adjust the retina to the focal plane of the eye (choroidal accommodation), and well as through the release of growth factors that have the potential to regulate scleral extracellular matrix remodeling. His discoveries prompted numerous investigations on the molecular composition of the choroid and changes in gene expression associated with visually guided ocular growth. This article will review molecular and functional studies of the choroid to provide support for the hypothesis that the choroid is a source of sclera growth regulators that effect changes in ocular growth in response to visual stimuli. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. The Choroid as a Sclera Growth Regulator

    PubMed Central

    Summers, Jody A.

    2013-01-01

    Emmetropization is a vision dependent mechanism that attempts to minimize refractive error through coordinated growth of the cornea, lens and sclera such that the axial length matches the focal length of the eye. It is generally accepted that this visually guided eye growth is controlled via a cascade of locally generated chemical events that are initiated in the retina and ultimately cause changes in scleral extracellular matrix (ECM) remodeling which lead to changes in eye size and refraction. Of much interest, therefore, are the molecular mechanisms that underpin emmetropization and visually guided ocular growth. The choroid, a highly vascularized layer located between the retina and the sclera is uniquely situated to relay retina-derived signals to the sclera to effect changes in ECM synthesis and ocular size. Studies initiated by Josh Wallman, Ph.D., clearly demonstrate that the choroid plays an active role in emmetropization, both by modulation of its thickness to adjust the retina to the focal plane of the eye (choroidal accommodation), and well as through the release of growth factors that have the potential to regulate scleral extracellular matrix remodeling. His discoveries prompted numerous investigations on the molecular composition of the choroid and changes in gene expression associated with visually guided ocular growth. This article will review molecular and functional studies of the choroid to provide support for the hypothesis that the choroid is a source of sclera growth regulators that effect changes in ocular growth in response to visual stimuli. PMID:23528534

  20. Choroid plexus papilloma with a hyperdiploid karyotype

    SciTech Connect

    Roland, B.; Pinto, A.

    1994-09-01

    An 11-month-old male underwent surgery for a choroid plexus neoplasm, which on histologic examination was diagnosed as a benign papilloma. Chromosome analysis showed a karyotype of 55,XY,+7+7,+8,+9,+12,+12,+15,+20,+21 in all 20 metaphases analyzed. This is only the third benign choroid plexus papilloma that has been karyotyped, with the others being normal and hypodiploid (33 chromosomes). Three malignant choroid plexus carcinomas have also been analyzed, two with normal karyotypes and one hypodiploid (34 - 35 chromosomes). The two hypoidiploid neoplasms lack chromosomes 2, 3, 4, 5, 10, 13, 14, 17 and 18. Since the chromosomes that are lost in the hypodiploid neoplasms are different from the chromosomes gained in our tumor, it appears that the dosage of specific chromosomes is important in the origin of choroid plexus neoplasms. Benign choroid plexus papillomas can be difficult to differentiate from choroid plexus carcinomas. With the data available so far, it does not appear that cytogenetics can assist in making the diagnosis.

  1. Presumed choroidal metastasis of Merkel cell carcinoma

    SciTech Connect

    Small, K.W.; Rosenwasser, G.O.; Alexander, E. III; Rossitch, G.; Dutton, J.J. )

    1990-05-01

    Merkel cell carcinoma is a rare skin tumor of neural crest origin and is part of the amine precursor uptake and decarboxylase system. It typically occurs on the face of elderly people. Distant metastasis is almost uniformly fatal. Choroidal metastasis, to our knowledge, has not been described. We report a patient with Merkel cell carcinoma who had a synchronous solid choroidal tumor and a biopsy-proven brain metastasis. Our 56-year-old patient presented with a rapidly growing, violaceous preauricular skin tumor. Computed tomography of the head disclosed incidental brain and choroidal tumors. Light and electron microscopy of biopsy specimens of both the skin and the brain lesions showed Merkel cell carcinoma. Ophthalmoscopy, fluorescein angiography, and A and B echography revealed a solid choroidal mass. The brain and skin tumors responded well to irradiation. A radioactive episcleral plaque was applied subsequently to the choroidal tumor. All tumors regressed, and the patient was doing well 28 months later. To our knowledge this is the first case of presumed choroidal metastasis of Merkel cell carcinoma.

  2. Radiogenic Side Effects After Hypofractionated Stereotactic Photon Radiotherapy of Choroidal Melanoma in 212 Patients Treated Between 1997 and 2007

    SciTech Connect

    Dunavoelgyi, Roman; Dieckmann, Karin; Gleiss, Andreas; Sacu, Stefan; Kircher, Karl; Georgopoulos, Michael; Georg, Dietmar; Zehetmayer, Martin; Poetter, Richard

    2012-05-01

    Purpose: To evaluate side effects of hypofractionated stereotactic photon radiotherapy for patients with choroidal melanoma. Patients and Methods: Two hundred and twelve patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at the Medical University of Vienna between 1997 and 2007 with a Linac with 6-MV photon beams in five fractions with 10, 12, or 14 Gy per fraction. Examinations for radiogenic side effects were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and then once a year thereafter until 10 years after radiotherapy. Adverse side effects were assessed using slit-lamp examination, funduscopy, gonioscopy, tonometry, and, if necessary, fundus photography and fluorescein angiography. Evaluations of incidence of side effects are based on an actuarial analysis. Results: One hundred and eighty-nine (89.2%) and 168 (79.2%) of the tumors were within 3 mm of the macula and the optic disc, respectively. The five most common radiotherapy side effects were retinopathy and optic neuropathy (114 cases and 107 cases, respectively), cataract development (87 cases), neovascular glaucoma (46 cases), and corneal epithelium defects (41 cases). In total, 33.6%, 38.5%, 51.2%, 75.5%, and 77.6% of the patients were free of any radiation retinopathy, optic neuropathy, cataract, neovascular glaucoma, or corneal epithelium defects 5 years after radiotherapy, respectively. Conclusion: In centrally located choroidal melanoma hypofractionated stereotactic photon radiotherapy shows a low to moderate rate of adverse long-term side effects comparable with those after proton beam radiotherapy. Future fractionation schemes should seek to further reduce adverse side effects rate while maintaining excellent local tumor control.

  3. Comparative effects of posterior eye cup tissues from myopic and hyperopic chick eyes on cultured scleral fibroblasts.

    PubMed

    Christian, Parul G; Harkin, Damien G; Rayner, Cassie; Schmid, Katrina L

    2013-02-01

    The role of individual ocular tissues in mediating changes to the sclera during myopia development is unclear. The aim of this study was to examine the effects of retina, RPE and choroidal tissues from myopic and hyperopic chick eyes on the DNA and glycosaminoglycan (GAG) content in cultures of chick scleral fibroblasts. Primary cultures of fibroblastic cells expressing vimentin and α-smooth muscle actin were established in serum-supplemented growth medium from 8-day-old normal chick sclera. The fibroblasts were subsequently co-cultured with posterior eye cup tissue (full thickness containing retina, RPE and choroid) obtained from untreated eyes and eyes wearing translucent diffusers (form-deprivation myopia, FDM) or -15D lenses (lens-induced myopia, LIM) for 3 days (post-hatch day 5-8) (n = 6 per treatment group). The effect of tissues (full thickness and individual retina, RPE, and choroid layers) from -15D (LIM) versus +15D (lens-induced hyperopia, LIH) treated eyes was also determined. Refraction changes in the direction predicted by the visual treatments were confirmed by retinoscopy prior to tissue collection. Glycosaminoglycan (GAG) and DNA content of the scleral fibroblast cultures were measured using GAG and PicoGreen assays. There was no significant difference in the effect of full thickness tissue from either FDM or LIM treated eyes on DNA and GAG content of scleral fibroblasts (DNA 8.9 ± 2.6 μg and 8.4 ± 1.1 μg, p = 0.12; GAG 11.2 ± 0.6 μg and 10.1 ± 1.0 μg, p = 0.34). Retina from LIM eyes did not alter fibroblast DNA or GAG content compared to retina from LIH eyes (DNA 27.2 ± 1.7 μg versus 23.2 ± 1.5 μg, p = 0.21; GAG 28.1 ± 1.7 μg versus. 28.7 ± 1.2 μg, p = 0.46). Similarly, the choroid from LIH and LIM eyes did not produce a differential effect on DNA content (DNA LIM 46.9 ± 6.4 versus LIH 51.5 ± 4.7 μg, p = 0.31). In contrast, scleral fibroblast DNA was greater in co-culture with RPE from LIM eyes than the empty basket and DNA

  4. Effect of the against the rule myopic astigmatism on the near vision of the elderly.

    PubMed

    Kordić, Rajko; Kalauz, Miro; Kuzman, Tomislav; Masnec, Sanja; Skegro, Ivan; Vidović, Tomislav; Suić-Popović, Smiljka; Cerovski, Branimir; Rezaković, Saida; Kutija, Marija Barisić

    2014-12-01

    In the two groups of patients with myopic astigmatism the uncorrected near vision was tested after catatract surgery. Each group with 20 patients ages 60-80. All patients enrolled in study have uncorrected far vision 0.5 or better on Snellen tables. In the first group patients were with the rule after surgery myopic astigmatism (1-1.50 Diopter), and in the second group were patients with against the rule after surgery myopic astigmatism (1-1.50 Diopter). Patients in the second group with against the rule astigmatism achieved significantly (p<0.01) better uncorrected near vision.

  5. Post-LASIK myopic shift after a trek in the North Pole.

    PubMed

    Fam, Han-Bor; Goh, E-Shawn; Lee, Hung-Ming; Lim, Kooi-Ling

    2005-01-01

    Bilateral laser in situ keratomileusis was performed in a 37-year-old male ethnic Chinese adventurer. Eight weeks postoperatively, the patient made an unassisted trek to the geographic North Pole. After 2 weeks in this environment, a myopic shift of more than -1.50 diopters occurred in both eyes. The myopic shift resolved over 2 months when the patient returned to a tropical climate. Using Orbscan corneal topography, we propose that the myopic shift was attributed to biomechanical changes in the cornea induced by corneal dehydration in the Arctic environment.

  6. Epithelial ion transport in rabbit corneas following myopic keratomileusis.

    PubMed

    Swinger, C A; Candia, O A; Marcus, S; Barker, B A; Kornmehl, E W

    1986-08-01

    In isolated rabbit corneas that had undergone lamellar keratectomy or myopic keratomileusis, the stimulation of chloride transport by 10(-5) M epinephrine was completely inhibited at 1 week following surgery. At 28 days following surgery, both groups responded to 10(-7) M epinephrine. The response to 10(-5) M amphotericin B was normal both at 1 week and at 28 days following surgery. We conclude that, although the Na-K pump was not affected by the lamellar keratectomy and cryolathing, that either the epithelial beta receptors and/or the cAMP pathway were temporarily inhibited for at least 1 week following surgery. A lamellar keratectomy, therefore, can have an adverse effect on the epithelial transport system of the corneal epithelium even though the epithelium may appear normal clinically.

  7. Choroidal thickness profiles in retinitis pigmentosa.

    PubMed

    Ayton, Lauren N; Guymer, Robyn H; Luu, Chi D

    2013-01-01

    Little quantitative information exists regarding the effect that retinitis pigmentosa (RP) has on the choroid. The aim of this study was to determine choroidal thickness profiles in patients with RP. Prospective. Forty-two RP and 22 control subjects participated in the study. RP patients had mild to severe disease, with a visual acuity range of logMAR 0.1 to no light perception. Images of the retina and choroid were obtained using the enhanced depth-imaging method and optical coherence tomography (OCT). Choroidal thickness measures were determined via manual segmentation of the OCT image. The thickness profiles of the normal and RP groups were compared. The associations between choroidal thickness, visual acuity and duration of RP were determined. The choroid was thickest in the control eyes at the subfoveal location (336.60 ± 70.42 μm), and the thickness gradually decreased towards the peripheral retina (temporal 8° = 295.55 ± 60.52 μm; nasal 8° = 251.68 ± 49.93 μm). In RP, the mean thickness was also greater at the fovea (215.60 ± 94.91 μm) than the temporal (191.66 ± 72.42 μm) and nasal (149.91 ± 57.42 μm) retina, but all values were significantly lower than those of the controls (P ≤ 0.001). Subfoveal choroidal thickness was significantly correlated with visual acuity (r = -0.46, P < 0.001) and duration of disease (r = -0.4, P = 0.001). Patients with RP have a thinner choroid than controls. Patients with poorer visual acuity or longer duration of symptoms tended to have thinner choroids. Knowledge of choroidal thickness profile in RP is important for the field of restorative vision research and the development of suprachoroidal retinal prostheses. © 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

  8. Macular choroidal thickness in unilateral amblyopic children.