Incidence and Clinical Features of Immunologic Rejection After Deep Anterior Lamellar Keratoplasty.

PURPOSE: The aim of this study was to investigate the incidence and clinical features of immunologic rejection after deep anterior lamellar keratoplasty (DALK). METHODS: This study included 411 patients (464 eyes, median age [interquartile range; IQR] 55.8 years [36.1-69.5]) who underwent DALK at Tokyo Dental College between June 1997 and 2021. Of 411 patients, 24 (24 eyes [5.2%], 51.9 years [IQR 31.6-65.4]) developed immunologic rejection. We characterized the clinical features, risk factors associated with immunologic rejection, and prognosis. RESULTS: The interval between DALK and immunologic rejection was 14.5 (range, 5-78) months. Immunologic rejection occurred after cessation/reduction of topical steroid in 9 (47.4%) and suture removal in 4 eyes (21.1%). The postoperative duration of topical steroid use in eyes with immunologic rejection was significantly shorter (10.0 months, [IQR 6.0-14.0]) than those without immunologic rejection (28.3 [IQR 15.8-42.7], P = 0.001). Immunologic rejection manifested as stromal edema in 19 (100.0%), ciliary hyperemia in 17 (89.5%), keratic precipitates in 13 (68.4%), epithelial edema in 13 (68.4%), infiltration in 9 (47.4%), corneal opacity in 4 (21.1%), and Descemet membrane detachment in 2 eyes (10.5%). After treatment, corneal clarity was restored in 17 eyes (89.5%); however, immunologic rejection led to corneal endothelial decompensation in 2 eyes (10.5%). Endothelial cell density decreased from 1795.7 ± 722.6 to 1651.6 ± 655.6 cells/mm2 after immunologic rejection (P = 0.074). CONCLUSIONS: Post-DALK immunologic rejection was associated with specific clinical triggers such as reduction/cessation of topical steroids or suture removal.

Risk Factors for Recurrence in the Treatment of Recurrent Pterygium.

PURPOSE: The aim of this study was to identify the postoperative recurrence rate of recurrent pterygium and to evaluate risk factors for the recurrence. METHODS: This study was a retrospective interventional nonrandomized consecutive case series. In this single-center study, 119 eyes of patients with recurrent pterygium who underwent surgery with a follow-up period of >12 months after the surgery were analyzed. The clinical characteristics of pterygium were classified according to the length of corneal involvement and Tan grade. The main outcome was the recurrence rate. The secondary outcome was the risk factors for recurrence. RESULTS: The mean follow-up period was 42 ± 28.6 months. Recurrence was observed in 15 patients (12.6%). The average postoperative recurrence period was 7.7 ± 6.7 months. Twelve patients experienced a recurrence within 12 months. Eyes with recurrence had a significantly greater length of corneal involvement (2.47 ± 0.72 mm) and number of previous surgery (1.9 ± 1.3) than those without (1.97 ± 0.74 mm, and 1.3 ± 0.7, both P = 0.04). Multivariate analysis showed that recurrence was significantly associated with the length of corneal involvement (odds ratio [OR] 2.38, 95% confidence interval [CI], 1.02-5.57, P = 0.05) and the number of previous surgeries (OR: 1.91, 95% CI, 1.03-3.58, P = 0.04) but not with sex (OR: 3.71, 95% CI, 0.90-15.2, P = 0.07), age (OR: 0.99, 95% CI, 0.94-1.04, P = 0.59), and use of mitomycin C (OR: 0.31, 95% CI, 0.07-1.21, P = 0.09). CONCLUSIONS: The postoperative recurrence rate of recurrent pterygium was 12.6%. The preoperative length of corneal involvement and number of previous pterygium surgeries were significantly correlated with recurrence. Male sex and nonuse of mitomycin C tended to correlate with recurrence.

Corneal higher-order aberrations in corneal endothelial decompensation secondary to obstetric forceps injury.

Forceps corneal injuries during infant delivery cause Descemet membrane (DM) breaks, that cause corneal astigmatism and corneal endothelial decompensation. The aim of this study is to characterise corneal higher-order aberrations (HOAs) and corneal topographic patterns in corneal endothelial decompensation due to obstetric forceps injury. This retrospective study included 23 eyes of 21 patients (54.0 ± 9.0 years old) with forceps corneal injury, and 18 healthy controls. HOAs and coma aberrations were significantly larger in forceps injury (1.05 [0.76-1.98] µm, and 0.83 [0.58-1.69], respectively) than in healthy controls (0.10 [0.08-0.11], and 0.06 [0.05-0.07], respectively, both P < 0.0001). Patient visual acuity was positively correlated with coma aberration (rs = 0.482, P = 0.023). The most common topographic patterns were those of protrusion and regular astigmatism (both, six eyes, 26.1%), followed by asymmetric (five eyes, 21.7%), and flattening (four eyes, 17.4%). These results indicate that increased corneal HOAs are associated with decreased visual acuity in corneal endothelial decompensation with DM breaks and corneal topography exhibits various patterns in forceps injury.

The predictability of graft thickness for Descemet's stripping automated endothelial keratoplasty using a mechanical microkeratome system.

Descemet's stripping automated endothelial keratoplasty (DSAEK) is used for treating corneal endothelial dysfunction, and the postoperative visual acuity outcome depends on the thickness of the graft. We created a simple nomogram using factors affecting the cutting thickness during graft preparation via a mechanical microkeratome system for DSAEK. This retrospective study was conducted from May 2018 through October 2022 and included donor eyes cut by automatic methods. We measured the graft thickness, cutting accuracy, and assessed ten variables with donor/cornea-related factors potentially affecting the cutting thickness. Subsequently, we created a simple nomogram. We analyzed 81 donor tissues, and the donor median age was 76 years. The mean central graft thickness was 122.2 µm, with 62% of the grafts that could be cut within the target central graft thickness range. Comparatively, donor corneas from those with cardiac diseases were cut deeper (P = 0.007). The developed nomogram provided a 83% probability of estimating the post-cutting graft thickness within 25 µm. Our nomogram, which considers cause of death, enables reproducible production of graft of a desired thickness. A detailed analysis of donor tissues, including the cause of donor death and the characteristics from pressurization to cutting, will enable more precise DSAEK graft preparation.

Donor-Related Risk Factors for Graft Decompensation Following Descemet's Stripping Automated Endothelial Keratoplasty.

AIMS: To identify donor-related risk factors associated with graft endothelial failure and postoperative endothelial cell density (ECD) reduction after Descemet's stripping automated endothelial keratoplasty (DSAEK). METHODS: This was a single-center retrospective study conducted from July 2006-December 2016. We included 584 consecutive eyes (482 patients) that underwent DSAEK for the treatment of laser iridotomy-related bullous keratopathy (192 eyes), pseudophakic bullous keratopathy (137 eyes), regraft (96 eyes), Fuchs' endothelial corneal dystrophy (FECD; 59 eyes) and others (100 eyes). Twenty-three donor- and recipient-related risk factors potentially associated with graft failure and ECD reduction were assessed using Cox hazard models and linear mixed effect models. RESULTS: The median age of the patients was 73.5 years (male; 35.6%). After DSAEK, ECD decreased from 2,674 cells/mm2 (95% confidence interval [CI]; 2,646-2,701) to 1,132 (1,076-1,190) at 12 months and 904 (845-963) at 24 months (P < 0.001). Fifty-five eyes (9.4%) had graft endothelial failure without rejection. This failure was associated with donor pseudophakic lens status (hazard ratio [HR]; 2.67, CI; 1.50-4.76, P = 0.001) and preoperative endothelial folds (HR; 2.82, CI; 1.20-6.62, P = 0.02). The incidence of graft endothelial failure in non-FECD patients was significantly higher among those receiving donor grafts with a pseudophakic lens status and preoperative presence of endothelial folds (P < 0.001). Postoperative ECD loss was significantly greater in eyes with these risk factors compared to those without (P = 0.007). CONCLUSIONS: Pseudophakic status and/or presence of preoperative endothelial folds are the significant donor risk factors for endothelial failure in non-FECD patients.

Elevated Cytokine Levels in Aqueous Humor Are Associated with Peripheral Anterior Synechiae after Penetrating Keratoplasty.

Peripheral anterior synechiae (PAS) after corneal transplantation leads to refractory glaucoma and permanent loss of vision. However, the exact mechanism remains elusive. This study aimed to evaluate the association between cytokine levels in the aqueous humor (AqH) and the progression of PAS after penetrating keratoplasty (PKP). We measured 20 cytokine levels in AqH and assessed the correlation with PAS progression after PKP in 85 consecutive patients who underwent PKP. We also evaluated age-dependent alterations in PAS and cytokine levels in DBA2J mice. PAS developed in 38 (44.7%) of 85 eyes after PKP. The incidence of intraocular pressure increase after PKP was significantly greater in eyes with PAS (26.3%) than in those without PAS (2%, p = 0.0009). The PAS area at 12 months after PKP was significantly positively correlated with the preoperative levels of interleukin (IL)-6, interferon (IFN)-γ and monocyte chemotactic protein (MCP)-1 (p ≤ 0.049). In the DBA2J mice, an experimental glaucoma model that developed PAS at 50 weeks, the AqH levels of IL-2, IL-6, IL-10, IFN-γ, tumor necrosis factor-α, MCP-1 and granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly increased at 50 weeks compared to 8 weeks (p ≤ 0.021). In conclusion, inflammatory alterations in the AqH microenvironment, such as high preoperative specific cytokine levels, can lead to PAS formation and glaucoma.

Aqueous Cytokine Levels Are Associated With Progression of Peripheral Anterior Synechiae After Descemet Stripping Automated Endothelial Keratoplasty.

Purpose: To evaluate the association between total protein and cytokine levels in aqueous humor (AqH) and the progression of peripheral anterior synechiae (PAS) after Descemet stripping automated endothelial keratoplasty (DSAEK). Methods: This prospective study included 146 consecutive patients who underwent DSAEK. Preoperative levels of total protein and 20 cytokines in AqH were measured. Using three-dimensional anterior segment optical coherence tomography, we assessed the iridotrabecular contact (ITC) area before and at 3, 6, and 12 months after DSAEK. Correlations between the total protein and cytokine levels in the AqH and ITC area were analyzed. Results: ITC was observed in 47 eyes (32.2%) after DSAEK. The ITC area increased from 2.00 ± 4.42 mm2 preoperatively to 3.00 ± 6.85 mm2 at 12 months. The total protein level in AqH was significantly higher in eyes with ITC progression than in those without (1.45 ± 1.03 mg/mL vs. 1.00 ± 0.57; P = 0.04) and was significantly positively correlated with the progression of ITC area after DSAEK (at 6 months, r = 0.311 and P = 0.005; at 12 months, r = 0.342 and P = 0.0004). The ITC area at 12 months was significantly correlated with the preoperative AqH levels of interleukin-8 (r = 0.252; P = 0.021), interferon-γ (r = 0.318; P = 0.009), and soluble intercellular adhesion molecule-1 (r = 0.292; P = 0.004). Multivariate analyses showed that the total protein levels in AqH and the presence of preoperative ITC were significant risk factors for increased ITC area after DSAEK (ß = 0.193-0.574; all P < 0.02). Conclusions: Higher preoperative total protein and specific cytokine levels in AqH were associated with ITC formation after DSAEK. Translational Relevance: Our findings indicate that chronic pathological changes in AqH can cause PAS progression and glaucoma after DSAEK.

Trends in surgical procedures and indications for corneal transplantation over 27 years in a tertiary hospital in Japan.

PURPOSE: To characterize trends in procedures, and indications for corneal transplantation over 27 years in a single referral center in Japan. STUDY DESIGN: Retrospective study. METHODS: Data from a consecutive series of corneal transplant surgery cases performed from 1991 to 2017at Ichikawa General Hospital were collected. The surgical procedures, indications, and causes of corneal endothelial dysfunction were evaluated. RESULTS: Among 6,025 transplantations, a total of 3,991 cases underwent penetrating keratoplasty (PKP), 1009 underwent (deep) anterior lamellar keratoplasty, 746 underwent endothelial keratoplasty, and 309 underwent epithelial transplantation. Over that period the frequency of PKP decreased, whereas the frequency of lamellar keratoplasty increased. The four major surgical indications were bullous keratoplasty (BK 30.0%), regraft (24.2%), post-keratitis scars (17.1%), and keratoconus (11.4%). After dividing the study period into four time periods, we found that BK and regraft increased (from 20.3% to 34.5% and 18.2% to 31.1%, respectively), whereas post-keratitis scars and keratoconus decreased (from 26.0% to 9.5% and 14.1% to 7.2%, respectively) between the first and last period. Pseudophakic or aphakic BK were the major causes of corneal endothelial dysfunction until 2010. Cases of laser-iridotomy-induced BK peaked in 35 eyes (34.3% of BK) in 2000 and declined after 2013. Cases of Fuchs endothelial corneal dystrophy increased from 0 in 1991, to 15 eyes (18.5% of BK) in 2017. CONCLUSION: Lamellar keratoplasty has replaced PKP in our hospital. BK and regraft have increased, whereas post-keratitis scars and keratoconus have decreased. Laser-iridotomy-induced BK has decreased during the past decade, whereas Fuchs endothelial corneal dystrophy has increased.

Comparison of Artificial Anterior Chamber Internal Pressures and Cutting Systems for Descemet's Stripping Automated Endothelial Keratoplasty.

PURPOSE: To optimize methods of preparing donor cornea tissue for Descemet's stripping automated endothelial keratoplasty (DSAEK), we compared five experimental conditions with different internal pressures and cutting systems. METHODS: The artificial anterior chamber internal pressure (IP) was set at 100 or 200 mm Hg. The microkeratome cut was performed with or without an artificial chamber pressurizer (ACP), using a CBm turbine (CBm) or one use-plus automated (OUP-A). Thirty human research corneas were divided into five groups, and compared after the cut with donor tissue quality parameters, including cutting depth, graft uniformity, cell evaluation, and smoothness of the stromal surface. RESULTS: The smallest variation in mean cut depth was observed in the condition, which had IP of 200 mm Hg used ACP and OUP-A. In experimental groups cut using CBm, significantly more consistent thicknesses were made at an IP of 200 than 100 mm Hg. There were no statistically significant differences among the groups in either endothelial cell density or cell viable assay results after cuts. Using an IP of 200 mm Hg with ACP and CBm produced the roughest stromal surface, and the roughness grading scores showed a positive correlation with the percentage of cut depth. CONCLUSIONS: An IP of 200 mm Hg was the best setting for DSAEK grafts with high predictability of cut depth and uniformity of graft thickness without endothelial cell damage. TRANSLATIONAL RELEVANCE: For successful DSAEK, it is recommended that a set internal pressure of 200 mm Hg be used during microkeratome cutting for donor tissue preparation.