Search

Background: Between 1962 and 1975, a chlor-alkali plant in Canada discharged approximately 9 metric tons of mercury (Hg) into the Wabigoon River. Over the following decades, biomarkers of Hg exposure of persons from Grassy Narrows First Nation (Asubpeeschoseewagong Anishinabek), located downriver from the discharge, reflected Hg concentrations in fish. Hg exposure is known to target the calcarine fissure, resulting in visual field (VF) loss. Most studies and clinical reports focus solely on peripheral VF loss; little is known about the impact of Hg on the central and paracentral portions. The present study sought to characterize the patterns of VF loss with respect to past and current Hg., Methods: A 28-year hair-Hg (HHg) database, created from a 1970-97 government biomonitoring program, served to select study participants with ≥ 4 year-based HHg measurements (n = 81). Blood-Hg was assessed for current exposure. Light sensitivity thresholds across the VF were analyzed monocularly, using a Humphrey Field Analyzer (HFA). Following post-hoc exclusions, based on HFA interpretation indices, 65 participants were retained. Both eyes were combined for analyses (n = 130 eyes). Unsupervised hierarchical clustering of HFA plot data was used to identify patterns of VF loss. A series of mixed effects models (MEM) were performed to test the associations for current Hg exposure with respect to HFA interpretation indices and clusters, as well as for longitudinal past Hg exposure., Results: The clustering approach decomposed the light sensitivity deficits into 5 concentric clusters, with greatest loss in the peripheral clusters. No relation was observed between any of the cluster scores and current blood-Hg. VF deficits increased with past Hg exposure. Longitudinal MEM showed that HHg was significantly (p < 0.05) associated with all peripheral, paracentral, and central cluster scores, as well as with HFA interpretation indices., Conclusions: Past Hg exposure in Grassy Narrows First Nation was associated with present day VF loss. The cluster-based location-specific approach identified patterns of VF loss associated with long-term Hg exposure, in both the peripheral and the central areas. The functional implications of this type of visual loss should be investigated., (© 2024. The Author(s).)

The eye is vulnerable to the adverse effects of air pollution. Previous experimental study found that fine particulate matter (PM 2.5 ) had a direct toxic effect on intraocular tissues. However, clinical evidence for the impact of air pollutants exposure on functional and structural changes in glaucoma remains scarce. A total of 120 patients with primary open-angle glaucoma (POAG) who met the inclusion criteria were included in this retrospective study. The standardized ophthalmic examination, such as intraocular pressure (IOP), visual field, optical coherence tomography, and comprehensive physical examination, were performed. The air pollution data, including PM 2.5 concentration and air quality index (AQI), were collected. PM 2.5 and AQI for the day of the medical examination, as well as one month, and three months before the medical examination date, were investigated. In our results, higher average exposure levels for one-month and three-month, were associated with increased IOP (r=0.229, P=0.013; r=0.204, P=0.028, respectively) and decreased visual field mean sensitivity (MS) (r=-0.212, P=0.037; r=-0.305, P=0.002, respectively). PM 2.5 concentrations for the day of the medical examination was not significantly associated with ocular parameters. In multiple linear regression analysis adjusted for demographic and clinical factors, higher PM 2.5 exposure for one month was associated with elevated IOP (P=0.040, β=0.173, 95 %CI=0.008-0.337). We also found an association between PM 2.5 and MS (one-month exposure: β=-0.160, P=0.029; three-month exposure: β=-0.238, P=0.002). The logistic regression analysis found that three-month average PM 2.5 exposure level was significantly associated with the disease severity (β=0.043, P=0.025, 95 %CI=1.005-1.084). In conclusion, this study is the first to investigate the relationship between air pollution and detailed ocular parameters of POAG patients in Shanghai over a three-year period, and to explore the effects of different exposure times of PM 2.5 on glaucoma. This study found that PM 2.5 exposure was correlated with elevated IOP and decreased MS. The one-month PM 2.5 exposure level had the most significant effects on IOP. The three-month PM 2.5 exposure level was an independent risk factor for POAG severity. Current evidence suggests there may be an association between PM 2.5 exposure and POAG., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To assess structural (optical coherence tomography, fundus autofluorescence) and functional (contrast sensitivity and visual field) test results which were used for detecting early retinal changes in patients using oral hydroxychloroquine., Methods: Patients using oral hydroxychloroquine for at least one year were divided into two groups according to the duration of drug use. Groups 1 and 2 consisted of patients with drug use for more than 5 years and 1-5 years, respectively. The drug-using groups were compared with the control group. The mean retinal nerve fiber layer (RNFL), central macular thickness (CMT), ganglion cell-inner plexiform layer (GC-IPL), static 10-2 visual field, fundus autofluorescence (FAF) imaging, and contrast sensitivity tests were performed and statistically compared between groups., Results: Median and temporal quadrant RNFL thicknesses were found to be statistically significantly lower in the drug groups. In the drug groups, the GC-IPL sectoral and mean thicknesses were found to be statistically lower in all quadrants. Central macular thickness was also found to be similar in all three groups. There was no significant difference between the groups in visual field parameters. Macular FAF images were significantly higher in the drug users, but there was no significant difference between the three groups in foveal FAF images. Contrast sensitivity measurements were significantly lower in the drug groups than in the control group at all spatial frequencies except 6 and 18 cycles/degree., Conclusions: The combined use of structural and functional tests in patients using hydroxychloroquine provides useful information in detecting early retinal changes., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

N, N-dimethyltryptamine (DMT) is a psychedelic tryptamine acting on 5-HT2A serotonin receptors, which is associated with intense visual hallucinatory phenomena and perceptual changes such as distortions in visual space. The neural underpinnings of these effects remain unknown. We hypothesised that changes in population receptive field (pRF) properties in the primary visual cortex (V1) might underlie visual perceptual experience. We tested this hypothesis using magnetic resonance imaging (MRI) in a within-subject design. We used a technique called pRF mapping, which measures neural population visual response properties and retinotopic maps in early visual areas. We show that in the presence of visual effects, as documented by the Hallucinogen Rating Scale (HRS), the mean pRF sizes in V1 significantly increase in the peripheral visual field for active condition (inhaled DMT) compared to the control. Eye and head movement differences were absent across conditions. This evidence for short-term effects of DMT in pRF may explain perceptual distortions induced by psychedelics such as field blurring, tunnel vision (peripheral vision becoming blurred while central vision remains sharp) and the enlargement of nearby visual space, particularly at the visual locations surrounding the fovea. Our findings are also consistent with a mechanistic framework whereby gain control of ongoing and evoked activity in the visual cortex is controlled by activation of 5-HT2A receptors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to investigate the efficacy and safety of orally administered branched-chain amino acids (BCAAs) on disease progression in patients with retinitis pigmentosa (RP)., Methods: A double-blind, randomized, placebo-controlled study was conducted at the Kyoto University Hospital. Seventy patients with RP aged 20 years or above were randomly assigned to the TK-98 (a combination of BCAAs in granule form) or placebo group. One packet (4.15 g) of the study drug was administered orally thrice daily for 78 weeks., Results: There was no significant difference in the rate of change in the total point score, the primary endpoint, between the TK-98 (-52.4 ± 10.3 dB/year) and placebo (-42.9 ± 13.8 dB/year) groups. Ellipsoid zone length decreased by -76.5 ± 8.9 and -95.5 ± 12.2 µm/year in the TK-98 and placebo groups, respectively; although this difference was not significant, the TK-98 group showed slower degeneration. No serious adverse events were associated with the oral administration of TK-98 in patients with RP., Conclusions: This study did not yield conclusive evidence supporting BCAA combination granules' effectiveness in slowing visual field progression in patients with RP. An insignificant trend toward a slower reduction in ellipsoid zone length was found in morphological tests. Further studies are required to fully understand the potential benefits of BCAA supplementation in RP., Translational Relevance: Our study demonstrates the safety of administering BCAAs to patients with RP. Accordingly, larger, more homogeneous clinical studies with longer durations may suggest their potential as therapeutic agents.

Purpose: Hydroxychloroquine (HCQ) can cause irreversible damage to the retina, especially when taken over longer periods. The American Academy of Ophthalmology recommends a regimen for dosing, screening, and monitoring of patients treated with HCQ. We present an unusual case of a rapid development of severe HCQ-associated retinopathy already after 2 years after commencing HCQ treatment., Methods: Observational case report. Clinical examination, optical coherence tomography, fundus autofluorescence imaging, perimetry, and full-field and multifocal electroretinography were performed. Ancillary tests included neoplastic and paraneoplastic work-up, vitamin levels, and whole-exome sequencing, to rule out other potential causes of a panretinal degeneration., Results: We report on a 58-year-old woman with rheumatoid arthritis, treated initially with 200 mg HCQ daily for 1 year (daily dose 3.6 mg/kg), then 400 mg daily for 1 year (daily dose 7.2 mg/kg), and a cumulative dose of 216 g. Her medical history was otherwise unremarkable. No family history for inherited retinal conditions. She was referred due to a rapid and sudden progressive and severe concentric visual field constriction, 2 years after commencing HCQ treatment., Conclusion: This case of a rapid-onset, severe panretinal degeneration shortly after start of HCQ treatment suggests underlying mechanisms and risk factors for HCQ toxicity in addition to those previously reported and a potential need for supplementary screening tests to prevent HCQ toxicity. American Academy of Ophthalmology dosing guidelines of 5 mg/kg should be strictly adhered to in patients receiving HCQ therapy., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: This study investigates the association between local retina structure and visual function in a cohort with long-term hydroxychloroquine (HCQ) use., Methods: The study included 84 participants (54 participants without toxicity and 30 participants with toxicity) with history of chronic HCQ use (14.5 ± 7.4 years) who had testing with spectral-domain optical coherence tomography (SD-OCT) imaging and Humphrey 10-2 visual fields. Optical coherence tomography (OCT) metrics (total and outer retina thickness [TRT and ORT], minimum intensity [MinI], and ellipsoid zone [EZ] loss) were sampled in regions corresponding to visual field test locations. Univariate linear correlations were investigated and a multivariate random forest regression using a combination of OCT metrics was used to predict visual field sensitivity by locus using a leave-one-out cross-validation strategy., Results: In univariate linear regression, EZ loss demonstrated the strongest relationship with visual field sensitivities in the parafoveal ring with R2 = 0.58. TRT and ORT revealed positive correlations with visual field sensitivity (R2 = 0.57 and 0.40, respectively), whereas total and outer retinal MinI yielded negative correlations (R2 = 0.10 and 0.22). The multivariate model improved correlations (R2 = 0.66) yielding a root mean squared error of 3.8 decibel (dB). Feature importance analysis identified EZ loss as the most relevant predictor of function., Conclusions: Multiple OCT-derived quantitative metrics used in combination can provide information to predict local sensitivities. The results indicate a strong relationship between retinal function and OCT measures, which contribute to the understanding of the retinal toxicity caused by HCQ as well as being applicable to outcome development for other degenerative diseases of the outer retina.

Purpose: To evaluate the effect of methylphenidate on visual field testing in healthy adults with abnormal visual field results., Methods: This prospective, randomized, controlled interventional clinical trial comprised all patients who had abnormal visual field test results and normal eye examination and ophthalmic history. Eligible patients were randomly assigned to either the study group or the control group. All patients repeated their visual field testing. Study group patients received a single dose of 10 mg methylphenidate prior to that. The main outcome measures were the percent difference in mean deviation and pattern standard deviation between the second and first visual fields., Results: The methylphenidate group had greater improvement in all parameters. Mean deviation improved by median 68% (IQR 19%-78%) in the methylphenidate group vs. 27% [-5% to 55%] in the controls. However, this was not statistically significant ( p = .83). Pattern standard deviation improved by median 49% (22%-59%) vs. 7% [-9% to 45%], respectively ( p = .012). The visual fields were also reviewed by 3 masked experienced ophthalmologists. They indicated that the second visual field improved in 76.2% of the methylphenidate group vs. 48.5% of the controls ( p = .04). A normal repeat visual field occurred in 57.7% vs. 21.2%, respectively. A subgroup analysis of patients with prior experience in visual field testing yielded an even more striking improvement in the methylphenidate group vs. controls., Conclusions: A single low dose of methylphenidate can improve visual field testing in subjects without ocular pathology, and even more in those with prior experience in perimetry.

Purpose: To investigate the association between hydroxychloroquine (HCQ) use and macular pigment optic densitometry (MPOD) abnormalities., Materials and Methods: Fifty patients that have been receiving HCQ treatment and forty-eight control subjects were randomly selected from patients with no visual impairment with similar age and gender. All participants underwent detailed ophthalmologic examination including fundus photography, fundus autofluorescence, optic coherence tomography, and visual field analysis. Macular pigment optical density (MPOD) was measured by fundus reflectometry using one-wavelength reflection method. Patients with ongoing HCQ treatment formed the HCQ group and healthy subjects formed the control group., Results: Mean age was 50.9 ± 7.9 and 47.9 ± 9.4 years in the HCQ and controls groups respectively ( p  = 0.098) Between the groups, there is no significant difference in central foveal thickness and mean deviation and pattern standard deviation in the visual field analysis. Parafoveal hyper fluorescence lesions were detected in 5 (%10) patients. Choroidal thickness was significantly decreased in the HCQ group ( p  = 0.001). Maximum and mean MPOD outcomes were significantly lower in the HCQ group ( p  = 0.005, p  = 0.003, respectively). Between the groups, there was no difference in mean MPOD volume and MPOD area., Conclusions: Patients with HCQ use have reduced MPOD. Further studies are required investigating the sensitivity and specificity of MPOD in detecting initial retinal changes in patients with HCQ use.

Competing Interests: The authors report no conflicts of interest.

Purpose: To present the multimodal retinal imaging findings in didanosine retinopathy in a patient who presented 6.5 years after stopping the use of didanosine and to highlight the absence of progression during a 1.5-year follow-up., Methods: Case report involving clinical examination, fundus photography, fundus autofluorescence, fluorescein angiography, optical coherence tomography, Goldmann kinetic perimetry, and full-field electroretinography., Results: A 52-year-old patient presented with bilateral retinopathy 6.5 years after stopping didanosine having used the medication for 8.5 years. Fundus examination showed a ring-shaped zone of atrophy of the retinal pigment epithelium involving the midperiphery. On autofluorescence imaging, there was diffuse hypoautofluorescence involving the midperipheral retina in both eyes. On fluorescein angiography, there was a granular mottled pattern of diffuse hyperfluorescence in the midperiphery in both eyes, with baring of the large choroidal vessels in some areas. On Goldmann kinetic perimetry, both eyes showed marked constriction of the isopter to the I4e stimulus, and there was a temporal scotoma to the III4e target in both eyes. Full-field electroretinography showed generalized rod and cone photoreceptor dysfunction in both eyes. During a follow-up for 1.5 years, there was no evidence of progression., Conclusion: Patients who have used didanosine should be evaluated for the presence of retinopathy, which involves the midperipheral retina.

Background/purpose: Retinal toxicity associated with antimalarial drug use in inflammatory conditions is well described and may be more common than previously recognized. Antimalarial drugs bind to melanin in ocular tissues, particularly the retinal pigment epithelium, but the mechanism of toxicity and its relation to light is unclear., Methods: Case report., Results: A 62-year-old white woman with erosive rheumatoid arthritis developed hydroxychloroquine toxicity in her phakic eye, with her aphakic fellow eye only mildly affected., Conclusion: We report the clinical evaluation of this rare case of asymmetrical hydroxychloroquine retinopathy and present a hypothesis regarding the mechanism of drug toxicity.

Importance: Treatment of acquired blepharoptosis (ptosis) is currently limited to surgical intervention., Objective: To examine the efficacy and safety of oxymetazoline hydrochloride, 0.1%, ophthalmic solution (oxymetazoline, 0.1%) in participants with acquired ptosis., Design, Setting, and Participants: This pooled analysis of 2 randomized, double-masked, placebo-controlled, multicenter phase 3 clinical trials included participants 9 years and older with acquired ptosis and superior visual field deficit. The 2 studies were conducted across 16 and 27 sites in the United States. Patients were enrolled from May 2015 to April 2019. Analyses for the individual trials were initiated after database lock and completed on September 6, 2017, and May 16, 2019. Pooled analysis was completed on August 25, 2019., Interventions: Participants (randomized 2:1) received oxymetazoline, 0.1%, or vehicle, self-administered as a single drop per eye, once daily, for 42 days., Main Outcomes and Measures: The primary efficacy end point was change from baseline in the number of points seen on the Leicester Peripheral Field Test, a test to detect superior visual field deficits due to ptosis, on days 1 (6 hours after instillation) and 14 (2 hours after instillation). The secondary end point, change from baseline in marginal reflex distance 1, was assessed at the same time points., Results: In total, 304 participants were enrolled (mean [SD] age, 63.8 [13.8] years; 222 women [73%]). Overall, 97.5% (198 of 203) of participants receiving oxymetazoline, 0.1%, and 97.0% (98 of 101) of participants receiving vehicle completed the studies. Oxymetazoline, 0.1%, was associated with a significant increase in the mean (SD) number of points seen on the Leicester Peripheral Field Test vs vehicle (day 1: 5.9 [6.4] vs 1.8 [4.1]; mean difference, 4.07 [95% CI, 2.74-5.39]; P < .001; day 14: 7.1 [5.9] vs 2.4 [5.5]; mean difference, 4.74 [95% CI, 3.43-6.04]; P < .001). Oxymetazoline, 0.1%, also was associated with a significant increase in marginal reflex distance 1 from baseline (mean [SD]: day 1: 0.96 [0.89] mm vs 0.50 [0.81] mm; mean difference, 0.47 mm [95% CI, 0.27-0.67]; P < .001; day 14: 1.16 [0.87] mm vs 0.50 [0.80] mm; mean difference, 0.67 mm [95% CI, 0.46-0.88]; P < .001). Treatment-emergent adverse events (TEAEs) occurred in 31.0% (63 of 203) of participants receiving oxymetazoline, 0.1%, and 35.6% (36 of 101) of participants receiving vehicle. Among participants receiving oxymetazoline, 0.1%, with a TEAE, 81% (51 of 63) had a maximum TEAE intensity of mild, and 62% (39 of 63) had no TEAE suspected of being treatment related., Conclusions and Relevance: Oxymetazoline, 0.1%, was associated with positive outcomes and was well tolerated in phase 3 trials after instillation at days 1 and 14, demonstrating its potential promise for the treatment of acquired ptosis, although further study is needed to elucidate the clinical relevance of these findings beyond 6 weeks.

Purpose: To increase our understanding of the mechanisms underlying hydroxychloroquine (HCQ) retinopathy, analyses by quantitative fundus autofluorescence (qAF) and near-infrared fundus autofluorescence (NIR-AF) were compared to results obtained by recommended screening tests., Methods: Thirty-one patients (28 females, 3 males) were evaluated with standard automated perimetry and spectral domain optical coherence tomography (SD-OCT); 28 also had multifocal electroretinography (mfERG). Measurement of short-wavelength fundus autofluorescence (SW-AF) by qAF involved the use of an internal fluorescent reference and intensity measurements in eight concentric segments at 7° to 9° eccentricity. For semiquantitative analysis of NIR-AF, intensities were acquired along a vertical axis through the fovea., Results: Four of 15 high-dose (total dose >1000 g, daily dose >5.0 mg/kg) patients and one of 16 low-dose (total dose <1000 g, daily dose 4.4 mg/kg) patients were diagnosed with HCQ-associated retinopathy based on abnormal 10-2 visual fields, SD-OCT, and SW-AF imaging. Three of the high-dose patients also had abnormal mfERG results. Of the five patients exhibiting retinopathy, two had qAF color-coded images revealing higher intensities inferior, nasal, and lateral to the fovea. The abnormal visual fields also exhibited superior-inferior differences. Mean NIR-AF gray-level intensities were increased in four high-dose patients with no evidence of retinopathy. In two patients with retinopathy, NIR-AF intensity within the parafovea was below the normal range. One high-dose patient (6.25 mg/kg) had only abnormal mfERG results., Conclusions: These findings indicate that screening for HCQ retinopathy should take into consideration superior-inferior differences in susceptibility to HCQ retinopathy.

Significance: There are several isolated reports of systemic medications or medical conditions that can cause acute transient myopic shifts along with other ocular sequelae, but rarely has this been reported for the combination antibiotic sulfamethoxazole-trimethoprim., Purpose: This case illustrates a rarely seen condition that may result from treatment with sulfamethoxazole-trimethoprim and result in serious, vision-threatening conditions. These can be treated by immediate discontinuation of the drug, steroids, ocular hypertensive medication, and cycloplegia, depending on the circumstances., Case Report: A 20-year-old woman presented complaining of blindness upon waking. She had been experiencing fever, malaise, and significant abdominal pain for weeks. Blood culture revealed infection with Staphylococcus aureus and Escherichia coli for which she was prescribed sulfamethoxazole (800 mg) and trimethoprim (160 mg) twice daily. After a week of treatment, she awoke unable to see. Examination revealed narrowed angles, bilateral 6-D myopic shift, macular folding with scattered microaneurysms, and intraretinal hemorrhages with mild macular edema and field defects. The condition resolved with discontinuation of the drug and use of steroids, ocular hypertensive, and cycloplegic agents. Her visual acuity returned to near normal within 3 days. Resolution of macular edema, field defects, and hemorrhages followed., Conclusions: An adverse reaction possibly caused by sulfamethoxazole-trimethoprim is described causing ciliochoroidal effusion resulting in acute myopic shift and other sequelae. Successful treatment is demonstrated, and implications are discussed.

Background: Glaucoma is a common ophthalmic neurodegenerative disease and the main cause of blindness, which seriously affects the life and work of patients, without more effective treatment for optic nerve damage. Bushen Huoxue (BSHX) method is a traditional Chinese medicine (TCM) therapy that has been widely used as an alternative therapy to treat optic nerve damage in glaucoma patients with growing beneficial effect evidence, however, there is no current systematic review has addressed its effect for glaucoma. This study will conduct a systematic review and meta-analysis of the currently published randomized controlled trials (RCTs) of BSHX method for the treatment of glaucoma, aim to assess the efficacy and safety of BSHX method for patients with glaucoma., Methods: We will thoroughly search literatures of RCTs related to BSHX method for glaucoma in PubMed, Medline, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP and Wanfang database and other databases from the establishment of the database to November 2019, with no language restriction. After reviewing the title, abstract and full text, 2 reviewers will independently select the study, extract the data, after assess the risk of bias, we will conduct a meta-analysis of the data extracted from the included RCTs, including total effective rate, intraocular pressure (IOP), visual acuity, visual field, TCM syndrome score, and adverse events. The meta-analysis will be performed using Review Manager 5.3 software and the results will be based on either random effects or fixed effects models, depending on the heterogeneity. Trial sequential analysis (TSA) and Grading of Recommendations, Development and Evaluate system (GRADE) will be conduct to evaluate the reliability and quality of evidence., Results: The results of the study will be published in a peer-reviewed journal, and provide a reasonable and high-quality evidence for the efficacy and safety of BSHX method for glaucoma., Conclusion: This study will be the first meta-analysis to evaluate the efficacy of BSHX method in the treatment of glaucoma comprehensively, and will to provide helpful evidence for the clinical treatment of this disease., Registration: PROSPERO CRD42020159897.

Glaucoma is a neurodegenerative disease, our study aimed to evaluate the potential effects of Palmitoylethanolamide (PEA) supplementation on RGCs function by PERG examination, and to record effects on intraocular pressure, visual field and quality of life. It was a single centre, randomized, prospective, single blind, two treatment, two period crossover study on stable glaucoma patients on topical monotherapy comparing current topical therapy alone or additioned with PEA 600 mg one tablet a day. At baseline, at 4 and at 8 months, all patients underwent to complete ophthalmic examination, pattern electroretinogram, visual field, and quality of life evaluation. 40 patients completed the study: mean age 66.6 ± 7.6 years; 21 (52.5%) male; 35 POAG (87.5%). At baseline, most patients had an early visual field defect, the IOP was well controlled. At the end of the PEA 600 mg supplementation, a significantly higher (mean 0.56 μV, 95% CI 0.30-0.73, p < 0.001) in the P50-wave amplitude was observed; in the PEA period a significantly lower IOP (- 1.6 mmHg, 95% CI - 2 to 1.2, p < 0.001) and higher quality of life scores (+ 6.7, 95% CI 4-9.9, p < 0.001) were observed. Our study is the first to show promising effects of PEA on PERG and on quality of life in glaucoma patients.

Nutritional supplementation with antioxidants and vitamins is widely recommended in the treatment of vascular disorders affecting the retina, although there is insufficient evidence on its effectiveness. The vitamin-like compound coenzyme Q10 (CoQ10) is a nutritional supplement of current interest to treat neurodegenerative diseases. Here, we report a retrospective clinical case series study of 48 patients diagnosed with retinal vascular diseases, including non-arteritic ischemic optic neuropathy (NAION), retinal artery occlusion (RAO), and homonymous hemianopia or quadrantanopia following stroke, treated with oral supplementation with CoQ10 (100 mg per day) and vitamins. Patient follow-up was performed using the Humphrey field analyzer and 30-2 testing algorithm to determine the visual field index (VFI) and progression rates. All treated patients showed positive VFI progression rates per year: +11.5 ± 15% for NAION patients ( n = 18), +22 ± 17% for RAO patients ( n = 7), +9.3 ± 10.5% for hemianopia/quadrantanopia patients ( n = 10), and +11 ± 21% for patients with other conditions ( n = 13). The interruption of CoQ10 supplementation in one patient resulted in a pronounced decrease of the VFI, which was partially recovered when treatment was restored. This study supports the role of CoQ10 as a nutritional therapeutic agent for vascular diseases affecting the retina. Owing to decreased VFI after interruption of CoQ10, its beneficial effects may be reversible.

Importance: Preservation of peripheral visual field (VF) is considered an advantage for anti-vascular endothelial growth factor agents compared with panretinal photocoagulation (PRP) for treatment of proliferative diabetic retinopathy. Long-term data on VF are important when considering either treatment approach., Objective: To further evaluate changes in VF throughout 5 years among eyes enrolled in the Protocol S clinical trial, conducted by the DRCR Retina Network., Design, Setting, and Participants: Post hoc analyses of an ancillary study within a multicenter (55 US sites) randomized clinical trial. Individuals with eyes with proliferative diabetic retinopathy enrolled in Protocol S were included. Data were collected from February 2012 to February 2018. Analysis began in June 2018., Interventions: Panretinal photocoagulation or intravitreous injections of 0.5-mg ranibizumab. Diabetic macular edema, whenever present, was treated with ranibizumab in both groups. Panretinal photocoagulation could be administered to eyes in the ranibizumab group when failure or futility criteria were met., Main Outcomes and Measures: Mean change in total point score on VF testing with the Humphrey Field Analyzer 30-2 and 60-4 test patterns., Results: Of 394 eyes enrolled in Protocol S, 234 (59.4%) were targeted for this ancillary study. Of these, 167 (71.4%) had VF meeting acceptable quality criteria at baseline (median [interquartile range] age, 50 [43-58] years; 90 men [53.9%]). At 5 years, 79 (33.8%) had results available. The mean (SD) change in total point score in the PRP and ranibizumab groups was -305 (521) dB and -36 (486) dB at 1 year, respectively, increasing to -527 (635) dB and -330 (645) dB at 5 years, respectively (P = .04). After censoring VF results after PRP treatments in the ranibizumab group, the 5-year mean change in total point score was -201 (442) dB. In a longitudinal regression analysis of change in total point score including both treatment groups, laser treatment was associated with a mean point decrease of 208 (95% CI, 112-304) dB for the initial PRP session, 77 (95% CI, 21-132) dB for additional PRP sessions, and 325 (95% CI, 211-439) dB for endolaser. No association was found between change in point score and the number of ranibizumab injections during the previous year (-9 per injection [95% CI, -22 to 3])., Conclusions and Relevance: The limited data available from Protocol S suggest that there are factors besides PRP associated with VF loss in eyes treated for proliferative diabetic retinopathy. Further clinical research is warranted to clarify the finding., Trial Registration: ClinicalTrials.gov identifier: NCT01489189.

Objectives: To investigate the application of ultra-widefield fundus autofluorescence (UWF-FAF) imaging in evaluating hydroxychloroquine (HCQ) retinopathy and to report peripheral autofluorescence findings in Asian patients with this condition., Design: Retrospective case series., Methods: Setting: institutional., Patient Population: 58 eyes of 29 patients with HCQ retinopathy., Observation Procedures: UWF-FAF imaging was performed, and the images were compared to conventional FAF images obtained using a confocal digital ophthalmoscope. The sensitivities of detecting retinopathy using the 2 modalities were compared. Peripheral autofluorescence findings in the eyes with HCQ retinopathy were assessed, and their association with the Humphrey visual field test results obtained using the 30-2 and full-field 120 (FF-120) protocols was analyzed. Main outcome measurements were abnormal FAF findings., Results: In 41 of 58 eyes (70.7%) with HCQ retinopathy, abnormal FAF findings were noted in the retinal periphery outside the field of view of conventional FAF as hypoautofluorescent (23 eyes, 39.7%) and hyperautofluorescent (38 eyes, 65.5%) lesions. In 5 eyes (8.6%), differences were revealed between conventional FAF and UWF-FAF in detecting retinopathy. Most of the eyes with severe retinopathy showed the most extensive hypoautofluorescence in the nasal peripheral retina. The areas with abnormal FAF findings were significantly correlated with the number of unseen spots on FF-120 results and mean deviation and pattern standard deviation of the 30-2 test results (all P < .001)., Conclusions: Peripheral autofluorescence findings varied in eyes with HCQ retinopathy according to the severity of the retinopathy. The retinal findings with UWF-FAF were functionally correlated to visual field results. UWF-FAF may be useful for evaluating HCQ retinopathy, particularly in Asian patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To study the pupillary system by combining mydriasis and multifocal pupillographic objective perimetry (mfPOP). In particular, we explored how the dynamics of recovery differ for concurrently measured direct and consensual sensitivity, response delay, and signal-to-noise ratios (SNRs) for binocular mydriasis., Methods: We recruited 26 normal participants, all with brown irides. The dichoptic mfPOP stimuli concurrently assessed 44-region/eye and both pupils. Two pre-dilation tests were followed by pairs of repeated tests at 1, 2, 4, 6, 8, 12, 24, and 48 h following dilation of both pupils with 1% tropicamide. Three subjects were retested with only the right pupil dilated. Linear models determined the independent effects of mydriasis upon the per-region and pupil measures over time., Results: Post-dilation, the per-region delays initially decreased by 16.3 ± 6.02 ms (mean ± SE) (p < 0.0001, cf. baseline of 471.1 ± 4.36 ms), then increased to slower than baseline by 17.42 ± 5.57 ms after 4 h (p < 0.002), recovering to baseline at 8 h. By comparison, per-region sensitivities (constriction amplitudes) were still reduced by - 6.20 ± 0.70 μm at 8 h (p < 0.0001, cf. baseline of 21.1 ± 0.55 μm), recovered at 24 h, but rebounded at 48 h (p = 0.005). The SNRs for sensitivities and delays both recovered by 8-12 h. Across all the data, sensitivities reduced by 2.67 ± 0.25 μm/decade of age, and delay increased by 15.4 ± 1.98 ms/decade (both p < 0.00001). Data from 3 of the 26 subjects who repeated the testing for monocular dilation found that consensual response sensitivities were larger than direct for 8 h (p < 0.018)., Conclusions: The per-region sensitivities were affected for longer than SNRs or delays. Strong early SNRs indicated proportionately lower pupil noise for larger pupil diameters. Following mydriasis with tropicamide 1%, the constriction amplitude measurements with mfPOP should be considered only after 48 h, but time-to-peak can be measured after 8-12 h.

This microinjectrode system is designed for drug infusion, electrophysiology, and delivery and retrieval of experimental probes, such as microelectrodes and nanosensors, optimized for repeated use in awake, behaving animals. The microinjectrode system can be configured for multiple purposes: (1) simple arrangement of the cannula for placement of an experimental probe that would otherwise be too fragile to penetrate the dura mater, (2) microfluidic infusion of a drug, either independently or coupled to a cannula containing an experimental probe (i.e., microelectrode, nanosensor). In this protocol we explain the step by step construction of the microinjectrode, its coupling to microfluidic components, and the protocol for use of the system in vivo. The microfluidic components of this system allow for delivery of volumes on the nanoliter scale, with minimal penetration damage. Drug infusion can be performed independently or simultaneously with experimental probes such as microelectrodes or nanosensors in an awake, behaving animal. Applications of this system range from measuring the effects of a drug on cortical electrical activity and behavior, to understanding the function of a specific region of cortex in the context of behavioral performance based on probe or nanosensor measurements. To demonstrate some of the capabilities of this system, we present an example of muscimol infusion for reversible inactivation of the frontal eye field (FEF) in rhesus macaque during a working memory task.

Purpose: To determine the association of statins, five classes of antihypertensive medications, and proton pump inhibitors with (1) primary open-angle glaucoma (POAG) progression and (2) conversion of POAG suspects to POAG., Methods: We retrospectively investigated the records of a cohort with POAG cases and suspects from the Groningen Longitudinal Glaucoma Study. To quantify visual field (VF) deterioration in cases, we used the rate of progression of the mean deviation (MD). Suspects were considered to have converted at the time point after which two consecutive VF tests for at least one eye were abnormal (glaucoma hemifield test outside normal limits). Progression and conversion were analyzed with quantile and logistic regression, respectively, with the systemic medications as predictors, controlling for age, sex, body mass index, pretreatment IOP, corneal thickness, and baseline MD. The multivariable models were built with and without IOP intervention., Results: No systemic medications were associated with POAG progression in the final IOP/treatment-adjusted or unadjusted model. However, angiotensin II receptor blockers (ARBs) appeared to slow progression in older patients (b = 0.014, P = 0.0001). Angiotensin-converting enzyme inhibitors (ACEIs) were significantly associated with a decrease in POAG suspect conversion in both the IOP/treatment-adjusted and -unadjusted model (odds ratio [OR] 0.23, 95% confidence interval [CI] 0.07-0.79, P = 0.012; OR=0.24, 95% CI 0.07-0.78, P = 0.021, respectively), as were ARBs (OR 0.12, 95% CI 0.01-0.98, P = 0.014; OR 0.11, 95% CI 0.01-0.87, P = 0.005, respectively)., Conclusions: No overall association of VF progression with systemic medication was found; ARBs delayed progression in older patients. ACEIs and ARBs were associated with lower risk of suspect conversion. The pathophysiology of this relationship is to be disentangled.

Background/aims: Hydroxychloroquine (HCQ) retinopathy may result in severe and irreversible vision loss, emphasising the importance of screening and early detection. The purpose of this study is to report the novel finding of early optical coherence tomography (OCT) abnormalities due to HCQ toxicity that may develop in the setting of normal Humphrey visual field (HVF) testing., Methods: Data from patients with chronic HCQ exposure was obtained from seven tertiary care retina centres. Ten patients with HCQ-associated OCT abnormalities and normal HVF testing were identified. Detailed analysis of the OCT findings and ancillary tests including colour fundus photography, fundus autofluorescence, multifocal electroretinography and microperimetry was performed in these patients., Results: Seventeen eyes from 10 patients illustrated abnormalities with OCT and normal HVF testing. These OCT alterations included (1) attenuation of the parafoveal ellipsoid zone and (2) loss of a clear continuous interdigitation zone. Several eyes progressed to advanced parafoveal outer retinal disruption and/or paracentral visual field defects., Conclusion: Patients with high risk HCQ exposure and normal HVF testing may develop subtle but characteristic OCT abnormalities. This novel finding indicates that, in some cases of early HCQ toxicity, structural alterations may precede functional impairment. It is therefore important to employ a screening approach that includes OCT to assess for these early findings. Ancillary testing should be considered in cases with suspicious OCT changes and normal HVFs., Competing Interests: Competing interests: NKW is a consultant for Optovue and receives research support from Carl Zeiss Meditec, Topcon Medical Systems and Nidek Medical Products. JSD is a consultant for and receives research support from Carl Zeiss Meditec and Optovue. EHS is a consultant for Novartis, Bayer Schering Pharma, Allergan Inc. and Farmila-Thea. KBF is a consultant to Genentech, Allergan, Optos, Optovue, Zeiss, Heidelberg Engineering and Novartis. He receives research funding from Genentech/Roche. DS is a consultant for Amgen, Bayer, Genentech, Novartis and Optovue and receives research funding from Genentech, Heidelberg, Optovue and Regeneron. All other authors have no conflict of interest to declare., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate multifocal electroretinography (mfERG) as a screening test for detecting hydroxychloroquine and chloroquine toxicity., Design: Diagnostic accuracy study., Methods: Patients referred to the University of Ottawa for hydroxychloroquine or chloroquine retinopathy screening during 2011-2014 underwent 10-2 automated visual field, spectral domain optical coherence tomography, and mfERG testing. Patients with amblyopia, high myopia or hyperopia, coexisting retinal disease, or prior surgery were excluded. Abnormalities in parafoveal ring amplitudes or ring ratios were considered a positive mfERG result. We used the definition for hydroxychloroquine and chloroquine toxicity provided by the 2016 American Academy of Ophthalmology recommendations. Area under the curve (AUC) for each mfERG parameter and the sensitivity and specificity of mfERG were calculated. Logistic regression was used to model the effect of covariates in receiver operating characteristic (ROC) analyses., Results: In total, 63 patients (47 female, 16 male) were included. Of 120 eyes, 16 (13.3%) had toxicity according to the American Academy of Ophthalmology guidelines, and 39 (32.5%) had positive mfERG findings. mfERG was found to have a sensitivity of 1.00 (95% CI 0.79-1.00) and a specificity of 0.78 (95% CI 0.69-0.85). Ring 2 amplitude had the best performance among all parameters (AUC 0.97, 95% CI 0.94-1.00). Ring 2 amplitude decreased linearly with increasing cumulative dose and daily dose., Conclusions: The high sensitivity of parafoveal depression on mfERG and its relationship to cumulative and daily dose illustrates an important role for objective functional testing. The high false-positive rate suggests a potential period where physiologic dysfunction is detected objectively on mfERG before structural change on spectral domain optical coherence tomography., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To investigate the neuroprotective effect of Copolymer-1 (Cop-1) in patients with acute primary angle closure (APAC) in a randomized double-masked controlled trial., Methods: After initial medical management, APAC patients were randomized to receive either subcutaneous Cop-1 or placebo within 24 hr and at 1 week. After laser peripheral iridotomy (LPI), subjects underwent serial visual field (VF) tests and retinal nerve fibre layer (RNFL) thickness measurements with spectral-domain optical coherence tomography. The primary outcome measure was mean number of progressing points (significant slope of ≥ 1 dB per year sensitivity loss) over 16 weeks based on pointwise linear regression analysis, and the secondary outcome measure was the change in RNFL thickness., Results: Thirty-eight patients (19 in each group) completed the study. Twenty-five (65.8%) were female, the majority being Chinese (86.8%) with mean age 62.5 years (SD 8.1). Patients in the Cop-1 group were found to have mean of 0.32 (SD 0.95) progressing points compared to 2.74 (SD 5.31) in the placebo group (p = 0.09), while 3/19 (15.8%) of Cop-1 treated patients had 1 or more progressing points compared to 7/19 (36.8%) in the placebo group (p = 0.14). There was no difference in change of RNFL thickness between groups (p = 0.57). We found improvement of mean deviation (MD) at week 16 in the Cop-1 group (p = 0.01) compared to worsening of MD in the placebo group (p = 0.04)., Conclusion: After APAC, there was no difference in VF progression (or RNFL thickness change) between Cop-1 and placebo groups. However, there was improvement of MD in Cop-1 treated patients., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: The morphology and between-eye symmetry of the visual field loss associated with the antiepileptic drug vigabatrin (VAVFL) has received little attention., Objective: Our objective was to model the appearance and ensuing staging of VAVFL derived with the European Medicines Agency-approved perimetric protocol., Methods: This was a retrospective, cross-sectional, observational study that identified 123 adults who had received vigabatrin for refractory seizures and who had no evidence of co-existing retino-geniculo-cortical visual pathway abnormality. A further 38 adults with refractory seizures and identical inclusion criteria but no exposure to vigabatrin acted as controls. For each group, the median outcome at each stimulus location in each eye (of absolute loss, relative loss or Pattern Deviation probability level, as appropriate) was derived for each successive ten pairs of fields, ranked for severity. Between-eye symmetry was quantified by an index that accounted for severity of loss and that was referenced to the likelihood of the occurrence of symmetry due to chance., Results: The modelled VAVFL was bilateral and highly symmetrical and was described by six stages that were all independent of the extent of vigabatrin exposure. The loss originated in the extreme temporal periphery and encroached centripetally along all meridians towards fixation. The initial appearance within the central field (Stage 2) occurred inferior-nasally. Subsequent stages exhibited increasing loss, which was greater nasally than temporally. Stage 6 described concentric loss extending to approximately 15° eccentricity from fixation., Conclusion: The model exhibited a consistent pattern of VAVFL. The staging of the loss could assist the risk:benefit analysis of vigabatrin for the treatment of epilepsy.

Objective: To find out the predictors of final visual outcome and recurrences in idiopathic intracranial hypertension (IIH)., Patients and Methods: Medical records of 75 patients with IIH were analyzed retrospectively. Gender, age of disease onset (AODO), body mass index (BMI), lumbar puncture opening pressure (LP-OP), visual acuity (VA) in logMAR, optical disc appearance (ODA), visual field (VF) mean deviation (MD), treatment results and recurrence rates were considered., Results: Mean age at onset age was 32.4 years, BMI was 311 kg/m² and median LP-OP was 380 mm H2O. All patients were treated with acetazolamide with a median dose of 1500 mg. The mean follow-up period was 44.8 months. AODO, BMI, LP-OP were not correlated with any of the examination parameters (VA, ODA, VF) at the first or last visit. The correlation between the VA and VF both at the first and last visit was not very powerful. VA of the last visit was fairly correlated with the VA of the first visit. However, the correlation between the last and first visit VF was very good. A very significant improvement in both VA and VF was recorded after treatment. Recurrences were noted in 23%. Demographic and clinical features of the recurring and non-recurring patients were not significantly different in terms of AODO, BMI, LP-OP, VA, VF or ODA., Conclusions: The patients with IIH respond to treatment with acetazolamide. First visit VF is the main determinant of the final visual outcome. Recurrences cannot be predicted by the demographic or clinical features at presentation., (Copyright © 2019. Published by Elsevier B.V.)

PRéCIS:: Instillation of brimonidine or timolol slowed visual field deterioration in patients with open-angle glaucoma; both brimonidine and timolol might improve the mean deviation (MD) slopes., Purpose: The purpose of this study was to investigate and compare the effects of 0.1% brimonidine and 0.5% timolol on the progressing visual field defects in open-angle glaucoma., Patients and Methods: We evaluated 1 eye each of 68 glaucoma patients who were treated with at least 1 prostaglandin analog. Their baseline MD slopes were < -0.5 dB/y based on at least 5 Humphrey field analyzer measurements within 3 years. Eligible eyes were randomly assigned to brimonidine or timolol treatment groups and treatments were administered without the wash-out period. Clinical examinations were performed every 4 months for 2 years. We designated the MD slope as the primary endpoint., Results: Ultimately, 56 eyes (brimonidine:timolol=26:30) were included in the present study (mean age=65.2 y). Dropout rates of brimonidine and timolol treatment groups were 27.8% and 6.3%, respectively. There were no significant differences in baseline intraocular pressure or MD slopes between brimonidine and timolol groups (12.7 and 12.9 mm Hg, P=0.77, and -1.22 and -1.08 dB/y, P=0.43, respectively). Intraocular pressure decreased significantly in the brimonidine group at 4, 8, 12, and 16 months, and in the timolol group at 4 months, without significant differences between the drugs (P=0.20). MD slopes significantly improved in both groups (brimonidine: -0.38 dB/y, P<0.001; timolol: -0.52 dB/y, P=0.04). Furthermore, there was no significant difference between groups in the primary endpoint (P=0.59)., Conclusion: Brimonidine and timolol treatments improved MD slopes in open-angle glaucoma.

Introduction: Although the introduction of BRAF and MEK inhibitors has greatly enhanced treatment possibilities in advanced BRAFV600-mutated melanoma, class-related toxicities are rather frequent and often involve the eye. Ophthalmologic side effects most commonly include central/diffuse serous retinopathy and retinal vein occlusion. Affection of the optic nerve head however has not been described clinically., Case Report: A 29-year-old man presented in our eye clinic with bilateral blurred vision. Seventeen days earlier, he had been started on trametinib and dabrafenib combination therapy for metastasized melanoma of unknown origin. Visual field testing revealed diffuse bilateral defects, which regressed spontaneously on pause of MEK and BRAF inhibitor treatment., Discussion: In addition to the widely known class-related retinal toxicity, MEK and BRAF inhibitor-associated adverse events may also involve the optic nerve head, causing visual field defects probably regressing spontaneously after discontinuation of targeted oncologic therapy. In such cases, repeat brain imaging and exclusion of melanoma-associated retinopathy is recommended. Reinitiation of treatment and subsequent dose escalation seem to be feasible, but should be monitored by an ophthalmologist.

Purpose: To assess the impact of glaucoma treatment and ocular surface disease (OSD) on the vision-specific quality-of-life (VS-QoL) of glaucoma patients attending Farhat Hached university hospital Sousse-Tunisia., Methods: This was a cross-sectional study enrolling one-hundred-twenty patients followed for primary open angle glaucoma. All patients successfully responded to the Arabic version of the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ 25). QoL was quantified in terms of scores (0-100) and correlated with the characteristics of glaucoma treatment and status of the ocular surface., Results: One hundred and twenty patients were studied. The mean number of medications and instilled drops was 1.95 (1-4) and 2.69 (1-7) respectively. A total of 66.7% patients reported side effects of treatment. On examination, moderate or severe dry eye syndrome was identified in 90% of cases. A total of 16.7% of patients had superficial punctate keratopathy. The number of instilled drops per day, the use of brimonidine or oral carbonic anhydrase inhibitors, and the presence of OSD had a negative impact on the NEI-VFQ 25 scores., Conclusions: Glaucoma treatment and OSD are 2 factors potentially reducing the QoL of glaucoma patients, on which the ophthalmologist can act by optimizing treatment and regularly examining the ocular surface of glaucoma patients., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Purpose: To investigate the posttreatment neuronal rescue effects of Lycium barbarum polysaccharides (LBP) in an acute ocular hypertensive (AOH) model., Methods: Intraocular pressure (IOP) was elevated manometrically to 80 mm Hg (AOH) or 15 mm Hg (sham) for 120 minutes in adult Sprague-Dawley rats. Five experimental groups were considered: Three AOH groups were pretreated with PBS (vehicle) (n = 9), LBP 1 mg/kg (n = 8), or 10 mg/kg (n = 13), and one AOH group was posttreated with LBP 10 mg/kg (n = 8), once daily. The sham cannulation group (n = 5) received no treatment. Pretreatments commenced 7 days before and posttreatment 6 hours after AOH, and continued up through postcannulation day 28. All the animals underwent optical coherence tomography and electroretinogram measurements at baseline and postcannulation days 10 and 28. The ganglion cell layer (GCL) densities were quantified at day 28., Results: Both inner retinal layer thickness (IRLT) and positive scotopic threshold response (pSTR) underwent significant reduction (≥50% of thickness and amplitude) in the vehicle group (P < 0.05). Pretreatment with LBP 1 and 10 mg/kg retained 77 ± 11% and 89 ± 8% of baseline IRLT, respectively, and preserved pSTR functions. The posttreatment group showed a significant reduction in IRLT (-35 ± 8%, P < 0.001) and pSTR (∼48% of baseline, P < 0.001) on day 10. By day 28, there was an improvement in functional pSTR (∼72% of baseline, P > 0.05) with no significant further thinning (-40 ± 8%, P = 0.15) relative to day 10. GCL density was reduced in vehicle control (P = 0.0001), but did not differ between sham and pre- and posttreated AOH groups., Conclusions: The rescue effect of LBP posttreatment was observed later, which arrested the secondary degeneration and improved the retinal function.

Background: The antiepileptic drug vigabatrin is associated with characteristic visual field loss (VAVFL) and thinning of the peripapillary retinal nerve fibre layer (PPRNFL); however, the relationship is equivocal., Objective: The aim of this study was to determine the function-structure relationship associated with long-term exposure to vigabatrin, thereby improving the risk/benefit analysis of the drug., Methods: A cross-sectional observational design identified 40 adults who had received long-term vigabatrin for refractory seizures, who had no evidence of co-existing retino-geniculo-cortical visual pathway abnormality, and who had undergone a standardized protocol of perimetry and of optical coherence tomography (OCT) of the PPRNFL. Vigabatrin toxicity was defined as the presence of VAVFL. The function-structure relationship for the superior and inferior retinal quadrants was evaluated by two established models applicable to other optic neuropathies., Results: The function-structure relationship for each model was consistent with an optic neuropathy. PPRNFL thinning, expressed in micrometres, asymptoted at an equivalent visual field loss of worse than approximately - 10.0 dB, thereby preventing assessment of more substantial thinning. Transformation of the outcomes to retinal ganglion cell soma and axon estimates, respectively, resulted in a linear relationship., Conclusions: Functional and structural abnormality is strongly related in individuals with vigabatrin toxicity and no evidence of visual pathway comorbidity, thereby implicating retinal ganglion cell dysfunction. OCT affords a limited measurement range compared with perimetry: severity cannot be directly assessed when the PPRNFL quadrant thickness is less than approximately 65 µm, depending on the tomographer. This limitation can be overcome by transformation of thickness to remaining axons, an outcome requiring input from perimetry.

Vigabatrin (VGB; (S)-(+)/(R)-(-) 4-aminohex-5-enoic acid), an antiepileptic irreversibly inactivating GABA transaminase (GABA-T), manifests use-limiting ocular toxicity. Hypothesizing that the active S enantiomer of VGB would preferentially accumulate in eye and visual cortex (VC) as one potential mechanism for ocular toxicity, we infused racemic VGB into mice via subcutaneous minipump at 35, 70, and 140 mg/kg/d (n = 6-8 animals/dose) for 12 days. VGB enantiomers, total GABA and β-alanine (BALA), 4-guanidinobutyrate (4-GBA), and creatine were quantified by mass spectrometry in eye, brain, liver, prefrontal cortex (PFC), and VC. Plasma VGB concentrations increased linearly by dose (3 ± 0.76 (35 mg/kg/d); 15.1 ± 1.4 (70 mg/kg/d); 34.6 ± 3.2 μmol/L (140 mg/kg/d); mean ± SEM) with an S / R ratio of 0.74 ± 0.02 (n = 14). Steady state S / R ratios (35, 70 mg/kg/d doses) were highest in eye (5.5 ± 0.2; P  < 0.0001), followed by VC (3.9 ± 0.4), PFC (3.6 ± 0.3), liver (2.9 ± 0.1), and brain (1.5 ± 0.1; n = 13-14 each). Total VGB content of eye exceeded that of brain, PFC and VC at all doses. High-dose VGB diminished endogenous metabolite production, especially in PFC and VC. GABA significantly increased in all tissues (all doses) except brain; BALA increases were confined to liver and VC; and 4-GBA was prominently increased in brain, PFC and VC (and eye at high dose). Linear correlations between enantiomers and GABA were observed in all tissues, but only in PFC/VC for BALA, 4-GBA, and creatine. Preferential accumulation of the VGB S isomer in eye and VC may provide new insight into VGB ocular toxicity.

Purpose: To evaluate the influence of hydroxychloroquine in visual field and retinal layer thickness., Methods: This is a retrospective cross-sectional study. Patients taking hydroxychloroquine without signs of hydroxychloroquine retinopathy were included. Optical coherence tomography segmentation was used to obtain the ETDRS map thickness of each retinal layer. Groups were divided into short-term (< 5 years) and long-term (≥5 years) drug use., Results: We included 93 eyes of 93 patients (short-term: 25 eyes; long-term: 68 eyes). The inner nuclear layer (INL) was thinner in the long-term group (32.86 ± 2.12 vs. 34.14 ± 2.37 μm; p = 0.014). Considering long-term cases, the parafoveal ganglion cell layer (GCL) showed an inverse correlation with cumulative dose (r = -0.37; p < 0.001). After adjusting for confounders, parafoveal ganglion cell complex thickness was associated with cumulative dose (β = -0.239; p = 0.011). The parafoveal outer retina and visual field indices were similar between groups and did not correlate with cumulative dose., Conclusion: Hydroxychloroquine leads to progressive thinning of the parafoveal inner retina, particularly the INL and GCL. Visual field indices do not reflect the long-term effects of the drug., (© 2019 S. Karger AG, Basel.)

Background: Multifocal visual evoked potential (MF-VEP) assesses a wider visual field than full-field VEP (FF-VEP) and potentially offers a more precise analysis of optic nerve injury and repair following optic neuritis. MF-VEP may offer advantages over FF-VEP as an endpoint in clinical trials of remyelinating therapies., Objective: MF-VEP testing was used to study changes in visual pathways in 48% of RENEW [phase II, opicinumab (anti-LINGO-1; BIIB033) vs. placebo after first acute unilateral optic neuritis] participants., Methods: This exploratory MF-VEP RENEW substudy compared mean outcomes at weeks 24 and 32 among participants in the intent-to-treat (ITT; n = 39; 72% female; mean age: 32.3 years) and per-protocol (PP; n = 31; 71% female; mean age: 32.2 years) populations in affected and fellow eye latency from fellow eye baseline latency and affected and fellow eye amplitude from their own baselines. Treatment differences were evaluated using analysis of covariance (week 24) and a mixed-effect model of repeated measures (week 32). Last observation carried forward was used to impute missing data at week 24., Results: A trend for improvement in affected eye MF-VEP latency with opicinumab versus placebo was seen in the ITT and PP populations at weeks 24 and 32. Both treatment groups in the ITT population experienced partial recovery of amplitude in the affected eye at week 32. Notably, the mean change in fellow eye amplitude at weeks 24 and 32 was - 17.57 and - 31.41 nanovolts (nV) in placebo but only - 0.59 and 1.93 nV in the opicinumab group [differences at weeks 24 and 32: 16.98 nV (p = 0.050) and 33.33 nV (p < 0.01), respectively]., Conclusion: Results from this substudy showed advantages of MF-VEP over FF-VEP in multicenter studies of central nervous system reparative therapies and provide novel evidence that fellow eye visual pathway amplitude loss occurs after optic neuritis but can potentially be prevented by opicinumab treatment., Registration: ClinicalTrials.gov identifier NCT01721161.

Purpose: To examine retinal sensitivity in patients on hydroxychloroquine (HCQ) with no evidence of retinopathy., Materials and Methods: Seventy patients on HCQ and 30 healthy control subjects were included prospectively. All subjects underwent complete ophthalmic examination including best corrected visual acuity, tonometry, colour vision testing, biomicroscopy of anterior segment, dilated fundoscopy, 10-2 visual field testing, and spectral domain optical coherence tomography. The patients and control subjects who met the inclusion criteria and had normal tests underwent microperimetry (MP) testing. First, all patients were compared with the control group. Secondly, patients were divided into three sets of groups based on (1) duration of use ≤5 years (DOU≤5) and >5 years (DOU>5), (2) daily dose ≤5 mg/kg/day (DD≤ 5) and >5 mg/kg/day (DD>5), and (3) a cumulative dose ≤1000 gr (CD≤ 1000) and >1000 gr (CD>1000), and these groups were compared to each other and to the control group. A correlation analysis was also performed between MP sensitivity and DOU, DD, and CD., Results: Seven patients on HCQ showing visual field abnormality were excluded which yielded 63 patients and 30 control subjects for the final analysis. We observed significant differences only in the central region but not in the paracentral or peripheral regions on MP in HCQ users. The median MP sensitivities in the central region were significantly lower in all the patients [84 (63-100) dB], and in subgroups of DOU >5 [84 (63-99) dB], DD >5 [82 (63-97) dB] and CD >1000 [82 (63-92) dB] when compared to controls [89.7 (83-98) dB]. A statistically significant correlation was found only between DD and MP sensitivity in the central region (r = -0.263; p = 0.02)., Conclusions: MP sensitivities in the central macula were significantly lower in patients taking HCQ for more than 5 years, at a daily dose more than 5 mg per day, and with a cumulative dose over 1000 gr. Further research investigating long-term follow-up changes in MP sensitivities is needed to determine cutoff values for early retinal toxicity.

Objective: To study the prevalence of the systemic use of some common classes of medications by glaucoma patients and their relationship to the prevalence and severity of chronic open-angle glaucoma (COAG) and primary-angle closure glaucoma (PACG)., Design: Observational prospective single-centre cross-sectional study., Methods: Glaucoma patients or their pharmacist provided an updated list of all systemic medications that they presently use. The relationship between glaucoma type and severity and medication use for diseases other than glaucoma was assessed by univariate statistics., Results: We studied 514 glaucoma patients. They use a mean of 4.9 oral medications prescribed by a mean of 2.1 doctors. Antihypertensives, medications with anticholinergic properties, steroids, anticoagulants, and thyroid hormones were the most frequently prescribed groups of medications, used by 251 (49%), 178 (35%), 100 (19%), 218 (42%), and 108 (21%) patients, respectively. Steroid usage was associated with advanced visual field loss in COAG patients. Antihypertensives and medications with anticholinergic properties were not associated with severity of COAG and PACG, respectively, and these 3 groups were not associated with an increased prevalence of diagnosis of COAG or PACG., Conclusion: Glaucoma patients take many systemic medications in addition to their topical glaucoma treatment., (Copyright © 2018 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Significance: This case illustrates a novel screening protocol for linezolid-induced toxic optic neuropathy., Purpose: To present a case report and analysis of linezolid-induced optic neuropathies in adult patients to develop screening recommendations., Case Report: A case report of optic neuropathy from extended use of linezolid illustrates its potential effects on vision. We conduct a retrospective analysis of 39 reported cases to derive a recommended screening protocol for linezolid-induced toxic optic neuropathy in adult patients. Of 39 reported adult cases, 32 presented with optic neuropathy within 90 to 365 days of treatment. Within this subset, the duration of linezolid dosage to first symptoms is 235 ± 71 days. Seven outliers either experienced optic neuropathy within the first 28 days or between 600 and 1125 days. Of the 33 cases that quantified visual recovery, 30 reported final binocular visual acuity equivalent to 20/40 or better when the medication was discontinued from 0 to 268 days after symptom onset. Recovery potential was reported over a period of 2 weeks to approximately 6 months after cessation. To evaluate the effect of cumulative dose, the data were separated into patients taking 600 mg twice daily and those at 600 mg once daily. At the higher dosage, a mean of 180 ± 96 days with a mean cumulative dosage of 216 ± 115 g was noted at first symptom, whereas at lower dosage, a mean of 201 ± 102 days was noted with a mean cumulative dose of 138 ± 69 g., Conclusions: We recommend screening adult patients within 1 month after initiating linezolid, followed by a subsequent evaluation every 30 to 60 days beginning 3 months from initiation. Substantial visual recovery is reported when linezolid is discontinued. Toxicity appears to be correlated to duration of treatment, rather than cumulative dose.

Purpose: To identify results from the Ocular Hypertension Study that can aid patients and clinicians to make evidence-based decisions about the management of ocular hypertension., Design: Perspective., Results: At 60 months, the cumulative frequency of developing primary open-angle glaucoma (POAG) was 4.4% in the medication group and 9.5% in the observation group (hazard ratio for medication, 0.40; 95% confidence interval [CI], 0.27-0.59; P < .0001). At 13 years the cumulative proportion of participants who developed POAG was 0.22 (95% CI 0.19-0.25) in the original observation group and 0.16 (95% CI 0.13-0.19) in the original medication group (complementary log-log x 2 P = .009). A 5-factor model (older age, higher IOP, thinner central corneal thickness, larger cup-to-disc ratio, and higher visual field pattern standard deviation) separated participants at high and low risk of developing POAG., Conclusions: Clinicians and patients can make evidence-based decisions about the management of ocular hypertension using the risk model and considering patient age, medical status, life expectancy, and personal preference., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: As optical coherence tomography (OCT) minimum intensity (MI) analysis provides a quantitative assessment of changes in the outer nuclear layer (ONL), we evaluated the ability of OCT-MI analysis to detect hydroxychloroquine toxicity., Methods: Fifty-seven predominantly female participants (91.2% female; mean age, 55.7 ± 10.4 years; mean time on hydroxychloroquine, 15.0 ± 7.5 years) were enrolled in a case-control study and categorized into affected (i.e., with toxicity, n = 19) and unaffected (n = 38) groups using objective multifocal electroretinographic (mfERG) criteria. Spectral-domain OCT scans of the macula were analyzed and OCT-MI values quantitated for each subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. A two-sample U-test and a cross-validation approach were used to assess the sensitivity and specificity of toxicity detection according to OCT-MI criteria., Results: The medians of the OCT-MI values in all nine of the ETDRS subfields were significantly elevated in the affected group relative to the unaffected group (P < 0.005 for all comparisons), with the largest difference found for the inner inferior subfield (P < 0.0001). The receiver operating characteristic analysis of median MI values of the inner inferior subfields showed high sensitivity and high specificity in the detection of toxicity with area under the curve = 0.99., Conclusions: Retinal changes secondary to hydroxychloroquine toxicity result in increased OCT reflectivity in the ONL that can be detected and quantitated using OCT-MI analysis. Analysis of OCT-MI values demonstrates high sensitivity and specificity for detecting the presence of hydroxychloroquine toxicity in this cohort and may contribute additionally to current screening practices.

Purpose: Pericentral visual field changes and disruption of the ellipsoid layer on spectral domain optical coherence tomography (SD-OCT) are the main features of antimalarial retinal toxicity. C-Scan OCT or "en face" enables a topographic frontal view of the changes observed within the different retinal layers in particular the ellipsoid layer. The aim of this prospective study was to compare multifocal ERG (mfERG) responses with the results of C-Scan OCT ("en face" OCT) in patients with abnormal visual field and to analyze relationships between the structural and functional abnormalities., Methods: In 354 consecutive patients screened for antimalarial toxicity between January 1, 2014 and December 31, 2016, central visual field, mfERG recording, C-Scan OCT and short-wavelength fundus autofluorescent imaging were performed., Results: Among the 17/354 patients with abnormal central visual field results, all presented with abnormalities on the mfERG at least in one eye. In 16/33 eyes, there was a good concordance between focal loss of the mfERG response and the disruption of the ellipsoid layer on C-Scan OCT. In one eye with characteristic changes in the ellipsoid layer on the C-Scan OCT, the mfERG was normal, whereas in three eyes the mfERG was abnormal in eyes with a normal C-Scan OCT., Conclusions: The contribution of the C-Scan OCT changes remains difficult to establish as there is no strict concordance with the local ERG responses. Although C-Scan OCT technology provides a new approach in analyzing focal abnormalities in the photoreceptor-retinal pigment epithelium interface, the sensitivity of this method compared with mfERG and other tests (central visual field, B-Scan OCT) needs to be evaluated. This study is still ongoing on a larger cohort.

Purpose of Review: This study will review the research on the effect of ginkgo biloba extract (GBE) on patients with glaucoma., Recent Findings: GBE appears to increase ocular blood flow in those with glaucoma. However, data on visual field outcomes are inconclusive., Summary: GBE has been shown to have antioxidant and vascular effects, making it potentially effective in treating glaucoma. Published data are limited but show an increase in ocular blood flow after GBE administration. Conclusive evidence is lacking regarding the effect of GBE on clinical outcomes in glaucoma patients such as visual field performance.

Purpose: To study the long-term clinical outcomes of uveitic glaucoma and to identify risk factors for progression., Methods: Retrospective study of uveitic glaucoma patients in two tertiary medical centers in 2003-2015. Patient- and disease-related data was retrieved. Clinical parameters and visual fields measured at predetermined time points were recorded. Outcome measures included maintaining intraocular pressure ≤21 mmHg and preserving visual fields., Results: Included were 34 patients (53 eyes), with a mean follow-up of 7 years. Idiopathic anterior uveitis and open-angle glaucoma were most common. In total, 62% of eyes were steroid responders. Higher IOP was associated with posterior synechiae, peripheral-anterior synechiae, steroidal, and immunomodulatory therapy (p<0.05). Glaucomatous field defects developed in 49%, with most showing no progression, despite elevation of cup-to-disc ratio (p<0.05)., Conclusions: Chronic severe uveitis, expressed by structural complications and immunomodulatory therapy, was associated with high IOP and the need for more IOP lowering medications, but was unrelated to glaucomatous damage.

Purpose: To evaluate the efficacy and safety of valproic acid (VPA) treatment in patients with retinitis pigmentosa (RP)., Methods: A total of 48 eyes of 24 patients (13 males, 11 females) with RP prescribed VPA were included. The length of VPA treatment was 6-12 months (mean 9.4 months). Parameters evaluated were best-corrected visual acuity (BCVA) (logarithm of the minimum angle of resolution [logMAR]), visual field analyses (VFAs) with Humprey automated perimetry, multifocal electroretinography (ERG) with Roland-RETI scan, and VPA side effects., Results: Mean age was 34.3 ± 10.3 years (range 18-56 years). Fifteen of the patients (30 eyes) had two ERG and VFA tracings, allowing comparison between baseline and follow-up (range 6-12 months). Mean BCVA before and after VPA therapy was 0.36 ± 0.38 and 0.36 ± 0.37 logMAR, respectively (P = 0.32). Quantitative perimetric indices including mean deviation and pattern standard deviation were not significantly changed after VPA therapy (P > 0.05). P1 amplitudes (in terms of nV/deg2 and mV) of ERG waves were significantly decreased in the rings 1, 3, and 4 after VPA therapy (P < 0.05). Regarding the N1 amplitudes, the only significant decrease was observed in area 1 (P = 0.03). In addition, N1 latency was significantly increased in area 3 after VPA therapy (P = 0.04)., Conclusions: VPA therapy did not have any significant benefit on BCVA and VFA. In addition, it may be associated with decline in some ERG parameters. Therefore, physicians should avoid prescribing VPA for RP until its safety and efficacy are appropriately evaluated.

A 40-year-old man presented with a sudden onset of diminution of vision in his left eye for 2 days. Anterior segment of both eyes was within normal limits. Right eye retinal evaluation was normal. However, the left eye retinal evaluation showed isolated subinternal limiting membrane haemorrhage at the fovea along with a white-centred haemorrhage above the fovea. There was no antecedent history of trauma or valsalva. He was normotensive and his glycaemic status was also normal. His blood investigations along with peripheral smear were done, which helped to clinch the diagnosis of an underlying chronic myeloid leukaemia., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)