The Impact of Corneal Epithelial Thickening and Inhomogeneity on Corneal Aberrations After Small Incision Lenticule Extraction.

PURPOSE: To investigate the corneal epithelial remodeling profile after small incision lenticule extraction (SMILE), the correlated explanatory variables, and its potential impact on corneal higher order aberrations (HOAs). METHODS: This single-center study prospectively evaluated 75 right eyes of 75 patients scheduled for SMILE. An anterior segment optical coherence tomography device was used to automatically obtain central 6-mm corneal epithelial thickness (ET), total corneal HOAs, and individual Zernike components before and after surgery. The ET inhomogeneity over the central 3- and 6-mm cornea was quantified with coefficient of variance (CV). RESULTS: Both ET and CV significantly increased 1 month postoperatively (all P < .05). The stepwise multiple regression analysis showed that ET and CV were significantly correlated with preoperative ET and CV, respectively (all P < .01). The corrected spherical equivalent also significantly influenced ET and CV (all P < .01). Over the central 6-mm zone, the alterations of total corneal HOAs and individual Zernike components such as vertical coma (Z7) and spherical aberration (Z12, Z24) were significantly correlated with ET and CV (all P < .05). CONCLUSIONS: The SMILE-induced epithelial remodeling involved both ET and ET inhomogeneity. The modulation was associated with preoperative and treatment parameters, and exerted a significant impact on corneal HOA alterations especially over the central 6-mm cornea. Together with the amount of correction and corneal curvature gradient change, preoperative assessment of ET and ET inhomogeneity might help predict postoperative epithelial remodeling. [J Refract Surg. 2023;39(1):23-32.].

Potential effects of angiogenesis-related factors on the severity of APAC and surgical outcomes of trabeculectomy.

BACKGROUND: EPO (erythropoietin) and PDGF (platelet derived growth factor) families are thought to be associated with angiogenesis under hypoxic condition. The sharp rise of intraocular pressure in acute primary angle closure (APAC) results in an inefficient supply of oxygen and nutrients. We aimed to measure the expression of EPO and PDGF family members in APAC eyes and demonstrate their associations with APAC's surgical success rate. METHODS: Concentrations of EPO, PDGF-AA, -BB, -CC and -DD collected in aqueous humor samples of 55 patients recruited were measured. Before operations, correlations between target proteins and IOP (intraocular pressure) were detected between APAC (acute primary angle closure) and cataract patients. Based on the post-operative follow-up, the effects of EPO and PDGF family members on the successful rate of trabeculectomy were tested. RESULTS: The levels of EPO, PDGF-CC and -DD were significantly elevated in the APAC group compared to the cataract group. During the post-operative follow-up, EPO, PDGF-CC and -DD showed significant differences between the success and failure groups. In multivariable linear regression analyses, failed filtration surgery was more likely in APAC eyes with higher EPO level. The Kaplan-Meier survival plot suggested that the success rate in eyes with low EPO level was significantly higher than that in eyes with high EPO level. CONCLUSION: The levels of EPO, PDGF-CC and -DD were significantly elevated in failure group. EPO level correlated with preoperative IOP and numbers of eyedrops, and higher EPO level in aqueous humor is a risk factor for trabeculectomy failure. It can be a biomarker to estimate the severity of APAC and the success rate of surgery. The investigation of mechanism of EPO in APAC a may have potential clinical applications for the surgical treatment of APAC.

Transient reduction in the retinal microvascular network following implantation surgery of implantable collamer lens: An OCT angiography study.

Purpose: To evaluate changes in the retinal microvascular network after posterior chamber phakic implantable collamer lens (ICL) surgery using optical coherence tomography angiography (OCTA) in patients with high myopia. Methods: Patients with high myopia who underwent ICL surgery were enrolled in this study. All patients underwent comprehensive ophthalmologic exams preoperatively and 1 week, 1 month, and 3 months postoperatively. The vascular densities (VDs) in the retina and the superficial and deep capillary plexuses of different annular and quadrantal areas were evaluated from OCTA images (Zeiss Cirrus 5000). Correlations between the variations in microvascular density and possible factors were further analyzed. Results: The study comprised 32 eyes of 32 patients. The mean age of the patients was 26.91±7.610 years (15 men and 17 women). A statistically significant reduction in microvascular density in the retina and the superficial plexus was found 1 week and 1 month postoperatively (p<0.05, repeated-measures ANOVA). Further fractal analysis found that the VD of the outer ring declined statistically significantly (p<0.05). A statistically significant decrease was also found in the inferior nasal sector 1 week postoperatively, with an overall decrease in all four quadrants 1 month postoperatively. The microvascular density recovered toward the baseline level 3 months postoperatively. No correlations were observed between the variation in microvascular density and the spherical equivalent (SE), axial length (AL), intraocular pressure (IOP), amplitude of accommodation (AA), or contrast sensitivity. Conclusions: Retinal microvascular density was decreased postoperatively and then recovered toward the baseline level after 3 months. ICL surgery may have a transient influence on the retinal microvascular network without affecting visual function.

Transient Alteration of Retinal Microvasculature after Refractive Surgery.

PURPOSE: The purpose of this study was to determine the retinal microvasculature in myopic patients after refractive surgery. METHODS: Thirty-six right eyes of 36 patients who undertook femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) were imaged using optical coherence tomography angiography preoperatively, 1-week, 1-month, and 3-month postoperation, respectively. Vessel density was analyzed after the correction of magnification, and results were correlated with clinical manifestations, including spherical equivalent (SE), amplitude of accommodation, intraocular pressure, and axial length. RESULTS: There was a significant decrease in microvascular density 1-week postoperation compared to preoperative measurement (p < 0.05), and it recovered 1-month postoperation. Microvascular densities in superficial vascular plexus (r = 0.528, p < 0.01), deep vascular plexus (r = 0.500, p < 0.01), and retinal vascular network (r = 0.390, p < 0.05) were all positively correlated with the decrease of the SE 1-week postoperation. CONCLUSION: The transient alteration of the retinal microvasculature after refractive surgery appeared to recover quickly, which may not impact the visual function after FS-LASIK.

Microbial Contamination of Rigid Gas Permeable (RGP) Trial Lenses and Lens Cases in China.

Purpose: This study aimed to evaluate the microbial contamination level and its influencing factors of rigid gas permeable (RGP) trial lenses and lens cases in China.Materials and Methods: A total of 107 RGP trial lenses and lens cases were collected from 7 main hospitals or optometric centers in China. Three sites including the lenses, case interiors and case screw tops were sampled for bacterial and fungal culture and identification. The contamination rates of these three sites and their relationship with lens care regimes were further analyzed.Results: The overall contamination rate was 73.8% for either lenses or cases, and 43.0% of lenses, 57.0% of case interiors and 65.4% of case screw tops respectively. The most frequently isolated microorganisms were Serratia spp., Burkholderia spp., Pandoraea spp., and Achromobacter spp. from all three sites. The contamination rate was positively related to the lens use frequency. Compared with dry-stored lenses, the contamination rate was significantly higher in wet-stored group (P < .001*). Inadequate disinfection and improper lens and case care regimes were also associated with higher contamination rates.Conclusions: Our study reported that the RGP trial lenses and cases used for fittings had a considerably high contamination rate. The safe use of RGP trial lenses and education of optometrists on the regular maintenance of trial lenses should be emphasized.

LY2109761, Transforming Growth Factor ß Receptor Type I and Type II Dual Inhibitor, is a Novel Approach to Suppress Endothelial Mesenchymal Transformation in Human Corneal Endothelial Cells.

BACKGROUND/AIMS: Preventing undesirable endothelial-mesenchymal transformation (EnMT) with repetitious in vitro expansion of human corneal endothelial cells (CECs) is a pivotal issue in cornea regeneration. Previous studies have shown that inhibition of the TGF-ß pathway reduces epithelial-mesenchymal transformation. However, its potential role in EnMT remains poorly understood. As such, the effect of LY2109761, a novel TGF-ß receptor type I and type II dual inhibitor, was investigated on EnMT. METHODS: CECs cultured with various concentrations of LY2109761 were evaluated for their growth rate and phenotype. Additionally, the expression of functional markers (sodium-potassium pump Na+/K+-ATPase and the tight junction protein ZO-1) and mesenchymal markers (CD73, fibronectin, and vimentin) was detected using immunostaining and western blot. The mRNA expressions were also assayed by real-time polymerase chain reaction analysis. RESULTS: At a 1 µM concentration, LY2109761 did not influence the proliferation of CECs and subsequent experiments were therefore performed using this concentration. Furthermore, CECs cultured in the presence of 1 µM LY2109761 maintained their ability to grow as a monolayer of hexagonal-shaped cells. The expression of functional markers increased in LY2109761-treated CECs, while the expression of mesenchymal markers decreased (both in protein and mRNA levels). CONCLUSION: Inhibition of TGF-ß receptor type I and type II by LY2109761 maintained the phenotype of CECs and inhibited the EnMT process. These results indicate the possible continuous in vitro expansion of CECs with normal function.

Effects of Tear Film Lipid Layer Thickness and Blinking Pattern on Tear Film Instability After Corneal Refractive Surgery.

PURPOSE: To investigate associations between changes in tear film instability and the lipid layer thickness (LLT) and blink pattern after corneal refractive surgery (CRS). METHODS: Forty patients were enrolled in this study. The LLT and blink pattern were evaluated 1 week before and 30 days after CRS using a novel interferometer and an ocular surface disease index (OSDI) questionnaire, and other tear film stability markers were also evaluated. RESULTS: Mean OSDI scores increased from 5.52 to 8.54 (P = 0.016), corneal fluorescence staining scores increased from 0.05 to 0.25 (P = 0.034), first noninvasive tear breakup time (NIBUT-F) decreased from 9.66 to 7.33 seconds (P = 0.014), and average noninvasive tear breakup time (NIBUT-Ave) decreased from 12.32 to 10.26 seconds (P = 0.047) 1 month after CRS. Meanwhile, mean total blink frequency in 20 seconds decreased significantly from 12.62 to 6.31 (P < 0.001); LLT did not change significantly (P = 0.447). The change in NIBUT-Ave was positively correlated with that in LLT (P = 0.003) and negatively correlated with that in the partial blink rate (P = 0.013). The changes in the OSDI questionnaire, NIBUT, LLT, and blink pattern were not different between the laser-assisted in situ keratomileusis and laser-assisted subepithelial keratomileusis groups. CONCLUSIONS: A decrease in tear film stability occurs 1 month after CRS, the change in the blink pattern and unchanged LLT preoperatively and postoperatively suggesting that these parameters play a role in maintaining tear film stability after CRS.

Wavefront Derived Refraction and Full Eye Biometry in Pseudophakic Eyes.

PURPOSE: To assess wavefront derived refraction and full eye biometry including ciliary muscle dimension and full eye axial geometry in pseudophakic eyes using spectral domain OCT equipped with a Shack-Hartmann wavefront sensor. METHODS: Twenty-eight adult subjects (32 pseudophakic eyes) having recently undergone cataract surgery were enrolled in this study. A custom system combining two optical coherence tomography systems with a Shack-Hartmann wavefront sensor was constructed to image and monitor changes in whole eye biometry, the ciliary muscle and ocular aberration in the pseudophakic eye. A Badal optical channel and a visual target aligning with the wavefront sensor were incorporated into the system for measuring the wavefront-derived refraction. The imaging acquisition was performed twice. The coefficients of repeatability (CoR) and intraclass correlation coefficient (ICC) were calculated. RESULTS: Images were acquired and processed successfully in all patients. No significant difference was detected between repeated measurements of ciliary muscle dimension, full-eye biometry or defocus aberration. The CoR of full-eye biometry ranged from 0.36% to 3.04% and the ICC ranged from 0.981 to 0.999. The CoR for ciliary muscle dimensions ranged from 12.2% to 41.6% and the ICC ranged from 0.767 to 0.919. The defocus aberrations of the two measurements were 0.443 ± 0.534 D and 0.447 ± 0.586 D and the ICC was 0.951. CONCLUSIONS: The combined system is capable of measuring full eye biometry and refraction with good repeatability. The system is suitable for future investigation of pseudoaccommodation in the pseudophakic eye.

Slitlamp Photography and Videography With High Magnifications.

PURPOSE: To demonstrate the use of the slitlamp photography and videography with extremely high magnifications for visualizing structures of the anterior segment of the eye. METHODS: A Canon 60D digital camera with Movie Crop Function was adapted into a Nikon FS-2 slitlamp to capture still images and video clips of the structures of the anterior segment of the eye. Images obtained using the slitlamp were tested for spatial resolution. The cornea of human eyes was imaged with the slitlamp, and the structures were compared with the pictures captured using the ultra-high-resolution optical coherence tomography (UHR-OCT). The central thickness of the corneal epithelium and total cornea was obtained using the slitlamp, and the results were compared with the thickness obtained using UHR-OCT. RESULTS: High-quality ocular images and higher spatial resolutions were obtained using the slitlamp with extremely high magnifications and Movie Crop Function, rather than the traditional slitlamp. The structures and characteristics of the cornea, such as the normal epithelium, abnormal epithelium of corneal intraepithelial neoplasia, laser in situ keratomileusis interface, and contact lenses, were clearly visualized using this device. These features were confirmed by comparing the obtained images with those acquired using UHR-OCT. Moreover, the tear film debris on the ocular surface and the corneal nerve in the anterior corneal stroma were also visualized. The thicknesses of the corneal epithelium and total cornea were similar to that measured using UHR-OCT (P<0.05). CONCLUSIONS: We demonstrated that the slitlamp photography and videography with extremely high magnifications allow better visualization of the anterior segment structures of the eye, especially of the epithelium, when compared with the traditional slitlamp.

Efficacy of treatment for pterygium by autologous conjunctival transplantation and mitomycin C.

BACKGROUND: The recurrence of pterygium after surgery is high. A variety of adjunctive treatment approaches have been developed to improve the clinical efficacy and many related articles have been published. This study aimed to determine the risk for postoperative pterygium recurrence comparing autologous conjunctival transplantation (ACT) versus mitomycin C (MMC). METHODS: Relevant literature published until December 2010 in Medline, Embase, Cochrane, Cochrane library, Science Citation Index, and Google Scholar were searched. Qualified random clinical trial (RCT) studies on the comparison of recurrence rate of pterygium after ACT and MMC treatment were included in this study. RESULTS: Eight RCTs with 663 eyes entered the final analysis. The recurrent rate of pterygium was 8.7% (30/343) for ACT and 18.75% (60/320) for MMC. Using fixed-effect meta analysis, we found that the recurrence was significantly lower after ACT than MMC treatment (odds ratio (OR) = 0.40, 95% confidence index (CI), 0.25 - 0.63, P < 0.0001). In sensitivity analyses, we employed random-effects model and excluded studies of low quality or studies in which MMC was administrated after the operation. All the sensitivity analyses confirmed that ACT led to lower recurrence rates than MMC. Sub-group analysis revealed that the recurrence rate was 20.2% (20/99) and 27.65% (26/94) for conjunctival autograft (CA) and MMC respectively, and no significant difference in the recurrence rate was detected (OR = 0.65, 95%CI 0.33 - 1.28, P = 0.22). However, we found that conjunctival limbal autograft (CLA) had lower recurrence rate than MMC (OR = 0.26, 95%CI 0.14 - 0.48, P = 0.0001). CONCLUSION: CLA has better therapy efficacy against the recurrence of pterygium than MMC.

Fibroblast growth factor 10 upregulates the expression of mucins in rat conjunctival epithelial cells.

PURPOSE: This in vitro study aimed to gain insight into the function of fibroblast growth factor 10 (FGF10) on the ocular surface, especially its effect on mRNA expression of the mucins Muc1, Muc4, and Muc5ac, and mucin protein synthesis. METHODS: We isolated primary cultured rat conjunctival epithelial cells (Cj-ECs) and treated them with FGF10 (1 ng/ml, 10 ng/ml, 100 ng/ml, and 200 ng/ml) and basic fibroblast growth factor 2 (FGF2; 10 ng/ml) for 24 h or 48 h. The proliferation of Cj-ECs was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS). mRNA levels of Muc1, Muc4, and Muc5ac were determined by real-time PCR. Synthesis levels of MUC1 and MUC4 were measured by western blot. Flow cytometry and Annexin V/PI double staining revealed degrees of apoptosis. RESULTS: In primary culture, the epithelial cells were compact and cobblestone pavement in shape. Most of the cells were positive for cytokeratin (CK). FGF10 and FGF2 significantly stimulated Muc1, Muc4, and Muc5ac mRNA expression, cell proliferation, and synthesis of MUC1 and MUC4 proteins. FGF10 was more potent than FGF2 in these regards. FGF10 did not restrain the apoptosis of Cj-ECs. CONCLUSIONS: The results of this study demonstrated that FGF10 is associated with the promotion of Cj-EC proliferation and mucin production. The effects of FGF10 on Cj-ECs support a rationale to investigate its therapeutic potential for ocular surface diseases.

Time course of Q value after myopic laser-assisted in situ keratomileusis.

OBJECTIVE: To assess the time course of Q value after myopic laser-assisted in situ keratomileusis (LASIK) and preliminarily evaluate the determinants of the difference of Q value between before and after LASIK. METHODS: We performed a retrospective, longitudinal investigation on patients undergoing wavefront optimized LASIK therapy for emmetropization. A total of 418 eyes from 222 cases were examined preoperatively, and partly followed up at one week (172 eyes), one month (134 eyes) and three months (51 eyes) after surgery. The horizontal, vertical and total Q values of cornea were calculated from eccentricity measured at the central 6-mm corneal zones respectively. Potential determinants of the change of Q value were analyzed using multiple linear regressions. RESULTS: The mean Q value was -0.17 +/- 0.13 preoperatively, and 0.99 +/- 0.70, 0.97 +/- 0.66, and 0.86 +/- 0.41 one week, one and three months postoperatively, respectively. One way analysis of variance (ANOVA) demonstrated significant differences between measurements made before surgery and at all postoperative times (at one week, one and three months; all P<0.0001, Bonferroni post hoc), but no significant differences were found among postoperative groups. Significant differences of Q values between horizontal and vertical meridians were found before surgery and at all postoperative times (all P<0.0001). Multiple regression analysis revealed that change of Q value significantly correlated with manifest refraction spherical equivalent (r=0.116, P<0.0001) and axial length (r=0.264, P<0.0001). CONCLUSIONS: Over the study period, the primary changes in Q value occur within 1 week after surgery, and then become slightly decreased and nearly stable. Manifest refraction spherical equivalent and axial length play a significant role in the change of postoperative Q value.

Improvement of retinal vascular injury in diabetic rats by statins is associated with the inhibition of mitochondrial reactive oxygen species pathway mediated by peroxisome proliferator-activated receptor gamma coactivator 1alpha.

OBJECTIVE: Mitochondrial reactive oxygen species (ROS) plays a key role in diabetic retinopathy (DR) pathogenesis. However, whether simvastatin decreases diabetes-induced mitochondrial ROS production remains uncertain. The aim of this study was to clarify the beneficial effects and mechanism of action of simvastatin against diabetes-induced retinal vascular damage. RESEARCH DESIGN AND METHODS: Diabetic rats and control animals were randomly assigned to receive simvastatin or vehicle for 24 weeks, and bovine retinal capillary endothelial cells (BRECs) were incubated with normal or high glucose with or without simvastatin. Vascular endothelial growth factor (VEGF) and peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) in the rat retinas or BRECs were examined by Western blotting and real-time RT-PCR, and poly (ADP-ribose) polymerase (PARP), and p38 MAPK were examined by Western blotting. Mitochondrial membrane potential (Deltapsim) and ROS production were assayed using the potentiometric dye 5,5',6,6'- Tetrachloro1,1',3,3'-tetraethyl-benzimidazolylcarbocyanine iodide (JC-1) or CM-H(2)DCFDA fluorescent probes. RESULTS: Simvastatin significantly upregulated PGC-1alpha (P < 0.01), subsequently decreased Deltapsim (P < 0.05) and ROS generation (P < 0.01), inhibited PARP activation (P < 0.01), and further reduced VEGF expression (P < 0.01) and p38 MAPK activity (P < 0.01). Those changes were associated with the decrease of retinal vascular permeability, retinal capillary cells apoptosis, and formation of acellular capillaries. CONCLUSIONS: Simvastatin decreases diabetes-induced mitochondrial ROS production and exerts protective effects against early retinal vascular damage in diabetic rats in association with the inhibition of mitochondrial ROS/PARP pathway mediated by PGC-1alpha. The understanding of the mechanisms of action of statins has important implications in the prevention and treatment of mitochondrial oxidative stress-related illness such as DR.