Purpose To describe in detail the central retinal structure of a large group of patients with Choroideremia (CHM). Design prospective, cross-sectional, descriptive study. Subjects Patients (n=97, age 6-71 years) with CHM and subjects with normal vision (n=44; ages 10-50 years) were included. Methods Subjects were examined with spectral domain optical coherence tomography (SD-OCT) and near infrared reflectance imaging. Visual acuity (VA) was measured during their encounter or obtained from recent ophthalmic examinations. Visual thresholds were measured in a subset of patients (n=24) with automated static perimetry within the central regions (±15°) examined with SD-OCT. Main outcome measures VA and visual thresholds, total, inner and outer nuclear layer (ONL) thicknesses, and the horizontal extent of the ONL and of the photoreceptor outer segment (POS) interdigitation zone. Results Earliest abnormalities in regions with normally appearing RPE were the loss of the POS and EZ zone associated with rod dysfunction. Transition zones (TZs) from relatively preserved retina to severe ONL thinning and inner retinal thickening moved centripetally with age. Most patients (88%) retained VAs better than 20/40 until their fifth decade of life. VA decline coincided with migration of the TZ near the foveal center. There were outer retinal tubulations in degenerated, non-atrophic retina in the majority (69%) of patients. In general, retinal pigment epithelium (RPE) abnormalities paralleled photoreceptor degeneration, although there were regions with detectable but abnormally thin ONL co-localizing with severe RPE depigmentation and choroidal thinning. Conclusions Abnormalities of the POS and rod dysfunction are the earliest central abnormalities observed in CHM. Foveal function is relatively preserved until late disease. TZ migration to the foveal center with foveal thinning and structural disorganization heralded central VA loss. The relationships established may help outline the eligibility criteria and outcome measures for clinical trials for CHM.

PURPOSE. To describe the retinal phenotype of pediatric patients with mutations in the retinol dehydrogenase 12 (RDH12) gene. METHODS. Twenty-one patients from 14 families (ages 2-17 years) with RDH12-associated inherited retinal degeneration (RDH12-IRD) underwent a complete ophthalmic exam and imaging with spectral domain optical coherence tomography (SD-OCT) and near infrared and short-wavelength fundus autofluorescence. Visual field extent was measured with Goldmann kinetic perimetry, visual thresholds with dark-adapted static perimetry or with dark-adapted chromatic full-field stimulus testing (FST) and transient pupillometry. RESULTS. Visual acuity ranged from 20/40 to light perception. There was parafoveal depigmentation or atrophic maculopathies accompanied by midperipheral intraretinal pigment migration. SD-OCT revealed foveal thinning in all patients and detectable but thinned outer nuclear layer (ONL) at greater eccentricities from the fovea. Photoreceptor outer segment (POS) signals were only detectable in small pockets within the central retina. Measurable kinetic visual fields were limited to small (<5-108) central islands of vision. Electroretinograms were reported as undetectable or severely reduced in amplitude. FST sensitivities to a 467 nm stimulus were rod-mediated and reduced on average by~2.5 log units. A thinned central ONL colocalized with severely reduced to nondetectable conemediated sensitivities. Pupillometry confirmed the psychophysically measured abnormalities. CONCLUSIONS. RDH12-IRD causes an early-onset, retina-wide disease with particularly severe central retinal abnormalities associated with relatively less severe rod photoreceptor dysfunction, a pattern consistent with an early-onset cone-rod dystrophy. Severely abnormal POS but detectable ONL in the pericentral and peripapillary retina suggest these regions may become targets for gene therapy.

Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC.