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.

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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.

Objectives To describe adverse events (AEs) and noteworthy clinical or ocular findings associated with retinopathy of prematurity (ROP) evaluation procedures. Study design Descriptive analysis of pre-defined AEs and noteworthy findings reported in a prospective observational cohort study of infants <1251 g birth weight (BW) who had ROP study visits consisting of both binocular indirect ophthalmoscopy (BIO) and digital retinal imaging. We compared infant characteristics during ROP visits with and without AEs. We compared respiratory support, nutrition, and number of apnea, bradycardia, or hypoxia events 12 hours before and after ROP visits. Results 1,257 infants, mean BW 802 g, had 4,263 BIO and 4,048 imaging sessions (total 8,311 procedures). No serious AEs were related to ROP visits. Sixty-five AEs were reported among 61 infants for an AE rate of 4.9% infants (61/1257) or 0.8% total procedures (65/8311 BIO + imaging). Most AEs were due to apnea, bradycardia, and/or hypoxia (68%), tachycardia (16%), or emesis (8%). At ROP visit, infants with AEs, compared with those without, were more likely to be on mechanical ventilation (26% versus 12%, p=0.04) even after adjustment for weight and PMA. Noteworthy clinical findings were reported during 8% BIO and 15% imaging exams. Respiratory and nutrition support were not significantly different before and after ROP evaluations. Conclusions Retinal imaging by non-physicians combined with BIO was safe. Noteworthy clinical findings occurred during both procedures. Ventilator support was a risk factor for AEs. Monitoring rates of AEs and noteworthy findings are important to the safe implementation of ROP imaging protocols. Trial registration Clinicaltrials.gov: NCT01264276