Visual Outcomes and Clinical Manifestations of Pediatric Optic Neuritis in Indian Population: An Institutional Study

Background: Optic neuritis in children is an uncommon disorder which usually occurs after a viral illness or vaccination and, less frequently, occurs as a manifestation of a demyelinating disorder. Pediatric optic neuritis usually is bilateral and presents with optic disc edema, recovers rapidly with steroid therapy, and generally has low conversion rate to multiple sclerosis or neuromyelitis optica spectrum disorder. We report the clinical features and treatment outcomes of pediatric optic neuritis in Indian population, for which little data are available. Methods: We reviewed the medical case records of patients with optic neuritis who were younger than 18 years, from 1999 to 2016. All patients were assessed and managed in the Neuro-Ophthalmology Department of Sankara Nethralaya, a unit of Medical Research Foundation and Pediatric Neurology Department of Kanchi Kamakoti-Childs Trust Hospital, Chennai, India. Results: One hundred seventeen eyes of 78 children with mean age of 11.84 (+/-4.58) years were identified. Forty-two (53.8%) were females and 36 (46.2%) were males. Thirty-nine patients (50%) had bilateral involvement and a similar number had unilateral involvement. Fifty-nine eyes (50.4%) had optic disc edema, 20 eyes (17.1%) had disc pallor, and 38 eyes (32.4%) had normal discs. Of 63 patients who had neuroimaging, 36 had MRI, and 27 underwent computed tomography. Eighty-four eyes (of 59 patients) received steroid therapy according to the protocol of the Optic Neuritis Treatment Trial (ONTT). Thirty-three eyes that were treated with other steroid protocols were excluded from the final visual outcome analyses. Sixty of the 84 eyes (72.3%) recovered visual acuity of 20/40 or better. Visual acuity improvement was statistically significant between initial and final visual acuity (logMAR) in our patients treated with the ONTT protocol (P <= 0.001). Conclusions: Our Indian pediatric population had good visual recovery after steroid treatment for optic neuritis. Profound loss of visual acuity on presentation and bilateral involvement were significantly associated with poor visual outcome.

Original Contribution Visual Outcomes and Clinical Manifestations of Pediatric Optic Neuritis in Indian Population: An Institutional Study Selvakumar Ambika, DO, DNB, Krishnakumar Padmalakshmi, DO, DNB, Viswanathan Venkatraman, MD, Olma V. Noronha, DNB Background: Optic neuritis in children is an uncommon disorder which usually occurs after a viral illness or vaccination and, less frequently, occurs as a manifestation of a demyelinating disorder. Pediatric optic neuritis usually is bilateral and presents with optic disc edema, recovers rapidly with steroid therapy, and generally has low conversion rate to multiple sclerosis or neuromyelitis optica spectrum disorder. We report the clinical features and treatment outcomes of pediatric optic neuritis in Indian population, for which little data are available. Methods: We reviewed the medical case records of patients with optic neuritis who were younger than 18 years, from 1999 to 2016. All patients were assessed and managed in the Neuro-Ophthalmology Department of Sankara Nethralaya, a unit of Medical Research Foundation and Pediatric Neurology Department of Kanchi Kamakoti-Childs Trust Hospital, Chennai, India. Results: One hundred seventeen eyes of 78 children with mean age of 11.84 (±4.58) years were identified. Fortytwo (53.8%) were females and 36 (46.2%) were males. Thirty-nine patients (50%) had bilateral involvement and a similar number had unilateral involvement. Fifty-nine eyes (50.4%) had optic disc edema, 20 eyes (17.1%) had disc pallor, and 38 eyes (32.4%) had normal discs. Of 63 patients who had neuroimaging, 36 had MRI, and 27 underwent computed tomography. Eighty-four eyes (of 59 patients) received steroid therapy according to the protocol of the Optic Neuritis Treatment Trial (ONTT). Thirty-three eyes that were treated with other steroid protocols were excluded from the final visual outcome analyses. Sixty of the 84 eyes (72.3%) recovered visual acuity of 20/40 or better. Visual acuity improvement was statistically significant between initial and final visual Departments of Neuro Ophthalmology (SA and PKL) and Radiology (OVN), Sankara Nethralaya, A Unit of Medical Research Foundation, Chennai, India; and Department of Neurology (VV), Kanchi Kamakoti Child Trust Hospital, Chennai, India. The authors report no conflicts of interest. Address correspondence to Selvakumar Ambika, DO, DNB, Department of Neuro Ophthalmology, Sankara Nethralaya, A Unit of Medical Research Foundation, 18 College Road, Nungambakkam, Chennai 600 006, India; E-mail: [e-mail] 462 acuity (logMAR) in our patients treated with the ONTT protocol (P # 0.001). Conclusions: Our Indian pediatric population had good visual recovery after steroid treatment for optic neuritis. Profound loss of visual acuity on presentation and bilateral involvement were significantly associated with poor visual outcome. Journal of Neuro-Ophthalmology 2018;38:462-465 doi: 10.1097/WNO.0000000000000646 © 2018 by North American Neuro-Ophthalmology Society O ptic neuritis in children is an uncommon disorder which usually occurs after a viral illness or vaccination and, less frequently, occurs as a manifestation of a demyelinating disorder. The reported incidence and prevalence of acquired demyelinating syndrome are 0.09-0.18 per 100,000 and 3.2 per 100,000, respectively (1-5). Pediatric optic neuritis usually is bilateral and presents with optic disc edema, recovers rapidly with steroid therapy, and generally has low conversion rate to multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) (6-8). We report the clinical features and treatment outcomes of pediatric optic neuritis in an Indian population, for which little data are available (9). PATIENTS AND METHODS We reviewed medical records from 1999 to 2016 of all patients with optic neuritis younger than 18 years seen by the neuroophthalmology services of Medical Research Foundation, Chennai India. We excluded children with other optic neuropathies including those of hereditary, toxic, vascular, compressive, and infectious etiologies. Patients with an uncertain diagnosis or inadequate follow-up also were excluded. All patients had an ophthalmic evaluation by a neuroophthalmologist. Additional data included results of automated (Humphrey) perimetry, visual evoked potentials, computed tomography (CT)/MRI brain and orbits (1.5T scanner; HDxt, Milwaukee, WI). All patients diagnosed with optic neuritis were referred for pediatric neurology examination at Kanchi Ambika et al: J Neuro-Ophthalmol 2018; 38: 462-465 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Kamakoti Child Trust Hospital. Patients evaluated within 2-3 weeks of onset of optic neuritis received intravenous methylpredninsolone therapy (20-30 mg/kg/day) for 5 days followed by an oral steroid taper that followed the Optic Neuritis Treatment Trial (ONTT) protocol (10). Children with poor visual recovery by 4 weeks received intravenous immunoglobulin (IVIg 1-2 gm/d for 2 days and repeated 2 weeks later). Patients were reviewed after 1 week, 1 month, 6 months, and then subsequent visits. All clinical details were recorded with each visit and the results of neuroimaging, if repeated, were noted. Statistical Analysis An excel spreadsheet was designed to collect and record the data. The logarithm of reciprocal decimal visual acuity (VA) was used to approximate the logarithm of minimal angle of resolution. A poor visual outcome was defined as VA less than 20/40 in the affected eye in unilateral cases and in the more affected eye in bilateral cases. Statistical analysis used life-table analysis by Kaplan-Meier method performed using SSPS (version 14 software) and logistic regression was performed for analysis of risk factors affecting final VA. A P value ,0.05 was considered statistically significant. RESULTS Demographic and clinical data of our patient cohort are summarized in Table 1. One hundred seventeen eyes of 78 patients with optic neuritis were analyzed, including 36 boys (46.2%) and 42 girls (53.8%) with a ratio of 1:1.2. Ages ranged from 2 to 18 years with mean of 11.84 ± 4.58 years. Thirty-nine patients (50%) had unilateral optic neuritis and the same number had bilateral involvement. Painful vision loss was noted in 36 children (46%), whereas pain was absent in 42 children (34%). Sixteen patients (20.5%) had documentation of a febrile illness and 4 patients (5.1%) had a history of vaccination before onset of optic neuritis. Mean follow-up was 4.72 ± 12.75 months (range: 3 days-7 years) of which 42 patients were seen up to 12-15 months. Neuro-ophthalmic examination was performed over an average period of 9.35 ± 7.93 days after onset of vision loss (range: 1-45 days). Our primary outcome measure was VA as determined by the affected eye in unilateral cases and worse eye in bilateral cases. Of 84 eyes (59 patients), 60 eyes (71.4%) recovered acuity better than 20/40. Color vision was assessed in 31 patients and all showed dyschromatopsia. Results of visual field testing were recorded in 38 children. Generalized reduction in sensitivity and central scotoma were the common visual field defects. Fundus examination of the 117 eyes showed optic disc edema in 59 (50.4%), a normal disc in 38 eyes (32.4%), and disc pallor in 20 eyes (17.1%). We assumed that disc pallor was present if a child had delayed presentation or had a previous episode of subclinical optic neuritis with mild or monocular vision loss. In our patients who presented with a pale disc, brain MRI was available in 5 children, of which 3 were normal. One child had white matter lesions and 1 had T2 hyperintense signals in both optic nerves. Ambika et al: J Neuro-Ophthalmol 2018; 38: 462-465 TABLE 1. Demographics and clinical characteristics of pediatric patients with optic neuritis in India Total eyes Total patients Age Range Mean Follow-up period Range Mean Sex Boys Girls Laterality Bilateral Unilateral Optic disc appearance at presentation Swelling Normal Pale Underlying diagnosis Isolated optic neuritis ADEM MS Steroid therapy IV methylprednisolone CSF study Normal Leukocytosis Oligoclonal bands 117 78 2-18 yr 11.84 ± 4.58 yr 3 d-7 yr 4.2 ± 12.75 mo 36 (46.2%) 42 (53.8%) 39 (50%) 39 (50%) 59 eyes (50.4%) 38 eyes (32.4%) 20 eyes (17.1%) 69 (88.5%) 4 (5.1%) 5 (6.4%) 59 patients 59 patients 52 6 1 ADEM, acute disseminated encephalomyelitis; CSF, cerebrospinal fluid; IV, intravenous; MS, multiple sclerosis. Of 63 patients who underwent neuroimaging, MRI was performed in 36 and CT in 27. Abnormalities consistent with optic neuritis and/or a demyelinating disorder were found in 24/36 patients who had MRI and 5/27 who underwent CT scanning. Lumbar puncture was performed in 59 patients and the results are summarized in Table 1. None of our patients were tested for AQP4-IgG antibody. Out of our entire patient cohort, 84 eyes of 59 patients received intravenous steroids followed by an oral steroid taper according to the ONTT protocol. These patients were included in the final visual outcome analysis. In addition to intravenous steroids, 2 patients were treated with IVIg, 1 with adrenocorticotropic hormone (for associated infantile spasm), and 1 was treated for sinusitis with endoscopic surgery and antibiotics. Of the patients treated with steroids per the ONTT, 60/84 eyes (71.4%) recovered VA better than 20/40. There was significant improvement between initial final VA (logMAR) (P # 0.001). Of the remaining 33 eyes of 19 patients, 14 eyes received only oral steroids and 19 eyes were lost to follow-up and were excluded for the final visual outcome analysis. Of the 14 eyes treated only with oral steroids, 8 (57.14%) recovered VA better than 20/40. The remaining 19 eyes were not treated and lost to follow-up. Univariate logistic regression was used to assess for risk factors for eyes recovering vision worse than 20/40. 463 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution 1. Eyes with initial VA worse than counting fingers (CFs) did not have final VA better than 20/40 compared with those with initial VA better than CF (P , 0.001). 2. Four patients (4/33 patients, 12.1%) in the unilateral optic neuritis group and 10 patients (10/26 patients, 38.5%) in the bilateral group recovered VA worse than 20/40. Poor visual outcome was higher in the bilateral group and was statistically significant (P = 0.018). 3. 21/27 eyes (77.8%) in the normal optic disc group, 32/ 45 eyes (71.1%) in the optic disc edema group, and 7/12 (58.3%) in the pale optic disc group attained final VA better than 20/40. Two proportion 2 test showed that there was no difference in the final VA between the disc edema group and normal disc group (P = 0.3374). 4. Bilateral optic neuritis was more common than unilateral optic neuritis in patients #10 years, whereas children .10 years of age more commonly presented with unilateral optic neuritis. Four children in our study were diagnosed with acute disseminated encephalomyelitis (ADEM). Three presented with optic neuritis and 1 patient had a previous history of vaccination. All had bilateral vision loss, 3 were males, 6 of 8 eyes had optic disc edema, and 3 patients had final VA better than 20/40. In addition to optic neuritis, all 4 patients presented with encephalopathic features including headache, irritability, and vomiting and 1 developed seizures and hemiparesis. Brain MRI revealed T2 hyperintense diffuse white matter lesions. One ADEM patient experienced recurrent optic neuritis during follow-up. Five children in our study developed probable MS based on imaging features on brain MRI, presence of oligoclonal bands in cerebrospinal fluid, and absence of features of encephalopathy. Optic neuritis was unilateral in 3 children, bilateral in 2, and 2 experienced recurrent optic neuritis. There were 3 boys and 2 girls in this subgroup. All patients had final VA better than 20/40. DISCUSSION Our study examined the clinical characteristics of optic neuritis in Indian children and the effects of steroid therapy on final visual outcome. In our patient cohort, 71.4% of patients with optic neuritis recovered VA better than 20/40. Profound visual loss on presentation and bilateral involvement were associated with poor visual outcome. We found that Indian children with optic neuritis had a high prevalence of optic disc edema, a female preponderance and better visual outcome with early steroid treatment. The mean age of our patients at presentation was 11.84 ± 4.58 years, similar to other reports (11-13). Painful vision loss was observed in 46% of children in our study similar to the series by Lucchinetti et al (11), but in contrast to 92% in adult optic neuritis (14). Unilateral and bilateral optic neuritis occurred with equal frequency in our patient cohort, whereas in other 464 reports, 42%-87% had bilateral involvement (15,16). Optic disc edema is more common in pediatric optic neuritis, detected in 50.4% of our patients and ranging from 47% to 67% in other series (11,12,17). Children with optic disc pallor on presentation (delayed presentation) had poorer visual recovery than children who presented with a normal optic disc or disc edema, although this was not statistically significant. Optic neuritis is a well-described feature of ADEM (12,17-19). Isolated optic neuritis in children may be the only presenting manifestation of this disease which is usually monophasic (20). However, multiphasic ADEM also has been reported where there is a relapse of encephalopathy with or without optic neuritis and development of at least 1 new white matter lesion on imaging (19). Clinical differentiation of ADEM and MS may be challenging early in the clinical course, particularly when optic neuritis is an isolated event without any other neurological features. Diagnosing MS in children with optic neuritis depends on dissemination of attacks in space and time. Isolated optic neuritis may be the first manifestation of pediatric MS (8,21). The risk of developing MS after an episode of optic neuritis has been studied extensively in the pediatric population (22,23). Because there are no prospective data and variable methodologies have been used in retrospective studies, the conversion rate of MS varies from 13% to 36% (11,15,24). There was no statistically significant difference in visual outcome among patients diagnosed as ADEM vs MS in our study (P = 0.76). Although not tested for in our patient cohort, NMOSD also must be kept in the differential diagnosis when evaluating children with optic neuritis. In addition, there is evolving evidence for a role for myelin oligodendrocyte glycoprotein in pediatric patients with optic neuritis (7). We recognize a number of limitations of our study. First, it was retrospective in design. Second, we did not have a control group. Third, brain MRI and AQP4-IgG antibody testing was not conducted on all patients, so we cannot draw meaningful conclusions regarding the prevalence of MS and NMOSD. Finally, there was lack of a standardized follow-up period. Despite these limitations, our study adds to a limited body of literature regarding pediatric optic neuritis in the Indian population. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: S. Ambika, P. K. Lakshmi, and V. Venkatraman; b. Acquisition of data: S. Ambika and P. K. Lakshmi; c. Analysis and interpretation of data: S. Ambika. Category 2: a. Drafting the manuscript: S. Ambika and P. K. Lakshmi; b. Revising it for intellectual content: S. Ambika. Category 3: a. Final approval of the completed manuscript: S. Ambika. REFERENCES 1. Pohl 4D, Hennemuth I, von Kries R, Hanefeld F. 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