Penny A. Asbell

Purpose/Aim: Corneal abrasions and nonhealing corneal epithelial defects are common conditions that cause pain and sometimes are slow to heal. Histatins, a family of histidine-rich peptides, have been implicated in oral and skin epithelial wound healing, and have been shown to be effective in vitro in human corneal epithelial cells. The objective of this study was to test the efficacy of histatin-1 on corneal epithelial wound healing in rabbits. Materials & Methods: Twenty-two (22) rabbits were separated into four treatment groups, each containing 3–7 rabbits. Treatments included three histatin-1 formulations (0.1 ug/ml. 1 ug/ml, and 10 ug/ml) and one inactive vehicle, one drop given three times per day. Eight (8) mm circular wounds were created using 0.5 ml of 20% ethyl alcohol in the right eye of each rabbit. A masked observer photographed each eye twice daily using slit-lamp biomicrophotography. Wound area was analyzed by using ImageJ. Statistical analysis was conducted using Graphpad Prism. Results: Wound recovery was faster in animals given 0.1 ug/ml, 1 ug/ml, and 10 ug/ml when compared to the vehicle solution at 6, 24, and 30 hours after wound creation (p < 0.01). No adverse events were observed in any eyes. When analyzing area under the curve, % recovered area was higher overall in the 0.1 ug/ml (p < 0.01), 1 ug/ml (p < 0.01), and 10 ug/ml (p < 0.001) groups when compared to the vehicle solution. Hourly healing rate was also observed to be faster in the 0.1 ug/ml, 1 ug/ml, and 10 ug/ml groups (p < 0.001) at 24 hours postinjury suggesting an accelerated healing process as compared to the vehicle group. Conclusion: This study represents the first in vivo experiment evaluating and confirming the efficacy of topical histatin on the corneal epithelium wound healing. Further studiesare warranted to better understand the mechanism and safety of topical histatin-1 in corneal epithelial wound-healing and its potential role for human disease treatment.

Purpose: To evaluate the clinical effects of using fixed (four times daily [QID]) versus as-needed (PRN) dosing of an artificial tear product (polyethylene glycol/propylene glycol [PEG/PG]; Systane Ultra) in individuals with dry eye disease. Methods: In this prospective, multicenter, observer-masked, active-control, parallel-group trial, participants were randomized (1:2 allocation) to receive 1 drop of PEG/PG QID (n = 34) or PRN (n = 63) for 28 days. The primary endpoint was change from baseline in the total ocular surface staining (TOSS) score (according to the Oxford scale) at day 28. Results: At day 28, the change from baseline in least squares mean (LSM) TOSS scores for QID and PRN groups were −1.19 and −0.94, respectively (treatment difference [TD]: −0.26; 95% confidence interval [CI]: −∞ to 0.21; P = 0.184); superiority of QID versus PRN dosing was not established, as the upper limit of one-sided 95% CI for TD was not P = 0.037); treatment effectiveness, 2.43 and 0.16 (TD: 2.28, P = 0.278); and treatment-related inconvenience, −11.56 and −2.77 (TD: −8.8, P = 0.996), respectively. Incidence of adverse events was low (≤3.2%) in both the groups; no serious adverse events were reported. Conclusions: QID dosing of PEG/PG was not superior to PRN dosing in terms of ocular staining. The IDEEL symptom-bother score favored QID dosing, suggesting that regular use of artificial tears may provide better symptomatic relief than PRN use. (ClinicalTrials.gov number, NCT02446015.)

Dry eye disease (DED) is a multifactorial disease of the ocular surface and is one of the most common reasons for patients to visit an eye care provider. Cyclosporine A (CsA) is an immune modulating drug that was approved in the US for topical use in the treatment of DED in 2003, which led to a paradigm change in our understanding and treatment of DED, turning attention to control of inflammation for treatment. This review summarizes the literature to date regarding the impact of CsA on the treatment of DED. A special focus is given to the patient and physician perspectives of CsA, including dry eye symptom improvement, medication side effects, and overall patient satisfaction. Studies evaluating CsA in DED have considerable heterogeneity making generalized conclusions about the effect of CsA difficult. However, most studies have demonstrated improvement in at least some symptoms of dry eye in CsA-treated patients. Side effects, most commonly ocular burning on administration of CsA, are common. The literature is sparse regarding long-term follow-up of patients treated with CsA, optimal duration of treatment, and identifying which patients may receive the most benefit from CsA.

Purpose: Biomarkers with minimally invasive and reproducible objective metrics provide the key to future paradigm shifts in understanding of the underlying causes of dry eye disease (DED) and approaches to treatment of DED. We review biomarkers and their validity in providing objective metrics for DED clinical research and patient care. Methods: The English-language literature in PubMed primarily over the last decade was surveyed for studies related to identification of biomarkers of DED: (1) inflammation, (2) point-of-care, (3) ocular imaging, and (4) genetics. Relevant studies in each group were individually evaluated for (1) methodological and analytical details, (2) data and concordance with other similar studies, and (3) potential to serve as validated biomarkers with objective metrics. Results: Significant work has been done to identify biomarkers for DED clinical trials and for patient care. Interstudy variation among studies dealing with the same biomarker type was high. This could be attributed to biologic variations and/or differences in processing, and data analysis. Correlation with other signs and symptoms of DED was not always clear or present. Conclusions: Many of the biomarkers reviewed show the potential to serve as validated and objective metrics for clinical research and patient care in DED. Interstudy variation for a given biomarker emphasizes the need for detailed reporting of study methodology, including information on subject characteristics, quality control, processing, and analysis methods to optimize development of nonsubjective metrics. Biomarker development offers a rich opportunity to significantly move forward clinical research and patient care in DED. Overview: DED is an unmet medical need — a chronic pain syndrome associated with variable vision that affects quality of life, is common with advancing age, interferes with the comfortable use of contact lenses, and can diminish results of eye surgeries, such as cataract extraction, LASIK, and glaucoma procedures. It is a worldwide medical challenge with a prevalence rate ranging from 8% to 50%. Many clinicians and researchers across the globe are searching for better answers to understand the mechanisms related to the development and chronicity of DED. Though there have been many clinical trials for DED, few new treatments have emerged over the last decade. Biomarkers may provide the needed breakthrough to propel our understanding of DED to the next level and the potential to realize our goal of truly personalized medicine based on scientific evidence. Clinical trials and research on DED have suffered from the lack of validated biomarkers and less than objective and reproducible endpoints. Current work on biomarkers has provided the groundwork to move forward. This review highlights primarily ocular biomarkers that have been investigated for use in DED, discusses the methodologic outcomes in providing objective metrics for clinical research, and suggests recommendations for further work.

Antimicrobial resistance has emerged as a major threat to global public health. Thus, the surveillance of changes in antimicrobial resistance in local and global settings is a paramount necessity. While many studies have tracked antimicrobial resistance, only a small percentage surveyed ocular isolates. The purpose of this study was to report the in vitro susceptibility of bacterial pathogens isolated from ocular samples in New York, NY from 2010 to 2015. A retrospective review of ocular isolates was conducted. All organisms were collected by 25 separate inpatient wards and outpatient clinics, and were analyzed by the clinical microbiology laboratory at Mount Sinai Hospital. Clinical Laboratory and Standards Institute (CLSI) guidelines were followed for susceptibility testing and breakpoint interpretations. A total of 549 bacterial organisms were isolated from 1664 cultures (33%) during the 6-year study period. Of these, 358 isolates (65.2%) underwent susceptibility testing. 182 (50.8%) isolates were Gram-positive. The most common Gram-positive bacterium was Staphylococcus aureus (62.1%). Methicillin-resistance decreased in S. aureus isolates (31.3% in 2010, 14.1% in 2015) but was without significant change (p = 0.25). When analyzing all S. aureus isolates recovered during the study period, there were significantly more methicillin-resistant S. aureus (MRSA) isolates resistant to fluoroquinolones (p <0.0001), erythromycin (p <0.0001), and trimethoprim/sulfamethoxazole (TMP/SMZ; p <0.05). Overall, Streptococcus pneumoniae isolates showed reduced susceptibility to erythromycin, but were otherwise susceptible to the other antimicrobials tested. Haemophilus influenzae (26.1%) and Pseudomonas aeruginosa (23.9%) were the most common Gram-negative bacteria isolated. Resistance to ampicillin and TMP/SMZ was observed in several of the H. influenzae isolates. P. aeruginosa isolates did not show high resistance overall, however, it was noted that isolates resistant to meropenem were also resistant to other antimicrobials (p < 0.01). Overall, antimicrobial resistance was infrequent for the Gram-negative and Gram-positive bacteria analyzed. While the MRSA isolates demonstrated increased resistance to multiple antimicrobial classes, this is expected for this pathogen. Due to the continued use of broad-spectrum oral and systemic antimicrobials to treat ocular infections, findings of this study and other surveillance studies specific to ocular isolates should be used as resources in effective decision making in the treatment of ocular disease.

Antibiotic resistance among ocular pathogens is a public health concern. The multicenter, prospective Antibiotic Resistance Monitoring in Ocular micRoorganisms (ARMOR) study is an ongoing surveillance study designed to report on antibiotic resistance rates and trends among Staphylococcus aureus , coagulase-negative staphylococci (CoNS; includes Staphylococcus epidermidis ), Streptococcus pneumoniae , Pseudomonas aeruginosa , and Haemophilus influenzae isolates from ocular infections. Results for more than 4,000 isolates collected from 2009 –2015, representing 7 years of ARMOR, were recently presented. More than a third of S. aureus and almost half of all CoNS isolates were found to be resistant to methicillin. Staphylococcal isolates also showed high levels of multidrug resistance (resistance to ≥3 antibacterial drug classes) with 76.4% and 73.7% of methicillin-resistant S. aureus (MRSA) and methicillin-resistant CoNS (MRCoNS) isolates, respectively, demonstrating multidrug resistance. Resistance among S. pneumoniae was notable for azithromycin (36.8%) and for penicillin (34.0%), whereas P. aeruginosa and H. influenzae were generally susceptible to the antibiotic classes tested. Longitudinal analyses demonstrated a small decrease in methicillin resistance among S. aureus over the 7-year study period, which may be a result of improved antibiotic stewardship. Continued surveillance of antibiotic resistance among ocular pathogens is warranted.