Progressive Neuroretinal Rim Loss as a Surrogate Endpoint for Development of VF Loss in Glaucoma
To evaluate the validity of using progressive loss of neuroretinal rim area as a surrogate endpoint for the development of visual field loss in glaucoma, this prospective, observational cohort study included 492 eyes of 328 patients classified with suspected glaucoma at the baseline visit.
These eyes had an average of 7.4 ± 2.8 confocal scanning laser ophthalmoscopy (CSLO) images during a mean follow-up time of 6.6 ± 1.6 years. Rim area measurements were acquired with CSLO during follow-up. The visual field endpoint was considered the development of three consecutive abnormal visual fields on standard automated perimetry. Strong predictive ability and large proportion of treatment effect (PTE) are requisites for a suitable surrogate end point. A joint longitudinal survival model was used to evaluate the ability of rates of rim area loss in predicting visual field development, adjusting for confounding variables (baseline age, race and corneal thickness and follow-up measurements of intraocular pressure [IOP] and pattern standard deviation). The PTE was calculated by comparing the effect of IOP on the risk of development of visual field loss when incorporating rim area loss in the same model with the effect of IOP in the model excluding rim area measurements. The main outcome measure was predictive strength, measured by survival-adapted R² and PTE.
It was reported that 62 of 492 eyes (13%) developed visual field loss during follow-up. It was also noted that the mean rate of rim area change in eyes that developed visual field loss was –0.011 mm²/year versus –0.003 mm²/year in eyes that did not (p<0.001). In the multivariable model, each 0.01 mm²/year faster rate of rim area loss was associated with a 2.94 higher risk of visual field loss (hazard ratio, 2.94; 95% confidence interval, 1.38 to 6.23; p=0.005). R² values were 62% and 81% for univariable and multivariable models, respectively. The PTE was 65%.
Progressive rim area loss was highly predictive of the development of visual field loss in glaucoma and explained a significant PTE on the clinically relevant outcome. These findings suggest that rim area measurements may be suitable surrogate endpoints in glaucoma clinical trials.