The cornea is the most commonly transplanted tissue in medicine. The main cause of corneal graft failure is allograft rejection. The incidence of graft rejection depends on the presence of high-risk characteristics, most notably corneal neovascularization. Although corneal graft has high success rates in the absence of these risk factors, high-risk keratoplasty is associated with low success rates due to a high incidence of immune-mediated graft rejection. To improve the survival of high-risk corneal transplantation, various preoperative, intraoperative, and postoperative measures can be considered. However, the key step in the management of these grafts is the long-term use of local and/or systemic immunosuppressive agents. Although a number of immunosuppressive agents have been employed for this purpose, the results vary significantly across different studies. This is partly due to the lack of an optimized method for their use as well as the lack of a precise stratification of the degree of risk in each individual patient. New targeted biologic treatments as well as tolerance-inducing methods show promising horizons in the management of high-risk corneal transplantation in near future.

Purpose To evaluate corneal endothelial cell density (ECD) in patients with dry eye disease (DED) compared to an age-matched control group. Design Cross-sectional, controlled study Methods This study included 90 eyes of 45 patients with moderate-to-severe DED (53.7 ± 9.8 years old) and 30 eyes of 15 normal controls (50.7 ± 9.8 years old). All subjects had a complete ophthalmic evaluation including symptom assessment using the Ocular Surface Disease Index (OSDI) and corneal fluorescein staining. In addition, laser scanning in vivo confocal microscopy was performed to measure the density of the following parameters in the central cornea: endothelial cells, subbasal nerves, and subbasal immune dendritic cells. Results Corneal ECD was significantly lower in the DED group (2595.8 ± 356.1 cells/mm2) than in the control group (2812.7 ± 395.2 cells/mm2, P=0.046). The DED group showed significantly lower corneal subbasal nerve density (17.1 ± 6.9 mm/mm2) compared to the control group (24.7 ± 4.4 mm/mm2, P<0.001). Dendritic cell density was significantly higher in the DED group than in the controls (111.7 ± 137.3 versus 32.0 ± 24.4 cells/mm2, respectively, P=0.002). There were statistically significant correlations between corneal ECD and dry eye severity parameters including the OSDI score (rs= −0.26, P=0.03), and corneal fluorescein staining (rs= −0.28, P=0.008). Conclusions There is a significant reduction in corneal ECD in DED which correlates with clinical severity of the disease.

Objective To assess the vision-related quality of life in a cohort of patients with ocular graft-versus-host disease (GVHD). Design Prospective study. Participants Eighty-four patients diagnosed with chronic ocular GVHD Methods We assessed the vision-related quality of life with the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). The symptoms of ocular GVHD were assessed using the Ocular Surface Disease Index (OSDI) and Symptom Assessment in Dry Eye (SANDE) questionnaires. Main outcome measures We assessed vision-related quality of life with NEI-VFQ-25 and compared the scores obtained from patients with ocular GVHD to those from a healthy population. In the ocular GVHD population, we also evaluated the associations between the NEI-VFQ-25 and dry eye symptoms measured by OSDI and SANDE questionnaires, age, duration of disease, best-corrected visual acuity, corneal fluorescein staining, tear break-up time, and Schirmer test. Results The mean composite NEI-VFQ-25 score in patients with ocular GVHD was 76.5 ± 17. Compared to healthy subjects, ocular GVHD patients reported reduced scores on all NEI-VFQ-25 subscales (each P < 0.001) with exception of color vision (P = 0.11). The NEI-VFQ-25 composite scores significantly correlated with OSDI (R = −0.81, P < 0.001), SANDE (R = −0.56, P < 0.001), corneal fluorescein staining (R = −0.36, P = 0.001) and best-corrected visual acuity (R = −0.30, P = 0.004). Conclusion Patients with ocular GVHD experience measurable impairment of vision-related quality of life. This study highlights the impact of ocular GVHD on the vision-related quality of life, and hence the importance of comprehensive diagnosis and treatment of this condition.

Purpose To evaluate the safety and efficacy of topical tacrolimus 0.05% vs. topical methylprednisolone 0.5% in patients with ocular graft-versus-host disease (GVHD). Design Phase I/II, prospective, randomized, double-masked clinical trial. Subjects Eighty eyes from 40 patients diagnosed with chronic ocular GVHD were enrolled. Methods Forty patients with ocular GVHD were randomized; 24 patients were treated with topical tacrolimus 0.05% and 16 patients with topical methylprednisolone 0.5% twice a day for 10 weeks, in addition to continuing their baseline treatment regimen. Main Outcome Measures Safety was evaluated based on occurrence of adverse events. Tolerability was assessed based on subjects’ reports of discomfort after drop instillation. Intraocular pressure (IOP) was monitored. The main efficacy endpoints were: corneal fluorescein staining (CFS), tear break-up time (TBUT), Schirmer test, and expression of the ocular surface inflammatory markers human leukocyte antigen-DR (HLA-DR) and intercellular adhesion molecule-1 (ICAM-1). Symptoms were evaluated using the Ocular Surface Disease Index (OSDI). Results After 10 weeks of treatment, no major adverse events occurred in either treatment group, and there was no significant difference in the composite tolerability scores between the two groups (P=0.06). However, burning sensation was more pronounced with tacrolimus (P=0.002). Topical tacrolimus was more effective than methylprednisolone in reducing the CFS score at week 10 (55% vs. 23% reduction, respectively; P=0.01), and achieved significant improvement in TBUT when compared to baseline (P<0.001). OSDI score reduction achieved statistical significance with tacrolimus (27% reduction; P=0.02) but was marginal with methylprednisolone (32% reduction; P=0.06). ICAM-1 expression by ocular surface epithelium decreased significantly in both groups (tacrolimus P=0.003; methylprednisolone P=0.008), while HLA-DR expression significantly decreased only in the tacrolimus group (P=0.03). Schirmer test scores did not change significantly in either group during the study; IOP increased significantly with methylprednisolone at week 10 (P=0.04). Conclusions Topical tacrolimus 0.05% is safe, generally well tolerated and effective for the treatment of ocular GVHD, without the hypertensive effects of topical corticosteroids.

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The cornea is the most commonly transplanted tissue in the body. Although corneal grafts generally have high success rates, transplantation onto inflamed and vascularized host beds, or so-called high-risk corneal transplantation, has a high rate of graft rejection. The management of this high-risk corneal transplantation is challenging and involves numerous measures. One of the key measures to prevent graft rejection in these cases is the use of systemic immunosuppressive agents. In this article, we will review the systemic immunosuppressive agents most commonly used for high-risk corneal transplantation, which include corticosteroids, cysclosporine A, tacrolimus, mycophenolate mofetil, and rapamycin. Benefits, risks, and published data on the use of these medications for high-risk corneal transplantation will be detailed. We will also summarize novel immunoregulatory approaches that may be used to prevent graft rejection in high-risk corneal transplantation.

Our data suggests that topical PEA (Defluxa) is a safe, effective, and generally well-tolerated treatment to prevent or suppress ocular surface inflammation attributable to chronic glaucoma treatment.

PurposeTo evaluate interobserver concordance in measured ocular redness among a group of raters using an objective computer-assisted method (ocular redness index [ORI]) and a group of clinicians using an ordinal comparative scale.MethodsWe conducted a prospective study to evaluate ocular redness in clinical photographs of 12 patients undergoing pterygium surgery. Photographs were acquired preoperatively, and at 1 week and 1 month postoperatively. One group of clinicians graded conjunctival redness in the photographs using an image-based comparative scale. A second group applied the ORI to measure redness in the same photographs. We evaluated redness change between time points, level of agreement among raters, and assessed redness score differences among observers within each group.ResultsInterobserver agreement using the image-based redness scale was 0.458 (P < 0.001). Interobserver agreement with the ORI was 0.997 (P < 0.001). We observed statistically significant differences among clinicians' measurements obtained with the image-based redness scale (P < 0.001). There were no significant differences among measurements obtained with the ORI (P = 0.27). We observed a significant change in redness between baseline and follow-up visits with all scoring methods. Detailed analysis of redness change was performed only in the ORI group due to availability of continuous scores.ConclusionOur findings suggest that the ORI scores provide higher consistency among raters than ordinal scales, and can discriminate redness changes that clinical observers often can miss.Translational RelevanceThe ORI may be a reliable alternative to measure ocular redness objectively in the clinic and in clinical trials.