Purpose To determine whether high-resolution retinal imaging measures of macular structure correlate with visual function over 36 months in retinal degeneration (RD) patients and normal subjects. Methods Twenty-six eyes of 16 RD patients and 16 eyes of 8 normal subjects were studied at baseline; 15 eyes (14 RD) and 11 eyes (6 normal) were studied 36 months later. Adaptive Optics Scanning Laser Ophthalmoscopy (AOSLO) was used to identify regions of interest (ROIs) with unambiguous cones at baseline to measure cone spacing. AOSLO images were aligned with spectral-domain optical coherence tomography (SD-OCT) and fundus-guided microperimetry results to correlate structure and function at the ROIs. SD-OCT images were segmented to measure inner segment (IS) and outer segment (OS) thickness. Correlations between cone spacing, IS and OS thickness and sensitivity were assessed using Spearman correlation coefficient ρ with bootstrap analyses clustered by person. Results Cone spacing (ρ = 0.57, P < 0.001) and macular sensitivity (ρ = 0.19, P = 0.14) were significantly correlated with eccentricity in patients. Controlling for eccentricity, cone spacing Z-scores were inversely correlated with IS (ρ = −0.29, P = 0.002) and OS thickness (ρ = −0.39, P < 0.001) in RD patients only, and with sensitivity in normal subjects (ρ = −0.22, P < 0.001) and RD patients (ρ = −0.38, P < 0.001). After 36 months, cone spacing increased ( P < 0.001) and macular sensitivity decreased ( P = 0.007) compared to baseline in RD patients. Conclusions Cone spacing increased and macular sensitivity declined significantly in RD patients over 36 months. High resolution images of cone structure correlated with retinal sensitivity, and may be appropriate outcome measures for clinical trials in RD.

Citation: Foote KG, Rinella N, Tang J, et al. Cone structure persists beyond margins of short-wavelength autofluorescence in choroideremia. Invest Ophthalmol Vis Sci. 2019;60:4931-4942. https://doi.org/10.1167/ iovs.19-27979 PURPOSE. We studied the relationship between structure and function of the choriocapillaris (CC), retinal pigment epithelium (RPE), and photoreceptors in patients with choroideremia (CHM). METHODS.Six CHM patients (12 eyes) and four normal subjects (six eyes) were studied with fundus-guided microperimetry, confocal and nonconfocal adaptive optics scanning laser ophthalmoscopy (AOSLO), near-infrared and color fundus photos, short wavelength fundus autofluorescence (SW-AF), and swept-source optical coherence tomography (SS-OCT) and angiography (SS-OCTA) images. Cone spacing was represented using Z-scores (standard deviations from the mean at that eccentricity). CC flow voids were defined using a threshold of 1 SD below the normal mean. RESULTS.Cone spacing Z-scores were not significantly correlated with distance from the borders of preserved RPE, determined using either the SS-OCT or SW-AF scans. Cone spacing Z-scores were significantly correlated with CC flow voids and retinal sensitivity. Flow voids were abnormal in regions of preserved RPE and increased progressively from within À28 of the preserved area to þ28 beyond the border. Visual sensitivity decreased as CC flow voids increased approaching and beyond the border of preserved structure. CONCLUSIONS.In CHM, cone spacing Z-scores correlated with CC flow voids, and were negatively correlated with retinal sensitivity, suggesting cone degeneration accompanied reduced CC perfusion. Functional cones were found outside the presumed borders of preserved outer-retina/RPE as defined by SW-AF, but not outside the borders determined by SS-OCT. The use of SW-AF to identify the border of preserved structures may underestimate regions with cells that may be amenable to treatment.

PURPOSE. To assess the relationship between cone spacing and visual acuity in eyes with rodcone degeneration (RCD) followed longitudinally. METHODS. High-resolution images of the retina were obtained using adaptive optics scanning laser ophthalmoscopy from 13 eyes of nine RCD patients and 13 eyes of eight healthy subjects at two sessions separated by 10 or more months (mean 765 days, range 311-1935 days). Cone spacing Z-score measured as close as possible (average <0.258) to the preferred retinal locus was compared with visual acuity (letters read on the Early Treatment of Diabetic Retinopathy Study [ETDRS] chart and logMAR) and foveal sensitivity. RESULTS. Cone spacing was significantly correlated with ETDRS letters read (q ¼ À0.47, 95%CI À0.67 to À0.24), logMAR (q ¼ 0.46, 95%CI 0.24 to 0.66), and foveal sensitivity (q ¼ À0.30, 95%CI À0.52 to À0.018). There was a small but significant increase in mean cone spacing Z-score during follow-up of þ0.97 (95%CI 0.57 to 1.4) in RCD patients, but not in healthy eyes, and there was no significant change in any measure of visual acuity. CONCLUSIONS. Cone spacing was correlated with visual acuity and foveal sensitivity. In RCD patients, cone spacing increased during follow-up, while visual acuity did not change significantly. Cone spacing Z-score may be a more sensitive measure of cone loss at the fovea than visual acuity in patients with RCD.

PurposeTo compare cone spacing and choriocapillaris (CC) perfusion adjacent to geographic atrophy (GA) in patients with age-related macular degeneration (AMD) and age-similar normal eyes.MethodsSubjects were imaged using adaptive optics scanning laser ophthalmoscopy (AOSLO), fundus autofluorescence (FAF), and swept-source optical coherence tomography angiography. The GA border was identified using FAF images; CC flow void was analyzed in 1° regions extending from the GA border. A grader masked to CC perfusion selected regions of interest (ROIs) with unambiguous cone mosaics in AOSLO images. At each ROI, cone spacing and CC flow void were converted to Z-scores (standard deviations from the mean of 12 normal eyes aged 50 to 81 years for cone spacing, and 60 normal eyes age 51 to 88 years for CC flow void).ResultsExcluding regions of GA and drusen, CC flow void in eight eyes of six patients with AMD was significantly greater than in four age-similar normal eyes (exact permutation test, P = 0.024). CC flow void was negatively correlated with distance from the GA margin (r = −0.35; 95% confidence interval [CI], −0.53 to −0.12). Increased cone spacing was significantly correlated with CC flow void (r = 0.33; 95% CI, 0.12 to 0.59). Cone spacing was increased in 39% of ROIs, while CC flow void was increased in 96% of ROIs.ConclusionsIn eyes with GA due to AMD, CC hypoperfusion was significantly correlated with, and more extensive than, cone photoreceptor loss. The results suggest that reduced CC perfusion contributes to the development of GA.

Background: The intravitreal injection has become one of the most commonly performed procedures in ophthalmology; however, there is no standardized approach to anesthesia during the procedure. The goal of this systematic review is to review approaches to anesthesia for intravitreal injection and look at comparative efficacy between these different anesthetics. Methods: A systematic review of literature was performed in the MEDLINE, PubMed, Cochrane Library, and Clinicaltrials.gov databases using the key words "anesthesia", "pain management", and "intravitreal injection". Of the initial 239 search matches, 30 articles were found to be relevant to the topic. 18 studies were excluded as they did not include primary data or did not include the visual analog scale as a primary outcome. The remaining 12 articles were assessed to look at the comparative efficacy of anesthesia and adverse events. Results: The anesthesia techniques reported include topical methods such as anesthetic eyedrops, anesthetic gels, and anesthetic-soaked pledgets as well as subconjunctival injection of anesthetic. Ultimately, no single anesthetic or delivery mechanism was shown to be superior to the others in a statistically significant way and adverse events were largely insignificant. Limitations of these studies include relatively small sizes of the studies, as well as the lack of masking which may introduce bias. Conclusion: In the current literature, no type of anesthetic method was found to be superior to another for intravitreal injection. Future studies in this area may lead to new insights into the efficacy of different forms of intravitreal anesthesia.