Adding Papillomacular Bundle Measurements to Standard Optical Coherence Tomography Does Not Increase Sensitivity to Detect Prior Optic Neuritis in Patients with Multiple Sclerosis.

PURPOSE: To improve the detection of retinal nerve fiber layer (RNFL) thinning in multiple sclerosis (MS), a special peripapillary ring scanning algorithm (N-site RNFL, N-RNFL) was developed for spectral domain optical coherence tomography (SD-OCT). In contrast to the standard protocol (ST-RNFL) scanning starts nasally, not temporally, and provides an additional sector of analysis, the papillomacular bundle (PMB). We aimed to ascertain whether the temporal RNFL differs between the two techniques, whether N-RNFL is more sensitive than ST-RNFL to detect previous optic neuritis (ON), and whether analyzing the PMB adds additional sensitivity. Furthermore, we investigated whether RNFL is associated with disease severity and/or disease duration. METHODS: We conducted a cross-sectional case-control study of 38 patients with MS, of whom 24 had a history of ON, and 40 healthy controls (HC). Subjects with ON within the previous 6 months were excluded. Records included clinical characteristics, visual evoked potentials (VEP), and SD-OCT in both techniques. RESULTS: In a total of 73 evaluable MS eyes, temporal N-RNFL was abnormal in 17.8%, temporal ST-RNFL in 19.2%, and the PMB-RNFL in 21.9%. In ON eyes, the sensitivity of temporal N-RNFL and ST-RNFL did not differ significantly (37.0%/33.3%, p = 0.556). The sensitivity of VEP was 85.2%. RNFL thickness was associated with disease severity in all eyes, with and without a history of ON, and with disease duration. CONCLUSION: The two OCT techniques detected previous ON with similar sensitivity, but the sensitivity of VEPs was superior to that of both N-RNFL and ST-RNFL. Our results indicate that the widely used ST-RNFL technique is appropriate for peripapillary RNFL measurements in MS patients.

SIPA1L3 identified by linkage analysis and whole-exome sequencing as a novel gene for autosomal recessive congenital cataract.

Congenital cataract (CC) is one of the most important causes for blindness or visual impairment in infancy. A substantial proportion of isolated CCs has monogenic causes. The disease is genetically heterogeneous, and all Mendelian modes of inheritance have been reported. We mapped a locus for isolated CC on 19p13.1-q13.2 in a distantly consanguineous German family with two sisters affected by dense white cataracts. Whole-exome sequencing identified a homozygous nonsense variant c.4489C>T (p.(R1497*)) in SIPA1L3 (signal-induced proliferation-associated 1 like 3) in both affected children. SIPA1L3 encodes a GTPase-activating protein (GAP), which interacts with small GTPases of the Rap family via its Rap-GAP-domain. The suggested role of Rap GTPases in cell growth, differentiation and organization of the cytoskeleton in the human lens, and lens-enriched expression of the murine ortholog gene Sipa1l3 in embryonic mice indicates that this gene is crucial for early lens development. Our results provide evidence that sequence variants in human SIPA1L3 cause autosomal recessive isolated CC and give new insight into the molecular pathogenesis underlying human cataracts.

Experiences with rituximab for the treatment of autoimmune diseases with ocular involvement.

OBJECTIVE: To report the efficacy of rituximab (RTX) in the treatment of ocular or orbital inflammation accompanying autoimmune diseases refractory to previous standard immunosuppressive therapy. METHODS: We reviewed medical records of 9 consecutive patients with noninfectious ocular or orbital inflammation treated with RTX. RESULTS: Over a mean followup of 42 months, 7 patients were in clinical remission, 1 had partial response to treatment, and 1 did not respond. Best corrected visual acuity improved ≥ 1 line in 4 patients, was stable in another 4 patients, and worsened in 1. Concomitant immunosuppressive therapy was tapered in 6 cases. Systemic corticosteroids were tapered or kept below 7.5 mg a day in 5 patients 1 year after the first RTX cycle. CONCLUSION: RTX therapy, in patients who are refractory to standard immunosuppressive therapy, was effective and showed a beneficial response to treatment including induction of clinical remission of inflammation in most patients.

An unusual case of optic neuritis.

Optic neuritis is a frequent disease with well established tests and therapeutic strategies. However, possible differential diagnoses cover a broad spectrum. Therefore, clinical work-up can be challenging and routine testing and therapies may not be sufficient. In this case, a 26 year old female is described who presented with clinical features of optic neuritis, yet failed to respond to common therapeutic strategies and lost vision on the affected eye. Diagnostic nerve transection was performed, histopathology suggested inflammation. As the second nerve became affected, immunosuppressive therapy with cyclophosphamide was started and stopped further deterioration. Although additional molecular work-up of the transected nerve revealed clonal rearrangement of the B-cell-receptor-locus IgH, overall histopathologic features and the absence of systemic disease suggested an aggressive inflammatory process rather than lymphoma. Additional B-cell depletion with rituximab prompted significant and sustained visual improvement. This case emphasizes the necessity to consider rare differential diagnoses of optic neuritis, when uncommon features arise during the course of disease. Aggressive immunosuppression might be required to achieve stable improvement of vision.