Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis.

BACKGROUND: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. METHODS: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. RESULTS: Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. CONCLUSIONS: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.

Impact of primary headache disorder on quality of life among school students in Kuwait.

BACKGROUND: Primary headache disorders have being increasingly reported in younger populations. They can have significant effects on their quality of life and academic achievement and may cause significant distress to their families. AIMS AND OBJECTIVES: To assess the burden of primary headache disorder and its impact on the quality of life on school student in Kuwait. METHODS: A cross-sectional study was conducted among Kuwaiti primary and middle school students of both genders in randomly selected schools located in two governorates in 2018/2019 academic year. Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire for children and adolescents was used to assess the impact of primary headaches on the quality of life. RESULTS: One thousand and ninety-one questionnaires were completed by primary and middle school students of both genders; of whom 466 students (girls 321 (68.88%) were diagnosed with primary headache disorders with mean age 11.98 ± 2.03 years. In the month prior to the survey, the effect of the headache was variable. The students lost a mean of 1.99 ± 2.015 days of school while they could not perform their usual activities for a mean of 2.84 ± 4.28 days. Their parents lost a mean of 2 ± 2.03 days of work because of headaches of their children and parents prohibited 5.7% of the students to engage in any activity due to their headaches. Difficulties in concentrations were reported as never sometimes (39.1%), often (24.8%), and always (26%). Majority of the students (51.5%) experienced a feeling of sadness ranging from sometimes to always. Most of the students (67.3%) struggled to cope with the headache and 22.4% were never able to cope. Additionally, 19.4% of students reported they did not want others noticing their headache. CONCLUSION: Primary headache disorder can have a significant impact on the quality of life in children. It can affect their engagement in activities and academic achievement. Implementing strategies to properly manage schoolchildren with primary headaches can have profound effects on their quality of life.

Risk of early relapse following the switch from injectables to oral agents for multiple sclerosis.

BACKGROUND AND PURPOSE: Early relapse outcomes in long-term stable patients switching from interferon ß/glatiramer acetate (IFNß/GA) to oral therapy are unknown. OBJECTIVE: The objective of this study was to compare early relapse and progression in multiple sclerosis (MS) patients switching to oral therapy following a period of stable disease on IFNß/GA, relative to a propensity-matched comparator of patients remaining on IFNß/GA. METHODS: The MSBase cohort study is a global, longitudinal registry for MS. Time to first 6-month relapse in previously stable MS patients switching from platform injectables ('switchers') to oral agents were compared with propensity-matched patients remaining on IFNß/GA ('stayers') using a Cox marginal model. RESULTS: Three-hundred and ninety-six switchers were successfully matched to 396 stayers on a 1:1 basis. There was no difference in the proportion of patients recording at least one relapse in the first 1-6 months by treatment arm (7.3% switchers, 6.6% stayers; P = 0.675). The mean annualized relapse rate (P = 0.493) and the rate of first 6-month relapse by treatment arm (hazard ratio 1.22, 95% confidence interval 0.70, 2.11) were also comparable. There was no difference in the rate of disability progression by treatment arm (hazard ratio 1.43, 95% confidence interval 0.63, 3.26). CONCLUSION: This is the first study to compare early relapse switch probability in the period immediately following switch to oral treatment in a population previously stable on injectable therapy. There was no evidence of disease reactivation within the first 6 months of switching to oral therapy.

BREMSO: a simple score to predict early the natural course of multiple sclerosis.

BACKGROUND AND PURPOSE: Early prediction of long-term disease evolution is a major challenge in the management of multiple sclerosis (MS). Our aim was to predict the natural course of MS using the Bayesian Risk Estimate for MS at Onset (BREMSO), which gives an individual risk score calculated from demographic and clinical variables collected at disease onset. METHODS: An observational study was carried out collecting data from MS patients included in MSBase, an international registry. Disease impact was studied using the Multiple Sclerosis Severity Score (MSSS) and time to secondary progression (SP). To evaluate the natural history of the disease, patients were analysed only if they did not receive immune therapies or only up to the time of starting these therapies. RESULTS: Data from 14 211 patients were analysed. The median BREMSO score was significantly higher in the subgroups of patients whose disease had a major clinical impact (MSSS≥ third quartile vs. ≤ first quartile, P < 0.00001) and who reached SP (P < 0.00001). The BREMSO showed good specificity (79%) as a tool for predicting the clinical impact of MS. CONCLUSIONS: BREMSO is a simple tool which can be used in the early stages of MS to predict its evolution, supporting therapeutic decisions in an observational setting.

Clinical predictors of disease progression in multiple sclerosis patients with relapsing onset in a nation-wide cohort.

BACKGROUND: Predicting disease progression over time is challenging despite the available literature data. AIM: To assess whether baseline clinical variables of MS patients would predict the conversion to progressive phase of the disease. MATERIALS & METHODS: Utilizing the national MS registry, patients who had relapsing onsets and had confirmed EDSS score at baseline and follow-up visits were included. Primary progressive MS and CIS patients were excluded. Clinical variables (gender, age at onset, disease duration, number of relapses, EDSS score) were collected. The end point was conversion to secondary progressive MS. Chi Square and multivariable logistic regression were used to determine the influence of clinical variables on disease progression. RESULTS: Data of 803 MS patients with relapsing onset were analyzed. Eighty five (10.6%) patients reached the end point. The risk of disease progression was significantly higher in men (p=0.015), in patients who developed MS≥40 years of age (p=0.041) and who had ≥3 relapses during their disease course (p<0.001). Spinal cord presentation at onset was predictive of progression (aOR=2.01; p=0.06) while optic neuritis at onset was associated with lower risk of progression (aOR=0.30; p=0.03). EDSS score at first visit did not influence disease progression when tested at 2 different cutoffs (EDSS<4 vs. ≥4 and EDSS<6 vs. ≥6) using multivariable logistic regression analysis (p=0.960 and p=0.866), respectively. CONCLUSION: Men and patients who presented at age 40 yeas or beyond had increased risk of MS progression. Spinal cord symptoms at onset and 3 or more relapses were predictive of progression.

Fingolimod-associated amenorrhea: a report of three cases.

Amenorrhea has not been reported as an adverse event in fingolimod phase III clinical trials in patients with multiple sclerosis (MS) with either 0.5 mg or 1.25 mg dosages. Here we report three cases of young women with MS who developed amenorrhea within 6 months of initiation of fingolimod. They experienced irregularities in their menstrual cycles in the first 3 months, which progressed to amenorrhea by 5(th) or 6(th) month. Gynecology evaluations showed no other etiologies. Menses returned to baseline after discontinuation of fingolimod for 2-3 months. Amenorrhea could be associated with fingolimod in the first year. Future surveillance is advised to determine the incidence rate of this adverse event.

Increasing prevalence and incidence rates of multiple sclerosis in Kuwait.

BACKGROUND: Kuwait was considered as low to intermediate risk area for MS. OBJECTIVES: To determine the prevalence and incidence rates of MS among Kuwaiti nationals based on 2011 population census. METHODS: This cross-sectional study was conducted between October 2010 and April 2013 using the newly developed national MS registry in Kuwait. Patients with a diagnosis of MS according to 2010 revised McDonald criteria were identified. The crude, age- and sex-specific prevalence and incidence rates among Kuwaiti patients were calculated. RESULTS: 1176 MS patients were identified of which 927 (78.8%) were Kuwaitis and 249 (21.2%) were expatriates. Among Kuwaiti patients, female to male ratio was 1.8:1 with a mean age of 35.40 ± 10.99 years. The prevalence rate of MS was 85.05 per 100,000 persons (95% CI: 82.80 - 87.04). There was a peak in prevalence among patients aged 30-39 years. The incidence of MS was 6.88 per 100,000 persons (95% CI 5.52-8.55). Between 2003 and 2011, the incidence increased 3.22 and 2.54 times in women and men respectively. CONCLUSION: Kuwait is considered a high-risk area for MS. The significant increase in prevalence and incidence rates may represent a true increase despite the improvement in case ascertainment and case definition.

Consensus recommendations for diagnosis and treatment of Multiple Sclerosis: 2023 revision of the MENACTRIMS guidelines.

With evolving diagnostic criteria and the advent of new oral and parenteral therapies for Multiple Sclerosis (MS), most current diagnostic and treatment algorithms need revision and updating. The diagnosis of MS relies on incorporating clinical and paraclinical findings to prove dissemination in space and time and exclude alternative diseases that can explain the findings at hand. The differential diagnostic workup should be guided by clinical and laboratory red flags to avoid unnecessary tests. Appropriate selection of MS therapies is critical to maximize patient benefit. The current guidelines review the current diagnostic criteria for MS and the scientific evidence supporting treatment of acute relapses, radiologically isolated syndrome, clinically isolated syndrome, relapsing remitting MS, progressive MS, pediatric cases and pregnant women. The purpose of these guidelines is to provide practical recommendations and algorithms for the diagnosis and treatment of MS based on current scientific evidence and clinical experience.

Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom.

AIM: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS). METHODS: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources. RESULTS: In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57-0.73) or BRACETD (RR = 0.46; 95% CI, 0.42-0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01-1.55) and BRACETD (HR = 1.46; 95% CI, 1.16-1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65-0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91-1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses. CONCLUSIONS: This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS.

There are several medications used to treat people with relapsing remitting multiple sclerosis, such as interferon-based therapies (Betaferon/Betaseron (US), Rebif, Avonex, Extavia), glatiramer acetate (Copaxone), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera), collectively named BRACETD. Other treatments for multiple sclerosis (MS) have a narrower use, such as natalizumab (Tysabri) or fingolimod (Gilenya), among others.This study objective was to assess how well natalizumab and fingolimod helped treating MS (clinical effectiveness) and subsequently estimate what the cost of these treatments is in comparison to the benefit they bring to people with rapidly evolving severe MS that use them in the United Kingdom (UK) (cost-effectiveness).We used an international disease registry (MSBase), which collects clinical data from people with MS in various centers around the world to compare the effectiveness of natalizumab, fingolimod and BRACETD treatments. We used a technique called propensity score matching to obtain results from comparable patient groups. People treated with natalizumab had better disease control, namely with fewer relapses and higher improvement on their disability level, than patients on fingolimod or BRACETD. Conversely, there were no differences between each group of people on a measure called disability worsening.Based on these clinical results, we built an economic model that simulates the lifetime costs and consequences of treating people with MS with natalizumab in comparison with fingolimod. We found that using natalizumab was less costly and was more effective compared to using fingolimod in UK patients.

Endovascular treatment of chronic cerebrospinal venous insufficiency in multiple sclerosis: a retrospective study.

BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI) has been proposed to be associated with multiple sclerosis (MS). Zamboni et al. reported significant improvement in neurological outcomes in MS patients who underwent percutaneous transluminal angioplasty (PTA). OBJECTIVES: To retrospectively evaluate the neurological outcomes in MS patients who underwent PTA. METHOD: Relapsing remitting MS patients who underwent PTA and completed at least 1 year post-PTA were assessed. Patients with clinically isolated syndrome or progressive forms of MS were excluded. Primary endpoint was the proportion of relapse-free patients at 1 year. Secondary endpoints were change in mean Expanded Disability Status Scale (EDSS) score and proportion of patients with new magnetic resonance imaging (MRI) activity (defined as either gadolinium-enhancing or new T2 lesions) at 1 year. RESULTS: Forty-five patients satisfied the inclusion criteria. Females constituted 71.1%. The mean age and mean disease duration were 33.76 and 7.16 years, respectively. At 1-year post-PTA, the proportion of relapse-free patients decreased from 84.44% to 66.67% (p = 0.085), whereas the mean EDSS score increased (p = 0.017). The proportion of patients with new MRI activity increased significantly from 17.78% to 44.44% (p = 0.012). A total of 35.6% of patients stopped their disease modifying therapies (DMTs). There was no difference among the patients who stopped their DMTs with respect to relapses, EDSS score or new MRI activity. CONCLUSION: The study revealed that PTA in relapsing remitting MS patients was not associated with any neurological improvement. However, there was an increase in disease activity irrespective of the adherence to DMTs. Further evidence of the association between CCSVI and MS is required.

Use of natalizumab in patients with active relapsing-remitting multiple sclerosis in Kuwait.

OBJECTIVE: To evaluate the outcomes of patients with multiple sclerosis (MS) who were treated with natalizumab in Kuwait. MATERIALS AND METHODS: A retrospective study using the MS registry to identify patients who were treated with natalizumab was conducted. Patients' demographics, clinical characteristics and treatment parameters were collected at baseline and last follow-up visit. Primary outcome was the proportion of relapse-free patients at the last follow-up while secondary outcomes were the change in the mean annual relapse rate, Expanded Disability Status Scale (EDSS) and the proportion of patients with magnetic resonance imaging (MRI) activity at the last follow-up visit. Forty-four patients were included in the study. RESULTS: Of the 44 patients, 27 (61.4%) were females and the remaining 17 (38.6%) males. Mean age of patients and mean disease duration were 29.05 ± 7.25 and 5.71 ± 3.37 years, respectively. The mean number of natalizumab infusions was 18.14. The proportion of relapse-free patients significantly increased from 11.36 to 90.91% (p < 0.0001). The EDSS significantly improved from 4.76 to 3.15 (p < 0.0001) over the observational period. There was no significant difference between patients with EDSS <3 compared to those with EDSS ≥ 3 (p < 0.67). The proportion of patients with MRI activity was significantly reduced from 95.5 to 18.2% (p < 0.0001) at their last visit. Six patients discontinued the drug, 5 due to positive JC virus and 1 due to pregnancy. CONCLUSIONS: Natalizumab induced a suppression of disease activity and was responsible for a significant improvement in disability status in highly active MS patients.

Clinical characteristics of multiple sclerosis in Kuwait: data from the new MS registry of Amiri Hospital.

OBJECTIVES: To study clinical characteristics of multiple sclerosis (MS) patients in Kuwait and to collect data on annual relapse rates and disability measures. METHOD: An MS Registry was created in Amiri Hospital. Demographic, clinical characteristics, and disability measures using Expanded Disability Status Scale (EDSS) score at last visit were collected. RESULTS: Data from 218 patients formed the basis of the study cohort. Female to male ratio was 1.95. Mean age of onset of MS was 26.8 years. Seventy-eight percent had a relapsing-remitting course, 9.2% had secondary progressive course, and 2.8% had primary progressive course. The clinically isolated syndrome (CIS) group constituted 10.1%. The mean disease duration was 8 ± 7.2 years. Forty-five percent of patients had ≤5 years of disease duration, followed by 24.3% and 25.2% in the 5-10 and 10-20 years durations. Only 5.5% had MS for >20 years; 77.1% of patients had <1 relapse per year, while 22% had 1-2 relapses per year; 67.89% of patients had EDSS score <4, whereas 17.89% were found to have EDSS of ≥6. SUMMARY: MS in Kuwait predominantly affects female. The mean age of onset and frequency of MS types are comparable to worldwide figures. The annual relapse rates and the EDSS scores were relatively low in our cohort.

Consensus recommendations for the diagnosis and treatment of multiple sclerosis: 2019 revisions to the MENACTRIMS guidelines.

With evolving diagnostic criteria and the advent of new oral and parenteral therapies for MS, most current diagnostic and treatment algorithms need revision and updating. The diagnosis of MS relies on incorporating clinical and paraclinical findings to prove dissemination in space and in time, and exclude alternative diseases that can explain the findings at hand. The differential diagnostic workup should be guided by clinical and laboratory red flags to avoid unnecessary tests. Appropriate selection of multiple sclerosis (MS) therapies is critical to maximize patient benefit. The current guidelines review the scientific evidence supporting treatment of acute relapses, radiologically isolated syndrome, clinically isolated syndrome, relapsing remitting MS, and progressive MS. The purpose of these guidelines is to provide practical recommendations and algorithms for the diagnosis and treatment of MS based on current scientific evidence and clinical experience.

Non-convulsive status epilepticus; the rate of occurrence in a general hospital.

BACKGROUND: Non-convulsive status epilepticus (NCSE) has been increasingly recognized as a cause of impaired level of consciousness in the ICU and emergency rooms. The diagnosis can be easily missed without an electroencephalogram (EEG) given the paucity of overt clinical signs in this condition. Recently few published data estimated the prevalence to be between 3% and 8%. OBJECTIVE: To assess the rate of occurrence of NCSE among patients with various degrees of impaired consciousness referred to the Neurophysiology Laboratory at Vancouver General Hospital. METHOD: We conducted a retrospective analysis of 451 adult patients (>16 years of age) with a question of NCSE or with an unknown cause of impaired level of consciousness between the years 2002 and 2004. NCSE was defined according to the Young's criteria of electrographic status epilepticus. NCSE was categorized into focal and generalized epileptic activity based on the continuous EEG monitoring (CEEG). Further analysis of age, gender and etiology was performed. RESULTS: Of 451 patients, EEG demonstrated electrographic status epilepticus with no overt clinical signs in 42 patients (9.3%). Median age was 61.8 years (range 21-94). According to etiology, 38.1% of patients with NCSE had hypoxic-anoxic injury, 19% had intracerebral hemorrhage (including trauma), 11.9% had the diagnosis of idiopathic or cryptogenic epilepsy, 7.1% had ischemic stroke, 4.8% were secondary to tumors and 4.8% to viral encephalitis. CONCLUSION: The rate of occurrence of NCSE in patients with decreased level of consciousness was 9.3%. The cohort represented a group of patients who were comatose and required assisted ventilation or had altered level of consciousness. Hypoxic brain injury was the most responsible etiology of NCSE in the cohort studied.

The prevalence of multiple sclerosis continues to increase in Kuwait.

BACKGROUND: The national MS registry was established in 2010 to assess the change in epidemiological status. The last reported data of the prevalence and incidence in Kuwait was in 2013. OBJECTIVES: To update the prevalence and incidence rates of MS among Kuwaiti nationals. METHODS: Using the national MS registry, a cross sectional study was conducted to estimate the number of all patients diagnosed with MS and clinically isolated syndrome suggestive of MS. The diagnosis was based on the revised 2017 McDonald criteria. The population census was acquired from the Public Authority of Civil Information. RESULTS: On 30th June 2018, 1454 Kuwaiti MS patients fulfilled the diagnostic criteria. Women represented 66.8% of the analyzed cohort with female to male ratio of 2.01:1. The crude prevalence of MS was 104.88 (95% CI: 89.5-121.9) per 100,000 persons, which increased 1.6 times since 2013. Age-adjusted prevalence peaked in the 30-39 and 40-49 year age groups in both females and male, with a decreasing tendency beyond 50 years of age. The incidence of MS was 5.39 (95% CI: 4.3-6.8) per 100,000 persons. The 5-year incidence was 6.4 per 100,000, which has been stable since the last reported rate. CONCLUSION: The prevalence of MS in Kuwaiti nationals continued to increase reflecting a better case ascertainment and improved awareness and referrals across the country. However, the incidence has stabilized in the last 5 years which was mostly driven by a slight decline in newly diagnosed cases in women compared to men despite the increase in the overall female to male ratio.

Alternative diagnoses in patients referred to specialized centers for suspected MS.

OBJECTIVES: The aim of this study is to explore the frequency, type, and predictors of alternative diagnoses among patients referred with a recent diagnosis of multiple sclerosis (MS) to two specialized MS centers in the Middle East. METHODS: This is a retrospective review of a prospectively followed cohort of MS patients at 2 University specialized MS centers. All patients referred for MS were included. The final diagnosis was recorded and demographic, clinical, laboratory, electrophysiological and radiological variables were collected. RESULTS: A total of 554 patients were included in this study of which 431 were referred for diagnostic confirmation. The final diagnosis of MS was confirmed in 300 (70%), while 114 (26%) turned out to have an alternative diagnosis and 15 (3.5%) fulfilled criteria for radiologically isolated syndrome (RIS). The most common alternative diagnoses were psychogenic (16.3%), non-specific MRI white matter lesions (14.7%), NMO (9.5%), migraine (8.6%) and systemic autoimmune disorders (8.6%). The strongest predictors of a final diagnosis of MS were: younger age, presence of oligoclonal bands in the CSF, periventricular, corpus callosum, spinal (P<0.0001), or enhancing lesions (P<0.005) on MRI. CONCLUSIONS: Our study shows that 30% of patients referred for a suspicion of MS end up with a different diagnosis. The most common alternative diagnoses of MS in the Middle East are not different from what has been described in Western countries. Age, MRI and CSF findings can help with the differential diagnosis.

Optic Nerve Sheath Meningioma Masquerading as Optic Neuritis.

Optic neuritis is a common presentation of demyelinating disorders such as multiple sclerosis. It typically presents with acute painful monocular vision loss, whereas chronic optic neuropathy can be caused by compressive lesions along the anterior visual pathway, genetic, toxic, or nutritional causes. We report an unusual presentation mimicking optic neuritis, which was subsequently diagnosed as optic nerve sheath meningioma (ONSM). Misinterpretation of white matter lesions on MRI of brain and the failure to image the optic nerves at the time of acute loss of vision led to the misdiagnosis of optic neuritis in this case. A comprehensive accurate history and ordering the appropriate imaging modality remain paramount in diagnosing progressive visual deterioration.

Ganglion cell analysis in acute optic neuritis.

BACKGROUND: Optic neuritis has a diagnostic and prognostic significance in predicting the development of multiple sclerosis. Optical coherence tomography is being increasingly used to detect and monitor axonal damage in MS by measuring the retinal nerve fiber layer (RNFL). However, RNFL can be affected by edema and inflammation and obscure early axonal damage. OBJECTIVE: To study the pattern of change in the ganglion cell and inner plexiform layer compared to retinal nerve fibber layer in acute optic neuritis using spectral domain OCT. METHODS: Ten patients with acute optic neuritis were followed prospectively for 6 months with spectral domain optical coherence tomography. A group of 40 of eyes of 20 healthy controls was used for baseline comparison. RESULTS: The ganglion cell and inner plexiform layer (GCIPL) was significantly lower (thinner) at onset in patients' affected (p=0.009) eyes. Both RNFL and GCIPL were significantly lower in affected eyes at 6 months (p=0.012 and p=0.007) respectively compared to baseline. CONCLUSION: The GCIPL is probably more sensitive index of axonal loss than the RNFL in acute optic neuritis and could be a better index to detect neurodegeneration in multiple sclerosis. This can helpful in estimating early axonal loss and can potentially be used in therapeutic trials of neuroprotective drugs.