Characterizing the Natural History of Foveal-Sparing Atrophic Late-Onset Retinal Degeneration

Abstract

Purpose: To identify quantifiable markers of disease progression in patients with foveal-sparing atrophic late-onset retinal degeneration using fundus autofluorescence and spectral-domain optical coherence tomography imaging. Methods: Natural history study evaluating patients within a 3-year interval. Disease progression was assessed based on the area of retinal atrophy, macular topographic distribution of lesions, retinal and choroidal thickness and volume, and choroidal vascularity index. Results: Twenty-four eyes (12 individuals) were included for fundus autofluorescence, and 31 eyes (16 individuals) for spectral-domain optical coherence tomography studies. Measurements were symmetrical between eyes of the same patient. The area of atrophy significantly enlarged (P = 0.002), with a growth rate of 2.67 mm2/year (SD: 2.13; square rooted: 0.57 mm/year, SD = 0.34). Baseline area of atrophy and progression both correlated with age. Most atrophic lesions were found in the temporal macula and progressed nasally at follow-up. Central choroidal and retinal thicknesses and volume in late-onset retinal degeneration cases were significantly reduced compared with controls, but only central retinal thickness decreased significantly at follow-up. Conclusion: This study identifies the area of atrophy and central retinal thickness, but not chorioretinal volume or choroidal thickness, as markers of short-term progression in late-onset retinal degeneration. These findings may be useful for disease monitoring and late-onset retinal degeneration interventional studies.

Longitudinal Changes of Retinal Structure in Molecularly ConfirmedC1QTNF5Patients With Late-Onset Retinal Degeneration

“… 24 , 40 , 41 Considering LORD, due to the configuration of scalloped atrophy in FAF images, AA appears to be a robust and easily measurable metric. 14 , 15 Measures of EZ width over the foveal B-scan also showed significant age-related loss and strong interocular correlation in our study. This is not surprising as EZ parameters have been established as robust outcome metrics for many inherited retinal diseases, as being a highly repeatable objective metrics and with excellent correlation to visual function.…”

“…Previous small cohort studies have provided qualitative description of LORD clinical course, 9 , 10 , 16 , 17 , 38 but only a few studies quantified age-related changes in this condition. 14 , 15 , 39 To the best of our knowledge, there is no previous work assessing rate of change of EZ parameters in LORD, whereas a few studies have provided progression rates for AA in FAF images. 14 , 15 A longitudinal study by Vanderford et al included four LORD patients all harboring the p.(Ser163Arg) mutation.…”

“… 14 , 15 , 39 To the best of our knowledge, there is no previous work assessing rate of change of EZ parameters in LORD, whereas a few studies have provided progression rates for AA in FAF images. 14 , 15 A longitudinal study by Vanderford et al included four LORD patients all harboring the p.(Ser163Arg) mutation. 14 Among the 5 eyes which developed atrophy (30 degrees field FAF images) the square root AA progression rate ranged between 0.53 and 1.97 mm/year, being 0.55 mm/year in the one with longer follow-up.…”

“… 9 , 13 , 14 Measurements of AA were square root transformed to reduce bias from baseline lesion size on growth rate estimates. 15 , 25 …”

Microperimetry in Foveal Sparing Atrophic Late-Onset Retinal Degeneration

“…Reprint requests: Shyamanga Borooah, MBBS, PhD, Shiley Eye Institute, UCSD, 9415 Campus Point Drive, La Jolla, CA 92093-0946; e-mail: sborooah@health.ucsd.edu the disease in the seventh decade of life. 4,7 Electrophysiology is normal in early disease. 8 However, a small chromatic perimetry study suggested that rod sensitivities were reduced across the macula up to 8 mm from the fovea whereas cone sensitivity was reduced paracentrally 9 even when the ellipsoid zone seemed intact.…”