The Evolution of Outer Retinal Tubulation, a Neurodegeneration and Gliosis Prominent in Macular Diseases

Abstract

Purpose: To document outer retinal tubulation (ORT) formation in advanced retinal disorders.

Design: Retrospective, observational study.

Participants: Consecutive cases with retinal diseases showing outer retinal disruption and atrophy of the retinal pigment epithelium (RPE) associated with ORT on spectral-domain (SD) optical coherence tomography (OCT) at the final available visit.

Methods: Cross-sectional SD OCT scans showing ORT at the last available visit were compared with eye-tracked baseline scans. Only patients showing the formation of ORT over time with absence of ORT at baseline were analyzed.

Main outcome measures: Steps in ORT formation based on shapes of the external limiting membrane (ELM) descent (flat, curved, reflected, and scrolled) at the border of outer retinal and RPE atrophy, ORT characteristics (open, closed), and time between steps through a long-term follow-up.

Results: From 170 eyes of 86 patients with ORT, 38 eyes of 30 patients (11 men, 19 women) with a mean age of 78.87 years (range, 56-96 years) met inclusion criteria. Of these 38 eyes, 23 (60%) had geographic atrophy secondary to age-related macular degeneration (AMD) and 2 eyes (5%) had geographic atrophy secondary to pattern dystrophy. Twelve eyes (32%) had neovascular AMD and 1 eye (3%) had neovascularization secondary to pseudoxanthoma elasticum, all showing similar ORT formative steps. Seventy-three different retinal areas (1434 cross-sectional images) were analyzed over a mean follow-up of 69.5 months (range, 21-93 months). At 73 borders, grading of eye-tracked follow-up SD OCT line scans showed a flat ELM descent at least once at 34 borders (47%), a curved ELM at 47 borders (64%), a reflected ELM at 37 borders (51%), and a scrolled ELM at 24 borders (33%). Of 81 ORTs, 73 (90%) were closed and 8 (10%) were open. The mean time for ORT formation was 14.9 months (range, 1.4-71.3 months).

Conclusions: We propose progressive steps in the development of ORT and analyze the time of progression between these steps. Analyzing the borders of atrophy to determine the origin of ORT provides new insights into the pathophysiology of advanced retinal disease highlighting a role for Müller cells and may inform future therapeutic strategies.