OUTER RETINAL TUBULATION MAY RESULT FROM FIBROSED TYPE 2 NEOVASCULARIZATION: Clinical Observations and Model of Pathogenesis

PURPOSE: To investigate the role of Type 2 macular neovascularization with subsequent subretinal fibrosis in the pathogenesis of outer retinal tubulation (ORT). METHODS: We conducted a retrospective cohort study of patients with stabilized inactive exudative macular degeneration who had been treated with intravitreal injections of antivascular endothelial growth factor agents. Baseline fluorescein and optical coherence tomography images were included. Macular neovascularizations (MNVs) were classified by type and size. Consecutive optical coherence tomography images analyzed for ORT development. RESULTS: One hundred forty-four eyes of 134 patients were included in this study. Sixty eyes presented with pure Type 1 MNV. Eighty-four eyes presented with some Type 2 component of MNV. In total, evidence of ORT is shown in 55 (38%) eyes. In the Type 1 group, 6.7% developed ORT. Outer retinal tubulation developed in 61% of eyes with some Type 2 component of the MNV. Among eyes that developed ORT, 92.7% presented with some Type 2 component. In a multivariate analysis, Type 2 membranes on optical coherence tomography (22.2 [6.1–80.8]; P < 0.001), larger MNV size {>1 DA (5.1 [1.1–24.2]; P = 0.041) and >1.5 DA (9.0 [1.8–44.0]; P = 0.007)}, and presence of subretinal fibrovascular material (3.1 [1.1—8.5]; P = < 0.03) are associated with higher odds of ORT formation. Once the ORT is formed, fibrosis was observed directly underlying the ORT on SD-optical coherence tomography in 70.9% of cases. CONCLUSION: Type 2 membranes at presentation predict ORT formation. Fibrosis often underlies ORT. This suggests that contraction of Type 2 MNV-derived fibrosis may be important in ORT formation.