Author reply
Authors: Balwantray C. Chauhan, Marcelo T. Nicolela, Paul H. Artes
Journal: Ophthalmology (2010)

We thank Drs. Medeiros and Weinreb for their critical evaluation and comments on our recent paper.1Chauhan B.C. Nicolela M.T. Artes P.H. Incidence and rates of visual field progression after longitudinally measured optic disc change in glaucoma.Ophthalmology. 2009; 116: 2110-2118Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar In glaucoma, there is no independent reference standard for progression. It was for this reason that we used 3 different criteria for the initial follow-up in the test (Topographic Change Analysis [TCA] with scanning laser tomography) and control (number of points in the visual field showing change) analyses. We had stated clearly that significant differences in the incidence of subsequent visual field progression between those showing and not showing optic disc change were present only in Protocol B (longer initial follow-up) and with conservative TCA criteria. This indicates that larger TCA changes are likely to provide a more practical and clinically meaningful measurement of change in optic disc topography. Unlike Drs. Medeiros and Weinreb, we were not surprised to find that a large proportion of patients did not show subsequent visual field progression after substantial topographic change in the initial follow-up. As we indicated in the article, published rates of visual field change are variable and depend on a host of factors such as disease severity, population, treatment, and length of follow-up. In our cohort, rates of visual field change were somewhat lower than previously published rates, but the salient point is that patients without disc change were less likely to show subsequent visual field progression. Inclusion of variables such as intraocular pressure and central corneal thickness in a multivariate analyses in addition to TCA may have increased the ability to predict which patients go on to develop subsequent visual field progression. However, this was not the purpose of our study. Furthermore, since ours was an observational rather than an interventional protocol, inferences about IOP would have been misleading. We included previous visual field change as a control analysis to previous TCA change to compare the incidence and rates of subsequent visual field progression. Unsurprisingly, we found that compared with previous TCA change, previous visual change was more predictive of subsequent visual field progression, though not by a large margin. We are not sure why Drs. Medeiros and Weinreb are confident that the predictive ability of TCA would be lower if other variables, including previous visual field change were taken into account. It is more plausible that factors predicting subsequent visual field progression are largely independent and that the predictive ability of TCA would not change significantly. We are fully aware of the subjective descriptors (“large,” “moderate,” “small,” and “insignificant” effects) associated with likelihood ratios. In our view, likelihood ratios and their confidence intervals should be interpreted more within the context of the disease, cost-benefit, study sample, and most importantly in comparison with other available tests, rather than with generic guidelines. A recent example may help clarify our point. It is thought that baseline optic disc abnormalities are associated with the development of open-angle glaucoma,2Zangwill L.M. Weinreb R.N. Beiser J.A. et al.Baseline topographic optic disc measurements are associated with the development of primary open-angle glaucoma: the Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study.Arch Ophthalmol. 2005; 123: 1188-1197Crossref PubMed Scopus (141) Google Scholar yet the Moorfields Regression Analysis, a widely used diagnostic tool of scanning laser tomography yielded a positive likelihood ratio of 1.87 and a negative likelihood ratio of 0.852Zangwill L.M. Weinreb R.N. Beiser J.A. et al.Baseline topographic optic disc measurements are associated with the development of primary open-angle glaucoma: the Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study.Arch Ophthalmol. 2005; 123: 1188-1197Crossref PubMed Scopus (141) Google Scholar; values which according to the interpretation suggested by Drs. Medeiros and Weinreb would render the baseline assessment of optic disc status as having an insignificant effect on the posttest probability of the outcome, in this case, development of glaucoma. Certainly, this is not our view. We argued the plausibility of using TCA endpoints on the basis of hit rate (proportion of patients identified as showing change) versus specificity. Logically, we compared TCA criteria to visual field criteria, in this case those used by the Early Manifest Glaucoma Trial.3Leske M.C. Heijl A. Hyman L. Bengtsson B. Early Manifest Glaucoma Trial: design and baseline data.Ophthalmology. 1999; 106: 2144-2153Abstract Full Text Full Text PDF PubMed Scopus (400) Google Scholar The latter yield high specificity,4Artes P.H. Chauhan B.C. Longitudinal changes in the visual field and optic disc in glaucoma.Prog Retin Eye Res. 2005; 24: 333-354Crossref PubMed Scopus (203) Google Scholar, 5Heijl A. Bengtsson B. Chauhan B.C. et al.A comparison of visual field progression criteria of 3 major glaucoma trials in early manifest glaucoma trial patients.Ophthalmology. 2008; 115: 1557-1565Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar however, we argued that the time required to detect change is longer than that required for similar specificity and hit rates with the TCA.1Chauhan B.C. Nicolela M.T. Artes P.H. Incidence and rates of visual field progression after longitudinally measured optic disc change in glaucoma.Ophthalmology. 2009; 116: 2110-2118Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar We do not suggest that using TCA endpoints serve as a substitute for predicting all patients who will go on develop subsequent visual field progression, but rather that given their specificity, hit rates and association with future visual field progression, they could provide viable endpoints depending on study design and objectives. We do not rule out the possibility that with further research, new methods of interpreting change with scanning laser tomography may be more efficacious. Visual Field ProgressionOphthalmologyVol. 117Issue 4PreviewWe read with great interest the article by Chauhan et al1 evaluating the ability of optic disc topography progression, as detected by confocal scanning laser ophthalmoscopy Topographic Change Analysis (TCA), to predict future visual field progression in glaucoma. This is a very important topic, and the authors are to be congratulated for attempting to address it. However, their conclusions seem largely unjustified based on the results. Full-Text PDF