Visual Field Sensitivity Prediction Using Optical Coherence Tomography Analysis in Hydroxychloroquine Toxicity.

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.

Macula pigment optical densitometry changes in hydroxychloroquine use.

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.

A Single Low-Dose of Methylphenidate Improves Abnormal Visual Field Testing.

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.

ASYMMETRIC HYDROXYCHLOROQUINE MACULAR TOXICITY WITH APHAKIC FELLOW EYE.

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.

MULTIMODAL IMAGING IN DIDANOSINE RETINOPATHY.

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.

Association of Oxymetazoline Hydrochloride, 0.1%, Solution Administration With Visual Field in Acquired Ptosis: A Pooled Analysis of 2 Randomized Clinical Trials.

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.

Quantitative Fundus Autofluorescence in HCQ Retinopathy.

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.

Case Report: Transient Myopic Shift and Other Sequelae in Response to Adverse Reaction to Sulfamethoxazole-trimethoprim.

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.

The effect of Bushen Huoxue method in treating glaucoma: A protocol for systematic review and meta-analysis.

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.

Effect of palmitoylethanolamide on inner retinal function in glaucoma: a randomized, single blind, crossover, clinical trial by pattern-electroretinogram.

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.

The Use of Vitamins and Coenzyme Q10 for the Treatment of Vascular Occlusion Diseases Affecting the Retina.

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.

Visual Field Changes Over 5 Years in Patients Treated With Panretinal Photocoagulation or Ranibizumab for Proliferative Diabetic Retinopathy.

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.

Evaluation of Hydroxychloroquine Retinopathy Using Ultra-Widefield Fundus Autofluorescence: Peripheral Findings in the Retinopathy.

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.

Recovery dynamics of multifocal pupillographic objective perimetry from tropicamide dilation.

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.

Microinjectrode System for Combined Drug Infusion and Electrophysiology.

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.

Association of Systemic Medication Exposure With Glaucoma Progression and Glaucoma Suspect Conversion in the Groningen Longitudinal Glaucoma Study.

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.

Objective Derivation of the Morphology and Staging of Visual Field Loss Associated with Long-Term Vigabatrin Therapy.

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.

Effects of Brimonidine and Timolol on the Progression of Visual Field Defects in Open-angle Glaucoma: A Single-center Randomized Trial.

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.