Suture Fixation to Reduce Graft Detachment in Descemet Stripping Endothelial Keratoplasty.

PURPOSE: The aim of this study was to report the outcomes of graft fixation using interrupted, full-thickness sutures on graft detachment after Descemet stripping endothelial keratoplasty (DSEK). METHODS: All DSEK procedures performed at Mayo Clinic, Rochester, MN, from 2015 through 2022 were retrospectively reviewed. Risk factors for graft detachment were defined as previous incisional glaucoma surgery, previous penetrating keratoplasty, or absence of the normal lens-capsule barrier. Cases were categorized into sutured, high-risk grafts; unsutured, high-risk grafts; and unsutured, low-risk grafts. The primary outcome was graft detachment, and secondary outcomes were early graft failure and graft clarity at 12 months after surgery. RESULTS: Demographics between the high-risk groups were similar for sex and age at the time of surgery. Graft detachment occurred in 4 of 97 sutured, high-risk eyes (4.1%) and 24 of 119 unsutured high-risk eyes (20.2%) ( P = 0.002). In comparison, graft detachment occurred in 18 of 181 unsutured low-risk eyes (9.9%). The incidence of early graft failure was 2.1%, 5.0%, and 3.3% and late graft failure by 12 months was 9.8%, 12.8%, and 4.2%, respectively. CONCLUSIONS: In eyes with high-risk factors for graft detachment, suture fixation of the graft in DSEK decreased graft detachment to a rate at least as low as that in low-risk eyes.

Outcomes of Flap Amputation After Laser In Situ Keratomileusis.

PURPOSE: The aim of this study was to describe the indications and outcomes of flap amputation after laser in situ keratomileusis (LASIK) at a referral-based institution. METHODS: In this retrospective consecutive case series, medical records of patients who underwent LASIK flap amputation at Mayo Clinic, Rochester, MN, between January 1, 1998, and January 31, 2023, were reviewed. RESULTS: Fifteen eyes (15 patients) underwent flap amputation during the study period. The median age was 45 years (range, 25-71 years), and 8 patients (53%) were men. The median uncorrected visual acuity before flap amputation was 20/200 (range 20/40-hand motions). Indications for flap amputation included epithelial ingrowth (n = 6, 40%), infectious keratitis (n = 6, 40%), diffuse lamellar keratitis (n = 1, 7%), vegetative foreign body (n = 1, 7%), and astigmatism from fixed flap striae (n = 1, 7%). The median duration of follow-up was 8 months (range 1-234 months). Subsequent corneal interventions included chelation of calcific band keratopathy (n = 1, 7%), lamellar keratoplasty (n = 1, 7%), penetrating keratoplasty (n = 2, 18%), keratoprosthesis (n = 1, 7%), and rigid contact lens wear (n = 4, 27%). The final median best visual acuity was 20/25 (range 20/20-20/200). Compared with noninfectious indications for flap amputation, eyes with infectious indications had worse baseline median uncorrected visual acuity (hand motions vs. 20/63, P < 0.001), were more likely to undergo major corneal surgical intervention (50% vs. 11%), and had worse final median best visual acuity (20/50 vs. 20/20, P = 0.018). CONCLUSIONS: LASIK flap amputation is sometimes necessary to control threatening corneal diseases. Excellent visual outcomes were achieved in most cases, albeit with additional intervention or rigid contact lens wear.

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

PURPOSE: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Comparison of TCF4 repeat expansion length in corneal endothelium and leukocytes of patients with Fuchs endothelial corneal dystrophy.

Expansion of CTG trinucleotide repeats (TNR) in the transcription factor 4 (TCF4) gene is highly associated with Fuchs Endothelial Corneal Dystrophy (FECD). Due to limitations in the availability of DNA from diseased corneal endothelium, sizing of CTG repeats in FECD patients has typically been determined using DNA samples isolated from peripheral blood leukocytes. However, it is non-feasible to extract enough DNA from surgically isolated FECD corneal endothelial tissue to determine repeat length based on current technology. To circumvent this issue, total RNA was isolated from FECD corneal endothelium and sequenced using long-read sequencing. Southern blotting of DNA samples isolated from primary cultures of corneal endothelium from these same affected individuals was also assessed. Both long read sequencing and Southern blot analysis showed significantly longer CTG TNR expansion (>1000 repeats) in the corneal endothelium from FECD patients than those characterized in leukocytes from the same individuals (<90 repeats). Our findings suggest that the TCF4 CTG repeat expansions in the FECD corneal endothelium are much longer than those found in leukocytes.

Characterization of a dual media system for culturing primary normal and Fuchs endothelial corneal dystrophy (FECD) endothelial cells.

Primary cultures of human corneal endothelial cells (HCECs) are an important model system for studying the pathophysiology of corneal endothelium. The purpose of this study was to identify and validate an optimal primary culture model of normal and Fuchs endothelial corneal dystrophy (FECD) endothelial cells by comparing cell morphology and marker expression under different media conditions to in vivo donor tissues. Primary and immortalized HCECs, isolated from normal and FECD donors, were cultured in proliferation media (Joyce, M4, Bartakova) alone or sequentially with maturation media (F99, Stabilization 1, M5). CD56, CD73 and CD166 expressions were quantified in confluent and matured cell lines by flow cytometry. HCECs that were allowed to proliferate in Joyce's medium followed by maturation in low-mitogen containing media yielded cells with similar morphology to corneal endothelial tissues. Elevated expression of CD56 and CD166 and low expression of CD73 correlated with regular, hexagonal-like HCEC morphology. CD56:CD73 > 2.5 was most consistent with normal HCEC morphology and mimicked corneal endothelial tissue. Immortalization of normal HCECs by hTERT transduction showed morphology and CD56:CD73 ratios similar to parental cell lines. HCECs established from FECD donors showed reduced CD56:CD73 ratios compared to normal HCECs which coincided with reduced uniformity and regularity of cell monolayers. Overall, a dual media system with Joyce's medium for proliferation and a low-mitogen media for maturation, provided normal cultures with regular, hexagonal-like cell morphologies consistent with corneal endothelial cells in vivo. CD56:CD73 expression ratio >2.5 was predictive of in vivo-like cellular morphology.

Crystal-Induced Podocytopathy Producing Collapsing Focal Segmental Glomerulosclerosis in Monoclonal Gammopathy of Renal Significance: A Case Report.

Monoclonal gammopathy-associated crystalline podocytopathy causing collapsing focal segmental glomerulosclerosis (FSGS) is very rare and has been associated with pamidronate therapy. We present the case of a 53-year-old man with vision loss secondary to corneal crystals deposition, nephrotic-range proteinuria, and reduced glomerular filtration rate without associated comorbid conditions. Two kidney biopsies were initially reported as primary FSGS but the patient did not respond to high-dose corticosteroid immunosuppression therapy. Repeat review of biopsies with additional electron microscopy analysis revealed crystalline inclusions in podocytes leading to collapsing FSGS. Subsequent workup revealed an immunoglobulin G κ serum monoclonal protein. Bone marrow biopsy revealed 5% κ-restricted plasma cells with cytoplasmic crystalline inclusions. To our knowledge, this is the first case of monoclonal gammopathy of clinical significance manifesting as crystalline podocytopathy leading to collapsing FSGS and keratopathy leading to vision loss. Crystalline podocytopathy should be considered in the differential diagnosis of collapsing glomerulopathy, and careful ultrastructural examination of the kidney biopsy specimen is crucial to establish this diagnosis.

Myopic shift after Salzmann nodule excision.

PURPOSE: To quantify changes in manifest refractive error and mean keratometric power (Km) at 1 month and ≥12 months after Salzmann nodule excision. SETTING: Cornea service at Mayo Clinic, Rochester, MN. DESIGN: Retrospective consecutive case series. METHODS: Changes in manifest refractive error (spherical equivalent), Km, and corrected distance visual acuity (CDVA) were compared for 73 eyes of 58 patients who underwent Salzmann nodule excision. Eyes with ocular comorbidities were excluded. Comparisons between preoperative and postoperative measurements were made by using generalized estimating equation models. RESULTS: Mean patient age was 66 years, and 53 patients (91%) were female. Spherical equivalent manifest refractive error was -0.27 ± 2.66 diopters (D) before nodule excision and became more myopic (-1.10 ± 2.78 D) at 1 month after nodule excision (n = 69, P < .001) with no change at 12 months (n = 14, P = .13). A myopic shift ≥0.5 D occurred in 65% of eyes and ≥1.0 D in 36% of eyes. Km increased from 42.7 ± 2.11 D before nodule excision to 44.2 ± 1.82 D at 1 month after excision (n = 49, P < .001). CDVA improved from 0.18 ± 0.15 logMAR (Snellen equivalent 20/30) before nodule excision to 0.05 ± 0.09 logMAR (20/22, n = 69, P < .001) at 1 month after excision with no change at 12 months (n = 14, P = .73). CONCLUSIONS: In addition to known changes in cylinder, Salzmann nodule excision is associated with a myopic shift in most eyes caused by corneal steepening. Patients should be counseled about the likelihood of refractive changes, and cataract surgery should be deferred until refractive stability is achieved.

Relationship of Body Mass Index With Fuchs Endothelial Corneal Dystrophy Severity and TCF4 CTG18.1 Trinucleotide Repeat Expansion.

PURPOSE: To investigate the association of body mass index (BMI) with Fuchs endothelial corneal dystrophy (FECD) severity and TCF4 CTG18.1 expansion. METHODS: A total of 343 patients with FECD were enrolled from the Mayo Clinic. FECD severity was graded by slit-lamp biomicroscopy. BMI values were obtained from the electronic medical records. DNA extracted from leukocytes was analyzed for CTG18.1 expansion length, with ≥40 repeats considered expanded. Wilcoxon signed-rank tests were used to compare FECD grade and CTG18.1 expansion length in patients by BMI (<25, ≥25 to <30, and ≥30 kg/m2). FECD grade was regressed on age, sex, BMI, and CTG18.1 expansion and, separately, BMI on CTG18.1 expansion. Models were investigated for effect modification by age and sex with an interaction term of P < 0.05 considered statistically significant. RESULTS: When examining the association between BMI and FECD, there was a significant interaction between BMI and sex (P for interaction = 0.004). When controlling for age and CTG18.1 expansion, a positive association was observed between BMI and FECD grade in women, but not in men. In addition, BMI was not associated with CTG18.1 expansion when controlling for age and sex. CONCLUSIONS: BMI was positively associated with FECD severity among women but not men. There was no significant association between BMI and CTG18.1 expansion. These findings suggest that increased BMI is potentially a modifiable risk factor for FECD disease progression among women.

Disease Expression and Familial Transmission of Fuchs Endothelial Corneal Dystrophy With and Without CTG18.1 Expansion.

Purpose: To characterize inheritance, penetrance, and trinucleotide repeat expansion stability in Fuchs endothelial corneal dystrophy (FECD). Methods: One thousand unrelated and related subjects with and without FECD were prospectively recruited. CTG18.1 repeat length (CTG18.1L) was determined via short tandem repeat assay and Southern blotting of leukocyte DNA. Multivariable logistic regression and generalized estimating equation models were employed. Results: There were 546 unrelated FECD cases (67.6% female; 70 ± 10 years) and 235 controls (63.8% female; 73 ± 8 years; all ≥ 50 years). CTG18.1 expansion (CTG18.1exp+) was observed in 424 (77.7%) cases and 18 (7.7%) controls (P = 2.48 × 10-44). CTG18.1 expansion was associated with FECD severity (P = 5.62 × 10-7). The family arm of the study included 331 members from 112 FECD-affected families; 87 families were CTG18.1exp+. Autosomal dominant inheritance with variable expression of FECD was observed, regardless of expansion status. FECD penetrance of CTG18.1 expansion increased with age, ranging from 44.4% in the youngest (19-46 years) to 86.2% in the oldest (64-91 years) age quartiles. Among 62 parent-offspring transmissions of CTG18.1exp+, 48 (77.4%) had a change in CTG18.1L ≤ 10 repeats, and eight (12.9%) were ≥50 repeats, including five large expansions (∼1000-2000 repeats) that contracted. Among 44 offspring who did not inherit the CTG18.1exp+ allele, eight (18.2%) exhibited FECD. Conclusions: CTG18.1 expansion was highly associated with FECD but demonstrated incomplete penetrance. CTG18.1L instability occurred in a minority of parent-offspring transmissions, with large expansions exhibiting contraction. The observation of FECD without CTG18.1 expansion among family members in CTG18.1exp+ families highlights the complexity of the relationship between the FECD phenotype and CTG18.1 expansion.

Gene Expression and Missplicing in the Corneal Endothelium of Patients With a TCF4 Trinucleotide Repeat Expansion Without Fuchs' Endothelial Corneal Dystrophy.

Purpose: CTG trinucleotide repeat (TNR) expansion in an intron of the TCF4 gene is the most common genetic variant associated with Fuchs' endothelial corneal dystrophy (FECD). Although several mechanisms have been implicated in the disease process, their exact pathophysiologic importance is unclear. To understand events leading from TCF4 TNR expansion to disease phenotype, we characterized splicing, gene expression, and exon sequence changes in a rare cohort of patients with TNR expansions but no phenotypic FECD (RE+/FECD-). Methods: Corneal endothelium and blood were collected from patients undergoing endothelial keratoplasty for non-FECD corneal edema. Total RNA was isolated from corneal endothelial tissue (n = 3) and used for RNASeq. Gene splicing and expression was assessed by Mixture of Isoforms (MISO) and MAP-RSeq software. Genomic DNA was isolated from blood mononuclear cells and used for whole genome exome sequencing. Base calling was performed using Illumina's Real-Time Analysis. Results: Three genes (MBNL1, KIF13A, AKAP13) that were previously identified as misspliced in patients with a CTG TNR expansion and FECD disease (RE+/FECD+) were found normally spliced in RE+/FECD- samples. Gene expression differences in pathways associated with the innate immune response, cell signaling (e.g., TGFß, WNT), and cell senescence markers were also identified between RE+/FECD- and RE+/FECD+ groups. No consistent genetic variants were identified in RE+/FECD- patient exomes. Conclusions: Identification of novel splicing patterns and differential gene expression in RE+/FECD- samples provides new insights and more relevant gene targets that may be protective against FECD disease in vulnerable patients with TCF4 CTG TNR expansions.

Crystalglobulin-Induced Nephropathy and Keratopathy.

Crystalglobulinemia, a rare manifestation of monoclonal gammopathy, results from vascular deposition of crystallized monoclonal proteins leading to tissue injury. A 56-year-old man initially presented several years earlier with migratory polyarthralgias and blurry vision with no unifying diagnosis. Following an acute episode of malignant hypertension and rapidly progressive kidney failure, kidney biopsy was performed and was interpreted as idiopathic thrombotic microangiopathy. Further evaluation revealed an underlying monoclonal protein disorder. Slit-lamp biomicroscopy evaluation showed crystalline keratopathy. Re-evaluation of the kidney biopsy material with pronase staining confirmed crystalglobulin-induced nephropathy. The patient was initially treated with cyclophosphamide, bortezomib, and dexamethasone with partial response, followed by autologous stem cell transplantation with normalization of monoclonal protein studies, improvement in kidney function and joint symptoms, and decreased corneal deposits. His disease recurred but did not require additional treatment 1 year later. This case exemplifies the unique systemic presentation of diseases in the monoclonal gammopathy spectrum and emphasizes the need for a multidisciplinary approach when caring for these patients.

Gene expression in the corneal endothelium of Fuchs endothelial corneal dystrophy patients with and without expansion of a trinucleotide repeat in TCF4.

Fuchs Endothelial Corneal Dystrophy (FECD) is a late onset, autosomal dominant eye disease that can lead to loss of vision. Expansion of a CTG trinucleotide repeat in the third intron of the transcription factor 4 (TCF4) gene is highly associated with FECD. However, only about 75% of FECD patients in the northern European population possess an expansion of this repeat. The remaining FECD cases appear to be associated with variants in other genes. To better understand the pathophysiology of this disease, we compared gene expression profiles of corneal endothelium from FECD patients with an expanded trinucleotide repeat (RE+) to those that do not have a repeat expansion (RE-). Comparative analysis of these two cohorts showed widespread RNA mis-splicing in RE+, but not in RE- samples. Quantitatively, we identified 39 genes in which expression was significantly different between RE+ and RE- samples. Examination of the mutation profiles in the RE- samples did not find any mutations in genes previously associated with FECD, but did reveal one sample with a rare variant of laminin subunit gamma 1 (LAMC1) and three samples with rare variants in the gene coding for the mitochondrial protein peripheral-type benzodiazepine receptor-associated protein 1 (TSPOAP1).

Trinucleotide Repeat Expansion in the Transcription Factor 4 (TCF4) Gene Leads to Widespread mRNA Splicing Changes in Fuchs' Endothelial Corneal Dystrophy.

Purpose: To identify RNA missplicing events in human corneal endothelial tissue isolated from Fuchs' endothelial corneal dystrophy (FECD). Methods: Total RNA was isolated and sequenced from corneal endothelial tissue obtained during keratoplasty from 12 patients with FECD and 4 patients undergoing keratoplasty or enucleation for other indications. The length of the trinucleotide repeat (TNR) CTG in the transcription factor 4 (TCF4) gene was determined using leukocyte-derived DNA analyzed by a combination of Southern blotting and Genescan analysis. Commercial statistical software was used to quantify expression of alternatively spliced genes. Validation of selected alternative splicing events was performed by using RT-PCR. Gene sets identified were analyzed for overrepresentation using Web-based analysis system. Results: Corneal endothelial tissue from FECD patients containing a CTG TNR expansion sequence in the TCF4 gene revealed widespread changes in mRNA splicing, including a novel splicing event involving FGFR2. Differential splicing of NUMA1, PPFIBP1, MBNL1, and MBNL2 transcripts were identified in all FECD samples containing a TNR expansion. The differentially spliced genes were enriched for products that localize to the cell cortex and bind cytoskeletal and cell adhesion proteins. Conclusions: Corneal endothelium from FECD patients harbors a unique signature of mis-splicing events due to CTG TNR expansion in the TCF4 gene, consistent with the hypothesis that RNA toxicity contributes to the pathogenesis of FECD. Changes to the endothelial barrier function, a known event in the development of FECD, was identified as a key biological process influenced by the missplicing events.

Descemet Stripping Endothelial Keratoplasty for Fuchs' Endothelial Corneal Dystrophy: Five-Year Results of a Prospective Study.

PURPOSE: To determine 5-year outcomes of Descemet stripping endothelial keratoplasty (DSEK) for Fuchs' endothelial corneal dystrophy (FECD). DESIGN: Prospective cohort study. PARTICIPANTS: Fifty-two eyes of 45 subjects with FECD undergoing primary DSEK. METHODS: Subjects were examined before and at fixed intervals through 60 months after DSEK. At each visit, graft survival was determined by slit-lamp examination; best spectacle-corrected visual acuity (BSCVA) was measured using the electronic Early Treatment Diabetic Retinopathy Study (ETDRS) protocol; total anterior corneal higher-order aberrations (HOAs) were derived from corneal topography; and corneal backscatter, corneal thickness, and endothelial cell density were measured from confocal microscopy images. Corneal thickness also was measured by ultrasonic pachymetry. Changes after DSEK were analyzed using generalized estimating equation models. MAIN OUTCOME MEASURES: Best-corrected visual acuity, HOAs, endothelial cell loss, corneal thickness, and corneal backscatter. RESULTS: Complete 60-month follow-up was possible in 34 eyes. Mean BSCVA±standard deviation improved from 0.45±0.19 logarithm of the minimum angle of resolution (logMAR) (Snellen equivalent, 20/56) before DSEK to 0.09±0.13 logMAR (Snellen equivalent, 20/25) at 5 years (P < 0.001). Between 1 and 5 years, BSCVA improved by 0.06 logMAR (or 3 ETDRS letters; 95% confidence interval, 0.05-0.07 logMAR) per year (P < 0.001), and 56% of eyes were 0.1 logMAR (20/25) or better at 5 years. Graft thickness (approximately 155 µm) and corneal thickness (approximately 700 µm) did not change after surgery. Anterior corneal HOAs and backscatter decreased between 1 and 5 years (P ≤ 0.002). Six grafts failed, of which 4 were primary (iatrogenic); mean endothelial cell loss±standard deviation was 55±15% at 5 years. CONCLUSIONS: Between 1 and 5 years after DSEK, BSCVA continues to improve such that at 5 years, more than half of eyes see better than 20/25 with a mean total corneal thickness of 700 µm. Improvement in vision is accompanied by continued reduction in corneal haze and aberrations, suggesting ongoing remodeling of the cornea after restoration of endothelial function.

Changes in Keratocyte Density and Visual Function Five Years After Laser In Situ Keratomileusis: Femtosecond Laser Versus Mechanical Microkeratome.

PURPOSE: To determine the effects of keratocyte loss on optical properties and vision after laser in situ keratomileusis (LASIK) with the flap created with a femtosecond laser or a mechanical microkeratome. DESIGN: Randomized clinical paired-eye study. METHODS: Both eyes of 21 patients received LASIK for myopia or myopic astigmatism. One eye of each patient was randomized by ocular dominance to flap creation with a femtosecond laser and the other eye to flap creation with a mechanical microkeratome. Before LASIK and at 1, 3, and 6 months and 1, 3, and 5 years after LASIK, keratocyte density was measured using confocal microscopy, and high-contrast visual acuity and anterior corneal wavefront aberrations were measured by standard methods. At each visit, all variables were compared between methods of creating the flap and to the same variable before treatment using paired tests with Bonferroni correction for multiple comparisons. RESULTS: Keratocyte density in the flap decreased by 20% during the first year after LASIK and remained low through 5 years (P < .001). High-order wavefront aberrations increased and uncorrected visual acuity improved immediately after surgery, but these variables did not change further to 5 years. There were no differences in any variables between treatments. CONCLUSIONS: A sustained reduction in keratocyte density does not affect vision or optical properties of the cornea through 5 years after LASIK. The method of creating a LASIK flap does not influence the changes in keratocyte density in the flap.

Vision-related quality of life before and after keratoplasty for Fuchs' endothelial dystrophy.

PURPOSE: To assess vision-related quality of life in Fuchs' dystrophy and changes in vision-related quality of life after 3 types of keratoplasty (penetrating keratoplasty [PK], deep lamellar endothelial keratoplasty [DLEK], and Descemet stripping endothelial keratoplasty [DSEK]). DESIGN: Prospective, observational case series. PARTICIPANTS: Sixty-three subjects with Fuchs' endothelial dystrophy: 12 subjects (12 eyes) received PK, 11 subjects (11 eyes) received DLEK, and 40 subjects (40 eyes) received DSEK. METHODS: Subjects were examined before keratoplasty and at regular intervals through 3 years after keratoplasty. At each examination, vision-related quality of life was assessed using the 25-item National Eye Institute Visual Functioning Questionnaire; best spectacle-corrected and uncorrected visual acuities were measured by using the electronic Early Treatment of Diabetic Retinopathy Study protocol; keratometric cylinder was measured by a manual keratometer. Disability glare was measured with a straylight meter. MAIN OUTCOME MEASURES: Vision-related quality of life composite score. RESULTS: Vision-related quality of life composite score for all eyes with Fuchs' dystrophy before keratoplasty was 72 ± 11 (n = 63) and did not differ between groups (P = 0.88). Vision-related quality of life improved by 6 months (PK, P = 0.008; DLEK, P = 0.03; DSEK, P < 0.001), with continued improvement between 6 months and 3 years after PK (P = 0.01) and DSEK (P = 0.004). At 6 months, the composite score was higher after DSEK than after PK (P = 0.006). At 3 years, there were no differences in composite scores between the 3 treatments (P = 0.33; mean minimum detectable difference, 8 [α = 0.05; ß = 0.20]). After keratoplasty, quality of life was correlated with uncorrected visual acuity at 1 year (r = -0.38; P = 0.001) and at 3 years (r = -0.36; P = 0.02), with disability glare at 3 years (r = -0.41; P = 0.02), and with best-corrected visual acuity at 6 months (r = -0.34; P = 0.03), but not thereafter. CONCLUSIONS: Vision-related quality of life in patients with Fuchs' endothelial dystrophy is significantly impaired but improves after keratoplasty, irrespective of the technique. The improvement is faster after DSEK than after PK, and this might be explained in part by rapid improvement in uncorrected visual acuity after DSEK. This study affirms an advantage of endothelial keratoplasty over PK with respect to patient-reported outcomes.

Anterior corneal aberrations after Descemet's stripping endothelial keratoplasty for Fuchs' endothelial dystrophy.

PURPOSE: To determine the change in anterior corneal high-order aberrations (HOAs) after Descemet's stripping endothelial keratoplasty (DSEK) for Fuchs' dystrophy, and to compare the HOAs with those of age-matched controls. DESIGN: Prospective cohort and cross-sectional study. PARTICIPANTS AND CONTROLS: Forty-eight eyes with Fuchs' dystrophy were examined before and after DSEK, and were compared with 52 eyes of age-matched controls with normal corneas. METHODS: Corneas of patients with Fuchs' dystrophy were examined prospectively before and at intervals through 2 years after DSEK. Wavefront errors from the anterior corneal surface were derived from corneal topograms and were expressed as Zernike polynomials through the sixth order. Best-corrected visual acuity (BCVA) was measured by the electronic Early Treatment of Diabetic Retinopathy Study protocol, and subepithelial haze was measured from the brightness of confocal images. Total HOAs were compared before and after DSEK, and with those of age-matched controls, by using generalized estimating equation models. Relationships between HOAs, BCVA, subepithelial haze, and recipient age were determined. MAIN OUTCOME MEASURES: Anterior corneal HOAs, BCVA, and subepithelial haze (backscattered light). RESULTS: In Fuchs' dystrophy before DSEK, total HOAs (4 mm optical zone) from the anterior corneal surface (0.29±0.13 µm) were higher than those of controls (0.17±0.08 µm; P<0.001). At 2 years after DSEK, total HOAs (0.26±0.13 µm) did not differ from preoperative aberrations (P = 0.99), and remained higher than in controls (P<0.001). At 2 years, total HOAs were correlated with BCVA (r = 0.59; P<0.001; n = 27), with subepithelial haze (r = 0.41; P = 0.01; n = 25), and with recipient age (r = 0.59; P<0.001; n = 27). CONCLUSIONS: Anterior corneal HOAs are higher in Fuchs' dystrophy than in controls, and remain higher through 2 years after DSEK. The aberrated anterior surface might be related to anterior corneal ultrastructural changes and haze formation in Fuchs' dystrophy, and should not be ignored as a source of decreased visual acuity after DSEK.

Corneal haze determined by confocal microscopy 2 years after Descemet stripping with endothelial keratoplasty for Fuchs corneal dystrophy.

OBJECTIVE: To quantify corneal light scatter and its relationship to vision after Descemet stripping with endothelial keratoplasty (DSEK). METHODS: Eyes with Fuchs corneal dystrophy were examined before and 1, 3, 6, 12, and 24 months after DSEK. Outcome measures were high- and low-contrast visual acuity, contrast sensitivity, and forward light scatter. Corneal reflectivity (backscatter), expressed in scatter units (SU), was quantified using in vivo confocal microscopy. RESULTS: Comparing 49 study eyes with 35 normal eyes, the mean (SD) corneal subepithelial layer was more reflective than normal before (2325 [613] vs 1208 [287] SU, P<.001) and through 24 months after DSEK (1760 [432] SU, P<.001). Interface reflectivity remained higher than in normal stroma through 24 months (1228 [287] vs 827 [188] SU, P<.001). At 1 year, forward light scatter correlated with subepithelial reflectivity (r=0.28, P=.01) but not interface reflectivity. Recipient age was correlated with improvement in subepithelial reflectivity at 12 months (r=­0.41, P=.01, 34 eyes) and 24 months (r=­0.36, P=.02, 26 eyes) after DSEK, and the improvement of subepithelial haze in eyes of participants aged 62 years or younger was correlated with improvement in forward light scatter at 12 months (r=0.52, P=.008) and 24 months (r=0.62, P=.004). CONCLUSIONS: In Fuchs corneal dystrophy, the corneal subepithelial region is a more important source of forward light scatter than the DSEK interface. Subepithelial haze improves more in younger patients and is associated with improvement in forward light scatter. CLINICAL RELEVANCE: Visual function after DSEK is affected by residual haze in the anterior host cornea more so than the surgical interface. Haze, which likely is experienced as glare disability, improves after surgical intervention but improves more in younger patients.

Host and graft thickness after Descemet stripping endothelial keratoplasty for Fuchs endothelial dystrophy.

PURPOSE: To determine relationships between vision, forward scatter, and total corneal and graft thicknesses after Descemet stripping endothelial keratoplasty (DSEK). DESIGN: Prospective, cohort study. METHODS: Forty-four eyes with Fuchs endothelial dystrophy were examined before and at 1, 3, 6, and 12 months after DSEK; all eyes were pseudophakic after surgery. Central total corneal and graft thicknesses were measured using confocal microscopy. Best-corrected high-contrast visual acuity (BCVA) was measured using the electronic Early Treatment Diabetic Retinopathy Study protocol, and forward light scatter was measured using a straylight meter. RESULTS: Total corneal thickness was 610 ± 50 µm (mean ± standard deviation) before DSEK, increased to 680 ± 74 µm by 1 month after DSEK (P < .001), and stabilized at 660 ± 68 µm by 3 months after DSEK (P = .03 vs 1 month). Graft thickness was 170 ± 57 µm at 1 month, decreased to 157 ± 49 µm by 3 months (P = .004), and then remained stable through 12 months (156 ± 51 µm; P = .99 vs 3 months). BCVA was 0.44 ± 0.21 logarithm of the minimal angle of resolution (logMAR) units (Snellen equivalent, 20/55) before DSEK, improved to 0.26 ± 0.20 logMAR units (Snellen equivalent, 20/36) by 3 months (P < .001), and improved to 0.16 ± 0.16 logMAR units (Snellen equivalent, 20/29) at 12 months (P < .001 vs 3 months). BCVA and forward light scatter did not correlate with corneal or graft thickness after DSEK. CONCLUSIONS: Stromal edema resolves by 3 months after DSEK for Fuchs dystrophy, whereas visual acuity continues to improve through 12 months. Thicker corneas and grafts are not associated with worse visual acuity or increased forward scatter.