Evaluation of progressive neuroretinal rim loss as a surrogate end point for development of visual field loss in glaucoma.
OBJECTIVE
To evaluate the validity of using progressive loss of neuroretinal rim area as a surrogate end point for the development of visual field loss in glaucoma.


METHODS
Prospective, observational cohort study.


METHODS
The study group 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.


METHODS
Rim area measurements were acquired with CSLO during follow-up. The visual field end point was considered the development of 3 consecutive abnormal visual fields on standard automated perimetry. Strong predictive ability and large proportion of treatment effect (PTE) explained 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.


METHODS
Predictive strength was measured by survival-adapted R(2) and PTE.


RESULTS
Sixty-two of 492 eyes (13%) developed visual field loss during follow-up. The mean rate of rim area change in eyes that developed visual field loss was -0.011 mm(2)/year versus -0.003 mm(2)/year in eyes that did not (P<0.001). In the multivariable model, each 0.01 mm(2)/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, 1.38-6.23; P = 0.005). R(2) values were 62% and 81% for univariable and multivariable models, respectively. The PTE was 65%.


CONCLUSIONS
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 end points in glaucoma clinical trials.
Hamilton Glaucoma Center, Department of Ophthalmology, University of California, San Diego, California. Electronic address: fmedeiros@glaucoma.ucsd.edu.
Felipe A
FA
Medeiros
Hamilton Glaucoma Center, Department of Ophthalmology, University of California, San Diego, California.
Renato
R
Lisboa
Hamilton Glaucoma Center, Department of Ophthalmology, University of California, San Diego, California.
Linda M
LM
Zangwill
New York Eye and Ear Infirmary, New York, New York.
Jeffrey M
JM
Liebmann
Department of Ophthalmology, University of Alabama, Birmingham, Alabama.
Christopher A
CA
Girkin
Hamilton Glaucoma Center, Department of Ophthalmology, University of California, San Diego, California.
Christopher
C
Bowd
Hamilton Glaucoma Center, Department of Ophthalmology, University of California, San Diego, California.
Robert N
RN
Weinreb
D015331:Cohort Studies; D023381:Endpoint Determination; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D009798:Ocular Hypertension / Q000175:diagnosis*; D009887:Ophthalmoscopy; D009898:Optic Disk / Q000473:pathology*; D011446:Prospective Studies; D012165:Retinal Ganglion Cells / Q000473:pathology*; D014065:Tonometry, Ocular; D014786:Vision Disorders / Q000175:diagnosis*; D058609:Visual Field Tests; D014794:Visual Fields