Faculty Bibliography

BACKGROUND:The randomized, phase 2 RENEW trial (NCT01721161) evaluated efficacy/safety of opicinumab (anti-LINGO-1) versus placebo in patients with first-episode unilateral acute optic neuritis (AON). Although no significant differences in the latency recovery of visual evoked potential (VEP) were observed between opicinumab and placebo groups in the intention to treat (ITT) population, the prespecified per-protocol (PP) population showed better recovery with opicinumab than with placebo. RENEWED (NCT02657915) was a one-visit, follow-up study 2 years after the last RENEW study visit (Week 32) designed to assess the long-term electrophysiological and clinical outcomes for participants previously enrolled and having received study treatment in RENEW. METHODS:In the original study (RENEW), participants (aged 18-55 years) with a first unilateral AON episode were enrolled ≤28 days from first symptom onset and after treatment with methylprednisolone 1 g/day intravenously for 3-5 days; these participants were randomized to receive opicinumab 100 mg/kg or placebo intravenously once every 4 weeks from baseline to Week 20, assessed up to Week 32. Participants who received ≥1 dose of opicinumab 100 mg/kg or placebo in RENEW were eligible for the RENEWED follow-up study. Participants enrolled in RENEWED at 2 years (with an additional up to 12-month window) after the last RENEW study visit (Week 32) in both ITT and PP populations. The primary endpoint was change in full-field VEP (FF-VEP) latency of the affected eye at RENEWED study visit versus baseline of the fellow eye in RENEW, comparing between participants who received opicinumab and placebo in RENEW. Clinical progression and severity of multiple sclerosis (MS) were assessed. A substudy evaluated latency recovery using multifocal VEP (mfVEP) as an exploratory endpoint. RESULTS:Of 82 RENEW participants, 52 (63.4 %; opicinumab n = 28, placebo n = 24) enrolled in and completed RENEWED. The adjusted mean (95 % CI) difference in FF-VEP latency delay between opicinumab and placebo groups was -6.0 (-14.6, 2.6) msec (p = 0.165) for the PP population and -4.5 (-12.6, 3.7) msec (p = 0.274) for the ITT population at the RENEWED study visit. Nominally significant improvement on mfVEP latency in the opicinumab group versus placebo was observed in participants of the mfVEP substudy (p = 0.009). In participants from the PP population without clinically definite MS (CDMS) at RENEW baseline,12 (55 %) in the opicinumab group and 12 (67 %) in the placebo group developed CDMS from enrollment in the RENEW study up to RENEWED Day 1; the estimated proportion of participants with CDMS at 2 years after the last study visit assessment in RENEW was lower when treated with opicinumab (0.50) than when treated with placebo (0.61) (hazard ratio p-value = 0.23). No benefit on visual acuity or other neurological functions was observed in the opicinumab group vs placebo in RENEWED. CONCLUSION/CONCLUSIONS:The numerically increased VEP latency recovery with opicinumab treatment in RENEWED was consistent with those observed in the parent study RENEW. However, the VEP latency and clinical data in RENEWED should be interpreted with caution, given the nature of the follow-up study, the small sample size and the limitation in study design.

BACKGROUND AND OBJECTIVES/UNASSIGNED:We determined inter-modality (in-person vs telemedicine examination) and inter-rater agreement for telemedicine assessments (2 different examiners) using the Telemedicine Buffalo Concussion Physical Examination (Tele-BCPE), a standardized concussion examination designed for remote use. METHODS/UNASSIGNED:Patients referred for an initial evaluation for concussion were invited to participate. Participants had a brief initial assessment by the treating neurologist. After a patient granted informed consent to participate in the study, the treating neurologist obtained a concussion-related history before leaving the examination room. Using the Tele-BCPE, 2 virtual examinations in no specific sequence were then performed from nearby rooms by the treating neurologist and another neurologist. After the 2 telemedicine examinations, the treating physician returned to the examination room to perform the in-person examination. Intraclass correlation coefficients (ICC) determined inter-modality validity (in-person vs remote examination by the same examiner) and inter-rater reliability (between remote examinations done by 2 examiners) of overall scores of the Tele-BCPE within the comparison datasets. Cohen's kappa, κ, measured levels of agreement of dichotomous ratings (abnormality present vs absent) on individual components of the Tele-BCPE to determine inter-modality and inter-rater agreement. RESULTS/UNASSIGNED:< 0.001]) were reliable (ICC >0.70). There was at least substantial inter-modality agreement (κ ≥ 0.61) for 25 of 29 examination elements. For inter-rater agreement (2 telemedicine examinations), there was at least substantial agreement for 8 of 29 examination elements. DISCUSSION/UNASSIGNED:Our study demonstrates that the Tele-BCPE yielded consistent clinical results, whether conducted in-person or virtually by the same examiner, or when performed virtually by 2 different examiners. The Tele-BCPE is a valid indicator of neurologic examination findings as determined by an in-person concussion assessment. The Tele-BCPE may also be performed with excellent levels of reliability by neurologists with different training and backgrounds in the virtual setting. These findings suggest that a combination of in-person and telemedicine modalities, or involvement of 2 telemedicine examiners for the same patient, can provide consistent concussion assessments across the continuum of care.

INTRODUCTION AND PROBLEM STATEMENT/UNASSIGNED:A chief resident's role incorporates administrative, academic, and interpersonal responsibilities essential to managing a successful residency program. However, rising chief residents receive little formal exposure to leadership training. OBJECTIVES/UNASSIGNED:To (1) define leadership styles; (2) understand the effect of cultural competence on leadership styles; (3) learn effective methods to advocate as the chief resident; (4) provide effective peer feedback; (5) provide effective supervisor feedback; (6) learn effective conflict management; (7) ensure psychological safety. METHODS AND CURRICULUM DESCRIPTION/UNASSIGNED:We developed a 1-day curriculum combining didactics and simulation activities for our program's rising chief residents. Implementation of our curricular design included a morning session focusing on small groups and didactic-based lectures on specific topics pertinent to leadership, along with a debriefing of a psychometric evaluation tool administered before the curriculum day. The simulation activity consisted of 3 group objective structured clinical examination (G-OSCE) scenarios: (1) providing a struggling junior trainee with feedback; (2) debriefing an adverse clinical outcome as the team leader; (3) navigating a challenging situation with a supervising physician. Standardized participants were surveyed for specific objectives. Learners completed precurricular and postcurricular surveys on their familiarity and preparedness for their chief year. RESULTS AND ASSESSMENT DATA/UNASSIGNED:= 0.421), learner-reported use of wellness resources was noted to be reduced after the curricular intervention and remains a result of further interest for exploration. DISCUSSION AND LESSONS LEARNED/UNASSIGNED:A 1-day leadership development curriculum combining didactics and simulation is an effective means of preparing rising chief residents to succeed in their transition to this leadership role.

BACKGROUND:Neuro-ophthalmology frequently requires a complex and multi-faceted clinical assessment supported by sophisticated imaging techniques in order to assess disease status. The current approach to diagnosis requires substantial expertise and time. The emergence of AI has brought forth innovative solutions to streamline and enhance this diagnostic process, which is especially valuable given the shortage of neuro-ophthalmologists. Machine learning algorithms, in particular, have demonstrated significant potential in interpreting imaging data, identifying subtle patterns, and aiding clinicians in making more accurate and timely diagnosis while also supplementing nonspecialist evaluations of neuro-ophthalmic disease. EVIDENCE ACQUISITION/METHODS:Electronic searches of published literature were conducted using PubMed and Google Scholar. A comprehensive search of the following terms was conducted within the Journal of Neuro-Ophthalmology: AI, artificial intelligence, machine learning, deep learning, natural language processing, computer vision, large language models, and generative AI. RESULTS:This review aims to provide a comprehensive overview of the evolving landscape of AI applications in neuro-ophthalmology. It will delve into the diverse applications of AI, optical coherence tomography (OCT), and fundus photography to the development of predictive models for disease progression. Additionally, the review will explore the integration of generative AI into neuro-ophthalmic education and clinical practice. CONCLUSIONS:We review the current state of AI in neuro-ophthalmology and its potentially transformative impact. The inclusion of AI in neuro-ophthalmic practice and research not only holds promise for improving diagnostic accuracy but also opens avenues for novel therapeutic interventions. We emphasize its potential to improve access to scarce subspecialty resources while examining the current challenges associated with the integration of AI into clinical practice and research.

OBJECTIVES/OBJECTIVE:Hospital readmissions are associated with poor health outcomes including illness severity and medical complications. The objective of this study was to identify characteristics associated with 30-day post-stroke readmission in an academic urban hospital network. MATERIALS AND METHODS/METHODS:We collected data on patients admitted with stroke from 2017 through 2022 who were readmitted within 30 days of discharge and compared them to a subset of non-readmitted stroke patients. Chart review was used to collect demographics, characteristics of the stroke, co-morbid conditions, in-hospital complications, and post-discharge care. Univariate analyses followed by regression analysis were used to assess characteristics associated with post-stroke readmission. RESULTS:We identified 4743 patients with stroke (18 % hemorrhagic, mean age 70.1 (standard deviation (SD) 17.2), 47.3 % female) discharged from the stroke services, of whom 282 (5.9 %) patients were readmitted within 30 days of index hospitalization. Univariate analyses identified 18 significantly different features between admitted and readmitted patients. Regression analysis revealed characteristics associated with readmission included private insurance (odds ratio (OR) 0.4, confidence interval (CI) 0.3-0.6, p < 0.001), comorbid peripheral vascular disease (PVD) (OR 2.7, CI 1.3-5.5, p = 0.009), malignancy (OR 1.6, CI 1.0-2.6, p = 0.04), seizure (OR 3.4, CI 1.4-8.2, p = 0.007), thrombolytic administration (OR 0.4, CI 0.2-0.7, p = 0.003), undergoing thrombectomy (OR 5.4, CI 2.9-10.1, p < 0.001), and higher discharge modified Rankin Scale score (OR 1.2, CI 1.0-1.3, p = 0.047). CONCLUSIONS:Our data demonstrate that thrombectomy, high discharge Rankin score, comorbid malignancy, seizure or PVD, and lack of thrombolytic administration or private insurance predict readmission.

BACKGROUND:Adult polyglucosan body disease (APBD) is caused by a deficiency in glycogen branching enzyme that leads to polyglucosan accumulation in multiple organs. It has a progressive clinical course with prominent neurologic manifestations. We aim to describe the neuro-ophthalmic manifestations of APBD. METHODS:This is a case series of 3 individuals with genetically proven APBD. Written informed consent was provided by the brothers. We also performed a literature review on the current state of knowledge on APBD through PubMed. RESULTS:Brother 1 developed gait imbalance and length-dependent polyneuropathy in his 40s followed by progressive urinary symptoms in his 50s. He reported diplopia and blurry vision in his 60s. Neuro-ophthalmic assessment revealed bilateral optic neuropathy, convergence insufficiency, and a right fourth nerve palsy. Genetic testing showed a homozygous pathogenic variant in GBE1 c.986A>C p.Tyr329Ser. Brother 2 developed progressive urinary symptoms in his 40s that were followed by cognitive deficits, length-dependent polyneuropathy, and lower extremity weakness in his 50s and 60s. He reported blurred vision, and neuro-ophthalmic evaluation revealed bilateral optic neuropathy. Genetic testing revealed the same variant as Brother 1, GBE1 c.986A>C p.Tyr329Ser. Brother 3 developed progressive urinary urgency and lower extremity weakness in his 50s followed by a length-dependent polyneuropathy in his 60s. He reported diplopia and blurry vision in his 70s. Neuro-ophthalmic assessment revealed bilateral optic neuropathy and convergence insufficiency. Genetic testing revealed the same variant as Brothers 1 and 2, GBE1 c.986A>C p.Tyr329Ser. CONCLUSIONS:There is an array of afferent and efferent neuro-ophthalmic manifestations in APBD. Neuro-ophthalmic evaluation is crucial in evaluating and treating patients with APBD, particularly in those with visual dysfunction.

BACKGROUND:Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a demyelinating disorder that most commonly presents with optic neuritis (ON) and affects children more often than adults. We report 8 pediatric patients with MOG-associated ON and characterize focal optical coherence tomography (OCT) abnormalities over time that help distinguish this condition from the trajectories of other demyelinating disorders. These OCT findings are examined in the context of longitudinal visual function testing. METHODS:This is a retrospective case series of 8 pediatric patients with MOG-associated ON who were referred for neuro-ophthalmic evaluation. Longitudinal data for demographics, clinical history, physical examination, and OCT obtained in the course of clinical evaluations were collected through retrospective medical record review. RESULTS:Patients demonstrated acute peripapillary retinal nerve fiber layer (RNFL) thickening in one or both eyes, consistent with optic disc swelling. This was followed by steady patterns of average RNFL thinning, with 9 of 16 eyes reaching significantly low RNFL thickness using OCT platform reference databases (P < 0.01), accompanied by paradoxical recovery of high-contrast visual acuity (HCVA) in every patient. There was no correlation between HCVA and any OCT measures, although contrast sensitivity (CS) was associated with global thickness, PMB thickness, and nasal/temporal (N/T) ratio, and color vision was associated with PMB thickness. There was a lower global and papillomacular bundle (PMB) thickness (P < 0.01) in clinically affected eyes compared with unaffected eyes. There was also a significantly higher N:T ratio in clinically affected eyes compared with unaffected eyes in the acute MOG-ON setting (P = 0.03), but not in the long-term setting. CONCLUSIONS:MOG shows a pattern of prominent retinal atrophy, as demonstrated by global RNFL thinning, with remarkable preservation of HCVA but remaining deficits in CS and color vision. These tests may be better clinical markers of vision changes secondary to MOG-ON. Of the OCT parameters measured, PMB thickness demonstrated the most consistent correlation between structural and functional measures. Thus, it may be a more sensitive marker of clinically significant retinal atrophy in MOG-ON. The N:T ratio in acute clinically affected MOG-ON eyes in our study was higher than the N:T ratio of neuromyelitis optica (NMO)-ON eyes and similar to the N:T ratio in multiple sclerosis (MS)-ON eyes as presented in the prior literature. Therefore, MOG may share a more similar pathophysiology to MS compared with NMO.