Short-Term Parafoveal Cone Loss Despite Preserved Ellipsoid Zone in Rod Cone Dystrophy

Abstract

Purpose Rod–cone dystrophy (RCD) is characterized by centripetal loss of rod followed by cone photoreceptors. In this prospective, observational cohort, we used flood-illumination adaptive optics (AO) imaging to investigate parafoveal cone loss in regions with preserved ellipsoid zone (EZ) in patients with RCD. Methods Eight patients with RCD and 10 age-matched healthy controls underwent spectral-domain optical coherence tomography and AO imaging. The RCD cohort underwent a follow-up examination after 6 months. Cone density (CD) and intercone distance (ICD) measurements were performed at 2° temporal from the fovea. Baseline CD and ICD values were compared between the control and patient groups, and longitudinal changes were calculated in the patient group. Residual EZ span in patients was measured in horizontal foveal B-scans. Results Between the control and patient groups, there was no significant difference in the baseline CD (2094 vs. 1750 cells/deg 2 , respectively; P = 0.09) and ICD (1.46 vs. 1.62 arcmin, respectively; P = 0.08). Mean CD declined by 198 cells/deg 2 (−11.3%; P < 0.01), and mean ICD increased by 0.09 arcmin (+5.6%; P = 0.01) at the 6-month follow-up in the patient group. Mean baseline and follow-up residual EZ spans in the six patients with EZ defect were 3189 µm and 3065 µm, respectively (−3.9%; P = 0.08). Conclusions AO imaging detected significant parafoveal cone loss over 6-month follow-up even in regions with preserved EZ. Further studies to refine AO imaging protocol and validate cone metrics as a structural endpoint in early RCD are warranted. Translational Relevance CD and ICD may change prior to EZ span shortening in RCD.

Microperimetry and Adaptive Optics Imaging Reveal Localized Functional and Structural Changes in Asymptomatic RPGR Mutation Carriers

“…AO imaging showed cone mosaic defects in asymptomatic patients with IRDs who had preserved retinal structure on SD-OCT and FAF. 17 , 18 RPGR carrier status is an example of retinal dystrophies associated with unremarkable retinal structure. 9 , 13 Kalitzeos and colleagues reported a significant (29.4%) reduction of cone density in TLR areas compared to areas unaffected by TLR using AOSLO in 7 RPGR mutation carriers.…”

“…AO imaging was performed using the rtx1 camera (Imagine Eyes, Orsay, France) with the protocol described before. 18 Briefly, 12 overlapping 4 degrees × 4 degrees image frames centered 2 degrees apart covering the central 6 degrees, focused at the photoreceptor level, were taken. Individual images were stitched together using MosaicJ plugin for ImageJ (Laboratory for Optical and Computational Instrumentation, Madison, WI, USA) and the resultant montage was overlaid on an IR image with marked foveal pit center ( Fig.…”

“… 16 Adaptive optics (AO) retinal imaging enables cone mosaic analysis at a cellular level which can provide additional structural information in patients with apparently preserved outer retinal layers on SD-OCT. We have previously shown that AO flood-illumination ophthalmoscopy can be used for diagnosing retinal dystrophy in asymptomatic patients and detecting disease progression in early-stage RP with preserved ellipsoid zone. 17 , 18 There are no reports of AO flood-illumination ophthalmoscopy findings in female RPGR carriers. In one study using an alternative imaging technique, AO scanning laser ophthalmoscopy (AOSLO) in female RPGR carriers ( N = 4) revealed cone density (CD) of >1 standard deviation (SD) lower than the normal average at 0.5 mm eccentricity, but not at 1.5 mm eccentricity.…”

Impact of Reference Center Choice on Adaptive Optics Imaging Cone Mosaic Analysis

“…Although this speculation cannot be supported by our MAIA 10-2 fixation data, we hypothesize that patients with RCD may tend to use more central fixation loci, as these loci are farthest from the affected perifoveal retina and the transitional zone. Additionally, compensatory hypersensitivity of the residual central foveal cones as a result of perifoveal cone loss in patients with RCD 23 may explain the dominance of central foveal fixation and deviation of the AMC toward the FPC. Increased visualization of foveal cones in flood-illumination AO imaging in patients with RCD has been reported in previous studies.…”

“…The clinical significance of any differences in cone metrics arising from the use of alternative reference coordinates also must be evaluated in the context of inter-observer variability (4%) 10 and the test–retest variability in both healthy and diseased eyes. 13 , 23 We recommend careful alignment of the AO montage with a FPC-marked en face fundus image derived from a registered SD-OCT scan to ensure precise and reproducible localization of the eccentricities and ROIs. However, our data suggest that, in the absence of en face images to enable alignment of anatomical landmarks, a precisely determined AMC can be used as a reference for retinal eccentricity, without a significant impact on cone metric analysis outcomes.…”