Demodex Blepharitis: A Comprehensive Review of the Disease, Current Management, and Emerging Therapies.

ABSTRACT: Demodex blepharitis is a common disease of the eyelid, affecting approximately 25 million Americans. This article reviews what is known about the mechanisms and impact of Demodex blepharitis, risk factors, signs and symptoms, diagnostic techniques, current management options, and emerging treatments. Demodex mites contribute to blepharitis in several ways: direct mechanical damage, as a vector for bacteria, and by inducing hypersensitivity and inflammation. Risk factors for Demodex blepharitis include increasing age, rosacea, and diabetes. The costs, symptom burden, and psychosocial effects of Demodex blepharitis are considerable. The presence of collarettes is pathognomonic for Demodex blepharitis. Redness, dryness, discomfort, foreign body sensation, lash anomalies, and itching are also hallmarks of the disease. Although a number of oral, topical, eyelid hygiene and device-based options have been used clinically and evaluated in studies for the management of Demodex blepharitis, none have been FDA approved to treat the disease. Recent randomized controlled clinical trials suggest that lotilaner ophthalmic solution, 0.25%, is a topical treatment with the potential to eradicate Demodex mites and eliminate collarettes and eyelid redness for an extended period.

Contralateral Forced Eyelid Closure Increases Intraocular Pressure.

OBJECTIVES: The purpose of the study was to describe the influence of contralateral forced eyelid closure on intraocular pressure (IOP). METHODS: Twenty-one healthy volunteers with no ophthalmic history had their IOP measured in the supine position to simulate the intraoperative environment. Intraocular pressure was measured with a handheld tonometer over three scenarios: (1) both eyes in a relaxed state, (2) eyelid speculum in the right eye with both eyes open and relaxed, (3) eyelid speculum in the right eye with the fellow eye squeezing tightly. RESULTS: Intraocular pressure significantly increased with forced contralateral eyelid squeezing compared with the relaxed state by a mean of 7.71±5.08 mm Hg (95% Confidence Interval of 5.40-7.37), P<0.001. CONCLUSIONS: Contralateral eyelid squeezing can significantly increase intraoperative IOP measurements.

Contact Lens Safety for the Correction of Refractive Error in Healthy Eyes.

ABSTRACT: Contact lenses are a safe and effective method for correction of refractive error and worn by an estimated 45 million Americans. Because of the widespread availability and commercial popularity of contact lenses, it is not well appreciated by the public that contact lenses are U.S. Food and Drug Administration (FDA)-regulated medical devices. Contact lenses are marketed in numerous hard and soft materials that have been improved over decades, worn in daily or extended wear, and replaced in range of schedules from daily to yearly or longer. Lens materials and wear and care regimens have impact on the risks of contact lens-related corneal inflammatory events and microbial keratitis. This article reviews contact lens safety, with specific focus on the correction of refractive error in healthy eyes.

Combined Therapy Using Human Corneal Stromal Stem Cells and Quiescent Keratocytes to Prevent Corneal Scarring after Injury.

Corneal blindness due to scarring is conventionally treated by corneal transplantation, but the shortage of donor materials has been a major issue affecting the global success of treatment. Pre-clinical and clinical studies have shown that cell-based therapies using either corneal stromal stem cells (CSSC) or corneal stromal keratocytes (CSK) suppress corneal scarring at lower levels. Further treatments or strategies are required to improve the treatment efficacy. This study examined a combined cell-based treatment using CSSC and CSK in a mouse model of anterior stromal injury. We hypothesize that the immuno-regulatory nature of CSSC is effective to control tissue inflammation and delay the onset of fibrosis, and a subsequent intrastromal CSK treatment deposited collagens and stromal specific proteoglycans to recover a native stromal matrix. Using optimized cell doses, our results showed that the effect of CSSC treatment for suppressing corneal opacities was augmented by an additional intrastromal CSK injection, resulting in better corneal clarity. These in vivo effects were substantiated by a further downregulated expression of stromal fibrosis genes and the restoration of stromal fibrillar organization and regularity. Hence, a combined treatment of CSSC and CSK could achieve a higher clinical efficacy and restore corneal transparency, when compared to a single CSSC treatment.

The Rcs Stress Response System Regulator GumB Modulates Serratia marcescens-Induced Inflammation and Bacterial Proliferation in a Rabbit Keratitis Model and Cytotoxicity In Vitro.

In this study, we tested the hypothesis that the conserved bacterial IgaA-family protein, GumB, mediates microbial pathogenesis associated with Serratia marcescens ocular infections through regulation of the Rcs stress response system. The role of the Rcs system and bacterial stress response systems for microbial keratitis is not known, and the role of IgaA proteins in mammalian pathogenesis models has only been tested with partial-function allele variants of Salmonella. Here, we observed that an Rcs-activated gumB mutant had a >50-fold reduction in proliferation compared to the wild type within rabbit corneas at 48 h and demonstrated a notable reduction in inflammation based on inflammatory signs, including the absence of hypopyons, and proinflammatory markers measured at the RNA and protein levels. The gumB mutant phenotypes could be complemented by wild-type gumB on a plasmid. We observed that bacteria with an inactivated Rcs stress response system induced high levels of ocular inflammation and restored corneal virulence to the gumB mutant. The high virulence of the ΔrcsB mutant was dependent upon the ShlA cytolysin transporter ShlB. Similar results were found for testing the cytotoxic effects of wild-type and mutant bacteria on a human corneal epithelial cell line in vitro. Together, these data indicate that GumB regulates virulence factor production through the Rcs system, and this overall stress response system is a key mediator of a bacterium's ability to induce vision-threatening keratitis.

The Prevalence of Bacteria, Fungi, Viruses, and Acanthamoeba From 3,004 Cases of Keratitis, Endophthalmitis, and Conjunctivitis.

PURPOSE: The definitive identification of ocular pathogens optimizes effective treatment. Although the types of ocular pathogens are known; there is less definitive information on the prevalence of causative infections including viruses, fungi, and protozoa, which is the focus of this retrospective laboratory review. METHODS: Data used for laboratory certification were reviewed for the detection of bacteria, viruses, fungi, and protozoa, from patients with infectious keratitis, endophthalmitis, and conjunctivitis. The main outcome parameter was laboratory-positive ocular infection. RESULTS: The distribution of infectious agents for keratitis (n=1,387) (2004-2018) was bacteria 72.1% (Staphylococcus aureus 20.3%, Pseudomonas aeruginosa 18%, Streptococcus spp. 8.5%, other gram-positives 12.4%, and other gram-negatives 12.9%), Herpes simplex virus 16%, fungi 6.7%, and Acanthamoeba 5.2%. For endophthalmitis, (n=770) (1993-2018), the bacterial distribution was coagulase-negative Staphylococcus 54%, Streptococcus spp. 21%, S. aureus 10%, other gram-positives 8%, and gram-negatives 7%. The distribution for conjunctivitis (n=847) (2004-2018) was Adenovirus 34%, S. aureus 25.5%, Streptococcus pneumoniae 9%, Haemophilus 9%, other gram-negatives 8.8%, other gram-positives 6%, coagulase-negative Staphylococcus 4.5% and Chlamydia 3.2%. CONCLUSION: An updated monitoring of ocular pathogens creates an awareness of the different infectious etiologies and the importance of laboratory studies. This information can determine treatment needs for infectious ocular diseases.

Corneal Infections Associated with Sleeping in Contact Lenses - Six Cases, United States, 2016-2018.

Contact lenses, when worn and cared for properly, are a safe and effective form of vision correction used by an estimated 45 million Americans. However, contact lens wearers are at risk for contact lens-related eye infections, especially when wearers do not practice proper contact lens wear and care habits. These infections, affecting the cornea and known as microbial keratitis (Figure), can lead to serious adverse health outcomes. Because contact lenses are regulated by the Food and Drug Administration (FDA) as medical devices, contact lens-related corneal infections should be reported to FDA as an adverse event. To illustrate their serious health implications, six cases of contact lens-related corneal infection, in which sleeping in lenses was reported as the main risk factor, are presented. Consequences of infection reported among the identified cases included the need for frequent administration of antibiotic eye drops, multiple follow-up medical appointments, and permanent eye damage. Health education measures directed toward contact lens wearers should emphasize raising awareness of the risks of sleeping in contact lenses as well as adherence to all recommendations for the wear and care of contact lenses. Additional measures are needed to educate eye care professionals about the need to report contact lens-related corneal infections to MedWatch, the FDA Safety Information and Adverse Event Reporting program (https://www.fda.gov/MedWatch/).

AmpliVue Is a Practical and Timely Test for the Detection of HSV From Keratitis Specimens.

OBJECTIVE: The laboratory diagnostic detection of herpes simplex virus (HSV) from eye samples must be practical, timely, and definitive for appropriate therapy. Although polymerase chain reaction (PCR) and/or cell culture can be definitive, HSV results can be delayed. Enzyme Linked Virus Inducible System (ELVIS) is a test that can provide results within 24 to 48 hr. We evaluated "AmpliVue HSV 1+2 Assay" as a molecular colorimetric test that can detect HSV (1 or 2) DNA within 1 hr. METHODS: Cornea/conjunctival samples were tested retrospectively with AmpliVue against 53 true-positive and 20 true-negative specimens collected in chlamydial transport medium. All clinical specimens were tested by cell culture isolation, PCR, and ELVIS for routine patient care. RESULTS: The sensitivity of AmpliVue against ocular samples that were both culture-positive and PCR-positive was 84%. The specificity of AmpliVue was 100%. Only one clinical sample was HSV-2 positive, whereas all others tested positive for HSV-1. Based on PCR-positive and cell culture-negative samples, AmpliVue (11 of 17) tested more positive than ELVIS (0 of 17) (P=0.003, Fisher Exact). CONCLUSIONS: AmpliVue is moderately sensitive and highly specific as a practical and timely diagnostic test for detecting ocular HSV. Expertise is readily achieved and the test is straightforward with easy interpretation. Negative AmpliVue testing must be confirmed with PCR. AmpliVue has potential as an office-based diagnostic test.

Release of Moxifloxacin From Corneal Collagen Shields.

OBJECTIVES: To investigate the diffusion of moxifloxacin through bandage contact lenses (BCLs) versus corneal collagen shields (CSs), the relative ability of BCLs and CSs to release moxifloxacin, and the potential of release of moxifloxacin from CSs in the clinical setting. METHODS: Using an in vitro model, the diffusion of 5% moxifloxacin across BCLs and CSs was compared. Next, the amount of drug release from BCLs and CSs soaked in 0.5% moxifloxacin was measured. Finally, based on a clinical model, CSs were soaked in Vigamox (commercial moxifloxacin) and the total concentration released was detected. Collagen shields remained intact after 24 hr; therefore, enzymatic digestion and mechanical grinding of the CS were performed to determine whether further drug could be released. The concentration of moxifloxacin was measured using a spectrophotometer at set time points up to 24 hr. RESULTS: In the diffusion assay, 35.7±10.5% diffused through the BCLs and 36.2±11.8% diffused through the CSs (P=0.77). The absorption assay demonstrated at 120 min, a total of 33.3±6.77 µg/mL was released from BCLs compared with 45.8±5.2 µg/mL from the CSs (P=0.0008). In vitro experiments to simulate clinical application of Vigamox-soaked CS found the concentration of moxifloxacin released of 127.7±7.25 µg/mL in 2 mL of phosphate-buffered saline over 24 hr. CONCLUSIONS: Moxifloxacin diffuses through BCLs and CSs at similar rates; however, CSs have greater capacity to absorb and release moxifloxacin compared with BCLs. Vigamox-soaked CSs released 250 µg of moxifloxacin and may be a useful method to prevent endophthalmitis.

Postsurgical Cataract Prophylaxis With Intravitreal "Triamcinolone-Moxifloxacin" May Not Be Optimal For Preventing Endophthalmitis.

PURPOSE: Intravitreal injections of antibiotics and anti-inflammatories are used by some cataract surgeons for surgical prophylaxis. To support this prophylaxis, intravitreal triamcinolone-moxifloxacin (TM) and triamcinolone-moxifloxacin-vancomycin (TMV) were tested for preventing Staphylococcus aureus (SA) endophthalmitis in rabbits. METHODS: Trademark formulations of TM (15/1 mg/mL) and TMV (15/1/10 mg/mL) were intravitreally injected into seven groups of eight rabbits each (A-G). Before intravitreal injection, the vitreous was first challenged with clinical SA endophthalmitis isolates (5,000 colony-forming unit) with varying minimum inhibitory concentrations (MICs in µg/mL) to moxifloxacin (denoted by the MIC at the end of each group listed): A) TMV-10, B) TM-10, C) Saline-10, D) TM-2, E) Saline-2, F) TM-0.032, and G) Saline-0.032. After 24 hr, the rabbit eyes were graded for clinical endophthalmitis and cultured for viable SA. RESULTS: Rabbits treated with TMV and challenged by SA with a moxifloxacin MIC of 10 µg/mL did not present with endophthalmitis (0/8, no eyes with endophthalmitis). For SA with moxifloxacin MICs of 10.0 and 2.0 µg/mL, TM did not prevent endophthalmitis (16/16, 100% of eyes with endophthalmitis). For SA with a moxifloxacin MIC of 0.032 µg/mL, endophthalmitis was prevented with TM (0/8, no eyes with endophthalmitis). All saline-treated eyes developed endophthalmitis (23/23, 100% of eyes with endophthalmitis). CONCLUSIONS: Intravitreal monotherapy with TM did not provide consistent prevention of SA endophthalmitis, whereas intravitreal TMV successfully prevented endophthalmitis because of SA with elevated MIC values to moxifloxacin. Cataract surgeons need to be aware that vancomycin seems to be essential for intravitreal prophylaxis to cover moxifloxacin resistance.

Food and Drug Administration, American Academy of Ophthalmology, American Academy of Optometry, American Association for Pediatric Ophthalmology and Strabismus, American Optometric Association, American Society of Cataract and Refractive Surgery, and Contact Lens Association of Ophthalmologists Co-Sponsored Workshop: Controlling the Progression of Myopia: Contact Lenses and Future Medical Devices.

The prevalence of myopia is high and increasing. Approximately 5 billion people around the world are expected to be myopic by the year 2050. Methods to slow the progression of myopia and therefore potentially decrease the associated sight-threatening complications have been the subject of a number of investigations. A workshop, sponsored by the United States Food and Drug Administration (FDA) Center for Devices and Radiological Health, American Academy of Ophthalmology, American Academy of Optometry, American Association for Pediatric Ophthalmology and Strabismus, American Optometric Association, American Society of Cataract and Refractive Surgery, and Contact Lens Association of Ophthalmologists, Inc, convened myopia experts from around the world to discuss principles to consider in the design of clinical trials investigating the effectiveness and safety of myopia control devices. Experts discussed parameters such as study endpoints, duration, enrollment criteria, patient-reported outcomes, recruitment, and retention. The discussions among the experts, FDA, and audience members should help to facilitate the development and evaluation of reasonably safe and effective myopia control devices.

Development of retrocorneal membrane following pig-to-monkey penetrating keratoplasty.

Recent reports of long-term survival after wild-type (WT) pig-to-monkey corneal xenotransplantation are encouraging. We experienced the rapid development of retrocorneal membranes, a rare complication after corneal allotransplantation (although seen in infants and young children). The original specific aim of the study was to determine the factors associated with successful (young) pig corneal transplantation in monkeys. However, when it was obvious that retrocorneal membranes rapidly developed, our aims became to determine the factors involved in its development after both WT and Genetically engineered (GE ) pig corneal xenotransplantation and to investigate the characteristics of the retrocorneal membrane. Rhesus monkeys were recipients of penetrating keratoplasty using WT and GE pigs (n=2, respectively, 1-3 months old). Local/systemic steroids were administered for 3 months. Grafts were evaluated by slit lamp for corneal transparency, edema, and neovascularization. Hematoxylin and eosin, Masson trichrome staining, and immunohistochemical analysis were performed. Gal staining was also carried out to distinguish the origin of the membrane. All penetrating keratoplasty recipients developed fibrous retrocorneal membranes in the early post-transplantation period, regardless of whether the graft was from a WT or GE pig. There were no features of rejection, with no cell infiltrate in the graft or anterior chamber during the three-month follow-up. There was no difference in the clinical course between the two groups (WT or GE corneas). Immunohistochemistry indicated that the retrocorneal membranes were CK negative, α-SMA positive, and vimentin positive, suggesting that they were of fibrous (keratocytic) origin. Also, the membrane was Gal positive, suggesting that it is derived from pig cornea. Following pig-to-monkey corneal xenotransplantation, we report that retrocorneal membranes are derived from donor pig keratocytes. Prevention of retrocorneal membranes will be necessary to achieve successful corneal xenotransplantation.

Diffusion of Antimicrobials Across Silicone Hydrogel Contact Lenses.

OBJECTIVES: To measure the diffusion of topical preparations of moxifloxacin, amphotericin B (AmB), and polyhexamethylene biguanide (PHMB) through silicone hydrogel (SH) contact lenses (CLs) in vitro. METHODS: Using an in vitro model, the diffusion of three antimicrobials through SH CLs was measured. Diffused compounds were measured using a spectrophotometer at set time points over a period of 4 hr. The amount of each diffused antimicrobial was determined by comparing the experimental value with a standard curve. A biological assay was performed to validate the CL diffusion assay by testing antimicrobial activity of diffused material against lawns of susceptible bacteria (Staphylococcus epidermidis) and yeast (Saccharomyces cerevisiae). Experiments were repeated at least two times with a total of at least four independent replicates. RESULTS: Our data show detectable moxifloxacin and PHMB diffusion through SH CLs at 30 min, whereas AmB diffusion remained below the limit of detection within the 4-hr experimental period. In the biological assay, diffused moxifloxacin demonstrated microbial killing starting at 20 min on bacterial lawns, whereas PHMB and AmB failed to demonstrate killing on microbial lawns over the course of the 60-min experiment. CONCLUSIONS: In vitro diffusion assays demonstrate limited penetration of certain anti-infective agents through SH CLs. Further studies regarding the clinical benefit of using these agents along with bandage CL for corneal pathologic condition are warranted.

Contact lens fitting and long-term management for the Boston keratoprosthesis.

OBJECTIVES: To examine the types of contact lenses used as bandage lenses in the postoperative management of patients with Boston type 1 keratoprosthesis (K-Pro). We examined the lens parameters, the number of trial lenses used to achieve successful fit, and lens replacement schedule. The strategies to achieving a successful fit in these complex patients are reviewed. METHODS: This was a single-center, retrospective chart review of patients who had undergone implantation of the Boston keratoprosthesis in 1 or more eyes from January 2006 to December 2011. Patients included male and female subjects aged 18 years or older who had been fit with bandage contact lenses as part of their postoperative management. RESULTS: Twenty-two eyes of 15 patients met the criteria for this review. The age range was 30 to 90 years. There were eight men and seven women. The average number of lenses to achieve a successful fit varied from 1 to 8, with an average of 2.22 trial lenses used per patient. By 6 months after the surgery, 12 K-Pro eyes showed visual acuity of 20/200 or better, with 7 of those eyes attaining better than 20/80 best-corrected Snellen distance acuity. CONCLUSIONS: Our results show that it is often necessary to use custom contact lenses for K-Pro patients. Management of poor tear film quality, protein deposition, inflammation, lens replacement schedule, and antibiotic resistance are related considerations.

Good manufacturing practice production of human corneal limbus-derived stromal stem cells and in vitro quality screening for therapeutic inhibition of corneal scarring.

BACKGROUND: Mesenchymal stem cells in the adult corneal stroma (named corneal stromal stem cells, CSSCs) inhibit corneal inflammation and scarring and restore corneal clarity in pre-clinical corneal injury models. This cell therapy could alleviate the heavy reliance on donor materials for corneal transplantation to treat corneal opacities. Herein, we established Good Manufacturing Practice (GMP) protocols for CSSC isolation, propagation, and cryostorage, and developed in vitro quality control (QC) metric for in vivo anti-scarring potency of CSSCs in treating corneal opacities. METHODS: A total of 24 donor corneal rims with informed consent were used-18 were processed for the GMP optimization of CSSC culture and QC assay development, while CSSCs from the remaining 6 were raised under GMP-optimized conditions and used for QC validation. The cell viability, growth, substrate adhesion, stem cell phenotypes, and differentiation into stromal keratocytes were assayed by monitoring the electric impedance changes using xCELLigence real-time cell analyzer, quantitative PCR, and immunofluorescence. CSSC's conditioned media were tested for the anti-inflammatory activity using an osteoclastogenesis assay with mouse macrophage RAW264.7 cells. In vivo scar inhibitory outcomes were verified using a mouse model of anterior stromal injury caused by mechanical ablation using an Algerbrush burring. RESULTS: By comparatively assessing various GMP-compliant reagents with the corresponding non-GMP research-grade chemicals used in the laboratory-based protocols, we finalized GMP protocols covering donor limbal stromal tissue processing, enzymatic digestion, primary CSSC culture, and cryopreservation. In establishing the in vitro QC metric, two parameters-stemness stability of ABCG2 and nestin and anti-inflammatory ability (rate of inflammation)-were factored into a novel formula to calculate a Scarring Index (SI) for each CSSC batch. Correlating with the in vivo scar inhibitory outcomes, the CSSC batches with SI < 10 had a predicted 50% scar reduction potency, whereas cells with SI > 10 were ineffective to inhibit scarring. CONCLUSIONS: We established a full GMP-compliant protocol for donor CSSC cultivation, which is essential toward clinical-grade cell manufacturing. A novel in vitro QC-in vivo potency correlation was developed to predict the anti-scarring efficacy of donor CSSCs in treating corneal opacities. This method is applicable to other cell-based therapies and pharmacological treatments.

Acanthamoeba keratitis associated with tap water use during contact lens cleaning: manufacturer guidelines need to change.

Contact lens-associated Acanthamoeba keratitis continues to be a significant cause of visual morbidity in the United States. Although exposure to water sources while wearing lenses has been a known risk factor for infection for decades, this behavior in several contact lens hygiene protocols continues to prevail. In this review, we surveyed the currently available contact lens cleaning solutions for both soft and rigid gas-permeable contact lenses and reviewed the cleaning instructions of the available solutions. Discrepancies between clinician recommendations and written instructions on a solution packages continues to persist, and we advocate a revision in current manufacturer guidelines to include explicit warnings against use of tap or distilled water sources for cleaning contact lenses or their storage cases.

A rise in the frequency of lasR mutant Pseudomonas aeruginosa among keratitis isolates between 1993 and 2021.

Introduction: Pseudomonas aeruginosa causes vision threatening keratitis. The LasR transcription factor regulates virulence factors in response to the quorum sensing molecule N-3-oxo-dodecanoyl-L-homoserine lactone. P. aeruginosa isolates with lasR mutations are characterized by an iridescent high sheen phenotype caused by a build-up of 2-heptyl-4-quinolone. A previous study demonstrated 22% (n=101) of P. aeruginosa keratitis isolates from India between 2010 and 2016 were sheen positive lasR mutants, and the sheen phenotype correlated with worse clinical outcomes for patients. In this study, a longitudinal collection of P. aeruginosa keratitis isolates from Eastern North America were screened for lasR mutations by the sheen phenotype and sequencing of the lasR gene. Methods: Keratitis isolates (n=399) were classified by sheen phenotype. The lasR gene was cloned from a subset of isolates, sequenced, and tested for loss of function or dominant-negative status based on an azocasein protease assay. A retrospective chart review compared outcomes of keratitis patients infected by sheen positive and negative isolates. Results: A significant increase in sheen positive isolates was observed between 1993 and 2021. Extracellular protease activity was reduced among the sheen positive isolates and a defined lasR mutant. Cloned lasR alleles from the sheen positive isolates were loss of function or dominant negative and differed in sequence from previously reported ocular lasR mutant alleles. Retrospective analysis of patient information suggested significantly better visual outcomes for patients infected by sheen positive isolates. Discussion: These results indicate an increase in lasR mutations among keratitis isolates in the United States and suggest that endemic lasR mutants can cause keratitis.

Rise in frequency of lasR mutant Pseudomonas aeruginosa among keratitis isolates between 1993 and 2021.

Pseudomonas aeruginosa causes severe vision threatening keratitis. LasR is a transcription factor that regulates virulence associated genes in response to the quorum sensing molecule N-3-oxo-dodecanoyl-L-homoserine lactone. P. aeruginosa isolates with lasR mutations are characterized by an iridescent high sheen phenotype caused by a build-up of 2-heptyl-4-quinolone. A previous study indicated a high proportion (22 out of 101) of P. aeruginosa keratitis isolates from India between 2010 and 2016 were sheen positive and had mutations in the lasR gene, and the sheen phenotype correlated with worse clinical outcomes for patients. In this study, a longitudinal collection of P. aeruginosa keratitis isolates from Eastern North America were screened for lasR mutations by the sheen phenotype and sequencing of the lasR gene. A significant increase in the frequency of isolates with the sheen positive phenotype was observed in isolates between 1993 and 2021. Extracellular protease activity was lower among the sheen positive isolates and a defined lasR mutant. Cloned lasR alleles from the sheen positive isolates were loss of function or dominant negative and differed in sequence from previously reported ocular lasR mutant alleles. Insertion elements were present in a subset of independent isolates and may represent an endemic source from some of the isolates. Retrospective analysis of patient information suggested significantly better visual outcomes for patients with infected by sheen positive isolates. Together, these results indicate an increasing trend towards lasR mutations among keratitis isolates at a tertiary eye care hospital in the United States.

Cost Burden of Endothelial Keratoplasty in Fuchs Endothelial Dystrophy: Real-World Analysis of a Commercially Insured US Population (2014-2019).

Purpose: To assess the incremental burden of corneal transplant surgery for US commercially insured patients with Fuchs endothelial corneal dystrophy (FECD) treated with endothelial keratoplasty (EK) compared to controls. Methods: The study design was retrospective cohort using IBM® MarketScan® claims (January 2014-September 2019) and included EK-treated (N=1562) and control patients (N=23,485) having ≥12 months' enrollment before and after diagnosis, who were subsequently matched on select characteristics. The index date was the beginning of the pre-operative period (3 months before EK); synthetic EK index was assigned for controls. All-cause, eye-disease, and complication-related healthcare resource utilization (HCRU) and costs were compared up to 36 months post index. For a small subset of patients, patient data were linked to the Health and Productivity Management supplemental database, which integrates data on productivity loss and disability payments. Results: Matched cohorts included 804 EK-treated and 1453 controls with average age 65.7 years, 1383 (61%) female. Over 12 months of follow-up, all-cause ($41,199 vs $20,222, p<0.001) and eye-disease related costs ($22,951 vs $1389, p<0.001) were higher among EK-treated patients than controls. The cost differential increased additionally by $1000-$2000 per annum by 36 months of follow-up. While balanced at baseline, over follow-up EK-treated patients had higher prevalence of glaucoma, elevated intraocular pressure, cataract, cataract surgery, diagnosis of cornea transplant rejection, retinal edema. By 36 month of follow-up, EK-treated patients had 9 more short-term disability days, resulting in $2992 additional burden of disability payments. Conclusion: This study found a higher cost burden among FECD patients receiving EK treatment versus those who did not. With a shift in management of FECD, cost burden estimates generated in this study could serve as an important benchmark for future studies.