Abstract
Purpose
Fundus albipunctatus is an inherited cause of congenital stationary night blindness. The objective of this report is to describe structural changes occurring in a macular phenotype of a novel RDH5 mutation producing fundus albipunctatus using high-resolution in vivo imaging. A 62-year-old male with longstanding night blindness underwent imaging and genetic evaluation. High-resolution images of the photoreceptor mosaic were compared to those of a healthy subject. Results of a comprehensive ophthalmic evaluation and genetic testing with imaging including fundus photography, spectral-domain optical coherence tomography (OCT), fluorescein angiography (FA), OCT angiography (OCT-A), and adaptive optics scanning light ophthalmoscopy (AOSLO) are described.
Observations
The patient presented with visual acuity of 20/25 in both eyes and longstanding poor dark adaptation. Anterior segment examination was unremarkable. Fundoscopy revealed well circumscribed bilateral perifoveal mottling and atrophy in both eyes. Discrete white-yellow flecks were present beyond the vascular arcades extending to the far periphery. Genetic testing revealed a novel compound heterozygous RDH5 mutation (c.388C > T, p.Gln130*; c.665T > C, p.Leu222Pro). OCT demonstrated perifoveal photoreceptor and outer retinal irregularities, which corresponded to a window defect with late staining on FA. OCT-A demonstrated normal retinal vasculature with patchy areas of non-perfusion in the choriocapillaris. Macular abnormalities in both eyes were imaged using AOSLO to assess cone and rod photoreceptor architecture. While clinical features are consistent with a primary rod disorder, confocal AOSLO showed a paucity of normal cones with a small spared central island in both eyes. Rods appeared larger and more irregular throughout the macula. Non-confocal split detection AOSLO imaging revealed the presence of cone inner segments in dark regions of confocal imaging, indicating some degree of photoreceptor preservation.
Conclusions and Importance
The AOSLO imaging of this particular macular phenotype of fundus albipunctatus demonstrates some of the structural photoreceptor abnormalities that occur in this condition, adding insight to the variable presentation of RDH5 retinopathy. The presence of preserved inner segment architecture suggests the possibility that gene therapy could play a future role in treating this condition.
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Introduction
Fundus albipunctatus is an autosomal recessive form of congenital stationary night blindness associated with 11- cis retinol dehydrogenase (RDH5) gene mutations. While phenotypic variability exists, the condition typically presents with numerous discrete white-yellow flecks in the retinal periphery, which vary in shape and density among patients and according to age. , Classic descriptions include normal visual acuity, visual fields, and color vision, with a stationary component of impaired scotopic vision that improves following prolonged dark adaptation. More recent reports describe variable macular dysfunction and cone dystrophy in older patients. Physiologic studies have characterized these photopic abnormalities, while very few investigations have examined the structural details of photoreceptors in patients with significant maculopathy. This report describes the findings of in-vivo high-resolution imaging of the photoreceptor changes in fundus albipunctatus with macular dystrophy, which include a degree of structural preservation revealed by AOSLO.
1.1
Case report
A 62-year-old male presented with longstanding poor night vision, beginning around 8 years of age, and stable visual acuity with little symptomatic progression over many years. On the basis of the clinical appearance, the patient carried a diagnosis of Stargardt’s disease without confirmatory genetic testing. He had no other past ocular or surgical history, denied any family history or use of any medications associated with ocular toxicity. His only past medical history included mild peripheral arterial disease. Review of systems was unremarkable for any systemic complaints.
Visual acuity was 20/25 in each eye. Pupillary examination and intraocular pressures were within normal limits. Ishihara color testing was reduced to six of 12 correct plates in each eye. The anterior segment was notable for mild nuclear sclerotic cataracts in both eyes. Fundoscopic examination revealed a clear vitreous with normal optic nerves and vasculature. In both eyes, there was a flat and well circumscribed area of perifoveal atrophy with retinal pigment epithelial (RPE) mottling ( Fig. 1 A). Discrete white-yellow flecks without areas of confluence were present peripheral to the vascular arcades, most dense in the mid peripheral retina ( Fig. 1 B). OCT revealed apparent elongation and splitting of the photoreceptors in areas of separation from the RPE, which itself had small variations in thickness and reflectance in the central macula, while the remaining inner retinal layers appeared normal ( Fig. 1 C). In the early phases of FA, hyperfluorescent areas appeared in the macula, which stained in later frames, corresponding to the atrophic bull’s eye pattern visible on fundoscopy ( Fig. 1 D). A granular staining was seen in the peripheral retina which appeared to coincide with retinal flecks. A 24–2 white stimulus III Humphrey visual field demonstrated bilateral central scotomas with intact foveal fixation. OCT-A confirmed normal retinal vasculature ( Fig. 2 A–C), with the exception of patchy areas of non-perfusion at the level of the choriocapillaris ( Fig. 2 D). Genetic testing (Spark Therapeutics, Inherited Retinal Disease Panel, Philadelphia, PA, USA), revealed a novel compound heterozygous RDH5 mutation (c.388C > T, p.Gln130*; c.665T > C, p.Leu222Pro), consistent with a diagnosis of autosomal recessive fundus albipunctatus.
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