Correlation between the Area of Increased Autofluorescence Surrounding Geographic Atrophy and Disease Progression in Patients with AMD

Self Cite

Valckenberg S; the GAP Study Group. Longitudinal analysis of reticular drusen associated with geographic atrophy in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2013;54:4054-4060. DOI:10. 1167/iovs.12-11538 PURPOSE. To characterize longitudinal changes of reticular drusen (RDR) in subjects with geographic atrophy (GA) secondary to age-related macular degeneration in the multicenter, prospective natural history Geographic Atrophy Progression Study.METHODS. Three-field confocal scanning laser ophthalmoscopy fundus autofluorescence (cSLO FAF, excitation [exc.] ¼ 488 nm; emission [em.] 500-800 nm, Heidelberg Retina Angiograph/ Spectralis) of 44 eyes of 22 patients with RDR (median age 77.6 years; range, 61-90 years) at baseline were identified in the study population and included for further analysis. Two independent readers determined the presence, topographic distribution, and pattern of RDR at baseline and at 18 months. Furthermore, the convex hull of the extent of RDR as the minimum polygon encompassing the entire area of RDR involvement was quantified.RESULTS. RDR lesion boundaries were clearly detectable in all directions within three-field FAF composite images in 16 eyes of 10 patients at both baseline and final visits. Over time, RDRaffected retinal area and RDR density increased. Quantitative analysis showed a mean average RDR extent of 53.7 mm 2 (95% confidence interval [95% CI]; 40.7; 66.8) at baseline. The mean differences for intraobserver agreements were 2.4 mm 2 (95% CI; À0.1; 4.9) for reader 1 and À0.6 mm 2 (95% CI; À2.3; 1.1) for reader 2. The mean difference of interobserver agreement was 0.9 mm 2 (95% CI; À0.8; 2.7). A mean growth rate of the RDR extent within the three-field FAF composite image of 4.4 mm 2 /y (95% CI; 1.9; 6.9) was measured.CONCLUSIONS. In vivo cSLO FAF imaging allows for both qualitative and quantitative mapping of longitudinal changes of RDR areas within a relatively short time period. Continuous enlargement of the affected retinal area indicates disease progression with regard to this phenotypic characteristic associated with GA in AMD. Systematic recordings of RDR progression appears warranted in future natural history and interventional studies in dry AMD. (ClinicalTrials.gov number, NCT00599846.)

Section: Discussionmentioning

confidence: 99%

Longitudinal Analysis of Reticular Drusen Associated With Geographic Atrophy in Age-Related Macular Degeneration

Steinberg

Auge

Jaffe

et al. 2013

Self Cite

“…[7][8][9][10][11] Extensive research in the past has been focused on the manifestation and progression, that is, enlargement of GA. [12][13][14] Different subphenotypes and prognostic factors for disease progression have been identified, particularly along with the advent of high-resolution imaging modalities. 15,16 Recently, several large-scale clinical studies have been initiated and completed, aiming to halt or slow GA lesion enlargement. [17][18][19] Typically, the minimum total atrophic lesion size for inclusion in clinical studies in GA is currently 0.5 to 1.0 disc areas (1.25-2.5 mm 2 ).…”

mentioning

confidence: 99%

Multimodal Imaging Patterns for Development of Central Atrophy Secondary to Age-Related Macular Degeneration

Thiele

Pfau

Larsen

et al. 2018

Self Cite

PURPOSE. To evaluate the development of central atrophy in eyes with age-related macular degeneration (AMD).METHODS. Six-year longitudinal multimodal retinal imaging data (MODIAMD study) from 98 eyes of 98 subjects with non-late-stage AMD in the study eye at baseline were analyzed for the presence of central atrophy at each annual follow-up visit. Development, manifestation, and further progression of complete retinal pigment epithelium and outer retinal atrophy (cRORA) by multimodal imaging data were compared with atrophy detection based on color fundus photography only.RESULTS. Seventeen study eyes with development of central cRORA within 6 years (cumulative rate: 17.4%) were identified based on multimodal imaging. In 10 (60%) of these eyes, presence of central manifest atrophy was initially not detectable by color fundus photography. In six (35%) eyes, central cRORA occurred by the spread of existing paracentral atrophy toward the fovea. Drusen-associated atrophy development was noted in eight eyes. In two eyes, atrophy development was associated with refractile deposits, while only pigmentary changes in absence of large drusen or refractile deposits were detectable before atrophy occurrence in one eye.CONCLUSIONS. The earlier and more precise detection of central cRORA by multimodal imaging as compared to atrophy detection solely based on color fundus photography allows for more accurate detection and identification of different pathways for atrophy development. In accordance with previous clinical and histopathologic reports, the results confirm that different precursor lesions may independently proceed to central cRORA in AMD.

“…A longitudinal comparison of these OCT-A alterations with the established FAF characteristics as prognostic determinants seems warranted. [60][61][62] Most recent advances in research led to currently ongoing and forthcoming trials probing new therapeutic strategies for STGD1 including visual cycle inhibitors, deuterated vitamin A, and gene therapy, [12][13][14][15] as well as complement inhibition and neuroprotection for late-stage dry AMD (Ghosn C, et al IOVS 2017;58:ARVO E-Abstract 1960). 16 In order to avoid incorrect inclusion of patients leading to potential misinterpretation, differentiation of mimicking phenotyping features in STGD1 and AMD is crucial.…”

Section: Discussionmentioning

confidence: 99%

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

Müller

Pfau

Möller

et al. 2018

Self Cite

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 agerelated 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 absenceof-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 6.86% vs. 31.68% 6 8.39%; P ¼ 0.517), while outside RPE atrophy rarefaction was less pronounced in STGD1 (AFS area fraction: 17.41% 6 5.67% vs. 21.59% 6 6.90%; P < 0.001), to the level of nonsignificance compared to controls (13.27% 6 2.99%, P ¼ 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.