Lycium barbarum glycopeptide ameliorates motor and visual deficits in autoimmune inflammatory diseases.

BACKGROUND: Lycium barbarum glycopeptide (LbGp), extracted from the traditional Chinese medicine (TCM) of Lycium barbarum (LB), provides a neuroprotective effect against neurodegenerative and neuroimmune disorders contributing to its immunomodulatory and anti-inflammatory roles. Neuromyelitis optica spectrum disorders (NMOSD) is an autoimmune-mediated central nervous system (CNS) demyelinating disease, clinically manifested as transverse myelitis (TM) and optic neuritis. However, no drug has been demonstrated to be effective in relieving limb weakness and visual impairment of NMOSD patients. PURPOSE: This study investigates the potential role of LbGp in ameliorating pathologic lesions and improving neurological dysfunction during NMOSD progression, and to elucidate the underlying mechanisms for the first time. STUDY DESIGN: We administrate LbGp in experimental NMOSD models in ex vivo and in vivo to explore its effect on NMOSD. METHODS: To evaluate motor function, both rotarod and gait tasks were performed in systemic NMOSD mice models. Furthermore, we assessed the severity of NMO-like lesions of astrocytes, organotypic cerebellar slices, as well as brain, spinal cord and optic nerve sections from NMOSD mouse models with LbGp treatment by immunofluorescent staining. In addition, demyelination levels in optic nerve were measured by G-ratio through Electro-microscopy (EM). And inflammation response was explored through detecting the protein levels of proinflammatory cytokines and NF-κB signaling in astrocytic culture medium and spinal cord homogenates respectively by Elisa and by Western blotting. RESULTS: LbGp could significantly reduce astrocytes injury, demyelination, and microglial activation in NMOSD models. In addition, LbGp also improved locomotor and visual dysfunction through preventing neuron and retinal ganglion cells (RGCs) from inflammatory attack in a systemic mouse model. Mechanistically, LbGp inhibits proinflammatory factors release via inhibition of NF-κB signaling in NMOSD models. CONCLUSION: This study provides evidence to develop LbGp as a functional TCM for the clinical treatment of NMOSD.

Characteristics of Ocular Inflammatory Side Effects Associated with Immune Checkpoint Inhibitors in a Northern California Population.

PURPOSE: To characterize the ocular inflammatory side effects associated with immune checkpoint inhibitor (CPI) treatment in a Northern California population. DESIGN: Retrospective case series. PARTICIPANTS: Patients receiving CPI within an integrated healthcare delivery system. METHODS: All patients within Kaiser Permanente Northern California receiving CPI between January 1, 2012 and November 1, 2018 were identified. Medical records of those seen in the ophthalmology clinic at least once were retrospectively reviewed. MAIN OUTCOME MEASURES: Type and duration of ocular inflammation, indication for and exposure to CPI, time from exposure to diagnosis of ocular inflammation. RESULTS: 31 cases of ocular inflammation were identified in 5061 patients (0.61%) receiving CPI. Mean ± SD age was 67 ± 11.9 (range 38-89). Mean time from exposure to diagnosis was 6.8 ± 5.5 months (range 0.5-17). 87% of cases were bilateral, and 43% of cases were chronic. Average ophthalmology follow-up was 16 ± 18 months (range 0-71). 16/31 (52%) had anterior uveitis, 7/31 (23%) had serous retinal detachment or panuveitis resembling Vogt-Koyanagi-Harada syndrome, 4/31 (13%) had papillitis, and 6/31 (19%) had diplopia or ocular motility defect. There was one case each (3.2%) of melanoma associated retinopathy, corneal edema, granulomatous lacrimal gland enlargement, and choroidal neovascularization. CONCLUSIONS: Ocular inflammation is a rare immune associated side effect of CPI treatment, the most common manifestation of which is anterior uveitis.

Unusual Presentation of Acute Hydroxychloroquine Retinopathy.

PURPOSE: To report a rare case of cystoid macular edema (CME) as a presentation of acute hydroxychloroquine-related retinal toxicity. OBSERVATIONS: A 37-year-old female patient visited our ophthalmology department in October 2019 complaining of bilateral blurred vision and metamorphopsia for 3 days. Best-corrected visual acuity (BCVA) was 6/6 in the right eye and 6/7.5 in the left eye under the Snellen E chart. Before presentation, she had taken hydroxychloroquine as a "reproduction-facilitating medication" prior to the in vitro fertilization (IVF) procedures with the daily dose of 200 mg for 1 week in March 2019 and 400 mg for 1 month in September 2019. She also took a combination of several herbal medicine including "Angelica sinensis" for 6 months in this period. On examination, typical signs of hydroxychloroquine maculopathy such as bilateral paracentral retinal pigment epithelium (RPE) change in blue autofluorescence and loss of the paracentral ellipsoid zone in optical coherence tomography ("flying saucer sign") were noted. CME was also found in fluorescein angiography. Her symptoms improved gradually after cessation of hydroxychloroquine and herb medicine without any further treatment. Resolution of bilateral CME was revealed at 16 weeks with final bilateral BCVA 6/6. CONCLUSIONS AND IMPORTANCE: Although rare, acute hydroxychloroquine maculopathy could occur in patients with concomitant usage of medications that could interfere with P450 enzymes system. Careful acquisition of drug history and serial ophthalmological examinations are advised in using hydroxychloroquine for disease management even for a short period of time.

Dietary Intervention With a Targeted Micronutrient Formulation Reduces the Visual Discomfort Associated With Vitreous Degeneration.

Purpose: To investigate the impact of supplementation with a targeted micronutrient formulation on the visual discomfort associated with vitreous degeneration. Methods: In this clinical trial, 61 patients with symptomatic vitreous floaters were randomized to consume daily, the active supplement consisting of 125 mg L-lysine, 40 mg vitamin C, 26.3 mg Vitis vinifera extract, 5 mg zinc, and 100 mg Citrus aurantium or placebo for 6 months. Change in visual discomfort from floaters, assessed with the Floater Disturbance Questionnaire, was the primary outcome measure. Secondary outcome measures included best-corrected visual acuity, letter contrast sensitivity, photopic functional contrast sensitivity with positive and negative contrast polarity, and quantitative vitreous opacity areas. Results: After supplementation, the active group reported a significant decrease in their visual discomfort from floaters (P < 0.001), whereas the placebo group had no significant change in their visual discomfort (P = 0.416). At 6 months, there was a significant decrease in vitreous opacity areas in the active group (P < 0.001) and an insignificant increase in vitreous opacity areas in the placebo group (P = 0.081). Also, there was a significant improvement in photopic functional contrast sensitivity with positive contrast polarity in the active group after supplementation (P = 0.047). Conclusions: The findings of this study indicate improvements in vision-related quality of life and visual function of patients suffering from vitreous floaters after supplementation with a formulation of antioxidative and antiglycation micronutrients. Notably, these improvements were confirmed by the decrease in vitreous opacity areas in the active group. Translational Relevance: This targeted dietary intervention should be considered to support patients with symptomatic vitreous degeneration.

High-dose vitamin B supplementation for persistent visual deficit in multiple sclerosis: a pilot study.

The aim of this study is to investigate the potential neuroprotective effect of high-doses vitamins B1, B6 and B12 in patients with relapsing-remitting multiple sclerosis (RRMS) and persistent visual loss after acute optic neuritis (AON). Sixteen patients (20 eyes) diagnosed with RRMS and visual permanent disability following AON were enrolled for the present open, pilot study. Each patient was treated with oral high-doses 300 mg of vitamin B1, 450 mg of vitamin B6 and 1,500 mcg of vitamin B12, as add-on treatment to concomitant disease-modifying therapies (DMTs) for consecutive 90 days. Outcome measures were to determine changes from baseline to month three in visual acuity (VA) and visual field (VF) testing, with correlations with clinical parameters. Logistical regression was performed to evaluate predictors of final VA. A statistically significant improvement was registered in visual acuity (p = 0.002) and foveal sensitivity threshold (FT) (p = 0.006) at follow-up compared to baseline. A similar trend was demonstrated for mean deviation (MD) (p < 0.0001), and pattern standard deviation (PSD) (p < 0.0001). Age at the time of inclusion was positively correlated with latency time (rho = 0.47, p = 0.03), while showing a negative correlation with visual acuity (rho = - 0.45, p = 0.04) and foveal sensitivity threshold (rho = - 0.6, p = 0.005) at follow up. A statistically significant correlation was demonstrated between foveal sensitivity threshold and visual acuity at baseline (rho = 0.79, p < 0.0001). In a linear regression model, the main predictor of visual acuity at follow up was the foveal sensitivity threshold (B = 1.39; p < 0.0001). Supplemental high-dose vitamins B1, B6 and B12 resulted as effective therapy to improve visual function parameters in MS-related visual persistent disability.

Cost-effectiveness of Anti-VEGF treatments for age-related macular degeneration: a Brazilian perspective.

PURPOSE: To study the cost-effectiveness of ranibizumab and bevacizumab for the treatment of age-related macular degeneration. METHODS: We used a decision tree model to analyze the cost-effectiveness of ranibizumab and bevacizumab for the treatment of age-related macular degeneration, from the Brazilian Public Health System (SUS) perspective. Ranibizumab and bevacizumab were administered to patients with the same treatment procedure, and the difference in treatment costs was calculated based on the cost of the drugs. Direct costs were estimated using the information provided by the Brazilian SUS. Effectiveness in terms of quality-adjusted life years (QALYs) was calculated based on the utility values for visual impairment. Incremental cost-effectiveness ratio was calculated by comparing both treatments. The analytical horizon was one year. RESULTS: The decision tree analysis showed that the difference in treatment effectiveness was 0.01 QALY. Incremental cost-effectiveness ratio showed that ranibizumab treatment required an incremental annual cost of more than R$ 2 million to generate 1 additional QALY, as compared to bevacizumab. CONCLUSIONS: From the Brazilian SUS perspective, bevacizumab is more cost-effective than ranibizumab for the treatment of neovascular age-related macular degeneration. Its use could allow potential annual savings in health budget.

Cost-effectiveness of Anti-VEGF treatments for age-related macular degeneration: a Brazilian perspective / Estudo de custo-efetividade de tratamentos para a degeneração macular relacionada à idade: uma perspectiva brasileira

ABSTRACT Purpose: To study the cost-effectiveness of ranibizumab and bevacizumab for the treatment of age-related macular degeneration. Methods: We used a decision tree model to analyze the cost-effectiveness of ranibizumab and bevacizumab for the treatment of age-related macular degeneration, from the Brazilian Public Health System (SUS) perspective. Ranibizumab and bevacizumab were administered to patients with the same treatment procedure, and the difference in treatment costs was calculated based on the cost of the drugs. Direct costs were estimated using the information provided by the Brazilian SUS. Effectiveness in terms of quality-adjusted life years (QALYs) was calculated based on the utility values for visual impairment. Incremental cost-effectiveness ratio was calculated by comparing both treatments. The analytical horizon was one year. Results: The decision tree analysis showed that the difference in treatment effectiveness was 0.01 QALY. Incremental cost-effectiveness ratio showed that ranibizumab treatment required an incremental annual cost of more than R$ 2 million to generate 1 additional QALY, as compared to bevacizumab. Conclusions: From the Brazilian SUS perspective, bevacizumab is more cost-effective than ranibizumab for the treatment of neovascular age-related macular degeneration. Its use could allow potential annual savings in health budget.

RESUMO Objetivo: Estudar o custo-efetividade do ranibizumabe e bevacizumabe no tratamento da degeneração macular relacionada à idade neovascular. Métodos: Utilizamos um modelo de árvore de decisão para analisar a relação custo-efetividade do ranibizumabe e bevacizumabe no tratamento da degeneração macular relacionada à idade, sob a perspectiva do Sistema Único de Saúde. O ranibizumabe e bevacizumabe foram administrados a pacientes com o mesmo procedimento de tratamento, e a diferença nos custos do tratamernto foi calculada com base no custo dos medicamentos. Os custos diretos foram estimados utilizando as informações fornecidas pelo SUS. A efetividade foi determinada em anos de vida ajustados pela qualidade (QALY) baseados em valores de utilidade em deficiênciavisual. A razãoincremental custo-efetividadefoicalculada comparando os dois tratamentos. O horizonte analítico foi de um ano. Resultados: A análise da árvore de decisão mostrou que a diferença na efetividade do tratamento foi de 0,01 QALY. A razão incremental de custo-efetividade mostrou que o tratamento com ranibizumabe exigiu um custo anual incremental de R$ 2 milhões para gerar um QALY adicional, em comparação ao bevacizumabe. Conclusões: Do ponto de vista do SUS, o bevacizumabe é mais custo-efetivo que o ranibizumabe no tratamento da degeneração macular relacionada à idade neovascular. O seu uso poderia gerar uma grande economia anual para o orçamento em saúde.

Corneal melt secondary to eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare antineutrophil cytoplasmic antibody-associated vasculitis that can affect any organ system. It is most often characterised by chronic airway inflammation along with prominent peripheral blood eosinophilia, although the disease can affect the cardiovascular, gastrointestinal, renal or central nervous systems. Ocular manifestations are uncommon and when they do occur, are varied in their clinical presentations. To the best of our knowledge, this is the first case of corneal melt secondary to EGPA to have been reported.

Corneal Toxicity after Self-Application of Calotropis procera (Ushaar) Latex: Case Report and Analysis of the Active Components.

Calotropis procera (ushaar) produces a copious amount of latex, which has both inflammatory and anti-inflammatory pharmacological properties. Local application produces an intense inflammatory response and causes significant ocular morbidity. We report corneal toxicity following self-application of latex from C. procera in a 74-year-old man. He reported painless decreased vision in the affected eye with diffuse corneal edema, and specular microscopy revealed a reduced endothelial cell count. After he was treated with topical corticosteroids, his visual acuity improved from hand motion to 20/80. The composition of the active compounds in the latex was analyzed. When topically administered, the latex may cause severe ocular injuries and a loss of endothelial cells over a period of time. Public education, early recognition of such injuries, and timely intervention may prevent permanent ocular damage.

Green tea catechins alleviate autoimmune symptoms and visual impairment in a murine model for human chronic intraocular inflammation by inhibiting Th17-associated pro-inflammatory gene expression.

Autoimmune uveitis is a sight-threatening disease mainly caused by dysregulation of immunity. We investigated the therapeutic effects of green tea extract (GTE) and its major component, epigallocatechin-3-gallate (EGCG), on a murine model of experimental autoimmune uveoretinitis (EAU). Oral administration of GTE, EGCG, dexamethasone, or water, which started 5 days before the induction, was fed every two days to each group. On day 21 post induction, the eyes were examined by confocal scanning laser ophthalmoscopy, optical coherence tomography (OCT), fundus fluorescein angiography (FFA) and electroretinography (ERG) prior to sacrificing the animals for histological assessments and gene expression studies. Retinal-choroidal thicknesses (RCT) and major retinal vessel diameter were measured on OCT sections and FFA images, respectively. Comparing to water-treated EAU animals, GTE attenuated uveitis clinical manifestations, RCT increase (1.100 ± 0.013 times vs 1.005 ± 0.012 times, P < 0.001), retinal vessel dilation (308.9 ± 6.189 units vs 240.8 units, P < 0.001), ERG amplitudes attenuation, histopathological ocular damages, and splenomegaly in EAU mice. The therapeutic effects of GTE were dose dependent and were comparable to dexamethasone. EGCG, a major active constituent of GTE, partially alleviated uveitic phenotypes including recovering visual function. Th-17 associated pro-inflammatory gene [interleukin 1 beta (IL-1ß), IL-6, IL-17A, and tumor necrosis factor alpha (TNF-α)] expressions were down regulated by GTE and EGCG treatments, which showed no detectable morphological defects in liver and kidney in non-induced and EAU mice. Our findings suggest that GTE consumption can serve as a potent therapeutic agent as well as a food supplement for developing alternative treatments against autoimmune uveitis.

MD1003 (High-Dose Pharmaceutical-Grade Biotin) for the Treatment of Chronic Visual Loss Related to Optic Neuritis in Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND: Chronic visual loss is a disabling feature in patients with multiple sclerosis (MS). It was recently shown that MD1003 (high-dose pharmaceutical-grade biotin or hdPB) may improve disability in patients with progressive MS. OBJECTIVE: The aim of this study was to evaluate whether MD1003 improves vision compared with placebo in MS patients with chronic visual loss. METHODS: The MS-ON was a 6-month, randomized, double-blind, placebo-controlled study with a 6-month open-label extension phase. Adult patients with MS-related chronic visual loss of at least one eye [visual acuity (VA) below 0.5 decimal chart] were randomized 2:1 to oral MD1003 300 mg/day or placebo. The selected eye had to show worsening of VA within the past 3 years following either acute optic neuritis (AON) or slowly progressive optic neuropathy (PON). The primary endpoint was the mean change from baseline to month 6 in VA measured in logarithm of the minimum angle of resolution (logMAR) at 100% contrast of the selected eye. Visually evoked potentials, visual field, retinal nerve fiber layer (RNFL) thickness, and health outcomes were also assessed. RESULTS: Ninety-three patients received MD1003 (n = 65) or placebo (n = 28). The study did not meet its primary endpoint, as the mean change in the primary endpoint was nonsignificantly larger (p = 0.66) with MD1003 (- 0.061 logMAR, + 3.1 letters) than with placebo (- 0.036 logMAR, + 1.8 letters). Pre-planned subgroup analyses showed that 100% contrast VA improved by a mean of + 2.8 letters (- 0.058 logMAR) with MD1003 and worsened by - 1.5 letters (+ 0.029 logMAR) with placebo (p = 0.45) in the subgroup of patients with PON. MD1003-treated patients also had nonsignificant improvement in logMAR at 5% contrast and in RNFL thickness and health outcome scores when compared with placebo-treated patients. There was no superiority of MD1003 vs placebo in patients with AON. The safety profile of MD1003 was similar to that of placebo. CONCLUSIONS: MD1003 did not significantly improve VA compared with placebo in patients with MS experiencing chronic visual loss. An interesting trend favoring MD1003 was observed in the subgroup of patients with PON. Treatment was overall well tolerated. TRIAL REGISTRATION: EudraCT identifier 2013-002112-27. ClinicalTrials.gov Identifier: NCT02220244 FUNDING: MedDay Pharmaceuticals.

Combined etiology for bilateral and simultaneous optic neuropathy in a patient with ciancobalamin deficit and hepatitis C treated with peg-interferon and ribavirin.

We report the case of a 53-year-old female patient who developed bilateral sudden visual acuity loss after 15 weeks from the initiation of Peg-Interferon and Ribavirin treatment for hepatitis C. Debut was simultaneous and asymmetric, reported in the morning, at awakening. No pain or other symptom was reported by the patient. Results. At presentation, visual acuity was 0.2 in RE and 3/ 50 in LE. Pupillary reflexes were sluggish and severe dyschromatopsia was documented in both eyes (Ishihara plates). Fundus examination revealed bilateral pale optic disc edema, more prominent in LE, with splinter hemorrhages in the RNFL around the optic disk. Visual field exam demonstrated severe defects in 3 quadrants of the RE, whereas in the LE, it was impossible to perform the investigation due to VA<0.1. Neurologic evaluation was normal; other possible causes of systemic vasculitis were excluded by negative lab tests. Acute inflammatory markers (fibrinogen and ESR) and mild pancytopenia were the only documented laboratory changes in this patient. Anamnesis cleared the traditional risk factors for conventional AION (hypertension, diabetes, ischemic heart disease, and hypercholesterolemia). Cranial and orbital CT scan and MRI findings were normal. Patient was withdrawn from the Interferon and Ribavirin treatment and was administered methyl prednisolone pulse therapy (1g/ day) for 3 days, continued with oral Prednisone (60 mg/ day) tapered slowly for over 12 weeks. VA increased to 0.8 during treatment in the RE, but visual recovery in the LE was not as spectacular (0.16) as in the fellow eye. Modified latencies and amplitudes in evoked visual potentials examination during 4 months time emphasized bilateral optic atrophy. Optic nerve sufferance was amplified by a low level of vitamin B12, detected by chance at the last eye visit. Due to the general condition, dietary supplementation was not possible. Conclusion. A case of a patient with bilateral and simultaneous NAION caused by IFN and Ribavirin treatment for hepatitis C, who was also vitamin B12 deficient, was analyzed. Therefore, a combined etiology for optic atrophy was explained.

Hypothalamic-pituitary sarcoidosis with vision loss and hypopituitarism: case series and literature review.

PURPOSE: Hypothalamic-pituitary (HP) neurosarcoidosis (NS) accounts for 0.5 % cases of sarcoidosis and 1 % of HP masses. Correlative data on endocrine and neurological outcomes is lacking. METHODS: Retrospective case series and literature review of presentation, treatment and outcome of HP NS. RESULTS: Our series includes 4 men, ages 34-59, followed for a median of 7.3 years (range 1.5-17). All had optic neuropathy, multiple pituitary hormone abnormalities (PHAs) and other organ involvement by sarcoidosis (lung, sino-nasal, brain/spine and facial nerve). Two patients had central diabetes insipidus and one impaired thirst with polydipsia. After treatment with high-dose glucocorticoids, optic neuropathy improved in one case and stabilized in the others. After treatment, HP lesions improved radiologically, but PHAs persisted in all cases. Review of four published series on HP NS in addition to ours yielded 46 patients, age 37 ± 11.8 years, 65 % male. PHAs consisted of anterior hypopituitarism (LH/FSH 88.8 %, TSH 67.4 %, GH 50.0 %, ACTH 48.8 %), hyperprolactinemia (48.8 %) and diabetes insipidus (65.2 %). PHAs were the first sign of disease in 54.3 % patients. Vision problems occurred in 28.3 % patients, but optic neuropathy was not well documented in previous series. Most patients (93.5 %) received high-dose glucocorticoids followed by taper; 50 % also received other immunomodulators, including methotrexate, mycophenolate mofetil, cyclosporine, azathioprine, infliximab and hydrochloroquine. Only 13 % patients showed improvement in PHAs. All-cause mortality was 8.7 %. CONCLUSION: HP NS is a serious disease requiring multidisciplinary treatment and lifelong follow-up. Prospective multicentric studies are needed to determine a more standardized approach to HP NS and outline predictors of disease outcome.

The Diabetes Visual Function Supplement Study (DiVFuSS).

BACKGROUND: Diabetes is known to affect visual function before onset of retinopathy (diabetic retinopathy (DR)). Protection of visual function may signal disruption of mechanisms underlying DR. METHODS: This was a 6-month randomised, controlled clinical trial of patients with type 1 and type 2 diabetes with no retinopathy or mild to moderate non-proliferative retinopathy assigned to twice daily consumption of placebo or a novel, multi-component formula containing xanthophyll pigments, antioxidants and selected botanical extracts. Measurement of contrast sensitivity, macular pigment optical density, colour discrimination, 5-2 macular threshold perimetry, Diabetic Peripheral Neuropathy Symptoms, foveal and retinal nerve fibre layer thickness, glycohaemoglobin (HbA1c), serum lipids, 25-OH-vitamin D, tumour necrosis factor α (TNF-a) and high-sensitivity C reactive protein (hsCRP) were taken at baseline and 6 months. Outcomes were assessed by differences between and within groups at baseline and at study conclusion using meand ± SDs and t tests (p<0.05) for continuous variables. RESULTS: There were no significant intergroup differences at baseline. At 6 months, subjects on active supplement compared with placebo had significantly better visual function on all measures (p values ranging from 0.008 to <0.0001), significant improvements in most serum lipids (p values ranging from 0.01 to 0.0004), hsCRP (p=0.01) and diabetic peripheral neuropathy (Fisher's exact test, p=0.0024) No significant changes in retinal thickness, HbA1c, total cholesterol or TNF-α were found between the groups. CONCLUSIONS: This study provides strong evidence of clinically meaningful improvements in visual function, hsCRP and peripheral neuropathy in patients with diabetes, both with and without retinopathy, and without affecting glycaemic control. TRIAL REGISTRATION NUMBER: www.ClinicalTrials.gov Identifier: NCT01646047.

Nutritional supplements in age-related macular degeneration.

Age-related macular degeneration (AMD) is the most frequent cause of blindness in the Western World. While with new therapies that are directed towards vascular endothelial growth factor (VEGF), a potentially efficient treatment option for the wet form of the disease has been introduced, a therapeutic regimen for dry AMD is still lacking. There is evidence from several studies that oral intake of supplements is beneficial in preventing progression of the disease. Several formulations of micronutrients are currently available. The present review focuses on the role of supplements in the treatment and prevention of AMD and sums up the current knowledge about the most frequently used micronutrients. In addition, regulatory issues are discussed, and future directions for the role of supplementation in AMD are highlighted.

Vasospastic transient monocular visual loss: effect of treatment with different doses of nifedipine.

Transient monocular visual loss (TMVL) usually is due to hypoperfusion of the optic nerve or retinal circulation. After the exclusion of thromboembolic and carotid artery diseases, retinal vasospasm should be considered as an underlying cause of TMVL. We report a patient with an increasing number of transient attacks of unilateral blindness. Vasospasm was confirmed as the etiology by fundus photography during an attack. Nifedipine 10 mg/d decreased the severity of the visual loss and the number of attacks. The patient was relieved of symptoms entirely with a nifedipine dose of 20 mg/d.

Ten-year follow-up of age-related macular degeneration in the age-related eye disease study: AREDS report no. 36.

IMPORTANCE: Providing long-term follow-up of the natural history of age-related macular degeneration (AMD) and associated risk factors will facilitate future epidemiologic studies and clinical trials. OBJECTIVE: To describe 10-year progression rates to intermediate or advanced AMD. DESIGN, SETTING, AND PARTICIPANTS: We observed the Age-Related Eye Disease Study (AREDS) participants for an additional 5 years after a randomized clinical trial of antioxidant vitamins and minerals was completed. Observation occurred at 11 clinical sites of medical retinal practices from academic institutions and community medical centers. Participants aged 55 to 80 years with no AMD or AMD of varying severity (n = 4757) were followed up in the AREDS trial for a median duration of 6.5 years. When the trial ended, 3549 of the 4203 surviving participants were followed for 5 additional years. EXPOSURE: Treatment with antioxidant vitamins and minerals. MAIN OUTCOMES AND MEASURES: Development of varying stages of AMD and changes in visual acuity. The rates of progression to large drusen and advanced AMD (neovascular AMD or central geographic atrophy) were evaluated using annual fundus photographs assessed centrally. Best-corrected visual acuity was measured at annual study visits. RESULTS: The risk of progression to advanced AMD increased with increasing age (P = .01) and severity of drusen. Women (P = .005) and current smokers (P < .001) were at increased risk of neovascular AMD. In the oldest participants with the most severe AMD status at baseline, the risks of developing neovascular AMD and central geographic atrophy by 10 years were 48.1% and 26.0%, respectively. Similarly, rates of progression to large drusen increased with increasing severity of drusen at baseline, with 70.9% of participants with bilateral medium drusen progressing to large drusen and 13.8% to advanced AMD in 10 years. Median visual acuity at 10 years in eyes that had large drusen at baseline but never developed advanced AMD was 20/25; eyes that developed advanced AMD had a median visual acuity of 20/200. CONCLUSIONS AND RELEVANCE: The natural history of AMD demonstrates relentless loss of vision in persons who developed advanced AMD. These progression data and the risk factor analyses may be helpful to investigators conducting research in clinic populations.

Effect of Ginkgo biloba extract on visual field progression in normal tension glaucoma.

PURPOSE: To evaluate the long-term effect of Ginkgo biloba extract (GBE) on progression of visual field (VF) defects in patients with normal tension glaucoma (NTG). METHODS: Forty-two eyes of 42 patients with treated NTG who received 80 mg GBE 2 times daily and who had at least 5 VF tests using the Humphrey Visual Field Analyzer for more than a 4-year period before and after GBE treatment were evaluated in this retrospective study. We evaluated the change of progression rate using mean deviation (MD), pattern standard deviation (PSD), and visual field index (VFI) after GBE treatment. The time course of mean total deviation in 10 zones corresponding to the glaucoma hemifield test was analyzed using a linear mixed effects model with unequal random effect variances. RESULTS: The mean follow-up period was 12.3 years. The posttherapeutic intraocular pressures before and after GBE treatment were not significantly different (P=0.509 paired t test). Before GBE treatment, the regression coefficients (RCs) of MD, PSD, and VFI change were -0.619 dB/y, 0.626 dB/y, and -2.153%/y, respectively. After GBE treatment, the RCs of MD, PSD, and VFI change improved significantly to -0.379 dB/y, 0.342 dB/y, and -1.212%/y (P <0.001), respectively. In zone 1, the RC of mean total deviation change was significantly increased after GBE administration (P <0.005). CONCLUSIONS: GBE administration slowed the progression of VF damage in patients with NTG, especially in zone 1 corresponding to the superior central field.

QLT091001, a 9-cis-retinal analog, is well-tolerated by retinas of mice with impaired visual cycles.

PURPOSE: Investigate whether retinas of mice with impaired retinal cycles exposed to light or kept in the dark tolerate prolonged high-dose administration of QLT091001, which contains as an active ingredient, the 9-cis-retinal precursor, 9-cis-retinyl acetate. METHODS: Four- to six-week-old Lrat(-/-) and Rpe65(-/-) mice (n = 126) as well as crossbred Gnat1(-/-) mice lacking rod phototransduction (n = 110) were gavaged weekly for 6 months with 50 mg/kg QLT091001, either after being kept in the dark or after light bleaching for 30 min/wk followed by maintenance in a 12-hour light ≤ 10 lux)/12-hour dark cycle. Retinal health was monitored by spectral-domain optical coherent tomography (SD-OCT) and scanning laser ophthalmoscopy (SLO) every other month and histological, biochemical, and visual functional analyses were performed at the end of the experiment. Two-photon microscopy (TPM) was used to observe retinoid-containing retinosome structures in the RPE. RESULTS: Retinal thickness and morphology examined by SD-OCT were well maintained in all strains treated with QLT091001. No significant increases of fundus autofluorescence were detected by SLO imaging of any strain. Accumulation of all-trans-retinyl esters varied with genetic background, types of administered compounds and lighting conditions but retinal health was not compromised. TPM imaging clearly revealed maintenance of retinosomes in the RPE of all mouse strains tested. CONCLUSIONS: Retinas of Lrat(-/-), Rpe65(-/-), and crossbred Gnat1(-/-) mice tolerated prolonged high-dose QLT091001 treatment well.