Published:September 26, 2021DOI:



      To evaluate the clinical characteristics, multimodal imaging features, and long-term treatment outcomes of eyes with neovascular age-related macular degeneration (nAMD) and bacillary layer detachment (BALAD) treated with intravitreal anti-vascular endothelial growth factor (VEGF) therapy.


      Retrospective, longitudinal, case series.


      Treatment-naive nAMD patients (n=30) showing BALAD on optical coherence tomography (OCT) and undergoing anti-VEGF therapy.


      Clinical records and multimodal imaging were reviewed up to 4 years after diagnosis.

      Main Outcomes Measures

      Best-corrected visual acuity (BCVA) values were compared over time. The cumulative risk and the risk factors of subretinal fibrosis were assessed with Cox regression analyses, and the adjusted hazard ratio (aHR) was computed.


      Thirty eyes of 30 patients were included. Macular neovascularization (MNV) subtypes were distributed as follows: type 1, 63%; type 2, 27%; mixed type 1 and type 2, 3%; type 3, 3%; aneurysmal type 1, 3%. The BCVA significantly improved after anti-VEGF loading phase (Snellen equivalent, from 20/118 to 20/71, P = 0.03), but it returned to baseline levels at 4 years (Snellen equivalent, 20/103, P = 0.6). The cumulative risk of subretinal fibrosis was 77% at 4 years. Risk factors associated with subretinal fibrosis included hemorrhagic BALAD (aHR, 2.02; 95% CI 1.54 to 3.22; P < 0.01) and the presence of subretinal hyperreflective material (aHR, 1.83; 95% CI 1.35 to 3.14; P < 0.01).


      BALAD was found in association with all types of MNV in nAMD patients. Long-term observation revealed poor functional outcomes related to the high risk of subretinal fibrosis.
      To read this article in full you will need to make a payment
      Subscribe to Ophthalmology Retina
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      1. Ramtohul P, Engelbert M, Malclès A, et al. Bacillary Layer Detachment: Multimodal Imaging And Histologic Evidence Of A Novel Optical Coherence Tomography Terminology. Retina. Published online May 18, 2021. doi:10.1097/IAE.0000000000003217

        • Cicinelli M.V.
        • Giuffré C.
        • Marchese A.
        • et al.
        The Bacillary Detachment in Posterior Segment Ocular Diseases.
        Ophthalmology Retina. 2020; 4: 454-456
      2. Liakopoulos S, Keane PA, Ristau T, Kirchhof B, Walsh AC, Sadda SR. Atypical Outer Retinal Fluid Accumulation in Choroidal Neovascularization: A Novel OCT Finding. Ophthalmic Surg Lasers Imaging Retina. 2013;44(6 (Suppl)):S11-S18. doi:10.3928/23258160-20131101-03

        • Fajnkuchen F.
        • Cohen S.Y.
        • Thay N.
        • et al.
        bridge arch-shaped serous retinal detachment in age-related macular degeneration.
        Retina. 2016; 36: 476-482
        • Ramtohul P.
        • Comet A.
        • Denis D.
        • Gascon P.
        Hemorrhagic Bacillary Layer Detachment in Macular Telangiectasia Type 2.
        Retina. 2021; 41: e42-e43
        • Spaide R.F.
        • Jaffe G.J.
        • Sarraf D.
        • et al.
        Consensus Nomenclature for Reporting Neovascular Age-Related Macular Degeneration Data: Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group.
        Ophthalmology. 2020; 127: 616-636
        • Sadda S.R.
        • Guymer R.
        • Holz F.G.
        • et al.
        Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration on OCT: Classification of Atrophy Report 3.
        Ophthalmology. 2018; 125: 537-548
        • Jung J.J.
        • Chen C.Y.
        • Mrejen S.
        • et al.
        The incidence of neovascular subtypes in newly diagnosed neovascular age-related macular degeneration.
        Am J Ophthalmol. 2014; 158 (e2): 769-779
      3. Jung JJ, Soh YQ, Yu DJG, et al. Bacillary Layer Detachment Due to Macular Neovascularization. Retina. Published online February 18, 2021. doi:10.1097/IAE.0000000000003153

        • Rosenfeld P.J.
        • Brown D.M.
        • Heier J.S.
        • et al.
        Ranibizumab for neovascular age-related macular degeneration.
        N Engl J Med. 2006; 355: 1419-1431
        • Daniel E.
        • Pan W.
        • Ying G.-S.
        • et al.
        Development and Course of Scars in the Comparison of Age-Related Macular Degeneration Treatments Trials.
        Ophthalmology. 2018; 125: 1037-1046
        • Teo K.Y.C.
        • Joe A.W.
        • Nguyen V.
        • et al.
        Prevalence And Risk Factors For The Development Of Physician-Graded Subretinal Fibrosis In Eyes Treated For Neovascular Age-Related Macular Degeneration.
        Retina. 2020; 40: 2285-2295
        • Kuiper E.J.
        • Van Nieuwenhoven F.A.
        • de Smet M.D.
        • et al.
        The angio-fibrotic switch of VEGF and CTGF in proliferative diabetic retinopathy.
        PLoS One. 2008; 3e2675
        • Roberts P.K.
        • Zotter S.
        • Montuoro A.
        • et al.
        Identification and Quantification of the Angiofibrotic Switch in Neovascular AMD.
        Invest Ophthalmol Vis Sci. 2019; 60: 304-311
        • Willoughby A.S.
        • Ying G.-S.
        • Toth C.A.
        • et al.
        Subretinal Hyperreflective Material in the Comparison of Age-Related Macular Degeneration Treatments Trials.
        Ophthalmology. 2015; 122 (e5): 1846-1853
        • Schmidt-Erfurth U.
        • Waldstein S.M.
        A paradigm shift in imaging biomarkers in neovascular age-related macular degeneration.
        Prog Retin Eye Res. 2016; 50: 1-24
        • Casalino G.
        • Stevenson M.R.
        • Bandello F.
        • Chakravarthy U.
        Tomographic Biomarkers Predicting Progression to Fibrosis in Treated Neovascular Age-Related Macular Degeneration: A Multimodal Imaging Study.
        Ophthalmol Retina. 2018; 2: 451-461
        • Stanescu-Segall D.
        • Balta F.
        • Jackson T.L.
        Submacular hemorrhage in neovascular age-related macular degeneration: A synthesis of the literature.
        Surv Ophthalmol. 2016; 61: 18-32
        • Toth C.A.
        • Morse L.S.
        • Hjelmeland L.M.
        • Landers M.B.
        Fibrin Directs Early Retinal Damage After Experimental Subretinal Hemorrhage.
        Arch Ophthalmol. 1991; 109: 723-729
        • Li M.
        • Dolz-Marco R.
        • Messinger J.D.
        • Ferrara D.
        • Freund K.B.
        • Curcio C.A.
        Neurodegeneration, gliosis, and resolution of haemorrhage in neovascular age-related macular degeneration, a clinicopathologic correlation.
        Eye (Lond). 2021; 35: 548-558
        • Zweifel S.A.
        • Engelbert M.
        • Laud K.
        • Margolis R.
        • Spaide R.F.
        • Freund K.B.
        Outer retinal tubulation: a novel optical coherence tomography finding.
        Arch Ophthalmol. 2009; 127: 1596-1602
        • Querques G.
        • Coscas F.
        • Forte R.
        • Massamba N.
        • Sterkers M.
        • Souied E.H.
        Cystoid macular degeneration in exudative age-related macular degeneration.
        Am J Ophthalmol. 2011; 152 (e2): 100-107
        • Schlegl T.
        • Waldstein S.M.
        • Bogunovic H.
        • et al.
        Fully Automated Detection and Quantification of Macular Fluid in OCT Using Deep Learning.
        Ophthalmology. 2018; 125: 549-558
        • Moraes G.
        • Fu D.J.
        • Wilson M.
        • et al.
        Quantitative Analysis of OCT for Neovascular Age-Related Macular Degeneration Using Deep Learning.
        Ophthalmology. 2021; 128: 693-705
        • Mantel I.
        • Mosinska A.
        • Bergin C.
        • et al.
        Automated Quantification of Pathological Fluids in Neovascular Age-Related Macular Degeneration, and Its Repeatability Using Deep Learning.
        Transl Vis Sci Technol. 2021; 10: 17
      4. Rofagha S, Bhisitkul RB, Boyer DS, Sadda SR, Zhang K, SEVEN-UP Study Group. Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP). Ophthalmology. 2013;120(11):2292-2299. doi:10.1016/j.ophtha.2013.03.046

        • Maguire M.G.
        • Martin D.F.
        • et al.
        • Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group
        Five-Year Outcomes with Anti-Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration: The Comparison of Age-Related Macular Degeneration Treatments Trials.
        Ophthalmology. 2016; 123: 1751-1761