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Purpose: To describe the changes seen on optical coherence tomography angiography [OCTA] in patients with PIC following immunosuppressive therapy.Methods: We reviewed serial OCTA scans from five consecutive PIC patients (5 eyes) with at least 3 months of follow-up, who underwent imaging before and after immunosuppressive therapy. Using ImageJ, superficial and deep retinal vasculature were analyzed for vessel area and foveal avascular zone. Choriocapillaris layer was analyzed for flow signal loss.Results: Five out of five patients received an orbital floor triamcinolone acetonide injection as the initial treatment for periods of activity. Mean choriocapillaris (CC) flow void area obtained after immunosuppressive therapy was significantly lower than the mean CC flow void area obtained prior to treatment (Pre-treatment: 0.270 vs Post-treatment: 0.144; p = .0068). In 2 out of 2 patients with longitudinal visual field testing, CC flow voids were spatially associated with visual field defects, and immunosuppressive therapy was associated with reduced CC flow void area and improved visual function.Conclusion: OCTA can detect alterations in choriocapillaris flow. Longitudinal follow-up demonstrates a centripetal restoration of choriocapillaris flow in response to immunosuppressive therapy. OCTA may be a useful adjunct for monitoring and evaluating treatment of PIC.

Purpose: To describe an atypical presentation of Tubulointerstitial Nephritis and Uveitis (TINU), with challenges in treatment course. Observations: A 12-year-old Hispanic female presented to the National Eye Institute's Uveitis clinic with bilateral blurred vision, red eyes and photophobia, not responsive to topical steroids. On exam, she had bilateral severe panuveitis with areas of subretinal fluid. During her evaluation, she was noted to have elevated serum creatinine. A kidney biopsy confirmed the presence of severe tubulointerstitial nephritis and interstitial fibrosis. She was treated with oral steroids with excellent resolution of symptoms and subretinal fluid. She continued to have anterior segment flares with attempts to taper oral prednisone which lead to treatment with multiple immunomodulatory agents. Associated hypertension and kidney damage complicated the choice of a secondary immunosuppressive agent. Conclusions and Importance: Although rare, TINU can present as panuveitis with choroidal involvement which may or may not be preceded by tubulointerstitial nephritis. A renal biopsy is required for definitive diagnosis, but abnormal urinalysis or renal function should raise suspicion for TINU. Keywords: Immunosuppression, Inflammation, Tubulointerstitial nephritis, Uveitis

The type III intermediate filament (IF) proteins vimentin and desmin are sequentially overexpressed in stromal myofibroblasts over the period when fibrosis sets in after corneal injury. Prior findings have revealed vimentin-deficient mice are significantly protected from corneal fibrosis after alkali injury, which has implicated this IF protein as an important regulator of corneal fibrosis. It has remained as yet unproven whether desmin contributes in any significant manner to corneal fibrosis. Here we have employed desmin-deficient (Des KO) mice in the corneal alkali injury model and show that injured Des KO mice develop fibrosis and show similar levels of corneal opacity at 14 days post-injury as wild type (WT) mice and retain this phenotype even at 30d post injury. Des KO corneas from injured mice show upregulation of vimentin and alpha-smooth muscle actin expression to equivalent levels as WT corneas, illuminating that desmin deficiency does not interfere with myofibrobast differentiation. Employing the small molecule withaferin A (WFA), an inhibitor of vimentin, we show that WFA treatment causes the decrease in steady state levels of vimentin and serine 38 phosphorylated vimentin, the latter a biomarker associated with corneal fibrosis, and improved corneal clarity through blockade of myofibroblast differentiation. To investigate further the mechanism of fibrosis in desmin deficiency, we examined keratin 8 expression in the epithelium, and found reduced levels of this cytokeratin in injured Des KO corneas compared to WT corneas. This finding also corroborates the decrease of cell proliferation in injured Des KO corneas compared to that in WT corneas. The fibrotic phenotype of Des KO corneas also features abundant vascularization, further exemplifying the magnitude of corneal pathology. Together, these findings illuminate that desmin does not contribute significantly to corneal fibrosis in this injury model.

Purpose To investigate the intravisit repeatability of optical coherence tomography angiography (OCTA) in a cohort of uveitis patients. Methods One hundred ten patients were imaged twice per eye, per visit, using the Zeiss Cirrus HD-OCT Model 5000 device. To calculate choriocapillaris flow void area (CC FV) 6 × 6-mm images were used, and 3 × 3-mm images were used to calculate vessel density (VD) and the foveal avascular zone area (FAZ) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Repeatability was measured using Bland-Altman analyses and intraclass correlation coefficients (ICC) with associated coefficient of variation (CV). Results The level of intravisit repeatability differed across indices ranging from moderate to excellent. CC FV had the highest intravisit repeatability with an ICC of 0.980 (95%CI, 0.966-0.989), a CV of 15.9% and Bland-Altman limits of agreement from -0.398 to 0.411 mm2. DCP FAZ had the lowest intravisit repeatability with an ICC of 0.677 (95%CI, 0.510-0.796), a CV of 17.4% and Bland-Altman limits of agreement from -0.395 to -0.355 mm2. Intraoperator repeatability was excellent across all indices. Conclusions This study demonstrates that OCTA is a reliable tool to quantitatively assess specific indices of vascular structure in uveitis patients with good intravisit repeatability. However, the range of variability for each index should be taken into account when evaluating clinically meaningful changes. Translational relevance The repeatability of the metrics we have described has implications in supporting the development of OCTA-derived quantitative assessments of the retinal and choroidal vasculature in uveitis patients as potential imaging biomarkers.