Ocular Manifestations of Multiple Sclerosis: A Population-Based Study.

BACKGROUND: To evaluate the population-based frequency and severity of multiple sclerosis (MS)-related ocular diseases. METHODS: Retrospective, population-based study examining patients with MS between January 1, 1998 and December 31, 2011. Patients were identified using the Rochester Epidemiology Project, which is a record-linkage system of medical records for all patient-physician encounters among Olmsted County, Minnesota residents. Diagnosis of MS was confirmed based on neuroimaging, cerebrospinal fluid studies, and serum studies for each patient according to the 2017 McDonald criteria. Patient data were obtained using the medical records and followed through April 1, 2018. RESULTS: Of the 116 patients with MS, 66% were female and the median age of onset was 36 years (interquartile range 27.5-43.5 years). About half (61/116, 53%) had MS-related neuro-ophthalmic manifestations during their disease course, and about one-fourth (33/116, 28%) had visual symptoms as their presenting symptom of MS, most commonly as optic neuritis (26/116, 22%). Optic neuritis was the leading MS-related ocular condition (37%), followed by internuclear ophthalmoplegia (16%) and nystagmus (13%). Optic neuritis was mostly unilateral (40/43, 93%), with 16% (6/43) having a visual acuity of 20/200 or worse at nadir but ultimately 95% (35/37) improving to a visual acuity of 20/40 or better. CONCLUSIONS: This study provides the population-based frequency of MS-related ocular disease, which demonstrates a high frequency of ocular manifestations in MS both at disease onset and during the disease course, emphasizing the utility of neuro-ophthalmologists, or collaboration between neurologists and ophthalmologists, in the care of patients with MS.

An update on optic neuritis.

Optic neuritis (ON) is the most common cause of subacute optic neuropathy in young adults. Although most cases of optic neuritis (ON) are classified as typical, meaning idiopathic or associated with multiple sclerosis, there is a growing understanding of atypical forms of optic neuritis such as antibody mediated aquaporin-4 (AQP4)-IgG neuromyelitis optica spectrum disorder (NMOSD) and the recently described entity, myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD). Differentiating typical ON from atypical ON is important because they have different prognoses and treatments. Findings of atypical ON, including severe vision loss with poor recovery with steroids or steroid dependence, prominent optic disc edema, bilateral vision loss, and childhood or late adult onset, should prompt serologic testing for AQP4-IgG and MOG-IgG. Although the traditional division of typical and atypical ON can be helpful, it should be noted that there can be severe presentations of otherwise typical ON and mild presentations of atypical ON that blur these traditional lines. Rare causes of autoimmune optic neuropathies, such as glial fibrillary acidic protein (GFAP) and collapsin response-mediator protein 5 (CRMP5) autoimmunity also should be considered in patients with bilateral painless optic neuropathy associated with optic disc edema, especially if there are other accompanying suggestive neurologic symptoms/signs. Typical ON usually recovers well without treatment, though recovery may be expedited by steroids. Atypical ON is usually treated with intravenous steroids, and some forms, such as NMOSD, often require plasma exchange for acute attacks and long-term immunosuppressive therapy to prevent relapses. Since treatment is tailored to the cause of the ON, elucidating the etiology of the ON is of the utmost importance.

Left-sided valvular heart disease and retinopathy in a 38-year-old woman with attenuated mucopolysaccharidosis: a case report.

Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders caused by deficient levels and/or activity of glycosaminoglycan (GAG)-degradative enzymes. MPS are characterized by accumulation of the mucopolysaccharides heparan sulfate, dermatan sulfate, keratan sulfate, or chondroitin sulfate in tissues. We report the case of a 38-year-old woman with a history of joint restriction and retinitis pigmentosa who developed bivalvular heart failure requiring surgery. It was not until pathological examination of surgically excised valvular tissue that a diagnosis of MPS I was made. Her musculoskeletal and ophthalmologic symptoms, when placed in the context of MPS I, painted the diagnostic picture of a genetic syndrome that was overlooked until a diagnosis was made in late middle age.

• A 38-year-old woman with heart failure had heart valve surgery. Examining her cardiac valve tissue under the microscope suggested a metabolic disorder called mucopolysaccharidosis type I (MPS I). • MPS I is due to defective breakdown of sugar molecules (called glycosaminoglycans or GAGs for short) in the body which then can accumulate, causing dysfunction. • Our patient had short stature, a curved spine, stiff joints, and a degenerative eye disease called retinitis pigmentosa, all of which were due to her undiagnosed MPS I. • Most patients with MPS I are discovered on newborn screening when they are babies, or at very young ages due to severe symptoms related to the disease. • Our patient had a form of MPS I that was less severe, and the first symptom she received medical care for was her eye symptoms. • A diagnosis of MPS I made in middle adulthood is unusual for MPS I, and so is an important learning case for providers as there were clues hidden in her medical history that suggested a genetic or inherited syndrome. • Our genetics specialists were able to make a definitive diagnosis of MPS I and begin treatment with enzyme replacement therapy, as well as provide information for the patient about her risk of passing this disease on to children.

PROGRESSION OF PARTIAL POSTERIOR VITREOUS DETACHMENT OVER TIME.

PURPOSE: We investigated interindividual differences in the rate of change of posterior vitreous detachment (PVD) stage and vitreomacular adhesion area (VMAA). Crosssectional studies demonstrated increasing PVD stage and decreasing VMAA with age, but population-level means may mask interindividual variation in the rate of change. METHODS: We retrospectively evaluated PVD stage and VMAA in asymptomatic eyes of subjects who underwent repeated optical coherence tomography screening for high-risk medication use or isolated retinal disease in the fellow eye. A Turnbull estimator modeled changes in the PVD stage, and linear mixed models evaluated VMAA change. RESULTS: We evaluated 101 eyes of 101 subjects. Seventy-six eyes remained in the same stage. Twenty-three eyes progressed to a higher stage. Modeling of longitudinal data predicts that at age 30, time to convert to Stage 4 is 26 years; at age 40, it is 16 years; at age 50, it is 9 years; and at age 60, it is 8 years. In 37 eyes with Stage 1 partial PVD, VMAA decreased at a similar rate. The average population level decline in VMAA was 0.13 mm2/year. CONCLUSION: Individuals vary in age at which they progress to complete PVD. In early partial PVD, VMAA decreases at a similar rate across individuals.

Assessing the Influence of OCT-A Device and Scan Size on Retinal Vascular Metrics.

Purpose: The purpose of this study was to investigate the effect of device and scan size on quantitative optical coherence tomography angiography (OCT-A) metrics. Methods: The 3 × 3 mm scans from Optovue AngioVue and Zeiss AngioPlex systems were included for 18 eyes of 18 subjects without ocular pathology. The foveal avascular zone (FAZ) was segmented manually by two observers, from which estimates of FAZ area (using both the nominal image scale and the axial length corrected image scale) and acircularity were derived. Three scan sizes (3 mm, 6 mm HD, and 8 mm) from the AngioVue system were included for 15 eyes of 15 subjects without ocular pathology. For each subject, larger image sizes were resized to the same resolution as 3 × 3 mm scans, aligned, then cropped to a common area. FAZ area, FAZ acircularity, average and total parafoveal intercapillary area, vessel density, and vessel end points were computed. Results: Between the devices used here, there were no significant differences in FAZ acircularity (P = 0.88) or FAZ area using scaled (P = 0.11) or unscaled images (P = 0.069). Although there was no significant difference in FAZ area across scan sizes (P = 0.30), vessel morphometry metrics were all significantly influenced by scan size. Conclusions: The scan devices and sizes used here do not affect FAZ area measures derived from manual segmentations. In contrast, vessel morphometry metrics are affected by scan size. As individual differences in axial length induce differences in absolute scan size, extreme care should be taken when interpreting metrics of vessel morphometry, both between and within OCT-A devices. Translational Relevance: A better characterization of the confounds surrounding OCT-A retinal vasculature metrics can lead to improved application of these metrics as biomarkers for retinal and systemic diseases.

Standard 6-mm Compared with Widefield 16.5-mm OCT for Staging of Posterior Vitreous Detachment.

PURPOSE: To assess whether 6-mm OCT scans, which image the macula, can distinguish complete from partial posterior vitreous detachment (PVD) in comparison with 16.5-mm OCT scans, which image the macula, optic nerve, and mid periphery. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: We compared 6-mm and 16.5-mm scans in 157 eyes of 157 retina clinic patients (mean age, 50 years; range, 10-64 years) with diabetic retinopathy (36%), no retinal disease (19%), and various retinal conditions (45%). We also analyzed 16.5-mm scans in 35 healthy eyes (asymptomatic fellow eyes of patients with unilateral retinal conditions; mean age, 46 years; range, 9-63 years). METHODS: Each participant underwent Heidelberg Spectralis imaging with the standard lens (6-mm scan) and/or the 55° lens (16.5-mm scan). On 6-mm scans, we classified eyes as stage 3 partial PVD when the posterior vitreous cortex was visualized without visible attachment. On 16.5-mm scans, we classified eyes as stage 3 when the vitreous was attached at the optic nerve and separated from the macula. On both scan types, we classified eyes as stage 4 when neither the premacular bursa nor the posterior vitreous cortex were visualized. We assessed the accuracy of this system for detecting complete PVD on 6-mm scans by calculating test characteristics using 16.5-mm scans as a reference standard. MAIN OUTCOME MEASURE: Posterior vitreous detachment stage (0-4). RESULTS: Posterior vitreous detachment stage was identical in 6-mm and 16.5-mm scans in 88% of eyes. Compared with 16.5-mm scans, 6-mm scans detected complete PVD (vs. earlier stages 0-3) with 91% sensitivity and 99% specificity. Seven eyes were classified as no PVD on 6-mm scans and were classified as partial PVD on 16.5-mm scans because vitreoretinal separation was localized to the mid periphery. All 16.5-mm scans showed some degree of PVD, including scans from 9 participants between 9 and 20 years of age. CONCLUSIONS: Six-millimeter scans distinguished complete from partial PVD with good sensitivity and specificity but missed the earliest stages of PVD, which occur in the mid periphery. Posterior vitreous detachment may begin as early as the second decade of life.

Accuracy of Spectral-Domain OCT of the Macula for Detection of Complete Posterior Vitreous Detachment.

PURPOSE: To assess the accuracy of macular spectral-domain OCT in detecting complete posterior vitreous detachment (PVD). DESIGN: Evaluation of diagnostic test or technology using a retrospective comparative study. PARTICIPANTS: One hundred seventy-five eyes in 175 patients (111 women and 64 men; mean age, 65 years) with preoperative OCT within 90 days of vitrectomy. METHODS: Posterior vitreous detachment status on preoperative macular OCT was compared with PVD determination during vitrectomy. Attached vitreous was identified on OCT by visualizing the posterior vitreous cortex or premacular bursa. Complete PVD was identified by the absence of these findings and considered a positive outcome for the purpose of analysis. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive value, and negative predictive value of macular OCT for detection of complete PVD compared with findings at surgery. RESULTS: Of the 38 eyes graded as showing complete PVD on OCT, 20 eyes were found to have pre-existing PVD at the time of surgery (true-positive results), and 18 eyes were found to have attached vitreous at the time of surgery (false-positive results). Of the 137 eyes graded as showing attached vitreous on OCT, 129 eyes had attached vitreous at the time of surgery (true-negative results), and 8 eyes had pre-existing PVD at the time of surgery (false-negative results). The sensitivity of OCT for detecting complete PVD was 71% and the specificity was 88%. In the study population, the positive predictive value of an OCT scan showing complete PVD was 53%, whereas the negative predictive value of an OCT scan showing attached vitreous was 94%. CONCLUSIONS: If the premacular bursa or posterior vitreous cortex are visualized on macular OCT, an accurate determination of attached vitreous can be made. The diagnosis of complete PVD by macular OCT is less accurate and requires ultrasound.