BACKGROUND/AIMS:The antiseizure medication, vigabatrin, is associated with visual field loss (VAVFL). However, the fields can be challenging to interpret due to unfamiliarity with the characteristics of the defect and/or to difficulty in obtaining a reliable examination, particularly in patients with cognitive limitations associated with the epilepsy. Two machine-learning pattern recognition algorithms were developed to identify VAVFL, objectively. METHODS:The algorithms adhered to the European Medicines Agency-approved protocol for the detection of VAVFL (Three Zone Age Corrected Full Field 135 Screening Test (FF135) and the Central C30-2 Threshold Test (C30-2T) with the Humphrey Field Analyzer). Each algorithm compared the similarity of the measured field from each eye to that of modelled reference patterns of VAVFL, matched for equivalent severity, and objectively derived from a previously described case series of 123 adults. The algorithms were augmented by the optional inclusion of symmetrisation, a signal-to-noise enhancement technique based on the between-eye mirror image symmetry of VAVFL. Utility of the algorithms for identifying VAVFL was evaluated against a case series of 89 consecutively identified individuals stratified across six diagnostic categories including homonymous and glaucomatous losses. RESULTS:The algorithms exhibited excellent agreement with a 'gold standard' clinical interpretation (sensitivity and specificity: FF135, 22/23; 30/30; C30-2T, 17/18; 48/51). Symmetrisation was particularly useful in identifying VAVFL when perimetric learning or fatigue influenced the outcome for one eye and for visualisation in the presence of concomitant homonymous loss. CONCLUSION:The directly interpretable machine-learning outcome correctly identified VAVFL and could assist patient management in community (neuro-)ophthalmology.

Purpose:To determine whether significant deteriorations in objective (electroretinography [ERG]) and subjective (standard automated and semi-automated kinetic perimetry; color discrimination; and best-corrected visual acuity) tests of visual function, potentially attributable to aging, occurred in the group randomized to placebo of a 3-year prospective multicenter ocular safety study of ivabradine for chronic stable angina pectoris.Methods:The multicenter trial was conducted at 11 international ophthalmic centers. Changes in visual function between baseline and month 36 were analyzed by means of a two-tailed Wilcoxon signed-rank test, based on the Hodges and Lehman estimator of the median difference, with the 95% confidence intervals derived by Walsh averages.Results:Thirty-eight participants from the placebo group completed the study (mean [SD], age, 62.7 [8.1] years). The group exhibited in each eye small, but statistically significant, reductions in the amplitudes of the dark-adapted (DA) ERG 3.0 a-wave, and light-adapted (LA) 3.0 b-wave, as well as increases in peak time for the DA 0.01 b-wave, DA 3.0 a-wave, LA 3.0 b-wave, and LA 3.0 30-Hz flicker response and in the isopter area I3e of the visual field.Conclusions:Statistically significant deteriorations occurred in visual function over a period of 3 years, potentially attributable to age, within a group of individuals with chronic stable angina pectoris and unremarkable ophthalmological findings other than those attributable to age.Translational Relevance:A longitudinal correction factor for age-related change in visual function may be useful in future trials to determine whether an observed deterioration in visual function is related to intervention or to aging.

Purpose:To describe quality control procedures and baseline values of electroretinography (ERG), kinetic and static perimetry, color discrimination, and best-corrected visual acuity from a multicenter ocular safety study. Methods:A multicenter prospective longitudinal randomized placebo-controlled study was conducted at 11 ophthalmic centers that had received certification following training, instruction, and monitoring. ERGs were obtained with the Espion E2 Ganzfeld console, perimetry with the Octopus 101 perimeter, color discrimination with the Lanthony desaturated D15 test, and best-corrected visual acuity with the Early Treatment Diabetic Retinopathy Study chart. Ophthalmic eligibility required satisfactory outcomes for ERG and perimetry by the second or third pre-inclusion attempts, respectively. Quality control for the ERG was undertaken by two central readers. Results:The mean (SD) age of the 97 individuals was 63.5 (7.9) range, 44-83 years. The overall coefficients of variation (CVs) for the ERG peak times were less than those of the only comparable single-center study. The CV for the mean defect of standard automated perimetry was approximately one-third that of the Ocular Hypertension Treatment Study. With increasing age, ERG peak times and color discrimination Total Error Score increased while ERG amplitudes and isopter area all decreased. Conclusions:The data illustrate the benefit of identical equipment, stringent on-site instruction and training, quality control, certification, and validation methods. The latter are recommended for planning and conducting multicenter trials using ERG and perimetry to monitor safety and/or efficacy of treatment intervention. Translational Relevance:Stringent quality control procedures and reliable reference values are indispensable prerequisites for informative clinical trials.

The morphology and between-eye symmetry of the visual field loss associated with the antiepileptic drug vigabatrin (VAVFL) has received little attention. Our objective was to model the appearance and ensuing staging of VAVFL derived with the European Medicines Agency-approved perimetric protocol. 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. 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. 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.

Purpose The “traffic light” color designation of differential light sensitivity used in a number of microperimeters does not encompass the conventional Total and Pattern Deviation probability analyses adopted by standard automated perimetry. We determined whether the color designation is indicative of abnormality as represented by the “gold standard” Pattern Deviation probability analysis. Methods Total and Pattern Deviation probability levels, using two different methods, were derived at each of 40 stimulus locations, within 7° eccentricity, from 66 ocular healthy individuals (66 eyes) who had undergone microperimetry with the Macular Integrity Assessment microperimeter. The probability levels were applied to the corresponding fields from each of 45 individuals (45 eyes) with age-related macular degeneration (AMD) and evaluated in relation to the color designation. Results Sensitivities designated in orange encompassed the entire range of Pattern Deviation probability levels (from normal to P ≤ 1%). Those designated in green were mostly normal; those in red/black generally corresponded to the ≤1% probability level. Conclusions The green and the red/black designations are generally indicative of normal and abnormal probability values, respectively. The orange designation encompassed all probability outcomes and should not be relied upon for visual field interpretation. The evidence base indicates replacement of the color designation of sensitivity in AMD by Total Deviation and Pattern Deviation analyses. Translational Relevance The use of Total and Pattern Deviation probability analyses is not universal in all microperimeters, and the derivation of these values indicates that color coding will lead to errors in evaluating visual field loss.

The antiepileptic drug vigabatrin is associated with characteristic visual field loss (VAVFL) and thinning of the peripapillary retinal nerve fibre layer (PPRNFL); however, the relationship is equivocal.

Microperimetry is a novel technique for assessing visual function that appears particularly suitable for age-related macular degeneration (AMD). Compared with standard automated perimetry, microperimetry offers several unique features. It simultaneously images the fundus, incorporates an eye-tracking system to correct the stimulus location for fixation loss, and identifies any preferred retinal loci. We identified 52 articles that met the inclusion criteria for a systematic review of microperimetry in the assessment of visual function in AMD. We discuss microperimetry and AMD in relation to disease severity, structural imaging outcomes, other measures of visual function, and evaluation of the efficacy of surgical and/or medical therapies in clinical trials. The evidence for the use of microperimetry in the functional assessment of AMD is encouraging. Disruptions of the ellipsoid zone band and retinal pigment epithelium are clearly associated with reduced differential light sensitivity despite the maintenance of good visual acuity. Reduced differential light sensitivity is also associated with outer segment thinning and retinal pigment epithelium thickening in early AMD and with both a thickening and a thinning of the whole retina in choroidal neovascularization. Microperimetry, however, lacks the robust diffuse and focal loss age-corrected probability analyses associated with standard automated perimetry, and the technique is currently limited by this omission.

Polypoidal choroidal vasculopathy (PCV) is a degenerative macular disease. The study determined the topographical concordance in the areal extent of PCV, defined by indocyanine green angiography (ICGA), and the corresponding outcomes from spectral-domain optical coherence tomography (SD-OCT) and microperimetry, in 25 individuals (25 eyes) who had undergone 3 months of anti-vascular endothelial growth factor treatment. The differential light sensitivity within 10° eccentricity was evaluated by Pattern Deviation probability analysis. The concordances and proportional areal extents of the abnormality for ICGA, SD-OCT and microperimetry were compared. The concordance in the areal extent between all three modalities was 59%. The median concordance between ICGA and microperimetry was 60%; between ICGA and SD-OCT, 70%; and between SD-OCT and microperimetry, 72%. SD-OCT and microperimetry each identified a greater areal extent (>20%) compared to ICGA in 13 and 19 eyes, respectively. A greater areal extent (>20%) was present in 9 eyes for microperimetry compared to SD-OCT and in 5 eyes for SD-OCT compared to microperimetry. SD-OCT and microperimetry each identified a greater area of abnormality than ICGA which supports the clinical utility of SD-OCT. Strong concordance was present between SD-OCT and microperimetry; however, microperimetry identified additional areas of functional abnormality.

Age-related macular degeneration (AMD) is of increasing concern given the ageing population, and the associated economic and social burdens. Vision-related quality-of-life (QoL) is arguably one of the most important factors in the management of those with AMD. Consequently, there is a clear need for an understanding of the clinical outcomes that influence vision-related QoL in order to inform management strategies. The principle aim of the studies described herein was to determine the factors that predict vision-related QoL in those with AMD, over 1 year. Experimental procedures were undertaken at baseline (n=52 individuals with AMD) and repeated after 1 year (n=32 individuals with AMD). These included: visual acuity, contrast sensitivity, reading speed, microperimetry, optical coherence tomography and fundus photography. A questionnaire interview included assessment of vision-related QoL (Impact of Visual Impairment questionnaire), health status (EQ-5D), level of depressive symptoms (PHQ-9) and well-being (Warwick-Edinburgh Well-Being Scale). At baseline, the optimum multiple regression model accounted for 41% of the variance in vision-related QoL and included Mean Total Deviation or Mean Sensitivity with level of depressive symptoms. After 1 year, the optimum model to predict change in vision-related QoL accounted for 43% of the variance and included baseline contrast sensitivity and change in health status and reading speed. The most clinically useful measures of visual function, in identifying those with a reduced QoL or those at risk of a reduced QoL were contrast sensitivity, microperimetry, and reading speed. These outcomes may allow a better understanding of vision-related QoL if they were adopted in a clinical setting. In conclusion, the studies provide sufficient evidence to encourage a review of the clinical outcome measures most relevant to vision-related QoL.

The antiepileptic drug vigabatrin has been used widely since 1989, but has only been approved for use in the US since 2009. The risk:benefit of vigabatrin is generally predicated upon an assumed frequency of associated visual field loss (VAVFL) of approximately 31 %. This estimate is based upon relatively short-term usage (up to 4–5 years) and it is essential to determine whether the frequency of VAVFL increases with longer-term usage.

PURPOSE:To determine the accuracy with which the optic disc can be diagnosed as normal or glaucomatous according to the ISNT rule, whereby, in the normal eye, the neuroretinal rim area follows the order inferior (I) > superior (S) > nasal (N) > temporal (T). DESIGN:Prospective, cross-sectional, observational, case series. PARTICIPANTS:Fifty-one normal individuals and 78 individuals with open-angle glaucoma exhibiting field loss (median mean deviation, -4.37 dB; interquartile range [IQR], -2.10 to -7.96 dB; median pattern standard deviation, 5.65 dB; IQR, 2.94 to 8.56 dB). The reference diagnosis was made by 2 experts on the basis of the appearance of the optic disc and of the corresponding visual field. METHODS:Stereoscopic optic disc photographs, acquired for each individual, were digitized at high resolution and analyzed using a digital, quad-buffered, stereoscopic viewing system in which a Z screen was used to dissociate the images to the 2 eyes of the observer. Three expert observers, trained to fellowship standard in glaucoma, independently undertook planimetry of the neuroretinal rim and of the disc margin from 1 eye of each individual, using a cursor moving in stereoscopic space to minimize parallax errors. Software automatically calculated the neuroretinal rim area in 10°, 30°, 40°, and 90° segments. For the ISNT rule to be obeyed, the 3 Boolean comparisons of the neuroretinal rim area, I>S, S>N, and N>T, had to be true. If any of the comparisons returned false, the rule was considered not to have been obeyed. Values were compared at a precision of 0.0001 mm(2). MAIN OUTCOME MEASURES:The outcome of the ISNT rule in terms of the 3 Boolean comparisons of the neuroretinal rim area was specified in terms of the sensitivity, specificity, and hence, the positive and negative likelihood ratios. RESULTS:Based on the ISNT rule being obeyed for 10° segments, the positive likelihood ratio among the 3 observers was 1.11 (95% confidence interval [CI], 0.99-1.25), 1.07 (95% CI, 0.94-1.21), and 1.06 (95% CI, 0.96-1.18), respectively. It was similar for the other segment sizes. Variants of the rule were not appreciably better. CONCLUSIONS:The ISNT rule has limited utility in the diagnosis of open-angle glaucoma.

Aim: The aim of this study was to determine whether the new, primary care based, Welsh Low Vision Service (WLVS) improved access to low vision services in Wales and was effective. Method: The impact of the WLVS was determined by measuring the number of low vision appointments; travel time to the nearest service provider; and waiting times for low vision services for 1 year before, and for 1 year after, its establishment. Change in self-report visual function (using the 7 item NEI-VFQ), near visual acuity, patient satisfaction and use of low vision aids were used to determine the effectiveness of the service. Results: Following instigation of the WLVS, the number of low vision assessments increased by 51.7%, the waiting time decreased from more than 6 months to less than 2 months for the majority of people, and journey time to the nearest service provider reduced for 80% of people. Visual disability scores improved significantly (p < 0.001) by 0.79 logits and 97.42% patients found the service helpful. Conclusions: The extension of low vision rehabilitation services into primary care identified a considerable unmet burden of need as evidenced by the substantial increase in the number of low vision assessments provided in Wales. The new service is effective and exhibits improved access.

Purpose: To investigate whether nasal peripapillary retinal nerve fiber layer (RNFL) attenuation is associated with visual field loss attributed to the anti-epileptic drug vigabatrin.Design: Prospective cross-sectional observational study.Participants: Twenty-seven individuals with focal-onset epilepsy exposed to vigabatrin and 13 individuals with focal-onset epilepsy exposed to non-GABAergic anti-epileptic drug monotherapy.Methods: At one visit, suprathreshold perimetry of the central and peripheral field (3-zone, age-corrected Full Field 135 Screening Test) and threshold perimetry of the central field (Program 30-2 and the FASTPAC strategy) were undertaken using the Humphrey Field Analyzer (Carl Zeiss Meditech, Dublin, CA). At a second visit, ocular coherence tomography was undertaken for the right eye using the 3.4 RNFL thickness protocol of the StratusOCT (Carl Zeiss Meditech).Main Outcome Measures: The magnitude, for each individual, of the RNFL thickness, averaged across the 4 oblique quadrants, and for each separate quadrant.Results: Of the 27 individuals exposed to vigabatrin, 11 (group I) exhibited vigabatrin-attributed visual field loss, 15 exhibited a normal field, and 1 exhibited a homonymous quadrantanopia (group II). All 13 individuals exposed to non-GABAergic therapy had normal fields (group III). All individuals in group I exhibited abnormal average and nasal quadrant RNFL thicknesses in the presence of a normal temporal quadrant thickness. Most also exhibited additional RNFL attenuation in either the superior or inferior quadrant, or both. Four individuals in group II exhibited an identical pattern of RNFL attenuation suggesting that nasal RNFL thinning is a more sensitive marker for vigabatrin toxicity than visual field loss. None of the 13 individuals in group III exhibited nasal quadrant RNFL attenuation.Conclusions: Vigabatrin-attributed visual field loss is associated with a characteristic pattern of RNFL attenuation: nasal quadrant thinning and normal temporal quadrant thickness with, or without, superior or inferior quadrant involvement. Nasal attenuation may precede visual field loss. Ocular coherence tomography of the peripapillary RNFL should be considered in patients previously exposed to vigabatrin. It should also be considered at baseline and follow-up in those commencing vigabatrin for treatment of epilepsy or in trials for anti-addiction therapy. The pattern of RNFL thinning seems to be a useful biomarker to identify vigabatrin toxicity.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2009; 116:565-571 (C) 2009 by the American Academy of Ophthalmology.

PURPOSE The quantification of early retinal ganglion cell damage in ocular hypertension and glaucoma. METHODS Thirty subjects under treatment for open-angle glaucoma, 23 subjects with ocular hypertension, and 28 healthy subjects in a control group were investigated by monocular pattern electroretinogram (ERG), L&M (long and medium wavelength) cone ERG, and S (short wavelength)-cone ERG. The diagnosis of glaucoma was based on masked assessment of digital stereoscopic optic nerve head images by three glaucoma specialists. The optic nerve head and retinal nerve fiber layer was assessed by scanning laser ophthalmoscopy and optical coherence tomography. RESULTS All types of ERG had reduced mean amplitudes in ocular hypertension and open-angle glaucoma groups compared with the control group. In the ocular hypertension group, the N95 and the L&M-pathway photopic negative response (PhNR) were significantly attenuated (by 19% and 18% compared with the control group, respectively; by 30% and 22%, respectively, in the open-angle glaucoma group compared with the control group). In the subjects with open-angle glaucoma, the pattern ERG P50-N95 was found to be the most sensitive electrophysiological test, and the cup-disc area ratio, when examined by scanning laser ophthalmoscopy, was the most sensitive imaging parameter. Modest but not statistically significant correlations were found between the imaging and electrophysiologic parameters. CONCLUSIONS With disc appearance used for the classification of open-angle glaucoma and ocular hypertension, significant electrophysiological losses were found in both conditions. The modest correlation between the structural and electrophysiological measures suggests that these assess different aspects of the pathologic process; electrophysiology can be used to quantify retinal ganglion cell dysfunction that occurs before cell death.

Background: Use of the antiepileptic drug vigabatrin is associated with an elevated risk of visual field loss.