BackgroundPars 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.MethodsA 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.ResultsRetinal 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).ConclusionsHigh 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.

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.

Edema in the central nervous system can rapidly result in life-threatening complications. Vasogenic edema is clinically manageable, but there is no established medical treatment for cytotoxic edema, which affects astrocytes and is a primary trigger of acute post-traumatic neuronal death. To test the hypothesis that adrenergic receptor agonists, including the stress stimulus epinephrine protects neural parenchyma from damage, we characterized its effects on hypotonicity-induced cellular edema in cortical astrocytes by in vivo and in vitro imaging. After epinephrine administration, hypotonicity-induced swelling of astrocytes was markedly reduced and cytosolic 3′-5′-cyclic adenosine monophosphate (cAMP) was increased, as shown by a fluorescence resonance energy transfer nanosensor. Although, the kinetics of epinephrine-induced cAMP signaling was slowed in primary cortical astrocytes exposed to hypotonicity, the swelling reduction by epinephrine was associated with an attenuated hypotonicity-induced cytosolic Ca2+ excitability, which may be the key to prevent astrocyte swelling. Furthermore, in a rat model of spinal cord injury, epinephrine applied locally markedly reduced neural edema around the contusion epicenter. These findings reveal new targets for the treatment of cellular edema in the central nervous system.

Our findings pave the way for ex vivo cultivation of conjunctival epithelial cells onto a scaffold using the cell suspension technique by means of animal-free media. This would allow us to obtain conjunctival grafts for clinical purposes, thus giving a therapeutic option to patients with conjunctival diseases refractory to current therapies.

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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 was 2.02 ± 0.72 mcg/dg in EpiOff group, 4.33 ± 0.12 mcg/g in EpiOff-RICROLIN+ group, 0.63 ± 0.21 mcg/dg in EpiOn-RICROLIN+ group, and 1.15 ± 0.27 mcg/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.

Background: Regulatory T cell (Treg)-based immunotherapies have been studied as potential cell-based modalities for promoting transplant survival. However, the efficacy of local delivery of Tregs in corneal transplantation has not been fully elucidated. Herein, we investigated the kinetics of migration of subconjunctivally injected Tregs and their role in promoting corneal allograft survival. Methods: GFP+CD4+CD25+Foxp3+ Tregs were isolated from draining lymph nodes (DLNs) of GFP transgenic mice and were subconjunctivally injected to corneal allograft recipients. Next, Tregs, 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 MHC-II+CD11b+ antigen presenting cells (APCs), IFNγ+CD4+ Th1 cells, and CD45+ cells in the DLNs and cornea were evaluated at week 2 posttransplantation using flow cytometry. Expression of IFNγ, IL-10 and TGF-β in the grafts were assessed using RT-PCR and ELISA. Results: GFP+ Tregs were detected in the ipsilateral cornea and DLNs of recipients 6 hours after injection. Subconjunctival injection of Tregs significantly decreased the frequencies of mature APCs in the graft and DLNs, suppressed Th1 frequencies in DLNs, and inhibited CD45+ cell infiltration to the graft. Finally, locally delivered Tregs 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 Tregs and shows their role in suppressing host immune response against the allograft.

Isolated limbal epithelial stem cells (LESCs) were cultured with or without a 3T3 murine fibroblast feeder-layer (FL) in 4 different culture media on culture plates or on denuded human amniotic membrane (AM) support and fibrin gel support: (1) control medium supplemented with fetal bovine serum; (2) control medium supplemented with the synthetic serum "XerumFree™ XF205" (XF); (3) CnT-20 medium supplemented with "XerumFree™ XF205" (CnT-XF) and (4) CnT-20 medium supplemented with human AB serum (CnT-AB). The three xenogeneic media were compared to standard condition (control + FL) and parameters assessed included cell morphology, proliferative potential, number of passages, assessment of clonogenic and abortive colonies, life span, ∆Np63α expression and epithelial morphology on AM. During serial cultivation of LESCs, most of the tested xeno-free media supported similar numbers of cell passages, total colony number, cumulative cell doublings (CCD) rates and expression of ∆Np63α compared to control. The conditions cultivated with a FL showed a non-statistically significant higher number of cell passages and CCD rates before senescence when compared to the same conditions cultured without FL. Except for the control medium, only XF medium enabled the growth of cells on AM. The expression of ∆Np63α was comparable in all the cultures grown onto AM, when compared to the controls on fibrin gel. In conclusion, the xeno-free media enabled LESC culture both on plastic and on denuded human AM. Despite the analyses were carried out in a statistically low number of samples and need re-assessment in a larger cohort, our results suggest that the production of a completely xeno-free LESC graft could be beneficial for future clinical applications.