Corneal Dystrophy Research Articles

Fuchs’ Endothelial Corneal Dystrophy evaluation using a high-resolution wavefront sensor

This study aims to evaluate the applicability of the high-resolution WaveFront Phase Imaging Sensor (WFPI) in eyes with Fuchs’ Endothelial Corneal Dystrophy (FECD) through qualitative and quantitative analysis using a custom-designed Automatic Guttae Detection Method (AGDM). The ocular phase was measured using the t·\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\cdot$$\\end{document}eyede aberrometer and then was processed to obtain its High-Pass Filter Map (HPFM). The subjects were pathological and healthy patients from the Fundación Jiménez-Díaz Hospital (Madrid, Spain). The AGDM was developed and applied in pupils with 3 and 5 mm of diameter. A set of metrics were extracted and evaluated like the Root-Mean-Square error (RMS), Number of guttae, Guttae Area, and Area of Delaunay Triangulation (DT). Finally, a Support Vector Machine (SVM) model was trained to classify between pathological and healthy eyes. Quantitatively, the HPFM reveals a dark spots pattern according to the ophthalmologist’s description of the slit-lamp examination of guttae distribution. There were significant statistical differences in all the metrics when FECD and Healthy groups were compared using the same pupil size; but comparing both pupil sizes for the same group there were significant differences in most of the variables. This sensor is a value tool to objectively diagnose and monitor this pathology through wavefront phase changes.

MitoQ relieves mitochondrial dysfunction in UVA and cigarette smoke-induced Fuchs endothelial corneal dystrophy

Fuchs endothelial corneal dystrophy (FECD), a degenerative corneal condition, is characterized by the droplet-like accumulation of the extracellular matrix, known as guttae and progressive loss of corneal endothelial cells ultimately leading to visual distortion and glare. FECD can be influenced by environmental stressors and genetic conditions. However, the role of mitochondrial dysfunction for advancing FECD pathogenesis is not yet fully studied. Therefore, in the present study we sought to determine whether a combination of environmental stressors (ultraviolet-A (UVA) light and cigarette smoke condensate (CSC)) can induce mitochondrial dysfunction leading to FECD. We also investigated if MitoQ, a water-soluble antioxidant, can target mitochondrial dysfunction induced by UVA and CSC in human corneal endothelial cells mitigating FECD pathogenesis. We modeled the FECD by increasing exogenous oxidative stress with CSC (0.2%), UVA (25J/cm2) and a combination of UVA + CSC and performed a temporal analysis of their cellular and mitochondrial effects on HCEnC-21T immortalized cells in vitro before and after MitoQ (0.05 μM) treatment. Interestingly, we observed that a combination of UVA + CSC exposure increased mitochondrial ROS and fragmentation leading to a lower mitochondrial membrane potential and increased levels of cytochrome c release leading to apoptosis and cell death. MitoQ intervention successfully mitigated these effects and restored cell viability. The UVA + CSC model could be used to study stress induced mitochondrial dysfunction. Additionally, MitoQ can serve as a viable antioxidant in attenuating mitochondrial dysfunction, underscoring its potential as a molecular-focused treatment approach to combat FECD pathogenesis.

Autosomal dominant stromal corneal dystrophy associated with a SPARCL1 missense variant.

Corneal dystrophies are phenotypically and genetically heterogeneous, often resulting in visual impairment caused by corneal opacification. We investigated the genetic cause of an autosomal dominant corneal stromal dystrophy in a pedigree with eight affected individuals in three generations. Affected individuals had diffuse central stromal opacity, with reduced visual acuity in older family members. Histopathology of affected cornea tissue removed during surgery revealed mild stromal textural alterations with alcianophilic deposits. Whole genome sequence data were generated for four affected individuals. No rare variants (MAF < 0.001) were identified in established corneal dystrophy genes. However, a novel heterozygous missense variant in exon 4 of SPARCL1, NM_004684: c.334G > A; p.(Glu112Lys), which is predicted to be damaging, segregated with disease. SPARC-like protein 1 (SPARCL1) is a secreted matricellular protein involved in cell migration, cell adhesion, tissue repair, and remodelling. Interestingly, SPARCL1 has been shown to regulate decorin. Heterozygous variants in DCN, encoding decorin, cause autosomal dominant congenital stromal corneal dystrophy, suggesting a common pathogenic pathway. Therefore, we performed immunohistochemistry to compare SPARCL1 and decorin localisation in corneal tissue from an affected family member and an unaffected control. Strikingly, the level of decorin was significantly decreased in the corneal stroma of the affected tissue, and SPARCL1 appeared to be retained in the epithelium. In summary, we describe a novel autosomal dominant corneal stromal dystrophy associated with a missense variant in SPARCL1, extending the phenotypic and genetic heterogeneity of inherited corneal disease.

Pre-Descemet Corneal Dystrophy – Changes in Corneal Morphology in Confocal Microscopy

PurposeTo identify and describe the in-vivo microstructural changes in the cornea of patients with pre-Descemet’s membrane corneal dystrophy.MethodsTen patients (20 eyes) were examined in the Laser Microsurgery Centre in Warsaw. The ophthalmic examination, including visual acuity and slit lamp biomicroscopy, was carried out. Because of suspicion of corneal dystrophy, in vivo confocal microscopy of the cornea was also performed.ResultsBiomicroscopy revealed bilateral, dust-like fine opacities in the deep parts of the corneal stroma. Confocal microscopy showed pleomorphic structures (enlarged keratocytes) containing dense, hyperreflective, granular inclusions in the posterior stroma, next to the Descemet’s membrane. In 3 patients (6 eyes) punctate particles were seen extracellularly also in the mid stroma. Superficial and basal epithelial layers, anterior stroma and endothelium cells appeared normal.Conclusions1. In vivo confocal microscopy findings of cornea with pre-Descemet’s membrane dystrophy are characteristic. 2. In vivo confocal microscopy is a useful tool in diagnosing rare corneal dystrophies in cases where classical examination methods give inconclusive results.

Neuropeptide alpha-Melanocyte stimulating hormone preserves corneal endothelial morphology in a murine model of Fuchs dystrophy

Fuchs endothelial corneal dystrophy is a heterogenous disease with multifactorial etiology, and genetic, epigenetic, and exogenous factors contributing to its pathogenesis. DNA damage plays a significant role, with ultraviolet-A (UV-A) emerging as a key contributing factor. We investigate the potential application of neuropeptide α-melanocyte stimulating hormone (α-MSH) in mitigating oxidative stress induced endothelial damage. First, we examined the effects of α-MSH on a cultured human corneal endothelial cell line (HCEnC-21T) exposed to hydrogen peroxide (H2O2) induced oxidative DNA damage. We performed immunofluorescence and flow cytometry to assess DNA damage and cell death in the cultured cells. Additionally, we used an established mouse model that utilizes ultraviolet light to induce corneal endothelial cell damage resulting in decreased CEnC number, increased cell size variability, and decreased percentage of hexagonal cells. This endothelial decompensation leads to an increase in corneal thickness. Following UV-A exposure, the mice were systemically treated with α-MSH, either immediately after exposure (early treatment) or beginning two weeks post-exposure (delayed treatment). To evaluate treatment efficacy, we analyzed CEnC density and morphology using in vivo confocal microscopy, and central corneal thickness using anterior segment optical coherence tomography. Our findings demonstrated that α-MSH treatment effectively protects HCEnC-21T from free-radical induced oxidative DNA damage and subsequent cell death. In vivo, α-MSH treatment, mitigated the loss of CEnC density, deterioration of cell morphology and suppression of the resultant corneal swelling. These results underline the potential application of α-MSH as a therapeutic agent for mitigating corneal endothelial damage.

Fuchs endothelial corneal dystrophy: aspects of pathogenesis

Fuchs endothelial corneal dystrophy (FECD) – multigenic bilateral disorder, characterized by dysfunction of corneal endothelium cells (CECs) that eventually results in loss of transparency. Purpose: To evaluate the pathogenesis of FECD with histological and immunohistochemical methods, immunofluorescence, scanning electron microscopy (SEM). Methods: Endothelium–Descemet membrane (EDM) complexes, corneal buttons were obtained from 76 patients (85 eyes) with FECD during keratoplasty and divided into 1A, 2A, 3A groups, 15 EDMs (donor tisuue) – 1B, 2B, 3B groups (control). Morphological (hematoxylin/eosin staining) and immunohistochemical (primary antibodies to cytokeratin AE1/AE3 and vimentin) studies (1A, 1B groups), phase-contrast microscopy and immunofluorescence analysis of tight junction protein ZO-1 (2A, 2B groups), SEM (3A, 3B groups) were performed. Results: FECD is characterized by decline of CECs, cell and nuclear enlargement. Nuclear-cytoplasmic ratio of CECs is relative to control. CECs expression ZO-1 is decreased in the area of guttae ingrowth. Coexpression of cytokeratin AE1/AE3 and vimentin is found. Morphological and immunohistochemical studies show DM’ thickening, stromal and epithelial edema and local fibrosis, vimentin (stromal cells) and cytokeratin AE1/AE3 (epithelium) expression in FECD. Conclusion: Pathogenesis of FECD include CECs’ epithelial-mesenchymal transition, followed by guttae formation – the excrescences, which destroy cytosketon and lead to progressive loss of CECs. Changes in permeability of endothelium cause edema and fibrosis of stroma and epithelial layer.

Prevalence of Certain Corneal Conditions and their Demographic Risk Factors; Tehran Geriatric Eye Study.

Corneal abnormalities are one of the important reasons for visual impairment. There is little evidence of the prevalence of different types of corneal abnormalities. The aim of this study was to assess the prevalence of various corneal abnormalities and identify the key risk factors associated with these abnormalities in an elderly population residing in Tehran. The Tehran Geriatric Eye Study (TGES) was conducted as a cross-sectional study, utilizing a population-based approach and employing stratified cluster random sampling. The study focused on individuals aged 60 years and above residing in Tehran. An ophthalmologist performed a slit lamp examination to evaluate the eyelid, cornea, and crystalline lens. The prevalence of posterior embryotoxon (PE), punctate epithelial defect (PED), pigment on endothelium (POE), corneal dystrophy (CDys), corneal vascularization (CV), and corneal degeneration (CDeg) were estimated to be 0.08% (95% confidence interval [CI]: 0.02 to 0.40), 8.77% (95% CI: 6.64 to 11.51), 0.57% (95% CI: 0.33 to 0.98), 0.53% (95% CI: 0.33 to 0.82), 0.95% (95% CI: 0.60 to 1.52), and 44.87% (95% CI: 41.80 to 47.98), respectively. Overall, approximately 49.08% of the participants exhibited some form of corneal abnormality in at least one eye. The multiple logistic regression model revealed that increasing age was significantly associated with PED, CV, and CD. Furthermore, illiterate participants had a significantly higher prevalence of PE. The findings of this study indicate that approximately half of the elderly population aged 60 years and above in Tehran have at least one corneal abnormality, with corneal degeneration being the most prevalent. Age was identified as the primary determinant of corneal abnormalities.

Prevalence of Transcription Factor 4 Gene Triplet Repeat Expansion Associated with Fuchs’ Endothelial Corneal Dystrophy in the United States and Global Populations

ObjectiveAn intronic CTG triplet repeat expansion in the transcription factor 4 gene (TCF4) gene (CTG18.1) confers significant risk for the development of Fuchs’ endothelial corneal dystrophy (FECD). The objective of this study was to conduct an unbiased survey of the CTG18.1 repeat expansion allele frequencies in a multi-ethnic, population-based cohort from the United States and in global populations. DesignCross-sectional study SubjectsDallas Heart Study (DHS) cohort including 1,599 African Americans (AAs), 1,028 European Americans (EAs), and 458 Latinos; 2,500 individuals from the 1000 Genomes Project (1KGP) sampled from 26 populations across 5 continents. MethodsWe genotyped the CTG18.1 short tandem repeat in DHS using targeted polymerase chain reaction amplification followed by fragment analysis. We also inferred the CTG18.1 repeat genotype based on short-read whole-genome sequencing in 1KGP using the computational tool ExpansionHunter. Main Outcome MeasuresThe prevalence of an expanded CTG18.1 allele with ≥40 repeats was determined in U.S. and global populations. ResultsThe carrier rates of the expanded allele were 3.1%, 8.1%, and 3.3% in AAs, EAs, and Latinos, respectively, in the DHS, and 2.7%, 9.5%, 5.2%, 7.2%, and 5.2% in the African (AFR), European (EUR), East Asian (EAS), South Asian (SAS), and admixed American (AMR) continental populations, respectively, in the 1KGP. The distributions of the CTG18.1 repeat in DHS and in 1KGP are similar. The median repeat length was ∼17 with the interquartile range (IQR) between 12 and 23 in the DHS populations. The median repeat length was ∼19 in all the 1KGP populations with the IQR between 13 and 26. The highest prevalence of the expanded allele carriers ranging from 12.1% to 12.5% was observed in some EUR and AMR subpopulations. The frequency of expanded alleles carriers was absent or low (0 - 1.9%) in subpopulations of East Africa but was present at 6.2% in a Kenyan subpopulation in West Africa. ConclusionsThe TCF4 repeat expansion is most prevalent in people of European ancestry and least in African ancestry, which is consistent with FECD prevalence. The expanded TCF4 CTG18.1 allele is the most common disease-causing short tandem repeat in humans with worldwide implications for corneal disease.

Corneal Transplant Rejection Following Durvalumab Therapy in a Patient With NSCLC: A Case Report.

We report the case of corneal transplant rejection in a 77-year-old male receiving durvalumab as consolidative therapy for stage IIIB non-small cell lung cancer (NSCLC). Following successful chemoradiation and initiation of durvalumab, the patient underwent a right corneal transplant for corneal dystrophy. Six months after an initially stable post-transplant course, he developed progressive visual decline culminating in graft failure 1 year later despite treatment with prednisone eye drops. This case adds to the limited evidence implicating immune checkpoint inhibitors (ICIs) in corneal graft rejection, emphasizing the need for multidisciplinary evaluation and close monitoring of corneal transplant recipients undergoing ICI therapy.

Comparison of Scheimpflug Imaging (Pentacam HR) and Swept-Source Optical Coherence Tomography (CASIA2) in Eyes With Macular Corneal Dystrophy.

Assessment of tomographic characteristics and interdevice comparability between Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany) and swept-source optical coherence tomography (CASIA2, Tomey Corp., Nagoya, Japan) in eyes with macular corneal dystrophy (MCD). Eyes with MCD were examined by Pentacam HR and CASIA2. Interdevice comparison was performed using a Wilcoxon matched pairs test and Bland-Altman plots with 95% limit of agreement. A Spearman rank correlation coefficient was used for correlating indices of both devices. This retrospective study included 31 eyes of 18 patients (mean age: 32.1 ± 10.7 years). Eyes with MCD demonstrated a moderate astigmatism with a Cylinder anterior of 2.56 ± 1.50 D (Pentacam HR) and 2.52 ± 1.57 D (CASIA2) without a difference between both devices. CASIA2 (0.34 ± 0.14 D) measured lower values of Cylinder posterior compared with Pentacam HR (0.96 ± 0.66 D) (P < 0.0001). Comparison of pachymetry (Pentacam HR vs. CASIA2) showed higher values of the central corneal thickness (619 ± 227 μm vs. 445 ± 67 μm, P = 0.0001) and the thinnest corneal thickness (499 ± 165 μm vs. 430 ± 60 μm, P = 0.0167) for Pentacam HR. Corneal densitometry measurement revealed that increasing gray scale units caused a greater interdevice difference for pachymetry values, as Pentacam HR measured higher than CASIA2 for more opaque corneas. Eyes with MCD tend to have thinner corneas and a higher amount of corneal astigmatism than healthy eyes. In advanced MCD, Scheimpflug technology may mistakenly overestimate corneal thickness. The pachymetry measurement of the optical coherence tomography should be used when planning corneal surgery such as excimer laser-assisted phototherapeutic keratectomy to determine the ablation depth.

Guttae Morphology After Cultured Corneal Endothelial Cell Transplant in Fuchs Endothelial Corneal Dystrophy

Whether guttae in Fuchs endothelial corneal dystrophy (FECD) can be removed by polishing without Descemet stripping and whether postoperative maintenance of reduced guttae can be achieved through cultured corneal endothelial cell (CEC) transplant therapy are critical issues to be addressed. To investigate the decrease of guttae through polishing degenerated CECs and abnormal extracellular matrix (ECM) without Descemet stripping and to observe the behavior of guttae following cultured CEC transplant. This case series prospective observational study was conducted in a hospital outpatient clinic setting. Between December 2013 and January 2019, 22 eyes with corneal endothelial failure caused by FECD received cultured CEC transplant therapy at Kyoto Prefectural University Hospital. Of these, 15 eyes were consistently monitored at the same central corneal area during the preoperative phase, as well as in the early (within 1 year) and late (after 3 years) postoperative phases. The images from these phases were categorized into 3 groups: typical guttae, atypical guttae, and no guttae. Cultured CEC transplant therapy. Proportion of guttae in the observable area was measured, comparing the early and late postoperative phases for each group. The mean age of the patients at the time of surgery was 69 years (range, 49-79 years). All 15 eyes exhibited the presence of confluent guttae preoperatively (100%). Among these, 3 of 15 eyes belonged to male patients. The early postoperative phase of guttae morphologies was classified into 3 groups: 5 eyes with typical guttae, 7 with atypical guttae, and 3 with no guttae. The decrease in the number of these guttae was achieved by surgical procedures. The median percentage of guttae in the typical guttae, atypical guttae, and no guttae groups was 41.8%, 44.4%, and 16.2%, respectively, in the early phase, and 42.2%, 38.2%, and 18.8%, respectively, in the late phase. The findings demonstrate that in some cases of FECD, guttae can be removed by scraping and polishing abnormal ECM and degenerated CECs, while preserving the Descemet membrane. Furthermore, cultured CEC transplant resulted in no increase in guttae for up to 3 years, providing insights into surgically eliminating guttae.

Nanotopography by chromatic confocal microscopy of the endothelium in Fuchs endothelial corneal dystrophy, pseudophakic bullous keratopathy and healthy corneas

AimTo investigate the interest of chromatic confocal microscopy (CCM) to characterise guttae in Fuchs endothelial corneal dystrophy (FECD).MethodsDescemet’s membranes (DM) were obtained during endothelial keratoplasty in patients with FECD and...

Enhanced Migration of Fuchs Corneal Endothelial Cells by Rho Kinase Inhibition: A Novel Ex Vivo Descemet's Stripping Only Model.

Descemet's Stripping Only (DSO) is a surgical technique that utilizes the peripheral corneal endothelial cell (CEnC) migration for wound closure. Ripasudil, a Rho-associated protein kinase (ROCK) inhibitor, has shown potential in DSO treatment; however, its mechanism in promoting CEnC migration remains unclear. We observed that ripasudil-treated immortalized normal and Fuchs endothelial corneal dystrophy (FECD) cells exhibited significantly enhanced migration and wound healing, particularly effective in FECD cells. Ripasudil upregulated mRNA expression of Snail Family Transcriptional Repressor (SNAI1/2) and Vimentin (VIM) while decreasing Cadherin (CDH1), indicating endothelial-to-mesenchymal transition (EMT) activation. Ripasudil activated Rac1, driving the actin-related protein complex (ARPC2) to the leading edge, facilitating enhanced migration. Ex vivo studies on cadaveric and FECD Descemet's membrane (DM) showed increased migration and proliferation of CEnCs after ripasudil treatment. An ex vivo DSO model demonstrated enhanced migration from the DM to the stroma with ripasudil. Coating small incision lenticule extraction (SMILE) tissues with an FNC coating mix and treating the cells in conjunction with ripasudil further improved migration and resulted in a monolayer formation, as detected by the ZO-1 junctional marker, thereby leading to the reduction in EMT. In conclusion, ripasudil effectively enhanced cellular migration, particularly in a novel ex vivo DSO model, when the stromal microenvironment was modulated. This suggests ripasudil as a promising adjuvant for DSO treatment, highlighting its potential clinical significance.

Repeat Femtosecond-Assisted Anterior Lamellar Keratoplasty for Recurrence of TGF B I Dystrophy in Eyes After Previous FALK.

To report the management of recurrent TGF BI dystrophy after prior femtosecond-assisted anterior lamellar keratoplasty (FALK) with repeat FALK. Clinical and histopathological study of 2 eyes of 2 patients with a recurrence of TGFBI dystrophy. Patient 1 had Reis-Buckler corneal dystrophy, and patient 2 had granular corneal dystrophy GCD type 1. Patient 1 had FALK 8 years ago, when she was 23 years old. Patient 2 had FALK 7 years ago at the age of 24 years. Slit-lamp examination showed recurrence in the subepithelial layer of the anterior lamellar graft as confluent chalky white granular deposits. Anterior segment optical coherence tomography highlighted the deposits in the subepithelial region of the anterior lamellar graft. The anterior lamellar graft with deposits was removed and replaced with another graft created using femtolaser dissection of a healthy donor. The parameters for femtosecond laser-assisted donor dissection was similar to the size and depth as the previously used donor. The best-corrected visual acuity was restored to 20/30 in patient 1 and 20/25 in patient 2. The histology of the anterior lamellar graft showed eosinophilic deposits between the epithelium and the Bowman layer in both samples. In addition, the corneal sample from patient 2 revealed Bowman layer breach at some places and few deposits at 1 edge of the lamellar graft. Repeat FALK with a healthy donor is effective in the management of recurrence of deposits. The histology of the recurrence in the anterior lamellar graft revealed eosinophilic deposits predominantly between the epithelium and Bowman layer.

Clinical applications of in vivo confocal microscopy enhance the detection and management of ocular surface disease in dogs and cats.

In vivo confocal microscopy (IVCM) is a unique imaging technique that permits noninvasive evaluation of the ocular surface on the cellular level. High-resolution images of all layers of the cornea are obtained in real-time with IVCM, and the acquired images are often comparable to ex vivo histochemical analysis of corneal biopsy specimens. The basic morphological features of the healthy living cornea as viewed by IVCM are reported in many domestic animal species, and the number of published descriptions of ocular surface pathologies in companion animals is progressively expanding. There is great potential for IVCM to improve the detection, characterization, and management of diverse ocular surface diseases in companion animals. This review summarizes several established and emerging clinical applications of IVCM in companion animal ocular surface disease, including infectious keratitis, corneal foreign bodies, corneal dystrophies and degenerations, ocular surface masses, corneal endotheliitis, pigmentary keratitis, and evaluation of corneal nerves.

TACSTD2 in gelatinous drop-like corneal dystrophy: variant functional analysis and expression in the cornea after limbal stem cell transplantation

Gelatinous drop-like corneal dystrophy (GDLD) is a rare autosomal recessive eye disease. GDLD is characterized by the loss of barrier function in corneal epithelial cells (CECs) and amyloid deposition due to pathogenic variants in the TACSTD2 gene. Limbal stem cell transplantation (LSCT) has been suggested as an effective therapeutic alternative for patients with GDLD. However, despite LSCT, amyloid deposition recurs in some patients. The pathogenesis of recurrence is poorly studied. We present the case of a patient with GDLD. Genetic analysis revealed a homozygous deletion, NM_002353.3:c.653del, in the TACSTD2 gene. Functional analysis in a cell model system revealed the loss of the transmembrane domain and subcellular protein mislocalization. The patient with GDLD underwent direct allogeneic LSCT with epithelial debridement followed by deep anterior lamellar keratoplasty 10 months later due to amyloid deposition and deterioration of vision. Taken together, the results of transcriptome analysis and immunofluorescence staining of post-LSCT corneal sample with amyloid deposits obtained during keratoplasty demonstrated complete restoration of wild-type TACSTD2 expression, indicating that donor CECs replaced host CECs. Our study provides experimental evidence that amyloid deposition can recur after LSCT despite complete restoration of wild-type TACSTD2 expression.

Microkeratome versus manually dissected donor tissue for Descemet stripping endothelial keratoplasty: A randomized prospective study.

To compare the visual outcomes, postoperative complications, and graft asymmetry between precut and manually dissected donor tissues for Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet stripping endothelial keratoplasty (DSEK) procedures, respectively. Seventy eyes of 70 patients undergoing DSEK/DSAEK at a tertiary eyecare center in eastern India were included in this prospective randomized control study. The 70 eyes were divided equally into two groups. Group A (n = 35) and Group B (n = 35) underwent DSEK and DSAEK procedures, respectively. the operating surgeons prepared the manually dissected corneal grafts using lamellar dissectors. the eye bank technicians prepared the precut corneal grafts using a microkeratome. The patients were investigated postoperatively after 1 day, 1 week, 1 month, 3 months, and 6 months. The data were compared for visual outcomes [uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), spherical and cylindrical refraction, and spherical equivalent], incidence of postoperative complications, and pachymetry. The mean age was 56.5 (±17.8) years, and the male-to-female ratio was 1.3:1. The most common indications were pseudophakic bullous keratopathy (45.71%, 32/70), failed graft (32.86%, 23/70), and Fuchs' endothelial corneal dystrophy (10%, 7/70). The indications for surgery (P = 0.732) and donor (P = 0.258) and host pachymetry (P = 0.986) were comparable between both groups. There was no significant difference in change of UCVA, BCVA, and postoperative refraction (mean spherical refraction, P = 0.849; mean cylindrical refraction, P = 0.516; spherical equivalent, P = 0.518) between the two groups. Postoperative complications like graft detachment (P = 0.179), graft failure (P = 0.513), graft infiltrate (P = 0.428), and endophthalmitis (P = 0.493) were higher in the DSAEK group; however, the difference between the groups was insignificant. The graft asymmetry index was higher in DSAEK than in DSEK; the difference was significant till the 1-month follow-up (P = 0.005). The outcome was similar in both groups. Therefore, manual donor dissection can be an alternative for microkeratome-assisted dissection in low-resource centers and countries to achieve good results.

Clinical Outcomes of Repeat Descemet Membrane Endothelial Keratoplasty After Graft Failure.

To evaluate the clinical outcomes after repeat Descemet membrane endothelial keratoplasty (DMEK) for technical failure (TF) and secondary graft failure (SGF). Retrospective analysis of 49 eyes that underwent repeat DMEK either for TF (ie, persistent graft detachment, n = 24) or for SGF (ie, late endothelial graft failure, n = 25). Surgery indications for primary DMEK were Fuchs endothelial corneal dystrophy (FECD, 80%) and bullous keratopathy (BK, 20%). Main outcome measures were best-corrected visual acuity (BCVA), endothelial cell density (ECD), corneal backscattering, pachymetry, and graft survival. Outcomes were compared with an age-matched control group of 49 primary DMEK eyes. Logarithm of the minimum angle of resolution BCVA improved from 0.92 ± 0.6 before to 0.20 ± 0.3 at 1 year after repeat DMEK with better outcomes for eyes with TF than those with SGF (P = 0.046). Donor ECD decreased from 2618 ± 171 cells/mm2 before to 1247 ± 422 cells/mm2 at 1 year postoperatively, with no difference between technical TF and SGF eyes (P > 0.05). One-year BCVA and ECD outcomes were better in the control group than in the repeat DMEK group (P < 0.05). Five-year graft survival probability after repeat DMEK was better for TF than for SGF eyes (100% vs. 75%, P = 0.010) and better for eyes with FECD than BK as primary indication for surgery (92% vs. 65%, P = 0.042). Repeat DMEK gives acceptable clinical outcomes especially when performed for TF in the early period after primary DMEK. Long-term graft survival probability after repeat DMEK is comparable to primary DMEK for FECD eyes, whereas BK eyes may show an elevated risk to develop graft failure again.

Change in Visual Acuity of Patients With Fuchs Endothelial Corneal Dystrophy Over 1 Year.

To determine whether the clinical and paraclinical course of Fuchs endothelial corneal dystrophy (FECD) over 1 year is related to the extent of triplet repetition in the transcription factor 4 (TCF4) gene. A prospective study with a 1-year follow-up was conducted. A total of 104 patients (160 eyes) with FECD and an equivalent number of age- and sex-matched control subjects without FECD were included. At inclusion, the corneas were graded using the modified Krachmer grade (KG) and patients were genotyped for the number of trinucleotide repeats (TNRs) in the TCF4 gene by the short tandem repeat assay. Visual acuity, Scheimpflug tomographic features, and the Visual Function and Corneal Health Status using a visual disability instrument were measured on 2 visits at 1-year intervals. KGs ranged from 1 to 6, and 46% of eyes had grades 1 to 4. 71% of the patients harbored TNR expansion (>40) versus 13% in control subjects ( P < 0.001). Severity at inclusion was higher in the presence of TNR expansion when considering eyes independently (mean grade ±SD, 4.08 ± 1.42) without TNR expansion and 4.66 ± 1.27 with TNR expansion ( P = 0.024). In 1 year, the ETDRS score significantly decreased by -2.97 (95% confidence interval -4.69 to -1.26, P = 0.001) and the ETDRS score with glare by -4.25 (95% confidence interval -6.22 to -2.27, P < 10 -5 ). There was no relationship between the rate of decline and TNR expansion or KG. Central corneal thickness and Visual Function and Corneal Health Status scores did not significantly vary. It is possible to measure a subtle progression of FECD over a period as short as 1 year. We did not find a relationship between the presence of TNR expansion and the speed of deterioration over 1 year. This work should facilitate the design of future clinical trials on FECD.

Corneal Opacity in the United States: An American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) Study

This study assesses the case frequencies, underlying causes, and vision outcomes in patients with a diagnosis of corneal opacity in the United States. Retrospective cohort study. Patients in the IRIS® Registry (Intelligent Research in Sight) who received a diagnosis of corneal opacity between January 1, 2013, and November 30,2020. The IRIS Registry contains demographic and clinical data of 79 887 324 patients who sought treatment at eye clinics during the study period. We identified patients with corneal opacity using International Classification of Diseases (ICD), Ninth and Tenth Revisions, codes of 371 (corneal scar) and H17 (corneal opacity), respectively. The analyzed data comprised demographic parameters including age, sex, race, ethnicity, and geographical location. We evaluated clinical data including laterality, cause, disease descriptors, and best-corrected visual acuity (VA) up to 1 year before the onset (± 30 days), at the time of diagnosis, and at 1 year after diagnosis (± 30 days). Case frequencies, causes, and vision outcomes in patients with a diagnosis of corneal opacity. We identified 5 220 382 patients who received a diagnosis of corneal opacity and scars using H17 (ICD, Tenth Revision) and 371.0 (ICD, Ninth Revision) codes over 7 years. The case frequency of corneal opacity during the study period was 6535 cases per 100 000 patients (6.5%). The mean age of the patients was 63.36 ± 18.14 years, and most were female (57.6%). In the cohort, 38.39% and 30.00% of patients had bilateral and unilateral corneal opacity, respectively. Most of the patients affected by corneal opacity were White (69.13%), followed by Black or African American (6.84%). Corneal dystrophies (64.66%) were the most common cause of corneal opacity in the study cohort. Visual acuity of the patients worsened significantly because of corneal opacity (0.46 ± 0.74 logarithm of the minimum angle of resolution [logMAR]) and did not improve to the baseline (0.37 ± 0.68 logMAR) after management (0.43 ± 0.77 logMAR). The multiple linear regression analysis showed worse vision outcomes in female patients (compared with male patients), and Asian, Black or African American, and American Indian or Alaska Native (compared with White) patients. Additionally, worse vision outcomes were observed in patients with opacity associated with corneal malformation, degenerative disorders, edema, injury, and ulcer compared with those with hereditary corneal dystrophy. Our study showed that corneal opacity was diagnosed in 6.5% of patients in the IRIS Registry and primarily associated with corneal dystrophies. The final vision outcomes in patients with corneal opacity were significantly worse compared with baseline. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.