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 · 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.

Open-angle glaucoma and Fuchs dystrophy.

A 62-year-old woman with a history of moderate myopia, long-standing open-angle glaucoma (OAG), and Fuchs dystrophy in both eyes was referred for consultative care. She had prior trabeculectomy in 1984 and 1992 in the left and right eyes, respectively. She is 3 months post-Descemet-stripping endothelial keratoplasty (DSEK) in the left eye, now referred with uncontrolled intraocular pressure (IOP) despite maximum tolerated medical therapy. Current medical therapy for IOP consists of acetazolamide 250 mg by mouth 2 times a day, brimonidine 2 times a day in the left eye, dorzolamide 2 times a day in the left eye, and timolol 2 times a day in the left eye. The patient has a history of presumed steroid response; however, her corneal surgeon has requested that the steroid be continued for the next several months because of the recent DSEK. The IOP in the left eye has ranged from the mid-20s to mid-30s since DSEK. The right eye has consistently had pressure in the low teens and below for many years without topical antihypertensive medications. Examination revealed stable visual acuity at 20/30 and 20/40 in the right and left eyes, respectively, IOP was 12 mm Hg in the right eye and 25 mm Hg in the left eye by Goldman applanation, irregular but reactive pupils without afferent defect, and full confrontational visual fields. Slitlamp examination showed superior low avascular bleb, moderate-to-severe guttae, and posterior chamber IOL in the right eye. The left eye showed superior low diffuse bleb, clear DSEK graft, quiet chamber, superonasal iridectomy, and posterior chamber IOL with an open posterior capsule. The conjunctiva was moderately scarred but a repeat trabeculectomy or Xen Gel stent (Abbvie) appeared possible. The angles were wide open in each eye. Fundus examination was normal aside from myopic, anomalous-appearing nerves with an approximate cup-to-disc ratio of 0.90 in both eyes. Humphrey visual field showed nonspecific changes on the right and moderate nasal defect on the left eye, stable to previous examinations dating back to 2018 (Figure 1JOURNAL/jcrs/04.03/02158034-202407000-00018/figure1/v/2024-07-10T174240Z/r/image-tiff and Figure 2JOURNAL/jcrs/04.03/02158034-202407000-00018/figure2/v/2024-07-10T174240Z/r/image-tiff). Optical coherence tomography (OCT) of the retinal nerve fiber layer (RNFL) revealed moderated thinning in both eyes that was also stable to prior examinations (Figure 3JOURNAL/jcrs/04.03/02158034-202407000-00018/figure3/v/2024-07-10T174240Z/r/image-tiff). Her axial length measured 25.23 and 26.34 mm in the right and left eyes, respectively. Central corneal thickness was 553 µm in the right eye and 563 µm in the left eye before her DSEK procedure. What would be your approach to management of this patient's left eye, addressing the following: Rationale for your procedure of choice? Would you over-rule the corneal surgeon and stop the steroid in an attempt to obviate the need for glaucoma surgery? Does the age of onset of glaucoma affect your surgical decision making? Note that patient age at the time of trabeculectomy was 22 years. Are some procedures better suited for patients after DSEK surgery?

Associations Between Visual Functions and Severity Gradings, Corneal Scatter, or Higher-Order Aberrations in Fuchs Endothelial Corneal Dystrophy.

Purpose: The purpose of this study was to investigate the associations between visual function and severity grading, corneal scatter, or higher-order aberrations (HOAs) in patients with Fuchs endothelial corneal dystrophy (FECD). Methods: This observational case series study included 49 eyes of 27 patients with FECD and 10 eyes of 10 healthy individuals. We evaluated corrected distance visual acuity (CDVA) using Landolt-C and Early Treatment Diabetic Retinopathy Study charts and contrast sensitivity using the CSV-1000E chart and CSV-1000RN letter chart. We analyzed the associations between visual function and explanatory variables, including age, modified Krachmer grade, central corneal thickness (CCT), anterior segment optical coherence tomography (AS-OCT)-based grade, HOAs, intraocular straylight, and corneal densitometry. We additionally conducted receiver operating characteristic (ROC) analysis to identify the corneal densitometry thresholds for decreased visual function. Results: There were significant associations between visual function and the modified Krachmer grade, CCT, AS-OCT-based grade, HOAs, intraocular straylight, and corneal densitometry. A modified Krachmer grade ≥ 3 was identified as a threshold for decreased visual function. Multivariate analysis showed that corneal densitometry was significantly associated with all visual function parameters, and HOAs were significantly associated with CDVA but not with contrast sensitivity. ROC analysis revealed that corneal densitometry of the posterior layer at 0 to 2 mm ≥ 10 grayscale units (GSU), was identified as a threshold for decreased visual function. Conclusions: HOAs, forward and backward light scatter affected visual function, with backward light scatter being the most influential. In patients with FECD, modified Krachmer grade ≥ 3 and corneal densitometry ≥ 10 GSU were thresholds for visual disturbance.

The surgical management of a patient with Fuchs endothelial dystrophy and cataracts.

Objective: To report the two different surgical approaches in the case of a patient with Fuchs endothelial dystrophy with low endothelial cell count and advanced cataracts. Methods: The chosen surgical approach differed between eyes, with the right eye undergoing a combined approach consisting of cataract surgery, intraocular lens implantation, and penetrating keratoplasty in 2022. One year later, for the left eye, a different approach was decided: cataract surgery followed by Descemet membrane endothelial keratoplasty (DMEK). The Descemet membrane graft was prepared by the surgeon using the liquid bubble technique. AS-OCT was used to monitor the patient before and after surgery. Results: Visual recovery was excellent for both eyes, however, visual acuity improved quickly in the left eye (DMEK), while, in the right eye (PK), the best corrected visual acuity was reached after several months post-surgery. Conclusion: Advanced stages of Fuchs dystrophy patients will most likely need corneal transplantation. Each type of corneal transplantation procedure comes with unique challenges, both intraoperative and postoperative. DMEK is a very good treatment option for patients with Fuchs endothelial dystrophy, with excellent visual recovery and good graft survival at the 10-year mark. Abbreviations: DMEK = Descemet membrane endothelial keratoplasty, PK = penetrating keratoplasty, AS-OCT = anterior segment optical coherence tomography, FECD = Fuchs endothelial corneal dystrophy, BCVA = best corrected visual acuity, US = ultrasound, CDE = cumulative dissipated energy, IOL = intraocular lens.

[Outcomes of hemi-Descemet membrane endothelial keratoplasty and phacoemulsification for the treatment of primary Fuchs' endothelial corneal dystrophy combined with cataract]. / Rezul'taty transplantatsii destsemetovoi membrany s endoteliem i fakoemul'sifikatsii pri pervichnoi endotelial'noi distrofii rogovitsy Fuksa, sochetannoi s kataraktoi.

PURPOSE: This study evaluates the long-term results of surgical treatment of patients with Fuchs' endothelial corneal dystrophy and cataract. MATERIAL AND METHODS: The study included 24 patients (24 eyes) with primary Fuchs' endothelial corneal dystrophy and cataract, who underwent cataract phacoemulsification with IOL implantation and of Descemet's membrane endothelial keratoplasty with a semicircular graft (hemi-DMEK). The effect of treatment was assessed by best corrected visual acuity (BCVA), central corneal thickness (CCT) and endothelial cell density (ECD). RESULTS: In total, surgical treatment involved 14 donor corneas that were divided in half during the preparation and isolation of the Descemet's membrane (DM). By month 12 after the surgery an increase in visual functions and graft transparency were observed in 23 patients (23 eyes) out of 24. Repeated keratoplasty was required in one case due to fibrosis of the posterior layers of recipient's corneal stroma. At 12 months postoperatively, the study group showed an increase in BCVA from 0.16±0.1 to 0.75±20, a decrease in CCT from 650.9±4.5 µm to 519.6±43.9, and a decreased in ECD from 2850.5±84.7 cells/mm2 up to 1285.5±277.2 cells/mm2. Thus, the loss of endothelial cells at one year after surgery amounted to 54.9%. CONCLUSIONS: The developed method for transplantation of a semicircular DM fragment provides a tissue-saving approach to endothelial keratoplasty, and considering the high percentage of transparent engraftment of grafts and complete visual rehabilitation, it can be recommended in the treatment of patients with cataract and Fuchs' endothelial corneal dystrophy.

Predictive factors for re-bubbling after DMEK: focus on the posterior corneal surface.

PURPOSE: To understand whether the preoperative morphology of the posterior corneal surface influences the rate of re-bubbling after Descemet membrane endothelial keratoplasty (DMEK). METHODS: After retrospectively analyzing the medical records of patients undergoing DMEK, in this multicentric cross-sectional study, we performed a binomial logistic regression analysis to assess significant predictors of re-bubbling and re-transplantation after surgery. Analyzed parameters included the preoperative diagnosis, anterior and posterior surface K1/K2, central corneal thickness, posterior Q value, and other posterior corneal surface parameters evaluated on the elevation maps produced by anterior segment optical coherence tomography. Results were stratified based on the surgeons' experience. RESULTS: We included 202 eyes of 202 patients with a mean age of 69.5 ± 12.4 years; 154 eyes were operated by a high-volume surgeon and 48 by one with less experience; 48 eyes (23.8%) underwent ≥ 1 re-bubbling and 14(6.9%) ≥ 1 re-transplantation. The presence of positive/less-negative posterior corneal irregularities and irregularities with greater absolute height had a significantly higher risk of re-bubbling in both the expert and less expert group (OR = 2.85 and 1.42, OR = 3.22 and 3.01, respectively, p < 0.05), whereas more negative posterior K1 and K2 were significant risk factors only in the former group (OR = 0.67 and 0.55, respectively, p < 0.05). Endothelial decompensation other than Fuchs and pseudophakic bullous keratopathy, more negative posterior Q values and smaller distances between center, and the highest/lowest posterior corneal surface irregularity correlated with an increased risk of graft failure (OR 1.23, 1.21, and 1.29, respectively, p < 0.05). CONCLUSION: Posterior corneal surface morphology significantly influences the risk of re-bubbling after DMEK.

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

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

Intraocular pressure-related side-effects after endothelial keratoplasty.

PURPOSE: To investigate circumpapillary retinal nerve fibre layer (RNFL) thickness, pupillary function and diameter after phacoemulsification and lens implantation alone or combined with endothelial keratoplasty (EK). METHODS: This study was a secondary analysis of data from a randomized, single-masked trial, that included 72 patients with Fuchs' endothelial dystrophy and cataract, equally allocated (1:1) to ultrathin Descemet's stripping automated endothelial keratoplasty or Descemet's membrane endothelial keratoplasty. The cataract extraction (CE) group included 40 patients undergoing cataract surgery only. All patients were treated with phacoemulsification and lens implantation. RESULTS: RNFL thickness was significantly lower in the CE group than after EK for the global (p < 0.01), nasal (p = 0.04), and temporal sectors (p = 0.01) 12 months after surgery. RNFL thickness was comparable between patients treated with rebubbling and others (p ≥ 0.16 for all comparisons) after 12 months. The CE group and patients treated with EK demonstrated a comparable scotopic (p = 0.34) and photopic pupil diameter (p = 0.95) as well as a comparable maximum (p = 0.83) and average pupillary constriction velocity (p = 0.95) after 12 months. In contrast, patients treated with rebubbling had a significantly smaller scotopic pupil diameter (p = 0.04). CONCLUSION: In this study, no evidence was found indicating a negative impact on the RNFL thickness after EK when compared to CE 12 months after surgery. Iris function and pupil diameter were comparable between the CE group and patients treated with EK after 12 months.

Fuchs endothelial corneal dystrophy: an updated review.

PURPOSE: The present review will summarize FECD-associated genes and pathophysiology, diagnosis, current  therapeutic approaches, and future treatment perspectives. METHODS: Literature review. RESULTS: Fuchs' endothelial corneal dystrophy (FECD) is the most common bilateral corneal dystrophy and accounts for one-third of all corneal transplants performed in the US. FECD is caused by a combination of genetic and non-heritable factors, and there are two types: early-onset FECD, which affects individuals from an early age and is usually more severe, and late-onset FECD, which is more common and typically manifests around the age of 40. The hallmark findings of FECD include progressive loss of corneal endothelial cells and the formation of focal excrescences (guttae) on the Descemet membrane. These pathophysiological changes result in progressive endothelial dysfunction, leading to a decrease in visual acuity and blindness in later stages. The present review will summarize FECD-associated genes and pathophysiology, diagnosis, current therapeutic approaches, and future treatment perspectives. CONCLUSION: With the characterization and understanding of FECD-related genes and ongoing research into regenerative therapies for corneal endothelium, we can hope to see more significant improvements in the future in the management and care of the disease.

Innate Immune Cytokine Levels in Eyes With Late Endothelial Keratoplasty Failure.

PURPOSE: The aim of this study was to compare aqueous humor cytokine levels in eyes with an initial endothelial keratoplasty (EK) that cleared and later decompensated versus control eyes. METHODS: In this prospective case-control study, aqueous humor samples were collected under sterile conditions at the start of planned cataract or EK surgery in normal controls (n = 10), Fuchs dystrophy controls with no previous surgery (n = 10) or previous cataract surgery only (n = 10), eyes with Descemet membrane EK (DMEK) endothelial decompensation (n = 5), and eyes with Descemet stripping EK (DSEK) endothelial decompensation (n = 9). Cytokine levels were quantified with the LUNARIS Human 11-Plex Cytokine Kit and compared using the Kruskal-Wallis nonparametric test and post hoc Wilcoxon pairwise 2-sided multiple comparison test. RESULTS: Levels of granulocyte-macrophage colony-stimulating factor, interferon gamma, interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-10, IL-12p70, and tumor necrosis factorα did not differ significantly between groups. However, IL-6 was significantly increased in DSEK regraft eyes versus controls without previous ocular surgery. IL-8 was significantly increased in eyes with previous cataract or EK surgery versus eyes without previous surgery, and IL-8 was significantly increased in DSEK regraft eyes versus eyes with previous cataract surgery. CONCLUSIONS: The levels of innate immune cytokines IL-6 and IL-8 were elevated in the aqueous humor of eyes with failed DSEK, but not with failed DMEK. The differences between DSEK and DMEK may be related to the lower inherent immunogenicity of DMEK grafts and/or the more advanced stage of some of the DSEK graft failures at the time of diagnosis and treatment.

The outcomes of postoperative eye patching after cataract surgery in patients with Fuchs' endothelial corneal dystrophy.

PURPOSE: To investigate the influence of post-operative eye patching on corneal thickness, endothelial cells' loss and visual acuity in patients diagnosed Fuchs' endothelial corneal dystrophy (FECD). SETTING: Public healthcare centre, Shamir Medical Centre, Israel. METHODS: This randomized controlled trial included patients with FECD undergoing routine cataract surgery in a public medical centre. Patients were randomly assigned to 2 groups: the eye undergoing surgery was covered with a patch for 24 h in the first group (patched group), and a plastic shield was used in the second (non-patched group). Both groups received a unique dose of a local steroid and antibiotic post-operatively. The eyes were examined pre-operatively, and on days 1, 7 and 30 post-surgery . Examination included: best corrected visual acuity (BCVA), comeplete slit lamp examination, intra ocular pressure (IOP), anterior chamber depth (ACD), central corneal thickness (CCT) using the IOL Master 700 (Zeiss, Germany) and endothelial cell density (ECD) using Specular microscopy. Cumulative dissipated energy (CDE) and operation time were recorded for all cases. RESULTS: The study included 46 eyes of 46 patients diagnosed with FECD. Twenty-three eyes in the patched group, and 23 eyes in the non-patched group . Thirty days post-operatively the CCT in the patched group decreased by 60 ± 38 mµ (9%) compared to 92 ± 80 mµ (13.5%) in the non- patched group (p = 0.04). Seven days post-operatively the CCT in the patched group decreased by 31 ± 35 mµ (5%) compared to 58 ± 76 (8%) in the non-patched group, but this difference did not reach statistical significance (p = 0.081). There was no statistically significant difference in endothelial cells loss as well as BCVA at 1, 7 and 30 days post-operatively between the study groups. CONCLUSIONS: Avoiding eye patch post-operatively after cataract surgery in patients with FECD results in better corneal clarity recovery and reduced corneal edema one month post-operatively. Visual acuity and endothelial cell's loss were not influenced by patching.

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

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

Three-Dimensional Assessment of Descemet Membrane Reflectivity by Optical Coherence Tomography in Fuchs Endothelial Corneal Dystrophy.

PURPOSE: This study aimed to evaluate Descemet membrane reflectivity using anterior segment optical coherence tomography (AS-OCT) in eyes with Fuchs endothelial corneal dystrophy (FECD). METHODS: We retrospectively assessed 144 eyes of 88 consecutive participants (41 FECD, 15 pseudophakic bullous keratopathies [BKs], and 32 healthy controls, 63.5 ± 16.5 years). FECD was graded 0 to 3 based on the guttae areas using specular microscopy. The sum of AS-OCT reflectivity of the 3-dimensional volume from 10 µm thickness from the endothelial surface of the cornea and residual stromal area was calculated as D sum (endo) and D sum (stroma) in the central area of 3- and 6-mm diameters, respectively. The D ES ratio was defined as the ratio of D sum (endo) to D sum (stroma). The percentage of the guttae area in the specular images was calculated using MATLAB. D sum (endo) and D ES ratio were compared among FECD, BK, and healthy controls. RESULTS: D sum (endo) in FECD grade 3 was significantly higher than that in healthy control eyes, FECD patients with mild and moderate guttae, and BK (all P ≤ 0.040). The D ES ratio in FECD patients with mild to severe guttae (grade 1-3) was significantly higher than that in healthy control eyes and BK (all P ≤ 0.035). The percentage of the guttae area was significantly correlated with D sum (endo) (R = 0.488, P < 0.001 for 3 mm, R = 0.512, P < 0.001 for 6 mm) and D ES ratio (R = 0.450, P < 0.001 for 3 mm, R = 0.588, P < 0.001 for 6 mm). CONCLUSIONS: Descemet membrane reflectivity in AS-OCT can be objective biomarkers for assessing guttae and FECD severity from early to end-stage FECD.

Phacoemulsification, pinhole pupilloplasty, and pre-Descemet's endothelial keratoplasty for keratoconus with Fuchs' endothelial dystrophy.

The comorbidity of keratoconus with Fuchs' endothelial dystrophy with cataract is a rare clinical combination. We present an amalgamation of surgical techniques to manage the above clinical conditions and its complications in single setting. The modified triple procedure, namely, the phacoemulsification, pinhole pupilloplasty, and pre-Descemet's endothelial keratoplasty (PDEK) in the order of description is followed in single sitting. Lens removal by phacoemulsification, correction of irregular astigmatism by pinhole pupilloplasty (pinhole optics), and exchanging the endothelial layer for PDEK forms the main segments of the triple procedure. This combination of techniques may decrease the risk of multiple surgeries and its related complications. Moreover, it will allow the patient for faster visual rehabilitation by improving the uncorrected visual acuity and visual quality.

Systematic Review of the Diagnostic Criteria and Severity Classification for Fuchs Endothelial Corneal Dystrophy.

PURPOSE: There are no defined diagnostic criteria and severity classification for Fuchs endothelial corneal dystrophy (FECD), which are required for objective standardized assessments. Therefore, we performed a systematic literature review of the current diagnosis and severity classification of FECD. METHODS: We searched the Ovid MEDLINE and Web of Science databases for studies published until January 13, 2021. We excluded review articles, conference abstracts, editorials, case reports with <5 patients, and letters. RESULTS: Among 468 articles identified, we excluded 173 and 165 articles in the first and second screenings, respectively. Among the 130 included articles, 61 (47%) and 99 (76%) mentioned the diagnostic criteria for FECD and described its severity classification, respectively. Regarding diagnosis, slitlamp microscope alone was the most frequently used device in 31 (51%) of 61 articles. Regarding diagnostic findings, corneal guttae alone was the most common parameter [adopted in 23 articles (38%)]. Regarding severity classification, slitlamp microscopes were used in 88 articles (89%). The original or modified Krachmer grading scale was used in 77 articles (78%), followed by Adami's classification in six (6%). Specular microscopes or Scheimpflug tomography were used in four articles (4%) and anterior segment optical coherence tomography in one (1%). CONCLUSIONS: FECD is globally diagnosed by the corneal guttae using slitlamp examination, and its severity is predominantly determined by the original or modified Krachmer grading scale. Objective severity grading using Scheimpflug or anterior segment optical coherence tomography can be applied in the future innovative therapies such as cell injection therapy or novel small molecules.

Association Between Fuchs Endothelial Corneal Dystrophy, Diabetes Mellitus, and Multimorbidity.

PURPOSE: The aim of this study was to assess risk for demographic variables and other health conditions that are associated with Fuchs endothelial corneal dystrophy (FECD). METHODS: We developed a FECD case-control algorithm based on structured electronic health record data and confirmed accuracy by individual review of charts at 3 Veterans Affairs (VA) Medical Centers. This algorithm was applied to the Department of VA Million Veteran Program cohort from whom sex, genetic ancestry, comorbidities, diagnostic phecodes, and laboratory values were extracted. Single-variable and multiple variable logistic regression models were used to determine the association of these risk factors with FECD diagnosis. RESULTS: Being a FECD case was associated with female sex, European genetic ancestry, and a greater number of comorbidities. Of 1417 diagnostic phecodes evaluated, 213 had a significant association with FECD, falling in both ocular and nonocular conditions, including diabetes mellitus (DM). Five of 69 laboratory values were associated with FECD, with the direction of change for 4 being consistent with DM. Insulin dependency and type 1 DM raised risk to a greater degree than type 2 DM, like other microvascular diabetic complications. CONCLUSIONS: Female sex, European ancestry, and multimorbidity increased FECD risk. Endocrine/metabolic clinic encounter codes and altered patterns of laboratory values support DM increasing FECD risk. Our results evoke a threshold model in which the FECD phenotype is intensified by DM and potentially other health conditions that alter corneal physiology. Further studies to better understand the relationship between FECD and DM are indicated and may help identify opportunities for slowing FECD progression.