INCIDENCE OF OUTER RETINAL TUBULATION IN RANIBIZUMAB-TREATED AGE-RELATED MACULAR DEGENERATION ALI DIRANI, MD, CHRISTINA GIANNIOU, MD, LAETITIA MARCHIONNO, DORIS DECUGIS, IRMELA MANTEL, MD Purpose: To investigate the incidence of outer retinal tubulation (ORT) in ranibizumab- treated neovascular age-related macular degeneration patients. Methods: We included 480 consecutive patients (546 eyes) with neovascular age-related macular degeneration, who were treated with variable-dosing intravitreal ranibizumab, evaluated with spectral domain optical coherence tomography, and followed-up for a minimum period of 6 months. Optical coherence tomographies were evaluated for the first appearance of ORT, precursor signs, and type of underlying lesion. Visual acuity was also recorded. Results: Outer retinal tubulation was observed in 30% of eyes during a mean follow-up period of 26.7 months (SD, 13.5). Kaplan–Meier survival analysis revealed that the ORT incidence (2.5, 17.5, 28.4, and 41.6% at baseline, after 1, 2, and 4 years, respectively) continuously increased, despite visually effective anti-vascular endothelial growth factor treatment. Outer retinal tubulation was associated with a poorer functional benefit. Lower baseline visual acuity was associated with a higher risk of developing ORT. Conclusion: Incidence of ORT continuously increases despite visually optimal anti– vascular endothelial growth factor treatment of age-related macular degeneration. Outer retinal tubulation might be considered a prognostic factor for functional outcome and is relevant to avoid overtreatment. RETINA 35:1166–1172, 2015 O uter retinal tubulation (ORT) is a term coined by Zweifel et al 1 to describe branching tubular struc- tures located in the outer nuclear layer of the retina. Outer retinal tubulation has been observed in a variety of degenerative diseases of the outer retina. 1–7 It is a rearrangement of the photoreceptors in response to disruption of the anatomical integrity of the photore- ceptor layer. 1 Outer retinal tubulation was first identi- fied in patients with neovascular age-related macular degeneration (nAMD), 1 and it has also been found in patients with atrophic AMD, 1,8,9 choroidal neovascu- larization of origin other than AMD, 1,5,7 and various outer retinal disorders (e.g., retinitis pigmentosa, 4 gyrate atrophy, 2,4 choroideremia, 1,4 cone dystrophy, 3 Bietti crystalline dystrophy, 1,3,6 central serous cho- roidopathy, 1 Stargardt disease, 4 pattern dystrophy, 1,4 and acute zonal occult outer retinopathy). 4 On conventional B-scan optical coherence tomogra- phy (OCT) sections, ORT appears as characteristic round to ovoid hyperreflective circular structures in the outer nuclear layer, sometimes communicating with the subretinal space. 1 Outer retinal tubulation may not indi- cate active leakage, but it rather represents a degenera- tive structural change. It is important to distinguish ORT from exudative intraretinal cysts, particularly in nAMD treated with variable-dosing anti–vascular endothelial growth factor (anti-VEGF), which is guided predominantly by exudative intraretinal cysts and sub- retinal fluid on OCT. The aim of the present study was to investigate the incidence and time course of ORT in a cohort of patients From the Department of Ophthalmology, University of Lausanne, Lausanne, Switzerland; and Jules Gonin Eye Hospital, Fondation Asile des Aveugles (Foundation Asylum for the Blind), Lausanne, Switzerland. None of the authors have any financial/conflicting interests to disclose. Reprint requests: Irmela Mantel, MD, Jules Gonin Eye Hospital, University of Lausanne, 15 Avenue de France, Case postale 133, CH-1000 Lausanne 7, Switzerland; e-mail: irmela. mantel@fa2.ch 1166