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.].

Chimeric deletion mutation of rpoC2 underlies the leaf-patterning of Clivia miniata var. variegata.

KEY MESSAGE: The deletion mutated rpoC2 leads to yellow stripes of Clivia miniata var. variegata by down regulating the transcription of 28 chloroplast genes and disturbing chloroplast biogenesis and thylakoid membrane development. Clivia miniata var. variegata (Cmvv) is a common mutant of Clivia miniata but its genetic basis is unclear. Here, we found that a 425 bp deletion mutation of chloroplast rpoC2 underlies the yellow stripes (YSs) of Cmvv. Both RNA polymerase PEP and NEP coexist in seed-plant chloroplasts and the ß″ subunit of PEP is encoded by rpoC2. The rpoC2 mutation changed the discontinuous cleft domain required to form the PEP central cleft for DNA binding from 1103 to 59 aa. RNA-Seq revealed that 28 chloroplast genes (cpDEGs) were all down-regulated in YSs, of which, four involved in chloroplast protein translation and 21 of photosynthesis system (PS)I, PSII, cytochrome b6/f complex and ATP synthase are crucial for chloroplast biogenesis/development. The accuracy and reliability of RNA-Seq was verified by qRT-PCR. Moreover, the chlorophyll (Chl) a/b content, ratio of Chla/Chlb and photosynthetic rate (Pn) of YS decreased significantly. Meanwhile, chloroplasts of the YS mesophyll cells were smaller, irregular in shape, contain almost no thylakoid membrane, and even proplastid was found in YS. These findings indicate that the rpoC2 mutation down-regulated expression of the 28 cpDEGs, which disturb chloroplast biogenesis and its thylakoid membrane development. Thus, there are not enough PSI and II components to bind Chl, so that the corresponding areas of the leaf are yellow and show a low Pn. In this study, the molecular mechanism of three phenotypes of F1 (Cmvv ♀ × C. miniata ♂) was revealed, which lays a foundation for the breeding of variegated plants.

Inter-examiner and intra-examiner reliability of optical coherence tomography angiography in vascular density measurement of retinal and choriocapillaris plexuses in healthy children aged 6-15 years.

Objective: This study aimed to test the inter-examiner and intra-examiner reliability of macular vascular density (VD) measurement of retinal and choriocapillaris plexuses in healthy children using optical coherence tomography angiography (OCTA). Materials and methods: Ninety-two school children were prospectively recruited. Macular OCTA images (6 × 6 mm2) were obtained thrice by two examiners using the RTVue-XR Avanti OCT system. The coefficient of variation (COV), intraclass correlation coefficient (ICC), and Bland-Altman plots were used to evaluate the repeatability and reproducibility. Results: Ninety participants aged 6-15 years were enrolled; two participants were excluded because of low-quality images. In the retina, the reproducibility and repeatability of VD became poorer from superficial to deep retinal capillary plexus (superficial: COV = 4.61-11.11%; intermediate: COV = 7.73-14.15%; deep: COV = 14.60-32.28%). For both reproducibility and repeatability, the ICC ranged from moderate to high (superficial plexus: ICC = 0.570-0.976; intermediate plexus: ICC = 0.720-0.968; deep plexus: ICC = 0.628-0.954). In the choroid, the inter-examiner reproducibility and intra-examiner repeatability of the VD measurement of choriocapillaris were excellent in the macula, fovea, parafovea, and perifovea (COV = 1.00-6.10%; ICC = 0.856-0.950). The parameters of the foveal avascular zone (FAZ) also showed significant reproducibility and repeatability (COV = 0.01-0.21%; ICC = 0.743-0.994). Conclusion: The VD measurements of the choriocapillaris and FAZ parameters using OCTA showed excellent inter-examiner and intra-examiner reliability in school children. The reproducibility and repeatability of the VD of three retinal capillary plexuses depended on the depth of the retinal capillary plexus.

An engineered lamellar bone mimicking full-scale hierarchical architecture for bone regeneration.

Lamellar bone, compactly and ingeniously organized in the hierarchical pattern with 6 ordered scales, is the structural motif of mature bone. Each hierarchical scale exerts an essential role in determining physiological behavior and osteogenic bioactivity of bone. Engineering lamellar bone with full-scale hierarchy remains a longstanding challenge. Herein, using bioskiving and mineralization, we attempt to engineer compact constructs resembling full-scale hierarchy of lamellar bone. Through systematically investigating the effect of mineralization on physicochemical properties and bioactivities of multi-sheeted collagen matrix fabricated by bioskiving, the hierarchical mimicry and hierarchy-property relationship are elucidated. With prolongation of mineralization, hierarchical mimicry and osteogenic bioactivity of constructs are performed in a bidirectional manner, i.e. first rising and then descending, which is supposed to be related with transformation of mineralization mechanism from nonclassical to classical crystallization. Construct mineralized 9 days can accurately mimic each hierarchical scale and efficiently promote osteogenesis. Bioinformatic analysis further reveals that this construct potently activates integrin α5-PI3K/AKT signaling pathway through mechanical and biophysical cues, and thereby repairing critical-sized bone defect. The present study provides a bioinspired strategy for completely resembling complex hierarchy of compact mineralized tissue, and offers a critical research model for in-depth studying the structure-function relationship of bone.

Precision (repeatability and reproducibility) of papillary and peripapillary vascular density measurements using optical coherence tomography angiography in children.

Importance: Optical coherence tomography angiography (OCTA) has been widely applied into children, however, few studies have assessed the repeatability and reproducibility of papillary and peripapillary VD in healthy children. Objective: To assess the precision of papillary and peripapillary vascular density (VD) measurements using optical coherence tomography angiography (OCTA) and analyze the effects of the signal strength index (SSI) and axial length (AL) on precision estimates. Design setting and participants: This was a prospective observational study. Seventy-eight children aged 6-16 years underwent 4.5 × 4.5 mm OCTA (RTVue XR Avanti) disc scans: two scans by one examiner (repeatability) and two additional scans by another examiner (reproducibility). Within-subject standard deviation (Sw), test-retest reproducibility (TRT), within-subject coefficient of variation (CoV), intraclass correlation coefficient (ICC), and Bland-Altman analysis were performed. Main outcomes and measures: In repeatability measurement, the fluctuation ranges (minimum to maximum) of VD between intraexaminer A/B in Sw, TRT, CoV, and ICC were (1.05-2.17)% / (1.16-2.32)%, (2.9-6)% / (3.21-6.44)%, (1.9-4.47)% / (2.08-5)%, and (0.588-0.783)% / (0.633-0.803)%, respectively. In reproducibility measurement, the fluctuation ranges of VD in Sw, TRT, CoV, and ICC were 1.11-2.13%, 3.07-5.91%, 1.99-4.41%, and 0.644-0.777%, respectively. VD was negatively correlated with SSI in most sectors of the peripapillary (e.g., inferior nasal, temporal inferior, temporal superior, superior temporal, and superior nasal). AL was positively correlated with inferior temporal VD and negatively correlated with superior nasal VD. Conclusion and relevance: Optical coherence tomography angiography showed moderate-to-good repeatability and reproducibility for papillary and peripapillary perfusion measurements in healthy children. The SSI value affects most of the peripapillary VD, while AL affects only the temporal inferior and nasal superior peripapillary VD.

Combinations of Scheimpflug tomography, ocular coherence tomography and air-puff tonometry improve the detection of keratoconus.

PURPOSE: To determine whether combinations of devices with different measuring principles, supported by artificial intelligence (AI), can improve the diagnosis of keratoconus (KC). METHODS: Scheimpflug tomography, spectral-domain optical coherence tomography (SD-OCT), and air-puff tonometry were performed in all eyes. The most relevant machine-derived parameters to diagnose KC were determined using feature selection. The normal and forme fruste KC (FFKC) eyes were divided into training and validation datasets. The selected features from a single device or different combinations of devices were used to develop models based on random forest (RF) or neural networks (NN) trained to distinguish FFKC from normal eyes. The accuracy was determined using receiver operating characteristic (ROC) curves, area under the curve (AUC), sensitivity, and specificity. RESULTS: 271 normal eyes, 84 FFKC eyes, 85 early KC eyes, and 159 advanced KC eyes were included. A total of 14 models were built. Air-puff tonometry had the highest AUC for detecting FFKC using a single device (AUC = 0.801). Among all two-device combinations, the highest AUC was accomplished using RF applied to selected features from SD-OCT and air-puff tonometry (AUC = 0.902), followed by the three-device combination with RF (AUC = 0.871) with the best accuracy. CONCLUSION: Existing parameters can precisely diagnose early and advanced KC, but their diagnostic ability for FFKC could be optimized. Applying an AI algorithm to a combination of air-puff tonometry with Scheimpflug tomography or SD-OCT could improve FFKC diagnostic ability. The improvement in diagnostic ability by combining three devices is modest.

Sucrose promotes branch-thorn occurrence of Lycium ruthenicum through dual effects of energy and signal.

Lycium ruthenicum is an important ecoeconomic thorny shrub. In this study, the L. ruthenicum plants of a clone showed two types of 'fewer leaves without thorn' and 'more leaves with thorns' under the same condition after transplanting. Microscopic observation revealed that the apical buds of the thornless (Thless) and thorny (Thorny) branches should be selected as materials for further study. RNA-Seq analysis showed that the KEGG pathway of starch and sucrose metabolism and differentially expressed genes of sugar transport protein 13 (SUT13), sucrose synthase (SUS), trehalose-phosphate phosphatase (TPP) and trehalose-phosphate synthase (TPS) were significantly up-regulated in Thorny. The results of qRT-PCR confirmed the accuracy and credibility of the RNA-Seq. The content of sucrose in Thorny was significantly higher than that in Thless, but the content of trehalose-6-phosphate (T6P) was opposite. Leaf-clipping treatments reduced sucrose content and inhibited the occurrence/development of branch-thorns; exogenous sucrose of 16 g l-1 significantly promoted the occurrence and growth of branch-thorns, and the promotion effects were significantly higher than those treated with non-metabolizable sucrose analogs (isomaltolose and melitose). These findings suggested that sucrose might play a dual role of energy and signal in the occurrence of branch-thorns. Higher sucrose supply in apical buds from more leaves promoted the occurrence of branch-thorns via a lower content of T6P and higher expression levels of SUS, TPP and TPS, whereas fewer leaves inhibited the occurrence. The molecular hypothesis model of the leaf number/sucrose supply regulating the occurrence of branch-thorns in L. ruthenicum was established in the study, which provides foundation for breeding both Thless L. ruthenicum and Thless types of other species.

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.].

Self-healing hybrid hydrogels with sustained bioactive components release for guided bone regeneration.

Guided bone regeneration (GBR) is widely used in treating oral bone defects to exclude the influence of non-osteogenic tissue on the bone healing process. The traditional method of GBR with a titanium mesh to treat large-area bone defects is limited by the deficiency of increased trauma and costs to patients. Herein, a bi-layered scaffold for GBR composed of a fiber barrier layer and a self-healing hydrogel repair layer is successfully fabricated. The barrier layer is a fibrous membrane material with specific porosity constructed by electrospinning, while the functional layer is a self-healing hydrogel material formed by multiple dynamic covalent bonds. The system can provide an osteogenic microenvironment by preventing the infiltration of connective tissue to bone defects, maintain the stability of the osteogenic space through the self-healing property, and regulate the release of bioactive substances in the dynamic physical condition, which is beneficial to osteoblast proliferation, differentiation, and bone regeneration. This study focused on exploring the effects of different crosslinkers and bonding methods on the comprehensive properties of hydrogels. and proved that the hybrid scaffold system has good biocompatibility, cell barrier function and can enhance bone regeneration activity. Thereby it could be a promising clinical strategy for bone regeneration.

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.].

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.

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.

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.

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).