Relationship between the distribution of intra-retinal hyper-reflective foci and the progression of intermediate age-related macular degeneration

Abstract

Purpose To assess the relationship between the distribution of intra-retinal hyper-reflective foci (IHRF) on optical coherence tomography (OCT) and progression of intermediate age-related macular degeneration (iAMD) over 2 years. Methods Cirrus OCT volumes of the macula of subjects enrolled in the Amish Eye Study with 2 years of follow-up were evaluated for the presence of iAMD and IHRF at baseline. The IHRF were counted in a series of 5 sequential en face slabs from outer to inner retina. The number of IHRF in each slab at baseline and the change in IHRF from baseline to year 2 were correlated with progression to late AMD at 2 years. Results Among 120 eyes from 71 patients with iAMD, 52 eyes (43.3%) of 42 patients had evidence of both iAMD and IHRF at baseline. Twenty-three eyes (19.0%) showed progression to late AMD after 2 years. The total IHRF count increased from 243 at baseline to 604 at 2 years, with a significant increase in the IHRF number in each slab, except for the innermost slab 5 which had no IHRF at baseline or follow-up. The IHRF count increased from 121 to 340 in eyes that showed progression to late AMD. The presence of IHRF in the outermost retinal slabs 1 and 2 was independently associated with a significant risk of progression to late AMD. A greater increase in IHRF count over 2 years in these same slabs 1 and 2 was also associated with a higher risk of conversion to late AMD. Conclusions The risk of progression to late AMD appears to be significantly associated with the distribution and extent of IHRF in the outermost retinal layers. This observation may point to significant pathophysiologic differences of IHRF in inner versus outer layers of the retina.

Longitudinal Evaluation of the Distribution of Intraretinal Hyper-Reflective Foci in Eyes with Intermediate Age-Related Macular Degeneration

“…The methodology for generating these slabs and quantitatively analyzing IHRF has been detailed in prior reports. 20,22,23 In brief, the procedure includes the following steps: 1) identi cation of the presence of IHRF on structural OCT B-scans (identi ed as well-circumscribed hyperre ective lesions ≥ 3 pixels in size, located within the neurosensory retina); 2) generation of 5 equidistant en-face slabs generated from the mid-retina (each representing 20% of the retinal thickness between the RPE and ILM with the inner surface of the slab following the ILM contour and the outer surface following the RPE contour, using the offset and range function); 3) thresholding and binarization of slabs with ImageJ (version 1.50; National Institutes of Health, Bethesda, MD; available at http://rsb.info.nih.gov/ij/index.html); 24 4) manual removal of other hyper-re ective artifacts surrounding the IHRF (drusen, subretinal drusenoid deposits, blood vessels etc); and nally, 5) automatic quanti cation (using 'analyze particles' function in Image J) of IHRF (number) from each retinal slab thus generated. This procedure was followed for each eye at baseline and at the 24-month follow up (Fig.…”

“…16,17 In a recent study, we identi ed that IHRF present in the outer retina, and in particular the outer nuclear layer, were most strongly associated with the risk for progression to late-stage AMD, though IHRF may be identi ed in more inner layers as well. 20 Given the differential risk for progression, we speculated that IHRF present in the more inner retinal layers may differ in their source compared to outer retinal IHRF, but this requires further histopathologic correlation.…”

Longitudinal evaluation of the distribution of intraretinal hyper-reflective foci in eyes with intermediate age-related macular degeneration

“…The methodology for generating these slabs and quantitatively analyzing IHRF has been detailed in prior reports. 20 , 22 , 23 In brief, the procedure includes the following steps: 1) identification of the presence of IHRF on structural OCT B-scans (identified as well-circumscribed hyperreflective lesions ≥ 3 pixels in size, located within the neurosensory retina); 2) generation of 5 equidistant en-face slabs generated from the mid-retina (each representing 20% of the retinal thickness between the RPE and ILM with the inner surface of the slab following the ILM contour and the outer surface following the RPE contour, using the offset and range function); 3) thresholding and binarization of slabs with ImageJ (version 1.50; National Institutes of Health, Bethesda, MD; available at http://rsb.info.nih.gov/ij/index.html ); 24 4) manual removal of other hyper-reflective artifacts surrounding the IHRF (drusen, subretinal drusenoid deposits, blood vessels etc); and finally, 5) automatic quantification (using ‘analyze particles’ function in Image J) of IHRF (number) from each retinal slab thus generated. This procedure was followed for each eye at baseline and at the 24-month follow up ( Fig.…”

“… 16 , 17 In a recent study, we identified that IHRF present in the outer retina, and in particular the outer nuclear layer, were most strongly associated with the risk for progression to late-stage AMD, though IHRF may be identified in more inner layers as well. 20 Given the differential risk for progression, we speculated that IHRF present in the more inner retinal layers may differ in their source compared to outer retinal IHRF, but this requires further histopathologic correlation.…”