Sarwar Zahid

Clinical phenotypes and prognostic full-field electroretinographic findings in Stargardt disease.

PURPOSE To investigate the relationships between clinical and full-field electroretinographic (ERG) findings and progressive loss of visual function in Stargardt disease. DESIGN Retrospective cohort study. METHODS We performed a retrospective review of data from 198 patients with Stargardt disease. Measures of visual function over time, including visual acuity, quantified Goldmann visual fields, and full-field ERG data were recorded. Data were analyzed using SAS statistical software. Subgroup analyses were performed on 148 patients with ERG phenotypic data, 46 patients with longitudinal visual field data, and 92 patients with identified ABCA4 mutations (46 with 1 mutation, and 47 with 2 or more mutations). RESULTS Of 46 patients with longitudinal visual field data, 8 patients with faster central scotoma progression rates had significantly worse scotopic B-wave amplitudes at their initial assessment than 20 patients with stable scotomata (P = .014) and were more likely to have atrophy beyond the arcades (P = .047). Overall, 47.3% of patients exhibited abnormal ERG results, with rod-cone dysfunction in 14.2% of patients, cone-rod dysfunction in 17.6% of patients, and isolated cone dysfunction in 15.5% of patients. Abnormal values in certain ERG parameters were associated significantly with (maximum-stimulation A- and B-wave amplitudes) or tended toward (photopic and scotopic B-wave amplitudes) a higher mean rate of central scotoma progression compared with those patients with normal ERG values. Scotoma size and ERG parameters differed significantly between those with a single mutation versus those with multiple mutations. CONCLUSIONS Full-field ERG examination provides clinically relevant information regarding the severity of Stargardt disease, likelihood of central scotoma expansion, and visual acuity deterioration. Patients also may exhibit an isolated cone dystrophy on ERG examination.

Diagnostic Fundus Autofluorescence Patterns in Achromatopsia

PURPOSE To describe the unique diagnostic fundus autofluorescence (FAF) patterns in patients with achromatopsia and the associated findings on optical coherence tomography (OCT). DESIGN Observational case series. METHODS We evaluated 10 patients with achromatopsia by means of best-corrected visual acuity (BCVA), ophthalmoscopy, Goldmann visual field, full-field electroretinography (ffERG), OCT, and FAF photography. FAF patterns were compared with patient age and foveal changes on OCT. RESULTS Patients fell into two dichotomous age groups at the time of evaluation: six patients ranged from 11 to 23 years of age, and 3 patients ranged from 52 to 63 years of age. All patients had severely reduced photopic ffERG responses, including those exhibiting preserved foveal structure on OCT. The younger patients had absent to mild foveal atrophy on OCT, and four of the six demonstrated foveal and parafoveal hyperfluorescence on FAF. In addition, a 7-month-old child with compound heterozygous mutations in CNGA3 demonstrated similar foveal hyperfluorescence. The older patients demonstrated advanced foveal atrophy and punched-out foveal hypofluorescence with discrete borders on FAF imaging corresponding to the area of outer retinal cavitation on OCT. CONCLUSIONS Foveal hyperfluorescence is an early sign of achromatopsia that can aid in clinical diagnosis. In our cohort, patients with achromatopsia demonstrated age-dependent changes in FAF, which are likely to be progressive and to correlate with foveal atrophy and cavitation on OCT. This finding may be useful in charting the natural course of the disease and in defining a therapeutic window for treatment.

Digital Quantification of Goldmann Visual Fields (GVFs) as a Means for Genotype–Phenotype Comparisons and Detection of Progression in Retinal Degenerations

PURPOSE To develop a reliable and efficient digital method to quantify planimetric Goldmann visual field (GVF) data to monitor disease course and treatment responses in retinal degenerative diseases. METHODS A novel method to digitally quantify GVFs using Adobe Photoshop CS3 was developed for comparison to traditional digital planimetry (Placom 45C digital planimeter; Engineer Supply, Lynchburg, Virginia, USA). GVFs from 20 eyes from 10 patients with Stargardt disease were quantified to assess the difference between the two methods (a total of 230 measurements per method). This quantification approach was also applied to 13 patients with X-linked retinitis pigmentosa (XLRP) with mutations in RPGR. RESULTS Overall, measurements using Adobe Photoshop were more rapidly performed than those using conventional planimetry. Photoshop measurements also exhibited less inter- and intraobserver variability. GVF areas for the I4e isopter in patients with the same mutation in RPGR who were nearby in age had similar qualitative and quantitative areas. CONCLUSIONS Quantification of GVFs using Adobe Photoshop is quicker, more reliable, and less user dependent than conventional digital planimetry. It will be a useful tool for both retrospective and prospective studies of disease course as well as for monitoring treatment response in clinical trials for retinal degenerative diseases.

Autofluorescence quantification of benign and malignant choroidal nevomelanocytic tumors.

IMPORTANCE Accurate diagnosis of choroidal melanoma is challenging and has important implications for both physicians and patients. We assessed the utility of quantification of fundus autofluorescence in the evaluation and follow-up of choroidal nevomelanocytic tumors. OBJECTIVE To assess the utility of autofluorescence quantification in distinguishing clinically diagnosed choroidal nevi, melanoma, and indeterminate nevomelanocytic lesions. DESIGN, SETTING, AND PARTICIPANTS A retrospective observational study from 2006 to 2012 of patients with choroidal nevomelanocytic lesions who had digital autofluorescence and color fundus imaging performed at the University of Michigan Kellogg Eye Center. INTERVENTION ImageJ software was used to output autofluorescence gray-scale values for each pixel of a 500 × 50-pixel region within each lesion and a corresponding adjacent control region. MAIN OUTCOME AND MEASURE A single value was generated, termed the Index of Retinal Autofluorescence (IRA), to represent the total difference in gray-scale values between the 2 regions in each affected eye. RESULTS Thirteen of the 14 clinically diagnosed nevi exhibited an IRA less than 150 gray-scale intensity squared (gsi2). Eight of 9 clinically diagnosed melanomas exhibited an IRA more than 150 gsi2. An IRA of 150 gsi2 distinguished nevi from melanomas with a sensitivity of 0.89 and specificity of 0.93. Fifteen of 19 patients with indeterminate nevomelanocytic lesions underwent clinical assessment and initial imaging with clinical follow-up at a median of 10 months. All 3 patients with an IRA less than 150 gsi2 showed no evidence of clinical progression and 6 of 12 lesions with an IRA more than 150 gsi2 showed clinical progression to melanoma. An IRA of 150 gsi2 identifies indeterminate lesions that progressed to melanoma with a sensitivity of 1.00 and specificity of 0.33. CONCLUSIONS AND RELEVANCE Quantification of digital autofluorescence images can differentiate between clinically benign and malignant choroidal nevomelanocytic lesions and may be predictive for clinical progression of indeterminate lesions.

Vision Loss After Central Retinal Artery Occlusion Secondary to Orbital Sarcoid Mass.

The authors describe the first report in the literature of central retinal artery occlusion as the presenting manifestation of sarcoidosis. A 33-year-old man with asthma, headache, and 6 days of intermittent, transient vision loss in the OS presented with persistent vision loss in the OS. Ophthalmic examination was consistent with diagnosis of central retinal artery occlusion in the OS. Vascular imaging with CT angiography revealed an incidental finding of an intraconal mass surrounding the left optic nerve and hilar lymphadenopathy. Broncho scopic lymph node biopsy demonstrated noncaseating granulomas consistent with sarcoidosis. This case proffers a unique mechanism of vision loss in sarcoidosis and highlights that atypical causes of central retinal artery occlusion must be considered in patients without typical risk factors.

Progression of Noncirrhotic Portal Hypertension in a Pediatric Population

BACKGROUND/OBJECTIVES The optimal management of children with noncirrhotic portal hypertension is controversial. Some groups suggest early and aggressive surgical intervention, while others report long-term success with conservative management. METHODS We conducted a retrospective study of 26 patients with noncirrhotic portal hypertension treated at our institution. We compared platelet counts, white blood cell (WBC) counts, spleen size, hospital admissions, gastrointestinal bleeds, and longitudinal trends of specific clinical parameters using standard univariate and time-trend analytic techniques. RESULTS Mean age at the time of diagnosis was 5.2 years. Portal vein thrombosis was found in 84.6% of patients (n=22). There was one mortality related to malignancy. There was not a progression of hypersplenism in patients that did not receive a shunt and conversely, we did not notice a significant decrease in spleen size following shunt surgery (P=0.2). Platelet and WBC counts trended downward among patients managed medically, while platelets increased and WBC counts remained stable in surgical patients. There was a significant decrease in hospital admissions for gastrointestinal bleeding following surgical intervention in the shunt group compared with nonshunt (P=0.0009). CONCLUSION While our analysis was limited given small sample sizes and selection bias, it suggests that the majority of pediatric patients with noncirrhotic portal hypertension will do well long-term without surgical intervention.

OPN1LW and OPN1MW

OPN1LW and OPN1MW lie side by side on the X-chromosome and encode the long-wavelength (red) and middle-wavelength (green) cone opsins, respectively. Mutations in these genes cause a wide array of X-linked conditions ranging from red-green dyschromatopsia, blue cone monochromacy (BCM), cone/cone-rod dystrophy, and high myopia.

Retinal Dystrophy Gene Atlas

Describes a gene and all its possible clinical phenotypes and patient characteristics, along with retinal photos depicting each possible phenotype Written by prominent retinal dystrophy specialists from the largest dystrophy centers worldwide Contains more than 80 chapters, each of which describes the clinical and photographic manifestations of a specific gene Includes stunning clinical color photographs of the retina, autofluorescence imaging, and electrophysiologic findings and cross-sectional imaging Serves as a resource to aid genetic diagnosis in patients with retinal dystrophies by retina specialists and pediatric ophthalmologists in the United States, as well as hundreds of fellows and residents that