Ten-Year Incidence of Fibrosis and Risk Factors for Its Development in Neovascular Age-Related Macular Degeneration

Am J Ophthalmol. 2023 Aug:252:170-181. doi: 10.1016/j.ajo.2023.03.033. Epub 2023 Apr 7.

Abstract

Purpose: To report the incidence and risk factors for fibrosis at 10 years in a large cohort of persons with neovascular age-related macular degeneration (nAMD).

Design: Retrospective, multicenter, cohort study.

Methods: We included 225 naive nAMD eyes that underwent intravitreal anti-vascular endothelial growth factor treatment over 10 years of follow-up at two Italian referral centers. Demographic and clinical data were reviewed at baseline and on an annual basis. Onset of fibrosis was defined by clinically assessing photographs, fundus descriptions, or fluorescein angiograms. Optical coherence tomography (OCT) scans of fibrosis were inspected by an external reading center and graded as subretinal pigment epithelium (RPE), mixed, or subretinal.

Results: The mean age at baseline was of 72.1 ± 6.9 years. The incidence rate of fibrosis was estimated to be 8.9 per 100 person-years, with a cumulative incidence of 62.7% at 10 years. Fibrotic lesions were sub-RPE in 46.1%, mixed in 29.8%, and subretinal in 22.7%. Independent factors associated with fibrosis included the following: larger central subfield thickness variation (P < .001), submacular hemorrhages (P = .008), higher number of injections (P = .01), and worse baseline visual acuity (VA) (P = .03). Type 2 macular neovascularization was significantly associated with mixed and subretinal fibrosis. VA significantly declined over 10 years (-16.4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters), particularly in eyes with mixed and subretinal fibrosis (P < .001).

Conclusions: We identified a 62.7% cumulative incidence of fibrosis in a large nAMD cohort at 10 years. Fibrosis was more common with frequent reactivations and lower baseline VA; its onset had a significant impact on final VA. This supports the hypothesis that nAMD patients should be promptly treated with proactive regimens.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / therapeutic use
  • Cohort Studies
  • Fibrosis
  • Humans
  • Incidence
  • Intravitreal Injections
  • Macular Degeneration* / diagnosis
  • Macular Degeneration* / drug therapy
  • Macular Degeneration* / epidemiology
  • Ranibizumab / therapeutic use
  • Retrospective Studies
  • Risk Factors
  • Tomography, Optical Coherence
  • Vascular Endothelial Growth Factor A
  • Wet Macular Degeneration* / diagnosis
  • Wet Macular Degeneration* / drug therapy
  • Wet Macular Degeneration* / epidemiology

Substances

  • Angiogenesis Inhibitors
  • Ranibizumab
  • Vascular Endothelial Growth Factor A