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.

Determinants of Reading Performance in Eyes with Foveal-Sparing Geographic Atrophy.

PURPOSE: To identify anatomic determinants of reading performance in eyes with foveal-sparing geographic atrophy (GA). DESIGN: Prospectively recruited, cross-sectional study, SIGHT (clinicaltrials.gov identifier, NCT02332343). PARTICIPANTS: Patients with foveal-sparing GA secondary to age-related macular degeneration (AMD). METHODS: Monocular best-corrected visual acuity and reading acuity together with reading speed were assessed using Radner charts. Fundus autofluorescence, near-infrared reflectance, and spectral-domain OCT images were acquired using a Spectralis device. The minimal required reading rectangle (M3R), 19 letters × 2.4 lines in the smallest readable print size of an individual eye, was computed. The status of the M3R was determined as either free of atrophy or involved in the atrophic process, and the impact on reading was assessed. MAIN OUTCOME MEASURES: Radner reading score (logRAD) and reading speed (words per minute [wpm]). RESULTS: A total of 45 eyes of 31 patients (30 women; mean age, 76.14 years [range, 64.17-89.22 years]) were included. Median best-corrected visual acuity was 0.20 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/32). Reading score was 0.52 logRAD (IQR, 0.30-1.4 logRAD) and maximum reading speed was 141.19 wpm (IQR, 105.52-164.62 wpm). In 27 eyes, the M3R was involved in the atrophic process. This was associated with a significant worsening in Radner score (1.21 logRAD [IQR, 0.46-1.40 logRAD] vs. 0.31 logRAD [IQR, 0.20-0.51 logRAD]; P < 0.001) and reading speed (110.84 wpm [IQR, 90.0-131.92 wpm] vs. 162.34 wpm [IQR, 137.51-176.66 wpm]; P = 0.002). Eyes in which the M3R was nonatrophic additionally showed an increase in reading speed with decreasing print size (peak increase, +73.08 wpm [IQR, 27.43-86.64 wpm] compared with the largest test sentence). CONCLUSIONS: The results indicate that a defined area on the retina that can be assessed by retinal imaging is required for unhindered reading in patients with foveal-sparing GA. The findings highlight that smaller test sentences can be read faster by patients with this AMD subphenotype. Our results allow prediction of reading impairment based on imaging parameters in clinical routine and may support establishing anatomic surrogate end points in clinical trials. Furthermore, the findings could be used to facilitate the adjustment of magnifying reading aids.

Combined Fundus Autofluorescence and Near Infrared Reflectance as Prognostic Biomarkers for Visual Acuity in Foveal-Sparing Geographic Atrophy.

Purpose: To identify predictors of best corrected visual acuity (BCVA) in eyes with foveal-sparing geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Methods: Best corrected visual acuity (Early Treatment Diabetic Retinopathy Study charts); serial fundus autofluorescence; and near-infrared reflectance images of patients participating in the FAM (NCT00393692) and DSGA (NCT02051998) studies were analyzed. The sizes of GA and spared fovea, and the minimal linear dimension of intact retinal pigment epithelium ("bridge") between the residual foveal island and the surrounding retina were quantified and associations with BCVA were assessed by local regression curves and mixed effects models. Results: A total of 65 eyes (51 patients, aged 75.68 ± 8.41 years) were included. Median time between baseline and last visit with detectable foveal sparing was 18 (quartiles: 12, 33) months. Median BCVA was 0.30 (0.20, 0.52) logMAR at baseline and 0.4 (0.3, 0.7) logMAR at follow-up. Local regression curves suggested no linear association of BCVA with GA size, sparing size or bridge size. Most contrasting values for BCVA were observed for >1.5 mm2 foveal-sparing size and for 400 µm bridge size. Employing these values as cutoff levels, mixed effects modeling revealed that both anatomic parameters, but not time, significantly impacted BCVA. Conclusions: During the review period eyes with foveal-sparing GA were likely to maintain the baseline BCVA. There was no linear correlation of BCVA with foveal-sparing size. Yet, BCVA was worse if the spared foveal area was <1.5 mm2 or if the bridge was smaller than 400 µm in width. These findings add to the understanding of the natural history of foveal-sparing GA and may support future clinical trial designs.

Distinct Genetic Risk Profile of the Rapidly Progressing Diffuse-Trickling Subtype of Geographic Atrophy in Age-Related Macular Degeneration (AMD).

PURPOSE: To genetically characterize a subphenotype of geographic atrophy (GA) in AMD associated with rapid progression and a diffuse-trickling appearance on fundus autofluorescence imaging. METHODS: Patients from the Fundus Autofluorescence in Age-Related Macular Degeneration Study were phenotyped for diffuse-trickling GA (dt-GA; n = 44). DNA was analyzed for 10 known AMD-associated genetic variants. A genetic risk score (GRS) was calculated and compared with patients with nondiffuse-trickling GA (ndt-GA; n = 311) and individuals from the 1000 genomes project (1000G; n = 267). Given the phenotypic overlap between diffuse-trickling and late-onset retinal degeneration (LORD), all C1QTNF5 exons and their exon/intron boundaries were sequenced. RESULTS: A statistically significant difference in allele frequencies between dt-GA and ndt-GA were found for CFH:rs1061170 and CFH:rs800292 (Pcorrected = 0.03). The ARMS2 variant rs10490924 was significantly more frequent in dt-GA than in 1000G individuals (Pcorrected < 0.01). The GRS of dt-GA patients was in-between the score of the 1000G individuals and that of patients with ndt-GA, significantly differing from both (Pcorrected <0.01). Sequencing of C1QTNF5 revealed 28 unique variants although none showed a statistically significant association with dt-GA when compared with 1000G individuals. CONCLUSIONS: The dt-GA phenotype shows a remarkably different genetic risk profile from other GA phenotypes secondary to AMD. Disease-associated C1QTNF5 mutations were not identified. Together, these results suggest that the dt-GA phenotype is associated with a genetic background substantially different from other GA phenotypes and underlines the necessity to refine the clinical phenotyping, specifically when aiming for individualized therapies in AMD.

Choroidal thickness in geographic atrophy secondary to age-related macular degeneration.

PURPOSE: To analyze choroidal thickness (CT) in eyes with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). METHODS: A total of 72 eyes of 72 patients (mean age, 75.97 ± 7.09 years) with GA and 37 eyes of 37 healthy controls (73.89 ± 6.19 years) were examined by confocal scanning laser ophthalmoscopy and enhanced depth imaging (EDI) spectral-domain optical coherence tomography. Choroidal thickness was measured at 25 defined points in horizontal and vertical scans. Geographic atrophy size was determined in fundus autofluorescence (FAF) images and GA subtypes were classified based on abnormal FAF in the perilesional zone. RESULTS: In GA, subfoveal CT (fCT) was significantly thinner compared to controls (173.03 ± 90.22 vs. 253.95 ± 69.19 µm, P < 0.001). Analysis of averaged measurements of all 25 points obtained per patient (mCT) revealed similar results (162.07 ± 76.26 vs. 228.00 ± 66.24 µm, P < 0.001). Spatial differences in CT between both groups were largest superior to the fovea. Addressing "diffuse-trickling" (n = 15) and "non-diffuse-trickling" (n = 57) GA independently, fCT was 114.67 ± 43.32 and 188.39 ± 93.26 µm, respectively (P = 0.002), with both groups being significantly thinner than controls (P < 0.001 for "diffuse-trickling" and P < 0.001 for "?non-diffuse-trickling"). Similar results were obtained for mCT, which was 110.21 ± 29.66 µm in "diffuse-trickling," 175.72 ± 79.02 µm in "?non-diffuse-trickling" and 228.00 ± 66.24 µm in controls. Differences were significant with P = 0.002 between both GA groups and P ≤ 0.001 toward controls for each GA group. CONCLUSIONS: The results indicate that the choroid in eyes with GA is thinner compared to normal eyes of similar age. Hereby, the extent of thinning is most pronounced in a specific subtype of GA identified by FAF imaging ("diffuse trickling"). Such GA subtype-related differences in choroidal thickness may reflect heterogeneity in the pathogenesis of disease. (ClinicalTrials.gov number, NCT02051998.).