Mutational screening of AGRN, SLC39A5, SCO2, P4HA2, BSG, ZNF644, and CPSF1 in a Chinese cohort of 103 patients with nonsyndromic high myopia.

Purpose: High myopia (HM) is one of the leading causes of irreversible vision loss in the world. Many myopia loci have been uncovered with linkage analysis, genome-wide association studies, and sequencing analysis. Numerous pathogenic genes within these loci have been detected in a portion of HM cases. In the present study, we aimed to investigate the genetic basis of 103 patients with nonsyndromic HM, focusing on the reported causal genes. Methods: A total of 103 affected individuals with nonsyndromic HM were recruited, including 101 patients with unrelated sporadic HM and a mother and son pair. All participants underwent comprehensive ophthalmic examinations, and genomic DNA samples were extracted from the peripheral blood. Whole exome sequencing was performed on the mother and son pair as well as on the unaffected father. Sanger sequencing was used to identify mutations in the remaining 101 patients. Bioinformatics analysis was subsequently applied to verify the mutations. Results: An extremely rare mutation in AGRN (c.2627A>T, p.K876M) was identified in the mother and son pair but not in the unaffected father. Another two mutations in AGRN (c.4787C>T, p.P1596L/c.5056G>A, p.G1686S) were identified in two unrelated patients. A total of eight heterozygous variants potentially affecting the protein function were detected in eight of the remaining 99 patients, including c.1350delC, p.V451Cfs*76 and c.1023_1024insA, p.P342Tfs*41 in SLC39A5; c.244_246delAAG, p.K82del in SCO2; c.545A>G, p.Y182C in P4HA2; c.415C>T, p.P139S in BSG; c.3266A>G, p.Y1089C in ZNF644; and c.2252C>T, p.S751L and c.1708C>T, p.R570C in CPSF1. Multiple bioinformatics analyses were conducted, and a comparison to a group with geographically matched controls was performed, which supported the potential pathogenicity of these variants. Conclusions: We provide further evidence for the potential role of AGRN in HM inheritance and enlarged the current genetic spectrum of nonsyndromic HM by comprehensively screening the reported causal genes.

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.

Clinicopathological features and surgical treatment of intratarsal keratinous cysts.

PURPOSE: To explore the clinical and histopathologic features and surgical outcome of intratarsal keratinous cyst (IKC). METHODS: The clinical findings, histopathologic evaluations, and immunohistochemical studies in 15 cases of IKC were investigated, retrospectively. RESULTS: Fifteen patients with an average age of 44.7 years had noninflamed eyelid cysts sized 1-6 mm in diameter. The cysts appeared as solid, whitish opalescent or yellow-white, mildly elevated lesions beneath the palpebral conjunctiva. The cysts embedded in the tarsus were completely excised with a portion of the adjacent tarsus by a surgical procedure through palpebral conjunctival approach. Histopathologic evaluations revealed stratified squamous epithelium linings and keratin contents, which were not identical to the common epidermal or epidermoid cysts. The results were negative for Alcian blue and periodic acid-Schiff staining and showed positive correlation to the immunoreaction for epithelial membrane antigen. No recurrence occurred in all patients who had their lesions removed completely. CONCLUSIONS: Our study revealed the clinical and pathological characteristics of IKC, including the absence of inflammatory sign, lesion partially embedded in the tarsus and protruding beneath the conjunctiva with the intracystic keratinous contents, stratified squamous epithelium linings, string-like keratin contents from the histopathology sections, and strongly immunoreactivity to antibodies against epithelial membrane antigen. A complete excision of cysts with adjacent tarsectomy by transconjunctival approach was proved to be an effective treatment for prevention of recurrence.

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.

A novel ophthalmic viscosurgical device-free phakic intraocular lens implantation makes myopic surgery safer.

PURPOSE: To assess the efficacy and safety of a novel ophthalmic viscosurgical device-free (OVD-free) method for posterior chamber phakic intraocular lens (PIOL) implantation in myopic eyes. METHODS: In this retrospective cohort study, the medical records of myopic eyes that underwent PIOL (Implantable Collamer Lens, ICL) implantation for myopia correction at the Eye Hospital of Wenzhou Medical University between May 2015 and March 2017 were reviewed. A total of 49 eyes with complete data that met follow up requirements (2 h, 1 day, 1 week, 3 months postoperatively) were recruited. Based on the surgical techniques used, the eyes were divided into the OVD-free method group and the standard method group. The clinical data, including intraocular pressure (IOP), corrected distance visual acuity (CDVA) and spherical equivalent (SE), at each follow-up were collected for comparison. Endothelial cell loss and complications were also investigated. RESULTS: Twenty-one eyes received the standard method, and 28 eyes received the OVD-free method. A rise in IOP > 22 mmHg at 2 h was noted in 14 eyes (66.7%) in the standard group and none (0%) in the OVD-free group (p < 0.001). The rise in IOP from baseline was significantly higher at 2 h in the standard group (10.5 ± 5.2 mmHg vs. 2.2 ± 3.3 mmHg, difference: 8.3, 95% CI 5.8 to 10.8; p < 0.001). There was a significant difference in the time course of LogMAR CDVA changes between the two groups (p = 0.047). The LogMAR CDVA was significantly better in the OVD-free method group compared to the standard group at 1 day (- 0.076, 95% CI - 0.134 to - 0.018; p = 0.012), 1 week (- 0.071, 95% CI - 0.135 to - 0.007; p = 0.03), but not at 3 months (- 0.046, 95% CI - 0.107 to 0.015; p = 0.134). There was no significant difference in the time course of SE changes between the two groups (p = 0.471; p = 0.705). In the OVD-free group, mean endothelial cell loss was 4.6% at 3 months (2522 ± 281 vs. 2407 ± 226 cells/mm2, difference: -115, 95% CI - 295 to 65; p = 0.187). No complications were reported in both groups except for the early IOP elevation in the standard group during the observation period. CONCLUSIONS: The OVD-free method is safe and efficient for ICL implantation. It can be a safer method of ICL implantation compared to the standard method in that it completely eliminates ophthalmic viscoelastic devices-related complications without causing additional complications.

Age-Related Changes in Corneal Spherical Aberration.

PURPOSE: To analyze the age-related changes in corneal spherical aberration (CSA) and higher order aberrations (HOAs) and to develop a novel model to estimate the change in CSA with age. METHODS: This was a cross-sectional study of the right eyes of 3,769 patients. Anterior corneal spherical aberration (ASA), posterior corneal spherical aberration (PSA), total corneal spherical aberration (TSA), and the root mean square of corneal HOAs were measured using a Scheimpflug tomographer. Smoothed fitting curves were plotted as a function of age and the average change in spherical aberration was calculated for different ages. RESULTS: The mean magnitude of ASA, PSA, TSA, and HOAs (6 and 4 mm) were 0.270 ± 0.111, -0.144 ± 0.031, 0.228 ± 0.120, 0.453 ± 0.194, and 0.141 ± 0.075 µm, respectively. All parameters showed a statistically significant non-linear change with age. The age after which the aberrations increased at a faster rate, namely the turning points of age, were 39 years for ASA, PSA, TSA, and 6-mm HOAs (95% confidence interval [CI]: 35 to 42, 36 to 41, 36 to 42, and 35 to 56 years, respectively) and 46 years for 4-mm HOAs (95% CI: 36 to 56 years). There were significant increases in increment rates after the turning points. The average change of TSA was -0.013 µm/10 years from 18 to 39 years and 0.057 µm/10 years after 39 years. There were statistically significant correlations between ASA and TSA (r = 0.976, P < .001) and PSA and TSA (r = 0.192, P < .001), but not between ASA and PSA (r = -0.003, P = .835). CONCLUSIONS: CSA and HOAs increased non-linearly with age and became more positive after 39 and 46 years of age, respectively. Based on the increment rates and turning points of age, a novel model is provided to help calculate the value required to compensate for the increasing CSA associated with the aging cornea. [J Refract Surg. 2018;34(11):760-767.].

Age-Related Changes in Corneal Astigmatism.

PURPOSE: To analyze the changes in corneal astigmatism as a function of age and develop a novel model to estimate corneal astigmatic change according to age. METHODS: This was a cross-sectional study of right eyes of 3,769 individuals. Total corneal astigmatism, keratometric astigmatism, anterior corneal astigmatism, and posterior corneal astigmatism were measured by a Scheimpflug tomographer. Smoothing fitting curves of polar values of corneal astigmatism as a function of age were drawn and average changes in corneal astigmatism at different ages were calculated. RESULTS: Two turning points of age on total corneal astigmatism were 36 and 69 years. The average change of total corneal astigmatism toward against-the-rule astigmatism was 0.13 diopters (D)/10 years from 18 to 35 years, 0.45 D/10 years from 36 to 68 years, and decreased after 69 years, mainly caused by anterior corneal astigmatism. The mean magnitude of posterior corneal astigmatism was -0.33 D and exceeded 0.50 D in 14.27% of eyes. The vectorial difference between total corneal astigmatism and keratometric astigmatism was correlated with posterior corneal astigmatism, polar value of anterior corneal astigmatism, age, and corneal higher order aberrations (r = 0.636; standard partial regression coefficients were 0.479, -0.466, 0.282, and 0.196, respectively; all P < .001). Based on the non-linear model to estimate corneal astigmatic change with age, a formula was developed to calculate recommended correction of astigmatism according to age and astigmatic type. CONCLUSIONS: The rate of change of total corneal astigmatism showed a non-linear trend toward against-the-rule astigmatism, which was low at young and old age, high at middle age, and should be taken into account when performing surgery to correct astigmatism. [J Refract Surg. 2017;33(10):696-703.].

In Vivo Observation of Lens Regeneration in Rat Using Ultra-Long Scan Depth Optical Coherence Tomography.

Purpose: To evaluate morphologic changes of lens regeneration in rats in vivo after extracapsular lens extraction (ECLE) by ultra-long scan depth optical coherence tomography (UL-OCT). Methods: A total of 42 Sprague-Dawley rats were used in this study. We performed ECLE on the right eyes of animals in the surgery group (n = 34). Biomicroscopy and UL-OCT scans were carried out for the surgery group immediately (within 1 hour postoperatively) and at days 1 and 3, weeks 1 and 2, and months 1, 2, and 3 postoperatively. After in vivo examination, three animals of the surgery group were euthanized at each time point for histology study, while the other 10 animals were examined continuously at those time points. The regenerated lens was evaluated in OCT images at 2 and 3 months postoperatively. The control group consisted of eight untreated rats that had OCT examination at the age of 5 months. Results: Lens regeneration could be observed from 2 weeks postoperatively. Regeneration was mainly at the peripheral capsular bag in the first month and central region thereafter. The average thickness of regenerated lenses was 2222 ± 309 and 2324 ± 352 µm at 2 and 3 months, respectively. Regeneration was faster in the first 2 months and slowed down thereafter. Although anterior capsule opening and posterior capsule adhesion and wrinkling existed, the regenerated lens still could form a relatively regular shape, however, the size was much smaller than that of the normal lenses from rats with the same age. Conclusions: Ultra-long OCT provides longitudinal data of the process of lens regeneration on a single individual rat in vivo, which may allow one to follow and compare the lens regenerative process under different interventions or therapy after ECLE in rats.