SD-OCT provides a non-invasive method of following long-term retinal changes in mice in vivo. Although rd10 and rd1 mice have mutations in the same gene, they demonstrate significantly different features on SD-OCT.

PURPOSE. To describe a standardized flood-illuminated adaptive optics (AO) imaging protocol suitable for the clinical setting and to assess sampling methods for measuring cone density.METHODS. Cone density was calculated following three measurement protocols: 50 3 50-lm sampling window values every 0.58 along the horizontal and vertical meridians (fixed-interval method), the mean density of expanding 0.58-wide arcuate areas in the nasal, temporal, superior, and inferior quadrants (arcuate mean method), and the peak cone density of a 50 3 50-lm sampling window within expanding arcuate areas near the meridian (peak density method). Repeated imaging was performed in nine subjects to determine intersession repeatability of cone density. RESULTS.Cone density montages could be created for 67 of the 74 subjects. Image quality was determined to be adequate for automated cone counting for 35 (52%) of the 67 subjects. We found that cone density varied with different sampling methods and regions tested. In the nasal and temporal quadrants, peak density most closely resembled histological data, whereas the arcuate mean and fixed-interval methods tended to underestimate the density compared with histological data. However, in the inferior and superior quadrants, arcuate mean and fixed-interval methods most closely matched histological data, whereas the peak density method overestimated cone density compared with histological data. Intersession repeatability testing showed that repeatability was greatest when sampling by arcuate mean and lowest when sampling by fixed interval. CONCLUSIONS.We show that different methods of sampling can significantly affect cone density measurements. Therefore, care must be taken when interpreting cone density results, even in a normal population.

IMPORTANCE While older children and adults with achromatopsia have been studied, less is known of young children with achromatopsia.OBJECTIVES To characterize the macular and foveal architecture of patients with achromatopsia during early childhood with handheld spectral-domain optical coherence tomographic imaging and to make phenotype-genotype correlations.DESIGN, SETTING, AND PARTICIPANTS Comparative case series of 9 patients with achromatopsia and 9 age-matched control participants at a tertiary ophthalmology referral center.MAIN OUTCOMES AND MEASURES Patients underwent complete ocular examination, full-field electroretinography, handheld spectral-domain optical coherence tomographic imaging, and screening for genetic mutations. RESULTSThe mean (SD) age of the patients with achromatopsia was 4.2 (2.4) years, and the mean (SD) age of the control participants was 4.0 (2.1) years. Cone-driven responses to photopic single-flash or 30-Hz stimuli were nonrecordable in 7 patients and severely attenuated in 2. Rod-driven responses to dim scotopic single-flash stimuli were normal in 7 patients and mildly subnormal in 2. Six patients (67%) had foveal ellipsoid zone disruption, of which 1 had a hyporeflective zone. Four patients (44%) had foveal hypoplasia. The average total retinal thicknesses of the macula and fovea in the patients with achromatopsia were 14% and 17% thinner than in the control participants (P < .001 and P = .001), which was mostly due to the outer retina that was 18% and 26% thinner than in control participants (both P < .001), respectively. Genetic testing revealed a common homozygous mutation in CNGB3 in 5 patients with complete achromatopsia and heterozygous mutations in CNGA3 in 2 patients with incomplete achromatopsia. The youngest and worst-affected patient harbored compound heterozygous mutations in CNGB3 and a single mutation in CNGA3. CONCLUSIONS AND RELEVANCEIn early childhood, there is a spectrum of foveal pathology that is milder than reported in older individuals with achromatopsia, which suggests the need for early therapeutic intervention. Neither age alone nor genotype alone predicts the degree of photoreceptor loss or preservation. Thus, in anticipation of future gene therapy trials in humans, we propose that handheld spectral-domain optical coherence tomography is an important tool for the early assessment and stratification of macular architecture in young children with achromatopsia.

The aim of this study was to assess the feasibility of using a commercially available high-resolution adaptive optics (AO) camera to image the cone mosaic in Japanese macaques (Macaca fuscata) with dominantly inherited drusen. The macaques examined develop drusen closely resembling those seen in humans with age-related macular degeneration (AMD). For each animal, we acquired and processed images from the AO camera, montaged the results into a composite image, applied custom cone-counting software to detect individual cone photoreceptors, and created a cone density map of the macular region. We conclude that flood-illuminated AO provides a promising method of visualizing the cone mosaic in nonhuman primates. Future studies will quantify the longitudinal change in the cone mosaic and its relationship to the severity of drusen in these animals.