Repeatability and agreement of total corneal astigmatism measured in keratoconic eyes using four current devices.

BACKGROUND: To evaluate repeatability and agreement in measurements of total corneal astigmatism (TCA) in keratoconic eyes, using four optical coherence tomography (OCT)-based devices: Anterion, Casia SS-1000, IOLMaster 700, and MS-39. METHODS: Three consecutive measurements were taken with each device in 136 eyes. TCA values were converted into components J0 and J45. The Anterion and the IOLMaster 700 also provided axial length (AL) measurements. The repeatability was calculated using pooled within-subject standard deviation (Sw). The agreement among the four devices was assessed by pairwise comparisons and Bland-Altman plots. RESULTS: For all devices, the repeatability of TCA measurements showed Sw ≤0.23 D for TCA magnitude, ≤0.14 D for J0, and ≤0.12 D for J45. There were statistically significant differences in TCA magnitude for each pair, except for IOLMaster 700 with MS-39, and Anterion with MS-39. The repeatability (Sw) of axis measurements had a statistically significant negative correlation with the TCA magnitude (p < 0.001 for all devices). Both Anterion and IOLMaster 700 had high repeatability in AL measurements (Sw: 0.007 mm for Anterion and 0.009 mm for IOLMaster 700). The difference in AL between the two was 0.015 ± 0.033 mm (p < 0.001). CONCLUSIONS: All four devices showed good repeatability in TCA measurements in keratoconic eyes, the agreement for TCA measurements between the tested devices was generally low. Anterion and IOLMaster 700 showed good repeatability and agreement in AL measurements.

Structure of lipoprotein lipase in complex with GPIHBP1.

Lipoprotein lipase (LPL) plays a central role in triglyceride (TG) metabolism. By catalyzing the hydrolysis of TGs present in TG-rich lipoproteins (TRLs), LPL facilitates TG utilization and regulates circulating TG and TRL concentrations. Until very recently, structural information for LPL was limited to homology models, presumably due to the propensity of LPL to unfold and aggregate. By coexpressing LPL with a soluble variant of its accessory protein glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) and with its chaperone protein lipase maturation factor 1 (LMF1), we obtained a stable and homogenous LPL/GPIHBP1 complex that was suitable for structure determination. We report here X-ray crystal structures of human LPL in complex with human GPIHBP1 at 2.5-3.0 Å resolution, including a structure with a novel inhibitor bound to LPL. Binding of the inhibitor resulted in ordering of the LPL lid and lipid-binding regions and thus enabled determination of the first crystal structure of LPL that includes these important regions of the protein. It was assumed for many years that LPL was only active as a homodimer. The structures and additional biochemical data reported here are consistent with a new report that LPL, in complex with GPIHBP1, can be active as a monomeric 1:1 complex. The crystal structures illuminate the structural basis for LPL-mediated TRL lipolysis as well as LPL stabilization and transport by GPIHBP1.

The Crystal Structure of Cancer Osaka Thyroid Kinase Reveals an Unexpected Kinase Domain Fold.

Macrophages are important cellular effectors in innate immune responses and play a major role in autoimmune diseases such as rheumatoid arthritis. Cancer Osaka thyroid (COT) kinase, also known as mitogen-activated protein kinase kinase kinase 8 (MAP3K8) and tumor progression locus 2 (Tpl-2), is a serine-threonine (ST) kinase and is a key regulator in the production of pro-inflammatory cytokines in macrophages. Due to its pivotal role in immune biology, COT kinase has been identified as an attractive target for pharmaceutical research that is directed at the discovery of orally available, selective, and potent inhibitors for the treatment of autoimmune disorders and cancer. The production of monomeric, recombinant COT kinase has proven to be very difficult, and issues with solubility and stability of the enzyme have hampered the discovery and optimization of potent and selective inhibitors. We developed a protocol for the production of recombinant human COT kinase that yields pure and highly active enzyme in sufficient yields for biochemical and structural studies. The quality of the enzyme allowed us to establish a robust in vitro phosphorylation assay for the efficient biochemical characterization of COT kinase inhibitors and to determine the x-ray co-crystal structures of the COT kinase domain in complex with two ATP-binding site inhibitors. The structures presented in this study reveal two distinct ligand binding modes and a unique kinase domain architecture that has not been observed previously. The structurally versatile active site significantly impacts the design of potent, low molecular weight COT kinase inhibitors.

Postoperative Changes in Corneal Epithelial and Stromal Thickness Profiles After Photorefractive Keratectomy in Treatment of Myopia.

PURPOSE: To study the corneal epithelial and stromal thickness profile changes after photorefractive keratectomy (PRK) for myopia. METHODS: Retrospective analysis of the postoperative corneal epithelial and stromal thickness profile changes in 46 left eyes of 46 patients treated with PRK for myopia. Corneal and epithelial thickness maps within the central 6 mm were obtained by anterior segment spectral-domain optical coherence tomography preoperatively and at 1, 3, and 6 months postoperatively. Stromal thickness was calculated by subtracting the epithelial thickness from the total corneal thickness. Correlations between postoperative thickness changes and the amount of correction, treatment zone, and preoperative epithelial thickness were analyzed. RESULTS: Compared to preoperative values, the central 2 mm and the paracentral 2- to 5-mm zone epithelium was 5.20 ± 3.43 and 5.72 ± 3.30 µm thicker, respectively, at 3 months postoperatively (P < .05). No significant difference was detected between 3 and 6 months postoperatively. The stromal thickness did not change between 1 and 6 months postoperatively. The spherical equivalent (SE) changed from -2.82 ± 1.54 diopters (D) preoperatively to -0.06 ± 0.42 D at 1 month postoperatively, and remained stable thereafter. There was a trend toward greater epithelial thickening with a larger amount of programmed SE correction, smaller treatment zone, and thinner preoperative epithelium. No correlation between epithelial thickness change and postoperative change in refraction was detected. CONCLUSIONS: The corneal epithelial thickness increased after PRK up to 3 months postoperatively. It was affected by the amount of myopia treated, treatment zone, and preoperative epithelial thickness. The postoperative epithelial thickening did not affect the refractive outcomes.

Heterogeneity in corporate payouts.

In this paper we empirically investigate dividends and repurchases of the UK, and the overarching pattern reveals that their determinants are more driven by payout size than they are by payout type. The overall corporate payout policy is influenced by the operating performance and tax framework. Aggregately, the determinants of dividends and repurchases are heterogenous, and for each payout's individual testing the determinants have shown varying influences when controlled for payout size; small, medium and large. Comparatively, the determinants of dividends and repurchases of small size show homogeneity, while those of medium and large sizes exhibit heterogeneity. From a variable-specific perspective, aggregately dividends are positively influenced by asset holdings and ROA, and negatively influenced by independent directions and EPS. While aggregately repurchases are positively influenced by debt exposure and negatively influenced by M/B Ratio.

Ray-Tracing Transepithelial Excimer Laser Central Corneal Remodeling Plus Pachymetry-Guided Accelerated Corneal Crosslinking for Keratoconus.

PURPOSE: The aim of this study was to report the 12 to 96 months results of a tissue-preservation algorithm based on ray-tracing-guided transepithelial excimer laser central corneal ablation (RT t-PRK) combined with individualized pachymetry-guided accelerated crosslinking (M nomogram ACXL) in young adult patients with stable keratoconus (KC). METHODS: This was a prospective interventional study including 38 eyes of 38 young adult patients (stage II KC) with a mean age of 35 years (range 26-46 years) who underwent simultaneous RT with t-PRK plus pachymetry-based ACXL in the worst eye. The treatments were performed using the iViS Suite iRES Excimer Laser (Ligi, Taranto, Italy). Ray-tracing-guided treatments were planned using the customized interactive programmed transepithelial ablation (CIPTA) 2 web software and diagnostic data were assessed by the Precisio 2 tomographer (Ligi, Taranto, Italy) and Sirius tomographer (C.S.O., Florence, Italy). The main outcome measures included uncorrected distance visual acuity, best spectacle-corrected visual acuity, Kmax, high-order aberrations, minimum corneal thickness, and posterior elevation, with a mean follow-up of 52 months (range 12-96 m). RESULTS: The mean UDVA improved + 3.5 ±1.28 Snellen lines (SL); 38% gained ≥ 4 ±1.34 SLs, 35% ≥ 3 ±1.21 SLs, 22% ≥ 2 ±1.12 SLs, and 5% ≥ 1 ±0.75 SLs. The mean best spectacle-corrected visual acuity increased by + 4.3 ±1.3 SL. Sixty-eight percent gained ≥ 4 ±0.88 SLs and 30% ≥ 3 ±0.78 SL. No SLs were lost. CONCLUSIONS: RT t-PRK plus ACXL significantly improved the quality of vision in patients with KC, preventing overcorrection and minimizing tissue consumption.

Ligandability Assessment of IL-1ß by Integrated Hit Identification Approaches.

Human interleukin-1ß (IL-1ß) is a pro-inflammatory cytokine that plays a critical role in the regulation of the immune response and the development of various inflammatory diseases. In this publication, we disclose our efforts toward the discovery of IL-1ß binders that interfere with IL-1ß signaling. To this end, several technologies were used in parallel, including fragment-based screening (FBS), DNA-encoded library (DEL) technology, peptide discovery platform (PDP), and virtual screening. The utilization of distinct technologies resulted in the identification of new chemical entities exploiting three different sites on IL-1ß, all of them also inhibiting the interaction with the IL-1R1 receptor. Moreover, we identified lysine 103 of IL-1ß as a target residue suitable for the development of covalent, low-molecular-weight IL-1ß antagonists.

Light microscopy applications in systems biology: opportunities and challenges.

Biological systems present multiple scales of complexity, ranging from molecules to entire populations. Light microscopy is one of the least invasive techniques used to access information from various biological scales in living cells. The combination of molecular biology and imaging provides a bottom-up tool for direct insight into how molecular processes work on a cellular scale. However, imaging can also be used as a top-down approach to study the behavior of a system without detailed prior knowledge about its underlying molecular mechanisms. In this review, we highlight the recent developments on microscopy-based systems analyses and discuss the complementary opportunities and different challenges with high-content screening and high-throughput imaging. Furthermore, we provide a comprehensive overview of the available platforms that can be used for image analysis, which enable community-driven efforts in the development of image-based systems biology.

Epithelial Thickness Mapping in Keratoconic Corneas: Repeatability and Agreement Between CSO MS-39, Heidelberg Anterion, and Optovue Avanti OCT Devices.

PURPOSE: To assess repeatability and agreement of corneal epithelial thickness mapping in eyes with keratoconus using three optical coherence tomography (OCT) devices featuring different technologies: spectral-domain (SD) OCT combined with Placido disk corneal topography (MS-39), swept-source OCT (Anterion), and SD-OCT (Avanti). METHODS: Three consecutive measurements were acquired with the three devices in 60 eyes with keratoconus. The mean epithelial thickness was calculated in the central 2-mm zone and in 2- to 5-mm and 5- to 7-mm diameter rings. The repeatability was calculated using pooled within-subject standard deviation (Sw). The agreement was assessed by paired t tests and Bland-Altman plots. RESULTS: The repeatability (Sw) of the epithelial thickness for the central 2-mm zone was 0.91, 0.71, and 0.93 µm for the MS-39, Anterion, and Avanti, respectively. All thicknesses with the MS-39 were greater than those of the Anterion and Avanti, with mean differences of 4.11 ± 1.34 µm (P < .001) and 0.52 ± 1.30 µm (P = .003), respectively. The 95% limits of agreement were 1.484 to 6.736 µm for the MS-39 and Anterion, -3.068 to 2.028 µm for the Avanti and MS-39, and 1.258 to 5.922 µm for for the Avanti and Anterion. CONCLUSIONS: Epithelial thickness mapping results were most repeatable with the Anterion, followed by the MS-39 and Avanti. The MS-39 gave the thickest values, followed by the Avanti and Anterion. The differences were significant, making the devices not interchangeable for epithelial thickness mapping in eyes with keratoconus. [J Refract Surg. 2023;39(7):474-480.].

High-dose imatinib induction followed by standard-dose maintenance in pre-treated chronic phase chronic myeloid leukemia patients--final analysis of a randomized, multicenter, phase III trial.

BACKGROUND: Previous data suggest that the response of chronic myeloid leukemia cells to imatinib is dose-dependent. The potential benefit of initial dose intensification of imatinib in pre-treated patients with chronic phase chronic myeloid leukemia remains unknown. DESIGN AND METHODS: Two hundred and twenty-seven pre-treated patients with chronic myeloid leukemia in chronic phase were randomly assigned to continuous treatment with a standard dose of imatinib (400 mg/day; n=113) or to 6 months of high-dose induction with imatinib (800 mg/day) followed by a standard dose of imatinib as maintenance therapy (n=114). RESULTS: The rates of major and complete cytogenetic responses were significantly higher in the high-dose arm than in the standard-dose arm at both 3 and 6 months (major cytogenetic responses: 36.8% versus 21.2%, P=0.01 and 50.0% versus 34.5%, P=0.018; complete cytogenetic responses: 22.8% versus 6.2%, P<0.001 and 40.4% versus 16.8%, P<0.001) on the basis of an intention-to-treat analysis. At 12 months, the difference between treatment arms remained statistically significant for complete cytogenetic responses (40.4% versus 24.8%, P=0.012) but not for major cytogenetic responses (49.1% versus 44.2%, P=0.462). The rate of major molecular responses was also significantly better at 3 and 6 months in the high-dose arm (month 3: 14.9% versus 3.5%, P=0.003; month 6: 32.5% versus 8.8%, P<0.001). Overall and progression-free survival rates were comparable between arms, but event-free survival was significantly worse in the high-dose arm (P=0.014). CONCLUSIONS: Standard-dose imatinib remains the standard of care for pre-treated patients with chronic phase chronic myeloid leukemia (Clinicaltrials.gov identifier: NCT00327262).

IntraLase femtosecond laser vs mechanical microkeratomes in LASIK for myopia: a systematic review and meta-analysis.

PURPOSE: To evaluate the safety, efficacy, and predictability of IntraLase (Abbott Medical Optics) femtosecond laser-assisted compared to microkeratome-assisted myopic LASIK. METHODS: A comprehensive literature search of Cochrane Library, PubMed, and EMBASE was conducted to identify relevant trials comparing LASIK with IntraLase femtosecond laser to LASIK with microkeratomes for the correction of myopia. Meta-analyses were performed on the primary outcomes (loss of ≥2 lines of corrected distance visual acuity [CDVA], uncorrected distance visual acuity [UDVA] 20/20 or better, manifest refraction spherical equivalent [MRSE] within ±0.50 diopters [D], final refractive SE, and astigmatism), and secondary outcomes (flap thickness predictability, changes in higher order aberrations [HOAs], and complications). RESULTS: Fifteen articles describing a total of 3679 eyes were identified. No significant differences were identified between the two groups in regards to a loss of ≥2 lines of CDVA (P=.44), patients achieving UDVA 20/20 or better (P=.24), final UDVA (P=.12), final mean refractive SE (P=.74), final astigmatism (P=.27), or changes in HOAs. The IntraLase group had more patients who were within ±0.50 D of target refraction (P=.05) compared to the microkeratome group, and flap thickness was more predictable in the IntraLase group (P<.0001). The microkeratome group had more epithelial defects (P=.04), whereas the IntraLase group had more cases of diffuse lamellar keratitis (P=.01). CONCLUSIONS: According to the available data, LASIK with the IntraLase femtosecond laser offers no significant benefits over LASIK with microkeratomes in regards to safety and efficacy, but has potential advantages in predictability.

Transepithelial, Topography-guided Ablation in the Treatment of Visual Disturbances in LASIK Flap or Interface Complications.

PURPOSE: To evaluate the efficacy and safety of a single-step, transepithelial, topography-guided surface ablation in the treatment of visual disturbances including irregular astigmatism and light scattering caused by LASIK flap or interface complications. METHODS: Seventeen eyes of 16 patients with LASIK flap or interface complications and central residual stromal thickness ≥300 µm were treated with a topography-guided custom transepithelial "no touch" (cTEN) technique using the iVIS Suite 1-kHz excimer laser (iVIS Technology). Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refraction, corneal irregularity, ocular higher order aberrations (HOAs), and visual symptoms were analyzed. RESULTS: Mean 15.9±11.0 months after surgery, mean UDVA improved from 20/87 to 20/25. Mean CDVA improved from 20/28 to 20/19 (P<.001), with 64.7% of eyes gaining two or more lines of CDVA. Mean corneal irregularity index decreased from 25.82 to 20.36 µm (P=.009). Mean root-mean-square (RMS) of total HOAs decreased from 1.30 to 0.49 (P=.042), whereas RMS of the odd-order (3rd and 5th) and even-order (4th and 6th) HOAs decreased from 0.85 to 0.38 (P=.001) and 0.43 to 0.24 (P=.036), respectively. All patients claimed their visual symptoms were better (8 eyes) or cured (9 eyes). CONCLUSIONS: Corneal regularization and removal of the underlying flap or interface pathology by cTEN ablation appears to be an effective treatment for LASIK flap or interface complications associated with visually disturbing irregular astigmatism and light scattering in cases with sufficient residual stromal thickness.

Effect of limbal marking prior to laser ablation on the magnitude of cyclotorsional error.

PURPOSE: To evaluate the residual registration error after limbal-marking-based manual adjustment in cyclotorsional tracker-controlled laser refractive surgery. METHODS: Two hundred eyes undergoing custom surface ablation with the iVIS Suite (iVIS Technologies) were divided into limbal marked (marked) and non-limbal marked (unmarked) groups. Iris registration information was acquired preoperatively from all eyes. Preoperatively, the horizontal axis was recorded in the marked group for use in manual cyclotorsional alignment prior to surgical iris registration. During iris registration, the preoperative iris information was compared to the eye-tracker captured image. The magnitudes of the registration error angle and cyclotorsional movement during the subsequent laser ablation were recorded and analyzed. RESULTS: Mean magnitude of registration error angle (absolute value) was 1.82°±1.31° (range: 0.00° to 5.50°) and 2.90°±2.40° (range: 0.00° to 13.50°) for the marked and unmarked groups, respectively (P<.001). Mean magnitude of cyclotorsional movement during the laser ablation (absolute value) was 1.15°±1.34° (range: 0.00° to 7.00°) and 0.68°±0.97° (range: 0.00° to 6.00°) for the marked and unmarked groups, respectively (P=.005). Forty-six percent and 60% of eyes had registration error >2°, whereas 22% and 20% of eyes had cyclotorsional movement during ablation >2° in the marked and unmarked groups, respectively. CONCLUSIONS: Limbal-marking-based manual alignment prior to laser ablation significantly reduced cyclotorsional registration error. However, residual registration misalignment and cyclotorsional movements remained during ablation.

Comparison of clinical outcomes between 'on-flap' and 'off-flap' epi-LASIK for myopia: a meta-analysis.

OBJECTIVE: To examine possible differences in clinical outcomes between off-flap and on-flap epipolis laser in situ keratomileusis (epi-LASIK) for myopia. METHODS: Pertinent studies were selected by extensive searches. A total of 9 studies reporting on a total of 958 eyes were included in the present meta-analysis. Statistical analysis was performed using RevMan 5.0 software. RESULTS: There were no significant differences in the final refractive spherical equivalent (p = 0.38), manifest refractive spherical equivalent within ±0.50 D of the target (p = 0.76), final uncorrected visual acuity (p = 0.90), loss of ≥1 line of best spectacle-corrected visual acuity (p = 0.99), and corneal haze at 3 months postoperatively (p = 0.96) or more than 6 months (p = 0.64). More patients felt severe pain in the on-flap group than in the off-flap group, although this finding was not statistically significant (p = 0.05). However, off-flap epi-LASIK had a better mean uncorrected visual acuity at 3 days (p = 0.04) and 5 days (p = 0.01), and faster re-epithelialization (p < 0.00001) after surgery. CONCLUSIONS: According to the available data, off-flap and on-flap epi-LASIK had equal visual and refractive outcomes for the treatment of myopia. Off-flap epi-LASIK had more rapid re-epithelialization and visual recovery compared to on-flap epi-LASIK.

The Impact of Epithelial Remodeling on Surgical Techniques Used in Topography-guided Surface Ablation in Irregular Corneas.

PURPOSE: To analyze the optical consequences of epithelial remodeling in irregular corneas and their impact on the choice of different surface ablation techniques. METHODS: Anterior corneal and stromal surface topographies and epithelial thickness maps were analyzed in 24 eyes with irregular corneal optics. On two of the eyes, four different surface ablation techniques were simulated: (1) conventional anterior topography-guided photorefractive keratectomy (PRK), (2) transepithelial phototherapeutic keratectomy (PTK), (3) transepithelial anterior topography-guided PRK, and (4) stromal topography-guided PRK. RESULTS: Stromal surface topographies showed higher keratometric values, astigmatism, asphericity, and corneal higher order aberrations compared to topographies of anterior corneas covered by epithelium. Transepithelial anterior topography-guided PRK and stromal topography-guided PRK both resulted in regularized stromal surface, transepithelial PTK achieved partial regularization corresponding to the smoothing effect of the epithelial remodeling, and conventional anterior topography-guided PRK delivered after epithelial removal resulted in residual stromal surface irregularities. CONCLUSIONS: The difference in optical landscapes between the stromal and anterior surfaces in irregular corneas will represent a source of error when anterior topography-guided treatments are delivered on the deepithelialized stroma, as in conventional PRK. In contrast, anterior topography-guided ablations performed as transepithelial PRK and stromal topography-guided PRK delivered after epithelial removal address the full stromal irregularity, whereas transepithelial PTK alone may be used when topography-guided treatments are not possible. The authors conclude topography-guided PRK of irregular corneas should lead to significantly improved regularization only if it includes the effect of epithelial remodeling. [J Refract Surg. 2022;38(8):529-537.].

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.

Effect of femtosecond laser cutting parameters on the results of small-incision lenticule extraction.

PURPOSE: To determine the effect of femtosecond laser cutting parameters on small-incision lenticule extraction (SMILE) results by evaluating cap thickness, interface light scattering, and visual and refractive outcomes. SETTING: SynsLaser Clinic, Oslo, Norway. DESIGN: Retrospective. METHODS: 58 right eyes treated with SMILE using a programmed cap thickness of 130 µm were divided into 2 groups according to laser settings: Group 1: 165 nJ pulse energy and 4.5 µm spot separation (n = 36); Group 2: 125 nJ pulse energy and 4.2 µm spot separation (n = 22). The cap thickness was measured within the central 5 mm of the horizontal meridian using spectral-domain optical coherence tomography. Postoperative interface light scattering was graded based on the percentage area showing light scattering: 0: no scattering; 1: ≤25%; 2: 26% to 50%; 3: 51% to 75%; and 4: &gt;75%. RESULTS: At 3 months postoperatively, cap thickness was 138.9 ± 6.2 µm in Group 1 and 149.4 ± 3.5 µm in Group 2 ( P &lt; .001). Interface scattering was 0.9 ± 1.0 in Group 1 and 0.3 ± 0.9 in Group 2 ( P &lt; .05), with no scattering in 33.3% and 86.4% of the eyes, respectively. The postoperative spherical equivalent refraction was -0.03 ± 0.44 diopters (D) in Group 1 and -0.04 ± 0.31 D in Group 2. In Group 1, 83.3% of the eyes were within ± 0.5 D of the desired outcome, and 69.4% achieved an uncorrected distance visual acuity of 20/20 or better. In Group 2, these values were 95.5% and 86.4%, respectively. CONCLUSIONS: Lower pulse energy with tighter spots seems to reduce interface light scattering and improve refractive outcomes while also significantly increasing cap thickness.

Heidelberg Anterion Swept-Source OCT Corneal Epithelial Thickness Mapping: Repeatability and Agreement With Optovue Avanti.

PURPOSE: To assess the repeatability of corneal epithelial thickness mapping in virgin, post-laser refractive surgery (PLRS), and keratoconic eyes using a novel swept-source optical coherence tomographer (SS-OCT), and to determine the agreement of the measurements with a validated spectral-domain (SD) OCT. METHODS: Analysis of 90 virgin, 46 PLRS, and 122 keratoconic eyes was performed. Three consecutive measurements of each eye were acquired with the Anterion SS-OCT and Avanti SD-OCT devices, and averages of the epithelial thickness mapping were calculated in the central 2-mm zone and in the 2- to 5-mm and 5- to 7-mm diameter rings. The repeatability was analyzed using pooled within-subject standard deviation (Sw). The agreement was assessed by Bland-Altman analysis and paired t tests. RESULTS: The repeatability ranges of the Anterion and Avanti epithelial thickness mapping measurements were Sw: 0.60 to 1.36 µm and Sw: 0.75 to 1.96 µm, respectively. The 95% limits of agreement of the Anterion and Avanti were 0.826 to 8.297. All values of the thickness measurements with the Anterion were lower than those of the Avanti, with the mean differences being 4.06 ± 1.81, 3.26 ± 2.52, and 3.68 ± 2.51 µm in virgin, PLRS, and keratoconic eyes, respectively (P < .001 for all). CONCLUSIONS: The repeatability of the Anterion's epithelial thickness mapping was higher than that of the Avanti. In terms of the agreement between the Anterion and Avanti, the epithelium measured by the Anterion was always thinner than that of the Avanti, making their interchangeable use unsuitable without corrections. [J Refract Surg. 2022;38(6):356-363.].

Paradoxical Increase of Permeability and Lipophilicity with the Increasing Topological Polar Surface Area within a Series of PRMT5 Inhibitors.

An imidazolone → triazolone replacement addressed the limited passive permeability of a series of protein arginine methyl transferase 5 (PRMT5) inhibitors. This increase in passive permeability was unexpected given the increase in the hydrogen bond acceptor (HBA) count and topological polar surface area (TPSA), two descriptors that are typically inversely correlated with permeability. Quantum mechanics (QM) calculations revealed that this unusual effect was due to an electronically driven disconnect between TPSA and 3D-PSA, which manifests in a reduction in overall HBA strength as indicated by the HBA moment descriptor from COSMO-RS (conductor-like screening model for real solvation). HBA moment was subsequently deployed as a design parameter leading to the discovery of inhibitors with not only improved passive permeability but also reduced P-glycoprotein (P-gp) transport. Our case study suggests that hidden polarity as quantified by TPSA-3DPSA can be rationally designed through QM calculations.

Meta-analysis of clinical outcomes comparing surface ablation for correction of myopia with and without 0.02% mitomycin C.

PURPOSE: To evaluate the current clinical evidence of safety and efficacy of intraoperative topical application of 0.02% mitomycin C (MMC) used for up to 2 minutes after surface ablation for correction of myopia. METHODS: A comprehensive literature search was conducted of Cochrane Library, MEDLINE, and EMBASE to identify relevant trials comparing surface ablation for correction of myopia with and without MMC. A meta-analysis was performed on the results of the reports and statistical analysis was performed. RESULTS: Eleven clinical trials were identified with MMC used in 534 eyes and no MMC in 726 eyes. Surface ablations with MMC led to significantly less corneal haze in photorefractive keratectomy, whereas the results were comparable in laser epithelial keratomileusis (LASEK) and epithelial laser in situ keratomileusis (epi-LASIK). Although proportionately more eyes in the MMC group achieved uncorrected distance visual acuity 20/25 or better and less frequently lost ≥ 2 lines of corrected distance visual acuity, the difference was not statistically significant. CONCLUSIONS: Our meta-analysis suggests that the topical intraoperative application of 0.02% MMC may reduce haze and improve visual acuity after surface ablation for correction of myopia. However, the advantage of using MMC in LASEK and epi-LASIK is unclear.