Improving explanation of motor disability with diffusion-based graph metrics at onset of the first demyelinating event.

BACKGROUND: Conventional magnetic resonance imaging (MRI) does not account for all disability in multiple sclerosis. OBJECTIVE: The objective was to assess the ability of graph metrics from diffusion-based structural connectomes to explain motor function beyond conventional MRI in early demyelinating clinically isolated syndrome (CIS). METHODS: A total of 73 people with CIS underwent conventional MRI, diffusion-weighted imaging and clinical assessment within 3 months from onset. A total of 28 healthy controls underwent MRI. Structural connectomes were produced. Differences between patients and controls were explored; clinical associations were assessed in patients. Linear regression models were compared to establish relevance of graph metrics over conventional MRI. RESULTS: Local efficiency (p = 0.045), clustering (p = 0.034) and transitivity (p = 0.036) were reduced in patients. Higher assortativity was associated with higher Expanded Disability Status Scale (EDSS) (ß = 74.9, p = 0.026) scores. Faster timed 25-foot walk (T25FW) was associated with higher assortativity (ß = 5.39, p = 0.026), local efficiency (ß = 27.1, p = 0.041) and clustering (ß = 36.1, p = 0.032) and lower small-worldness (ß = -3.27, p = 0.015). Adding graph metrics to conventional MRI improved EDSS (p = 0.045, ΔR2 = 4) and T25FW (p < 0.001, ΔR2 = 13.6) prediction. CONCLUSION: Graph metrics are relevant early in demyelination. They show differences between patients and controls and have relationships with clinical outcomes. Segregation (local efficiency, clustering, transitivity) was particularly relevant. Combining graph metrics with conventional MRI better explained disability.

Observational cohort study of 100 patients presenting with functional visual loss: clinical characteristics and comparison with other functional neurologic disorders.

OBJECTIVE: Recent research has helped to develop a more detailed understanding of many functional neurologic disorders. The aim of this study was to increase our knowledge of functional visual loss and to compare the findings with those of other functional syndromes. DESIGN: Prospective and retrospective observational cohort study. METHODS: This study took place at neuro-ophthalmology clinics at 3 major hospitals in London, United Kingdom, over a 12-month period. The study population consisted of 157 participants, 100 with functional visual loss, 21 pathologic control subjects with organic visual loss, and 36 healthy nonpathologic control subjects. All participants had their diagnosis confirmed with a full neuro-ophthalmic examination, neuroimaging, and visual electrophysiology. A full assessment of all participants' medical history was obtained from their general practitioner, and all participants completed a series of questionnaires assessing relevant associations. RESULTS: Data were obtained on 157 participants, 100 with functional visual loss, 21 pathologic control subjects with organic visual loss, and 36 healthy nonpathologic control subjects. Participants with functional visual loss were typically female (74%) with a mean age at vision loss of 40.0 ± 16 years. Sixty-four percent of participants had bilateral vision loss; the remainder, unilateral loss. Twenty-six percent of the total cohort had organic visual loss with functional overlay. Fifty percent of participants with functional visual loss had a preexisting psychiatric diagnosis, the most common being a depressive disorder. Sixty-two percent of participants had an ocular history, and 87% had a previously diagnosed medical illness, most commonly neurologic (45%). Thirty-five percent of participants self-reported at least 1 additional functional symptom. CONCLUSIONS: Our population of functional visual loss subjects shares many similarities with the majority of patients with other functional neurologic disorders. They are generally young and female and have a greater than expected rate of psychiatric, medical, and coexisting ocular conditions. We found increased rates of precipitating stressors, clinical depression, and organic eye problems in subjects with functional visual loss.

Associations between cortical lesions, optic nerve damage, and disability at the onset of multiple sclerosis: insights into neurodegenerative processes.

BACKGROUND: Multiple sclerosis cortical lesions are areas of demyelination and neuroaxonal loss. Retinal layer thickness, measured with optical coherence tomography (OCT), is an emerging biomarker of neuroaxonal loss. Studies have reported correlations between cortical lesions and retinal layer thinning in established multiple sclerosis, suggesting a shared pathophysiological process. Here, we assessed the correlation between cortical lesions and OCT metrics at the onset of multiple sclerosis, examining, for the first time, associations with physical or cognitive disability. OBJECTIVE: To examine the relationship between cortical lesions, optic nerve and retinal layer thicknesses, and physical and cognitive disability at the first demyelinating event. METHODS: Thirty-nine patients and 22 controls underwent 3T-MRI, optical coherence tomography, and clinical tests. We identified cortical lesions on phase-sensitive inversion recovery sequences, including occipital cortex lesions. We measured the estimated total intracranial volume and the white matter lesion volume. OCT metrics included peripapillary retinal nerve fibre layer (pRNFL), ganglion cell and inner plexiform layer (GCIPL) and inner nuclear layer (INL) thicknesses. RESULTS: Higher total cortical and leukocortical lesion volumes correlated with thinner pRNFL (B = -0.0005, 95 % CI -0.0008 to -0.0001, p = 0.01; B = -0.0005, 95 % CI -0.0008 to -0.0001, p = 0.01, respectively). Leukocortical lesion number correlated with colour vision deficits (B = 0.58, 95 %CI 0.039 to 1,11, p = 0.036). Thinner GCIPL correlated with a higher Expanded Disability Status Scale (B = -0.06, 95 % CI -1.1 to -0.008, p = 0.026). MS diagnosis (n = 18) correlated with higher cortical and leukocortical lesion numbers (p = 0.004 and p = 0.003), thinner GCIPL (p = 0.029) and INL (p = 0.041). CONCLUSION: The association between cortical lesions and axonal damage in the optic nerve reinforces the role of neurodegenerative processes in MS pathogenesis at onset.

Automated Pupillometry Using a Prototype Binocular Optical Coherence Tomography System.

PURPOSE: To determine the test-retest reliability and diagnostic accuracy of a binocular optical coherence tomography (OCT) prototype (Envision Diagnostics, El Segundo, California, USA) for pupillometry. DESIGN: Assessment of diagnostic reliability and accuracy. METHODS: Fifty participants with relative afferent pupillary defects (RAPDs) confirmed using the swinging flashlight method (mean age 49.6 years) and 50 healthy control subjects (mean age 31.3 years) were examined. Participants twice underwent an automated pupillometry examination using a binocular OCT system that presents a stimulus and simultaneously captures OCT images of the iris-pupil plane of both eyes. Participants underwent a single examination on the RAPDx (Konan Medical, Irvine, California, USA), an automated infrared pupillometer. Pupil parameters including maximum and minimum diameter, and anisocoria were measured. The magnitude of RAPD was calculated using the log of the ratio of the constriction amplitude between the eyes. A pathological RAPD was above ±0.5 log units on both devices. RESULTS: The intraclass correlation coefficient was >0.90 for OCT-derived maximum pupil diameter, minimum pupil diameter, and anisocoria. The RAPDx had a sensitivity of 82% and a specificity of 94% for detection of RAPD whereas the binocular OCT had a sensitivity of 74% and specificity of 86%. The diagnostic accuracy of the RAPDx and binocular OCT was 88% (95% confidence interval 80%-94%) and 80% (95% confidence interval 71%-87%) respectively. CONCLUSIONS: Binocular OCT-derived pupil parameters had excellent test-retest reliability. The diagnostic accuracy of RAPD was inferior to the RAPDx and is likely related to factors such as eye movement during OCT capture. As OCT becomes ubiquitous, OCT-derived measurements may provide an efficient method of objectively quantifying the pupil responses.

Sensitivity and specificity of the AdenoPlus point-of-care system in detecting adenovirus in conjunctivitis patients at an ophthalmic emergency department: a diagnostic accuracy study.

BACKGROUND: To estimate the diagnostic accuracy (sensitivity and specificity) of the AdenoPlus point-of-care adenoviral test compared to PCR in an ophthalmic accident and emergency service. These findings were compared with those of a previous study. METHODS: This was a prospective diagnostic accuracy study on 121 patients presenting to an emergency eye unit with a clinical picture of acute adenoviral conjunctivitis. AdenoPlus testing was carried out on one eye of each patient and a PCR analysis was also performed on a swab taken from the same eye. AdenoPlus and PCR results were interpreted by masked personnel. Sensitivity and specificity for the AdenoPlus test were calculated using PCR results as the reference standard. RESULTS: 121 patients were enrolled and 109 met the inclusion criteria. 43 patients (39.4%) tested positive for adenovirus by PCR analysis. The sensitivity of the AdenoPlus swab in detecting adenovirus was 39.5% (17/43, 95% CI 26% to 54%) and specificity was 95.5% (63/66, 95% CI 87% to 98%) compared to PCR. CONCLUSIONS: The AdenoPlus test has a high specificity for diagnosing adenoviral conjunctivitis, but in this clinical setting, we could not reproduce the high sensitivity that has been previously published.

Intravitreal bevacizumab in refractory neovascular glaucoma: a prospective, observational case series.

OBJECTIVE: To examine the efficacy of intravitreal bevacizumab for pain relief in eyes with refractory neovascular glaucoma. METHODS: In this prospective case series, 52 eyes with neovascular glaucoma were administered intravitreal bevacizumab, 1.25 mg, and monitored for 6 months. The primary outcome measure was change in subjective pain score. Intraocular pressure and iris neovascularization were evaluated at each visit. Surgical intervention for control of intraocular pressure was performed according to clinical need. RESULTS: Forty-two patients (44 eyes) completed the 6-month follow-up. Subjective pain score was reduced significantly 1 week after intravitreal bevacizumab injection and lasted throughout the follow-up period (median [interquartile range]: baseline, 3 [0-6]; week 1, 1 [0-3]; month 1, 0 [0-1]; month 3, 0 [0-1]; and month 6, 0 [0-0]; Kruskal-Wallis χ(2) 31.03; P < .001). A rapid, yet relatively transient, reduction in iris neovascularization was also noted (iris neovascularization grade at baseline, 4.0 [3-4]; week 1, 2.5 [1-4]; month 1, 2.0 [1-4]; month 3, 3.0 [2-4]; and month 6, 3.0 [2-4], χ(2) 23.33; P < .001). Four eyes (8%) required more than 1 injection to facilitate further intraocular surgery. CONCLUSIONS: Intravitreal bevacizumab is a useful adjunct in the management of refractory neovascular glaucoma, producing rapid relief of pain. However, we found no evidence to suggest that intravitreal bevacizumab lowers intraocular pressure in eyes with angle closure; conventional medical, laser, and surgical treatment are still needed in these eyes.