Swept source OCTA reveals a link between choriocapillaris blood flow and vision loss in a case of tubercular serpiginous-like choroiditis.

Optical coherence tomography angiography (OCTA) is a non-invasive technique that is useful in the diagnosis and management of patients with posterior uveitis. Here we report the use of swept source OCTA (SS-OCTA) in a patient with tuberculosis (TB) associated serpiginous like choroiditis (TB-SLC) that made a full visual recovery following treatment with ATT, local and systemic corticosteroids, and systemic immune modulation. By comparing en face images of choriocapillaris (CC) blood flow before and after treatment, we conclude that the patient's visual recovery was associated with resolution of extensive CC flow deficits. This case highlights the utility of SS-OCTA in the multimodal evaluation of patients with choroidal inflammation, and the potential for good visual recovery in patients treated for TB-SLC.

Characterization of Gene Therapy Associated Uveitis Following Intravitreal Adeno-Associated Virus Injection in Mice.

Purpose: To characterize the intraocular immune cell infiltrate induced by intravitreal adeno-associated virus (AAV) gene therapy. Methods: AAV vectors carrying plasmids expressing green fluorescent protein under the control of PR2.1 were injected intravitreally into AAV naive and AAV primed C57Bl/6 mice. Clinical inflammation was assessed using optical coherence tomography. Intraocular immune cell populations were identified and quantified by flow cytometry on days 1, 7, and 29 after intravitreal injection and compared with sham and fellow eye controls. Results: Optical coherence tomography inflammation score and total CD45+ cell number were significantly higher in AAV injected eyes compared to uninjected fellow eye and sham injected controls. Clinically apparent inflammation (vitritis on optical coherence tomography) and cellular inflammation (CD45+ cell number) was significantly increased in AAV injected eyes and peaked around day 7. Vitritis resolved by day 29, but cellular inflammation persisted through day 29. On day 1, neutrophils and activated monocytes were the dominant cell populations in all AAV injected eyes. On day 7, eyes of AAV exposed animals had significantly more dendritic cells and T cells than eyes of AAV naive animals. By day 29, CD8- T cells were the dominant CD45+ cell population in AAV injected eyes. Conclusions: Intravitreal AAV injection in mice generates clinically evident inflammation that is mild and seems to resolve spontaneously. However, the total number of intraocular CD45+ cells, particularly T cells, remain elevated. Both innate and adaptive immune cells respond to intravitreal AAV regardless of prior immune status, but the adaptive response is delayed in AAV naive eyes.

Interleukin-6 neutralization prolongs corneal allograft survival.

The purpose of this study is to determine the effect of systemic blockade of Interleukin-6 (IL-6) on allosensitization, regulatory T cell frequencies and suppressive phenotype, and allograft survival rates in a mouse model of corneal transplantation. Allogeneic corneal transplantation was performed using C57BL/6 mice as donors and BALB/c mice as recipients. Graft recipients were injected daily with either anti-IL-6 antibody or an isotype control antibody (1.25 mg/ml) for the first 7 days and on alternate days thereafter until week 8 after transplantation. Allograft survival was evaluated for 8 weeks using Kaplan-Meier survival analysis. Draining lymph nodes (DLN) were harvested at week 3 after transplantation, and proliferation of isolated recipient T cells through direct and indirect pathways was determined using mixed lymphocyte reaction assay. Frequencies of CD4+CD25+Foxp3+ regulatory T cells, their expression of Foxp3, and frequencies of IFNy+CD4+ Th1 cells were determined in DLN using flow cytometry. Finally, CD4+ T cells were cultured with bone marrow-derived dendritic cells from either C57BL/6 or BALB/c mice in the presence of IL-6-blocking antibody to determine Treg induction through direct and indirect pathways, respectively. Treatment with anti-IL-6 antibody suppressed both the direct and indirect pathways of allosensitization in graft recipients and significantly improved allograft survival rates. Furthermore, in vivo blockade of IL-6 enhanced Foxp3 expression by Tregs in graft recipients undergoing rejection, but did not exert a significant effect on Treg frequencies. Finally, IL-6 neutralization in vitro enhanced the differentiation of Tregs from CD4+ T cells through both direct and indirect pathways. Our results demonstrate that systemic administration of IL-6-blocking antibody to corneal allograft recipients suppresses direct and indirect routes of allosensitization, is associated with increased expression of Foxp3 by Tregs, and improves allograft survival rates.