Infrared scanning laser ophthalmoscope imaging of the macula and its correlation with functional loss and structural changes in patients with stargardt disease.

PURPOSE: To correlate the degree of functional loss with structural changes in patients with Stargardt disease. METHODS: Eighteen eyes of 10 patients with Stargardt disease were studied. Scanning laser ophthalmoscope infrared images were compared with corresponding spectral-domain optical coherence tomography scans. Additionally, scanning laser ophthalmoscope microperimetry was performed, and results were superimposed on scanning laser ophthalmoscope infrared images and in selected cases on fundus autofluorescence images. RESULTS: Seventeen of 18 eyes showed a distinct hyporeflective foveal and/or perifoveal area with distinct borders on scanning laser ophthalmoscope infrared images, which was less evident on funduscopy and incompletely depicted in fundus autofluorescence images. This hyporeflective zone corresponded to areas of significantly elevated psychophysical thresholds on microperimetry testing, in addition to thinning of the retinal pigment epithelium and disorganization or loss of the photoreceptor cell inner segment-outer segment junction and external-limiting membrane on spectral-domain optical coherence tomography. CONCLUSION: Scanning laser ophthalmoscope infrared fundus images are useful for depicting retinal structural changes in patients with Stargardt disease. A spectral-domain optical coherence tomography/scanning laser ophthalmoscope microperimetry device allows for a direct correlation of structural abnormalities with functional defects that will likely be applicable for the determination of retinal areas for potential improvement of retinal function in these patients during future clinical trials and for the monitoring of the diseases' natural history.

Structural and functional characteristics in carriers of X-linked retinitis pigmentosa with a tapetal-like reflex.

PURPOSE: The purpose of this study was to identify the functional and structural characteristics in three female obligate carriers of X-linked retinitis pigmentosa from the same family by using spectral domain optical coherence tomography, fundus autofluorescence, and microperimetry. METHODS: Three female obligate carriers with a tapetal-like reflex, 21, 49, and 57 years of age, from a single family of X-linked retinitis pigmentosa that was seen in the ophthalmology department at the University of Illinois at Chicago, were enrolled in the study. All carriers underwent a complete ophthalmic examination. Spectral domain optical coherence tomography measurements, a macular microperimetry examination, and fundus autofluorescence testing were performed. RESULTS: The spectral domain optical coherence tomography examination in all three carriers showed a normal retinal microstructure and thickness. Microperimeter testing showed subnormal retinal sensitivity in the areas of the tapetal-like reflex. Fundus autofluorescence examination showed the presence of speckled areas of enhanced autofluorescence. CONCLUSION: Our study demonstrates that the carriers of X-linked retinitis pigmentosa with a tapetal-like reflex can show an enhanced reflectance on infrared images, abnormal autofluorescence properties, elevated retinal thresholds, and a normal retinal morphology within the posterior pole on spectral domain optical coherence tomography testing.

Macular vitelliform lesion in desferrioxamine-related retinopathy.

To report a case of a macular vitelliform lesion associated with desferrioxamine treatment. Ocular, electrophysiological, psychophysical, perimetric, fluorescein angiographic, fundus autofluorescence, and spectral-domain OCT examinations were obtained on a 45-year-old Caucasian woman with thalassemia major treated with blood transfusions and desferrioxamine. The patient was observed to have a vitelliform macular lesion in the right eye with a hypopigmented macular lesion and retinal pigment mottling in the left. At the most recent follow-up visit, best-corrected visual acuity was 20/70 in the right eye and 20/25 in left. Full-field electroretinogram (ERG) testing showed normal cone and rod responses. Mild localized elevations of rod psychophysical thresholds were found. A vitelliform macular lesion can develop in patients treated with desferrioxamine. Some such patients may not show diffuse photoreceptor cell functional loss as determined by electrophysiological testing.

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.

Differential macular morphology in patients with RPE65-, CEP290-, GUCY2D-, and AIPL1-related Leber congenital amaurosis.

PURPOSE: To evaluate genotypic and macular morphologic correlations in patients with RPE65-, CEP290-, GUCY2D-, or AIPL1-related Leber congenital amaurosis (LCA) using spectral-domain optical coherence tomography (SD-OCT). METHODS: SD-OCT macular scans were performed in 21 patients, including 10 with RPE65, 7 with CEP290, 3 with GUCY2D, and 1 with AIPL1 mutations. An image processing software was used to manually draw segmentation lines by three observers. Lamellar structure was evaluated based on the number of retinal layers on segmented images. Total retinal thickness was measured at the central macular and perifoveal areas by using an automated algorithm. RESULTS: All three patients with GUCY2D mutations (age range, 20-53 years) retained six retinal layers with visible photoreceptor inner/outer segment juncture (PSJ). However, the preservation of lamellar structures did not parallel better visual acuity. Patients with other mutations had poorly defined PSJ and disorganized retinal lamellar structures, where only one to three retinal layers could be observed. Patients with CEP290 mutations trended to have retention of the outer nuclear layer at the fovea and macular thickening, especially at younger ages. In patients with RPE65 (age range, 20-71 years) and AIPL1 mutations (age, 22 years), macular thickness was markedly decreased. Disorganization of retinal lamellar structures in the RPE65 group trended toward a worsening with increasing age. CONCLUSIONS: Variations of macular microstructures were observed among LCA patients with different genotypes. Disorganization of retinal lamellar structure was generally age related. Preservation of retinal microanatomic structures may not be associated with better visual acuity.

Fundus white spots and acquired night blindness due to vitamin A deficiency.

To report a successfully treated case of acquired night blindness associated with fundus white spots secondary to vitamin A deficiency. An ocular examination, electrophysiologic testing, as well as visual field and OCT examinations were obtained on a 61-year-old man with vitamin A deficiency who had previously undergone gastric bypass surgery. The patient had a re-evaluation after treatment with high doses of oral vitamin A. The patient was observed to have numerous white spots in the retina of each eye. Best-corrected visual acuity was initially 20/80 in each eye, which improved to 20/40-1 OU after oral vitamin A therapy for 2 months. Full field electroretinogram (ERG) testing, showed non-detectable rod function and a 34 and 41% reduction for 32-Hz flicker and single flash cone responses, respectively, below the lower limits of normal. Both rod and cone functions markedly improved after initiation of vitamin A therapy. Vitamin A deficiency needs to be considered in a patient with white spots of the retina in the presence of poor night vision.

Diagnosis in a patient with fundus albipunctatus and atypical fundus changes.

We report a case of an 11-year old Caucasian female with nyctalopia since early childhood with an atypical clinical presentation of fundus albipunctatus (FA), and a novel mutation in the RDH5 gene. In addition to white spots in the fundus, patchy areas of hypopigmentation were noted, which were reminiscent for an early stage of retinitis punctata albescens (RPA). Electroretinographic testing (ERG) showed a non-detectable, dark adapted, isolated rod response and a markedly decreased combined rod and cone response to an achromatic stimulus. After patching one eye overnight, both the isolated rod response and combined rod and cone scotopic white flash response were normal. A Goldmann-Weekers dark adapted final threshold response was also within the normal range. The patient showed a previously reported heterozygous mutation for Gly238Trp, and a novel Arg157Gln mutation. Genetic testing and extended ERG and psychophysical testing may be necessary to diagnose FA from early stages of progressive RPA.

Discordant phenotypes in fraternal twins having an identical mutation in exon ORF15 of the RPGR gene.

OBJECTIVE: To report discordant phenotypes, resulting from the same mutation in exon ORF15 (GenBank AF286472) of the retinitis pigmentosa GTPase regulator gene (RPGR) (GenBank U57629), in 2 presumed dizygotic twin brothers with X-linked retinal disease. METHODS: The 2 brothers underwent complete ophthalmic examination that included best-corrected visual acuity, slitlamp biomicroscopy, and detailed fundus examination. Visual field recording using Goldmann kinetic perimetry and a full-field electroretinogram were also obtained in both patients. Mutational screening was performed for RPGR because of an X-linked pattern of inheritance indicated by pedigree analysis. RESULTS: One brother had a phenotypic expression of cone-rod dystrophy, while the other exhibited X-linked retinitis pigmentosa. A 1-nucleotide deletion was identified in the 3' region of exon ORF15 of RPGR (ORF15 + 1339delA). CONCLUSIONS: An identical mutation in RPGR-ORF15 manifested distinct clinical phenotypes in individuals of the same family. Our data provide strong evidence in support of additional modifier genes that can produce diverse disease phenotypes in patients with RPGR mutations. CLINICAL RELEVANCE: The clinical observation of different retinal phenotypes in a family with the same mutation in exon ORF15 of RPGR implicates the potential importance of modifier genes for the phenotypic expression of this form of X-linked retinal disease.

Retinal nerve fiber layer defects in RP patients.

PURPOSE: To determine, with the use of optical coherence tomography (OCT), the peripapillary retinal nerve fiber layer (RNFL) thickness among patients with retinitis pigmentosa (RP) of different degrees of disease severity. METHODS: One eye in each of 25 RP patients was included. All patients underwent complete ocular examination, including the measurement of intraocular pressure, corneal thickness, and detailed fundus examination. Visual fields were evaluated by Goldmann perimetry. An RNFL thickness protocol was used to acquire circular scans of 3.46 mm in diameter around the optic nerve. For each eye, RNFL thickness was studied in the temporal (316 degrees -45 degrees ), superior (46 degrees -135 degrees ), nasal (136 degrees -225 degrees ), and inferior (226 degrees -315 degrees ) quadrants. Three smaller segments were also measured within each quadrant, all automatically calculated by the existing OCT software. The severity of damage to the peripapillary nerve fiber layer was compared with the clinical appearance of the optic disc, severity of field loss, and mode of inheritance for RP. RESULTS: The mean age of patients included in the study was 48.6 years (range, 23-73 years). Of the 25 patients examined, 10 had abnormal thinning of the peripapillary RNFL in 2 or more segments, and 7 of those had abnormal thinning in at least 1 quadrant. The number of patients with abnormal thinning of the RNFL was considerably greater in those with clinically observed moderately severe or severe pallor of the optic disc than in those with normal appearance or mild pallor of the optic disc. No consistent association was noted between the remaining visual field and the presence of a RNFL defect (P > 0.05). CONCLUSIONS: Patients with retinitis pigmentosa may have a measurable degree of RNFL thinning as determined by OCT. These observations could have an impact on future treatment strategies and imply that patients considered for various treatment options would benefit by an evaluation of nerve fiber layer thickness.

ABCA4 gene sequence variations in patients with autosomal recessive cone-rod dystrophy.

OBJECTIVE: To identify sequence variations in the ABCA4 gene in a cohort of patients with autosomal recessive cone-rod dystrophy. METHODS: The coding sequences of the ABCA4 gene were analyzed in 30 unrelated probands. In those patients with plausible disease-causing variations, correlations were made between genotype and fundus phenotype as well as with electrophysiological and visual field findings. RESULTS: Sixteen (53%) of 30 probands were found to harbor plausible disease-causing variations in the ABCA4 gene. Two distinctly different fundus phenotypes were observed in our cohort of patients. Twelve patients showed diffuse pigmentary degenerative changes, whereas 4 showed either no pigmentary changes or only a mild degree of peripheral pigment degeneration. An associa-tion between certain sequence variations and each of these 2 different phenotypes was observed. CONCLUSIONS: Our findings confirm that a substantial percentage of patients with autosomal recessive cone-rod dystrophy are likely to harbor a mutation in the ABCA4 gene as the cause of their disease. The fundus phenotype observed in such patients is quite variable, and certain fundus phenotypes may be more associated with certain genotypes. Clinical Relevance Identification of the molecular genetic basis for various inherited human retinal dystrophies, such as cone-rod dystrophy, facilitates a potentially better understanding of the mechanisms by which photoreceptor cells degenerate. This in turn provides guidance as to how to better proceed in identifying the most optimal future therapeutic strategies.