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Original Investigation
January 2019

Association of Disorganization of Retinal Inner Layers With Visual Acuity Response to Anti–Vascular Endothelial Growth Factor Therapy for Macular Edema Secondary to Retinal Vein Occlusion

Author Affiliations
  • 1Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio
  • 2Case Western Reserve University School of Medicine, Cleveland, Ohio
  • 3Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil
JAMA Ophthalmol. 2019;137(1):38-46. doi:10.1001/jamaophthalmol.2018.4484
Key Points

Question  Is disorganization of inner retinal layers a biomarker of visual acuity at baseline and treatment response in retinal vein occlusion?

Findings  In this study of 147 eyes of 147 patients with retinal vein occlusion, the presence or absence of disorganization of inner retinal layers at baseline was a biomarker of visual acuity improvement; furthermore, increasing disorganization of inner retinal layers burden in patients with central retinal vein occlusion was associated with reduced visual acuity gains.

Meaning  These results suggest that disorganization of inner retinal layers may be a useful biomarker for visual acuity prognostication at baseline and during treatment in patients with retinal vein occlusion.


Importance  Disorganization of retinal inner layers (DRIL) has demonstrated significant correlations with visual acuity (VA) in center-involved diabetic macular edema. In patients with retinal vein occlusion (RVO) and secondary macular edema, DRIL may be a useful biomarker in determining VA outcomes.

Objective  To examine whether DRIL at baseline and after treatment is associated with VA in RVO.

Design, Setting, and Participants  A retrospective review of records of 147 patients 18 years or older with treatment-naive branch RVO (BRVO), central RVO (CRVO), or hemispheric RVO (HRVO), with a minimum of 12 months of follow-up, who presented to a tertiary ophthalmic center from December 1, 2010, to January 1, 2016, was conducted. Data collection continued through January 2017. Exclusion criteria included active confounding retinal or ocular disease, history of pars plana vitrectomy, or prior intravitreal injections. Two masked graders calculated a DRIL score based on DRIL presence in 3 predefined regions on spectral-domain optical coherence tomography at baseline, 6 months, and 12 months. A third masked grader was used for discrepancies.

Exposures  Anti–vascular endothelial growth factor (AVF) therapy (ranibizumab, aflibercept, or bevacizumab) determined by the treating physician.

Main Outcomes and Measures  The DRIL score at baseline for determining VA outcomes and correlation of VA with changes in DRIL burden in response to AVF therapy.

Results  In the 147 patients (mean [SD] age, 68.9 [13.1] years; 75 [51.0%] female), baseline DRIL was seen in 91 eyes (61.9%). In the BRVO group but not the CRVO group, baseline DRIL was associated with lower baseline Early Treatment Diabetic Retinopathy Study (ETDRS) score (score of 66.7 for no DRIL vs 54.6 for DRIL, P = .002). Absence of DRIL at baseline in the CRVO/HRVO group correlated with greater VA gains at 6 months, adjusting for baseline VA (score change of 19.50 for no DRIL vs 12.72 for DRIL; P = .04). During 12 months, continued DRIL presence in BRVO was associated with less VA gain up to 6 months (score change of 6.2 for the DRIL increase group vs 18.6 for the DRIL decrease group vs 2.9 for the DRIL stable group; P = .02). Increasing DRIL scores in CRVO/HRVO were associated with reduced VA improvement at 6 months (score change of –0.12 for the DRIL increase group vs 16.90 for the DRIL decrease group vs 8.45 for the DRIL stable group; P = .002) and 12 months (score change of –1.91 for the DRIL increase group vs 17.83 for the DRIL decrease group vs 6.97 for the DRIL stable group; P < .001).

Conclusions and Relevance  Baseline DRIL presence and DRIL burden changes with AVF therapy for macular edema secondary to RVO may be useful biomarkers of ETDRS score improvements.