In general, optic neuritis is a clinical diagnosis based upon the history and examination findings. Because important findings on fundoscopic examination help differentiate typical from atypical cases of optic neuritis, an ophthalmologic examination should be considered an essential feature of the clinical evaluation. Magnetic resonance imaging (MRI) study of the brain and orbits with gadolinium contrast provides confirmation of the diagnosis in most cases and also provides an assessment of the risk of subsequent multiple sclerosis (MS) [1]. An MRI study of the brain and orbits with gadolinium contrast provides confirmation of the diagnosis of acute demyelinating optic neuritis and important prognostic information regarding the risk of developing MS. When there are relevant clues to an alternative diagnosis and measurement of the erythrocyte sedimentation rate, antinuclear antibodies, and angiotensin converting enzyme levels and serologic and CSF tests for Lyme disease and syphilis should be obtained [2,3]. A delay in the P100 of the visual evoked response (VER) is the electrophysiologic manifestation of slowed conduction in the optic nerve as a result of axonal demyelination [4]. This test is not usually helpful in the diagnosis of acute optic neuritis, unless there is a suspicion that the visual loss is functional. Abnormalities in the VER can persist after recovery of full vision. At one year, 80 to 90 percent will be abnormal; 35 percent will return to normal at two years [5]. The VER is often employed to find evidence of previous, asymptomatic episodes of optic neuritis, but the sensitivity and specificity are imperfect [6].The multifocal VER is a technical advance that appears to be more sensitive and specific for identifying optic neuritis, but this technology is not generally available [7] Optical coherence tomography (OCT) measures the thickness in the retinal nerve fiber layer and detects thinning in most (85 percent) of patients with optic neuritis [8]. These abnormalities are also common in patients with MS who do not have a clinical history of optic neuritis [9]. While lower values correlate with impaired visual outcome, the utility of OCT as a prognostic tool is limited in that abnormal values do not show up until early swelling disappears. In one study, OCT was less sensitive than VER in detecting subclinical optic neuritis [10]. Optic Neuritis Treatment Trial (ONTT) was the first major study that provided information on the natural history, role of steroids in treatment and risk of development of MS [11]. ONTT was a multi-institutional study of 454 patients with acute unilateral ON carried out between 1988 and 1991. Patients in the study were randomized to 1 of 3 treatment arms: intravenous followed by oral corticosteroids, and placebo. Results from this study have previously suggested that visual function did not statistically differ between the 3 arms of the study [12]. All 3 groups had excellent long-term visual outcomes 10 years after study enrolment. Patients with multiple sclerosis (MS) were more likely to have poorer visual outcomes than those without MS. This current report is the final, 15-year (for examinations conducted 15-18 years after the acute event) outcome data regarding visual function from the ONTT. Various studies from South East Asia observed tend to have more atypical presentations of optic neuritis and a lower prevalence of multiple sclerosis [13].However limited information is available on the clinical profile, causes, and outcomes of optic neuritis in Indian populations. The present study was thus planned to study the epidemiology and systemic associations of the patients of optic neuritis coming to a tertiary care hospital of India.

This Prospective interventional time based study was conducted in the Department of Ophthalmology, Shri Guru Ram Rai Institute Of Medical and Health Sciences associated Shri Mahant Indresh Hospital,Patel nagar,Dehradun over a duration of one and a half years from 2016 to 2019 in patients of age >=15 years diagnosed with optic neuritis presenting in eye OPD, Sample Size Total of 16 patients diagnosed with acute optic neuritis were selected to participate in this study. Each patient was followed up for a period of at least 6 months. Inclusion Criteria We included the patients in our study fulfilling the following criteria: • Aged >=15 years of either sex. • Patients diagnosed with optic neuritis. • Patient giving consent for the study. The diagnosis of ON was based on clinical findings, including the presence of decreased visual acuity, painful eye movements, colour vision loss, relative afferent pupillary defect, and fundus examination. Exclusion Criteria We excluded all patients who had any of the following features: • Patients <15 years of age. • Patients who were unable to cooperate. • Patients who had other causes of vision loss in the clinically affected eye (including amblyopia, any retinal pathology or glaucoma,). • Patients who had contraindications for systemic steroid use like Diabetes Mellitus, Severe Hypertension, Miliary Tuberculosis and other systemic infections, etc. • Optic nerve involvement in uveitic disease. • Traumatic optic neuropathy. Written informed consent was taken from all participants in the study. After relevant history was taken, each patient underwent a comprehensive systemic and ophthalmological examination including Complete general physical examination, Visual Acuity (best corrected) using Snellen’s chart, Evaluation for Relative Afferent Pupillary Defect (RAPD), Fundus examination (using +78 D lens on slit lamp)), Colour vision testing using Ishihara pseudo isochromatic colour plates, Intra ocular pressure measurement using Non Contact Tonometer., Visual Field analysis using Humphrey field analyser (Swedish Interactive Threshold Algorithm SITA central 30-2 program), Pattern VEP, RNFL thickness by SD-OCT(Optical Coherence Tomography RS-3000 Advance a product of NIDEK CO., LTD. gamagori, aichi 443-0038, JAPAN), MRI brain and orbit enhanced with gadolinium contrast if possible and Systemic investigations (blood sugar testing, serum electrolytes, complete blood counts, CRP,ANA,ANCA, Serum ACE, Montoux test, Serum Anti NMO IgGAb chest X-ray).Neurology opinion was taken. Patients were evaluated and followed up for a period of at least 6 months. Evaluation was done at presentation, after 2 weeks post treatment, after 1 month, 3 months and 6 months post treatment. • BCVA, RAPD evaluation, IOP, fundus examination after 2 weeks. • OCT RNFL thickness at presentation, 1 month, 3 months and 6 months. • MRI (Gadolinium contrast enhanced) and systemic investigations at presentation. Statistical Analysis The data was analyzed using Statistical Package for the Social Sciences (SPSS) [version 17.0; SPSS Inc., Chicago, IL,USA]. Pretreatment, post-treatment and follow-up parameters for affected eyes were compared using the Paired‘t’ test, or non-parametric Wilcoxon signed- rank test (in case distribution was not normal). Parameters between affected eyes of the patients were compared using unpaired ‘t‘ test, or non- parametric Mann Whitney test (in case distribution was not normal). For qualitative data Chi-square test/ Fisher’s exact test was used. P value <0.05 was considered as statistically significant.

Mean age of the patients was- 33.0 +11.8 years. The maximum number of patients were seen in age group (21-30 years). Out of the 16 patients, 5 patients were Male (31.3%) while 11 patients were Females (68.8%). There was more bilateral involvement (56.3%) among cases than unilateral involvement i.e.(25%) left eye and (18%) right eye. Table 1. Mean visual evoked potential(VEP) values P100 latency Variable N Mean SD VEP 25 145.12 18.96 Table 2. Mean comparison of Retinal nerve fiber layer thickness Variables Group N Mean SD p- value OCT RNFL thickness At Presentation 25 119.04 28.12 <0.01 1 month 25 102.92 16.10 OCT RNFL thickness 1 month 25 102.92 16.10 <0.01 3 month 25 94.52 15.36 OCT RNFL thickness 3 month 25 94.52 15.36 0.917 6 month 25 94.76 15.14 Mean comparison of RNFL thickness measured by SD-OCT. The mean RNFL thickness at presentation was 119.04+28.12. After 1 month post treatment RNFL thickness was reduced with mean of 102.92+16.10 with a p-value of <0.01. On follow up on 3 months was further reduced with mean 94.52+15.36. After 6 months on follow up the mean RNFL thickness was 94.76+15.14 showing further reduction with a p-value of 0.917. Table 3. Distribution as per MRI Findings MRI Brain N % Demyelinating foci 2 8.0% Optic neuritis 2 8.0% Optic neuritis with multiple sclerosis 3 12.0% RBN 2 8.0% Tubercular meningitis 1 4.0% No abnormality 14 56.0% Not Done 1 4.0% Total 25 100.0% Table 4. Distribution as per other positive findings Other Investigation N % 6th Nerve palsy 1 4.0% Anti NMO POSITIVE 2 8.0% CSF micro-proteins present 2 8.0% H/o ATT 2 8.0% Table 5. Distribution of cases as per incidence of recurrence Recurrence N % No 23 92.0% Yes 2 8.0% Total 25 100.0% Table 6. Correlation between visual acuity and Retinal nerve fiber layer thickness as measured by OCT Pearson's correlation OCT vs Visual Acuity (LogMar) r- value p- value At Presentation 0.218 0.296 At 2 weeks 0.076 0.718 No significant correlation was observed between retinal nerve fiber layer thickness and visual acuity at presentation or after 2 weeks (p>0.05). Table 7. Correlation between visual acuity and Visual evoked potential Pearson's correlation VEP vs Visual Acuity (LogMar) r- value p- value At Presentation 0.267 0.198 At 2 weeks 0.062 0.769 No significant correlation was observed between visual evoked potentialand visual acuity at presentation or after 2 weeks (p>0.05).

Optical coherence tomography (OCT) is a non-invasive imaging technique routinely used in ophthalmology to visualize and quantify the layers of the retina. OCT allows direct visualization and measurement of the optic nerve head topography, and of retinal nerve fiber layer (RNFL) thickness with micron-scale resolution. RFNL values were recorder at the time of presentation,1 month, 3months and 6 months. It was found that there was significant reduction in retinal thickness over the period of 3-6 months. Parisi et al. [14] compared average peripapillary RNFL thickness in 14 MS-related optic neuritis patients, at least 1 year after the optic neuritis, and in 14 controls. Not surprisingly, they found a significant thinning of the RNFL average thickness and RNFL temporal thickness in the optic neuritis group compared to controls.This shows OCT as an important tool for documenting RNFL thinning in ON patients. Visual evoked potential can be used as diagnostic tool to find subclinical cases of optic neuritis. VEP mean value in our study was 145.12. This confirms the pathology in anterior visual pathway. Various other lab investigations like ESR, CRP, ANA, ANCA were done to correlate the associations of optic neuritis.None of these parameters showed consistent associations in our study.8% patients (2 patients) showed presence of CSF microproteins which on further evaluation were diagnosed with MS. A useful serum marker for Neuromyelitis optica (NMO) is the presence of NMO–IgG, which is believed to cause demyelination, both in NMO and in isolated ON. In our study only 8%patients(one patient) showed the presence of anti-NMO positive antibodies and also showed recurrence. This patient was 18 yr old Female, presented with first episode of ON with visual acuity of 6/36 in right eye and FCCF in left eye. The patient was treated with IVMP and she gained visual acuity of 6/6 in both eyes, meanwhile the patient was also found Anti-NMO positive .The patient was followed up and showed recurrence after two months with visual acuity of 6/36 in both eyes. The patient was again treated with IVMP and gained visual acuity of 6/6 in both eyes. After 4 months the patient again showed recurrence with diminution of vision in both eyes. Upon Neurologists opinion the patient was again given systemic steroids and started on systemic steroid sparing agent (Azathioprine) as well. Now the patient is maintaining 6/9 vision in both eyes and is on Azathioprine. Thus the prognosis of ON with NMO was not good in our study with three episodes of recurrences which is also supported by literature. This was in accordance to study done by Sethi et al. [15], which showed 19% recurrence during follow up. Large clinical trials have reported that around 20% show recurrence during 5 years of follow up. Small sample size may be the cause of less recurrence in our study. ATT therapy is known to cause optic neuritis. In our study one patient had history of ATT intake many years back. The patient presented in our OPD as fresh case of ON with no previous history. Temporal disc pallor was present at time of presentation. The patient was treated with IVMP and the visual acuity was improved to 6/6. ATT may not be the cause of ON in this study as the patient presented as a newly diagnosed case of ON and had no history of prior diminution of vision. One patient presented was diagnosed with tubercular meningitis with ON with 6th nerve palsy with visual acuity of FCCF. Upon treatment with oral steroids, under cover of ATT, the patient showed improvement in visual acuity to upto 6/18 after 2 weeks. The correlation between ON and tuberculosis could not be established as only one patient presented with tuberculosis with ON. In our study MRI brain showed that 56% had no abnormality, 12 % showed optic neuritis associated with multiple sclerosis and only 8%patients reported demyelinating lesions. Study done by Saxena et al. [16] on 32 patients showed that on MRI brain, no lesion was seen in 12 cases and 8 cases had shown enhancement of the optic nerve in the affected eye only. Demyelinating lesions in the brain were present in 12 patients and in four patients some of the periventricular lesions enhanced with contrast. In our study one patient was diagnosed with multiple sclerosis on MRI brain and orbit. The patient had undergone treatment for MS i.e. inj avonex (Interferon beta 1-a) 30µg/0.5 ml once weekly. Patient was treated with IVMP and is presently on inj avonex (Interferon beta 1-a) 30µg/0.5 ml once weekly. The patient showed sequential involvement of both the eyes. So, it can be inferred that ON is a clinical diagnosis, MRI may or may not support the diagnosis. Retinal nerve fiber layer (RNFL) thinning has been demonstrated in cases of optic neuritis (ON) and multiple sclerosis (MS), but no definite RNFL loss pattern or association with visual functions is known in Indian eyes. Our study found no significant correlation between the thickness of retinal nerve fibre layer and visual acuity. Study done Saxena et al. [16] evaluated the changes in retinal nerve fiber thickness and visual acuity. RNFL thickness was reduced significantly in the ON and MS patients compared to the controls (P-0.001). Maximum loss is in the temporal quadrant. Lower visual function scores are associated with reduced average overall RNFL thickness. In ON group, RNFL thinning is associated with severe visual field defects while contrast sensitivity has strongest correlation with RNFL in the MS group. The visual evoked response (VER) in the optic neuritis patients showed decreased amplitude as well as increased latency in comparison to the controls. The increase in latency seen in demyelinating diseases is due to the impaired saltatory conduction and the consequent reduction in the speed of transmission of nerve impulses. The decreased amplitude points to the actual decrease in number of axons carrying the impulses, possibly secondary to axonal loss in optic neuritis patients.

Our study didn’t find any significant correlation between visual evoked potential and the visual acuity though almost all patients had abnormal VEP at presentation. Results were comparable to the study done by Costello et al. [21] where there was significant decrease in visual evoked potential but no significant relation was found between the visual acuity and VEP. The reason for poor correlation between vision and RNFL thinning may be evaluation of Contrast sensitivity, colour vision and perimetry in follow-up period may correlate better to RNFL function. Snellen’s visual acuity may not correlate well with RNFL function. So most of our results are supported by literature especially studies done in Asian region. Larger sample size and longer follow up duration may help us in establishing a better correlation of optic neuritis with other factors.

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