Elsevier

Ophthalmology Retina

Volume 4, Issue 9, September 2020, Pages 881-888
Ophthalmology Retina

Original Article
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

https://doi.org/10.1016/j.oret.2020.03.015Get rights and content

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.

Section snippets

Participants

Participants were recruited as part of the LEAD Study, an investigator-initiated, multicenter, double-masked, randomized sham-controlled clinical trial.5 The trial was conducted at 5 Australian sites and 1 site in Northern Ireland. The coordinating center and sponsor was the Centre for Eye Research Australia, and the study is registered with the Australian New Zealand Clinical Trials Registry (identifier, ACTRN12612000704897). This study was conducted according to the tenets of the Declaration

Participants

From April 2015, 292 participants were enrolled into the LEAD Study, and 145 were allocated to the sham treatment group (49.7%). Of these, 141 (97.2%) completed both the NVQ-10 and the IVI-28 at baseline (see Fig S1, available at www.ophthalmologyretina.org, for flow chart of participants). At enrollment, participants were between 50 and 88 years of age (mean age, 69.8 years; standard deviation, 8.2 years), and 109 (77.3%) were women. Baseline characteristics and measures of visual function for

Discussion

In this study of participants with bilateral large drusen at enrollment, PRO scores derived from the IVI-28 were found be associated with the development of MMI-defined atrophy but not of nAMD. Although the scores from both questionnaires were skewed heavily toward higher functional vision, we found increasing baseline IVI-28 scores were associated both with a decreased rate of progression to atrophy and with decreased odds of atrophy at the 36-month visit. Insufficient evidence was found of an

Conclusions

Functional vision as measured via PROs was found to be associated with progression from iAMD to MMI-defined atrophy. Further developments in this field have the potential to produce additional tools that may be of value to assist in determination of disease severity and risk of AMD progression.

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    • Supplemental material available at www.ophthalmologyretina.org.

    Financial Disclosure(s): The author(s) have made the following disclosure(s): R.P.F.: Financial support – Novartis, Bayer, Roche/Genentech, Allergan, Alimera, Böhringer-Ingelheim, Ellex, Ophthea, Inositec, Santhera, CentreVue

    J.J.A.: Consultant – Bayer, Alcon; Board membership -- Allergan, Alcon, Bayer, Novartis; Lecturer – Allergan, Bayer

    R.H.G.: Board membership – Novartis, Roche

    The Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) Study was funded by the National Health and Medical Research Council of Australia (project grant no.: 1027624 [R.H.G. and C.D.L.); the BUPA Health Foundation, Australia; and Ellex Medical Lasers, Ltd., who also provided funds and the investigational devices. Supported by the National Health and Medical Research Council (principal research fellowship no.: 1103013 [R.H.G.]; fellowship grant no.: 1104985 [Z.W.]; early career fellowship no.: 1054712 [F.K.C.]; and career development fellowship no.: 1142962 [F.K.C.]); and the Victorian government and the National Health and Medical Research Council (Centre for Research Excellence grant 529923 [Centre for Eye Research Australia]). The funding organizations had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

    HUMAN SUBJECTS: Human subjects were included in this study. The human ethics committees at the Royal Victorian Eye and Ear Hospital, Belfast Health and Social Care Trust, Cabrini Hospital, Bellberry Limited, and the Sir Charles Gairdner Group approved the study. All research adhered to the tenets of the Declaration of Helsinki. All participants provided informed consent.

    No animal subjects were included in this study.

    Author Contributions:

    Conception and design: McGuinness, Finger, Wu, Luu, Chen, Arnold, Chakravarthy, Guymer

    Analysis and interpretation: McGuinness, Finger, Wu, Luu, Chen, Arnold, Chakravarthy, Guymer

    Data collection: McGuinness, Finger, Wu, Luu, Chen, Arnold, Chakravarthy, Guymer

    Obtained funding: Guymer, Luu

    Overall responsibility: McGuinness, Finger, Wu, Luu, Chen, Arnold, Chakravarthy, Guymer

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    © 2020 by the American Academy of Ophthalmology