Restoration of Outer Retinal Layers After Aflibercept Therapy in Exudative AMD: Prognostic Value

Invest Ophthalmol Vis Sci. 2015 Jun;56(6):4129-34. doi: 10.1167/iovs.15-16735.


Purpose: To evaluate the outer retinal layer (ellipsoid zone [EZ] and external limiting membrane [ELM]) changes following intravitreal aflibercept injections in eyes with treatment-naïve exudative age-related macular degeneration (eAMD) and to correlate these changes with fluid response and visual improvement.

Methods: A retrospective case series of 50 treatment-naïve eAMD eyes followed-up for 18 months. All patients underwent regular comprehensive ophthalmic examinations. The presence of EZ disruption, ELM disruption, EZ swelling, subretinal hyper-reflective exudation (SHE), central macular thickness (CMT), cystoid spaces, subretinal fluid, and pigmented epithelium detachment were evaluated by two different retinal specialists at baseline and final visits, and correlated with best corrected visual acuity (BCVA) improvement.

Results: At 18 months, BCVA, EZ disruption, ELM disruption, EZ swelling and SHE improved significantly (P = 0.001) at 18 months. Improvement of BCVA showed a statistically significant correlation with ELM restoration (P = 0.018), but not with EZ restoration (P = 0.581). Swelling of the EZ decreased from 72% of the cases at baseline to 30% in 18 months while SHE decreased from 52% to 6% in 18 months (P = 0.001). We observed a statistically significant (P = 0.001) reduction between the baseline and final value of CMT.

Conclusions: Aflibercept is safe and effective in treating exudative AMD with the restoration of the outer retinal layers. Restoration of the EZ is not statistically correlated with the final BCVA, even though persistent EZ changes could be associated with irreversible decrease in vision. On the contrary, the final status of the ELM is directly correlated with final BCVA. Also, baseline changes in outer retinal layers, especially the ELM, appear to predict photoreceptor restoration and final BCVA, and must be comprehensively analyzed to enable and determine a future prognosis.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use*
  • Basement Membrane / pathology
  • Female
  • Humans
  • Intravitreal Injections
  • Male
  • Middle Aged
  • Receptors, Vascular Endothelial Growth Factor / therapeutic use*
  • Recombinant Fusion Proteins / therapeutic use*
  • Retrospective Studies
  • Visual Acuity / physiology
  • Wet Macular Degeneration / drug therapy*
  • Wet Macular Degeneration / pathology
  • Wet Macular Degeneration / physiopathology


  • Angiogenesis Inhibitors
  • Recombinant Fusion Proteins
  • aflibercept
  • Receptors, Vascular Endothelial Growth Factor