Conjunctival Fluid Secretion Impairment via CaCC-CFTR Dysfunction Is the Key Mechanism in Environmental Dry Eye.

Dry eye disease (DED) is a multifactorial disease with an incidence of approximately 50% worldwide. DED seriously affects quality of life and work. The prevalence of environmental DED (eDED) ranges from 35 to 48%. Conjunctival fluid secretion dysfunction may be one of the major causes of DED. Notably, the Cl- flux corresponds to the conjunctival fluid secretion and could be affected by ATP. Both the cystic fibrosis transmembrane conductance regulator (CFTR) and the Ca2+-activated Cl- channel (CaCC) are Cl- channels involved in epithelial fluid secretion. Conjunctival fluid secretion could be increased by activating P2Y2R (an ATP receptor) in DED. However, the role of the CaCC and CFTR channels regulated by P2Y2R in eDED remains unclear. In this study, we established a rabbit eDED model using a controlled drying system. A Ussing chamber was used to perform a conjunctival short-circuit current induced by ATP to evaluate the reactivity of the ion channels to the ATP. Our results revealed that eDED accompanied by conjunctival fluid secretion impairment was caused by a P2Y2R dysfunction, which is related to CaCC-CFTR signaling in the conjunctiva epithelium. Notably, the coupling effect of the ATP-induced CaCC-CFTR activation and intracellular Ca2+ may represent a promising therapeutic target for treating eDED.

Screening Candidates for Refractive Surgery With Corneal Tomographic-Based Deep Learning.

Importance: Evaluating corneal morphologic characteristics with corneal tomographic scans before refractive surgery is necessary to exclude patients with at-risk corneas and keratoconus. In previous studies, researchers performed screening with machine learning methods based on specific corneal parameters. To date, a deep learning algorithm has not been used in combination with corneal tomographic scans. Objective: To examine the use of a deep learning model in the screening of candidates for refractive surgery. Design, Setting, and Participants: A diagnostic, cross-sectional study was conducted at the Zhongshan Ophthalmic Center, Guangzhou, China, with examination dates extending from July 18, 2016, to March 29, 2019. The investigation was performed from July 2, 2018, to June 28, 2019. Participants included 1385 patients; 6465 corneal tomographic images were used to generate the artificial intelligence (AI) model. The Pentacam HR system was used for data collection. Interventions: The deidentified images were analyzed by ophthalmologists and the AI model. Main Outcomes and Measures: The performance of the AI classification system. Results: A classification system centered on the AI model Pentacam InceptionResNetV2 Screening System (PIRSS) was developed for screening potential candidates for refractive surgery. The model achieved an overall detection accuracy of 94.7% (95% CI, 93.3%-95.8%) on the validation data set. Moreover, on the independent test data set, the PIRSS model achieved an overall detection accuracy of 95% (95% CI, 88.8%-97.8%), which was comparable with that of senior ophthalmologists who are refractive surgeons (92.8%; 95% CI, 91.2%-94.4%) (P = .72). In distinguishing corneas with contraindications for refractive surgery, the PIRSS model performed better than the classifiers (95% vs 81%; P < .001) in the Pentacam HR system on an Asian patient database. Conclusions and Relevance: PIRSS appears to be useful in classifying images to provide corneal information and preliminarily identify at-risk corneas. PIRSS may provide guidance to refractive surgeons in screening candidates for refractive surgery as well as for generalized clinical application for Asian patients, but its use needs to be confirmed in other populations.

Development of low laser energy levels in small-incision lenticule extraction: clinical results, black area, and ultrastructural evaluation.

PURPOSE: To evaluate the outcomes of 4 low laser energy levels after small-incision lenticule extraction (SMILE) surgery. SETTING: Zhongshan Ophthalmic Center, Guangzhou, China. DESIGN: Prospective randomized clinical trial. METHODS: This study evaluated consecutive patients who had SMILE to correct myopia or myopia with astigmatism. Eyes were placed into groups based on the laser energy used during surgery (ie, 105 nJ, 110 nJ, 115 nJ, or 120 nJ). All patients had a thorough ophthalmic examination preoperative and at 4 timepoints over 3 months postoperatively. Black areas and surface regularity of the extracted lenticules were observed and evaluated qualitatively and quantitatively. RESULTS: The study comprised 124 eyes of 62 patients (40 women, 22 men), with 31 eyes in each laser energy group. The incidence of black areas was 45.16% (14 of 31 eyes), 12.90% (4 of 31 eyes), 16.13% (5 of 31 eyes), and 12.90% (4 of 31 eyes) for 105 nJ, 110 nJ, 115 nJ, and 120 nJ, respectively. The mean time for lenticule creation was the longest in the 105 nJ group (P = .015). The greatest increase in corneal thickness postoperatively occurred with 105 nJ (P < .05). Regression was highest in the 105 nJ group at 3 months (P < .01). However, corneal horizontal coma (C8) was lowest in the 105 nJ group at 1 week (P = .032). The lenticular surface in the 110 nJ group was the smoothest (P = .011). All contrast sensitivity values varied with time and recovered to preoperative levels by 1 week or 1 month. In all eyes, the uncorrected distance visual acuity and corrected distance visual acuity were good, with no statistically significant differences between the 4 energy groups. CONCLUSIONS: The 105 nJ group, in which the lowest energy was used, had the highest risk for black areas, serious postoperative corneal edema, and a significant healing response.

Optimal Parameters of Scanning Mode in Small Incision Lenticule Extraction (SMILE): Clinical Results and Ultrastructural Analysis.

PURPOSE: To compare the effect of two scanning modes with different femtosecond laser settings on clinical outcomes and ultrastructural analysis of the lenticule surface in small incision lenticule extraction (SMILE). METHODS: A total of 78 eyes from 39 consecutive patients were included with the standard scanning mode (energy level of 105 nJ vs spot distance of 3 mm) in one eye and the fast scanning mode (energy level of 110 nJ vs spot distance of 4.5 mm) in the other eye, all eyes being randomly assigned. Patients received complete ophthalmic examinations preoperatively and at different follow-up visits after SMILE. Ten human corneal lenticules were analyzed using scanning electron microscopy. RESULTS: Uncorrected distance visual acuity at 1 day and 1 week postoperatively was -0.06 ± 0.10 and -0.11 ± 0.05 logMAR, respectively, in the fast scanning group, which was significantly better than in the standard scanning group (-0.11 ± 0.08 and -0.12 ± 0.05 logMAR, respectively), and no significant difference was found between the groups at 1 and 3 months. The contrast sensitivity was higher at different time points in the fast scanning mode group compared with the standard scanning group (all P < .05). Ultrastructurally, the corneal lenticules from the fast scanning group showed a smoother surface than those from the standard scanning mode group qualitatively and quantitatively (all P < .001). CONCLUSIONS: SMILE using the fast scanning mode facilitates better visual acuity with improved contrast sensitivity in the early postoperative period. Experimental studies on the ultrastructure of corneal lenticules support these clinical results. [J Refract Surg. 2020;36(1):34-41.].

Review on Centration, Astigmatic Axis Alignment, Pupil Size and Optical Zone in SMILE.

The advent of "flapless" small-incision lenticule extraction (SMILE), employing all-in-one technology, has resulted in a revolutionary breakthrough in refractive surgeries. SMILE has been gaining popularity due to fewer potential complications, such as postoperative dry eyes and greater biomechanical stability, etc. However, attention must be given to 1) the centration on the corneal vertex, 2) the proper alignment of the astigmatic axis, and 3) the relationship between pupil size and treatment diameter, to achieve good SMILE results. There is no pupil-tracking system to ascertain the accuracy of centration during the SMILE surgery. To improve the centration accuracy, our center uses two corneal topographers (Pentacam and Sirius) to measure and determine corneal vertex. Proper predicted optical zone diameter is not clearly defined yet in SMILE. Some scholars insist that mesopic pupil size should be taken into consideration when setting the predicted optical zone. Meanwhile, the issue of "functional optical zone" still has many unresolved issues and warrants further studies.

Effect of Cyclotorsion Compensation With a Novel Technique in Small Incision Lenticule Extraction Surgery for the Correction of Myopic Astigmatism.

PURPOSE: To comparatively investigate the clinical outcomes of small incision lenticule extraction (SMILE) surgery with or without cyclotorsion compensation for the correction of myopic astigmatism. METHODS: This prospective, double-blinded, randomized controlled trial included patients who underwent SMILE surgery with bilateral myopic astigmatism. Two eyes of a single patient were randomly divided into the static cyclotorsion compensation (SCC) group and the control group. In the SCC group, the intraoperative cyclotorsion was manually compensated with a novel technique. In the control group, the cyclotorsion was not compensated. Visual acuity, manifest refraction, aberrations, objective visual quality, and contrast sensitivity were measured preoperatively and postoperatively. RESULTS: A total of 132 eyes from 66 patients were analyzed at the 3-month follow-up. The mean preoperative cylinder values in the SCC and control groups were -1.52 ± 0.81 and -1.57 ± 0.82 diopters (D), respectively. The mean cyclotorsion during surgery was 0.60° ± 0.63° (range: 0° to 3.2°) in the SCC group and 3.21° ± 2.33° (range: 0.1° to 10.8°) in the control group (P < .001). Both groups showed favorable results in the correction of myopic astigmatism. No statistically significant difference was found between the two groups in visual and refractive outcomes, vector parameters, entire eye aberrations, objective visual quality, or contrast sensitivity. No significant benefit was gained from cyclotorsion compensation, even in the high astigmatism subgroup. CONCLUSIONS: The cyclotorsion compensation technique used in this study helped minimize the alignment error but was not compulsory because the ocular rotation in SMILE surgery using a well-controlled position was too small to affect the astigmatic outcomes or postoperative visual quality. [J Refract Surg. 2019;35(5):301-308.].

Fasudil hydrochloride, a potent ROCK inhibitor, inhibits corneal neovascularization after alkali burns in mice.

PURPOSE: To investigate the effects and mechanisms of fasudil hydrochloride (fasudil) on and in alkali burn-induced corneal neovascularization (CNV) in mice. METHODS: To observe the effect of fasudil, mice with alkali-burned corneas were treated with either fasudil eye drops or phosphate-buffered saline (PBS) four times per day for 14 consecutive days. After injury, CNV and corneal epithelial defects were measured. The production of reactive oxygen species (ROS) and heme oxygenase-1(HO-1) was measured. The infiltration of polymorphonuclear neutrophils (PMNs) and the mRNA expressions of CNV-related genes were analyzed on day 14. RESULTS: The incidence of CNV was significantly lower after treatment with 100 µM and 300 µM fasudil than with PBS, especially with 100 µM fasudil. Meanwhile, the incidences of corneal epithelial defects was lower (n=15, all p<0.01). After treatment with 100 µM fasudil, the intensity of DHE fluorescence was reduced in the corneal epithelium and stroma than with PBS treatment (n=5, all p<0.01), and the number of filtrated PMNs decreased. There were significant differences between the expressions of VEGF, TNF-a, MMP-8, and MMP-9 in the 100 µM fasudil group and the PBS group (n=8, all p<0.05). The production of HO-1 protein in the 100 µM fasudil group was 1.52±0.34 times more than in the PBS group (n=5 sample, p<0.05). CONCLUSIONS: 100 µM fasudil eye drops administered four times daily can significantly inhibit alkali burn-induced CNV and promote the healing of corneal epithelial defects in mice. These effects are attributed to a decrease in inflammatory cell infiltration, reduction of ROS, and upregulation of HO-1 protein after fasudil treatment.