Fuchs Corneal Endothelial Dystrophy Research Articles

Clinical characteristics, risk factor analysis and outcomes in 61 eyes with graft rejection after descemet stripping endothelial keratoplasty, with a review of literature.

To report the demographic profile, clinical characteristics, risk factors and outcomes of graft rejection after DSEK. A total of 3073 eyes had DSEK between 2012 and 2019, of which 1710 eyes that had follow up of more than one year. Sixty-one eyes who had graft rejection during this period were studied. Overall, incidence of graft rejection during the study period was 3.6% (61/1710 eyes) in those with follow up more than one year. The median age of patients was 58 (IQR 37.5-68) years. The indications were prior failed graft (34 eyes: 28 penetrating keratoplasty; 6 DSEK), post cataract surgery edema (12 eyes), Fuchs corneal endothelial dystrophy (6 eyes), corneal edema post inflammation (5 eyes) and iridocorneal endothelial syndrome (4 eyes). Of the 34 eyes with failed grafts, nine were post-rejection graft failures (two after endothelial keratoplasty and seven after penetrating keratoplasty), remaining 25 eyes were non-rejection graft failures. Ocular co-morbidities were noted in 41 eyes, of which secondary glaucoma was the most common (14 eyes). Clinical signs of graft rejection were diffuse edema, keratic precipitates and endothelial rejection line. Rejection episode occurred between 6-12months after surgery in 20 (33%) eyes, 12-24months in 15 (25%) eyes, 2-3years in 12 (20%) eyes, and beyond 3years in 14(23%) eyes. Graft clarity was restored in 55 (90%) eyes, which was complete in 41 (67%) eyes, partial in 14 (23%) eyes, and clarity was not restored in 6 (10%) eyes. The statistically significant risk factors for rejection were non-use of steroids (p value < 0.001), DSEK for failed graft (p value < 0.02) and DSEK for corneal edema post-inflammation (p value < 0.0014). DSEK for failed graft was a significant risk factor for graft failure after the rejection episode (p value < 0.05). Graft rejection may occur as late as 5years post-DSEK, emphasizing the need for long-term steroids instillation. Non-use of topical steroids, DSEK for failed graft and corneal edema post inflammation are risk factors for graft rejection. DSEK for failed graft was also seen as a risk factor for failure after the rejection episode The graft survival rate after the rejection episode was 90% at 6months, 50% at 2years and 10% at 5years.

Assessing Fuchs Corneal Endothelial Dystrophy Using Artificial Intelligence-Derived Morphometric Parameters From Specular Microscopy Images.

The aim of this study was to evaluate the efficacy of artificial intelligence-derived morphometric parameters in characterizing Fuchs corneal endothelial dystrophy (FECD) from specular microscopy images. This cross-sectional study recruited patients diagnosed with FECD, who underwent ophthalmologic evaluations, including slit-lamp examinations and corneal endothelial assessments using specular microscopy. The modified Krachmer grading scale was used for clinical FECD classification. The images were processed using a convolutional neural network for segmentation and morphometric parameter estimation, including effective endothelial cell density, guttae area ratio, coefficient of variation of size, and hexagonality. A mixed-effects model was used to assess relationships between the FECD clinical classification and measured parameters. Of 52 patients (104 eyes) recruited, 76 eyes were analyzed because of the exclusion of 26 eyes for poor quality retroillumination photographs. The study revealed significant discrepancies between artificial intelligence-based and built-in microscope software cell density measurements (1322 ± 489 cells/mm 2 vs. 2216 ± 509 cells/mm 2 , P < 0.001). In the central region, guttae area ratio showed the strongest correlation with modified Krachmer grades (0.60, P < 0.001). In peripheral areas, only guttae area ratio in the inferior region exhibited a marginally significant positive correlation (0.29, P < 0.05). This study confirms the utility of CNNs for precise FECD evaluation through specular microscopy. Guttae area ratio emerges as a compelling morphometric parameter aligning closely with modified Krachmer clinical grading. These findings set the stage for future large-scale studies, with potential applications in the assessment of irreversible corneal edema risk after phacoemulsification in FECD patients, as well as in monitoring novel FECD therapies.

Investigation of the functional impact of CHED- and FECD4-associated SLC4A11 mutations in human corneal endothelial cells.

Mutations in the solute linked carrier family 4 member 11 (SLC4A11) gene are associated with congenital hereditary endothelial dystrophy (CHED) and Fuchs corneal endothelial dystrophy type 4 (FECD4), both characterized by corneal endothelial cell (CEnC) dysfunction and/or cell loss leading to corneal edema and visual impairment. In this study, we characterize the impact of CHED-/FECD4-associated SLC4A11 mutations on CEnC function and SLC4A11 protein localization by generating and comparing human CEnC (hCEnC) lines expressing wild type SLC4A11 (SLC4A11WT) or mutant SLC4A11 harboring CHED-/FECD4-associated SLC4A11 mutations (SLC4A11MU). SLC4A11WT and SLC4A11MU hCEnC lines were generated to express either SLC4A11 variant 2 (V2WT and V2MU) or variant 3 (V3WT and V3MU), the two major variants expressed in ex vivo hCEnC. Functional assays were performed to assess cell barrier, proliferation, viability, migration, and NH3-induced membrane conductance. We demonstrate SLC4A11-/- and SLC4A11MU hCEnC lines exhibited increased migration rates, altered proliferation and decreased cell viability compared to SLC4A11WT hCEnC. Additionally, SLC4A11-/- hCEnC demonstrated decreased cell-substrate adhesion and membrane capacitances compared to SLC4A11WT hCEnC. Induction with 10mM NH4Cl led SLC4A11WT hCEnC to depolarize; conversely, SLC4A11-/- hCEnC hyperpolarized and the majority of SLC4A11MU hCEnC either hyperpolarized or had minimal membrane potential changes following NH4Cl induction. Immunostaining of primary hCEnC and SLC4A11WT hCEnC lines for SLC4A11 demonstrated predominately plasma membrane staining with poor or partial colocalization with mitochondrial marker COX4 within a subset of punctate subcellular structures. Overall, our findings suggest CHED-associated SLC4A11 mutations likely lead to hCEnC dysfunction, and ultimately CHED, by interfering with cell migration, proliferation, viability, membrane conductance, barrier function, and/or cell surface localization of the SLC4A11 protein in hCEnC. Additionally, based on their similar subcellular localization and exhibiting similar cell functional profiles, protein isoforms encoded by SLC4A11 variant 2 and variant 3 likely have highly overlapping functional roles in hCEnC.

Glaucoma surgical procedure choice in vulnerable corneal endothelium

This talk will focus on the decision making in patients with vulnerable corneal endothelium requiring glaucoma surgical intervention. The effect of glaucoma surgical procedures on corneal endothelium will be briefly analysed and conditions with vulnerable corneal endothelium and co‐existent intraocular pressure (IOP) elevation, such as Fuchs corneal endothelial dystrophy with primary open angle glaucoma or post‐keratoplasty steroid response, will be adequately described. The aim of the talk is to indicate the most appropriate glaucoma surgical interventions depending on the status of corneal endothelium and the desired IOP lowering effect, covering a wide spectrum of surgical procedures including minimally invasive interventions, such as Preserflow implantation, as well as ab interno/ab externo viscocanaloplasty or conventional procedures such as trabeculectomy or big tube implantation. Finally, the talk will highlight useful surgical tips for the abovementioned surgical procedures, and it will provide suggestions for patient selection in order to optimize clinical outcomes.

Nanopore sequencing method for CTG18.1 expansion in TCF4 in late-onset Fuchs endothelial corneal dystrophy and a comparison of the structural features of cornea with first-degree relatives.

To evaluate the relationship between the number of trinucleotide repeats (TNR) in late-onset Fuchs corneal endothelial dystrophy (FCED) and to compare the endothelial properties of FCED, first-degree relatives, and controls. Blood samples were collected from FCEDs to determine TNR number. The FCED patients, first-degree relatives, and controls were examined with specular microscopy for central corneal thickness (CCT), endothelial cell density (ECD), pleomorphism and polymegatism, and with corneal topography for specific indicators such as (i) displacement of thinnest point of cornea, (ii) loss of isopachs, (iii) focal posterior surface depression towards anterior chamber. This study included 92 patients with FCED, 92 first-degree relatives, and 96 controls. CCT was thickest in FCEDs (558.0 μm) (p < 0.05) while there was no difference between relatives (533.0 μm) and controls (530.4 μm) (p = 0.845). ECD was decreased in both FCED (2069.2 mm2) and relatives (2171.4 mm2) than controls (2822.9 mm2) (p < 0.05 in both). The presence of pleomorphism and polymegatism was significant in patients with FCED (93.4% and 93.4%, respectively), relatives (86.9% and 86.04%, respectively), and controls (8.33% and 1.04%, respectively) (p < 0.05). Specific topographic indicators differed among the groups (p < 0.05). The mean repeat number of the FCED patients was 17.48 ± 4.54 (12-25) times. The TNR number of FCED cases correlated with the relative CCT (p < 0.05, R = 0.615) and cell density (p = 0.009, R = -0.499). A strong association between the corneal endothelium in relatives and TNR number of FCEDs was defined. Relatives tended to have fewer corneal endothelial cells, even though they did not have clinical findings.

Capsular bag distension syndrome after uneventful DMEK for Fuchs corneal endothelial dystrophy

AbstractPurpose: Capsular bag distension syndrome or capsular block syndrome is a rare complication of cataract surgery characterized by accumulation of fluid between the intraocular lens and the posterior lens capsule, leading to visual deterioration. A small continuous curvilinear capsulorhexis, residual cortical lens material, as well as residual viscoelastic material behind the intraocular lens are associated with increased risk of fluid entrapment. Capsular bag syndrome usually occurs in the early postoperative period, but it has also been described as late as 14 years after cataract surgery. Nd‐YAG laser posterior capsulotomy is the treatment of choice in most cases, facilitating the drainage of the fluid in the vitreous cavity. Late‐onset capsular block syndrome is often associated with Propionibacterium acnes, requiring surgical management.Methods: Hereby we report a case of a 72‐year‐old female patient with Fuchs corneal endothelial dystrophy, who developed a capsular block syndrome after an uneventful endothelial keratoplasty (DMEK).Results: In the early postoperative period after the DMEK, we observed the development of capsular block syndrome OS. The patient was subjected to bilateral cataract surgery 6 years ago. After intensive follow‐up examination for excluding Propionibacterium acnes‐related endophthalmitis, we proceeded with Nd‐YAG capsulotomy, which resulted in drainage of the fluid in the vitreous cavity and immediate visual recovery.Conclusions: To our knowledge this is the first report of capsular bag syndrome after DMEK and therefore anterior segment surgeons should be aware of this rare complication.

Characterization of Descemet membrane of Fuchs endothelial corneal dystrophy by chromatic confocal microscopy

AbstractPurpose: Fuchs corneal endothelial dystrophy (FECD) causes chronic corneal edema and vision loss, and accounts for more than 50% of keratoplasty indications in occidental countries. The Descemet membrane (DM) gradually thickens because of extracellular matrix deposition and round excrescences named guttae accumulate. Chromatic confocal microscopy (CCM) is on optical device that analyses the nanotopography of surfaces.Aim: to study the feasibility of CCM technology to characterize guttae in FECD.Methods: Descemetorhexis of approximately 8 mm in diameter were obtained during endothelial grafts in 11 patients with FECD and control corneas were obtained from 3 donor corneas. The DM were fixed in 0.5% paraformaldehyde immediately after dissection. The CCM analysis was performed at room temperature on surfaces of 400 x 400 μm to characterize the DM with and without guttae. We measured positive and negative heights (peaks and valleys) relative to the mean altitude, as well as their distribution by asymmetry coefficient.Results: CCM resolution allowed to map nanotopography of the DM of FECD patients and controls. The surface of DM control was flat and homogeneous with maximum positive and negative heights of 1.07 ± 0.09 μm and 1.05 ± 0.07 μm, respectively. The height distribution was uniform with an asymmetry coefficient of 0.002 ± 0.23 μm, reflecting a Gaussian distribution (npeaks = nvalleys). The surface of FECD membranes was completely altered with a maximum peak of 6.05 ± 1.49 μm, up to 5.7 times higher than the control. The height distribution was disturbed with asymmetry value of 1.61 ± 0.79 μm (npeaks &gt; nvalleys) and a maximum valley height (3.09 ± 0.79 μm) that was half that of the peak one.Conclusions: CCM is a promising technology to quantitatively characterize the 3D organization of the DM surface. CCM can be used to classify the different types of surface lesions of the FECD corneas and to follow evolution of DM alteration at different stages of the disease.

Rock inhibitors and antisense oligonucleotides for Fuchs corneal endothelial dystrophy

AbstractFuchs corneal dystrophy (FECD) is the most common primary cause of corneal endothelial dystrophy. FECD is a complex disease where interaction between multiple genetic and environmental factors results in endothelial cells apoptosis and atypical extracellular matrix deposition. Due to the shortage of donor tissue, and high costs of transplants, a topical therapy for treating corneal endothelial dysfunction is urgently required. The topical treatment of several agents has been investigated as therapies for FECD, by the promotion of endothelial cell proliferation and migration, in experimental models of the disorder. ROCK1 and ROCK2 inhibition promotes cell adhesion, prevents apoptosis, and enhances the proliferation of and human corneal endothelial cells. These therapies have involved the knockdown of connexin by siRNA, the release of cell–cell contact inhibition with EDTA, and inhibition of Rho‐associated protein kinase (ROCK) with Y‐27632. Recently several papers showed that Ripasudil, a rho kinase inhibitor, has been shown to promote corneal endothelial wound healing in animal models and in clinical trials. An antisense oligonucleotide (ASO) has also been developed to target the repetitive RNA. This has been shown to decrease foci formation and reversal of misplacing in ex‐vivo FECD specimens. Antisense oligonucleotides (ASO) reduced the RNA aggregates and their toxic downstream events in patient cells. ASO has to be designed to target a particular genetic mutation. This new medical‐based regenerative therapy may provide a less invasive and more effective method for treating patients with FECD.

Surgical Management of Fuchs Endothelial Corneal Dystrophy: A Treatment Algorithm and Individual Patient Meta-Analysis of Descemet Stripping Only.

This study aims to determine predictive factors for success of Descemet stripping only (DSO) in Fuchs corneal endothelial dystrophy and propose a DSO treatment algorithm. Ovid MEDLINE, Embase, and Cochrane CENTRAL databases were searched to evaluate DSO case series, including combined phacoemulsification and DSO, and the use of Rho-kinase inhibitors (ROC-i). Our primary outcome was success of corneal clearance. Secondary outcomes included the time to corneal clearance, the postoperative endothelial cell count (ECC), and the impact of ROC-i. Sixty-eight cases were evaluated with a mean follow-up of 12.4 months. DSO corneal clearance was achieved in 85% (n = 58) with a mean time of 4.9 weeks for the ROC-i group compared with 10.1 weeks in the observation group (P < 0.0001). The mean central ECC postoperatively was higher in the ROC-i group compared with the observation group 1151 ± 245 versus 765 ± 169 cells/mm2, respectively (P < 0.018). The postoperative best-corrected visual acuity (BCVA) improved in 61 eyes (90%), with mean final BCVA of 0.17 (0.26) logMAR (P = 0.001), which was statistically significant compared with preoperative BCVA. Factors influencing success were 4-mm descemetorhexis size, a clear peripheral ECC with no clinical sequelae of decompensation or guttae, and a low central corneal thickness. No intraoperative complications were noted. The commonest postoperative complication was deep corneal stromal scars noted at the descemetorhexis edge (n = 9). DSO has a role in the treatment of a subset of patients with Fuchs corneal endothelial dystrophy and that adjuvant treatment with ROC-i may lead to faster corneal clearance.

Еvaluate the Effectiveness of Accelerated Collagen Crosslinking in the Treatment of Corneal Endothelial Decompensation

The article discusses the effectiveness of accelerated collagen crosslinking in the treatment of patients with corneal diseases, a common basic pathogenetic link of which is endothelial corneal decompensation. This method was used to treat patients with bullous keratopathy and endothelial dystrophy of Fuchs’ cornea with a long postoperative follow-up. In connection with the controversial results of researchers, reflecting the positive dynamics of the postoperative period, the question of the expediency of accelerated collagen cross-linking in patients with this pathology as a monotherapy is discussed.The study included 25 patients (26 eyes) with mean age 69.10 ± 10.61 years (40 to 82 years). There was Fuchs corneal endothelial dystrophy in 16 patients (17 eyes), in 9 patients (10 eyes) — stage II, in 7 patients (7 eyes) — stage III. Bullous keratopathy was present in 9 patients (9 eyes). All patients underwent treatment according to the method of accelerated collagen corneal crosslinking. In patients with bullous keratopathy (9 eyes), the data on the central thickness of the cornea and the maximum corrected visual acuity did not differ from the initial data at any of the postoperative visits, and did not differ from each other (p &gt; 0.83). On the contrary, in some patients the dystrophic process progressed in the form of the appearance of fibrotic changes in the stroma of the cornea. Corneal transplantation was recommended to all patients under observation after treatment at different periods of observation. In patients with Fuchs endothelial dystrophy, a significant difference in the maximum corrected visual acuity from the initial data was observed only 6 months after surgery.The expediency of accelerated collagen cross-linking in the treatment of patients with corneal diseases accompanied by endothelial decompensation as monotherapy is very doubtful. The study of combined surgical methods for treating this complex corneal pathology using cross-linking as an auxiliary method seems promising.

Corneal Tomography Changes and Refractive Outcomes After Descemet Stripping Without Endothelial Keratoplasty.

To investigate corneal tomography changes and refractive outcomes after Descemetorhexis without endothelial keratoplasty (DWEK). Retrospective chart review of 25 eyes from 16 patients with Fuchs corneal endothelial dystrophy that underwent successful DWEK combined with cataract surgery. There was no significant change in anterior corneal curvature on tomography maps. However, all tomography maps demonstrated an increase in central posterior float and all but one demonstrated a decrease in pachymetry after DWEK. Only 7 of 25 eyes had increased irregular astigmatism on tomography after DWEK, of which 57% had preexisting irregular astigmatism before the procedure. The mean difference between the targeted and outcome refraction was +0.65 diopters (D) at the time of corneal clearance, but this improved to +0.38 D 1 month after corneal clearance. Postoperative refraction was within 1 D of target refraction for 92% of cases (23 eyes) but within 0.5 D of target refraction for only 48% of cases (12 eyes). The differences between expected and actual refractive outcomes were correlated with change in posterior corneal curvature and pachymetry. DWEK induces an increased central posterior float localized to the site of Descemet membrane stripping, confirming the need for centralized stripping. Irregular astigmatism can occur after DWEK but is typically minimal and occurs more commonly in the setting of preoperative irregular astigmatism. DWEK induces about a 0.5 D hyperopic shift, which should be considered when determining intraocular lens power with simultaneous surgery.

Experience in personalized cell therapy clinical implementation for treatment of patients with primary endothelial dystrophy after phacoemulsification

The article presents treatment results of the personalized cell therapy (PCT) method in patients with early post-operative bullous keratopathy which developed in eyes with pre-existing primary Fuchs corneal endothelial dystrophy (ED). The patented PCT consists in incubating in vitro the patients blood with the stimulator (polyA:polyU), collecting serum with activated leukocytes weighted in it, and introducing the obtained cell preparation in the anterior chamber of the patients eye. The study included 12 patients with ED and pseudophakia. The observation period ranged from 8 to 12 months. The therapeutic effect of PCT was obtained in 58.3% of cases, allowing to avoid further surgical procedures. To achieve a good therapeutic effect, several PCT sessions are recommended. To date, PCT is the only effective therapeutic treatment method for early corneal edema after phacoemulsification.

Predictive Factors for Corneal Clearance After Descemetorhexis Without Endothelial Keratoplasty.

To study preoperative factors that possibly contribute to corneal clearance after Descemetorhexis without endothelial keratoplasty (DWEK) and to determine the most successful surgical technique for the procedure. Retrospective chart review of 17 eyes of 13 patients with Fuchs corneal endothelial dystrophy that underwent central 4-mm DWEK. Baseline age, pachymetry, and endothelial cell count were not statistically significantly different between eyes that cleared 0 to 2 months, 3 to 5 months, 6 to 8 months, or that failed to clear. All eyes that failed to clear had DWEK performed using scoring followed by the stripping technique. Postoperative endothelial cell counts steadily increased over time after the procedure, even in eyes that failed to clear. DWEK when performed with a Descemetorhexis technique results in corneal clearance in the majority of cases regardless of baseline demographics, with clearance typically 3 months after the procedure. Further studies are needed to investigate environmental factors, such as possible growth factors in the anterior chamber, that may influence clearing in these cases.

New therapeutic modality for corneal endothelial disease using Rho-associated kinase inhibitor eye drops.

Corneal endothelial dysfunction accompanied by visual disturbance is a primary indication for corneal endothelial transplantation. However, despite the value and potential of endothelial graft surgery, a strictly pharmacological approach for treating corneal endothelial dysfunction remains an attractive proposition. Previously, we reported that the selective Rho-associated kinase (ROCK) inhibitor Y-27632 promotes cell adhesion and proliferation, and inhibits the apoptosis of primate corneal endothelial cells in culture. These findings have led us to develop a novel medical treatment for the early phase of corneal endothelial disease using ROCK inhibitor eye drops. In rabbit and monkey models of partial endothelial dysfunction, we showed that corneal endothelial wound healing was accelerated via the topical application of ROCK inhibitor to the ocular surface, resulting in the regeneration of a corneal endothelial monolayer with a high endothelial cell density. Based on these animal studies, we are now attempting to advance the clinical application of ROCK inhibitor eye drops for patients with corneal endothelial dysfunction. A pilot clinical study was performed at the Kyoto Prefectural University of Medicine, and the effects of Y-27632 eye drops after transcorneal freezing were evaluated in 8 patients with corneal endothelial dysfunction. We observed a positive effect of ROCK inhibitor eye drops in treating patients with central edema caused by Fuchs corneal endothelial dystrophy. We believe that our new findings will contribute to the establishment of a new approach for the treatment of corneal endothelial dysfunction.

Descemet Stripping Endothelial Keratoplasty for the Treatment of Combined Fuchs Corneal Endothelial Dystrophy and Keratoconus

To report the first case series of patients with Fuchs corneal endothelial dystrophy (FCD) and keratoconus (KCN) who underwent Descemet stripping endothelial keratoplasty (DSEK). This is a retrospective case series of 6 eyes of 4 patients with combined FCD and KCN who underwent DSEK at 3 different centers. Clinical information collected included corneal topography measurements, central corneal thickness, and endothelial cell count. Visual outcomes and change in keratometric measurements were evaluated. The follow-up for patients ranged from 10 to 72 months. The best-corrected visual acuity was 20/40 or better in all 6 eyes. The mean keratometric measurements decreased in all cases (range of 0.5-5.8 diopters); however, topography still demonstrated an inferior steepening in each case. Patients with FCD and KCN have been previously reported as being managed with penetrating keratoplasty. We present 6 eyes of 4 patients who were managed with DSEK for the FCD. Topographically, the characteristic inferior steepening of KCN did not change; however, all patients with DSEK had flatter postoperative keratometric measurements with improved visual acuity. If a DSEK is performed for FCD before apical corneal scarring from KCN, a good visual outcome may be achieved.

Detection of Herpes Simplex Virus Type 1 in Failed Descemet Stripping Automated Endothelial Keratoplasty Grafts

To determine the prevalence of herpes simplex virus type 1 (HSV-1) DNA in failed Descemet membrane stripping automated endothelial keratoplasty (DSAEK) grafts. A retrospective interventional case series of patients with DSAEK graft failure treated at the New York Eye and Ear Infirmary between January 2009 and July 2012 was performed. Repeat DSAEK, penetrating keratoplasty, or keratoprosthesis procedure was subsequently performed on eyes with failed grafts. All failed grafts were examined immunohistochemically and with qualitative real-time polymerase chain reaction for HSV-1 DNA. In HSV-1-positive cases, corneoscleral donor rims from the original DSAEK procedures were also examined immunohistochemically and with polymerase chain reaction. Fifty-one failed DSAEK grafts from 50 eyes of 49 patients were identified. Indications for DSAEK were pseudophakic bullous keratopathy (28/51, 55%), Fuchs corneal endothelial dystrophy (12/51, 23%), failed penetrating keratoplasty (7/51, 14%), corneal decompensation from glaucoma (2/51, 4%), herpetic endotheliitis (1/51, 2%), and failed DSAEK (1/51, 2%). Forty-three grafts (83%) were primary DSAEK graft failure. HSV-1 DNA was isolated from 2 of 51 failed DSAEK grafts (4.0%). The corresponding corneoscleral donor rims did not demonstrate the presence of HSV-1. Based on our results, HSV-1 infection plays a minor role in DSAEK graft failure. The data suggest that recipient reactivation, rather than donor transmission, plays a role in HSV infection.

Corneal Transplant Rejection Rate and Severity After Endothelial Keratoplasty

To examine the corneal transplant rejection rate and the rate of graft failure subsequent to rejection in the first 2 years after endothelial keratoplasty (EK) and to compare this to background data for similar cases of penetrating keratoplasty (PK). Anonymized data from consecutive cases of EK [deep lamellar (DLEK) or Descemet stripping (DSEK)] for Fuchs corneal endothelial dystrophy or pseudophakic bullous keratopathy operated on before August 2004 were collected in 4 participating centers. The number and timing of rejection episodes and cases of subsequent graft failure were recorded, together with the time to cessation of topical steroid medication. Two-year postoperative findings were compared with background data for similar patients undergoing PK recorded in the Swedish Corneal Transplant Registry. Rejection episodes were less frequent after EK than PK (P = 0.035). Fifteen (7.5%) of 199 EK cases had a rejection episode in the first 2 years after surgery versus 92 (13%) of 708 PK cases. Graft failure after rejection in EK may have been less frequent than in PK (P = 0.063), with only 1 (6.7%) case of rejection after EK versus 26 (28.3%) cases of rejection after PK proceeding to graft failure. A strong trend toward continued use of low-dose topical steroid medication was observed in the EK group. Eighty percent of EK patients were still taking topical steroid medication 2 years after surgery, whereas topical steroid medication had been ceased within a year of surgery in almost all PK patients in the comparator group. Corneal transplant rejection is less frequent and may be less severe after EK than after PK. It is not yet clear whether these apparent differences are simply a product of relatively prolonged postoperative topical steroid cover in EK patients.

Genetics of corneal endothelial dystropies

Abstract Purpose: Purpose‐ To determine whether mutations in genes SLC4A11 and TCF8 causative of recessive CHED and PPCD, respectively, may also play a pathogenic role in the more common Fuchs corneal endothelial dystrophy. The endothelial (posterior) corneal dystrophies, which result from primary endothelial dysfunction, include Fuchs endothelial dystrophy (FECD), posterior polymorphism dystrophy (PPCD) and congenital hereditary endothelial dystrophy (CHED). As they share common features of disease it is possible that a proportion of them could be clinical manifestations of different mutations of the same gene. Methods: Method‐Exons SLC4A11 and TCF8 gene were PCR amplified in 64 Chinese FECD cases and then subjected to bi‐directional sequencing. Eighty Chinese samples were used as normal age matched controls. To characterise SLC4A11 mutations wild type and mutant cDNA constructs were transfected in to HEK293 cells and protein extracts used for immunoblot analysis and cell surface processing assays. Confocal immunolocalization were also performed using established protocols. Results: Results‐Three heterozygous mutations were identified in this screen of 64 FECD patients. These were two missense mutations (G709E and T754M) and one deletion mutation (99‐100delTC). Missense mutations involved amino acid residues showing high interspecies conservation indicating that mutations at these sites would be deleterious. Accordingly, immunoblot analysis, biochemical assay of cell surface localization and confocal immunolocalization showed that missense mutants were defective in localization to the cell surface. No convincing pathogenic mutations were identified in the TCF8 gene. Conclusions: Conclusion‐ Our data suggests that 4.7% (95% CI=0.98% to 13.1%) of FECD in the Chinese can be attributable to SLC4A11 mutations.

Clinical Study of Fuchs Corneal Endothelial Dystrophy Leading to Penetrating Keratoplasty

To review 30 years' clinical experience with Fuchs corneal endothelial dystrophy leading to penetrating keratoplasty (PK). We reviewed the clinical records of patients diagnosed histopathologically as having Fuchs corneal endothelial dystrophy who underwent PK at Duke University Medical Center between January 1, 1972, and December 31, 2001. This observational case series included 424 patients (546 eyes). Women represented 77.6% of patients. Mean age at the time of PK for all patients was 69.2 years. Bilateral PK was required in 28.8% of patients, and the mean interval between the 2 PKs was 3.2 years. There was no difference with regard to sex in the likelihood of requiring bilateral PK (P=.59). Among 376 documented family histories, 13.6% were known to be positive for Fuchs dystrophy. Patients with a positive family history underwent PK a mean of 5 years earlier (P<.002) and were more likely to require bilateral PK (P<.003). Patients who underwent bilateral PK were twice as likely to have a positive family history compared with those undergoing unilateral PK (P<.001). Mean visual acuities at corneal thicknesses of 539 to 650 microm, 651 to 750 microm, and greater than 750 microm were 20/60, 20/60, and 20/80, respectively. Patients who underwent bilateral PK and had a preceding cataract extraction on 1 eye required PK of the pseudophakic eye on average 3.2 years earlier than the fellow eye. The mean time from cataract extraction to PK was 2.2 years. This large study affirms that Fuchs dystrophy is a disorder of aging that predominantly affects women (3.5:1) and is often familial. Pachymetry-determined corneal thickness was a poor predictor of visual acuity until extreme levels of corneal edema were reached. Cataract extraction in an eye with Fuchs dystrophy leads to earlier PK.

Factors influencing visual outcome after penetrating keratoplasty combined with intraocular lens implantation.

To establish which factors influence visual outcome after penetrating keratoplasty combined with intraocular lens implantation. This retrospective noncomparative clinical interventional case series study included 135 consecutive patients (mean age 70.2 +/- 13.6 years) who underwent central penetrating allogenic keratoplasty combined with intraocular lens (IOL) implantation, all operated by the same surgeon. There were 79 triple procedures, 33 keratoplasties combined t with an exchange of OL, and 23 penetrating keratoplasties combined with a secondary implantation of posterior chamber lens. Mean follow-up was 28.3 +/- 18.7 months (range 3.3-112 months). Reasons for keratoplasty were herpetic or traumatic corneal scars or defects (46), Fuchs corneal endothelial dystrophy (22), pseudophakic or aphakic bullous keratopathy (49), corneal endothelial decompensation due to other reasons (15), and keratoconus (3). Main outcome measures were postoperative visual acuity and agin in visual acuitvy Mean postoperative visual acuity and mean gain in visual acuity were 0.33 +/- 0.21 (median 0.30) and 0.25 +/- 0.20 (median 0.20), respectively. Compared with the preoperative measurements, mean visual acuity increased in 129 patients (129 /135, 95.6%). Factors influencing postoperative visual outcome and gain in visual acuity were preoperative visual acuity (p < 0.005), reason for keratoplasty (p < 0.005), and diameter of the graft (p = 0.046). ostoperative visual outcome was independent of age, sex, right or left eye, presence of diabetes mellitus, preoperative refractive error, length of follow-up, duration of surgery, and preoperative intraocular pressure. The most important factors influencing visual outcome after central penetrating allogenic keratoplasty combined with IOL surgery are preoperative visual acuity, graft size, and reason for keratoplasty. Other factors such as age, sex, diabetes mellitus, and preoperative refractive error do not substantially influence postoperative visual outcome.