Nolte, K B
Light stand photography with direct illumination of the retina is a common method of demonstrating retinal hemorrhages. The lack of contrast between dark hemorrhages and surrounding dark retina, and the difficulty of photographing into the concavity of an eye limit this technique. Transillumination of a bivalved globe with a bright external light source such as a colonoscope or microscope light yields high contrast superior photographs. This technique is useful to document retinal hemorrhages, and provides quality photographs for courtroom demonstrations.
Errera, M-H; Dupas, B; Man, H; Gualino, V; Gaudric, A; Massin, P
A diet restricted to rice and boiled fruit and vegetables leads to vitamin C deficiency. We describe the third case, to our knowledge, of retinal hemorrhages related to scurvy. Reduced bilateral visual acuity in a 50-year-old patient was associated with macrocytic anemia, denutrition, and cutaneous ecchymoses. Oral vitamin C treatment provided subjective clinical improvement and regression of the retinal hemorrhages on fundus examination, with no side effects. Vitamin C plays an important role in collagen stability in vascular and bone walls.
Binenbaum, Gil; Christian, Cindy W.; Guttmann, Katy; Huang, Jiayan; Ying, Gui-shuang; Forbes, Brian J.
Importance Vaccinations have been proposed as a cause of retinal hemorrhage in children, primarily as part of a defense strategy in high-stakes abusive head trauma cases. If vaccination injections cause retinal hemorrhage, this consideration would affect the evaluation of children for suspected child abuse. Objectives To describe the prevalence and causes of retinal hemorrhage among infants and young children in an outpatient ophthalmology clinic and to test the hypothesis that, if vaccination injections cause retinal hemorrhage, then retinal hemorrhage would be seen frequently and be temporally associated with immunization. Design, Setting, and Participants Retrospective cohort study between June 1, 2009, and August 30, 2012, at The Children's Hospital of Philadelphia pediatric ophthalmology clinics among 5177 children 1 to 23 months old undergoing a dilated fundus examination as an outpatient for any reason. Children with intraocular surgery or active retinal neovascularization were excluded from the study. Main outcomes and Measures The prevalence and causes of retinal hemorrhage, as well as the temporal association between vaccination injection within 7, 14, or 21 days preceding examination and retinal hemorrhage. Results Among 7675 outpatient fundus examinations, 9 of 5177 children had retinal hemorrhage for a prevalence of 0.17% (95% CI, 0.09%-0.33%). All 9 had abusive head trauma diagnosable with nonocular findings. Among a subset of 2210 children who had complete immunization records and underwent 3425 fundoscopic examinations, 163 children had an eye examination within 7 days of vaccination, 323 within 14 days, and 494 within 21 days. No children had retinal hemorrhage within 7 days of vaccination, 1 child had hemorrhage within 14 days, and no additional child had hemorrhage within 21 days. There was no temporal association between vaccination injection and retinal hemorrhage in the prior 7 days (P > .99), 14 days (P = .33), or 21 days (P = .46
Muraoka, Yuki; Uji, Akihito; Tsujikawa, Akitaka; Murakami, Tomoaki; Ooto, Sotaro; Suzuma, Kiyoshi; Takahashi, Ayako; Iida, Yuto; Miwa, Yuko; Hata, Masayuki; Yoshimura, Nagahisa
This prospective study included 63 eyes with acute branch retinal vein occlusion (BRVO) to evaluate the retinal hemorrhagic patterns at the posterior poles and explore their clinical relevance in macular perfusion differentiation. Retinal hemorrhagic patterns and macular perfusion status were evaluated via fundus photography and fluorescein angiography, respectively. Macular perfusion was judged as nonischemic in 30, ischemic in 28, and undeterminable in 5 among the 63 eyes. Predominant hemorrhagic patterns were flame-shaped in 39 (67.2%) and non-flame-shaped in 19 (32.8%) eyes. All 39 eyes with a flame-shaped hemorrhage showed a nonischemic macula. Of the 19 eyes classified as having a non-flame-shaped hemorrhage, 13 (68.4%) had an ischemic macula and 6 (31.6%) had a nonischemic macula (P < 0.001). Parallelism in eyes with a flame-shaped hemorrhage was higher than in those with a non-flame-shaped hemorrhage (P < 0.001), and in those with a nonischemic macula versus those with an ischemic macula (P < 0.001). The area under the curve for parallelism was 0.975 (P < 0.001), suggesting an accurate diagnostic parameter for macular perfusion differentiation. In conclusion, we objectively evaluated retinal hemorrhagic patterns at the posterior pole in BRVO using the parallelism method, which was useful in differentiating macular perfusion status. PMID:27334338
Miller, Matthew A; Lenci, Lucas T; Reddy, Chittaranjan V; Russell, Stephen R
We present the case of a 75-year-old man who had uneventful cataract surgery and administration of intracameral vancomycin for endophthalmitis prophylaxis, followed by the same procedure in the fellow eye 1 week later. The patient subsequently developed bilateral hemorrhagic occlusive retinal vasculitis, resulting in profound vision loss in both eyes. A second case of hemorrhagic occlusive retinal vasculitis previously reported from our institution is summarized. That case was characterized by a far milder course, with rapid resolution of vision loss. The 2 cases illustrate the broad range of toxicity potentially associated with intracameral vancomycin, suggest that bilateral administration results in a worse prognosis, and indicate that this disorder may be underrecognized due to the potential for a mild course. We recommend that intracameral vancomycin not be used for endophthalmitis prophylaxis.
Takashima, Yuko; Sugimoto, Masahiko; Kato, Kumiko; Kozawa, Maki; Ikesugi, Kengo; Matsubara, Hisashi; Kondo, Mineo
Purpose. To describe a method of quantifying the size of the retinal hemorrhages in branch retinal vein occlusion (BRVO) and to determine the interrater and intrarater reliabilities of these measurements. Methods. Thirty-five fundus photographs from 35 consecutive eyes with BRVO were studied. The fundus images were analyzed with Power-Point® software, and a grid of 14 squares was laid over the fundus image. Raters were asked to judge the percentage of each of the 14 squares that was covered by the hemorrhages, and the average of the 14 squares was taken to be the relative size of the retinal hemorrhage. Results. Interrater reliability between three raters was higher when a grid with 14 squares was used (intraclass correlation coefficient (ICC), 0.96) than that when a box with no grid was used (ICC, 0.78). Intrarater reliability, which was calculated by the retinal hemorrhage area measured on two different days, was also higher (ICC, 0.97) than that with no grid (ICC, 0.86). Interrater reliability for five fundus pictures with poor image quality was also good when a grid with 14 squares was used (ICC, 0.88). Conclusions. Although our method is subjective, excellent interrater and intrarater reliabilities indicate that this method can be adapted for clinical use.
Takashima, Yuko; Sugimoto, Masahiko; Kato, Kumiko; Kozawa, Maki; Ikesugi, Kengo
Purpose. To describe a method of quantifying the size of the retinal hemorrhages in branch retinal vein occlusion (BRVO) and to determine the interrater and intrarater reliabilities of these measurements. Methods. Thirty-five fundus photographs from 35 consecutive eyes with BRVO were studied. The fundus images were analyzed with Power-Point® software, and a grid of 14 squares was laid over the fundus image. Raters were asked to judge the percentage of each of the 14 squares that was covered by the hemorrhages, and the average of the 14 squares was taken to be the relative size of the retinal hemorrhage. Results. Interrater reliability between three raters was higher when a grid with 14 squares was used (intraclass correlation coefficient (ICC), 0.96) than that when a box with no grid was used (ICC, 0.78). Intrarater reliability, which was calculated by the retinal hemorrhage area measured on two different days, was also higher (ICC, 0.97) than that with no grid (ICC, 0.86). Interrater reliability for five fundus pictures with poor image quality was also good when a grid with 14 squares was used (ICC, 0.88). Conclusions. Although our method is subjective, excellent interrater and intrarater reliabilities indicate that this method can be adapted for clinical use. PMID:27867657
Botte, A; Mars, A; Wibaut, B; De Foort-Dhellemmes, S; Vinchon, M; Leclerc, F
We report on 2 cases associating retinal (RH) and cerebral hemorrhages (CH), which first suggested the diagnosis of shaken baby syndrome (SBS). After an etiologic search, the diagnosis was corrected: the first case was a late hemorrhagic disease of the newborn and the second case hemophilia A. RH is a major feature of SBS, although not pathognomonic. There is no specific RH of SBS but they usually affect the posterior retinal pole. Typically, RHs of SBS are present in both eyes, although unilateral RHs do not exclude the diagnosis of SBS. The relationship between RH and CH has been reported in SBS but also in other diseases. Thus, one must search for hemostasis abnormalities, even though the clinical presentation suggests SBS. Ignoring SBS as well as coming to the conclusion of SBS too quickly should be avoided. Diagnostic difficulties may be related to the number of physicians involved and their interpretation of the facts. These 2 cases underline the need for working as a team that includes hematologists able to interpret coagulation parameters.
Gabaeff, Steven C.
Child abuse experts use diagnostic findings of subdural hematoma and retinal hemorrhages as near-pathognomonic findings to diagnose shaken baby syndrome. This article reviews the origin of this link and casts serious doubt on the specificity of the pathophysiologic connection. The forces required to cause brain injury were derived from an experiment of high velocity impacts on monkeys, that generated forces far above those which might occur with a shaking mechanism. These forces, if present, would invariably cause neck trauma, which is conspicuously absent in most babies allegedly injured by shaking. Subdural hematoma may also be the result of common birth trauma, complicated by prenatal vitamin D deficiency, which also contributes to the appearance of long bone fractures commonly associated with child abuse. Retinal hemorrhage is a non-specific finding that occurs with many causes of increased intracranial pressure, including infection and hypoxic brain injury. The evidence challenging these connections should prompt emergency physicians and others who care for children to consider a broad differential diagnosis before settling on occult shaking as the de-facto cause. While childhood non-accidental trauma is certainly a serious problem, the wide exposure of this information may have the potential to exonerate some innocent care-givers who have been convicted, or may be accused, of child abuse. PMID:21691518
Weiss, Miriam; Clusmann, Hans; Fuest, Matthias; Mueller, Marguerite; Brockmann, Marc Alexander; Vilser, Walthard; Schmidt-Trucksäss, Arno; Hoellig, Anke; Seiz, Marcel; Thomé, Claudius; Kotliar, Konstantin; Schubert, Gerrit Alexander
Background Timely detection of impending delayed cerebral ischemia after subarachnoid hemorrhage (SAH) is essential to improve outcome, but poses a diagnostic challenge. Retinal vessels as an embryological part of the intracranial vasculature are easily accessible for analysis and may hold the key to a new and non-invasive monitoring technique. This investigation aims to determine the feasibility of standardized retinal vessel analysis (RVA) in the context of SAH. Methods In a prospective pilot study, we performed RVA in six patients awake and cooperative with SAH in the acute phase (day 2–14) and eight patients at the time of follow-up (mean 4.6±1.7months after SAH), and included 33 age-matched healthy controls. Data was acquired using a manoeuvrable Dynamic Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and neurovascular coupling. Results Image quality was satisfactory in the majority of cases (93.3%). In the acute phase after SAH, retinal arteries were significantly dilated when compared to the control group (124.2±4.3MU vs 110.9±11.4MU, p<0.01), a difference that persisted to a lesser extent in the later stage of the disease (122.7±17.2MU, p<0.05). Testing for neurovascular coupling showed a trend towards impaired primary vasodilation and secondary vasoconstriction (p = 0.08, p = 0.09 resp.) initially and partial recovery at the time of follow-up, indicating a relative improvement in a time-dependent fashion. Conclusion RVA is technically feasible in patients with SAH and can detect fluctuations in vessel diameter and autoregulation even in less severely affected patients. Preliminary data suggests potential for RVA as a new and non-invasive tool for advanced SAH monitoring, but clinical relevance and prognostic value will have to be determined in a larger cohort. PMID:27388619
Kim, Ko Eun; Kim, Dong Myung; Flammer, Josef; Kim, Kyoung Nam
Objective To compare central retinal venous pressure (CRVP) among eyes with and without optic disc hemorrhage (ODH) in bilateral normal-tension glaucoma (NTG) patients and NTG eyes without an episode of ODH. Methods In this prospective study, 22 bilateral NTG patients showing a unilateral ODH and 29 bilateral NTG patients without an episode of ODH were included. Eyes were categorized into group A (n = 22, eyes with ODH), group B (n = 22, fellow eyes without ODH), and group C (n = 29, NTG eyes without an episode of ODH). A contact lens ophthalmodynamometer was used to measure CRVP and central retinal arterial pressure (CRAP). Results Intraocular pressure (IOP) measured on the day of contact lens ophthalmodynamometry showed no difference among groups. However, the mean baseline IOP in group A was significantly lower than that in group C (P = .008). The CRVP in group A (29.1 ± 10.8 mmHg) was significantly lower than that in group C (40.1 ± 8.8 mmHg, P = .001), but similar to that in group B (30.5 ± 8.7 mmHg, P = .409). A similar relationship was noted for CRAP. No significant eye-associated variable for ODH was found in group A and B by conditional logistic regression analysis (all P > 0.05). However, multivariate logistic regression analysis in groups A and C revealed that low mean baseline IOP (odds ratio [OR] = 0.69, 95% confidence interval [CI] 0.49-0.98, P = 0.043) and low CRVP (OR = 0.88, 95% CI 0.80-0.95, P = 0.003) were associated with ODH. Conclusions CRVP was lower in NTG eyes with ODH than in eyes without an episode of ODH, but similar to that of fellow eyes without ODH. These imply less likelihood of association between increased central retinal venous resistance and ODH. PMID:25996599
Lawton, Andrew W.; Frisard, Nicholas E.
Background: Vision loss resulting from thiamine deficiency is a recognized complication of bariatric surgery. Most patients with such vision loss have Wernicke encephalopathy with characteristic changes seen on neuroimaging. Other patients may have retinal hemorrhages, optic disc edema, and peripheral neuropathy without Wernicke encephalopathy. The risk for thiamine deficiency is potentiated by the presence of prolonged vomiting. Case Report: A 37-year-old female presented with abrupt onset of vision loss and peripheral neuropathy following bariatric surgery. She had a history of prolonged vomiting postoperatively. Examination of the posterior segment of the eye revealed optic disc edema and large retinal hemorrhages bilaterally. Metabolic workup demonstrated thiamine deficiency. She responded quickly to parenteral thiamine therapy with recovery of normal vision and resolution of ophthalmologic findings. Conclusion: Patients who undergo bariatric surgery and have a thiamine deficiency can present with visual symptoms and ophthalmologic findings only visible by fundoscopy prior to developing more severe and potentially irreversible complications from the vitamin deficiency. Early detection of intraocular changes resulting from thiamine deficiency and initiation of therapy could prevent more devastating neurologic manifestations. Our case supports the consideration of a prospective study aimed at determining the true incidence of ocular and visual changes such as retinal hemorrhage, optic disc edema, and peripapillary telangiectasia in patients following bariatric surgery. PMID:28331457
Yoshida, Makoto; Yamazaki, Junpei; Mizunuma, Hiroshi
We aimed to elucidate the mechanism of the retinal hemorrhage (RH) accompanied by shaken baby syndrome or abusive head trauma (SBS/AHT) by analyses using a computational model. We focused on a hypothesis that the vitreoretinal traction due to acceleration and deceleration caused by abusive shaking leads to retinal hemorrhage. A finite element (FE) mechanical model with simple spherical geometry was constructed. When the FE mechanical model was virtually shaken, the intensity of the stress applied to the retinal plane agreed well with the results from an analysis using a physical model made of agar gel. Impacts due to falling events induced more intensive tensile stresses, but with shorter duration, than the shake did. By applying a mathematical theory on tackiness, we propose a hypothesis that the time integration of the stress, in the unit of Pa·s, would be a good predictor of the RH accompanied by SBS/AHT. A single cycle of abusive shake amounted to 101Pa·s of time integration of inflicted stress, while a single impact event amounted to 36Pa·s. This would explain the paradoxical observation that shaking induces RH while RH due to impact events is only seen in a major event such as a fatal motor vehicle accident.
Wang, Shih Hao; Lim, Chen Chee; Teng, Yu Ti
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
Aziz, Hassan A.; Kim, Jonathan W.; Munier, Francis L.; Berry, Jesse L.
Aims To report the occurrence of acute hemorrhagic retinopathy following intravitreal melphalan injection for retinoblastoma. Methods This is a retrospective case series of 2 patients with retinoblastoma treated with intravitreal melphalan for vitreous seeding who developed acute hemorrhagic retinopathy. Results Patient 1 is a 6-month-old female with bilateral retinoblastoma (Group D right eye and Group B left eye) treated with 4 cycles of systemic chemotherapy and 2 intravitreal melphalan injections in each eye. Patient 2 is a 10-month-old male with unilateral Group D retinoblastoma treated with 6 cycles of systemic chemotherapy and 2 injections of intravitreal melphalan. At the 1-week follow-up after the second injection, both patients had an acute hemorrhagic retinopathy that resulted in chorioretinal toxicity with a sharp demarcation line between the normal and abnormal retina. At the last follow-up (22 and 12 months, respectively), there was total tumor control and resolution of vitreous seeding in both patients. Conclusions Although intravitreal melphalan injection is effective for vitreous seeding in eyes with retinoblastoma, acute hemorrhagic retinopathy and diffuse chorioretinal atrophy is a possible complication of this treatment modality. Given the clinical findings observed in these patients, the development of this retinal toxicity most likely results from a retrohyaloid overdose. Consequently we suggest preventive measures aimed at limiting the risk of retrohyaloid injection.
Pneumatic displacement and intra-vitreal bevacizumab in management of sub-retinal and sub-retinal pigment epithelial hemorrhage at macula in polypoidal choroidal vasculopathy (PCV): rationale and outcome.
Nayak, Sameera; Padhi, Tapas Ranjan; Basu, Soumyava; Das, Taraprasad
We report three cases of submacular haemorrhage due to polypoidal choroidal vasculopathy (PCV) treated with intravitreal bevacizumab and pneumatic displacement with perfluoropropane (C3F8) gas. The patients were between 45 to 55 years and presented with reduction of vision (20/400 to 20/80) within two weeks of onset of symptoms. The submacular (sub-retinal plus sub-retinal pigment epithelium [RPE]) hemorrhages was confirmed as PCV on indocyanine green angiography and optical coherence tomography in all of them. They were treated with intravitreal bevacizumab (1.25 mg/0.05 ml) and 0.3 ml of 100% C3F8 gas in the affected eye followed by prone positioning for two weeks. The vision and macular anatomy started improving within a week and continued up to three months. These cases demonstrate that pneumatic displacement combined with intravitreal anti-VEGF injection could be a promising option in patients with PCV and sub-macular blood, even when the blood is beneath the RPE.
... Action You are here Home › Retinal Diseases Listen Retinitis Pigmentosa What is retinitis pigmentosa? What are the symptoms? ... is available? What treatment is available? What is retinitis pigmentosa? Retinitis pigmentosa, also known as RP, refers to ...
A stroke is a medical emergency. There are two types - ischemic and hemorrhagic. Hemorrhagic stroke is the less common type. It happens when ... an artery wall that breaks open. Symptoms of stroke are Sudden numbness or weakness of the face, ...
Carr, Ronald E.
The author describes the etiology of retinitis pigmentosa, a visual dysfunction which results from progressive loss of the retinal photoreceptors. Sections address signs and symptoms, ancillary findings, heredity, clinical diagnosis, therapy, and research. (SBH)
... men more than women and whites more than African Americans. A retinal detachment is also more likely to occur in people who Are extremely nearsighted Have had a retinal detachment in the other eye Have a family history of retinal detachment Have had cataract surgery Have ...
Alexander, James M; Wortman, Alison C
Intrapartum hemorrhage is a serious and sometimes life-threatening event. Several etiologies are known and include placental abruption, uterine atony, placenta accreta, and genital tract lacerations. Prompt recognition of blood loss, identification of the source of the hemorrhage, volume resuscitation, including red blood cells and blood products when required, will result in excellent maternal outcomes.
Filipe, J A; Pinto, A M; Rosas, V; Castro-Correia, J
Bungee jumping is becoming a popular sport in the Western world with some cases of ophthalmic complications being reported in recent literature. The authors reported a case of a 23-year-old healthy female who presented retinal complications following a bungee jumping. Her fundi showed superficial retinal hemorrhages in the right eye and a sub-internal limiting membrane hemorrhage affecting the left eye. A general examination, including a full neurological examination, was normal and laboratorial investigations were all within normal values. More studies are necessary to identify risk factors and the true incidence of related ocular lesions, but until then, we think this sport activity should be desencouraged, especially to those that are not psychological and physically fit.
... genetic terms used on this page Learning About Retinitis Pigmentosa What is retinitis pigmentosa? What are the symptoms ... Pigmentosa Additional Resources for Retinitis Pigmentosa What is retinitis pigmentosa? Retinitis pigmentosa (RP) is the name given to ...
... snapping feeling in the head. Other symptoms: Decreased consciousness and alertness Eye discomfort in bright light ( photophobia ) ... time, the outlook is much worse. Changes in consciousness and alertness due to a subarachnoid hemorrhage may ...
Parrot, A; Fartoukh, M; Cadranel, J
Alveolar hemorrhage occurs relatively rarely and is a therapeutic emergency because it can quickly lead to acute respiratory failure, which can be fatal. Hemoptysis associated with anemia and pulmonary infiltrates suggest the diagnosis of alveolar hemorrhage, but may be absent in one third of cases including patients in respiratory distress. The diagnosis of alveolar hemorrhage is based on the findings of a bronchoalveolar lavage. The causes are numerous. It is important to identify alveolar hemorrhage due to sepsis, then separate an autoimmune cause (vasculitis associated with antineutrophil cytoplasmic antibody, connective tissue disease and Goodpasture's syndrome) with the search for autoantibodies and biopsies from readily accessible organs, from a non-immune cause, performing echocardiography. Lung biopsy should be necessary only in exceptional cases. If the hemorrhage has an immune cause, treatment with steroids and cyclophosphamide may be started. The indications for treatment with rituximab are beginning to be established (forms that are not severe and refractory forms). The benefit of plasma exchange is unquestionable in Goodpasture's syndrome. In patients with an immune disease that can lead to an alveolar hemorrhage, removing any source of infection is the first priority.
Jones, B W; Kondo, M; Terasaki, H; Lin, Y; McCall, M; Marc, R E
Retinal photoreceptor degeneration takes many forms. Mutations in rhodopsin genes or disorders of the retinal pigment epithelium, defects in the adenosine triphosphate binding cassette transporter, ABCR gene defects, receptor tyrosine kinase defects, ciliopathies and transport defects, defects in both transducin and arrestin, defects in rod cyclic guanosine 3',5'-monophosphate phosphodiesterase, peripherin defects, defects in metabotropic glutamate receptors, synthetic enzymatic defects, defects in genes associated with signaling, and many more can all result in retinal degenerative disease like retinitis pigmentosa (RP) or RP-like disorders. Age-related macular degeneration (AMD) and AMD-like disorders are possibly due to a constellation of potential gene targets and gene/gene interactions, while other defects result in diabetic retinopathy or glaucoma. However, all of these insults as well as traumatic insults to the retina result in retinal remodeling. Retinal remodeling is a universal finding subsequent to retinal degenerative disease that results in deafferentation of the neural retina from photoreceptor input as downstream neuronal elements respond to loss of input with negative plasticity. This negative plasticity is not passive in the face of photoreceptor degeneration, with a phased revision of retinal structure and function found at the molecular, synaptic, cell, and tissue levels involving all cell classes in the retina, including neurons and glia. Retinal remodeling has direct implications for the rescue of vision loss through bionic or biological approaches, as circuit revision in the retina corrupts any potential surrogate photoreceptor input to a remnant neural retina. However, there are a number of potential opportunities for intervention that are revealed through the study of retinal remodeling, including therapies that are designed to slow down photoreceptor loss, interventions that are designed to limit or arrest remodeling events, and
Weiland, James D.; Humayun, Mark S.
Retinal prosthesis have been translated from the laboratory to the clinical over the past two decades. Currently, two devices have regulatory approval for the treatment of retinitis pigmentosa. These devices provide partial sight restoration and patients use this improved vision in their everyday lives. Improved mobility and object detection are some of the more notable findings from the clinical trials. However, significant vision restoration will require both better technology and improved understanding of the interaction between electrical stimulation and the retina. This paper reviews the recent clinical trials, highlights technology breakthroughs that will contribute to next generation of retinal prostheses. PMID:24710817
Newman-Gerhardt, Shoshana; Muiruri, Samuel; Muchiri, Eric; Peters, Clarence J; Morrill, John; Lucas, Alexander H; King, Charles H; Kazura, James; LaBeaud, Angelle Desiree
Rift Valley Fever (RVF) is a significant threat to human health because it can progress to retinitis, encephalitis, and hemorrhagic fever. The timing of onset of Rift Valley Fever virus (RVFV) retinitis suggests an autoimmune origin. To determine whether RVFV retinitis is associated with increased levels of IgG against retinal tissue, we measured and compared levels of IgG against healthy human eye tissue by immunohistochemical analysis. We found that serum samples from RVFV-exposed Kenyans with retinitis (n = 8) were slightly more likely to have antibodies against retinal tissue than control populations, but the correlation was not statistically significant. Further investigation into the possible immune pathogenesis of RVFV retinitis could lead to improved therapies to prevent or treat this severe complication.
Newman-Gerhardt, Shoshana; Muiruri, Samuel; Muchiri, Eric; Peters, Clarence J.; Morrill, John; Lucas, Alexander H.; King, Charles H.; Kazura, James; LaBeaud, Angelle Desiree
Rift Valley Fever (RVF) is a significant threat to human health because it can progress to retinitis, encephalitis, and hemorrhagic fever. The timing of onset of Rift Valley Fever virus (RVFV) retinitis suggests an autoimmune origin. To determine whether RVFV retinitis is associated with increased levels of IgG against retinal tissue, we measured and compared levels of IgG against healthy human eye tissue by immunohistochemical analysis. We found that serum samples from RVFV-exposed Kenyans with retinitis (n = 8) were slightly more likely to have antibodies against retinal tissue than control populations, but the correlation was not statistically significant. Further investigation into the possible immune pathogenesis of RVFV retinitis could lead to improved therapies to prevent or treat this severe complication. PMID:23918215
... immediately. Treatment How is retinal detachment treated? Small holes and tears are treated with laser surgery or ... laser surgery tiny burns are made around the hole to “weld” the retina back into place. Cryopexy ...
... be serious enough to cause blindness. Examples are Macular degeneration - a disease that destroys your sharp, central vision Diabetic eye disease Retinal detachment - a medical emergency, when the retina is ... children. Macular pucker - scar tissue on the macula Macular hole - ...
Wu, Hui-Qun; Wu, Huan; Shi, Li-Li; Yu, Li-Yuan; Wang, Li-Yuan; Chen, Ya-Lan; Geng, Jin-Song; Shi, Jian; Jiang, Kui; Dong, Jian-Cheng
AIM To determine the association between retinal vasculature changes and stroke. METHODS MEDLINE and EMBASE were searched for relevant human studies to September 2015 that investigated the association between retinal vasculature changes and the prevalence or incidence of stroke; the studies were independently examined for their qualities. Data on clinical characteristics and calculated summary odds ratios (ORs) were extracted for associations between retinal microvascular abnormalities and stroke, including stroke subtypes where possible, and adjusted for key variables. RESULTS Nine cases were included in the study comprising 20 659 patients, 1178 of whom were stroke patients. The retinal microvascular morphological markers used were hemorrhage, microaneurysm, vessel caliber, arteriovenous nicking, and fractal dimension. OR of retinal arteriole narrowing and retinal arteriovenous nicking and stroke was 1.42 and 1.91, respectively, indicating that a small-caliber retinal arteriole and retinal arteriovenous nicking were associated with stroke. OR of retinal hemorrhage and retinal microaneurysm and stroke was 3.21 and 3.83, respectively, indicating that retinal microvascular lesions were highly associated with stroke. Results also showed that retinal fractal dimension reduction was associated with stroke (OR: 2.28 for arteriole network, OR: 1.80 for venular network). CONCLUSION Retinal vasculature changes have a specific relationship to stroke, which is promising evidence for the prediction of stroke using computerized retinal vessel analysis. PMID:28149786
Pitts, R E; Awan, K J; Yanoff, M
An unusual case of choroidal malignant melanoma with heterochromia iridis, massive subretinal hemorrhage and fibrosis, spontaneously resolving retinal detachment, and subretinal seeding is reported. Clinical and pathological findings are presented and discussed. The unusual aspects of the case are further considered by Drs. Andrew Ferry and Mark Tso.
Douglas, D E
Retine, so named by Albert Szent-Györgyi, an inhibitor of the growth of transplanted malignant tumours in animals, is present in all mammalian tissues and in urine. Its inhibitory activity was extensively investigated by Szent-Györgyi, but its exact chemical identity was not determined. Details of the reported physical and chemical properties of retine and its ubiquitous occurrence identify it as being identical to a complex mixture of lipid 2,4-diketones of similar ubiquitous occurrence. This lipid mixture has been extensively studied, and individual members have been synthesized.
In acute vitreal hemorrhage, echography is the method of choice for evaluation of the vitreous body. Echography ist capable of providing information on the localization, the density, and the mobility, and in certain diseases, also on the cause of the hemorrhage. The echographic findings (standardized echography) recorded in 216 patients with acute vitreal hemorrhage examined within 14 months (Jan. 1988 to Feb. 1989) were evaluated. In 91 patients (42%) diabetic retinopathy was known: in such cases echography can disclose proliferative changes and traction-detachment of the retina. In 58 patients (27%) echography revealed a posterior vitreous detachment, while in 17 patients (8%) an additional retinal detachment was found. In 39 patients (18%) a degenerative, disciform lesion of the macula was revealed as the cause of the hemorrhage, in 5 patients (2%) a malignant melanoma of the choroid, and in 2 patients a (large) retinal tear. In 5 patients, apart from the vitreous opacities no changes in the posterior segment could be found.
Su, Cindy W
Postpartum hemorrhage (PPH) is a very common obstetric emergency with high morbidity and mortality rates worldwide. Understanding its etiology is fundamental to effectively managing PPH in an acute setting. Active management of the third stage of labor is also a key component in its prevention. Management strategies include conservative measures (medications, uterine tamponade, and arterial embolization) as well as surgical interventions (arterial ligations, compression sutures, and hysterectomy). Creating a standardized PPH protocol and running simulation-based drills with a multidisciplinary team may also help decrease maternal morbidity and improve perinatal outcomes, although further studies are needed.
Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of photoreceptors and characterized by retinal pigment deposits visible on fundus examination. Prevalence of non syndromic RP is approximately 1/4,000. The most common form of RP is a rod-cone dystrophy, in which the first symptom is night blindness, followed by the progressive loss in the peripheral visual field in daylight, and eventually leading to blindness after several decades. Some extreme cases may have a rapid evolution over two decades or a slow progression that never leads to blindness. In some cases, the clinical presentation is a cone-rod dystrophy, in which the decrease in visual acuity predominates over the visual field loss. RP is usually non syndromic but there are also many syndromic forms, the most frequent being Usher syndrome. To date, 45 causative genes/loci have been identified in non syndromic RP (for the autosomal dominant, autosomal recessive, X-linked, and digenic forms). Clinical diagnosis is based on the presence of night blindness and peripheral visual field defects, lesions in the fundus, hypovolted electroretinogram traces, and progressive worsening of these signs. Molecular diagnosis can be made for some genes, but is not usually performed due to the tremendous genetic heterogeneity of the disease. Genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, so the visual prognosis is poor. The therapeutic approach is restricted to slowing down the degenerative process by sunlight protection and vitaminotherapy, treating the complications (cataract and macular edema), and helping patients to cope with the social and psychological impact of blindness. However, new therapeutic strategies are emerging from intensive research (gene therapy, neuroprotection, retinal prosthesis). PMID:17032466
Management of traumatic hemorrhagic retinal detachment with pars plana vitrectomy . Arch. Ophthalmol. 1990; 108:1281-1286 46. Hanscom TA, Diddle KR. Early... plana vitrectomy and internal drainage. Arch. Ophthalmol. 1990;108:973-978 44. Vander JF, Federman JL, Greven C et al. Surgical removal of massive...hotocoagulation. A. Periphery of the lesion. The inner par of the OPL was replaced by processes of the Muller cells (Mu). Degenerated synaptic terminals
Heit, Jeremy J.; Iv, Michael; Wintermark, Max
Intracranial hemorrhage is common and is caused by diverse pathology, including trauma, hypertension, cerebral amyloid angiopathy, hemorrhagic conversion of ischemic infarction, cerebral aneurysms, cerebral arteriovenous malformations, dural arteriovenous fistula, vasculitis, and venous sinus thrombosis, among other causes. Neuroimaging is essential for the treating physician to identify the cause of hemorrhage and to understand the location and severity of hemorrhage, the risk of impending cerebral injury, and to guide often emergent patient treatment. We review CT and MRI evaluation of intracranial hemorrhage with the goal of providing a broad overview of the diverse causes and varied appearances of intracranial hemorrhage. PMID:28030895
Alavi, Marcel V.; Mao, Mao; Pawlikowski, Bradley T.; Kvezereli, Manana; Duncan, Jacque L.; Libby, Richard T.; John, Simon W. M.; Gould, Douglas B.
Mutations in collagen, type IV, alpha 1 (COL4A1), a major component of basement membranes, cause multisystem disorders in humans and mice. In the eye, these include anterior segment dysgenesis, optic nerve hypoplasia and retinal vascular tortuosity. Here we investigate the retinal pathology in mice carrying dominant-negative Col4a1 mutations. To this end, we examined retinas longitudinally in vivo using fluorescein angiography, funduscopy and optical coherence tomography. We assessed retinal function by electroretinography and studied the retinal ultrastructural pathology. Retinal examinations revealed serous chorioretinopathy, retinal hemorrhages, fibrosis or signs of pathogenic angiogenesis with chorioretinal anastomosis in up to approximately 90% of Col4a1 mutant eyes depending on age and the specific mutation. To identify the cell-type responsible for pathogenesis we generated a conditional Col4a1 mutation and determined that primary vascular defects underlie Col4a1-associated retinopathy. We also found focal activation of Müller cells and increased expression of pro-angiogenic factors in retinas from Col4a1+/Δex41mice. Together, our findings suggest that patients with COL4A1 and COL4A2 mutations may be at elevated risk of retinal hemorrhages and that retinal examinations may be useful for identifying patients with COL4A1 and COL4A2 mutations who are also at elevated risk of hemorrhagic strokes. PMID:26813606
Takkar, Brijesh; Azad, Shorya; Shashni, Adarsh; Pujari, Amar; Bhatia, Indrish; Azad, Rajvardhan
AIM To evaluate the causes and associations of missed retinal breaks (MRBs) and posterior vitreous detachment (PVD) in patients with rhegmatogenous retinal detachment (RRD). METHODS Case sheets of patients undergoing vitreo retinal surgery for RRD at a tertiary eye care centre were evaluated retrospectively. Out of the 378 records screened, 253 were included for analysis of MRBs and 191 patients were included for analysis of PVD, depending on the inclusion criteria. Features of RRD and retinal breaks noted on examination were compared to the status of MRBs and PVD detected during surgery for possible associations. RESULTS Overall, 27% patients had MRBs. Retinal holes were commonly missed in patients with lattice degeneration while missed retinal tears were associated with presence of complete PVD. Patients operated for cataract surgery were significantly associated with MRBs (P=0.033) with the odds of missing a retinal break being 1.91 as compared to patients with natural lens. Advanced proliferative vitreo retinopathy (PVR) and retinal bullae were the most common reasons for missing a retinal break during examination. PVD was present in 52% of the cases and was wrongly assessed in 16%. Retinal bullae, pseudophakia/aphakia, myopia, and horse shoe retinal tears were strongly associated with presence of PVD. Traumatic RRDs were rarely associated with PVD. CONCLUSION Pseudophakic patients, and patients with retinal bullae or advanced PVR should be carefully screened for MRBs. Though Weiss ring is a good indicator of PVD, it may still be over diagnosed in some cases. PVD is associated with retinal bullae and pseudophakia, and inversely with traumatic RRD. PMID:27990367
Azzi, Tatiana Tarules; Zacharias, Leandro Cabral; Pimentel, Sérgio Luis Gianotti
The Shaken Baby Syndrome (SBS) is characterized by subdural hematomas (SH), retinal hemorrhages (RH), and multiple fractures of long bones without external evidence of head trauma. Subinternal limiting membrane (ILM) hemorrhage, also known as macular schisis, is a characteristic finding of this entity. There is no guideline on the right time to indicate surgical treatment. This report describes an abused child with massive sub-ILM hemorrhage, which showed spontaneous absorption after less than two months of follow-up. Due to the possible spontaneous resolution, we suggest an initial conservative treatment in cases of sub-ILM hemorrhage related to SBS. PMID:25548698
Fischbein, Nancy J; Wijman, Christine A C
Nontraumatic (or spontaneous) intracranial hemorrhage most commonly involves the brain parenchyma and subarachnoid space. This entity accounts for at least 10% of strokes and is a leading cause of death and disability in adults. Important causes of spontaneous intracranial hemorrhage include hypertension, cerebral amyloid angiopathy, aneurysms, vascular malformations, and hemorrhagic infarcts (both venous and arterial). Imaging findings in common and less common causes of spontaneous intracranial hemorrhage are reviewed.
Mutlu, Unal; Ikram, M Arfan; Hofman, Albert; de Jong, Paulus T V M; Uitterlinden, Andre G; Klaver, Caroline C W; Ikram, M Kamran
Abstract Vitamin D has been linked to various cardiovascular risk factors including indices of large-vessel disease. However, it remains unclear whether vitamin D is also associated with microvascular damage. In a community-dwelling population, we studied associations between vitamin D serum levels and retinal microvascular damage defined as retinopathy signs, narrower arterioles, and wider venules. From the population-based Rotterdam Study, we included 5675 participants (age ≥45 years) with vitamin D data and gradable retinal photographs. Serum levels of vitamin D were measured using an antibody-based assay. Retinal exudates, microaneurysms, cotton wool spots, and dot/blot hemorrhages were graded on fundus photographs by experienced graders in the whole sample; retinal vascular calibers, that is, arteriolar and venular diameters, were semiautomatically measured in a subsample (n = 2973). We examined the cross-sectional association between vitamin D and retinal microvascular damage using logistic and linear regression models, adjusting for age, sex, and cardiovascular risk factors. We found that persons with lower vitamin D levels were more likely to have retinopathy (adjusted odds ratio per standard deviation (SD) decrease of vitamin D = 1.30; 95% confidence interval (CI): = 1.12–1.49). Furthermore, lower vitamin D levels were associated with wider venular calibers (adjusted mean difference per SD decrease in vitamin D = 1.35; 95% CI = 0.64–2.06). This association was strongest among men (P for interaction = 0.023). Lower levels of vitamin D are associated with retinal microvascular damage, suggesting that the link with cardiovascular risk may partly run through changes in the microvasculature. PMID:27930528
Donovan, Christopher P; Pecen, Paula E; Baynes, Kimberly; Ehlers, Justis P; Srivastava, Sunil K
A 31-year-old woman with a history of anti-synthetase syndrome-related myositis and interstitial lung disease presented with acute-onset blurry vision and rash on her hands and feet. Visual acuity was hand motion in her right eye and 20/40 in her left eye. Dilated fundus exam showed extensive retinal vasculitis, diffuse intraretinal hemorrhages, and subretinal fluid. Optical coherence tomography revealed significant macular thickening, and fluorescein angiography revealed vascular leakage with peripheral nonperfusion. Aggressive systemic immunosuppression was initiated, with gradual resolution of her disease during 8 months of follow-up. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:874-879.].
Mokhammad, I; Cherkasov, I S
Emoxipin, a home-made preparation approved by the Pharmacological Committee for clinical usage in 1986, is a retinal protector. Its usage is indicated for treatment of chorioretinitis, diabetic retinopathy, thrombosis of retinal vessels as well as to protects the retina from a damaging action of light of high intensity. In order to study therapeutic effectiveness of emoxipin in intraocular hemorrhages of different genesis, the preparation was used subconjunctivally, 0.5 ml of a 1% solution daily for 10-15 days. Emoxipin was used in 29 patients (29 eyes) with intraocular hemorrhages, of them, due to contusion of the eye--in 19, hypertonic disease--in 6, thrombosis of the central retinal vein--in 2, after intraocular operations--in 2 patients. As a result of the treatment, partial or almost total resolution of hemorrhages and a rise of visual acuity of different degree were recorded in all patients. Before treatment, visual acuity was from light perception to 0.04 in 26 eyes, from 0.09 to 0.3 in 3 eyes. After treatment, it rose to 0.1-0.2 in 12 eyes, to 0.3-1.0--in 17 eyes.
Jones, B W; Pfeiffer, R L; Ferrell, W D; Watt, C B; Marmor, M; Marc, R E
Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt the function or architecture of the photoreceptors. While RP can initially be a disease of photoreceptors, there is increasing evidence that the inner retina becomes progressively disorganized as the outer retina degenerates. These alterations have been extensively described in animal models, but remodeling in humans has not been as well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding of the retinal remodeling process in humans. We describe cone mediated preservation of overall topology, retinal reprogramming in the earliest stages of the disease in retinal bipolar cells, and alterations in both small molecule and protein signatures of neurons and glia. Furthermore, while Müller glia appear to be some of the last cells left in the degenerate retina, they are also one of the first cell classes in the neural retina to respond to stress which may reveal mechanisms related to remodeling and cell death in other retinal cell classes. Also fundamentally important is the finding that retinal network topologies are altered. Our results suggest interventions that presume substantial preservation of the neural retina will likely fail in late stages of the disease. Even early intervention offers no guarantee that the interventions will be immune to progressive remodeling. Fundamental work in the biology and mechanisms of disease progression are needed to support vision rescue strategies.
Almeida, David R.P.; Mammo, Zaid; Chin, Eric K.
Purpose: To describe a technique of surgical intraocular embolectomy in patients with acute fovea-threatening branch retinal artery occlusion. Methods: Pars plana vitrectomy with embolectomy involving embolus isolation, dissection, and removal in patients with an acute fovea-threatening arterial occlusion without a patent cilioretinal artery. Results: The surgical technique involves a core vitrectomy. The blocked artery is incised using a microvitreoretinal blade, and microsurgical forceps are used to retrieve the embolus. No significant complications were noted. The study technique offers an excellent safety profile and minimizes the risk of vitreous hemorrhage by carefully dissecting the vascular adventitial sheath and isolating the embolus. Conclusion: Surgical embolectomy is a viable technique for patients with acute fovea-threatening arterial occlusions without patent cilioretinal artery. Careful dissection and retrieval of the embolus minimizes the risk of vitreous hemorrhage, which is an important improvement in previous techniques for management of acute retinal arterial occlusions. PMID:26674278
Greiner, Jesse; Dorovini-Zis, Katerina; Taylor, Terrie E.; Molyneux, Malcolm E.; Beare, Nicholas A. V.; Kamiza, Steve; White, Valerie A.
Background: The retinal and brain histopathological findings in children who died from cerebral malaria (CM) have been recently described. Similar changes occur in both structures, but the findings have not been directly compared in the same patients. In this study, we compared clinical retinal findings and retinal and cerebral histopathological changes in a series of patients in Blantyre, Malawi, who died of CM. Methods: The features systematically compared in the same patient were: (1) clinical, gross and microscopic retinal hemorrhages with microscopic cerebral hemorrhages, (2) retinal and cerebral hemorrhage-associated and -unassociated axonal damage, and fibrinogen leakage, and (3) differences in the above features between the pathological categories of CM without microvascular pathology (CM1) and CM with microvascular pathology (CM2) in retina and brain. Results: Forty-seven patients were included: seven CM1, 28 CM2, and 12 controls. In the 35 malaria cases retinal and cerebral pathology correlated in all features except for non-hemorrhage associated fibrinogen leakage. Regarding CM1 and CM2 cases, the only differences were in the proportion of patients with hemorrhage-associated cerebral pathology, and this was expected, based on the definitions of CM1 and CM2. The retina did not show this difference. Non-hemorrhage associated pathology was similar for the two groups. Comment: As postulated, histopathological features of hemorrhages, axonal damage and non-hemorrhage associated fibrinogen leakage correlated in the retina and brain of individual patients, although the difference in hemorrhages between the CM1 and CM2 groups was not consistently observed in the retina. These results help to underpin the utility of ophthalmoscopic examination and fundus findings to help in diagnosis and assessment of cerebral malaria patients, but may not help in distinguishing between CM1 and CM2 patients during life. PMID:25853095
Scleral buckling; Vitrectomy; Pneumatic retinopexy; Laser retinopexy; Rhegmatogenous retinal detachment repair ... it meets the hole in the retina. Scleral buckling can be done using numbing medicine while you ...
Pigott, David C
This article reviews the epidemiology, pathophysiology, and clinical management of patients with suspected or confirmed viral hemorrhagic fever infection. The focus is on clinical management based on case series from naturally occuring outbreaks of viral hemorrhagic fever infection as well as imported cases of viral hemorrhagic fever encountered in industrialized nations. The potential risk of bioterrorism involving these agents is discussed as well as emergency department and critical care management of isolated cases or larger outbreaks. Important aspects of management, including recognition of infected patients, isolation and decontamination procedures, as well as available vaccines and therapies are emphasized.
We have been able to create a reproducible experimental model of nonexpulsive massive suprachoroidal hemorrhage in a rabbit eye. Massive suprachoroidal hemorrhage was demonstrated on echography and confirmed on histopathologic examination in all eyes. The natural course of the disease suggests that there is very little change in the size of the choroidal detachment in the first 7 days. Maximum liquefaction of the suprachoroidal hemorrhage clot was seen to occur between 7 and 14 days. However, increased retinal and ciliary body atrophy was also noted at 14 days. Therefore, the optimum time to drain massive suprachoroidal hemorrhage appears to be between 7 and 14 days. Immediate sclerotomy during the acute formation of massive suprachoroidal hemorrhage resulted in further increase in the suprachoroidal hemorrhage, with marked extension of the hemorrhage into the retina and vitreous. Therefore, in our opinion, immediate sclerotomy during massive suprachoroidal hemorrhage is detrimental to the eye. Our clinical data have shown that eyes with massive suprachoroidal hemorrhage can be treated successfully by secondary surgery, and the majority of the eyes can be salvaged with good visual results. No serious complications of this surgery were encountered in our cases. We advocate early surgical intervention between 7 and 14 days. Aggressive anterior and posterior segment reconstruction by anterior and posterior vitrectomy after sclerotomy drainage of the suprachoroidal hemorrhage is essential for better anatomic and visual results. Our animal data and clinical experience suggest that the optimum time of drainage of massive suprachoroidal hemorrhage is between 7 and 14 days. The results of our animal experiments in relation to human clinical application should be taken with caution. Furthermore, we had a small number of animals to study the various groups. In addition, longer follow-up may be needed for comparing controls with the treatment groups. Our animal model may help
Pruett, R C
This thesis presents the results of a study of 384 eyes of 192 patients with a mean age of 39.1 years who presented with typical retinitis pigmentosa. The major findings are outlined below, together with suggested hypotheses: Cataract was found in 46.4% of the eyes. Among these, 93.6% showed posterior subcapsular opacification. The incidence of cataract increased with age. The vitreous degeneration that is characteristic of the RP syndrome and begins in childhood was described as showing dust-like, particulate matter throughout the gel; posterior vitreous separation; formation of a posterior matrix of coarse, white, interconnected strands and opacities; and final collapse of the residual gel. Ultrastructural studies of vitreous material from eight eyes revealed that the particles were isolated pigment granules and the coarse strands were composed of condensed collagen fibers. Notwithstanding the vitreous degeneration and prevalence of myopia in RP, neurosensory retinal breaks and/or rhegmatogenous detachment were found in only 7 (1.8%) of the 384 eyes studied. Premature separation of the vitreous from the retina, absence of lattice retinal degeneration, and perhaps a stronger than normal RPE-neurosensory retinal bond are thought to be possible protective factors. Rather than searching for a "toxin," elaborated by diseased retina, that causes vitreous degeneration and cataract formation, it is suggested that the ocular media be studied for an absence of moieties that are normally produced by healthy retina for vitreous and lens maintenance. The classic criteria for diagnosis of RP were met by 96.3% of eyes that showed retinal vascular attenuation and by 52.0% that showed pallor of the optic disc. Less frequent manifestations included solitary retinal hemorrhage, peripheral microaneurysms, telangiectasia, and fluorescein leakage at the macula and disc. Seven additional cases with a Coats'-like retinal detachment were added to the 14 already presented in the
Sternfeld, Amir; Axer-Siegel, Ruth; Stiebel-Kalish, Hadas; Weinberger, Dov; Ehrlich, Rita
Purpose To evaluate the outcomes and complications of patients with diabetic tractional retinal detachment (TRD) treated with pars plana vitrectomy (PPV). Patients and methods We retrospectively studied a case series of 24 eyes of 21 patients at a single tertiary, university-affiliated medical center. A review was carried out on patients who underwent PPV for the management of TRD due to proliferative diabetic retinopathy from October 2011 to November 2013. Preoperative and final visual outcomes, intraoperative and postoperative complications, and medical background were evaluated. Results A 23 G instrumentation was used in 23 eyes (95.8%), and a 25 G instrumentation in one (4.2%). Mean postoperative follow-up time was 13.3 months (4–30 months). Visual acuity significantly improved from logarithm of the minimum angle of resolution (LogMAR) 1.48 to LogMAR 1.05 (P<0.05). Visual acuity improved by ≥3 lines in 75% of patients. Intraoperative complications included iatrogenic retinal breaks in seven eyes (22.9%) and vitreal hemorrhage in nine eyes (37.5%). In two eyes, one sclerotomy was enlarged to 20 G (8.3%). Postoperative complications included reoperation in five eyes (20.8%) due to persistent subretinal fluid (n=3), vitreous hemorrhage (n=1), and dislocated intraocular lens (n=1). Thirteen patients (54.2%) had postoperative vitreous hemorrhage that cleared spontaneously, five patients (20.8%) required antiglaucoma medications for increased intraocular pressure, seven patients (29.2%) developed an epiretinal membrane, and two patients (8.3%) developed a macular hole. Conclusion Patients with diabetic TRD can benefit from PPV surgery. Intraoperative and postoperative complications can be attributed to the complexity of this disease. PMID:26604667
Joshi, V.; Agurto, C.; Barriga, S.; Nemeth, S.; Soliz, P.; MacCormick, I.; Taylor, T.; Lewallen, S.; Harding, S.
Cerebral malaria (CM) is a severe neurological complication associated with malarial infection. Malaria affects approximately 200 million people worldwide, and claims 600,000 lives annually, 75% of whom are African children under five years of age. Because most of these mortalities are caused by the high incidence of CM misdiagnosis, there is a need for an accurate diagnostic to confirm the presence of CM. The retinal lesions associated with malarial retinopathy (MR) such as retinal whitening, vessel discoloration, and hemorrhages, are highly specific to CM, and their detection can improve the accuracy of CM diagnosis. This paper will focus on development of an automated method for the detection of retinal whitening which is a unique sign of MR that manifests due to retinal ischemia resulting from CM. We propose to detect the whitening region in retinal color images based on multiple color and textural features. First, we preprocess the image using color and textural features of the CMYK and CIE-XYZ color spaces to minimize camera reflex. Next, we utilize color features of the HSL, CMYK, and CIE-XYZ channels, along with the structural features of difference of Gaussians. A watershed segmentation algorithm is used to assign each image region a probability of being inside the whitening, based on extracted features. The algorithm was applied to a dataset of 54 images (40 with whitening and 14 controls) that resulted in an image-based (binary) classification with an AUC of 0.80. This provides 88% sensitivity at a specificity of 65%. For a clinical application that requires a high specificity setting, the algorithm can be tuned to a specificity of 89% at a sensitivity of 82%. This is the first published method for retinal whitening detection and combining it with the detection methods for vessel discoloration and hemorrhages can further improve the detection accuracy for malarial retinopathy.
Wubben, Thomas J; Besirli, Cagri G; Zacks, David N
Retinal detachment is an important cause of visual loss. Currently, surgical techniques, including vitrectomy, scleral buckle, and pneumatic retinopexy, are the only means to repair retinal detachment and restore vision. However, surgical failure rates may be as high as 20%, and visual outcomes continue to vary secondary to multiple processes, including postoperative cystoid macular edema, epiretinal membrane formation, macular folds, and, ultimately, photoreceptor death. Therefore, pharmacotherapies are being sought to aid the success rates of modern surgical techniques and reduce or slow the degeneration of photoreceptors during retinal detachment. This review discusses potential therapeutic avenues that aid in retinal reattachment, reduce the rate of retinal redetachment by limiting proliferative vitreoretinopathy, and protect against photoreceptor cell death.
Haddad, Waleed S.; Trebes, James E.
The microwave hemorrhagic stroke detector includes a low power pulsed microwave transmitter with a broad-band antenna for producing a directional beam of microwaves, an index of refraction matching cap placed over the patients head, and an array of broad-band microwave receivers with collection antennae. The system of microwave transmitter and receivers are scanned around, and can also be positioned up and down the axis of the patients head. The microwave hemorrhagic stroke detector is a completely non-invasive device designed to detect and localize blood pooling and clots or to measure blood flow within the head or body. The device is based on low power pulsed microwave technology combined with specialized antennas and tomographic methods. The system can be used for rapid, non-invasive detection of blood pooling such as occurs with hemorrhagic stroke in human or animal patients as well as for the detection of hemorrhage within a patient's body.
Haddad, Waleed S.; Trebes, James E.
The microwave hemorrhagic stroke detector includes a low power pulsed microwave transmitter with a broad-band antenna for producing a directional beam of microwaves, an index of refraction matching cap placed over the patients head, and an array of broad-band microwave receivers with collection antennae. The system of microwave transmitter and receivers are scanned around, and can also be positioned up and down the axis of the patients head. The microwave hemorrhagic stroke detector is a completely non-invasive device designed to detect and localize blood pooling and clots or to measure blood flow within the head or body. The device is based on low power pulsed microwave technology combined with specialized antennas and tomographic methods. The system can be used for rapid, non-invasive detection of blood pooling such as occurs with hemorrhagic stoke in human or animal patients as well as for the detection of hemorrhage within a patient's body.
This book chapter describes the taxonomic classification of Simian hemorrhagic fever virus (SHFV). Included are: host, genome, classification, morphology, physicochemical and physical properties, nucleic acid, proteins, lipids, carbohydrates, geographic range, phylogenetic properties, biological pro...
Burnett, Mark W
Ebola hemorrhagic fever is an often-fatal disease caused by a virus of the Filoviridae family, genus Ebolavirus. Initial signs and symptoms of the disease are nonspecific, often progressing on to a severe hemorrhagic illness. Special Operations Forces Medical Providers should be aware of this disease, which occurs in sporadic outbreaks throughout Africa. Treatment at the present time is mainly supportive. Special care should be taken to prevent contact with bodily fluids of those infected, which can transmit the virus to caregivers.
Rishi, Pukhraj; Rishi, Ekta; Sen, Pratik Ranjan; Sharma, Tarun
Retinal ‘cysts’ may be single or multiple, ranging from two-to-ten disc diameters in size, and occur in eyes with longstanding retinal detachment. The authors describe a retinal macrocyst larger than ten disc diameters, with a blood-filled cavity, and its ultrasound findings. Improved retinal nourishment following retinal reattachment gradually reverses the process responsible for cystic degeneration, with the eventual collapse of the cyst (within days or weeks). Surprisingly, this giant cyst did not collapse for almost three years despite retinal reattachment. The internal mobile echogenic contents were suggestive of blood. The possible reason of blood in the cyst could be rupture of the retinal blood vessels in the cyst cavity. This could be a recurrent phenomenon, which did not allow the cyst to collapse. The Hemorrhagic Intraretinal Macrocyst needs to be differentiated from mimicking clinical conditions, namely, retinoschisis, choroidal melanoma, subretinal abscess, choroidal hemangioma, and the like. It could take up to a few years to collapse spontaneously, following successful retinal reattachment. PMID:21713238
Otani, Atsushi; Friedlander, Martin
We discuss the potential use of stem cells for therapeutic angiogenesis in the treatment of retinal diseases. We demonstrate that the clinical utility of these EPC may be not limited in the treatment of ischemic retinal diseases but may also have application for the treatment of retinal degenerative disorders and for a form of cell-based gene therapy. One of the greatest potential benefits of bone marrow derived EPC therapy is the possible use of autologous grafts. Nonetheless, potential toxicities and unregulated cell growth will need to be carefully evaluated before this approach is brought to the clinics.
Rilvén, Sandra; Torp, Thomas Lee; Grauslund, Jakob
The retinal oximeter is a new tool for non-invasive measurement of retinal oxygen saturation in humans. Several studies have investigated the associations between retinal oxygen saturation and retinal diseases. In the present systematic review, we examine whether there are associations between retinal oxygen saturation and retinal ischaemic diseases. We used PubMed and Embase to search for retinal oxygen saturation and retinal ischaemic diseases. Three separate searches identified a total of 79 publications. After two levels of manual screening, 10 studies were included: six about diabetic retinopathy (DR) and four about retinal vein occlusion. No studies about retinal artery occlusion were included. In diabetes, all studies found that increases in retinal venous oxygen saturation (rvSatO2 ) were associated with present as well as increasing levels of DR. Four of six studies also found increased retinal arterial oxygen saturation (raSatO2 ) in patients with DR. In patients with central retinal vein occlusion (CRVO), all studies found that rvSatO2 was reduced, but raSatO2 remained unchanged. Branch retinal vein occlusion was not associated with changes in retinal oxygen saturation, but this was based on a single study. In conclusion, DR is associated with increased rvSatO2 and might also be related to increased raSatO2 . Central retinal vein occlusion (CRVO) is correlated with increased rvSatO2 but unrelated to raSatO2 . Prospective studies are needed to expand these findings. These would tell whether retinal oximetry could be a potential tool for screening or a biomarker of treatment outcome in patients with ischaemic retinal diseases.
Galin, M A; Poole, T A; Obstbaum, S A
In a series of cataract patients excluding myopic individuals, under age 60 years, and cases in which vitreous loss occurred, retinal detachment was no less frequent after intracapsular cataract extraction and Sputnik iris supported lenses than in controls. Both groups were followed up for a minimum of two years. The detachments predominantly occurred from retinal breaks in areas of the retina that looked normal preoperatively.
Gorovoy, Ian R; Layer, Noelle; de Alba Campomanes, Alejandra G
Retinal dysplasia occurs in the setting of sporadic and syndromic holoprosencephaly, which often has associated ocular malformations. The pathology of this dysplasia, which includes rosettes, has been previously described. However, its funduscopic findings have not been well documented. The authors present the fundus images of a patient with severe holoprosencephaly with retinal dysplasia and bilateral optic nerve colobomas that resulted in death 2 weeks after birth.
Kawaguchi, Tatsushi; Spencer, Doran B; Mochizuki, Manabu
Acute retinal necrosis is a progressive necrotizing retinopathy caused by herpes simplex virus (HSV) or varicella zoster virus (VZV). The mainstay of its treatment is antiviral therapy against these pathogenic organisms, such as intravenous acyclovir or oral valacyclovir. Systemic and topical corticosteroids together with antiviral therapy are used as an anti-inflammatory treatment to minimize damages to the optic nerve and retinal blood vessels. Because the majority of severe cases of the disease show occlusive retinal vasculitis, a low dosage of aspirin is used as anti-thrombotic treatment. Vitreo-retinal surgery is useful to repair rhegmatogenous retinal detachment, one of the main late-stage complications. Moreover, recent articles have reported some encouraging results of prophylactic vitrectomy before rhegmatogenous retinal detachment occurs. The efficacy of laser photocoagulation to prevent the development or extension of rhegmatogenous retinal detachment is controversial. Despite these treatments, the visual prognosis of acute retinal necrosis is still poor, in particular VZV-induced acute retinal necrosis.
Batts, William N.; Winton, James R.
Viral hemorrhagic septicemia (VHS) is one of the most important viral diseases of finfish worldwide. In the past, VHS was thought to affect mainly rainbow trout Oncorhynchus mykiss reared at freshwater facilities in Western Europe where it was known by various names including Egtved disease and infectious kidney swelling and liver degeneration (Wolf 1988). Today, VHS is known as an important source of mortality for cultured and wild fish in freshwater and marine environments in several regions of the northern hemisphere (Dixon 1999; Gagné et al. 2007; Kim and Faisal 2011; Lumsden et al. 2007; Marty et al. 1998, 2003; Meyers and Winton 1995; Skall et al. 2005b; Smail 1999; Takano et al. 2001). Viral hemorrhagic septicemia is caused by the fish rhabdovirus, viral hemorrhagic septicemia virus (VHSV), a member of the genus Novirhabdovirus of the family Rhabdoviridae
... VHFs) are caused by several families of enveloped RNA viruses: filoviruses (Ebola and Marburg hemorrhagic fever), arenaviruses ( ... in hemorrhagic fever with high death rates. Old World (Eastern Hemisphere) and New World (Western Hemisphere) viruses ...
... hypertension) Other eye conditions, such as glaucoma , macular edema, or vitreous hemorrhage The risk of these disorders ... in the front part of the eye Macular edema, caused by the leakage of fluid in the ...
AD-A<m 761 KOREA UNIV SEOUL COLL OF MEDICINE KOREAN HEM0RRHA6IC FEVER.(U) MAR 80 H W LEE UNCLASSIFIED ICFI F/6 6/5 DAM017-79-6-9<*55 NL...I» > I,,iu. •Uli ••-. SUMMARY There were 364 hospitalized cases of Korean hemorrhagic fever (KHF) in 1979 in Korea . Lee et al...STANDARDS-1963-A ?H "LEVEtf® AD <o KOREAN HEMORRHAGIC F EVER A D A 09 47 Final Report HO WANG LEE, M. D. March 1980 i MIL. IIB«I . Mm k iw
Wu, Chris Y; Riangwiwat, Tanawan; Nakamoto, Beau K
Longitudinally extensive transverse myelitis (LETM) may be associated with viral triggers, including both infections and vaccinations. We present a case of a healthy immunocompetent 33-year-old woman who developed a hemorrhagic LETM 2 weeks after seasonal influenza vaccination. Hemorrhagic LETM has not to our knowledge been reported after influenza vaccination. It may represent a forme fruste variant of acute hemorrhagic leukoencephalitis.
Chawla, Rohan; Tripathy, Koushik; Gogia, Varun; Venkatesh, Pradeep
We describe two young immunocompetent women presenting with bilateral retinitis with outer retinal necrosis involving posterior pole with centrifugal spread and multifocal lesions simulating progressive outer retinal necrosis (PORN) like retinitis. Serology was negative for HIV and CD4 counts were normal; however, both women were on oral steroids at presentation for suspected autoimmune chorioretinitis. The retinitis in both eyes responded well to oral valaciclovir therapy. However, the eye with the more fulminant involvement developed retinal detachment with a loss of vision. Retinal atrophy was seen in the less involved eye with preservation of vision. Through these cases, we aim to describe a unique evolution of PORN-like retinitis in immunocompetent women, which was probably aggravated by a short-term immunosuppression secondary to oral steroids.
RD-RI55 255 KOREAN HEMORRHAGIC FEVER (HEMORRHAGIC FEVER WITH RENAL 11 SYNDROME (HFRS))(U) KOREA UNIV SEOUL DEPT OF MICROBIOLOGY H U LEE RUG 83 DRMDi...the first time in Korea (4,13). WHO has recently adapted to call Korean hemorrhagic fever and clinically similar diseases with a different name, HFRS...AD_______ I •. KOREAN HEMORRHAGIC FEVER • (HEMORRHAGIC FEVER WITH RENAL SYNDROME (HFRS)) I Final Report 0 In HO WANG LEE, M.D. August 1983 Supported by U.S
Loudin, James; Mathieson, Keith; Kamins, Ted; Wang, Lele; Galambos, Ludwig; Huie, Philip; Sher, Alexander; Harris, James; Palanker, Daniel
Electronic retinal prostheses seek to restore sight to patients suffering from retinal degenerative disorders. Implanted electrode arrays apply patterned electrical stimulation to surviving retinal neurons, producing visual sensations. All current designs employ inductively coupled coils to transmit power and/or data to the implant. We present here the design and initial testing of a photovoltaic retinal prosthesis fabricated with a pixel density of up to 177 pixels/mm2. Photodiodes within each pixel of the subretinal array directly convert light to stimulation current, avoiding the use of bulky coil implants, decoding electronics, and wiring, and thereby reducing surgical complexity. A goggles-mounted camera captures the visual scene and transmits the data stream to a pocket processor. The resulting images are projected into the eyes by video goggles using pulsed, near infrared (~900 nm) light. Prostheses with three pixel densities (15, 55, and 177 pix/mm2) are being fabricated, and tests indicate a charge injection limit of 1.62 mC/cm2 at 25Hz. In vitro tests of the photovoltaic retinal stimulation using a 512-element microelectrode array have recorded stimulated spikes from the ganglion cells, with latencies in the 1-100ms range, and with peak irradiance stimulation thresholds varying from 0.1 to 1 mW/mm2. With 1ms pulses at 25Hz the average irradiance is more than 100 times below the IR retinal safety limit. Elicited retinal response disappeared upon the addition of synaptic blockers, indicating that the inner retina is stimulated rather than the ganglion cells directly, and raising hopes that the prosthesis will preserve some of the retina's natural signal processing.
Gutierrez, Guillermo; Reines, H David; Wulf-Gutierrez, Marian E
This review addresses the pathophysiology and treatment of hemorrhagic shock – a condition produced by rapid and significant loss of intravascular volume, which may lead sequentially to hemodynamic instability, decreases in oxygen delivery, decreased tissue perfusion, cellular hypoxia, organ damage, and death. Hemorrhagic shock can be rapidly fatal. The primary goals are to stop the bleeding and to restore circulating blood volume. Resuscitation may well depend on the estimated severity of hemorrhage. It now appears that patients with moderate hypotension from bleeding may benefit by delaying massive fluid resuscitation until they reach a definitive care facility. On the other hand, the use of intravenous fluids, crystalloids or colloids, and blood products can be life saving in those patients who are in severe hemorrhagic shock. The optimal method of resuscitation has not been clearly established. A hemoglobin level of 7–8 g/dl appears to be an appropriate threshold for transfusion in critically ill patients with no evidence of tissue hypoxia. However, maintaining a higher hemoglobin level of 10 g/dl is a reasonable goal in actively bleeding patients, the elderly, or individuals who are at risk for myocardial infarction. Moreover, hemoglobin concentration should not be the only therapeutic guide in actively bleeding patients. Instead, therapy should be aimed at restoring intravascular volume and adequate hemodynamic parameters. PMID:15469601
Korean hemorrhagic fever (KHF) occurred for the first time in Korea , 1951, although it had previously been known to both the Japanese and Russians...After Korean war, the disease has been fixed in the areas of DMZ as an endemic one, and from 100 to 400 cases have been being reportee every year
Sonka, Milan; Abràmoff, Michael D
Clinical acceptance of 3-D OCT retinal imaging brought rapid development of quantitative 3-D analysis of retinal layers, vasculature, retinal lesions as well as facilitated new research in retinal diseases. One of the cornerstones of many such analyses is segmentation and thickness quantification of retinal layers and the choroid, with an inherently 3-D simultaneous multi-layer LOGISMOS (Layered Optimal Graph Image Segmentation for Multiple Objects and Surfaces) segmentation approach being extremely well suited for the task. Once retinal layers are segmented, regional thickness, brightness, or texture-based indices of individual layers can be easily determined and thus contribute to our understanding of retinal or optic nerve head (ONH) disease processes and can be employed for determination of disease status, treatment responses, visual function, etc. Out of many applications, examples provided in this paper focus on image-guided therapy and outcome prediction in age-related macular degeneration and on assessing visual function from retinal layer structure in glaucoma.
MacLaren, R E
Blindness due to outer retinal degeneration still remains largely untreatable. Photoreceptor loss removes light sensitivity, but the remaining inner retinal layers, the optic nerve, and indeed the physical structure of the eye itself may be unaffected by the degenerative processes. This provides the opportunity to restore some degree of vision with an electronic device in the subretinal space. In this lecture I will provide an overview of our experiences with the first-generation retinal implant Alpha IMS, developed by Retina Implant AG and based on the technology developed by Eberhart Zrenner as part of a multicentre clinical trial (NCT01024803). We are currently in the process of running a second NIHR-funded clinical trial to assess the next-generation device. The positive results from both studies to date indicate that the retinal implant should be included as a potential treatment for patients who are completely blind from retinitis pigmentosa. Evolution of the technology in future may provide further opportunities for earlier intervention or for other diseases.
36) However, vascularization of the RPE is not known to occur in human diseases of photoreceptor degeneration, such as retinitis pigmentosa ...A.C. (1986) Retinitis pigmentosa and retinal neovascularization. Ophthalmology 91, 1599- 1603. Figure la: Control rat retina, 8 weeks of age, central...TITLE (Include Security Classification) Intracellular Signalling in Retinal Ischemia 12. PERSONAL AUTHOR(S) Burns, Margaret Sue; Bellhorn, Roy William
Wu, Chang-Hua; Agam, Gady
Optic fundus assessment is widely used for diagnosing vascular and non-vascular pathology. Inspection of the retinal vasculature may reveal hypertension, diabetes, arteriosclerosis, cardiovascular disease and stroke. Due to various imaging conditions retinal images may be degraded. Consequently, the enhancement of such images and vessels in them is an important task with direct clinical applications. We propose a novel technique for vessel enhancement in retinal images that is capable of enhancing vessel junctions in addition to linear vessel segments. This is an extension of vessel filters we have previously developed for vessel enhancement in thoracic CT scans. The proposed approach is based on probabilistic models which can discern vessels and junctions. Evaluation shows the proposed filter is better than several known techniques and is comparable to the state of the art when evaluated on a standard dataset. A ridge-based vessel tracking process is applied on the enhanced image to demonstrate the effectiveness of the enhancement filter.
Kiser, Philip D.; Palczewski, Krzysztof
Recent progress in molecular understanding of the retinoid cycle in mammalian retina stems from painstaking biochemical reconstitution studies supported by natural or engineered animal models with known genetic lesions and studies of humans with specific genetic blinding diseases. Structural and membrane biology have been used to detect critical retinal enzymes and proteins and their substrates and ligands, placing them in a cellular context. These studies have been supplemented by analytical chemistry methods that have identified small molecules by their spectral characteristics, often in conjunction with the evaluation of models of animal retinal disease. It is from this background that rational therapeutic interventions to correct genetic defects or environmental insults are identified. Thus, most presently accepted modulators of the retinoid cycle already have demonstrated promising results in animal models of retinal degeneration. These encouraging signs indicate that some human blinding diseases can be alleviated by pharmacological interventions. PMID:27917399
Weiland, James D.
Retinal prosthesis have been translated to clinical use over the past two decades. Currently, two devices have regulatory approval for the treatment of retinitis pigmentosa and one device is in clinical trials for treatment of age-related macular degeneration. These devices provide partial sight restoration and patients use this improved vision in their everyday lives to navigate and to detect large objects. However, significant vision restoration will require both better technology and improved understanding of the interaction between electrical stimulation and the retina. In particular, current retinal prostheses do not provide peripheral visions due to technical and surgical limitations, thus limiting the effectiveness of the treatment. This paper reviews recent results from human implant patients and presents technical approaches for peripheral vision.
Halldorsson, G. H.; Karlsson, R. A.; Hardarson, S. H.; Mura, M. Dalla; Eysteinsson, T.; Beach, J. M.; Stefansson, E.; Benediktsson, J. A.
This paper presents a method for automating the evaluation of hemoglobin oxygen saturation in the retina. This method should prove useful for monitoring ischemic retinal diseases and the effect of treatment. In order to obtain saturation values automatically, spectral images must be registered in pairs, the vessels of the retina located and measurement points must be selected. The registration algorithm is based on a data driven approach that circumvents many of the problems that have plagued previous methods. The vessels are extracted using an algorithm based on morphological profiles and supervised classifiers. Measurement points on retinal arterioles and venules as well as reference points on the adjacent fundus are automatically selected. Oxygen saturation values along vessels are averaged to arrive at a more accurate estimate of the retinal vessel oxygen saturation. The system yields reproducible results as well as being sensitive to changes in oxygen saturation.
Gray, Ellyn J; Gardner, Thomas W
Physiologic adaptations mediate normal responses to short-term and long-term stresses to ensure organ function. Organ failure results if adaptive responses fail to resolve persistent stresses or maladaptive reactions develop. The retinal neurovascular unit likewise undergoes adaptive responses to diabetes resulting in a retinal sensory neuropathy analogous to other sensory neuropathies. Vision-threatening diabetic retinal neuropathy results from unremitting metabolic and inflammatory stresses, leading to macular edema and proliferative diabetic retinopathy, states of "retinal failure." Current regulatory strategies focus primarily on the retinal failure stages, but new diagnostic modalities and understanding of the pathophysiology of diabetic retinopathy may facilitate earlier treatment to maintain vision in persons with diabetes.
Events and discoveries in oxygen monitoring over the past two centuries are presented as the background from which oximetry of the human retina evolved. Achievements and the people behind them are discussed, showing parallels between the work in tissue measurements and later in the eye. Developments in the two-wavelength technique for oxygen saturation measurements in retinal vessels are shown to exploit the forms of imaging technology available over time. The last section provides a short summary of the recent research in retinal diseases using vessel oximetry. PMID:25237591
Hohman, Thomas C
As our understanding of the genetic basis for inherited retinal disease has expanded, gene therapy has advanced into clinical development. When the gene mutations associated with inherited retinal dystrophies were identified, it became possible to create animal models in which individual gene were altered to match the human mutations. The retina of these animals were then characterized to assess whether the mutated genes produced retinal phenotypes characteristic of disease-affected patients. Following the identification of a subpopulation of patients with the affected gene and the development of techniques for the viral gene transduction of retinal cells, it has become possible to deliver a copy of the normal gene into the retinal sites of the mutated genes. When this was performed in animal models of monogenic diseases, at an early stage of retinal degeneration when the affected cells remained viable, successful gene augmentation corrected the structural and functional lesions characteristic of the specific diseases in the areas of the retina that were successfully transduced. These studies provided the essential proof-of-concept needed to advance monogenic gene therapies into clinic development; these therapies include treatments for: Leber's congenital amaurosis type 2, caused by mutations to RPE65, retinoid isomerohydrolase; choroideremia, caused by mutations to REP1, Rab escort protein 1; autosomal recessive Stargardt disease, caused by mutations to ABCA4, the photoreceptor-specific ATP-binding transporter; Usher 1B disease caused by mutations to MYO7A, myosin heavy chain 7; X-linked juvenile retinoschisis caused by mutations to RS1, retinoschisin; autosomal recessive retinitis pigmentosa caused by mutations to MERTK, the proto-oncogene tyrosine-protein kinase MER; Leber's hereditary optic neuropathy caused by mutations to ND4, mitochondrial nicotinamide adenine dinucleotide ubiquinone oxidoreductase (complex I) subunit 4 and achromatopsia, caused by
Events and discoveries in oxygen monitoring over the past two centuries are presented as the background from which oximetry of the human retina evolved. Achievements and the people behind them are discussed, showing parallels between the work in tissue measurements and later in the eye. Developments in the two-wavelength technique for oxygen saturation measurements in retinal vessels are shown to exploit the forms of imaging technology available over time. The last section provides a short summary of the recent research in retinal diseases using vessel oximetry.
The hypothesis that an occlusion of the central retinal artery is an essential prerequisite for haemorrhage formation after central retinal vein obstruction has been investigated by examining the fundus changes in patients with a cilio-retinal arterial circulation; the findings are at variance with the 'combined occlusion hypothesis'. Comparisons were made between the pathological features in two retinal capillary beds with independent sources of arterial supply--namely, the central retinal and cilio-retinal arteries--but with an obstructed venous drainage channel common to both--namely, the central retinal vein. The importance of intraluminal pressure changes (as distinct from perfusion changes) in the causation of haemorrhages and oedema after venous occlusion is stressed, and the role of arterial disease in the pathogenesis of venous occlusions is distinguished from its role in determining the sequelae of such occlusions. Images PMID:1203235
Hussain, Rehan M.; Abbey, Ashkan M.; Shah, Ankoor R.; Drenser, Kimberly A.; Trese, Michael T.; Capone, Antonio
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
Guven, Dilek; Acar, Zeynep; Demir, Mehmet; Sendul, Yekta; Demir, Atilla Gokce; Ergen, Erdem
A 21-year-old female presented with a 4-day history of decreased vision in her only functional eye (right eye, OD). She had a history of multiple ocular surgeries in both eyes because of congenital glaucoma and had lost light perception in her left eye several years prior. Ophthalmological examination revealed 0.15 Snellen visual acuity, and fundoscopy revealed nearly total cupping and pallor of the optic disc and multiple retinal hemorrhagic foci in the macula in OD. Lesions spontaneously resolved over a few months. Gravitational forces during a roller coaster ride may have caused this macular hemorrhage.
The treatment of retinal thrombosis is an unresolved problem, mainly because of the numerous factors which participate in their formation; modifications in the walls of veins and arteries, external compressions, changes in the blood count--particularly of the platelets--slowing down of the blood flow, increase in blood viscosity etc. No drug provides constant results. Some widely employed drugs such as vasodilators may be useless or even contra-indicated. Emphasis is placed on anti-coagulants, fibrinolytics, antiaggregating agents and methods of lowering blood viscosity. Their action is difficult to test objectively. Some do appear to be useful, especially in cases of central vein thrombosis. Thrombi of branches of the central vein are apparently inacessible to medical therapy, but occasionally improvement is seen after laser coagulation. This seems to apply also to hemorrhagic glaucoma secondary to retinal obstruction.
Kim, Tae Jin; Koh, Eun Jung
Very rarely, spinal subarachnoid hemorrhage (SSAH) can occur without any direct spinal injury in patients with traumatic intracranial SAH. A-59-year-old male with traumatic intracranial subarachnoid hemorrhage (SAH) presented with pain and numbness in his buttock and thigh two days after trauma. Pain and numbness rapidly worsened and perianal numbness and voiding difficulty began on the next day. Magnetic resonance imaging showed intraspinal hemorrhage in the lumbosacral region. The cauda equina was displaced and compressed. Emergent laminectomy and drainage of hemorrhage were performed and SSAH was found intraoperatively. The symptoms were relieved immediately after the surgery. Patients with traumatic intracranial hemorrhage who present with delayed pain or neurological deficits should be evaluated for intraspinal hemorrhage promptly, even when the patients had no history of direct spinal injury and had no apparent symptoms related to the spinal injury in the initial period of trauma. PMID:27857928
Radian, A B; Corşatea, L; Alupei, L
The paper presents the evolution at ten eyes (nine patients) that presented expulsive hemorrhage during surgical act of extracapsular extraction with implant of crystalline lens. There are several cases of extracapsular extraction than intracapsular extraction which were more short like duration. The frequency of female was 90% from cases. The good results show the efficiency of associated treatment: closing of the eyeball with scleral punctura and internal tamponing. Only one eye was lost functionally.
Hilsden, R. J.; Shaffer, E. A.
Acute gastrointestinal hemorrhage is a common problem that requires prompt recognition and management to prevent serious morbidity and mortality. Management goals are stabilization of the patient with vigorous fluid resuscitation followed by investigation and definitive treatment of the bleeding source. Endoscopy is often the initial diagnostic test and allows therapeutic measures to be performed at the same time. Images Figure 1 Figure 2 PMID:8563510
Medicine Seoul, Korea * S 0 0 0 0 0 0 0 0 0 0 0 0 0 0 SUM ARY Urban rats captured in Seoul and four nearby Korean cities were found to have...rattus, urban Korean cities, 1980. . . . 15 Table 2. Isolation of Hantaan virus from antigen-positive wild house rats, Korea , 1980 .... ........... .. 16...Figures Figure 1. Map of Seoul City, South Korea and metropolitan area showing locations of urban Korean hemorrhagic fever cases, andRattu s positive
53 INTRODUCTION During the Korean War more than 3,200 United Nations troops in Korea devel6ped a rare hemorrhagic fever which attracted...patients in the Republic of Korea . Year Korean Korean US Total civilian soldiers soldiers 1951 ...... 627 827 1952 .... 833 833 1953 ... ... 455 455...0 RI m HEMORRHAGIC FEVER WITH RENAL SYNDROME ( KOREAN HEMORRHAGIC FEVER) ANNUAL SUMMARY REPORT HO WANG LEE, M.D. June 30, 1988 Door., Supported by U.S
Timberlake, George T; Sharma, Manoj K; Grose, Susan A; Maino, Joseph H
A method of mapping the retinal location of text during reading is described in which text position is plotted cumulatively on scanning laser ophthalmoscope retinal images. Retinal locations that contain text most often are the brightest in the cumulative plot, and locations that contain text least often are the darkest. In this way, the retinal area that most often contains text is determined. Text maps were plotted for eight control subjects without vision loss and eight subjects with central scotomas from macular degeneration. Control subjects' text maps showed that the fovea contained text most often. Text maps of five of the subjects with scotomas showed that they used the same peripheral retinal area to scan text and fixate. Text maps of the other three subjects with scotomas showed that they used separate areas to scan text and fixate. Retinal text maps may help evaluate rehabilitative strategies for training individuals with central scotomas to use a particular retinal area to scan text.
The neuroretina should be considered as a potential site of nanomaterial toxicity. Engineered nanomaterials may reach the retina through three potential routes of exposure including; intra vitreal injection of therapeutics; blood-borne delivery in the retinal vasculature an...
Wu, Chris Y.; Riangwiwat, Tanawan
Longitudinally extensive transverse myelitis (LETM) may be associated with viral triggers, including both infections and vaccinations. We present a case of a healthy immunocompetent 33-year-old woman who developed a hemorrhagic LETM 2 weeks after seasonal influenza vaccination. Hemorrhagic LETM has not to our knowledge been reported after influenza vaccination. It may represent a forme fruste variant of acute hemorrhagic leukoencephalitis. PMID:27847660
Sarohia, Dani; Javan, Ramin; Aziz, Salim
We present a case in which intraocular silicone injection for complex retinal detachment resulted in migration and distribution of silicone along the intracranial visual pathway, and ultimately throughout the ventricular system. Misinterpretation of this material as intracranial hemorrhage on outside computed tomography imaging delayed emergent repair of a Type A aortic dissection until the diagnosis was made on repeat imaging. A discussion of this case and salient computed tomography and magnetic resonance imaging characteristics of silicone is provided. PMID:27761189
Tsunekawa, Taichi; Hwang, Shiang-Jyi; Oishi, Akio; Nagasaka, Yosuke; Iwase, Takeshi; Nonobe, Norie; Ueno, Shinji; Ito, Yasuki; Yasuda, Shunsuke; Shimizu, Hideyuki; Suzumura, Ayana; Kataoka, Keiko; Terasaki, Hiroko
Purpose. We had earlier reported positive hsa-miR-148a-3p expression in eyes with rhegmatogenous retinal detachment (RRD) and its involvement in the epithelial-mesenchymal transition of retinal pigment epithelium in vitro. Here we investigated the association of hsa-miR-148a-3p expression levels in the vitreous fluid of patients with RRD with severity of RRD. Methods. The hsa-miR-148a-3p expression levels in the vitreous fluid, range (degree) of retinal detachment (RD), and pixels of retinal break were measured in 27 eyes with RRD. The association of hsa-miR-148a-3p expression levels with other factors was evaluated by multiple regression analysis. Results. The hsa-miR-148a-3p expression levels, time from onset of RRD to vitrectomy, range of RD, and pixels of retinal breaks were 23.68 ± 43.00, 12.07 ± 15.36 days, 155.85 ± 86.67 degrees, and 37000 ± 67100 pixels, respectively. Five eyes with RRD had vitreous hemorrhage preoperatively. The hsa-miR-148a-3p expression levels were significantly associated with pixels of retinal breaks (β = 0.699) and the time from onset of RRD to vitrectomy (β = 0.358) but not with the range of RD or presence of vitreous hemorrhage. Conclusion. The hsa-miR-148a-3p expression levels in the vitreous fluid were significantly associated with the size of retinal break and disease duration. PMID:28261609
Korean hemorrhagic fever (KHF) occurred for the first time in Korea , 1951, although it had previously been known to both the Japanese and Russians...After Korean war, the disease has been fixed in the areas of DMZ as an endemic one, and from 100 to 300 cases have been reported every year. The aims...but in 1971 affected the middle districts and in 1972 invaded the southern parts of South Korea . The number of patients and the areas of KHF in 1972
Choi, WooJhon; Drexler, Wolfgang; Fujimoto, James G.
Developing and validating new techniques and methods for small animal imaging is an important research area because there are many small animal models of retinal diseases such as diabetic retinopathy, age-related macular degeneration, and glaucoma [1-6]. Because the retina is a multilayered structure with distinct abnormalities occurring in different intraretinal layers at different stages of disease progression, there is a need for imaging techniques that enable visualization of these layers individually at different time points. Although postmortem histology and ultrastructural analysis can be performed for investigating microscopic changes in the retina in small animal models, this requires sacrificing animals, which makes repeated assessment of the same animal at different time points impossible and increases the number of animals required. Furthermore, some retinal processes such as neurovascular coupling cannot be fully characterized postmortem.
Eye Diseases Hereditary; Retinal Disease; Achromatopsia; Bardet-Biedl Syndrome; Bassen-Kornzweig Syndrome; Batten Disease; Best Disease; Choroidal Dystrophy; Choroideremia; Cone Dystrophy; Cone-Rod Dystrophy; Congenital Stationary Night Blindness; Enhanced S-Cone Syndrome; Fundus Albipunctatus; Goldmann-Favre Syndrome; Gyrate Atrophy; Juvenile Macular Degeneration; Kearns-Sayre Syndrome; Leber Congenital Amaurosis; Refsum Syndrome; Retinitis Pigmentosa; Retinitis Punctata Albescens; Retinoschisis; Rod-Cone Dystrophy; Rod Dystrophy; Rod Monochromacy; Stargardt Disease; Usher Syndrome
Spontaneous activity patterns propagate through many parts of the developing nervous system and shape the wiring of emerging circuits. Prior to vision, waves of activity originating in the retina propagate through the lateral geniculate nucleus (LGN) of the thalamus to primary visual cortex (V1). Retinal waves have been shown to instruct the wiring of ganglion cell axons in LGN and of thalamocortical axons in V1 via correlation-based plasticity rules. Across species, retinal waves mature in three stereotypic stages (I–III), in which distinct circuit mechanisms give rise to unique activity patterns that serve specific functions in visual system refinement. Here, I review insights into the patterns, mechanisms, and functions of stage III retinal waves, which rely on glutamatergic signaling. As glutamatergic waves spread across the retina, neighboring ganglion cells with opposite light responses (ON vs. OFF) are activated sequentially. Recent studies identified lateral excitatory networks in the inner retina that generate and propagate glutamatergic waves, and vertical inhibitory networks that desynchronize the activity of ON and OFF cells in the wavefront. Stage III wave activity patterns may help segregate axons of ON and OFF ganglion cells in the LGN, and could contribute to the emergence of orientation selectivity in V1. PMID:27242446
Ambrosio, Ana; Saavedra, Maria; Mariani, Mauricio; Gamboa, Graciela; Maiza, Andrea
Argentine hemorrhagic fever (AHF), an acute disease caused by Junin virus (JUNV, Arenaviridae), has been an important issue to public health in Argentina since the early 1950s. The field rodent Calomys musculinus is JUNV natural reservoir and human disease is a consequence of contact with infected rodents. A steady extention of AHF endemic area is being observed since the first reports of the disease. Important achievements have been made in: (a) improvement of methods for the etiological diagnosis; (b) implementation and validation of therapeutical measures; (c) development of vaccines to protect against AHF. Reference is made to different research strategies used to obtain anti-AHF vaccines in the past and anti-arenaviral diseases in the present. Information is updated on features and field performance of Candid #1 vaccine, a live attenuted vaccine currently used to prevent AHF. This vaccine was developed through a joint international effort that envisioned it as an orphan drug. With transferred technology, Argentine government was committed to be Candid #1 manufacturer and to register this vaccine as a novel medical product under the Argentine regulatory authority. Candid #1 vaccine is the first one used to control an arenaviral hemorrhagic fever, the first live viral vaccine to be manufactured and registered in Argentina, reaching its target population through governmental effort.
Li, Jing; Ma, Jianmin; Wang, Ningli
Retinal oximeter is a new machine which has been used in the diagnose, treatment and research of several ophthalmic diseases for recent years. It allows ophthalmologists to gain retinal oxygen saturation directly. Therefore, retinal oximeter might be useful for ophthalmologists to understand ophthalmic diseases more deeper and clarify the impact of ischemia on retinal function. It has been reported in the literatures that retinal oximeter has potentially useful diagnostic and therapeutic indications in various eye diseases such as diabetic retinopathy, central retinal vein and artery occlusion, retinitis pigmentosa, glaucomatous optic neuropathy, et al. In this thesis, the application of retinal oximeter in ophthalmology is reviewed.
Humayun, M S
PURPOSE: An electronic implant that can bypass the damaged photoreceptors and electrically stimulate the remaining retinal neurons to restore useful vision has been proposed. A number of key questions remain to make this approach feasible. The goal of this thesis is to address the following 2 specific null hypotheses: (1) Stimulus parameters make no difference in the electrically elicited retinal responses. (2) Just as we have millions of photoreceptors, so it will take a device that can generate millions of pixels/light points to create useful vision. METHODS: For electrophysiologic experiments, 2 different setups were used. In the first setup, charge-balanced pulses were delivered to the retinal surface via electrodes inserted through an open sky approach in normal or blind retinal degenerate (rd) mice. In the second setup, the rabbit retina was removed under red light conditions from an enucleated eye and then maintained in a chamber while being superfused with oxygenated, heated Ames media. In both setups, stimulating electrodes and recording electrodes were positioned on the retinal surface to evaluate the effect of varying stimulation parameters on the orthodromic retinal responses (i.e., recording electrode placed between stimulating electrodes and optic nerve head). For psychophysical experiments, visual images were divided into pixels of light that could be projected in a pattern on the retina in up to 8 sighted volunteers. Subjects were asked to perform various tasks ranging from reading and face recognition to various activities of daily living. RESULTS: Electrophysiologic experiments: In a normal mouse, a single cycle of a 1-kHz sine wave was significantly more efficient than a 1-kHz square wave (P < .05), but no such difference was noted in either of the 8- or 16-week-old rd mouse groups (8-week-old, P = .426; 16-week-old, P = .078). Charge threshold was significantly higher in 16-week-old rd mouse versus both 8-week-old rd and normal mouse for every
AD-Ai55 228 KOREAN HEMORRHAGIC FEVER (HEMORRHAGIC FEVER WITH RENAL in. SYNDROME (HFRS))(U) KOREA UNIV SEOUL DEPT OF MICROBIOLOGY H W LEE JUL 84...INTRODUCTION During the Korean War, more than 2,400 United Nations troops stationed in the 38th Parallel in Korea developed a rare disease which had not... Korean hemorrhagic fever patients in urban areas of Seoul. Korean J. Virol. 10: 1-6, 1980. 8. Lee, H. W. New epidemiological findings of HFRS in Korea . J
Racsa, Lori D.; Kraft, Colleen S.; Olinger, Gene G.; Hensley, Lisa E.
There are 4 families of viruses that cause viral hemorrhagic fever (VHF), including Filoviridae. Ebola virus is one virus within the family Filoviridae and the cause of the current outbreak of VHF in West Africa. VHF-endemic areas are found throughout the world, yet traditional diagnosis of VHF has been performed in large reference laboratories centered in Europe and the United States. The large amount of capital needed, as well as highly trained and skilled personnel, has limited the availability of diagnostics in endemic areas except in conjunction with governmental and nongovernmental entities. However, rapid diagnosis of VHF is essential to efforts that will limit outbreaks. In addition, increased global travel suggests VHF diagnoses may be made outside of the endemic areas. Thus, understanding how to diagnose VHF is imperative for laboratories worldwide. This article reviews traditional and current diagnostic modalities for VHF. PMID:26354968
Mracsko, Eva; Veltkamp, Roland
Spontaneous intracerebral hemorrhage (ICH) is a particularly severe type of stroke for which no specific treatment has been established yet. Although preclinical models of ICH have substantial methodological limitations, important insight into the pathophysiology has been gained. Mounting evidence suggests an important contribution of inflammatory mechanisms to brain damage and potential repair. Neuroinflammation evoked by intracerebral blood involves the activation of resident microglia, the infiltration of systemic immune cells and the production of cytokines, chemokines, extracellular proteases and reactive oxygen species (ROS). Previous studies focused on innate immunity including microglia, monocytes and granulocytes. More recently, the role of adaptive immune cells has received increasing attention. Little is currently known about the interactions among different immune cell populations in the setting of ICH. Nevertheless, immunomodulatory strategies are already being explored in ICH. To improve the chances of translation from preclinical models to patients, a better characterization of the neuroinflammation in patients is desirable. PMID:25477782
Hassan, Ali; Ahmad, Bakhtiar; Ahmed, Zahoor; Al-Quliti, Khalid W.
Ruptured cerebral aneurysm is the most common cause of spontaneous subarachnoid hemorrhage (SAH). Rarely cerebral venous sinus thrombosis (CVST) may present initially as acute SAH, and clinically mimics aneurysmal bleed. We report 2 cases of CVST who presented with severe headache associated with neck pain and focal seizures. Non-contrast brain CT showed SAH, involving the sulci of the convexity of hemisphere (cSAH) without involving the basal cisterns. Both patients received treatment with anticoagulants and improved. Awareness of this unusual presentation of CVST is important for early diagnosis and treatment. The purpose of this paper is to emphasize the inclusion of vascular neuroimaging like MRI with venography or CT venography in the diagnostic workup of SAH, especially in a patient with strong clinical suspicion of CVST or in a patient where neuroimaging showed cSAH. PMID:25630784
Gulati, Deepak; Dua, Dharti; Torbey, Michel T.
Spontaneous non-traumatic intracerebral hemorrhage (ICH) is associated with high morbidity and mortality throughout the world with no proven effective treatment. Majority of hematoma expansion occur within 4 h after symptom onset and is associated with early deterioration and poor clinical outcome. There is a vital role of ultra-early hemostatic therapy in ICH to limit hematoma expansion. Patients at risk for hematoma expansion are with underlying hemostatic abnormalities. Treatment strategy should include appropriate intervention based on the history of use of antithrombotic use or an underlying coagulopathy in patients with ICH. For antiplatelet-associated ICH, recommendation is to discontinue antiplatelet agent and transfuse platelets to those who will undergo neurosurgical procedure with moderate quality of evidence. For vitamin K antagonist-associated ICH, administration of 3-factor or 4-factor prothrombin complex concentrates (PCCs) rather than fresh frozen plasma to patients with INR >1.4 is strongly recommended. For patients with novel oral anticoagulant-associated ICH, administering activated charcoal to those who present within 2 h of ingestion is recommended. Idarucizumab, a humanized monoclonal antibody fragment against dabigatran (direct thrombin inhibitor) is approved by FDA for emergency situations. Administer activated PCC (50 U/kg) or 4-factor PCC (50 U/kg) to patients with ICH associated with direct thrombin inhibitors (DTI) if idarucizumab is not available or if the hemorrhage is associated with a DTI other than dabigatran. For factor Xa inhibitor-associated ICH, administration of 4-factor PCC or aPCC is preferred over recombinant FVIIa because of the lower risk of adverse thrombotic events. PMID:28360881
Loudin, Jim; Dinyari, Rostam; Huie, Phil; Butterwick, Alex; Peumans, Peter; Palanker, Daniel
Electronic retinal prostheses seek to restore sight in patients with retinal degeneration by delivering pulsed electric currents to retinal neurons via an array of microelectrodes. Most implants use inductive or optical transmission of information and power to an intraocular receiver, with decoded signals subsequently distributed to retinal electrodes through an intraocular cable. Surgical complexity could be minimized by an "integrated" prosthesis, in which both power and data are delivered directly to the stimulating array without any discrete components or cables. We present here an integrated retinal prosthesis system based on a photodiode array implant. Video frames are processed and imaged onto the retinal implant by a video goggle projection system operating at near-infrared wavelengths (~ 900 nm). Photodiodes convert light into pulsed electric current, with charge injection maximized by specially optimized series photodiode circuits. Prostheses of three different pixel densities (16 pix/mm2, 64 pix/mm2, and 256 pix/mm2) have been designed, simulated, and prototyped. Retinal tissue response to subretinal implants made of various materials has been investigated in RCS rats. The resulting prosthesis can provide sufficient charge injection for high resolution retinal stimulation without the need for implantation of any bulky discrete elements such as coils or tethers. In addition, since every pixel functions independently, pixel arrays may be placed separately in the subretinal space, providing visual stimulation to a larger field of view.
Abràmoff, Michael D.; Garvin, Mona K.; Sonka, Milan
Many important eye diseases as well as systemic diseases manifest themselves in the retina. While a number of other anatomical structures contribute to the process of vision, this review focuses on retinal imaging and image analysis. Following a brief overview of the most prevalent causes of blindness in the industrialized world that includes age-related macular degeneration, diabetic retinopathy, and glaucoma, the review is devoted to retinal imaging and image analysis methods and their clinical implications. Methods for 2-D fundus imaging and techniques for 3-D optical coherence tomography (OCT) imaging are reviewed. Special attention is given to quantitative techniques for analysis of fundus photographs with a focus on clinically relevant assessment of retinal vasculature, identification of retinal lesions, assessment of optic nerve head (ONH) shape, building retinal atlases, and to automated methods for population screening for retinal diseases. A separate section is devoted to 3-D analysis of OCT images, describing methods for segmentation and analysis of retinal layers, retinal vasculature, and 2-D/3-D detection of symptomatic exudate-associated derangements, as well as to OCT-based analysis of ONH morphology and shape. Throughout the paper, aspects of image acquisition, image analysis, and clinical relevance are treated together considering their mutually interlinked relationships. PMID:21743764
A number of research groups are developing electrical implants that can be attached directly to the retina in an attempt to restore vision to patients suffering from retinal degeneration. However, despite promising results in animal experiments, there are still several major obstacles to overcome before retinal prostheses can be used clinically.
18 Related Projects ........................ . . ....... 20 References . . . . .......................... 22 2 INTRODUCTION The objectives of...fluorescein is a potent phototoxic agent in the retina.26 The damage threshold for blue light retinal damage is lowered by a factor of ten after an... Related to the Probiem of Retinal Light Damage 1. Corneal Holography 2. Hematoporphyrin Studies 3. Fluorescein Fluorescence Measurements 7 EQUIPMENT
Hsieh, Po-Jang; Colas, Jaron T.
A retinally stabilized object readily undergoes perceptual fading and disappears from consciousness. This startling phenomenon is commonly believed to arise from local bottom-up sensory adaptation to edge information that occurs early in the visual pathway, such as in the lateral geniculate nucleus of the thalamus or retinal ganglion cells. Here…
Traumatic retinal detachments are a significant cause of morbidity. There are currently no evidence-based guidelines on the appropriate time to perform vitreoretinal surgery to repair a traumatic retinal detachment. Early intervention, within seven days of the inciting trauma, may decrease proliferative vitreoretinopathy and postoperative endophthalmitis. Later intervention may yield a reduced risk of inflammation and hemorrhage, particularly in cases of concomitant open globe injuries. This article reviews the literature on the management of retinal detachments associated with ocular trauma from the years 2006 to 2016. Particular focus was placed on the timing of surgery, concomitant open globe injury, anatomical success rates, visual acuity, and complication rates. In this review, anatomical success was not significantly related to timing of intervention when compared between early and delayed intervention in eyes with and without concomitant open globe injuries. Visual acuities postoperatively varied widely despite timing of intervention due to the large variation in mechanism and extent of ocular injuries. Proliferative vitreoretinopathy was a common complication. Preliminary data indicate that endophthalmitis rates may be lower when early vitreoretinal surgery is performed. There is insufficient data to conclude whether early or delayed surgery leads to improved outcomes, highlighting the need for further research in this domain. PMID:27999681
36 DISTRIBUTION LIST. .................... 40 INTRODUCTION During the Korean War more than 3,200 United Nations troops in Korea developed a rare...hemorrhagic fever, a situa- tion that attracted worldwide attention (1). Since then it has been known as Korean hemorrhagic fever (KHF) in Korea . This...Kyunggido and Kangwondo, northern parts of South Korea . All of the 97 HFRS patients among Korean soldiers occurred in Kyunggido, Kangwondo and Seoul
DISTRIBUTION LIST .............. .................... 47 5 INTRODUCTION During the Korean War more than 3,200 United Nations troops in Korea developed a...rare hemorrhagic fever, a situa- tion that attracted worldwide attention (1). Since then it has been known as Korean hemorrhagic fever (KHF) in Korea ...Chungchoongnsmdo, and Kangwendo, norLhern parts of South Korea . Almost all HFRS patients among Korean soldiers occurred in Kyunggido aind Ksngwmndo where
13 Table 5. Monthly incidence of HFRS among Korean in the Republic of Korea , 1966-1985 . . . . . . . 14 A Table 6. Incidence of HFRS by...GRANT SUPPORT .. ........ 57.... 5 INTRODUCTION During the Korean War more than 3,000 United Nations .00 troops in Korea developed a rare hemorrhagic...8217;.-.* * S.’ . " 10 ... Table 1. Hospitalized cases of Hemorrhagic fever with renal syndrome patients in the Republic of Korea Year US Korean Korean
Préterre, Cécile; Godeneche, Gaelle; Vandamme, Xavier; Ronzière, Thomas; Lamy, Matthias; Breuilly, Christophe; Urbanczyk, Cédric; Wolff, Valérie; Lebranchu, Pierre; Sevin-Allouet, Mathieu; Guillon, Benoit
Background Although acute central retinal artery occlusion is as a stroke in the carotid territory (retinal artery), its management remains controversial. The aim of this study was to assess the feasibility and safety of intravenous thrombolysis delivered within 6 h of central retinal artery occlusion in French stroke units. Methods We performed a retrospective analysis of patients treated with intravenous alteplase (recombinant tissue-plasminogen activator), based on stroke units thrombolysis registers from June 2005 to June 2015, and we selected those who had acute central retinal artery occlusion. The feasibility was assessed by the ratio of patients that had received intravenous alteplase within 6 h after central retinal artery occlusion onset among those who had been admitted to the same hospital for acute central retinal artery occlusion. All adverse events were documented. Results Thirty patients were included. Visual acuity before treatment was limited to "hand motion", or worse, in 90% of the cases. The mean onset-to-needle time was 273 min. The individuals treated with intravenous alteplase for central retinal artery occlusion represented 10.2% of all of the patients hospitalized for central retinal artery occlusion in 2013 and 2014. We observed one occurrence of major bleeding, a symptomatic intracerebral hemorrhage. Conclusion When applied early on, intravenous thrombolysis appears to be feasible and safe, provided that contraindications are given due consideration. Whether intravenous thrombolysis is more effective than conservative therapy remains to be determined. In order to conduct a well-designed prospective randomized control trial, an organized network should be in place.
Moraz, Marie-Laurence; Kunz, Stefan
Viral hemorrhagic fevers (VHFs) caused by arenaviruses belong to the most devastating emerging human diseases and represent serious public health problems. Arenavirus VHFs in humans are acute diseases characterized by fever and, in severe cases, different degrees of hemorrhages associated with a shock syndrome in the terminal stage. Over the past years, much has been learned about the pathogenesis of arenaviruses at the cellular level, in particular their ability to subvert the host cell's innate antiviral defenses. Clinical studies and novel animal models have provided important new information about the interaction of hemorrhagic arenaviruses with the host's adaptive immune system, in particular virus-induced immunosuppression, and have provided the first hints towards an understanding of the terminal hemorrhagic shock syndrome. The scope of this article is to review our current knowledge on arenavirus VHF pathogenesis with an emphasis on recent developments.
Postpartum hemorrhage remains a major cause of maternal morbidity and mortality. The incidence of postpartum hemorrhage appears to be increasing in developed countries due to an increased number of placenta accreta or percreta after previous Cesarean deliveries. The initial therapy of postpartum hemorrhage consists of uterotonic drugs and inspection of the uterine cavum. At the same time, optimization of the clotting potential should be initiated early. Tranexamic acid may be considered as a first line choice, followed by fibrinogen if necessary. If bleeding continues, fresh frozen plasma and packed red cells should be ordered in a ratio of 1:1, as this ratio has been shown to improve survival in trauma victims. All labor and delivery suites should have standard operating procedures for the management of postpartum hemorrhage in place with regular drills.
Bunick, Christopher G.; Aasi, Sumaira Z.
The ability to recognize, manage, and, most importantly, prevent hemorrhagic complications is critical to performing dermatologic procedures that have safe and high quality outcomes. This article reviews the preoperative, intraoperative, and postoperative factors and patient dynamics that are central to preventing such an adverse outcome. Specifically, the role that anticoagulants and antiplatelet agents, hypertension, and other medical conditions play in the development of postoperative hemorrhage are discussed. In addition, this article provides practical guidelines on managing bleeding during and after surgery. PMID:22515669
Manusow, Joshua S; Khoja, Leila; Pesin, Nataly; Joshua, Anthony M; Mandelcorn, Efrem D
We report on a 36-year-old woman treated with the anti PD-1 antibody Pembrolizumab for metastatic cutaneous melanoma in the first line setting. She achieved a complete response and then relapsed with metastases to the vitreous cavity with an associated angiographically determined retinal vasculitis. Vitreous metastasis without choroidal involvement is unusual and may be due to individual cell extravasation, vitreous hemorrhage containing malignant cells, or direct spread through the optic nerve. This finding highlights the need for immune sanctuary sites to be monitored in the presence of PD-1 inhibition and we hypothesize that the use of PD-1 inhibitor potentiated the patient's angiographically determined retinal vasculitis.
Kim, Jun Yup; Bae, Hee-Joon
Spontaneous non-traumatic intracerebral hemorrhage (ICH) remains a significant cause of mortality and morbidity throughout the world. To improve the devastating course of ICH, various clinical trials for medical and surgical interventions have been conducted in the last 10 years. Recent large-scale clinical trials have reported that early intensive blood pressure reduction can be a safe and feasible strategy for ICH, and have suggested a safe target range for systolic blood pressure. While new medical therapies associated with warfarin and non-vitamin K antagonist oral anticoagulants have been developed to treat ICH, recent trials have not been able to demonstrate the overall beneficial effects of surgical intervention on mortality and functional outcomes. However, some patients with ICH may benefit from surgical management in specific clinical contexts and/or at specific times. Furthermore, clinical trials for minimally invasive surgical evacuation methods are ongoing and may provide positive evidence. Upon understanding the current guidelines for the management of ICH, clinicians can administer appropriate treatment and attempt to improve the clinical outcome of ICH. The purpose of this review is to help in the decision-making of the medical and surgical management of ICH. PMID:28178413
Campa, Claudio; Alivernini, Giuseppe; Bolletta, Elena; Parodi, Maurizio Battaglia; Perri, Paolo
Retinal vein occlusion (RVO) is the second most common cause of visual loss in the Western World. RVO is usually classified into branch RVO (BRVO) and central RVO (CRVO) according to the anatomical site of the vascular occlusion. The pathogenesis of RVO is not yet fully understood, however an important event is the intraluminal thrombus formation, which is usually secondary to several conditions such as hypertension, hyperlipidemia, diabetes and thrombophilia. The blockage of venous circulation causes an elevation of intraluminal pressure in the capillaries, leading to hemorrhages and leakage of fluid within the retina, increase of interstitial pressure and a consequent reduction of retinal perfusion. Ischemia may develop resulting in secretion of vascular endothelial growth factor (VEGF) that causes further vascular leakage and retinal oedema. VEGF has therefore a leading role in RVO pathogenesis and symptoms. As a consequence use of anti-VEGF agents by intravitreal injections has become very common with the aim to improve the clinical outcomes in these patients. Currently 2 anti-VEGF agents (ranimizumab and aflibercept) have been FDA (Food and Drug Administration) and EMA (European Medicine Agency) approved for the treatment of RVO, while another VEGF inhibitor (bevacizumab) is often used "off-label" in clinical practice. Many treatment regimens have been suggested in the clinical trials with these drugs, as monthly injections or injections when needed, however the ideal regimen has not been defined yet. We conducted a systematic review searching MEDLINE for the following terms: retinal vein occlusion, ranibizumab, bevacizumab, aflibercept, vascular endothelial growth factor, macular oedema. Data were extracted by one author (AG and BE) and checked by a second (BPM, CC). Aim of this article was to review available data for each drug, focusing on their efficacy and safety trying to compare their advantages and limits.
AlAli, Alaa; Bushehri, Ahmad; Park, Jonathan C.; Krema, Hatem
Purpose: To report a case of multifocal serous retinal detachments associated with pimasertib. Methods: The authors report a 26-year-old patient who developed bilateral multifocal serous retinal detachments appearing 2 days after starting pimasertib (as part of a clinical trial investigating its use in low-grade metastatic ovarian cancer) and rapidly resolving 3 days after stopping it. Conclusion: The mechanism of MEK inhibitor induced visual toxicity remains unclear. The pathophysiology of multifocal serous retinal detachments as a complication of pimasertib is still poorly understood. PMID:26444523
García-Campos, Jose Manuel; García-Basterra, Ignacio; Kamal-Salah, Radua; Baquero-Aranda, Isabel
We present a case of a 40-year-old woman with a fundus image similar to frosted retinal angiitis after undergoing pars plana vitrectomy and intravitreal triamcinolone injection. The patient with diabetic retinopathy was referred to our hospital with vision loss in her right eye secondary to vitreous haemorrhage. After pars plana vitrectomy and injection of triamcinolone acetonide a funduscopy examination revealed deposits of triamcinolone along the retinal vessels simulating a frosted retinal angiitis. Triamcinolone deposits along blood vessels could be the result of the reabsorption process of these crystals by the perivascular macrophages. Further studies are needed. PMID:25678611
Lin, Jonathan H.; LaVail, Matthew M.
Many mutations associated with retinal degeneration lead to the production of misfolded proteins by cells of the retina. Emerging evidence suggests that these abnormal proteins cause cell death by activating the Unfolded Protein Response, a set of conserved intracellular signaling pathways that detect protein misfolding within the endoplasmic reticulum and control protective and proapoptotic signal transduction pathways. Here, we review the misfolded proteins associated with select types of retinitis pigmentosa, Stargadt-like macular degeneration, and Doyne Honeycomb Retinal Dystrophy and discuss the role that endoplasmic reticulum stress and UPR signaling play in their pathogenesis. Last, we review new therapies for these diseases based on preventing protein misfolding in the retina. PMID:20238009
Ocular vascular diseases such as diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration, whose population increases along with aging, have become leading causes of severe visual disturbance. Macular edema and serous retinal detachment are associated with abnormal vascular leakage and tractional retinal detachment, and neovascular glaucoma is caused by retinal neovascularization. Such ocular vascular diseases are caused by vascular cell aging and vascular damage associated with lifestyle-related diseases including diabetes mellitus, hypertension, hyperlipidemia, and obesity. In the present study, we investigated molecular mechanisms in such vascular deficiencies using vascular cell biology methodology, and we propose novel strategies for the treatment of such vascular diseases. Along with aging, oxidative stress and physical stress, such as mechanical stretch, continuously and directly insult vascular cells. Such stress induces apoptosis by intracellular signaling through stress kinases in cultured retinal vascular cells. Inhibition of such stress kinases could be an effective treatment to protect the vascular cells against age-related damage. In a retinal vascular developmental model, pericyte loss causes pathology mimicking macular edema and proliferative diabetic retinopathy. Angiopoietin 1 (Ang 1) secreted by pericytes suppresses oxidative stress-induced intracellular signaling through stress kinases linked to cell apoptosis and normalizes such retinal pathology. This suggests that the paracrine action of Ang 1 in the pericytes is necessary to sustain normal retinal vasculature, and that Ang 1-triggered intracellular signaling is useful for the treatment of vascular cell pathology associated with pericyte loss. In diabetic retinopathy and retinal vein occlusion, retinal vessels regress along with retinal vascular cell apoptosis, and the retina becomes ischemic followed by pathological retinal neovascularization. VEGF has been
Okandan, Murat; Wessendorf, Kurt O.; Christenson, Todd R.
An electrode array which has applications for neural stimulation and sensing. The electrode array can include a large number of electrodes each of which is flexibly attached to a common substrate using a plurality of springs to allow the electrodes to move independently. The electrode array can be formed from a combination of bulk and surface micromachining, with electrode tips that can include an electroplated metal (e.g. platinum, iridium, gold or titanium) or a metal oxide (e.g. iridium oxide) for biocompatibility. The electrode array can be used to form a part of a neural prosthesis, and is particularly well adapted for use in an implantable retinal prosthesis where the electrodes can be tailored to provide a uniform gentle contact pressure with optional sensing of this contact pressure at one or more of the electrodes.
Ivanov, A N
The paper is devoted to the actual problem of ophthalmology--removal of cysts and retinal detachments caused by cystoid retinal lesions. 3 stages of treatment are identified: stage 1 used YAG-laser dissection of the external wall of the retinal cyst with drainage of its contents. Stage 2 involved extrascleral filling reinforced by argon coagulation of the zone of the emptied cyst or by endolaser coagulation. Laser intervention was performed by the laser combine "Visulas-YAG II" produced by the firm "Karl Zeiss" (Germany) and fitted up by endolaser output. Coagulation energy was 0.2-0.7 W, the power of YAG-laser was 0.1-5.7 mJ with impulses of 120. Almost in all of the cases laser action was realized during one session. The laser's action was associated with hemorrhage in 11 cases (57.9%), and within 1 year of observations 2 relapses were noted (10.5%). YAG perforation of the external wall of a retinal cyst brings on its drainage and evacuation that is a perspective factor in subsequent surgical interventions during operations for retinal detachment due to cystoid degeneration.
Kao, Alex; Hsi, Brian; Lee, Shwu-Huey; Chen, Yau-Hung; Wang, I-Jong
Retinopathy of prematurity, formerly known as a retrolental fibroplasia, is a leading cause of infantile blindness worldwide. Retinopathy of prematurity is caused by the failure of central retinal vessels to reach the retinal periphery, creating a nonperfused peripheral retina, resulting in retinal hypoxia, neovascularization, vitreous hemorrhage, vitreoretinal fibrosis, and loss of vision. We established a potential retinopathy of prematurity model by using a green fluorescent vascular endothelium zebrafish transgenic line treated with cobalt chloride (a hypoxia-inducing agent), followed by GS4012 (a vascular endothelial growth factor inducer) at 24 hours postfertilization, and observed that the number of vascular branches and sprouts significantly increased in the central retinal vascular trunks 2–4 days after treatment. We created an angiography method by using tetramethylrhodamine dextran, which exhibited severe vascular leakage through the vessel wall into the surrounding retinal tissues. The quantification of mRNA extracted from the heads of the larvae by using real-time quantitative polymerase chain reaction revealed a twofold increase in vegfaa and vegfr2 expression compared with the control group, indicating increased vascular endothelial growth factor signaling in the hypoxic condition. In addition, we demonstrated that the hypoxic insult could be effectively rescued by several antivascular endothelial growth factor agents such as SU5416, bevacizumab, and ranibizumab. In conclusion, we provide a simple, highly reproducible, and clinically relevant retinopathy of prematurity model based on zebrafish embryos; this model may serve as a useful platform for clarifying the mechanisms of human retinopathy of prematurity and its progression. PMID:25978439
Wu, Yu-Ching; Chang, Chao-Yuan; Kao, Alex; Hsi, Brian; Lee, Shwu-Huey; Chen, Yau-Hung; Wang, I-Jong
Retinopathy of prematurity, formerly known as a retrolental fibroplasia, is a leading cause of infantile blindness worldwide. Retinopathy of prematurity is caused by the failure of central retinal vessels to reach the retinal periphery, creating a nonperfused peripheral retina, resulting in retinal hypoxia, neovascularization, vitreous hemorrhage, vitreoretinal fibrosis, and loss of vision. We established a potential retinopathy of prematurity model by using a green fluorescent vascular endothelium zebrafish transgenic line treated with cobalt chloride (a hypoxia-inducing agent), followed by GS4012 (a vascular endothelial growth factor inducer) at 24 hours postfertilization, and observed that the number of vascular branches and sprouts significantly increased in the central retinal vascular trunks 2-4 days after treatment. We created an angiography method by using tetramethylrhodamine dextran, which exhibited severe vascular leakage through the vessel wall into the surrounding retinal tissues. The quantification of mRNA extracted from the heads of the larvae by using real-time quantitative polymerase chain reaction revealed a twofold increase in vegfaa and vegfr2 expression compared with the control group, indicating increased vascular endothelial growth factor signaling in the hypoxic condition. In addition, we demonstrated that the hypoxic insult could be effectively rescued by several antivascular endothelial growth factor agents such as SU5416, bevacizumab, and ranibizumab. In conclusion, we provide a simple, highly reproducible, and clinically relevant retinopathy of prematurity model based on zebrafish embryos; this model may serve as a useful platform for clarifying the mechanisms of human retinopathy of prematurity and its progression.
Feng, Jun; Brown, Michael F.; Mertz, Blake
Rhodopsin is a well-characterized structural model of a G protein-coupled receptor. Photoisomerization of the covalently bound retinal triggers activation. Surprisingly, the x-ray crystal structure of the active Meta-II state has a 180° rotation about the long-axis of the retinal polyene chain. Unbiased microsecond-timescale all-atom molecular dynamics simulations show that the retinal cofactor can flip back to the orientation observed in the inactive state of rhodopsin under conditions favoring the Meta-I state. Our results provide, to our knowledge, the first evidence from molecular dynamics simulations showing how rotation of the retinal ligand within its binding pocket can occur in the activation mechanism of rhodopsin. PMID:26083914
Tzekov, Radouil; Stein, Linda; Kaushal, Shalesh
The retina is a highly complex and specialized organ that performs preliminary analysis of visual information. Composed of highly metabolically active tissue, the retina requires a precise and well-balanced means of maintaining its functional activity during extended periods of time. Maintenance and regulation of a vast array of different structural and functional proteins is required for normal function of the retina. This process is referred to as protein homeostasis and involves a variety of activities, including protein synthesis, folding, transport, degradation, elimination, and recycling. Deregulation of any of these activities can lead to malfunctioning of the retina, from subtle subclinical signs to severe retinal degenerative diseases leading to blindness. Examples of retinal degenerative diseases caused by disruption of protein homeostasis include retinitis pigmentosa and Stargardt’s disease. A detailed discussion of the role of disruption in protein homeostasis in these and other retinal diseases is presented, followed by examples of some existing and potential treatments. PMID:21825021
Aneurysmal subarachnoid hemorrhage (SAH) is a worldwide health burden with high fatality and permanent disability rates. The overall prognosis depends on the volume of the initial bleed, rebleeding, and degree of delayed cerebral ischemia (DCI). Cardiac manifestations and neurogenic pulmonary edema indicate the severity of SAH. The International Subarachnoid Aneurysm Trial (ISAT) reported a favorable neurological outcome with the endovascular coiling procedure compared with surgical clipping at the end of 1 year. The ISAT trial recruits were primarily neurologically good grade patients with smaller anterior circulation aneurysms, and therefore the results cannot be reliably extrapolated to larger aneurysms, posterior circulation aneurysms, patients presenting with complex aneurysm morphology, and poor neurological grades. The role of hypothermia is not proven to be neuroprotective according to a large randomized controlled trial, Intraoperative Hypothermia for Aneurysms Surgery Trial (IHAST II), which recruited patients with good neurological grades. Patients in this trial were subjected to slow cooling and inadequate cooling time and were rewarmed rapidly. This methodology would have reduced the beneficial effects of hypothermia. Adenosine is found to be beneficial for transient induced hypotension in 2 retrospective analyses, without increasing the risk for cardiac and neurological morbidity. The neurological benefit of pharmacological neuroprotection and neuromonitoring is not proven in patients undergoing clipping of aneurysms. DCI is an important cause of morbidity and mortality following SAH, and the pathophysiology is likely multifactorial and not yet understood. At present, oral nimodipine has an established role in the management of DCI, along with maintenance of euvolemia and induced hypertension. Following SAH, hypernatremia, although less common than hyponatremia, is a predictor of poor neurological outcome.
Aneurysmal subarachnoid hemorrhage (SAH) is a worldwide health burden with high fatality and permanent disability rates. The overall prognosis depends on the volume of the initial bleed, rebleeding, and degree of delayed cerebral ischemia (DCI). Cardiac manifestations and neurogenic pulmonary edema indicate the severity of SAH. The International Subarachnoid Aneurysm Trial (ISAT) reported a favorable neurological outcome with the endovascular coiling procedure compared with surgical clipping at the end of 1 year. The ISAT trial recruits were primarily neurologically good grade patients with smaller anterior circulation aneurysms, and therefore the results cannot be reliably extrapolated to larger aneurysms, posterior circulation aneurysms, patients presenting with complex aneurysm morphology, and poor neurological grades. The role of hypothermia is not proven to be neuroprotective according to a large randomized controlled trial, Intraoperative Hypothermia for Aneurysms Surgery Trial (IHAST II), which recruited patients with good neurological grades. Patients in this trial were subjected to slow cooling and inadequate cooling time and were rewarmed rapidly. This methodology would have reduced the beneficial effects of hypothermia. Adenosine is found to be beneficial for transient induced hypotension in 2 retrospective analyses, without increasing the risk for cardiac and neurological morbidity. The neurological benefit of pharmacological neuroprotection and neuromonitoring is not proven in patients undergoing clipping of aneurysms. DCI is an important cause of morbidity and mortality following SAH, and the pathophysiology is likely multifactorial and not yet understood. At present, oral nimodipine has an established role in the management of DCI, along with maintenance of euvolemia and induced hypertension. Following SAH, hypernatremia, although less common than hyponatremia, is a predictor of poor neurological outcome. PMID:25272066
The retinal prosthesis is targeted to treat age-related macular degeneration, retinitis pigmentosa, and other outer retinal degenerations. Simulations of artificial vision have predicted that 600-1000 individual pixels will be needed if a retinal prosthesis is to restore function such as reading large print and face recognition. An implantable device with this many electrode contacts will require microsystems technology as part of its design. An implantable retinal prosthesis will consist of several subsystems including an electrode array and hermetic packaging. Microsystems and microtechnology approaches are being investigated as possible solutions for these design problems. Flexible polydimethylsiloxane (PDMS) substrate electrode arrays and silicon micromachined electrode arrays are under development. Inactive PDMS electrodes have been implanted in 3 dogs to assess mechanical biocompatibility. 3 dogs were followed for 6 months. The implanted was securely fastened to the retina with a single retinal tack. No post-operative complications were evident. The array remained within 100 microns of the retinal surface. Histological evaluation showed a well preserved retina underneath the electrode array. A silicon device with electrodes suspended on micromachined springs has been implanted in 4 dogs (2 acute implants, 2 chronic implants). The device, though large, could be inserted into the eye and positioned on the retina. Histological analysis of the retina from the spring electrode implants showed that spring mounted posts penetrated the retina, thus the device will be redesigned to reduce the strength of the springs. These initial implants will provide information for the designers to make the next generation silicon device. We conclude that microsystems technology has the potential to make possible a retinal prosthesis with 1000 individual contacts in close proximity to the retina.
Goffman, Dena; Nathan, Lisa; Chazotte, Cynthia
Postpartum hemorrhage remains the number one cause of maternal death globally despite the fact that it is largely a preventable and most often a treatable condition. While the global problem is appreciated, some may not realize that in the United States postpartum hemorrhage is a leading cause of mortality and unfortunately, the incidence is on the rise. In New York, obstetric hemorrhage is the second leading cause of maternal mortality in the state. National data suggests that hemorrhage is disproportionally overrepresented as a contributor to severe maternal morbidity and we suspect as we explore further this will be true in New York State as well. Given the persistent and significant contribution to maternal mortality, it may be useful to analyze the persistence of this largely preventable cause of death within the framework of the historic "Three Delays" model of maternal mortality. The ongoing national and statewide problem with postpartum hemorrhage will be reviewed in this context of delays in an effort to inform potential solutions.
Wert, Katherine J.; Lin, Jonathan H.; Tsang, Stephen H.
Retinal degeneration, including that seen in age-related macular degeneration and retinitis pigmentosa (RP), is the most common form of neural degenerative disease in the world. There is great genetic and allelic heterogeneity of the various retinal dystrophies. Classifications of these diseases can be ambiguous, as there are similar clinical presentations in retinal degenerations arising from different genetic mechanisms. As would be expected, alterations in the activity of the phototransduction cascade, such as changes affecting the renewal and shedding of the photoreceptor OS, visual transduction, and/ or retinol metabolism have a great impact on the health of the retina. Mutations within any of the molecules responsible for these visual processes cause several types of retinal and retinal pigment epithelium degenerative diseases. Apoptosis has been implicated in the rod cell loss seen in a mouse model of RP, but the precise mechanisms that connect the activation of these pathways to the loss of phosphodiesterase (PDE6β) function has yet to be defined. Additionally, the activation of apoptosis by CCAAT/-enhancer-binding protein homologous protein (CHOP), after activation of the unfolded protein response pathway, may be responsible for cell death, although the mechanism remains unknown. However, the mechanisms of cell death after loss of function of PDE6, which is a commonly studied mammalian model in research, may be generalizable to loss of function of different key proteins involved in the phototransduction cascade. PMID:24732759
Larimer, James; Piantanida, Thomas
The optics of the eye form an image on a surface at the back of the eyeball called the retina. The retina contains the photoreceptors that sample the image and convert it into a neural signal. The spacing of the photoreceptors in the retina is not uniform and varies with retinal locus. The central retinal field, called the macula, is densely packed with photoreceptors. The packing density falls off rapidly as a function of retinal eccentricity with respect to the macular region and there are regions in which there are no photoreceptors at all. The retinal regions without photoreceptors are called blind spots or scotomas. The neural transformations which convert retinal image signals into percepts fills in the gaps and regularizes the inhomogeneities of the retinal photoreceptor sampling mosaic. The filling-in mechamism plays an important role in understanding visual performance. The filling-in mechanism is not well understood. A systematic collaborative research program at the Ames Research Center and SRI in Menlo Park, California, was designed to explore this mechanism. It was shown that the perceived fields which are in fact different from the image on the retina due to filling-in, control some aspects of performance and not others. Researchers have linked these mechanisms to putative mechanisms of color coding and color constancy.
Chuang, Alice T; Margo, Curtis E; Greenberg, Paul B
Retinal implants present an innovative way of restoring sight in degenerative retinal diseases. Previous reviews of research progress were written by groups developing their own devices. This systematic review objectively compares selected models by examining publications describing five representative retinal prostheses: Argus II, Boston Retinal Implant Project, Epi-Ret 3, Intelligent Medical Implants (IMI) and Alpha-IMS (Retina Implant AG). Publications were analysed using three criteria for interim success: clinical availability, vision restoration potential and long-term biocompatibility. Clinical availability: Argus II is the only device with FDA approval. Argus II and Alpha-IMS have both received the European CE Marking. All others are in clinical trials, except the Boston Retinal Implant, which is in animal studies. Vision restoration: resolution theoretically correlates with electrode number. Among devices with external cameras, the Boston Retinal Implant leads with 100 electrodes, followed by Argus II with 60 electrodes and visual acuity of 20/1262. Instead of an external camera, Alpha-IMS uses a photodiode system dependent on natural eye movements and can deliver visual acuity up to 20/546. Long-term compatibility: IMI offers iterative learning; Epi-Ret 3 is a fully intraocular device; Alpha-IMS uses intraocular photosensitive elements. Merging the results of these three criteria, Alpha-IMS is the most likely to achieve long-term success decades later, beyond current clinical availability.
Werkmeister, René M.; Schmidl, Doreen; Aschinger, Gerold; Doblhoff-Dier, Veronika; Palkovits, Stefan; Wirth, Magdalena; Garhöfer, Gerhard; Linsenmeier, Robert A.; Leitgeb, Rainer A.; Schmetterer, Leopold
Adequate function of the retina is dependent on proper oxygen supply. In humans, the inner retina is oxygenated via the retinal circulation. We present a method to calculate total retinal oxygen extraction based on measurement of total retinal blood flow using dual-beam bidirectional Doppler optical coherence tomography and measurement of oxygen saturation by spectrophotometry. These measurements were done on 8 healthy subjects while breathing ambient room air and 100% oxygen. Total retinal blood flow was 44.3 ± 9.0 μl/min during baseline and decreased to 18.7 ± 4.2 μl/min during 100% oxygen breathing (P < 0.001) resulting in a pronounced decrease in retinal oxygen extraction from 2.33 ± 0.51 μl(O2)/min to 0.88 ± 0.14 μl(O2)/min during breathing of 100% oxygen. The method presented in this paper may have significant potential to study oxygen metabolism in hypoxic retinal diseases such as diabetic retinopathy.
Werkmeister, René M.; Schmidl, Doreen; Aschinger, Gerold; Doblhoff-Dier, Veronika; Palkovits, Stefan; Wirth, Magdalena; Garhöfer, Gerhard; Linsenmeier, Robert A.; Leitgeb, Rainer A.; Schmetterer, Leopold
Adequate function of the retina is dependent on proper oxygen supply. In humans, the inner retina is oxygenated via the retinal circulation. We present a method to calculate total retinal oxygen extraction based on measurement of total retinal blood flow using dual-beam bidirectional Doppler optical coherence tomography and measurement of oxygen saturation by spectrophotometry. These measurements were done on 8 healthy subjects while breathing ambient room air and 100% oxygen. Total retinal blood flow was 44.3 ± 9.0 μl/min during baseline and decreased to 18.7 ± 4.2 μl/min during 100% oxygen breathing (P < 0.001) resulting in a pronounced decrease in retinal oxygen extraction from 2.33 ± 0.51 μl(O2)/min to 0.88 ± 0.14 μl(O2)/min during breathing of 100% oxygen. The method presented in this paper may have significant potential to study oxygen metabolism in hypoxic retinal diseases such as diabetic retinopathy. PMID:26503332
Patel, Yogin P.; Saraf, Steven S.; Desai, Uday R.
Purpose: Traumatic head injuries not involving the eye have been known to cause retinal injury through multiple mechanisms. Abusive head trauma remains the prototypical example. We propose to demonstrate the first case of bilateral multiple retinal hemorrhages in a young healthy adult related to riding multiple theme park roller coasters. Methods: The patient was evaluated with a complete ophthalmic examination including dilated extended ophthalmoscopy, fluorescein angiography, optical coherence tomography, and fundus photography. Results: The patient was found to have a bilateral symptomatic macular retinopathy characterized by multiple intraretinal hemorrhages. Given the lack of other systemic findings and negative medical workup, her signs and symptoms were thought to be attributed to the same day attendance of a theme park and riding of multiple roller coasters. Conclusion: Theme park roller coasters, as well as other attractions, may affect the eye at the vitreoretinal interface. This type of acceleration–deceleration injury should be considered in the differential of an adolescent or adult patient with retinal hemorrhage in the absence of other pathologic processes to explain clinical findings. PMID:26630245
Speilburg, Ashley M; Klemencic, Stephanie A
Retinal arterial macroaneurysm is an acquired, focal dilation of a retinal artery, typically occurring within the first three bifurcations of the central retinal artery. The clinical presentation of a retinal arterial macroaneurysm is highly variable, making initial diagnosis difficult and differentials many. Identification of retinal arterial macroaneurysms is crucial to appropriately co-manage with the primary care physician for hypertension control. Prognosis is generally good and observation is often an adequate treatment. However, in cases of macular threat or involvement, some treatment options are available and referral to a retinal specialist is indicated.
... Congo Hemorrhagic Fever (CCHF) [PDF - 2 pages] Virus Ecology Viral Hemorrhagic Fever (VHF) Information for Specific Groups ... Diagnosis Treatment Prevention Outbreak Distribution Map Resources Virus Ecology File Formats Help: How do I view different ...
Tomii, M; Nakajima, M; Ikeuchi, S; Ogawa, T; Abe, T
Hemorrhage in regions remote from the site of initial intracranial operations is rare, but does occur. We report three cases of cerebellar hemorrhage that developed after supratentorial surgery, all of which had similar clinical findings and CT images. The first case was a 37-year-old man with a craniopharyngioma in the suprasellar lesion. Partial removal of the tumor was performed through frontal craniotomy and the translaminaterminals approach. A large quantity of cerebospinal fluid (CSF) was suctioned from the third ventricle during the operation, resulting in marked brain shrinkage. The second and third cases were 34- and 51-year-old women with unruptured right middle cerebral aneurysms. Clipping of the aneurysms through the pterional approach was performed in both cases. In the second case, CSF was suctioned in large quantity from the carotid and prechiasmal cistern at the operation, resulting in marked brain shrinkage. In the third case, however, only a small volume of CSF was suctioned from the carotid and prechiasmal cistern during the operation, and no marked brain shrinkage was observed. CT scan showed that the hematomas were located mainly in the subdural or the subarachnoid spaces over the cerebellar hemisphere and partially extending into the cerebellar cortex. The mechanism of cerebellar hemorrhage in these series of patients was thought to be multifactorial. The possible etiology for cerebellar hemorrhage in the three cases presented was examined, including the role of CSF suction during surgery and disturbance of venous circulation in the posterior fossa. Suction of the CSF may cause intracranial hypotension. Further reduction of intracranial pressure leads to an increased transluminal venous pressure. There was no episode of hypertension or disturbed blood coagulation during or after the operation. The preoperative angiogram also revealed no abnormality at the region of the posterior fossa. Neuroimaging of infratentorial hemorrhage after
Gelal, Fazıl; Gurkan, Gokhan; Feran, Hamit
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
Hartman, Amy L; Towner, Jonathan S; Nichol, Stuart T
Ebola and Marburg viruses cause a severe viral hemorrhagic fever disease mainly in Sub-Saharan Africa. Although outbreaks are sporadic, there is the potential for filoviruses to spread to other continents unintentionally because of air travel or intentionally because of bioterrorism. This article discusses the natural history, epidemiology, and clinical presentation of patients infected with Ebola and Marburg viruses. Clinicians in the United States should be aware of the symptoms of these viral infections in humans and know the appropriate procedures for contacting local, state, and national reference laboratories in the event of a suspected case of filoviral hemorrhagic fever.
Ramos-López, L; Pons-Canosa, V; Juncal-Díaz, J L; Núñez-Centeno, M B
Sheehan's syndrome is described as panhypopituitarism secondary to a pituitary hypoperfusion during or just after obstetric hemorrhage. Advances in obstetric care make this syndrome quite unusual, but some cases are reported in underdeveloped countries. Clinical presentation may change depending on the severity of the hormone deficiencies. The diagnosis is clinical, but abnormalities are observed in the magnetic resonance in up to 70% of patients. We present a case of a woman with hypotension, hypothermia and edemas in relation to a previous massive postpartum hemorrhage. Failure in lactation was the clue to the diagnosis. A review of its main features, its diagnosis and treatment in the current literature is also presented.
trauma victims occur within 1 hourvOf injury and are due to rapid hemorrhage or CNS trauma . We developed a rapid hemorrhage model in unanesthetized swine...UNCLASSIFIED SECURITY CLASSIFICATION OF THIS PAGErmUen Data Enteed) q g ABSTRACT One-half of deaths among trauma victims occur within 1 hour of injury and...are due to rapid hemorrhage or CNS trauma . We developed a rapid hemorrhage model in unanesthetized swine to simulate human exsanguination. We compared
Kong, Woo Keun; Cho, Keun-Tae; Hong, Seung-Koan
Most of Tarlov or perineurial cysts remain asymptomatic throughout the patient's life. The pathogenesis is still unclear. Hemorrhage has been suggested as one of the possible causes and trauma with resultant hemorrhage into subarachnoid space has been suggested as an origin of these cysts. However, Tarlov cysts related to spontaneous subarachnoid hemorrhage has not been reported. The authors report a case of Tarlov cyst which was symptomatic following spontaneous subarachnoid hemorrhage.
Kong, Woo Keun; Hong, Seung-Koan
Most of Tarlov or perineurial cysts remain asymptomatic throughout the patient's life. The pathogenesis is still unclear. Hemorrhage has been suggested as one of the possible causes and trauma with resultant hemorrhage into subarachnoid space has been suggested as an origin of these cysts. However, Tarlov cysts related to spontaneous subarachnoid hemorrhage has not been reported. The authors report a case of Tarlov cyst which was symptomatic following spontaneous subarachnoid hemorrhage. PMID:22053232
Ozdal, Pınar Çakar; Teke, Mehmet Yasin
Purpose. To report a case of unilateral frosted branch angiitis (FBA) resembling central retinal vein occlusion associated with Familial Mediterranean Fever (FMF). Case Report. A 32-year-old woman presented with progressive, painless vision loss in her left eye lasting for 2 days. She was clinically diagnosed with FMF 2 months ago. The best-corrected visual acuity (BCVA) was 20/20 in her right eye and there was light perception in the left. Ophthalmologic examination revealed severe retinal vasculitis showing clinical features of FBA in the left eye. 64 mg/day oral methylprednisolone was started. A significant improvement in retinal vasculitis was observed in two weeks. However, BCVA did not increase significantly due to subhyaloid premacular hemorrhage. Argon laser posterior hyaloidotomy was performed. One week after hyaloidotomy, visual acuity improved to 20/20 and intravitreal hemorrhage disappeared. Four months after the first attack, FBA recurred. Oral methylprednisolone dosage was increased to 64 mg/day and combined with azathioprine 150 mg. At the end of 12-month follow-up, the BCVA was 20/25 and development of epiretinal membrane was observed in the left eye. Conclusions. Frosted branch angiitis may occur with gene abnormalities as an underlying condition. Our case showed that FMF might be a causative disease. PMID:28044118
Ling, D.; Korobkin, M.; Silverman, P.M.; Dunnick, N.R.
Bilateral adrenal hemorrhage with subsequent adrenal insufficiency is a recognized complication of anticoagulant therapy. Because the clinical manifestations are often nonspecific, the antemortem diagnosis of adrenal hemorrhage has been a difficult clinical problem. Computed tomography (CT) provides detailed images of the adrenal glands that are not possible with conventional imaging methods. The CT findings of bilateral adrenal hemorrhage in an anticoagulated patient are reported.
Zawadzki, Robert J.; Miller, Donald T.
The last two decades have witnessed extraordinary advances in optical technology to image noninvasively and at high resolution the posterior segment of the eye. Two of the most impactful technological advancements over this period have arguably been optical coherence tomography (OCT) and adaptive optics (AO). The strengths of these technologies complement each other and when combined have been shown to provide unprecedented, micron-scale resolution (<3 μm) in all three dimensions and sensitivity to image the cellular retina in the living eye. This powerful extension of OCT, that is AO-OCT, is the focus of this chapter. It presents key aspects of designing and implementing AO-OCT systems. Particular attention is devoted to the relevant optical properties of the eye that ultimately define these systems, AO componentry and operation tailored for ophthalmic use, and of course use of the latest technologies and methods in OCT for ocular imaging. It surveys the wide range of AO-OCT designs that have been developed for retinal imaging, with AO integrated into every major OCT design configuration. Finally, it reviews the scientific and clinical studies reported to date that show the exciting potential of AO-OCT to image the microscopic retina and fundus in ways not previously possible with other noninvasive methods and a look to future developments in this rapidly growing field.
García-Arumí, J; Martínez-Castillo, V; Boixadera, A; Blasco, H; Marticorena, J; Zapata, M Á; Macià, C; Badal, J; Distéfano, L; Rafart, J M; Berrocal, M; Zambrano, A; Ruíz-Moreno, J M; Figueroa, M S
This paper outlines general guidelines following the initial diagnosis of rhegmatogenous retinal detachment. These include preoperative evaluation, treatment, possible intra- and post-operative complications, retinal re-detachment, and all therapeutic options available for each case. Treatment of the traumatic retinal detachment is also described, due to its importance and peculiarities. Treatment or prophylactic guidelines are suggested for the different types of retinal detachment described. These are based on both the experience of the ophthalmologists that have participated in preparing the guidelines, and also on evidence-based grading linked to bibliographical sources. However, these guidelines should not be interpreted as being mandatory. Given that there is a wide spectrum of options for treatment of retinal detachment, the surgeons' experience with one or other surgical technique will be of utmost importance in obtaining the best surgical result. As guidelines, they are intended as an additional aid to the surgeon during the decision-making process, with the expectation that the final choice will still be left to the surgeon's judgment and past experience.
Sheward, S E; Davis, M; Amparo, E G; Gogel, H K
We report a case of benign gastric ulcer with secondary extensive intramural hemorrhage causing a radiographic appearance consistent with a large ulcerated gastric neoplasm. This is the second such case reported and the first studied with sonography and computed tomographic scan. A brief review of the literature on intramural gastric hematoma is presented.
We present 12 clinical cases of congenital retinal folds with different etiologies: posterior primitive vitreous persistency and hyperplasia (7 cases),retinocytoma (1 case). retinopathy of prematurity (1 case), astrocytoma of the retina (1 case), retinal vasculitis (1 case), Goldmann-Favre syndrome (1 case). Etiopathogenic and nosological aspects are discussed; the congenital retinal folds are interpreted as a symptom in a context of a congenital or acquired vitreo-retinal pathology.
Aktaş, Serdar; Tetikoğlu, Mehmet; İnan, Sibel; Aktaş, Hatice; Özcura, Fatih
A 55-year-old male presented with a complaint of a painless and sudden loss of vision in the right eye. Fundus photography revealed loss of transparency and edema in the central macular region. Optical coherence tomography showed increased reflectivity and diffused swelling in the inner retinal layers. Fluorescein angiography revealed a large area of capillary non-perfusion with a pronounced hypofluorescent area with distinct borders. To our knowledge, this is the first report of a hemorrhagic macular infarction associated with marijuana and pregabalin misuse.
Shields, J A; Joffe, L; Guibor, P
An amelanotic fundus lesion in a 35-year-old man was associated with a dilated retinal vessel, thus suggesting the diagnosis of retinal angioma. Fluorescein angiography and B-scan ultrasonography were not diagnostic, but a radioactive phosphorus uptake test suggested the lesion was malignant. The enucleated globe showed a malignant choroidal melanoma drained by a large retinal vein.
Retinitis Pigmentosa; Macula Off; Primary Open Angle Glaucoma; Hereditary Macular Degeneration; Treated Retina Detachment; Retinal Artery Occlusion; Retinal Vein Occlusion; Non-Arthritic-Anterior-Ischemic Optic-Neuropathy; Hereditary Autosomal Dominant Optic Atrophy; Dry Age Related Macular Degeneration; Ischemic Macula Edema
ending in blindness. In the United States, the total number of individuals affected by retinitis pigmentosa (RP) and other forms of rare inherited...AD_________________ AWARD NUMBER: W81XWH-07-1-0720 TITLE: Inherited Retinal Degenerative...Final 3. DATES COVERED 27 Sep 2007 – 29 Sep 2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Inherited Retinal Degenerative Clinical Trial Network
Rotenstreich, Ygal; Tzameret, Adi; Kalish, Sapir E.; Belkin, Michael; Meir, Amilia; Treves, Avraham J.; Nagler, Arnon; Sher, Ifat
Incurable retinal degenerations affect millions worldwide. Stem cell transplantation rescued visual functions in animal models of retinal degeneration. In those studies cells were transplanted in subretinal "blebs", limited number of cells could be injected and photoreceptor rescue was restricted to areas in proximity to the injection sites. We developed a minimally-invasive surgical platform for drug and cell delivery in a thin layer across the subretina and extravascular spaces of the choroid. The novel system is comprised of a syringe with a blunt-tipped needle and an adjustable separator. Human bone marrow mesenchymal stem cells (hBM-MSCs) were transplanted in eyes of RCS rats and NZW rabbits through a longitudinal triangular scleral incision. No immunosuppressants were used. Retinal function was determined by electroretinogram analysis and retinal structure was determined by histological analysis and OCT. Transplanted cells were identified as a thin layer across the subretina and extravascular spaces of the choroid. In RCS rats, cell transplantation delayed photoreceptor degeneration across the entire retina and significantly enhanced retinal functions. No retinal detachment or choroidal hemorrhages were observed in rabbits following transplantation. This novel platform opens a new avenue for drug and cell delivery, placing the transplanted cells in close proximity to the damaged RPE and retina as a thin layer, across the subretina and thereby slowing down cell death and photoreceptor degeneration, without retinal detachment or choroidal hemorrhage. This new transplantation system may increase the therapeutic effect of other cell-based therapies and therapeutic agents. This study is expected to directly lead to phase I/II clinical trials for autologous hBM-MSCs transplantation in retinal degeneration patients.
Anderson, James R.; Jones, Bryan W.; Watt, Carl B.; Shaw, Margaret V.; Yang, Jia-Hui; DeMill, David; Lauritzen, James S.; Lin, Yanhua; Rapp, Kevin D.; Mastronarde, David; Koshevoy, Pavel; Grimm, Bradley; Tasdizen, Tolga; Whitaker, Ross
Purpose A connectome is a comprehensive description of synaptic connectivity for a neural domain. Our goal was to produce a connectome data set for the inner plexiform layer of the mammalian retina. This paper describes our first retinal connectome, validates the method, and provides key initial findings. Methods We acquired and assembled a 16.5 terabyte connectome data set RC1 for the rabbit retina at ≈2 nm resolution using automated transmission electron microscope imaging, automated mosaicking, and automated volume registration. RC1 represents a column of tissue 0.25 mm in diameter, spanning the inner nuclear, inner plexiform, and ganglion cell layers. To enhance ultrastructural tracing, we included molecular markers for 4-aminobutyrate (GABA), glutamate, glycine, taurine, glutamine, and the in vivo activity marker, 1-amino-4-guanidobutane. This enabled us to distinguish GABAergic and glycinergic amacrine cells; to identify ON bipolar cells coupled to glycinergic cells; and to discriminate different kinds of bipolar, amacrine, and ganglion cells based on their molecular signatures and activity. The data set was explored and annotated with Viking, our multiuser navigation tool. Annotations were exported to additional applications to render cells, visualize network graphs, and query the database. Results Exploration of RC1 showed that the 2 nm resolution readily recapitulated well known connections and revealed several new features of retinal organization: (1) The well known AII amacrine cell pathway displayed more complexity than previously reported, with no less than 17 distinct signaling modes, including ribbon synapse inputs from OFF bipolar cells, wide-field ON cone bipolar cells and rod bipolar cells, and extensive input from cone-pathway amacrine cells. (2) The axons of most cone bipolar cells formed a distinct signal integration compartment, with ON cone bipolar cell axonal synapses targeting diverse cell types. Both ON and OFF bipolar cells receive
Grob, Seanna R.; Finn, Avni; Papakostas, Thanos D.; Eliott, Dean
Research development is burgeoning for genetic and cellular therapy for retinal dystrophies. These dystrophies are the focus of many research efforts due to the unique biology and accessibility of the eye, the transformative advances in ocular imaging technology that allows for in vivo monitoring, and the potential benefit people would gain from success in the field – the gift of renewed sight. Progress in the field has revealed the immense complexity of retinal dystrophies and the challenges faced by researchers in the development of this technology. This study reviews the current trials and advancements in genetic and cellular therapy in the treatment of retinal dystrophies and also discusses the current and potential future challenges. PMID:26957839
Kozhevnikova, Oyuna S.; Korbolina, Elena E.; Ershov, Nikita I.; Kolosova, Natalia G.
Pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly, remains poorly understood due to the paucity of animal models that fully replicate the human disease. Recently, we showed that senescence-accelerated OXYS rats develop a retinopathy similar to human AMD. To identify alterations in response to normal aging and progression of AMD-like retinopathy, we compared gene expression profiles of retina from 3- and 18-mo-old OXYS and control Wistar rats by means of high-throughput RNA sequencing (RNA-Seq). We identified 160 and 146 age-regulated genes in Wistar and OXYS retinas, respectively. The majority of them are related to the immune system and extracellular matrix turnover. Only 24 age-regulated genes were common for the two strains, suggestive of different rates and mechanisms of aging. Over 600 genes showed significant differences in expression between the two strains. These genes are involved in disease-associated pathways such as immune response, inflammation, apoptosis, Ca2+ homeostasis and oxidative stress. The altered expression for selected genes was confirmed by qRT-PCR analysis. To our knowledge, this study represents the first analysis of retinal transcriptome from young and old rats with biologic replicates generated by RNA-Seq technology. We can conclude that the development of AMD-like retinopathy in OXYS rats is associated with an imbalance in immune and inflammatory responses. Aging alters the expression profile of numerous genes in the retina, and the genetic background of OXYS rats has a profound impact on the development of AMD-like retinopathy. PMID:23656783
Wu, Hai-Jian; Wu, Cheng; Niu, Huan-Jiang; Wang, Kun; Mo, Lian-Jie; Shao, An-Wen; Dixon, Brandon J; Zhang, Jian-Min; Yang, Shu-Xu; Wang, Yi-Rong
Hemorrhagic stroke which consists of subarachnoid hemorrhage and intracerebral hemorrhage is a dominant cause of death and disability worldwide. Although great efforts have been made, the physiological mechanisms of these diseases are not fully understood and effective pharmacological interventions are still lacking. Melatonin (N-acetyl-5-methoxytryptamine), a neurohormone produced by the pineal gland, is a broad-spectrum antioxidant and potent free radical scavenger. More importantly, there is extensive evidence demonstrating that melatonin confers neuroprotective effects in experimental models of hemorrhagic stroke. Multiple molecular mechanisms such as antioxidant, anti-apoptosis, and anti-inflammation, contribute to melatonin-mediated neuroprotection against brain injury after hemorrhagic stroke. This review article aims to summarize current knowledge regarding the beneficial effects of melatonin in experimental models of hemorrhagic stroke and explores the underlying mechanisms. We propose that melatonin is a promising neuroprotective candidate that is worthy of further evaluation for its potential therapeutic applications in hemorrhagic stroke.
Drexler, Wolfgang; Fujimoto, James G.
The eye is essentially transparent, transmitting light with only minimal optical attenuation and scattering providing easy optical access to the anterior segment as well as the retina. For this reason, ophthalmic and especially retinal imaging has been not only the first but also most successful clinical application for optical coherence tomography (OCT). This chapter focuses on the development of OCT technology for retinal imaging. OCT has significantly improved the potential for early diagnosis, understanding of retinal disease pathogenesis, as well as monitoring disease progression and response to therapy. Development of ultrabroad bandwidth light sources and high-speed detection techniques has enabled significant improvements in ophthalmic OCT imaging performance, demonstrating the potential of three-dimensional, ultrahigh-resolution OCT (UHR OCT) to perform noninvasive optical biopsy of the living human retina, i.e., the in vivo visualization of microstructural, intraretinal morphology in situ approaching the resolution of conventional histopathology. Significant improvements in axial resolution and speed not only enable three-dimensional rendering of retinal volumes but also high-definition, two-dimensional tomograms, topographic thickness maps of all major intraretinal layers, as well as volumetric quantification of pathologic intraretinal changes. These advances in OCT technology have also been successfully applied in several animal models of retinal pathologies. The development of light sources emitting at alternative wavelengths, e.g., around #1,060 nm, not only enabled three-dimensional OCT imaging with enhanced choroidal visualization but also improved OCT performance in cataract patients due to reduced scattering losses in this wavelength region. Adaptive optics using deformable mirror technology, with unique high stroke to correct higher-order ocular aberrations, with specially designed optics to compensate chromatic aberration of the human eye, in
López-Gil, N.; Martin, J.; Liu, T.; Bradley, A.; Díaz-Muñoz, D.; Thibos, L.
Purpose We asked if retinal image quality is maximum during accommodation, or sub-optimal due to accommodative error, when subjects perform an acuity task. Methods Subjects viewed a monochromatic (552nm), high-contrast letter target placed at various viewing distances. Wavefront aberrations of the accommodating eye were measured near the endpoint of an acuity staircase paradigm. Refractive state, defined as the optimum target vergence for maximising retinal image quality, was computed by through-focus wavefront analysis to find the power of the virtual correcting lens that maximizes visual Strehl ratio. Results Despite changes in ocular aberrations and pupil size during binocular viewing, retinal image quality and visual acuity typically remain high for all target vergences. When accommodative errors lead to sub-optimal retinal image quality, acuity and measured image quality both decline. However, the effect of accommodation errors of on visual acuity are mitigated by pupillary constriction associated with accommodation and binocular convergence and also to binocular summation of dissimilar retinal image blur. Under monocular viewing conditions some subjects displayed significant accommodative lag that reduced visual performance, an effect that was exacerbated by pharmacological dilation of the pupil. Conclusions Spurious measurement of accommodative error can be avoided when the image quality metric used to determine refractive state is compatible with the focusing criteria used by the visual system to control accommodation. Real focusing errors of the accommodating eye do not necessarily produce a reliably measurable loss of image quality or clinically significant loss of visual performance, probably because of increased depth-of-focus due to pupil constriction. When retinal image quality is close to maximum achievable (given the eye’s higher-order aberrations), acuity is also near maximum. A combination of accommodative lag, reduced image quality, and reduced
Dai, Bing-Fa; Hu, Jian-Min; Xu, Duan-Lian
Preferred retinal locus (PRL) is always found in the age-related macular degeneration and other macular damages in patients with low vision, and it is a very important anatomic position in patients with central vision impairment to achieve the rehabilitation. In recent years, the training of preferred retinal locus (PRL) has become a research hotspot of low vision rehabilitation, it can clearly improve functional vision and quality of life. The authors reviewed relevant literatures, and summarized the definition, position, characteristics, training and clinical implications of the PRL.
Greenberg, J; Bartmann, L; Ramesar, R; Beighton, P
Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal disorders which are a common cause of genetic blindness. The relative frequencies of the different forms of RP in South Africa, as determined from the register at the DNA banking centre for RP at the Department of Human Genetics, University of Cape Town, are presented and discussed. Of the 125 families analysed, 29 (23%) showed autosomal dominant, 33 (27%) autosomal recessive and 3 (3%) X-linked inheritance. In 10 families the pedigree data were insufficient to allow accurate genetic subtyping and a further 50 patients were sporadic without a family history of RP or other syndromic features which would allow categorization.
Hillman N, Peoples JB (1982): The effects of dehydration on the dynamics of transcapillary refill. Am Surg 48:412-416. Becker H, Hottenrott C ...hemorrhagic shock: improved outcome with hypertonic saline/6% Dextran 70. Am J Emerg Med 7:357-363. Coli G, Frascaroli C , Guibilei G, Grillone G, Nanni...Di Nino GF, Melcni C ’, Rossi R (1982a): Considerazioni sulle modificaziomi della viscosita del sangue nel circolo polmonare ed in quello sistemico
Hayreh, Sohan Singh
The initial section deals with basic sciences; among the various topics briefly discussed are the anatomical features of ophthalmic, central retinal and cilioretinal arteries which may play a role in acute retinal arterial ischemic disorders. Crucial information required in the management of central retinal artery occlusion (CRAO) is the length of time the retina can survive following that. An experimental study shows that CRAO for 97 minutes produces no detectable permanent retinal damage but there is a progressive ischemic damage thereafter, and by 4 hours the retina has suffered irreversible damage. In the clinical section, I discuss at length various controversies on acute retinal arterial ischemic disorders. Classification of acute retinal arterial ischemic disorders These are of 4 types: CRAO, branch retinal artery occlusion (BRAO), cotton wools spots and amaurosis fugax. Both CRAO and BRAO further comprise multiple clinical entities. Contrary to the universal belief, pathogenetically, clinically and for management, CRAO is not one clinical entity but 4 distinct clinical entities – non-arteritic CRAO, non-arteritic CRAO with cilioretinal artery sparing, arteritic CRAO associated with giant cell arteritis (GCA) and transient non-arteritic CRAO. Similarly, BRAO comprises permanent BRAO, transient BRAO and cilioretinal artery occlusion (CLRAO), and the latter further consists of 3 distinct clinical entities - non-arteritic CLRAO alone, non-arteritic CLRAO associated with central retinal vein occlusion and arteritic CLRAO associated with GCA. Understanding these classifications is essential to comprehend fully various aspects of these disorders. Central retinal artery occlusion The pathogeneses, clinical features and management of the various types of CRAO are discussed in detail. Contrary to the prevalent belief, spontaneous improvement in both visual acuity and visual fields does occur, mainly during the first 7 days. The incidence of spontaneous visual
Barrett, Steven F.; Jerath, Maya R.; Rylander, Henry G.; Welch, Ashley J.
Laser-induced retinal lesions are used to treat a variety of eye disorders such as diabetic retinopathy and retinal tears. An instrumentation system has been developed to track a specific lesion coordinate on the retinal surface and provide corrective signals to maintain laser position on the coordinate. High-resolution retinal images are acquired via a CCD camera coupled to a fundus camera and video frame grabber. Optical filtering and histogram modification are used to enhance the retinal vessel network against the lighter retinal background. Six distinct retinal landmarks are tracked on the high contrast image obtained from the frame grabber using 2D blood vessel templates. An overview of the robotic laser system design is followed by implementation and testing of a development system for proof of concept and, finally, specifications for a real-time system are provided.
Nakayama, Yuri; Yokoi, Tadashi; Sachiko, Nishina; Okuyama, Makiko; Azuma, Noriyuki
In order to correlate anatomical changes with visual function in shaken baby syndrome, we performed electroretinography and spectral domain optical coherence tomography on a 2-month-old girl and a 9-month-old girl after the retinal hemorrhages absorbed. Both patients had significant abnormalities in spectral domain optical coherence tomography images of the macular area. The amplitudes of the focal macular electroretinograms were more severely decreased than those of the full-field electroretinograms. Combining spectral domain coherence tomography with focal macular electroretinograms might better estimate the functional damage to the macula in patients with shaken baby syndrome.
Greenwood, Gregory T
Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by chronic, uncontrolled activation of the alternative complement pathway, leading to thrombotic microangiopathy. Renal impairment and progression to end-stage renal disease are common in untreated patients with aHUS, and extrarenal manifestations are being increasingly characterized in the literature. Ocular involvement remains rare in aHUS. This report describes a patient with aHUS with bilateral central retinal artery and vein occlusion, vitreous hemorrhage, and blindness in addition to renal impairment. The patient’s hematologic and renal parameters and ocular manifestation improved following initiation of eculizumab therapy. PMID:26508891
Hammond, Nancy A; Lostumbo, Antonella; Adam, Sharon Z; Remer, Erick M; Nikolaidis, Paul; Yaghmai, Vahid; Berggruen, Senta M; Miller, Frank H
Hemorrhage of the kidneys and adrenal glands has many etiologies. In the adrenal glands, trauma, anticoagulation, stress, sepsis, surgery, and neoplasms are common causes of hemorrhage. In the kidneys, reasons for hemorrhage include trauma, bleeding diathesis, vascular diseases, infection, infarction, hemorrhagic cyst rupture, the Antopol-Goldman lesion, and neoplasms. Angiomyolipoma and renal cell carcinoma are the neoplasms most commonly associated with hemorrhage in the kidneys and adrenal cortical carcinoma, metastases, and pheochromocytoma are associated with hemorrhage in the adrenal glands. Understanding the computed tomography and magnetic resonance imaging features, and causes of hemorrhage in the kidneys and adrenal glands is critical. It is also important to keep in mind that mimickers of hemorrhage exist, including lymphoma in both the kidneys and adrenal glands, and melanoma metastases in the adrenal glands. Appropriate imaging follow-up of renal and adrenal hemorrhage should occur to exclude an underlying malignancy as the cause. If there is suspicion for malignancy that cannot be definitively diagnosed on imaging, surgery or biopsy may be warranted. Angiography may be indicated when there is a suspected underlying vascular disease. Unnecessary intervention, such as nephrectomy, may be avoided in patients with benign causes or no underlying disease. Appropriate management is dependent on accurate diagnosis of the cause of renal or adrenal hemorrhage and it is incumbent upon the radiologist to determine the etiology.
Godard, Clémence; Berhoune, Malik; Bertrand, Eric; Schlatter, Joël; Chiadmi, Fouad; Toledano, Audrey; Cisternino, Salvatore; Fontan, Jean-Eudes
Postpartum hemorrhage is defined by bleeding > 500 mL through the vagina. It is one of the obstetrical complications that obstetricians fear most. It is the leading cause of maternal mortality in the world, especially in developing countries. The reference treatments in France are parenteral oxytocin and sulprostone. Sulprostone involves sometimes fatal side effects, and must be administered only in appropriate health care facilities. It also has the major disadvantage of requiring refrigeration. Misoprostol has uterotonic properties that have led to its occasional off-label use in the treatment of postpartum hemorrhage, by rectal or sublingual administration, as an alternative to sulprostone. A careful review of the literature on this particular use of misoprostol is essential.
Shayan, Sara; Bokaean, Mohammad; Shahrivar, Mona Ranjvar; Chinikar, Sadegh
Crimean-Congo hemorrhagic fever virus (CCHFV) is a member of the Bunyaviridae family and Nairovirus genus. The viral genome consists of 3 RNA segments of 12 kb (L), 6.8 kb (M), and 3 kb (S). Crimean-Congo hemorrhagic fever (CCHF) is the most widespread tickborne viral infection worldwide: it has been reported in many regions of Africa, the Middle East, and Asia. The geographical distribution of CCHFV corresponds most closely with the distribution of members of the tick genera, and Hyalomma ticks are the principal source of human infection. In contrast to human infection, CCHFV infection is asymptomatic in all species. Treatment options for CCHF are limited; immunotherapy and ribavirin are effective in the treatment of CCHF; the efficacy of ribavirin in the treatment of CCHF has not yet been proven. This article reviews the history, epidemiology, clinical symptoms, pathogenesis, diagnosis, and treatment of CCHFV, as well as the development of a vaccine against it.
Welch, Claude E.
In the past few years gastric resection has become the therapy of choice for patients with massive hemorrhage from duodenal ulcer. When this is done as an emergency procedure the ability of the surgeon is often taxed to the limit. Although sometimes easy, control is often extraordinarily difficult. Many important technical details must be considered in order to attain a successful outcome. This method of therapy has proved to be very satisfactory with patients who are in good condition for operation, and even in the poorer risks seen on ward service has resulted in a surgical mortality of only 7 per cent in all patients less than 60 years of age treated for this extremely severe type of hemorrhage. In the older age groups mortality rates still remain high. PMID:13284635
Serra E Moura Garcia, C; Sokolova, A; Torre, M L; Amaro, C
Acute Hemorrhagic Edema of Infancy is a small vessel leucocytoclastic vasculitis affecting young infants. It is characterized by large, target-like, macular to purpuric plaques predominantly affecting the face, ear lobes and extremities. Non-pitting edema of the distal extremities and low-grade fever may also be present. Extra-cutaneous involvement is very rare. Although the lesions have a dramatic onset in a twenty-four to forty-eight hour period, usually the child has a non-toxic appearance. In most cases there are no changes in laboratory parameters. The cutaneous biopsy reveals an inflammatory perivascular infiltrate. It is a benign and auto-limited disease, with complete resolution within two to three weeks leaving no sequelae in the majority of cases. No recurrences are described. We report a case of a 42-day old girl admitted at our hospital with Acute Hemorrhagic Edema of Infancy.
Schlott, Kerstin; Koinzer, Stefan; Ptaszynski, Lars; Bever, Marco; Baade, Alex; Roider, Johann; Birngruber, Reginald; Brinkmann, Ralf
Laser coagulation is a treatment method for many retinal diseases. Due to variations in fundus pigmentation and light scattering inside the eye globe, different lesion strengths are often achieved. The aim of this work is to realize an automatic feedback algorithm to generate desired lesion strengths by controlling the retinal temperature increase with the irradiation time. Optoacoustics afford non-invasive retinal temperature monitoring during laser treatment. A 75 ns/523 nm Q-switched Nd:YLF laser was used to excite the temperature-dependent pressure amplitudes, which were detected at the cornea by an ultrasonic transducer embedded in a contact lens. A 532 nm continuous wave Nd:YAG laser served for photocoagulation. The ED50 temperatures, for which the probability of ophthalmoscopically visible lesions after one hour in vivo in rabbits was 50%, varied from 63°C for 20 ms to 49°C for 400 ms. Arrhenius parameters were extracted as ΔE=273 J mol-1 and A=3.1044 s-1. Control algorithms for mild and strong lesions were developed, which led to average lesion diameters of 162+/-34 μm and 189+/-34 μm, respectively. It could be demonstrated that the sizes of the automatically controlled lesions were widely independent of the treatment laser power and the retinal pigmentation.
Brown, Thomas J.
Retinitis Pigmentosa includes a number of inherited diseases which usually result in blindness. The disease is progressive in nature and begins with the deterioration of cells in the eye responsible for peripheral vision. As the condition worsens there is a gradual loss of peripheral vision and night blindness. Proper educational planning requires…
Schlott, Kerstin; Koinzer, Stefan; Ptaszynski, Lars; Bever, Marco; Baade, Alex; Roider, Johann; Birngruber, Reginald; Brinkmann, Ralf
Laser coagulation is a treatment method for many retinal diseases. Due to variations in fundus pigmentation and light scattering inside the eye globe, different lesion strengths are often achieved. The aim of this work is to realize an automatic feedback algorithm to generate desired lesion strengths by controlling the retinal temperature increase with the irradiation time. Optoacoustics afford non-invasive retinal temperature monitoring during laser treatment. A 75 ns/523 nm Q-switched Nd:YLF laser was used to excite the temperature-dependent pressure amplitudes, which were detected at the cornea by an ultrasonic transducer embedded in a contact lens. A 532 nm continuous wave Nd:YAG laser served for photocoagulation. The ED50 temperatures, for which the probability of ophthalmoscopically visible lesions after one hour in vivo in rabbits was 50%, varied from 63°C for 20 ms to 49°C for 400 ms. Arrhenius parameters were extracted as ΔE=273 J mol(-1) and A=3 x 10(44) s(-1). Control algorithms for mild and strong lesions were developed, which led to average lesion diameters of 162 ± 34 μm and 189 ± 34 μm, respectively. It could be demonstrated that the sizes of the automatically controlled lesions were widely independent of the treatment laser power and the retinal pigmentation.
Burnett, Mark W
In mid-September 2009, a 22-year-old critically ill Soldier was medically evacuated from a treatment facility in southern Afghanistan to Landstuhl Regional Medical Center in Germany. Despite the efforts of the team at Landstuhl, this patient died and became the US military's first known victim of Crimean-Congo hemorrhagic fever (CCHF). CCHF is caused by a virus, which bears the same name. Because a vaccine is lacking, as well as an effective antiviral treatment, prevention is key.
Aydogan, Kenan; Karadogan, Serap Koran; Tunali, Sukran
A 20-year-old woman with a 2-year history of histologically confirmed palmoplantar keratoderma due to psoriasis, resistant to several topical agents, was admitted to the Department of Dermatology, Uludag University, Bursa, Turkey. Therapy with oral acitretin (0.5 mg/kg/day, 35 mg/day) was initiated. A month after starting acitretin treatment, she noted slight reddening of the second left fingernail. Clinical examination revealed red-brown discoloration of the second fingernail associated with subungual hemorrhage involving the proximal nail bed (lunula region) (Fig. 1). The nail change was asymptomatic. The patient complained only of discoloration underneath the nail plate. No abnormalities were detected on the skin, mucous membranes, or toenails/other fingernails. The patient denied exposure to microtrauma or any other drugs. The erythrocyte sedimentation rate, full blood cell count, electrolytes, renal and hepatic tests, and serum lipids were normal. Coagulation tests, including blood clotting time, international normalized ratio, activated partial thromboplastin time, thrombin time, platelet number, and function tests, were within normal levels. Treatment with acitretin was discontinued, and the nail change resolved completely after 3 weeks. A similar episode of subungual hemorrhage recurred, however, within 48 h after re-challenge with a lower dose of acitretin (25 mg/day). The drug was definitively stopped and the eruption faded again within a week. An objective causality assessment suggests that subungual hemorrhage was probably related to acitretin in this patient.
Chen, Muh-Shy; Ho, Tzyy-Chang; Chang, Ching-Chung; Hou, Ping-Kang
We report extensive myelinated retinal nerve fibers in a 42-year-old patient with retinal detachment. Fundus examination revealed a horseshoe-shaped tear near the temporal edge. Pars plana vitrectomy was performed and firm vitreo-retinal adhesion was noticed in the area of extensive myelinated retinal nerve fibers. Following vitrectomy with silicone oil tamponade, the retina was reattached successfully. In conclusion, retinal detachment may develop in patients with extensive myelinated retinal nerve fibers. Vitrectomy may be performed to treat this condition.
Viral hemorrhagic fever (VHF) is defined as virus infections that usually cause pyrexia and hemorrhagic symptoms with multiple organ failure. VHF includes following viral infections: Ebola hemorrhagic fever (EHF), Marburg hemorrhagic fever (MHF), Crimean-Congo hemorrhagic fever (CCHF) and Lassa fever. In particular, the causative agents of EHF, MHF, CCHF, and Lassa fever are Ebola, Marburg, CCHF, Lassa viruses, respectively, and regarded as biosafety level-4 pathogens because of their high virulence to humans. Recently, relatively large outbreaks of EHF and MHF have occurred in Africa, and areas of EHF- and MHF-outbreaks seem to be expanding. Although outbreaks of VHF have not been reported in Japan, there is a possibility that the deadly hemorrhagic fever viruses would be introduced to Japan in future. Therefore, preparedness for possible future outbreaks of VHF is necessary in areas without VHF outbreaks.
Manos, Daria; Hamer, Okka; Müller, Nestor L
Pulmonary hemorrhage is a relatively common complication of blunt chest trauma. Occasionally, it may result from pulmonary barotrauma after scuba diving or from sports activities not associated with barotrauma such as long breath-hold diving. We report a case of symmetric diffuse upper lobe hemorrhage resulting from a bungee jump in a previously healthy man. Bungee jumping is an increasingly popular sport with relatively few reported injuries. To our knowledge pulmonary hemorrhage in this setting has not yet been described.
tlll AD111 CONTRACT NO: DAMDI7-91-C-1006 TITLE: SIMIAN HEMORRHAGIC FEVER (SHF) VIRUS PRINCIPAL INVESTIGATOR: Margo A. Brinton, Ph.D. CONTRACTING...SUBTITLE S. FUNDING NUMBERS Simian Hemorrhagic Fever (SHF) Virus DAMD17-91-C-1006 6. AUTHOR(S) Margo A. Brinton, Ph.D. 7. PERFORMING ORGANIZATION...simian hemorrhagic fever (SHF) virus -specific hybridoma cultures, expand two clones from each clone as well as 50 ml of supernatant fluid from
Ding, Y.; Ward, W. O. C.; Duan, Jinming; Auer, D. P.; Gowland, Penny; Bai, L.
Retinal blood vessels have been implicated in a large number of diseases including diabetic retinopathy and cardiovascular diseases, which cause damages to retinal blood vessels. The availability of retinal vessel imaging provides an excellent opportunity for monitoring and diagnosis of retinal diseases, and automatic analysis of retinal vessels will help with the processes. However, state of the art vascular analysis methods such as counting the number of branches or measuring the curvature and diameter of individual vessels are unsuitable for the microvasculature. There has been published research using fractal analysis to calculate fractal dimensions of retinal blood vessels, but so far there has been no systematic research extracting discriminant features from retinal vessels for classifications. This paper introduces new methods for feature extraction from multifractal spectra of retinal vessels for classification. Two publicly available retinal vascular image databases are used for the experiments, and the proposed methods have produced accuracies of 85.5% and 77% for classification of healthy and diabetic retinal vasculatures. Experiments show that classification with multiple fractal features produces better rates compared with methods using a single fractal dimension value. In addition to this, experiments also show that classification accuracy can be affected by the accuracy of vessel segmentation algorithms.
Abstract Adrenal hemorrhage (AH) is a rare but life-threatening condition. Small focal hemorrhage may present subclinically, but massive hemorrhage may lead to rapid cardiovascular collapse and ultimately death if not diagnosed appropriately and treated quickly. Most cases reported in the literature have been treated conservatively. In an event of increasing hemorrhage during conservative management, it may be tricky to intervene surgically because of the hematoma around the gland. Here we describe a case where we managed a large spontaneous AH by a combination of angioembolization and laparoscopic adrenalectomy. PMID:27579389
Manikandan, R.; Kumar, Santosh; Dorairajan, Lalgudi N.
Severe hemorrhagic cystitis often arises from anticancer chemotherapy or radiotherapy for pelvic malignancies. Infectious etiologies are less common causes except in immunocompromised hosts. These cases can be challenging problems for the urologist and a source of substantial morbidity and sometimes mortality for the patients. A variety of modalities of treatment have been described for the management of hemorrhagic cystitis but there is none that is uniformly effective. Some progress has been made in the understanding and management of viral hemorrhagic cystitis. This article reviews the common causes of severe hemorrhagic cystitis and the currently available management options. PMID:20877590
Ebrahem, Rawaa; Munguti, Cyrus; Mortada, Rami
Spontaneous adrenal hemorrhage (SAH) is a serious medical condition associated with variable clinical presentation depending on the extent of the hemorrhage. Pregnancy-induced adrenal hemorrhage is poorly understood. A low cortisol level in the peripartum period with radiological findings is sufficient to establish the diagnosis. Prompt hormone replacement and supportive care to ensure good clinical outcomes is crucial. Due to the potentially life-threatening complications, physicians should have a high suspicion for adrenal hemorrhage when they evaluate patients with hypotension, fatigue, and abdominal pain during the peripartum period. PMID:28191381
Mrejen, Sarah; Audo, Isabelle; Bonnel, Sébastien; Sahel, José-Alain
Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerations characterized by progressive degeneration of rod and cone cells that affects predominantly peripheral visual fields. Macular edema may cause additional central visual acuity decrease. Cystoid macular edema (CME) is one of the few treatable causes of visual loss in RP. The prevalence of CME in RP has been found to be between 10 and 20% on fluorescein angiography-based studies, and as high as 49% on reports based on optical coherence tomography. Macular edema can manifest at any stage of the disease and may be unilateral or bilateral. It can be found in any genetic form, but is more often associated with RP caused by CRB1 mutations. The origin of macular edema in RP patients still remains poorly understood. Some mechanisms have been suggested, including antiretinal antibodies (retinal, carbonic anhydrase, and enolase antibodies), vitreous traction, retinal pigment epithelium dysfunction, and Müller cell edema. There is no gold standard therapeutic strategy. Drug therapy is the primary treatment. Systemic carbonic anhydrase inhibitors, such as oral acetazolamide or topical dorzolamide, are still the mainstays of initial therapy. If CME is refractory to acetazolamide, intravitreal corticosteroid injections may be a therapeutic option. However, antivascular endothelium growth factor injections have limited effect and should be avoided. Vitrectomy has also been evaluated, but its exact role remains to be determined. The benefits of these therapies are variable among patients. The establishment of therapeutic approaches is limited by our poor understanding of the pathophysiology of CME in patients with RP. Autoimmune retinopathies (AIRs) are a group of rare diseases characterized by acute or subacute progressive vision loss and are thought to be mediated by autoantibodies specific to retinal antigens. The AIRs encompass paraneoplastic syndromes, such as cancer-associated retinopathy and
Wang, J Z
93 eyes (93 patients) of complicated retinal detachment were treated with vitreo-retinal surgery. Among the series, 75 eyes were rhegmatogenous with PVR C3-D3 in 66 eyes (88.0%), while the remaining 18 eyes were traction induced. None of the cases had giant tears or complicating diabetes. On discharge from the hospital, the operation was effective in 62 cases (66.7%), in whom the retina was totally reattached or only a small amount of subretinal fluid remained. In a group of 40 eyes where the inert gas SF6 was used, the operation was effective in 30 cases (75.0%). 41 cases were followed up postoperatively for over 3 months, averaging 13.7 months, to find the operative results stable in 33 eyes (80.5%), with the visual acuity improved in 22 cases (66.7%), unchanged in 9 cases (27.3%), and decreased in 2 cases (6.0%). The operative procedures, the peeling of pre-retinal membrane, the effect of PVR severity on the operative results, and the promotion of operative efficacy by application of wide encircling buckle and inert gas tamponade were discussed.
Bhoiwala, Devang L.; Dunaief, Joshua L.
Patients with beta (β)-thalassemia (β-TM: thalassemia major, β-TI: thalassemia intermedia) have a variety of complications that may affect all organs, including the eye. Ocular abnormalities include retinal pigment epithelium degeneration, angioid streaks, venous tortuosity, night blindness, visual field defects, decreased visual acuity, color vision abnormalities, and acute visual loss. Patients with β-TM are transfusion dependent and require iron chelation therapy (ICT) in order to survive. Retinal degeneration may result from either retinal iron accumulation from transfusion-induced iron overload or retinal toxicity induced by ICT. Some who were never treated with ICT exhibited retinopathy, and others receiving ICT had chelator-induced retinopathy. We will focus on retinal abnormalities present in individuals with β-TM viewed in light of new findings on the mechanisms and manifestations of retinal iron toxicity. PMID:26325202
Kaba, Djibril; Wang, Chuang; Li, Yongmin; Salazar-Gonzalez, Ana; Liu, Xiaohui; Serag, Ahmed
The analysis of retinal blood vessels plays an important role in detecting and treating retinal diseases. In this review, we present an automated method to segment blood vessels of fundus retinal image. The proposed method could be used to support a non-intrusive diagnosis in modern ophthalmology for early detection of retinal diseases, treatment evaluation or clinical study. This study combines the bias correction and an adaptive histogram equalisation to enhance the appearance of the blood vessels. Then the blood vessels are extracted using probabilistic modelling that is optimised by the expectation maximisation algorithm. The method is evaluated on fundus retinal images of STARE and DRIVE datasets. The experimental results are compared with some recently published methods of retinal blood vessels segmentation. The experimental results show that our method achieved the best overall performance and it is comparable to the performance of human experts.
Oulmaati, A; Hays, S; Mory-Thomas, N; Bretones, P; Bensaid, M; Jordan, I; Bonfils, M; Godbert, I; Picaud, J-C
The clinical presentation of adrenal hemorrhage varies, depending on the extent of hemorrhage as well as the amount of adrenal cortex involved by the hemorrhage. We report here a case of neonatal adrenal hemorrhage revealed by late onset of neonatal jaundice. This adrenal hemorrhage most probably resulted from shoulder dystocia. The aim of this work was to focus on the fact that jaundice can be caused by adrenal hemorrhage and to emphasize the crucial importance of abdominal ultrasound in cases of persistent jaundice.
Neroev, V V; Arkhipova, M M
Retinal ischemia is the main chain in the pathogenesis of vascular diseases of the eye. It was established that nitric oxide (NO) plays the key role in the development of ischemia. Recent understanding of the NO role, as a universal regulator of the cellular and tissue metabolism, is presented. The authors' and published data were used to design a scheme of pathogenesis of retinal ischemia with regard for the NO role. NO can produce both positive and negative effects depending on a stage of the process, NO concentration and on a number of other factors if they are present. Initial stages of hypoxia/ischemia are accompanied by an activation of all forms of NO-synthases (NOS) caused by the influence of biologically active substances (cytokines, prostaglandins, serotonin, bradykinin, glycolisis suboxide products etc.). The activation of inducible NOS, which synthesize a bigger quantity of NO possessing a direct cytotoxic action and contributing to the production of highly toxic radical of peroxinitrit, is in the focus of attention. The damage of cellular structures due to free-radical processes leads to the development of endothelial, macrophage and thrombocyte malfunctions, which manifest itself through a reduced activity of endothelial NOS and through disruption of NO-dependent processes (vasospasm, an increased aggregation of platelets and a reduced fibrinolytic activity). A sharp reduction of NO synthesis substrate (L-arginine) is observed in patients with retinal ischemia. The aggravation of ischemia causes a decrease of NO synthesis due to an exhaustion of L-arginine and its intensified consumption in the course of free-radical processes. The use of NO-inhibitors and of NO-donors at different stages of retinal ischemia prevents the development of neovascularization and proliferation.
from diseases such as retinitis pigmentosa and age-related macular degeneration are the leading causes of blindness in the developing world...53featured research 2005 NRL Review Microelectronic Array for Stimulation of Retinal Tissue D. Scribner,1 L. Johnson,4 P. Skeath,4 R. Klein,4...GOALS The development of a high-resolution retinal prosthesis device at the Naval Research Laboratory (NRL) was first discussed in the late 1990s
visual impairment usually ending in blindness. In the United States, the total number of individuals affected by retinitis pigmentosa (RP) and other...linica l trial in the NEER network for autosomal dominant retinitis pigmentosa , and the ProgSTAR studies for Stargardt disease) . As new interventions b... retinitis pigmentosa continues at six sites- the CTEC site at University of Utah and five additional recruitment sites- the Retina Foundation of the
Doyle, Susan E.; Yoshikawa, Tomoko; Hillson, Holly; Menaker, Michael
In mammals, light input from the retina entrains central circadian oscillators located in the suprachiasmatic nuclei (SCN). The phase of circadian activity rhythms with respect to the external light:dark cycle is reversed in diurnal and nocturnal species, although the phase of SCN rhythms relative to the light cycle remains unchanged. Neural mechanisms downstream from the SCN are therefore believed to determine diurnality or nocturnality. Here, we report a switch from nocturnal to diurnal entrainment of circadian activity rhythms in double-knockout mice lacking the inner-retinal photopigment melanopsin (OPN4) and RPE65, a key protein used in retinal chromophore recycling. These mice retained only a small amount of rod function. The change in entrainment phase of Rpe65−/−;Opn4−/− mice was accompanied by a reversal of the rhythm of clock gene expression in the SCN and a reversal in acute masking effects of both light and darkness on activity, suggesting that the nocturnal to diurnal switch is due to a change in the neural response to light upstream from the SCN. A switch from nocturnal to diurnal activity rhythms was also found in wild-type mice transferred from standard intensity light:dark cycles to light:dark cycles in which the intensity of the light phase was reduced to scotopic levels. These results reveal a novel mechanism by which changes in retinal input can mediate acute temporal-niche switching. PMID:18695249
de Hoz, Rosa; Rojas, Blanca; Ramírez, Ana I.; Salazar, Juan J.; Gallego, Beatriz I.; Triviño, Alberto; Ramírez, José M.
Due to their permanent and close proximity to neurons, glial cells perform essential tasks for the normal physiology of the retina. Astrocytes and Müller cells (retinal macroglia) provide physical support to neurons and supplement them with several metabolites and growth factors. Macroglia are involved in maintaining the homeostasis of extracellular ions and neurotransmitters, are essential for information processing in neural circuits, participate in retinal glucose metabolism and in removing metabolic waste products, regulate local blood flow, induce the blood-retinal barrier (BRB), play fundamental roles in local immune response, and protect neurons from oxidative damage. In response to polyetiological insults, glia cells react with a process called reactive gliosis, seeking to maintain retinal homeostasis. When malfunctioning, macroglial cells can become primary pathogenic elements. A reactive gliosis has been described in different retinal pathologies, including age-related macular degeneration (AMD), diabetes, glaucoma, retinal detachment, or retinitis pigmentosa. A better understanding of the dual, neuroprotective, or cytotoxic effect of macroglial involvement in retinal pathologies would help in treating the physiopathology of these diseases. The extensive participation of the macroglia in retinal diseases points to these cells as innovative targets for new drug therapies. PMID:27294114
Lefevere, Evy; Toft-Kehler, Anne Katrine; Vohra, Rupali; Kolko, Miriam; Moons, Lieve; Van Hove, Inge
Dysfunction of photoreceptors, retinal pigment epithelium (RPE) or both contribute to the initiation and progression of several outer retinal disorders. Disrupted Müller glia function might additionally subsidize to these diseases. Mitochondrial malfunctioning is importantly associated with outer retina pathologies, which can be classified as primary and secondary mitochondrial disorders. This review highlights the importance of oxidative stress and mitochondrial DNA damage, underlying outer retinal disorders. Indeed, the metabolically active photoreceptors/RPE are highly prone to these hallmarks of mitochondrial dysfunction, indicating that mitochondria represent a weak link in the antioxidant defenses of outer retinal cells.
Dahan, Meryl; Lim, Chetana; Salloum, Chady
Postoperative bilateral adrenal hemorrhage is a rare but potentially life-threatening complication. This diagnosis is often missed because the symptoms and laboratory results are usually nonspecific. We report a case of bilateral adrenal hemorrhage associated with acute primary adrenal insufficiency following laparoscopic cholecystectomy. The knowledge of this uncommon complication following any abdominal surgery allows timey diagnosis and rapid treatment. PMID:27275469
Gonzalez Valverde, F.M. Balsalobre, M.; Torregrosa, N.; Molto, M.; Gomez Ramos, M.J.; Vazquez Rojas, J.L.
Spontaneous adrenal hemorrhage is a very rare but serious disorder of the adrenal gland that can require emergent treatment. We report on a 42-year-old man who underwent selective angiography for diagnosis and treatment of retroperitoneal hemorrhage from small adrenal artery aneurysm. This case gives further details about the value of transluminal artery embolization in the management of visceral aneurysm rupture.
Zhao, Shu-Lei; Li, Peng; Ji, Ming; Zong, Ye; Zhang, Shu-Tian
Superwarfarins are a class of rodenticides. Gastrointestinal hemorrhage is a fatal complication of superwarfarin poisoning, requiring immediate treatment. Here, we report a 55-year-old woman with tardive upper gastrointestinal hemorrhage caused by superwarfarin poisoning after endoscopic cold mucosal biopsy. PMID:20355251
Dahan, Meryl; Lim, Chetana; Salloum, Chady; Azoulay, Daniel
Postoperative bilateral adrenal hemorrhage is a rare but potentially life-threatening complication. This diagnosis is often missed because the symptoms and laboratory results are usually nonspecific. We report a case of bilateral adrenal hemorrhage associated with acute primary adrenal insufficiency following laparoscopic cholecystectomy. The knowledge of this uncommon complication following any abdominal surgery allows timey diagnosis and rapid treatment.
Enria, Delia A; Briggiler, Ana M; Sánchez, Zaida
Argentine hemorrhagic fever (AHF) is a rodent-borne illness caused by the arenavirus Junin that is endemic to the humid pampas of Argentina. AHF has had significant morbidity since its emergence in the 1950s, with a case-fatality rate of the illness without treatment between 15% and 30%. The use of a live attenuated vaccine has markedly reduced the incidence of AHF. Present specific therapy involves the transfusion of immune plasma in defined doses of neutralizing antibodies during the prodromal phase of illness. However, alternative forms of treatment are called for due to current difficulties in early detection of AHF, related to its decrease in incidence, troubles in maintaining adequate stocks of immune plasma, and the absence of effective therapies for severely ill patients that progress to a neurologic-hemorrhagic phase. Ribavirin might be a substitute for immune plasma, provided that the supply is guaranteed. Immune immunoglobulin or monoclonal antibodies should also be considered. New therapeutic options such as those being developed for systemic inflammatory syndromes should also be valuated in severe forms of AHF.
Alexander, Russell T; Jentzen, Jeffrey M
The determination of the cause and manner of death for a body recovered from the water can be difficult because of a lack of autopsy findings specific for drowning. This case report describes a 30-year-old man found submerged at the bottom of a hotel pool. An autopsy revealed scleral hemorrhages and fascial hemorrhages of multiple muscles of the anterior and posterior neck bilaterally. No evidence of traumatic injury was on the surface of the body. An investigation by law enforcement found no evidence of foul play. The occurrence of petechial and neck hemorrhage in a body recovered from the water is controversial, and a review of this literature will be given. We suggest that fascial hemorrhages of the muscles of the neck, as well as cephalic hemorrhages, can be explained by drowning-related elevated central venous pressure that is communicated to the head through the valveless veins of the neck.
Alex, Anne F; Heiduschka, Peter; Eter, Nicole
The development of in vivo retinal fundus imaging in mice has opened a new research horizon, not only in ophthalmic research. The ability to monitor the dynamics of vascular and cellular changes in pathological conditions, such as neovascularization or degeneration, longitudinally without the need to sacrifice the mouse, permits longer observation periods in the same animal. With the application of the high-resolution confocal scanning laser ophthalmoscopy in experimental mouse models, access to a large spectrum of imaging modalities in vivo is provided.
Guadagni, Viviana; Cerri, Chiara; Piano, Ilaria; Novelli, Elena; Gargini, Claudia; Fiorentini, Carla; Caleo, Matteo; Strettoi, Enrica
Retinitis pigmentosa (RP) comprises a group of inherited pathologies characterized by progressive photoreceptor degeneration. In rodent models of RP, expression of defective genes and retinal degeneration usually manifest during the first weeks of postnatal life, making it difficult to distinguish consequences of primary genetic defects from abnormalities in retinal development. Moreover, mouse eyes are small and not always adequate to test pharmacological and surgical treatments. An inducible paradigm of retinal degeneration potentially extensible to large animals is therefore desirable. Starting from the serendipitous observation that intraocular injections of a Rho GTPase activator, the bacterial toxin Cytotoxic Necrotizing Factor 1 (CNF1), lead to retinal degeneration, we implemented an inducible model recapitulating most of the key features of Retinitis Pigmentosa. The model also unmasks an intrinsic vulnerability of photoreceptors to the mechanism of CNF1 action, indicating still unexplored molecular pathways potentially leading to the death of these cells in inherited forms of retinal degeneration. PMID:27775019
Padhi, T R; Das, T; Rath, S; Pradhan, L; Sutar, S; Panda, K G; Modi, R; Jalali, S
Purpose To evaluate the serial changes in retinal vasculature in infants treated with intravitreal bevacizumab (IVB) for aggressive posterior retinopathy of prematurity (APROP) in zone I. Methods Retrospective analysis of serial changes in retinal vasculature after IVB in the seven eyes of four babies with APROP in zone I. Results The initial regression, following IVB, was dramatic with reduction in vessel caliber and marked thinning and invisibility of the bridging shunts. Resurgent vascular development was very slow radially though there was continued abnormal vascular growth circumferentially. Common findings in all eyes were tangled vasculature and fine saw-toothed shunts. The variable findings were (1) new closely packed multilayered bridging shunts, long arching mature looking vessels, and finally a ridge at the periphery (n=3 eyes) at 52 weeks of postmenstrual age (PMA); (2) status quo at the stage of saw-toothed shunt and ridge in both eyes for a long time (n=2 eyes); and (3) multiple retinal hemorrhages within the vascularized retina and thick preretinal hemorrhage overlying the saw-toothed shunts and ridge that persisted for another 3 weeks and regressed 2 weeks after laser (n=1). The eyes that received bevacizumab alone (3) did not show any abnormal vascularization at 56 weeks of PMA or beyond. Conclusions The retinal vascularization following IVB was different than normal in terms of its time, speed, and morphology; few of these changes are first to be reported in the literature (Medline search) and warrants further studies. PMID:26584796
Radius, R L; de Bruin, J
Anatomy of the retinal nerve fiber layer in rabbit eyes is studied by light microscopy, transmission electron microscopy, and scanning electron microscopy. It is demonstrated that retinal striations noted ophthalmoscopically in these eyes represent individual fiber bundles, Axon bundles are compartmentalized within tissue tunnels comprised of elongated processes of glial cell origin.
Gabai, Andrea; Veritti, Daniele; Lanzetta, Paolo
Fundus autofluorescence (FAF) is a relatively new imaging technique that can be used to study retinal diseases. It provides information on retinal metabolism and health. Several different pathologies can be detected. Peculiar AF alterations can help the clinician to monitor disease progression and to better understand its pathogenesis. In the present article, we review FAF principles and clinical applications. PMID:26139802
Gabai, Andrea; Veritti, Daniele; Lanzetta, Paolo
Fundus autofluorescence (FAF) is a relatively new imaging technique that can be used to study retinal diseases. It provides information on retinal metabolism and health. Several different pathologies can be detected. Peculiar AF alterations can help the clinician to monitor disease progression and to better understand its pathogenesis. In the present article, we review FAF principles and clinical applications.
Gao, Billy; Pollock, Jeffrey A; Hinson, Holly E
Introduction Paroxysmal sympathetic hyperactivity (PSH) is a hyperadrenergic syndrome that may follow acute brain injury characterized by episodic, hyperadrenergic alterations in vital signs. Identifying commonality in lesion localization in patients with PSH is challenging, but intraparenchymal hemorrhage (IPH) represents a focal injury that might provide insight. We describe a series of patients with IPH that developed PSH, and review the literature. Methods Patients with IPH who developed PSH were identified from OHSU hospital records. A literature review was conducted to identify similar cases through PUBMED, OVID, and Google Scholar. Results Three cases meeting criteria for PSH were identified. Hemorrhage volume ranged from 70 to 128 mL, and intracranial hemorrhage score ranged from 2 to 3. The laterality of the hemorrhage and significant volume of hemorrhage was similar in each of the patients, specifically all hemorrhages were large, subcortical, and right-sided. A literature search identified six additional cases, half of whom reported a right hemisphere hemorrhage and the majority also had subcortical localization. Conclusions Our literature review identified six cases of IPH associated with PSH with five cases having subcortical lesion locations, echoing the areas of disruption in our three cases. On the basis of these observations, we hypothesize that injuries along the pathway from the insular cortex to downstream sympathetic centers may remove tonic inhibition leading to unchecked sympathetic outflow. Prospective investigations of lesion location in patients with IPH and PSH are warranted to test this hypothesis, especially with advanced neuroimaging techniques. PMID:24904923
Johnson, Adiv A; Guziewicz, Karina E; Lee, C Justin; Kalathur, Ravi C; Pulido, Jose S; Marmorstein, Lihua Y; Marmorstein, Alan D
Mutations in the gene BEST1 are causally associated with as many as five clinically distinct retinal degenerative diseases, which are collectively referred to as the "bestrophinopathies". These five associated diseases are: Best vitelliform macular dystrophy, autosomal recessive bestrophinopathy, adult-onset vitelliform macular dystrophy, autosomal dominant vitreoretinochoroidopathy, and retinitis pigmentosa. The most common of these is Best vitelliform macular dystrophy. Bestrophin 1 (Best1), the protein encoded by the gene BEST1, has been the subject of a great deal of research since it was first identified nearly two decades ago. Today we know that Best1 functions as both a pentameric anion channel and a regulator of intracellular Ca(2+) signaling. Best1 is an integral membrane protein which, within the eye, is uniquely expressed in the retinal pigment epithelium where it predominantly localizes to the basolateral plasma membrane. Within the brain, Best1 expression has been documented in both glial cells and astrocytes where it functions in both tonic GABA release and glutamate transport. The crystal structure of Best1 has revealed critical information about how Best1 functions as an ion channel and how Ca(2+) regulates that function. Studies using animal models have led to critical insights into the physiological roles of Best1 and advances in stem cell technology have allowed for the development of patient-derived, "disease in a dish" models. In this article we review our knowledge of Best1 and discuss prospects for near-term clinical trials to test therapies for the bestrophinopathies, a currently incurable and untreatable set of diseases.
Marc, Robert E.; Jones, Bryan W.; Anderson, James R.; Kinard, Krista; Marshak, David W.; Wilson, John H.; Wensel, Theodore; Lucas, Robert J.
Purpose Early visual defects in degenerative diseases such as retinitis pigmentosa (RP) may arise from phased remodeling of the neural retina. We sought to explore the functional expression of ionotropic (iGluR) and group III, type 6 metabotropic (mGluR6) glutamate receptors in late-stage photoreceptor degenerations. Methods Excitation mapping with organic cations and computational molecular phenotyping were used to determine whether retinal neurons displayed functional glutamate receptor signaling in rodent models of retinal degenerations and a sample of human RP. Results After photoreceptor loss in rodent models of RP, bipolar cells lose mGluR6 and iGluR glutamate-activated currents, while amacrine and ganglion cells retain iGluR-mediated responsivity. Paradoxically, amacrine and ganglion cells show spontaneous iGluR signals in vivo even though bipolar cells lack glutamate-coupled depolarization mechanisms. Cone survival can rescue iGluR expression by OFF bipolar cells. In a case of human RP with cone sparing, iGluR signaling appeared intact, but the numbers of bipolar cells expressing functional iGluRs was double that of normal retina. Conclusions RP triggers permanent loss of bipolar cell glutamate receptor expression, though spontaneous iGluR-mediated signaling by amacrine and ganglion cells implies that such truncated bipolar cells still release glutamate in response to some non-glutamatergic depolarization. Focal cone-sparing can preserve iGluR display by nearby bipolar cells, which may facilitate late-RP photoreceptor transplant attempts. An instance of human RP provides evidence that rod bipolar cell dendrite switching likely triggers new gene expression patterns and may impair cone pathway function. PMID:17591910
Carette, Marie-France Nedelcu, Cosmina; Tassart, Marc; Grange, Jean-Didier; Wislez, Marie; Khalil, Antoine
This pictorial review is based on our experience of the follow-up of 120 patients at our multidisciplinary center for hereditary hemorrhagic telangiectasia (HHT). Rendu-Osler-Weber disease or HHT is a multiorgan autosomal dominant disorder with high penetrance, characterized by epistaxis, mucocutaneous telangiectasis, and visceral arteriovenous malformations (AVMs). The research on gene mutations is fundamental and family screening by clinical examination, chest X-ray, research of pulmonary shunting, and abdominal color Doppler sonography is absolutely necessary. The angioarchitecture of pulmonary AVMs can be studied by unenhanced multidetector computed tomography; however, all other explorations of liver, digestive bowels, or brain require administration of contrast media. Magnetic resonance angiography is helpful for central nervous system screening, in particular for the spinal cord, but also for pulmonary, hepatic, and pelvic AVMs. Knowledge of the multiorgan involvement of HHT, mechanism of complications, and radiologic findings is fundamental for the correct management of these patients.
Zghal, I; Malek, I; Amel, C; Soumaya, O; Bouguila, H; Nacef, L
Necrotizing viral retinitis is associated with infection by the Herpes family of viruses, especially herpes simplex virus (HSV), varicella zoster virus (VZV) and occasionally cytomegalovirus (CMV). When the diagnosis is suspected clinically, antiviral therapy must be instituted immediately. We report the case of a patient presenting with necrotizing viral retinitis 3 months following intravitreal injection of triamcinolone acetonide for diabetic macular edema. Fluorescein angiography demonstrated a superior temporal occlusive vasculitis. A diagnostic anterior chamber paracentesis was performed to obtain deoxyribo-nucleic acid (DNA) for a polymerase chain reaction (PCR) test for viral retinitis. PCR was positive for CMV. The patient was placed on intravenous ganciclovir. CMV retinitis is exceedingly rare in immunocompetent patients; however, it remains the most common cause of posterior uveitis in immunocompromised patients. The incidence of this entity remains unknown. Local immunosuppression, the dose and the frequency of injections may explain the occurrence of this severe retinitis.
Athanasiou, Dimitra; Aguilà, Monica; Bevilacqua, Dalila; Novoselov, Sergey S; Parfitt, David A; Cheetham, Michael E
Retinal degenerations are a group of clinically and genetically heterogeneous disorders characterised by progressive loss of vision due to neurodegeneration. The retina is a highly specialised tissue with a unique architecture and maintaining homeostasis in all the different retinal cell types is crucial for healthy vision. The retina can be exposed to a variety of environmental insults and stress, including light-induced damage, oxidative stress and inherited mutations that can lead to protein misfolding. Within retinal cells there are different mechanisms to cope with disturbances in proteostasis, such as the heat shock response, the unfolded protein response and autophagy. In this review, we discuss the multiple responses of the retina to different types of stress involved in retinal degenerations, such as retinitis pigmentosa, age-related macular degeneration and glaucoma. Understanding the mechanisms that maintain and re-establish proteostasis in the retina is important for developing new therapeutic approaches to fight blindness.
Furukawa, Hiromitsu; Arimoto, Hidenobu; Shirai, Tomohiro; Ooto, Sotaro; Hangai, Masanori; Yoshimura, Nagahisa
Retinal oximetry of capillaries was performed for early detection of retinal vascular abnormalities, which are caused predominantly by complications of systemic circulatory diseases. As the conventional method for determining absorbance is not applicable to capillaries, multicomponent analysis was used to estimate the absorbance spectra of the retinal blood vessels. In this analysis, the capillary spectrum was classified as intermediate between those of the retinal arteries and veins, enabling relative estimation of oxygen saturation in the capillaries. This method could be useful for early recognition of disturbances in the peripheral circulation. Furthermore, a spectroscopic ophthalmoscope system based on the proposed method was developed to examine the human retina. A clinical trial of this system demonstrated that oximetry of the retinal capillaries may be an improvement over the present diagnosis for patients of malignant hypertension.
Enria, D A; Maiztegui, J I
Argentine hemorrhagic fever is a systemic viral disease caused by Junin virus, with a mortality of 15-30% in untreated individuals. Current specific therapy is highly effective in reducing mortality, and consists of the early administration of immune plasma in defined doses of specific neutralizing antibodies per kg of body weight. However, several reasons suggest the need to investigate alternative therapies. Ribavirin, a broad spectrum antiviral agent, is effective in the treatment of other viral hemorrhagic fevers, and the studies done with Junin virus infections to date indicate that this drug may also have a beneficial effect in Argentine hemorrhagic fever.
Yamamoto, Takatsugu; Abe, Koichiro; Kuyama, Yasushi
Selective serotonin reuptake inhibitors (SSRI) are widely used antidepressants characterized by less-frequent adverse effects compared with classical anti-depressive agents. On the other hand, SSRI can cause hemorrhagic events more due to impaired platelet aggregation induced by a depletion of serotonin in the peripheral platelet. Epidemiological studies have indicated that patients taking SSRI are predisposed to gastrointestinal hemorrhage, especially in case that nonsteroidal anti-inflammatory drugs are prescribed concomitantly. Here we describe a risk of the gastrointestinal hemorrhage in patients taking SSRI.
Rosenberg, G A; Herz, D A; Leeds, N; Strully, K
Two patients with Meckel's Cave meningiomas were initially hospitalized as a result of subarachnoid hemorrhage. Four-vessel angiography was necessary to exclude other causes of bleeding while demonstrating these lesions. Apoplectic presentation in both cases led to early diagnosis and successful surgical therapy. A review of the literature reveals subarachnoid hemorrhage to be a rarity in association with meningiomas. The two patients currently reported are believed to be the only examples on record of hemorrhagic meningiomas arising from the region of Meckel's Cave.
Monov, Simeon; Hristova, Ruska; Dacheva, Rositza; Toncheva, Reni; Shumnalieva, Russka; Shoumnalieva-Ivanova, Viara; Monova, Daniela
Abstract Rationale: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production, complement activation, and deposition of immune complexes in tissues and organs. SLE can involve any region of the visual system. Although ocular manifestations are not part of the classification criteria for SLE, they can be observed in up to one-third of the patients with SLE. They are rarely reported at the time of disease onset. Retinal vasculitis is usually associated with active generalized disease. Due to its low frequency, we report a case of acute necrotizing retinal vasculitis as onset of SLE. Patient concerns and diagnosis: A 25-year-old white female was referred to the rheumatology clinic with gradually and rapid deterioration of the vision due to abnormal vessel permeability in the right fundus with edema along the vessels, occlusion of arterial branches in the middle periphery with leakage of the dye in these areas and indentical but less prominent changes with cotton wool spots in the papillomacular area and extensive hemorrhages in the left eye. The onset of malar rash, arthralgias and positive antinuclear, anti-double stranded DNA, anti-ribosomal P and anti-β2 glycoprotein I antibodies with decreased C4 complement levels, as well as the positive lupus-band test confirmed the diagnosis of SLE. Interventions: Aggressive immunomodulating therapy with high-dose methylprednisolone, intravenous immunoglobulin, and cyclophosphamide was used for suppression of the disease activity followed by azathioprine as maintaince therapy. Outcomes: Substantial improvement and partial resorption of the vasculitic changes, including central retinal artery and vein, was achieved prominently in the left eye. The study was conducted in accordance with the Declaration of Helsinki and written informed consent was obtained from the patient. Because of this, there is no need to conduct special ethic review and the ethical approval is not necessary
Wilkinson, Charles P
Background Asymptomatic retinal breaks and lattice degeneration are visible lesions that are risk factors for later retinal detachment. Retinal detachments occur when fluid in the vitreous cavity passes through tears or holes in the retina and separates the retina from the underlying retinal pigment epithelium. Creation of an adhesion surrounding retinal breaks and lattice degeneration, with laser photocoagulation or cryotherapy, has been recommended as an effective means of preventing retinal detachment. This therapy is of value in the management of retinal tears associated with the symptoms of flashes and floaters and persistent vitreous traction upon the retina in the region of the retinal break, because such symptomatic retinal tears are associated with a high rate of progression to retinal detachment. Retinal tears and holes unassociated with acute symptoms and lattice degeneration are significantly less likely to be the sites of retinal breaks that are responsible for later retinal detachment. Nevertheless, treatment of these problems is frequently recommended, in spite of the fact that the effectiveness of this therapy is unproven. Objectives The purpose of this review was to evaluate the effectiveness of interventions for asymptomatic retinal breaks and lattice degeneration. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 1), MEDLINE (January 1950 to January 2012), EMBASE (January 1980 to January 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 28 January 2012. Textbooks regarding retinal detachment and the reference lists of relevant reports were reviewed for additional
Zheng, Linda; Gillies, Mark; Martin, Frank J
We describe the case of an otherwise healthy 13-year-old boy who presented with blurred vision and deteriorating visual acuity in his left eye. Fundus examination showed left optic disk swelling, exudates, and hemorrhages. He was found to have an elevated left central retinal venous pressure to the level of arterial diastolic pressure, an elevated left central macular thickness and a prolonged disk-to-disk transit time on fluorescein angiography, which confirmed the diagnosis of unilateral central retinal vein occlusion (CRVO). The child was treated with one injection of bevacizumab. He has maintained visual acuity of 6/6 for 2 years following treatment, despite persistent elevated left central venous pressure and chronic optic disk edema.
Stradleigh, Tyler W; Ishida, Andrew T
Immunohistochemical and ex vivo anatomical studies have provided many glimpses of the variety, distribution, and signaling components of vertebrate retinal neurons. The beauty of numerous images published to date, and the qualitative and quantitative information they provide, indicate that these approaches are fundamentally useful. However, obtaining these images entailed tissue handling and exposure to chemical solutions that differ from normal extracellular fluid in composition, temperature, and osmolarity. Because the differences are large enough to alter intercellular and intracellular signaling in neurons, and because retinae are susceptible to crush, shear, and fray, it is natural to wonder if immunohistochemical and anatomical methods disturb or damage the cells they are designed to examine. Tissue fixation is typically incorporated to guard against this damage and is therefore critically important to the quality and significance of the harvested data. Here, we describe mechanisms of fixation; advantages and disadvantages of using formaldehyde and glutaraldehyde as fixatives during immunohistochemistry; and modifications of widely used protocols that have recently been found to improve cell shape preservation and immunostaining patterns, especially in proximal retinal neurons.
Winchester, Leonard W., Jr.; Chou, Nee-Yin
A fundus camera was modified to illuminate the retina of a rabbit model with low power laser light in order to obtain laser speckle images. A fast-exposure charge-coupled device (CCD) camera was used to capture laser speckle images of the retina. Image acquisition was synchronized with the arterial pulses of the rabbit to ensure that all images are obtained at the same point in the cardiac cycle. The rabbits were sedated and a speculum was inserted to prevent the eyelid from closing. Both albino (New Zealand; pigmented (Dutch belted) rabbits were used in the study. The rabbit retina is almost avascular. The measurements are obtained for choroidal tissue as well as retinal tissue. Because the retina is in a region of high metabolism, blood velocity is strongly affected by blood oxygen saturation. Measurements of blood velocity obtained over a wide range of O II saturations (58%-100%) showed that blood velocity increases with decreasing O II saturation. For most experiments, the left eye of the rabbit was used for laser measurements whereas the right eye served as a control. No observable difference between pre- and post-experimented eye was noted. Histological examinations of retinal tissue subjected to repeated laser measurements showed no indication of tissue damage.
Stradleigh, Tyler W.; Ishida, Andrew T.
Immunohistochemical and ex vivo anatomical studies have provided many glimpses of the variety, distribution, and signaling components of vertebrate retinal neurons. The beauty of numerous images published to date, and the qualitative and quantitative information they provide, indicate that these approaches are fundamentally useful. However, obtaining these images entailed tissue handling and exposure to chemical solutions that differ from normal extracellular fluid in composition, temperature, and osmolarity. Because the differences are large enough to alter intercellular and intracellular signaling in neurons, and because retinae are susceptible to crush, shear, and fray, it is natural to wonder if immunohistochemical and anatomical methods disturb or damage the cells they are designed to examine. Tissue fixation is typically incorporated to guard against this damage and is therefore critically important to the quality and significance of the harvested data. Here, we describe mechanisms of fixation; advantages and disadvantages of using formaldehyde and glutaraldehyde as fixatives during immunohistochemistry; and modifications of widely used protocols that have recently been found to improve cell shape preservation and immunostaining patterns, especially in proximal retinal neurons. PMID:25892361
Marc, Robert E; Jones, Bryan W; Watt, Carl B; Strettoi, Enrica
Mammalian retinal degenerations initiated by gene defects in rods, cones or the retinal pigmented epithelium (RPE) often trigger loss of the sensory retina, effectively leaving the neural retina deafferented. The neural retina responds to this challenge by remodeling, first by subtle changes in neuronal structure and later by large-scale reorganization. Retinal degenerations in the mammalian retina generally progress through three phases. Phase 1 initiates with expression of a primary insult, followed by phase 2 photoreceptor death that ablates the sensory retina via initial photoreceptor stress, phenotype deconstruction, irreversible stress and cell death, including bystander effects or loss of trophic support. The loss of cones heralds phase 3: a protracted period of global remodeling of the remnant neural retina. Remodeling resembles the responses of many CNS assemblies to deafferentation or trauma, and includes neuronal cell death, neuronal and glial migration, elaboration of new neurites and synapses, rewiring of retinal circuits, glial hypertrophy and the evolution of a fibrotic glial seal that isolates the remnant neural retina from the surviving RPE and choroid. In early phase 2, stressed photoreceptors sprout anomalous neurites that often reach the inner plexiform and ganglion cell layers. As death of rods and cones progresses, bipolar and horizontal cells are deafferented and retract most of their dendrites. Horizontal cells develop anomalous axonal processes and dendritic stalks that enter the inner plexiform layer. Dendrite truncation in rod bipolar cells is accompanied by revision of their macromolecular phenotype, including the loss of functioning mGluR6 transduction. After ablation of the sensory retina, Müller cells increase intermediate filament synthesis, forming a dense fibrotic layer in the remnant subretinal space. This layer invests the remnant retina and seals it from access via the choroidal route. Evidence of bipolar cell death begins in
Hugar, Basappa S; Praveen, Shivaramareddy; Hosahally, Jayanth S; Kainoor, Sunilkumar; Shetty, Akshith Raj S
Poisoning, both accidental and intentional, is a significant contributor to the mortality and morbidity throughout the world. The commonest pesticide poisoning is organophosphates followed by phosphides. Ingestion of phosphides can induce severe gastrointestinal irritation leading to hemorrhage and ulcerations. Gastrointestinal hemorrhages and ulcerations beyond the duodenum have not been reported in the literature. Here, we report a case of severe hemorrhages and ulcerations in stomach, duodenum, jejunum, and ileum observed in a 45-year-old male who had consumed five tablets of Celphos(®) (each 3 g with 56% aluminum phosphide and 44% Ammonium carbonate) to commit suicide. He started vomiting after consumption, and the vomitus was blood-tinged. Once the treatment was instituted, he was stable for a day and thereafter his condition gradually deteriorated. He died on the 4th day of hospitalization, and autopsy revealed features of multiorgan failure and extensive gastrointestinal hemorrhages.
Mehedi, Masfique; Groseth, Allison; Feldmann, Heinz; Ebihara, Hideki
Marburg virus belongs to the genus Marburgvirus in the family Filoviridae and causes a severe hemorrhagic fever, known as Marburg hemorrhagic fever (MHF), in both humans and nonhuman primates. Similar to the more widely known Ebola hemorrhagic fever, MHF is characterized by systemic viral replication, immunosuppression and abnormal inflammatory responses. These pathological features of the disease contribute to a number of systemic dysfunctions including hemorrhages, edema, coagulation abnormalities and, ultimately, multiorgan failure and shock, often resulting in death. A detailed understanding of the pathological processes that lead to this devastating disease remains elusive, a fact that contributes to the lack of licensed vaccines or effective therapeutics. This article will review the clinical aspects of MHF and discuss the pathogenesis and possible options for diagnosis, treatment and prevention. PMID:22046196
Garft, Kyla; Burt, Peter; Burt, Benjamin
We report a case of bilateral orbital hemorrhage as a complication of peribulbar anesthesia in a 78 year old man. Initially, unilateral orbital hemorrhage occurred but quickly spread to the contralateral side. Neuroophthalmological assessment revealed a proptosed tense globe with normal retinovascular findings. Visual acuity was adversely affected and this was conservatively managed with no lasting ophthalmic sequela. This patient’s case was reported as it illustrates an unusual complication of bilateral spread of orbital hemorrhage secondary to peribulbar anesthesia. It highlights how early ophthalmic assessment can ensure a good visual outcome in the setting of appropriate ophthalmic monitoring. The mechanisms of orbital hemorrhage spread and appropriate management options are discussed. PMID:27013899
Sato, Kota; Kato, Shunsuke; Nagano, Hiroto; Ohtsukasa, Shunro; Kawachi, Yasuyuki
A 33-year-old man who presented with prolonged epigastric pain was referred to our hospital. He had experienced recurrent epistaxis and had a family history of hereditary hemorrhagic telangiectasia. Computed tomography and magnetic resonance imaging revealed splenomegaly and a 9 cm hypervascular mass in his spleen. Computed tomography also showed a pulmonary arteriovenous malformation and heterogeneous enhancement of the liver parenchyma, suggesting the presence of arteriosystemic shunts and telangiectases. Based on these findings, the patient was definitely diagnosed with hereditary hemorrhagic telangiectasia according to Curaçao criteria. He underwent splenectomy, and his symptoms disappeared after surgery. Pathological examination of the resected specimen revealed that the hypervascular lesion of the spleen was not a tumor but was composed of abnormal vessels associated with hereditary hemorrhagic telangiectasia. Symptomatic splenic involvement may be a rare manifestation of hereditary hemorrhagic telangiectasia but can be revealed by imaging modalities. PMID:27807449
... telangiectases (the singular is telangiectasia). Without the normal buffer of the capillaries, the blood moves from the ... Bailly S, Plauchu H. Hereditary hemorrhagic telangiectasia: from molecular biology to patient care. J Thromb Haemost. 2010 Jul; ...
Costa, Ana Luiza Fontes de Azevedo; Martins, Thiago Gonçalves dos Santos; Moncada, Francisco Javier Solano; Motta, Mário Martins dos Santos
ABSTRACT We report the case of a patient with congenital toxoplasmosis and submacular hemorrhage caused by a neovascular membrane who underwent an intravitreal injection of C3F8 and bevacizumab, and had a good visual recovery. PMID:24728255
Massalha, R; Valdman, S; Farkash, P; Merkin, L; Herishanu, Y
Although chronic arterial hypertension is the leading cause of intracranial hemorrhage, an abrupt rise in systemic arterial pressure in normotensive people may sometimes induce a hemorrhagic stroke. Dental treatment is rarely associated with such an event. We report here on two middle-aged women, apparently healthy, who suffered from a fatal intracerebral hemorrhage following a dental treatment. On admission, high levels of arterial hypertension were found. It seems that trigeminal manipulation during dental treatment as well as increased serum levels of induced epinephrine mainly by stress and pain, and the small amounts absorbed from the site of local anesthesia might produce abrupt elevation of blood pressure, subsequent increase in cerebral blood flow and severe, even fatal intracerebral hemorrhage. The addition of catecholamines to local anesthetics should be considered. We recommend the use of benzodiazepin as a premedication drug to reduce stress during dental treatment.
Takamatsu, Susumu; Sato, Kota; Kato, Shunsuke; Nagano, Hiroto; Ohtsukasa, Shunro; Kawachi, Yasuyuki
A 33-year-old man who presented with prolonged epigastric pain was referred to our hospital. He had experienced recurrent epistaxis and had a family history of hereditary hemorrhagic telangiectasia. Computed tomography and magnetic resonance imaging revealed splenomegaly and a 9 cm hypervascular mass in his spleen. Computed tomography also showed a pulmonary arteriovenous malformation and heterogeneous enhancement of the liver parenchyma, suggesting the presence of arteriosystemic shunts and telangiectases. Based on these findings, the patient was definitely diagnosed with hereditary hemorrhagic telangiectasia according to Curaçao criteria. He underwent splenectomy, and his symptoms disappeared after surgery. Pathological examination of the resected specimen revealed that the hypervascular lesion of the spleen was not a tumor but was composed of abnormal vessels associated with hereditary hemorrhagic telangiectasia. Symptomatic splenic involvement may be a rare manifestation of hereditary hemorrhagic telangiectasia but can be revealed by imaging modalities.
Lategan, Belinda; Chodirker, Bernard N; Del Bigio, Marc R
Cryptic intracerebral hemorrhage as an etiological factor in fetal hydrocephalus has been postulated but not described at autopsy. Four fetuses with overt hydrocephalus diagnosed by in utero ultrasound examination were examined at autopsy at 19-22 weeks gestation. Although a hemorrhagic etiology was not evident on ultrasound, hemosiderin-containing macrophages and associated reactive changes were found to obstruct the otherwise well-formed cerebral aqueduct in all four. Coagulopathy due to thrombocytopenia was implicated in one case. Anomalies involving other parts of the body were identified in two cases, although a direct link to the hydrocephalus was not obvious. The abnormality was isolated in one case. In three cases, possible sites of hemorrhage in the ventricles were identified. This abnormality represents a significant proportion of the fetuses examined for hydrocephalus in our referral center. We discuss the importance of careful autopsy examination in the diagnosis of cryptic intracerebral hemorrhage and the implications for counseling.
Tsai, Chia-Ling; Madore, Benjamin; Leotta, Matthew J; Sofka, Michal; Yang, Gehua; Majerovics, Anna; Tanenbaum, Howard L; Stewart, Charles V; Roysam, Badrinath
Retinal clinicians and researchers make extensive use of images, and the current emphasis is on digital imaging of the retinal fundus. The goal of this paper is to introduce a system, known as retinal image vessel extraction and registration system, which provides the community of retinal clinicians, researchers, and study directors an integrated suite of advanced digital retinal image analysis tools over the Internet. The capabilities include vasculature tracing and morphometry, joint (simultaneous) montaging of multiple retinal fields, cross-modality registration (color/red-free fundus photographs and fluorescein angiograms), and generation of flicker animations for visualization of changes from longitudinal image sequences. Each capability has been carefully validated in our previous research work. The integrated Internet-based system can enable significant advances in retina-related clinical diagnosis, visualization of the complete fundus at full resolution from multiple low-angle views, analysis of longitudinal changes, research on the retinal vasculature, and objective, quantitative computer-assisted scoring of clinical trials imagery. It could pave the way for future screening services from optometry facilities.
Javadzadeh, Alireza; Argani, Hassan; Nezami, Nariman; Rashtchizadeh, Nadereh; Rafeey, Mandana; Rohbaninoubar, Mohammad; Rahimi-Ardabili, Babak
Purpose Elevated levels of lipoprotein(a) [Lp(a)] and homocysteine (Hcy) have been implicated as risk factors for vascular diseases. The study was performed to explore the possible relationship between retinal arteriosclerosis and serum Lp(a) and Hcy levels. Methods Study subjects consisted of 80 nonsmoking male patients with retinal arteriosclerosis and 54 healthy nonsmoker males as controls. Retinal arteriosclerosis was graded according to the Scheie classification. Serum levels of lipids, lipoproteins, Lp(a), and Hcy were measured by standard methods. Results The serum level of Hcy was higher in patients (24.2±8.1 μmol/l) than controls (10.5±4.1 μmol/l); p<0.01. Serum levels of Lp(a) in patients (47.9±33.1 mg/dl) was also higher than controls (11.7±7.6 mg/dl); p<0.01. There was a significant direct linear correlation between the degree of retinal arteriosclerosis and Lp(a) level (r=0.61, p<0.01), the degree of retinal arteriosclerosis and Hcy level (r=0.72, p<0.01), and also between Lp(a) and Hcy levels (r=0.67, p<0.01). Conclusions The association between retinal arteriosclerosis and serum Lp(a) and Hcy levels suggests that Lp(a) as well as Hcy could play a role in the development of retinal arteriosclerosis. PMID:18806883
Barrett, Steven F.; Jerath, Maya R.; Rylander, Henry G., III; Welch, Ashley J.
Laser induced retinal lesions are used to treat a variety of eye diseases such as diabetic retinopathy and retinal detachment. An instrumentation system has been developed to track a specific lesion coordinate on the retinal surface and provide corrective signals to maintain laser position on the coordinate. High resolution retinal images are acquired via a CCD camera coupled to a fundus camera and video frame grabber. Optical filtering and histogram modification are used to enhance the retinal vessel network against the lighter retinal background. Six distinct retinal landmarks are tracked on the high contrast image obtained from the frame grabber using two-dimensional blood vessel templates. The frame grabber is hosted on a 486 PC. The PC performs correction signal calculations using an exhaustive search on selected image portions. An X and Y laser correction signal is derived from the landmark tracking information and provided to a pair of galvanometer steered mirrors via a data acquisition and control subsystem. This subsystem also responds to patient inputs and the system monitoring lesion growth. This paper begins with an overview of the robotic laser system design followed by implementation and testing of a development system for proof of concept. The paper concludes with specifications for a real time system.
Jha, Onkar; Nair, Vidya; Talwar, Deepak
Involvement of pleura by sarcoidosis remains a rare manifestation and varies from pleural effusion, pneumothorax, pleural thickening, hydropneumothorax, trapped lung, hemothorax, or chylothorax. Sarcoid pleural effusions presenting as hemorrhagic effusions are even more rare. We report a case of active pulmonary sarcoidosis presenting as hemorrhagic pleural effusion requiring tissue diagnosis to rule out malignancy. The rarity of the presentation prompted us to report this case. PMID:27625449
Yin, Ming; Tian, Qing; Shen, Hong
Roller coasters are probably one of the more popular rides at amusement parks around the world, and there are few reported injuries. We report a case of symmetric diffuse upper lobe hemorrhage resulting from roller coaster in a previously healthy woman. The clinical course, management, and etiology of her case are discussed; and the literature is reviewed. To our knowledge, pulmonary hemorrhage in this setting has not yet been described.
Moore, Michael; McSweeney, Sean; Fulton, Gregory; Buckley, John; Maher, Michael Guiney, Michael
Percutaneous transluminal angioplasty and stent placement is now an established treatment option for chronic mesenteric ischemia and is associated with low mortality and morbidity rates. We present a case of reperfusion hemorrhage complicating endovascular repair of superior mesenteric artery stenosis. Although a recognized complication following repair of carotid stenosis, hemorrhage has not previously been reported following mesenteric endovascular reperfusion. We describe both spontaneous cessation of bleeding and treatment with coil embolization.
Tiboni, Sonia; Abdulmajid, Umar; Pooboni, Suneel; Wighton, Christopher; Eradi, Balgopal; Dagash, Haitham
Spontaneous splenic hemorrhage in the newborn is a rare entity. The presentation is usually with a triad of bleeding, abdominal distension, and hemoperitoneum. Rapid diagnosis is essential as left untreated, death is inevitable. We present a case with an unusual initial presentation of a scrotal hematocele and ultrasonography suggesting an adrenal hemorrhage. At laparotomy, splenic preservation was unsuccessful, and therefore, splenectomy was performed. The child recovered well from the procedure. PMID:26788451
Schmeisser, Elmar T.
Seven Cynomolgus fasciculata who had graded laser lesions placed in own eye 6 years previously were evaluated for their vernier acuity by electrophysiologic recording techniques. In these experiments, 95 percent contrast vernier acuity targets were presented at high luminance levels to anesthetized primates. Visual evoked potentials were recorded by conventional means form scalp electrodes through hospital grade amplifiers. All animal testing was performed under IACUC approved protocols. The single q-switched pulses form a neodymium-YAG laser had produced lesions of 4 types: no visible change, minimal visible lesions, 'white dot' lesions and 'red dot' lesions in the eye at the time of placement. Single exposures had been made in four locations: 5 degrees superior, inferior and temporal to the fovea, and one foveally. Vernier recording proved somewhat successful in smaller animals with less than contained retinal hemorrhage lesions in the fovea. Initial analyses demonstrated a significant decrease of the pattern response signal/noise in the experimental eye overall, and an apparent relative loss of vernier signal in some lesioned eyes. Animals with the more severe lesions have somewhat degraded small patten responses and no recordable vernier response. Apparent lesser losses produced less effect.
Ma, Wenxin; Wong, Wai T
Age-related retinal diseases, such as age-related macular degeneration (AMD) and glaucoma, contain features of chronic retinal inflammation that may promote disease progression. However, the relationship between aging and neuroinflammation is unclear. Microglia are long-lived, resident immune cells of the retina, and mediate local neuroinflammatory reactions. We hypothesize that aging changes in microglia may be causally linked to neuroinflammatory changes underlying age-dependent retinal diseases. Here, we review the evidence for (1) how the retinal microglial phenotype changes with aging, (2) the factors that drive microglial aging in the retina, and (3) aging-related changes in microglial gene expression. We examine how these aspects of microglial aging changes may relate to pathogenic mechanisms of immune dysregulation driving the progression of age-related retinal disease. These relationships can highlight microglial aging as a novel target for the prevention and treatment of retinal disease.
Ni, Qingqiang; Zhang, Minfeng; Yang, Cheng; Cai, Wenchang; Zhao, Qian; Shen, Weifeng; Yang, Jiamei
Abstract Introduction: Fast-growing congenital hepatic cysts with intracystic hemorrhage are rare in clinical practice. Additionally, the clinical manifestations of and laboratory and imaging findings for this condition are often nonspecific and are particularly difficult to differentiate from those of hepatobiliary cystadenoma and cystadenocarcinoma, thus posing great challenges for diagnosis and treatment. The 2 case reports presented here aim to analyze the diagnosis and treatment of 2 rare cases of congenital hepatic cysts with intracystic hemorrhage in the Chinese Han population to provide an important reference for the clinical diagnosis and treatment of this condition. Diagnoses: These 2 case reports present 2 rare cases of congenital hepatic cysts with intracystic hemorrhage. Case 1 involved a 31-year-old patient with a very large, fast-growing hepatic cyst with intracystic hemorrhage and elevated carbohydrate antigen 199. Case 2 involved a patient with intense, paroxysmal right upper abdominal pain; computed tomography suggested a hepatic cyst with intracystic hemorrhage and possibly hepatobiliary cystadenoma. Outcomes: Both patients underwent liver resection. Postoperative follow-up showed that for both patients, the symptoms improved, the laboratory findings returned to normal levels, and the surgical outcomes were satisfactory. Conclusion: Liver resection is an ideal treatment for patients with congenital hepatic cysts with intracystic hemorrhage, and especially those with fast-growing, symptomatic hepatic cysts or hepatic cysts that are difficult to differentiate from hepatobiliary cystadenoma and cystadenocarcinoma. PMID:27759646
Lichte, Philipp; Kobbe, Philipp; Pfeifer, Roman; Campbell, Graeme C; Beckmann, Rainer; Tohidnezhad, Mersedeh; Bergmann, Christian; Kadyrov, Mamed; Fischer, Horst; Glüer, Christian C; Hildebrand, Frank; Pape, Hans-Christoph; Pufe, Thomas
Impaired fracture healing can occur in severely injured patients with hemorrhagic shock due to decreased soft tissue perfusion after trauma. We investigated the effects of fracture healing in a standardized pressure controlled hemorrhagic shock model in mice, to test the hypothesis that bleeding is relevant in the bone healing response. Male C57/BL6 mice were subjected to a closed femoral shaft fracture stabilized by intramedullary nailing. One group was additionally subjected to pressure controlled hemorrhagic shock (HS, mean arterial pressure (MAP) of 35 mmHg for 90 minutes). Serum cytokines (IL-6, KC, MCP-1, and TNF-α) were analyzed 6 hours after shock. Fracture healing was assessed 21 days after fracture. Hemorrhagic shock is associated with a significant increase in serum inflammatory cytokines in the early phase. Histologic analysis demonstrated a significantly decreased number of osteoclasts, a decrease in bone quality, and more cartilage islands after hemorrhagic shock. μCT analysis showed a trend towards decreased bone tissue mineral density in the HS group. Mechanical testing revealed no difference in tensile failure. Our results suggest a delay in fracture healing after hemorrhagic shock. This may be due to significantly diminished osteoclast recruitment. The exact mechanisms should be studied further, particularly during earlier stages of fracture healing.
Knowledge about retinal photoreceptor signal transduction and the visual cycle required for normal eyesight has increased exponentially over the past decade. Substantial progress in human genetics has facilitated the identification of candidate genes and complex networks underlying inherited retinal diseases. Natural mutations in animal models that mimic human diseases have been characterized and advanced genetic manipulation can now be used to generate small mammalian models of human retinal diseases. Pharmacological repair of defective visual processes in animal models not only validates their involvement in vision, but also provides great promise for the development of improved therapies for millions who are progressing towards blindness or are almost completely robbed of their eyesight.
Saxena, S; Gopal, L
Advances in the surgical instrumentation and vitreoretinal techniques have allowed intraoperative reapproximation of retina to a more normal position. The use of intravitreally injected liquid materials (viscoelastic liquids, liquid perfluorocarbons and silicone oil), as adjunctive agents to vitreo-retinal surgery play an important role in facilitating retinal reattachment. These materials are used as intraoperative instruments to re-establish intraocular volume, assist in separating membranes adherent to the retina, manipulate retinal detachments and mechanically flatten detached retina. Over the longer term, silicone oil maintains intraocular tamponade. One should be cognizant of the potential uses, benefits and risks of each of these vitreous substitutes.
Knowledge about retinal photoreceptor signal transduction and the visual cycle required for normal eyesight has expanded exponentially over the past decade. Substantial progress in human genetics has allowed identification of candidate genes and complex networks underlying inherited retinal diseases. Natural mutations in animal models that mimic human diseases have been characterized and advanced genetic manipulation now permits generation of small mammalian models of human retinal diseases. Pharmacological repair of defective visual processes in animal models not only validates their involvement in vision but also provides great promise for developing improved therapies for the millions that are progressing towards blindness or are almost completely robbed of eyesight. PMID:20435355
Werner, J S; Keltner, J L; Zawadzki, R J; Choi, S S
Inner and outer retinal morphology were quantified in vivo for 6 nonglaucomatous and 10 glaucomatous optic neuropathy patients. Custom, ultrahigh-resolution imaging modalities were used to evaluate segmented retinal layer thickness in 3D volumes (Fourier-domain optical coherence tomography), cone photoreceptor density (adaptive optics fundus camera), and the length of inner and outer segments of cone photoreceptors (adaptive optics–optical coherence tomography). Quantitative comparisons were made with age-matched controls, or by comparing affected and nonaffected retinal areas defined by changes in visual fields. The integrity of outer retinal layers on optical coherence tomography B-scans and density of cone photoreceptors were correlated with visual field sensitivity at corresponding retinal locations following reductions in inner retinal thickness. The photoreceptor outer segments were shorter and exhibited greater variability in retinal areas associated with visual field losses compared with normal or less affected areas of the same patient's visual field. These results demonstrate that nonglaucomatous and glaucomatous optic neuropathies are associated with outer retinal changes following long-term inner retinal pathology. PMID:21293495
Gaucher disease (GD) is an inherited lysosomal disorder, originating from deficient activity of the lysosomal enzyme glucocerebrosidase (GCase). Normally, GCase hydrolyzes glucocerebroside (GC) to glucose and ceramide; however, impaired activity of this enzyme leads to the accumulation of GC in macrophages, termed “Gaucher cells.” Gaucher disease is associated with hepatosplenomegaly, cytopenias, skeletal complications and in some forms involves the central nervous system. Coagulation abnormalities are common among GD patients due to impaired production and chronic consumption of coagulation factors. Bleeding phenomena are variable (as are other symptoms of GD) and include mucosal and surgical hemorrhages. Four main etiological factors account for the hemostatic defect in GD: thrombocytopenia, abnormal platelet function, reduced production of coagulation factors, and activation of fibrinolysis. Thrombocytopenia relates not only to hypersplenism and decreased megakaryopoiesis by the infiltrated bone marrow but also to immune thrombocytopenia. Autoimmunity, especially the induction of platelet antibody production, might cause persistent thrombocytopenia. Enzyme replacement therapy reverses only part of the impaired coagulation system in Gaucher disease. Other therapeutic and supportive measures should be considered to prevent and/or treat bleeding in GD. Gaucher patients should be evaluated routinely for coagulation abnormalities especially prior to surgery and dental and obstetric procedures. PMID:25386355
Gaucher disease (GD) is an inherited lysosomal disorder, originating from deficient activity of the lysosomal enzyme glucocerebrosidase (GCase). Normally, GCase hydrolyzes glucocerebroside (GC) to glucose and ceramide; however, impaired activity of this enzyme leads to the accumulation of GC in macrophages, termed "Gaucher cells." Gaucher disease is associated with hepatosplenomegaly, cytopenias, skeletal complications and in some forms involves the central nervous system. Coagulation abnormalities are common among GD patients due to impaired production and chronic consumption of coagulation factors. Bleeding phenomena are variable (as are other symptoms of GD) and include mucosal and surgical hemorrhages. FOUR MAIN ETIOLOGICAL FACTORS ACCOUNT FOR THE HEMOSTATIC DEFECT IN GD: thrombocytopenia, abnormal platelet function, reduced production of coagulation factors, and activation of fibrinolysis. Thrombocytopenia relates not only to hypersplenism and decreased megakaryopoiesis by the infiltrated bone marrow but also to immune thrombocytopenia. Autoimmunity, especially the induction of platelet antibody production, might cause persistent thrombocytopenia. Enzyme replacement therapy reverses only part of the impaired coagulation system in Gaucher disease. Other therapeutic and supportive measures should be considered to prevent and/or treat bleeding in GD. Gaucher patients should be evaluated routinely for coagulation abnormalities especially prior to surgery and dental and obstetric procedures.
Edwards, Malia M; Lefebvre, Olivier
The mechanisms controlling vascular development, both normal and pathological, are not yet fully understood. Many diseases, including cancer and diabetic retinopathy, involve abnormal blood vessel formation. Therefore, increasing knowledge of these mechanisms may help develop novel therapeutic targets. The identification of novel proteins or cells involved in this process would be particularly useful. The retina is an ideal model for studying vascular development because it is easy to access, particularly in rodents where this process occurs post-natally. Recent studies have suggested potential roles for laminin chains in vascular development of the retina. This review will provide an overview of these studies, demonstrating the importance of further research into the involvement of laminins in retinal blood vessel formation.
Conley, Shannon M.; Naash, Muna I.
Ocular gene therapy is becoming a well-established field. Viral gene therapies for the treatment of Leber’s congentinal amaurosis (LCA) are in clinical trials, and many other gene therapy approaches are being rapidly developed for application to diverse ophthalmic pathologies. Of late, development of non-viral gene therapies has been an area of intense focus and one technology, polymer-compacted DNA nanoparticles, is especially promising. However, development of pharmaceutically and clinically viable therapeutics depends not only on having an effective and safe vector but also on a practical treatment strategy. Inherited retinal pathologies are caused by mutations in over 220 genes, some of which contain over 200 individual disease-causing mutations, which are individually very rare. This review will focus on both the progress and future of nanoparticles and also on what will be required to make them relevant ocular pharmaceutics. PMID:20452457
In this paper a method for noise reduction in ocular fundus image sequences is described. The eye is the only part of the human body where the capillary network can be observed along with the arterial and venous circulation using a non invasive technique. The study of the retinal vessels is very important both for the study of the local pathology (retinal disease) and for the large amount of information it offers on systematic haemodynamics, such as hypertension, arteriosclerosis, and diabetes. In this paper a method for image integration of ocular fundus image sequences is described. The procedure can be divided in two step: registration and fusion. First we describe an automatic alignment algorithm for registration of ocular fundus images. In order to enhance vessel structures, we used a spatially oriented bank of filters designed to match the properties of the objects of interest. To evaluate interframe misalignment we adopted a fast cross-correlation algorithm. The performances of the alignment method have been estimated by simulating shifts between image pairs and by using a cross-validation approach. Then we propose a temporal integration technique of image sequences so as to compute enhanced pictures of the overall capillary network. Image registration is combined with image enhancement by fusing subsequent frames of a same region. To evaluate the attainable results, the signal-to-noise ratio was estimated before and after integration. Experimental results on synthetic images of vessel-like structures with different kind of Gaussian additive noise as well as on real fundus images are reported.
Hong, Felix T.
Retinal proteins are membrane-bound protein pigments that contain vitamin A aldehyde (retinal) as the chromophore. They include the visual pigment rhodopsin and four additional ones in the plasma membrane of Halobacterium salinarium (formerly Halobacterium halobium). These proteins maintain a fixed and asymmetric orientation in the membranes, and respond to a light stimulus by generating vectorial charge movement, which can be detected as an electric potential across the membrane or an electric current through the membrane. These phenomena are collectively called the photoelectric effects, which defy a rigorous quantitative treatment by means of either conventional (solution phase) photochemistry or conventional electrophysiology. As an alternative to the mainstream approach, we utilize the analytic tools of electrochemical surface science and electrophysiology to analyze two molecular models of light-induced charge separation and recombination. Being tutorial in nature, this article demands no prior knowledge about the subject. A parsimonious equivalent circuit model is developed. Data obtained from reconstituted bacteriorhodopsin membranes are used to validate the theoretical model and the analytical approach. Data generated and used by critics to refute our approach is shown to actually support it. The present analysis is sufficiently general to be applicable to other pigment-containing membranes, such as the visual photoreceptor membrane and the chlorophyll-based photosynthetic membranes. It provides a coherent description of a wide range of light-induced phenomena associated with various pigment-containing membranes. In contrast, the mainstream approach has been plagued with self-contradictions and paradoxes. Last, but not least, the alternative bioelectrochemical approach also exhibits a predictive power that has hitherto been generally lacking. Comparison of the photoelectric effects is made with regard to bacteriorhodopsin, rhodopsin, and the chlorophyll
Loudin, J D; Cogan, S F; Mathieson, K; Sher, A; Palanker, D V
Photodiode circuits show promise for the development of high-resolution retinal prostheses. While several of these systems have been constructed and some even implanted in humans, existing descriptions of the complex optoelectronic interaction between light, photodiode, and the electrode/electrolyte load are limited. This study examines this interaction in depth with theoretical calculations and experimental measurements. Actively biased photoconductive and passive photovoltaic circuits are investigated, with the photovoltaic circuits consisting of one or more diodes connected in series, and the photoconductive circuits consisting of a single diode in series with a pulsed bias voltage. Circuit behavior and charge injection levels were markedly different for platinum and sputtered iridium-oxide film (SIROF) electrodes. Photovoltaic circuits were able to deliver 0.038 mC/cm(2) (0.75 nC/phase) per photodiode with 50- μm platinum electrodes, and 0.54-mC/cm(2) (11 nC/phase) per photodiode with 50-μ m SIROF electrodes driven with 0.5-ms pulses of light at 25 Hz. The same pulses applied to photoconductive circuits with the same electrodes were able to deliver charge injections as high as 0.38 and 7.6 mC/cm(2) (7.5 and 150 nC/phase), respectively. We demonstrate photovoltaic stimulation of rabbit retina in-vitro, with 0.5-ms pulses of 905-nm light using peak irradiance of 1 mW/mm(2). Based on the experimental data, we derive electrochemical and optical safety limits for pixel density and charge injection in various circuits. While photoconductive circuits offer smaller pixels, photovoltaic systems do not require an external bias voltage. Both classes of circuits show promise for the development of high-resolution optoelectronic retinal prostheses.
Cheung, Ning; Liew, Gerald; Lindley, Richard I; Liu, Erica Y; Wang, Jie Jin; Hand, Peter; Baker, Michelle; Mitchell, Paul; Wong, Tien Y
This study aimed to determine whether retinal fractal dimension, a quantitative measure of microvascular branching complexity and density, is associated with lacunar stroke. A total of 392 patients presenting with acute ischemic stroke had retinal fractal dimension measured from digital photographs, and lacunar infarct ascertained from brain imaging. After adjusting for age, gender, and vascular risk factors, higher retinal fractal dimension (highest vs lowest quartile and per standard deviation increase) was independently and positively associated with lacunar stroke (odds ratio [OR], 4.27; 95% confidence interval [CI], 1.49-12.17 and OR, 1.85; 95% CI, 1.20-2.84, respectively). Increased retinal microvascular complexity and density is associated with lacunar stroke.
Individual photoreceptor waveguiding suggests that the entire retina can be considered as a composite fiber-optic element relating a retinal image to a corresponding waveguided image. In such a scheme, a visual sensation is produced only when the latter interacts with the pigments of the outer photoreceptor segments. Here the possible consequences of photoreceptor waveguiding on vision are studied with important implications for the pupil-apodization method commonly used to incorporate directional effects of the retina. In the absence of aberrations, it is found that the two approaches give identical predictions for an effective retinal image only when the pupil apodization is chosen twice as narrow as suggested by the traditional Stiles-Crawford effect. In addition, phase variations in the retinal field due to ocular aberrations can delicately alter a waveguided image, and this may provide plausible justification for an improved visual sensation as compared with what should be expected on the grounds of a retinal image only.
Shah, Ankoor R; Williams, George A
The advent of anti-VEGF therapy for neovascular age-related macular degeneration and macular edema secondary to retinal vein occlusion and diabetes mellitus has prevented blindness in tens of thousands of people. However, the costs of these drugs are without precedent in ophthalmic drug therapeutics. An analysis of the financial implications of retinal drugs and the impact of the Food and Drug Administration on treatment of retinal disease must include not only an evaluation of the direct costs of the drugs and the costs associated with their administration, but also the cost savings which accrue from their clinical benefit. This chapter will discuss the financial and regulatory issues associated with retinal drugs.
Li, Qin; Jin, Xue-Min; Gao, Quan-Xue; You, Jane; Bhattacharya, Prabir
Diabetic Retinopathy (DR) is a common complication of diabetes that damages the eye's retina. Recognition DR as early as possible is very important to protect patients' vision. We propose a method for screening DR and distin-guishing Prolifetive Diabetic Retinopathy (PDR) from Non-Prolifetive Retino-pathy (NPDR) automatatically through color retinal images. This method evaluates the severity of DR by analyzing the appearnce of bright lesions and retinal vessel patterns. The bright lesions are extracted through morphlogical re-consturction. After that, the retinal vessels are automatically extracted using multiscale matched filters. Then the vessel patterns are analyzed by extracting the vessel net density. The experimental results domonstrate that it is a effective solution to screen DR and distinguish PDR from NPDR by only using color retinal images.
Zemba, Mihail; Ochinciuc, Uliana; Sarbu, Laura; Avram, Corina; Camburu, Raluca; Stamate, Alina
We present a case report of a 27 years old pacient with central retinal vein occlussion and macular edema. The pacient has a significant reduction of the macular aedema with complete recovery of vision after the treatment.
Muşat, O; Cristescu, R; Coman, Corina; Asandi, R
This papers presents a case of a patient with retinal detachement, 3 days ago operated (posterior vitrectomy internal tamponament with silicon oil 1000) who develop increased ocular pressure following silicon oil output in the anterior chamber.
Alexander, Matthew D; Hetts, Steven W; Young, William L; Halbach, Van V; Dowd, Christopher F; Higashida, Randall T; English, Joey D
Hemorrhage represents the most feared complication of cerebral arteriovenous malformations (AVMs) in both untreated patients and those treated with gamma knife radiosurgery. Radiosurgery does not immediately lead to obliteration of the malformation, which often does not occur until years following treatment. Post-obliteration hemorrhage is rare, occurring months to years after radiosurgery, and has been associated with residual or recurrent AVM despite prior apparent nidus elimination. Three cases are reported of delayed intracranial hemorrhage in patients with cerebral AVMs treated with radiosurgery in which no residual AVM was found on catheter angiography at the time of delayed post-treatment hemorrhage. That the pathophysiology of these hemorrhages involves progressive venous outflow occlusion is speculated and the possible mechanistic link to subsequent vascular rupture is discussed.
Park, Jeong Jin; Jeong, Se Won; Lee, Jae Wook
Sudden hearing deterioration may occur in our population, but it is difficult to explain the exact pathophysiology and the cause. Magnetic resonance imaging (MRI) in sudden sensorineural hearing loss (SSNHL) is usually useful to evaluate neural lesions such as acoustic schwannoma and hemorrhage in labyrinth. Recently some cases of SSNHL caused by intralabyrintine hemorrhage were reported by the advance of MRI. In the case of intralabyrintine hemorrhage, MRI showed a hyperintense signal in the labyrinth on the pre-contrast and contrast enhanced T1-weighted image and relatively weak intensity on T2-weighted image. The prognosis SSNHL by intralabyrintine hemorrhage is generally known to be poor. We report a case of sudden deafness with intralabyrintine hemorrhage who has a history of anticoagulant administration, with a review of literature. PMID:26771018
Lee, Jung Pil; Park, Jun Sang; Kwon, Oh Woong; You, Yong Sung
Purpose To evaluate the visual and anatomical outcomes for neovascular age-related macular degeneration with submacular hemorrhage after intravitreal injections of tenecteplase (TNK), anti-vascular endothelial growth factor (VEGF) and expansile gas. Methods This study was a retrospective clinical case series following 25 eyes of 25 patients. All patients received a triple injection using 0.05 mL TNK (50 µg), 0.05 mL anti-VEGF and 0.3 mL of perfluoropropane gas. Retreatment with anti-VEGF was performed as needed. Preoperative and postoperative best-corrected visual acuity and central retinal thickness were analyzed. Results The mean logarithm of the minimum angle of resolution of best-corrected visual acuity improved significantly from 1.09 ± 0.77 at baseline to 0.52 ± 0.60 at 12 months (p < 0.001). The mean central retinal thickness also improved significantly from 545 ± 156 at baseline to 266 ± 107 at 12 months (p < 0.001). A visual improvement of 0.3 logarithm of the minimum angle of resolution unit or more was achieved in 15 eyes (60%). During the 12 postoperative months, an average of 4.04 intravitreal anti-VEGF injections was applied. Conclusions A triple injection of TNK, anti-VEGF, and a gas appears to be safe and effective for the treatment of submacular hemorrhage secondary to neovascular age-related macular degeneration. PMID:27247518
Diseases .............. 18 2.2.1 Diabetic Retinopathy ....... ...................... 18 2.2.2 Macular Degeneration ............................ 20 2.2.3...retinal diseases includ- ing diabetic retinopathy, macular degeneration , and retinal breaks and tears. During treatment for these diseases an argon...photocoagulated [211. 2.2.2 Macular Degeneration Macular degeneration is also called senile macular degeneration because it is most common in the elderly
de Jong, F.J.; Schrijvers, E.M.C.; Ikram, M.K.; Koudstaal, P.J.; de Jong, P.T.V.M.; Hofman, A.; Vingerling, J.R.
Background: Retinal vessels provide a unique opportunity to study both systemic and cerebrovascular disease. Smaller retinal arteriolar calibers are strongly related to hypertension, whereas larger retinal venular calibers are more related to inflammation, cerebral hypoperfusion, and cerebrovascular disease. Whether retinal vessel calibers are related to dementia remains unclear. Methods: We investigated whether retinal arteriolar and venular calibers are associated with risk of dementia, and its subtypes Alzheimer disease (AD) and vascular dementia, in the prospective population-based Rotterdam Study. Digitized retinal images were available in 5,553 participants aged 55 years or over and dementia-free at baseline (1990–1993). Participants were re-examined in 1993–1994, 1997–1999, and 2002–2004 and were continuously monitored for development of dementia. Results: During a mean follow-up of 11.6 years, 655 participants developed dementia. AD was diagnosed in 519 and vascular dementia in 73 participants. Larger venular calibers were associated with an increased risk of dementia, in particular vascular dementia (age- and sex-adjusted hazard ratio per SD increase: 1.31; 95% confidence interval 1.06–1.64), but not AD. The association remained significant after adjustment for stroke and cardiovascular risk factors. Smaller arteriolar calibers were also associated with an increased risk of vascular dementia, yet only when adjusted for venular calibers. Conclusions: Retinal venular widening is associated with an increased risk of vascular dementia. Our findings are in line with previous observations in stroke and cerebral small-vessel disease and suggest that the association between larger retinal venular calibers and dementia may reflect cerebral hypoperfusion and subsequent ischemia. PMID:21288987
Arboleda-Velasquez, Joseph F.; Primo, Vincent; Graham, Mark; James, Alexandra; Manent, Jan; D'Amore, Patricia A.
Purpose. Pericytes, the vascular cells that constitute the outer layer of capillaries, have been shown to have a crucial role in vascular development and stability. Loss of pericytes precedes endothelial cell dysfunction and vascular degeneration in small-vessel diseases, including diabetic retinopathy. Despite their clinical relevance, the cellular pathways controlling survival of retinal pericytes remain largely uncharacterized. Therefore, we investigated the role of Notch signaling, a master regulator of cell fate decisions, in retinal pericyte survival. Methods. A coculture system of ligand-dependent Notch signaling was developed using primary cultured retinal pericytes and a mesenchymal cell line derived from an inducible mouse model expressing the Delta-like 1 Notch ligand. This model was used to examine the effect of Notch activity on pericyte survival using quantitative PCR (qPCR) and a light-induced cell death assay. The effect of Notch gain- and loss-of-function was analyzed in monocultures of retinal pericytes using antibody arrays to interrogate the expression of apoptosis-related proteins. Results. Primary cultured retinal pericytes differentially expressed key molecules of the Notch pathway and displayed strong expression of canonical Notch/RBPJK (recombination signal-binding protein 1 for J-kappa) downstream targets. A gene expression screen using gain- and loss-of-function approaches identified genes relevant to cell survival as downstream targets of Notch activity in retinal pericytes. Ligand-mediated Notch activity protected retinal pericytes from light-induced cell death. Conclusions. Our results have identified signature genes downstream of Notch activity in retinal pericytes and suggest that tight regulation of Notch signaling is crucial for pericyte survival. PMID:25015359
to program human stem cells directly into cones. Using RNA -seq, we identified several genes that are upregulated in advance of the earliest...reverse vision loss. 15. SUBJECT TERMS Cone photoreceptor, retina, retinal stem cell, Otx2, Onecut1, Blimp1, RNA -seq., transcription factors, and...1 Keywords: 1. Cone photoreceptor 2. Retina 3. Retinal stem cell 4. Otx2 5. Onecut1 6. Blimp1 7. RNA -seq. 8. Transcription factors 9
Smith, Matthew H.; Denninghoff, Kurt R.; Lompado, Arthur; Hillman, Lloyd W.
Accurately measuring the oxygen saturation of blood within retinal arteries and veins has proven to be a deceptively difficult task. Despite the excellent optical accessibility of the vessels and a wide range of reported instrumentation, we are unaware of any measurement technique that has proven to be calibrated across wide ranges of vessel diameter and fundus pigmentation. We present an overview of our retinal oximetry technique, present the results of an in vitro calibration experiment, and present preliminary human data.
Huang, Yiming; Enzmann, Volker; Ildstad, Suzanne T.
Retinal degenerative diseases that target photoreceptors or the adjacent retinal pigment epithelium (RPE) affect millions of people worldwide. Retinal degeneration (RD) is found in many different forms of retinal diseases including retinitis pigmentosa (RP), age-related macular degeneration (AMD), diabetic retinopathy, cataracts, and glaucoma. Effective treatment for retinal degeneration has been widely investigated. Gene-replacement therapy has been shown to improve visual function in inherited retinal disease. However, this treatment was less effective with advanced disease. Stem cell-based therapy is being pursued as a potential alternative approach in the treatment of retinal degenerative diseases. In this review, we will focus on stem cell-based therapies in the pipeline and summarize progress in treatment of retinal degenerative disease. PMID:20859770
Campochiaro, Peter A; Aiello, Lloyd Paul; Rosenfeld, Philip J
The association of retinal hypoxia with retinal neovascularization has been recognized for decades, causing Michaelson to postulate in 1948 that a factor secreted by hypoxic retina was involved. The isolation of vascular endothelial growth factor (VEGF), characterization of its angiogenic activity, and demonstration that its expression was increased in hypoxic tissue made it a prime candidate. Intraocular levels of VEGF are elevated in patients with retinal or iris neovascularization, and VEGF-specific antagonists markedly suppress retinal neovascularization in mice and primates with ischemic retinopathy. Vascular endothelial growth factor antagonists also suppress choroidal neovascularization, and transgenic expression of VEGF in the retina of mice causes subretinal neovascularization. Clinical trials using a VEGF antagonist that blocks all isoforms of VEGF-A in patients with neovascular age-related macular degeneration (nAMD) demonstrated dramatic benefit. Similar results have been obtained with 2 other VEGF antagonists. Retinal hypoxia also contributes to diabetic macular edema (DME), and because of the absence of good animal models, small clinical trials were used to test the role of VEGF. The results clearly implicated VEGF as a major contributor to DME and have been confirmed by several large multicenter trials. A similar strategy demonstrated that VEGF is a major contributor to macular edema resulting from retinal vein occlusion, also confirmed in multicenter trials. Secondary outcomes in these large clinical trials have shown that VEGF inhibition improves retinal hemorrhages, retinal vessel closure, and progression of nonproliferative diabetic retinopathy. Anti-VEGF agents also provide therapeutic benefits in proliferative diabetic retinopathy. Thus, the development of VEGF antagonists has revolutionized the treatment of nAMD, diabetic retinopathy, and other ischemic retinopathies, but in many patients, the upregulation of VEGF is prolonged. Although the
Liu, Haitao; Tang, Jie; Du, Yunpeng; Saadane, Aicha; Tonade, Deoye; Samuels, Ivy; Veenstra, Alex; Palczewski, Krzysztof; Kern, Timothy S.
Purpose Loss of photoreceptor cells is associated with retinal vascular degeneration in retinitis pigmentosa, whereas the presence of photoreceptor cells is implicated in vascular degeneration in diabetic retinopathy. To investigate how both the absence and presence of photoreceptors could damage the retinal vasculature, we compared two mouse models of photoreceptor degeneration (opsin−/− and RhoP23H/P23H ) and control C57Bl/5J mice, each with and without diabetes. Methods Retinal thickness, superoxide, expression of inflammatory proteins, ERG and optokinetic responses, leukocyte cytotoxicity, and capillary degeneration were evaluated at 1 to 10 months of age using published methods. Results Retinal photoreceptor cells degenerated completely in the opsin mutants by 2 to 4 months of age, and visual function subsided correspondingly. Retinal capillary degeneration was substantial while photoreceptors were still present, but slowed after the photoreceptors degenerated. Diabetes did not further exacerbate capillary degeneration in these models of photoreceptor degeneration, but did cause capillary degeneration in wild-type animals. Photoreceptor cells, however, did not degenerate in wild-type diabetic mice, presumably because the stress responses in these cells were less than in the opsin mutants. Retinal superoxide and leukocyte damage to retinal endothelium contributed to the degeneration of retinal capillaries in diabetes, and leukocyte-mediated damage was increased in both opsin mutants during photoreceptor cell degeneration. Conclusions Photoreceptor cells affect the integrity of the retinal microvasculature. Deterioration of retinal capillaries in opsin mutants was appreciable while photoreceptor cells were present and stressed, but was less after photoreceptors degenerated. This finding proves relevant to diabetes, where persistent stress in photoreceptors likewise contributes to capillary degeneration. PMID:27548901
Adaptive optics (AO) is a technology used to improve the performance of optical systems by reducing the effect of wave front distortions. Retinal imaging using AO aims to compensate for higher order aberrations originating from the cornea and the lens by using deformable mirror. The main application of AO retinal imaging has been to assess photoreceptor cell density, spacing, and mosaic regularity in normal and diseased eyes. Apart from photoreceptors, the retinal pigment epithelium, retinal nerve fiber layer, retinal vessel wall and lamina cribrosa can also be visualized with AO technology. Recent interest in AO technology in eye research has resulted in growing number of reports and publications utilizing this technology in both animals and humans. With the availability of first commercially available instruments we are making transformation of AO technology from a research tool to diagnostic instrument. The current challenges include imaging eyes with less than perfect optical media, formation of normative databases for acquired images such as cone mosaics, and the cost of the technology. The opportunities for AO will include more detailed diagnosis with description of some new findings in retinal diseases and glaucoma as well as expansion of AO into clinical trials which has already started. PMID:24843304
Jones, Bryan W; Watt, Carl B; Frederick, Jeanne M; Baehr, Wolfgang; Chen, Ching-Kang; Levine, Edward M; Milam, Ann H; Lavail, Matthew M; Marc, Robert E
Many photoreceptor degenerations initially affect rods, secondarily leading to cone death. It has long been assumed that the surviving neural retina is largely resistant to this sensory deafferentation. New evidence from fast retinal degenerations reveals that subtle plasticities in neuronal form and connectivity emerge early in disease. By screening mature natural, transgenic, and knockout retinal degeneration models with computational molecular phenotyping, we have found an extended late phase of negative remodeling that radically changes retinal structure. Three major transformations emerge: 1) Müller cell hypertrophy and elaboration of a distal glial seal between retina and the choroid/retinal pigmented epithelium; 2) apparent neuronal migration along glial surfaces to ectopic sites; and 3) rewiring through evolution of complex neurite fascicles, new synaptic foci in the remnant inner nuclear layer, and new connections throughout the retina. Although some neurons die, survivors express molecular signatures characteristic of normal bipolar, amacrine, and ganglion cells. Remodeling in human and rodent retinas is independent of the initial molecular targets of retinal degenerations, including defects in the retinal pigmented epithelium, rhodopsin, or downstream phototransduction elements. Although remodeling may constrain therapeutic intervals for molecular, cellular, or bionic rescue, it suggests that the neural retina may be more plastic than previously believed.
Song, Delu; Dunaief, Joshua L.
Iron is essential for life, but excess iron can be toxic. As a potent free radical creator, iron generates hydroxyl radicals leading to significant oxidative stress. Since iron is not excreted from the body, it accumulates with age in tissues, including the retina, predisposing to age-related oxidative insult. Both hereditary and acquired retinal diseases are associated with increased iron levels. For example, retinal degenerations have been found in hereditary iron overload disorders, like aceruloplasminemia, Friedreich's ataxia, and pantothenate kinase-associated neurodegeneration. Similarly, mice with targeted mutation of the iron exporter ceruloplasmin and its homolog hephaestin showed age-related retinal iron accumulation and retinal degeneration with features resembling human age-related macular degeneration (AMD). Post mortem AMD eyes have increased levels of iron in retina compared to age-matched healthy donors. Iron accumulation in AMD is likely to result, in part, from inflammation, hypoxia, and oxidative stress, all of which can cause iron dysregulation. Fortunately, it has been demonstrated by in vitro and in vivo studies that iron in the retinal pigment epithelium (RPE) and retina is chelatable. Iron chelation protects photoreceptors and retinal pigment epithelial cells (RPE) in a variety of mouse models. This has therapeutic potential for diminishing iron-induced oxidative damage to prevent or treat AMD. PMID:23825457
Su, Ping-Jung; Liu, Zongbin; Zhang, Kai; Han, Xin; Saito, Yuki; Xia, Xiaojun; Yokoi, Kenji; Shen, Haifa; Qin, Lidong
In vitro culture of dissociated retinal neurons is an important model for investigating retinal synaptic regeneration (RSR) and exploring potentials in artificial retina. Here, retinal precursor cells were cultured in a microfluidic chip with multiple arrays of microchannels in order to reconstruct the retinal neuronal synapse. The cultured retinal cells were physically connected through microchannels. Activation of electric signal transduction by the cells through the microchannels was demonstrated by administration of glycinergic factors. In addition, an image-based analytical method was used to quantify the synaptic connections and to assess the kinetics of synaptic regeneration. The rate of RSR decreased significantly below 100 μM of inhibitor glycine and then approached to a relatively constant level at higher concentrations. Furthermore, RSR was enhanced by chemical stimulation with potassium chloride. Collectively, the microfluidic synaptic regeneration chip provides a novel tool for high-throughput investigation of RSR at the cellular level and may be useful in quality control of retinal precursor cell transplantation. PMID:26314276
Adaptive optics (AO) is a technology used to improve the performance of optical systems by reducing the effect of wave front distortions. Retinal imaging using AO aims to compensate for higher order aberrations originating from the cornea and the lens by using deformable mirror. The main application of AO retinal imaging has been to assess photoreceptor cell density, spacing, and mosaic regularity in normal and diseased eyes. Apart from photoreceptors, the retinal pigment epithelium, retinal nerve fiber layer, retinal vessel wall and lamina cribrosa can also be visualized with AO technology. Recent interest in AO technology in eye research has resulted in growing number of reports and publications utilizing this technology in both animals and humans. With the availability of first commercially available instruments we are making transformation of AO technology from a research tool to diagnostic instrument. The current challenges include imaging eyes with less than perfect optical media, formation of normative databases for acquired images such as cone mosaics, and the cost of the technology. The opportunities for AO will include more detailed diagnosis with description of some new findings in retinal diseases and glaucoma as well as expansion of AO into clinical trials which has already started.
Côco, Monique; Han, Sang Won; Sallum, Juliana Maria Ferraz
The inherited retinal dystrophies comprise a large number of disorders characterized by a slow and progressive retinal degeneration. They are the result of mutations in genes that express in either the photoreceptor cells or the retinal pigment epithelium. The mode of inheritance can be autosomal dominant, autosomal recessive, X linked recessive, digenic or mitochondrial DNA inherited. At the moment, there is no treatment for these conditions and the patients can expect a progressive loss of vision. Accurate genetic counseling and support for rehabilitation are indicated. Research into the molecular and genetic basis of disease is continually expanding and improving the prospects for rational treatments. In this way, gene therapy, defined as the introduction of exogenous genetic material into human cells for therapeutic purposes, may ultimately offer the greatest treatment for the inherited retinal dystrophies. The eye is an attractive target for gene therapy because of its accessibility, immune privilege and translucent media. A number of retinal diseases affecting the eye have known gene defects. Besides, there is a well characterized animal model for many of these conditions. Proposals for clinical trials of gene therapy for inherited retinal degenerations owing to defects in the gene RPE65, have recently received ethical approval and the obtained preliminary results brought large prospects in the improvement on patient's quality of life.
Meenink, Thijs C. M.; Janssens, Tom; Vanheukelom, Valerie; Naus, Gerrit J. L.; Beelen, Maarten J.; Meers, Caroline; Jonckx, Bart; Stassen, Jean-Marie
Purpose To develop a methodology for cannulating porcine retinal venules using a robotic assistive arm after inducing a retinal vein occlusion using the photosensitizer rose bengal. Methodology Retinal vein occlusions proximal to the first vascular branch point were induced following intravenous injection of rose bengal by exposure to 532nm laser light delivered by slit-lamp or endolaser probe. Retinal veins were cannulated by positioning a glass catheter tip using a robotically controlled micromanipulator above venules with an outer diameter of 80μm or more and performing a preset piercing maneuver, controlled robotically. The ability of a balanced salt (BSS) solution to remove an occlusion by repeat distention of the retinal vein was also assessed. Results Cannulation using the preset piercing program was successful in 9 of 9 eyes. Piercing using the micromanipulator under manual control was successful in only 24 of 52 attempts, with several attempts leading to double piercing. The best location for cannulation was directly proximal to the occlusion. Infusion of BSS did not result in the resolution of the occlusion. Conclusion Cannulation of venules using a robotic microassistive arm can be achieved with consistency, provided the piercing is robotically driven. The model appears robust enough to allow testing of therapeutic strategies aimed at eliminating a retinal vein thrombus and its evolution over time. PMID:27676261
Mitamura, Yoshinori; Mitamura-Aizawa, Sayaka; Nagasawa, Toshihiko; Katome, Takashi; Eguchi, Hiroshi; Naito, Takeshi
Retinitis pigmentosa (RP) is a progressive inherited retinal disease, and patients with RP have reduced visual function caused by a degeneration of the photoreceptors and retinal pigment epithelium (RPE). At the end stage of RP, the degeneration of the photoreceptors in the fovea reduces central vision, and RP is one of the main causes of acquired blindness in developed countries. Therefore, morphological and functional assessments of the photoreceptors in the macula area can be useful in estimating the residual retinal function in RP patients. Optical coherence tomography (OCT) is a well-established method of examining the retinal architecture in situ. The photoreceptor inner/outer segment (IS/OS) junction is observed as a distinct, highly reflective line by OCT. The presence of the IS/OS junction in the OCT images is essential for normal visual function. Fundus autofluorescence (FAF) results from the accumulation of lipofuscin in the RPE cells and has been used to investigate RPE and retinal function. More than one-half of RP patients have an abnormally high density parafoveal FAF ring (AF ring). The AF ring represents the border between functional and dysfunctional retina. In this review, we shall summarize recent progress on diagnostic imaging in eyes with RP.
A number of concerns have been raised regarding the advisability of the classic principles of aggressive crystalloid resuscitation in traumatic hemorrhagic shock. This issue reviews the advances that have led to a shift in the emergency department (ED) protocols in resuscitation from shock state, including recent literature regarding the new paradigm for the treatment of traumatic hemorrhagic shock, which is most generally known as damage control resuscitation (DCR). Goals and endpoints for resuscitation and a review of initial fluid choice are discussed, along with the coagulopathy of trauma and its management, how to address hemorrhagic shock in traumatic brain injury (TBI), and new pharmacologic treatment for hemorrhagic shock. The primary conclusions include the administration of tranexamic acid (TXA) for all patients with uncontrolled hemorrhage (Class I), the implementation of a massive transfusion protocol (MTP) with fixed blood product ratios (Class II), avoidance of large-volume crystalloid resuscitation (Class III), and appropriate usage of permissive hypotension (Class III). The choice of fluid for initial resuscitation has not been shown to affect outcomes in trauma (Class I).
Montgomery, Brian D.; Boorjian, Stephen A.; Ziegelmann, Matthew J.; Joyce, Daniel D.; Linder, Brian J.
Objective Hemorrhagic cystitis is a challenging clinical entity with limited evidence available to guide treatment. The use of intravesical silver nitrate has been reported, though supporting literature is sparse. Here, we sought to assess outcomes of patients treated with intravesical silver nitrate for refractory hemorrhagic cystitis. Material and methods We identified nine patients with refractory hemorrhagic cystitis treated at our institution with intravesical silver nitrate between 2000–2015. All patients had failed previous continuous bladder irrigation with normal saline and clot evacuation. Treatment success was defined as requiring no additional therapy beyond normal saline irrigation after silver nitrate instillation prior to hospital discharge. Results Median patient age was 80 years (IQR 73, 82). Radiation was the most common etiology for hemorrhagic cystitis 89% (8/9). Two patients underwent high dose (0.1%–0.4%) silver nitrate under anesthesia, while the remaining seven were treated with doses from 0.01% to 0.1% via continuous bladder irrigation for a median of 3 days (range 2–4). All nine patients (100%) had persistent hematuria despite intravesical silver nitrate therapy, requiring additional interventions and red blood cell transfusion during the hospitalization. There were no identified complications related to intravesical silver nitrate instillation. Conclusion Although well tolerated, we found that intravesical silver nitrate was ineffective for bleeding control, suggesting a limited role for this agent in the management of patients with hemorrhagic cystitis. PMID:27635296
Chaudhary, Neeraj; Pandey, Aditya S; Gemmete, Joseph J; Hua, Ya; Huang, Yining; Gu, Yuxiang; Xi, Guohua
Diffusion Tensor Imaging (DTI) has evolved considerably over the last decade to now be knocking on the doors of wider clinical applications. There have been several efforts over the last decade to seek valuable and reliable application of DTI in different neurological disorders. The role of DTI in predicting outcomes in patients with brain tumors has been extensively studied and has become a fairly established clinical tool in this scenario. More recently DTI has been applied in mild traumatic brain injury to predict clinical outcomes based on DTI of the white matter tracts. The resolution of white matter fiber tractography based on DTI has improved over the years with increased magnet strength and better tractography post processing. The role of DTI in hemorrhagic stroke has been studied preliminarily in the scientific literature. There is some evidence that DTI may be efficacious in predicting outcomes of motor function in animal models of intracranial hemorrhage. Only a handful of studies of DTI have been performed in subarachnoid hemorrhage or intraventricular hemorrhage scenarios. In this manuscript we will review the evolution of DTI, the existing evidence for its role in hemorrhagic stroke and discuss possible application of this non-invasive evaluation technique of human cerebral white matter tracts in the future. PMID:26015333
Yaguchi, Yukari; Katagiri, Satoshi; Fukushima, Yoko; Yokoi, Tadashi; Nishina, Sachiko; Kondo, Mineo; Azuma, Noriyuki
We evaluated the retinal function of retinal dragging (Rdrag) and radial retinal folds (Rfolds) in eyes with familial exudative vitreoretinopathy (FEVR) using full-field electroretinography (ERG). Seventeen eyes of nine patients with FEVR who had Rdrag or Rfolds were retrospectively studied. Eyes were classified into four groups according to the severity of the retinal alterations: Group 1, without Rdrag or Rfolds (5 eyes); Group 2, with Rdrag (4 eyes); Group 3, with Rfolds (6 eyes); and Group 4, with Rfolds in which all major retinal vessels were involved (2 eyes). The amplitudes of all ERG components and the implicit times of the photopic a- and b-waves and 30-Hz flicker responses were decreased or prolonged as the severity of the retinal alterations increased (P < 0.01). The photopic negative response was most severely affected and nearly undetectable in all eyes in Groups 3 and 4, although the other ERG components were detectable in all eyes in Group 3 and one eye in Group 4. These results suggest the decrease of retinal functions was correlated with the degree of severity of Rdrag and Rfolds in eyes with FEVR. In addition, the function of the retinal ganglion cells appears to be more severely affected compared with the others. PMID:27456314
Nagasaka, Yosuke; Ito, Yasuki; Ueno, Shinji; Terasaki, Hiroko
Retinitis pigmentosa(RP) is a hereditary retinal disease that causes photoreceptor, outer retinal, degeneration. Although the pathogenesis is still unclear, there have been numerous reports regarding inner retinal changes in RP eyes. The aim of this study is to retrospectively evaluate the changes in the thicknesses of different retinal layers of RP eyes, and its association with aqueous flare, which is used for measuring the intensity of intraocular inflammation. A total of 125 eyes of 64 patients with RP and 13 normal eyes were studied. The thicknesses of total neural retina,nerve fiber layer(NFL),ganglion cell layer(GCL),inner plexiform layer(IPL),inner nuclear layer(INL),outer layers and foveal thickness were measured in the optical coherence tomographic images. Aqueous flare was measured with a laser flare-cell meter. The associations between those parameters, visual acuity and visual field were determined in RP eyes using multivariate analysis. The results of this study showed the significant thickening of NFL, GCL and INL, the significant thinning of outer layers and the association of them with increased aqueous flare, whereas NFL and INL thickening associated with outer retinal thinning. These results can suggest the involvement of intraocular inflammation in the pathogenesis of inner retinal thickening as a secondary change following outer retinal degeneration. PMID:27653207
Yu, Jian; Gu, Ruiping; Zong, Yuan; Xu, Huan; Wang, Xiaolei; Sun, Xinghuai; Jiang, Chunhui; Xie, Bing; Jia, Yali; Huang, David
Purpose To investigate the relationship between retinal perfusion and retinal thickness in the peripapillary and macular areas of healthy subjects. Methods Using spectral-domain optic coherence tomography and split-spectrum amplitude decorrelation angiography (SSADA) algorithm, retinal perfusion and retinal thicknesses in the macular and peripapillary areas were measured in healthy volunteers, and correlations among these variables were analyzed. Results Overall, 64 subjects (121 eyes) including 28 males and 36 females with a mean ± SD age of 38 ± 13 years participated. Linear mixed-models showed that vessel area density was significantly correlated with the inner retinal thickness (from the inner limiting membrane to the outer border of the inner nucleus layer; P < 0.05), but not with the thickness of the full retina (P > 0.05) in the parafoveal area. The area of the foveal capillary-free zone was negatively correlated with the inner and full foveal thicknesses (all P < 0.001). In the peripapillary area, the vessel area density was positively correlated with the thickness of the retinal nerve fiber layer (P < 0.001). Conclusions In healthy subjects, retinal perfusion in small vessels was closely correlated with the thickness of the inner retinal layers in both the macular and peripapillary areas. PMID:27409474
Wei, Y; Zhou, R; Xu, K; Wang, J; Zu, Z
PurposeTo evaluate the anatomic and functional outcome of pars plana vitrectomy (PPV) combined with scleral buckling (SB) vs retinectomy in treating posterior segment open-globe injuries with retinal incarceration.MethodsPatients (38 eyes) with posterior segment open-globe injuries and retinal incarceration were identified, and they underwent either PPV combined with SB (PPV+SB, n=19) or retinectomy (n=19). The two groups were matched in the following categories: the severity of injury (including wound length), the location of the incarceration site and the presence of retinal detachment. Anatomic reattachment of the retina and best-corrected visual acuity (BCVA) were measured at the time of 12 months after operation.ResultsAt 12 months after operation, the PPV+SB group demonstrated a better anatomic retinal attachment rate (84.2% vs 68.4%, P=0.252) and BCVA (73.7% vs 47.4%, P=0.247) compared with the retinectomy group, however, the differences failed to reach statistical significance. Compared with the PPV+SB group, the rectinectomy group had significantly higher rates of hemorrhage (47.4% vs 15.8%, P=0.036), inflammation (42.1% vs 10.5%, P=0.027), and a lower intraocular pressure (IOP, 9.8±3.1 vs 13.6±4.1 mmHg, P=0.002) after silicone oil (SO) removal.ConclusionsFor patients with posterior segment open-globe injuries and retinal incarceration, PPV and SB treatments resulted in a better anatomic and functional outcome and less post-operation complications compared with the retinectomy.
Post-clipping intraparenchymal hemorrhage of the contralateral hemisphere is a very unusual phenomenon in a patient with aneurysmal subarachnoid hemorrhage, unless there is an underlying condition. We report a complicated case of 47-year-old man, who underwent uneventful clipping of ruptured aneurysm and experienced vasospasm two weeks later. Vasospasm was treated by intra-arterial nimodipine and systemic hyperdynamic therapy. One week thereafter, he became unconscious due to intraparenchymal hemorrhage on the anterior border-zone of contalateral hemisphere, but intraoperative and pathologic findings failed to disclose any vascular anomaly. We suggest that the anti-spastic regimens cause local hemodynamic redistribution through the vasodilatory effect and in turn, resulted in such an unexpected bleeding. PMID:19096626
Agarwal, Amit; Kanekar, Sangam; Thamburaj, Krishnamurthy; Vijay, Kanupriya
Intraspinal hemorrhage is very rare and intramedullary hemorrhage, also called hematomyelia, is the rarest form of intraspinal hemorrhage, usually related to trauma. Spinal vascular malformations such intradural arteriovenous malformations are the most common cause of atraumatic hematomyelia. Other considerations include warfarin or heparin anticoagulation, bleeding disorders, spinal cord tumors. Radiation-induced hematomyelia of the cord is exceedingly rare with only one case in literature to date. We report the case of an 8 year old girl with Ewing's sarcoma of the thoracic vertebra, under radiation therapy, presenting with hematomyelia. We describe the clinical course, the findings on imaging studies and the available information in the literature. Recognition of the clinical pattern of spinal cord injury should lead clinicians to perform imaging studies to evaluate for compressive etiologies.
Akhavan, Reza; Zandi, Behrouz; Pezeshki-Rad, Masoud; Farrokh, Donya
Colloid cysts are benign slow-growing cystic lesions located on the roof of the third ventricle that usually present with symptoms related to gradual rise of intracranial pressure. They mostly remain asymptomatic and sometimes grow progressively and cause diverse symptoms associated with increased intracranial pressure such as headache, diplopia, and sixth cranial nerve palsy. Here we report a 47-year-old female who presented to the emergency department with acute severe headache and nausea/vomiting. On MRI examination acute hydrocephaly due to hemorrhagic colloid cyst was detected. Acute hemorrhage in colloid cysts is extremely rare and may present with symptoms of acute increase in the intracranial pressure. Intracystic hemorrhage is very rarely reported as a complication of colloid cyst presenting with paroxysmal symptoms of acute hydrocephaly. PMID:28210514
Lima, Raquel Sucupira Andrade; Maquiné, Gustavo Ávila; Schettini, Antônio Pedro Mendes; Santos, Mônica
Lichen sclerosus is a chronic inflammatory disease, usually located in the genital area. The etiology of lichen sclerosus is multifactorial, with participation of genetic, autoimmune, infectious and hormonal factors. Bullous clinical form stems from hydropic degeneration of the basal membrane, constituting a less frequent variant of the disease. In this work, we report the case of a female patient, 55 years old, who in the last three years presented whitish plaques, with horny spikes, located on back and arms. Some of these lesions evolved with hemorrhagic blisters, which after histopathological examination confirmed the diagnosis of bullous and hemorrhagic lichen sclerosus. The patient was treated with high-potency topical corticosteroid for two months, resulting in remission of bullous and hemorrhagic lesions. PMID:26312692
Davuluri, Pavani; Wu, Jie; Tang, Yang; Cockrell, Charles H.; Ward, Kevin R.; Najarian, Kayvan; Hargraves, Rosalyn H.
Automated hemorrhage detection and segmentation in traumatic pelvic injuries is vital for fast and accurate treatment decision making. Hemorrhage is the main cause of deaths in patients within first 24 hours after the injury. It is very time consuming for physicians to analyze all Computed Tomography (CT) images manually. As time is crucial in emergence medicine, analyzing medical images manually delays the decision-making process. Automated hemorrhage detection and segmentation can significantly help physicians to analyze these images and make fast and accurate decisions. Hemorrhage segmentation is a crucial step in the accurate diagnosis and treatment decision-making process. This paper presents a novel rule-based hemorrhage segmentation technique that utilizes pelvic anatomical information to segment hemorrhage accurately. An evaluation measure is used to quantify the accuracy of hemorrhage segmentation. The results show that the proposed method is able to segment hemorrhage very well, and the results are promising. PMID:22919433
Lee, Mun-Young; Yang, Dong Kwon; Kim, Shang-Jin
Hemorrhagic shock is generally characterized by hemodynamic instability with cellular hypoxia and diminishing cellular function, resulting from an imbalance between systemic oxygen delivery and consumption and redistribution of fluid and electrolytes. Magnesium (Mg) is the fourth most abundant cation overall and second most abundant intracellular cation in the body and an essential cofactor for the energy production and cellular metabolism. Data for blood total Mg (tMg; free-ionized, protein-bound, and anion-bound forms) and free Mg(2+) levels after a traumatic injury are inconsistent and only limited information is available on hemorrhagic effects on free Mg(2+) as the physiologically active form. The aim of this study was to determine changes in blood Mg(2+) and tMg after hemorrhage in rats identifying mechanism and origin of the changes in blood Mg(2+). Hemorrhagic shock produced significant increases in blood Mg(2+), plasma tMg, Na(+), K(+), Cl(-), anion gap, partial pressures of oxygen, glucose, and blood urea nitrogen but significant decreases in RBC tMg, blood Ca(2+), HCO3(-), pH, partial pressures of carbon dioxide, hematocrit, hemoglobin, total cholesterol, and plasma/RBC ATP. During hemorrhagic shock, K(+), anion gap, and BUN showed significant positive correlations with changes in blood Mg(2+) level, while Ca(2+), pH, and T-CHO correlated to Mg(2+) in a negative manner. In conclusion, hemorrhagic shock induced an increase in both blood-free Mg(2+) and tMg, resulted from Mg(2+) efflux from metabolic damaged cell with acidosis and ATP depletion.
Dalkara, Deniz; Kolstad, Kathleen D; Guerin, Karen I; Hoffmann, Natalie V; Visel, Meike; Klimczak, Ryan R; Schaffer, David V; Flannery, John G
Mutations in over 80 identified genes can induce apoptosis in photoreceptors, resulting in blindness with a prevalence of 1 in 3,000 individuals. This broad genetic heterogeneity of disease impacting a wide range of photoreceptor functions renders the design of gene-specific therapies for photoreceptor degeneration impractical and necessitates the development of mutation-independent treatments to slow photoreceptor cell death. One promising strategy for photoreceptor neuroprotection is neurotrophin secretion from Müller cells, the primary retinal glia. Müller glia are excellent targets for secreting neurotrophins as they span the entire tissue, ensheath all neuronal populations, are numerous, and persist through retinal degeneration. We previously engineered an adeno-associated virus (AAV) variant (ShH10) capable of efficient and selective glial cell transduction through intravitreal injection. ShH10-mediated glial-derived neurotrophic factor (GDNF) secretion from glia, generates high GDNF levels in treated retinas, leading to sustained functional rescue for over 5 months. This GDNF secretion from glia following intravitreal vector administration is a safe and effective means to slow the progression of retinal degeneration in a rat model of retinitis pigmentosa (RP) and shows significant promise as a gene therapy to treat human retinal degenerations. These findings also demonstrate for the first time that glia-mediated secretion of neurotrophins is a promising treatment that may be applicable to other neurodegenerative conditions. PMID:21522134
Palanker, Daniel; Huie, Philip; Vankov, Alexander; Asher, Alon; Baccus, Steven
It has been already demonstrated that electrical stimulation of retina can produce visual percepts in blind patients suffering from macular degeneration and retinitis pigmentosa. Current retinal implants provide very low resolution (just a few electrodes), while several thousand pixels are required for functional restoration of sight. We present a design of the optoelectronic retinal prosthetic system that can activate a retinal stimulating array with pixel density up to 2,500 pix/mm2 (geometrically corresponding to a visual acuity of 20/80), and allows for natural eye scanning rather than scanning with a head-mounted camera. The system operates similarly to "virtual reality" imaging devices used in military and medical applications. An image from a video camera is projected by a goggle-mounted infrared LED-LCD display onto the retina, activating an array of powered photodiodes in the retinal implant. Such a system provides a broad field of vision by allowing for natural eye scanning. The goggles are transparent to visible light, thus allowing for simultaneous utilization of remaining natural vision along with prosthetic stimulation. Optical control of the implant allows for simple adjustment of image processing algorithms and for learning. A major prerequisite for high resolution stimulation is the proximity of neural cells to the stimulation sites. This can be achieved with sub-retinal implants constructed in a manner that directs migration of retinal cells to target areas. Two basic implant geometries are described: perforated membranes and protruding electrode arrays. Possibility of the tactile neural stimulation is also examined.
Stanescu-Segall, Dinu; Balta, Florian; Jackson, Timothy L
Large submacular hemorrhage, an uncommon manifestation of neovascular age-related macular degeneration, may also occur with idiopathic polypoidal choroidal vasculopathy. Submacular hemorrhage damages photoreceptors owing to iron toxicity, fibrin meshwork contraction, and reduced nutrient flux, with subsequent macular scarring. Clinical and experimental studies support prompt treatment, as tissue damage can occur within 24 hours. Without treatment the natural history is poor, with a mean final visual acuity (VA) of 20/1600. Reported treatments include retinal pigment epithelial patch, macular translocation, pneumatic displacement, intravitreal or subretinal tissue plasminogen activator, intravitreal anti-vascular endothelial growth factor (VEGF) drugs, and combinations thereof. In the absence of comparative studies, we combined eligible studies to assess the VA change before and after each treatment option. The greatest improvement occurred after combined pars plana vitrectomy, subretinal tissue plasminogen activator, intravitreal gas, and anti-vascular endothelial growth factor treatment, with VA improving from 20/1000 to 20/400. The best final VA occurred using combined intravitreal tissue plasminogen activator, gas, and anti-vascular endothelial growth factor therapy, with VA improving from 20/200 to 20/100. Both treatments had an acceptable safety profile, but most studies were small, and larger randomized controlled trials are needed to determine both safety and efficacy.
Chaidemenos, George C; Mourellou, Olga; Karakatsanis, George; Koussidou, Thallia; Xenidis, Efthimios; Charalampidou, Haroula; Avgoloupis, Dimitris
We report a peculiar case of hemorrhagic pellagra in an exhausted Albanian refugee who had walked for 3 days under sunny skies on his way from his country to Greece. The peculiarities of the case are the fulminant course of the disorder; the "terrifying" appearance of the patient (initially he was admitted to an emergency unit); the gangrenous appearance of the hemorrhagic lesions of the palms and fingernails; the disturbed hepatic function that gradually returned to normal; and the absence of a history of alcohol consumption, alcohol malabsorption, or drug intake.
thank ONR for the last 9 years of basic and applied research on titrated fluid therapy of hypovolemic shock . This grant was instrumental in not only the...Phone: 409-772-3969 Fax: 409-772-8895 Project Title: Closed-Loop Resuscitation of Hemorrhagic Shock ONR Award No: N000140610300 Organization...Resuscitation Of Hemorrhagic Shock 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK
Ruffini, E; De Petris, L; Zorzi, G; Paoletti, P; Mambelli, G; Carlucci, A
The adrenal hemorrhage is a relatively rare event in newborns but must be considered in the presence of a persistent unexplained jaundice, especially in presence of predisposing factors. Serial ultrasonography is the modality of choice for initial diagnosis and follow-up of neonatal adrenal hemorrhage. We report two cases of neonatal adrenal hemorrhage presenting with persistent jaundice. The causes of the neonatal adrenal hemorrhages were a difficult vaginal delivery in macrosomic infant and a neonatal infection.
Masuzzo, Ambra; Dinet, Virginie; Cavanagh, Chelsea; Mascarelli, Frederic; Krantic, Slavica
As a part of the central nervous system, the retina may reflect both physiological processes and abnormalities related to pathologies that affect the brain. Amyloidosis due to the accumulation of amyloid-beta (Aβ) was initially regarded as a specific and exclusive characteristic of neurodegenerative alterations seen in the brain of Alzheimer’s disease (AD) patients. More recently, it was discovered that amyloidosis-related alterations, similar to those seen in the brain of Alzheimer’s patients, also occur in the retina. Remarkably, these alterations were identified not only in primary retinal pathologies, such as age-related macular degeneration (AMD) and glaucoma, but also in the retinas of Alzheimer’s patients. In this review, we first briefly discuss the biogenesis of Aβ, a peptide involved in amyloidosis. We then discuss some pathological aspects (synaptic dysfunction, mitochondrial failure, glial activation, and vascular abnormalities) related to the neurotoxic effects of Aβ. We finally highlight common features shared by AD, AMD, and glaucoma in the context of Aβ amyloidosis and further discuss why the retina, due to the transparency of the eye, can be considered as a “window” to the brain. PMID:27551275
Finnamore, Helen; Le Couteur, James; Hickson, Mary; Busbridge, Mark; Whelan, Kevin; Shovlin, Claire L.
Background Iron deficiency anemia remains a major global health problem. Higher iron demands provide the potential for a targeted preventative approach before anemia develops. The primary study objective was to develop and validate a metric that stratifies recommended dietary iron intake to compensate for patient-specific non-menstrual hemorrhagic losses. The secondary objective was to examine whether iron deficiency can be attributed to under-replacement of epistaxis (nosebleed) hemorrhagic iron losses in hereditary hemorrhagic telangiectasia (HHT). Methodology/Principal Findings The hemorrhage adjusted iron requirement (HAIR) sums the recommended dietary allowance, and iron required to replace additional quantified hemorrhagic losses, based on the pre-menopausal increment to compensate for menstrual losses (formula provided). In a study population of 50 HHT patients completing concurrent dietary and nosebleed questionnaires, 43/50 (86%) met their recommended dietary allowance, but only 10/50 (20%) met their HAIR. Higher HAIR was a powerful predictor of lower hemoglobin (p = 0.009), lower mean corpuscular hemoglobin content (p<0.001), lower log-transformed serum iron (p = 0.009), and higher log-transformed red cell distribution width (p<0.001). There was no evidence of generalised abnormalities in iron handling Ferritin and ferritin2 explained 60% of the hepcidin variance (p<0.001), and the mean hepcidinferritin ratio was similar to reported controls. Iron supplement use increased the proportion of individuals meeting their HAIR, and blunted associations between HAIR and hematinic indices. Once adjusted for supplement use however, reciprocal relationships between HAIR and hemoglobin/serum iron persisted. Of 568 individuals using iron tablets, most reported problems completing the course. For patients with hereditary hemorrhagic telangiectasia, persistent anemia was reported three-times more frequently if iron tablets caused diarrhea or needed to be stopped
Drewes, Jonathan Jensen
This dissertation documents the design and construction of a four-wavelength retinal vessel oximeter, the Eye Oximeter (EOX). The EOX scans low-powered laser beams (at 629, 678, 821 and 899 nm) into the eye and across a targeted retinal vessel to measure the transmittance of the blood within the vessel. From the transmittance measurements, the oxygen saturation of the blood within the vessel is computed. Retinal vessel oxygen saturation has been suggested as a useful parameter for monitoring a wide range of conditions including occult blood loss and a variety of ophthalmic diseases. An artificial eye that simulates the geometry of a human retinal vessel was constructed and used to calibrate the EOX saturation measurement. A number of different oximetry equations were developed and tested. From measurements made on whole human blood in the artificial eye, an oximetry equation that places a linear wavelength dependance on the scattering losses (3% decrease from 629 to 899 nm) is found to best calibrate the EOX oxygen saturation measurement. This calibration also requires that an adjustment be made to the absorption coefficient of hemoglobin at 629 nm that has been reported in the literature. More than 4,000 measurements were made in the eyes of three human subjects during the development of the EOX. Applying the oximetry equation developed through the in vitro experiments to human data, the average human retinal venous oxygen saturation is estimated to be 0.63 +/- 0.07 and the average human retinal arterial oxygen saturation is 0.99 +/- 0.03. Furthermore, measurements made away from the optic disk resulted in a larger variance in the calculated saturation when compared to measurements made on the optic disk. A series of EOX experiments using anesthetized swine helped to verify the sensitivity of the EOX measurement of oxygen saturation. It is found that the calibration in swine differed from the calibration in the artificial eye. An empirical calibration from the
Marc, Robert E; Jones, Bryan W
Photoreceptor degenerations initiated in rods or the retinal pigmented epithelium usually evoke secondary cone death and sensory deafferentation of the surviving neural retina. In the mature central nervous system, deafferentation evokes atrophy and connective re-patterning. It has been assumed that the neural retina does not remodel, and that it is a passive survivor. Screening of advanced stages of human and rodent retinal degenerations with computational molecular phenotyping has exposed a prolonged period of aggressive negative remodeling in which neurons migrate along aberrant glial columns and seals, restructuring the adult neural retina (1). Many neurons die, but survivors rewire the remnant inner plexiform layer (IPL), forming thousands of novel ectopic microneuromas in the remnant inner nuclear layer (INL). Bipolar and amacrine cells engage in new circuits that are most likely corruptive. Remodeling in human and rodent retinas emerges regardless of the molecular defects that initially trigger retinal degenerations. Although remodeling may constrain therapeutic intervals for molecular, cellular, or bionic rescue, the exposure of intrinsic retinal remodeling by the removal of sensory control in retinal degenerations suggests that neuronal organization in the normal retina may be more plastic than previously believed.
Capozzi, Megan E.; Hammer, Sandra S.; McCollum, Gary W.; Penn, John S.
The objective of the present study was to assess the effect of elevating epoxygenated fatty acids on retinal vascular inflammation. To stimulate inflammation we utilized TNFα, a potent pro-inflammatory mediator that is elevated in the serum and vitreous of diabetic patients. In TNFα-stimulated primary human retinal microvascular endothelial cells, total levels of epoxyeicosatrienoic acids (EETs), but not epoxydocosapentaenoic acids (EDPs), were significantly decreased. Exogenous addition of 11,12-EET or 19,20-EDP when combined with 12-(3-adamantane-1-yl-ureido)-dodecanoic acid (AUDA), an inhibitor of epoxide hydrolysis, inhibited VCAM-1 and ICAM-1 expression and protein levels; conversely the diol product of 19,20-EDP hydrolysis, 19,20-DHDP, induced VCAM1 and ICAM1 expression. 11,12-EET and 19,20-EDP also inhibited leukocyte adherence to human retinal microvascular endothelial cell monolayers and leukostasis in an acute mouse model of retinal inflammation. Our results indicate that this inhibition may be mediated through an indirect effect on NFκB activation. This is the first study demonstrating a direct comparison of EET and EDP on vascular inflammatory endpoints, and we have confirmed a comparable efficacy from each isomer, suggesting a similar mechanism of action. Taken together, these data establish that epoxygenated fatty acid elevation will inhibit early pathology related to TNFα-induced inflammation in retinal vascular diseases. PMID:27966642
Chen, Yun; Londraville, Richard; Brickner, Sarah; El-Shaar, Lana; Fankhauser, Kelsee; Dearth, Cassandra; Fulton, Leah; Sochacka, Alicja; Bhattarai, Sunil; Marrs, James A.; Liu, Qin
Cadherin cell adhesion molecules play crucial roles in vertebrate development including the development of the retina. Most studies have focused on examining functions of classic cadherins (e.g. N-cadherin) in retinal development. There is little information on the function of protocadherins in the development of the vertebrate visual system. We previously showed that protocadherin-17 mRNA was expressed in developing zebrafish retina during critical stages of the retinal development. To gain insight into protocadherin-17 function in the formation of the retina, we analyzed eye development and differentiation of retinal cells in zebrafish embryos injected with protocadherin-17 specific antisense morpholino oligonucleotides (MOs). Protocadherin-17 knockdown embryos (pcdh17 morphants) had significantly reduced eyes due mainly to decreased cell proliferation. Differentiation of several retinal cell types (e.g. retinal ganglion cells) was also disrupted in the pcdh17 morphants. Phenotypic rescue was achieved by injection of protocadherin-17 mRNA. Injection of a vivo-protocadherin-17 MO into one eye of embryonic zebrafish resulted in similar eye defects. Our results suggest that protocadherin-17 plays an important role in the normal formation of the zebrafish retina. PMID:22927092
Kohl, S; Biskup, S
Inherited retinal dystrophies are clinically and genetically highly heterogeneous. They can be divided according to the clinical phenotype and course of the disease, as well as the underlying mode of inheritance. Isolated retinal dystrophies (i.e., retinitis pigmentosa, Leber's congenital amaurosis, cone and cone-rod dystrophy, macular dystrophy, achromatopsia, congenital stationary nightblindness) and syndromal forms (i.e., Usher syndrome, Bardet-Biedl syndrome) can be differentiated. To date almost 180 genes and thousands of distinct mutations have been identified that are responsible for the different forms of these blinding illnesses. Until recently, there was no adequate diagnostic genetic testing available. With the development of the next generation sequencing technologies, a comprehensive genetic screening analysis for all known genes for inherited retinal dystrophies has been established at reasonable costs and in appropriate turn-around times. Depending on the primary clinical diagnosis and the presumed mode of inheritance, different diagnostic panels can be chosen for genetic testing. Statistics show that in 55-80 % of the cases the genetic defect of the inherited retinal dystrophy can be identified with this approach, depending on the initial clinical diagnosis. The aim of any genetic diagnostics is to define the genetic cause of a given illness within the affected patient and family and thereby i) confirm the clinical diagnosis, ii) provide targeted genetic testing in family members, iii) enable therapeutic intervention, iv) give a prognosis on disease course and progression and v) in the long run provide the basis for novel therapeutic approaches and personalised medicine.
The neuroretina should be considered as a potential site of nanomaterial toxicity. Engineered nanomaterials may reach the retina through three potential routes of exposure including; intra vitreal injection of therapeutics; blood-borne delivery in the retinal vasculature and then crossing the blood-retinal barrier; and through the choroidal blood supply, crossing the Bruch's membrane and the retinal pigment epithelium (RPE). The blood-retinal barrier is functionally similar to the blood-brain barrier, normally restricting transport of larger sized materials, but particles in the lower nanomaterial size range can be expected to transit. The blood flow to the retinal choroid is, on a tissue mass basis, one of the highest in the body raising the potential for rapid delivery of nanomaterials to the RPE. In vitro, RPE cells rapidly uptake nano particles, transport and agglomerate them in the perinuclear cytoplasm. In vivo studies have shown that the eye can uptake nanomaterials and retain them longer than many other tissues after cessation of exposure. Toxicity from nanomaterials to the neural retina or the RPE would be expected to follow common mechanisms identified for other tissues including generation of reactive oxygen species, alteration of cellular redox status, altered intracellular signaling, and release of toxic metal ions from soluble metallic particles. The retina and other ocular tissues, however, have potential for additional phototoxic mechanism
Lipinski, Daniel M; Thake, Miriam; MacLaren, Robert E
Many currently incurable forms of blindness affecting the retina have a genetic etiology and several others, such as those resulting from retinal vascular disturbances, respond to repeated, potentially indefinite administration of molecular based treatments. The recent clinical advances in retinal gene therapy have shown that viral vectors can deliver genes safely to the retina and the promising initial results from a number of clinical trials suggest that certain diseases may potentially be treatable. Gene therapy provides a means of expressing proteins within directly transduced cells with far greater efficacy than might be achieved by traditional systemic pharmacological approaches. Recent developments have demonstrated how vector gene expression may be regulated and further improvements to vector design have limited side effects and improved safety profiles. These recent steps have been most significant in bringing gene therapy into the mainstream of ophthalmology. Nevertheless translating retinal gene therapy from animal research into clinical trials is still a lengthy process, including complexities in human retinal diseases that have been difficult to model in the laboratory. The focus of this review is to summarize the genetic background of the most common retinal diseases, highlight current concepts of gene delivery technology, and relate those technologies to pre-clinical and clinical gene therapy studies.
Lund, David J; Stuck, Bruce E; Edsall, Peter
The interaction mechanism leading to laser-induced retinal alteration can be thermal or non-thermal, depending upon the wavelength of the laser radiation and the duration of the exposure. To investigate the effect of exposure duration on the interaction mechanism, retinal injury thresholds in the rhesus monkey were experimentally measured for exposure to laser radiation at wavelengths of 441.6, 457.9, 476.5, and 496.5 nm. Exposure durations were 0.1, 1, 5, 16, and 100 s; and 1/e retinal irradiance diameters were 50, 125, and 327 microm. Tissue response was observed via ophthalmoscope 1 h and 48 h post exposure. Thermal and non-thermal damage thresholds were obtained depending upon the exposure duration. These threshold data are in agreement with data previously reported in the literature for 100-s duration exposures, but differences were noted for shorter exposures. The current study yielded an estimated injury threshold for 1-s duration, 327-microm retinal irradiance diameter exposures at 441.6 nm, which is an order of magnitude higher than that previously reported. This study provides evidence that laser-induced retinal damage is primarily induced via thermal mechanisms for exposures shorter than 5 s in duration. Arguments are presented that support an amendment of the thermal hazard function, R(lambda).
Balendra, S I; Normando, E M; Bloom, P A; Cordeiro, M F
Glaucoma is one of the leading causes of blindness worldwide and will affect 79.6 million people worldwide by 2020. It is caused by the progressive loss of retinal ganglion cells (RGCs), predominantly via apoptosis, within the retinal nerve fibre layer and the corresponding loss of axons of the optic nerve head. One of its most devastating features is its late diagnosis and the resulting irreversible visual loss that is often predictable. Current diagnostic tools require significant RGC or functional visual field loss before the threshold for detection of glaucoma may be reached. To propel the efficacy of therapeutics in glaucoma, an earlier diagnostic tool is required. Recent advances in retinal imaging, including optical coherence tomography, confocal scanning laser ophthalmoscopy, and adaptive optics, have propelled both glaucoma research and clinical diagnostics and therapeutics. However, an ideal imaging technique to diagnose and monitor glaucoma would image RGCs non-invasively with high specificity and sensitivity in vivo. It may confirm the presence of healthy RGCs, such as in transgenic models or retrograde labelling, or detect subtle changes in the number of unhealthy or apoptotic RGCs, such as detection of apoptosing retinal cells (DARC). Although many of these advances have not yet been introduced to the clinical arena, their successes in animal studies are enthralling. This review will illustrate the challenges of imaging RGCs, the main retinal imaging modalities, the in vivo techniques to augment these as specific RGC-imaging tools and their potential for translation to the glaucoma clinic. PMID:26293138
Coombs, J; van der List, D; Wang, G-Y; Chalupa, L M
The mouse retina offers an increasingly valuable model for vision research given the possibilities for genetic manipulation. Here we assess how the structural properties of mouse retinal ganglion cells relate to the stratification pattern of the dendrites of these neurons within the inner plexiform layer. For this purpose, we used 14 morphological measures to classify mouse retinal ganglion cells parametrically into different clusters. Retinal ganglion cells were labeled in one of three ways: Lucifer Yellow injection, 'DiOlistics' or transgenic expression of yellow fluorescent protein. The resulting analysis of 182 cells revealed 10 clusters of monostratified cells, with dendrites confined to either On or Off sublaminae of the inner plexiform layer, and four clusters of bistratified cells, dendrites spanning the On and Off sublaminae. We also sought to establish how these parametrically identified retinal ganglion cell clusters relate to cell types identified previously on the basis of immunocytochemical staining and the expression of yellow fluorescent protein. Cells labeled with an antibody against melanopsin were found to be located within a single cluster, while those labeled with the SMI-32 antibody were in four different clusters. Yellow fluorescent protein expressing cells were distributed within 13 of the 14 clusters identified here, which demonstrates that yellow fluorescent protein expression is a useful method for labeling virtually the entire population of mouse retinal ganglion cells. Collectively, these findings provide a valuable baseline for future studies dealing with the effects of genetic mutations on the morphological development of these neurons.
Garg, Aakriti; Yang, Jin; Lee, Winston; Tsang, Stephen H.
Stem cell therapy has long been considered a promising mode of treatment for retinal conditions. While human embryonic stem cells (ESCs) have provided the precedent for regenerative medicine, the development of induced pluripotent stem cells (iPSCs) revolutionized this field. iPSCs allow for the development of many types of retinal cells, including those of the retinal pigment epithelium, photoreceptors, and ganglion cells, and can model polygenic diseases such as age-related macular degeneration. Cellular programming and reprogramming technology is especially useful in retinal diseases, as it allows for the study of living cells that have genetic variants that are specific to patients’ diseases. Since iPSCs are a self-renewing resource, scientists can experiment with an unlimited number of pluripotent cells to perfect the process of targeted differentiation, transplantation, and more, for personalized medicine. Challenges in the use of stem cells are present from the scientific, ethical, and political realms. These include transplant complications leading to anatomically incorrect placement, concern for tumorigenesis, and incomplete targeting of differentiation leading to contamination by different types of cells. Despite these limitations, human ESCs and iPSCs specific to individual patients can revolutionize the study of retinal disease and may be effective therapies for conditions currently considered incurable. PMID:28157165
Liu, Qin; Londraville, Richard; Marrs, James A.; Wilson, Amy L.; Mbimba, Thomas; Murakami, Tohru; Kubota, Fumitaka; Zheng, Weiping; Fatkins, David G.
Cadherin cell adhesion molecules play crucial roles in vertebrate development including the development of the visual system. Most studies have focused on examining functions of classical type I cadherins (e.g. cadherin-2) in visual system development. There is little information on the function of classical type II cadherins (e.g. cadherin-6) in the development of the vertebrate visual system. To gain insight into cadherin-6 role in the formation of the retina, we analyzed differentiation of retinal ganglion cells, amacrine cells and photoreceptors in zebrafish embryos injected with cadherin-6 specific antisense morpholino oligonucleotides. Differentiation of the retinal neurons in cadherin-6 knockdown embryos (cdh6 morphants) was analyzed using multiple markers. We found that expression of transcription factors important for retinal development was greatly reduced, and expression of Notch-Delta genes and proneural gene ath5 was altered in the cdh6 morphant retina. The retinal lamination was present in the morphants, although the morphant eyes were significantly smaller than control embryos due mainly to decreased cell proliferation. Differentiation of the retinal ganglion cells, amacrine cells and photoreceptors was severely disrupted in the cdh6 morphants due to a significant delay in neuronal differentiation. Our results suggest that cadherin-6 plays an important role in the normal formation of the zebrafish retina. PMID:18506771
L Srinidhi, Chetan; Aparna, P; Rajan, Jeny
Retinal vessel segmentation is a key step towards the accurate visualization, diagnosis, early treatment and surgery planning of ocular diseases. For the last two decades, a tremendous amount of research has been dedicated in developing automated methods for segmentation of blood vessels from retinal fundus images. Despite the fact, segmentation of retinal vessels still remains a challenging task due to the presence of abnormalities, varying size and shape of the vessels, non-uniform illumination and anatomical variability between subjects. In this paper, we carry out a systematic review of the most recent advancements in retinal vessel segmentation methods published in last five years. The objectives of this study are as follows: first, we discuss the most crucial preprocessing steps that are involved in accurate segmentation of vessels. Second, we review most recent state-of-the-art retinal vessel segmentation techniques which are classified into different categories based on their main principle. Third, we quantitatively analyse these methods in terms of its sensitivity, specificity, accuracy, area under the curve and discuss newly introduced performance metrics in current literature. Fourth, we discuss the advantages and limitations of the existing segmentation techniques. Finally, we provide an insight into active problems and possible future directions towards building successful computer-aided diagnostic system.
electronic retinal prosthesis is under development to treat retinitis pigmentosa and age-related macular degeneration, two presently incurable...34Preservation of the inner retina in retinitis pigmentosa . A morphometric analysis," Arch Ophthalmol, vol. 115, no. 4, pp. 511-515, Apr.1997...Towards a completely implantable, light-sensitive intraocular retinal prosthesis. M.S. Humayun, J.D. Weiland, B. Justus1, C. Merrit1, J. Whalen, D
pigmentosa , and retinal detachment10. mfERG response characteristics have been shown to vary depending on the part of the retina that is affected by a...DoD Controlling Office is (insert controlling DoD office). 20100715258 Functional and behavioral metrics for evaluating laser retinal damage Cheryl...potential for and severity of laser eye injury and retinal damage is increasing . Sensitive and accurate methods to evaluate and follow laser retinal
Sugahara, Masako; Miyata, Manabu; Ishihara, Kenji; Gotoh, Norimoto; Morooka, Satoshi; Ogino, Ken; Hasegawa, Tomoko; Hirashima, Takako; Yoshikawa, Munemitsu; Hata, Masayuki; Muraoka, Yuki; Ooto, Sotaro; Yamashiro, Kenji; Yoshimura, Nagahisa
Ophthalmologists sometimes face difficulties in identifying the origin of visual acuity (VA) loss in a retinitis pigmentosa (RP) patient, particularly before cataract surgery: cataract or the retinal disease state. Therefore, it is important to identify the significant factors correlating with VA. Nowadays, retinal blood flow in superficial and deep layers can be estimated non-invasively using optical coherence tomography angiography (OCTA). We estimated blood flow per retinal layer by using OCTA; investigated the correlation between VA and other parameters including blood flow and retinal thickness; and identified the most associated factor with VA in patients with RP. OCTA images in 68 of consecutive 110 Japanese RP patients were analysable (analysable RP group). Thirty-two age- and axial length-matched healthy eyes (control group) were studied. In the analysable RP group, the parafoveal flow density in superficial and deep layers was 47.0 ± 4.9% and 52.4 ± 5.5%, respectively, which was significantly lower than that in controls. Using multivariate analysis, we found that the parafoveal flow density in the deep layer and superficial foveal avascular area were the factors associated with VA. Non-invasive estimation of retinal blood flow per retinal layer using OCTA is useful for predicting VA in RP patients.
Liu, Zhi; Li, Qiang; Cui, Gaoyu; Zhu, Gang; Tang, Weihua; Zhao, Hengli; Zhang, John H; Chen, Yujie; Feng, Hua
Previously, it was widely accepted that the delayed ischemic injury and poor clinical outcome following subarachnoid hemorrhage (SAH) was caused by cerebral vasospasm. This classical theory was challenged by a clazosentan clinical trial, which failed to improve patient outcome, despite reversing angiographic vasospasm. One possible explanation for the results of this trial is the changes in microcirculation following SAH, particularly in pericytes, which are the primary cell type controlling microcirculation in the brain parenchyma. However, as a result of technical limitations and the lack of suitable models, there was no direct evidence of microvessel dysfunction following SAH. In the present study, whole-mount retinal microvasculature has been introduced to study microcirculation in the brain following experimental SAH in vitro. Artificial blood-filled cerebrospinal fluid (BSCF) was applied to the retinal microvasculature to test the hypothesis that the presence of subarachnoid blood affects the contractile properties of the pericytes containing cerebral microcirculation during the early phase of SAH. It was observed that BCSF induced retina microvessel contraction and that this contraction could be resolved by BCSF wash-out. Furthermore, BCSF application accelerated pericyte-populated collagen gel contraction and increased the expression of α-smooth muscle actin. In addition, BCSF induced an influx of calcium in cultured retinal pericytes. In conclusion, the present study demonstrates increased contractility of retinal microvessels and pericytes in the presence of BCSF in vitro. These findings suggest that pericyte contraction and microvascular dysfunction is induced following SAH, which could lead to greater susceptibility to SAH-induced ischemia.
Ozgun, B; Castillo, M
We describe a case of bilateral basal ganglia hemorrhage after a lightning strike to the head documented by a CT scan. Review of the literature shows this to be the most common brain imaging finding that can be attributed to a lightning strike. Several mechanistic theories are discussed, with the most plausible one being related to preferential conduction pathways through the brain.
Pybus, Margo J; Ravi, Madhu; Pollock, Colleen
Epizootic hemorrhagic disease (EHD) virus serotype 2 was identified by reverse-transcription (RT)-PCR in a white-tailed deer (Odocoileus virginianus) found dead in southern Alberta in September 2013. Field observations indicate at least 50 deer, primarily white-tailed deer, and three pronghorn antelope (Antilocapra americana) died during a suspected localized EHD outbreak.
Papa, Anna; Sidira, Persefoni; Larichev, Victor; Gavrilova, Ludmila; Kuzmina, Ksenia; Mousavi-Jazi, Mehrdad; Mirazimi, Ali; Ströher, Ute; Nichol, Stuart
Seroprevalence of Crimean-Congo hemorrhagic fever virus (CCHFV) is high in some regions of Greece, but only 1 case of disease has been reported. We used 4 methods to test 118 serum samples that were positive for CCHFV IgG by commercial ELISA and confirmed the positive results. A nonpathogenic or low-pathogenicity strain may be circulating.
Guasch, E; Gilsanz, F
Massive obstetric hemorrhage is a major cause of maternal mortality and morbidity worldwide. It is defined (among others) as the loss of>2,500ml of blood, and is associated to a need for admission to critical care and/or hysterectomy. The relative hemodilution and high cardiac output found in normal pregnancy allows substantial bleeding before a drop in hemoglobin and/or hematocrit can be identified. Some comorbidities associated with pregnancy can contribute to the occurrence of catastrophic bleeding with consumption coagulopathy, which makes the situation even worse. Optimization, preparation, rational use of resources and protocolization of actions are often useful to improve outcomes in patients with postpartum hemorrhage. Using massive obstetric hemorrhage protocols is useful for facilitating rapid transfusion if needed, and can also be cost-effective. If hypofibrinogenemia during the bleeding episode is identified, early fibrinogen administration can be very useful. Other coagulation factors in addition to fibrinogen may be necessary during postpartum hemorrhage replacement measures in order to effectively correct coagulopathy. A hysterectomy is recommended if the medical and surgical measures prove ineffective.
Alen, Jose F.; Ramos, Ana; Lobato, Ramiro D.; Lagares, Alfonso
Lumbar synovial cysts frequently present with back pain, chronic radiculopathy and/or progressive symptoms of spinal canal compromise. These cysts generally appear in the context of degenerative lumbar spinal disease. Few cases of spontaneous hemorrhage into synovial cysts have been reported in the literature. PMID:20174835
Mansencal, Nicolas; N'Guetta, Roland; Desperramons, Julien; Dubourg, Olivier
We present the case of an 89-year-old woman with no previous cardiovascular disease who presented a stress cardiomyopathy secondary to acute hemorrhagic stroke. Contrast and two-dimensional speckle tracking echocardiography was helpful to perform the diagnosis and the follow-up.
Burnet, G; Lambert, M; Annet, L; Lefebvre, C
Adrenal hemorrhage is a rare disease associated with various conditions. We report a case of a 68-year-old woman with abdominal and back pain. The diagnostic work-up showed a left adrenal gland infarction associated with essential thrombocythemia. Treatment consisted in painkillers and treating the underlying condition in order to prevent further thrombotic events.
Franklin, Stanley S.; Hunt, Marshall T.; Vogt, Thomas; Walsh, Gregory; Paglia, Donald E.
The plaintiff alleged that failure of the attending physician to manage her husband's hypertension properly resulted in his death from intracerebral hemorrhage. Four lines of evidence supported the defendant: (1) In 1970 to 1971 there was uncertainty in the medical community whether mild hypertension should be treated with drugs; this uncertainty still existed at the time of the trial. (2) Severe hypertension and advanced age are the two most important predisposing factors leading to intracerebral hemorrhage; the deceased patient had neither. (3) Hemorrhage into the cerebral cortex and underlying white matter is not typical of hypertensive intracerebral bleeding; more likely, rupture of an arteriovenous malformation occurred. (4) A diagnosis of hypertensive intracerebral hemorrhage is not one of exclusion but requires objective evidence of vascular change in the brain, heart and kidney; these changes were not found in the deceased patient. In conclusion, an expert witness should testify objectively rather than be the advocate of a lawyer's theory of liability. ImagesFig. 6.Fig. 7.Fig. 9.Fig. 10. PMID:7233893
Rotenstreich, Ygal; Tzameret, Adi; Levi, Nir; Kalish, Sapir; Sher, Ifat; Zangen, Avraham; Belkin, Michael
Vision incapacitation and blindness associated with retinal dystrophies affect millions of people worldwide. Retinal degeneration is characterized by photoreceptor cell death and concomitant remodeling of remaining retinal cells. Repetitive Magnetic Stimulation (RMS) is a non-invasive technique that creates alternating magnetic fields by brief electric currents transmitted through an insulated coil. These magnetic field generate action potentials in neurons, and modulate the expression of neurotransmitter receptors, growth factors and transcription factors which mediate plasticity. This technology has been proven effective and safe in various psychiatric disorders. Here we determined the effect of RMS on retinal function in Royal College of Surgeons (RCS) rats, a model for retinal dystrophy. Four week-old RCS and control Spargue Dawley (SD) rats received sham or RMS treatment over the right eye (12 sessions on 4 weeks). RMS treatment at intensity of at 40% of the maximal output of a Rapid2 stimulator significantly increased the electroretinogram (ERG) b-wave responses by up to 6- or 10-fold in the left and right eye respectively, 3-5 weeks following end of treatment. RMS treatment at intensity of 25% of the maximal output did not significant effect b-wave responses following end of treatment with no adverse effect on ERG response or retinal structure of SD rats. Our findings suggest that RMS treatment induces delayed improvement of retinal functions and may induce plasticity in the retinal tissue. Furthermore, this non-invasive treatment may possibly be used in the future as a primary or adjuvant treatment for retinal dystrophy.
Glickman, Gena; Hanifin, John P.; Rollag, Mark D.; Wang, Jenny; Cooper, Howard; Brainard, George C.
Illumination of different areas of the human retina elicits differences in acute light-induced suppression of melatonin. The aim of this study was to compare changes in plasma melatonin levels when light exposures of equal illuminance and equal photon dose were administered to superior, inferior, and full retinal fields. Nine healthy subjects participated in the study. Plexiglass eye shields were modified to permit selective exposure of the superior and inferior halves of the retinas of each subject. The Humphrey Visual Field Analyzer was used both to confirm intact full visual fields and to quantify exposure of upper and lower visual fields. On study nights, eyes were dilated, and subjects were exposed to patternless white light for 90 min between 0200 and 0330 under five conditions: (1) full retinal exposure at 200 lux, (2) full retinal exposure at 100 lux, (3) inferior retinal exposure at 200 lux, (4) superior retinal exposure at 200 lux, and (5) a dark-exposed control. Plasma melatonin levels were determined by radioimmunoassay. ANOVA demonstrated a significant effect of exposure condition (F = 5.91, p < 0.005). Post hoc Fisher PLSD tests showed significant (p < 0.05) melatonin suppression of both full retinal exposures as well as the inferior retinal exposure; however, superior retinal exposure was significantly less effective in suppressing melatonin. Furthermore, suppression with superior retinal exposure was not significantly different from that of the dark control condition. The results indicate that the inferior retina contributes more to the light-induced suppression of melatonin than the superior retina at the photon dosages tested in this study. Findings suggest a greater sensitivity or denser distribution of photoreceptors in the inferior retina are involved in light detection for the retinohypothalamic tract of humans.
Pichon, Nicolas E-mail: email@example.com; Francois, Bruno; Pichon-Lefievre, Florence; Mathonnet, Murielle; Maubon, Antoine; Vignon, Philippe
Rectal injuries caused by foreign bodies or iatrogenic insertions may lead to severe complications whose therapeutic management remains controversial. At times, both the rapid identification and treatment of subsequent active rectal bleeding may be challenging, especially when endoscopy fails to locate and control the arterial hemorrhage. We present the first two successful cases of middle rectal artery embolization in patients presenting with sustained bleeding and hemorrhagic shock.
Stewart, Michael W
Cytomegalovirus (CMV) retinitis is the most common cause of vision loss in patients with acquired immunodeficiency syndrome (AIDS). CMV retinitis afflicted 25% to 42% of AIDS patients in the pre-highly active antiretroviral therapy (HAART) era, with most vision loss due to macula-involving retinitis or retinal detachment. The introduction of HAART significantly decreased the incidence and severity of CMV retinitis. Optimal treatment of CMV retinitis requires a thorough evaluation of the patient’s immune status and an accurate classification of the retinal lesions. When retinitis is diagnosed, HAART therapy should be started or improved, and anti-CMV therapy with oral valganciclovir, intravenous ganciclovir, foscarnet, or cidofovir should be administered. Selected patients, especially those with zone 1 retinitis, may receive intravitreal drug injections or surgical implantation of a sustained-release ganciclovir reservoir. Effective anti-CMV therapy coupled with HAART significantly decreases the incidence of vision loss and improves patient survival. Immune recovery uveitis and retinal detachments are important causes of moderate to severe loss of vision. Compared with the early years of the AIDS epidemic, the treatment emphasis in the post- HAART era has changed from short-term control of retinitis to long-term preservation of vision. Developing countries face shortages of health care professionals and inadequate supplies of anti-CMV and anti-HIV medications. Intravitreal ganciclovir injections may be the most cost effective strategy to treat CMV retinitis in these areas. PMID:20463796
Retinitis pigmentosa is a rod-cone dystrophy, commonly genetic in nature. Approximately 60-80% of those with retinitis pigmentosa inherit it by an autosomal recessive transmission (Brilliant, 1999). There have been some reported cases with no known family history. The symptoms of retinitis pigmentosa are decreased acuity, photophobia, night…
Grosso, Andrea; Cheung, Ning; Veglio, Franco; Wong, Tien Yin
The use of retinal photography in clinical practice and research has substantially increased the knowledge about the epidemiology, natural history and significance of diabetic and hypertensive retinopathy. Early retinopathy signs, including retinal microaneurysms, blot hemorrhages, cotton-wool spots and hard exudates, are common vascular abnormalities found in middle-aged to older people with diabetes and hypertension. The presence of these early retinopathy signs is associated with an increased risk of systemic vascular diseases, such as stroke, cognitive impairment, coronary heart disease, heart failure and nephropathy. These retinopathy lesions may therefore be considered as biomarkers of systemic microvascular processes caused by diabetes and hypertension. Nevertheless, whereas the interest in retinopathy assessment continues to grow, a core concept remains undefined: what is the relative importance and contribution of diabetes and hypertension in the development of early retinopathy signs? The answer of this fundamental question holds the key to better understanding of the systemic associations of early hypertensive and diabetic retinopathy. In this review, we summarize the similarities and differences of early retinopathy signs seen in diabetes and hypertension, and discuss the conceptual relevance from epidemiological, pathophysiological, and clinical perspectives.
Castro-Navarro, Verónica; Saktanasate, Jarin; Say, Emil Anthony T.; Chiang, Allen; Shields, Carol Lally
To report a case of retinal vasoproliferative tumor (VPT) with secondary epiretinal membrane (ERM) formation and vitreo-macular traction managed by pars plana vitrectomy (PPV) and membrane peel. A 29-year-old male was referred for management of decreased vision in the right eye (OD) for 1 week. Presenting visual acuity was 20/50 Snellen feet (ft) OD, and fundus examination showed an ERM associated with a reddish-yellow mass in the inferotemporal quadrant with overlying exudation, hemorrhage, and subretinal fluid consistent with VPT, and cryotherapy was recommended. Two months later, there was complete tumor regression, but there was decreased vision from progressive vitreomacular traction to 20/400 ft. PPV with combined ERM and internal limiting membrane (ILM) peel were performed with resolution of vitreomacular traction and improvement of visual acuity to 20/50 ft at 6 months. PPV with combined ERM and ILM peel is effective for vision loss secondary to ERM and vitreomacular traction associated with retinal VPT. PMID:27843233
Chen, Yu; Perusek, Lindsay; Maeda, Akiko
Vision is reliant upon converting photon signals to electrical information which is interpreted by the brain and therefore allowing us to receive information about our surroundings. However, when exposed to excessive light, photoreceptors and other types of cells in the retina can undergo light-induced cell death, termed light-induced retinal damage. In this review, we summarize our current knowledge regarding molecular events in the retina after excessive light exposure and mechanisms of light-induced retinal damage. We also introduce works which investigate potential roles of autophagy, an essential cellular mechanism required for maintaining homeostasis under stress conditions, in the illuminated retina and animal models of light-induced retinal damage. PMID:26325327
Wand, Amir; Gdor, Itay; Zhu, Jingyi; Sheves, Mordechai; Ruhman, Sanford
The ultrafast spectroscopic investigation of novel retinal proteins challenges existing notions concerning the course of primary events in these natural photoreceptors. We review two illustrations here. The first demonstrates that changes in the initial retinal configuration can alter the duration of photochemistry by nearly an order of magnitude in Anabaena sensory rhodopsin, making it as rapid as the ballistic photoisomerization in visual pigments. This prompted a reinvestigation of the much studied bacteriorhodopsin, leading to a similar trend as well, contrary to earlier reports. The second involves the study of xanthorhodopsin, an archaeal proton pump that includes an attached light-harvesting carotenoid. Pump-probe experiments demonstrate the efficient transfer of energy from carotenoid to retinal, providing a first glimpse at a cooperative multichromophore function, which is probably characteristic of many other proteins as well. Finally, we discuss measures required to advance our knowledge from kinetics to mode-specific dynamics concerning this expanding family of biological photoreceptors.
Barrett, Steven F.; Wright, Cameron H. G.; Oberg, Erik D.; Rockwell, Benjamin A.; Cain, Clarence P.; Jerath, Maya R.; Rylander, Henry G., III; Welch, Ashley J.
Successful retinal tracking subsystem testing results in vivo on rhesus monkeys using an argon continuous wave laser and an ultra-short pulse laser are presented. Progress on developing an integrated robotic retinal laser surgery system is also presented. Several interesting areas of study have developed: (1) 'doughnut' shaped lesions that occur under certain combinations of laser power, spot size, and irradiation time complicating measurements of central lesion reflectance, (2) the optimal retinal field of view to achieve simultaneous tracking and lesion parameter control, and (3) a fully digital versus a hybrid analog/digital tracker using confocal reflectometry integrated system implementation. These areas are investigated in detail in this paper. The hybrid system warrants a separate presentation and appears in another paper at this conference.
Chen, Yu; Perusek, Lindsay; Maeda, Akiko
Vision is reliant upon converting photon signals to electrical information which is interpreted by the brain and therefore allowing us to receive information about our surroundings. However, when exposed to excessive light, photoreceptors and other types of cells in the retina can undergo light-induced cell death, termed light-induced retinal damage. In this review, we summarize our current knowledge regarding molecular events in the retina after excessive light exposure and mechanisms of light-induced retinal damage. We also introduce works which investigate potential roles of autophagy, an essential cellular mechanism required for maintaining homeostasis under stress conditions, in the illuminated retina and animal models of light-induced retinal damage.
Fleming, Ioana; Balicki, Marcin; Koo, John; Iordachita, Iulian; Mitchell, Ben; Handa, James; Hager, Gregory; Taylor, Russell
This paper describes the development and results of initial testing of a cooperative robot assistant for retinal microsurgery. In the cooperative control paradigm, the surgeon and the robot share control of a tool attached to the robot through a force sensor. The system senses forces exerted by the operator on the tool and uses this information in various control modes to provide smooth, tremor-free, precise positional control and force scaling. The robot manipulator is specifically designed with retinal microsurgery in mind, having high efficacy, flexibility and ergonomics while meeting the accuracy and safety requirements of microsurgery. We have tested this robot on a biological model and we report the results for reliably cannulating approximately 80 microm diameter veins (equivalent in size to human retinal veins). We also describe improvements to the robot and the experimental setup facilitating more advanced set of experiments.
Luisi, Jonathan; Briley, David; Boretsky, Adam; Motamedi, Massoud
Spectral Domain Optical Coherence Tomography (SD-OCT) is a valuable diagnostic tool in both clinical and research settings. The depth-resolved intensity profiles generated by light backscattered from discrete layers of the retina provide a non-invasive method of investigating progressive diseases and injury within the eye. This study demonstrates the application of steerable convolution filters capable of automatically separating gradient orientations to identify edges and delineate tissue boundaries. The edge maps were recombined to measure thickness of individual retinal layers. This technique was successfully applied to longitudinally monitor changes in retinal morphology in a mouse model of laser-induced choroidal neovascularization (CNV) and human data from age-related macular degeneration patients. The steerable filters allow for direct segmentation of noisy images, while novel recombination of weaker segmentations allow for denoising post-segmentation. The segmentation before denoising strategy allows the rapid detection of thin retinal layers even under suboptimal imaging conditions.
Heaton, Larry C.; Smith, Matthew H.; Denninghoff, Kurt R.; Hillman, Lloyd W.
Several techniques for measuring the oxygen saturation of blood in retinal vessels have been reported. One interesting application of retinal vessel oximetry is the identification of occult blood loss in trauma victims. However, all the devices described to date are too bulky and cumbersome to be used in a trauma bay or in the field. We present a design for a handheld instrument that performs four-wavelength retinal vessel oximetry. This device is comparable in size and weight to a commercially available camcorder, and is suitable for use in the trauma bay. The compact size of this device could also extend its applications beyond traditional clinical settings, as it could be used by primary care physicians and home health care workers for the screening and monitoring of ophthalmic diseases. Principles of operation and preliminary data from the device will be described.
Lee, Joo Yong; Yoon, Young Hee; Kim, Ha Kyoung; Yoon, Hee Seong; Kang, Se Woong; Kim, June-Gone; Park, Kyu Hyung; Jo, Young Joon
We investigated the demographic characteristics and risk factors of Korean patients with naÏve central or branch retinal vein occlusion (CRVO or BRVO). This study enrolled 41 clinical sites throughout Korea and included 557 consecutive patients with retinal vein occlusion (RVO) from May through November 2010. A total of 557 patients with new-onset RVO participated in this study. Two hundred and three (36.4%) patients were diagnosed with CRVO and 354 (63.6%) patients were diagnosed with BRVO. Comparisons between the two groups showed that the prevalence of diabetes mellitus was significantly higher in CRVO patients and hypertension was significantly higher in BRVO patients (P = 0.001 and 0.002, respectively). Poor baseline visual acuity was significantly associated with female and old age in BRVO patients (P = 0.002 and 0.013, respectively), whereas the wide intraretinal hemorrhage (CRVO, P = 0.029; BRVO, P < 0.001) and the macular ischemia (CRVO, P < 0.001; BRVO, P < 0.001) were associated with both groups. The study results show the clinical features of RVO in Korean patients. Hypertension is strongly associated with BRVO and diabetes mellitus is more strongly associated with CRVO in Korean patients with RVO. As the first nationwide study performed by the Korean Retinal Society, the results of this study can be applied to future studies on RVO.
Kyogoku, T; Manabe, T; Tobe, T
Ischemia has been considered to play a role in the development of acute pancreatitis. The aim of this study was to investigate the effect of ischemia, caused by hemorrhagic shock, on cerulein-induced acute pancreatitis in rats. Acute pancreatitis was induced by the intravenous infusion of a supramaximally stimulating dose of cerulein (10 micrograms/kg/hr) for 6 hr. Hemorrhagic shock was induced by the removal of blood until the mean arterial blood pressure reached 35 mm Hg. This level was maintained for 30 min, after which time all the blood was reinfused. Hemorrhagic shock alone induced no morphological change in the pancreas. However, after the induction of hemorrhagic shock in animals treated with cerulein, hemorrhage and parenchymal necrosis were frequently observed in the pancreas. Seven of 20 rats (35%) receiving cerulein plus hemorrhagic shock had died by 48 hr after the start of cerulein infusion, whereas none of the rats in the cerulein or shock group died during this experiment. Cathepsin B activity in the pancreas of the cerulein plus shock group was significantly higher than in the other groups at 48 hr. These results suggest that ischemia may be a contributing factor in the pathogenesis of acute pancreatitis.
de Souza, Raoni Almeida; Díaz, Natalia; Nagem, Ronaldo Alves Pinto; Ferreira, Rafaela Salgado; Suárez, Dimas
Snake venom metalloproteinases are important toxins that play fundamental roles during envenomation. They share a structurally similar catalytic domain, but with diverse hemorrhagic capabilities. To understand the structural basis for this difference, we build and compare two dynamical models, one for the hemorrhagic atroxlysin-I from Bothrops atrox and the other for the non-hemorraghic leucurolysin-a from Bothrops leucurus. The analysis of the extended molecular dynamics simulations shows some changes in the local structure, flexibility and surface determinants that can contribute to explain the different hemorrhagic activity of the two enzymes. In agreement with previous results, the long Ω-loop (from residue 149 to 177) has a larger mobility in the hemorrhagic protein. In addition, we find some potentially-relevant differences at the base of the S1' pocket, what may be interesting for the structure-based design of new anti-venom agents. However, the sharpest differences in the computational models of atroxlysin-I and leucurolysin-a are observed in the surface electrostatic potential around the active site region, suggesting thus that the hemorrhagic versus non-hemorrhagic activity is probably determined by protein surface determinants.
Phillips, Courtney K; Lepor, Herbert
Spontaneous retroperitoneal hemorrhage is a rare clinical entity; signs and symptoms include pain, hematuria, and shock. Spontaneous retroperitoneal hemorrhage can be caused by tumors, such as renal cell carcinoma and angiomyolipoma; polyarteritis nodosa; and nephritis. The least common cause is segmental arterial mediolysis. Although computed tomography is used for the diagnosis of spontaneous retroperitoneal hemorrhage, it can miss segmental arterial mediolysis as the cause of the hemorrhage. The diagnosis of segmental arterial mediolysis as a cause of spontaneous retroperitoneal hemorrhage requires angiography, with pathologic confirmation for a definitive diagnosis.
Phillips, Courtney K; Lepor, Herbert
Spontaneous retroperitoneal hemorrhage is a rare clinical entity; signs and symptoms include pain, hematuria, and shock. Spontaneous retroperitoneal hemorrhage can be caused by tumors, such as renal cell carcinoma and angiomyolipoma; polyarteritis nodosa; and nephritis. The least common cause is segmental arterial mediolysis. Although computed tomography is used for the diagnosis of spontaneous retroperitoneal hemorrhage, it can miss segmental arterial mediolysis as the cause of the hemorrhage. The diagnosis of segmental arterial mediolysis as a cause of spontaneous retroperitoneal hemorrhage requires angiography, with pathologic confirmation for a definitive diagnosis. PMID:16985559
Assawachananont, Juthaporn; Mandai, Michiko; Okamoto, Satoshi; Yamada, Chikako; Eiraku, Mototsugu; Yonemura, Shigenobu; Sasai, Yoshiki; Takahashi, Masayo
Summary In this article, we show that mouse embryonic stem cell- or induced pluripotent stem cell-derived 3D retinal tissue developed a structured outer nuclear layer (ONL) with complete inner and outer segments even in an advanced retinal degeneration model (rd1) that lacked ONL. We also observed host-graft synaptic connections by immunohistochemistry. This study provides a “proof of concept” for retinal sheet transplantation therapy for advanced retinal degenerative diseases. PMID:24936453
Patton, Niall; Aslam, Tariq M; MacGillivray, Thomas; Deary, Ian J; Dhillon, Baljean; Eikelboom, Robert H; Yogesan, Kanagasingam; Constable, Ian J
As digital imaging and computing power increasingly develop, so too does the potential to use these technologies in ophthalmology. Image processing, analysis and computer vision techniques are increasing in prominence in all fields of medical science, and are especially pertinent to modern ophthalmology, as it is heavily dependent on visually oriented signs. The retinal microvasculature is unique in that it is the only part of the human circulation that can be directly visualised non-invasively in vivo, readily photographed and subject to digital image analysis. Exciting developments in image processing relevant to ophthalmology over the past 15 years includes the progress being made towards developing automated diagnostic systems for conditions, such as diabetic retinopathy, age-related macular degeneration and retinopathy of prematurity. These diagnostic systems offer the potential to be used in large-scale screening programs, with the potential for significant resource savings, as well as being free from observer bias and fatigue. In addition, quantitative measurements of retinal vascular topography using digital image analysis from retinal photography have been used as research tools to better understand the relationship between the retinal microvasculature and cardiovascular disease. Furthermore, advances in electronic media transmission increase the relevance of using image processing in 'teleophthalmology' as an aid in clinical decision-making, with particular relevance to large rural-based communities. In this review, we outline the principles upon which retinal digital image analysis is based. We discuss current techniques used to automatically detect landmark features of the fundus, such as the optic disc, fovea and blood vessels. We review the use of image analysis in the automated diagnosis of pathology (with particular reference to diabetic retinopathy). We also review its role in defining and performing quantitative measurements of vascular topography
Lauritzen, Thomas Z; Harris, Jordan; Mohand-Said, Saddek; Sahel, Jose A; Dorn, Jessy D; McClure, Kelly; Greenberg, Robert J
Retinal prostheses, which restore partial vision to patients blinded by outer retinal degeneration, are currently in clinical trial. The Argus II retinal prosthesis system was recently awarded CE approval for commercial use in Europe. While retinal prosthesis users have achieved remarkable visual improvement to the point of reading letters and short sentences, the reading process is still fairly cumbersome. This study investigates the possibility of using an epiretinal prosthesis to stimulate visual braille as a sensory substitution for reading written letters and words. The Argus II retinal prosthesis system, used in this study, includes a 10 × 6 electrode array implanted epiretinally, a tiny video camera mounted on a pair of glasses, and a wearable computer that processes the video and determines the stimulation current of each electrode in real time. In the braille reading system, individual letters are created by a subset of dots from a 3 by 2 array of six dots. For the visual braille experiment, a grid of six electrodes was chosen out of the 10 × 6 Argus II array. Groups of these electrodes were then directly stimulated (bypassing the camera) to create visual percepts of individual braille letters. Experiments were performed in a single subject. Single letters were stimulated in an alternative forced choice (AFC) paradigm, and short 2-4-letter words were stimulated (one letter at a time) in an open-choice reading paradigm. The subject correctly identified 89% of single letters, 80% of 2-letter, 60% of 3-letter, and 70% of 4-letter words. This work suggests that text can successfully be stimulated and read as visual braille in retinal prosthesis patients.
Nakano, Yuki; Shimazaki, Takeru; Kobayashi, Nobuko; Miyoshi, Yukiko; Ono, Aoi; Kobayashi, Mamoru; Shiragami, Chieko; Hirooka, Kazuyuki; Tsujikawa, Akitaka
Purpose To establish the normative database of retinal oximetry using Oxymap T1 in a healthy Japanese population, and study the reproducibility of the measurements in Japanese. Methods We measured oxygen saturation in the major retinal vessels with Oxymap T1 in 252 eyes of 252 healthy Japanese subjects. Fundus images acquired using Oxymap T1 were processed using built-in Oxymap Analyzer software. Reproducibility of retinal oximetry was investigated using 20 eyes of 20 healthy subjects. Results The mean retinal oxygen saturation of 4 quadrants in healthy Japanese was 97.0 ± 6.9% in arteries and 52.8 ± 8.3% in veins. The mean arteriovenous difference in oxygen saturation was 44.2 ± 9.2%. Both arterial and venous oxygen saturation were significantly lower in the temporal side of the retina, especially in the temporal-inferior vessels. However, the arteriovenous difference in oxygen saturation was limited in the 4 quadrants. Interphotograph, intervisit, and interevaluator intraclass correlation coefficients were 0.936–0.979, 0.809–0.837, and 0.732–0.947, respectively. In the major retinal arteries, oxygen saturation increased with age (r = 0.18, p<0.01), at a rate of 0.67% per 10 years. However, venous oxygen saturation showed no correlation with age. Conclusions This study provides the normative database for the Japanese population. The arterial saturation value appears to be higher than other previous studies. Mean retinal oximetry in 4 quadrants with Oxymap T1 has high reproducibility. PMID:27434373
Wang, Chih-Hung; Chen, Nai-Chuan; Tsai, Min-Shan; Yu, Ping-Hsun; Wang, An-Yi; Chang, Wei-Tien; Huang, Chien-Hua; Chen, Wen-Jone
Abstract Current guidelines recommend a period of moderate therapeutic hypothermia (TH) for comatose patients after cardiac arrest to improve clinical outcomes. However, in-vitro studies have reported platelet dysfunction, thrombocytopenia, and coagulopathy, results that might discourage clinicians from applying TH in clinical practice. We aimed to quantify the risks of hemorrhage observed in clinical studies. Medline and Embase were searched from inception to October 2015. Randomized controlled trials (RCTs) comparing patients undergoing TH with controls were selected, irrespective of the indications for TH. There were no restrictions for language, population, or publication year. Data on study characteristics, which included patients, details of intervention, and outcome measures, were extracted. Forty-three trials that included 7528 patients were identified from 2692 potentially relevant references. Any hemorrhage was designated as the primary outcome and was reported in 28 studies. The pooled results showed no significant increase in hemorrhage risk associated with TH (risk difference [RD] 0.005; 95% confidence interval [CI] −0.001–0.011; I2, 0%). Among secondary outcomes, patients undergoing TH were found to have increased risk of thrombocytopenia (RD 0.109; 95% CI 0.038–0.179; I2 57.3%) and transfusion requirements (RD 0.021; 95% CI 0.003–0.040; I2 0%). The meta-regression analysis indicated that prolonged duration of cooling may be associated with increased risk of hemorrhage. TH was not associated with increased risk of hemorrhage despite the increased risk of thrombocytopenia and transfusion requirements. Clinicians should cautiously assess each patient's risk-benefit profile before applying TH. PMID:26632746
McKeever, Tricia M.; Hall, Ian P.; Hubbard, Richard B.; Fogarty, Andrew W.
Objectives: Studies report that the risks of significant neurologic complications (including stroke, cerebral abscess, and migraine) and hemorrhagic sequelae are high in patients with hereditary hemorrhagic telangiectasia (HHT), and that life expectancy in this cohort is reduced. However, most published cohorts derive from specialist centers, which may be susceptible to bias. Methods: We used a population-based approach to estimate the risks of developing neurologic and hemorrhagic complications of HHT, the association of a diagnosis of HHT with common cardiovascular and malignant comorbidities, and also long-term survival of those with the disease. Results: From a UK primary care database of 3.5 million patients (The Health Improvement Network), we identified 675 cases with a diagnosis of HHT and compared them with 6,696 controls matched by age, sex, and primary care practice. Risks of stroke (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.2–2.6), cerebral abscess (OR 30.0, CI 3.1–288), and migraine (OR 1.7, CI 1.3–2.2) were elevated over controls. Bleeding complications including epistaxis (OR 11.6, CI 9.1–14.7) and gastrointestinal hemorrhage (OR 6.1, CI 2.8–13.4) were more common in cases with HHT. Survival of cases with HHT was poorer than controls with a hazard ratio for death of 2.0 (CI 1.6–2.6) and a median age at death 3 years younger. Conclusions: Patients with HHT are at substantially increased risk of serious neurologic and hemorrhagic complications of the disease. Because a diagnosis of HHT is associated with a significantly poorer survival compared with those who have no disease, evaluation of new strategies to improve clinical management is required. PMID:25862798
Shenkar, R; Abraham, E
Injury and blood loss are often followed by infection and the rapid development of organ system dysfunction, frequently involving mucosal sites, such as the lung and intestine. To examine possible mechanisms contributing to these conditions, we used semiquantitative polymerase chain reactions to determine cytokine mRNA expression among cellular populations isolated from mucosal and systemic anatomic sites of mice at predetermined time points following 30% blood volume hemorrhage with resuscitation 1 hr later. Within 1 hr after hemorrhage, significant increases were observed in mRNA levels for IL-1 alpha, IL-1 beta, IL-5, and TGF-beta in intraparenchymal pulmonary mononuclear cells. The levels of TGF-beta transcripts among alveolar macrophages were increased 1 hr following blood loss, and increase in IL-1 alpha transcripts was found starting 2 hr posthemorrhage. Cells from Peyer's patches showed significant increases in mRNA levels for IL-1 beta, IL-2, IL-5, IL-6, IFN-gamma, and TGF-beta during the 4 hr following hemorrhage. Significant increases in mRNA levels for IL-1 beta, TNF-alpha, and TGF-beta were present within 4 hr of blood loss among cells isolated from mesenteric lymph nodes. The expression of mRNA for most cytokines was not significantly altered in splenocytes or peripheral blood mononuclear cells at any time point following hemorrhage. These experiments demonstrate that blood loss, even if resuscitated, produces significant increases in proinflammatory and immunoregulatory cytokine gene transcription as early as 1 hr following hemorrhage. These posthemorrhage alterations in cytokine mRNA expression were particularly prominent at mucosal sites, suggesting a mechanism for the increased incidence of pulmonary and intestinal involvement in organ system failure following severe blood loss and injury.
Wang, Runsheng; Qian, Lu; Wang, Yi; Zheng, Yi; Du, Shanshuang; Lei, Tao; Lv, Peilin; Long, Tan; Wang, Wenjun
Background Central retinal artery occlusion (CRAO) is the occlusion of the central retinal artery resulting in retinal infarction and acute vision loss. Digital subtraction angiography (DSA)–guided superselective ophthalmic artery or selective carotid thrombolysis remains the preferred treatment method for CRAO. This study aimed to evaluate the safety and clinical efficacy of the novel ophthalmic artery branch retrograde thrombolytic intervention for CRAO. Material/Methods Fifty patients with monocular CRAO were enrolled, including 28 males and 22 females (mean age: 55.7±2.3 years). The patients were randomly divided into two groups for thrombolysis with urokinase (400,000 U) and papaverine (30 mg) by either ophthalmic artery branch retrograde intervention (group A, n=26) or superselective ophthalmic artery/selective carotid intervention (group B, n=24). There was no significant difference in age (P=0.58), gender ratio (P=0.49), and time to onset (P=1.00) between the two groups. The adverse reactions and clinical efficacy were evaluated by postoperative DSA, fundus fluorescein angiography (FFA), and visual acuity tests. Results No serious complications, abnormal eye movement, or vitreous hemorrhage occurred in either group. DSA showed that group A had an effective rate (92.30%) comparable to that of group B (100%, χ2=2.08, P=0.25). FFA suggested that both groups had similar treatment efficacy (χ2=3.09, P=0.21). Visual acuity tests also confirmed a similar efficacy of the two intervention approaches (χ2=0.25, P=0.88). Conclusions The developed novel ophthalmic artery branch retrograde intervention is highly effective and safe for CRAO, and may be a superior method compared with the conventional approach. PMID:28064304
Velez-Montoya, Raul; Guerrero-Naranjo, Jose Luis; Garcia-Aguirre, Gerardo; Morales-Cantón, Virgilio; Fromow-Guerra, Jans; Quiroz-Mercado, Hugo
Background Perfluorocarbon liquid (PCL)-perfused vitrectomy has been shown in previous studies to be feasible, safe, and to have advantages in managing complicated cases of tractional retinal detachment. The present study had the objectives of describing the anatomical results and measuring surgical time and PCL consumption when combining PCL-perfused techniques with modern vitrectomy equipment. Methods A prospective, interventional consecutive case series was investigated. We enrolled patients with diabetic tractional retinal detachment, complicated by proliferative vitreoretinopathy and poor vision. A 23 gauge PCL-perfused vitrectomy was done with three-dimensional settings. During the procedure, we assessed the degree of surgical bleeding, visualization quality, and difficulty of membrane dissections. Visual acuity, intraocular pressure, and anatomical success were assessed at one and 3 months of follow-up. Results Twelve patients were enrolled in this study. There were no statistical significant changes in intraocular pressure and visual acuity throughout the follow-up period. Surgery was performed in a hemorrhage-free environment in almost all cases, with good visualization and low technical difficulty. The mean complete surgical time was 94.92 ± 25.03 minutes. The mean effective vitrectomy time was 22.50 ± 19.04 minutes and the mean PCL consumption was 25.08 ± 9.76 mL, with a speed of 1.11 mL/minute. Anatomical success was 67% at 3 months. Conclusion Although the technique proved to have some advantages in managing complicated cases of diabetic tractional retinal detachment, there was a high consumption of PCL. A redesign of the entire system is needed in order to decrease the amount of PCL needed for the technique. PMID:22267907
Background One of the promises in regenerative medicine is to regenerate or replace damaged tissues. The embryonic chick can regenerate its retina by transdifferentiation of the retinal pigmented epithelium (RPE) and by activation of stem/progenitor cells present in the ciliary margin. These two ways of regeneration occur concomitantly when an external source of fibroblast growth factor 2 (FGF2) is present after injury (retinectomy). During the process of transdifferentiation, the RPE loses its pigmentation and is reprogrammed to become neuroepithelium, which differentiates to reconstitute the different cell types of the neural retina. Somatic mammalian cells can be reprogrammed to become induced pluripotent stem cells by ectopic expression of pluripotency-inducing factors such as Oct4, Sox2, Klf4, c-Myc and in some cases Nanog and Lin-28. However, there is limited information concerning the expression of these factors during natural regenerative processes. Organisms that are able to regenerate their organs could share similar mechanisms and factors with the reprogramming process of somatic cells. Herein, we investigate the expression of pluripotency-inducing factors in the RPE after retinectomy (injury) and during transdifferentiation in the presence of FGF2. Results We present evidence that upon injury, the quiescent (p27Kip1+/BrdU-) RPE cells transiently dedifferentiate and express sox2, c-myc and klf4 along with eye field transcriptional factors and display a differential up-regulation of alternative splice variants of pax6. However, this transient process of dedifferentiation is not sustained unless FGF2 is present. We have identified lin-28 as a downstream target of FGF2 during the process of retina regeneration. Moreover, we show that overexpression of lin-28 after retinectomy was sufficient to induce transdifferentiation of the RPE in the absence of FGF2. Conclusion These findings delineate in detail the molecular changes that take place in the RPE during
Wessendorf, Kurt O.; Christenson, Todd R.; Myers, Ramona Lynn; Lemp, Thomas; Okandan, Murat; James, Conrad D.; Shul, Randy John; Stein, David J.; Baker, Michael Sean
Retinal prosthesis projects around the world have been pursuing a functional replacement system for patients with retinal degeneration. In this paper, the concept for a micromachined conformal electrode array is outlined. Individual electrodes are designed to float on micromachined springs on a substrate that will enable the adjustment of spring constants-and therefore contact force-by adjusting the dimensions of the springs at each electrode. This also allows the accommodation of the varying curvature/topography of the retina. We believe that this approach provides several advantages by improving the electrode/tissue interface as well as generating some new options for in-situ measurements and overall system design.
Pardue, Machelle T; Chrenek, Micah A; Schmidt, Robin H; Nickerson, John M; Boatright, Jeffrey H
For many patients suffering vision loss due to retinal degeneration, the potential exists for therapeutic intervention to halt or delay disease progression. Proposed molecular, pharmacological, and surgical treatments are expensive and complicated. Finding low-cost interventions to sustain vision and thereby quality of life is vitally important. This chapter reviews findings from animal model and human subject studies indicating that physical exercise has direct, beneficial effects on regions of the central nervous system and is protective against neurodegenerative disease, including recent data from animal models showing similar effects for retina and vision. Potential local and systemic mechanistic pathways for exercise-induced retinal neuroprotection are discussed.
Maksymowicz, Małgorzata; Raczyńska, Krystyna; Maksymowicz, Jarosław
The study covered 79 patients after treatment of retinal detachment. Double vision, strabismus and disturbances of eyeballs motility were found. Up to 12 months after intervention, the deterioration of binocular vision was observed in 48.28 to 89.66% of patients, depending on the method used. The majority of disturbances were observed during the first 3 months with tendency to gradual subsidence during consecutive 9 months. A patient, after treatment of retinal detachment, can be qualified to return to work where stereopsis is needed under condition that ophthalmologic examination is done every three months during the first year after operation and than once a year.
Pappin, A; Shenker, N; Hack, M; Redline, R W
To assess the possible relationship between exogenous surfactant therapy and pulmonary hemorrhage in premature infants, we compared autopsy findings in 15 infants treated with exogenous surfactant and in 29 who died before the introduction of surfactant therapy. Infants who met the following criteria were included: birth weight 501 to 1500 gm, survival 4 hours to 7 days, and no congenital anomalies. Average birth weight, gestational age, and age at death were equivalent for the two groups. High rates of pulmonary hemorrhage were present in both groups (treated 80% vs untreated 83%). The untreated group had higher incidences of interstitial hemorrhage and lung hematomas and significantly more large interstitial hemorrhages: 31% untreated versus 0% treated (p < 0.05). The overall rate of intraalveolar hemorrhage was similar in the two groups, but surfactant-treated infants were more likely to have extensive intraalveolar hemorrhage: 53% versus 14% (p < 0.05). Most surfactant-treated infants who survived more than 24 hours had extensive intraalveolar hemorrhage (8/9). Patients who had extensive intraalveolar hemorrhage, with or without prior surfactant therapy, frequently had clinically significant pulmonary hemorrhage (7/12). These findings indicate that infants who die after surfactant therapy have higher rates of a specific type of pulmonary hemorrhage--extensive intraalveolar hemorrhage.
Noble, M J; Alvarez, E V
A healthy young woman suffered complete loss of the vision of one eye following a blunt ocular injury. She sustained a combined occlusion of the central retinal artery and central retinal vein of the affected eye. Initially few retinal haemorrhages were present, but they increased considerably in number and size during the day following injury. Images PMID:3689734
Ferraz, Daniel Araújo; Bressanim, Gláucio Luciano; Morita, Celso; Takahashi, Walter Yukihiko
The purpose of this case series is to describe if the intravitreal use of bevacizumab and perfluoropropane gas (C3F8) would be beneficial to the displacement of subretinal hemorrhage in patients with age-related macular degeneration (AMD). A retrospective study of 5 eyes that received concurrent intravitreal injection of bevacizumab and C3F8 was performed. The results were graded according to blood displacement under the fovea, best final visual acuity and intraoperative complications. At the initial presentation, mean age of patients was 72.6 +/- 8.9 years-old and duration of symptoms was 13 +/- 9.7 days. From the 5 patients, 3 (60%) were male and 2 (40%) female. The success of submacular hemorrhage full displacement was achieved in 4 patients. The mean preoperative visual acuity (VA) was 1.12 +/- 0.34 logMAR and the mean postoperative VA was 0.92 +/- 0.4 logMAR. No cases of retinal detachment, endophthalmitis, vitreous hemorrhage, uveitis, cataracts and increased intraocular pressure were noted during the follow-up period. Intravitreal bevacizumab and C3F8 injection, associated to prone position can be a valuable therapeutic option for eyes with neovascular age-related macular degeneration and subretinal hemorrhage to the blood displacement out of the foveal area.
Salehi, Hossein; Amirpour, Noushin; Razavi, Shahnaz; Esfandiari, Ebrahim; Zavar, Reihaneh
Retinal disease caused by retinal cell apoptosis leads to irreversible vision loss. Stem cell investigation efforts have been made to solve and cure retinal disorders. There are several sources of stem cells which have been used in these experiments. Numerous studies demonstrated that transplanted stem cells can migrate into and integrate in different layers of retina. Among these, mesenchymal stem cells (MSCs) were considered a promising source for cell therapy. Here, we review the literature assessing the potential of MSCs to differentiate into retinal cells in vivo and in vitro as well as their clinical application. However, more investigation is required to define the protocols that optimize stem cell differentiation and their functional integration in the retina.
Shalev, Idan; Moffitt, Terrie E; Wong, Tien Y; Meier, Madeline H; Houts, Renate M; Ding, Jie; Cheung, Carol Y; Ikram, M Kamran; Caspi, Avshalom; Poulton, Richie
Why do more intelligent people live healthier and longer lives? One possibility is that intelligence tests assess health of the brain, but psychological science has lacked technology to evaluate this hypothesis. Digital retinal imaging, a new, noninvasive method to visualize microcirculation in the eye, may reflect vascular conditions in the brain. We studied the association between retinal vessel caliber and neuropsychological functioning in the representative Dunedin birth cohort. Wider venular caliber was associated with poorer neuropsychological functioning at midlife, independently of potentially confounding factors. This association was not limited to any specific test domain and extended to informants' reports of cohort members' cognitive difficulties in everyday life. Moreover, wider venular caliber was associated with lower childhood IQ tested 25 years earlier. The findings indicate that retinal venular caliber may be an indicator of neuropsychological health years before the onset of dementing diseases and suggest that digital retinal imaging may be a useful investigative tool for psychological science.
Retinal diseases are the main causes of blindness in the Western world. Diabetic retinopathy and age-related macular degeneration continue to increase in prevalence and as main causes of vision loss. Intravitreal anti-VEGF and steroid injections have raised new expectations for their successful treatment. These agents act by stabilizing the blood-retinal barrier (BRB). Our group defined the BRB by identifying for the first time the tight junctions that unite retinal endothelial cells and are the basis for the inner BRB, an observation later confirmed in retinal pigment epithelial cells and in brain vessels. A major role of active transport processes was also identified. Today, the BRB is understood to play a fundamental role in retinal function in both health and disease. Retinal edema, an ubiquitous manifestation of retinal disease, is directly associated with breakdown of the BRB and with vision loss. In its most common form (i.e., vasogenic edema), due to breakdown of the BRB, Starling's law of capillary filtration may be used to interpret the mechanisms of fluid accumulation in the retina. The main factors involved in the development of retinal edema are BRB permeability, capillary hydrostatic pressure, tissue hydrostatic pressure, tissue osmotic pressure, and plasma osmotic pressure. In the clinical environment, breakdown of the BRB has been identified by fluorescein angiography and vitreous fluorometry, requiring the intravenous administration of fluorescein. An OCT-based method, OCT-Leakage, recently introduced by our group is capable of noninvasively identifying and quantifying sites of alteration of the BRB by mapping areas of lower-than-normal optical reflectivity, thus reflecting changes in the retinal extracellular fluid. We found good correspondence between the location of increased areas of low optical reflectivity identified by OCT-Leakage and the main sites of leakage on fluorescein angiography. Furthermore, with OCT-Leakage the areas of abnormal
Light, Jacob G; Fransen, James W; Adekunle, Adewumi N; Adkins, Alice; Pangeni, Gobinda; Loudin, James; Mathieson, Keith; Palanker, Daniel V; McCall, Maureen A; Pardue, Machelle T
Photovoltaic arrays (PVA) implanted into the subretinal space of patients with retinitis pigmentosa (RP) are designed to electrically stimulate the remaining inner retinal circuitry in response to incident light, thereby recreating a visual signal when photoreceptor function declines or is lost. Preservation of inner retinal circuitry is critical to the fidelity of this transmitted signal to ganglion cells and beyond to higher visual targets. Post-implantation loss of retinal interneurons or excessive glial scarring could diminish and/or eliminate PVA-evoked signal transmission. As such, assessing the morphology of the inner retina in RP animal models with subretinal PVAs is an important step in defining biocompatibility and predicting success of signal transmission. In this study, we used immunohistochemical methods to qualitatively and quantitatively compare inner retinal morphology after the implantation of a PVA in two RP models: the Royal College of Surgeons (RCS) or transgenic S334ter-line 3 (S334ter-3) rhodopsin mutant rat. Two PVA designs were compared. In the RCS rat, we implanted devices in the subretinal space at 4 weeks of age and histologically examined them at 8 weeks of age and found inner retinal morphology preservation with both PVA devices. In the S334ter-3 rat, we implanted devices at 6-12 weeks of age and again, inner retinal morphology was generally preserved with either PVA design 16-26 weeks post-implantation. Specifically, the length of rod bipolar cells and numbers of cholinergic amacrine cells were maintained along with their characteristic inner plexiform lamination patterns. Throughout the implanted retinas we found nonspecific glial reaction, but none showed additional glial scarring at the implant site. Our results indicate that subretinally implanted PVAs are well-tolerated in rodent RP models and that the inner retinal circuitry is preserved, consistent with our published results showing implant-evoked signal transmission.
Aplin, Felix P; Vessey, Kirstan A; Luu, Chi D; Guymer, Robyn H; Shepherd, Robert K; Fletcher, Erica L
In rodents and felines, intravitreal administration of adenosine triphosphate (ATP) has been shown to induce photoreceptor death providing a tractable model of retinal degeneration in these species. This study investigated the long term effects of photoreceptor loss in an ATP induced feline model of retinal degeneration. Six normal sighted felines were unilaterally blinded using intravitreal ATP injections and assessed using electroretinography (ERG) and optical coherence tomography (OCT). At 30 h (n = 3) or 12 weeks (n = 3) post-injection, the animals were euthanized and the eyes enucleated. Retinae were sectioned and labeled using immunohistochemistry for markers of cell death, neural remodeling and gliosis. Ongoing cell death and retinal degeneration was observed in the outer retina at both 30 h and 12 weeks following unilateral ATP injection. Markers of mid to late-stage retinal remodeling such as cell displacement and aberrant neurite growth were observed in the inner retina at 12 weeks post-injection. Ganglion cells appeared to remain intact in ATP injected eyes. Müller cell gliosis was observed throughout the inner and outer retina, in some parts completely enveloping and/or displacing the surviving neural tissue. Our data suggests that the ATP injected feline retina continues to undergo progressive retinal degeneration and exhibits abnormalities consistent with a description of retinal remodeling commonly seen in other models of retinal degeneration. These findings validate the use of intravitreal ATP injection in feline as a large animal model of retinal degeneration which may aid in development of therapies aiming to restore visual function after photoreceptor degeneration.
Chen, San-Ni; Hwang, Jiunn-Feng; Wu, Wen-Chuan
This is an observational study of fluorescein angiography (FA) in consecutive patients with rhegmatogenous retinal detachment (RRD) in Changhua Christian Hospital to investigate the peripheral retinal vascular patterns in those patients. All patients had their age, sex, axial length (AXL), and refraction status (RF) recorded. According to the findings in FA of the peripheral retina, the eyes were divided into 4 groups: in group 1, there was a ramified pattern of peripheral retinal vasculature with gradual tapering; in group 2, there was an abrupt ending of peripheral vasculature with peripheral non-perfusion; in group 3, there was a curving route of peripheral vasculature forming vascular arcades or anastomosis; and in group 4, the same as in group 3, but with one or more wedge-shaped avascular notches. Comparisons of age, sex, AXL, and RF, association of breaks with lattice degeneration and retinal non-perfusion, surgical procedures utilized, and mean numbers of operations were made among the four groups. Of the 73 eyes studied, there were 13 eyes (17.8%) in group 1, 3 eyes (4.1%) in group 2, 40 eyes (54.8%) in group 3 and 17 eyes (23.3%) in group 4. Significant differences in age, AXL and RF, and association of retinal breaks to non-perfusion were noted among the four groups. Patients in group 1 had older ages, while younger ages were noted in groups 3 and 4. Eyes in group 1 had the shortest average AXL and were least myopic in contrast to the eyes in groups 3 and 4. Association of retinal breaks and retinal non-perfusion was significantly higher in groups 2, 3 and 4 than in group 1. In conclusion, peripheral vascular anomalies are common in cases with RRD. Patients with peripheral non-perfusion tend to be younger, with longer axial length and have the breaks associated with retinal non-perfusion. PMID:26909812
Aplin, Felix P.; Vessey, Kirstan A.; Luu, Chi D.; Guymer, Robyn H.; Shepherd, Robert K.; Fletcher, Erica L.
In rodents and felines, intravitreal administration of adenosine triphosphate (ATP) has been shown to induce photoreceptor death providing a tractable model of retinal degeneration in these species. This study investigated the long term effects of photoreceptor loss in an ATP induced feline model of retinal degeneration. Six normal sighted felines were unilaterally blinded using intravitreal ATP injections and assessed using electroretinography (ERG) and optical coherence tomography (OCT). At 30 h (n = 3) or 12 weeks (n = 3) post-injection, the animals were euthanized and the eyes enucleated. Retinae were sectioned and labeled using immunohistochemistry for markers of cell death, neural remodeling and gliosis. Ongoing cell death and retinal degeneration was observed in the outer retina at both 30 h and 12 weeks following unilateral ATP injection. Markers of mid to late-stage retinal remodeling such as cell displacement and aberrant neurite growth were observed in the inner retina at 12 weeks post-injection. Ganglion cells appeared to remain intact in ATP injected eyes. Müller cell gliosis was observed throughout the inner and outer retina, in some parts completely enveloping and/or displacing the surviving neural tissue. Our data suggests that the ATP injected feline retina continues to undergo progressive retinal degeneration and exhibits abnormalities consistent with a description of retinal remodeling commonly seen in other models of retinal degeneration. These findings validate the use of intravitreal ATP injection in feline as a large animal model of retinal degeneration which may aid in development of therapies aiming to restore visual function after photoreceptor degeneration. PMID:27199678
Tokuda, Takashi; Sugitani, Sachie; Asano, Ryosuke; Taniyama, Mari; Terasawa, Yasuo; Uehara, Akihiro; Kagawa, Keiichiro; Nunoshita, Masahiro; Tano, Yasuo; Ohta, Jun
A CMOS LSI-based neural stimulator was developed for retinal prosthesis. The stimulator was designed with “multi-chip” architecture. Small LSI neural stimulators named “Unit Chip” were assembled on a flexible substrate into a flexible, multi-site retinal stimulator. An experimental system equipped with the fabricated LSI-based flexible stimulator was configured and current injection functionality was demonstrated in saline solution. Materials for improved charge injection were also discussed.
Boeckaert, J; Vandewalle, E; Stalmans, I
This review will highlight a new technology and recent insights into measuring retinal oxygen saturation in several ophthalmic diseases. A growing body of evidence suggests that disturbances in retinal blood flow and oxygenation are related to several retinopathies and glaucoma, which can severely impair vision. The retinal oximeter may allow researchers and physicians to gain deeper insights into retinal physiology and clarify the impact of ischemia on retinal health and function. There are two commercially available systems to measure retinal oxygen saturation: the Oxymap retinal oximeter (Reykjavik, Iceland) and the Imedos Systems UG (Jena, Germany). In this review we will focus on the results obtained with Oxymap. Direct and non-invasive measurement of retinal oxygen saturation have potentially useful diagnostic and therapeutic indications in various eye diseases such as diabetic retinopathy, age-related macular degeneration, central retinal vein and artery occlusion, anterior ischemic optic neuropathy and retinopathy of prematurity. Despite several limitations, oxygen saturation assessment in the retinal vessels is a significant advancement in the understanding of ocular diseases. Nevertheless, further studies are needed to validate the use of oximetry in retinal vasopathies and glaucoma.
Moss, Heather E
The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross-sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease, and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion, and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk.
Cohn, Brian A.; Collin, Shaun P.; Wainwright, Peter C.; Schmitz, Lars
Retinal topography maps are a widely used tool in vision science, neuroscience, and visual ecology, providing an informative visualization of the spatial distribution of cell densities across the retinal hemisphere. Here, we introduce Retina, an R package for computational mapping, inspection of topographic model fits, and generation of average maps. Functions in Retina take cell count data obtained from retinal wholemounts using stereology software. Accurate visualizations and comparisons between different eyes have been difficult in the past, because of deformation and incisions of retinal wholemounts. We account for these issues by incorporation of the R package Retistruct, which results in a retrodeformation of the wholemount into a hemispherical shape, similar to the original eyecup. The maps are generated by thin plate splines, after the data were transformed into a two-dimensional space with an azimuthal equidistant plot projection. Retina users can compute retinal topography maps independent of stereology software choice and assess model fits with a variety of diagnostic plots. Functionality of Retina also includes species average maps, an essential feature for interspecific analyses. The Retina package will facilitate rigorous comparative studies in visual ecology by providing a robust quantitative approach to generate retinal topography maps. PMID:26230981
Palkovits, Stefan; Lasta, Michael; Told, Reinhard; Schmidl, Doreen; Werkmeister, René; Cherecheanu, Alina Popa; Garhöfer, Gerhard; Schmetterer, Leopold
Cerebral and retinal blood flow are dependent on local neuronal activity. Several studies quantified the increase in cerebral blood flow and oxygen consumption during activity. In the present study we investigated the relation between changes in retinal blood flow and oxygen extraction during stimulation with diffuse luminance flicker and the influence of breathing gas mixtures with different fractions of O2 (FiO2; 100% 15% and 12%). Twenty-four healthy subjects were included. Retinal blood flow was studied by combining measurement of vessel diameters using the Dynamic Vessel Analyser with measurements of blood velocity using laser Doppler velocimetry. Oxygen saturation was measured using spectroscopic reflectometry and oxygen extraction was calculated. Flicker stimulation increased retinal blood flow (57.7 ± 17.8%) and oxygen extraction (34.6 ± 24.1%; p < 0.001 each). During 100% oxygen breathing the response of retinal blood flow and oxygen extraction was increased (p < 0.01 each). By contrast, breathing gas mixtures with 12% and 15% FiO2 did not alter flicker-induced retinal haemodynamic changes. The present study indicates that at a comparable increase in blood flow the increase in oxygen extraction in the retina is larger than in the brain. During systemic hyperoxia the blood flow and oxygen extraction responses to neural stimulation are augmented. The underlying mechanism is unknown.
Lawson, Eric C.; Han, Moon K.; Sellers, Jana T.; Chrenek, Micah A.; Hanif, Adam; Gogniat, Marissa A.
Aerobic exercise is a common intervention for rehabilitation of motor, and more recently, cognitive function (Intlekofer and Cotman, 2013; Wood et al., 2012). While the underlying mechanisms are complex, BDNF may mediate much of the beneficial effects of exercise to these neurons (Ploughman et al., 2007; Griffin et al., 2011; Real et al., 2013). We studied the effects of aerobic exercise on retinal neurons undergoing degeneration. We exercised wild-type BALB/c mice on a treadmill (10 m/min for 1 h) for 5 d/week or placed control mice on static treadmills. After 2 weeks of exercise, mice were exposed to either toxic bright light (10,000 lux) for 4 h to induce photoreceptor degeneration or maintenance dim light (25 lux). Bright light caused 75% loss of both retinal function and photoreceptor numbers. However, exercised mice exposed to bright light had 2 times greater retinal function and photoreceptor nuclei than inactive mice exposed to bright light. In addition, exercise increased retinal BDNF protein levels by 20% compared with inactive mice. Systemic injections of a BDNF tropomyosin-receptor-kinase (TrkB) receptor antagonist reduced retinal function and photoreceptor nuclei counts in exercised mice to inactive levels, effectively blocking the protective effects seen with aerobic exercise. The data suggest that aerobic exercise is neuroprotective for retinal degeneration and that this effect is mediated by BDNF signaling. PMID:24523530
Heßler, Henning; Zimmermann, Hanna; Oberwahrenbrock, Timm; Kadas, Ella Maria; Mikolajczak, Janine; Brandt, Alexander U.; Kauert, Andreas; Paul, Friedemann; Schreiber, Stephan J.
Introduction. Carotid artery disease (CAD) comprising high-grade internal carotid artery stenosis (CAS) or carotid artery occlusion (CAO) may lead to ipsilateral impaired cerebral blood flow and reduced retinal blood supply. Objective. To examine the influence of chronic CAD on retinal blood flow, retinal morphology, and visual function. Methods. Patients with unilateral CAS ≥ 50% (ECST criteria) or CAO were grouped according to the grade of the stenosis and to the flow direction of the ophthalmic artery (OA). Retinal perfusion was measured by transorbital duplex ultrasound, assessing central retinal artery (CRA) blood flow velocities. In addition, optic nerve and optic nerve sheath diameter were measured. Optical coherence tomography (OCT) was performed to study retinal morphology. Visual function was assessed using high- and low-contrast visual paradigms. Results. Twenty-seven patients were enrolled. Eyes with CAS ≥ 80%/CAO and retrograde OA blood flow showed a significant reduction in CRA peak systolic velocity (no-CAD side: 0.130 ± 0.035 m/s, CAS/CAO side: 0.098 ± 0.028; p = 0.005; n = 12). OCT, optic nerve thicknesses, and visual functional parameters did not show a significant difference. Conclusion. Despite assessable hemodynamic effects, chronic high-grade CAD does not lead to gaugeable morphological or functional changes of the retina. PMID:26558275
Pavesio, C E; Mitchell, S M; Barton, K; Schwartz, S D; Towler, H M; Lightman, S
Retinal infections caused by the varicella-zoster virus (VZV) have been reported in immunocompetent and immunocompromised individuals. Two cases of a VZV-related retinitis are described with the characteristic features of the recently described progressive outer retinal necrosis (PORN) syndrome. Both patients suffered from the acquired immunodeficiency syndrome (AIDS) with greatly reduced peripheral blood CD4+ T lymphocyte counts, and presented with macular retinitis without vitritis. The disease was bilateral in one case and unilateral in the other. The clinical course was rapidly progressive with widespread retinal involvement and the development of rhegmatogenous retinal detachment with complete loss of vision in the affected eyes despite intensive intravenous antiviral therapy. VZV DNA was identified in vitreous biopsies, by molecular techniques based on the polymerase chain reaction (PCR), in both patients. At present, the use of very high-dose intravenous acyclovir may be the best therapeutic option in these patients for whom the visual prognosis is poor. Intravitreal antiviral drugs could also contribute to the management of these cases.
Lawson, Eric C; Han, Moon K; Sellers, Jana T; Chrenek, Micah A; Hanif, Adam; Gogniat, Marissa A; Boatright, Jeffrey H; Pardue, Machelle T
Aerobic exercise is a common intervention for rehabilitation of motor, and more recently, cognitive function (Intlekofer and Cotman, 2013; Wood et al., 2012). While the underlying mechanisms are complex, BDNF may mediate much of the beneficial effects of exercise to these neurons (Ploughman et al., 2007; Griffin et al., 2011; Real et al., 2013). We studied the effects of aerobic exercise on retinal neurons undergoing degeneration. We exercised wild-type BALB/c mice on a treadmill (10 m/min for 1 h) for 5 d/week or placed control mice on static treadmills. After 2 weeks of exercise, mice were exposed to either toxic bright light (10,000 lux) for 4 h to induce photoreceptor degeneration or maintenance dim light (25 lux). Bright light caused 75% loss of both retinal function and photoreceptor numbers. However, exercised mice exposed to bright light had 2 times greater retinal function and photoreceptor nuclei than inactive mice exposed to bright light. In addition, exercise increased retinal BDNF protein levels by 20% compared with inactive mice. Systemic injections of a BDNF tropomyosin-receptor-kinase (TrkB) receptor antagonist reduced retinal function and photoreceptor nuclei counts in exercised mice to inactive levels, effectively blocking the protective effects seen with aerobic exercise. The data suggest that aerobic exercise is neuroprotective for retinal degeneration and that this effect is mediated by BDNF signaling.
Gerth, C; Zawadzki, RJ; Werner, JS; Héon, E
Objectives To investigate retinal microstructure of patients affected with malattia leventinese (MLVT) and mutation in the EFEMP1 gene using high-resolution optical coherence tomography (OCT). Methods Patients diagnosed with MLVT received a comprehensive eye exam, full-field and multifocal electroretinogram testing and imaging with a high-resolution Fourier domain OCT (Fd-OCT, UC Davis Medical Center, Davis, USA; axial resolution: 4.5 μm, acquisition speed: 9 frames s−1, 1000 A scans s−1) combined with a flexible scanning head (Bioptigen Inc. Durham, NC, USA). Results Two related patients aged 30 and 60 years, with MLVT and identified c.R345W mutation in the EFEMP1 gene, were tested. Mother and daughter showed a variable phenotype with reduced vision function in the younger patient, whereas the mother had a ‘form frustre’. Fd-OCT revealed extensive or focal sub-retinal pigment epithelium (RPE) deposits, separation of RPE and Bruch's membrane, and disruption of the photoreceptor outer and inner segment layers. No outer retinal changes were visible outside areas with sub-RPE deposits. Conclusion Retinal structure in EFEMP1 retinal dystrophy is reflected by morphological changes within the RPE/Bruch's membrane complex with accumulation of sub-RPE material associated with disrupted photoreceptor integrity. The pattern of microstructural retinal abnormalities is similar but with a different extent in patients with variable phenotypes. PMID:18791549
Palkovits, Stefan; Lasta, Michael; Told, Reinhard; Schmidl, Doreen; Werkmeister, René; Cherecheanu, Alina Popa; Garhöfer, Gerhard; Schmetterer, Leopold
Cerebral and retinal blood flow are dependent on local neuronal activity. Several studies quantified the increase in cerebral blood flow and oxygen consumption during activity. In the present study we investigated the relation between changes in retinal blood flow and oxygen extraction during stimulation with diffuse luminance flicker and the influence of breathing gas mixtures with different fractions of O2 (FiO2; 100% 15% and 12%). Twenty-four healthy subjects were included. Retinal blood flow was studied by combining measurement of vessel diameters using the Dynamic Vessel Analyser with measurements of blood velocity using laser Doppler velocimetry. Oxygen saturation was measured using spectroscopic reflectometry and oxygen extraction was calculated. Flicker stimulation increased retinal blood flow (57.7 ± 17.8%) and oxygen extraction (34.6 ± 24.1%; p < 0.001 each). During 100% oxygen breathing the response of retinal blood flow and oxygen extraction was increased (p < 0.01 each). By contrast, breathing gas mixtures with 12% and 15% FiO2 did not alter flicker–induced retinal haemodynamic changes. The present study indicates that at a comparable increase in blood flow the increase in oxygen extraction in the retina is larger than in the brain. During systemic hyperoxia the blood flow and oxygen extraction responses to neural stimulation are augmented. The underlying mechanism is unknown. PMID:26672758
Retinal proteins are excellent systems for understanding essential physiological processes such as signal transduction and ion pumping. Although the conjugated polyene system of the retinal chromophore is best described with quantum mechanics, simulations of the long-timescale dynamics of a retinal protein in its physiological, flexible, lipid-membrane environment can only be performed at the classical mechanical level. Torsional energy barriers are a critical ingredient of the classical force-field parameters. Here we review briefly current retinal force fields and discuss new quantum mechanical computations to assess how the retinal Schiff base model and the approach used to derive the force-field parameters may influence the torsional potentials.
Gahlaut, Nivriti; Suarez, Sandra; Uddin, Md Imam; Gordon, Andrew Y; Evans, Stephanie M; Jayagopal, Ashwath
Retinal vascular diseases, including diabetic retinopathy, neovascular age related macular degeneration, and retinal vein occlusion, are leading causes of blindness in the Western world. These diseases share several common disease mechanisms, including vascular endothelial growth factor (VEGF) signaling, hypoxia, and inflammation, which provide opportunities for common therapeutic strategies. Treatment of these diseases using laser therapy, anti-VEGF injections, and/or steroids has significantly improved clinical outcomes. However, these strategies do not address the underlying root causes of pathology, and may have deleterious side effects. Furthermore, many patients continue to progress toward legal blindness despite receiving regular therapy. Nanomedicine, the engineering of therapeutics at the 1-100 nm scale, is a promising approach for improving clinical management of retinal vascular diseases. Nanomedicine-based technologies have the potential to revolutionize the treatment of ophthalmology, through enabling sustained release of drugs over several months, reducing side effects due to specific targeting of dysfunctional cells, and interfacing with currently "undruggable" targets. We will discuss emerging nanomedicine-based applications for the treatment of complications associated with retinal vascular diseases, including angiogenesis and inflammation.
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.
Mathieson, Keith; Loudin, James; Goetz, Georges; Huie, Philip; Wang, Lele; Kamins, Theodore I.; Galambos, Ludwig; Smith, Richard; Harris, James S.; Sher, Alexander; Palanker, Daniel
Retinal degenerative diseases lead to blindness due to loss of the “image capturing” photoreceptors, while neurons in the “image processing” inner retinal layers are relatively well preserved. Electronic retinal prostheses seek to restore sight by electrically stimulating surviving neurons. Most implants are powered through inductive coils, requiring complex surgical methods to implant the coil-decoder-cable-array systems, which deliver energy to stimulating electrodes via intraocular cables. We present a photovoltaic subretinal prosthesis, in which silicon photodiodes in each pixel receive power and data directly through pulsed near-infrared illumination and electrically stimulate neurons. Stimulation was produced in normal and degenerate rat retinas, with pulse durations from 0.5 to 4 ms, and threshold peak irradiances from 0.2 to 10 mW/mm2, two orders of magnitude below the ocular safety limit. Neural responses were elicited by illuminating a single 70 μm bipolar pixel, demonstrating the possibility of a fully-integrated photovoltaic retinal prosthesis with high pixel density. PMID:23049619
Mathieson, Keith; Loudin, James; Goetz, Georges; Huie, Philip; Wang, Lele; Kamins, Theodore I.; Galambos, Ludwig; Smith, Richard; Harris, James S.; Sher, Alexander; Palanker, Daniel
Retinal degenerative diseases lead to blindness due to loss of the `image capturing' photoreceptors, while neurons in the `image-processing' inner retinal layers are relatively well preserved. Electronic retinal prostheses seek to restore sight by electrically stimulating the surviving neurons. Most implants are powered through inductive coils, requiring complex surgical methods to implant the coil-decoder-cable-array systems that deliver energy to stimulating electrodes via intraocular cables. We present a photovoltaic subretinal prosthesis, in which silicon photodiodes in each pixel receive power and data directly through pulsed near-infrared illumination and electrically stimulate neurons. Stimulation is produced in normal and degenerate rat retinas, with pulse durations of 0.5-4 ms, and threshold peak irradiances of 0.2-10 mW mm-2, two orders of magnitude below the ocular safety limit. Neural responses were elicited by illuminating a single 70 µm bipolar pixel, demonstrating the possibility of a fully integrated photovoltaic retinal prosthesis with high pixel density.
Goh, James Kang Hao; Cheung, Carol Y.; Sim, Shaun Sebastian; Tan, Pok Chien; Tan, Gavin Siew Wei; Wong, Tien Yin
Due to the increasing prevalence of diabetes mellitus, demand for diabetic retinopathy (DR) screening platforms is steeply increasing. Early detection and treatment of DR are key public health interventions that can greatly reduce the likelihood of vision loss. Current DR screening programs typically employ retinal fundus photography, which relies on skilled readers for manual DR assessment. However, this is labor-intensive and suffers from inconsistency across sites. Hence, there has been a recent proliferation of automated retinal image analysis software that may potentially alleviate this burden cost-effectively. Furthermore, current screening programs based on 2-dimensional fundus photography do not effectively screen for diabetic macular edema (DME). Optical coherence tomography is becoming increasingly recognized as the reference standard for DME assessment and can potentially provide a cost-effective solution for improving DME detection in large-scale DR screening programs. Current screening techniques are also unable to image the peripheral retina and require pharmacological pupil dilation; ultra-widefield imaging and confocal scanning laser ophthalmoscopy, which address these drawbacks, possess great potential. In this review, we summarize the current DR screening methods using various retinal imaging techniques, and also outline future possibilities. Advances in retinal imaging techniques can potentially transform the management of patients with diabetes, providing savings in health care costs and resources. PMID:26830491
Corwin, Thomas R; Mancini, Michael
A new test designed to detect an hereditary eye disease called retinitis pigmentosa (RP) is described. This condition is revealed by pigmentation in the retina, but early diagnosis is difficult because the symptoms are subtle, and since it is genetically recessive it frequently occurs in families with no history of early blindness. In many cases…
Sullivan, Franklin N.
The characteristic features of RP (retinitis pigmentosa-an untreatable conditions usually resulting in night blindness) are discussed and functioning considerations in the classroom (including the use of protective devices and mobility aids) are noted. Classroom modifications such as darklined paper and black pens are suggested. (CL)
Smith, Ricardo Luiz; Sivaprasad, Sobha; Chong, Victor
The vitreous, the vasculature of the retina, macular pigments, phototransduction, retinal pigment epithelium, Bruch's membrane and the extracellular matrix, all play an important role in the normal function of the retina as well as in diseases. Understanding the pathophysiology allows us to target treatment. As ocular angiogenesis, immunity and inflammation are covered elsewhere, those subjects will not be discussed in this chapter.
Kandasamy, Y; Hartley, L; Smith, R
Dilation and abnormal tortuosity of retinal vessels are the hallmarks of severe retinopathy of prematurity (ROP) in premature infants. The stages of ROP are defined by vessel appearance at the interface between the vascular and avascular retinal areas. Deregulated signaling pathways involving hypoxia-inducible factors such as vascular endothelial growth factor (VEGF) are involved in the pathogenesis of ROP. VEGF-antagonists are increasingly being used as 'off-label medication' to treat this condition, with some success. We present Baby SM (female), who was born prematurely at 24 weeks gestation in a tertiary neonatal intensive care unit, and with a birth weight of 640 g. On screening at 35 weeks postmenstrual age (PMA), she was noted to have ROP, which became severe by 37 weeks PMA. She received one dose of intravitreal VEGF antagonist (Bevacizumab), resulting in a decrease in vessel tortuosity and dilation. However, repeat imaging at 4 weeks showed a re-emergence of vessel tortuosity. We believe the observed changes demonstrate an inherent retinal microvascular plasticity in premature neonates. With improved survival of extremely premature neonates and the availability of retinal imaging technology, we are now able to observe this plasticity.
Rosenberg, P. R.; Walsh, J. B.
Hamartoma of the retinal pigment epithelium is an uncommon tumour of young adults. We have seen 2 patients with this clinical diagnosis, both with unusual manifestations. In one patient growth of the tumour was observed over a 5-year period. In the second patient arterial-arterial anastomoses were detected at a site distal to the tumour. Images PMID:6722077
Kien, Tran Trung; Maul, Tomas; Bargiela, Andrzej
Age-related macular degeneration and retinitis pigmentosa are two of the most common diseases that cause degeneration in the outer retina, which can lead to several visual impairments up to blindness. Vision restoration is an important goal for which several different research approaches are currently being pursued. We are concerned with restoration via retinal prosthetic devices. Prostheses can be implemented intraocularly and extraocularly, which leads to different categories of devices. Cortical Prostheses and Optic Nerve Prostheses are examples of extraocular solutions while Epiretinal Prostheses and Subretinal Prostheses are examples of intraocular solutions. Some of the prostheses that are successfully implanted and tested in animals as well as humans can restore basic visual functions but still have limitations. This paper will give an overview of the current state of art of Retinal Prostheses and compare the advantages and limitations of each type. The purpose of this review is thus to summarize the current technologies and approaches used in developing Retinal Prostheses and therefore to lay a foundation for future designs and research directions.
Lemaillet, Paul; Ramella-Roman, Jessica C.
Measurements of oxygen saturation and flow in the retina can yield information about eye health and the onset of eye pathologies such as diabetic retinopathy. Recently, we developed a multiaperture camera that uses the division of the retinal image into several wavelength-sensitive subimages to compute retinal oxygen saturation. The calibration of such instruments is particularly difficult due to the layered structure of the eye and the lack of alternative measurement techniques. For this purpose, we realize an in vitro model of the human eye composed of a lens, the retina vessel, and three layers: the choroid, the retinal pigmented epithelium, and the sclera. The retinal vessel is modeled with a microtube connected to a micropump and a hemoglobin reservoir in a closed circulatory system. Hemoglobin oxygenation in the vessel could be altered using a reversible fuel cell. The sclera is represented by a Spectralon slab. The optical properties of the other layers are mimicked using titanium dioxide as a scatterer, ink as an absorber, and epoxy as a supporting structure. The optical thickness of each layer of the eye phantom is matched to each respective eye layer. PMID:20059246
Agrawal, Rupesh; Sherwood, Joseph; Chhablani, Jay; Ricchariya, Ashutosh; Kim, Sangho; Jones, Philip H; Balabani, Stavroula; Shima, David
Microvascular circulation plays a vital role in regulating physiological functions, such as vascular resistance, and maintaining organ health. Pathologies such as hypertension, diabetes, or hematologic diseases affect the microcirculation posing a significant risk to human health. The retinal vasculature provides a unique window for non-invasive visualisation of the human circulation in vivo and retinal vascular image analysis has been established to predict the development of both clinical and subclinical cardiovascular, metabolic, renal and retinal disease in epidemiologic studies. Blood viscosity which was otherwise thought to play a negligible role in determining blood flow based on Poiseuille's law up to the 1970s has now been shown to play an equally if not a more important role in controlling microcirculation and quantifying blood flow. Understanding the hemodynamics/rheology of the microcirculation and its changes in diseased states remains a challenging task; this is due to the particulate nature of blood, the mechanical properties of the cells (such as deformability and aggregability) and the complex architecture of the microvasculature. In our review, we have tried to postulate a possible role of red blood cell (RBC) biomechanical properties and laid down future framework for research related to hemorrheological aspects of blood in patients with retinal vascular disorders.
Joarder, Saiful A.; Abramian, Miganoosh; Suaning, Gregg J.; Lovell, Nigel H.; Dokos, Socrates
A continuum mathematical model of retinal electrical stimulation is described. The model is represented by a passive vitreous domain, a thin layer of active retinal ganglion cell (RGC) tissue adjacent to deeper passive neural layers of the retina, the retinal pigmented epithelium (RPE) and choroid thus ending at the sclera. To validate the model, in vitro epiretinal responses to stimuli from 50 µm disk electrodes, arranged in a hexagonal mosaic, were recorded from rabbit retinas. 100 µs/phase anodic-first biphasic current pulses were delivered to the retinal surface in both the mathematical model and experiments. RGC responses were simulated and recorded using extracellular microelectrodes. The model's epiretinal thresholds compared favorably with the in vitro data. In addition, simulations showed that single-return bipolar electrodes recruited a larger area of the retina than twin-return or six-return electrodes arranged in a hexagonal layout in which a central stimulating electrode is surrounded by six, eqi-spaced returns. Simulations were also undertaken to investigate the patterns of RGC activation in an anatomically-accurate model of the retina, as well as RGC activation patterns for subretinal and suprachoroidal bipolar stimulation. This paper was originally submitted for the special issue containing contributions from the Sixth Biennial Research Congress of The Eye and the Chip.
Lemaillet, Paul; Ramella-Roman, Jessica C
Measurements of oxygen saturation and flow in the retina can yield information about eye health and the onset of eye pathologies such as diabetic retinopathy. Recently, we developed a multiaperture camera that uses the division of the retinal image into several wavelength-sensitive subimages to compute retinal oxygen saturation. The calibration of such instruments is particularly difficult due to the layered structure of the eye and the lack of alternative measurement techniques. For this purpose, we realize an in vitro model of the human eye composed of a lens, the retina vessel, and three layers: the choroid, the retinal pigmented epithelium, and the sclera. The retinal vessel is modeled with a microtube connected to a micropump and a hemoglobin reservoir in a closed circulatory system. Hemoglobin oxygenation in the vessel could be altered using a reversible fuel cell. The sclera is represented by a Spectralon slab. The optical properties of the other layers are mimicked using titanium dioxide as a scatterer, ink as an absorber, and epoxy as a supporting structure. The optical thickness of each layer of the eye phantom is matched to each respective eye layer.
Oliveira, Wendeson S; Teixeira, Joyce Vitor; Ren, Tsang Ing; Cavalcanti, George D C; Sijbers, Jan
Image segmentation of retinal blood vessels is a process that can help to predict and diagnose cardiovascular related diseases, such as hypertension and diabetes, which are known to affect the retinal blood vessels' appearance. This work proposes an unsupervised method for the segmentation of retinal vessels images using a combined matched filter, Frangi's filter and Gabor Wavelet filter to enhance the images. The combination of these three filters in order to improve the segmentation is the main motivation of this work. We investigate two approaches to perform the filter combination: weighted mean and median ranking. Segmentation methods are tested after the vessel enhancement. Enhanced images with median ranking are segmented using a simple threshold criterion. Two segmentation procedures are applied when considering enhanced retinal images using the weighted mean approach. The first method is based on deformable models and the second uses fuzzy C-means for the image segmentation. The procedure is evaluated using two public image databases, Drive and Stare. The experimental results demonstrate that the proposed methods perform well for vessel segmentation in comparison with state-of-the-art methods.
Cristescu, R; Muşat, O; Toma, Oana; Coma, Corina; Gabej, Ioana; Burcea, M
We present the case of a 43 year old patient diagnosed with rhegmatogenous retinal detachment and retinoschizis, a rare case of disease association. Surgery is recommended and we practice 23 gauge vitrectomy, laser retinopexy, criopexy in the periphery and internal heavy oil tamponade. Postoperatory evolution was favorable.
Lemaillet, Paul; Ramella-Roman, Jessica C.
Measurements of oxygen saturation and flow in the retina can yield information about eye health and the onset of eye pathologies such as diabetic retinopathy. Recently, we developed a multiaperture camera that uses the division of the retinal image into several wavelength-sensitive subimages to compute retinal oxygen saturation. The calibration of such instruments is particularly difficult due to the layered structure of the eye and the lack of alternative measurement techniques. For this purpose, we realize an in vitro model of the human eye composed of a lens, the retina vessel, and three layers: the choroid, the retinal pigmented epithelium, and the sclera. The retinal vessel is modeled with a microtube connected to a micropump and a hemoglobin reservoir in a closed circulatory system. Hemoglobin oxygenation in the vessel could be altered using a reversible fuel cell. The sclera is represented by a Spectralon slab. The optical properties of the other layers are mimicked using titanium dioxide as a scatterer, ink as an absorber, and epoxy as a supporting structure. The optical thickness of each layer of the eye phantom is matched to each respective eye layer.
Retinal degenerations encompass a large number of diseases in which the retina and associated retinal pigment epithelial (RPE) cells progressively degenerate leading to severe visual disorders or blindness. Retinal degenerations can be divided into two groups, a group in which the defect has been linked to a specific gene and a second group that has a complex etiology that includes environmental and genetic influences. The first group encompasses a number of relatively rare diseases with the most prevalent being Retinitis pigmentosa that affects approximately 1 million individuals worldwide. Attempts have been made to correct the defective gene by transfecting the appropriate cells with the wild-type gene and while these attempts have been successful in animal models, human gene therapy for these inherited retinal degenerations has only begun recently and the results are promising. To the second group belong glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR). These retinal degenerations have a genetic component since they occur more often in families with affected probands but they are also linked to environmental factors, specifically elevated intraocular pressure, age and high blood sugar levels respectively. The economic and medical impact of these three diseases can be assessed by the number of individuals affected; AMD affects over 30 million, DR over 40 million and glaucoma over 65 million individuals worldwide. The basic defect in these diseases appears to be the relative lack of a neurogenic environment; the neovascularization that often accompanies these diseases has suggested that a decrease in pigment epithelium-derived factor (PEDF), at least in part, may be responsible for the neurodegeneration since PEDF is not only an effective neurogenic and neuroprotective agent but also a potent inhibitor of neovascularization. In the last few years inhibitors of vascularization, especially antibodies against vascular endothelial cell
Viral hemorrhagic fevers are diseases caused by viruses which belong to different families, many of them causing severe diseases. These viruses may produce different symptomatology together with a severe multisystem syndrome, and the final result might be the production of hemorrhages in several sites of the body. The majority of them have no other treatment than supportive therapy, although some antiviral drugs can be used in some circumstances. Transmission of VHF has been demonstrated through contact with animal vectors or person-to-person through the contact with body fluids. No risk of transmission has been found during the incubation period, but when the viral load is high the risk of transmission is greatest. Both health care and clinical laboratory workers must safely handle patients and specimens by taking all required precautions during their management. PMID:27014378
Vanessa, N Raabe; Matthias, Borchert
Breaking the human-to-human transmission cycle remains the cornerstone of infection control during filoviral (Ebola and Marburg) hemorrhagic fever outbreaks. This requires effective identification and isolation of cases, timely contact tracing and monitoring, proper usage of barrier personal protection gear by health workers, and safely conducted burials. Solely implementing these measures is insufficient for infection control; control efforts must be culturally sensitive and conducted in a transparent manner to promote the necessary trust between the community and infection control team in order to succeed. This article provides a review of the literature on infection control during filoviral hemorrhagic fever outbreaks focusing on outbreaks in a developing setting and lessons learned from previous outbreaks. The primary search database used to review the literature was PUBMED, the National Library of Medicine website. PMID:22529631
Liver involvement in hereditary hemorrhagic telangiectasia (HHT) consists of extensive intrahepatic vascular malformations associated with blood shunting (arteriovenous, arterioportal and/or portovenous). It is a rare disorder that nevertheless can result in significant systemic and hepatobiliary abnormalities. Although hepatic vascular malformations are present in a majority of patients with HHT, symptoms occur in a only a minority with a clear predominance for the female gender. Symptoms from liver vascular malformations are often misdiagnosed and this can lead to potentially harmful interventions. In this review article, clinical findings of liver involvement in HHT and their pathophysiology are discussed as well as diagnostic methodologies, therapies used and their outcome. Data presented is based on a review of the literature performed in October 2006 using the following MEDLINE search terms: (hereditary hemorrhagic telangiectasia [ALL] OR Rendu-Osler-Weber [ALL]) AND (liver OR hepatic [ALL]). Papers were considered if they were published in English and if they included specific cases that were sufficiently described.
Duan, Xiaochun; Wen, Zunjia; Shen, Haitao; Shen, Meifen
Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH). Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI) following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER) stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches. PMID:27190572
Rajani, Ravi R; Ball, Chad G; Feliciano, David V; Vercruysse, Gary A
Trauma with resultant hypovolemic shock remains both prevalent and difficult to treat. Standard strategies using volume resuscitation and catecholamine support have historically yielded poor results. Vasopressin has emerged as a possible pharmacologic adjunct, particularly in patients with shock refractory to the administration of fluids and catecholamines. Much of the data regarding vasopressin is extrapolated from its usefulness in cases of nonhypovolemic human shock, which are supported by convincing animal studies. It is true that humans show a deficiency in vasopressin minutes after significant hemorrhage that can respond to administration of exogenous vasopressin. When given in physiological dosing regimens, vasopressin appears to be a safe adjunct to other therapy. Definite recommendations regarding indications for use, recommended dose, and long-term outcome in patients with hemorrhagic shock await a much needed prospective, randomized, controlled trial.
Raabea, Vanessa N; Borcherta, Matthias
Breaking the human-to-human transmission cycle remains the cornerstone of infection control during filoviral (Ebola and Marburg) hemorrhagic fever outbreaks. This requires effective identification and isolation of cases, timely contact tracing and monitoring, proper usage of barrier personal protection gear by health workers, and safely conducted burials. Solely implementing these measures is insufficient for infection control; control efforts must be culturally sensitive and conducted in a transparent manner to promote the necessary trust between the community and infection control team in order to succeed. This article provides a review of the literature on infection control during filoviral hemorrhagic fever outbreaks focusing on outbreaks in a developing setting and lessons learned from previous outbreaks. The primary search database used to review the literature was PUBMED, the National Library of Medicine website.
Duan, Xiaochun; Wen, Zunjia; Shen, Haitao; Shen, Meifen; Chen, Gang
Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH). Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI) following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER) stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches.
Macdonald, Robert Loch; Leung, Ming; Tice, Tom
Tice and colleagues pioneered site-specific, sustained-release drug delivery to the brain almost 30 years ago. Currently there is one drug approved for use in this manner. Clinical trials in subarachnoid hemorrhage have led to approval of nimodipine for oral and intravenous use, but other drugs, such as clazosentan, hydroxymethylglutaryl CoA reductase inhibitors (statins) and magnesium, have not shown consistent clinical efficacy. We propose that intracranial delivery of drugs such as nimodipine, formulated in sustained-release preparations, are good candidates for improving outcome after subarachnoid hemorrhage because they can be administered to patients that are already undergoing surgery and who have a self-limited condition from which full recovery is possible.
Ussia, Anastasia; Betsas, George; Corona, Roberta; De Cicco, Carlo; Koninckx, Philippe R
Massive hemorrhagic ascites (4470 mL, range 1-10 L) in women with endometriosis is a rare condition occurring predominantly in black women. Of the 43 case reports published, 42 are compatible with the hypothesis that the hemorrhagic ascites is predominantly a consequence of excessive ovarian transudation similar to a Meigs syndrome. Indeed, bilateral ovariectomy cures the condition without recurrences, whereas after unilateral ovariectomy or cystectomy recurrence rate is more than 50%; during ovarian suppression by luteinizing hormone-releasing hormone agonist ascites disappears, but reappears after treatment. Superficial pelvic endometriosis also contributes to the ascites because after superficial endometriosis destruction the recurrence rate is only 4 in 14. Based on these data, it is suggested, to scrutinize the ovaries for tumors given the analogy with Meigs syndrome. In women desiring fertility, conservative treatment with destruction of endometriosis only can be attempted given the cure rate of some 20%. It is unknown what the effect of ovulation induction would be.
Background Post partum hemorrhage is defined as blood loss of 500 ml or above. It is the most common cause of pre-mature mortality of women world wide. Our objective was to evaluate the most common etiology and method of management of Post partum Hemorrhage in a tertiary care hospital of Karachi. Findings It was a cross sectional study conducted at Liaquat National Hospital Karachi, during the period of July 2011 to May 2012. Review include mode of delivery, possible cause of postpartum hemorrhage, supportive, medical and surgical interventions. All the women admitted with post partum hemorrhage or develop PPH in hospital after delivery were included in our study. Bleeding disorder and use of anticoagulants were set as exclusion criteria. Diagnosis was made on the basis of blood loss assessment which was made via subjective and objective evaluation. During the targeted months, out of total 1493 deliveries (26/1493 = 1.741%) 26 cases of post partum hemorrhage were reported with a mean age of 26.153 ± 7.37. No deaths were reported and all cases were referred and unbooked cases. All Patients were conscious, tachycardiac and hypotensive. Most of the women were suffering from hemorrhage during or after the birth of their 1st child. Primary post partum hemorrhage emerge as the most common type of post partum hemorrhage and uterine atony was detected as the most common cause of primary post partum hemorrhage. Retained products of conception was the most common cause of secondary post partum hemorrhage and hysterectomy was found to be the most frequent method of management of post partum hemorrhage. Conclusion This study highlights the existing variable practices for the management of postpartum hemorrhage. Hemorrhage associated morbidity and mortality can be prevented by critical judgment, early referral and resuscitation by attendants. Introduction of an evidence-based management model can potentially reduce the practice variability and improve the quality of
Yan, Panshi; Qian, Cheng; Wang, Wenzhan; Dong, Yi; Wan, Guangming; Chen, Yue
Background This study was designed to examine the clinical effects of treating diabetic macular edema with an intravitreal injection of ranibizumab in combination with retinal photocoagulation. Methods Sixty-two cases (75 eyes) with confirmed severe proliferative diabetic retinopathy or proliferative diabetic retinopathy in combination with macular edema were randomly divided into the observation group (37 eyes were given an intravitreal injection of ranibizumab combined with retinal photocoagulation) and the control group (38 eyes received retinal photocoagulation only). Vision, fundus condition, central macular thickness, and the macular leakage area were recorded before and after treatment. Results The best-corrected visual acuity and macular leakage area were similar between the observation and control groups (P>0.05). The best-corrected visual acuity in the observation group was higher than that in the control group 3 and 6 months after treatment (P<0.05) and showed a rising tendency. The macular leakage area in the observation group was significantly lower than that in the control group 1 and 3 months after treatment (P<0.05). However, the macular leakage area was similar 6 months after treatment (P>0.05). The central macular thickness of the observation group was lower than that in the control group 1, 3, and 6 months after treatment (P<0.05). The laser energy used in the observation group was also smaller than that in the control group (P<0.05). The intraocular pressure was not significantly different between the groups (P<0.05). No patients in the two groups developed eye or systemic complications, such as glaucoma, cataract, or vitreous hemorrhage during treatment. Conclusion Intravitreal injection of ranibizumab combined with retinal photocoagulation was proven to be effective in treating diabetic macular edema as it improved vision and resulted in fewer complications. PMID:27103811
Abdallah, Walid; Ameri, Hossein; Barron, Ernesto; Chader, Gerald J.; Greenbaum, Elias; Hinton, David R.
Purpose. To study the feasibility of anterior vitreal oxygenation for the treatment of acute retinal ischemia. Methods. Twenty rabbits were randomized into an oxygenation group, a sham treatment group, and a no treatment group. Baseline electroretinography (ERG) and preretinal oxygen (Po2) measurements were obtained 3 to 5 days before surgery. Intraocular pressure was raised to 100 mm Hg for 90 minutes and then normalized. The oxygenation group underwent vitreal oxygenation for 30 minutes using intravitreal electrodes. The sham treatment group received inactive electrodes for 30 minutes while there was no intervention for the no treatment group. Preretinal Po2 in the posterior vitreous was measured 30 minutes after intervention or 30 minutes after reperfusion (no treatment group) and on postoperative days (d) 3, 6, 9, and 12. On d14, rabbits underwent ERG and were euthanatized. Results. Mean final (d12) Po2 was 10.64 ± 0.77 mm Hg for the oxygenation group, 2.14 ± 0.61 mm Hg for the sham group, and 1.98 ± 0.63 mm Hg for the no treatment group. On ERG, scotopic b-wave amplitude was significantly preserved in the oxygenation group compared with the other two groups. Superoxide dismutase assay showed higher activity in the operated eyes than in the nonoperated control eyes in the sham treatment group and no treatment group only. Histopathology showed preservation of retinal architecture and choroidal vasculature in the oxygenation group, whereas the sham-treated and nontreated groups showed retinal thinning and choroidal atrophy. Conclusions. In severe total ocular ischemia, anterior vitreal oxygenation supplies enough oxygen to penetrate the retinal thickness, resulting in rescue of the RPE/choriocapillaris that continues to perfuse, hence sparing the retinal tissue from damage. PMID:21051734
Sibony, Patrick A.; Kupersmith, Mark J.; Feldon, Steven E.; Wang, Jui-Kai; Garvin, Mona
Purpose To determine the frequency, patterns, associations, and biomechanical implications of retinal and choroidal folds in papilledema due to idiopathic intracranial hypertension (IIH). Methods Retinal and choroidal folds were studied in patients enrolled in the IIH Treatment Trial using fundus photography (n = 165 study eyes) and spectral-domain optical coherence tomography (SD-OCT; n = 125). We examined the association between folds and peripapillary shape, retinal nerve fiber layer (RNFL) thickness, disc volume, Frisén grade, acuity, perimetric mean deviation, intraocular pressure, intracranial pressure, and refractive error. Results We identified three types of folds in IIH patients with papilledema: peripapillary wrinkles (PPW), retinal folds (RF), and choroidal folds (CF). Frequency, with photos, was 26%, 19%, and 1%, respectively; SD-OCT frequency was 46%, 47%, and 10%. At least one type of fold was present in 41% of patients with photos and 73% with SD-OCT. Spectral-domain OCT was more sensitive. Structural parameters related to the severity of papilledema were associated with PPW and RF, whereas anterior deformation of the peripapillary RPE/basement membrane layer was associated with CF and RF. Folds were not associated with vision loss at baseline. Conclusions Folds in papilledema are biomechanical signs of stress/strain on the optic nerve head and load-bearing structures induced by intracranial hypertension. Folds are best imaged with SD-OCT. The patterns of retinal and choroidal folds are the products of a complex interplay between the degree of papilledema and anterior deformation of the load-bearing structures (sclera and possibly the lamina cribrosa), both modulated by structural geometry and material properties of the optic nerve head. (ClinicalTrials.gov number, NCT01003639.) PMID:26335066
Larciprete, Giovanni; Romanini, Maria Elisabetta; Arduini, Domenico; Cirese, Elio; Slowikowska-Hilczer, Jolanta; Kula, Krzysztof
We describe an unexplained case of umbilical cord segmental hemorrhage linked with meconium-stained amniotic fluid. A severely asphyxiated infant was delivered at term by Caesarean section. There were poor prognostic signs on fetal cardiotocography with rupture of membranes with meconium-stained amniotic fluid. The pathophysiologic mechanism in this case is still unknown, even if we argued a possible role of the umbilical cord shortness. PMID:23674981
Peden, Marc C.; Bhatti, M. Tariq
Subperiosteal orbital hemorrhage (SPOH) following cardiac surgery has not been previously reported. We present a patient who developed diplopia and right eye proptosis immediately after cardiac surgery for a mitral valve repair and coronary artery bypass graft. A computed tomography (CT) study demonstrated a right superior SPOH. The diplopia and proptosis resolved spontaneously within 4 weeks. Follow-up CT showed complete resolution of the SPOH.
Hughes, Adrienne; Brown, Alisha; Valento, Matthew
Baking soda is a readily available household product composed of sodium bicarbonate. It can be used as a home remedy to treat dyspepsia. If used in excessive amounts, baking soda has the potential to cause a variety of serious metabolic abnormalities. We believe this is the first reported case of hemorrhagic encephalopathy induced by baking soda ingestion. Healthcare providers should be aware of the dangers of baking soda misuse and the associated adverse effects.
Hughes, Adrienne; Brown, Alisha; Valento, Matthew
Baking soda is a readily available household product composed of sodium bicarbonate. It can be used as a home remedy to treat dyspepsia. If used in excessive amounts, baking soda has the potential to cause a variety of serious metabolic abnormalities. We believe this is the first reported case of hemorrhagic encephalopathy induced by baking soda ingestion. Healthcare providers should be aware of the dangers of baking soda misuse and the associated adverse effects. PMID:27625729
Xu, Shao-Yan; Sun, Ke; Xie, Hai-Yang; Zhou, Lin; Zheng, Shu-Sen; Wang, Wei-Lin
Abstract Background: Schwannomas are mesenchymal tumors arising from the neural sheaths of peripheral nerves. They can almost develop in any part of the body, while head, neck and extremities are the most common sites. Occurrence in the retroperitoneum is rare. Schwannomas can show secondary degenerative changes including cyst formation, hyalinization, hemorrhage, and calcification, whereas the ossified retroperitoneal schwannoma was only reported in a malignant one. Case summary: We first present a benign ossified retroperitoneal schwannoma in a 61-year-old female. The mass was found by a routine health examination. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a well-defined mass in the area among duodenum, right liver, and kidney. Definitive preoperative diagnosis of the mass was difficult. By laparotomy, the mass was found in the retroperitoneum. We completely removed the tumor and gross specimen showed a mass with a capsule and 6 × 6 × 4.8 cm in size. Microscopic examination showed the tumor is composed of spindle-shaped cells with degenerative changes of hemorrhage, calcification, and ossification. Immunohistochemically, S-100 protein was strongly positive. Finally, the mass was diagnosed as a hemorrhagic, calcified, and ossified benign schwannoma in the retroperitoneum. The patient was followed up for a period of 21 months, during which she was well with no evidence of recurrence. Conclusion: We report the first case of a benign retroperitoneal schwannoma with secondary degenerative changes including hemorrhage, calcification, and ossification. Precise preoperative diagnosis of the tumor is challenging even with multiple preoperative imaging modalities. After complete resection, patients with benign retroperitoneal schwanommas generally have good prognosis. PMID:27472709
irreversible cardiovascular collapse (Pope et al., 1999), and is manifested clinically as the loss of ability to mount a hemodynamic response to aggressive...chemical substances have been proposed as markers for tracking the evolution of hemorrhagic shock and impending collapse ; these include pH, lactate...left heart ventricle, renal medulla , diaphragm, right lobe of liver, and 0.3 ml of blood (subsequently fractionated into red blood cells and plasma
Lee, Christine; Tu, Hong Anh; Weir, Mark; Holubowich, Corinne
Background Retinitis pigmentosa is a group of genetic disorders that involves the breakdown and loss of photoreceptors in the retina, resulting in progressive retinal degeneration and eventual blindness. The Argus II Retinal Prosthesis System is the only currently available surgical implantable device approved by Health Canada. It has been shown to improve visual function in patients with severe visual loss from advanced retinitis pigmentosa. The objective of this analysis was to examine the clinical effectiveness, cost-effectiveness, budget impact, and safety of the Argus II system in improving visual function, as well as exploring patient experiences with the system. Methods We performed a systematic search of the literature for studies examining the effects of the Argus II retinal prosthesis system in patients with advanced retinitis pigmentosa, and appraised the evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria, focusing on visual function, functional outcomes, quality of life, and adverse events. We developed a Markov decision-analytic model to assess the cost-effectiveness of the Argus II system compared with standard care over a 10-year time horizon. We also conducted a 5-year budget impact analysis. We used a qualitative design and an interview methodology to examine patients’ lived experience, and we used a modified grounded theory methodology to analyze information from interviews. Transcripts were coded, and themes were compared against one another. Results One multicentre international study and one single-centre study were included in the clinical review. In both studies, patients showed improved visual function with the Argus II system. However, the sight-threatening surgical complication rate was substantial. In the base-case analysis, the Argus II system was cost-effective compared with standard care only if willingness-to-pay was more than $207,616 per quality-adjusted life
Mandel, Yossi; Manivanh, Richard; Dalal, Roopa; Huie, Phil; Wang, Jenny; Brinton, Mark; Palanker, Daniel
Non-compressible hemorrhages are the most common preventable cause of death on battlefield or in civilian traumatic injuries. We report the use of sub-millisecond pulses of electric current to induce rapid constriction in femoral and mesenteric arteries and veins in rats. Extent of vascular constriction could be modulated by pulse duration, amplitude and repetition rate. Electrically-induced vasoconstriction could be maintained at steady level until the end of stimulation, and blood vessels dilated back to their original size within a few minutes after the end of stimulation. At higher settings, a blood clotting could be introduced, leading to complete and permanent occlusion of the vessels. The latter regime dramatically decreased the bleeding rate in the injured femoral and mesenteric arteries, with a complete hemorrhage arrest achieved within seconds. The average blood loss from the treated femoral artery was about 7 times less than that of a non-treated control. This new treatment modality offers a promising approach to non-damaging control of bleeding during surgery, and to efficient hemorrhage arrest in trauma patients.
Peedin, Alexis R; Mazepa, Marshall A; Park, Yara A; Weimer, Eric T; Schmitz, John L; Raval, Jay S
Evaluation of fetomaternal hemorrhage (FMH) in the immediate postpartum period is critical for the timely administration of Rh immunoglobulin (RhIG) prophylaxis to minimize the risk of alloimmunization in D-negative mothers of D-positive newborns. We report a series of two clinically-unsuspected cases of massive FMHs identified at our university medical center. Retrospective records of two cases of massive FMH were investigated using the electronic medical record. After positive fetal bleed screens, flow cytometric analysis for hemoglobin F was performed to quantify the volume of the hemorrhages in both cases. Flow cytometric enumeration with anti-D was also performed in one case. The two patients had 209.5 and 75 mL of fetal blood in circulation, resulting in 8 and 4 doses of RhIG administered, respectively. For the former patient, flow cytometric analysis with anti-D ruled out hereditary persistence of fetal hemoglobin and supported the fetal origin of the red cells. Due to the clinically-silent nature of both hemorrhages, further evaluation of the newborns' blood was not performed. These cases highlight the importance of rapidly obtaining accurate measurements of fetal blood loss via flow cytometric analysis in cases of FMH, particularly in clinically-unsuspected cases, to ensure timely administration of adequate immunoprophylaxis to D-negative mothers.
Kalloniatis, Michael; Loh, Chee Seang; Acosta, Monica L; Tomisich, Guido; Zhu, Yuan; Nivison-Smith, Lisa; Fletcher, Erica L; Chua, Jacqueline; Sun, Daniel; Arunthavasothy, Niru
Advances in basic retinal anatomy, genetics, biochemical pathways and neurochemistry have not only provided a better understanding of retinal function but have also allowed us to link basic science to retinal disease. The link with disease allowed measures to be developed that now provide an opportunity to intervene and slow down or even restore sight in previously 'untreatable' retinal diseases. One of the critical advances has been the understanding of the retinal amino acid neurotransmitters, related amino acids, their metabolites and functional receptors. This review provides an overview of amino acid localisation in the retina and examples of how retinal anatomy and amino acid neurochemistry directly links to understanding retinal disease. Also, the implications of retinal remodelling involving amino acid (glutamate) receptors are outlined in this review and insights are presented on how understanding of detrimental and beneficial retinal remodelling will provide better outcomes for patients using strategies for the preservation or restoration of vision. An internet-based database of retinal images of amino acid labelling patterns and other amino acid-related images in health and disease is located at http://www.aminoacidimmunoreactivity.com.
Greferath, Ursula; Anderson, Emily E.; Jobling, Andrew I.; Vessey, Kirstan A.; Martinez, Gemma; de Iongh, Robb U.; Kalloniatis, Michael; Fletcher, Erica L.
While photoreceptor loss is the most devastating result of inherited retinal degenerations such as retinitis pigmentosa, inner retinal neurons also undergo significant alteration. Detailing these changes has become important as many vision restorative therapies target the remaining neurons. In this study, the rd1-Fos-Tau-LacZ (rd1-FTL) mouse model was used to explore inner retinal change at a late stage of retinal degeneration, after the loss of photoreceptor nuclei. The rd1-FTL model carries a mutation in the phosphodiesterase gene, Pde6b, and an axonally targeted transgenic beta galactosidase reporter system under the control of the c-fos promoter. Retinae of transgenic rd1-FTL mice and control FTL animals aged 2–12 months were processed for indirect fluorescence immunocytochemistry. At 2 months of age, a time when the majority of photoreceptor nuclei are lost, there was negligible c-fos reporter (FTL) expression, however, from 4 months, reporter expression was observed to increase within subpopulations of amacrine and ganglion cells within the central retina. These areas of inner retinal FTL expression coincided with regions that contained aberrant Müller cells. Specifically, these cells exhibited reduced glutamine synthetase and Kir4.1 immunolabelling, whilst showing evidence of proliferative gliosis (increased cyclinD1 and glial fibrillary acidic protein expression). These changes were limited to distinct regions where cone photoreceptor terminals were absent. Overall, these results highlight that distinct areas of the rd1-FTL central retina undergo significant glial alterations after cone photoreceptor loss. These areas coincide with up-regulation of the c-fos reporter in the inner retina, which may represent a change in neuronal function/plasticity. The rd1-FTL mouse is a useful model system to probe changes that occur in the inner retina at later stages of retinal degeneration. PMID:26283925
Bhagavati, Satyakam; Choi, Jan
Cerebral toxoplasmosis is a frequent complication in immunosuppressed patients such as AIDS (acquired immunodeficiency syndrome). Frequently, lesions are located deep in the brain which are inaccessible for biopsy making rapid diagnosis dependent on accurate interpretation of neuroimaging findings. The commonest cranial CT findings reported in toxoplasmosis are ring enhancing hypodense lesions in basal ganglia or cortical gray matter. Hemorrhage has only rarely been described and is usually seen following antitoxoplasma treatment. We reviewed the records of 11 AIDS patients with cerebral toxoplasmosis and found multiple hemorrhagic cerebral, cerebellar, or brain stem lesions in 7 of 11 patients. Six patients had hemorrhage at the time of initial clinical presentation and one developed hemorrhage following 2 weeks of antitoxoplasma treatment. We conclude that hemorrhagic lesions are frequently found on cranial MRI scans in cerebral toxoplasmosis. AIDS patients presenting with hemorrhagic cerebral lesions should be considered for a trial of presumptive antitoxoplasma treatment.
Banaama, Saeed; van Overbeeke, Jacobus; Temel, Yasin
Background: Symptomatic intratumoral hemorrhage (ITH) in vestibular schwannoma (VS) is rare. A repeated hemorrhage is, therefore, even more exceptional. Repeated ITH has been reported in four cases thus far in English literature. Here, we describe a patient with a Koos grade D VS who presented to our Skull Base team with repeated ITH and an unexpected disease course. Case Description: A 76-year-old woman presented with hearing loss due to polycystic VS on the left side. Five years later, the patient was presented with facial palsy caused by hemorrhage in the VS. The patient had an eventful medical history that necessitated the use of anti-coagulants. The patient suffered from three subsequent hemorrhages preoperatively and one hemorrhage 36 h postoperatively. Conclusion: We have experienced multiple repeated hemorrhages in a patient with a polycystic VS, and despite surgical intervention, the outcome was unfavorable. PMID:27999710
Akbar, Shahzad; Akram, Muhammad Usman; Sharif, Muhammad; Tariq, Anam; Yasin, Ubaid Ullah
A condition in which the optic nerve inside the eye is swelled due to increased intracranial pressure is known as papilledema. The abnormalities due to papilledema such as opacification of Retinal Nerve Fiber Layer (RNFL), dilated optic disc capillaries, blurred disc margins, absence of venous pulsations, elevation of optic disc, obscuration of optic disc vessels, dilation of optic disc veins, optic disc splinter hemorrhages, cotton wool spots and hard exudates may result in complete vision loss. The ophthalmologists detect papilledema by means of an ophthalmoscope, Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and ultrasound. Rapid development of computer aided diagnostic systems has revolutionized the world. There is a need to develop such type of system that automatically detects the papilledema. In this paper, an automated system is presented that detects and grades the papilledema through analysis of fundus retinal images. The proposed system extracts 23 features from which six textural features are extracted from Gray-Level Co-occurrence Matrix (GLCM), eight features from optic disc margin obscuration, three color based features and seven vascular features are extracted. A feature vector consisting of these features is used for classification of normal and papilledema images using Support Vector Machine (SVM) with Radial Basis Function (RBF) kernel. The variations in retinal blood vessels, color properties, texture deviation of optic disc and its peripapillary region, and fluctuation of obscured disc margin are effectively identified and used by the proposed system for the detection and grading of papilledema. A dataset of 160 fundus retinal images is used which is taken from publicly available STARE database and local dataset collected from Armed Forces Institute of Ophthalmology (AFIO) Pakistan. The proposed system shows an average accuracy of 92.86% for classification of papilledema and normal images. It also shows an average accuracy of 97
Wan, Tony; Tsang, Peter
This is a case report of catastrophic antiphospholipid syndrome (APLS) involving the rare manifestation of pulmonary hemorrhage. This rare variant of APLS is frequently life threatening despite medical therapy. The pathogenesis of pulmonary hemorrhage in catastrophic APLS remains incompletely understood. The optimal approach to managing pulmonary hemorrhage in the setting of catastrophic APLS is still unclear, however this case report demonstrates the success of combination therapy with anticoagulation, corticosteroids and plasma exchange.
Bilguvar, Kaya; DiLuna, Michael L; Bizzarro, Matthew J; Bayri, Yasar; Schneider, Karen C; Lifton, Richard P; Gunel, Murat; Ment, Laura R
Intraventricular hemorrhage is a common complication of preterm infants. Mutations in the type IV procollagen gene, COL4A1, are associated with cerebral small vessel disease with hemorrhage in adults and fetuses. We report a rare variant in COL4A1 associated with intraventricular hemorrhage in dizygotic preterm twins. These results expand the spectrum of diseases attributable to mutations in type IV procollagens.
Martynov, M Iu; Koplik, E V; Shchukin, I A; Smolina, N V; Kapel'nitskiĭ, P V; Chubykin, V I; Glukhareva, A P; Makarov, A N; Sudakov, K V
Authors studied the influence of the psychoemotional stress preceding the stroke on the dynamics of neurological symptoms (Glasgo coma scale, Scandinavian stroke scale and Barthel index) and on the conformational changes of albumin in 59 patients with intracerebral hemorrhage due to arterial hypertension. The psychoemotional stress was associated with less favorable clinical course and outcome of intracerebral hemorrhage. Conformational properties of albumin were changed in all patients with intracerebral hemorrhage compared to controls. Psychoemotional stress preceding stroke aggravated changes in albumin molecule.
The effort to isolate and maintain alive in vitro an intact mammalian eye is rewarded by the full control provided over the arterial input and exclusion of systemic regulatory or compensatory mechanisms. Electrical recording of typical light-evoked field potentials from retina and optic nerve can be complemented by single-cell recording. Thus, light-induced electrical activity reflects the function of the retinal pigment epithelium, of the layers of the retina and of the ganglion cells or their axons. Retinal function in vitro is documented by electrophysiological and morphological methods revealing subtle features of retinal information processing as well as optic nerve signals that approach-at threshold stimulus intensity-the human psychophysical threshold. Such sensitivity of third-order retinal neurons is described for the first time. This well controlled in vitro preparation has been used successfully for biophysical, metabolic and pharmacological studies. Examples are provided that demonstrate the marked sensibility of the rod system to changes in glucose supply. Moreover, histochemical identification of glycogen stores revealed labeling of the second- and third-order neurons subserving the rod system, in addition to labeling of Müller (glial) cells in the cat retina. The glycogen content of the cat retina is augmented by prolonged anesthesia, largely depleted by ischemia after enucleation and enhanced by insulin. Pharmacological experiments using agonists and antagonists of putative retinal neurotransmitters are summarized and outlined using the muscarinic cholinergic agonist QNB as an example. Actions and uptake of the neuromodulator adenosine are presented in detail, including inhibitory effects on physiologically characterized ganglion cells. Neuronal effects of adenosine are distinguished from those resulting from vasodilatation and from glycogenolysis induced by the neuromodulator. To open the blood-retina barrier, a hyperosmotic challenge can be
Kaplan, V; Baur, X; Czuppon, A; Ruegger, M; Russi, E; Speich, R
Pulmonary hemorrhage due to inhalation of fumes or powders containing trimellitic anhydride (TMA) is well known. We report pulmonary hemorrhage in a young man exposed to epoxy resin vapor containing pyromellitic dianhydride (PMDA). Serum IgG antibodies to PMDA could be detected. We conclude that the pulmonary hemorrhage was mediated by a reaction to PMDA in analogy to the TMA-induced disease. We suggest that exposure to any acid anhydride should be considered a possible cause of pulmonary hemorrhage since these compounds share structural and functional similarities.
Harada, Yukinori; Hara, Yuuta
Herpes simplex encephalitis (HSE) can be complicated by adverse events in the acute phase. We herein present the case of a 71-year-old woman with HSE complicated by cerebral hemorrhage. She presented with acute deterioration of consciousness and fever and was diagnosed with HSE based on the detection of herpes simplex virus-1 in the cerebrospinal fluid by a polymerase chain reaction. The cerebral hemorrhage developed during acyclovir therapy; however, its diagnosis was delayed for 2 days. After the conservative treatment of the cerebral hemorrhage, the patient made a near-complete recovery. Cerebral hemorrhage should be considered as an acute-phase complication of HSE. PMID:28090058
Arboix, Adrià; García-Eroles, Luis; Vicens, Adela; Oliveres, Montserrat; Massons, Joan
Purpose. Primary hemorrhage in the ventricular system without a recognizable parenchymal component is very rare. This single-center retrospective study aimed to further characterize the clinical characteristics and early outcome of this stroke subtype. Methods. All patients with primary intraventricular hemorrhage included in a prospective hospital-based stroke registry over a 19-year period were assessed. A standardized protocol with 161 items, including demographics, risk factors, clinical data, neuroimaging findings, and outcome, was used for data collection. A comparison was made between the groups of primary intraventricular hemorrhage and subcortical intracerebral hemorrhage. Predictors of primary intraventricular hemorrhage were identified by logistic regression analysis. Results. There were 12 patients with primary intraventricular hemorrhage (0.31% of all cases of stroke included in the database) and 133 in the cohort of subcortical hemorrhage. Very old age (≥85 years) (odds ratio (OR) 9.89), atrial fibrillation (OR 8.92), headache (OR 6.89), and altered consciousness (OR 4.36) were independent predictors of intraventricular hemorrhage. The overall in-hospital mortality rate was 41.7% (5/12) but increased to 60% (3/5) in patients aged 85 years or older. Conclusion. Although primary intraventricular hemorrhage is uncommon, it is a severe clinical condition with a high early mortality. The prognosis is particularly poor in very old patients. PMID:22966468
Grimes, D A; Kafrissen, M E; O'Reilly, K R; Binkin, N J
Deaths from hemorrhage associated with legal induced abortion should not occur. Yet hemorrhage was the third most frequent cause of death from legal abortion in the United States between 1972 and 1979. This study was undertaken to document the scope of the problem, to identify risk factors for fatal hemorrhage and to recommend ways of preventing these deaths. Deaths were identified through the CDC's nationwide surveillance of deaths from abortions; information on numbers and characteristics of women having legal abortions was obtained from CDC and the Alan Guttmacher Institute. Twenty-four women died from hemorrhage after legal abortion in the United States from 1972 to 1979, for a death-to-case rate of 0.3 deaths per 100,000 abortions (95 per cent confidence interval 0.2 to 0.5). Women who died from hemorrhage were significantly older than those who died from other causes (27.6 versus 24.4 years; p less than 0.05). Documented uterine perforation or rupture was far more frequent among women who died from hemorrhage than those who died from other causes (71 versus 8 per cent; p less than 0.001). Women who sustained uterine perforation or rupture were over 1,000 times more likely to die from hemorrhage than those who did not. Deaths from hemorrhage can be eliminated by preventing uterine trauma during abortion and by rapidly diagnosing and treating hemorrhage if it occurs.
Samada, Kazunori; Shiraishi, Hirohiko; Aoyagi, Jun; Momoi, Mariko Y
A case of cerebral hemorrhage associated with sildenafil (Revatio) use in an infant is presented. Sildenafil is increasingly used in the treatment of primary and secondary pulmonary arterial hypertension and pulmonary arteriovenous fistula. In the reported case, sildenafil used to treat pulmonary arteriovenous fistula improved right-to-left shunting across the pulmonary fistula but resulted in cerebral hemorrhage. Cerebral hemorrhage, a previously reported complication of sildenafil, developed in an infant after a rapid increase in dose, to 4.7 mg/kg/day. Therefore, sildenafil doses must be increased only with care, and cerebral hemorrhage must be considered a potential complication.
Nie, Quanmin; Guo, Pin; Ge, Jianwei; Qiu, Yongming
Cerebral venous sinus thrombosis (CVST) rarely induces cerebral hemorrhage, and CVST with cerebral hemorrhage during early pregnancy is extremely rare. Upon literature review, we are able to find only one case of CVST with cerebral hemorrhage in early pregnancy. In this paper, we report another case of a 27-year-old patient who developed CVST with cerebral hemorrhage in her fifth week of pregnancy. Although the optimal treatment for this infrequent condition remains controversial, we adopted anticoagulation as the first choice of treatment and obtained favorable results. PMID:25630781
Harada, Yukinori; Hara, Yuuta
Herpes simplex encephalitis (HSE) can be complicated by adverse events in the acute phase. We herein present the case of a 71-year-old woman with HSE complicated by cerebral hemorrhage. She presented with acute deterioration of consciousness and fever and was diagnosed with HSE based on the detection of herpes simplex virus-1 in the cerebrospinal fluid by a polymerase chain reaction. The cerebral hemorrhage developed during acyclovir therapy; however, its diagnosis was delayed for 2 days. After the conservative treatment of the cerebral hemorrhage, the patient made a near-complete recovery. Cerebral hemorrhage should be considered as an acute-phase complication of HSE.
Lombardo, Marco; Serrao, Sebastiano; Devaney, Nicholas; Parravano, Mariacristina; Lombardo, Giuseppe
Adaptive optics (AO) is a technology used to improve the performance of optical systems by reducing the effects of optical aberrations. The direct visualization of the photoreceptor cells, capillaries and nerve fiber bundles represents the major benefit of adding AO to retinal imaging. Adaptive optics is opening a new frontier for clinical research in ophthalmology, providing new information on the early pathological changes of the retinal microstructures in various retinal diseases. We have reviewed AO technology for retinal imaging, providing information on the core components of an AO retinal camera. The most commonly used wavefront sensing and correcting elements are discussed. Furthermore, we discuss current applications of AO imaging to a population of healthy adults and to the most frequent causes of blindness, including diabetic retinopathy, age-related macular degeneration and glaucoma. We conclude our work with a discussion on future clinical prospects for AO retinal imaging.
Xiao, Di; Frost, Shaun; Vignarajan, Janardhan; An, Dong; Tay-Kearney, Mei-Ling; Kanagasingam, Yogi
Retinal photography is a non-invasive and well-accepted clinical diagnosis of ocular diseases. Qualitative and quantitative assessment of retinal images is crucial in ocular diseases related clinical application. Pulsatile properties caused by cardiac rhythm, such as spontaneous venous pulsation (SVP) and pulsatile motion of small arterioles, can be visualized by dynamic retinal imaging techniques and provide clinical significance. In this paper, we aim at vessel pulsatile motion detection and measurement. We proposed a novel approach for pulsatile motion measurement of retinal blood vessels by applying retinal image registration, blood vessel detection and blood vessel motion detection and measurement on infrared retinal image sequences. The performance of the proposed methods was evaluated on 8 image sequences with 240 images. A preliminary result has demonstrated the good performance of the method for blood vessel pulsatile motion observation and measurement.
Oishi, Akio; Nagai, Takayuki; Mandai, Michiko Takahashi, Masayo; Yoshimura, Nagahisa
The potential of bone marrow cell-derived immature dendritic cells (myeloid iDCs) in modulating the efficacy of retinal cell transplantation therapy was investigated. (1) In vitro, myeloid iDCs but not BMCs enhanced the survival and proliferation of embryonic retinal cells, and the expression of various neurotrophic factors by myeloid iDCs was confirmed with RT-PCR. (2) In subretinal transplantation, neonatal retinal cells co-transplanted with myeloid iDCs showed higher survival rate compared to those transplanted without myeloid iDCs. (3) CD8 T-cells reactive against donor retinal cells were significantly increased in the mice with transplantation of retinal cells alone. These results suggested the beneficial effects of the use of myeloid iDCs in retinal cell transplantation therapy.
Lombardo, Marco; Serrao, Sebastiano; Devaney, Nicholas; Parravano, Mariacristina; Lombardo, Giuseppe
Adaptive optics (AO) is a technology used to improve the performance of optical systems by reducing the effects of optical aberrations. The direct visualization of the photoreceptor cells, capillaries and nerve fiber bundles represents the major benefit of adding AO to retinal imaging. Adaptive optics is opening a new frontier for clinical research in ophthalmology, providing new information on the early pathological changes of the retinal microstructures in various retinal diseases. We have reviewed AO technology for retinal imaging, providing information on the core components of an AO retinal camera. The most commonly used wavefront sensing and correcting elements are discussed. Furthermore, we discuss current applications of AO imaging to a population of healthy adults and to the most frequent causes of blindness, including diabetic retinopathy, age-related macular degeneration and glaucoma. We conclude our work with a discussion on future clinical prospects for AO retinal imaging. PMID:23271600
Hudson, Lauren E.; Mendoza, Pia R.; Yan, Jiong; Grossniklaus, Hans E.
Purpose To report the clinical and histopathological findings of a reactive retinal astrocytic tumor (RRAT) that progressed to massive retinal gliosis. Observations The patient presented with an elevated, white-yellow retinal mass and extensive retinal exudation in the left eye. Progressive enlargement of the mass and proliferative vitreoretinopathy eventually led to phthisis bulbi and enucleation. Histologically, the mass showed a predominant astrocytic component with intense glial fibrillary acidic protein staining, hyperplasia, fibrous metaplasia, and osseous metaplasia of the retinal pigment epithelium. The Ki-67 proliferative index was <5%, and few scattered vascular channels were observed. Conclusions and Importance These findings show that this tumor is the result of a reactive glial process rather than of neoplastic vascular proliferation. Massive retinal gliosis probably represents the advanced stage of RRAT.
Fraz, M M; Remagnino, P; Hoppe, A; Uyyanonvara, B; Rudnicka, A R; Owen, C G; Barman, S A
Retinal vessel segmentation algorithms are a fundamental component of automatic retinal disease screening systems. This work examines the blood vessel segmentation methodologies in two dimensional retinal images acquired from a fundus camera and a survey of techniques is presented. The aim of this paper is to review, analyze and categorize the retinal vessel extraction algorithms, techniques and methodologies, giving a brief description, highlighting the key points and the performance measures. We intend to give the reader a framework for the existing research; to introduce the range of retinal vessel segmentation algorithms; to discuss the current trends and future directions and summarize the open problems. The performance of algorithms is compared and analyzed on two publicly available databases (DRIVE and STARE) of retinal images using a number of measures which include accuracy, true positive rate, false positive rate, sensitivity, specificity and area under receiver operating characteristic (ROC) curve.
Li, Zehua; Dai, Jiapei
The discovery of dark noise in retinal photoreceptors resulted in a long-lasting controversy over its origin and the underlying mechanisms. Here, we used a novel ultra-weak biophoton imaging system (UBIS) to detect biophotonic activity (emission) under dark conditions in rat and bullfrog (Rana catesbeiana) retinas in vitro. We found a significant temperature-dependent increase in biophotonic activity that was completely blocked either by removing intracellular and extracellular Ca(2+) together or inhibiting phosphodiesterase 6. These findings suggest that the photon-like component of discrete dark noise may not be caused by a direct contribution of the thermal activation of rhodopsin, but rather by an indirect thermal induction of biophotonic activity, which then activates the retinal chromophore of rhodopsin. Therefore, this study suggests a possible solution regarding the thermal activation energy barrier for discrete dark noise, which has been debated for almost half a century.
Szabadfi, Krisztina; Mester, Laszlo; Reglodi, Dora; Kiss, Peter; Babai, Norbert; Racz, Boglarka; Kovacs, Krisztina; Szabo, Aliz; Tamas, Andrea; Gabriel, Robert; Atlasz, Tamas
Retinal ischemia can be effectively modeled by permanent bilateral common carotid artery occlusion, which leads to chronic hypoperfusion-induced degeneration in the entire rat retina. The complex pathways leading to retinal cell death offer a complex approach of neuroprotective strategies. In the present review we summarize recent findings with different neuroprotective candidate molecules. We describe the protective effects of intravitreal treatment with: (i) urocortin 2; (ii) a mitochondrial ATP-sensitive K+ channel opener, diazoxide; (iii) a neurotrophic factor, pituitary adenylate cyclase activating polypeptide; and (iv) a novel poly(ADP-ribose) polymerase inhibitor (HO3089). The retinoprotective effects are demonstrated with morphological description and effects on apoptotic pathways using molecular biological techniques. PMID:20386654
Federici, Thomas J
A 63-year-old man suffered a central retinal vein occlusion 2 months after he began taking leuprolide acetate for prostate cancer. Despite control for possible systemic hypertension (126/90 mm Hg) and mild hypercholesterolemia (total cholesterol level =246 mg/dL [range: 16 to 200 mg/dL], high-density lipoprotein level =67 mg/dL [range: 40 to 59 mg/dL], and low-density lipoprotein level =144 mg/dL [range: 0 to 130 mg/dL]), progression of the venous occlusive disease occurred. Leuprolide acetate, which is associated with thromboembolic events and diffuse intravascular coagulation, may be implicated in central retinal vein occlusion.
Virtual Retinal DisplayTM technology is a retinal scanning display (RSD) technology being developed at Microvision, Inc., for a variety of applications including microdisplays. An RSD scans a modulated light beam onto a viewer's retina to produce a perceived image. Red, green and blue light sources, such as lasers, laser diodes or LEDs combine with Microvision's proprietary miniaturized scanner designs to make the RSD very well suited for head-worn and helmet-mounted displays (HMD). This paper compares the features of RSD technology to other display technologies such as the cathode ray tubes or matrix-based displays for HMD and other wearable display applications, and notes important performance advantages due to the number of pixel- generating elements. Also discussed are some fundamental optical limitations for virtual displays used in the HMD applications.
Al-Halafi, Ali M.
We are approaching a new era of retinal pharmacotherapy where new drugs are rapidly being worked out for the treatment of posterior-segment disease. Recent development in ocular drug delivery systems research has provided new insights into drug development, and the use of nanoparticles for drug delivery is thus a promising excellent approach for advanced therapy of ocular diseases. The primary goal is to develop a variety of drug delivery systems to complement and further enhance the efficacy of the available new medications. The ideal sustained release technology will provide a high level of safety with continuous release over an extended period of time while maintaining almost total drug bioactivity. The use of nanocarriers, such as cyclodextrin nanoparticle suspension, liposomes, nanospheres and, nanoemulsions for gene therapy of retinal diseases has been highlighted in this review. PMID:25473348
Perches, Sara; Collados, M Victoria; Ares, Jorge
Refraction techniques make it possible to determine the most appropriate sphero-cylindrical lens prescription to achieve the best possible visual quality. Among these techniques, subjective refraction (i.e., patient's response-guided refraction) is the most commonly used approach. In this context, this paper's main goal is to present a simulation software that implements in a virtual manner various subjective-refraction techniques--including Jackson's Cross-Cylinder test (JCC)--relying all on the observation of computer-generated retinal images. This software has also been used to evaluate visual quality when the JCC test is performed in multifocal-contact-lens wearers. The results reveal this software's usefulness to simulate the retinal image quality that a particular visual compensation provides. Moreover, it can help to gain a deeper insight and to improve existing refraction techniques and it can be used for simulated training.
Azemin, Mohd Zulfaezal Che; Kumar, Dinesh K; Sugavaneswaran, Lakshmi; Krishnan, Sridhar
Retinal image has been considered for number of health and biometrics applications. However, the reliability of these has not been investigated thoroughly. The variation observed in retina scans taken at different times is attributable to differences in illumination and positioning of the camera. It causes some missing bifurcations and crossovers from the retinal vessels. Exhaustive selection of optimal parameters is needed to construct the best similarity metrics equation to overcome the incomplete landmarks. In this paper, we extracted multiple features from the retina scans and employs supervised classification to overcome the shortcomings of the current techniques. The experimental results of 60 retina scans with different lightning conditions demonstrate the efficacy of this technique. The results were compared with the existing methods.
Anastasi, M; Lauricella, M; Ponte, F
The persistence of a residual flicker electroretinogram 20 Hz response in many cases of retinitis pigmentosa, when the Oscillatory Potentials (OPs) were no longer recordable, led the authors to an investigation by Fourier analysis. The study was carried out in 33 patients affected by different hereditary forms of retinitis pigmentosa revealing recordable 20 Hz flash ERG responses. We applied the Fourier analysis to this ERG response and compared the weight percentage of the first two components to the OP added amplitude. The analysis showed that the 20 Hz flash ERG response contains only the first harmonic in patients with no recordable OPs and both harmonics in patients with recordable OPs. This relationship between OPs and 20 Hz second component, that is possibly related to the activity of inner retina as well as the OPs, can demonstrate an alteration of the inner retina which evolves with distinct electrophysiological features from the ERG photoreceptor impairment.
Tanimoto, Naoyuki; Brombas, Arne; Müller, Frank; Seeliger, Mathias W
In this chapter, the impact of HCN1 channels on the retinal functional properties was presented. HCN1 channel loss led to an intensity-dependent prolongation of the rod system response, in agreement with the threshold mechanism of activation of the channel. Rod outer segment functionality was not altered, supporting the main site of action in the inner segment. Fixed-intensity variable frequency flicker series showed a regular amplitude decline near threshold and a reduced flicker fusion frequency above threshold due to increased waveform width. It was suggested that shortening and shaping of light responses by activation of HCN1 is an important step at least in the scotopic pathways. The retina of HCN1 knockout animals provides a valuable system with which to study the role of HCN1 in the shaping and processing of retinal light responses especially to repetitive stimulation.
Lund, David J.; Edsall, Peter R.
The action spectrum for light-induced damage to the retina results from the wavelength dependence transmission of the preretinal ocular media, wavelength dependent absorption in retinal chromophores and chromatic aberration of the eye optics. While various light/tissue interaction mechanisms have been implicated, thermal mechanisms dominate in the red and near-infrared for all exposure durations and in the visible for exposures shorter than a few seconds. A number of investigators have measured the transmission of the eye and the spectra of retinal absorbers, and thermal models based on these data predict the broad features of the action spectrum. Dose/response studies with lasers and incoherent light sources, conducted over the past 10 years mainly validate the thermal models.
Perches, Sara; Collados, M. Victoria; Ares, Jorge
Refraction techniques make it possible to determine the most appropriate sphero-cylindrical lens prescription to achieve the best possible visual quality. Among these techniques, subjective refraction (i.e., patient’s response-guided refraction) is the most commonly used approach. In this context, this paper’s main goal is to present a simulation software that implements in a virtual manner various subjective-refraction techniques—including Jackson’s Cross-Cylinder test (JCC)—relying all on the observation of computer-generated retinal images. This software has also been used to evaluate visual quality when the JCC test is performed in multifocal-contact-lens wearers. The results reveal this software’s usefulness to simulate the retinal image quality that a particular visual compensation provides. Moreover, it can help to gain a deeper insight and to improve existing refraction techniques and it can be used for simulated training. PMID:26938648
Sznitman, Raphael; Rother, Diego; Handa, Jim; Gehlbach, Peter; Hager, Gregory D; Taylor, Russell
It has been shown that excessive white light exposure during retinal microsurgery can induce retinal damage. To address this problem, one can illuminate the retina with a device that alternates between white, and less damaging limited-spectrum light. The surgeon is then presented with a fully colored video by recoloring the limited-spectrum light frames, using information from the white-light frames. To obtain accurately colored images, while reducing phototoxicity, we have developed a novel algorithm that monitors the quality of the recolored images and determines when white light may be substituted by limited-spectrum light. We show qualitatively and quantitatively that our system can provide reliable images using a significantly smaller light dose as compared to other state-of-the-art coloring schemes.
Noble, Carl; Blice, Jeffrey
This case report was performed to display the visually significant damage to the retina that can occur with brief exposure to a handheld laser pointer. Laser use in the military is ever increasing in form of target designators, rangefinders, or radar warning systems with powers far greater than used in this case. There is great potential for future cases of retinal damage among active duty members, and the importance of prevention through laser safety programs and recognition through trained medical personnel is paramount.
Marc, Robert; Pfeiffer, Rebecca; Jones, Bryan
Three technologies have emerged as therapies to restore light sensing to profoundly blind patients suffering from late-stage retinal degenerations: (1) retinal prosthetics, (2) optogenetics, and (3) chemical photoswitches. Prosthetics are the most mature and the only approach in clinical practice. Prosthetic implants require complex surgical intervention and provide only limited visual resolution but can potentially restore navigational ability to many blind patients. Optogenetics uses viral delivery of type 1 opsin genes from prokaryotes or eukaryote algae to restore light responses in survivor neurons. Targeting and expression remain major problems, but are potentially soluble. Importantly, optogenetics could provide the ultimate in high-resolution vision due to the long persistence of gene expression achieved in animal models. Nevertheless, optogenetics remains challenging to implement in human eyes with large volumes, complex disease progression, and physical barriers to viral penetration. Now, a new generation of photochromic ligands or chemical photoswitches (azobenzene-quaternary ammonium derivatives) can be injected into a degenerated mouse eye and, in minutes to hours, activate light responses in neurons. These photoswitches offer the potential for rapidly and reversibly screening the vision restoration expected in an individual patient. Chemical photoswitch variants that persist in the cell membrane could make them a simple therapy of choice, with resolution and sensitivity equivalent to optogenetics approaches. A major complexity in treating retinal degenerations is retinal remodeling: pathologic network rewiring, molecular reprogramming, and cell death that compromise signaling in the surviving retina. Remodeling forces a choice between upstream and downstream targeting, each engaging different benefits and defects. Prosthetics and optogenetics can be implemented in either mode, but the use of chemical photoswitches is currently limited to downstream
raster scans were performed with the Spectralis SD-OCT(Heidelberg Engineering) through 2,624 drusen in 14 eyes with clinically dry AMD who had been...NOTES 14 . ABSTRACT See next page 15. SUBJECT TERMS Retinal Degenerations; Clinical Trial Network; non-invasive imaging; treatment 16. SECURITY...THIS PAGE U UU 78 19b. TELEPHONE NUMBER (include area code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 14 . ABSTRACT The
Petersen-Jones, Simon M; Komáromy, András M
Spontaneous canine models exist for several inherited retinal dystrophies. This review will summarize the models and indicate where they have been used in translational gene therapy trials. The RPE65 gene therapy trials to treat childhood blindness are a good example of how studies in dogs have contributed to therapy development. Outcomes in human clinical trials are compared and contrasted with the result of the preclinical dog trials.
Komáromy, András M.
Abstract Spontaneous canine models exist for several inherited retinal dystrophies. This review will summarize the models and indicate where they have been used in translational gene therapy trials. The RPE65 gene therapy trials to treat childhood blindness are a good example of how studies in dogs have contributed to therapy development. Outcomes in human clinical trials are compared and contrasted with the result of the preclinical dog trials. PMID:25671556
temperature rise is a function of the energy must relied on suitable animal model for their density, duration, and wavelength of the expos- investigations in... model was based on the similarity of its retinal tions of less than a microsecond. Theoretical anatomy, physiology, and visual sensitivities models ...absorbing calorimeter i experimental chamber also indicating that the (Scientech, Model 363) and were expressed in shock had no lasting psychological
macular degeneration (AMD) and diabetic retinopathy. Intraocular injection can place the drug directly into the vitreous cavity but is not recommended...drugs for treatment of other ocular diseases such as retinal tumors, diabetic retinopathy, age related macular degeneration and cytomegalovirus...with the changes in mobile phase as indicated in each section. Data was collected for 10 min and the peak area was analyzed using the standard
Jarrett, W H
The author reports 16 cases of rhegmatogenous retinal detachment in which, for a variety of reasons, immediate reparative surgery was not carried out. To date, one-half of these cases have not been operated, and four have been followed for 6 years or longer. No case suffered visual loss because of the delay in surgery, nor has chronic inflammation, glaucoma, or rubeosis been a problem. The clinical characteristics of this group of cases is defined. PMID:2979020
Barrett, Steven F.; Wright, Cameron H. G.; Jerath, Maya R.; Lewis, R. Stephen, II; Dillard, Bryan C.; Rylander, Henry G., III; Welch, Ashley J.
Researchers at the University of Texas at Austin's Biomedical Engineering Laser Laboratory investigating the medical applications of lasers have worked toward the development of a retinal robotic laser system. The ultimate goal of this ongoing project is to precisely place and control the depth of laser lesions for the treatment of various retinal diseases such as diabetic retinopathy and retinal tears. Researchers at the USAF Academy's Department of Electrical Engineering have also become involved with this research due to similar interests. Separate low speed prototype subsystems have been developed to control lesion depth using lesion reflectance feedback parameters and lesion placement using retinal vessels as tracking landmarks. Both subsystems have been successfully demonstrated in vivo on pigmented rabbits using an argon continuous wave laser. Work is ongoing to build a prototype system to simultaneously control lesion depth and placement. The instrumentation aspects of the prototype subsystems were presented at SPIE Conference 1877 in January 1993. Since then our efforts have concentrated on combining the lesion depth control subsystem and the lesion placement subsystem into a single prototype capable of simultaneously controlling both parameters. We have designed this combined system CALOSOS for Computer Aided Laser Optics System for Ophthalmic Surgery. An initial CALOSOS prototype design is provided. We have also investigated methods to improve system response time. The use of high speed non-standard frame rate CCD cameras and high speed local bus frame grabbers hosted on personal computers are being investigated. A review of system testing in vivo to date is provided in SPIE Conference proceedings 2374-49 (Novel Applications of Lasers and Pulsed Power, Dual-Use Applications of Lasers: Medical session).
Artal, P; Herreros de Tejada, P; Muñoz Tedó, C; Green, D G
Many rodents do not see well. For a target to be resolved by a rat or a mouse, it must subtend a visual angle of a degree or more. It is commonly assumed that this poor spatial resolving capacity is due to neural rather than optical limitations, but the quality of the retinal image has not been well characterized in these animals. We have modified a double-pass apparatus, initially designed for the human eye, so it could be used with rodents to measure the modulation transfer function (MTF) of the eye's optics. That is, the double-pass retinal image of a monochromatic (lambda = 632.8 nm) point source was digitized with a CCD camera. From these double-pass measurements, the single-pass MTF was computed under a variety of conditions of focus and with different pupil sizes. Even with the eye in best focus, the image quality in both rats and mice is exceedingly poor. With a 1-mm pupil, for example, the MTF in the rat had an upper limit of about 2.5 cycles/deg, rather than the 28 cycles/deg one would obtain if the eye were a diffraction-limited system. These images are about 10 times worse than the comparable retinal images in the human eye. Using our measurements of the optics and the published behavioral and electrophysiological contrast sensitivity functions (CSFs) of rats, we have calculated the CSF that the rat would have if it had perfect rather than poor optics. We find, interestingly, that diffraction-limited optics would produce only slight improvement overall. That is, in spite of retinal images which are of very low quality, the upper limit of visual resolution in rodents is neurally determined. Rats and mice seem to have eyes in which the optics and retina/brain are well matched.
Iezzi, Raymond; Finlayson, Paul; Xu, Yong; Katragadda, Rakesh
Natural inter-neuronal communication is mediated primarily via neurotransmitter-gated ion channels. While most of the methods for neural interfacing have been based upon electrical stimulation, neurotransmitter-based approaches for the spatially and temporally controlled delivery of neurotransmitters are relatively new. Methods of neurotransmitter stimulation retinal prosthesis may provide new ways to control neural excitation. Experimental results for retinal ganglion cell stimulation demonstrate the feasibility of a neurotransmitter-based retinal prosthesis.
Joondeph, Stephanie A.; Joondeph, Brian C.
The purpose of this paper is to describe a traumatic retinal detachment occurring as a result of CrossFit training using an elastic exercise band. The patient sustained an ocular injury from an elastic band during CrossFit training, resulting in a giant retinal dialysis and retinal detachment, which were successfully repaired. Trainers and athletes need to be aware of the potential for ocular injury from elastic exercise bands and take appropriate precautions. PMID:24106626
Joondeph, Stephanie A; Joondeph, Brian C
The purpose of this paper is to describe a traumatic retinal detachment occurring as a result of CrossFit training using an elastic exercise band. The patient sustained an ocular injury from an elastic band during CrossFit training, resulting in a giant retinal dialysis and retinal detachment, which were successfully repaired. Trainers and athletes need to be aware of the potential for ocular injury from elastic exercise bands and take appropriate precautions.
Radius, R L
Thickness of the retinal nerve fiber layer is studied in the eyes of three primate species. Measurements are made at various points throughout the fundus, including the peripapillary, arcuate, macular (area centralis), equatorial, and peripheral parts of the retina. Anatomic findings are compared with the clinical appearance of retinal light reflexes in these way. It is proposed that the nature of this light reflex is, in part, determined by the thickness of the retinal nerve fiber layer.
REPORT Carotenoid antenna binding and function in retinal proteins 14. ABSTRACT 16. SECURITY CLASSIFICATION OF: Xanthorhodopsin, a proton pump from the...eubacterium Salinibacter ruber, is a unique dual chromophore system that contains, in addition to retinal, the carotenoid salinixanthin as a light... carotenoid ring near the retinal ring. Substitution of the small glycine with bulky tryptophan in this site eliminates binding. The second factor is the 4
Miyake, Ayumi; Araki, Masasuke
Our research group has extensively studied retinal regeneration in adult Xenopus laevis. However, X. laevis does not represent a suitable model for multigenerational genetics and genomic approaches. Instead, Xenopus tropicalis is considered as the ideal model for these studies, although little is known about retinal regeneration in X. tropicalis. In the present study, we showed that a complete retina regenerates at approximately 30 days after whole retinal removal. The regenerating retina was derived from the stem/progenitor cells in the ciliary marginal zone (CMZ), indicating a novel mode of vertebrate retinal regeneration, which has not been previously reported. In a previous study, we showed that in X. laevis, retinal regeneration occurs primarily through the transdifferentiation of retinal pigmented epithelial (RPE) cells. RPE cells migrate to the retinal vascular membrane and reform a new epithelium, which then differentiates into the retina. In X. tropicalis, RPE cells also migrated to the vascular membrane, but transdifferentiation was not evident. Using two tissue culture models of RPE tissues, it was shown that in X. laevis RPE culture neuronal differentiation and reconstruction of the retinal three-dimensional (3-D) structure were clearly observed, while in X. tropicalis RPE culture neither ßIII tubulin-positive cells nor 3-D retinal structure were seen. These results indicate that the two Xenopus species are excellent models to clarify the cellular and molecular mechanisms of retinal regeneration, as these animals have contrasting modes of regeneration; one mode primarily involves RPE cells and the other mode involves stem/progenitor cells in the CMZ.
Fan, Wen-juan; Li, Xue; Yao, Huan-ling; Deng, Jie-xin; Liu, Hong-liang; Cui, Zhan-jun; Wang, Qiang; Wu, Ping; Deng, Jin-bo
To investigate the pattern of neural differentiation and synaptogenesis in the mouse retina, immunolabeling, BrdU assay and transmission electron microscopy were used. We show that the neuroblastic cell layer is the germinal zone for neural differentiation and retinal lamination. Ganglion cells differentiated initially at embryonic day 13 (E13), and at E18 horizontal cells appeared in the neuroblastic cell layer. Neural stem cells in the outer neuroblastic cell layer differentiated into photoreceptor cells as early as postnatal day 0 (P0), and neural stem cells in the inner neuroblastic cell layer differentiated into bipolar cells at P7. Synapses in the retina were mainly located in the outer and inner plexiform layers. At P7, synaptophysin immunostaining appeared in presynaptic terminals in the outer and inner plexiform layers with button-like structures. After P14, presynaptic buttons were concentrated in outer and inner plexiform layers with strong staining. These data indicate that neural differentiation and synaptogenesis in the retina play important roles in the formation of retinal neural circuitry. Our study showed that the period before P14, especially between P0 and P14, represents a critical period during retinal development. Mouse eye opening occurs during that period, suggesting that cell differentiation and synaptic formation lead to the attainment of visual function. PMID:27073386
Vukojević, Nenad; Sikić, Jakov; Curković, Tihomir; Juratovac, Zlatko; Katusić, Damir; Sarić, Borna; Jukić, Tomislav
Changes in the eye axial diameter were studied to assess the eye globe impact of conventional operation for retinal detachment. The study included 69 eyes in 69 patients operated on for rhegmatogenous retinal detachment. There were 46.4% of men and 53.6% of women, mean age 52.7 (+/- 15.21) years. Results of preoperative and postoperative ultrasonographic measurement of axial diameter are presented. The mean preoperative and postoperative eye axial diameter was 23.69 (+/- 1.84) mm and 24.43 (+/- 1.91) mm, respectively. Postoperative results showed the axial eye length to increase by a mean of 0.74 (+/- 0.44) mm, yielding a statistically significant difference from the preoperative measurement (p < 0.001). The mean myopia induced by this eyeball elongation was 1.77 D. The encircling band with and without segmental buckling used in surgical repair of retinal detachment creates circular and segmental indentation of the eyeball, thus increasing its axial length. The myopia induced by elongation of the eyeball results in considerable myopia, which requires appropriate correction in the early postoperative period to achieve favorable vision rehabilitation.
Schön, Christian; Biel, Martin; Michalakis, Stylianos
Visual phototransduction relies on the function of cyclic nucleotide-gated channels in the rod and cone photoreceptor outer segment plasma membranes. The role of these ion channels is to translate light-triggered changes in the second messenger cyclic guanosine 3'-5'-monophosphate levels into an electrical signal that is further processed within the retinal network and then sent to higher visual centers. Rod and cone photoreceptors express distinct CNG channels. The rod photoreceptor CNG channel is composed of one CNGB1 and three CNGA1 subunits, whereas the cone channel is formed by one CNGB3 and three CNGA3 subunits. Mutations in any of these channel subunits result in severe and currently untreatable retinal degenerative diseases like retinitis pigmentosa or achromatopsia. In this review, we provide an overview of the human diseases and relevant animal models of CNG channelopathies. Furthermore, we summarize recent results from preclinical gene therapy studies using adeno-associated viral vectors and discuss the efficacy and translational potential of these gene therapeutic approaches.
Gerard, Xavier; Garanto, Alejandro; Rozet, Jean-Michel; Collin, Rob W J
Inherited retinal dystrophies (IRDs) are an extremely heterogeneous group of genetic diseases for which currently no effective treatment strategies exist. Over the last decade, significant progress has been made utilizing gene augmentation therapy for a few genetic subtypes of IRD, although several technical challenges so far prevent a broad clinical application of this approach for other forms of IRD. Many of the mutations leading to these retinal diseases affect pre-mRNA splicing of the mutated genes . Antisense oligonucleotide (AON)-mediated splice modulation appears to be a powerful approach to correct the consequences of such mutations at the pre-mRNA level , as demonstrated by promising results in clinical trials for several inherited disorders like Duchenne muscular dystrophy, hypercholesterolemia and various types of cancer. In this mini-review, we summarize ongoing pre-clinical research on AON-based therapy for a few genetic subtypes of IRD , speculate on other potential therapeutic targets, and discuss the opportunities and challenges that lie ahead to translate splice modulation therapy for retinal disorders to the clinic.
Godara, Pooja; Dubis, Adam M; Roorda, Austin; Duncan, Jacque L; Carroll, Joseph
The human retina is a uniquely accessible tissue. Tools like scanning laser ophthalmoscopy and spectral domain-optical coherence tomography provide clinicians with remarkably clear pictures of the living retina. Although the anterior optics of the eye permit such non-invasive visualization of the retina and associated pathology, the same optics induce significant aberrations that obviate cellular-resolution imaging in most cases. Adaptive optics (AO) imaging systems use active optical elements to compensate for aberrations in the optical path between the object and the camera. When applied to the human eye, AO allows direct visualization of individual rod and cone photoreceptor cells, retinal pigment epithelium cells, and white blood cells. AO imaging has changed the way vision scientists and ophthalmologists see the retina, helping to clarify our understanding of retinal structure, function, and the etiology of various retinal pathologies. Here, we review some of the advances that were made possible with AO imaging of the human retina and discuss applications and future prospects for clinical imaging.
Fan, Wen-Juan; Li, Xue; Yao, Huan-Ling; Deng, Jie-Xin; Liu, Hong-Liang; Cui, Zhan-Jun; Wang, Qiang; Wu, Ping; Deng, Jin-Bo
To investigate the pattern of neural differentiation and synaptogenesis in the mouse retina, immunolabeling, BrdU assay and transmission electron microscopy were used. We show that the neuroblastic cell layer is the germinal zone for neural differentiation and retinal lamination. Ganglion cells differentiated initially at embryonic day 13 (E13), and at E18 horizontal cells appeared in the neuroblastic cell layer. Neural stem cells in the outer neuroblastic cell layer differentiated into photoreceptor cells as early as postnatal day 0 (P0), and neural stem cells in the inner neuroblastic cell layer differentiated into bipolar cells at P7. Synapses in the retina were mainly located in the outer and inner plexiform layers. At P7, synaptophysin immunostaining appeared in presynaptic terminals in the outer and inner plexiform layers with button-like structures. After P14, presynaptic buttons were concentrated in outer and inner plexiform layers with strong staining. These data indicate that neural differentiation and synaptogenesis in the retina play important roles in the formation of retinal neural circuitry. Our study showed that the period before P14, especially between P0 and P14, represents a critical period during retinal development. Mouse eye opening occurs during that period, suggesting that cell differentiation and synaptic formation lead to the attainment of visual function.
Dalkara, Deniz; Sahel, José-Alain
Gene therapy is quickly becoming a reality applicable in the clinic for inherited retinal diseases. Progress over the past decade has moved proof-of-concept gene therapies from bench to bedside. The remarkable success in safety and efficacy, in the phase I/II clinical trials for the form of the severe childhood-onset blindness, Leber's Congenital Amaurosis (LCA) type II (due to mutations in the RPE65 gene) generated significant interest and opened up possibilities for a new era of retinal gene therapies. Success in these clinical trials was due to combining the favorable features of both the retina as a target organ and adeno-associated virus (AAV) as a vector. The retina offers several advantages for gene therapy approaches. It is an anatomically defined structure that is readily accessible for therapy and has some degree of immune privilege, making it suitable for application of viral vectors. AAV, on the other hand, is a non-pathogenic helper dependent virus that has little immunogenicity. This viral vector transduces quiescent cells efficiently and thanks to its small size diffuses well in the interneural matrix, making it suitable for applications in neural tissue. Building on this initial clinical success with LCA II, we have now many opportunities to extend this proof-of-concept to other retinal diseases. This article will discuss what are some of the most imminent targets for such therapies and what are the challenges that we face in moving these therapies to the clinic.
Barile, Gaetano R; Schmidt, Ann M
RAGE, the receptor for advanced glycation endproducts (AGEs), is a multiligand signal transduction receptor of the immunoglobulin superfamily of cell surface molecules that has been implicated in the pathogenesis of diabetic complications, neurodegenerative diseases, inflammatory disorders, and cancer. These diverse biologic disorders reflect the multiplicity of ligands capable of cellular interaction via RAGE that include, in addition to AGEs, amyloid-beta (Abeta) peptide, the S100/calgranulin family of proinflammatory cytokines, and amphoterin, a member of the High Mobility Group Box (HMGB) DNA-binding proteins. In the retina, RAGE expression is present in neural cells, the vasculature, and RPE cells, and it has also been detected in pathologic cellular retinal responses including epiretinal and neovascular membrane formation. Ligands for RAGE, in particular AGEs, have emerged as relevant to the pathogenesis of diabetic retinopathy and age-related macular disease. While the understanding of RAGE and its role in retinal dysfunction with aging, diabetes mellitus, and/or activation of pro-inflammatory pathways is less complete compared to other organ systems, increasing evidence indicates that RAGE can initiate and sustain significant cellular perturbations in the inner and outer retina. For these reasons, antagonism of RAGE interactions with its ligands may be a worthwhile therapeutic target in such seemingly disparate, visually threatening retinal diseases as diabetic retinopathy, age-related macular degeneration, and proliferative vitreoretinopathy.