Rates of Retinal Nerve Fiber Layer Thinning in Glaucoma Suspect Eyes

Abstract

Purpose To compare the rates of retinal nerve fiber layer (RNFL) loss in patients suspect of having glaucoma who developed visual field damage (VFD) to those who did not develop VFD, and to determine whether the rate of RNFL loss can be used to predict who will develop VFD.. Design Prospective observational cohort study Participants Glaucoma suspects, defined as having glaucomatous optic neuropathy or ocular hypertension (Intraocular pressure (IOP)>21 mmHg) without repeatable VFD at baseline from the Diagnostic Innovations in Glaucoma Study, and the African Descent and Glaucoma Evaluation Study. Methods Global and quadrant RNFL thickness (RNFLT) were measured with the Spectralis spectral-domain optical coherence tomography (SD-OCT). VFD was defined as having 3 consecutive abnormal visual fields. The rate of RNFL loss in eyes developing VFD was compared with eyes not developing VFD using multivariable linear mixed-effects models. A joint longitudinal survival model utilized the estimated RNFLT slope to predict the risk of developing VFD, while adjusting for potential confounding variables. Main Outcome Measures The rate of RNFL thinning and the probability of developing VFD. Results Four hundred and fifty-four eyes of 294 glaucoma suspects were included. The average number of SD-OCT examinations was 4.6 (range, 2–9) with median follow-up time of 2.2 (0.4–4.1) years. Forty eyes (8.8%) developed VFD. The estimated mean rate of global RNFL loss was significantly faster in eyes developing VFD compared with eyes that did not (−2.02μm/year vs. −0.82μm/year, P<0.001). The joint longitudinal survival model showed that each 1μm/year faster rate of global RNFL loss corresponded to a 2.05 times higher risk of developing VFD (Hazards Ratio (HR)=2.05, 95% Confidence Interval (CI): 1.14–3.71; p=0.017). Conclusions The rate of global RNFL loss was more than twice as fast in eyes developing VFD compared with eyes that did not develop them. Joint longitudinal survival model showed that a 1μm/year faster rate of RNFLT loss corresponded to a 2.05 times higher risk of developing VFD. These results suggest that measuring the rate of SD-OCT RNFL loss may be a useful tool to help identify patients who are at a high risk of developing visual field loss.

How to detect progression in glaucoma

“…Additionally, the Cirrus GPA printout also presents evaluation of changes in the RNFLT profile (arrow, dashed line), and trend analyses of average and sectoral indexes (black arrows). Medeiros et al, 2009;Miki et al, 2014;Wessel et al, 2013), healthy subjects also have significant age-related loss of RNFLT (Leung et al, 2012). There is no consensus on thresholds to separate age-related decline from glaucoma progression.…”

5-year disease progression of patients across the glaucoma spectrum assessed by structural and functional tools

“…There have been few studies that have used GPA on Cirrus-OCT for detecting progression in glaucoma 18 23–27. Miki et al 24 and Na et al ,17 in their study on progression assessment using SD-OCT in glaucoma suspects, reported a faster decline in RNFL and macular thickness measurements in progressors than non-progressors. Leung et al 26 used the RNFL thickness map provided by GPA-OCT for detecting and identifying patterns of RNFL progression.…”

Biomarkers and surrogate endpoints in glaucoma clinical trials

“…In several studies, changes in neuroretinal rim area, as measured by CSLO, were shown to predict future visual field losses 35–40. More recently, longitudinal studies using spectral domain OCT have shown that changes in RNFL thickness were also highly predictive of future functional losses in glaucoma suspects 41 42. However, in order to show that structural measurements can be used as reliable surrogate endpoints, one has to also demonstrate that the effect of treatment on changes in structure is a reliable predictor of the effect of treatment on changes in function.…”