Person:

Kheirkhah, Ahmad

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.

Purpose

To evaluate density and morphology of corneal epithelial immune dendritic cells (DCs) in different subtypes of dry eye disease (DED) using in vivo confocal microscopy (IVCM).

Methods

This retrospective study included 59 eyes of 37 patients with DED and 40 eyes of 20 age-matched healthy controls. Based on clinical tests, eyes with DED were categorized into two subtypes: aqueous-deficient (n = 35) and evaporative (n = 24). For all subjects, images of laser scanning in vivo confocal microscopy (IVCM) of the central cornea were analyzed for DC density and DC morphology (DC size, number of dendrites, and DC field). These DC parameters were compared among all dry eye and control groups.

Results

Compared with the controls, patients with DED had significantly higher DC density, larger DC size, higher number of dendrites, and larger DC field (all P < 0.001). Comparison between aqueous-deficient and evaporative subtypes demonstrated that DC density was significantly higher in aqueous-deficient subtype (189.8 ± 36.9 vs. 58.9 ± 9.4 cells/mm2, P = 0.001). However, there were no significant differences in morphologic parameters between DED subtypes. When aqueous-deficient DED with underlying systemic immune disease (Sjögren's syndrome and graft versus host disease) were compared with nonimmune conditions, the immunologic subgroup showed significantly higher DC density, DC size, and number of dendrites (all P < 0.05).

Conclusions

Corneal IVCM demonstrated differential changes in DC density and morphologic DC parameters between subtypes of DED. These changes, which reflect the degree of immune activation and inflammation in DED, can be used for clinical practice and endpoints in clinical trials.

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.

Purpose

To evaluate whether levels of corneal subbasal nerve fiber length (SNFL) in dry eye disease (DED) could prognosticate the level of improvement in signs and symptoms after treatment.

Design

Phase IV, double-masked, randomized clinical trial.

Participants

Sixty patients with meibomian gland dysfunction-associated DED and 27 age-matched controls.

Methods

Patients with DED were randomized to receive topical artificial tears, loteprednol etabonate 0.5%, or loteprednol etabonate 0.5%/tobramycin 0.3% twice daily for 4 weeks. At baseline, in vivo confocal microscopy of central cornea was performed in both eyes. Patients with DED were divided into 2 subgroups, those with low baseline SNFL and those with near-normal baseline SNFL (the cut-off point: mean SNFL in controls minus 2 standard deviations). Clinical signs and symptoms at baseline and after 4 weeks of treatment were compared between the subgroups with low and near-normal SNFL for all therapeutic groups.

Main Outcome Measures

Symptom questionnaires, corneal fluorescein staining (CFS), conjunctival staining with lissamine green, tear break-up time, Schirmer’s test, and SNFL.

Results

In patients with DED, baseline SNFL (17.06 ± 5.78 mm/mm2) was significantly lower than in controls (23.68 ± 3.42, P=0.001). In the artificial tear and loteprednol groups, although no significant improvement in any sign or symptom was noted in patients with low baseline SNFL (<16.84 mm/mm2), subjects with near-normal baseline SNFL (≥16.84 mm/mm2) showed significant improvement in both symptoms and corneal fluorescein staining (CFS) score (all P<0.05). In the loteprednol/tobramycin group, no significant change was evident for any sign or symptom in either subgroup of low or near-normal baseline SNFL.

Conclusions

Significant improvements in CFS and patient symptomatology after DED treatment were evident only in the subgroup with near-normal corneal SNFL. Consideration of SNFL may thus assist in explaining the variability of patients’ response to DED therapy.