Saloni Walia

Natural History of Phenotypic Changes in Stargardt Macular Dystrophy

Stargardt macular dystrophy is the most common form of juvenile onset macular degeneration. This article reviews the four stages through which this dystrophy may progress. Also, reviewed here are the variations that may be observed in the visual acuity of patients with Stargardt disease.

Visual Acuity in Patients with Leber's Congenital Amaurosis and Early Childhood-Onset Retinitis Pigmentosa

PURPOSE To correlate visual acuity of patients with Lebers congenital amaurosis (LCA) and early childhood-onset retinitis pigmentosa (RP) with mutations in underlying LCA genes. DESIGN Multicentered retrospective observational study. PARTICIPANTS After exclusion of 28 subjects, 169 patients with the diagnosis of LCA and 27 patients with early childhood-onset RP were included in the study because the underlying mutations in AIPL1, GUCY2D, RDH12, RPE65, CRX, CRB1, RPGRIP1, CEP290, LCA5, and TULP1 genes could be identified in this cohort of patients. METHODS We collected data on best-corrected visual acuity as recorded at the time of the patients most recent visit to one of the participating ophthalmology departments. The median and range of visual acuities for each genetic subtype were calculated separately for the LCA and early childhood-onset RP groups. MAIN OUTCOME MEASURES The range and median best-corrected visual acuities for each genetic subtype and age-related mean visual acuities for each genetic subtype. RESULTS A wide variation in visual acuity was observed in patients with LCA and RPE65, RDH12, and CRB1 mutations, whereas AIPL1, GUCY2D, CRX, and RPGRIP1 gene mutations were associated with severely decreased visual acuities beginning within the first year of life. It was also noted that patients with either an RPE65 or CRB1 mutation have progressive visual loss with advancing age. Onset of visual symptoms after infancy was associated with a relatively better visual prognosis. CONCLUSIONS The data obtained from this study will help clinicians provide counseling on visual prognosis to patients with known mutations in LCA genes and be of value in future studies aimed at the treatment of LCA and early childhood-onset RP.

Efficacy of Sustained Topical Dorzolamide Therapy for Cystic Macular Lesions in Patients With X-Linked Retinoschisis

OBJECTIVE To determine the efficacy of sustained topical therapy with dorzolamide hydrochloride, 2%, on visual acuity and cystic macular lesions in patients with juvenile X-linked retinoschisis (XLRS). DESIGN Retrospective analysis. SETTING University hospital, tertiary care referral center. PATIENTS Twenty-nine eyes of 15 patients with XLRS receiving treatment with the topical dorzolamide formulation for 4 to 41 months were enrolled. MAIN OUTCOME MEASURES Changes in visual acuity, cystic macular lesions, and central foveal zone thickness on optical coherence tomography during follow-up for the duration of treatment. RESULTS Among the 15 patients with XLRS, 20 eyes (69%) of 11 patients showed a positive response to treatment. Five of the 20 eyes (25%) in 3 of the 11 patients showed an initial response and a subsequent rebound of macular cysts. In 4 eyes (14%) of 3 patients, there was no response to treatment, but the macular cysts did not worsen compared with the baseline level. In 5 additional eyes (17%) of 4 patients, there was no response to treatment, and the macular cysts worsened when compared with the baseline level. Sixteen eyes (55%) of 12 patients had improvement in best-corrected visual acuity by at least 7 letters in at least 1 eye at the most recent follow-up visit. Seventeen eyes (59%) of 10 patients showed a reduction in the central foveal zone thickness in at least 1 eye when compared with the pretreatment level. CONCLUSION Patients with XLRS have the potential to experience a beneficial effect from sustained treatment with dorzolamide, 2%.

Retinal nerve fiber layer analysis in RP patients using Fourier-domain OCT.

PURPOSE To determine peripapillary retinal nerve fiber layer thickness (RNFL) abnormalities in patients with retinitis pigmentosa (RP) using Fourier-domain optical coherence tomography (Fd-OCT) and to evaluate the potential effect of cystoid macular edema (CME) or axial length on RNFL measurements in such patients. METHODS Ninety-seven eyes of 52 patients with diagnoses of retinitis pigmentosa or Usher syndrome type II underwent complete ocular examination. Peripapillary RNFL thickness was measured using Fd-OCT in 16 segments from 4 quadrants--temporal (316 degrees -45 degrees ), superior (46 degrees -135 degrees ), nasal (136 degrees -225 degrees ), and inferior (226 degrees -315 degrees ). These measurements were compared with age- and disc size-adjusted control values. Further analyses were performed to determine the correlation of axial length or CME with RNFL thickness. RESULTS Thinning of the RNFL was observed in 37 eyes (38.14%) of 23 patients (44.23%). A maximum number of eyes had thinning in the nasal quadrant followed by the inferior quadrant; the superior and temporal quadrants were abnormally thin in fewer eyes. No correlation was found between axial length and RNFL thickness in the total cohort (correlation coefficient, 0.039). An abnormal increase in RNFL thickness was observed in 21.65% eyes, but no association was found between the presence of CME and increased RNFL thickness. CONCLUSIONS RP eyes may show abnormal thinning or increased thickness of RNFL measurements on testing with Fd-OCT. RNFL defects observed by OCT testing document the presence of anatomic defects in more anterior structures within the retina in a notable number of patients with RP.

Relation of Response to Treatment with Dorzolamide in X-Linked Retinoschisis to the Mechanism of Functional Loss in Retinoschisin

PURPOSE To determine if a positive response of macular cysts to treatment with dorzolamide eye drops in patients with juvenile X-linked retinoschisis (XLRS) can occur with mutations that result in different types of retinoschisin protein dysfunction. DESIGN Retrospective case series. METHODS Thirteen eyes of seven patients seen at the University of Illinois at Chicago with a known diagnosis of XLRS were included. Each patient had received or currently was receiving treatment with topical dorzolamide. One patient from each family was screened for a genetic mutation. Using the method of cell transfection and protein preparation, the mutation in each patient was analyzed further and was categorized into one of three groups: 1) total absence of retinoschisin protein secretion, 2) decreased expression of the secreted protein, or 3) secretion of a nonfunctional protein. The response to dorzolamide was observed using optical coherence tomography. RESULTS Significant improvement in the foveal zone thickness was observed with the use of dorzolamide in three of four patients with absence of protein secretion, in two patients with a lack of protein expression, and in one patient with a nonfunctional protein secretion. CONCLUSIONS This study showed that the response of macular cysts to dorzolamide in patients with XLRS may be observed independent of the mechanism responsible for retinoschisin protein dysfunction. Hence, treatment with dorzolamide may be effective in patients with different mechanisms of dysfunction in retinoschisin.

Visual Acuity Changes in Patients With Leber Congenital Amaurosis and Mutations in CEP290

OBJECTIVE To evaluate changes in visual acuity (VA) over time in patients with Leber congenital amaurosis (LCA) and mutations in the CEP290 gene. METHODS Visual acuity was determined at the initial and most recent visits of 43 patients with LCA and CEP290 mutations. The main outcome measures included the best-corrected VA at the initial and most recent visits, as well as the correlation between age and VA. RESULTS At the initial visit, 14 patients had measurable chart VA in the better-seeing eye, 25 patients had nonmeasurable chart VA, and 4 young patients did not have VA assessed. At the most recent visit, 15 patients had measurable chart VA and 28 had nonmeasurable chart VA. The average interval between the 2 visits was 10.4 years (range, 2-47 years). For patients with measurable chart VA, the median logMAR value at the initial visit (0.75; range, 0.10-2.30) and at the most recent visit (0.70; range, 0.10-2.00) did not differ significantly (P> .05). There was no significant relationship between VA and age. CONCLUSIONS Patients with LCA and CEP290 mutations had a wide spectrum of VA that was not related to age or length of follow-up. Severe VA loss was observed in most, but not all, patients in the first decade. These data will help clinicians provide counseling on VA changes in patients with CEP290 mutations and could be of value for future treatment trials.

Phenotypic Expression of a PRPF8 Gene Mutation in a Large African American Family

OBJECTIVES To describe the phenotype and determine the genetic cause of autosomal dominant retinitis pigmentosa (adRP) in a large African American family. METHODS Fourteen members from 4 generations were evaluated clinically. Visual field measurements were made for most, and electroretinography, Tübinger perimetry, and optical coherence tomographic testing were done for individual family members. Genetic screening was performed on a recently introduced adRP microarray that contains approximately 400 mutations from 13 genes. RESULTS All of the affected members had a type 1 form of adRP, characterized by early onset of symptoms for visual impairment, marked central and peripheral vision loss, nondetectable electroretinographic responses, and decreased macular thickness on optical coherence tomographic testing. Two variants in the PRPF8 gene were identified in the proband, H2309R and IVS41-4G-->A. The H2309R mutation segregated with the disease in the family, whereas the IVS41-4G-->A variant did not. CONCLUSIONS The severe form of adRP was caused by the PRPF8 H2309R variant, whereas the IVS41-4G-->A variant was benign. CLINICAL RELEVANCE PRPF8 mutations should be suspected in patients with a type 1 form of adRP. A combination of advanced clinical workup and comprehensive genetic testing is essential for the precise diagnosis of diseases with high genetic heterogeneity such as RP.

Flecked-Retina Syndromes

A number of retinal disorders may present with fleck-like lesions in the retina. We describe the case of a 13-year-old girl who presented with a complaint of decreased vision and prior diagnosis of “fleck-retina.” Further examination revealed that the patient had an autosomal recessive disorder associated with systemic manifestations. In the current article, the authors describe the case report and briefly review the various autosomal-recessive disorders that may present with “retinal flecks.”