Long-term Outcomes of Descemet Stripping Endothelial Keratoplasty: Ten-Year Graft Survival and Endothelial Cell Loss.

PURPOSE: To determine 10-year outcomes for graft and endothelial cell survival after Descemet stripping endothelial keratoplasty (DSEK), including risk factors for graft failure. DESIGN: Retrospective clinical cohort study. METHODS: Three hundred fifty-six consecutive DSEK grafts performed by 10 surgeons using a standardized protocol were analyzed. Primary outcomes were cumulative graft survival and percentage endothelial cell loss (ECL) from 6 months to 10 years; secondary outcomes included risk factors for graft failure, postoperative complications, visual outcomes, and central corneal thickness. RESULTS: Indications include Fuchs endothelial dystrophy (n = 209), bullous keratopathy (n = 88), and previous graft failure (n = 39). One hundred and four eyes (29%) had preoperative glaucoma. Cumulative graft survival rates of all eyes at 1, 3, 5, and 10 years were 97%, 90%, 85%, and 79%, respectively. Ten-year graft survival for Fuchs endothelial dystrophy was 92%. Mean ± SD percentage ECL of all grafts was 46.6% ± 17.3% at year 1, 54.9% ± 18.7% at year 3, 59.6% ± 17.4% at year 5, and 73.1% ± 9.7% at year 10. Cox regression identified preoperative glaucoma (hazard ratio [HR]: 8.41; 95% CI, 1.30-54.5; P = .026), including previous glaucoma surgery (HR: 3.63; 95% CI: 1.03-12.74; P = .04) and regrafts (HR: 5.29; 95% CI: 2.02-13.89; P = .001) as significant risk factors for graft failure. CONCLUSIONS: At 10 years, DSEK survival rate was 79% for all eyes, including complex grafts, and ECL was 73%. For Fuchs endothelial dystrophy, 10-year graft survival rate was 92%. Despite a mean 10-year endothelial cell count of only 692 cells/mm2, graft survival remained high with good vision. DSEK continues to be a viable treatment option, especially in complex eyes with comorbidity.

Ultraviolet A light induces DNA damage and estrogen-DNA adducts in Fuchs endothelial corneal dystrophy causing females to be more affected.

Fuchs endothelial corneal dystrophy (FECD) is a leading cause of corneal endothelial (CE) degeneration resulting in impaired visual acuity. It is a genetically complex and age-related disorder, with higher incidence in females. In this study, we established a nongenetic FECD animal model based on the physiologic outcome of CE susceptibility to oxidative stress by demonstrating that corneal exposure to ultraviolet A (UVA) recapitulates the morphological and molecular changes of FECD. Targeted irradiation of mouse corneas with UVA induced reactive oxygen species (ROS) production in the aqueous humor, and caused greater CE cell loss, including loss of ZO-1 junctional contacts and corneal edema, in female than male mice, characteristic of late-onset FECD. UVA irradiation caused greater mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) damage in female mice, indicative of the sex-driven differential response of the CE to UVA, thus accounting for more severe phenotype in females. The sex-dependent effect of UVA was driven by the activation of estrogen-metabolizing enzyme CYP1B1 and formation of reactive estrogen metabolites and estrogen-DNA adducts in female but not male mice. Supplementation of N-acetylcysteine (NAC), a scavenger of reactive oxygen species (ROS), diminished the morphological and molecular changes induced by UVA in vivo. This study investigates the molecular mechanisms of environmental factors in FECD pathogenesis and demonstrates a strong link between UVA-induced estrogen metabolism and increased susceptibility of females for FECD development.

Preoperative Risk Assessment for Progression to Descemet Membrane Endothelial Keratoplasty Following Cataract Surgery in Fuchs Endothelial Corneal Dystrophy.

PURPOSE: To identify preoperative corneal tomographic features that predict progression to endothelial keratoplasty (EK) following cataract surgery in Fuchs endothelial corneal dystrophy (FECD) and establish a regression model to identify high-risk patients. DESIGN: Prospective, observational cohort study. METHODS: Setting: Hospital Universitario Ramón y Cajal, Madrid, Spain. STUDY POPULATION: Sixty-eight patients (84 eyes) with FECD who underwent phacoemulsification. INTERVENTION: We assessed preoperative best-corrected visual acuity; ultrasound central corneal thickness; pachymetric, anterior chamber depth, and corneal backscatter variables using Scheimpflug imaging; and endothelial cell density. MAIN OUTCOME MEASURES: Progression to EK. RESULTS: A total of 33 eyes (39.3%) needed EK after phacoemulsification to rehabilitate vision. On multivariate analysis, anterior layer (AL) corneal backscatter between 0 and 2 mm from the apex and relative increase in central corneal thickness from the "relative pachymetry display" by the Pentacam were significant predictors of the risk of progression to EK. Using these 2 variables, a risk score (RISC score) was derived from the regression model (area under the curve = 0.973; best cutoff point with a specificity of 95% representing a sensitivity of 96%). Excluding corneal backscatter data from the multivariate regression model, corneal thickness at the pupil center by the Pentacam and relative increase in central corneal thickness were significant predictors and provided a modified risk score (RIPT score) with similar performance. CONCLUSION: Both scores demonstrated accuracy in predicting progression to EK using easily accessible preoperative data. This approach, which can be readily implemented by surgeons, allows for individualized risk assessment.

Descemet Membrane Endothelial Keratoplasty for Epithelial Downgrowth After Clear Corneal Cataract Surgery.

OBJECTIVES: To describe the first case of Descemet membrane endothelial keratoplasty (DMEK) combined with argon laser photocoagulation and intracameral 5-fluorouracil (5-FU) injection in a patient with epithelial downgrowth after cataract surgery. METHODS: Case report and review of the literature. RESULTS: A 77-year-old female underwent uneventful cataract surgery using a clear corneal incision in her left eye. Six months after surgery, an epithelial cell sheet began to cover the posterior cornea and then spread to the anterior chamber structures, leading to anterior synechia and corectopia at 2 years. Argon laser photocoagulation was used to remove epithelial downgrowth on the iris surface. However, retrocorneal epithelial downgrowth gradually progressed, resulting in bullous keratopathy. DMEK with intracameral 5-FU injection was performed to remove epithelial tissue and replace the diseased endothelium with healthy endothelium. One year after surgery, her vision improved to 20/50 and the endothelial cell count was 1,643 cells/mm in her left eye. There were no further complications or recurrence of epithelial downgrowth. CONCLUSIONS: DMEK with preoperative argon laser and intraoperative 5-FU is a useful option for the treatment of diffuse epithelial downgrowths.

[Fuchs endothelial corneal dystrophy]. / Éndotelial'naia distrofiia rogovitsy Fuksa.

Fuchs endothelial dystrophy is a severe disease characterized by slowly progressing bilateral asymmetric corneal edema usually seen in elderly patients. The primary purpose of treatment is to minimize edema-related symptoms, such as ocular discomfort and visual acuity loss. Conservative therapy is symptomatic and has a short-term positive effect that does not lead to full functional rehabilitation of the patient, while endothelial keratoplasty is pathogenetically oriented. Intentional replacement of pathologically altered corneal layers has several advantages: preservation of corneal architectonics, rapid recovery of visual function, 'closed eye' surgery with corneal tunnel approach, and independence from expensive equipment. However, principle indications and contraindications for various modifications of endothelial keratoplasty in the presence of comorbidity are still to be defined. Further improvement of the methods and their broader implementation into clinical practice are the most pressing and promising issues of corneal transplantation.

Interface Fluid Syndrome After Laser In Situ Keratomileusis (LASIK) Because of Fuchs Endothelial Dystrophy Reversed by Descemet Membrane Endothelial Keratoplasty (DMEK).

PURPOSE: To describe a case that developed "interface fluid syndrome" after previous laser in situ keratomileusis (LASIK) because of Fuchs endothelial dystrophy (FED), which was reversed by Descemet membrane endothelial keratoplasty (DMEK). METHODS: A 58-year-old male patient presented with bilateral visual impairment owing to FED and visually significant cataract. Cataract surgery was carried out in both eyes followed by DMEK in his left eye. RESULTS: After cataract surgery, visual acuity did not improve sufficiently because corneal thickness increased and a fine cleft with interface fluid developed between the LASIK-flap and the residual stromal bed. After uneventful DMEK in his left eye, the fluid resolved within a week and visual acuity improved rapidly. CONCLUSIONS: This case demonstrates that "interface fluid syndrome" after LASIK caused by concomitant endothelial dysfunction may be reversed by DMEK allowing fast visual recovery.

Descemet stripping automated endothelial keratoplasty in Fuchs' corneal endothelial dystrophy: anterior segment optical coherence tomography and in vivo confocal microscopy analysis.

BACKGROUND: To evaluate the in vivo corneal changes using in vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT) in patients with Fuchs' dystrophy who underwent Descemet stripping automated endothelial keratoplasty (DSAEK) and the relationship between these changes and the postoperative visual recovery up to 1-year follow-up. METHODS: Before DSAEK and 1 day, 3, 6 and 12 months after surgery 31 patients (39 pseudophakic eyes) underwent a complete ophthalmological evaluation including best corrected visual acuity (BCVA), IVCM (subepithelial haze, interface haze, graft thickness) and AS-OCT (graft thickness). RESULTS: Graft thickness measurements by AS-OCT were strongly correlated to those obtained using IVCM at every follow-up stage (intraclass correlation coefficient = 0.95 to 0.97 between 3 and 12 months, P < 0.001 for all coefficients). No correlation between BCVA and graft thickness measured by AS-OCT at any follow-up stage was found, while at 3 and 6 postoperative months the correlations between BCVA and preoperative subepithelial haze (r = 0.61, P < 0.001 and r = 0.46, P = 0.002), interface haze (r = 0.51, P < 0.001 and r = 0.46, P = 0.003), postoperative subepithelial haze (r = 0.43, P = 0.004 and r = 0.39, P = 0.001) were significant. CONCLUSIONS: The study confirmed corneal subepithelial haze and interface haze as important factors limiting visual acuity after DSAEK, while graft thickness was not related to BCVA.

[Complications in endothelial keratoplasty performed by cornea fellows]. / Complicações em transplantes endoteliais realizados por estagiários de córnea.

PURPOSE: To report early complications in endothelial keratoplasty performed by cornea fellows. METHODS: Retrospective study of endothelial keratoplasty performed by second-year cornea fellows. Described the early complications and its treatments. RESULTS: Thirty four endothelial keratoplasty were performed by cornea fellows, from July 2007 to August 2008. From this, 29 were Descemet stripping endothelial keratoplasty and 5 Descemet stripping automated endothelial keratoplasty; 14 combined with phacoemulsification and 1 with extracapsular cataract surgery. The main indication was Fuchs' dystrophy (18 cases), followed by bullous keratopathy (11 cases), primary failure after endothelial keratoplasty (4 cases) and congenital hereditary endothelial dystrophy (1 case). Main surgery complication was donor button detachment in 8 eyes (23.5%), followed by primary graft failure in 7 eyes (20.6%) and acute glaucoma after pupillary block in 1 eye (2.9%). CONCLUSIONS: The complication rate in this series, which were the first ever in a group of six cornea fellows, was high. This shows the steep learning curve for this surgical procedure. The assistance of an experienced surgeon could help to achieve a less steep learning curve with a lower complication rate.

Complicações em transplantes endoteliais realizados por estagiários de córnea / Complications in endothelial keratoplasty performed by cornea fellows

OBJETIVO: Reportar complicações precoces numa série de transplantes endoteliais realizados por estagiários de córnea. MÉTODOS: Revisão retrospectiva dos transplantes endoteliais realizados por estagiários de córnea do segundo ano. Descritas as complicações precoces e respectivo tratamento. RESULTADOS: Foram realizados 34 transplantes endoteliais pelos estagiários de córnea entre julho de 2007 e agosto de 2008. Destes, 29 foram realizados pela técnica de "Descemet stripping endothelial keratoplasty" e 5 "Descemet stripping automated endothelial keratoplasty". Foram realizadas 15 cirurgias combinadas, 14 associadas a facoemulsificação com implante de lente intraocular e 1 associada a facectomia com implante de lente intraocular. A principal indicação foi por distrofia de Fuchs com 18 casos, 11 foram indicados por ceratopatia bolhosa após cirurgia de catarata, 4 por falência primária após transplante endotelial e 1 por distrofia endotelial congênita hereditária. A complicação mais encontrada foi descolamentos do botão doado em 8 olhos (23,5%). Falência primária foi encontrado em 7 olhos (20,6%). Glaucoma agudo por bloqueio pupilar foi encontrado em 1 paciente (2,9%). CONCLUSÕES: O alto número de complicações encontradas nestas cirurgias, que foram as primeiras de um grupo de 6 estagiários de córnea, mostra a longa curva de aprendizado para este procedimento cirúrgico. A orientação das primeiras cirurgias por cirurgiões mais experientes pode diminuir a curva de aprendizado e a taxa de complicações.

PURPOSE: To report early complications in endothelial keratoplasty performed by cornea fellows. METHODS: Retrospective study of endothelial keratoplasty performed by second-year cornea fellows. Described the early complications and its treatments. RESULTS: Thirty four endothelial keratoplasty were performed by cornea fellows, from July 2007 to August 2008. From this, 29 were Descemet stripping endothelial keratoplasty and 5 Descemet stripping automated endothelial keratoplasty; 14 combined with phacoemulsification and 1 with extracapsular cataract surgery. The main indication was Fuchs' dystrophy (18 cases), followed by bullous keratopathy (11 cases), primary failure after endothelial keratoplasty (4 cases) and congenital hereditary endothelial dystrophy (1 case). Main surgery complication was donor button detachment in 8 eyes (23.5%), followed by primary graft failure in 7 eyes (20.6%) and acute glaucoma after pupillary block in 1 eye (2.9%). CONCLUSIONS: The complication rate in this series, which were the first ever in a group of six cornea fellows, was high. This shows the steep learning curve for this surgical procedure. The assistance of an experienced surgeon could help to achieve a less steep learning curve with a lower complication rate.

Association of smoking and other risk factors with Fuchs' endothelial corneal dystrophy severity and corneal thickness.

PURPOSE: We investigated effects of smoking and other risk factors on the development of advanced Fuchs' endothelial corneal dystrophy (FECD) and on central corneal thickness (CCT). METHODS: Eyes from Caucasian probands, affected and unaffected family members, and unrelated controls matched for age from the FECD Genetics Multi-Center Study (n = 2044 subjects) were examined. Univariate and multivariate models, adjusted for family correlations, were used to determine the effect of smoking, sex, diabetes, and age on FECD case/control status and CCT. RESULTS: In a multivariate model, sex and smoking were associated significantly with advanced FECD (grades 4-6) development (P = 0.016 and P = 0.047, respectively). Female sex increased odds by 34%. Smoking increased odds by 30%. In a multivariate model, diabetes was associated with an increase of 9.1 µm in average CCT (P = 0.021). Female sex was associated significantly with a decrease in average CCT by 6.9 µm (P = 0.015). Smoking had no significant effect on CCT in any model. As shown previously, advanced FECD was associated with large increases in CCT (31.4-94.2 µm). CONCLUSIONS: Smoking was associated with an increased risk of advanced FECD and self-reported diabetes was associated with increased CCT. Further study of the impact of smoking and diabetes on FECD development and changes in corneal thickness is warranted.

Pseudophakic/aphakic corneal edema--morphometric predisposing factors analysis based on the fellow eye examination.

PURPOSE: To find morphometric factors predisposing to the development of corneal decompensation following cataract surgery. MATERIAL AND METHODS: Study group consisted of 50 patients after keratoplasty performed as pseudophakic/aphakic corneal edema (PCE/ACE) treatment. Control group formed 50 patients after cataract removal without signs of corneal decompensation. Specific subgroups were analyzed too. The morphometric data of the fellow eye anterior chamber were obtained with Visante OCTTM. RESULTS: Anterior chamber depth and anterior chamber angle width were significantly smaller in study group (p < 0.00001, U-test). With excluded preoperative risk factors: Fuchs dystrophy, acute angle closure glaucoma attack history the significant differences were also observed (p < 0.01). In Fuchs' dystrophy and intraoperative complication subgroups comparison these two anterior chamber parameters were smaller too (p < 0.001). Anterior chamber width was also smaller in study group with p = 0.001. Central corneal thickness was higher in study group with p = 0.013. After exclusion of patients with Fuchs' dystrophy there was no difference in comparison (p = 0.34). The difference in total axial length comparison was insignificant (p = 0.18). Relative anterior microphthalmos was diagnosed in 31 patients of study group (62%) and in 17 of control (34%). CONCLUSIONS: Small anterior chamber dimensions and higher central corneal thickness due to Fuchs' dystrophy are factors influencing the risk of PCE/ACE development.

Extracellular matrix and Na+,K+-ATPase in human corneas following cataract surgery: comparison with bullous keratopathy and Fuchs' dystrophy corneas.

PURPOSE: To examine the distribution of extracellular matrix (ECM) and basement membrane (BM) components and of Na+,K+-ATPase in postcataract surgery (PCS) corneas. These corneas were from patients who never developed pseudophakic or aphakic bullous keratopathy (PBK/ABK) after cataract surgery. PCS corneas were compared with PBK/ABK and Fuchs' dystrophy corneas. METHODS: The distribution of PBKIABK ECM and BM markers and of all three Na+,K+-ATPase alpha subunits was studied by immunofluorescence in 10 healthy, 11 PCS, 16 PBK/ABK, and 12 Fuchs' dystrophy corneas. RESULTS: Fibrotic ECM proteins, tenascin-C and fibrillin-1, were found in only 1 of 10 healthy and in 2 of 11 PCS corneas. In contrast, these proteins were expressed in all PBK/ABK and more than half of the Fuchs' dystrophy corneas. BM components in PCS corneas were altered to a greater extent (40-60%), especially fibronectin and laminin-10. A decreased epithelial immunostaining for Na+,K+-ATPase alpha subunits was seen in approximately 40% of PCS corneas and in approximately two thirds of PBK/ABK and Fuchs' dystrophy corneas. However, the endothelial staining was normal in all groups. CONCLUSIONS: Because tenascin-C and fibrillin-1 were mostly found in diseased but not in PCS corneas, their expression may be related to later, clinical stages of corneal edema development. However, BM components abnormal in PBK/ABK and Fuchs' dystrophy corneas were also altered in PCS corneas without clinical evidence of ocular disease. This may result from subclinical corneal changes resulting from cataract surgery, lens removal, exposure to the intraocular lens, or endothelial cell damage. Alterations of epithelial Na+,K+-ATPase point to the importance of epithelial changes in the development of corneal edematous diseases.

The role of apoptosis in the pathogenesis of Fuchs endothelial dystrophy of the cornea.

OBJECTIVE: To investigate the potential role of apoptosis in the pathogenesis of Fuchs endothelial dystrophy of the cornea. METHODS: Twenty-one corneal buttons from patients with Fuchs dystrophy and 15 control corneas were studied. Apoptosis was assessed by the in situ end-labeling of double-stranded DNA breaks, and by immunohistochemical characterization of cellular markers associated with apoptosis (Fas, FasL, Bcl-2, and Bax). Expression of Bcl-2 and Bax mRNA in the corneal stroma and endothelium was separately analyzed by a semiquantitative reverse transcriptase polymerase chain reaction. Furthermore, cultivated keratocytes generated from diseased corneal buttons and donor rims were exposed to camptothecin, an apoptotic inducer, for 6 and 24 hours. They were then examined for protein and messenger RNA (mRNA) expression of apoptotic regulatory molecules. RESULTS: DNA fragmentation was seen in the epithelium, stroma, and endothelium in 6 of 7 corneas with Fuchs dystrophy. A statistically significant difference was identified in the expression of Bax and its mRNA in the stroma, but not in the endothelium of Fuchs dystrophy corneas. Following exposure to camptothecin, keratocytes from patients with Fuchs dystrophy responded with an increased level of Bax and a low level of Bcl-2. This trend was distinctively different from the response of normal keratocytes. CONCLUSIONS: The evidence in this study points to a disease-related disturbance in the regulation of apoptosis in Fuchs dystrophy. Our findings suggest that excessive apoptosis may be an important mechanism in the pathogenesis of Fuchs dystrophy.