Ocular manifestations of Blau syndrome.

PURPOSE OF REVIEW: This article summarizes the systemic and ocular manifestations of Blau syndrome, its genetic basis, and reviews recently published literature. RECENT FINDINGS: A large multicenter prospective case series is underway, with 3-year preliminary results indicating the prevalence of uveitis, clinical characteristics and early data on its visual prognosis. Case reports have demonstrated the successful use of newer biologic agents. SUMMARY: Blau syndrome is an exceedingly rare autoinflammatory disorder with skin, joint and eye manifestations. It is caused by autosomal dominant mutations of the NOD2 protein. Eye involvement is typically a chronic bilateral granulomatous iridocyclitis, often with multifocal choroiditis in the posterior segment. Treatment starts with topical and systemic steroids and often requires antimetabolites or biologic agents.

RhoC maintains vascular homeostasis by regulating VEGF-induced signaling in endothelial cells.

Vasculogenesis and angiogenesis are controlled by vascular endothelial growth factor A (VEGF-A). Dysregulation of these physiological processes contributes to the pathologies of heart disease, cancer and stroke. Rho GTPase proteins play an integral role in VEGF-mediated formation and maintenance of blood vessels. The regulatory functions of RhoA and RhoB in vasculogenesis and angiogenesis are well defined, whereas the purpose of RhoC remains poorly understood. Here, we describe how RhoC promotes vascular homeostasis by modulating endothelial cell migration, proliferation and permeability. RhoC stimulates proliferation of human umbilical vein endothelial cells (HUVECs) by stabilizing nuclear ß-catenin, which promotes transcription of cyclin D1 and subsequently drives cell cycle progression. RhoC negatively regulates endothelial cell migration through MAPKs and downstream MLC2 signaling, and decreases vascular permeability through downregulation of the phospholipase Cγ (PLCγ)-Ca(2+)-eNOS cascade in HUVECs. Using a VEGF-inducible zebrafish (Danio rerio) model, we observed significantly increased vascular permeability in RhoC morpholino (MO)-injected zebrafish compared with control MO-injected zebrafish. Taken together, our findings suggest that RhoC is a key regulator of vascular homeostasis in endothelial cells.

The effects of fundus photography on the multifocal electroretinogram.

PURPOSE: To determine the effect of flash fundus photography (FFP) on the multifocal electroretinogram (mfERG). METHODS: Ten subjects underwent mfERG testing on three separate dates. Subjects received either mfERG without FFP, mfERG at 5 and 15 min after FFP, or mfERG at 30 and 45 min after FFP on each date. The FFP groups received 10 fundus photographs followed by mfERG testing, first of the right eye then of the left eye 10 min later. Data were averaged and analyzed in six concentric rings at each time point. Average amplitude and implicit times of the N1, P1, and N2 peaks for each concentric ring at each time point after FFP were compared to baseline. RESULTS: Flash fundus photography did not lead to a significant change of amplitude or implicit times of N1, P1, or N2 at 5 min after light exposure. CONCLUSIONS: These findings suggest that it is acceptable to perform mfERG testing without delay after performance of FFP.

Revealing the role of phospholipase Cß3 in the regulation of VEGF-induced vascular permeability.

VEGF induces vascular permeability (VP) in ischemic diseases and cancer, leading to many pathophysiological consequences. The molecular mechanisms by which VEGF acts to induce hyperpermeability are poorly understood and in vivo models that easily facilitate real-time, genetic studies of VP do not exist. In the present study, we report a heat-inducible VEGF transgenic zebrafish (Danio rerio) model through which VP can be monitored in real time. Using this approach with morpholino-mediated gene knock-down and knockout mice, we describe a novel role of phospholipase Cß3 as a negative regulator of VEGF-mediated VP by regulating intracellular Ca2+ release. Our results suggest an important effect of PLCß3 on VP and provide a new model with which to identify genetic regulators of VP crucial to several disease processes.

Occlusive retinal vasculitis associated with systemic sclerosis and antiphospholipid antibodies.

PURPOSE: To report a series of patients with occlusive retinal vasculitis associated with systemic sclerosis (SSc) and elevated antiphospholipid antibody titers. METHOD: Case series. Main outcome measures included clinical and fluorescein angiographic findings at presentation and over time. OBSERVATIONS: Case 1 - A 61-year-old woman initially diagnosed with idiopathic, bilateral panuveitis and retinal vasculitis causing peripheral nonperfusion was subsequently diagnosed with limited cutaneous systemic sclerosis (lcSSc). Her ocular inflammation and retinal vasculitis were controlled with topical and periocular corticosteroids, but she eventually developed peripheral retinal vascular occlusion that progressed to macular ischemia 11 years after presentation. Repeat serologic evaluation detected interval development of antiphospholipid antibodies. Case 2 - A 58-year-old woman was found to have bilateral peripheral nonperfusion and retinal neovascularization in her right eye. Given her elevated hemoglobin A1c of 8.5%, she was diagnosed with presumed proliferative diabetic retinopathy. Three years after initial presentation, she was diagnosed with lcSSc. Subsequent serum workup detected elevated B2-glycoprotein antibody titers. Her peripheral nonperfusion progressed despite adequate glycemic control, resulting in further neovascularization in each eye. Case 3 - A 40-year-old woman with diffuse cutaneous systemic sclerosis (dcSSc) and elevated titers of anti-cardiolipin antibodies developed multiple branch retinal artery occlusions with subsequent neovascularization of the retina, optic disc, and angle in the right eye. CONCLUSION AND IMPORTANCE: Vision-threatening occlusive retinal vasculitis may develop in select patients with SSc. The presence of elevated anti-phospholipid antibody titers may confer increased risk for this vision-threatening complication.

Isolated optic nerve sarcoidosis.

Objective: To report three cases of sarcoidosis confined to the optic nerve. Methods: Chart review of clinical, laboratory, imaging, and optic nerve biopsy findings and a review of the literature. Results: All three cases presented with progressive visual loss and showed enhancement of the intraorbital optic nerve on magnetic resonance imaging. There was no evidence for systemic disease, including a negative workup for sarcoidosis or other infiltrative pathologies. Optic nerve biopsy in each case showed non-caseating granulomas consistent with sarcoidosis. Conclusions: Sarcoidosis confined to the optic nerve is a rare phenomenon but should still be considered in the differential diagnosis of progressive optic neuropathy, even in the absence of systemic disease. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 179-183).

Practice Patterns After Acute Embolic Retinal Artery Occlusion.

PURPOSE: To compare stroke evaluations recommended by retina special-ists and neurologists for retinal artery occlusion (RAO). DESIGN: A cross-sectional survey. METHODS: An anonymous survey was emailed to members of the American Academy of Neurology Stroke Section listserv and vitreoretinal specialists registered with the American Academy of Ophthalmology. The survey was divided based on duration of symptoms before encounter: less than 12 hours, 24-48 hours, and more than 1 week. Institutional review board approval was obtained before data collection. RESULTS: Four hundred forty-eight surveys were completed (281 retinologists and 167 neurologists). Within 12 hours of RAO, most neurologists (75%) pursue a hospital-based evaluation, whereas the majority of retinologists (82%) pursue outpatient workup (P < 0.0001). Most neurologists (92%) and retinologists (98%) pursue outpatient stroke workup if symptoms have been present for more than 7 days. CONCLUSIONS: Neurologists pursue higher acuity care after RAO, whereas most retinologists order outpatient evaluations. Retina specialists should consider urgent stroke evaluation to mitigate stroke risk factors.

Masses in the membranes.

A 24-year-old woman with systemic lupus erythematosus presented with a 1-year history of painless vision loss in the right eye. Examination was notable for a bitemporal hemianopia. Brain imaging revealed multiple contrast enhancing dural masses, including one along the planum sphenoidale. She underwent excisional biopsy for a presumed diagnosis of multiple meningiomas. Five years later, she developed worsening vision in the left eye, hypesthesia in the V1 distribution, and oculomotor nerve palsy. Repeat imaging showed an enhancing mass in the cavernous sinus and orbital apex. Biopsy demonstrated a lymphoplasmacyte rich infiltrate in dense extracellular material. She was diagnosed with lupus-induced hypertrophic pachymeningitis and started on immunosuppressive therapy. On further worsening of symptoms, her initial biopsy was reexamined and revealed a kappa light chain restricted B-cell and plasmacyte population. This led to the final diagnosis of central nervous system extranodal marginal zone lymphoma.