Early GnRH-agonist therapy does not negatively impact the endometrial repair process or live birth rate.

Study objective: To investigate whether different timings of GnRH-a downregulation affected assisted reproductive outcomes in infertile women with moderate-to-severe intrauterine adhesions (IUAs) accompanied by adenomyosis. Design: A retrospective case series. Setting: An assisted reproductive technology center. Patients: The study reviewed 123 infertile women with moderate-to-severe IUAs accompanied by adenomyosis undergoing their first frozen-thawed embryo transfer (FET) cycles between January 2019 and December 2021. Measurements and main results: The majority of patients had moderate IUA (n=116, 94.31%). The average Basal uterine volume was 73.58 ± 36.50 cm3. The mean interval from operation to the first downregulation was 21.07 ± 18.02 days (range, 1-79 days). The mean duration of hormone replacement therapy (HRT) was 16.93 ± 6.29 days. The average endometrial thickness on the day before transfer was 10.83 ± 1.75 mm. A total of 70 women achieved clinical pregnancy (56.91%). Perinatal outcomes included live birth (n=47, 67.14%), early miscarriage (n=18, 25.71%), and late miscarriage (n=5, 7.14%). The time interval between uterine operation and the first downregulation was not a significant variable affecting live birth. Maternal age was the only risk factor associated with live birth (OR:0.89; 95% CI: 0.79-0.99, P=0.041). Conclusions: The earlier initiation of GnRH-a to suppress adenomyosis prior to endometrial preparation for frozen embryo transfer did not negatively impact repair of the endometrium after resection.

Genome Editing VEGFA Prevents Corneal Neovascularization In Vivo.

Corneal neovascularization (CNV) is a common clinical finding seen in a range of eye diseases. Current therapeutic approaches to treat corneal angiogenesis, in which vascular endothelial growth factor (VEGF) A plays a central role, can cause a variety of adverse side effects. The technology of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 can edit VEGFA gene to suppress its expression. CRISPR offers a novel opportunity to treat CNV. This study shows that depletion of VEGFA with a novel CRISPR/Cas9 system inhibits proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. Importantly, subconjunctival injection of this dual AAV-SpCas9/sgRNA-VEGFA system is demonstrated which blocks suture-induced expression of VEGFA, CD31, and α-smooth muscle actin as well as corneal neovascularization in mice. This study has established a strong foundation for the treatment of corneal neovascularization via a gene editing approach for the first time.

Effect of visual perception training on binocular visual function reconstruction in patients after strabismus surgery.

AIM: To explore the effect of visual perception learning software training (VPT) on binocular visual function reconstruction in children with intermittent exotropia after strabismus surgery. METHODS: Ninety children with intermittent exotropia admitted to our hospital from June 2018 to December 2018 were included, and randomly divided into VPT and control groups. Children in the control group received basic binocular vision training, while those in the VPT group received VPT after strabismus surgery. Tertiary visual function, visual perception function, Newcastle Control Score (NCS), and ocular position retraction rate were compared at 3 and 12mo after the surgery. RESULTS: At 3 and 12mo after the surgery, the proportion of simultaneous perception, binocular fusion version and binocular stereo vision in the VPT group was conspicuously higher than that in the control group (P<0.05). After the vision training, the binocular visual perception functions of children in both groups were significantly improved compared with that before training (P<0.05). Interestingly, the grating sharpness, texture perception and texture motion perception in the VPT group were dramatically better than control group (P<0.01). The NCS in the VPT group was significantly lower than that in the control group (P<0.05). The ocular position retraction rate in the VPT group was significantly lower than that in the control group at 12mo (8.89% vs 26.67%, P=0.03). CONCLUSION: VPT effectively promotes binocular visual function reconstruction in intermittent exotropia children after strabismus surgery and reduces the strabismus severity and ocular position retraction rate.

Diffusion Depth and Efficacy of Different Infiltration Times for Rose Bengal/Green Light Corneal Cross-linking in Rabbit Eyes.

PURPOSE: To explore the diffusion depth and green light corneal cross-linking efficacy of different rose bengal (Rb) infiltration times in rabbit eyes. METHODS: Twenty-eight fresh rabbit eyes were deepithelialized and infiltrated in 0.1% Rb solution for 2 to 30 minutes. Corneal frozen sections were cut and Rb diffusion depth was observed under the confocal microscope. A further 36 rabbits were randomly divided into eight groups according to the type of treatment (control, Rb infiltration only without irradiation, rose bengal/green light [RGX] for different infiltration times, or riboflavin/ultraviolet radiation [UVX]). The corneas' resistance to keratolysis and biomechanical properties were measured after treatment. RESULTS: After 2, 10, 20, and 30 minutes of infiltration, Rb penetration depths in the corneal stroma were 100, 150, 200, and 270 µm, respectively. The times for complete digestion of the RGX 10 minutes (14.0 ± 1.4 hours), RGX 20 minutes (18.8 ± 1.1 hours), and UVX (51.2 ± 7.2 hours) groups were statistically greater than that of the control group (7.2 ± 1.1 hours). At 10% extension, the Young's modulus of the RGX 20 minutes (36.59 ± 4.90 MPa) and UVX (40.89 ± 2.57 MPa) groups was statistically greater than that of the control group (21.76 ± 5.69 MPa). CONCLUSIONS: The diffusion depth of Rb in corneal stroma increased by prolonging the infiltration time. The longer the infiltration time, the better the RGX effect. RGX for 20 minutes showed the best cross-linking efficacy among all RGX groups, albeit not as good as UVX. [J Refract Surg. 2023;39(9):620-626.].

Corneal Epithelial Remodeling in a 6-Month Follow-up Period in Myopic Corneal Refractive Surgeries.

PURPOSE: To investigate corneal epithelial thickness changes during a 6-month follow-up period after transepithelial photorefractive keratectomy (tPRK), femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK), and small incision lenticule extraction (SMILE). METHODS: This prospective study included 76 eyes of 76 participants who underwent myopic refractive surgery (23 FS-LASIK, 22 SMILE, and 31 tPRK). Epithelial thickness and anterior curvature were averaged over 4 regions (subdivided into 25 areas) and measured by spectral-domain optical coherence tomography and Scheimpflug tomography before the operation (pre) and at 1 or 3 days (pos1-3d), 1 week (pos1w), and 1 month (pos1m), 3 months (pos3m), and 6 months (pos6m) postoperatively. RESULTS: The epithelial thickness of the three groups was similar in both the pre and pos6m (all P > .05), but the tPRK group fluctuated the most during the follow-up period. The largest increase was in the inferior-temporal paracentral area (7.25 ± 2.58 µm for FS-LASIK; 5.79 ± 2.41 µm for SMILE; 4.88 ± 5.84 µm for tPRK; all P < .001). Only the epithelial thickness of tPRK increased from pos3m to pos6m (P < .05), whereas all changes for FS-LASIK and SMILE were not significant (P > .05). A positive correlation of thickness changes with curvature gradient in the paracentral region of tPRK was found (r = 0.549, P = .018), but not in other regions in all groups. CONCLUSIONS: Epithelial remodeling followed different trends after different surgeries from the early postoperative stage onward, but exhibited similar values at pos6m. Although remodeling after FS-LASIK and SMILE stabilized by pos3m, it remained unstable at pos6m after tPRK. These changes may affect corneal profile and lead to deviation from the intended surgical outcome. [J Refract Surg. 2023;39(3):187-196.].

Dually Crosslinked Copper-Poly(tannic acid) Nanoparticles with Microenvironment-Responsiveness for Infected Wound Treatment.

Reducing the burden of death due to wound infection is an urgent global public health priority. Metal-phenolic networks (MPNs) have received widespread attention in antimicrobial infections due to their facile synthesis process, excellent biocompatibility, and antimicrobial properties brought about by polyphenols and metal ions. However, typical therapeutic MPNs show rapid release of metal ions due to their poor solution stability, impeding long-acting efficacy in multiple wound healing stages. To address these issues, copper-poly (tannic acid) nanoparticles (Cu-PTA NPs): robust (dually crosslinked), microenvironment-responsive, antibacterial, antioxidative, and anti-inflammatory are prepared, which hierarchically modulate the infected wound healing process. Covalently polymerized via phenol-formaldehyde condensation and crosslinked with bioactive Cu2+ , reactive polyphenols are preserved, and Cu2+ is efficiently entrapped in the PTA scaffold. The proposed strategy relieves the systemic toxicity, and only high reactive oxygen species (ROS)level as stimuli can "turn on" the catalytic activity of Cu2+ to implement antibacterial therapy specifically in an infected wound. Systematic tissue regeneration assessment on the infected full-thickness skin wounds of rats demonstrates enhanced wound healing rate. Cu-PTA NPs enables the direct application in infected wound and exertion of long-acting healing efficacy. This synergetic therapy strategy will pave the way for more complicated infections and inflammatory diseases.

Combined Self-Assembled iRGD Polymersomes for Effective Targeted siRNA Anti-Tumor Therapy.

Introduction: iRGD is usually used as a motif to modify siRNA-nanodelivery vectors to improve tumor-targeting and penetration. However, most of the modifications are realized by covalent conjugation, which normally requires complex preparation processes possibly with low conjugation efficiency and yield, and might lower its bioactivity. To avoid this, here, we presented an alternative physical method to decorate iRGD on nanopolymersomes via facile self-assembly in water. Methods: siVEGF was chosen as a siRNA model, and lipopolysaccharide-amine nanopolymersomes (NPs), an efficient cytosolic delivery vector developed by our group, was used as an original vector. By successively incubating siVEGF with NPs, followed by adding iRGD, a siVEGF-loaded NPs functionalized with iRGD (siRNA/iRGD-NPs) was obtained. The properties of iRGD-NPs or siRNA/iRGD-NPs were evaluated in vitro and in vivo. Results: iRGD is efficiently introduced onto NPs with different amounts, which can be precisely controlled by the feeding ratio. The introduced iRGD keeps tumor-targeting and -penetrating bioactivity, which endows iRGD-NPs with ~100% of tumor-cell uptake and excellent tumor spheroid-penetration, and thus iRGD-NPs can efficiently deliver siVEGF to significantly inhibit angiogenesis in zebrafish and tumor growth in nude mice bearing breast cancer without obvious toxicity. Conclusion: This study provides a facile physical method to decorate nanodelivery vectors with iRGD for effective targeted siRNA anti-tumor therapy.

Regional Changes in Posterior Corneal Surface During a 6-Month Follow-up Period After tPRK, FS-LASIK, and SMILE.

PURPOSE: To investigate changes in corneal curvature in different zones of the posterior corneal surface during a 6-month follow-up period after transepithelial photorefractive keratectomy (tPRK), femtosecond laser-assisted excimer laser in situ keratomileusis (FS-LASIK), and small incision lenticule extraction (SMILE). METHODS: The study included a total of 202 eyes, including 65, 77, and 60 that underwent tPRK, FS-LASIK, and SMILE, respectively. Elevation data for the posterior surface were obtained preoperatively (pre), as well as 1 week (pos1w), 1 month (pos1m), 3 months (pos3m), and 6 months (pos6m) postoperatively. Changes in posterior corneal curvature (M) were analyzed in the central (diameter: 0 to 3 mm), paracentral (diameter: 3 to 6 mm), and peripheral (diameter: 6 to 9 mm) regions. RESULTS: Over all follow-up periods, the central region of the posterior surface in all patients became flatter (P < .05), with FS-LASIK showing the largest change, whereas the paracentral and peripheral regions became steeper. The posterior curvature changes between pre and pos6m, determined before and after correction for ablated stromal depth, tended to follow similar trends in the three regions and after the three surgeries. There was also no significant correlation (P > .05) between the changes in the mean curvature (M, recorded between pre and pos6m) and each of the refractive error corrections, the changes in spherical aberration postoperatively, the optical zone diameter, ablated stromal depth, and residual stromal bed thickness in the central and peripheral regions, but the correlation was significant in the paracentral region. CONCLUSIONS: The postoperative changes in posterior corneal shape followed different trends in the central, paracentral, and peripheral regions. The FS-LASIK group exhibited the most notable changes in posterior corneal curvature, especially in the central region. These changes were statistically correlated with variations in spherical aberration, and ablated and residential stromal thickness in the paracentral region. [J Refract Surg. 2022;38(11):708-715.].

The Impact of Different Rose Bengal Formulations on Corneal Thickness and the Efficacy of Rose Bengal/Green Light Corneal Cross-linking in the Rabbit Eye.

PURPOSE: To examine central corneal thickness (CCT) changes during in vivo rose bengal-green light corneal cross-linking (RG-CXL) and compare the CXL efficacy of different rose bengal formulations. METHODS: After epithelium removal, the right eyes of rabbits were immersed in rose bengal solution prepared by different solvents (water, phosphate buffered saline, dextran, and hydroxypropyl methylcellulos [HPMC]) for 2 or 20 minutes, then the rose bengal distribution in the corneal stroma was analyzed by confocal fluorescence detection. During the RG-CXL process, the CCT was measured at seven time points. The left eyes served as the untreated control group. Corneal enzymatic resistance and corneal biomechanics were tested to compare the RG-CXL efficacy. RESULTS: The rose bengal infiltration depths were 120 and 200 µm for the 2- and 20-minute groups, respectively. CCT increased significantly after infiltration, then decreased significantly in the first 200 seconds of irradiation and decreased slowly for the next 400 seconds. The CCT of the 20-minute groups was significantly thicker than that of the 2-minute groups (P < .0001). All RG-CXL treatments improved the corneal enzymatic resistance and corneal biomechanics, with the effects being greater in the 20-minute groups. The inclusion of 1.1% HPMC in the rose bengal formulation helped to maintain CCT during irradiation while not affecting either the infiltration of rose bengal or the efficacy of RG-CXL. CONCLUSIONS: Within the range studied, RG-CXL efficacy increased with infiltration time. The incorporation of a 20-minute infiltration of 0.1% rose bengal-1.1% HPMC into the RG-CXL procedure may further improve the safety of the treatment and its prospects for clinical use. [J Refract Surg. 2022;38(7):450-458.].

Laser In Situ Keratomileusis (LASIK) Combined with Prophylactic Corneal Cross-Linking for Correction of Myopia: Regional Analysis of Corneal Morphology.

INTRODUCTION: This study evaluated the outcomes of laser in situ keratomileusis (LASIK) combined with prophylactic corneal collagen cross-linking (CXL) in correcting myopia in cases with increased estimated risk of postoperative corneal ectasia, detected by regional analysis of corneal morphology. METHODS: The retrospective study included 180 eyes of 99 patients. Group 1 (94 eyes of 49 patients) with increased risk of postoperative corneal ectasia, as detected by "Ectasia Risk Factor Score System for LASIK", underwent femtosecond laser-assisted LASIK (FS-LASIK) combined with prophylactic CXL, using short riboflavin soaking time and low UV energy. Group 2 (86 eyes of 50 patients) with normal corneal topography, who underwent FS-LASIK alone, were used as controls. Refractive and visual outcomes and Scheimpflug topo/tomography were analyzed preoperatively and 1 week, 1 month, and 12 months postoperatively. Mean regional corneal curvature (M) values for three subregions (the central 3.0 mm region, the paracentral 3.0-6.0 mm region, and the peripheral 6.0-9.0 mm region) of both anterior and posterior surfaces were calculated. RESULTS: An increase in flattening of the peripheral anterior region and more steepening of the posterior paracentral region were shown at 12 months compared to 1 month postoperatively in group 1. The findings were significantly more pronounced than in group 2 (P < 0.001 and P = 0.035, respectively). The refractive and visual outcomes were comparable in the two groups. CONCLUSIONS: Prophylactic CXL seems to influence corneal regional reshaping after surgery, while not affecting the 1-year visual and refractive results.

Clinical outcomes of single-step transepithelial photorefractive keratectomy and off-flap epipolis-laser in situ keratomileusis in moderate to high myopia: 12-month follow-up.

BACKGROUND: To compare the quantitative and qualitative optical outcomes of single-step transepithelial photorefractive keratectomy (TPRK) and off-flap epipolis-laser in situ keratomileusis (Epi-LASIK) in moderate to high myopia. METHODS: In this prospective self-control study, we included patients with moderate to high myopia who were randomized to undergo TPRK in one eye and Epi-LASIK in the other eye. Twelve-month follow-up results for visual acuity, refraction, ocular high-order aberrations, contrast sensitivity, postoperative pain, epithelial healing, and haze grade were assessed. RESULTS: A total of 64 eyes (32 patients) were enrolled in the study. More eyes completed re-epithelialization in the TPRK group than in the Off-flap Epi-LASIK group 3-4 days postoperatively, while all eyes completed re-epithelialization by 7 days. More eyes achieved a visual acuity (both UDVA and CDVA) of better than 20/20 in the TPRK group than in the Off-flap Epi-LASIK group. The ±0.50 D predictability for correction of the spherical equivalent (SE) was higher in the eyes of the TPRK group (91%) than in those of the off-flap Epi-LASIK group (80%) 12 months after surgery. No significant differences in ocular aberrations, including coma, spherical, and trefoil, were found between the two groups at 12 months. There were also no significant differences in visual acuity, contrast sensitivity, pain, and haze grading between the two groups. CONCLUSIONS: Both TPRK and off-flap Epi-LASIK are safe, effective, and predictable treatments for moderate to high myopia with comparable surgical outcomes. TRIAL REGISTRATION: This study was retrospectively registered on ClinicalTrial.gov ( NCT05060094 , 17/09/2021).

Biomechanical Effects of tPRK, FS-LASIK, and SMILE on the Cornea.

Purpose: The objective of this study is to evaluate the in vivo corneal biomechanical response to three laser refractive surgeries. Methods: Two hundred and twenty-seven patients who submitted to transepithelial photorefractive keratectomy (tPRK), femtosecond laser-assisted in-situ keratomileusis (FS-LASIK), or small-incision lenticule extraction (SMILE) were included in this study. All cases were examined with the Corvis ST preoperatively (up to 3 months) and postoperatively at 1, 3, and 6 months, and the differences in the main device parameters were assessed. The three groups were matched in age, gender ratio, corneal thickness, refractive error corrections, optical zone diameter, and intraocular pressure. They were also matched in the preoperative biomechanical metrics provided by the Corvis ST including stiffness parameter at first applanation (SP-A1), integrated inverse radius (IIR), deformation amplitude (DA), and deformation amplitude 2 mm away from apex and the apical deformation (DARatio2mm). Results: The results demonstrated a significant decrease post-operation in SP-A1 and significant increases in IIR, DA, and DARatio2mm (p < 0.05), all of which indicated reductions in overall corneal stiffness. Inter-procedure comparisons provided evidence that the smallest overall stiffness reduction was in the tPRK group, followed by the SMILE, and then the FS-LASIK group (p < 0.05). These results remained valid after correction for the change in CCT between pre and 6 months post-operation and for the percentage tissue altered. In all three surgery groups, higher degrees of refractive correction resulted in larger overall stiffness losses based on most of the biomechanical metrics. Conclusion: The corneal biomechanical response to the three surgery procedures varied significantly. With similar corneal thickness loss, the reductions in overall corneal stiffness were the highest in FS-LASIK and the lowest in tPRK.

Clinical Outcomes of Aberration-Free All Surface Laser Ablation (ASLA) vs. Aberration-Free ASLA Assisted by Smart Pulse Technology in High Myopia: A One-Year Follow-Up Study.

PURPOSE: To compare the clinical outcomes of aberration-free all surface laser ablation (ASLA) with and without the use of smart pulse technology (SPT) in high myopia. METHODS: This study retrospectively analyzed 138 eyes (138 patients, only the right eye was selected) treated for high myopia (spherical equivalent ≥-6.00 diopters) using aberration-free ASLA (non-SPT group; 85 eyes) and aberration-free ASLA assisted by SPT (SPT group; 53 eyes). Examinations such as visual acuity, refraction, and haze were performed before the 12-month follow-up. Corneal epithelial healing time was assessed in the first postoperative day. Visual acuity and refraction examination were performed at 7 days and 1, 3, 6, and 12 months postoperatively. Corneal haze was evaluated in 1, 3, 6, and 12 months. Safety, efficacy, and corneal wavefront aberrations were assessed 12 months after the treatment. RESULTS: At 12 months postoperatively, 60% versus 40% of eyes achieved 20/16 Snellen lines or better, and 92% versus 82% of eyes achieved 20/20 Snellen lines or better visual acuity in the SPT and the non-SPT groups, respectively. The average postoperative epithelial healing time was 3.75 ± 1.00 days in the SPT group and 3.73 ± 1.30 days in the non-SPT group (P ≥ 0.05). The safety and the efficacy index of the SPT group were better than those of the non-SPT group in the follow-ups. The attempted spherical equivalent before the surgery and the achieved spherical equivalent at 12 months were comparable between the two groups. Regarding the aberrations, the results of Coma 90° in the SPT group were better than those in the non-SPT group (P ≤ 0.05), but the increase of RMS HOAs (root mean square higher order aberrations), Coma 0°, and spherical aberration postoperatively had no statistical difference between the two groups (P ≥ 0.05). Conclusions: Both aberration-free ASLA with and without SPT showed favorable safety, effectiveness, and predictability within 12 months for high myopia. And, ASLA using SPT might have potential advantages in the long-term visual quality.

The Precision of a New Anterior Segment Optical Coherence Tomographer and Its Comparison With a Swept-Source OCT-Based Optical Biometer in Patients With Cataract.

PURPOSE: To assess the precision of a new spectral-domain optical coherence tomographer (SD-OCT)/Placido topographer (MS-39; CSO) and its comparison with a swept-source OCT (SS-OCT) biometer (Argos; Movu, Inc) in patients with cataract. METHODS: Fifty-three right eyes from 53 patients were examined by two experienced operators three times using both devices randomly. Employing the within-subject standard deviation (Sw), test-retest variability, coefficient of variation, and intraclass correlation coefficient to evaluate intraoperator repeatability and interoperator reproducibility; the double-angle plots to analyze astigmatism; and Bland-Altman plots and 95% limits of agreement to verify the agreement between devices. RESULTS: The SD-OCT/Placido tomographer showed high precision, with coefficient of variation of 0.44% or less, intraclass correlation coefficient of 0.945 or greater for all parameters, test-retest variability of 4.21 µm or less for central corneal thickness (CCT), 0.03 mm or less for anterior chamber depth (ACD) and aqueous depth (AQD), and 0.25 diopters (D) or less for mean keratometry (Km), J0, and J45. The inter-device differences in Km, J0, and J45 were statistically insignificant, whereas the remaining were statistically but not clinically significant. The 95% limits of agreement of CCT, ACD, AQD, Km, J0, and J45 were -3.70 to 15.25 µm, -0.06 to 0.04 mm, -0.06 to 0.04 mm, -0.28 to 0.35 D, -0.27 to 0.26 D, and -0.27 to 0.21 D, respectively. The double-angle plot confirmed the high agreement in astigmatism. CONCLUSIONS: For CCT, ACD, AQD, Km, and astigmatism measurements in patients with cataract, the new SD-OCT/Placido tomographer has excellent precision and high agreement with the Argos SS-OCT biometer, and can be used interchangeably. [J Refract Surg. 2021;37(9):616-622.].

Unintended changes in ocular biometric parameters during a 6-month follow-up period after FS-LASIK and SMILE.

BACKGROUND: Corneal refractive surgery has become reliable for correcting refractive errors, but it can induce unintended ocular changes that alter refractive outcomes. This study is to evaluate the unintended changes in ocular biometric parameters over a 6-month follow-up period after femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) and small incision lenticule extraction (SMILE). METHODS: 156 consecutive myopic patients scheduled for FS-LASIK and SMILE were included in this study. Central corneal thickness (CCT), mean curvature of the corneal posterior surface (Kpm), internal anterior chamber depth (IACD) and the length from corneal endothelium to retina (ER) were evaluated before and after surgery over a 6-month period. RESULTS: Both the FS-LASIK and SMILE groups (closely matched at the pre-surgery stage) experienced flatter Kpm, shallower IACD and decreased ER 1 week post-surgery (P < 0.01), and these changes were larger in FS-LASIK than in SMILE group. During the 1 week to 6 months follow up period, Kpm, IACD and ER remained stable unlike CCT which increased significantly (P < 0.05), more in the FS-LASIK group. CONCLUSIONS: During the follow up, the posterior corneal surface became flatter and shifted posteriorly, the anterior chamber depth and the length from the corneal endothelium to retina decreased significantly compared with the pre-surgery stage. These unintended changes in ocular biometric parameters were greater in patients undergoing FS-LASIK than SMILE. The changes present clear challenges for IOL power calculations and should be considered to avoid affecting the outcome of cataract surgery.

The effect of nerve growth factor on corneal nerve regeneration and dry eye after LASIK.

Dry eye is the most common complication after refractive surgery, especially after laser in situ keratomileusis (LASIK), in which nerves may be cut when making the corneal flap. Nerve growth factor (NGF) has been demonstrated to stimulate corneal sensitivity and nerve regeneration and NGF has been suggested as a potential treatment for dry eye disease (DED). Hence, this study aimed to investigate the effect of NGF on corneal nerve regeneration, sensitivity and dry eye symptoms after LASIK, compared to hycosan and normal saline (NS) treatments. Thirty-eight New Zealand white rabbits that underwent LASIK procedures were randomly assigned to three groups. Each group underwent NGF, hycosan, and NS treatment. The nerve densities and the number of corneal sub-basal and superficial stromal nerves were measured with confocal microscopy, and the results were compared before surgery and at one month and three months postoperatively. Corneal sensitivity was assessed with an esthesiometer. The tear breakup time (TBUT) was recorded to check for signs of dry eye. The whole corneas of the experimental animals were excised at three months after the surgery for immunohistochemically analysis. After LASIK, treatment with NGF significantly accelerated the recovery of sub-basal and superficial stromal nerve densities and the numbers, compared to hycosan and NS treatments at one month and three months postoperatively (NGF vs. hycosan, P < 0.01 each; NGF vs. NS, P < 0.01 each). The recovery of corneal sensitivity was significantly enhanced in the NGF group compared to the hycosan or NS treatment groups after surgery (P < 0.05). Also, the TBUT data showed a statistically significant longer time in the NGF group at one month, and three months postoperatively (P < 0.05). Immunofluorescence analysis showed the nerve fiber quantity of the NGF group was larger than in the hycosan and NS groups. Taken together, the experimental results suggested that mNGF had an obvious effect on promoting corneal nerve repairing and the potential to improve dry eye in different periods following LASIK.

A Coincident Thinning Index for Keratoconus Identification Using OCT Pachymetry and Epithelial Thickness Maps.

PURPOSE: To develop a coincident thinning (CTN) index to differentiate between keratoconic and healthy corneas using optical coherence tomography (OCT) measurements of pachymetry and epithelial thickness. METHODS: Pattern deviation maps of pachymetry and epithelial thickness were generated using Fourier-domain OCT images of the cornea. The co-localized thinning of the two maps was quantified using a novel CTN index, which was calculated from Gaussian fits of the regions of maximum relative thinning. The CTN index was validated using k-fold cross-validation, and its classification performance was compared to minimum pachymetry and maximum keratometry. RESULTS: A total of 82 normal eyes and 133 eyes within three groups of keratoconus severity were evaluated. The pattern deviation maps for the keratoconic eyes showed relative thinning that was larger in magnitude and more strongly correlated with the Gaussian function compared to normal eyes (all P < .01). The distance between the pachymetric and epithelial maximum relative thinning locations was significantly smaller for the keratoconic eyes than for the normal eyes (all P < .02). The CTN index was significantly larger for all three keratoconus groups compared to normal eyes (all P < .0001). The CTN index demonstrated a sensitivity of 100% in detecting manifest keratoconus, 100% for subclinical keratoconus, and 56% for forme fruste keratoconus. The overall classification accuracy was better for the CTN index (93%) than for minimum pachymetry (86%) and maximum keratometry (86%). CONCLUSIONS: The CTN index is a highly sensitive measure of coincident pachymetric and epithelial thinning. It provides valuable information for detecting and monitoring early to moderate keratoconus. [J Refract Surg. 2020;36(11):757-765.].

Microenvironment-Triggered Degradable Hydrogel for Imaging Diagnosis and Combined Treatment of Intraocular Choroidal Melanoma.

Human choroidal melanoma (HCM) is one of the most common primary intraocular tumors and easily provokes liver metastases owing to the lack of sensitive and noninvasive therapeutic methods. Concerning the imaging diagnostics and therapeutic predicaments for choroidal melanoma, we designed microenvironment-triggered degradable hydrogels (RENP-ICG@PNIPAM:Dox-FA) based on ultrasmall (<5 nm) rare-earth nanoparticles (RENPs) with enhanced NIR-II luminescence. The ultrasmall diameter can significantly enhance the NIR-II luminescence performance of RENPs. RENPs were encapsulated by a dual-response PNIPAM hydrogel, which could release drug by responding to heat energy and glutathione under the tumor microenvironment. The in vitro/in vivo NIR-II imaging detection and antitumor activity were also compared systematically after different treatment conditions on ocular choroidal melanoma-1 cells and tumor-bearing mice, respectively. Besides, the degradability of the hydrogel composites under physiological conditions could be conducive to enhance the photothermal-chemotherapeutic effect and alleviate long-term biological toxicity. Our work on the microenvironment-triggered hydrogels with enhanced NIR imaging and easy metabolism may provide a promising strategy for sensitive and noninvasive imaging and phototherapy in ocular tumors.

A Comprehensive Strategy for Laser Corneal Refractive Surgery during the COVID-19 Epidemic in a Tertiary Teaching Hospital in Wenzhou, China.

The novel coronavirus pneumonia COVID-19 is caused by the novel coronavirus SARS-CoV-2, which is highly contagious, has a long incubation period, and can be detected in patients' tears and conjunctival secretions. In this study, we describe our experience regarding the necessary protective measures that need to be taken during ophthalmic examination and treatment. The authors reviewed the clinical work arrangements during the epidemic situation at the Eye Hospital of Wenzhou Medical University in China and analyzed the prevention and control measures that were applied during the laser corneal refractive surgery process. The comprehensive protection protocol, which was established throughout the entire process, included both horizontal (medical staff-patient, medical staff-medical staff, and patient-patient) and vertical (preoperative, intraoperative, and postoperative transmission assessment) approach and was mainly focused on strengthening the protection against potential aerosol transmission that may occur during intraocular pressure measurements and laser ablation. The described and proposed protocol, along with the further guidelines followed by the medical personnel, proved to be efficacious and contributed significantly to the control of the COVID-19 outbreak and the protection of both the patients and the medical staff.

Network Meta-analysis of No-History Methods to Calculate Intraocular Lens Power in Eyes With Previous Myopic Laser Refractive Surgery.

PURPOSE: To systematically compare and rank the predictability of no-history intraocular lens (IOL) power calculation methods after myopic laser refractive surgery. METHODS: PubMed, Embase, the Cochrane Library, and the U.S. trial registry (www.ClinicalTrial.gov) were used to systematically search trials published up to August 2019. Included were case series studies reporting the following outcomes in patients with cataract undergoing phacoemulsification after laser refractive surgery: percentage of eyes with a refractive prediction error (PE) within ±0.50 and ±1.00 diopters (D), mean absolute error (MAE), and median absolute error (MedAE). A network meta-analysis was conducted using the STATA software version 13.1 (STATACorp LLC). RESULTS: Nineteen studies involving 1,098 eyes and 19 formulas were identified. A network meta-analysis for the percentage of eyes with a PE within ±0.50 D found that ray-tracing (Okulix), intraoperative aberrometry (Optiwave Refractive Analysis [ORA]), BESSt, and Seitz/Speicher/Savini (Triple-S) (D-K SRK/T), and Fourier-Domain OCT-Based formulas were more predictive than the Wang/Koch/Maloney, Shammas-PL, modified Rosa, Ferrara, and Equivalent K reading at 4.5 mm using the Double-K Holladay 1 formulas. With regard to ranking, the top four formulas as per the surface under the cumulative ranking curve (SUCRA) values for the percentage of eyes with a PE within ±0.50 D were the Okulix, ORA, BESSt, and Triple-S (D-K SRK/T). With regard to MAE, the ORA showed lower errors when compared to the Shammas-PL formula. In this regard, the top four formulas based on the SUCRA values were the Triple-S, BESSt, ORA, and Fourier-Domain OCT-Based formulas. The SToP (SRK/T), ORA, Fourier-Domain OCT-Based, and BESSt formulas had the lowest MedAE. CONCLUSIONS: Considering all three outcome measures of highest percentages of eyes with a PE within ±0.50 and ±1.00 D, lowest MAE, and lowest MedAE, the top three no-history formulas for IOL power calculation in eyes with previous myopic corneal laser refractive surgery were: ORA, BESSt, and Triple-S (D-K SRK/T). [J Refract Surg. 2020;36(7):481-490.].