EW Weekly, December 6, 2019

Top-line results announced from Phase 3 RENEW trial for dry eye disease
Positive top-line results were announced from part one of the Phase 3 RENEW trial of topical ocular reproxalap (Aldeyra Therapeutics), according to an Aldeyra press release. Reproxalap is a small-molecule, immune-modulating covalent inhibitor of reactive aldehyde species. RENEW is an ongoing adaptive, two-part, multicenter, randomized, vehicle-controlled trial of 0.25% topical ocular reproxalap compared with vehicle in patients with moderate to severe dry eye disease. The goal of the first part of the RENEW trial was to confirm the dosing regimen, endpoints, and sample size to be used in second part. Four hundred and twenty-two patients were randomized to receive reproxalap four times daily or vehicle for 12 weeks (called the constant dosing group) or reproxalap or vehicle four times daily for 4 weeks, and then reproxalap or vehicle twice a day for 8 weeks. The latter was called the induction-maintenance dosing group. Observed activity in the induction-maintenance group was greater than that of the constant dosing group. The induction-maintenance group achieved the co-primary endpoint of patient-reported visual analog scale ocular dryness during weeks 2 to 12. Activity was observed by week 1 after starting therapy and continued throughout the trial. The induction-maintenance regimen will be used in second part of the trial, which is expected to begin in the first half of 2020 and will include an estimated 400 patients per arm.

Phase 1 results announced from varenicline spray under development for dry eye disease
Top-line results from the Phase 1 ZEN study of varenicline administered as a preservative-free nasal spray (OC-01 nasal spray, Oyster Point Pharmaceuticals) for dry eye disease found that the relative bioavailability was 13 times lower for a single dose of the highest strength compared with a single dose of the highest strength Chantix tablet (7.46 vs. 99.67 h*ng/ml). Chantix (Pfizer) is an oral form of varenicline currently approved for smoking cessation. The treatment cohort included 22 healthy volunteers. The maximum concentration was 14 times lower compared with the highest strength Chantix tablet. The nasal spray was safe and well-tolerated at the doses tested, according to the press release. Sneezing and cough occurred in 33.3% and 28.6% of volunteers among the nasal spray users. In the oral administration group, nausea and vomiting occurred in 22.7% and 18.1% of users. All adverse events were mild.

Data announced from PRK pivotal study of the Ocular Bandage Gel
In its corneal wound repair pivotal study, EyeGate Pharmaceuticals found a statistically significant improvement in corneal re-epithelialization in patients treated with its Ocular Bandage Gel eye drop compared with a standard-of-care bandage contact lens after PRK. Those receiving the Ocular Bandage Gel also had faster corneal wound closure over the standard-of-care as early as day 2. Patients were randomized and received identical surgery in both eyes. By day 3, 80.2% of those receiving the Ocular Bandage Gel were completely healed compared with 67% receiving the bandage contact lens. There were no safety concerns with the Ocular Bandage Gel. Company leaders plan to submit a de novo application for commercialization in the first half of 2020.

Breakthrough Device Designation given by FDA to RightEye Vision System
The U.S. FDA has given a Breakthrough Device Designation to the RightEye Vision System (RightEye LLC), a device that uses objective eye movement measurements to help assess patients with Parkinson’s disease. The device helps to address the misdiagnosis of Parkinson’s, which occurs in 60% of patients at least once, according to RightEye company leaders. The vision system is designed to identify persistent ocular tremors found in those with Parkinson’s disease.

Glaukos completes Avedro acquisition
Glaukos completed its acquisition of Avedro, known for its FDA-approved crosslinking system, according to a Glaukos press release. Common stock from Avedro will no longer trade on NASDAQ.

Research briefs
  • Ophthalmologists should be aware of the possibility for meibomian gland dysfunction among adolescents, reported Anna Tichenor, OD, PhD, and coauthors. Their study aimed to establish normative values of ocular surface parameters in 225 subjects between the ages of 8 and 17. All subjects received dry eye and lifestyle questionnaires. Tear film assessments and meibography also were performed. Among the subjects, 15% reported ocular discomfort, primarily in the form of itching. Tear meniscus height also rose with age and was highest among the oldest subjects. Meibography showed that 39% of the upper and 39% of the lower eyelids had meibomian gland dropout. The mean meibomian gland dropout score was 0.50 in the upper eyelids and 0.67 in the lower eyelids. No correlation was found between phone/tablet usage and meibomian gland dropout. However, study researchers note that it is still unclear what the effects of long-term digital device usage may be as subjects age. The research is published in Cornea.
  • Crowdsourced research was able to identify people with diagnosed and undiagnosed symptomatic dry eye, reported Yewon Kim, MD, and coresearchers. Using a smartphone app called DryEyeRhythm, the researchers’ cross-sectional study included individuals in Japan who downloaded the app and completed its questionnaire. Researchers also collected information on demographics, medical history, lifestyle, subjective symptoms, and disease-specific symptoms based use of the Ocular Surface Disease Index and the Zung Self-Rating Depression Scale. Among 4,454 users, 27.3% had diagnosed dry eye, and 72.7% had undiagnosed symptomatic dry eye. Identified risk factors for symptomatic vs. asymptomatic dry eye included younger age, female sex, hay fever, depression, mental illnesses (other than depression or schizophrenia), current contact lens use, extended screen exposure, and smoking. Risk factors for undiagnosed dry eye included younger age, male sex, absence of collagen disease, mental illnesses (other than depression or schizophrenia), ophthalmic surgery (other that cataract surgery and LASIK), and current or past contact lens use. The findings could potentially help with prevention and detection or more effective interventions for dry eye disease, the researchers concluded. The study is published in JAMA Ophthalmology.
  • Complications were not common among patients who had refractive surgery and are HIV-positive, according to Carter Tisdale, MD, and coresearchers. The research was part of the U.S. Military HIV Natural History Study, a prospective observational cohort study of service members and beneficiaries who are HIV-positive. Covariates included age, sex, antiretroviral therapy, time since HIV diagnosis, history of AIDS, and CD4 count and viral load. Among the 2,073 participants, 79 had refractive surgery—53 PRK, 23 LASIK, two radial keratotomy, and one astigmatic correction. There were complications in six of the 79 participants, including five ulcers and one unspecified keratitis. The complications occurred in five patients who had PRK and one who had radial keratotomy, occurring at 8 to 217 days post-surgery. The type of surgery and history of AIDS were risk factors for complications (P = .02 for both). Advanced HIV, reflected by previous AIDS, may be associated with a higher risk for complications, but further study is needed to confirm the findings, according to the researchers. The study appears in the Journal of Cataract & Refractive Surgery.
Product news
  • The TECNIS Toric II 1-piece IOL (Johnson & Johnson Vision) is now available in the U.S. According to a company press release, the IOL features a more textured surface and haptics to aid in stability.

This issue of EyeWorld Weekly was edited by Stacy Jablonski and Vanessa Caceres.

EyeWorld Weekly (ISSN 1089-0319), a digital publication of the American Society of Cataract and Refractive Surgery (ASCRS), is published every Friday, distributed by email, and posted live on Friday.

Medical Editors: Eric Donnenfeld, MD, Chief Medical Editor; Rosa Braga-Mele, MD, Cataract Editor; Clara Chan, MD, Cornea Editor; Nathan Radcliffe, MD, Glaucoma Editor; and Vance Thompson, MD, Refractive Editor

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