Monique Leys

Autosomal Recessive Vitelliform Macular Dystrophy In a Large Cohort Of Vitelliform Macular Dystrophy Patients

Purpose: To report 11 cases of autosomal recessive vitelliform macular dystrophy and to compare their molecular findings and phenotypic characteristics with those of patients with the more common and well-described dominant form of the disease. Methods: Blood samples were obtained from 435 unrelated individuals with a clinical diagnosis of vitelliform macular dystrophy and screened for mutations in the coding sequences of BEST1. Medical records and retinal photographs of selected patients were reviewed. Results: Nine of the 435 probands were found to have 2 plausible disease-causing variations in BEST1, while 198 individuals were found to have heterozygous variations compatible with autosomal dominant inheritance. Inheritance phase was determined in three of the recessive families. Six novel disease-causing mutations were identified among these recessive patients: Arg47Cys, IVS7−2A>G, IVS7+4G>A, Ile205del12ATCCTGCTCCAGAG, Pro274Arg, and Ile366delCAGGTGTGGC. Forty-four novel disease-causing mutations were identified among the patients with presumed autosomal dominant disease. The phenotype of patients with recessive alleles for BEST1 ranged from typical vitelliform lesions to extensive extramacular deposits. Conclusion: The authors provide evidence that two abnormal BEST1 alleles, neither of which causes macular disease alone, can act in concert to cause early-onset vitelliform macular dystrophy.

West Virginia survey of visual health: Low vision and barriers to access

The West Virginia Survey of Visual Health was conducted to determine the types and frequency of barriers to vision treatment experienced by persons with visual health problems and low vision in West Virginia. The study used a Random Digit Dial (RDD) sample to gather information from 1026 households. Cross-tabulation of two variables were used to classify respondents or their family members as having low vision. Among the 1026 homes surveyed, 233 households reported having at least one or more persons with vision health problems. Out of the 233 households, 57 individuals were classified as having low vision. West Virginians who report vision health problems are older and tend to rate their physical health lower compared to those with normal vision. Treatment patterns illustrate that a large number of respondents see an eye doctor on an irregular basis. Economic barriers for the vision health population appear substantial. Transportation barriers are common among the low vision population. The impact of vis...

Intravitreal bevacizumab for the treatment of choroidal neovascularization secondary to pseudotumor cerebri.

Background In pseudotumor cerebri (PTC), elevated intracranial pressure (ICP) results in papilledema and, rarely, choroidal neovascularization (CNV). Pseudotumor cerebri-induced CNV often regresses following medical or surgical ICP reduction, but additional treatments, such as photocoagulation, photodynamic therapy, peri-ocular steroid injections and/or subretinal surgery, may be necessary. Anti-angiogenic intravitreal injections have been shown to cause regression of both CNV and optic nerve edema. Case report We describe a patient with PTC and CNV whose CNV regressed and vision normalized after a single intravitreal injection of bevacizumab (Avastin; Genentech, San Francisco, CA).

Parallel pathways, noise masking and glaucoma detection: behavioral and electrophysiological measures.

AbstractPurpose: We tested the hypothesis that because of their reduced neural efficiency, glaucoma patients should have increasingly impaired thresholds as external noise is added to a stimulus. Method: We compared the performance of 20 normals (mean age = 39 years) with that of 15 patients with early glaucoma or at very high risk for glaucoma (mean age 45 years). All patients had normal visual acuity. Contrast thresholds were measured on two sets of tasks: (1) behavioral and (2) sweep visually evoked potentials (VEPs). Two stimuli were used (a) 7.5 Hz reversing gratings of 0.69 cpd, and (b) 5.5 cpd gratings. Noise was binary and contrast varied from 0 to 80%. Psychophysical thresholds were determined using a staircase which employed a spatial four alternative forced choice procedure (4AFC) and converged on 50% correct. Sweep VEP thresholds were determined by extrapolation to zero volts as a function of log contrast. Results: Differences between normal subjects and patients with early glaucoma were not significant without noise. Both the absolute size of the difference and its significance increased as noise level increased. For the behavioral thresholds these trends were clearer with the 5.5 cpd grating, while for the sweep VEPs they were more clear for the 0.69 cpd grating. Conclusion: The performance deficit of glaucoma patients which may be minimal under normal testing conditions is magnified when external noise is added to the stimulus. VEPs and psychophysical thresholds show interesting differences in their sensitivity to this effect. Implications for the early detection of glaucoma are discussed.

A UNIQUE CASE OF ACUTE MACULAR NEURORETINOPATHY ASSOCIATED WITH COTTON WOOL SPOTS AND INTRARETINAL FLUID.

PURPOSE To discuss the clinical findings in a unique case of acute macular neuroretinopathy with a focus on the pathophysiology of this rare entity. METHODS The patients clinical course was documented with color fundus photography and spectral domain ocular coherence tomography registered to infrared reflectance imaging. The visual field was assessed using the Amsler grid testing and Humphrey visual field 24-2. RESULTS Initial fundus photography showed cotton wool spots and slight darkening of the central macula in each eye. Optical coherence tomography showed initial hyperreflective plaques at the level of the outer plexiform layer/outer nuclear layer junction with subsequent thinning of the outer nuclear layer and corresponding disruption of the ellipsoid and outer segment/retinal pigment epithelium. Infrared reflectance imaging revealed perifoveal hyporeflective lesions in each eye with corresponding visual field defects on the Amsler grid and visual field testing. The hyporeflective infrared lesions became more discreet during the ensuing weeks and remained stable beyond 11 weeks. CONCLUSION The authors present the case of a 15-year-old girl diagnosed with acute macular neuroretinopathy. This case is notable in that she presented with cotton wool spots and intraretinal fluid, both of which are unusual for acute macular neuroretinopathy. The authors suggest that the presence of cotton wool spots and several small foci of intraretinal fluid seen in their patient may lend support to the ischemic hypothesis described by Sarraf et al. The optical coherence tomography images obtained in this case have the typical wedge-shaped or petaloid configuration, and the authors suggest that the shape of the lesions themselves also lends support to a vascular mechanism.

Clinical Features of a Retinopathy Associated With a Dominant Allele of the RGR Gene

Purpose We describe the clinical features in two pedigrees with dominantly inherited retinopathy segregating the previously reported frameshifting mutation, c.836dupG (p.Ile280Asn*78) in the terminal exon of the RGR gene, and compare their haplotypes to that of the previously reported pedigree. Methods The probands were ascertained at West Virginia University Eye Institute (WVU) and Moorfields Eye Hospital (MEH) through next generation sequencing (NGS) and whole genome sequencing (WGS) respectively. Clinical data included visual acuity (VA), visual fields, fundus autofluorescence (FAF), optical coherence tomography (OCT), and electroretinography (ERG). Haplotype analysis was performed using Sanger sequencing of the DNA from the molecularly ascertained individuals from the three pedigrees. Results Nine heterozygous mutation carriers were identified in two families. Four carriers were asymptomatic; five carriers had variable VA reduction, visual field constriction, and experienced difficulty under dim illumination. Fundus examination of the asymptomatic carriers showed diffuse or reticular pigmentation of the retina; the symptomatic carriers had chorioretinal atrophy. FAF imaging showed widespread signal loss in advanced retinopathy, and reticular hyperautofluorescence in mild cases. OCT showed loss of outer retinal lamina in advanced disease. ERG showed moderate-to-severe rod–cone dysfunction in two symptomatic carriers; and was normal in three asymptomatic carriers. A shared haplotype flanking the mutation of up to 6.67 Mb was identified in both families. Within this region, 1.27 Mb were shared with the first family reported with this retinopathy. Conclusions The clinical data suggest a variable and slow degeneration of the RPE. A shared chromosomal segment surrounding the RGR gene suggests a single ancestral mutational event underlying all three families.

Fulminant idiopathic intracranial hypertension and venous stasis retinopathy resulting in severe bilateral visual impairment.

Purpose To report a complicated case of fulminant idiopathic intracranial hypertension and concomitant venous stasis retinopathy leading to postpapilledema optic atrophy. Methods Case report. Results A 34-year-old morbidly obese woman with a history of idiopathic intracranial hypertension (IIH) presented with a 1-month history of bilateral vision loss, diplopia, and left eye pain after being lost to follow-up for 6 years. Fundus examination revealed florid papilledema with venous tortuosity bilaterally. Brain and orbit magnetic resonance imaging showed bilateral globe flattening, intraocular optic nerve swelling in both eyes, and no abnormality on magnetic resonance venography. After additional workup including lumbar puncture with an opening pressure of 55 cm H2O, a diagnosis of IIH was confirmed. Medical treatment with oral carbonic anhydrase inhibitors was initiated, followed by same-day bilateral optic nerve sheath decompression and ventriculoperitoneal shunt placement the following week. Fundus examination 2 months later revealed a persistent blood and thunder fundus suggestive of bilateral central retinal vein occlusions. Over the course of 6 months, both eyes displayed postpapilledema optic atrophy with light perception and hand motion vision in the right and left eyes, respectively. On Goldmann perimetry, the patient had vague limited isolated responses in both eyes to the largest target. Conclusions Fulminant IIH can present with profoundly blinding complications recalcitrant to aggressive medical and surgical intervention. Central retinal vein occlusion is an uncommon blinding complication of IIH.

Central retinal artery occlusion following laser treatment for ocular ischemic aortic arch syndrome

Objective: Ocular ischemic syndrome is a rare blinding condition generally caused by disease of the carotid artery. We describe a 69-year-old female with a 50 pack-year smoking history with aortic arch syndrome causing bilateral ocular ischemic syndrome. Methods: The patient presented with progressive visual loss and temple pain. Slit lamp biomicroscopy revealed bilateral iris neovascularization. This finding prompted a cardiovascular work up. Panretinal photocoagulation with retrobulbar block was performed in the right eye. Results: A temporal artery biopsy was negative. The carotid duplex ultrasound showed only a 1–39% stenosis. MRA revealed a more proximal occlusion of the aortic branch for which she underwent subclavian carotid bypass surgery. At the one month follow up, the right eye suffered profound vision loss secondary to a central retinal artery occlusion. Conclusion: Ocular neovascularization may be one of the clinical manifestations of aortic arch syndrome. This case also illustrates the limitations of relying solely on carotid duplex ultrasound testing. We caution against overly aggressive panretinal photocoagulation utilizing retrobulbar anesthesia.

Editorial: Abstracts of the 46th symposium of ISCEV, Morgantown, WV, USA

The field of electrodiagnostics is rapidly expanding. Improved computing power has expanded our ability to control stimuli and to analyze the biologic signals elicited by them. Similar trends are also affecting other areas ranging from biochemistry and genetics to imaging of the retina and brain. Natural, fertile areas of study are the overlap of these factors. Thus, we had invited papers by Aina Puce and Paul Sieving directed toward structure and function relationships in the cortex and retina. Additionally, we had several sessions related to imaging and electrophysiology.

Detecting glaucomatous damage: evaluation with contrast independent tasks

Several studies have indicated that contrast-dependent tasks, such as detecting threshold stimuli, may be more effective in discriminating glaucoma from normal groups if external noise is added to the stimulus. We sought to determine if the same were true for contrast-independent tasks. Subjects were 15 patients with glaucoma and a group of 20 normals with the same mean age. We employed two contrast-independent tasks, orientation defined texture and dot numerosity discrimination. The stimulus was presented on a computer controlled video monitor. One side of the display contained a standard and the other contained a non-standard target. For each task, noise was added by perturbing the main feature of the display, dot number or line orientation, by a Gaussian distribution truncated at 2 standard deviation units. There were four noise levels for each task. Subjects viewed the stimulus display and made a spatial two-alternative forced choice judgment. Subjects judged the side of the orientation texture which contained a sub-region with a different angle and the side of the dot figures which had the larger number of dots. Glaucoma patients performed more poorly than normals in discriminating the orientation texture (p < 0.05) and in judging dot numerosity (p < 0.05). This was true even in the absence of added external noise. Adding external noise did not increase the differences between glaucoma patients and normals. Unlike contrast-dependent tasks in which the differences between normal and glaucoma patients are increased when external noise is added, contrast-independent tasks show maximal differentiation between the two groups without added noise. Tasks such as texture discrimination and dot numerosity may be useful in detecting glaucoma.