Cytokine analysis of aqueous humor in patients with cytomegalovirus corneal endotheliitis.

PURPOSE: To evaluate cytokine levels of aqueous humor in patients with cytomegalovirus (CMV) corneal endotheliitis and their relationships with CMV DNA load. METHODS: 44 aqueous humor samples were obtained from 26 patients with CMV corneal endotheliitis at various stages of treatment. 33 samples obtained from cataract patients during the same period were selected as a control group. Each sample was used to measure the concentration of the CMV DNA load using real-time quantitative polymerase chain reaction, and to examine the levels of IL-6, IL-8, IL-10, MCP-1, VCAM-1, VEGF, IP-10, G-CSF, ICAM-1 and IFN-γ using a cytometric bead array. RESULTS: All 10 cytokines were found to have statistically significant differences between the CMV endotheliitis and cataract groups. The Spearman correlation test showed that the concentration of CMV DNA load was significantly associated with the levels of IL-6 (P = 0.005, r = 0.417), IL-8 (P < 0.001, r = 0.514), IL-10 (P < 0.001, r = 0.700), MCP-1 (P = 0.001, r = 0.487), VEGF (P < 0.001, r = 0.690), IP-10 (P = 0.001, r = 0.469), G-CSF (P < 0.001, r = 0.554) and ICAM-1 (P < 0.001, r = 0.635), but not significantly associated with VCAM-1 (P = 0.056) and IFN-γ (P = 0.219). CONCLUSIONS: There was a combined innate and adaptive immune response in aqueous humor in patients with CMV endotheliitis. Levels of multiple cytokines were significantly correlated with viral particle. Cytokines are potential indicators to help diagnose CMV endotheliitis, evaluate disease activity and assess treatment response.

The outcomes of corneal sight rehabilitating surgery in Stevens-Johnson syndrome: case series.

PURPOSE: To summarize the outcomes of corneal sight rehabilitating surgery in Stevens-Johnson syndrome (SJS). METHODS: This is a retrospective analysis of a consecutive case series. Twenty-four eyes of 18 SJS patients were included in this study. The ocular parameters, surgical procedures, postoperative complications, and additional treatments of the cases were reviewed. RESULTS: A total of 29 corneal sight rehabilitating surgeries, which consists of 9 keratoplasties, 8 Keratolimbal allograft (KLAL) and 12 combined surgeries (keratoplasty and KLAL simultaneously) were performed on the 24 eyes. All patients were treated with glucocorticoid eyedrops and tacrolimus eyedrops for anti-rejection treatment without combining systemic immunosuppression, except two patients who were prescribed prednisone tablets for the management of systemic conditions. The mean follow-up period was 50.6 ± 28.1 months. The optimal visual acuity (VA) (0.74 ± 0.60 logarithm of the minimum angle of resolution [logMAR]) and endpoint VA (1.06 ± 0.82 logMAR) were both significantly better than the preoperative VA (1.96 ± 0.43 logMAR) (95% CI, p = 0.000). 57.1% patients (8/14) were no longer in the low vision spectrum, and 88.9% patients (8/9) were no longer blind. The mean epithelialization time was 7.1 ± 7.6 weeks. The success rate was 86.7%. Additional treatments for improving epithelialization included administration of serum eyedrops (n = 10), contact lens (n = 15), amniotic membrane transplantation (n = 6), and tarsorrhaphy (n = 8). Complications included delayed epithelialization (n = 4, over 12 weeks), glaucoma (n = 11), and severe allograft opacity (n = 4). Only one graft rejection was observed. CONCLUSIONS: Keratoplasty and KLAL can remarkably enhance VA and improve low vision or even eliminate blindness for ocular complications of SJS. The outcome of the surgeries was correlated with the preoperative ocular situation and choice of operative methods.

Outcomes of Donor Corneas of Different Thicknesses From Endothelial Keratoplasty in Deep Anterior Lamellar Keratoplasty for Keratoconus.

PURPOSE: To evaluate the outcomes of divided residual donor corneas obtained from endothelial keratoplasty in keratoconus with deep anterior lamellar keratoplasty (DALK). METHODS: In this retrospective, comparative, clinical study, 103 keratoconic eyes that underwent DALK were enrolled; 67 eyes received thin grafts from Descemet stripping automated endothelial keratoplasty, and 36 received thick grafts from Descemet membrane endothelial keratoplasty. Baseline and postoperative central corneal thickness (CCT), inferior corneal thickness, uncorrected distance visual acuity, corrected distance visual acuity, corneal astigmatism, mean keratometry, biomechanical properties, and complication rates were measured. RESULTS: Six months after transplantation, the group receiving thin grafts had a CCT of only 455.1 ± 43.0 µm, whereas that of the group receiving thick grafts was 546.7 ± 44.2 µm. Both CCT and inferior corneal thickness in the thin group were significantly lower than those in the thick group (measured with Pentacam at 36 months, P < 0.001) and remained throughout the 5-year follow-up period. Both procedures had comparable postoperative logarithm of the minimum angle of resolution UDVAs, logarithm of the minimum angle of resolution corrected distance visual acuity, astigmatism, and mean keratometry values (36 months; P = 0.335, 0.286, 0.680, and 0.365, respectively). Corneal biomechanical analysis revealed that the thin group had a significantly higher stiffness parameter at the first applanation than the thick group at the 2-year follow-up (P = 0.036) while other parameters were equivalent. CONCLUSIONS: The outcomes of keratoplasty with donor tissue are comparable regardless of the thickness of the graft, which suggests that transplantation with either type of the split corneal procedure for DALK in patients with keratoconus is feasible.

Incidence of Cytomegalovirus Infection After Repeat Keratoplasty and Associated Rate of Graft Failure.

INTRODUCTION: The aim of this work was to compare the prognosis and characteristics of patients with Cytomegalovirus (CMV) infection (CMV+) with those of patients without virus infection (Virus-) undergoing repeat keratoplasty. METHODS: This prospective propensity score-matched cohort study enrolled patients who underwent repeat keratoplasty for graft failure at the Peking University Third Hospital between January 2016 and May 2022. Patients with prior viral keratitis before the first keratoplasty were excluded. The primary outcome measure was the graft failure rate. The secondary outcome measures included the anterior segment characteristics, intraocular pressure (IOP), and endothelial cell density. RESULTS: Ninety-four matched patient pairs were included. The graft failure rate in the CMV+ group (71%) was higher than that in the Virus- group (29%) (P < 0.001). CMV infection in the cornea increased the risk of repeat graft failure and shortened the median survival time (hazard ratio, 3.876; 95% confidence intervals, 2.554-5.884; P < 0.001). The characteristics of graft failure included exacerbation of ocular surface inflammation, neovascularization, and opacification. Epithelial defects, high IOP, and endothelial decompensation were observed at an increased frequency in the CMV+ group (all P < 0.005). Recurrent CMV infection presented as early endothelial infection in the CMV+ group. Recurrence of CMV infection was confined to the graft endothelium without involving the stroma and epithelium post-repeat endothelial keratoplasty. CONCLUSIONS: CMV infection post-keratoplasty leads to persistent endothelial damage and graft opacification and significantly increases the risk of repeat graft failure. Localized recurrence of CMV infection in the endothelial grafts underscores the importance of monitoring and treatment. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR1800014684.

Water-Free Cyclosporine Ophthalmic Solution vs Vehicle for Dry Eye Disease: A Randomized Clinical Trial.

Importance: Dry eye disease (DED) is a prevalent eye disorder. Cyclosporine is an effective immunomodulator that is widely used in DED; however, due to its highly hydrophobic nature, delivery of cyclosporine to the ocular surface is challenging. Objective: To evaluate the efficacy and safety of SHR8028, a water-free cyclosporine ophthalmic solution, 0.1%, compared with vehicle in Chinese participants with DED. Design, Setting, and Participants: This was a multicenter, double-blind, vehicle-controlled, phase 3 randomized clinical trial conducted from March 4, 2021, to July 22, 2022. Adult participants with moderate to severe DED were recruited from 12 hospitals in China. Study data were analyzed April 2, 2022, for the primary analysis. Interventions: Following a 14-day run-in period with an artificial tear, participants were randomly assigned (1:1) to receive water-free cyclosporine or vehicle (1 eye drop in each eye twice daily). After a 29-day treatment, participants of both groups were given the option to receive water-free cyclosporine for an additional 12 weeks for longer-term safety assessment. Main Outcomes and Measures: The primary end points were changes from baseline in total corneal fluorescein staining (tCFS) using the National Eye Institute scale and in dryness score on a visual analog scale at day 29. Results: A total of 206 participants (mean [SD] age, 47.8 [14.2] years; 185 female [90%]) were enrolled, with 103 each in the cyclosporine group and the vehicle group. At day 29, the cyclosporine group experienced improved tCFS compared with vehicle (change [Δ] = -1.8; 95% CI, -2.7 to -1.0; P < .001), with a tCFS score decrease from baseline of -4.8 in the cyclosporine group and -3.0 in the vehicle group. Dryness score decreased from baseline in both groups (-19.2 vs -15.4; Δ = -3.8; 95% CI, -9.2 to 1.6; P = .17). During the 29-day treatment, treatment-related adverse events were reported in 15 participants (14.6%) in the cyclosporine group and 11 participants (10.7%) in the vehicle group. Conclusions And Relevance: Results demonstrated superiority of a water-free cyclosporine, 0.1%, eye solution over vehicle in improving tCFS score at day 29 in Chinese participants with DED. However, dryness score (VAS) was not improved at day 29. Trial Registration: ClinicalTrials.gov Identifier: NCT05841043.

Deep Anterior Lamellar Keratoplasty-Treated Keratoconic Eyes With Descemet Membrane Rupture.

PURPOSE: The aim of this study was to evaluate the outcomes of deep anterior lamellar keratoplasty (DALK) and compare it with penetrating keratoplasty (PKP) in keratoconic eyes with Descemet membrane (DM) rupture. METHODS: In this comparative retrospective case series, 33 keratoconic eyes with a history of hydrops underwent DALK and 27 received PKP. Baseline and postoperative visual acuity, corneal astigmatism, mean keratometry, endothelial cell density, and complication rates were measured. RESULTS: The median follow-up of patients who underwent DALK was 45 months (range, 4-76 months) and that of patients who underwent PKP was 84 months (range, 4-136 months). Both procedures had comparable postoperative visual acuity, astigmatism, and mean keratometry. Significantly higher endothelial cell densities were observed in DALK than in PKP at 2, 3, and 5 years postsurgery (2043 ± 767 vs. 1165 ± 683 cell/mm2, P = 0.007, n = 12 in both groups at 2 years). Intra-DALK, 15 perforations occurred (44.12%) and 1 (2.94%) was converted to PKP. Graft rejection was diagnosed in 1 (3.03%) DALK procedure versus 8 (29.63%) PKP (P = 0.008), and other long-term complication rates were equivalent. Kaplan-Meier survival analysis also revealed a higher rejection-free survival rate for the DALK group (P = 0.012). Subgroup analysis within both groups based on the severity of preoperative DM rupture revealed no significant difference in any major 2-year outcomes. CONCLUSIONS: DALK showed similar beneficial visual outcome and safety but significantly better endothelial protection over PKP in eyes with keratoconus and previous hydrops. Therefore, DALK is recommended in posthydrops cases irrespective of the DM rupture severity.