Comparison between a new transepithelial PRK vs. conventional alcohol-assisted PRK: Corneal densitometry and aberrometry study.

PURPOSE: To describe and compare corneal densitometry, subjective refraction, visual acuity, and corneal higher order aberrations (HOA) after corneal refractive surgery using either alcohol-assisted photorefractive keratectomy (aaPRK) or single-step transepithelial PRK (tPRK). METHODS: We conducted a retrospective and observational study. We analyzed 120 right eyes from 120 healthy consecutive myopic patients who underwent aaPRK or tPRK to correct myopia of up to 6 diopters and astigmatism of up to 2 diopters. The WaveLight EX500 excimer laser (Alcon Laboratories, Inc.) was used in all cases. Visual acuity, subjective refraction, and Pentacam AXL® measurements were performed at the preoperative visit and at 6-months follow-up visit. Pentacam AXL® software was used to assess corneal optical density in various annuli for different corneal depths and anterior corneal HOA (6 mm area of analysis). RESULTS: Preoperative spherical equivalent values were similar between groups preoperatively (-3.07 ± 1.52 and -3.38 ± 1.46 in the aaPRK and tPRK groups, respectively). There were no statistically significant differences in visual acuity and postoperative refraction between groups. Postoperative corneal densitometry did not show statistically significant differences in any of the areas studied and both surgical procedures obtained similar results. However, analysis of HOA showed statistically significant differences between the techniques (1.42 ± 0.39 and 1.80 ± 0.62 for the aaPRK and tPRK groups, respectively; p = 0.000). CONCLUSIONS: Both aaPRK and single-step tPRK gave comparable visual, refractive, and corneal density outcomes. Some differences were observed in HOA but were not clinically relevant.

Early elastic and viscoelastic corneal biomechanical changes after photorefractive keratectomy and small incision lenticule extraction.

PURPOSE: To compare early changes in the corneal biomechanical parameters after photorefractive keratectomy (PRK) and small incision lenticule extraction (SMILE) and their correlations with corneal shape parameters. METHODS: One hundred twenty four eyes received myopic PRK and SMILE for similar amounts of myopia. Corneal tomography with Pentacam HR, biomechanical parameters using Corvis ST, and Ocular Response Analyzer (ORA) were evaluated before and 2 weeks after surgery. The change in each parameter was compared between groups, while the difference in central corneal thickness and cornea-compensated intraocular pressure measured before and after surgery were considered as covariates. RESULTS: A significant reduction was seen in the corneal stiffness parameter at first applanation, and an increase in deformation amplitude ratio (DAR), and integrated inverse radius (IIR) in both groups after surgery (p < 0.001) Changes in DAR, and IIR were significantly greater in the SMILE than in the PRK group (p < 0.001) Corneal hysteresis (CH) and corneal resistance factor (CRF) decreased in both SMILE and PRK groups after surgery, (p < 0.001) with no statistically significant difference between groups (p > 0.05) Among new Corvis ST parameters, DAR showed a significant correlation with changes in Ambrosio relational thickness in both groups (p < 0.05). CONCLUSIONS: Both techniques caused significant changes in corneal biomechanics in the early postoperative period, with greater elastic changes in the SMILE group compared to the PRK group, likely due to lower tension in the SMILE cap and thinner residual stromal bed in SMILE. There were no differences in viscoelastic changes between them, so the lower CH may reflect the volume of tissue removed.

Molecular insights into the regulatory landscape of PKC-related kinase-2 (PRK2/PKN2) using targeted small compounds.

The PKC-related kinases (PRKs, also termed PKNs) are important in cell migration, cancer, hepatitis C infection, and nutrient sensing. They belong to a group of protein kinases called AGC kinases that share common features like a C-terminal extension to the catalytic domain comprising a hydrophobic motif. PRKs are regulated by N-terminal domains, a pseudosubstrate sequence, Rho-binding domains, and a C2 domain involved in inhibition and dimerization, while Rho and lipids are activators. We investigated the allosteric regulation of PRK2 and its interaction with its upstream kinase PDK1 using a chemical biology approach. We confirmed the phosphoinositide-dependent protein kinase 1 (PDK1)-interacting fragment (PIF)-mediated docking interaction of PRK2 with PDK1 and showed that this interaction can be modulated allosterically. We showed that the polypeptide PIFtide and a small compound binding to the PIF-pocket of PRK2 were allosteric activators, by displacing the pseudosubstrate PKL region from the active site. In addition, a small compound binding to the PIF-pocket allosterically inhibited the catalytic activity of PRK2. Together, we confirmed the docking interaction and allostery between PRK2 and PDK1 and described an allosteric communication between the PIF-pocket and the active site of PRK2, both modulating the conformation of the ATP-binding site and the pseudosubstrate PKL-binding site. Our study highlights the allosteric modulation of the activity and the conformation of PRK2 in addition to the existence of at least two different complexes between PRK2 and its upstream kinase PDK1. Finally, the study highlights the potential for developing allosteric drugs to modulate PRK2 kinase conformations and catalytic activity.

To Investigate the Changes in Corneal Curvature and Its Correlation with Corneal Epithelial Remodeling After Trans-PRK and FS-LASIK.

PURPOSE: To evaluate curvature changes in different regions and their correlation with corneal epithelial remodeling in myopic patients undergoing femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and transepithelial refractive keratectomy (Trans-PRK) after surgery. METHODS: One hundred and sixty-three patients (163 right eyes) undergoing Trans-PRK and LASIK were evaluated for up to 6 months using anterior segment optical coherence tomography (OCT) to measure the epithelial thickness and corneal topography to measure corneal curvature in different areas (2 mm, 5 mm, and 7 mm). We calculated the curvature ΔK (ΔK = preoperative - postoperative), ΔK5-2 (ΔK5-2 = K5mm - K2mm), ΔK7-5 (ΔK7-5 = K7mm - K5mm), and the epithelial thickness ΔET5-2 (ΔET5-2 = ET5mm - ET2mm) and ΔET7-5 (ΔET7-5= ET7mm - ET5mm). RESULTS: Corneal curvature flattened in each region of the two groups (all p < 0.001) and gradually steepened during the follow-up period. The Trans-PRK group flattened more significantly within 2 mm and 5 mm, while the FS-LASIK group at 7 mm. Both groups of ΔK decreased over time. Both groups of ΔK5-2 and ΔK7-5 gradually decreased during the follow-up period (P5-2=0.025 and P7-5 < 0.001 for Trans-PRK, P5-2 = 0.011 and P7-5 < 0.001 for FS-LASIK). The corneal epithelium of the two groups gradually thickened during the follow-up period, with Trans-PRK significantly thickening in the central and peripheral regions and FS-LASIK in the central and paracentral regions. There is a significant correlation between the ΔK5-2 and ΔET5-2, ΔK7-5 and ΔET7-5 (all r > 0.37, p < 0.001). CONCLUSIONS: All groups showed significant curvature flattening after surgery and gradually steepening during the follow-up period. The corneal epithelium thickness in both groups of 17 regions became thicker,. In contrast, Trans-PRK group showed more significant thickening to the periphery and the central 5 mm area of the FS-LASIK. This study indicates a significant positive correlation between differences in epithelial thickening in different regions and differences in curvature changes in the corresponding areas PRK, FS-LASIK, curvature, corneal epithelial thickness.

BCLA CLEAR Presbyopia: Management with corneal techniques.

Corneal techniques for enhancing near and intermediate vision to correct presbyopia include surgical and contact lens treatment modalities. Broad approaches used independently or in combination include correcting one eye for distant and the other for near or intermediate vision, (termed monovision or mini-monovision depending on the degree of anisometropia) and/or extending the eye's depth of focus [1]. This report reviews the evidence for the treatment profile, safety, and efficacy of the current range of corneal techniques for managing presbyopia. The visual needs and expectations of the patient, their ocular characteristics, and prior history of surgery are critical considerations for patient selection and preoperative evaluation. Contraindications to refractive surgery include unstable refraction, corneal abnormalities, inadequate corneal thickness for the proposed ablation depth, ocular and systemic co-morbidities, uncontrolled mental health issues and unrealistic patient expectations. Laser refractive options for monovision include surface/stromal ablation techniques and keratorefractive lenticule extraction. Alteration of spherical aberration and multifocal ablation profiles are the primary means for increasing ocular depth of focus, using surface and non-surface laser refractive techniques. Corneal inlays use either small aperture optics to increase depth of field or modify the anterior corneal curvature to induce corneal multifocality. In presbyopia correction by conductive keratoplasty, radiofrequency energy is applied to the mid-peripheral corneal stroma, leading to mid-peripheral corneal shrinkage and central corneal steepening. Hyperopic orthokeratology lens fitting can induce spherical aberration and correct some level of presbyopia. Postoperative management, and consideration of potential complications, varies according to technique applied and the time to restore corneal stability, but a minimum of 3 months of follow-up is recommended after corneal refractive procedures. Ongoing follow-up is important in orthokeratology and longer-term follow-up may be required in the event of late complications following corneal inlay surgery.

Tear Proteins Altered in Patients with Persistent Eye Pain after Refractive Surgery: Biomarker Candidate Discovery.

Some patients develop persistent eye pain after refractive surgery, but factors that cause or sustain pain are unknown. We tested whether tear proteins of patients with pain 3 months after surgery differ from those of patients without pain. Patients undergoing refractive surgery (laser in situ keratomileusis or photorefractive keratectomy ) were recruited from 2 clinics, and tears were collected 3 months after surgery. Participants rated their eye pain using a numerical rating scale (NRS, 0-10; no pain-worst pain) at baseline, 1 day, and 3 months after surgery. Using tandem mass tag proteomic analysis, we examined tears from patients with pain [NRS ≥ 3 at 3 months (n = 16)] and patients with no pain [NRS ≤ 1 at 3 months (n = 32)] after surgery. A subset of proteins (83 of 2748 detected, 3.0%) were associated with pain 3 months after surgery. High-dimensional statistical models showed that the magnitude of differential expression was not the only important factor in classifying tear samples from pain patients. Models utilizing 3 or 4 proteins had better classification performance than single proteins and represented differences in both directions (higher or lower in pain). Thus, patterns of protein differences may serve as biomarkers of postsurgical eye pain as well as potential therapeutic targets.

[Effect of refractive surgery on Maklakov tonometry results]. / Vliyanie keratorefraktsionnoi khirurgii na rezul'taty tonometrii po Maklakovu.

PURPOSE: The study investigates the influence of changes in keratometric parameters after refractive surgery on the results of Maklakov tonometry. MATERIAL AND METHODS: The study examined a total of 61 people (121 eyes). The patients were divided into a control group with no history of surgery (16 people, 31 eyes), a LASIK group (13 people, 26 eyes), a femtosecond-assisted LASIK (FS-LASIK) group (16 people, 32 eyes), and a photorefractive keratectomy (PRK) group (16 people, 32 eyes). The patients underwent standard examination, keratometry (Km), Maklakov tonometry with a 10 g weight, and elastotonometry with 5, 7.5, and 15 g weights. RESULTS: In the LASIK group, the indentation diameter with 5 and 7.5 g weights correlated with Km in the central and near-paracentral zone (r=0.3-0.5). Tonometry with a 10 g weight did not correlate with anything. Tonometry with a 15 g weight inversely correlated with Km in the paracentral points (4 mm) of the strong meridian (r= -0.5 ... -0.7). In the FS-LASIK group, a significant inverse correlation with Km was observed only for the indentation diameter with a 10 g weight in the paracentral (3-4 mm) zone (r= -0.4 ... -0.5). In the PRK group, weak (r<0.4) correlations were found between Km and the indentation diameter of the 7.5 and 10 g weights for the central zone (1-2 mm). No significant correlations were found for 5 and 15 g weights.In the control group, there were practically no correlations for 5 and 7.5 g weights. The indentation diameter of the 10 g weight evenly correlated with Km at all points (r= -0.38 ... -0.60), the indentation of the 15 g weight correlated mainly with the curvature of the horizontal meridian (r= -0.37 ... -0.49). CONCLUSION: Tonometry readings with the 10 g weight are the most dependent on Km in different groups, and the readings with the 5 g weight are the least dependent. LASIK is characterized by the largest scatter of dependencies for weights of different masses, FS-LASIK - by the smallest. Tonometry readings with the 5 g weight correlated with Km only in the LASIK group, and this was the only direct correlation. Considering the inverse nature of most correlations, higher Km may be associated with an overestimation of tonometry results, and lower Km - with its underestimation.

Antimycobacterial and healing effects of Pranlukast against MTB infection and pathogenesis in a preclinical mouse model of tuberculosis.

It is essential to understand the interactions and relationships between Mycobacterium tuberculosis (Mtb) and macrophages during the infection in order to design host-directed, immunomodulation-dependent therapeutics to control Mtb. We had reported previously that ornithine acetyltransferase (MtArgJ), a crucial enzyme of the arginine biosynthesis pathway of Mtb, is allosterically inhibited by pranlukast (PRK), which significantly reduces bacterial growth. The present investigation is centered on the immunomodulation in the host by PRK particularly the activation of the host's immune response to counteract bacterial survival and pathogenicity. Here, we show that PRK decreased the bacterial burden in the lungs by upregulating the population of pro-inflammatory interstitial macrophages (IMs) and reducing the population of Mtb susceptible alveolar macrophages (AMs), dendritic cells (DCs), and monocytes (MO). Additionally, we deduce that PRK causes the host macrophages to change their metabolic pathway from fatty acid metabolism to glycolytic metabolism around the log phage of bacterial multiplication. Further, we report that PRK reduced tissue injury by downregulating the Ly6C-positive population of monocytes. Interestingly, PRK treatment improved tissue repair and inflammation resolution by increasing the populations of arginase 1 (Arg-1) and Ym1+Ym2 (chitinase 3-like 3) positive macrophages. In summary, our study found that PRK is useful not only for reducing the tubercular burden but also for promoting the healing of the diseased tissue.

Comparative Analysis of Corneal Higher-Order Aberrations after Laser-Assisted In Situ Keratomileusis, Photorefractive Keratectomy, and Small Incision Lenticule Extraction with Correlations to Change in Myopic Q-Value and Spherical Equivalent with and without Astigmatism.

Background: This retrospective chart review compared the higher-order aberrations (HOAs) among photorefractive keratectomy (PRK), laser-assisted in situ keratomileusis (LASIK), and small incision lenticule extraction (SMILE) alongside changes in spherical equivalent (SEQ) and corneal shape (Q-value). Methods: Analyzing 371 myopic eyes, including 154 LASIK, 173 PRK, and 44 SMILE cases, Pentacam imaging was utilized pre-operatively and at one-year post-operative visits. Results: All procedures resulted in 100% of patients achieving an uncorrected distance visual acuity (UDVA) of 20/40 or better, with 87% of LASIK and PRK, and 91% of SMILE patients having 20/20 or better. Significant increases in HOAs were observed across all procedures (p < 0.05), correlating positively with SEQ and Q-value changes (LASIK (0.686, p < 0.05), followed by PRK (0.4503, p < 0.05), and SMILE (0.386, p < 0.05)). Vertical coma and spherical aberration (SA) were the primary factors for heightened aberration magnitude among the procedures (p < 0.05), with the largest contribution in SMILE, which is likely attributed to the centration at the corneal apex. Notably, PRK showed insignificant changes in vertical coma (-0.197 µm ± 0.0168 to -0.192 µm ± 0.0198, p = 0.78), with an increase in oblique trefoil (p < 0.05). Conclusions: These findings underscore differences in HOAs among PRK, LASIK, and SMILE, helping to guide clinicians.

Advances in Transepithelial Photorefractive Keratectomy versus Laser-Assisted In Situ Keratomileusis.

(1) Background: Laser-assisted refractive surgery is a safe and effective surgical correction of refractive error. For most patients, both the newer Trans-PRK and the established LASIK technique can produce the required surgical correction, sparking the question of which technique should be opted for. (2) Methods: The study prospectively evaluated 121 patients (230 eyes) for at least one month postoperatively; 66 patients (126 eyes) and 45 patients (85 eyes) returned for 6 months and 1 year follow-up. (3) Results: No statistical difference was recorded at 1 week or 1 month post-operation. At 6 months, a difference was found for spherical diopters (Trans-PRK -0.0476 ± 0.7012 versus FS-LASIK +0.425 ± 0.874, p = 0.004) and spherical equivalent (Trans-PRK -0.1994 ± 0.0294 versus FS-LASIK +0.225 ± 0.646, p = 0.025) but not for CYL D (Trans-PRK -0.3036 ± 0.5251 versus FS-LASIK -0.4 ± 0.820, p = 0.499). Uncorrected visual acuity was better for Trans-PRK 6 months post-operation (UCVA logMAR 0.02523 versus 0.0768 logMAR; p = 0.015 logMAR). At 1-year, Trans-PRK was favored for spherical diopters (Trans-PRK -0.0294 ± 0.6493 versus FS-LASIK +0.646 ± 0.909, p < 0.001) and spherical equivalent (Trans-PRK -0.218 ± 0.784 versus FS-LASIK 0.372 ± 1.08, p = 0.007). Overall speed in visual recovery, variance of results and surgically induced astigmatism were in favor of Trans-PRK. (4) Conclusions: The study reported improvements for Trans-PRK patients, with both techniques found to be safe and effective.

Transepithelial Photorefractive Keratectomy-Review.

The type and nature of refractive surgery procedures has greatly increased over the past few decades, allowing for almost all patient populations to be treated to extremely high satisfaction. Conventional photorefractive keratectomy involves the removal of the corneal epithelium through mechanical debridement or dilute alcohol instillation. An improvement to this method utilises laser epithelial removal in a single-step process termed transepithelial photorefractive keratectomy (transPRK). We explore the history of transPRK from its early adoption as a two-step process, identify different transPRK platforms from major manufacturers, and describe the role of transPRK in the refractive surgery armamentarium. This is a narrative review of the literature. This review finds that TransPRK is a safe and effective procedure that works across a variety of patient populations. Though often not seen as a primary treatment option when compared to other corneal-based procedures that offer a faster and more comfortable recovery, there are many scenarios in which these procedures are not possible. These include, but are not limited to, cases of corneal instability, previous refractive surgery, or transplant where higher-order aberrations can impair vision in a manner not amenable to spectacle or contact lens correction. We discuss refinements to the procedure that would help improve outcomes, including optimising patient discomfort after surgery as well as reducing corneal haze and refractive regression.

Headache Attributed to Refractive Error: Improvement after Topography-Guided Photorefractive Keratectomy with Corneal Cross-Linking in Patients with Keratoconus.

PURPOSE: To investigate if topography-guided photorefractive keratectomy (TGPRK) alleviates headache, particularly headache attributed to refractive errors (HARE) in keratoconus. METHODS: Patients diagnosed with keratoconus undergoing TGPRK for refractive correction were included. Best spectacle corrected visual acuity (BSCVA) using the logMAR scale and refractive error were measured. Patients answered a questionnaire exploring headaches, characteristics, treatment, and the Headache Impact Test (HIT-6) before and 6 months after the surgery. RESULTS: 40 patients were included. Preoperatively, 24 patients (60%) met criteria for headaches: five for migraine, 14 for HARE, and five for tension-type headache (TTH). Patients with headaches preoperatively were more likely to require bilateral TGPRK, and the mean sphere and cylindrical power were higher. Postoperatively, 15 out of the 24 patients of the headache group experienced complete resolution of headaches, and only nine patients met diagnostic criteria for headaches: two for migraine, six for HARE, and one for TTH. The number of headaches reduced from 4.4 ± 2.4 to 0.5 ± 0.7 days/week (p < 0.001). Headache duration decreased from 108.5 ± 100.7 min to 34.4 ± 63.5 min (p = 0.002). Postoperatively, the consumption of analgesia decreased. The HIT-6 revealed an improvement in the quality-of-life post-procedure (p < 0.001). CONCLUSIONS: Surgical correction of irregular astigmatism in patients with keratoconus can alleviate or resolve headaches in a large proportion of patients, resulting in an improvement in their quality of life. Physicians should consider keratoconus in patients fitting criteria for HARE not alleviated by spectacle correction and suboptimal vision in glasses.

Limitations of and Solutions to Using 6 mm Corneal Spherical Aberration and Q Value after Laser Refractive Surgery.

This study aimed to evaluate the spherical aberration (SA) in different corneal areas before and after femtosecond laser-assisted in situ keratomileusis (fLASIK) and transepithelial photorefractive keratectomy (tPRK), with the goal of identifying the limitations of and potential improvements in using SA within a 6 mm area. The study included 62 patients who underwent fLASIK and tPRK. Complete eye examinations including keratometry, corneal epithelial thickness, central corneal thickness, and topography were performed preoperatively and postoperatively. Anterior, posterior, and total corneal aberrations were measured preoperatively and three months postoperatively, with pupil diameters ranging from 2 to 8 mm. In the fLASIK group, compared to the preoperative SA, the anterior and total SA increased postoperatively in the 6 and 7 mm areas. In the tPRK group, meanwhile, the anterior and total SA of the 5 mm or larger areas increased postoperatively. An area of 6 mm or larger showed an increase in correlation with the changes in Q value and refractive correction. As the corneal SA and asphericity in the 6 mm zone cannot specifically demonstrate the status of areas smaller than 6 mm or changes in the optical zone after laser refractive surgery, comparison with normal values in various areas of the cornea is necessary.

Redox regulation of the Calvin-Benson-Bassham cycle during cold acclimation.

NADPH-dependent thioredoxin reductase C (NTRC) redox interaction with protein CP12 plays a role in cold acclimation. A recent study by Teh et al. describes the underlying molecular mechanisms that leads to dissociation of the autoinhibitory PRK/CP12/GAPDH (phosphoribulokinase/CP12/glyceraldehyde-3-phosphate dehydrogenase) supracomplex. We propose that chloroplast-to-nucleus retrograde signaling precedes the described mechanism.

Accuracy of intraoperative aberrometry versus modern preoperative methods in post-myopic laser vision correction eyes undergoing cataract surgery with capsular tension ring placement.

PURPOSE: To assess the accuracy of intraoperative wavefront aberrometry (IWA) versus modern intraocular lens formulas in post-myopic laser vision correction (LVC) patients undergoing cataract surgery with capsular tension ring placement. METHODS: This is a retrospective chart review conducted at an academic outpatient center. All post-myopic LVC eyes undergoing cataract surgery with IWA from a single surgeon from 05/2017 to 12/2019 were included. All patients received a capsular tension ring (CTR). Mean numerical error (MNE), median numerical error (MedNE), and percentages of prediction error within 0.50D, 0.75D, and 1.00D were calculated for the above formulas. RESULTS: Twenty-seven post-myopic LVC eyes from 18 patients were included. In post-myopic LVC, MNE with Optiwave Refractive Analysis (ORA), Barrett True K (BTK), Haigis, Haigis-L, Shammas, SRK/T, Hill-RBF v3.0, and W-K AL-adjusted Holladay 1 were + 0.224, - 0.094, + 0.193, - 0.231, - 0.372, + 1.013, + 0.860, and + 0.630 (F = 8.49, p < 0.001). MedNE were + 0.125, - 0.145, + 0.175, + 0.333, + 0.333, + 1.100, + 0.880, and + 0.765 (F = 7.89, p < 0.001), respectively. BTK provided improved accuracy in both MNE (p < 0.001) and MedNE (p = .033) when compared to ORA in pairwise analysis. If the ORA vs. BTK-suggested IOL power were routinely selected, 30% and 15% of eyes would have projected hyperopic outcomes, respectively (p = 0.09). CONCLUSIONS: Our study suggests that in post-myopic LVC eyes undergoing cataract surgery with CTRs, BTK performed more accurately than ORA with regard to accuracy and yielded a lower percentage of eyes with hyperopic outcomes. Haigis, Haigis-L, and Shammas yielded similar results to ORA with regard to accuracy and percentage of eyes with hyperopic outcomes. On average, Shammas and Haigis-L suggested IOLs that would yield outcomes more myopic than expected when compared to BTK.

Visual Outcomes of a Second-Generation, Enhanced UV Protected Light Adjustable Lens in Cataract Patients with Previous LASIK and/or PRK.

Purpose: To report on the visual outcomes of the second-generation (ActivShieldTM) Light Adjustable Lens (LAL) used in cataract surgery for patients with a history of laser refractive surgery (LASIK and/or photorefractive keratectomy [PRK]) using a co-managed, open-access methodology. Patients and Methods: This retrospective case series of consecutive patients with history of laser refractive surgery implanted with the second-generation LAL with an emmetropic target were included in the study. Following surgery, all patients received their ultraviolet (UV) light treatments at a separate open-access facility through a co-managed arrangement. Uncorrected distance visual acuity (UDVA), spherical equivalent (SE), and residual cylinder for eyes with an emmetropic refractive target were the primary outcome measures as documented at the patient's final, stable, refractive postoperative exam. Results: Thirty-three patients (34 eyes) with a history of laser refractive surgery were included in the study and implanted with the second-generation LAL with a postoperative emmetropic refractive target. Twenty-eight (82.4%) saw 20/20 or better and 9 (26.5%) saw 20/15 or better. The mean SE was 0.01 ± 0.31 D and 33 (97.1%) were within ±0.50 D SE of plano. The mean residual cylinder was -0.28 ± 0.32 D and 30 (88.2%) were within ±0.50 D. Conclusion: Use of the second-generation LAL was efficacious in cataract surgical patients with a history of LASIK and/or PRK using a co-managed, open-access methodology.

High-throughput chemogenetic drug screening reveals PKC-RhoA/PKN as a targetable signaling vulnerability in GNAQ-driven uveal melanoma.

Uveal melanoma (UM) is the most prevalent cancer of the eye in adults, driven by activating mutation of GNAQ/GNA11; however, there are limited therapies against UM and metastatic UM (mUM). Here, we perform a high-throughput chemogenetic drug screen in GNAQ-mutant UM contrasted with BRAF-mutant cutaneous melanoma, defining the druggable landscape of these distinct melanoma subtypes. Across all compounds, darovasertib demonstrates the highest preferential activity against UM. Our investigation reveals that darovasertib potently inhibits PKC as well as PKN/PRK, an AGC kinase family that is part of the "dark kinome." We find that downstream of the Gαq-RhoA signaling axis, PKN converges with ROCK to control FAK, a mediator of non-canonical Gαq-driven signaling. Strikingly, darovasertib synergizes with FAK inhibitors to halt UM growth and promote cytotoxic cell death in vitro and in preclinical metastatic mouse models, thus exposing a signaling vulnerability that can be exploited as a multimodal precision therapy against mUM.

Co-cultivation of Saccharomyces cerevisiae strains combines advantages of different metabolic engineering strategies for improved ethanol yield.

Glycerol is the major organic byproduct of industrial ethanol production with the yeast Saccharomyces cerevisiae. Improved ethanol yields have been achieved with engineered S. cerevisiae strains in which heterologous pathways replace glycerol formation as the predominant mechanism for anaerobic re-oxidation of surplus NADH generated in biosynthetic reactions. Functional expression of heterologous phosphoribulokinase (PRK) and ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) genes enables yeast cells to couple a net oxidation of NADH to the conversion of glucose to ethanol. In another strategy, NADH-dependent reduction of exogenous acetate to ethanol is enabled by introduction of a heterologous acetylating acetaldehyde dehydrogenase (A-ALD). This study explores potential advantages of co-cultivating engineered PRK-RuBisCO-based and A-ALD-based strains in anaerobic bioreactor batch cultures. Co-cultivation of these strains, which in monocultures showed reduced glycerol yields and improved ethanol yields, strongly reduced the formation of acetaldehyde and acetate, two byproducts that were formed in anaerobic monocultures of a PRK-RuBisCO-based strain. In addition, co-cultures on medium with low acetate-to-glucose ratios that mimicked those in industrial feedstocks completely removed acetate from the medium. Kinetics of co-cultivation processes and glycerol production could be optimized by tuning the relative inoculum sizes of the two strains. Co-cultivation of a PRK-RuBisCO strain with a Δgpd1 Δgpd2 A-ALD strain, which was unable to grow in the absence of acetate and evolved for faster anaerobic growth in acetate-supplemented batch cultures, further reduced glycerol formation but led to extended fermentation times. These results demonstrate the potential of using defined consortia of engineered S. cerevisiae strains for high-yield, minimal-waste ethanol production.

Preservative-Free Topical Anesthetic Unit-Dose Eye Drops for the Management of Postoperative Pain Following Photorefractive Keratectomy.

INTRODUCTION: Ocular pain is a common complication following photorefractive keratectomy (PRK). The level of patient satisfaction with current pain control strategies is not high. This study aims to assess the efficacy and safety of a novel regimen of preservative-free oxybuprocaine hydrochloride 0.4% unit-dose eye drops for post-PRK pain control. METHODS: In a contralateral eye study, 144 eyes of 72 patients who underwent bilateral transepithelial PRK (TransPRK) were stratified into experimental and control groups. The experimental group received preservative-free oxybuprocaine hydrochloride 0.4% unit-dose eye drops five times daily postoperatively until complete epithelial healing, while the control group received sodium hyaluronate 0.2% instead. The main outcome measures were pain scores assessed by the verbal rating scale and visual analogue scale (VRS, VAS), the corneal epithelial defect (CED) area, epithelial healing duration evaluated by slit-lamp biomicroscopy and anterior segment optical coherence tomography (AS-OCT), and endothelial cell density (ECD) measured before and 1 month after surgery. RESULTS: Pain scores assessed by VRS and VAS were significantly lower in the experimental group 8 h after surgery, and 1, 2, and 3 days postoperatively (P < 0.001). The mean CED area showed no significant differences between the two groups at different follow-ups (P value > 0.05). The corneal epithelial healing had a mean duration of 3.32 ± 0.47 days in both studied groups and was parallel in both eyes of each patient. In each group, 49 eyes (68%) and 72 eyes (100%) had a fully epithelialized surface on the third and fourth postoperative days, respectively. No significant changes were observed in the mean ECD 1 month following surgery in both groups (P value > 0.05). CONCLUSION: Preservative-free oxybuprocaine hydrochloride 0.4% unit-dose eye drops are effective and safe in controlling early postoperative pain following TransPRK. The availability of the single-dose unit preparation can overcome the problem of topical anesthetic abuse. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05733741.

Assessment of Pupil Size and Angle Kappa in Refractive Surgery: A Population-Based Epidemiological Study in Predominantly American Caucasians.

Purpose This retrospective study aims to establish normative values for pupil size, angle kappa, higher-order aberration, and astigmatism type in a largely Caucasian population in Utah, United States, utilizing the NIDEK OPD-Scan III system (Gamagori, Japan). Methods This study included 716 patients (1432 eyes) grouped based on spherical equivalence and age. Measurements were conducted under mesopic and photopic conditions. Statistical analysis involved Pearson's correlation and linear regression using the generalized estimating equation. NIDEK OPD-Scan III measured mesopic and photopic pupil size and angle kappa. The subjects were then grouped based on their spherical equivalence in diopters (D) and age in decades. The spherical equivalence groups were defined: >-6 D, -5.99 to -3 D, -2.99 to -0.25 D, -0.24 to 0.24 D, and >0.25 D (range 0.25-5.75 D). The higher-order aberration groups were based on the reason for the visit: laser-assisted in situ keratomileusis, photorefractive keratectomy, and small incision lenticule extraction as one group; cataract evaluation; and keratoconus. Astigmatism measurements were grouped into with-the-rule (WRT), against-the-rule (ATR), and oblique astigmatism, with further subgrouping into a young cohort (20-40 years) and an old cohort (>65 years).  Results Among 716 participants, 49.2% were men; the mean age was 42.1±15.5 (range 7-88 years). The average spherical equivalence for myopia eyes was -3.28±2.34 D, and 1.51±1.46 D for hyperopia eyes. The mean mesopic pupil size was 5.68 ± 1.09 mm; the photopic pupil size was 4.65±1.09 mm. Pearson's correlation coefficient for mesopic pupil size versus age was -0.551, and -0.42 for photopic pupil (p < 0.001); sphere vs mesopic pupil size was -0.200, and -0.173 for photopic pupil (p < 0.001). The regression analysis for mesopic pupil size versus age revealed a 0.39 mm decrease in average pupil size per decade increase in age, and 0.25 mm decrease per decade for photopic pupil. The regression analysis for mesopic pupil size versus sphere revealed a 0.22 mm decrease in average pupil size per 3D increase in sphere, and a 0.16 mm decrease 3 D increase in sphere for the photopic pupil. The mean mesopic angle kappa was 0.33 ± 0.15 mm; photopic angle kappa was 0.31±0.15 mm. Pearson's correlation coefficient for mesopic angle kappa vs spherical equivalence was 0.32, and 0.296 for photopic angle kappa (p <0.001 for both). Regression analysis for mesopic angle kappa vs spherical equivalence demonstrated a 0.051 mm increase in angle kappa per 3 D increase in spherical equivalence, and a 0.048 mm increase for photopic angle kappa (p < 0.001 for both). Among the higher-order aberration groups, the keratoconus group exhibited the highest levels. In terms of astigmatism type, WRT astigmatism was the most common in the young cohort, while ATR astigmatism was most prevalent in the older cohort. Conclusions The results of this study reveal significant associations between pupil size and increasing age, as well as between pupil size and increasingly positive refractive errors. These findings hold particular clinical relevance to older patients and individuals with hyperopia, as they undergo photoablative corneal refractive surgery or multifocal intraocular lens implantation. Understanding the established normative values for pupil size, angle kappa, higher-order aberration, and astigmatism type can aid clinicians in making more informed decisions and improving patient outcomes.