Is Multiple Sclerosis Associated With a Lower Intraocular Pressure?

To determine if multiple sclerosis (MS) is associated with lower intraocular pressure (IOP) compared with individuals without MS. Thirty patients with clinically definite MS were identified and a retrospective chart review was conducted. Each patient with MS underwent IOP recording by a single investigator using kinetic applanation tonometry. Measurement of central corneal thickness (CCT) also was obtained. Similarly, 30 study controls were identified and kinetic applanation tonometry and CCT were recorded. Univariate analysis of covariance was conducted to determine a statistically significant difference between IOP between MS and control groups, controlling for age. Analyses were adjusted for age and 2 subjects were excluded because of steroid use. The average IOP in MS group was 12.3 mm Hg (right eye = 12.3 mm Hg, left eye = 12.2 mm Hg) and in the control group was 17 mm Hg (right eye = 16.9 mm Hg, left eye = 17 mm Hg). There was a significant effect of presence of MS on IOP accounting for 53% variability in mean IOP (F(1,55) = 60.7; P < 0.001) when compared with the control group. This study demonstrated that IOP was significantly lower in patients with MS compared with controls. A more in-depth prospective study design is required, along with further investigation of possible etiologies. Identifying the mechanism of decreased IOP in patients with MS might allow development of new-targeted therapies for the treatment of glaucoma.

Original Contribution Is Multiple Sclerosis Associated With a Lower Intraocular Pressure? Norah S. Lincoff, MD, Andrea Buccilli, MD, Bianca Weinstock-Guttman, MD, Sandra Sieminski, MD, Sirin Gandhi, MD Objective: To determine if multiple sclerosis (MS) is associated with lower intraocular pressure (IOP) compared with individuals without MS. Methods: Thirty patients with clinically definite MS were identified and a retrospective chart review was conducted. Each patient with MS underwent IOP recording by a single investigator using kinetic applanation tonometry. Measurement of central corneal thickness (CCT) also was obtained. Similarly, 30 study controls were identified and kinetic applanation tonometry and CCT were recorded. Univariate analysis of covariance was conducted to determine a statistically significant difference between IOP between MS and control groups, controlling for age. Results: Analyses were adjusted for age and 2 subjects were excluded because of steroid use. The average IOP in MS group was 12.3 mm Hg (right eye = 12.3 mm Hg, left eye = 12.2 mm Hg) and in the control group was 17 mm Hg (right eye = 16.9 mm Hg, left eye = 17 mm Hg). There was a significant effect of presence of MS on IOP accounting for 53% variability in mean IOP (F(1,55) = 60.7; P , 0.001) when compared with the control group. Conclusions: This study demonstrated that IOP was significantly lower in patients with MS compared with controls. A more in-depth prospective study design is required, along with further investigation of possible etiologies. Identifying the mechanism of decreased IOP in patients with MS might Department of Neurology and Ophthalmology (NSL), State University of New York at Buffalo School of Medicine, Buffalo, New York; Jacobs MS Center (NSL, BW-G, SG), UBMD Neurology, State University of New York, Buffalo, New York; Ophthalmology Clinic (AB), Lockport, New York; and Ross Eye Institute (SS), University at Buffalo, Buffalo, New York. Supported by Jog for the Jake Grant. B. Weinstock-Guttman has participated in speaker's bureaus and served as a consultant for Biogen, Teva Neurosciences, EMD Serono, Novartis, Genzyme and Genentech. She also has received grant/research support from the agencies listed above. No other industry financial relationships exist. The remaining authors report no conflicts of interest. Address correspondence to Norah S. Lincoff, MD, Department of Neurology and Ophthalmology, Jacobs Neurological Institute, School of Medicine and Biomedical sciences, University at Buffalo, 100 High Street, Buffalo, NY 14203; E-mail: [e-mail] Lincoff et al: J Neuro-Ophthalmol 2017; 37: 265-267 allow development of new-targeted therapies for the treatment of glaucoma. Journal of Neuro-Ophthalmology 2017;37:265-267 doi: 10.1097/WNO.0000000000000520 © 2017 by North American Neuro-Ophthalmology Society L ow intraocular pressure (IOP), unless of an extreme degree, is considered an innocuous entity. There is paucity of literature on this topic, with an established association in a few diseases including myotonic dystrophy, leprosy, and giant cell arteritis (1-6). At our institution, we observed that patients with MS tend to have lower IOP compared with individuals without MS. To the best of our knowledge, this observation has never previously been reported in the literature. Therefore, we conducted a pilot study to verify the observation. If confirmed, and understanding the mechanism of reduced IOP, there is the potential to develop new targets for glaucoma therapy. METHODS An observational retrospective study was conducted in the neuro-ophthalmology clinic at the University at Buffalo. Thirty patients with MS (60 eyes) were identified meeting the inclusion criteria for the study. The inclusion criteria were: 1) diagnosis of clinically definite multiple sclerosis(MS) using revised McDonald criteria; 2) evidence of radiological (MRI) lesions consistent with MS; 3) no history of glaucoma or laser refractive surgery; 4) no recent use of corticosteroids. A chart review was conducted to obtain demographic information on all subjects along with use of steroids at the time of testing. From the progress note of the corresponding clinic visit, the patient's kinetic applanation tonometry pressure was recorded for the right and left eye as well as the time, if available. All pressures 265 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution were taken between 11:00 AM and 3:00 PM All applanation tonometry readings were obtained using a HaagStreit slit lamp and performed by one investigator (N. S.L.). These patients also had central corneal thickness (CCT) measured using an ultrasonic corneal pachymeter during the same clinic visit. Similarly, 30 controls without a diagnosis of MS were identified and recruited from the same neuroophthalmology clinic. Inclusion criteria for controls were: 1) no history of glaucoma, laser refractive surgery or MS; 2) No recent steroid use. CCT by ultrasound, IOP by kinetic applanation tonometry and time of day of measurement were recorded. Informed consent was obtained from all participants, and the study had received previous institutional review board approval. Statistical analysis was performed using Statistical Package for Social Sciences version 24.0 and the data was analyzed by independent sample t test and univariate analysis of covariance (ANCOVA) test between subjects. The statistical significance was set at P , 0.05. FIG. 1. Mean intraocular pressure in patients with multiple sclerosis and controls. IOP, intraocular pressure; OD, right eye; OS, left eye; OU, both eyes; MS, multiple sclerosis. No significant difference (P = 0.25) was found between the CCT of the MS group with mean of 556 ± 38.9 mm (median = 563 mm) vs the control group with a mean of 560 ± 37.0 mm (median = 561 mm). RESULTS Both the control and MS study groups consisted of 28 women and 2 men (Table 1). The MS group ranged from 21 to 63 years old with a mean age of 45.1 years. The control group ranged from 19 to 71 years with a mean age of 41.1 years. No significant difference in age was found between the groups (P = 0.22). Most patients in both groups were Caucasian. One subject in the control group and one subject in the MS group were on prednisone 20 mg daily, and were therefore excluded from the statistical analysis. Figure 1 shows the mean IOP of the MS group compared with the control group. The IOP in the control group ranged from 14 to 21 mm Hg with the mean IOP 16.9 ± 2.1 mm Hg (median = 17 mm Hg). The IOP in the MS group ranged from 7 to 18 mm Hg with the mean IOP 12.3 ± 2.4 mm Hg (median = 13 mm Hg). Univariate ANCOVA was conducted to compare the difference in IOP between the 2 groups. There was a significant effect of presence of MS on IOP accounting for 52.5% variability in the IOP measurements between groups (F(1,55) = 60.7; P , 0.001) after controlling for age. DISCUSSION The current study findings indicate that patients with MS have significantly lower IOP than as compared to the control group. We found this association to be a useful supplemental diagnostic tool for the diagnosis of MS, especially when the diagnosis is uncertain. Low IOP has been documented only in a few other diseases, including myotonic dystrophy, leprosy, and giant cell arteritis. The hypotheses proposed for the mechanism of reduced IOP include reduction in aqueous production because of inflammation of the ciliary body in giant cell arteritis (7), autonomic dysfunction in patients with leprosy (8), and atrophy of ciliary muscle leading to ciliary body detachment and increased uveoscleral outflow in myotonic dystrophy (4). Proposed etiologies of low IOP in MS could be related to inflammation or autonomic dysfunction. Support for an inflammatory cause is supported by 2 observations. First, Green et al (9) reported evidence of inflammation of the retina and iris, along with varying degrees of retinal atrophy, in early and the progressive phase of MS. Second, up to 29% of patients with MS suffer from retinal venular Table 1. Demographic data of patients with MS and controls Sex Study Group MS Controls Race Age, yr Male Female Caucasian Others Unknown ,30 30-50 50-70 .70 2 2 28 28 16 28 3 2 11 0 2 7 21 13 7 9 0 1 MS, multiple sclerosis. 266 Lincoff et al: J Neuro-Ophthalmol 2017; 37: 265-267 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution periphlebitis or pars planitis sometime during the course of their disease (9). There also is evidence of autonomic dysfunction in patients with MS affecting both sympathetic and parasympathetic pathways in varying patterns (10). Lesions in the periventricular region of the fourth ventricle and medullary lesions have been linked to autonomic disease in MS (11). The autonomic symptoms in MS range from cardiovascular dysregulation, bladder, or bowel and sexual dysfunction. It is known that autonomic regulation of the ciliary epithelium is an important determinant of aqueous humor formation (12). CCT and corneal hysteresis have been shown to affect the accuracy of IOP measurements (13-15). A thinner cornea gives a falsely low measurement, whereas the opposite is true for greater corneal thickness. Khan (16) found that the maximum independent effect of variation in CCT on kinetic IOP was estimated at 1.9 mm Hg per 100 mm. We found no difference in corneal thickness between our 2 groups to explain the difference in IOP found. No significant corneal disease or history of refractive surgery was present in either group. The strengths of the current study are that all IOP measurements were obtained by applanation tonometry and each study group had only one physician obtaining the measurements. This allows for increased consistency and lesser interpersonal or equipment variability in IOP measurements. The weaknesses of the current study include a small sample size and its retrospective design. A prospective study may provide us further insight into this interesting clinical finding. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: N. S. Lincoff; b. Acquisition of data: N. S. Lincoff, A. Buccilli, and S. Sieminski; c. Analysis and interpretation of data: S. Gandhi and N. S. Lincoff. Category 2: a. Drafting the manuscript: S. Gandhi and N. S. Lincoff; b. Revising it for intellectual content: S. Gandhi, B. Weinstock-Guttman, and S. Sieminski. Category 3: a. Final approval of the completed manuscript: N. S. Lincoff. Lincoff et al: J Neuro-Ophthalmol 2017; 37: 265-267 REFERENCES 1. Huna-Baron R, Mizrachi IB, Glovinsky Y. Intraocular pressure is low in eyes with giant cell arteritis. J Neuroophthalmol. 2006;26:273-275. 2. Rosa N, Lanza M, Borrelli M, Palladino A, Di Gregorio MG, Politano L. 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