Diplopia and Giant Cell Arteritis

Letters to the Editor exactly when damage occurred; however, with humans, we do not know when damage began—only when symptoms were first detected. Positive studies are of most value. If drug studies in rodents and other lower animals (e.g., rodents, rabbits, and hamsters) work, then we have a basis on which to test drugs in nonhuman primates or, in some cases, directly in humans. However, if they do not work, we still do not know with certainty that they would not work in humans. Such negative studies do have value in that they serve as essential building blocks, providing direction for future studies and at times justification for funding. Dr. Harvey voices several specific concerns. He asserts that laser-induced optic AION should be viewed as “a homolog” to end-stage AION. This presumption may or may not be accurate. But, even if accurate, our findings would still suggest that steroids lack benefit at this stage of disease, which may be at or shortly after appreciation of visual symptoms. He further argues that edema may play a role in the pathophysiology of AION, at different phases of the disease, and in some cases, preceding infarction. This likely is correct, and it is possible that steroids could have benefit in a subset of patients, specifically those with progressive axonal ischemia related to secondary compartmental compression. As we stated in our discussion section, we agree that our findings do not negate the possibility that steroids may have benefit in all or possibly a subset of human patients. In closing, we agree with Dr. Harvey that findings in a rodent model of AION far from perfectly parallel human disease. However, it would be unwise to assume animal studies such as this are entirely without value. They are, in many cases, the most appropriate initial step. We maintain that our data are sufficient to exclude a significant impact of intravitreal triamcinolone, with a final intravitreal concentration of 1 mg/mL, on retinal ganglion cells number in rodent eyes with nonarteritic ischemic optic neuropathy (NAION). Our findings do not exclude the possibility that anti- Diplopia and Giant Cell Arteritis W e read with interest the article by Ross et al that discussed 27 patients with diplopia and giant cell arteritis (GCA) (1). We contribute the perspective of 40 additional patients with diplopia and biopsy-proven GCA, based on our recent retrospective study of 1,666 subjects who underwent consecutive temporal artery biopsy for suspected GCA at 12 medical centers that did not contribute to the Ross paper (2). Diplopia-related data were available on 1,593 patients, of whom 137 (8.6%) had diplopia. We did not differentiate subjects with transient diplopia from those with constant diplopia. Of 392 patients with biopsy-proven GCA, 40 (10.2%) had diplopia. The characteristics of the subjects with diplopia and biopsy-proven GCA vs. those with a negative temporal 546 inflammatory therapy may be beneficial in all or in subsets of human patients with NAION. A detailed account of our study's limitations and implications comprises the bulk of the discussion section of the article (1). We are hopeful that these data will benefit future the design of more focused studies. Luciano S. Pereira, MD, PhD Marcos Pereira Ávila, MD, PhD Department of Ophthalmology, Universidade Federal de Goiás, Goiânia, Brazil Luciana X. Salustiano, MD, PhD Department of Pathology, Universidade Federal de Goiás, Goiânia, Brazil Alcio C. Paula, MD, PhD Department of Ophthalmology, Universidade Federal de Goiás, Goiânia, Brazil Emmanuel Arnhold, PhD Department of Statistics, Universidade Federal de Goiás, Goiânia, Brazil Timothy J. McCulley, MD The Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland The authors report no conflicts of interest. REFERENCE 1. Pereira LS, Ávila MP, Salustiano LX, Paula AC, Arnhold E, McCulley TJ. Intravitreal triamcinolone acetonide injection in a rodent model of anterior ischemic optic neuropathy. J Neuroophthalmology 2018:38;561–565. artery biopsy are shown in Table 1. Patients with diplopia and GCA had statistically significant greater age, jaw claudication, vision loss, erythrocyte sedimentation rate, C-reactive protein, and platelet levels than patients with diplopia and a negative temporal artery biopsy. Notwithstanding, on multivariable logistic regression model of the 1,201 subjects with complete data, diplopia was not a statistically significant predictor for biopsy-proven GCA (P = 0.659; Table 2). This result did not change with multiple imputation missing data analysis. Edsel B. Ing, MD, MPH Department of Ophthalmology, University of Toronto, Toronto, Canada Letters to the Editor: J Neuro-Ophthalmol 2019; 39: 545-547 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor TABLE 1. Characteristic of patients with diplopia and positive vs. negative temporal artery biopsy Predictor Positive TABx (n) Age (yrs) % Female % Headache % Temporal artery ab'n % Jaw claudication % Vision loss ESR (mm/hr) CRP (/ULN) Platelets (·109/L) 80.2 0.66 0.81 0.51 0.53 0.35 57.7 11.5 362 t test Negative TABx (n) (39) (39) (37) (37) (40) (40) (36) (36) (34) 72.7 0.64 0.69 0.36 0.22 0.13 37.8 4.9 280 ,0.001 0.516 0.157 0.107 ,0.001 0.002 0.001 0.002 ,0.001 (97) (97) (96) (92) (94) (96) (87) (82) (82) TABLE 2. Multivariable logistic regression for giant cell arteritis Predictor Age Female Headache Temporal artery ab'n Jaw claudication Vision loss Diplopia Log ESR Log CRP Platelets Constant Odds Ratio P 95% Confidence Interval 1.060 0.923 1.540 1.466 3.399 2.611 1.128 1.200 1.370 1.005 0.0001 ,0.001 0.644 0.027 0.024 ,0.001 ,0.001 0.659 0.116 ,0.001 ,0.001 1.041–1.078 0.658–1.296 1.050–2.257 1.051–2.044 2.432–4.749 1.783–3.824 0.662–1.922 0.956–1.508 1.207–1.556 1.003–1.006 n = 1,201, LR x2(10) = 328.21, pseudo R2 = 0.2431, log likelihood = 2510.984. Neil R. Miller, MD Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland Martin Ten Hove, MD, MEng Department of Ophthalmology, Queens University, Kingston, Canada Nurhan Torun, MD Department of Ophthalmology, Beth Israel Deaconess Hospital, Boston, Massachusetts Letters to the Editor: J Neuro-Ophthalmol 2019; 39: 545-547 The authors report no conflicts of interest. REFERENCE 1. Ross AG, Jivraj I, Rodriguez G, Pistilli M, Chen JJ, Sergott RC, Moster M, Sheldon CA, Liu GT, Foroozan R, Ko MW, Francis CE, Williams ZR, Lee AG, McClelland CM, Shindler KS, Yalamanchili S, Osborne B, Hedges III TR, Van Stavern GP, Puckett E, Rigi M, Garcia-Basterra I, Tamhankar MA. Retrospective, multicenter comparison of the clinical presentation of patients presenting with diplopia from giant cell arteritis vs other causes. J Neuroophthalmol. 2019;39:8–13. 2. Ing EB, Miller NR, Nguyen A, Su W, Bursztyn LLCD, Poole M, Kansal V, Toren A, Albreki D, Mouhanna JG, Muladzanov A, Bernier M, Gans M, Lee D, Wendel C, Sheldon C, Shields M, Bellan L, Lee-Wing M, Mohadjer Y, Nijhawan N, Tyndel F, Sundaram ANE, Ten Hove MW, Chen JJ, Rodriguez AR, Hu A, Khalidi N, Ing R, Wong SWK, Torun N. Neural network and logistic regression diagnostic prediction models for giant cell arteritis: development and validation. Clin Ophthalmol. 2019;13:421–430. 547 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.