Regulatory T cells (Tregs) are crucial mediators of immune homeostasis. They regulate immune response by suppressing inflammation and promoting self-tolerance. In addition to their immunoregulatory role, a growing body of evidence highlights the dynamic role of Tregs in angiogenesis, the process of forming new blood vessels. Although angiogenesis is critically important for normal tissue regeneration, it is also a hallmark of pathological processes, including malignancy and chronic inflammation. Interestingly, the role of Tregs in angiogenesis has been shown to be highly tissue- and context-specific and as a result can yield either pro- or antiangiogenic effects. For these reasons, there is considerable interest in determining the molecular underpinnings of Treg-mediated modulation of angiogenesis in different disease states. The present review summarizes the role of Tregs in angiogenesis and mechanisms by which Tregs regulate angiogenesis and discusses how these mechanisms differ in homeostatic and pathological settings.

Pars plana vitrectomy (PPV) is preferred surgical procedure for the management of complex rhegmatogenous retinal detachment (RRD). The purpose of this study was to evaluate the anatomical results of primary PPV for the treatment of primary complex RRD and to determine the influence of lens status, tamponading agent, preoperative proliferative vitreoretinopathy (PVR) and axial length (AL) of the eye upon the anatomical outcome. A retrospective consecutive chart analysis was performed on 117 eyes from 117 patients with complex RRD managed with PPV. Fifty-nine eyes were phakic and 58 pseudophakic eyes. All patients had a minimum follow-up period of 12 months. Eyes were classified into groups using independent variables (first classification based upon lens status and tamponade used, second classification based upon lens and PVR status and third classification based upon AL of the eye). The groups were compared for anatomical outcomes (dependent variables) using nonparametric- or, in case of normally distributed data, parametric- statistical tests. Retinal reattachment rate in phakic eyes was 94.9% compared to 93.1% in pseudophakic, with no statistically significant difference between the two. The overall retinal reattachment rate with single surgery was 94.0%. Final reattachment rate was 97.4%. In case of established PVR ≥ C1, the reattachment rate was not statistically different (92.6%) from eyes with no PVR (91.1%) irrespective of lens status. A statistically significant difference was found between redetachment rates only between phakic eyes with gas tamponade compared to silicon oil (SO) (p = 0.001). Reattachment rate proved to be similar in both AL groups (≤24 mm and > 24 mm). High anatomical success rate of primary vitrectomy for complex RRD with either gas or SO tamponade was achieved in phakic as well as pseudophakic eyes irrespective of AL of the eye.

Background: Metastases of thyroid carcinomas to the choroid and/or orbit are infrequent. PubMed was searched for English-language articles and case reports published from 1977 to 2012. In our survey, we looked for reports of orbital and/or ocular metastases from the thyroid and found 31 reported cases from 1979 to 2012. Summary: At the time of onset of ocular symptoms, the vast majority of patients had a long history of thyroid malignancy and evidence of widely disseminated metastatic disease. The age of the reported patients ranged from 29 to 83 years. Among the 22 reported cases of thyroid carcinomas with metastases to the choroid from 1979 to 2012, the most common primary tumor was papillary thyroid carcinoma (PTC); this occurred in seven patients. This was followed by medullary thyroid carcinoma in six cases and follicular thyroid carcinoma (FTC) in five cases. Orbital metastases were reported in nine patients with thyroid carcinomas (PTC=4, FTC=3, Hürthle cell=1, not specified=1). Patients with choroidal metastases presented with decreased or blurred vision, eye pain, and flashes in 81%, 5%, and 5% of cases, respectively. The diagnosis of a choroidal tumor was usually based on noninvasive diagnostic techniques such as ultrasonography, transillumination, computer tomography (CT), and/or magnetic resonance imaging (MRI) scanning. ¹³¹I scanning revealed uptake in the orbit in 26% of cases with choroidal and/or orbital PTC or FTC. For a metastasis that causes a definitive loss of vision and/or persistent pain, the treatment of choice was enucleation. The other treatment options were brachyradiotherapy using ¹²⁵I episcleral radioactive plaque insertion, external beam radiation, ¹³¹I therapy, chemotherapy, and/or targeted therapy with small molecules. Conclusions: The orbit and globe are not common sites for metastatic thyroid carcinomas. Diagnosis of a choroidal tumor is usually based on clinical judgment and results of noninvasive diagnostic techniques such as ultrasonography, transillumination, CT, and/or MRI scanning. Fundoscopic examination and ocular ultrasonography by an ophthalmologist are recommended for identification and monitoring of choroidal metastatic deposits.

Background: Regulatory T (Treg) cell-based immunotherapies have been studied as potential cell-based modalities for promoting transplant survival. However, the efficacy of local delivery of Treg cells in corneal transplantation has not been fully elucidated. Herein, we investigated the kinetics of migration of subconjunctivally injected Treg cells and their role in promoting corneal allograft survival. Methods: GFP⁺CD4⁺CD25⁺Foxp3⁺ Treg cells were isolated from draining lymph nodes (DLNs) of GFP transgenic mice and were subconjunctivally injected to corneal allograft recipients. Next, Treg cells, conventional T cells (Tconv) or a combination of both was locally injected to graft recipients, and graft survival was determined by evaluating opacity scores for 10 weeks. Transplanted mice without treatment served as controls. The frequencies of major histocompatibility complex-II⁺CD11b⁺ antigen-presenting cells, IFNγ⁺CD4⁺ Th1 cells, and CD45⁺ cells in the DLNs and cornea were evaluated at week 2 posttransplantation using flow cytometry. Expressions of IFNγ, IL-10 and TGF-β in the grafts were assessed using reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Results: GFP⁺ Treg cells were detected in the ipsilateral cornea and DLNs of recipients 6 hours after injection. Subconjunctival injection of Treg cells significantly decreased the frequencies of mature antigen-presenting cells in the graft and DLNs, suppressed Th1 frequencies in DLNs, and inhibited CD45⁺ cell infiltration to the graft. Finally, locally delivered Treg cells significantly reduced the expression of IFN-γ, enhanced the levels of IL-10 and TGF-β in the graft, and promoted long-term allograft survival. Conclusions: Our study elucidates the kinetics of migration of locally delivered Treg cells and shows their role in suppressing host immune response against the allograft.

Purpose. To compare stromal riboflavin concentration after three corneal cross-linking (CXL) imbibition procedures: standard (EpiOff), transepithelial corneal (EpiOn), and iontophoresis-assisted technique (Ionto) using 0.1% hypotonic riboflavin phosphate.Methods. Randomized open-label pilot clinical study. Twelve corneas/12 patients with advanced keratoconus were randomly divided into 4 groups for CXL (n=3). The corneas underwent imbibition with standard riboflavin EpiOff and with enhanced riboflavin solution (RICROLIN+) EpiOff, EpiOn, and iontophoresis techniques. Thereafter, deep anterior lamellar keratectomy procedure was performed and the obtained debrided corneal tissues were frozen. The maximal intrastromal riboflavin concentration was measured by high-performance liquid chromatography/mass spectrometry (mcg/dg).Results. The mean stromal concentration of riboflavin was2.02±0.72mcg/dg in EpiOff group,4.33±0.12mcg/g in EpiOff-RICROLIN+ group,0.63±0.21mcg/dg in EpiOn-RICROLIN+ group, and1.15±0.27mcg/dg in iontophoresis RICROLIN+ group. A 7-fold decrease in intrastromal riboflavin concentration was observed comparing EpiOn-RICROLIN+ and EpiOff-RICROLIN+ groups.Conclusion. The present pilot study indicates that both transepithelial CXL techniques in combination with hypotonic enhanced riboflavin formulation (RICROLIN+) were still inferior to the standard CXL technique; however, larger clinical studies to further validate the results are needed and in progress.