Correlation Between Localized Choriocapillaris Perfusion and Macular Function in Eyes with Geographic Atrophy.

PURPOSE: To test the hypothesis that choriocapillaris perfusion correlates with visual function in geographic atrophy (GA). DESIGN: Cross-sectional, single-center study. METHODS: We imaged choriocapillaris flow using 6 × 6-mm swept-source optical coherence tomography angiography scans and measured retinal sensitivity using fundus-guided microperimetry in the central 20° in 18 eyes of 12 patients with GA and 7 eyes of 4 healthy persons. Optical coherence tomography angiography scans were divided into a grid and microperimetry results were superimposed using retinal vascular landmarks. The main outcome measure correlated choriocapillaris flow deficit with retinal sensitivity at each localized region. Robust linear mixed effects regression compared flow deficit or sensitivity with distance from the fovea. The Pearson r correlation described the relationship between flow deficit or retinal sensitivity and distance from the GA border. RESULTS: Choriocapillaris flow deficit was significantly greater in patients with GA than in healthy persons (mean ± SD: 24.2% ± 7.9% vs 7.9% ± 2.3%; P = .0015) and retinal sensitivity was significantly lower in patients with GA than in healthy persons (mean difference ± SD: -17.0 ± 1.2 dB; P < .001). In GA, choriocapillaris flow deficit decreased (r = -0.40; 95% CI: -0.54 to -0.27) and retinal sensitivity increased (r = +0.63; 95% CI: 0.30 to 0.81) with distance from the GA margin. Choriocapillaris flow deficits inversely correlated with retinal sensitivity (r = -0.61; 95% CI: -0.75 to -0.42). CONCLUSIONS: Choriocapillaris flow and retinal sensitivity improved with distance from the GA margin. Choriocapillaris flow deficit was inversely correlated with sensitivity, supporting the hypothesis that choriocapillaris perfusion correlated with macular function.

OCT Angiography to Predict Geographic Atrophy Progression using Choriocapillaris Flow Void as a Biomarker.

Purpose: To investigate the relationship between choriocapillaris (CC) flow void (FV) percentage and geographic atrophy (GA) growth rate, and study how variations in FV percentage surrounding GA predict regional GA growth. Methods: This prospective, longitudinal study enrolled subjects with GA secondary to nonexudative age-related macular degeneration. Optical coherence tomography angiography imaged the CC and FV percentage was evaluated using a validated algorithm. GA growth rate was measured as the difference in the square root of GA area divided by the months between baseline and follow-up imaging. Results: Twelve eyes from 7 subjects with a mean age of 80 ± 5 years (range 74-86) were studied once at baseline and 7 to 16 months later. GA expansion rate was positively correlated with increased CC FV percentage (Spearman rank correlation coefficient r = 0.69 [P = 0.038] and 0.76 [P = 0.013]) within the 6 x 6 mm scanned macular region and the 2° margin surrounding each GA lesion, respectively. Regions with CC FV at baseline located within 480 µm from the GA margin showed 33% greater chance of becoming atrophic compared with regions within 480 µm from the GA margin that did not show CC FV at baseline. Conclusions: GA expansion rate and CC FV density throughout the macular region and surrounding the GA margin were significantly correlated. The regional magnitude of FV immediately surrounding GA was associated with GA growth into that region. Translational Relevance: CC FV analysis may facilitate prediction of GA growth over time for patients with advanced nonneovascular age-related macular degeneration.

Anesthesia for Intravitreal Injection: A Systematic Review.

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.

Cone Structure Persists Beyond Margins of Short-Wavelength Autofluorescence in Choroideremia.

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 -2° of the preserved area to +2° 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.

Quantifying choriocapillaris hypoperfusion in patients with choroidal neovascularization using swept-source OCT angiography.

PURPOSE: To compare choriocapillaris flow voids (FV) in patients with neovascular age-related macular degeneration (AMD) with age-matched normal controls using swept-source optical coherence tomography angiography (SS-OCTA). PATIENTS AND METHODS: Eleven eyes of 11 subjects with neovascular AMD and 11 eyes of 11 age-similar normal subjects were imaged using SS-OCTA with a 6x6mm scanning pattern. Choriocapillaris FV, defined as a percentage of regions determined to have flow deficits divided by the total scanned region, was measured using a one standard deviation thresholding algorithm developed from a database of age-similar normal subjects. RESULTS: Choriocapillaris FV was more extensive in patients with choroidal neovascularization (CNV) compared to age-similar normal subjects (FV: 20.56±4.95, 95% CI: 17.64-23.49 vs FV: 10.95±2.08, 95% CI: 9.73-12.18, respectively; P=0.0001). FV within a two-degree margin surrounding CNV in wet AMD subjects (FV: 35.04±9.34; 95% CI: 29.52-40.56) was increased compared to normal subjects (P<0.001). FV of the region outside the two-degree margin surrounding CNV (FV: 19.61±6.08, 95% CI: 16.02-23.20) was increased compared to age-similar controls (P=0.0002). In neovascular AMD eyes, FV was greater within two degrees of the margin of CNV than in the remainder of the macula (margin: 35.04±9.34; outside: 19.61±6.08; P=0.002), and CNV lesion area was positively correlated with FV (correlation coefficient =0.84; 95% CI: 0.49-0.96; P=0.001). CONCLUSION: Choriocapillaris flow deficits were significantly greater in wet AMD subjects than age-similar normal subjects, suggesting that choroidal hypo-perfusion likely plays a role in the pathogenesis of neovascular AMD. Recognition of choriocapillaris flow deficits in patients with AMD may facilitate earlier diagnosis and identify alternative therapeutic targets for this multifactorial disease.

Quantifying Choriocapillaris Flow Voids in Patients With Geographic Atrophy Using Swept-Source OCT Angiography.

BACKGROUND AND OBJECTIVE: To compare choriocapillaris (CC) flow voids (FVs) throughout the macula in patients with age-related macular degeneration (AMD) and geographic atrophy (GA) to age-similar controls using swept-source optical coherence tomography angiography (SS-OCTA). PATIENTS AND METHODS: In this cross-sectional study, 12 subjects with GA secondary to nonexudative AMD and 12 age-similar controls participated. SS-OCTA was performed using a 6 mm × 6 mm scanning pattern. CC FVs were calculated using a one-standard deviation thresholding method developed from a normal database. RESULTS: CC FVs were significantly increased in patients with GA compared with age-similar controls (P < .001). FVs within 2° of GA were significantly increased compared with the area outside 2° (P < .001). FVs beyond 2° of GA were significantly increased compared with age-similar controls (P < .001). CONCLUSIONS: FV analysis of in vivo CC images revealed diffuse CC perfusion deficits throughout the macular region in subjects with GA secondary to nonexudative AMD. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e229-e235.].

Loss of Foveal Cone Structure Precedes Loss of Visual Acuity in Patients With Rod-Cone Degeneration.

Purpose: To assess the relationship between cone spacing and visual acuity in eyes with rod-cone 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 <0.25°) 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 (ρ = -0.47, 95%CI -0.67 to -0.24), logMAR (ρ = 0.46, 95%CI 0.24 to 0.66), and foveal sensitivity (ρ = -0.30, 95%CI -0.52 to -0.018). There was a small but significant increase in mean cone spacing Z-score during follow-up of +0.97 (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.

Cone Spacing Correlates With Retinal Thickness and Microperimetry in Patients With Inherited Retinal Degenerations.

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.

OCT Angiography and Cone Photoreceptor Imaging in Geographic Atrophy.

Purpose: To 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. Methods: Subjects 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). Results: Excluding 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. Conclusions: In 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.

High-resolution Imaging in Male Germ Cell-Associated Kinase (MAK)-related Retinal Degeneration.

PURPOSE: To describe the characteristics of MAK-related retinal degeneration using optical coherence tomography angiography (OCTA) and adaptive optics scanning laser ophthalmoscopy (AOSLO). DESIGN: Cross-sectional study. METHODS: Six patients with rod-cone degeneration and disease-causing mutations in MAK were evaluated with visual acuity, spectral-domain OCT, confocal AOSLO, and OCTA. Foveal avascular zone (FAZ) area, vessel densities, and perfusion densities of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in the central macula in all 6 patients were compared with 5 normal subjects. Cone spacing was measured in 4 patients from AOSLO images and compared with 37 normal subjects. RESULTS: Patients ranged from 25 to 81 years of age (mean, 52 years). Visual acuity varied from 20/13 to 20/40+2, except in 1 patient with cystoid macular edema whose vision was 20/60- and 20/70+1. The SCP (P = .012) and DCP (P = .013) vessel density and perfusion density (P =.015 and .013, respectively) were significantly lower in patients compared to normal subjects in the parafoveal region 1.0-3.0 mm from the fovea, but were similar to normal subjects within 1.0 mm of the fovea. The FAZ area was not significantly different from normal (all P ≥ .24). Cone spacing was normal at almost all locations in 2 patients with early disease and increased in 2 patients with advanced disease. CONCLUSIONS: Although retinal vascular densities are reduced and cone spacing is increased in advanced disease, central foveal structure is maintained until late stages of disease, which may contribute to preservation of foveal vision in eyes with MAK-related retinal degeneration.