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.

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.

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.].

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.

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.].

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.].

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.

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.

Intraoperative Swept-Source OCT-Based Corneal Topography for Measurement and Analysis of Stromal Surface After Epithelial Removal.

PURPOSE: To assess intraoperative stromal topography measurements using swept-source optical coherence tomography (OCT)-based topography/tomography after epithelial removal and to analyze the epithelial contribution to the corneal topography and optics. METHODS: This was a prospective series of 22 eyes of 19 patients referred to receive phototherapeutic keratotomy (PTK) for treatment of recurrent corneal erosion and a control group of 22 virgin eyes. Swept-source OCT corneal topography/tomography was obtained immediately before and immediately after mechanical deepithelialization before PTK. Epithelial thickness maps were obtained before the surgery using spectral-domain OCT in the control group and as a reference in the group with anterior basement membrane dystrophy. Topographic and optical characteristics, including the curvature, astigmatism, asphericity, and higher order aberrations of the cornea before and after deepithelialization were compared, and their differences correlated with the measurements derived from the epithelial thickness maps. RESULTS: Stromal topography measurements after deepithelialization were easily obtained and showed excellent repeatability. Assessment of corneal edema induced by deepithelialization revealed that it did not significantly affect the measured parameters. The stromal surface was steeper by 1.28 diopters, had higher with-the-rule astigmatism by 0.41 diopters, was more prolate, and had more higher order aberrations compared to the intact epithelialized corneal surface. These differences correlated well with the parameters derived from epithelial thickness maps. CONCLUSIONS: Measurement of stromal topography using swept-source OCT immediately after mechanical deepithelialization may be a viable method in therapeutic refractive surgery, where stromal topography-guided ablation is needed. A significant epithelial contribution to anterior corneal topography and optics was confirmed. [J Refract Surg. 2021;37(7):484-492.].

Coma Influence on Manifest Astigmatism in Coma-Dominant Irregular Corneal Optics.

PURPOSE: To evaluate the influence of coma on manifest refractive cylinder (MRC) in eyes with coma-dominated corneal optics and suggest alternative guidelines for surgical planning of astigmatism correction in topography-guided ablation and toric intraocular lens (IOL) exchange surgery. METHODS: Twelve eyes with coma-dominant corneal optics and low lenticular astigmatism were selected. The astigmatism remaining after subtraction of total corneal astigmatism (TCA) and lenticular astigmatism from MRC, termed discrepant astigmatism, was calculated and correlated to corneal coma at the anterior surface. Refractive and topography data were then used to simulate topography-guided refractive surgery (topography-guided group) in 7 eyes and lenticular exchange surgery with toric intraocular lens (IOL) implantation (toric IOL group) in 5 eyes. The estimated postoperative MRC after correction of TCA or MRC for each group was compared. RESULTS: The axis and amplitude of discrepant astigmatism correlated strongly with the axis and amplitude of coma. In the topography-guided group, where topography-guided ablation eliminated corneal higher order aberrations (HOAs), TCA-based correction led to less estimated postoperative manifest astigmatism than MRC-based correction. In the toric IOL group, where removal of the crystalline lens did not affect corneal HOAs, MRC-based correction via toric IOL implantation led to less estimated postoperative astigmatism than TCA-based correction. CONCLUSIONS: Discrepant astigmatism in eyes with coma-dominant corneal optics correlates with coma. In such eyes, treating TCA, along with corneal HOAs, instead of MRC, seems appropriate in topography-guided treatments, whereas treating MRC may be a better choice in lenticular exchange surgery with toric IOL implantation, where corneal HOAs are not treated. [J Refract Surg. 2021;37(4):274-282.].

Sex and age differences in symptoms and signs of dry eye disease in a Norwegian cohort of patients.

PURPOSE: To investigate sex and age differences in symptoms and signs in a Norwegian clinic-based cohort of patients with dry eye disease (DED). METHODS: Visitors at the Norwegian Dry Eye Clinic were examined using Ocular Surface Disease Index (OSDI) questionnaire score, tear osmolarity, tear break-up time (TFBUT), ocular surface staining, corneal sensitivity, Schirmer I test, and meibum expressibility (ME) and quality (MQ). A diagnosis of DED was made by an ophthalmologist based on symptoms and signs, and only DED patients were enrolled in the study: 1823 patients (338 males; mean age 51.2 ± 16.2 years; 1485 females; mean age 52.5 ± 16.0 years). The patients were divided into age subgroups: 20-39 years, 40-59 years and ≥60 years. Sex differences in the aforementioned tests were analyzed. Values were reported as mean ± standard deviation (SD), and intergroup comparisons were performed using Mann-Whitney U test. Multiple regression was used to analyze sex and age influences on symptoms and signs. RESULTS: When patients of all ages were analyzed, females had increased osmolarity, shorter TFBUT, reduced MQ and ME and higher corneal sensitivity. OSDI, Schirmer I test, ocular surface staining and corneal staining were not significantly different between the sexes. Only with TFBUT and ME were the sex difference present in all age subgroups. Multiple regression showed that all parameters were influenced by either sex or age, but only TFBUT and ME were influenced by both sex and age. (all p < 0.05). CONCLUSIONS: Sex and age differences in dry eye were most consistent in TFBUT and ME, that indicate differences in meibomian gland functionality. Sex and age subgroup stratification is important in future studies investigating DED in other populations.

Temporal redistribution of cap and residual stromal thickness after SMILE.

PURPOSE: To investigate corneal sublayer alterations during the postoperative period after small-incision lenticule extraction (SMILE). SETTING: Synslaser clinic, Oslo, Norway. STUDY DESIGN: Retrospective. METHODS: Patients who underwent SMILE for treating myopia were included. The thicknesses of the corneal epithelium, cap, stromal part of the cap (StromaCap), residual stromal bed (StromaRes), and total stroma (StromaTot) were measured using spectral-domain optical coherence tomography at 1 day, 1 week, 1 month, 3 months, and 6 months postoperatively. Postoperative changes in the corneal sublayer thicknesses were analyzed and correlated with changes in spherical equivalence and anterior and posterior keratometry (K). RESULTS: The study was based on analyses of the right eyes of 51 patients. From 1 day to 6 months postoperatively, the corneal epithelium, cap, StromaCap, StromaRes, and StromaTot thicknesses increased from 54.4 ± 4.0 µm to 57.3 ± 5.2 µm; 137.1 ± 5.5 µm to 140.3 ± 5.1 µm; 82.7 ± 5.9 µm to 82.8 ± 6.3 µm; 375.0 ± 40.8 µm to 381.4 ± 30.6 µm; and 457.6 ± 41.1 µm to 462.1 ± 36.7 µm, respectively. Between 1 month and 6 months postoperatively, the increase in anterior K correlated significantly with the thickening of the cap (r = 0.37, P = .03) and the stromal component of the cap (r = 0.36, P = .04) within the central cornea. CONCLUSIONS: The post-SMILE remodeling behavior between the anterior (StromaCap) and posterior (StromaRes) stroma were dissimilar. There was a significant correlation between changes in anterior K and the central cap and the stromal component of the cap. This might be because of biomechanical changes, tissue remodeling, and wound healing or a combination of some or all of the aforementioned processes.

Parasitoids of jumping plant-lice (Psylloidea, Hemiptera) from the family Encyrtidae (Hymenoptera, Chalcidoidea) in Serbia.

The aim of this research was to study the diversity of jumping plant-lice parasitoids and to investigate their potential in biological control applicable to cultivated and ornamental plants. Thirteen species from six genera of encyrtid wasps (Hymenoptera, Chalcidoidea, Encyrtidae) were reared from 24 species of jumping plant-lice (Hemiptera, Psylloidea) in Serbia. A total of 689 encyrtid wasps were collected since 2003 from 51 localities, reared from hosts. The richest genera are Psyllaephagus with four species (P. belanensis (Hoffer), P. fulvipes Erdös, P. procerus Mercet and Psyllaephagus sp.) and Syrphophagus with three species (S. aphidivorus (Mayr), S. taeniatus (Förster) and S. ariantes (Walker)). The most common species, comprising about half of the reared specimens, is Prionomitus mitratus (Dalman). Eight species are new to Serbia: Microterys annulatus (Erdös, 1957), Prionomitus tiliaris (Dalman), Psyllaephagus belanensis, P. fulvipes, P. procerus, Sectiliclava cleone (Walker), Syrphophagus ariantes and Trechnites flavipes (Mercet). Psyllaephagus fulvipes was reared from the nymphs of Craspedolepta conspersa (Löw), the only known host of this species so far. In the present study, 27 new host associations were found.

Transepithelial Topography-Guided Ablation Assisted by Epithelial Thickness Mapping for Treatment of Regression After Myopic Refractive Surgery.

PURPOSE: To evaluate the outcomes of transepithelial, topography-guided, epithelial mapping-assisted ablation in the treatment of regression after myopic refractive surgery. METHODS: A retrospective consecutive case series of 70 eyes of 52 patients with regression after previous corneal refractive surgery for treatment of myopic and compound myopic astigmatism underwent re-treatment using transepithelial topography-guided and epithelial mapping-assisted custom ablation with a wide and smooth transition zone design. The ablation profile was based on data from corneal topography, whereas the epithelial ablation depth was decided by corneal epithelial mapping obtained by optical coherence tomography. RESULTS: The mean follow-up time after re-treatment was 13.6 ± 9.4 months (range: 6 to 51 months). At the patients' last follow-up visit, 98.5% and 76.5% had uncorrected distance visual acuity of 20/40 and 20/20 or better. Safety and efficacy indexes were 1.05 and 0.92, respectively. The mean spherical equivalent was reduced from -1.10 ± 0.65 to -0.16 ± 0.34 diopters. Both total root mean square, odd-order, and even-order higher order aberrations improved significantly (P = .021, .040, and .030, respectively), whereas corneal asphericity remained unchanged (P = .662). Epithelial thickness profile showed significant smoothing between the central 2-mm and 2- to 5-mm paracentral areas. CONCLUSIONS: Transepithelial topography-guided and epithelial mapping-assisted custom re-treatment with a wide and smooth transition zone design is safe and effective for addressing myopic regression in patients who have previously undergone myopic refractive surgery. [J Refract Surg. 2019;35(8):525-533.].

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.

Evaluation of the Ocular Surface Disease Index Questionnaire as a Discriminative Test for Clinical Findings in Dry Eye Disease Patients.

Purpose: To investigate to what extent the OSDI can be utilized as a discriminative test for clinical findings. Methods: One thousand and ninety patients with dry eye disease (DED) were consecutively included and examined for osmolarity, tear film break-up time (TFBUT), ocular protection index (OPI), ocular surface staining (OSS), Schirmer I test (ST), meibum expressibility (ME), meibum quality (MQ), and diagnosis of meibomian gland dysfunction (MGD). Receiver-operating characteristic curve (ROC) analysis considering optimum balanced sensitivity and specificity (close to 50%) was used for assessment. Results: The present study on more than 1,000 patients indicates that the OSDI in the ROC curve analysis is a poor discriminator of pathological scores for TFBUT ≤ 5 (AUC = 0.553; p = .012) and ≤10 s (AUC = 0.608; p = .002), OSS ≥ 3 (AUC = 0.54; p = .043), ST ≤ 5 (AUC = 0.550; p = .032) and ≤10 mm/5 min (AUC = 0.544; p = .016), and ME ≥ 1 (AUC = 0.594; p = <0.001). Pathological scores for osmolarity >308 and >316 mOsm/L, OPI, OSS > 1, MQ, and MGD could not be discriminated by OSDI (p > .05). Conclusion: Cut-off values for the OSDI can be defined to discriminate pathological TFBUT (≤5 and ≤10), OSS (≥3), ST (≤5 and ≤10) and ME, however, the discriminability was low. Our comprehensive study emphasises the importance of taking both symptoms and signs into account in DED management.

Central corneal regularization (CCR): an alternative approach in keratoconus treatment.

BACKGROUND: To evaluate the safety and efficacy of an approach that combines corneal customized transepithelial therapeutic ablation to treat irregular corneal optics and accelerated corneal collagen cross-linking (CXL) to strengthen the corneal tissue and stop the progression of keratoconus. The transepithelial therapeutic ablation applied a novel concept named central corneal regularization (CCR) which could correct the corneal morphological irregularities and the eye's spherocylindrical refractive error with minimal stromal tissue removal. METHODS: Retrospective study. Eyes that underwent CCR combined with CXL were evaluated preoperatively and up to 12 months postoperatively for visual acuity, subjective refraction, corneal haze, pachymetry and maximum keratometry (Kmax). RESULTS: Twenty four eyes of 24 patients with a mean age of 28.92 ± 9.88 years were treated. The mean spherical equivalent (SE) refractive error changed from - 0.74 ± 1.17 D preoperatively to - 1.05 ± 1.52 D at 12 months postoperatively. The mean uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) improved. No eye lost lines of CDVA, 21 had a mean improvement of 3.21 lines. The mean cylinder error and Kmax value dropped from - 3.06 ± 1.83 D and 51.38 ± 3.29 D to - 1.04 ± 0.80 D and 48.70 ± 2.58 D, respectively. The mean haze score at 3, 6 and 12 months was 0.56, 0.19 and 0.06, respectively. CONCLUSIONS: CCR combined with CXL offers promising results as a safe and effective treatment in keratoconic patients.

Tear Production Levels and Dry Eye Disease Severity in a Large Norwegian Cohort.

PURPOSE: To determine if the Schirmer I test (without anesthesia) cut-off value is a predictor of dry eye severity in a large Norwegian cohort of dry eye disease (DED) patients, which are grouped into six levels of tear production. METHODS: Patients (n = 1090) with DED of different etiologies received an extensive dry eye work-up: osmolarity (Osm), tear meniscus height (TMH), tear film break-up time (TFBUT), ocular protection index (OPI), ocular surface staining (OSS), Schirmer I test (ST), meibum expressibility (ME), and meibum quality (MQ). Classification of dry eye severity level (DESL) and diagnosis of meibomian gland dysfunction (MGD) were also included. The cohort was divided into six groups: below and above cut-off values of 5 (groups 1 and 2), 10 (groups 3 and 4), and 15 mm (groups 5 and 6) of ST. Mann-Whitney test and Chi-Square test were used for group comparison of parameters (p ≤ 0.05). RESULTS: The groups 1, 3, and 5 had values indicating more severe DED than the groups 2, 4, 6 with significant difference in DESL, Osm, TFBUT, OPI, OSS, and TMH. Regardless of the choice of cut-off values, there was no statistically significant difference in ME, MQ, and MGD between groups below and above selected cut-off value. When gender difference was considered in each group, significant difference was only observed for DESL (groups 2, 4, and 5), TFBUT (groups 2, 4, and 5), OPI (groups 2 and 6), and ME (group1). CONCLUSIONS: Schirmer I is a robust discriminator for DESL, Osm, TFBUT, OPI, OSS, and TMH, but not for ME, MQ, and MGD. Patients with lower tear production levels presented with more severe DED at all three defined cut-off values. Interestingly, the differences in the mean values of DESL were minimal although statistically significant. Thus, the clinical value of different Schirmer levels appears to be limited.