Cases Of Severe Vision Loss Research Articles

Novel Approaches to the Treatment of Idiopathic Intracranial Hypertension.

Idiopathic intracranial hypertension (IIH) typically affects women of childbearing age, is associated with recent weight gain, and can result in debilitating headache as well as papilledema that can cause vision loss. There have been advances in the medical and surgical treatment of affected patients with IIH that can improve outcomes and tolerability of therapy. Medical treatment with agents that lower intracranial pressure through pathways other than carbonic anhydrase inhibition are being developed, and medically-directed weight loss as well as bariatric surgery now may be considered as primary therapy. New surgical options including venous sinus stenting have shown efficacy even with cases of severe vision loss. Our treatment options for IIH patients are becoming more diverse, and individualized treatment decisions are now possible to address specific components of the patient's disease manifestations and to lead to IIH remission.

Visual Acuity and Visual Field Changes in Patients with End-Stage PACG with Tubular Visual Field after Cataract Surgery

Introduction: To investigate the impact of cataract surgery on visual acuity and visual field (VF) in patients with end-stage glaucoma with tubular VF, and assess the risk of severe visual impairment. Methods: Retrospective analysis of the case data of patients with end-stage glaucoma with tubular VF who underwent cataract surgery in our hospital in the past 7 years. Results: A total of 59 patients with 63 eyes were enrolled, 62 eyes were primary angle-closure glaucoma (PACG) and 1 eye was primary open-angle glaucoma. The last follow-up time was an average of 9 months, and no cases of severe vision loss occurred. Best corrected visual acuity (BCVA) improved significantly after surgery (0.57 ± 0.46 vs. 0.45 ± 0.43 logarithm of the minimum angle of resolution, p < 0.01), and there was a significant drop in intraocular pressure (IOP; 22.85 ± 9.7 vs. 16.07 ± 3.38, p < 0.01), a reduced number of glaucoma medications (2 ± 1.32 vs. 0.5 ± 1, p < 0.01), statistical improvement in VF index (VFI) and mean defect (MD) (12.3% ± 7.65% vs. 16.1% ± 9.84%, p < 0.01; −29.09 ± 2.16 vs. −28.31 ± 3.01, p < 0.01) after surgery. The higher the preoperative VFI and MD were, the better the postoperative BCVA (r = −0.387, r = −0.347, respectively). The degree of postoperative VFI improvement was significantly correlated with preoperative MD (r = 0.372, p < 0.01). During the follow-up period, 5 eyes (8%) underwent anti-glaucoma surgery due to elevated IOP. Conclusion: Cataract surgery can significantly improve visual acuity and VF in patients with end-stage PACG with tubular VF, and no patients have severe visual impairment. The less preoperative VF damage there is, the greater the postoperative visual acuity and VF improvement. Poor IOP control is the main cause of further damage to postoperative visual acuity and VF.

Ube3d, a New Gene Associated with Age-Related Macular Degeneration, Induces Functional Changes in Both In Vivo and In Vitro Studies

Neovascular age-related macular degeneration (AMD) is characterized by the formation of choroidal neovascularization, which is responsible for more than 80% of cases of severe vision loss. Ubiquitin protein ligase E3D (UBE3D) gene missense has been proven to be associated with neovascular AMD in the East Asian population based on our previous study. In vivo, we explored the role of ube3d in eye development and the mechanisms underlying the development of neovascular AMD in a zebrafish model. In vitro, we investigated the function and mechanism of ube3d in oxidative damage in human retinal pigment epithelium (hRPE) cells. The ube3d gene was knocked down in zebrafish in our experiments, and rescue of ube3d morphants was also performed. We observed the zebrafish model at the molecular level and functional and morphological changes in vivo. Lentivirus-based gene transfer technology was used to overexpress/knockdown ube3d expression in hRPE cells in vitro. hRPE oxidative damage was induced by tert-butyl hydroperoxide (t-TBH). Cell proliferation and migration were assessed. Quantitative real-time PCR and western blot were used to measure the expression levels of UBE3D and CyclinB1. Abnormal eye development was found in zebrafish in this study, including small eyes, delayed retinal development, delayed retrograde melanosome transport, and reduced dark-induced hyper-locomotor activity under light-off conditions. In addition, increased angiogenesis was observed in ube3d morphants. A negative correlation between UBE3D and CyclinB1 was observed. Low UBE3D expression can promote oxidative damage and inflammatory reactions. UBE3D and autophagy have a synergetic effect on anti-oxidative damage. These findings indicate that ube3d may play an important role in the pathogenesis of AMD by affecting retinal development, oxidative damage, and autophagy.

Orbital apex syndrome from bacterial sinusitis without orbital cellulitis

PurposeTo describe a case of orbital apex syndrome as a result of isolated bacterial sinusitis. ObservationsA 63-year-old woman presented with an orbital apex syndrome from isolated bacterial sinusitis with rapidly declining visual acuity to no light perception. We compared our case with 6 similar cases of severe vision loss from isolated bacterial sinusitis. In contrast to previously published cases, our patient presented with good vision yet deteriorated to no light perception despite appropriate treatment. Conclusions and importanceOrbital apex syndrome can present as a constellation of cranial neuropathies including optic neuropathy from conditions affecting the orbital apex. Although vision loss remained permanent, prompt initiation of broad-spectrum antibiotics and antifungals and surgical intervention prevented further extension of infection into intracranial structures.

Neovascular age-related macular degeneration in Austria

Age-related macular degeneration (AMD) is the leading cause of blindness in patients over 50 years of age in developed countries. It is estimated that the projected number of people with AMD will be 196 million worldwide by the year 2020, increasing to 288 million by 2040. Of these patients, 10–20% suffering from the fast progressing neovascular form of the disease (nAMD) account for 90% of all cases of severe vision loss. In fact, AMD is responsible for 8.7% of all cases of blindness worldwide. These numbers indicate the substantial burden of the disease. The WHO estimates that 246 million people worldwide currently have low vision and 39 million are blind. A literature (Medline) and Internet research was performed to better understand the prevalence of AMD and how health care could be prepared to cope with it in the future. In 2015, there were 90,010 intravitreal injections (IVI) in Austrian hospitals and primary care units. In 2016, this number rose to >100,000 IVI as the applications increase by approx. 15–20% every year. Since health insurances do not refund IVI in primary care, these services are channeled toward clinical wards, causing overcrowded waiting rooms and dissatisfied patients. Despite this high number of IVI in Austria, real-life data show that the number of IVI given today is not sufficient to keep visual acuity on a steady level. Therefore, new and long-acting treatment options are needed to end the burden for clinics and patients and to increase treatment efficiency by simplified protocols. Herein, a potential new gene-therapeutic approach using nonviral vectors and somatic pigment epithelial cells to overcome the imbalance of pigment epithelium-derived factor and vascular endothelial growth factor in nAMD is described.

Phosphatidylserine (PS) Is Exposed in Choroidal Neovascular Endothelium: PS-Targeting Antibodies Inhibit Choroidal Angiogenesis In Vivo and Ex Vivo.

Choroidal neovascularization (CNV) accounts for 90% of cases of severe vision loss in patients with advanced age-related macular degeneration. Identifying new therapeutic targets for CNV may lead to novel combination therapies to improve outcomes and reduce treatment burden. Our goal was to test whether phosphatidylserine (PS) becomes exposed in the outer membrane of choroidal neovascular endothelium, and whether this could provide a new therapeutic target for CNV. Choroidal neovascularization was induced in C57BL/6J mice using laser photocoagulation. Choroidal neovascularization lesions costained for exposed PS and for intercellular adhesion molecule 2 (or isolectin B4) were imaged in flat mounts and in cross sections. The laser CNV model and a choroidal sprouting assay were used to test the effect of PS-targeting antibodies on choroidal angiogenesis. Choroidal neovascularization lesion size was determined by intercellular adhesion molecule 2 (ICAM-2) staining of flat mounts. We found that PS was exposed in CNV lesions and colocalized with vascular endothelial staining. Treatment with PS-targeting antibodies led to a 40% to 80% reduction in CNV lesion area when compared to treatment with a control antibody. The effect was the same as that seen using an equal dose of an anti-VEGF antibody. Results were confirmed using the choroid sprouting assay, an ex vivo model of choroidal angiogenesis. We demonstrated that PS is exposed in choroidal neovascular endothelium. Furthermore, targeting this exposed PS with antibodies may be of therapeutic value in CNV.

Diabetic retinopathy screening and monitoring of early stage disease in general practice: Design and methods

Diabetic retinopathy is the leading cause of preventable blindness in Australians younger than 60years, mainly from the development of diabetic macular oedema and the sequelae of advanced proliferative diabetic retinopathy. However, early detection and subsequent treatment of diabetic retinopathy, as recommended in Australian national guidelines, can prevent nearly all cases of severe vision loss and blindness, but few people achieve this goal. This paper describes the design and methods of an open controlled trial that aims to assess the feasibility, acceptability, and relative costs and benefits of identification and management of early stages of diabetic retinopathy in primary care, with tele-ophthalmic support and education. A mix of urban, regional and rural general practices across Queensland, Australia are participating in this study, with control practices matched to intervention practices by geographic location, size, patient profile, and shared hospital referral pathways. Outcome measures include the quality of the retinal photographs, the general practitioners' diagnostic accuracy, the acceptability of this intervention to patients, general practice staff and ophthalmologists, screening rates, appropriate monitoring of early stage disease, and the cost-effectiveness of this model, compared to usual care. If proven to be effective, this model of diabetic retinopathy screening and early disease stage monitoring has the potential to improve access to appropriate care. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN 00336192).

Neovascular Age-Related Macular Degeneration

Age-related macular degeneration (AMD) affects an estimated 14 million people worldwide, and is the leading cause of severe, irreversible vision loss in individuals over the age of 50 years in Western societies. Choroidal neovascularization (CNV), the hallmark of 'wet', 'exudative' or 'neovascular' AMD, is responsible for approximately 90% of cases of severe vision loss due to AMD. Vascular endothelial growth factor (VEGF) has been shown to play a key role in the regulation of CNV and vascular permeability. Ranibizumab, the current gold standard in the US for the treatment of neovascular AMD, exerts its effect through binding and inhibition of all isoforms of VEGF. Randomized controlled clinical trials have established ranibizumab as the first US FDA-approved therapy for neovascular AMD to result in improvement in visual acuity. Despite impressive outcomes, treatment with ranibizumab requires sustained treatment regimens and frequent intravitreal injections. In this review, we discuss promising emerging therapies for neovascular AMD that aim to improve outcomes, safety and treatment burden through novel mechanisms of action. Currently in phase III clinical trials, VEGF Trap is a receptor decoy that targets VEGF with higher affinity than ranibizumab and other currently available anti-VEGF agents. Another promising therapeutic strategy is the blockade of VEGF effects by inhibition of the tyrosine kinase cascade downstream from the VEGF receptor; such therapies currently in development include vatalanib, TG100801, pazopanib, AG013958 and AL39324. Small interfering RNA technology-based therapies have been designed to downregulate the production of VEGF (bevasiranib) or VEGF receptors (AGN211745) by degradation of specific messenger RNA. Other potential therapies include pigment epithelium-derived factor-based therapies, nicotinic acetylcholine receptor antagonists, integrin antagonists and sirolimus.

A Modeled Economic Analysis of a Digital Teleophthalmology System As Used by Three Federal Healthcare Agencies for Detecting Proliferative Diabetic Retinopathy

The objective of this study was to compare, using a 12-month time frame, the cost-effectiveness of a non-mydriatic digital tele-ophthalmology system (Joslin Vision Network) versus traditional clinic-based ophthalmoscopy examinations with pupil dilation to detect proliferative diabetic retinopathy and its consequences. Decision analysis techniques, including Monte Carlo simulation, were used to model the use of the Joslin Vision Network versus conventional clinic-based ophthalmoscopy among the entire diabetic populations served by the Indian Health Service, the Department of Veterans Affairs, and the active duty Department of Defense. The economic perspective analyzed was that of each federal agency. Data sources for costs and outcomes included the published literature, epidemiologic data, administrative data, market prices, and expert opinion. Outcome measures included the number of true positive cases of proliferative diabetic retinopathy detected, the number of patients treated with panretinal laser photocoagulation, and the number of cases of severe vision loss averted. In the base-case analyses, the Joslin Vision Network was the dominant strategy in all but two of the nine modeled scenarios, meaning that it was both less costly and more effective. In the active duty Department of Defense population, the Joslin Vision Network would be more effective but cost an extra 1,618 dollars per additional patient treated with panretinal laser photo-coagulation and an additional 13,748 dollars per severe vision loss event averted. Based on our economic model, the Joslin Vision Network has the potential to be more effective than clinic-based ophthalmoscopy for detecting proliferative diabetic retinopathy and averting cases of severe vision loss, and may do so at lower cost.