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The role of microglia in the pathophysiology of ischemic retinal diseases has been extensively studied. Retinal microglial activation may be correlated with retinal neovascularization in oxygen-induced retinopathy (OIR), an animal model that has been widely used in retinopathy of prematurity (ROP) research. Minocycline is an antibiotic that decreases microglial activation following hyperoxic and hypoxic-ischemic phases in neonatal rodents. Here, we investigated the effects of minocycline on vascularization and visual function. In our results, we found that after the administration of minocycline, microglial reactivity was reduced in the retina, which was accompanied by an increase in the avascular area at P12, P14 and P17. Although microglial reactivity was reduced at P17, minocycline treatment did not attenuate retinal neovascularization. A changing trend in microglial number was observed, and the apoptosis and proliferation states on different days partly contributed to this change. Further study also revealed that although minocycline downregulated the levels of proinflammatory factors, visual function appeared to be significantly worsened. Collectively, we demonstrated that minocycline disturbed the physiological vascularization of the avascular area and exacerbated visual dysfunction, indicating that minocycline may not be an effective drug and may even be detrimental for the treatment of ischemic retinopathy in immature mammals.

Background: Optic nerve disease can occur from a variety of different causes, with vascular, inflammatory or toxic pathologies. In such cases, it is hardly possible to clarify the aetiology. These diseases of the optic nerve are usually accompanied by progressive loss of visual field and visual impairment. Patient: We report a case of a 74-year-old woman complaining of loss of visual acuity, visual and blurred vision in the left eye in 2010. We made the diagnosis of non-arteritic ischemic optic neuropathy (NAION). With steroid therapy, there was an improvement in both visual acuity and visual field defects. But if an attempt was made to reduce steroids, her condition progressed. Except for a very small optic disk and arterial hypotension, there were no typical risk factors for NAION. We started treatment with methotrexate (MTX), with a starting dose of 10 mg per week, and observed the patient over two years. Results: Using MTX therapy, the swelling of the optic nerve head and visual field loss were reversible, so we increased the dose of MTX up to 15 mg/week. Steroid therapy could be stopped and the patient's visual acuity and visual field have now been stable for two years. There was no visible pallor in the optic nerve head, as normally occurs after AION, so we considered different underlying pathologies, including autoimmune disease. There were no adverse events with MTX therapy. Conclusion: If the course of the disease is atypical, the pathology may include an autoimmune component. Immunosuppressive MTX therapy may be started in order to avoid long-term steroid use. It may then be possible to maintain a stable visual field and prevent remitting episodes., Competing Interests: Interessenkonflikt: Nein., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Vigabatrin (VGB) is currently served as an effective adjunctive therapy for patients with partial epilepsy worldwide. In this study, meta-analysis was conducted to comprehensively evaluate the changes in peripapillary retinal nerve fiber layer (RNFL) thickness assessed by optical coherence tomography (OCT) in epilepsy patients who were treated by VGB., Material and Methods: Publications on PubMed, Wiley Online Library and the Elsevier Science databases were searched by September 2016. The statistical analysis was performed by RevMan 5.3 software., Results: Four studies were identified, and 202 eyes in VGB-exposed patients (VGB group) as well as 162 eyes in patients who never received VGB treatment (NON-VGB group) were included. The studies demonstrated that the total RNFL thickness is attenuated in VGB treated patients (weighted mean differences in μm, WMD=-15.96, 95% CI: -23.69 to -8.23, P<0.0001). RNFL thickness in 3 quadrants were significantly reduced in VGB group: superior (WMD=-18.15, 95% CI: -23.31 to -12.98, P<0.00001), inferior (WMD=-23.19, 95% CI: -32.23 to -14.15, P<0.00001) and nasal (WMD=-19.29, 95% CI: -35.57 to -3.02, P=0.02). However, the temporal RNFL thickness in these two groups showed no significant difference: temporal (WMD=-2.41, 95% CI: -6.67 to 1.85, P=0.27)., Conclusion: Based on the meta-analysis, RNFL thickness appears to reduce in epilepsy patients who received VGB treatment, and OCT could be a useful tool to help clinicians assessing its retinal toxicity and guiding its dosage., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease of unknown etiology with many clinical manifestations. We report the first case of SLE in which visual alterations were evaluated with multichannel perimetry. Some achromatic and color vision alterations may be present in SLE, especially when treated with hydroxychloroquine. The sensitivity losses detected in the chromatic channels in the central zone of the visual field were consistent with the results of the FM 100 Hue color test. Likewise, the multichannel perimetry detected sensitivity losses in the parafoveal area for both chromatic channels, especially for the blue-yellow., (Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.)

Steroid medications may cause elevation of intraocular pressure, sometimes with permanent damage to the optic nerve. These therapies, via various routes of administration, are commonly prescribed for children, but the potential sequelae of elevated intraocular pressure and glaucomatous optic nerve damage can be even more severe and devastating in children than in adults. This review discusses the pathophysiology and potential risk factors, including the impact of intraocular pressure elevation via the different common routes of administration of steroids, clinical evaluation, and management of steroid response and steroid-induced glaucoma in children., (Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Introduction: Vitamin A and its metabolites (called retinoids) have been thought to play a role in the development of idiopathic intracranial hypertension (IIH). The IIH Treatment Trial (IIHTT) showed the efficacy of acetazolamide (ACZ) in improving visual field function, papilledema grade, quality of life and cerebrospinal fluid (CSF) pressure. We postulated that IIH patients would demonstrate elevated measures of vitamin A metabolites in the serum and CSF., Methods: Comprehensive measures of serum vitamin A and its metabolites were obtained from 96 IIHTT subjects, randomly assigned to treatment with ACZ or placebo, and 25 controls with similar gender, age and body mass index (BMI). These included retinol, retinol binding protein, all-trans retinoic acid (ATRA), alpha- and beta-carotenes, and beta-cryptoxanthin. The IIHTT subjects also had CSF and serum vitamin A and metabolite measurements obtained at study entry and at six months., Results: At study entry, of the vitamin A metabolites only serum ATRA was significantly different in IIHTT subjects (median 4.33nM) and controls (median 5.04nM, p=0.02). The BMI of IIHTT subjects showed mild significant negative correlations with serum ATRA, alpha- and beta-carotene, and beta-cryptoxanthin. In contrast, the control subject BMI correlated only with serum ATRA. At six months, the serum retinol, alpha-carotene, beta-carotene, and CSF retinol were increased from baseline in the ACZ treated group, but only increases in alpha-carotene (p=0.02) and CSF ATRA (p=0.04) were significantly greater in the ACZ group compared with the placebo group. No other vitamin A measures were significantly altered over the six months in either treatment group. Weight loss correlated with only with the change in serum beta-carotene (r=-0.44, p=0.006) and the change in CSF retinol (r=-0.61, p=0.02)., Conclusion: Vitamin A toxicity is unlikely a contributory factor in the causation of IIH. Our findings differ from those of prior reports in part because of our use of more accurate quantitative methods and measuring vitamin A metabolites in both serum and CSF. ACZ may alter retinoid metabolism in IIH patients., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Gamma-vinyl-γ-aminobutyric acid (GABA) (vigabatrin) is an antiepileptic drug and irreversible GABA transaminase inhibitor associated with visual field impairment, which limits its clinical utility. We sought to relate altered visual evoked potentials associated with vigabatrin intake to transcriptional changes in the mechanistic target of rapamycin (mTOR) pathway and GABA receptors to expose further mechanisms of vigabatrin-induced visual field loss., Methods: Vigabatrin was administered to mice via an osmotic pump for two weeks to increase GABA levels. Visual evoked potentials were examined, eye samples were collected, and gene expression was measured by quantitative reverse transcription-polymerase chain reaction. Similarly, human retinal pigment epithelial cells (ARPE19) were exposed to vigabatrin and treated with mTOR inhibitors for mTOR pathway analysis and to assess alterations in organelle accumulation by microscopy., Results: Dysregulated expression of transcripts in the mTOR pathway, GABA A/B receptors, metabotropic glutamate (Glu) receptors 1/6, and GABA/glutamate transporters in the eye were found in association with visual evoked potential changes during vigabatrin administration. Rrag genes were upregulated in both mouse eye and ARPE19 cells. Immunoblot of whole eye revealed greater than three fold upregulation of a 200 kDa band when immunoblotted for ras-related guanosine triphosphate binding D. Microscopy of ARPE19 cells revealed selective reversal of vigabatrin-induced organelle accumulation by autophagy-inducing drugs, notably Torin 2. Changes in the mTOR pathway gene expression, including Rrag genes, were corrected by Torin 2 in ARPE19 cells., Conclusions: Our studies, indicating GABA-associated augmentation of RRAG and mTOR signaling, support further preclinical evaluation of mTOR inhibitors as a therapeutic strategy to potentially mitigate vigabatrin-induced ocular toxicity., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: Pseudotumor cerebri (PTC) is a condition characterized by symptoms and signs of increased intracranial pressure (ICP) with no intracranial mass or hydrocephalus, and with normal cerebrospinal fluid (CSF) composition. A variant of PTC known as "Normal Pressure Pseudotumor Cerebri" has the same features of PTC except for normal opening pressure., Material and Methods: This is a series of 6 patients with typical symptoms and signs of increased ICP and normal neuroimaging, but with normal CSF opening pressure. A second lumbar puncture (LP) was done to re-measure the CSF opening pressure., Results: The mean age of the patients at diagnosis was 25 years (ranging from 19 to 31 years). All patients were female. All patients were obese with a mean body mass index (BMI) of 32.8 (ranging from 30 to 35). The mean duration of symptoms before presentation was 2.8 weeks (ranging from 1 to 8 weeks). The mean CSF opening pressure during the first LP was 11 cm H2O (ranging from 9 to 15 cm H2O). The CSF chemistry and culture of all patients were normal. The mean CSF opening pressure in the second LP was 7.3 cm H2O (ranging from 6 to 10 cm H2O). All patients were symptom free after one week of treatment, but the medications were continued till the complete disappearance of papilledema and the normalization of the visual field. The mean duration of treatment was 8 weeks (ranging from 5 to 12 weeks)., Conclusion: Normal pressure PTC should be treated by medical treatment to avoid visual loss.

Introduction: Nicotine and methylphenidate are putative cognitive enhancers in healthy and patient populations. Although they stimulate different neurotransmitter systems, they have been shown to enhance performance on overlapping measures of attention. So far, there has been no direct comparison of the effects of these two stimulants on behavioural performance or brain function in healthy humans. Here, we directly compare the two compounds using a well-established oculomotor biomarker in order to explore common and distinct behavioural and neural effects., Methods: Eighty-two healthy male non-smokers performed a smooth pursuit eye movement task while lying in an fMRI scanner. In a between-subjects, double-blind design, subjects either received placebo (placebo patch and capsule), nicotine (7mg nicotine patch and placebo capsule), or methylphenidate (placebo patch and 40mg methylphenidate capsule)., Results: There were no significant drug effects on behavioural measures. At the neural level, methylphenidate elicited higher activation in left frontal eye field compared to nicotine, with an intermediate response under placebo., Discussion: The reduced activation of task-related regions under nicotine could be associated with more efficient neural processing, while increased hemodynamic response under methylphenidate is interpretable as enhanced processing of task-relevant networks. Together, these findings suggest dissociable neural effects of these putative cognitive enhancers., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Nonarteritic ischemic optic neuropathy is characterized by sudden, painless, unilateral vision loss. A case of an acute NAION patient who was treated with subtenon methyl prednisolone acetate was presented. The patient, a 65-year-old male, presented vision loss for two days. The total ophthalmologic examination, fundus photography, and automated perimetry were applied to the patient before and after 1, 3, and 6 months from injection. The visual acuity increased from 0,1 to 0,3 in the first month and to 0,7 at the last visit, the visual field defect being mostly improved. This case showed that 40 mg of subtenon methyl prednisolone acetate injection was an effective and safe treatment method for acute NAION. However, a large randomized controlled trial is needed to assess the efficacy of subtenon methyl prednisolone acetate as a treatment for NAION.

Objective: Evaluate visual-field and retinal-structure changes following adjunctive vigabatrin treatment in vigabatrin-naive adults with refractory complex partial seizures (rCPS)., Methods: Prospective, longitudinal, single-arm, open-label study (NCT01278173). Eligible patients (≥2 seizures/month who failed ≥3 therapies) who could reliably perform perimetry (Humphrey automated static) and retinal-structure assessment (spectral-domain optical coherence tomography) prior to vigabatrin exposure. Following vigabatrin initiation, testing occurred within 1 month (reference) and 3, 6, 9, and 12 months. End points included mean change from reference in mean deviation (dB) and average retinal nerve fiber layer (RNFL) thickness, visual-acuity changes from baseline, and number of patients who met predefined vision-parameter changes at two (confirmed) or three (persistent) consecutive visits., Results: Sixty-five of 91 screened patients received ≥1 vigabatrin dose (all-patients-treated set [APTS]); 55 had valid reference and ≥1 post-reference assessments (full-analysis set [FAS]). Thirty-six APTS patients with valid pre-/post-reference values completed all planned visits (per-protocol set [PPS]). Thirty-eight (59%) APTS patients completed the study; 27 (42%) withdrew (none for visual-field changes); 32% and 15% had abnormally thin RNFL and abnormal visual acuity at baseline, respectively; 20% had abnormal central 30 degree visual fields in the reference period. No significant mean near visual-field changes were observed (PPS); mean change in average RNFL thickness increased significantly (1-year data: Left-eye: 6.37 μm, confidence interval (CI) 4.66-8.09; right-eye: 7.24 μm CI 5.47-9.01; PPS). No confirmed three-line decreases in visual acuity (FAS) were observed; five patients had predefined confirmed/persistent visual-field changes (FAS). All vision-related adverse events were nonserious; the most common was vision blurred (9%)., Significance: Prior to vigabatrin initiation, rCPS patients may already exhibit vision deficits. Up to 1 year of adjunctive vigabatrin treatment did not significantly change population near visual fields. Five patients met predefined visual-field-change criteria. RNFL thickening of unknown clinical significance was observed. Limitations include single-arm, open-label design; patients' inability to perform ophthalmic/visual-field examinations; and limited vigabatrin-exposure duration., (Wiley Periodicals, Inc. © 2016 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.)

Context: Tuberculosis in developed countries is on the rise, and the main treatment ethambutol is known to induce ocular toxicity. However, to date, there are unknown tests or protocols for detecting subclinical ethambutol-induced ocular toxicity, which is important as early detection is related to symptom reversibility. We defined the ethambutol induced ocular toxicity as stastically siginificant change of visual function which was induced by ethambutol., Objective: We aimed to identify a visual function test for the early detection of subclinical ethambutol-induced ocular toxicity. Furthermore, we also investigated the continuity or reversibility of early subclinical changes that were observed during the visual function tests after stopping ethambutol treatment., Materials and Methods: The age range of 31 patients was from 13 to 72 years. The range of dosage was 15-19 mg/kg/day. The average period of dosage was 5 months. We performed a visual acuity test, visual field test, color vision test, contrast sensitivity test, fundus examination, retinal nerve fiver layer optical coherence tomography test (RNFL OCT) per month and pattern visual evoked potential test (pattern VEP) every 2 months before and during ethambutol treatment in 62 eyes of 31 patients. Among these patients, selected 21 patients were rexamined by these tests at the 3, 6 and 12 months after stopping ethambutol treatment. We compared the test results from the last follow-up during ethambutol treatment and after ethambutol stoppage with those obtained before ethambutol treatment (baseline)., Results: RNFL OCT showed that average RNFL thickness increased 5 months after ethambutol treatment (p = 0.032), and pattern VEP showed that P100 latency was delayed in 2 and 4 months after ethambutol treatment (p = 0.001; p < 0.001, respectively). These early changes observed on RNFL OCT and pattern VEP progressed 6 months after ethambutol stoppage in 21 patients. Twelve months after ethambutol stoppage, these early changes returned to baseline levels. During the study, no changes in visual acuity, color vision, fundus, contrast sensitivity or visual field were observed., Conclusions: Pattern VEP and RNFL OCT are suitable tests for the early detection of subclinical ethambutol-induced ocular toxicity. These tests should be performed until 12 months after ethambutol stoppage.

We report a 34-years-old woman who presented with bilateral incongruous inferior visual field defects after the commencement of topiramate for management of migraine. Investigations did not reveal any underlying angle closure glaucoma, reported in current literature to be associated commonly with topiramate associated visual field defects. The changes in the peripheral visual fields gradually improved over several months after the medication was withdrawn. There were only minor changes persistent on the left side on a background of pre-existing myopia and keratoconus. Visual field deficits secondary to topiramate are more commonly attributed to angle closure glaucoma due to ciliochoroidal effusion syndrome. In such instance, the visual field defects are associated with considerable pain due to raised intra-ocular pressure. There have also been reports of visual scotomas due to retinal damage and maculopathy in patients taking topiramate. It is worthwhile to obtain a baseline perimetry in patients being considered for topiramate therapy in order to gauge any changes in their peripheral field of vision during the treatment. Changes in visual fields during the course of medication use and after cessation can be easily compared especially if there are other possible confounders such as refractive errors or a history of migraine., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Psychotropic medications may cause many ocular adverse effects including toxic optic neuropathy. We present a unique case of a 44-year-old woman using duloxetine who presented with unilateral visual loss due to retrobulbar neuritis. Physicians and patients should be alerted to this potential side effect. To the best of our knowledge, this is the first case of developing retrobulbar neuritis related to duloxetine usage.

Introduction: Previous studies have described septooptic dysplasia (SOD) to describe patients who have optic nerve hypoplasia, the absence of septum pellucidum, and pituitary hypoplasia. Other rare ophthalmic associations have been described, such as low-tension glaucoma. We report the ocular findings of a patient with SOD who had high intraocular pressure (IOP) and glaucoma as a part of the syndrome., Objectives: To report the ocular findings in a Puerto Rican patient with SOD and increased IOP., Patients and Methods: A patient with De Morsier syndrome underwent a comprehensive eye examination, Humphrey visual fields, and Stratus optical coherence tomography, and was referred for neuroradiologic examination. The patient had increased IOP, visual field loss, and asymmetric optic nerve hypoplasia. The IOP was lowered with topical hypotensive medications., Conclusions: The patient with the De Morsier syndrome had poor visual acuity, high IOP, visual field, and optical coherence tomography results that were all compatible with glaucoma. Further studies comparing ocular findings in patients with several mutations leading to De Morsier syndrome are warranted. To our knowledge, this is the first report on a patient with glaucoma as a part of the syndrome.

Background: We assessed central and peripheral visual field processing in children with epilepsy who were exposed to vigabatrin during infancy., Methods: Steady-state visual evoked potentials and pattern electroretinograms to field-specific radial checkerboards flickering at two cycle frequencies (7.5 and 6 Hz for central and peripheral stimulations, respectively) were recorded from Oz and at the eye in seven school-age children (10.1 ± 3.5 years) exposed to vigabatrin early in life, compared with children early exposed to other antiepileptic drugs (n = 9) and healthy children (n = 8). The stimulation was made of two concentric circles (0 to 5 and 30 to 60 degrees of angle) and presented at four contrast levels (96%, 64%, 32%, and 16%)., Results: Ocular responses were similar in all groups for central but not for the peripheral stimulations, which were significantly lower in the vigabatrin-exposed group at high contrast level. This peripheral retinal response was negatively correlated to vigabatrin exposure duration. Cortical responses to central stimulations, including contrast response functions in the children with epilepsy in both groups, were lower than those in normally developing children., Conclusions: Alteration of ocular processing was found only in the vigabatrin-exposed children. Central cortical processing, however, was impaired in both epileptic groups, with more pronounced effects in vigabatrin-exposed children. Our study suggests that asymptomatic long-term visual toxicity may still be present at school age, even several years after discontinuation of drug therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The American Academy of Ophthalmology recommendations on screening for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy are revised in light of new information about the prevalence of toxicity, risk factors, fundus distribution, and effectiveness of screening tools., Pattern of Retinopathy: Although the locus of toxic damage is parafoveal in many eyes, Asian patients often show an extramacular pattern of damage. DOSE: We recommend a maximum daily HCQ use of ≤5.0 mg/kg real weight, which correlates better with risk than ideal weight. There are no similar demographic data for CQ, but dose comparisons in older literature suggest using ≤2.3 mg/kg real weight., Risk of Toxicity: The risk of toxicity is dependent on daily dose and duration of use. At recommended doses, the risk of toxicity up to 5 years is under 1% and up to 10 years is under 2%, but it rises to almost 20% after 20 years. However, even after 20 years, a patient without toxicity has only a 4% risk of converting in the subsequent year., Major Risk Factors: High dose and long duration of use are the most significant risks. Other major factors are concomitant renal disease, or use of tamoxifen., Screening Schedule: A baseline fundus examination should be performed to rule out preexisting maculopathy. Begin annual screening after 5 years for patients on acceptable doses and without major risk factors., Screening Tests: The primary screening tests are automated visual fields plus spectral-domain optical coherence tomography (SD OCT). These should look beyond the central macula in Asian patients. The multifocal electroretinogram (mfERG) can provide objective corroboration for visual fields, and fundus autofluorescence (FAF) can show damage topographically. Modern screening should detect retinopathy before it is visible in the fundus., Toxicity: Retinopathy is not reversible, and there is no present therapy. Recognition at an early stage (before any RPE loss) is important to prevent central visual loss. However, questionable test results should be repeated or validated with additional procedures to avoid unnecessary cessation of valuable medication., Counseling: Patients (and prescribing physicians) should be informed about risk of toxicity, proper dose levels, and the importance of regular annual screening., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the clinical effectiveness and potential neuroprotection of levodopa in improving visual acuity, visual field, and retinal nerve fiber layer (RNFL) thickness in eyes affected by NAION., Method: Retrospective cohort study involving 59 eyes of 59 participants with NAION who were evaluated within 15 days of NAION onset. Participants received 25 mg carbidopa/100 mg levodopa three times daily with meals for 12 weeks (levodopa group) or were untreated (control group). Best-corrected visual acuity converted to logMAR, mean deviation (MD) threshold sensitivity on automated perimetry, and mean RNFL thickness on optical coherence tomography (OCT) were assessed. The primary outcome was the categorization of eyes into improved visual acuity (by 0.3 logMAR difference), worsened visual acuity (by 0.3 logMAR difference), or no change in visual acuity. The proportions in each category were compared between the levodopa and control groups., Results: Among participants with 20/60 or worse initial visual acuity, levodopa-treated participants had significant improvement (P < 0.0001) in the mean change from initial to final logMAR visual acuity of -0.74 ± 0.56 (95 % CI, -0.98 to -0.50), while the mean change for the control group at -0.37 ± 1.09 (95 % confidence interval estimate, -1.00 to +0.26) was not significant (P = 0.23). A significant difference between groups was observed (P = 0.0086) such that 19/23 (83 %) in the levodopa group improved and none got worse, as compared with 6/14 (43 %) in the control group improving while four (29 %) worsened. The change in visual field MD and RNFL thickness on OCT showed no significant difference at P = 0.23 and P = 0.75 respectively. No levodopa-treated participant had any adverse event from the levodopa., Conclusions: Treatment within 15 days of onset of NAION with levodopa improved central visual acuity by an average of 6 lines on Snellen acuity chart. Levodopa may promote neuroprotection of the maculopapular retinal ganglion cell fibers in NAION.

Purpose: The antiepileptic drug vigabatrin is known to cause permanent loss of vision. Both visual field testing and electroretinogram are used to detect retinal damage. Adult data on optical coherence tomography (OCT) shows that retinal nerve fiber layer (RNFL) thinning may be an early indicator of vigabatrin-induced retinal toxicity. The purpose of this study was to investigate whether OCT can detect early vigabatrin-induced retinal toxicity in children., Methods: Pediatric patients (≤18 years of age) requiring vigabatrin for seizure control who were followed at our institution were invited to participate. Patients were examined according to manufacturer guidelines, with most examinations taking place under general anesthesia. RNFL thickness was measured by OCT (Stratus Model 3000, Zeiss) and compared to total cumulative dose of vigabatrin. In most cases, indirect ophthalmoscopy, fundus photography, and electroretinography were also performed., Results: OCT and complete dosing data was available for 19 patients. Patients with tuberous sclerosis (TS, n = 12) received higher cumulative doses (mean, 1463 g) than non-TS patients (mean, 351 g, P = 0.044). RNFL thinning was detected in the nasal (P < 0.01), superior (P < 0.01), and inferior (P < 0.05) quadrants in patients with TS, particularly once cumulative dose exceeded 1500 g., Conclusions: In our study population of patients with TS, higher cumulative doses of vigabatrin were associated with RNFL thinning in the nasal, superior, and inferior quadrants. These findings were pronounced once cumulative dose exceeded 1500 g. This pattern of RNFL thinning is similar to what has been shown in adult patients taking vigabatrin., (Copyright © 2016 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose: The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) showed that acetazolamide provided a modest, significant improvement in mean deviation (MD). Here, we further analyze visual field changes over the 6-month study period., Methods: Of 165 subjects with mild visual loss in the IIHTT, 125 had perimetry at baseline and 6 months. We evaluated pointwise linear regression of visual sensitivity versus time to classify test locations in the worst MD (study) eye as improving or not; pointwise changes from baseline to month 6 in decibels; and clinical consensus of change from baseline to 6 months., Results: The average study eye had 36 of 52 test locations with improving sensitivity over 6 months using pointwise linear regression, but differences between the acetazolamide and placebo groups were not significant. Pointwise results mostly improved in both treatment groups with the magnitude of the mean change within groups greatest and statistically significant around the blind spot and the nasal area, especially in the acetazolamide group. The consensus classification of visual field change from baseline to 6 months in the study eye yielded percentages (acetazolamide, placebo) of 7.2% and 17.5% worse, 35.1% and 31.7% with no change, and 56.1% and 50.8% improved; group differences were not statistically significant., Conclusions: In the IIHTT, compared to the placebo group, the acetazolamide group had a significant pointwise improvement in visual field function, particularly in the nasal and pericecal areas; the latter is likely due to reduction in blind spot size related to improvement in papilledema. (ClinicalTrials.gov number, NCT01003639.).

Objective: To examine the tolerability and adverse events reported in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT)., Methods: Randomized, double-masked, placebo-controlled clinical trial. Trial participants (n = 165) with mild visual loss concurrently receiving low-sodium weight-reduction diet plus the maximally tolerated dosage of acetazolamide (up to 4 g/d) or placebo for 6 months., Main Outcomes Measures: adverse events (AEs), assessment of clinical and laboratory findings at study visits., Results: Thirty-eight of 86 participants randomized to the acetazolamide group (44.1%) tolerated the maximum allowed dosage of 4 g/d. The average time to achieve maximum study dosage in the acetazolamide group was 13 weeks (median 12 weeks; range 10-24 weeks). A total of 676 AEs (acetazolamide, n = 480; placebo, n = 196) and 9 serious AEs (acetazolamide, n = 6; placebo, n = 3) were reported. Notably, the percentages of participants reporting at least 1 AE in the nervous, gastrointestinal, metabolic, and renal organ systems were significantly higher in the acetazolamide group (P < 0.05). The odds of paresthesia (OR 9.82; 95% CI 3.87-27.82), dysgeusia (OR ∞; 95% CI 3.99-∞), vomiting and diarrhea (OR 4.11; 95% CI 1.04-23.41), nausea (OR 2.99; 95% CI 1.26-7.49) and fatigue (OR 16.48; 95% CI 2.39-702.40) were higher in the acetazolamide group than in the placebo group., Conclusion: Acetazolamide appears to have an acceptable safety profile at dosages up to 4 g/d in the treatment of idiopathic intracranial hypertension. The majority of participants in the Idiopathic Intracranial Hypertension Treatment Trial were able to tolerate acetazolamide above 1 g/d for 6 months.

Purpose: To report a rare toxic optic neuropathy after long-term use of two medications: ethambutol and linezolid., Case Report: A 65-year-old man presented to the Miami Veterans Affairs Medical Center in December 2014 for evaluation of progressive vision decrease in both eyes. The patient presented with best-corrected visual acuities of 20/400 in the right eye and counting fingers at 5 feet in the left eye. Color vision was significantly reduced in both eyes. Visual fields revealed a cecocentral defect in both eyes. His fundus and optic nerve examination was unremarkable. Because vision continued to decline after discontinuation of ethambutol, linezolid was also discontinued, after which vision, color vision, and visual fields improved. Because of these findings, the final diagnosis was toxic optic neuropathy. Final visual outcome was 20/30 in the right eye and 20/40 in the left eye., Conclusions: Drug-associated toxic optic neuropathy is a rare but vision-threatening condition. Diagnosis is made based on an extensive case history and careful clinical examination. The examination findings include varying decrease in vision, normal pupils and extraocular muscles, and unremarkable fundoscopy, with the possibility of swollen optic discs in the acute stage of the optic neuropathy. Other important findings descriptive of toxic optic neuropathy include decreased color vision and cecocentral visual field defects. This case illustrates the importance of knowledge of all medications and/or substances a patient consumes that may cause a toxic reaction and discontinuing them immediately if the visual functions are worsening or not improving.

Paediatric optic pathway gliomas are low-grade brain tumours characterized by slow progression and invalidating visual loss. Presently there is no strategy to prevent visual loss in this kind of tumour. This study evaluated the effects of nerve growth factor administration in protecting visual function in patients with optic pathway glioma-related visual impairment. A prospective randomized double-blind phase II clinical trial was conducted in 18 optic pathway glioma patients, aged from 2 to 23 years, with stable disease and severe visual loss. Ten patients were randomly assigned to receive a single 10-day course of 0.5 mg murine nerve growth factor as eye drops, while eight patients received placebo. All patients were evaluated before and after treatment, testing visual acuity, visual field, visual-evoked potentials, optic coherence tomography, electroretinographic photopic negative response, and magnetic resonance imaging. Post-treatment evaluations were repeated at 15, 30, 90, and 180 days Brain magnetic resonance imaging was performed at baseline and at 180 days. Treatment with nerve growth factor led to statistically significant improvements in objective electrophysiological parameters (electroretinographic photopic negative response amplitude at 180 days and visual-evoked potentials at 30 days), which were not observed in placebo-treated patients. Furthermore, in patients in whom visual fields could still be measured, visual field worsening was only observed in placebo-treated cases, while three of four nerve growth factor-treated subjects showed significant visual field enlargement. This corresponded to improved visually guided behaviour, as reported by the patients and/or the caregivers. There was no evidence of side effects related to nerve growth factor treatment. Nerve growth factor eye drop administration appears a safe, easy and effective strategy for the treatment of visual loss associated with optic pathway gliomas., (© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Preclinical trials have shown beneficial effects of nerve growth factor (NGF) administration on visual function in animal models of retinitis pigmentosa (RP). The aim of this pilot study was to explore the potential efficacy of short term NGF eye drops treatment in patients affected by RP., Methods: The trial consisted in 10 days daily administration of murine NGF as eye-drops for a total dose of 1 mg NGF/pt. Eight RP patients at an advanced stage of the disease were included in the trial. To monitor safety and potential adverse effects subjects underwent standard clinical measures and were requested to report any general or topic alterations following NGF assumption. Retinal function was assessed at baseline and after treatment by best-corrected visual acuity measurement (BCVA), macular focal electroretinogram (fERG) recording and Goldmann visual field testing., Results: A transient tolerable local corneal irritation was the only adverse effect reported. fERG and BCVA remained within the limits determined by test-retest analysis of a large cohort of RP patients. Three patients reported a subjective feeling of improved visual performance. This was associated to a temporary enlargement of the visual field in all three patients and to improved fERG in two of the three., Conclusions: Short-term administration of NGF eye-drops caused neither significant adverse effects nor visual function losses in the tested RP patients. A minority of patients experienced an improvement of visual performance as shown by Goldmann visual field and fERG. This study supports the safety and possible efficacy of NGF eye-drops administration in RP patients., Trial Registration: EudraCT n. 2008-004561-26.

Previous studies report that retinitis pigmentosa (RP) patients treated with the histone deacetylase inhibitor (HDACi) valproic acid (VPA) present with improved visual fields and delayed vision loss. However, other studies report poor efficacy and safety of HDACi in other cohorts of retinal degeneration patients. Furthermore, the molecular mechanisms by which HDACi can improve visual function is unknown, albeit HDACi can attenuate pro-apoptotic stimuli and induce expression of neuroprotective factors. Thus, further analysis of HDACi is warranted in pre-clinical models of retinal degeneration including zebrafish. Analysis of HDAC expression in developing zebrafish reveals diverse temporal expression patterns during development and maturation of visual function.

Purpose: To determine if a fogging lens ameliorates accommodative effects driven by the closed-view design of the BHVI-EyeMapper (EM) instrument. We compared cycloplegic refraction and higher-order aberration measurements of the EM with those obtained with a fogging lens., Methods: Twenty-six, young, participants (15F, 25±5 years, range: 18-35 years, SE: +0.25 D and -3.50 D) with good ocular health were recruited. Five independent measurements of on- and off-axis refraction and higher-order aberrations were recorded across the horizontal visual field, under two conditions: non-cycloplegic measurements with +1.00 D fogging lens and cycloplegia, always in the same sequence. The contralateral eye was occluded during the measurements. Two drops of 1% Tropicamide delivered within 5 min facilitated cycloplegic measurements. All participants were refracted 30 min after installation of the second drop., Results: Mean spherical equivalent measures of the non-cycloplegic condition were significantly more myopic than their cycloplegic counterparts (p<0.05); approximately by 0.50 D centrally, increasing to 1.00 D towards the periphery. The horizontal astigmatic component, J180, demonstrated small but statistically significant differences between the test conditions. Differences were predominant for eccentricities greater than 30°, in both nasal and temporal meridians. The oblique astigmatic component, J45, was not significantly different between the test conditions. The primary spherical aberration coefficient C(4, 0) was significantly less positive for the non-cycloplegic state than its cycloplegic counterpart. This result held true across the entire horizontal visual field. The horizontal coma and trefoil coefficients C(3, 1) and C(3, 3) were not significantly different between the two conditions., Conclusions: The use of +1.00 D fogging lens without cycloplegia did not provide complete relaxation of accommodation. The discrepancies between cycloplegic and non-cycloplegic EM measurements were found to be more pronounced for peripheral field angles than central measures, for both M and J180 components., (Copyright © 2015 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.)

A 13-year-old male with suprasellar cystic craniopharyngioma initially controlled with sequential subtotal resections and proton-beam irradiation was later treated with intracystic pegylated interferon α-2b due to progression and a lack of further surgical options. After initial successful control of recurrent cyst enlargement and stabilization of the ophthalmic examination, progressive and irreversible visual field loss ensued. Imaging revealed intracranial leakage from the intracystic catheter, and direct administration of interferon α-2b was discontinued. Given the recent interest in interferon α-2b, oncologists are advised to vigilantly monitor patients for signs of local toxicity that may result from unintended leakage during intracystic delivery.

The aim of this study was to measure the extent to which alcohol intoxication restricts the scope of attention in the visual field. A group of intoxicated (n = 31; mean BAC ≈ .08%) and placebo control (n = 31; mean BAC ≈ .00%) participants were required to correctly identify visual probes while performing two verbal categorization tasks: one designed to widen the scope of visual attention on to each stimulus word, the other to narrow attention on to the central letter of each word. Response times to surprise probes interpolated between categorization trials were measured and these catch trials could appear in any of the stimulus word letter positions. As predicted by alcohol myopia theory (AMT), which assumes that the drug narrows focal attention, intoxicated participants made slower responses than the sober controls to probes displayed in non-central letter positions, although right-field probe reaction times (RTs) were slower than those for left-field targets. This response asymmetry and the wider theoretical implications of these findings are discussed.

Unlabelled: Restoring vision in inherited retinal degenerations remains an unmet medical need. In mice exhibiting a genetically engineered block of the visual cycle, vision was recently successfully restored by oral administration of 9-cis-retinyl acetate (QLT091001). Safety and visual outcomes of a once-daily oral dose of 40 mg/m2/day QLT091001 for 7 consecutive days was investigated in an international, multi-center, open-label, proof-of-concept study in 18 patients with RPE65- or LRAT-related retinitis pigmentosa. Eight of 18 patients (44%) showed a ≥20% increase and 4 of 18 (22%) showed a ≥40% increase in functional retinal area determined from Goldmann visual fields; 12 (67%) and 5 (28%) of 18 patients showed a ≥5 and ≥10 ETDRS letter score increase of visual acuity, respectively, in one or both eyes at two or more visits within 2 months of treatment. In two patients who underwent fMRI, a significant positive response was measured to stimuli of medium contrast, moving, pattern targets in both left and right hemispheres of the occipital cortex. There were no serious adverse events. Treatment-related adverse events were transient and the most common included headache, photophobia, nausea, vomiting, and minor biochemical abnormalities. Measuring the outer segment length of the photoreceptor layer with high-definition optical coherence tomography was highly predictive of treatment responses with responders having a significantly larger baseline outer segment thickness (11.7 ± 4.8 μm, mean ± 95% CI) than non-responders (3.5 ± 1.2 μm). This structure-function relationship suggests that treatment with QLT091001 is more likely to be efficacious if there is sufficient photoreceptor integrity., Trial Registration: ClinicalTrials.gov NCT01014052.

Background: Glaucoma is a leading cause of irreversible blindness worldwide. A major symptom of this pathology is the loss to the visual field in a peripheral to central pattern. Flavonoids are polyphenol compounds sourced from plants, commonly found in green tea, red wine and cocoa, and they have neuroprotective and antioxidant characteristics proposed to be advantageous within the context of glaucoma. Currently, the literature presents conflicting evidence regarding the effect of flavonoids on patients with glaucoma and ocular hypertension; hence a systematic review and meta-analysis was conducted., Method: Databases included in our literature search were EMBASE (1980-present), MEDLINE Ovid, Alternative and Complementary Medicine Database (AMED), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Central Register of Controlled Trials (CENTRAL). Meta-analysis was performed using RevMan 5 (Review Manager) 5 software, version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen). The primary outcomes were visual field mean deviation (MD) and intraocular pressure (IOP). Secondary outcomes were ocular blood flow and blood pressure (BP)., Conclusion: Meta-analyses showed that flavonoids have a promising role in improving visual function in patients with glaucoma and ocular hypertension (OHT), and appear to play a part in both improving and slowing the progression of visual field loss.

Purpose: Docosahexaenoic acid (DHA) was supplemented in a single-site, placebo-controlled, randomized clinical trial designed to slow vision loss associated with X-linked retinitis pigmentosa (XLRP); the DHAX Trial. We previously reported no significant differences between supplemented and placebo groups in intent-to-treat analysis of primary ERG outcomes. Assessed herein are hypothesis-generating measures of ancillary visual function outcomes in participants fully adhering to trial protocol., Methods: Male participants with XLRP (range, 7-31 years) received 30 mg DHA/kg/d (n = 29) or placebo (n = 22) for 4 years. Visual outcomes were measured annually and red blood cell (RBC) DHA determined every 6 months., Results: Oral DHA supplementation increased mean RBC-DHA levels by 4-fold (P < 0.0001) over placebo. No group differences in progression were found for visual acuity (P = 0.11), shape discrimination (P = 0.18), or fundus appearance (P = 0.70). Optical coherence tomography (OCT) became available during year 2 of the trial; no group differences were seen in ellipsoid zone constriction (P = 0.87) over 2 years. Yearly rates of progression were reduced for dark-adapted thresholds (P = 0.06) and visual field sensitivity for foveal, macular, peripheral, total, and ellipsoid zone regions by DHA supplementation (P = 0.039, P = 0.031, P < 0.0001, P < 0.0001, and P = 0.033). Rates of visual field sensitivity decline were dependent on RBC-DHA (P = 0.046 to <0.0001)., Conclusions: Supplementation of DHA significantly elevated blood DHA levels and reduced the rate of progression in final dark-adapted thresholds and visual field sensitivity. From the relationship between RBC-DHA and the rate of field sensitivity loss, we can extrapolate that an RBC-DHA level of 17% could minimize the decline in field sensitivity. (ClinicalTrials.gov number, NCT00100230.)

Much of the computational power of the retina derives from the activity of amacrine cells, a large and diverse group of GABAergic and glycinergic inhibitory interneurons. Here, we identify an ON-type orientation-selective, wide-field, polyaxonal amacrine cell (PAC) in the rabbit retina and demonstrate how its orientation selectivity arises from the structure of the dendritic arbor and the pattern of excitatory and inhibitory inputs. Excitation from ON bipolar cells and inhibition arising from the OFF pathway converge to generate a quasi-linear integration of visual signals in the receptive field center. This serves to suppress responses to high spatial frequencies, thereby improving sensitivity to larger objects and enhancing orientation selectivity. Inhibition also regulates the magnitude and time course of excitatory inputs to this PAC through serial inhibitory connections onto the presynaptic terminals of ON bipolar cells. This presynaptic inhibition is driven by graded potentials within local microcircuits, similar in extent to the size of single bipolar cell receptive fields. Additional presynaptic inhibition is generated by spiking amacrine cells on a larger spatial scale covering several hundred microns. The orientation selectivity of this PAC may be a substrate for the inhibition that mediates orientation selectivity in some types of ganglion cells. Significance statement: The retina comprises numerous excitatory and inhibitory circuits that encode specific features in the visual scene, such as orientation, contrast, or motion. Here, we identify a wide-field inhibitory neuron that responds to visual stimuli of a particular orientation, a feature selectivity that is primarily due to the elongated shape of the dendritic arbor. Integration of convergent excitatory and inhibitory inputs from the ON and OFF visual pathways suppress responses to small objects and fine textures, thus enhancing selectivity for larger objects. Feedback inhibition regulates the strength and speed of excitation on both local and wide-field spatial scales. This study demonstrates how different synaptic inputs are regulated to tune a neuron to respond to specific features in the visual scene., (Copyright © 2015 the authors 0270-6474/15/3513336-15$15.00/0.)

Purpose: To evaluate the effect of oral antioxidant supplementation (OAS) on primary open-angle glaucoma (POAG) over a 2-year follow-up period., Patients and Methods: In this open-label, randomized controlled trial, 117 eyes of 117 patients with mild or moderate POAG and intraocular pressure under control with topical antiglaucoma medications were recruited and randomly divided into three groups according to supplementation: (1) OAS with (ICAPS R(®) - Alcon Laboratories, n = 26); (2) OAS without ω-3 fatty acids (OFTAN MACULA(®) - Laboratorios Esteve, n = 28); and (3) a control group without OAS (n = 63). They all underwent visual field (VF) tests (Humphrey 24-2) and scans using a Fourier-domain optical coherence tomography (FD-OCT) device (RTVue-100) at the beginning of the study and 2 years later. Mean deviation (MD), standard pattern deviation (PSD), peripapillary retinal nerve fibre layer (RNFL) and macular ganglion cell complex (GCC) parameters were considered for the analysis. Patients were also classified according to MD deterioration (fast deterioration vs. slow deterioration)., Results: Visual field global indices, peripapillary RNFL thickness and macular GCC thickness showed no differences among the groups at the beginning and end of the follow-up. Besides all the comparisons among groups for differences before and after the follow-up of the MD, PSD, RNFL and GCC parameters were also non-significant. The proportions of patients according to MD deterioration were similar among the groups and subgroups (p > 0.05 for all the comparisons)., Conclusion: Oral antioxidant supplementation with or without ω-3 fatty acids does not appear useful as an adjuvant treatment of mild/moderate POAG in the short term., (© 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate possible changes in corneal hysteresis (CH) after topical treatment with a prostaglandin analogue in medication-naïve eyes., Methods: This was a prospective, observational cohort study. Sixty-eight eyes of 68 patients were prospectively included who were newly diagnosed with primary open-angle glaucoma or ocular hypertension in our institution. All patients were treatment-naïve. Patients were evaluated at baseline and after 6 months of treatment with latanoprost in the eye with the lower intraocular pressure (IOP) measured by Goldmann applanation tonometry (GAT). The ocular response analyzer was used to measure CH., Results: CH increased significantly (p = 0.0001) from 8.96 ± 2.3 mmHg to 9.79 ± 1.97 mmHg, and this increase was correlated significantly (p = 0.0001, r = 0.64, r(2) = 0.41) with the basal CH. We identified a weak but significant (r(2) = 0.06, p = 0.01) relationship between the basal CH and the drug-induced reduction of the GAT IOP. Nevertheless, the increase in the drug-induced CH was not correlated with the decrease in the GAT IOP., Conclusion: Treatment with latanoprost increases CH. The CH increase was not correlated with the drug-induced decrease in the GAT IOP, which suggested a direct effect of latanoprost on the viscoelastic corneal properties., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Ipilimumab is a novel monoclonal antibody targeting the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) receptor that has been shown to improve survival in metastatic melanoma. Previous case reports have documented its association with drug-induced uveitis. We report a patient who developed bilateral optic neuropathy with disc edema while taking this medication.

Glaucoma causes damage to the optic nerve and compromises the visual field. The main risk factor of the disease is the level of the intra-ocular pressure. Therapeutic options include medical and surgical treatment, aimed to lower the intra-ocular pressure. Consumption of the cannabis plant (Cannabis Satival has been known since ancient times. It can be consumed orally, topically, intra-venous or by inhalation. The main active ingredient of cannabis is THC (Tetra-Hydro-Cannabinol). One of THC's reported effects is the reduction of intra-ocular pressure. Several studies have demonstrated temporary intra-ocular pressure decrease in both healthy subjects and glaucoma patients following topical application or systemic consumption. The effect was a short term one. It was followed by the development of resistance to the drug after prolonged intake and it was also accompanied by topical and systemic side effects. Cannabis may be considered as a therapeutic option in glaucoma. Its limited effect, development of resistance, acquired side effects and the accompanying psycho-active influence limit its advantage and cause its efficacy to be dubious. Therefore, cannabis treatment for glaucoma currently seems impractical and is not recommended by either the Israeli or the American glaucoma societies.

Local and global forms of inhibition controlling directionally selective ganglion cells (DSGCs) in the mammalian retina are well documented. It is established that local inhibition arising from GABAergic starburst amacrine cells (SACs) strongly contributes to direction selectivity. Here, we demonstrate that increasing ambient illumination leads to the recruitment of GABAergic wide-field amacrine cells (WACs) endowing the DS circuit with an additional feature: size selectivity. Using a combination of electrophysiology, pharmacology, and light/electron microscopy, we show that WACs predominantly contact presynaptic bipolar cells, which drive direct excitation and feedforward inhibition (through SACs) to DSGCs, thus maintaining the appropriate balance of inhibition/excitation required for generating DS. This circuit arrangement permits high-fidelity direction coding over a range of ambient light levels, over which size selectivity is adjusted. Together, these results provide novel insights into the anatomical and functional arrangement of multiple inhibitory interneurons within a single computational module in the retina., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo., Methods: In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140., Findings: We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28-0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug., Interpretation: This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period., Funding: Pfizer, UK National Institute for Health Research Biomedical Research Centre., (Copyright © 2015 Garway-Heath et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.)

Objective: To compare subjective and objective clinical tests used in the screening for hydroxychloroquine retinal toxicity to multifocal electroretinography (mfERG) reference testing., Design: Prospective, single-center, case control study., Participants: Fifty-seven patients with a previous or current history of hydroxychloroquine treatment of more than 5 years' duration., Methods: Participants were evaluated with a detailed medical history, dilated ophthalmologic examination, color fundus photography, fundus autofluorescence (FAF) imaging, spectral-domain (SD) optical coherence tomography (OCT), automated visual field testing (10-2 visual field mean deviation [VFMD]), and mfERG testing. We used mfERG test parameters as a gold standard to divide participants into 2 groups: those affected by hydroxychloroquine-induced retinal toxicity and those unaffected., Main Outcome Measures: We assessed the association of various imaging and psychophysical variables in the affected versus the unaffected group., Results: Fifty-seven study participants (91.2% female; mean age, 55.7±10.4 years; mean duration of hydroxychloroquine treatment, 15.0±7.5 years) were divided into affected (n = 19) and unaffected (n = 38) groups based on mfERG criteria. Mean age and duration of hydroxychloroquine treatment did not differ statistically between groups. Mean OCT retinal thickness measurements in all 9 macular subfields were significantly lower (<40 μm) in the affected group (P < 0.01 for all comparisons) compared with those in the unaffected group. Mean VFMD was 11 dB lower in the affected group (P < 0.0001). Clinical features indicative of retinal toxicity were scored for the 2 groups and were detected in 68.4% versus 0.0% using color fundus photographs, 73.3% versus 9.1% using FAF images, and 84.2% versus 0.0% on the scoring for the perifoveal loss of the photoreceptor ellipsoid zone on SD-OCT for affected and unaffected participants, respectively. Using a polynomial modeling approach, OCT inner ring retinal thickness measurements and Humphrey 10-2 VFMD were identified as the variables associated most strongly with the presence of hydroxychloroquine as defined by mfERG testing., Conclusions: Optical coherence tomography retinal thickness and 10-2 VFMD are objective measures demonstrating clinically useful sensitivity and specificity for the detection of hydroxychloroquine toxicity as identified by mfERG, and thus may be suitable surrogate tests., (Published by Elsevier Inc.)

The saccadic eye movements declining given the development of Parkinson's disease (PD) still deserves thorough analysis. Recent studies confirmed that PD patients show poor saccadic control in visuomotor tasks. The purpose of this study was to investigate the dynamics of saccades parameters at the development of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. The gradual decline of saccadic control was studied in two monkeys that executed the visuomotor task with low doses of MPTP being injected at a prolonged period of time. The experiment included investigating the horizontal, vertical, oblique visually guided saccades as well as the corrective saccades triggered by stimuli onset in various loci within a two-dimensional visual field in the Gap-Step-Overlap paradigm. Our study revealed that the execution of visually guided saccades with small amplitude and corrective saccades changed dramatically with MPTP-model progressing. These changes are also confirmed statistically at the presymptomatic stage of MPTP syndrome. Not only our study gives a robust report of PD dynamics development and saccadic control but the obtained data could also be helpful in developing methods for the early diagnosis of PD., (© The Author(s) 2015.)

Aim: The aim of this study was to examine whether vigabatrin treatment had caused visual field defects (VFDs) in children of school age who had received the drug in infancy., Method: In total, 35 children (14 males, 21 females; median age 11y, SD 3.4y, range 8-23y) were examined by static Humphrey perimetry, Goldmann kinetic perimetry, or Octopus perimetry. The aetiologies of infantile spasms identified were tuberous sclerosis (n=10), other symptomatic causes (n=3), or cryptogenic (n=22)., Results: Typical vigabatrin-attributed VFDs were found in 11 out of 32 (34%) children: in one out of 11 children (9%) who received vigabatrin for <1 year (group 1), in three out of 10 children (30%) who received vigabatrin for 12 to 24 months (group 2), and in seven out of 11 children (63%) who received vigabatrin treatment for longer than 2 years (group 3). VFDs were mild in five and severe in six children. Patients with tuberous sclerosis were at higher risk of VFDs (six out of 10 children). The mean cumulative doses of vigabatrin were 140.5, 758.8, and 2712g in group 1, 2, and 3, respectively., Interpretation: VFDs were found in 34% of the cohort of children in this study. The rate of VFD increased from 9% to 63% as duration of treatment increased. The results of this study showed that the risk-benefit ratio should always be considered when using vigabatrin., (© 2014 Mac Keith Press.)

Primary open angle glaucoma (POAG) is a multifactorial disease characterized by progressive retinal ganglion cell death and visual field loss. It is known that alterations in intraocular pressure (IOP), blood pressure (BP), and ocular perfusion pressure (OPP) can play a significant role in the pathogenesis of the disease. Impaired autoregulatory capacity of ocular blood vessels may render tissues vulnerable to OPP changes and potentially harmful tissue ischemia-reperfusion damage. Vascular risk factors should be considered more important in a subgroup of patients with POAG, and especially in patients with normal tension glaucoma (NTG) with evidence of unphysiological BP response. For example, reduction of BP during the nighttime has an influence on OPP, and increased circadian OPP fluctuation, which might stand for unstable ocular blood flow, has been found to be the consistent risk factor for NTG development and progression. Central visual field may be affected more severely than peripheral visual field in NTG patients with higher 24-hour fluctuation of OPP. This review will discuss the current understanding of allegedly major systemic and ocular hemodynamic risk factors for glaucoma including systemic hypertension, arterial stiffness, antihypertensive medication, exaggerated nocturnal hypotension, OPP, and autonomic dysregulation.