Intensive topical steroid regimen for enhanced very early recovery after small incision lenticule extraction.

OBJECTIVE: This study aims to investigate the topical steroid regimen after small incision lenticule extraction (SMILE) for its effect on very early restoration of visual quality. METHODS: A total of 180 patients (360 eyes) who underwent SMILE were enrolled. These patients were randomly assigned to three groups, with 60 patients in each group. The only difference among these three groups was the administration of 0.1% fluorometholone (FML) eye drops within two hours after SMILE: no FML in group A, 0.1% FML once every hour in group B and 0.1% FML once every half hour in group C. The corrected distance visual acuity (CDVA), objective scattering index (OSI), modulation transfer function (MTF) cut-off, Strehl ratio (SR) and incidence of subjective symptoms were evaluated preoperatively, at 2, 4 and 24 h and one week after SMILE. RESULTS: The CDVA, MTF cut-off and SR values were significantly higher in group C, when compared to the other two groups, at 2 and 4 h after SMILE (p < 0.05). Furthermore, the OSI and incidence of subjective symptoms were significantly lower in group C, when compared to the other two groups, at 2 and 4 h after SMILE (p < 0.05). However, no significant differences in CDVA, MTF cut-off, SR, OSI and the incidence of subjective symptoms were detected among the three groups at 24 h and one week after SMILE (p > 0.05). CONCLUSION: The administration of 0.1% FML eye drops every half hour within two hours after SMILE accelerates the restoration of visual and optical quality, and reduces the incidence of subjective symptoms during the very early phase after surgery.

New splice site mutations in MYO7A causing Usher syndrome type 1: a study on a Chinese consanguineous family.

PURPOSE: This study investigated the new splice site mutations of Myosin VIIA (MYO7A) in patients with Usher syndrome type 1 (USH1) from a three-generation Chinese consanguineous family. METHODS: All subjects underwent comprehensive ophthalmic examinations and an audiometric test. Demographic data, family history, and peripheral blood leukocytes were collected. We performed whole exome sequencing (WES) to analyze the genomic DNA of the family. DNA sequence and restriction fragment length polymorphism (RFLP) analyses were also done. The identified genetic variants were validated by conducting polymerase chain reaction (PCR) in 100 healthy control subjects and comparing with the NCBI VARIANT database and the 1000 Genomes Project. The functional consequences were further analyzed. RESULTS: WES identified two new splice site mutations (c.5648G > A(rs111033215) and c.6238-1G > C) in MYO7A in two patients with USH1, i.e., the proband and her elder brother. DNA sequence and RFLP analyses showed that other members without USH1 carried only one of the two mutations. In the analysis of healthy controls, neither mutation existed. Both mutations were predicted to be damaging and were most likely associated with USH1. CONCLUSION: In the three-generation Chinese consanguineous family with USH1, c.5648G > A(rs111033215) and c.6238-1G > C mutations in MYO7A are most likely associated with the disease. Our findings expand the mutational spectrum of MYO7A, which will enhance the understanding of the genetic abnormalities in USH1 and provide more evidence for future investigations on therapeutic strategies such as precise gene replacement or gene editing.

Effect of white-to-white corneal diameter on biomechanical indices assessed by Pentacam Scheimpflug corneal tomography and corneal visualization Scheimpflug technology.

PURPOSE: To provide evidence for more accurate evaluation of refractive surgery candidates in clinics, this retrospective study investigated the effect of corneal diameter on the biomechanical indices assessed by Pentacam Scheimpflug cornea tomography (Pentacam) and corneal visualization Scheimpflug technology (Corvis ST). METHODS: The relevant data were collected of 132 eyes from 132 participants with moderate myopia who were candidates for refractive surgery. Eligible participants were apportioned to 2 groups based on the white-to-white (WTW) corneal diameter: Group A, ≤ 11.5 mm, and Group B, ≥ 11.6 mm. A single clinician performed Pentacam and Corvis ST imaging on each subject for 3 consecutive measurements, and the means were used for statistical analyses. RESULTS: Each group comprised 66 eyes. As measured by Pentacam, the 2 groups were comparable regarding Df and Da. For other measurements, Group A had significantly higher K1, K2, Db, Dp, Dt, Do, PPImin, PPImax, PPIavg, while Group B had significantly higher CCT, BFSf, BFSb, and ARTmax. Corvis ST data included DA ratio, SPA1, CBI, TBI, and ARTh. Only the latter showed a significant difference, with ARTh of group A (437.04 ± 76.60) larger than group B (470.46 ± 103.36, p = 0.04). CONCLUSION: In a Chinese population, WTW corneal diameter showed effect on biomechanical indices assessed by Pentacam and Corvis ST. Personalized evaluation of these measurements based on corneal diameter should improve the sensitivity and specificity for screening of keratoconus by these devices.

A novel variant in TGFBI causes keratoconus in a two-generation Chinese family.

BACKGROUND: This study aims to investigate the genetic abnormalities in a two-generation Chinese family affected by keratoconus (KC). A two-generation Chinese family affected by KC was studied. MATERIALS AND METHODS: A total of 118 unrelated healthy individuals without KC were recruited as controls. The family history, clinical data, and peripheral blood leukocytes were collected from all subjects. Whole exome sequencing was performed using the genomic DNA of the proband (II.2) and the other two affected family members (I.1 and II.3). Afterwards, polymerase chain reaction was performed for the other enrolled subjects to verify the variants identified in family members with KC. The PolyPhen2, SIFT, PROVEIN and Mutation Taster software programs were applied to analyze the functional consequences of the variants. RESULTS: A single nucleotide polymorphism (VARIANT) (c.1406 G > A [rs759370852]) in the transforming growth factor beta-induced (TGFBI) gene was identified in all affected family members, which resulted in a p.R469H amino acid change. This variant was not detected in the controls. The variant c.1406 G > A in TGFBI was predicted as probably damaging with software programs. CONCLUSION: A novel variant c.1406 G > A in TGFBI has been identified, and probably contributes to the pathogenesis of KC.

Changes in Corneal Morphology with Age in Asian Population: A Multicenter Study of 30,618 Cases.

INTRODUCTION: To evaluate normal reference ranges for corneal morphological parameters and investigate age-related changes in these parameters in Asian subjects with healthy eyes in order to provide reference data for preoperative evaluation of corneal refractive surgery and the early differential diagnosis of subclinical and asymptomatic keratoconus. METHODS: This cross-sectional, multicenter, observational study was conducted in five provinces of China, from January 2014 through October 2019. It is a retrospective analysis. Examiner-blinded clinical measurements were performed after stratification of the subjects into the following age groups: < 18, 18-30, 31-40, 41-50. We evaluated 30,618 healthy eyes of Chinese subjects who exhibited a normal corneal morphology, had no history of eye surgery or trauma, stopped wearing soft contact lenses for at least 2 weeks (rigid contact lenses for at least 4 weeks), and underwent topographic studies for both eyes on the same day. RESULTS: While the anterior and posterior corneal curvatures (K1 and K2) increased with age, corneal astigmatism of the anterior and posterior surfaces (ΔK) and central, minimum, and overall corneal thicknesses decreased with age. Age-related decrease of the overall corneal thickness was more obvious toward the periphery. The anterior and posterior corneal surface heights exhibited a decrease and an increase, respectively. Both index of height asymmetry (IHA) and index of vertical asymmetry (IVA) exhibited an increase with age. CONCLUSIONS: The cornea exhibits overall thinning with age and gradually changes from a flat ellipse to an elongated ellipse in Asian individuals with healthy eyes. However, the anterior and posterior surfaces become smoother with age. Owing to the very large number of cases, these small differences are statistically significant. The results obtained are consistent with the hypothesis that a normal cornea seems to withstand quite well the effect of IOP, external pressures, and the natural cross-linking.

The best thickness of cornea graft from SMILE surgery as patch graft in glaucoma drainage implant surgery.

OBJECTIVE: The aim of this study was to determine the best thickness of corneal slices acquired from femtosecond laser surgery-small incision lenticule extraction (SMILE surgery) as patch graft in glaucoma drainage implantation surgery. METHODS: This study is a prospective randomized study. Patients who received glaucoma drainage implantation from September 2016 to November 2018 were observed. The patients were randomly divided into 3 groups. Group A included 102 cases (104 eyes), receiving 1 layer (120-150 µm) of allogeneic lamellar corneal tissue as the graft. Group B included 117 cases (120 eyes), receiving 2 layers of lamellar corneal tissue from one donor. Group C included 109 cases (111 eyes), using 3 layers of lamellar corneal tissue from 2 donors. The intraocular pressure, corneal graft, conjunctiva stromalysis, drainage tube exposure, and drainage plate were observed. RESULTS: Patients were followed up for 6 to 33 months. The intraocular pressure was significantly reduced after surgery in all three groups. Conjunctiva stromalysis and drainage tubes were exposed in 3 eyes (3%) in group A and 1 eye (0.8%, a special case which has nystagmus and the plate was placed infratemporally) in group B, whereas no conjunctiva stromalysis or tube exposure was reported in group C. CONCLUSIONS: The corneal graft acquired from SMILE surgery can effectively prevent drainage tube exposure and give patients a better cosmetic appearance. Two layers of lamellar corneal tissue (240-300 µm) may be the best suitable thickness because it can effectively reduce tube exposure and rejection. In some special cases, 3 layers of lamellar corneal tissue are needed.

A Novel Splice-Site Variation in COL5A1 Causes Keratoconus in an Indian Family.

OBJECTIVE: This study aims to clarify the association between keratoconus (KC) and potential pathogenic genetic variants in a three-generation South Indian family. METHODS: In the present study, a three-generation KC family, which comprised 10 affected patients and nine unaffected individuals, was recruited. The family history and necessary ophthalmological exams, such as visual acuity and slit-lamp, were performed for all participants. Genomic DNA was extracted from peripheral blood leukocytes, and whole exome sequencing (WES) was performed using the genomic DNA of the proband (III:4) and two other family members (III:2, III:3). The acceptor-splice-site mutation was validated and verified using polymerase chain reaction (PCR) and Sanger sequencing. Gene functions and pathways associated with the identified mutations were subjected to in silico analysis. RESULTS: A novel COL5A1 acceptor-splice-site mutation IVS50-4C > G was found in the 10 affected individuals in the three-generation KC family, but this was not found in any of the unaffected family members or unrelated healthy individuals. Gene functional analysis using the SpliceMan and ExonScan software predicted that the splice-site mutation was potentially associated with KC pathogenesis. This mutation might affect the assembly of the collagen triple helix. CONCLUSION: The present study confirmed the association between the COL5A1 gene and KC and identified a novel COL5A1 acceptor-splice-site mutation (IVS50-4C > G) in intron 50, which may affect the splicing of the adjacent exon 50.

Distribution and Trends in Corneal Thickness Parameters in a Large Population-Based Multicenter Study of Young Chinese Adults.

Purpose: The purpose of this study was to characterize corneal thickness from multiple regions and determine accurate reference values in young adults for diagnosis and treatment. Methods: This cross-sectional observational study was conducted from January 2008 through October 2016 using examiner-blinded clinical measurements and included 37,375 healthy eyes from young adults who exhibited normal corneal morphology, had no history of eye surgery or trauma, had stopped wearing soft contact lenses for ≥2 weeks (rigid contact lenses for ≥4 weeks), and had undergone topographies of both eyes on same day. Keratoconus and subclinical keratoconus were excluded. This multicenter study was conducted in four provinces of China: Tianjin, Shandong, Hubei, and Xinjiang. Results: Central corneal, corneal vertex, and thinnest corneal thicknesses were higher in eyes from Hubei than other provinces. The left eye was thicker than the right in patients from Shandong, Tianjin, and Hubei, but not Xinjiang. Overall corneal thickness was higher in eyes from Hubei than from other provinces. Changing trend of the whole-cornea thickness in eyes from Xinjiang differed from eyes from other provinces. Trends in maximum and minimum axial for change of corneal thickness were similar between eyes from Hubei and Xinjiang and between Shandong and Tianjin. Conclusions: Corneal thickness differs among eyes from different regions. Corneal thickness parameters are influenced by ethnicity and geographical location, as increasing proximity to the equator was related to increasing corneal thickness. Design of refractive surgery and diagnosis of related diseases in patients of a certain area should be based on reference values from its population.

A Morphological identification cell cytotoxicity assay using cytoplasm-localized fluorescent probe (CLFP) to distinguish living and dead cells.

Cell cytotoxicity assays include cell activity assays and morphological identification assays. Currently, all frequently used cytotoxicity assays belong to cell activity assays but suffer from detection limitations. Morphological identification of cell death remains as the gold standard, although the method is difficult to scale up. At present there is no generally accepted morphological identification based cell cytotoxicity assay. In this study, we applied previous developed cell cytoplasm-localized fluorescent probe (CLFP) to display cell morphologies. Under fluorescence microscopy, the fluorescence morphology and intensity of living cells are distinct from dead cells. Based on these characters we extracted the images of living cells from series of samples via computational analysis. Thus, a novel cell morphological identification cytotoxicity assay (CLFP assay) is developed. The performance of the CLFP assay was similar to cell activity assay (MTT assay), but the accuracy of the CLFP assay was superior when measuring the cytotoxicity of active compounds.