Endothelial Corneal Dystrophy Research Articles

Frequency of Different Types of Endothelial Corneal Dystrophies by Age, Gender, and Visual Acuity in Punjab, Pakistan

Endothelial Corneal Dystrophy (ECD) is, by definition, an endogenous degeneration that progresses slowly in the corneal endothelium as a result of genetic predisposition. A transverse study was conducted from September 2018 to June 2019, and the subjects affected with ECD were examined by visiting various city hospitals in Punjab including Sahiwal, Narowal, Okara, Gujranwala, Kasur, Lahore, and Multan. The basic objective of the current investigation was to find the frequency of different types of ECD in the population of different cities in Punjab. Data was collected based on relevant parameters such as age, gender, and visual acuity. The visual acuity was assessed by ophthalmologists via Snellen chart and Visual acuity test. Among 3000 patients, 6.6 % (n=198) cases of ECD were recognized which includes more males 52.52 % (n=104) as compared to females 47.48 % (n=94). Maximum cases of ECD 31.82 % (n=63) were observed in the 41-50 years of age group. In all types of ECD, FECD was observed most abundant with 38.38 % (n=76) and XECD with the least abundance of 6.67 % (n=13). The frequency of CHED and PPCD was 25.25 % (n=50) and 29.79 % (n=59) respectively. The results of recent research finalize that endothelial corneal dystrophy is a rare disease prevailing in Pakistan with a proportion of only 6.6 %. This study benefits in updating the data about the frequency of endothelial corneal dystrophy in Pakistan. Careful clinical evaluation, initial diagnosis, genetic counseling, genotyping, and correct treatment are necessary for the restoration of vision loss due to ECD.

Correlation of Clinical Fibrillar Layer Detection and Corneal Thickness in Advanced Fuchs Endothelial Corneal Dystrophy.

Central subendothelial geographic deposits are formed as a fibrillar layer (FL) in advanced Fuchs endothelial corneal dystrophy (FECD). Previous studies demonstrated a significant decrease in corneal endothelial cell (CEC) density and an increase in focal corneal backscatter in the FL area. The present study investigated the association of the FL with edema formation and its localization. Patients (n = 96) presenting for Descemet membrane endothelial keratoplasty (DMEK) for advanced FECD were included. Slit-lamp biomicroscopy with FECD grading was followed by Scheimpflug imaging with en face backscatter analysis and pachymetric analysis. FL dimensions were measured, and correlation with pachymetric values was performed. An FL was detected in 74% of all eyes (n = 71). Pachymetric values in FL-positive versus FL-negative eyes were for corneal thickness at the apex (ACT) 614 ± 52 µm and 575 ± 46 µm (p = 0.001), for peripheral corneal thickness at 1 mm (PCT1mm) 616 ± 50 µm and 580 ± 44 µm (p = 0.002), for PCT2mm 625 ± 48 µm and 599 ± 41 µm (p = 0.017), for PCT3mm 651 ± 46 µm and 635 ± 40 µm (p = 0.128) and for PCT4mm 695 ± 52 µm and 686 ± 43 µm (p = 0.435), respectively. Correlation analysis indicated a weak correlation for the FL maximum vertical caliper diameter with ACT and PCT1mm values but no further relevant correlations. In FL-positive eyes, increased focal corneal backscatter and increased corneal thickness showed primarily central and inferotemporal localization. In conclusion, Scheimpflug imaging shows an association of the FL with increased corneal thickness in advanced FECD and shows localization of the FL and increased corneal thickness in the central and inferotemporal region. This may provide important information for progression assessment and therapeutic decision making in FECD patients in the future.

Comparison of triple-DMEK to pseudophakic-DMEK: A cohort study of 95 eyes.

Previous comparative studies show that triple Descemet membrane endothelial keratoplasty (DMEK) (i.e. phacoemulsification followed immediately by DMEK) has either equivalent or better visual outcomes than DMEK in pseudophakic patients. To resolve this discrepancy, a retrospective cohort study was conducted. All consecutive patients with Fuchs Endothelial Corneal Dystrophy who underwent triple or pseudophakic DMEK in 2015-2019 in a tertiary-care hospital (France) and were followed for >12 months were compared in terms of best spectacle-corrected visual acuity (BSCVA), final refractive outcomes, and endothelial-cell loss at 12 months as well as rebubbling rates. The triple-DMEK (40 eyes, 34 patients) and pseudophakic-DMEK (55 eyes, 43 patients) groups were similar in terms of age and other baseline variables. They also did not differ in final BSCVA (both 0.03 logMAR), final endothelial-cell loss (54% vs. 48%), or astigmatism (-1.25 vs. -1 D). At 12 months, triple-DMEK associated with significantly smaller residual hyperopia (0.75 vs. 1 D; p = 0.04) and spherical equivalence (0 vs. 0.5 D; p = 0.02). Triple-DMEK also tended to associate with more frequent rebubbling (40% vs. 24%, p = 0.09). In conclusion, while triple-DMEK and pseudophakic-DMEK achieved similar visual acuity improvement, triple-DMEK was superior in terms of final sphere and spherical refraction but also tended to have higher complication rates.

Graft Survival, Graft Rejection, and Glaucoma in a Consecutive Series of Descemet Stripping Endothelial Keratoplasty.

The goal of this study was to compare outcomes of Descemet stripping endothelial keratoplasty (DSEK) in eyes with glaucoma and abnormal anatomy to eyes with Fuchs endothelial corneal dystrophy (FECD). In a retrospective interventional series of all cases of DSEK between April 1, 2006, and November 30, 2015, recipient diagnosis, preoperative glaucoma status, concurrent surgical procedures, and graft outcomes were recorded. Graft survival, risk of rejection, and subsequent glaucoma surgery were estimated by using Kaplan-Meier analysis with risk factors determined by proportional hazard models. Of 703 DSEKs in 666 eyes (509 subjects), the main recipient diagnoses were FECD (n = 496), pseudophakic corneal edema (n = 112), and failed graft (n = 83). Glaucoma was present in 150 cases before DSEK. Overall graft survival was 85%, 75%, and 71% at 5, 10, and 12 years, respectively, and for FECD without glaucoma was 95%, 89%, and 87% at 5, 10, and 12 years, respectively. Independent risk factors for graft failure included recipient diagnoses of pseudophakic corneal edema (HR = 8.3, P < 0.001), failed graft (HR = 6.4, P < 0.001), and preoperative medical glaucoma (HR = 7.1, P < 0.001) or surgical glaucoma (HR = 12.3, P < 0.001). Preoperative glaucoma treated by previous surgery resulted in graft survival of 28% at 10 years. Preoperative glaucoma was associated with an increased risk of graft rejection (HR = 6.8, P < 0.001) and subsequent glaucoma surgery (HR > 17.4, P < 0.001). Preoperative glaucoma increases the risk of graft failure, graft rejection, and needing subsequent glaucoma surgery in the first decade after DSEK. With previous glaucoma surgery, DSEK graft survival was more favorable compared with published reports of Descemet membrane endothelial keratoplasty.

Comparing surgical efficiencies between phacoemulsification systems: a single surgeon retrospective study of 2000 eyes.

To compare under similar conditions intraoperative surgical efficiencies metrics between an active fluidics and a gravity based phacoemulsification systems. Adult patients who were diagnosed with a cataract that compromised visual acuity inferior to 20/40 were included in the study. Patients were excluded from the study if they had a history of severe retinal disorders, clinically significant corneal endothelial dystrophy or history of corneal disease. All phacoemulsification surgeries were performed by a single surgeon. Both phacoemulsification systems used the 0.9 mm 45-degree aspiration bypass system Intrepid Balanced tip and the 0.9 mm Intrepid Ultra infusion sleeve. All cataracts were classified using the Lens Opacities Classification System III, cumulative dissipated energy (CDE) and aspiration fluids were measured in each surgery. Totally 2000 eyes were included in the study. Phacoemulsification was performed in 1000 (50%) eyes with an active fluid dynamics system and in 1000 (50%) eyes with a gravity-based fluidic system. Mean CDE until fracture of the lens was 1.1 and 1.9 percent-seconds and total mean CDE used was 5.6 and 7.2 percent-seconds using an active fluidics dynamics system and gravity-based fluidic system, respectively (P<0.001). Mean aspiration fluids used were 70 mL using an active fluidics dynamics system and 85 mL using a gravity-based fluidic system (P<0.001). This study evidences that surgeries performed under similar conditions (same surgeon, phaco tip and sleeve) with the active fluidics dynamics system required significantly lower CDE and aspiration fluids.

Global Prevalence of Fuchs Endothelial Corneal Dystrophy (FECD) in Adult Population: A Systematic Review and Meta-Analysis.

Purpose To evaluate the global prevalence of Fuchs endothelial corneal dystrophy (FECD). Design Systematic review and meta-analysis. Methods A systematic electronic literature search was conducted on PubMed/MedLine, Cochrane Library, and Google Scholar, in order to select papers analysing the prevalence rate of FECD. Two authors independently conducted the electronic search. After removal of duplicates, title and abstract screening, and full-text analysis, data from selected articles were archived in a customized Excel spreadsheet. Risk of bias assessment was performed using the Joanna Briggs Institute Prevalence Critical Appraisal Tool. Meta-analysis was conducted using R (version 1.4.1106, package “meta”). Results A total of 6660 eligible articles were retrieved from the initial electronic search. Only 4 original works were included in the qualitative and quantitative analysis. Of the 4746 patients included in this meta-analysis (i.e., 2232 male (M) and 2322 female (F)), we retrieved 269 FECD cases (81 M; 188 F), with a pooled prevalence estimates of 7.33% (95% CI: 4.08–12.8%). Statistically significant gender-related differences in the prevalence of FECD emerged by the analysis (OR: 2.22; 95% CI: 1.66–2.96, p=0.0016). While the total number of people aged >30 years with FECD is nowadays estimated at nearly 300 million, an increase of 41.7% in the number of FECD-affected patients is expected by 2050, when the overall figure is supposed to rise up to 415 million. Conclusion This study provides a reliable figure of the present and future epidemiological burden of FECD globally, which might be useful for the design of FECD screening, treatment, rehabilitation, and related public health strategies.

Disparities in Visual Acuity Outcomes after Endothelial Keratoplasty: An Intelligent Research in Sight Registry Analysis

To assess risk factors for lack of vision improvement after endothelial keratoplasty (EK). Retrospective cohort study. Patients aged 18 years and older in the Intelligent Research in Sight (IRIS®) Registry who underwent EK surgery in the United States between 2013 and2018. Change in visual acuity (VA) relative to baseline were determined at 6 months and 1 year. A multivariable population-average marginal model estimated using generalized estimating equations adjusting for sociodemographic factors, baseline vision, surgical indication, ocular comorbidities, and postoperative complications was used to identify factors associated with worse VA outcomes. Visual acuity and lack of VA improvement at 1 year compared with preoperative status. A total of 30 600 EK procedures (N= 25 666 unique patients) were included in the analysis. Overall, VA improved from median logarithm of the minimum angle of resolution (logMAR) 0.54 (Snellen 20/69) (interquartile range [IQR] ± 0.70) preoperatively to median logMAR 0.40 (20/50) (IQR ± 0.36) at 6 months and median logMAR 0.30 (20/40) (IQR ± 0.36) at 1 year postoperatively. A total of 30.3% of the overall cohort, 29.8% of Fuchs' endothelial corneal dystrophy (FECD) subgroup, and 27.4% of the bullous keratopathy (BK) subgroup did not show visual improvement at 1 year postoperatively. In the FECD subgroup, older age (risk ratio [RR], 1.05 per 5-year increase, 95% confidence interval [CI], 1.03-1.07) and female sex (RR, 1.10, 95% CI, 1.04-1.16) were associated with VA worse than or equal to baseline at 1 year postoperatively. In both FECD and BK subgroups, eyes with higher baseline logMAR VA (per 0.1 unit increase in logMAR) were more likely to have visual improvement postoperatively (FECD: RR, 0.82, 95% CI, 0.81-0.84; BK: RR, 0.91, 95% CI, 0.91-0.92), whereas postoperative rebubbling (FECD: RR, 1.10, 95% CI, 1.02-1.19; BK: RR, 1.31, 95% CI, 1.17-1.48) and repeat keratoplasties (FECD: RR, 1.41, 95% CI, 1.32-1.52; BK: RR, 1.42, 95% CI, 1.28-1.57) were associated with higher risk of no VA improvement. In this large national cohort, postoperative rebubblings and repeat keratoplasties were identified as independent factors associated with worse VA outcomes after EK for both FECD and BK subgroups. Older age and female gender were associated with worse VA outcomes after EK in the FECD subgroup.

Beneficial Effects of Polydeoxyribonucleotide (PDRN) in an In Vitro Model of Fuchs Endothelial Corneal Dystrophy.

Fuchs endothelial corneal dystrophy (FECD) is a bilateral, hereditary syndrome characterized by progressive irreversible injury in the corneal endothelium; it is the most frequent cause for corneal transplantation worldwide. Oxidative stress induces the apoptosis of corneal endothelial cells (CECs), and has a crucial function in FECD pathogenesis. The stimulation of the adenosine A2A receptor (A2Ar) inhibits oxidative stress, reduces inflammation and modulates apoptosis. Polydeoxyribonucleotide (PDRN) is a registered drug that acts through adenosine A2Ar. Thus, the goal of this study was to assess the effect of PDRN in an in vitro FECD model. Human Corneal Endothelial Cells (IHCE) were challenged with H2O2 (200 μM) alone or in combination with PDRN (100 μg/mL), PDRN plus ZM241385 (1 μM) as an A2Ar antagonist, and CGS21680 (1 μM) as a well-known A2Ar agonist. H2O2 reduced the cells’ viability and increased the expression of the pro-inflammatory markers NF-κB, IL-6, IL-1β, and TNF-α; by contrast, it decreased the expression of the anti-inflammatory IL-10. Moreover, the pro-apoptotic genes Bax, Caspase-3 and Caspase-8 were concurrently upregulated with a decrease of Bcl-2 expression. PDRN and CGS21680 reverted the negative effects of H2O2. Co-incubation with ZM241385 abolished the effects of PDRN, indicating that A2Ar is involved in the mode of action of PDRN. These data suggest that PDRN defends IHCE cells against H2O2-induced damage, potentially as a result of its antioxidant, anti-inflammatory and antiapoptotic properties, suggesting that PDRN could be used as an FECD therapy.

Cost Burden of Endothelial Keratoplasty in Fuchs Endothelial Dystrophy: Real-World Analysis of a Commercially Insured US Population (2014-2019).

PurposeTo assess the incremental burden of corneal transplant surgery for US commercially insured patients with Fuchs endothelial corneal dystrophy (FECD) treated with endothelial keratoplasty (EK) compared to controls.MethodsThe study design was retrospective cohort using IBM® MarketScan® claims (January 2014–September 2019) and included EK-treated (N=1562) and control patients (N=23,485) having ≥12 months’ enrollment before and after diagnosis, who were subsequently matched on select characteristics. The index date was the beginning of the pre-operative period (3 months before EK); synthetic EK index was assigned for controls. All-cause, eye-disease, and complication-related healthcare resource utilization (HCRU) and costs were compared up to 36 months post index. For a small subset of patients, patient data were linked to the Health and Productivity Management supplemental database, which integrates data on productivity loss and disability payments.ResultsMatched cohorts included 804 EK-treated and 1453 controls with average age 65.7 years, 1383 (61%) female. Over 12 months of follow-up, all-cause ($41,199 vs $20,222, p<0.001) and eye-disease related costs ($22,951 vs $1389, p<0.001) were higher among EK-treated patients than controls. The cost differential increased additionally by $1000–$2000 per annum by 36 months of follow-up. While balanced at baseline, over follow-up EK-treated patients had higher prevalence of glaucoma, elevated intraocular pressure, cataract, cataract surgery, diagnosis of cornea transplant rejection, retinal edema. By 36 month of follow-up, EK-treated patients had 9 more short-term disability days, resulting in $2992 additional burden of disability payments.ConclusionThis study found a higher cost burden among FECD patients receiving EK treatment versus those who did not. With a shift in management of FECD, cost burden estimates generated in this study could serve as an important benchmark for future studies.

Identification of novel therapeutic targets for Fuchs' endothelial corneal dystrophy based on gene bioinformatics analysis.

Fuchs’ endothelial corneal dystrophy (FECD) is a disease where progressive visual impairment occurs by the thickening of the Descemet’s membrane and the gradual degeneration and loss of corneal endothelial cells. This study aimed to investigate the key changes in gene expression associated with FECD and explore potential biomarkers and new therapeutic strategies for FECD. To explore the potential therapeutic targets of FECD, we downloaded the gene expression dataset GSE171830 from the Gene Expression Omnibus (GEO) database. A total of 303 differentially expressed genes (DEGs) were identified by the limma package. The enriched Gene Ontology (GO) annotations and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs mostly included the extracellular matrix organization, collagen-containing extracellular matrix, and the structural constituents of the extracellular matrix. Fifteen hub genes from the most significant module were ascertained by Cytoscape. Both collagen-containing extracellular matrix and extracellular matrix hit to ANXA1, VCAN, GPC3, TNC, IGFBP7, MATN3, and SPARCL1 genes in the GO cellular components. Among these genes, the expression of SPARCL1 was down-regulated in the FECD samples, whereas the expression of GPC3, MATN3, IGFBP7, TNC, VCAN, and ANXA1 was up-regulated in the FECD samples. Gene set enrichment analysis (GSEA) plots showed that among the 20,937 genes, SPARCL1 played an important role in three pathways, cytokine-cytokine receptor interaction, the TGF-beta signaling pathway, and antigen processing and presentation. The top three pathways enriched by the GPC3, MATN3, IGFBP7, TNC, VCAN, and ANXA1 genes were those for cytokine-cytokine receptor interaction, TGF-beta signaling, and RIG-I-like receptor signaling. In conclusion, the DEGs identified here might assist clinicians in understanding the pathogenesis of FECD. Furthermore, these identified biomarkers might serve as potential therapeutic targets for the treatment of FECD.

Predicting Corneal Improvement after Descemet Membrane Endothelial Keratoplasty for Fuchs Endothelial CornealDystrophy.

PurposeTo develop a model to predict corneal improvement after Descemet membrane endothelial keratoplasty (DMEK) for Fuchs endothelial corneal dystrophy (FECD) from Scheimpflug tomography.DesignCross-sectional study.ParticipantsForty-eight eyes (derivation group) and 45 eyes (validation group) with a range of severity of FECD undergoing DMEK.MethodsScheimpflug images were obtained before and after DMEK. Before DMEK, pachymetry map and posterior elevation map patterns were quantified by a special image analysis program measuring tomographic features of edema (loss of regular isopachs, displacement of the thinnest point of the cornea, posterior surface depression). Image-derived novel parameters were combined with instrument-derived parameters, and the relative influences of parameters associated with the change in central corneal thickness (CCT) after DMEK in the derivation group were determined by using a gradient boosting machine learning model. The parameters with highest relative influence were then fit in a linear regression model. The derived model was applied to the validation group. Correlations and agreement were assessed between predicted and observed changes in CCT.Main Outcome MeasuresPredictive power (R2) and mean difference between predicted and observed change in CCT.ResultsThe gradient boosting machine model identified 4 novel parameters of isopach circularity and eccentricity and 1 instrument-derived parameter (posterior surface radius); preoperative CCT was a poor predictor. In the derivation group, the model strongly predicted the change in CCT after DMEK (R2 = 0.80; 95% confidence interval [CI], 0.71–0.89) and the mean difference between predicted and observed change was, by definition, 0 μm. When the same 5 parameters were fit to the validation group, the model performed very highly (R2 = 0.89; 95% CI, 0.84–0.94). When the coefficient estimates from the derivation model were used to predict the change in CCT in the validation group, the predictive power was also high (R2 = 0.78; 95% CI, 0.68–0.88), and the mean difference was 4 μm (predicted minus observed).ConclusionsScheimpflug tomography maps of corneas with FECD can predict the improvement in CCT after DMEK, independent of preoperative corneal thickness measurement. The model could be applied in clinical practice or for clinical research of FECD.

Who first described Descemetorhexis without endothelial keratoplasty (DWEK) for the management of Fuchs’ corneal endothelial dystrophy?

We present here in a historical focus on the first descriptions in the 1950's by Louis Paufique of Descemetorhexis without endothelial keratoplasty (DWEK) for the treatment of Fuchs' endothelial dystrophy. This article places the introduction of this surgical technique in the context of its time, describes its principles, and puts into perspective the place of this relevant treatment in the therapeutic arsenal of today and tomorrow.

Visual Function in Pseudophakic Eyes with Fuchs’ Endothelial Corneal Dystrophy

To assess vision in pseudophakic eyes with Fuchs' endothelial corneal dystrophy (FECD) before the onset of clinically detectable corneal edema. Cross-sectional study. Sixty-one otherwise healthy pseudophakic eyes of 38 subjects with FECD (without clinically detectable edema) and 17 otherwise healthy pseudophakic eyes of 9 subjects with normal corneas. Subjects underwent clinical examination to determine the morphologic distribution of guttae (severity grading). Standardized best-corrected high-contract and low-contrast (photopic and mesopic) visual acuity (HCVA, LCVA) and straylight were measured. Scheimpflug tomography posterior elevation and pachymetry maps were interpreted for 3 tomographic features of subclinical edema: loss of regular isopachs, displacement of the thinnest point of the cornea, and presence of posterior surface depression. In FECD without tomographic features of edema (ie, normal tomography patterns), HCVA, LCVA, and straylight did not differ from that of eyes with normal corneas (P ≥ .09); these eyes encompassed the full range of severity grading of guttae. In FECD with all 3 tomographic features of edema, the same parameters were worse compared with eyes with normal corneas (P ≤ .02). In FECD with 1 or 2 tomographic abnormalities, mesopic LCVA (P=.04) and straylight (P=.003) were worse compared with eyes with normal corneas. Impairment of vision was associated with the presence of tomographic edema in eyes with FECD. When tomography patterns were normal in FECD (ie, guttae were present without tomographic edema), visual acuity and straylight were normal, and therefore corneal surgical intervention would not typically be indicated to improve vision.

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

AimsTo 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).MethodsThis 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.ResultsThe 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).ConclusionsPseudophakic status and/or presence of preoperative endothelial folds are the significant donor risk factors for endothelial failure in non-FECD patients.

Diurnal Variation in Straylight in Patients With Fuchs Endothelial Corneal Dystrophy and Controls.

The goal of this study was to investigate diurnal changes in intraocular straylight in relation to other corneal parameters and subjective complaints in patients with Fuchs endothelial dystrophy and healthy controls. This is a prospective study conducted in 2 tertiary care hospitals in Germany and the Netherlands. Patients with Fuchs endothelial dystrophy (n = 71) and healthy controls (n = 34) were included. Patients with Fuchs dystrophy were grouped by the presence of subjective complaints and measured over multiple time points during the day. Measurements included intraocular straylight using the C-Quant and corneal thickness and backscatter using a Scheimpflug camera. A separate group of healthy controls was measured intensively with repeated straylight measurements directly after waking. An exponential decay model was used to model the diurnal change. Healthy controls showed an average straylight baseline of 1.17 log(s) with an increase in straylight after waking of 0.22 log(s). In the repeated measurements subgroup, the increase in morning straylight lasted for 22 minutes. Patients with Fuchs dystrophy showed a morning increase in straylight of 0.21 log(s) present up to 4 hours after waking before reaching an average baseline of 1.30 log(s). Straylight was positively correlated with anterior corneal backscatter, r = 0.21, P = 0.022, and corneal thickness, r = 0.46, P < 0.01. Healthy eyes experience a diurnal straylight increase similar to patients with Fuchs dystrophy in intensity. However, in Fuchs dystrophy, the resolution of increased straylight is prolonged over multiple hours compared with minutes in healthy eyes. This suggests pathological exacerbation of a physiological diurnal change. This mechanism can play a role in subjective complaints experienced by patients with Fuchs dystrophy.

DMEK Without Postoperative Supine Posturing.

The purpose of this study was to describe the incidence of graft detachment after Descemet membrane endothelial keratoplasty (DMEK) without postoperative supine posturing. A total of 106 eyes of 84 patients with Fuchs endothelial corneal dystrophy or bullous keratopathy (BK) were operated by a single experienced surgeon with DMEK with a 99% anterior chamber air bubble fill, recovered in an upright (seated) position, and then discharged without instructions to remain supine. Postoperatively, all eyes were evaluated for graft detachment through anterior segment optical coherence tomography at predetermined intervals (1 d, 1 wk, and 1 mo). Detachments were regarded as clinically significant if they subtended 30% of the total graft surface area or involved the visual axis. Clinically significant graft detachments were observed in 23 of 106 eyes (22%) in the no-supine posturing cohort, including 22 of 85 eyes (26%) operated for Fuchs endothelial corneal dystrophy and 1 of 21 eyes (5%) operated for BK. Compared with a historical comparison group of eyes undergoing DMEK with 48 hours of postoperative supine posturing, the risk of graft detachment was not increased. In both cohorts, 6% of operated eyes required regrafting for either persistent detachment or primary graft failure. No additional intraoperative or postoperative complications were experienced. Particularly in eyes operated for BK, the supine posturing requirement after DMEK may be eliminated without increasing the absolute risk for clinically significant graft detachment.

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.

Evidence against involvement of kynurenate branch of kynurenine pathway in pathophysiology of Fuchs’ dystrophy and keratoconus

Kynurenine aminotransferases (KAT) are enzymes catalyzing formation of kynurenic acid (KYNA) from kynurenine. KYNA is a Janus-faced molecule of high biological activity. On the one hand KYNA was identified as a UV filter and neuroprotectant with free radical scavenging properties, but on the other hand it may contribute to photodamage of lens proteins resulting in cataract formation. Fuchs endothelial corneal dystrophy (FECD) and keratoconus (KC) are common, vision threatening corneal dystrophies whose etiology is not fully understood. In our previous works, we confirmed the presence of KATs in the human cornea together with GPR35, a receptor for KYNA. This prompted us to investigate the potential changes in the expression of three isoforms: KAT I, KAT II, and KAT III in normal and FECD- and KC-affected corneas. Immunohistochemistry accompanied by gene expression data mining revealed that the levels of neither KAT I, KAT II, nor KAT III are affected in FECD and KC. This constitutes evidence against the involvement of KATs in the pathophysiology of FECD and KC.

Fuchs Endothelial Corneal Dystrophy associated risk variant, rs3768617 in LAMC1 shows allele specific binding of GFI1B

AimsTo investigate the genetic and functional association of an intronic variant of LAMC1, rs3768617 with Fuchs endothelial corneal dystrophy (FECD) in the Indian population. MethodsBlood samples were collected from age and sex matched 356 controls and 120 FECD patients after a detailed assessment via specular microscopy. Genomic DNA was extracted and genotyping was done by fluorescence based capillary electrophoresis. The genetic association of rs3768617 polymorphisms was computed by the chi-square (χ2) test. Bioinformatics studies were performed to find the allele specific binding of different transcription factors in the region of rs3768617 and functional evaluation assessed by luciferase assay followed by Electrophoretic Mobility Shift Assay (EMSA) and Chromatin Immunoprecipitation assay (ChIP). Immunofluorescence assay was carried out to check for any differential expression of GFI1B between control and FECD endothelium samples. ResultsSNP rs3768617 {chr1:183123365 (GRCh38.p13)} was found to be genetically associated with FECD in Indian population (p = 2.646 × 10−8). Luciferase assay suggested that the rs3768617 locus has a regulatory role. In silico analysis showed that the transcription factor, GFI1B binds to the risk allele ‘G' of rs3768617, but not to the protective allele ‘A’ which was also experimentally validated by EMSA. High enrichment of DNA flanking the surrounding region of rs3768617 was also found in presence of GFI1B specific antibody in ChIP assay. There was a 0.63 fold decrease in GFI1B expression in FECD affected corneal endothelium compared to control endothelium. ConclusionsThe genetic association of rs3768617 in LAMC1 with FECD pathogenesis is mediated by GFI1B, thus finding the functional role of LAMC1 in FECD pathogenesis.

Heterogeneity of human corneal endothelium implicates lncRNA NEAT1 in Fuchs endothelial corneal dystrophy

The corneal endothelium is critical for maintaining corneal clarity by mediating hydration through barrier and pump functions. Progressive loss of corneal endothelial cells during aging has been associated with the development of Fuchs endothelial corneal dystrophy (FECD), one of the main causes of cornea-related vision loss. The mechanisms underlying FECD development remain elusive. Single-cell RNA sequencing of isolated healthy human corneas discovered 4 subpopulations of corneal endothelial cells with distinctive signatures. Unsupervised clustering analysis uncovered nuclear enriched abundant transcript 1 (NEAT1), a long non-coding RNA (lncRNA), as the top expressed gene in the C0-endothelial subpopulation, but markedly downregulated in FECD. Consistent with human corneas, a UVA-induced mouse FECD model validated the loss of NEAT1 expression. Loss of NEAT1 function by an in vivo genetic approach reproduced the exacerbated phenotype of FECD by ablating corneal endothelial cells. Conversely, gain of function by a CRISPR-activated adenoviral delivery system protected corneas from UVA-induced FECD. Our findings provide novel mechanistic insights into the development of FECD, and targeting NEAT1 offers an attractive approach for treating FECD.