Association between Patient-Reported Outcomes and Time to Late Age-Related Macular Degeneration in the Laser Intervention in Early Stages of Age-Related Macular Degeneration Study

Ophthalmol Retina. 2020 Sep;4(9):881-888. doi: 10.1016/j.oret.2020.03.015. Epub 2020 Mar 30.


Purpose: To investigate the relationship between patient-reported outcome (PRO) questionnaire responses and time to late age-related macular degeneration (AMD; neovascular AMD [nAMD] or multimodal imaging [MMI]-defined atrophy) among individuals with bilateral large drusen, and the prognostic value of baseline PROs for 36-month AMD status.

Design: Exploratory analyses from a multicenter randomized controlled trial of an AMD intervention (Australian New Zealand Clinical Trials Registry identifier, ACTRN12612000704897).

Participants: Sham treatment group of the Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) Study (n = 141; age, 50-88 years; 77% female).

Methods: The 28-item Impact of Vision Impairment (IVI-28) and 10-item Night Vision Questionnaire (NVQ-10) were administered at the baseline visit. The PRO scores were derived using rating scale models. Multivariate Cox regression adjusting for demographics and clinical measures of vision (low-luminance visual acuity, low-luminance deficit, and microperimetric sensitivity) from the poorer-performing eye was used to investigate the association between PRO scores and time to late AMD in either eye. Multivariate competing-risk regression was used to estimate cause-specific subhazard ratios for nAMD and atrophy in either eye. Cross-validated logistic lasso models were used to estimate the predicted probability of AMD at 36 months. The area under the receiver operating characteristic curve was assessed to compare prognostic accuracy between models with and without PROs.

Main outcome measure: Time until nAMD or atrophy in either eye.

Results: The PRO scores were skewed toward higher functional vision. Higher IVI-28 scores were associated with a lower risk of progression to MMI-defined atrophy (20 events: adjusted hazard ratio, 0.65/logit increase; P = 0.002) but not nAMD (10 events; P = 0.562). Insufficient evidence was found of an association between NVQ-10 score and rate of progression to late AMD (P ≥0.149). Baseline IVI-28 scores were found to contribute to the prognosis of atrophy at the 36-month visit (P = 0.010).

Conclusions: On average, PROs were associated with an increased risk of progression from intermediate AMD to MMI-defined atrophy. Continuing development of instruments to record PROs in the early stages of AMD have the potential to produce inexpensive and efficient tools to assist in the assessment of disease severity and risk of AMD progression.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / administration & dosage*
  • Disease Progression
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Intravitreal Injections
  • Laser Therapy / methods*
  • Male
  • Middle Aged
  • Time Factors
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Visual Acuity*
  • Wet Macular Degeneration / diagnosis
  • Wet Macular Degeneration / therapy*


  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A