Selective Modulation of the Keratoconic Stromal Microenvironment by FSH and LH.

Keratoconus (KC) affects the corneal structure, with thinning and bulging outward into a conelike shape. Irregular astigmatism and decreased visual acuity appear during puberty and progress into the mid-30s, with unpredictable disease severity. The cause of KC is recognized as multifactorial, but remains poorly understood. Hormone imbalances are a significant modulator of the onset of KC. This study sought to investigate the role of gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in KC, using a three-dimensional, self-assembled matrix in vitro model. Healthy corneal fibroblasts and human KC cells in the corneal stroma were isolated, cultured, and stimulated with stable vitamin C to promote extracellular matrix assembly. Cultures were further stimulated with 2.5 or 10 mIU/mL FSH and 5 or 35 mIU/mL LH. Samples were evaluated for cell proliferation and morphology via BrdU assay and imaging; protein expression was assessed via Western blot analysis. Proliferation was significantly greater in human KC cells compared to healthy corneal fibroblasts with LH stimulation, but no changes were found with FSH stimulation. Additionally, in sex hormone receptors, fibrotic markers, proteoglycans, and members of the gonadotropin signaling pathway were significantly changed, largely driven by exogenous LH. The impact of exogenous FSH/LH in the KC stromal microenvironment was demonstrated. These results highlight the need to further examine the role of FSH/LH in KC and in human corneal homeostasis.

Optimizing Oxygen-Production Kinetics of Manganese Dioxide Nanoparticles Improves Hypoxia Reversal and Survival in Mice with Bone Metastases.

Persistent hypoxia in bone metastases induces an immunosuppressive environment, limiting the effectiveness of immunotherapies. To address chronic hypoxia, we have developed manganese dioxide (MnO2) nanoparticles with tunable oxygen production kinetics for sustained oxygenation in bone metastases lesions. Using polyethylene glycol (PEG)-stabilized MnO2 or poly(lactic[50]-co-glycolic[50] acid) (50:50 PLGA), poly(lactic[75]-co-glycolic[25] acid) (75:25 PLGA), and polylactic acid (PLA)-encapsulated MnO2 NPs, we demonstrate that polymer hydrophobicity attenuates burst oxygen production and enables tunable oxygen production kinetics. The PEG-MnO2 NPs resulted in rapid hypoxia reduction in spheroids, which was rapidly attenuated, while the PLA-MnO2 NPs exhibited delayed hypoxia control in cancer spheroids. The 50:50 PLGA-MnO2 NPs exhibited the best short- and long-term control of hypoxia in cancer spheroids, resulting in sustained regulation of the expression of HIF-1α and immunosuppressive genes. The sustained control of hypoxia by the 50:50 PLGA-MnO2 NPs enhanced the cytotoxicity of natural killer cells against cancer spheroids. In vivo, 50:50 PLGA-MnO2 showed greater accumulation in the long bones and pelvis, common sites for bone metastases. The NPs decreased hypoxia in bone metastases and decreased regulatory T cell levels, resulting in enhanced survival of mice with established bone metastases.

Changes in life history and population size can explain the relative neutral diversity levels on X and autosomes in extant human populations.

In human populations, the relative levels of neutral diversity on the X and autosomes differ markedly from each other and from the naïve theoretical expectation of 3/4. Here we propose an explanation for these differences based on new theory about the effects of sex-specific life history and given pedigree-based estimates of the dependence of human mutation rates on sex and age. We demonstrate that life history effects, particularly longer generation times in males than in females, are expected to have had multiple effects on human X-to-autosome (X:A) diversity ratios, as a result of male-biased mutation rates, the equilibrium X:A ratio of effective population sizes, and the differential responses to changes in population size. We also show that the standard approach of using divergence between species to correct for male mutation bias results in biased estimates of X:A effective population size ratios. We obtain alternative estimates using pedigree-based estimates of the male mutation bias, which reveal that X:A ratios of effective population sizes are considerably greater than previously appreciated. Finally, we find that the joint effects of historical changes in life history and population size can explain the observed X:A diversity ratios in extant human populations. Our results suggest that ancestral human populations were highly polygynous, that non-African populations experienced a substantial reduction in polygyny and/or increase in the male-to-female ratio of generation times around the Out-of-Africa bottleneck, and that current diversity levels were affected by fairly recent changes in sex-specific life history.

The Role of Estriol and Estrone in Keratoconic Stromal Sex Hormone Receptors.

Keratoconus (KC) is a progressive corneal thinning disease that manifests in puberty and worsens during pregnancy. KC onset and progression are attributed to diverse factors that include: environmental, genetics, and hormonal imbalances; however, the pathobiology remains elusive. This study aims to determine the role of corneal stroma sex hormone receptors in KC and their interplay with estrone (E1) and estriol (E3) using our established 3D in vitro model. Healthy cornea stromal cells (HCFs) and KC cornea stromal cells (HKCs), both male and female, were stimulated with various concentrations of E1 and E3. Significant changes were observed between cell types, as well as between males and females in the sex hormone receptors tested; androgen receptor (AR), progesterone receptor (PR), estrogen receptor alpha (ERα), and estrogen receptor beta (ERß) using Western blot analysis. E1 and E3 stimulations in HCF females showed AR, PR, and ERß were significantly upregulated compared to HCF males. In contrast, ERα and ERß had significantly higher expression in HKC's females than HKC's males. Our data suggest that the human cornea is a sex-dependent, hormone-responsive tissue that is significantly influenced by E1 and E3. Therefore, it is plausible that E1, E3, and sex hormone receptors are involved in the KC pathobiology, warranting further investigation.

Reversing Hypoxia with PLGA-Encapsulated Manganese Dioxide Nanoparticles Improves Natural Killer Cell Response to Tumor Spheroids.

The adoptive transfer of natural killer (NK) cells, which can recognize and obliterate cancer cells, provides a practical alternative to current treatment modalities to improve cancer patients' survival. However, translating NK cell therapies to treat solid tumors has proven challenging due to the tumor microenvironment (TME). Hypoxia in the TME induces immunosuppression that inhibits the cytotoxic function of NK cells. Thus, reversing hypoxia-induced immunosuppression is critical for effective adoptive NK cell immunotherapy. In this study, we use manganese dioxide nanoparticles (MnO2 NPs) to catalyze the degradation of tumor-produced hydrogen peroxide, thereby generating oxygen. For improved biocompatibility and modulation of oxygen production, the MnO2 NPs were encapsulated into poly(lactic-co-glycolic) to produce particles that are 116 nm in size and with a ζ-potential of +17 mV (PLGA-MnO2 NPs). The PLGA-MnO2 NPs showed first-order oxygen production and sustained high oxygen tension compared to equivalent amounts of bare MnO2 NPs in the presence of H2O2. The PLGA-MnO2 NPs were biocompatible, reduced hypoxia after penetration into the core of cancer spheroids, and decreased hypoxia-induced factor 1 α expression. Reducing hypoxia in the spheroid resulted in a decrease in the potent immunosuppressors, adenosine, and lactate, which was confirmed by electrospray ionization mass spectroscopy (ESI-MS). ESI-MS also showed a change in the metabolism of the amino acids aspartate, glutamine, and glutamate after hypoxia reduction in the cancer cells. Notably, the spheroids' microenvironment changes enhanced NK cells' cytotoxicity, which obliterated the spheroids. These results demonstrate that reducing hypoxia-induced immunosuppression in tumors is a potent strategy to increase the potency of cytotoxic immune cells in the TME. The developed NPs are promising new tools to improve adoptive NK cell therapy.

Progression From Soft Lens to Piggyback Soft-Scleral Contact Lens System to Facilitate Scleral Lens Use in a Pediatric Patient.

ABSTRACT: Traumatic injury in the pediatric population often results in significant refractive errors that if left untreated can lead to amblyopia. Scleral contact lenses (ScCLs) have recently gained popularity in this population for efficacy in treatment of significant refractive errors, including irregularity astigmatism and corneal abnormalities. Scleral contact lens intolerance may limit the ability of practitioners to use this modality. Although a soft contact lens (SCL) is generally well tolerated, it cannot treat refractive error as effectively as an ScCL. We recently used an SCL followed by an SCL-ScCL combination ("piggyback" system) sequence in a pediatric patient to facilitate use of an ScCL alone. We hope that our results may provide practitioners with an additional option when treating this challenging patient population.

Massively parallel reporter assay confirms regulatory potential of hQTLs and reveals important variants in lupus and other autoimmune diseases.

We designed a massively parallel reporter assay (MPRA) in an Epstein-Barr virus transformed B cell line to directly characterize the potential for histone post-translational modifications, i.e., histone quantitative trait loci (hQTLs), expression QTLs (eQTLs), and variants on systemic lupus erythematosus (SLE) and autoimmune (AI) disease risk haplotypes to modulate regulatory activity in an allele-dependent manner. Our study demonstrates that hQTLs, as a group, are more likely to modulate regulatory activity in an MPRA compared with other variant classes tested, including a set of eQTLs previously shown to interact with hQTLs and tested AI risk variants. In addition, we nominate 17 variants (including 11 previously unreported) as putative causal variants for SLE and another 14 for various other AI diseases, prioritizing these variants for future functional studies in primary and immortalized B cells. Thus, we uncover important insights into the mechanistic relationships among genotype, epigenetics, and gene expression in SLE and AI disease phenotypes.

Refractive Astigmatism Outcomes of Femtosecond Laser-Assisted Arcuate Keratotomies Combined with Femtosecond Laser-Assisted Cataract Surgery: Two-Year Results.

PURPOSE: To evaluate the effectiveness and stability of refractive astigmatism reduction after penetrating femtosecond laser-assisted arcuate keratotomy performed at the time of femtosecond laser-assisted cataract surgery. METHODS: Non-randomized retrospective data analysis of all patients that underwent femtosecond laser-assisted cataract surgery with femtosecond laser-assisted arcuate keratotomy over a 4-year period with a non-toric monofocal intraocular lens (2017-2021) at a tertiary care academic center. Postoperative visual acuity, manifest refraction, and predicted residual refractive error were also recorded at 1 month, 3-6 months, 12-18 months, and 2 years postoperatively. Preoperative keratometric astigmatism was compared to postoperative refractive astigmatism using vector calculations and the ASCRS double-angle plot tool. RESULTS: This study comprised 266 eyes (179 patients) that met inclusion criteria. The mean preoperative keratometric astigmatism magnitude was 0.99 ± 0.53 D. At 1 month, 3-6 months, 12-18 months, and 2 years postoperatively, the mean refractive cylinder was 0.49 ± 0.45 D, 0.49 ± 0.45 D, 0.55 ± 0.54 D, and 0.52 ± 0.46 D, respectively. Horizontal against-the-rule astigmatism showed a higher tendency toward undercorrection than vertical with-the-rule astigmatism, which had a slightly higher tendency toward overcorrection. With-the-rule astigmatism had smaller difference vectors between target-induced astigmatism and surgically induced astigmatism. CONCLUSIONS: Femtosecond laser-assisted arcuate keratotomy performed at the time of femtosecond laser-assisted cataract surgery was an effective option for correcting low-to-moderate corneal astigmatism for up to 2 years.

Comparison of Legacy and New No-History IOL Power Calculation Formulas in Postmyopic Laser Vision Correction Eyes.

PURPOSE: To compare the refractive accuracy of legacy and new no-history formulas in eyes with previous myopic laser vision correction (M-LVC). DESIGN: Retrospective cohort study. METHODS: Setting: Two academic centers Study Population: 576 eyes (400 patients) with previous M-LVC that underwent cataract surgery between 2019-2023. A SS-OCT biometer was used to obtain biometric measurements, including standard (K), posterior (PK), and total keratometry values (TK). OBSERVATION PROCEDURES: Refractive prediction errors were calculated for 11 no-history formulas: two legacy M-LVC formulas, four new M-LVC formulas using K values only, and five new M-LVC formulas using K with PK or TK. MAIN OUTCOME MEASURES: Heteroscedastic testing was used to evaluate relative formula performance, and formulas were ranked by root mean square error (RMSE). RESULTS: New M-LVC formulas performed better than legacy M-LVC formulas. New M-LVC formulas with PK/TK values performed better than versions without PK/TK values. Among new M-LVC formulas with PK/TK values, EVO 2.0-PK was superior to Hoffer QST-PK (P < 0.005). Among new M-LVC formulas using K only, Pearl DGS-K and EVO 2.0-K were both superior to Hoffer QST-K and Barrett True K NH-K formulas (all P < 0.005). CONCLUSIONS: Surgeons should favor using new no-history post M-LVC formulas over legacy post M-LVC formulas whenever possible. The top-performing M-LVC formulas (EVO 2.0-PK, Pearl DGS-PK, and Barrett True K-TK) utilized posterior corneal power values. Among formulas utilizing K alone, the EVO 2.0-K and Pearl DGS-K performed best.

Broad-scale variation in human genetic diversity levels is predicted by purifying selection on coding and non-coding elements.

Analyses of genetic variation in many taxa have established that neutral genetic diversity is shaped by natural selection at linked sites. Whether the mode of selection is primarily the fixation of strongly beneficial alleles (selective sweeps) or purifying selection on deleterious mutations (background selection) remains unknown, however. We address this question in humans by fitting a model of the joint effects of selective sweeps and background selection to autosomal polymorphism data from the 1000 Genomes Project. After controlling for variation in mutation rates along the genome, a model of background selection alone explains ~60% of the variance in diversity levels at the megabase scale. Adding the effects of selective sweeps driven by adaptive substitutions to the model does not improve the fit, and when both modes of selection are considered jointly, selective sweeps are estimated to have had little or no effect on linked neutral diversity. The regions under purifying selection are best predicted by phylogenetic conservation, with ~80% of the deleterious mutations affecting neutral diversity occurring in non-exonic regions. Thus, background selection is the dominant mode of linked selection in humans, with marked effects on diversity levels throughout autosomes.

Surgical Management of Intraocular Pressure With Ab Interno Canaloplasty in Postkeratoplasty Patients: 12-Month Results.

PURPOSE: The purpose of this study was to report clinical outcomes of ab interno canaloplasty (ABiC) with the iTrack microcatheter (Nova Eye Medical, Fremont, CA) for surgical management of intraocular pressure (IOP) in postkeratoplasty patients. METHODS: This study was a single-center retrospective case series of postkeratoplasty eyes undergoing ABiC. Efficacy was evaluated based on graft survivability and mean reduction in IOP at 12 months postoperatively. Secondary end points consisted of visual acuity outcomes, number of topical hypotensive medications, and rate of complications. RESULTS: ABiC was successfully performed in 17 eyes after keratoplasty (8 penetrating keratoplasty, 6 DSAEK, 2 penetrating keratoplasty + DSAEK, and 1 DMEK) with elevated IOP refractory to topical hypotensive medications. The baseline mean IOP was 26.2 ± 8.4 mm Hg and reduced significantly to 15.0 ± 4.21 mm Hg at 6 months and 13.0 ± 2.99 mm Hg at 12 months ( P < 0.005). The best-corrected visual acuity improved from 0.61 ± 0.55 logMAR at baseline to 0.47 ± 0.59 and 0.49 ± 0.64 at 6 and 12 months, respectively, following ABiC (not statistically significant: P = 0.6769). The baseline mean number of topical hypotensive medications was 3.7 ± 1.8 and reduced to 2.7 ± 1.4 and 2.9 ± 1.3 at 6 and 12 months, respectively ( P = 0.096). One patient developed a hyphema which required anterior chamber washout. One patient required additional glaucoma surgery 19 months after ABiC. No patients experienced graft failure. CONCLUSIONS: ABiC is a clinically safe and effective treatment that can be performed in postkeratoplasty patients to reduce IOP for at least 1 year without any significant complications.

Fill levels, cost comparisons, and expulsion force requirements of commonly used topical ophthalmic nonsteroidal anti-inflammatory drugs.

PURPOSE: To determine volume fill levels, estimated costs, and force expulsion requirements per bottle of topical ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) commonly perioperatively in the United States. SETTING: Tertiary care academic medical center. DESIGN: Prospective laboratory investigation. METHODS: 8 commercially available NSAIDs (3 branded, 5 generic) were tested: branded bromfenac 0.07%, generic bromfenac 0.09%, diclofenac 0.1%, flurbiprofen 0.03%, generic ketorolac 0.5%, branded ketorolac 0.5%, ketorolac 0.47%, and branded nepafenac 0.3%. 10 bottles of each medication were tested, with an additional bottle tested for expulsion force requirements. A double-blinded method was used to measure the actual bottle fill volume and number of drops per bottle. The total cost per drop was calculated using published cash prices. Force requirements were measured using a customized force gauge apparatus. Formulations were compared using the Kruskal-Wallis test, followed by pairwise comparisons with the Dwass, Steel, Critchlow-Fligner Method. RESULTS: 2 branded NSAIDs (bromfenac and nepafenac) had slightly lower-than-sticker volumes while generics other than ketorolac had higher-than-sticker volumes. Diclofenac and branded bromfenac had the highest and lowest adjusted number of drops respectively. Generic bromfenac and generic ketorolac had the highest and lowest adjusted volume compared with sticker volume respectively. Branded bromfenac was the most expensive medication, while generic diclofenac was the least expensive. Force expulsion requirements varied significantly among generic and branded NSAIDs. CONCLUSIONS: Volume fill levels, patient-incurred costs, and expulsion force requirements per bottle of topical NSAID medications vary significantly. Surgeons may wish to consider these factors when deciding how best to use these medications perioperatively.

Standard vs total keratometry for intraocular lens power calculation in cataract surgery combined with DMEK.

PURPOSE: To compare the prediction accuracy of standard keratometry (K) and total keratometry (TK) for intraocular lens (IOL) power calculation in eyes undergoing combined cataract surgery and Descemet membrane endothelial keratoplasty (triple DMEK). SETTING: Tertiary care academic referral center. DESIGN: Retrospective case series. METHODS: Review of 83 eyes (63 patients) that underwent triple DMEK between 2019 and 2021. Biometry measurements were obtained using a swept-source optical biometer (IOLMaster 700). 63 eyes were used for statistical analysis. Mean error, mean absolute error (MAE), SD, median absolute error, maximum absolute error, root mean squared prediction error, and the percentage of eyes within prediction errors of ±0.50 diopters (D) and ±1.00 D were calculated for 9 multivariate and third-generation formulas using K and TK values (Barrett Universal II, Yeo EVO 2.0, Cooke K6, Kane, Pearl-DGS, Haigis, Holladay 1, Hoffer Q, and SRK/T). Formulas were additionally tested by using the prediction for an IOL power 1 D below the IOL used (IOLup1D). RESULTS: For all formulas, MAE was lower for K than for TK by an average of 0.21 D. The lowest MAE value observed was 0.67 D for "adjusted" SRK/T using K, and the highest MAE values observed were 1.24 D and 1.24 D for nonadjusted Hoffer Q and Haigis using TK, respectively. Overall, lower MAE values were observed for multivariate formulas and SRK/T. CONCLUSIONS: In triple DMEK eyes, the prediction accuracy of K was higher than that of TK. The most accurate formulas were SRK/T and multivariate formulas using K with the IOLup1D adjustment.

Massively Parallel Reporter Assay Confirms Regulatory Potential of hQTLs and Reveals Important Variants in Lupus and Other Autoimmune Diseases.

Objective: To systematically characterize the potential for histone post-translational modifications, i.e., histone quantitative trait loci (hQTLs), expression QTLs (eQTLs), and variants on systemic lupus erythematosus (SLE) and autoimmune (AI) disease risk haplotypes to modulate gene expression in an allele dependent manner. Methods: We designed a massively parallel reporter assay (MPRA) containing ~32K variants and transfected it into an Epstein-Barr virus transformed B cell line generated from an SLE case. Results: Our study expands our understanding of hQTLs, illustrating that epigenetic QTLs are more likely to contribute to functional mechanisms than eQTLs and other variant types, and a large proportion of hQTLs overlap transcription start sites (TSS) of noncoding RNAs. In addition, we nominate 17 variants (including 11 novel) as putative causal variants for SLE and another 14 for various other AI diseases, prioritizing these variants for future functional studies primary and immortalized B cells. Conclusion: We uncover important insights into the mechanistic relationships between genotype, epigenetics, gene expression, and SLE and AI disease phenotypes.

Intraocular Lens Power Calculations in Keratoconus Eyes Comparing Keratometry, Total Keratometry, and Newer Formulae.

PURPOSE: To compare the utility of keratometry vs total keratometry (TK) for intraocular lens power calculations in eyes with keratoconus (KCN) using KCN and non-KCN formulae. DESIGN: Retrospective cohort study. METHODS: This study was conducted at 2 academic centers and included 87 eyes in 67 patients who underwent cataract surgery between 2019 and 2021. Biometry measurements were obtained using a swept-source optical coherence tomography biometer (IOL Master 700). Refractive prediction errors, including root mean square error (RMSE), were calculated for 13 formulae. These included 4 classical formulae (Haigis, Hoffer Q, Holladay 1 [H1], and SRK/T), 5 new formulae (NF) (Barrett Universal II [BU2], Cooke K6, EVO 2.0, Kane, and Pearl-DGS), 3 KCN formulae (BU2 KCN: M-PCA, BU2 KCN: P-PCA, and Kane KCN), and H1 with equivalent keratometry reading values (H1-EKR). Formulae were ranked by RMSE. Friedman analysis of variance with post hoc analysis and H-testing was used for statistical significance testing. RESULTS: KCN formulae had the lowest RMSEs in all eyes, and BU2 KCN:M-PCA performed the best among KCN formulae in all subgroups. In eyes with severe KCN, if TK values are unavailable, the BU2 KCN: P-PCA performed better than the top-ranked non-KCN formula (SRK/T). In eyes with nonsevere KCN, if TK values are unavailable, EVO 2.0 K was statistically superior to the next competitor (Kane K). H1-EKR had the highest RMSE. CONCLUSIONS: KCN formulae and TK are useful for intraocular lens power calculations in KCN eyes, especially in eyes with severe KCN. The BU2 KCN: M-PCA using TK values performed best for eyes with all severities of KCN. For eyes with nonsevere KCN, the EVO 2.0 TK or K can also be used.

The CRW1 Index: Identification of Eyes with Previous Myopic Laser Vision Correction Using Only a Swept-Source OCT Biometer.

PURPOSE: To develop and test a novel index (Cooke-Riaz-Wendelstein [CRW1]) that uses swept-source optical coherence tomography (SS-OCT) biometry measurements (IOLMaster700, Zeiss Meditec), including total keratometry, to alert clinicians that previous myopic laser vision correction (M-LVC) was present in a measured eye. DESIGN: Retrospective, multicenter, comparative diagnostic analysis. METHODS: The study took place at 6 centers in the United States and Austria. Anonymized SS-OCT biometry datasets acquired between 2018 and 2020 and containing 49,199 eyes were analyzed. The LVC status, as identified by the biometrist, was used to segregate eyes into LVC and non-LVC eyes. Data were split into training (10,780 eyes) and validation (38,419 eyes) sets. Subset analysis was performed for CRW1 Index accuracy compared to posterior/anterior corneal curvature ratio (Rpost/Rant), topography with corneal analysis software (Atlas 9000 with Pathfinder II, Zeiss Meditec), tomography (Pentacam, Oculus), dual Scheimpflug-Placido system (Galilei G6, Ziemer), and a cloud-based platform for cataract surgery planning (Veracity, Zeiss Meditec). A positive predictive value (PPV) of ≥90% was targeted for the CRW1 index. True positives, true negatives, sensitivity, and specificity were recorded. RESULTS: The CRW1 Index compared favorably against Rpost/Rant showing a higher PPV (93% vs 65%), with fewer false-positive results (29 vs 180). CRW1 performed similarly to topography software and better than the corneal imaging devices. The CRW1 cutoff value can be adjusted to increase sensitivity (CRW1-IS) to detect additional M-LVC eyes. CONCLUSIONS: The CRW1 and CRW1-IS indices offer surgeons and researchers a readily accessible method to use only SS-OCT biometry measurements to detect eyes with a high probability of previous M-LVC.

Fill levels, cost comparisons, and expulsion force requirements of commonly used topical ophthalmic steroids.

PURPOSE: To determine volume fill levels, estimated costs, and force expulsion requirements per bottle of topical ophthalmic steroids commonly used in the United States. SETTING: Tertiary care academic referral center. DESIGN: Prospective laboratory investigation. METHODS: 8 commercially available medications were tested: loteprednol 0.5%, loteprednol gel 0.5%, loteprednol gel 0.38%, difluprednate 0.05%, generic fluorometholone 0.1%, branded fluorometholone 0.1%, generic prednisolone 1.0%, and branded prednisolone 1.0%. 10 bottles of each medication were tested. A double-blinded method was used to measure actual bottle fill volume and number of drops dispensed per bottle. The total perioperative cost per drop was calculated for each medication using a mean cash price. Force requirements were measured using a customized force gauge apparatus. Formulations were compared using Kruskal-Wallis 1way analysis of variances. RESULTS: All formulations were able to cover postoperative periods commensurate with commonly used dosing regimens for cataract surgery. All medications had greater than sticker volume. Loteprednol 0.5% suspension and branded fluorometholone had the highest and lowest number of drops among the medications tested, respectively. Loteprednol 0.38% gel was the most expensive medication, whereas generic prednisolone 1.0% was the least expensive. Gel and branded formulations of ophthalmic steroids required less expulsion force compared with other tested formulations. CONCLUSIONS: Volume fill levels, patient-incurred costs, and expulsion force requirements per bottle of topical steroid medications vary widely. Clinicians may wish to consider these findings when determining their perioperative prescribing regimen.

Immersion ultrasound biometry vs optical biometry.

PURPOSE: To compare axial length (AL) measurements obtained by optical biometry (OB) and immersion ultrasound (iUS) to investigate the agreement between the 2 techniques and how to use OB constants for eyes with AL by iUS. SETTING: Multicenter study. DESIGN: Retrospective observational case series. METHODS: Agreement between OB and iUS ALs was investigated in 4 subsets. Also, in a test database, the prediction error (PE) for iUS AL was assessed with 4 methods: (1) data-optimized constants; (2) user group for laser interference biometry (ULIB) constants with iUS biometry; (3) with recalibrated AL; and (4) ULIB A-constant - 0.23. RESULTS: A Combined 1970 eyes were measured with both OB and iUS biometry. OB mean AL was 0.0873 mm longer than iUS AL. The latter was made equivalent to OB ALs with this equation: Recalibrated iUS AL = 1.0228 × iUS AL - 0.4556. In a fifth database (n = 1079) with OB AL measurements only, after AL was artificially shortened by 0.0873 mm, the original A-constant had to be reduced by 0.23 to maintain a zero PE. In a sixth database (n = 127) with iUS AL, the original ULIB A-constant provided the poorest outcomes. Using either recalibrated iUS AL or ULIB A-constant - 0.23 zeroed out the mean PE and achieved the lowest median absolute error. CONCLUSIONS: AL measurements by iUS can be used with ULIB constants for OB by subtracting 0.23 from the A-constant; alternatively, the iUS AL may be recalibrated. The recalibrated iUS AL should be treated as AL measurements obtained by OB. It is longer than iUS AL in long eyes.

Surgeons' perspectives on intraoperative gray area surgical complications of cataract surgery.

PURPOSE: To explore surgeons' perspectives and practice patterns in gray area surgical complications (GASCs) within cataract surgery. SETTING: Tertiary care academic referral center. DESIGN: Retrospective observational cross-sectional study. METHODS: An anonymous, online survey consisting of 11 potential intraoperative GASC scenarios was developed and distributed to practicing and resident ophthalmologists in the U.S. Demographic data such as gender, experience, and practice settings were recorded. Using a Likert scale, respondents scaled their perception of likelihood that a GASC could lead to postoperative complications and their obligation toward patient disclosure and documentation in the operative report. Respondents also scaled their likelihood of agreement with a series of statements inserted to assess baseline anxiety levels and inherent perspectives regarding disclosure. RESULTS: 389 responses were analyzed. Female surgeons were more likely than male surgeons to disclose GASCs to their patients and experience psychological anxiety regarding patient outcomes. Both early- and late-stage residents were more likely to believe that GASCs could lead to vision-limiting outcomes when compared with attending surgeons. Surgeons at academic centers were more likely than community-based surgeons to disclose GASCs in the operative report and experience psychological anxiety regarding patient outcomes. CONCLUSIONS: Significant differences based on gender, practice setting, and level of experience exist in disclosure and documentation of intraoperative GASCs. Additional studies are needed to further explore reasons for these differences, as reporting patterns may affect patient satisfaction, medicolegal risks, and postoperative surgeon-experienced anxiety.

Scleral Fixation of a Toric Lens to Treat Corneal Astigmatism in Eyes without Capsular Support.

PURPOSE: To describe surgical technique and report short-term visual outcomes after suture-fixation of a single-piece eyelet-toric (SET) intraocular lens (IOL) for treatment of concurrent aphakia and astigmatism. DESIGN: Retrospective, noncomparative, and non-consecutive case series. METHODS: This was a case series of eleven eyes who underwent successful SET. Eligible eyes had loss of capsular support or aphakia with a minimum of symmetric corneal astigmatism 1.75 diopters (D). Outcome measures included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), magnitude of residual refractive cylinder, and complications resulting from the SET procedure. RESULTS: Preoperative UDVA and CDVA in logMAR scale were 1.46 and 0.45, respectively. Mean preoperative keratometric and refractive cylinder were 3.67 D and 2.52D, respectively. Postoperative UDVA and CDVA were 0.51 and 0.27, respectively, three months after surgery (POM3). Residual refractive cylinder at POM3 was 0.93 D. CONCLUSION: SET technique reduced refractive cylinder and improved UDVA and CDVA. SET may be adapted by surgeons using a readily available IOL and familiar scleral-fixation maneuvers.