Faculty Bibliography

Digital health technologies (DHTs) can transform neurological assessments, improving quality and continuity of care. In the United States, the Food & Drug Administration (FDA) oversees the safety and efficacy of these technologies, employing a detailed regulatory process that classifies devices based on risk and requires rigorous review and post-market surveillance. Following FDA approval, DHTs enter the Current Procedural Terminology, Relative Value Scale Update Committee, and Centers for Medicare & Medicaid Services coding and valuation processes leading to coverage and payment decisions. DHT adoption is challenged by rapid technologic advancements, an inconsistent evidence base, marketing discrepancies, ambiguous coding guidance, and variable health insurance coverage. Regulators, policymakers, and payers will need to develop better methods to evaluate these promising technologies and guide their deployment. This includes striking a balance between patient safety and clinical effectiveness versus promotion of innovation, especially as DHTs increasingly incorporate artificial intelligence. Data validity, cybersecurity, risk management, societal, and ethical responsibilities should be addressed. Regulatory advances can support adoption of these promising tools by ensuring DHTs are safe, effective, accessible, and equitable.

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.

A 16-year-old adolescent boy presented with recurrent episodes of weakness and numbness. Brain MRI demonstrated subcortical, juxtacortical, and periventricular white matter T2 hyperintensities with gadolinium enhancement. CSF was positive for oligoclonal bands that were not present in serum. Despite treatment with steroids, IV immunoglobulins, plasmapheresis, and rituximab, he continued to have episodes of weakness and numbness and new areas of T2 hyperintensity on imaging. Neuro-ophthalmologic examination revealed a subclinical optic neuropathy with predominant involvement of the papillomacular bundle. Genetic evaluation and brain biopsy led to an unexpected diagnosis.

BACKGROUND:Spectral Optical Coherence Tomography (OCT) and Visual Evoked Potentials (VEPs) have both emerged as potentially useful biomarkers of cognitive decline in people with multiple sclerosis (PwMS). Their combined use may provide additional predictive value for identifying disease impact, progression, and remyelination capacity above-and-beyond what is captured using either approach alone. OBJECTIVE:We examined the relationship between OCT/VEP measures and cognitive functioning in 205 PwMS. OCT measures included Retinal Nerve Fiber Layer Volume (RNFLV), Papillo-Macular Bundle Volume (PBMV), and Macular Volume (MV). VEP measures included latency of the P100, and inter-ocular latency. Cognitive performance was evaluated across seven separate domains of performance, and for overall cognition, using the NeuroTrax computerized testing battery. RESULTS:Both OCT and VEP measures were significantly correlated with cognitive performance across several domains. Linear regression models that controlled for the influence of visual acuity revealed (1) that reduced MV was significantly predictive of poorer visual-spatial functioning, and (2) that delayed VEP latency was significantly predictive of performance in global cognitive functioning and visual-spatial functioning, after controlling for multiple comparisons. Among PwMS with normal visual acuity, PwMS with a combination of both relatively low MV and delayed VEP latency tended to have poorer performance in the domains of global, executive, and visual-spatial functioning compared to PwMS with both high MV and normal VEP latency. CONCLUSION/CONCLUSIONS:Approaches that combine the use of OCT and VEP measures can enhance insight into underlying factors that contribute to variance in cognitive functioning in PwMS.

Optic neuritis has long been considered a characteristic finding of multiple sclerosis and the initial manifestation of the disorder in about 25% of patients. Approximately 70% of patients will experience optic nerve dysfunction during their disease course.¹.

A 74-year-old man with chronic obstructive pulmonary disease, glaucoma, and Stage IIIB squamous cell lung cancer experienced several minutes of flashing lights in his right visual hemifield, followed by onset of a right visual field defect. On examination, the patient had a right homonymous hemianopsia that was most dense inferiorly by confrontation testing. Emergent CT scan of the head revealed a 2.5 × 3 cm hypodensity in the left occipital lobe, which was interpreted as an acute stroke. Continuous EEG monitoring captured left posterior quadrant seizures that were temporally correlated to the positive visual phenomena. Subsequent MRI of the brain with and without contrast revealed a conglomerate of centrally necrotic and peripherally enhancing mass lesions. On biopsy, a thick purulent material was drained and Gram stain of the sample revealed gram-positive beaded rods, which speciated to Nocardia farcinica. The patient was treated with a six-week course of intravenous meropenem and a one-year course of oral trimethroprim-sulfamethoxazole. On follow-up, the patient experienced resolution of the right visual field deficit.

Approximately half of the brain's circuits are involved in vision and control of eye movements. Therefore, visual dysfunction is a common symptom of concussion, the mildest form of traumatic brain injury (TBI). Photosensitivity, vergence dysfunction, saccadic abnormalities, and distortions in visual perception have been reported as vision-related symptoms following concussion. Impaired visual function has also been reported in populations with a lifetime history of TBI. Consequently, vision-based tools have been developed to detect and diagnose concussion in the acute setting, and characterize visual and cognitive function in those with a lifetime history of TBI. Rapid automatized naming (RAN) tasks have provided widely accessible and quantitative measures of visual-cognitive function. Laboratory-based eye tracking approaches demonstrate promise in measuring visual function and validating results from RAN tasks in patients with concussion. Optical coherence tomography (OCT) has detected neurodegeneration in patients with Alzheimer's disease and multiple sclerosis and may provide critical insight into chronic conditions related to TBI, such as traumatic encephalopathy syndrome. Here, we review the literature and discuss the future directions of vision-based assessments of concussion and conditions related to TBI.