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.

Comparison of Scheimpflug and Anterior Segment Optical Coherence Tomography Imaging Parameters for Japanese Patients With Fuchs Endothelial Corneal Dystrophy With and Without TCF4 Repeat Expansions.

PURPOSE: The aim of this study was to investigate the association between cytosine-thymine-guanine trinucleotide repeat (TNR) expansion in TCF4 and the clinical phenotypes of corneal densitometry or anterior segment morphology in Fuchs endothelial corneal dystrophy. METHODS: This retrospective cross-sectional study included 150 eyes from 75 Japanese consecutive patients with Fuchs endothelial corneal dystrophy. Cytosine-thymine-guanine repeat expansion of leukocyte-derived genomic DNA was analyzed through fragment analysis using polymerase chain reaction and triplet repeat primed polymerase chain reaction. Scheimpflug-based densitometry and anterior segment optical coherence tomography were applied. Corneal densitometry, and corneal and anterior segment morphology parameters were compared between patients with and without TNR expansion of 50 or more (expansion and nonexpansion groups, respectively) using a mixed model. RESULTS: The average age of the patients was 66.8 ± 13.0 years, and the modified Krachmer grading scale was 1, 2, 3, 4, 5, and 6 for 7, 32, 28, 51, 6, and 18 eyes, respectively. Sixteen patients (21%) exhibited ≥50 TNR expansion. No significant differences in sex, age, history of keratoplasty, modified Krachmer grade, and corneal densitometry in either diameter or depth were observed between the 2 groups. No significant differences in anterior segment morphology, including the anterior chamber depth and anterior chamber angle width parameters, were observed using a univariate mixed model, except for central corneal thickness (P = 0.047). However, according to the multivariate mixed model, repeat expansion was not significantly associated with central corneal thickness (P = 0.27). CONCLUSIONS: No significant differences in clinical phenotypes were found between Japanese patients having Fuchs endothelial corneal dystrophy with and without TNR expansion.

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.

High-fat diet during pregnancy lowers fetal weight and has a long-lasting adverse effect on brown adipose tissue in the offspring.

Maternal obesity and malnutrition during gestation and lactation have been recognized to increase the risk of obesity and metabolic disorders in the offspring across their lifespan. However, the gestational period during which malnutrition exerts a decisive effect is unclear. Brown adipose tissue (BAT) plays a critical role in energy metabolism owing to its high efficiency in oxidizing glucose and fatty acids. This study aimed to determine the impact of maternal high-fat diet (HFD) consumption only during pregnancy on BAT and energy metabolism in offspring mice. Dams were fed an HFD or a normal chow diet from embryonic day 2.5. HFD consumption during pregnancy induced glucose intolerance and hypertension in dams. In the offspring of HFD-fed dams, maternal HFD lowered fetal weight without affecting placental weight, whereas HFD consumption after birth exacerbated oxygen consumption and cold-induced thermogenesis at 12 months of age, accompanied by increased lipid droplet size in BAT. These data demonstrate that HFD consumption only during pregnancy exerts a long-lasting effect on BAT. Collectively, these findings indicate the importance of nutrition during pregnancy with respect to the energy metabolism of the offspring, and pregnant women should thus ensure proper nutrition during pregnancy to ensure normal energy metabolism in the offspring.

Fourier Analysis on Regular and Irregular Astigmatism of Anterior and Posterior Corneal Surfaces in Fuchs Endothelial Corneal Dystrophy.

PURPOSE: To conduct Fourier analysis on regular and irregular astigmatism of the anterior and posterior corneal surfaces using anterior segment optical coherence tomography in patients with Fuchs endothelial corneal dystrophy (FECD) DESIGN: Observational case series. METHODS: This study included 75 eyes of 43 FECD patients and 34 eyes of 34 healthy subjects in Osaka University Hospital. Corneal dioptric data from the central 6-mm zone of the anterior and posterior corneal surface were expanded into spherical, regular astigmatism, asymmetry, and higher-order irregularity components using Fourier analysis. We analyzed the association between each component and modified Krachmer grade. RESULTS: There were significant differences in regular astigmatism, asymmetry, and higher-order irregularity components of the anterior corneal surface, and spherical, regular astigmatism, asymmetry, and higher-order irregularity components of the posterior corneal surface among modified Krachmer grades (P = .036, <.001, <.001, <.001, <.001, <.001, and <.001, respectively). Asymmetry component of the anterior and posterior corneal surfaces gradually increased with FECD progression. Higher-order irregularity components of the anterior and posterior corneal surfaces drastically increased in Grade 6. Many eyes had an axis of 0°-180° for the asymmetry component of the anterior surface and 180°-360° for that of the posterior surface. CONCLUSION: Patients with severe FECD had a larger amount of asymmetry and higher-order irregularity components of the anterior and posterior corneal surfaces. Patients with FECD up to Grade 5 were characterized by anterior and posterior flattening in the inferior cornea, and those with Grade 6 showed irregularity in the anterior and posterior corneal surfaces.

Quantitative Analysis of the Association Between Follow-Up Duration and Severity of Limbal Stem Cell Deficiency or Visual Acuity in Aniridia.

Purpose: This study aimed to quantitatively analyze the association between follow-up duration and the severity of limbal stem cell deficiency (LSCD) or visual acuity in patients with aniridia. Methods: A total of 52 eyes of 27 patients with aniridia were enrolled at Osaka University Hospital. Medical records were retrospectively reviewed to obtain information on the severity of LSCD and corrected distance visual acuity (CDVA). LSCD severity was based on a modified severity grading scale. We used an ordered logistic regression model to examine the association between follow-up duration and LSCD severity, and a linear regression model with a generalized linear mixed model for the association between follow-up duration and visual acuity. Results: The mean follow-up duration was 5.2 ± 6.3 years. The mean age at the last follow-up visit was 40.5 ± 18.9 years. The mean CDVA was 1.52 ± 1.09 logMAR. At the last follow-up, 1 examined eye (1.9%) was categorized as stage 0, 7 (13.5%) as Ia, 9 (17.3%) as Ib, 5 (9.6%) as Ic, 2 (3.8%) as IIb, 12 (23.1%) as IIc, and 11 (21.2%) as III. Five eyes (9.6%) were unclassifiable. There was a significant association between follow-up duration and LSCD severity (odds ratio per +1 year, 1.41; P < 0.001). CDVA significantly decreased as follow-up duration increased. Each increase of 1 year in the follow-up duration was associated with a mean difference of +0.021 logMAR (95% confidence interval [CI] 0.01-0.03; P < 0.001). Conclusion: We quantitatively demonstrate that LSCD severity and visual impairment significantly progress as follow-up duration increases.

Novel PAX6 mutation reported in an aniridia patient.

An aniridia patient was found to have a novel PAX6 mutation. A genetic duplication within PAX6, which caused a frameshift mutation, ultimately created a nonsense stop codon and premature truncation of the protein. Consequently, the patient presented with a clouded cornea as a result of partial limbal stem cell deficiency, foveal hypoplasia, nystagmus and a pale, cupped optic disc caused by glaucoma.