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Show Letters to the Editor Optic Nerve Head Drusen: The Relationship Between Intraocular Pressure and Optic Nerve Structure and Function: Comment I n their article, Nolan et al (1) retrospectively reviewed the records of 236 eyes of 146 patients with optic nerve head drusen (ONHD). The authors found no correlation between intraocular pressure (IOP) and perimetric mean deviation (PMD) as assessed by either Octopus or Humphrey automated perimetry. They found no correlation between IOP and mean retinal nerve fiber layer (RNFL) thickness. Based on these observations, they concluded that, ". . .lowering IOP in normotensive eyes may not be beneficial in preventing vision loss in patients with ONHD." As noted in the article, lowering IOP has been proposed as a means of slowing the loss of visual field in eyes with ONHD, but that there are no data to support this proposition. However, their conclusion that IOP-lowering therapy may be ineffective does not follow from the data presented: a noninterventional study by design cannot answer this question or lead to such a conclusion. To settle the issue of whether or not lowering IOP is beneficial, one would ideally design a prospective study in which eyes with ONHD were randomized to IOP-lowering therapy. The authors acknowledge several limitations of their study. Among them is the fact that only one visual field and only one IOP measurement were considered for each eye. A limitation not listed is that each eye was considered a separate data point. This methodology does not take into account the fact that IOP, PMD, and RNFL thickness are likely to be correlated between the 2 eyes of a single individual. Based on these Optic Nerve Head Drusen: The Relationship Between Intraocular Pressure and Optic Nerve Structure and Function: Response W e thank Dr. Katz for his interest in our study evaluating the relationship between intraocular pressure (IOP) and visual field loss in eyes with optic nerve head drusen (ONHD). We agree that a multicenter, double-blinded randomized control trial would represent the best study design to prove or disprove the efficacy of IOP lowering medications in ONHD eyes. The slow rate of visual field loss progression in most patients with ONHD combined with the inherent high costs of prospective treatment trials has hindered such a study. In the absence of a prospective treatment trial, our multicenter Letters to the Editor: J Neuro-Ophthalmol 2019; 39: 142-145 limitations and on the noninterventional design of the study, it is premature to conclude that IOP-lowering therapy is ineffective. Patients with ONHD and visual field loss have few, if any, therapeutic options. Medical IOP-lowering therapy is relatively inexpensive and causes few side effects. Concluding that one should not offer these therapies to our patients with ONHD is without merit and potentially a disservice to patients. The authors could have been more circumspect in their conclusions: there are no data to suggest that IOPlowering therapy is effective or ineffective. In the absence of any data indicating that IOP-lowering therapy is harmful, physicians caring for these patients should openly discuss our uncertainty about the treatment of ONHD and, at least, offer to prescribe medical IOPlowering therapy. In this way, patients and the physicians caring for them can continue to make informed decisions using the best data available. Bradley J. Katz, MD, PhD Departments of Ophthalmology and Visual Sciences, and Neurology, John A Moran Eye Center, University of Utah Health Sciences Center, Salt Lake City, Utah The author reports no conflicts of interest. REFERENCE 1. Nolan KW, Lee MS, Jalalizadeh RA, Firl KC, Van Stavern GP, McClelland CM. Optic nerve head drusen: the relationship between intraocular pressure and optic nerve structure and function. J Neuroophthalmol. 2018;38:147-150. retrospective analysis of 236 eyes (more than double the next largest published study on the topic) to evaluate for evidence of a relationship between IOP and perimetric field depression was an achievable study with significant clinical merit. As enumerated in our study discussion and reiterated by Dr. Katz, our study design had flaws, although we do not believe that it should be discredited to the level of "no evidence." If neuro-ophthalmology relied exclusively on prospective studies as the only forms of medical literature with value, we would not have the foundation of knowledge to complete more highly regarded research. In regards to the opinion that we could have been "more circumspect" in our conclusions and that "it is premature to conclude that IOP lowering therapy is ineffective," we both disagree and agree, respectively. Acknowledging the limitations of our study design including low numbers of ocular hypertensive eyes, we were careful in the wording of our conclusion that based 143 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor on our data "lowering IOP may not be beneficial in preventing visual loss in normotensive eyes with ONHD." We believe the strength of our statement is commensurate with the level of evidence provided by our data and does not hinder future studies from further evaluating this issue from a different perspective. Dr. Katz correctly noted that the statistical analyses performed "by eye" did not take into account that the measurements involved are likely correlated between eyes of a single subject. The data were thus reanalyzed using 2 methods to account for intrasubject correlation, reducing the sample to one eye per subject and using mixed effects models with a random effect by the subject. For most tests reported in our manuscript, the new analyses came to the same conclusions. Tests with nonsignificant results remained nonsignificant. In fact, P values generally increased with the reanalysis. The significant findings of the association of ocular hypertension (IOP $ 22 mm Hg) and less depressed perimetric mean deviation were found to be nonsignificant on reanalysis. However, as noted in the text, these results were suspect already due to the low sample of patients with ocular hypertension. We are confident that our overall statistical conclusions are valid. Dr. Katz portrays ONHD patients as medically vulnerable in the sense that there are few reasonable treatment options and states that "concluding that one should not offer these therapies (IOP lowering drops) to our patients with ONHD is without merit and potentially a disservice to patients." The notion that our study concluded that providers should not offer IOP lowering therapies in ONHD is erroneous and does not appear in our manuscript text. In fact, the study authors as a group will, in certain circumstances (e.g., significant progressive visual field defects, moderate to severe visual field loss, and ocular hypertension), discuss with and offer IOP lowering therapies to patients. Although we agree that, in general, topical IOP lowering treatments are safe, one must consider that many of the 1%-2% of the population with ONHD are diagnosed in childhood and that there is no endpoint for treatment. Those who have no significant progression will believe the drops are working, whereas those who have visual field progression may be tempted to "double down" on IOP lowering by seeking out multiple drops or high-risk incisional glaucoma surgery. The financial burden of drops can also become significant over decades of use. The notion of treatment without supportive evidence can quickly become a slippery slope. We believe that the lack of definitive evidence against the efficacy of IOP lowering medications in ONHD-related optic neuropathy should not serve as a carte blanche for providers to prescribe treatment under the flawed logic that doing something is better than doing nothing. Historically, the appeal to cure has been used to support other "relatively inexpensive" and safe treatments of questionable efficacy including vision therapy for a broad range of ocular motility disorders and antibiotics for chronic Lyme disease. Neuro-Ophthalmology in South India (where consultation and surgeries [mainly cataract] are free). In our retrospective analysis from January 2017 to December 2017, there were 143, 946 referrals to various specialty clinics, of which 9,238 (6.4%) were referred for neuroophthalmic evaluation. Of these, 7,387 patients were referred from paying hospitals and 1851 were referred from free direct and camp sections. For our analysis, we included only the paying section referrals, of which 1851 patients (25%) were excluded as they turned out to be non-neuroophthalmic cases, compared to 16% in the study by Dhiman et al. Thus, our patient cohort comprised 5,402 patients. We compared our results with those of Dhiman et al. Optic nerve disorders were seen in 64.6% (n = 3,511) W e were greatly interested in the article by Dhiman et al (1) discussing their experience with neuroophthalmology in a central government-funded tertiary eye care hospital in North India. We wish to share our experience from a private nongovernmental organization (NGO) tertiary eye care hospital in South India. Our hospital offers services to patients in 3 tiers as per their choice: (1) paying section (where patient pays for the services); (2) free direct section (where consultation is free and the surgeries are steeply subsidized); (3) camp section 144 Michael Shyne, MS Biostatistical Design and Analysis Center, University of Minnesota, Minneapolis, Minnesota Gregory P. Van Stavern, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, Missouri Kaitlyn W. Nolan, MD Michael S. Lee, MD Collin M. McClelland, MD Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota The authors report no conflicts of interest. Letters to the Editor: J Neuro-Ophthalmol 2019; 39: 142-145 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |
