High-resolution in vivo fundus angiography using a non-adaptive optics imaging system

Purpose: We provide a proof of concept for the detailed characterization of retinal capillary features and surrounding photoreceptor mosaic using a customized nonadaptive optics angiography imaging system. Methods: High-resolution fluorescein angiography (FFA) and/or indocyanine green angiography (ICGA) images were obtained using a modified Heidelberg retina angiograph (HRA2) device with a reduced scan angle enabling 3° field of view. Colocalized images of the photoreceptor mosaic also were captured in vivo using the same instrument. Visibility of vascular subbranches were compared between high-resolution images and conventional fundus angiography (FA) with a 30° field of view. Results: High-resolution angiographic and infrared images (3° × 3° field of view, a 10-fold magnification) were obtained in 10 participants. These included seven patients with various retinal diseases, including myopic degeneration, diabetic retinopathy, macular telangiectasia, and central serous chorioretinopathy, as well as three healthy controls. Images of the retinal vasculature down to the capillary level were obtained on angiography with the ability to visualize a mean 1.2 levels more subbranches compared to conventional FA. In addition, imaging of the photoreceptor cone mosaic, to a sufficient resolution to calculate cone density, was possible. Movement of blood cells within the vasculature also was discernible on infrared videography. Conclusions: This exploratory study demonstrates that fast high-resolution angiography and cone visualization is feasible using a commercially available imaging system. Translational Relevance: This offers potential to better understand the relationship between the retinal neurovascular system in health and disease and the timing of therapeutic interventions in disease states

Relationship between psychophysical measures of retinal ganglion cell density and in vivo measures of cone density in glaucoma

Purpose: Considerable between-individual variation in retinal ganglion cell (RGC) density exists in healthy individuals, making identification of change from normal to glaucoma difficult. In ascertaining local cone-to-RGC density ratios in healthy individuals, we wished to investigate the usefulness of objective cone density estimates as a surrogate of baseline RGC density in glaucoma patients, and thus a more efficient way of identifying early changes. Design: Exploratory cohort study. Participants: Twenty glaucoma patients (60% women) with a median age of 54 years and mean deviation (MD) in the visual field of –5 dB and 20 healthy controls (70% women) with a median age of 57 years and a mean MD of 0 dB were included. Methods: Glaucoma patients and healthy participants underwent in vivo cone imaging at 4 locations of 8.8° eccentricity with a modified Heidelberg Retina Angiograph HRA2 (scan angle, 3°). Cones were counted using an automated program. Retinal ganglion cell density was estimated at the same test locations from peripheral grating resolution acuity thresholds. Main Outcome Measures: Retinal cone density, estimated RGC density, and cone-to-RGC ratios in glaucoma patients and healthy controls. Results: Median cone-to-RGC density was 3.51:1 (interquartile range [IQR], 2.59:1–6.81:1) in glaucoma patients compared with 2.35:1 (IQR, 1.83:1–2.82:1) in healthy participants. Retinal ganglion cell density was 33% lower in glaucoma patients than in healthy participants; however, cone density was very similar in glaucoma patients (7248 cells/mm2) and healthy controls (7242 cells/mm2). The area under the receiver operator characteristic curve was 0.79 (95% confidence interval [CI], 0.71–0.86) for both RGC density and cone-to-RGC ratio and 0.49 (95% CI, 0.39–0.58) for cone density. Conclusions: Local measurements of cone density do not differ significantly from normal in glaucoma patients despite large differences in RGC density. There was no statistically significant association between RGC density and cone density in the normal participants, and the range of cone-to-RGC density ratios was relatively large in healthy controls. These findings suggest that estimates of baseline RGC density from cone density are unlikely to be precise and offer little advantage over determination of RGC alone in the identification of early glaucomatous change

Ageing changes in retinal outer nuclear layer thickness and cone photoreceptor density using adaptive optics-free imaging

Purpose: To investigate age-related changes of the outer nuclear layer (ONL) thickness and cone density, and their associations in healthy participants using a modified, narrow scan-angle Heidelberg Retina Angiograph (HRA2). Methods: Retinal cones were imaged outside the fovea at 8.8° eccentricity and cone density was compared to ONL thickness measurements obtained by Spectral-Domain Optical Coherence Tomography (SD-OCT) at the same locations. Fifty-six eyes of 56 healthy participants with a median age (interquartile range, IQR) of 37 years (29–55) were included. Results: Median (IQR) cone count was 7,472 (7,188, 7,746) cones/mm2 and median (IQR) ONL thickness was 56 (52, 60) µm for healthy participants. Both cone density and ONL thickness were negatively associated with age: cone density, R2 = 0.16 (F(1,54) = 10.41, P = 0.002); ONL thickness, R2 = 0.12 (F(1,54) = 7.41, P = 0.009). No significant association was seen between cone density and ONL thickness (R2 = 0.03; F(1,54) = 1.66, P = 0.20). Conclusion: Cone density was lower, and ONL thinner, in older compared to younger participants, therefore, image-based structural measures should be compared to age-related data. However, cone density and ONL thickness were not strongly associated, indicating that determinants of ONL thickness measurements other than cone density measurements, and including measurement error, have a major influence