Association of Lesion Location and Functional Parameters with Vision-Related Quality of Life in Geographic Atrophy Secondary to Age-related Macular Degeneration.

OBJECTIVE: The primary goal of this study was to determine how structural and functional parameters influence the vision-related quality of life (VRQoL) in patients suffering from geographic atrophy (GA) secondary to age-related macular degeneration. DESIGN: This study was designed as a prospective, noninterventional, natural-history study (Directional Spread in Geographic-Atrophy study, NCT02051998). SUBJECTS: The research involved 82 patients with bilateral GA. METHODS: The study examined parameters including GA location as assessed by the ETDRS grid, best-corrected visual acuity, low-luminance visual acuity (LLVA), reading acuity, and speed. These parameters were then correlated with VRQoL, which was gauged using the National Eye Institute Visual Function Questionnaire 25. The analysis method employed was the least absolute shrinkage and selection operator with linear mixed-effects models. MAIN OUTCOME MEASURES: The central parameters measured in this study encompassed GA area, VRQoL scores associated with different GA subfields, and the significance of LLVA for foveal-sparing patients. RESULTS: On average, patients showed a total GA area of 2.9 ± 1.2 mm2 in the better eye (BE) and 3.1 ± 1.3 mm2 in the worse eye. The most significant associations with VRQoL scores for distance and near activities were observed in the inner lower and inner left subfields of the BE, respectively. For patients with foveal-sparing GA, the LLVA of the BE stood out as the most influential variable across all VRQoL scales. CONCLUSIONS: The study's findings point toward the pivotal role of GA location, especially the inner lower and inner left subfields of the BE, in relation to VRQoL in GA patients. The LLVA's importance becomes even more pronounced for foveal-sparing patients. These observations highlight the need for health care professionals to better understand the association between lesion location and patient-reported outcomes. This is critical for informing treatment decisions and refining the planning of interventional trials. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Impact of lesion location and functional parameters on vision-related quality of life in geographic atrophy secondary to AMD.

Background/Aims: The primary objective was to determine how structural and functional parameters influence the vision-related quality of life (VRQoL) in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Methods: This prospective, non-interventional, natural-history 'Directional Spread in Geographic-Atrophy' study was conducted at the University Eye Hospital in Bonn, enrolling 82 patients with bilateral GA. Parameters such as GA location (assessed by the Early Treatment Diabetic Retinopathy Study grid), best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), reading acuity, and speed were examined. The association between these parameters and VRQoL, as gauged using the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25), was analyzed through least absolute shrinkage and selection operator with linear mixed-effects models. Results: The average total GA area observed was 2.9 ± 1.2 mm2 (better eye) and 3.1 ± 1.3 mm2 (worse eye). The VRQoL scores for distance and near activities were most associated with the inner lower and inner left subfields of the better eye. For foveal-sparing patients, the LLVA of the better eye was the predominant determinate impacting all VRQoL scales. Conclusion: GA location, specifically the inner lower and inner left subfields of the better eye, has a notable effect on VRQoL in GA patients. LLVA stands out as especially vital in foveal-sparing patients, underscoring the importance for clinicians to incorporate considerations of GA location and functional parameters into their risk-benefit assessments for emerging treatments.

Repeatability of Quantitative Autofluorescence Imaging in a Multicenter Study Involving Patients With Recessive Stargardt Disease 1.

Purpose: This study assesses the repeatability of quantitative autofluorescence (qAF) in a multicenter setting and evaluates qAF as the end point for clinical trials in recessive Stargardt disease 1 (STGD1). Methods: A total of 102 patients with STGD1 underwent qAF imaging as part of the Stargardt Remofuscin Treatment Trial (STARTT; EudraCT No. 2018-001496-20). For 166 eyes, we obtained qAF imaging at 2 visits, with 2 recordings per visit. The qAF8 values were independently determined by the study site and a central reading center. Intra- and inter-visit reproducibility, as well as interobserver (study site versus reading center) reproducibility were obtained using intraclass correlation (ICC), one-sample t-test, and Bland-Altman coefficient of repeatability. Results: The qAF repeatability was ± 26.1% for intra-visit, ± 40.5% for inter-visit, and ± 20.2% for the interobserver reproducibility measures. Intra-visit repeatability was good to excellent for all sites (ICC of 0.88-0.96). Variability between visits was higher with an overall ICC of 0.76 (0.69-0.81). We observed no significant difference in qAF values across sites between visits (7.06 ± 93.33, P = 0.238). Conclusions: Real-life test-retest variability of qAF is higher in this set of data than previously reported in single center settings. With improved operator training and by selecting the better of two recordings for evaluation, qAF serves as a useful method for assessing changes in autofluorescence signal. Translational Relevance: The qAF can be adopted as a clinical trial end point, but steps to counterbalance variability should be considered.

Association of Reading Performance in Geographic Atrophy Secondary to Age-Related Macular Degeneration With Visual Function and Structural Biomarkers.

IMPORTANCE: As a disabling and frequent disease, geographic atrophy secondary to age-related macular degeneration (AMD) constitutes an important study subject. Emerging clinical trials require suitable end points. The characterization and validation of reading performance as a functional outcome parameter is warranted. OBJECTIVE: To prospectively evaluate reading performance in geographic atrophy and to assess its association with established visual function assessments and structural biomarkers. DESIGN, SETTING, AND PARTICIPANTS: The noninterventional, prospective natural history Directional Spread in Geographic Atrophy study included patients with geographic atrophy secondary to AMD who were recruited at the University Hospital in Bonn, Germany. Participants were enrolled from June 2013 to June 2016. Analysis began December 2019 and ended January 2021. MAIN OUTCOMES AND MEASURES: Reading acuity and reading speed were assessed using Radner charts. Longitudinal fundus autofluorescence and infrared reflectance images were semiautomatically annotated for geographic atrophy, followed by extraction of shape-descriptive variables. Linear mixed-effects models were applied to investigate the association of those variables with reading performance. RESULTS: A total of 150 eyes of 85 participants were included in this study (median [IQR] age, 77.9 [72.4-82.1] years; 51 women [60%]; 34 men [40%]). Reading performance was impaired with a median (IQR) monocular reading acuity of 0.9 (0.4-1.3) logarithm of the reading acuity determination and a reading speed of 52.8 (0-123) words per minute. In the multivariable cross-sectional analysis, best-corrected visual acuity, area of geographic atrophy in the central Early Treatment Diabetic Retinopathy Study (ETDRS) subfield, classification of noncenter vs center-involving geographic atrophy, and area of geographic atrophy in the inner-right ETDRS subfield showed strongest associations with reading acuity (cross-validated R2for reading acuity = 0.69). Regarding reading speed, the most relevant variables were best-corrected visual acuity, low-luminance visual acuity, area of geographic atrophy in the central ETDRS subfield, in the inner-right ETDRS subfield, and in the inner-upper ETDRS subfield (R2 for reading speed = 0.67). In the longitudinal analysis, a similar prediction accuracy for reading performance was determined (R2 for reading acuity = 0.73; R2 for reading speed = 0.70). Prediction accuracy did not improve when follow-up time was added as an independent variable. Binocular reading performance did not differ from reading performance in the better-seeing eye. CONCLUSIONS AND RELEVANCE: The association of reading acuity and speed with visual functional and structural biomarkers supports the validity of reading performance as a meaningful end point in clinical trials. These findings suggest that measures in clinical and low-vision care for patients with geographic atrophy should focus primarily on the better-seeing eye.

The STArgardt Remofuscin Treatment Trial (STARTT): design and baseline characteristics of enrolled Stargardt patients.

Background: This report describes the study design and baseline characteristics of patients with Stargardt disease (STGD1) enrolled in the STArgardt Remofuscin Treatment Trial (STARTT). Methods: In total, 87 patients with genetically confirmed STGD1 were randomized in a double-masked, placebo-controlled proof of concept trial to evaluate the safety and efficacy of 20 milligram oral remofuscin for 24 months. The primary outcome measure is change in mean quantitative autofluorescence value of an 8-segment ring centred on the fovea (qAF 8). Secondary efficacy variables are best corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), mesopic microperimetry (mMP),  spectral domain optical coherence tomography (SD-OCT), reading speed on Radner reading charts, and patient-reported visual function as assessed by the National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) and Functional Reading Independence (FRI) Index. Results: Mean age of participants was 35±11 years with 49 (56%) female. Median qAF 8 value was 438 Units (range 210-729). Median BCVA and LLVA in decimal units were 0.50 (range 0.13-0.80) and 0.20 (range 0.06-0.63), respectively. The median of the mean retinal sensitivity with mMP was 20.4 dB (range 0.0-28.8). SD-OCT showed median central subfield retinal thickness of 142 µm (range 72-265) and median macular volume of 1.65 mm 3 (range 1.13-2.19). Compared to persons without vision impairment, both reading performance and patient-reported visual function were significantly lower (p<0.001, one sample t-test). Mean reading speed was 108±39 words/minute with logRAD-score of 0.45±0.28. Mean VFQ-25 composite score was 72±13. Mean FRI Index score 2.8±0.6. Conclusions: This trial design may serve as reference for future clinical trials as it explores the utility of qAF 8 as primary outcome measure. The baseline data represent the largest, multi-national, STGD1 cohort to date that underwent standardized qAF imaging, reading speed assessment and vision-related quality of life measures which all contribute to the characterization of STGD1. EudraCT registration: 2018-001496-20 (09/05/2019).

Determinants of Quality of Life in Geographic Atrophy Secondary to Age-Related Macular Degeneration.

Purpose: To longitudinally evaluate vision-related quality of life (VRQoL) in geographic atrophy (GA) secondary to age-related macular degeneration (AMD) and define its relation to visual function and structural biomarkers. Methods: Patients with GA secondary to AMD were recruited in the context of the prospective, non-interventional, natural-history Directional Spread in Geographic-Atrophy study (NCT02051998). Fundus autofluorescence and infrared reflectance images were semi-automatically annotated for GA. Linear mixed-effects models were applied to investigate the association of putative determinants with the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) VRQoL. Results: A total of 87 patients with a mean age ± SD of 77.07 ± 7.49 years were included in the analysis. At baseline, median (IQR) best-corrected visual acuity (BCVA) was 0.3 (0.51) for the better eye and 0.89 (0.76) for the worse eye; 46% of the patients showed binocular and 25.3% monocular non-central GA. The VRQoL composite score was impaired: 69.96 (24.03). Sixty-six patients with a median of 2 (2) follow-up visits after 1.08 (0.78) years were examined longitudinally. Conclusions: Vision-related quality of life is significantly impaired in patients with GA secondary to AMD. The cross-sectional and longitudinal association of VRQoL with visual functional and structural biomarkers supports the validity of the NEI VFQ-25 VRQoL.

Determinants of Cone and Rod Functions in Geographic Atrophy: AI-Based Structure-Function Correlation.

PURPOSE: To investigate the association between retinal microstructure and cone and rod function in geographic atrophy (GA) secondary to age-related macular degeneration (AMD) by using artificial intelligence (AI) algorithms. DESIGN: Prospective, observational case series. METHODS: A total of 41 eyes of 41 patients (75.8 ± 8.4 years old; 22 females) from a tertiary referral hospital were included. Mesopic, dark-adapted (DA) cyan and red sensitivities were assessed by using fundus-controlled perimetry ("microperimetry"); and retinal microstructure was assessed by using spectral-domain optical-coherence-tomography (SD-OCT), fundus autofluorescence (FAF), and near-infrared-reflectance (IR) imaging. Layer thicknesses and intensities and FAF and IR intensities were extracted for each test point. The cross-validated mean absolute error (MAE) was evaluated for random forest-based predictions of retinal sensitivity with and without patient-specific training data and percentage of increased mean-squared error (%IncMSE) as measurement of feature importance. RESULTS: Retinal sensitivity was predicted with a MAE of 4.64 dB for mesopic, 4.89 dB for DA cyan, and 4.40 dB for DA red testing in the absence of patient-specific data. Partial addition of patient-specific sensitivity data to the training sets decreased the MAE to 2.89 dB, 2.86 dB, and 2.77 dB. For all 3 types of testing, the outer nuclear layer thickness constituted the most important predictive feature (35.0, 42.22, and 53.74 %IncMSE). Spatially resolved mapping of "inferred sensitivity" revealed regions with differential degrees of mesopic and DA cyan sensitivity loss outside of the GA lesions. CONCLUSIONS: "Inferred sensitivity" accurately reflected retinal function in patients with GA. Mapping of "inferred sensitivity" could facilitate monitoring of disease progression and serve as "quasi functional" surrogate outcome in clinical trials, especially in consideration of retinal regions beyond areas of GA.

MESOPIC AND DARK-ADAPTED TWO-COLOR FUNDUS-CONTROLLED PERIMETRY IN GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate retinal sensitivity in the junctional zone of geographic atrophy (GA) secondary to age-related macular degeneration using patient-tailored perimetry grids for mesopic and dark-adapted two-color fundus-controlled perimetry. METHODS: Twenty-five eyes with GA of 25 patients (prospective, natural-history Directional Spread in Geographic Atrophy study [DSGA; NCT02051998]) and 40 eyes of 40 normal subjects were included. Patient-tailored perimetry grids were generated using annotated fundus autofluorescence data. Customized software positioned test-points along iso-hulls surrounding the GA boundary at distances of 0.43°, 0.86°, 1.29°, 2.15°, and 3.01°. The grids were used for duplicate mesopic and dark-adapted two-color (cyan and red) fundus-controlled perimetry. Age-adjusted reference-data were obtained through regression analysis of normative data followed by spatial interpolation. RESULTS: The mean sensitivity loss for mesopic testing decreased with the distance to GA (-10.3 dB [0.43°], -8.2 dB [0.86°], -7.1 dB [1.29°], -6.8 dB [2.15°], and -6.6 dB [3.01°]; P < 0.01). Dark-adapted cyan sensitivity loss exceeded dark-adapted red sensitivity loss for all iso-hulls (-14.8 vs. -11.7 dB, -13.5 vs. -10.1 dB, -12.8 vs. -9.1 dB, -11.6 vs. -8.2 dB, -10.7 vs. -8.0 dB; P < 0.01). CONCLUSION: Patient-tailored fundus-controlled perimetry grids allowed for testing of retinal function in the junctional zone of GA with high spatial resolution. A distinct decrease in mesopic sensitivity loss between 0.43° (125 µm) and 1.29° (375 µm) was observed that leveled off at more distant test-points. In proximity to the GA boundary, the results indicate that rod exceeded cone dysfunction.

Type 1 Choroidal Neovascularization Is Associated with Reduced Localized Progression of Atrophy in Age-Related Macular Degeneration.

PURPOSE: To investigate the association between the presence of type 1 choroidal neovascularization (CNV) and the localized progression of atrophy in age-related macular degeneration (AMD). DESIGN: Analysis of patients' data collected in the context of 2 noninterventional, prospective studies conducted at the Department of Ophthalmology, University of Bonn, Germany. PARTICIPANTS: A total of 98 eyes diagnosed with AMD of 59 patients (40 female, 19 male) with a mean (±standard deviation) age at baseline of 76.60±6.65 years and median (interquartile range) review period of 1.17 years (1.01-1.55) were included. Eyes were subdivided into 3 categories based on multimodal imaging and ocular history: retinal pigment epithelium (RPE) atrophy with treatment-naïve quiescent CNV (n=7), RPE atrophy with a history of exudative CNV (n=10), and RPE atrophy without evidence of coexisting CNV (n=81). METHODS: Retinal pigment epithelium atrophy was delineated on the basis of serial fundus-autofluorescence and infrared-reflectance images. If CNV was detected by OCT angiography (OCTA), its location and dimension were spatially mapped to RPE atrophy. The localized progression of RPE atrophy in topographic relation to the CNV lesion was then analyzed using mixed-effects logistic regression. The spatial overlap (Dice coefficient) between predicted and observed RPE atrophy progression was evaluated to estimate the model accuracy. MAIN OUTCOME MEASURES: Odds ratio (OR) for localized RPE atrophy progression in areas overlying type 1 CNV. RESULTS: The prediction model achieved a high overlap between predicted and observed RPE atrophy progression with a cross-validated Dice coefficient of 0.87 (95% confidence interval [CI], 0.85-0.89) reflecting a high accuracy. The odds for future RPE atrophy involvement were reduced by a factor of 0.21 (95% CI, 0.19-0.24) in the presence of treatment-naïve quiescent type 1 CNV and by a factor of 0.46 (95% CI, 0.41-0.51) in the presence of exudative type 1 CNV. CONCLUSIONS: The results indicate that there is markedly reduced RPE atrophy progression in areas co-localizing with quiescent and exudative type 1 CNV. This observation is compatible with a potential protective effect of type 1 CNV on the RPE and overlying neurosensory retina. These results may have relevant clinical implications for the management of CNV and lead to new therapeutic strategies to prevent atrophy progression.

Assessment of Exudative Activity of Choroidal Neovascularization in Age-Related Macular Degeneration by OCT Angiography.

PURPOSE: Based on exudative activity, choroidal neovascularization (CNV) in age-related macular degeneration (AMD) can be classified as "active" aCNV, pretherapied "silent" sCNV (i.e., a treatment-free interval >12 weeks), or treatment-naïve "quiescent" qCNV. We evaluated the qualitative and quantitative optical coherence tomography angiography (OCTA) features of these CNV subgroups. METHODS: The presence of small-caliber vessels, peripheral arcades, and a -perilesional OCTA signal attenuation as well as values for vessel length, density, and branching index were evaluated for each CNV network in a 6 × 6 mm OCTA scan pattern. RESULTS: Fifty-one eyes of 51 patients with AMD (age 75.9 ± 7.5 years; 20 males [39.2%]) were included. The qCNV subgroup (n = 8) showed the highest prevalence of qualitative and quantitative values for OCTA activity criteria, reaching significance with regard to small-caliber vessels (p = 0.003), peripheral arcades (p = 0.039), vessel length (p = 0.020), and branching index (p < 0.001) when compared to the aCNV (n = 32) and sCNV (n = 11) subgroups. Qualitative criteria were inversely associated with the number of previous anti-VEGF injections (each p < 0.03), while quantitative metrics also suggested lower values. CONCLUSIONS: These findings suggest that OCTA may be supportive in the phenotypical differentiation of CNV lesions secondary to AMD, while the assessed structural changes appeared to be more indicative of previously administered anti-VEGF therapy than current exudative activity.

Light Sensitivity Within Areas of Geographic Atrophy Secondary to Age-Related Macular Degeneration.

Purpose: To investigate residual sensitivity within geographic atrophy (GA) secondary to age-related macular degeneration. Methods: Mesopic and dark-adapted (DA) cyan and red light sensitivity (Goldmann III) were investigated using fundus-controlled perimetry (microperimetry). Test points were placed within GA along an "iso-hull" with a distance of -0.645° to the atrophy boundary. The false-positive response rate was determined with suprathreshold stimuli to the optic disc (Heijl-Krakau method) and used to compute the expected sensitivity measurements for the assumption of absolute scotomata. The outermost visible retinal layer on spectral-domain optical coherence tomography at the location of each test point was determined. Results: Thirty eyes of 36 patients (75.55 ± 7.93 years; 19 female) from the prospective natural history study Directional Spread in Geographic Atrophy (NCT02051998), with a total of 1380 threshold determinations were analyzed. The measured sensitivities were significantly (P < 0.01) higher than the expected values for absolute scotomata (mean ± standard error of +6.92 ± 0.86 dB for mesopic, +2.57 ± 0.56 dB for DA cyan, and +4.93 ± 0.74 dB for DA red testing). For mesopic testing and DA red testing, the presence of a residual outer nuclear layer had a significant effect on this discrepancy (P < 0.001). There was no effect of fixation stability or any other reliability index on this discrepancy. Conclusions: Measured sensitivities within the inner junctional zone of GA may not be purely explained by patient-specific false-positive response rates or other reliability indices. The marked influence of the outer retinal configuration on measured sensitivity may be indicative of residual cone function within GA at the inner junctional zone.

Artificial intelligence for morphology-based function prediction in neovascular age-related macular degeneration.

Spatially-resolved mapping of rod- and cone-function may facilitate monitoring of macular diseases and serve as a functional outcome parameter. However, mesopic and dark-adapted two-color fundus-controlled perimetry (FCP, also called "microperimetry") constitute laborious examinations. We have devised a machine-learning-based approach to predict mesopic and dark-adapted (DA) retinal sensitivity in eyes with neovascular age-related macular degeneration (nAMD). Extensive psychophysical testing and volumetric multimodal retinal imaging data were acquired including mesopic, DA red and DA cyan FCP, spectral-domain optical coherence tomography and confocal scanning laser ophthalmoscopy infrared reflectance and fundus autofluorescence imaging. With patient-wise leave-one-out cross-validation, we have been able to achieve prediction accuracies of (mean absolute error, MAE [95% CI]) 3.94 dB [3.38, 4.5] for mesopic, 4.93 dB [4.59, 5.27] for DA cyan and 4.02 dB [3.63, 4.42] for DA red testing. Partial addition of patient-specific sensitivity data decreased the cross-validated MAE to 2.8 dB [2.51, 3.09], 3.71 dB [3.46, 3.96], and 2.85 dB [2.62, 3.08]. The most important predictive feature was outer nuclear layer thickness. This artificial intelligence-based analysis strategy, termed "inferred sensitivity", herein, enables to estimate differential effects of retinal structural abnormalities on cone- and rod-function in nAMD, and may be used as quasi-functional surrogate endpoint in future clinical trials.

Mesopic and Dark-Adapted Two-Color Fundus-Controlled Perimetry in Choroidal Neovascularization Secondary to Age-Related Macular Degeneration.

PURPOSE: To determine the retest variability of mesopic and two-color dark-adapted (DA) fundus-controlled perimetry (FCP), to evaluate the predictive value of patient reliability indices, and to analyze the extent of impairment of rod- and cone function in neovascular age-related macular degeneration (nAMD). METHODS: A total of 50 eyes of 50 patients with nAMD (mean age, 76.1 years) and 70 eyes of 70 age-similar normal subjects underwent multimodal imaging as well as mesopic and DA two-color perimetry using the S-MAIA device. A subset of patients (n = 28) underwent duplicate testing for retest reliability assessment. Mixed models were used for analysis of the hierarchical data. RESULTS: In eyes with nAMD, the coefficient of repeatability was (mean ± standard deviation [SD]) 5.99 ± 1.55 dB for mesopic, 6.14 ± 2.19 dB for DA cyan, and 6.06 ± 1.09 dB for DA red testing. "Patient reliability indices" explained 55%, 54.2%, and 64.2% of the variance in retest variability. The mean sensitivity loss was greater for DA cyan compared to DA red testing (cyan-red differences [mean ± SD] -2.63 ± 3.87 dB, P < 0.001). CONCLUSIONS: The relatively greater degree of DA cyan versus DA red sensitivity loss indicates preferential rod vulnerability in nAMD, and qualifies rod function-based outcomes measures as potential sensitive and early markers of treatment response in nAMD. TRANSLATIONAL RELEVANCE: The S-MAIA allows reliable testing of mesopic, DA cyan, and DA red sensitivity in patients with nAMD. Patient reliability indices may serve as eligibility criteria for clinical trials to identify patients with adequate retest reliability.

Comparison of Green Versus Blue Fundus Autofluorescence in ABCA4-Related Retinopathy.

PURPOSE: To investigate the interreader and intermodality agreement for grading of retinal pigment epithelium (RPE) atrophy lesion size in ABCA4-related retinopathy using green (GAF) and blue fundus autofluorescence (BAF) imaging. METHODS: In this cross-sectional case series, 97 eyes of 49 patients with RPE atrophy secondary to ABCA4-related retinopathy underwent GAF- (518 nm excitation light) and BAF- (488 nm excitation light) imaging using confocal scanning laser ophthalmoscopy (Spectralis HRA, Heidelberg Engineering, Heidelberg, Germany). Lesions with definitely decreased autofluorescence (DDAF) and questionably decreased autofluorescence (QDAF) in GAF and BAF imaging were analyzed separately by five independent readers using semiautomated software (RegionFinder, Heidelberg Engineering). Intermodality and interreader agreements were assessed for the square-root lesion size, lesion perimeter, and circularity. RESULTS: GAF- and BAF-based measurements of DDAF and QDAF showed high intermodality and interreader agreement concerning square-root lesion size, as well as shape descriptive parameters (perimeter and circularity). Interreader agreement of square-root lesion size was slightly, hence not significantly higher for GAF-based grading ([95% coefficients of repeatability, intraclass correlation coefficient] DDAF: 0.215 mm, 0.997; QDAF: 0.712 mm, 0.981) compared to BAF-based grading (DDAF: 0.232 mm, 0.997; QDAF: 0.764 mm, 0.978). However, DDAF-measurements revealed distinctly more reproducible results than QDAF-measurements. Foveal sparing did not interfere with intermodality agreement. CONCLUSIONS: Both GAF- and BAF-based quantification of RPE atrophy showed very reliable results with possible superiority of GAF in the context of less energetic excitation light. TRANSLATIONAL RELEVANCE: The high interreader agreement qualifies the use of DDAF progression in GAF and BAF imaging as potential morphologic outcome measure for interventional clinical trials and disease monitoring.

Choroidal Flow Signal in Late-Onset Stargardt Disease and Age-Related Macular Degeneration: An OCT-Angiography Study.

Purpose: To investigate the choroidal blood flow in areas within and adjacent to retinal pigment epithelium (RPE) atrophy secondary to late-onset Stargardt disease (STGD1) and age-related macular degeneration (AMD). Methods: A total of 43 eyes (23 STGD1 and 20 AMD) of patients with RPE atrophy and 25 eyes of healthy controls without ocular pathology underwent multimodal imaging including optical coherence tomography angiography (OCT-A; PLEX Elite 9000 Swept-Source OCT). Using an exploratory approach, choriocapillaris and deeper choroid OCT-A slabs were evaluated in order to detect differences between STGD1 and AMD. The magnitude of absence-of-flow signal (AFS) was investigated in terms of area-fraction and size-frequency distribution. Results: Qualitative and quantitative analysis of areas of RPE atrophy revealed more pronounced rarefaction of the choriocapillaris flow signal in STGD1 as compared to AMD (AFS area fraction: 33.15% ± 6.86% vs. 31.68% ± 8.39%; P = 0.517), while outside RPE atrophy rarefaction was less pronounced in STGD1 (AFS area fraction: 17.41% ± 5.67% vs. 21.59% ± 6.90%; P < 0.001), to the level of nonsignificance compared to controls (13.27% ± 2.99%, P = 0.368). Given this discrepancy, the ratio of the AFS area fraction within/outside of RPE atrophy could be used to differentiate between STGD1 and AMD with 65.0% sensitivity and 92.3% specificity. Conclusions: Using OCT-A, comparison of choroidal flow signal within and outside the area of RPE atrophy revealed distinct differences between STGD1 and AMD, potentially implicating a differential role of the choroid in the pathogenesis of RPE atrophy in these two diseases.