A rare missense PAX6 mutation causes atypical aniridia in a three-generation Chinese family.

AIM: To investigate the molecular diagnosis of a three-generation Chinese family affected with aniridia, and further to identify clinically a PAX6 missense mutation in members with atypical aniridia. METHODS: Eleven family members with and without atypical aniridia were recruited. All family members underwent comprehensive ophthalmic examinations. A combination of whole exome sequencing (WES) and direct Sanger sequencing were performed to uncover the causative mutation. RESULTS: Among the 11 family members, 8 were clinically diagnosed with congenital aniridia (atypical aniridia phenotype). A rare heterozygous mutation c.622C>T (p.Arg208Trp) in exon 8 of PAX6 was identified in all affected family members but not in the unaffected members or in healthy control subjects. CONCLUSION: A rare missense mutation in the PAX6 gene is found in members of a three-generation Chinese family with congenital atypical aniridia. This result contributes to an increase in the phenotypic spectrum caused by PAX6 missense heterozygous variants and provides useful information for the clinical diagnosis of atypical aniridia, which may also contribute to genetic counselling and family planning.

Repeatability and Agreement of 4 Biometers Measuring Corneal Astigmatism in Eyes With Irregular Corneal Astigmatism Component.

PURPOSE: To investigate the repeatability and agreement of corneal astigmatism measurements in eyes with irregular corneal astigmatism component (ICAC) using four devices: IOLMaster 700 biometer, Lenstar 900 biometer, iTrace, and Pentacam. DESIGN: Prospective cross-sectional reliability analysis. METHODS: Sixty-four eyes (52 patients) with ICAC were examined three times using the four devices. The eye with ICAC in this study is defined as the cornea has a certain degree of irregular astigmatism (asymmetric and/or skewed bowtie pattern of corneal topography according to corneal topography classification), accompanied with total corneal higher-order aberrations in the 4 mm zone of 0.3 µm or greater. Corneal astigmatism was evaluated using three categories: anterior corneal astigmatism (ACA), posterior corneal astigmatism, and total corneal astigmatism (TCA). The repeatability was determined using the ∆Ast (arithmetic mean of vector differences among three repeated corneal astigmatism measurements). Bland-Altman plots and astigmatism vector analyses were employed to assess agreement. RESULTS: The IOLMaster 700 (∆Ast = 0.27 ± 0.20 D) showcased higher repeatability in ACA measurements compared to iTrace (∆Ast = 0.37 ± 0.38 D, P = .040) and Pentacam (∆Ast = 0.50 ± 0.22 D, P < .001), and paralleled the performance of Lenstar 900 (∆Ast = 0.31 ± 0.26 D, P = .338). The Pentacam (∆Ast = 0.09 ± 0.07 D, P < .001) demonstrated superior repeatability in posterior corneal astigmatism, whereas the IOLMaster 700 (∆Ast = 0.33 ± 0.23 D, P < .001) excelled in TCA. The IOLMaster 700 exhibited good agreement with either Lenstar 900 or iTrace, characterized by narrow 95% limits of agreement and clinically acceptable vector differences. Conversely, vector differences between Pentacam and the other three devices in ACA and TCA measurements were clinically significant, exceeding 0.50 D (all P < .05). CONCLUSIONS: In terms of repeatability of corneal astigmatism measurements in eyes with ICAC, the IOLMaster 700 and Lenstar 900 outperformed iTrace and Pentacam. While the IOLMaster 700 can be used interchangeably with either Lenstar 900 or iTrace, the Pentacam is not interchangeable with the other three devices.

Preliminary Application of a Continuous Functional Contrast Visual Acuity System in the Assessment of Visual Function in Dry Eye Patients.

Purpose: To investigate the feasibility and efficacy of a continuous functional contrast visual acuity (CFCVA) system in the assessment of visual function in dry eye disease (DED). Methods: Twenty patients with DED and 15 normal controls were recruited. Subjective symptoms were evaluated using the Ocular Surface Disease Index (OSDI) questionnaire, and tear film stability was assessed by a noninvasive corneal topographer. Under natural blinking conditions, the custom-built CFCVA system was used to take serial visual acuity measurements at 100%, 25%, 10%, and 5% contrast for 60 seconds. A 5-minute measurement at a 100% contrast level was defined as the stress test (ST). Mean CFCVA was defined, and visual maintenance ratio (VMR) was the ratio of mean CFCVA divided by baseline visual acuity. Results: In both groups, VMR decreased and mean CFCVA (logarithm of the minimum angle of resolution) increased with decreasing optotype contrast (from 100% to 5%). In ST, the ST VMR at the fourth and fifth minutes (VMR54 and VMR55) showed the strongest correlations with OSDI total, ocular symptoms, and vision-related function (-0.646 and -0.598, -0.688 and -0.693, and -0.599 and -0.555, respectively, P < 0.05). VMR54 and VMR55 also demonstrated the best discriminating ability for detecting DED, with areas under the curve of 0.903 and 0.867, respectively. Conclusions: Extending the continuous measuring time was more effective for detecting vision-related functional abnormalities in patients with DED than simply decreasing the optotype contrast level. Translational Relevance: The proposed CFCVA system and associated parameters offer a potential method for quantifying and interpreting the visual symptoms of DED in clinical care.

Expanded phenotypic spectrum of FOXL2 Variant c.672_701dup revealed by whole-exome sequencing in a rare blepharophimosis, ptosis, and epicanthus inversus syndrome family.

INTRODUCTION: Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is a rare genetic disease with diverse ocular malformations. This study aimed to investigate the disease-causing gene in members of a BPES pedigree presenting with the rare features of anisometropia, unilateral pathologic myopia (PM), and congenital cataracts. METHODS: The related BPES patients underwent a comprehensive ocular examination. Next, whole-exome sequencing (WES) was performed to screen for the disease-causing genetic variants. A step-wise variant filtering was performed to select candidate variants combined with the annotation of the variant's pathogenicity, which was assessed using several bioinformatic approaches. Co-segregation analysis and Sanger sequencing were then conducted to validate the candidate variant. RESULTS: The variant c.672_701dup in FOXL2 was identified to be the disease-causing variant in this rare BPES family. Combined with clinical manifestations, the two affected individuals were diagnosed with type II BPES. CONCLUSION: This study uncovered the variant c.672_701dup in FOXL2 as a disease causal variant in a rare-presenting BPES family with anisometropia, unilateral pathogenic myopia, and/or congenital cataracts, thus expanding the phenotypic spectrum of FOXL2.

Safety and efficacy of cataract surgery performed with a low-energy femtosecond laser compared with conventional phacoemulsification in Chinese patients: a randomized clinical trial.

BACKGROUND: To compare the safety and efficacy of femtosecond laser-assisted cataract surgery (FLACS) performed with the low-energy FEMTO LDV Z8 (Ziemer Ophthalmic Systems AG, Port, Switzerland) laser compared with conventional phacoemulsification (CP) in Chinese patients. METHODS: This prospective, multicenter, interventional study included 126 patients who were randomized (1:1) to undergo either FLACS or CP followed by intraocular lens (IOL) implantation between January 2019 and April 2020. The primary endpoint included the comparison of the endothelial cell loss (ECL) between the two groups at 3 months. Secondary endpoints included the comparison of cumulative dissipated energy (CDE), change in central corneal thickness (CCT) from baseline, and postoperative uncorrected and corrected distance visual acuities (UDVA and CDVA) in the two groups. RESULTS: At all postoperative time points, the FLACS group was found to be non-inferior to CP for the mean ECL (- 409.3 versus - 436.9 cells/mm2 at 3 months) and mean CDE (4.1 versus 4.5 percent-seconds). The increase in CCT was significantly lower in the FLACS group compared with the CP group at Day 7 (4.9 versus 9.2 µm; P = 0.04); however, the difference was not statistically significant at 1 and 3 months. Postoperatively, mean UDVA and CDVA were comparable between the two groups. No intraoperative complications occurred. CONCLUSIONS: Cataract surgery performed with a low-energy femtosecond laser was non-inferior to CP; however, the FLACS group had a statistically significantly lower increase in CCT at Day 7 compared with CP. Trial registration This trial is registered at ClinicalTrials.gov on May 15, 2019, with trial registration number: NCT03953053.

Simultaneous real-time analysis of tear film optical quality dynamics and functional visual acuity in dry eye disease.

BACKGROUND: To assess the effect of tear film instability in dry eye disease (DED) by measuring visual performance and tear film optical quality in a simultaneous real-time analysis system. METHODS: Thirty-seven DED participants and 20 normal controls were recruited. A simultaneous real-time analysis system was developed by adding a functional visual acuity (FVA) channel to a double-pass system. Repeated measurements of FVA and objective scatter index (OSI) were performed simultaneously with this system under blink suppression condition for 20 s. Patient-reported symptoms was evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. Mean FVA, mean OSI, and visual acuity break-up time were defined. The OSI maintenance ratio was calculated as an evaluation index to assess the difference between dynamic OSI changes and baseline OSI. The visual maintenance ratio was also calculated in the same way. RESULTS: Moderate correlations were noted between mean OSI and FVA-related parameters (mean FVA, visual maintenance ratio, visual acuity break-up time: 0.53, - 0.56, - 0.53, respectively, P < 0.01 for all). Moderate to high correlations were noted between OSI maintenance ratio and FVA-related parameters (mean FVA, visual maintenance ratio, visual acuity break-up time: - 0.62, 0.71, 0.64, respectively, all P < 0.01). The metrics derived from the simultaneous real-time analysis system were moderately correlated with the patient-reported symptoms and the visual acuity break-up time possessed the highest correlation coefficients with OSDI total, ocular symptoms, and vision-related function (- 0.64, - 0.63, - 0.62, respectively, P < 0.01). The OSI-maintenance ratio alone appeared to exhibit the best performance of the metrics for the detection of DED with sensitivity of 95.0% and specificity of 83.8% and the combinations of FVA parameters and OSI parameters were valid and can further improve the discriminating abilities. CONCLUSIONS: OSI-related metrics were found to be potential indicators for assessing and diagnosing DED which correlated with both subjective visual performance and patient-reported symptoms; the FVA-related metrics were quantifiable indicators for evaluating visual acuity decline in DED. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR2100051650. Registered 29 September 2021, https://www.chictr.org.cn/showproj.aspx?proj=134612.

Comparison of Refractive Prediction Accuracy With Three Optical Devices.

PURPOSE: To investigate refractive prediction accuracy with the OA-2000 (Tomey), Anterion (Heidelberg Engineering), and IOLMaster 500 (Carl Zeiss Meditec AG) in patients with cataract. METHODS: Patients with cataract referred for phacoemulsification were enrolled and scanned with the OA-2000, Anterion, and IOLMaster 500 in random order. The success rate of axial length (AL) measurements per device was calculated and a chi-square test was used to identify the differences in acquisition rate between the three devices. The Bland-Altman method was used to appraise the agreement of biometric parameters between the three devices. Four different formulas (Barrett Universal II [BUII], Haigis, Holladay 1, and SRK/T) were included in the study. The parameters of refractive prediction accuracy comprised predictive error (PE), absolute PE (AE), and percentages of eyes with a PE within ±0.50, ±0.75, and ±1.00 diopters (D). RESULTS: The acquisition rates of AL measurements with the OA-2000 and Anterion were 97.35% and 94.70%, respectively (chi-square = 3.82, P > .05). A significantly lower acquisition rate of 84.82% was obtained with the IOLMaster 500 compared with the other two devices (P < .05). Bland-Altman analysis identified good agreement between the three biometers with narrow 95% limits of agreement for flat and steep keratometry (K1 and K2), anterior chamber depth (ACD), and AL. For PE, only the differences between the Anterion and IOLMaster 500 with the Barrett UII and Haigis formulas were statistically significant (P < .05). The three devices revealed no statistically significant differences in MAE, MedAE, and the proportion of eyes with a PE within ±0.50, ±0.75, and ±1.00 D (P > .05). CONCLUSIONS: The OA-2000 and Anterion showed a similarly higher acquisition rate of AL measurements than the IOLMaster 500 in patients with cataract. Good agreement for K1, K2, ACD, and AL was found between the three biometers. Regarding refractive prediction accuracy, the Anterion did not significantly outperform both the OA-2000 and IOLMaster 500. [J Refract Surg. 2023;39(1):48-55.].

Agreement Between Predicted and Actual Measured Ablation Depth After FS-LASIK Using Different Rotating Scheimpflug Cameras and OCT.

Purpose: To compare the predicted ablation depth (AD) with the postoperatively measured corneal ablation depth (postop-AD) at central, paracentral, and midperipheral locations using two rotating Scheimpflug analyzers and a Fourier-domain optical coherence tomographer in eyes that underwent femtosecond laser-assisted LASIK (FS-LASIK). Methods: The values of corneal thickness were measured preoperatively and postoperatively at one and three months. The difference between preoperative and postoperative was defined as postop-AD. Measurements were performed at the corneal vertex and mid-peripheral area. The mid-peripheral corneal thickness was measured at the superior, inferior, nasal, and temporal locations at a distance of 1.0 or 2.5 mm from the corneal vertex. The predicted AD was calculated by ORK-CAM software (Schwind eye tech-solutions GmbH, Kleinostheim, Germany), and the difference between the predicted AD and postop-AD was defined as Δ-AD. Paired t-test analysis was employed to evaluate the differences, agreement was assessed by the Bland-Altman method. Results: Forty-two eyes of 42 patients were investigated. At one month, the predicted AD in the central and paracentral areas was underestimated by the Pentacam HR (Oculus, Wetzlar, Germany), Sirius (Costruzione Strumenti Oftalmici, Florence, Italy) and RTVue OCT (Optovue Inc., Freemont, CA, United States), whereas Δ-AD was negative as established by all devices and predominantly statistically significant. The Δ-AD values approximated zero at three months. The mean difference of Δ-AD at three months at the corneal vertex was 0.67 ± 9.39 mm, -7.92 ± 9.05 mm and -1.36 ± 8.31 mm, respectively. The mid-peripheral measurements had positive values at one month and even more highly positive at three months (with statistically significant differences in most of the cases). The agreement between the predicted and postop-AD was moderate with all devices, but slightly better with RTVue. Conclusion: The predicted AD seems to be underestimated in the central and paracentral corneal area and overestimated in the mid-periphery. Translational Relevance: The study could help to partly explain and prevent the refractive errors after FS-LASIK.

Repeatability and Agreement of Two Swept-Source Optical Coherence Tomographers for Anterior Segment Parameter Measurements.

PURPOSE: The aim was to evaluate the repeatability and agreement of two swept-source optical coherence tomographers for anterior segment parameters in healthy subjects. PATIENTS AND METHODS: Automated mark of scleral spur and angle recess for the CASIA2 and manual mark of scleral spur and angle recess for the Anterion were performed, and then the measurement values of the related parameters were automatically generated. Subjects with pupil diameter (PD) differing by <15% between the 2 devices were included. PD, lens vault (LV), anterior chamber depth (ACD), angle to angle distance (ATA), anterior chamber width (ACW), anterior chamber angle (ACA), angle opening distance (AOD), and trabecular iris space area (TISA) were measured in the horizontal images with both CASIA2 and Anterion. Intraclass correlation coefficient (ICC) was used to evaluate intradevice repeatability. Bland-Altman plots were performed to assess the agreement between the 2 devices. RESULTS: Thirty-five right eyes of 35 subjects were included with a mean age of 25.60±3.00 years. The CASIA2 showed moderate to good intradevice repeatability (ICCs ranged from 0.786 to 0.989) whereas the Anterion showed good intradevice repeatability (ICCs ranged from 0.921 to 0.998) for anterior segment parameters. Compared with the CASIA2, the Anterion offered larger values of ACA500/750, AOD500/750, and TISA500/750 but smaller values of PD, LV, ACD, ATA, and ACW. Good agreement for PD, ACD, ATA, and ACW was detected with 95% limits of agreement of -1.02 to 1.02 mm, -0.11 to 0.14 mm, -0.17 to 0.19 mm, -0.13 to 0.28 mm, respectively. Poor agreement for LV, ACA500/750, AOD500/750, and TISA500/750 was achieved with the 2 devices. CONCLUSIONS: Anterion outperformed CASIA2 on intradevice repeatability. While agreement was noted for some parameters using manual Anterion and automated CASIA2 approaches, poor agreement of LV and angle parameters indicates that measurements from these optical coherence tomography devices should not be considered interchangeable.

Habitual Coffee Consumption Increases Risk of Primary Open-Angle Glaucoma: A Mendelian Randomization Study.

PURPOSE: To explore whether there is a causal relationship between coffee consumption and primary open-angle glaucoma (POAG). DESIGN: Two-sample Mendelian randomization (MR). PARTICIPANTS: The single-nucleotide polymorphisms (SNPs) associated with coffee consumption (including phenotypes 1 and 2) were selected from a genome-wide association study (GWAS) involving 121 824 individuals of European descent. Coffee intake from the MRC-IEU UK Biobank was also used to identify instruments for coffee intake. Summary-level data for POAG were obtained from the largest publicly available meta-analyses involving 16 677 POAG cases and 199 580 controls of European descent. METHODS: The inverse variance-weighted (IVW) method was the main MR analysis, whereas weighted-median, weighted mode-based estimate (MBE), MR Pleiotropy RESidual Sum and Outlier (PRESSO) test, and MR-Egger regression were used for sensitivity analysis. MAIN OUTCOME MEASURES: Diagnosis of POAG. RESULTS: Three sets of instrumental variables were used to evaluate the causal association between coffee consumption and POAG risk. Results showed that genetically predicted higher coffee consumption phenotype 1 (cups/day) was significantly associated with higher risk of POAG (odds ratio [OR], 1.241; 95% confidence interval [CI], 1.041-1.480; P = 0.016). Genetically predicted higher coffee consumption phenotype 2 (high vs. no/low) was also significantly associated with higher risk of POAG (OR, 1.155; 95% CI, 1.038-1.284; P = 0.008, using the IVW method). Moreover, genetically predicted higher coffee intake from the MRC-IEU UK Biobank OpenGWAS was significantly associated with a higher risk of POAG (OR, 1.727; 95% CI, 1.230-2.425; P = 0.002, using the IVW method). Sensitivity analyses confirmed that the findings were robust to possible pleiotropy. CONCLUSIONS: These findings provide the genetic evidence that higher coffee consumption is associated with a higher risk of POAG. Given that coffee is widely consumed, our findings provide new insights into potential strategies to prevent and manage POAG.

A One-Step Electrochemical Aptasensor Based on Signal Amplification of Metallo Nanoenzyme Particles for Vascular Endothelial Growth Factor.

In this study, a one-step electrochemical aptasensor was developed to detect the biomarker vascular endothelial growth factor (VEGF), an important protein in the pathogenesis of many retinal diseases, including age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, and retinal vein occlusion. The aptamer has a good affinity and can rapidly identify and capture VEGF based on its unique structure. We designed a VEGF aptasensor based on the aptamer recognition and complex metallo nanoenzyme particles as an electron exchange center and bridge between capture DNA and electrode. The aptamers maintained the hairpin structure to avoid nonspecific surface adsorption and expose the capture sequence outwards when the target was inexistent. Conversely, the aptamers opened the hairpin structure to release space to accomplish binding between VEGF and DNA, resulting in increased impedance. The performance of the electrochemical aptasensor is detected by electrochemical impedance spectroscopy (EIS). The limit of detection by EIS was as low as 8.2 pg ml-1, and the linear range was 10 pg ml-1-1 µg ml-1. The electrochemical aptasensor also showed high specificity and reproducibility.

Comparison of acquisition rate and agreement of axial length with two swept-source optical coherence tomographers and a partial coherence interferometer.

PURPOSE: To assess the acquisition rate and agreement of axial length (AL) measurements with the OA-2000, Anterion, and IOLMaster 500 in cataractous patients. METHODS: In total, 298 eyes of 191 cataractous patients were enrolled and scanned with the three devices in random order. The success rate of AL measurements per device was calculated and a chi-square test was utilized to identify the differences in acquisition rate between the three devices. Logistic regression analysis was applied to evaluate the association of different cataract types and severity with the AL measurement acquisition rate. Bland-Altman plots were mapped to appraise the agreement of AL values. RESULTS: AL measurements were successfully achieved in 288 eyes (96.64%) with the OA-2000, in 282 eyes (94.30%) with the Anteiron, and in 246 eyes (82.55%) with the IOLMaster 500. Significant differences in the acquisition rate were found between either of the SS-OCT devices and IOLMaster 500 by chi-square analysis (P < 0.001). No significant difference was noted between OA-2000 and Anterion. Increasing severity of posterior subcapsular cataract was associated with a higher failure rate with the IOLMaster 500. Bland-Altman analysis identified good agreement between the three biometers with narrow 95% limits of agreement. CONCLUSIONS: The OA-2000 and Anterion showed similarly higher acquisition rate of AL measurements than IOLMaster 500 in cataractous patients. Good agreement for AL values was found between the three biometers in cataractous patients.

Novel SOX2 mutation in autosomal dominant cataract-microcornea syndrome.

BACKGROUND: Congenital cataract-microcornea syndrome (CCMC) is characterized by the association of congenital cataract and microcornea without any other systemic anomaly or dysmorphism. Although several causative genes have been reported in patients with CCMC, the genetic etiology of CCMC is yet to be clearly understood. PURPOSE: To unravel the genetic cause of autosomal dominant family with CCMC. METHODS: All patients and available family members underwent a comprehensive ophthalmologic clinical examination in the hospital by expert ophthalmologists and carried out to clinically diagnosis. All the patients were screened by whole-exome sequencing and then validated using co-segregation by Sanger sequencing. RESULTS: Four CCMC patients from a Chinese family and five unaffected family members were enrolled in this study. Using whole-exome sequencing, a missense mutation c.295G > T (p.A99S, NM_003106.4) in the SOX2 gene was identified and validated by segregation analysis. In addition, this missense mutation was predicted to be damaging by multiple predictive tools. Variant p.Ala99Ser was located in a conservation high mobility group (HMG)-box domain in SOX2 protein, with a potential pathogenic impact of p.Ala99Ser on protein level. CONCLUSIONS: A novel missense mutation (c.295G > T, p.Ala99Ser) in the SOX2 gene was found in this Han Chinese family with congenital cataract and microcornea. Our study determined that mutations in SOX2 were associated with CCMC, warranting further investigations on the pathogenesis of this disorder. This result expands the mutation spectrum of SOX2 and provides useful information to study the molecular pathogenesis of CCMC.

Causal Associations of Thyroid Function and Age-Related Macular Degeneration: A Two-Sample Mendelian Randomization Study.

PURPOSE: To determine whether causal association lies between thyroid function and age-related macular degeneration (AMD) risk in human beings. DESIGN: Two-sample Mendelian randomization (MR) study. METHODS: The single-nucleotide polymorphisms associated with free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were selected from a genome-wide association study (GWAS) of 72,167 individuals of European descent. Summary-level data for AMD were obtained from a GWAS published by the International Age-related Macular Degeneration Genomics Consortium of 33,526 individuals (16,144 cases and 17,832 controls). An inverse-variance-weighted (IVW) method was the main MR analysis. Maximum likelihood, weighted median, MR-Egger, MR-pleiotropy residual sum outlier methods were used for the sensitivity analysis. RESULTS: An increase of 1 SD in genetically predicted FT4 levels was found to be significantly associated with an 18.9 % increase in the overall AMD risk (P = .005). In the multivariable MR analysis controlling for TSH level, the causal effect of FT4 level on the risk of AMD remained (odds ratio [OR] = 1.207, P = .004). A 1-SD increase in TSH levels was nominally associated with a 10.0% decrease in the overall AMD risk (P = .032). After adjusting for FT4 level by multivariable MR analysis, no direct causal relationship was found between TSH level and AMD risk (95% CI = 0.810, 1.125, P = .582). CONCLUSIONS: Genetic variants predisposing to higher FT4 levels within the normal range were associated with higher AMD risk. Further studies are required to understand the mechanism underlying this putative causal relationship.

Repeatability of a new swept-source optical coherence tomographer and agreement with other three optical biometers.

PURPOSE: To investigate the repeatability of Anterion and compare the agreement of ocular biometric measurements and predicted intraocular lens (IOL) powers with other three optical biometers. METHODS: Flat keratometry (Kf), steep keratometry (Ks), J0 and 45 vectors, central cornea thickness (CCT), anterior chamber depth (ACD), and axial length (AL) from the Anterion, IOLMaster 700, Lenstar LS 900, and OA-2000 were recorded. The IOL powers were calculated with the Hoffer Q, Holladay 1, SRK/T, and Haigis formulas. The repeatability was evaluated using the within-subject standard deviation (Sw), repeatability coefficient (RC), coefficient of variation (COV), and intraclass correlation coefficient (ICC). Inter-device agreement between the four biometers was assessed with the 95% limits of agreement. RESULTS: In total, 101 right eyes of 101 participants were enrolled. The Anterion showed good repeatability for all the included biometric parameters with all the CoV ≤ 0.30% and ICC ≥ 0.930 except for J45 with moderate repeatability (ICC was 0.849). Good agreement was found among the four devices for Kf, Ks, J0, J45, ACD, and AL. Generally, wide 95% LoA was found for the predicted IOL powers with the four IOL calculation formulas between the four devices. CONCLUSIONS: The Anterion showed good repeatability of biometric measurements for most parameters. Good agreement among the four optical biometers was achieved for all the parameters except for CCT and the predicted IOL power. The AL values exhibited the best repeatability with Anterion and the best agreement among the biometers in our study.

Effect of travoprost, latanoprost and bimatoprost PGF2α treatments on the biomechanical properties of in-vivo rabbit cornea.

Prostaglandin F2α analogues (PGF2α), one of the most commonly prescribed classes of hypotensive agents, could decrease collagen fibril density and remodel the extracellular matrix in cornea. We hypothesized that PGF2α's would induce corneal softening, reduce the accuracy of intraocular pressure (IOP) measurement and lead to uncertainty in the effectiveness of the therapy. We determined the stress-strain behavior of rabbit cornea after PGF2α usage and evaluated the effect of biomechanical changes associated with PGF2α treatment on IOP measurements by Goldmann Applanation Tonometry (GAT). The tangent modulus decreased after PGF2α treatment, while the stromal interfibrillar spacing increased. PGF2α was shown to also affect the lateral eye with lower effect, which did not undergo direct eyedrop treatment. Significant decreases in the numerical predictions of GAT-IOP were predicted in all treated groups relative to control groups. Different PGF2α's (travoprost, latanoprost and bimatoprost) were associated with different extents of reduction in tissue stiffness and changes in corneal microstructure. PGF2α-induced changes in corneal mechanical properties could reduce the accuracy of IOP measurement and may cause an overestimation of the effect of PGF2α in lowering IOP, possibly leading to uncertainties in glaucoma management.

Topography-Guided Versus Wavefront-Optimized LASIK for Myopia With and Without Astigmatism: A Meta-analysis.

PURPOSE: To evaluate the differences in efficacy, predictability, safety, and visual quality between topography-guided customized ablation treatment (TCAT) and wavefront-optimized (WFO) laser in situ keratomileusis (LASIK) for the treatment of myopia with and without astigmatism. METHODS: A comprehensive literature search of PubMed, Embase, the Cochrane library, Web of Science, and ClinicalTrials was used to identify randomized controlled trials (RCTs) comparing TCAT-LASIK with WFO-LASIK for myopia with and without astigmatism up to September 2020. The references of all searched literature were checked as supplements. Literature was screened according to the inclusion and exclusion criteria and relative data were extracted. RevMan software version 5.3.0 (Cochrane Collaboration) was used for meta-analysis. RESULTS: A total of seven RCTs (1,168 eyes) were included. There were no statistically significant differences in the ratio of uncorrected distance visual acuity of 20/20 or better (relative risk [RR] = 1.01, 95% CI [0.97 to 1.06], P = .64) and 20/16 or better (RR = 0.96, 95% CI [0.80 to 1.16], P = .69). Compared with WFO-LASIK, TCAT-LASIK achieved a higher proportion of postoperative manifest refractive spherical equivalent within ±0.50 diopters of the target (RR = 1.06, 95% CI [1.02 to 1.11], P = .003) and less surgically induced higher order aberrations (weighted mean difference [WMD] = -0.11, 95% CI [-0.15 to -0.0], P < .00001), spherical aberrations (WMD = -0.04, 95% CI [-0.05 to -0.03], P < .00001), and coma (WMD = -0.15, 95% CI [-0.28 to -0.01], P = .03). No patient lost two or more lines of distance-corrected visual acuity postoperatively in the two groups. CONCLUSIONS: This meta-analysis suggests that both TCATLASIK and WFO-LASIK show excellent efficacy, predictability, and safety for myopia. TCAT-LASIK exhibited more accurate postoperative refraction predictability and less surgically induced higher order aberrations, spherical aberrations, and coma. More randomized, prospective, and large sample-sized studies are needed to confirm these conclusions in the long term. [J Refract Surg. 2021;37(10):707-714.].

Reliability and agreement of the central and mid-peripheral corneal thickness measured by a new Scheimpflug based imaging.

BACKGROUND: To assess the intra-observer repeatability and inter-observer reproducibility of central corneal thickness (CCT) and mid-peripheral corneal thickness (MPCT) measurements using a new Scheimpflug imaging instrument (Scansys) and compare the agreement with the rotating Scheimpflug corneal tomographer (Pentacam HR). METHODS: The same well-trained operator performed the measuring using the two devices, after which Scansys measurements were repeated by another operator. Both instruments required three consecutive measurements per subject. Corneal thickness measurements were obtained by each instrument, including CCT, thinnest corneal thickness (TCT), pupil corneal thickness (PCT), and MPCT. Test-retest repeatability (TRT), within-subject coefficient of variation (CoV), and intra-class correlation coefficient (ICC) were used to evaluate repeatability and reproducibility. A paired t-test was used to compare the differences between Scansys and Pentacam, and the agreement was compared with Bland-Altman plots. RESULTS: This study enrolled 112 healthy subjects. The CoV were <0.91% and 0.55% for repeatability and reproducibility, respectively. The ICC was close to 1 in all measurements. For intra-observer repeatability in the CT2mm region, TRT was <10.30 µm. Moreover, TRT was <15.26 µm within the CT5mm region. The paired t-test showed significant differences in all corneal thickness measurements (P<0.001). The central region and CT2mm agreement were high, but the largest range of 95% limits of agreement (LoA) appeared in the CTnasal-5mm. CONCLUSIONS: The new Scheimpflug imaging instrument showed excellent intra-observer repeatability and inter-observer reproducibility for corneal thickness measurements. The agreement analysis suggested that Scansys and Pentacam could be interchangeably used between the central region and CT2mm, except CT5mm.

Biomechanical Effects of Two Forms of PGF2α on Ex-vivo Rabbit Cornea.

PURPOSE: To investigate the biomechanical effects of two synthetic prostaglandin F2α analogues (PGF2α), namely Travoprost and Tafluprost, on the ex-vivo rabbit cornea. MATERIALS AND METHODS: Ninety-six eyes of 48 Japanese white rabbits were divided into 3 equal groups randomly; the Travoprost treated group (Tra), the Tafluprost treated group (Taf) and the control group (Co). Eyes in Tra and Taf groups were preserved in storage medium for 10 days with 1:10 Travoprost and Tafluprost diluents, respectively; while the Co eyes were preserved in a similar but PGF2α-free medium. Twenty-four corneas of each group were tested under inflation conditions with up to 30 mmHg posterior pressure. The pressure-deformation data obtained experimentally were used in an inverse analysis process to derive the stress-strain behavior of the tissue, using which the tangent modulus, a direct measure of the tissue's material stiffness, was calculated. The remaining eight specimens of each group were analyzed using electron microscopy for fibril diameter and interfibrillar spacing. RESULTS: Although the central corneal thickness increased significantly in the three groups after storage (p < .01), it was similar in all groups both before (p = .598) and after storage (p = .181). After treatment with Travoprost and Tafluprost, the corneas exhibited lower tangent modulus (by 29.2% and 29.8%, respectively, at 6 kPa stress) and larger stromal interfibril spacing (by 21.9% and 23.6%) compared with the control group. There was no significant change in fibril diameter with either Travoprost or Tafluprost treatment (p = .769). CONCLUSIONS: The results demonstrated significant reductions in tangent modulus and increases in interfibrillar spacing, which were of similar magnitudes, with the application of two different forms of PGF2α.