Topical Atropine for Childhood Myopia Control: The Atropine Treatment Long-Term Assessment Study.

Importance: Clinical trial results of topical atropine eye drops for childhood myopia control have shown inconsistent outcomes across short-term studies, with little long-term safety or other outcomes reported. Objective: To report the long-term safety and outcomes of topical atropine for childhood myopia control. Design, Setting, and Participants: This prospective, double-masked observational study of the Atropine for the Treatment of Myopia (ATOM) 1 and ATOM2 randomized clinical trials took place at 2 single centers and included adults reviewed in 2021 through 2022 from the ATOM1 study (atropine 1% vs placebo; 1999 through 2003) and the ATOM2 study (atropine 0.01% vs 0.1% vs 0.5%; 2006 through 2012). Main Outcome Measures: Change in cycloplegic spherical equivalent (SE) with axial length (AL); incidence of ocular complications. Results: Among the original 400 participants in each original cohort, the study team evaluated 71 of 400 ATOM1 adult participants (17.8% of original cohort; study age, mean [SD] 30.5 [1.2] years; 40.6% female) and 158 of 400 ATOM2 adult participants (39.5% of original cohort; study age, mean [SD], 24.5 [1.5] years; 42.9% female) whose baseline characteristics (SE and AL) were representative of the original cohort. In this study, evaluating ATOM1 participants, the mean (SD) SE and AL were -5.20 (2.46) diopters (D), 25.87 (1.23) mm and -6.00 (1.63) D, 25.90 (1.21) mm in the 1% atropine-treated and placebo groups, respectively (difference of SE, 0.80 D; 95% CI, -0.25 to 1.85 D; P = .13; difference of AL, -0.03 mm; 95% CI, -0.65 to 0.58 mm; P = .92). In ATOM2 participants, the mean (SD) SE and AL was -6.40 (2.21) D; 26.25 (1.34) mm; -6.81 (1.92) D, 26.28 (0.99) mm; and -7.19 (2.87) D, 26.31 (1.31) mm in the 0.01%, 0.1%, and 0.5% atropine groups, respectively. There was no difference in the 20-year incidence of cataract/lens opacities, myopic macular degeneration, or parapapillary atrophy (ß/γ zone) comparing the 1% atropine-treated group vs the placebo group. Conclusions and Relevance: Among approximately one-quarter of the original participants, use of short-term topical atropine eye drops ranging from 0.01% to 1.0% for a duration of 2 to 4 years during childhood was not associated with differences in final refractive errors 10 to 20 years after treatment. There was no increased incidence of treatment or myopia-related ocular complications in the 1% atropine-treated group vs the placebo group. These findings may affect the design of future clinical trials, as further studies are required to investigate the duration and concentration of atropine for childhood myopia control.

Comparison of ocular surface assessment and adherence between preserved and preservative-free latanoprost in glaucoma: a parallel-grouped randomized trial.

Given that nonadherence is related to subject characteristics and drug tolerance and preserved eye drops tend to be more intolerable than preservative-free ones, we conducted a phase 4, parallel-grouped, investigator-blind, active-control, randomized, multicenter study. A total of 51 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open-angle glaucoma or ocular hypertension were randomly assigned to the preserved latanoprost group (n = 26) and the preservative-free latanoprost group (n = 25). The efficacy variables were corneal/conjunctival staining grade, Ocular Surface Disease Index (OSDI), adherence at 12 weeks after the first administration; corneal/conjunctival staining grade at 4 weeks; and IOP, tear break-up time (TBUT), and hyperemia score at 4 and 12 weeks. The safety variables included visual acuity and drug tolerance questionnaire results. There was no statistically significant difference in corneal/conjunctival staining grade, OSDI, or TBUT between the groups at 4 and 12 weeks. However, the adherence rate was higher and the hyperemia score was lower in the preservative-free group than in the preserved group. The severity and duration of stinging/burning sensation were lower in the preservative-free group than in the preserved group. Overall, preservative-free latanoprost showed better ocular tolerance assessed by hyperemia scores and stinging/burning symptoms following higher adherence than preserved latanoprost.

Medication Adherence Among Patients With Corneal Diseases.

PURPOSE: Medication nonadherence is a ubiquitous problem. However, the adherence of patients to medications to manage corneal conditions is unknown. A prospective cohort study investigated the patterns of eye drop adherence among patients with corneal conditions. METHODS: Patients older than or equal to 18 years taking prescription eye medications were recruited from an academic center's corneal clinic. Data collected included age, sex, total doses of eye medications, and category of primary corneal diagnosis. Participants completed adapted versions of the 12-question Adherence to Refills and Medications Scale (ARMS) and the 3-question Voils' Medication Adherence Scale (VMAS). Survey data were dichotomized as "adherent" and "nonadherent," and subscales reported for reasons of nonadherence. Logistic regression analyses were used to test associations with adherence. RESULTS: A total of 199 participants were surveyed from February to March 2019 (95% response rate). Participants were aged 19 to 93 years with a mean age of 59 years (SD 17.8). The percent of participants considered nonadherent was 72% by the ARMS and 33% by the VMAS. Older age was associated with higher adherence by the ARMS (odds ratio = 1.48, 95% confidence interval, 1.14-1.93, P = 0.004) and by the VMAS (odds ratio = 1.24, confidence interval, 1.04-1.48, P = 0.012). Adherence was not significantly associated with race, sex, education, total doses of eye medications, or primary cornea diagnosis. CONCLUSIONS: Medication adherence was lower than expected, particularly on the ARMS scale that asks more detailed questions. Clinicians should engage in conversations about adherence, especially with younger patients, if they are not seeing an expected clinical response.

Assessment of mucin-related gene alterations following treatment with rebamipide ophthalmic suspension in Sjögren's syndrome-associated dry eyes.

Ocular surface mucins are thought to play vital roles in maintaining the homeostasis of the pre-ocular surface tear film. We performed ocular surface tests with impression cytology to assess the expression levels of mucin-related genes on the ocular surface in healthy eyes. In addition, we investigated alterations in mucin-related gene expression secondary to treatment with rebamipide ophthalmic suspension in patients with Sjögren's syndrome-associated dry eyes (SS-DE). Thirty-three healthy individuals (control group) and 13 patients from our hospital with SS-DE were enrolled. Impression cytology was performed using Schirmer's test paper for RNA sampling. The mRNA levels of SAM-pointed domain-containing ETS-like factor (SPDEF), mucin 5AC (MUC5AC), and mucin 16 (MUC16) were determined using a real-time reverse transcription-polymerase chain reaction. The ocular surface test was performed once for the control group, and at baseline as well as 2, 4, 8, and 12 weeks after treatment in the Sjögren's syndrome-associated dry eyes group. mRNA levels of SPDEF, MUC5AC, and MUC16 were not significantly different between the control and SS-DE groups before rebamipide ophthalmic suspension treatment. SPDEF mRNA levels in control subjects were significantly correlated with levels of MUC5AC. Among SS-DE patients, SPDEF mRNA levels were significantly increased at 2, 4, and 8 weeks after treatment compared with baseline levels. MUC16 mRNA levels were significantly decreased from baseline levels at 4 and 8 weeks post-treatment. Ocular surface test using impression cytology is a clinically useful tool for assessing mucous conditions on the ocular surface and can be used to determine the effects of instillation treatment with eye drops that affect mucin production at the ocular surface.

Comparative Assessment of Distribution Characteristics and Ocular Pharmacokinetics of Norvancomycin Between Continuous Topical Ocular Instillation and Hourly Administration of Eye Drop.

BACKGROUND: The aim of this study was to compare the distribution characteristics and ocular pharmacokinetics of norvancomycin (NVCM) in ocular tissues of the anterior segment between continuous topical ocular instillation and hourly administration of eye drop in rabbits. METHODS: Sixty rabbits were randomly divided into two groups: continuous topical ocular instillation drug delivery (CTOIDD) group and eye drop (control) group. In the CTOIDD group, NVCM solution (50 mg/mL) was perfused to the ocular surface using the CTOIDD system at 2 mL/h up to 10 h and the same solution was administered at one drop (50 µL) per hour for 10 h in the control group. Animals (N=6 per time-point per group) were humanely killed at 2, 4, 6, 10, and 24 h to analyze their ocular tissues and plasma. The concentrations of NVCM in the conjunctiva, cornea, aqueous humour, iris, ciliary body and plasma were measured by HPLC with photodiode array detector. The pharmacokinetic parameters were calculated by Kinetica 5.1. RESULTS: The highest concentrations of NVCM for the CTOIDD group and control group were 2105.45±919.89 µg/g and 97.18±43.14 µg/g in cornea, 3033.92±1061.95 µg/g and 806.99±563.02 µg/g in conjunctiva, 1570.19±402.87 µg/g and 46.93±23.46 µg/g in iris, 181.94±47.11 µg/g and 15.38±4.00 µg/g in ciliary body, 29.78±4.90 µg/mL and 3.20±1.48 µg/mL in aqueous humour, and 26.89±5.57 µg/mL and 1.90±1.87 µg/mL in plasma, respectively. The mean NVCM levels significantly increased at all time-points in cornea, iris, and ciliary body (p<0.05) in the CTOIDD group. The AUC0-24 values in the CTOIDD group were 27,543.70 µg·h/g in cornea, 32,514.48 µg·h/g in conjunctiva, 8631.05 µg·h/g in iris, 2194.36 µg·h/g in ciliary body and 343.9 µg·h/mL in aqueous humour, which were higher than for the eye drop group in all tissues. CONCLUSION: Since continuous instillation of NVCM with CTOIDD could reach significantly higher concentrations and was sustained for a longer period compared with hourly administration of eye drop, CTOIDD administered NVCM could be a possible method to treat bacterial keratitis.

Prescribing Patterns and Costs Associated with Postoperative Eye Drop Use in Medicare Beneficiaries Undergoing Cataract Surgery.

PURPOSE: To determine costs and prescribing patterns of postoperative eye drops for cataract surgery and estimate potential savings of generic or therapeutic drug substitutions. DESIGN: Retrospective, cross-sectional analysis. PARTICIPANTS: Medicare beneficiaries aged ≥65 years with Part D coverage who underwent cataract surgery in 2016. METHODS: Medicare Part D claims were used to extract information on eye drop prescriptions that were filled during the postoperative period of cataract surgery. Savings from generic or therapeutic drug substitutions were estimated for brand medications. MAIN OUTCOME MEASURES: Total cost of postoperative eye drops for cataract surgery and physician and patient factors associated with medication cost. RESULTS: Postoperative eye drops were prescribed in 2016 to 88% of 591 733 Medicare beneficiaries who underwent cataract surgery during that calendar year, with brand medications accounting for 57.5% of prescription volume. The overall cost totaled more than $167 million, 76.5% of which was attributable to use of brand medications. The mean costs of medications were $228 and $324 for those undergoing 1 and 2 surgeries, respectively. Topical antibiotics (89%) were the most commonly prescribed drug class by volume, followed by topical steroids (86%) and nonsteroidal anti-inflammatory drugs (66%), and accounted for 26%, 37%, and 36% of the total cataract surgery eye drop cost, respectively. Use of therapeutic and generic alternatives could have resulted in cost savings of as much as $118 million, or 70% of the total cost of postoperative eye drops. In adjusted analysis, patient factors associated with increased eye drop cost included older age, female gender, and race or ethnicity. Physician characteristics associated with increased eye drop cost included female gender, greater number of years in practice, practicing in metropolitan versus nonmetropolitan areas, and practicing in the Northeast versus the South and in the South versus the Midwest. CONCLUSIONS: The cost to the Centers for Medicare and Medicaid Services for eye drops prescribed for postoperative use after cataract surgery in 2016 was approximately $170 million. In the absence of evidence of clinical superiority of expensive versus less costly options, substantial opportunity exists to improve the value of care delivered to Medicare beneficiaries.

Autologous Serum-Based Eye Drops for Treatment of Ocular Surface Disease: A Report by the American Academy of Ophthalmology.

PURPOSE: To describe the safety and effectiveness of using autologous serum-based eye drops for the treatment of severe dry eye and persistent corneal epithelial defect. METHODS: Literature searches of the PubMed and Cochrane Library databases were conducted most recently in March 2019. The searches identified 281 citations, which were reviewed in abstract form. Of these, 48 were selected for a full-text review, and 13 met the inclusion criteria and were assigned a quality-of-evidence rating by the panel methodologist. Eight of these studies were rated level II and 5 were rated level III; there were no level I studies. RESULTS: This analysis included 10 studies of the use of autologous serum-based eye drops for severe dry eye disease and 4 studies of persistent epithelial defect. Several studies showed good effectiveness, with some improvement in symptoms, signs, or both. Eight of the studies reported improved symptoms for severe dry eye disease, and all noted improvement in at least 1 clinical sign. For persistent epithelial defects, all of the studies showed improvement, with 3 of the 4 demonstrating an improvement rate of more than 90%. Adverse events were rare. CONCLUSIONS: Although autologous serum-based tears may be effective in the treatment of severe dry eye and persistent epithelial defect, conclusions are limited owing to the absence of controlled trials.

Eye-Drop Abstinence in Glaucoma Patients Admitted to the Hospital Service: A Single Institution Assessment.

PURPOSE: Anecdotally, many patients admitted to an inpatient general medicine service do not have their glaucoma eye drops started. The purpose of this study was to determine the extent of eye-drop abstinence after inpatient admission. DESIGN: Retrospective, cross-sectional, hospital-based study. PARTICIPANTS: Four hundred seventy-five patients admitted to the general medicine regional hospital service from January 2016 through February 2018 with a known past medical diagnosis of or active outpatient medications for glaucoma. METHODS: The combination of an administrative database and cross-referenced patient charts were reviewed for demographic data, past medical problems, inpatient orders, intake history and physical, length of stay, and admitting diagnosis. MAIN OUTCOME MEASURES: The effect of (1) outpatient glaucoma drops reconciliation and (2) recognition of glaucoma as a pertinent past medical problem in a patient's intake history and physical on inpatient eye-drop administration. The overall rate of eye-drop abstinence also was recorded. RESULTS: Of 475 patients, 46.3% were women, with an average age of 80.2 years (standard deviation, 11.1 years). Average length of stay was 4.61 days (standard deviation, 3.7 days). In total, 63.8% achieved successful administration of medication on the hospital floor, resulting in a 36.2% eye-drop abstinence rate during the hospital stay. Three hundred eighty-six of 475 patients (81.3%) achieved successful glaucoma medication reconciliation. Patients with successful reconciliation had a significantly different rate of eye-drop administration (73.3% vs. 21.0%; P ≤ 0.001). Recognition of glaucoma in the history and physical occurred in only 42.5% of patients. There was a significant difference in eye-drop administration when glaucoma was included in the history and physical (75.7% vs. 55.0%; P ≤ 0.001). CONCLUSIONS: Glaucoma treatment incurs a high rate of medication noncompliance, especially in the elderly. The present study demonstrates that more than one third of patients admitted to an academic medical center do not receive their glaucoma medications. Patients discharged to nursing homes, subacute rehabilitation, and assisted living facilities rely on appropriate discharge medication reconciliation, resulting in forced abstinence during transition of care. An emphasis on appropriate medical reconciliation and recognition of glaucoma as a pertinent past medical problem will improve rates of eye-drop discontinuation on inpatient admission significantly.

Psychometric Properties of the Reduced Version of the Glaucoma Treatment Compliance Assessment Tool (GTCAT).

PURPOSE: To measure the psychometric properties of a reduced, 27-statement version of the Glaucoma Treatment Compliance Assessment Tool (GTCAT). METHODS: We administered the GTCAT to 183 participants who were using a single bottle of an ocular hypotensive agent, and objectively measured adherence with Medication Event Monitoring System devices over 60 days. Adherence was the number of days with correctly timed bottle openings divided by the total number of study days. Using the 47-statement GTCAT, we created a reduced GTCAT by removing statements that: (1) did not load using Principal Components Analysis (PCA); (2) did not have a univariable association with adherence; or (3) were highly correlated (.75 or higher) with another statement. We assessed the construct validity of the remaining statements using PCA and assessed the predictive validity using multiple logistic regression analysis. RESULTS: We removed 20 statements because they did not appear in the PCA analysis; were not predictive of adherence; and/or had high correlation. PCA of the reduced GTCAT (27 statements) extracted 5 components of the Health Belief Model (knowledge, susceptibility, cues-to-action, self-efficacy, and barriers). Multiple regression showed that the 27 statements predicted adherence (Rsq = .11, p = .03). CONCLUSIONS: The reduced version of the GTCAT is associated with adherence, which suggests that after external validation, future glaucoma medication adherence studies could use the reduced version to efficiently measure health behaviors and determine the benefit of the GTCAT to develop personalized interventions in glaucoma adherence.

Assessment of Dry Eye Symptoms: Current Trends and Issues of Dry Eye Questionnaires in Japan.

Dry eye disease (DED) is one of the most common disease in the ophthalmic clinic, and the reasons DED patients visit ophthalmic clinics are symptoms such as stinging, burning, or scratchy sensations. The symptoms and visual disturbances of DED have a negative impact on the daily routines and social lives of the patients (i.e., their quality of life [QOL]). The presence of symptoms was required in the definition of DED by the National Eye Institute/Industry Workshop in 1995; therefore, disease-specific questionnaires were essential for monitoring and managing patients with DED. Thereafter, many questionnaires have been developed to evaluate the specific symptoms of dry eyes. Although many questionnaires are available to assess the dry eye symptoms, it is essential that they provide valid answers and are easy to use to assess the effects of DED on the QOL. The Asia Dry Eye Society and Japan Dry Eye Society have proposed a new definition of DED that is a combination of symptoms and an unstable tear film, and information on these two factors is sufficient to make a definitive diagnosis of DED. Therefore, the assessments of the symptoms are fundamental in the diagnosis of DED.

Assessment of ocular redness measurements obtained with keratograph 5M and correlation with subjective grading scales.

OBJECTIVE: To examine correlations between ocular redness scores provided by the Keratograph 5M and those determined using two image-based grading scales. METHODS: Observational prospective cross-sectional study. Two hundred and twenty six eyes of two hundred and twenty six participants (175 patients using anti-glaucoma eye drops and 51 subjects untreated). All subjects were scored automatically using the keratograph 5M. These redness scores (RS) were then correlated with the gradings provided by the Efron and McMonnies/Chapman-Davies scale (MC-D) scales (two observers). RESULTS: Excellent reproducibility was observed for both the Efron (weighted K=0.897, 95% CI 0.823-0.904) and MC-D (weighted K=0.783, 95% CI 0.752-0.795) scales. Keratograph RS and the scores obtained with both Efron (Spearman's Rho=0.43, P<0.001) and MC-D (Spearman's Rho=0.48, P<0.001) scales were significantly correlated. RS for the bulbar and limbal - nasal and temporal quadrants also correlated moderately with the two subjective scales. Through Bland Altman analysis, poor agreement was detected between the objective and subjective methods: agreement values for the Efron scale or MC-D scale (matching scorers between observers) versus overall RS showed high biases (-15.58 and -22.05 respectively) and wide limits of agreement (LOA) (-46.169 to 15.005 and -52.534 to 8.19 respectively). Lowest bias was observed between temporal limbal RS and Observer 2 Efron score (-0.04). CONCLUSIONS: Although it emerged as a reliable objective method, the keratograph 5M overestimated the scores compared with the subjective grading scales when used to grade the degree of ocular redness. Therefore, they should not be interchangeable methods.