Dry eye disease (DED) is highly prevalent in the US, affecting approximately 6.8% of the population — more than 22 million people — with numbers expected to rise as the population ages1. In addition to the disease’s detrimental impact on vision, productivity, and quality of life, patients with DED also experience higher rates of major depression and anxiety.1 For years, optometrists have had a limited amount of treatment options at their disposal. However, with several therapeutic options in the pipeline set to debut in 2023, clinicians may be able to amass some additional tools for treating and managing DED in the near future.
“Diagnosis and treatment can be an emotional and psychological journey for patients,” explained Kambiz Silani, OD, the chief clinical director of Beverly Hills Optometry. As an individual who was diagnosed with DED 20 years ago, Dr Silani can empathize with his patients and understand their frustration with the small handful of available treatment options.
“We don’t have many tools in the toolbox, and I think a lot of doctors get frustrated because what they are using isn’t really making a difference for their particular patients,” according to Kelly K. Nichols, OD, MPH, PhD, FAAO, dean of the school of optometry at the University of Alabama Birmingham.
Despite their concerns over current treatment options, both Dr Silani and Dr Nichols expressed some optimism regarding a few DED medications that are expected to gain US Food and Drug Administration (FDA) approval this year.
TP-03 (Lotaliner Ophthalmic Solution, 0.25%)
Research shows that 45% of patients with blepharitis have concomitant Demodex infestation or pathologic overgrowth of Demodex mites in the eyelid tissue.2 TP-03 (Tarsus Pharmaceuticals Inc., Irvine, CA) would be the first treatment for Demodex blepharitis approved by the US FDA. The 0.25% lotilaner solution paralyzes and eliminates Demodex mites by selectively hindering parasite-specific γ-aminobutyric acid chloride channels. In recent studies, the solution demonstrated safety, tolerability, and efficacy in reducing collarettes and mite density in as little as 28 days.2 In the most recent trial, after 43 days of treatment, a significantly higher proportion of patients in the study group achieved clinically meaningful collarette cure (81.3% vs 23.0%), complete collarette cure (44.0% vs 7.4%), mite eradication (67.9% vs 17.6%), erythema cure (19.1% vs 6.9%), and composite cure (13.9% vs 1.0%) compared with control group participants (P ≤.0001 for all).2
The majority of patients (92.0%) rated the drop as “neutral” to “very comfortable” and the most common complaint was pain at the instillation site.2
“An overgrowth of Demodex mites can cause the tear film to become unstable, creating a dry eye situation,” Dr Nichols said. “This medication has been shown to eradicate mites, which can return homeostasis to the ocular surface and the tear film.”
Dr. Silani expressed similar optimism regarding the medication’s potential to treat Demodex
“The early data on TP-03 looks quite promising,” he said. “Mites can be stubborn, and while patients can use tea tree oil, it can be toxic. There hasn’t been a drop formulation before, so it would be great to have a first-in-class option that patients can use at home.”
Both clinicians agree that while a new therapeutic tool for controlling Demodex mites is a significant advancement, the first step is properly diagnosing the condition, which is often misdiagnosed as optical allergies.
Reproxalap (Aldeyra Therapeutics, Lexington, MA) is another DED medication working its way through the approval process. A novel reactive aldehyde species (RASP) inhibitor, this non-steroidal eye drop may improve inflammation without increasing ocular pressure.
“Because it’s a reactive aldehyde species molecule, it acts higher up on the inflammatory cascade than most of the current treatments do,” Dr. Nichols explained. “It tamps down the inflammatory cascade without using a steroid — which can increase eye pressure and cataract development.”
In a phase 2a trial of 3 reproxalap formulations (0.1% ophthalmic solut, 0.5% ophthalmic solution, and 0.5% lipid ophthalmic solution), all 3 formulations improved key measures from baseline, including Symptom Assessment in Dry Eye Disease score (P =.003), Ocular Discomfort Scale score (P <.0001), Ocular Discomfort Score and 4-Symptom Questionnaire overall score (P = 0.0004), Schirmer test (P =.008), tear osmolarity (P =.003), and lissamine green total staining score (P =.002) during a 28-day treatment duration.1
Researchers noted improvements in DED symptoms within 1 week of therapy, but patients reported transient ocular discomfort with the reproxalap 0.5% formulation — and more than 20% discontinued its use.1 Going forward, only the 0.1% formulation will be used in clinical testing.
In another study, 2 formulations of reproxalap 0.25% were evaluated against lifitegrast ophthalmic solution 5% in patients with DED. Patients reported less ocular discomfort, blurry vision, and dysgeusia when treated with reproxalap compared with lifitegrast and fewer negative quality of life impacts.3
NovaTears+Omega 3 (NOV03)
Omega-3 fatty acids have antioxidant and anti-inflammatory properties and may help prevent DED.4 Research shows that patients with DED and meibomian gland dysfunction (MGD) have lower levels of polyunsaturated fatty acids in their tear film.4 NOV03 (Bausch + Lomb, Rochester, NY) is a water-free eye drop that combines perfluorohexyloctane, known to reduce signs and symptoms of dry eye, with omega-3 fatty acid esters, which may influence evaporation and oxidative stress resistance.4
In a recent study of patients with mild to moderate evaporative DED, NOV03 demonstrated a clinically and statistically significant ability to improve DED signs and symptoms after bilateral treatment 4 times per day for 8 weeks.4 Corneal fluorescein staining and MGD scores improved significantly at 8 weeks compared with baseline (7.1 vs 3.0 and 5.0 vs 1.6, respectively, P <.0001 for both) and no adverse events were reported.4
“The data for NOV03 also looks very promising. All of the studies reported statistically significant findings,” Dr Nichols said. “It’s important to note that the patients enrolled in these studies have the signs and symptoms of dry eye with MGD, but researchers aren’t reporting on how the medication may impact short- and long-term meibomian gland health. It will be interesting to see what the label says and how clinicians determine what kinds of patients are best suited for this particular medication.”
Dr Nichols predicted that clinicians may pair NOV03 with other treatments, such as in-office warming treatments or an anti-inflammatory dry eye medication. The Prescription Drug User Fee Act (PDUFA) date for NOV03 is June 23, 2023.
A new ophthalmic keratolytic, AZR-MD-001 (Azura Ophthalmics, Tel Aviv, Israel) may be able to loosen blockages and allow for improved meibum secretion in the upper and lower eyelids in patients with MGD.
During the phase 2b study (ClinicalTrials.gov Identifier: NCT04391959), patients with MGD applied AZR-MD-001 0.5% to their lower eyelid twice weekly at bedtime. During the 3-month study duration,the medication met its co-primary endpoints of improved Meibomian Glands Yielding Liquid Secretion and Ocular Surface Disease Index (OSDI) scores (1.8 improvement from baseline; P =.0004 and 3.5 improvement from baseline; P =.0438, respectively), according to a press release issued by Azura.5 The manufacturer also claims patients experienced improvements in Standard Patient Evaluation of Eye Dryness (SPEED; P <.0001) and average visual analog scale score (P <.0001), and reduced eye discomfort (P <.0001), eye dryness (P <.0001), and ocular itch (P <.0001).
“This modality is exciting,” Dr. Silani said. “The ointment prevents protein buildup and blocks oil secretion, promoting healthy oil production and reducing dry eye.”
“It’s essentially like the same product used in dandruff shampoos,” according to Dr. Nichols. “I haven’t seen all the data, but I don’t think it’s something patients would use daily. Instead, it may be released for in-office use only as a sporadic maintenance measure.”
The ointment is expected to advance to phase 3 clinical trials in 2023.
“I’ve been in the field for a long time, before there were any prescription medications for dry eye,” Dr Nichols said. “I think it’s very encouraging because it means venture capital folks are still supporting ocular surface research. If the data looks strong, I hope all these options make it through the clinical trial process.”
- Clark D, Sheppard J, Brady TC. A randomized double-masked phase 2a trial to evaluate activity and safety of topical ocular reproxalap, a novel rasp inhibitor, in dry eye disease. J Ocul Pharmacol Ther. 2021;37(4):193-199. doi:10.1089/jop.2020.0087
- Yeu E, Wirta DL, Karpecki P, et al. Lotilaner ophthalmic solution, 0.25%, for the treatment of demodex blepharitis: results of a prospective, randomized, vehicle-controlled, double-masked, pivotal trial (Saturn-1). Cornea. Published online August 11, 2022. doi:10.1097/ico.0000000000003097
- McMullin D, Clark D, Cavanagh B, Karpecki P, Brady TC. A post-acute ocular tolerability comparison of topical reproxalap 0.25% and lifitegrast 5% in patients with dry eye disease. Clin Ophthalmol. 2021;15:3889-3900. doi:10.2147/opth.s327691
- Jacobi C, Angstmann-Mehr S, Lange A, Kaercher T. A water-free omega-3 fatty acid eye drop formulation for the treatment of evaporative dry eye disease: a prospective, multicenter noninterventional study. J Ocul Pharmacol Ther. 2022;38(5):348-353. doi:10.1089/jop.2021.0102
- Azura Ophthalmics announces positive results from phase 2b clinical trial of AZR-MD-001 in meibomian gland dysfunction. Azura Ophthalmics. Published November 17, 2022. Accessed January 12, 2022. https://azuraophthalmics.com/press-releases/azura-ophthalmics-announces-positive-results-from-phase-2b-clinical-trial-of-azr-md-001-in-meibomian-gland-dysfunction/