Mohamed A. Genead

Photoreceptor Structure and Function in Patients with Congenital Achromatopsia

PURPOSE To assess photoreceptor structure and function in patients with congenital achromatopsia. METHODS Twelve patients were enrolled. All patients underwent a complete ocular examination, spectral-domain optical coherence tomography (SD-OCT), full-field electroretinographic (ERG), and color vision testing. Macular microperimetry (MP; in four patients) and adaptive optics (AO) imaging (in nine patients) were also performed. Blood was drawn for screening of disease-causing genetic mutations. RESULTS Mean (± SD) age was 30.8 (± 16.6) years. Mean best-corrected visual acuity was 0.85 (± 0.14) logarithm of the minimal angle of resolution (logMAR) units. Seven patients (58.3%) showed either an absent foveal reflex or nonspecific retinal pigment epithelium mottling to mild hypopigmentary changes on fundus examination. Two patients showed an atrophic-appearing macular lesion. On anomaloscopy, only 5 patients matched over the entire range from 0 to 73. SD-OCT examination showed a disruption or loss of the macular inner/outer segments (IS/OS) junction of the photoreceptors in 10 patients (83.3%). Seven of these patients showed an optically empty space at the level of the photoreceptors in the fovea. AO images of the photoreceptor mosaic were highly variable but significantly disrupted from normal. On ERG testing, 10 patients (83.3%) showed evidence of residual cone responses to a single-flash stimulus response. The macular MP testing showed that the overall mean retinal sensitivity was significantly lower than normal (12.0 vs. 16.9 dB, P < 0.0001). CONCLUSIONS The current approach of using high-resolution techniques to assess photoreceptor structure and function in patients with achromatopsia should be useful in guiding selection of patients for future therapeutic trials as well as monitoring therapeutic response in these trials.

Efficacy of Sustained Topical Dorzolamide Therapy for Cystic Macular Lesions in Patients With Retinitis Pigmentosa and Usher Syndrome

OBJECTIVE To determine the efficacy of sustained topical therapy with dorzolamide hydrochloride, 2%, on visual acuity and cystic macular lesions in patients with retinitis pigmentosa and Usher syndrome. METHODS In a retrospective case series at a university hospital, 64 eyes of 32 patients with retinitis pigmentosa or Usher syndrome receiving treatment with the topical dorzolamide formulation for 6 to 58 months were enrolled. Changes in visual acuity on the Early Treatment Diabetic Retinopathy Study chart and central foveal zone thickness on optical coherence tomography were measured during follow-up for the duration of treatment. RESULTS Among the study cohort, 20 of 32 patients (63%) showed a positive response to treatment in at least 1 eye and 13 patients (41%) showed a positive response in both eyes. Four patients (20%) showed an initial response and a subsequent rebound of macular cysts. In 8 patients (25%), there was no response to treatment and the macular cysts worsened when compared with the pretreatment level. Ten patients (31%) had improvement in visual acuity by 7 or more letters in at least 1 eye at the most recent follow-up visit. Sixteen patients (67%) showed a reduction of more than 11% in the central foveal zone thickness in at least 1 eye when compared with the pretreatment level. CONCLUSIONS Patients with either retinitis pigmentosa or Usher syndrome who received treatment of cystoid macular edema with topical dorzolamide followed by an optical coherence tomography-guided strategy showed a decrease in central foveal zone thickness in most cases. Visual acuity improved in almost one-third of the cases, suggesting a potential corresponding visual benefit.

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%.

Assessing retinal structure in complete congenital stationary night blindness and oguchi disease

PURPOSE To examine retinal structure and changes in photoreceptor intensity after dark adaptation in patients with complete congenital stationary night blindness and Oguchi disease. DESIGN Prospective, observational case series. METHODS We recruited 3 patients with complete congenital stationary night blindness caused by mutations in GRM6, 2 brothers with Oguchi disease caused by mutations in GRK1, and 1 normal control. Retinal thickness was measured from optical coherence tomography images. Integrity of the rod and cone mosaic was assessed using adaptive optics scanning light ophthalmoscopy. We imaged 5 of the patients after a period of dark adaptation and examined layer reflectivity on optical coherence tomography in a patient with Oguchi disease under light- and dark-adapted conditions. RESULTS Retinal thickness was reduced in the parafoveal region in patients with GRM6 mutations as a result of decreased thickness of the inner retinal layers. All patients had normal photoreceptor density at all locations analyzed. On removal from dark adaptation, the intensity of the rods (but not cones) in the patients with Oguchi disease gradually and significantly increased. In 1 Oguchi disease patient, the outer segment layer contrast on optical coherence tomography was 4-fold higher under dark-adapted versus light-adapted conditions. CONCLUSIONS The selective thinning of the inner retinal layers in patients with GRM6 mutations suggests either reduced bipolar or ganglion cell numbers or altered synaptic structure in the inner retina. Our finding that rods, but not cones, change intensity after dark adaptation suggests that fundus changes in Oguchi disease are the result of changes within the rods as opposed to changes at a different retinal locus.

The natural history of Stargardt disease with specific sequence mutation in the ABCA4 gene.

PURPOSE To determine longitudinal changes in fundus appearance and visual function in patients with Stargardt with at least one allelic mutation (Gly1961Glu) in the ABCA4 gene. METHODS Sixteen patients with a diagnosis of Stargardt disease and a Gly1961Glu mutation were enrolled. All patients underwent a complete ocular examination including best corrected visual acuity, Goldmann visual field (GVF), and full-field ERG examinations. The percentage of patients who showed at least a doubling in the log of the minimum angle of visual resolution (logMAR) between their initial and most recent visits was determined, as was the percentage of patients who showed a doubling in the size of the central scotoma over this duration. RESULTS Nine patients had at least a doubling of the logMAR visual acuity in their right eyes and 10 patients in their left eyes, over a mean follow-up (FU) period of 18.6 years. Of 15 patients, 46.7% had equal to or more than a doubling of the central scotoma area in response to a II2e test stimulus in the right eye and 60.0% in the left eyes. Among 10 patients whose ERGs were initially normal for rod and cone responses, 8 remained normal at their most recent FU visit. CONCLUSIONS In these patients with Stargardt disease and a Gly1961Glu mutation, most showed a clinical phenotype characterized by fundus changes localized to the foveal and parafoveal regions, normal ERG amplitudes, absence of a silent or masked choroid, and a mean age at initial presentation in the third decade.

Spectral-Domain Optical Coherence Tomography and Fundus Autofluorescence Characteristics in Patients with Fundus Albipunctatus and Retinitis Punctata Albescens

Purpose: Fundus albipunctatus is a form of congenital stationary night blindness characterized by an early onset and nonprogressive impairment of night vision and the presence of numerous dull-white punctate lesions scattered throughout the fundus, while retinitis punctata albescens patients often show similar fundus changes but manifest a severe and progressive hereditary retinal dystrophy. Conclusions: In this study, we report the optical coherence tomography and fundus autofluorescence measurements in patients with these hereditary night blinding diseases.

Treatment of cystic macular lesions in hereditary retinal dystrophies

Cystic macular lesions frequently contribute to impaired visual acuity in hereditary retinal dystrophies. Their pathogenesis varies and is not entirely understood. Carbonic anhydrase inhibitors have proven to be potentially efficacious, although not in all cases. We discuss the various factors and mechanisms implicated in the etiology of cystic macular lesions (anatomical abnormalities, impairment of the blood-retinal barrier, tangential vitreous traction, and mutations in retinoschin, etc.) and the various treatments that have been proposed.

Cystic macular oedema on spectral-domain optical coherence tomography in choroideremia patients without cystic changes on fundus examination

PurposeTo determine the prevalence of cystic macular oedema (CME) in patients with choroideremia (CHM) by using spectral-domain optical coherence tomography (SD-OCT).MethodsA total 16 patients affected with CHM were enroled in the study. All patients underwent a complete eye examination. SD-OCT was performed using an OPKO spectral-domain OCT/SLO instrument.ResultsThe average age of the study patients was 44.0±16.0 years (range, 13–63 years). Out of the 16 patients with CHM, 10 patients (62.5%) showed a degree of CME on SD-OCT testing in at least one eye, and 8 patients (50%) showed CME in both eyes.ConclusionsBecause of its notable prevalence, it would seem prudent to screen CHM patients by SD-OCT for the possible presence of CME and to identify those amenable to future treatment strategies for their macular oedema.

Topical Dorzolamide for Treatment of Cystoid Macular Edema in Patients with Choroideremia

Purpose: To determine the value of a topical carbonic anhydrase inhibitor on the macular thickness and function in choroideremia patients with cystoid macular edema. Methods: Two choroideremia patients with cystoid macular edema, observed by spectral-domain optical coherence tomography, were treated with a topical form of carbonic anhydrase inhibitor. Examinations performed before and during treatment included best-corrected visual acuity by using the Early Treatment Diabetic Retinopathy Study charts and contrast sensitivity measured with briefly presented grating targets and the Pelli–Robson letter contrast sensitivity chart, microperimetry, and spectral-domain optical coherence tomography. Results: The 2 choroideremia patients treated with dorzolamide 2% formulation had a noticeable reduction in macular thickness by spectral-domain optical coherence tomography. This reduction was found in both eyes after 2 months of treatment. After an additional 3 months of the same treatment regimen, a more noticeable reduction in macular thickness was observed. The two study patients had improvement of their visual acuity, in at least one eye, on Early Treatment Diabetic Retinopathy Study charts, but no clinically significant changes for the other measures of visual function. Conclusion: The present study shows the potential efficacy of topical dorzolamide for treating choroideremia patients with cystoid macular edema.

Evaluation of retinal nerve fiber layer thickness in patients with retinitis pigmentosa using spectral-domain optical coherence tomography

Purpose To measure the peripapillary retinal nerve fiber layer (RNFL) thickness using spectral-domain optical coherence tomography in patients with retinitis pigmentosa. Methods Fifty eyes of 30 patients with retinitis pigmentosa underwent a complete ocular examination, including best-corrected visual acuity using a Snellen chart, slit-lamp biomicroscopic examination, and Goldmann applanation intraocular pressure measurement. Dilated fundus examination was performed using both direct and indirect ophthalmoscopy. In addition, all patients underwent peripapillary RNFL thickness measurements using an OPKO spectral-domain optical coherence tomography (OPKO Instrumentations, Miami, FL). Results The mean (±SD) age of the study cohort was 45.8 (±16.3) years. Of the 50 eyes, 18 (36%) showed a thinning of the peripapillary RNFL in 1 or more quadrants and 21 (42%) showed a thickening of the peripapillary RNFL in 1 or more quadrants. Four eyes (8%) showed both thinning and thickening of the peripapillary RNFL thickness. The overall circumferential RNFL thickness of the 14 eyes that showed only thinning in at least 1 quadrant was 78.78 &mgr;m. For the 17 eyes that showed only thickening in at least 1 quadrant, the RNFL thickness was 119.69 &mgr;m. The values of the eyes with thinning and the eyes with thickening were significantly different from normal (t = 6.31 and P < 0.01 for thickening; t = 3.62 and P < 0.01 for thinning). Conclusion Using spectral-domain optical coherence tomography testing, we demonstrated in the current study that the peripapillary RNFL thickness in patients with RP can be decreased, increased, or maintained within normal limits. Assessment of the RNFL thickness seems prudent in these patients, particularly for identifying notable degrees of RNFL thinning in those being considered for future therapeutic trials.