Dry eye disease (DED) affects millions of Americans and is one of the most common ocular surface disorders. Anti-inflammatories, immunomodulators, and tear stimulators are the current standard of prescription care for DED, but they target only two of the three key contributors of DED — aqueous deficiency and inflammation — leaving excessive evaporation unaddressed. Without directly addressing tear evaporation, the vicious cycle of symptoms may persist.
Excessive tear evaporation is a leading driver of DED and triggers a chronic cycle of inflammation and friction, damaging the ocular surface. The continuation of this cycle can contribute to the loss of ocular surface homeostasis. The recently approved perfluorohexyloctane ophthalmic solution (Miebo) is the first prescription eye drop approved for the treatment of the signs and symptoms of DED that directly targets tear evaporation.
New Prescription Therapeutic
“Miebo is a welcome addition to our armamentarium for the treatment of DED,” said Alice Epitropoulos MD, of Ophthalmic Surgeons & Consultants of Ohio in Columbus. To date, no head-to-head clinical studies have been conducted comparing the perfluorohexyloctane solution with other treatments for the signs and symptoms of DED. Perfluorohexyloctane eye drops should be prescribed for dry eye patients on a case-by-case basis, she said.
David Wirta, MD, of Eye Research Foundation in Newport Beach, California, added: “Miebo is very well tolerated, and the benefits are seen shortly after dosing begins. This should lead to easy patient acceptance of the therapy and good compliance, helping it become a useful tool for the dry eye population.”
John Sheppard, MD, of Virginia Eye Consultants in Norfolk, believes the perfluorohexyloctane eye drops will “shift the dry eye treatment paradigm once doctors start using it. There are no side effects, it’s a small drop, causes no blurred vision, and lasts 6 hours.”
Approximately 86% of patients with DED have excessive tear evaporation associated with meibomian gland dysfunction (MGD). MGD is characterized by the functional abnormality of the meibomian glands and changes in meibum composition and reduced meibum secretion. This results in breakdown of the tear film lipid layer and excessive tear evaporation, making MGD a leading cause of DED signs and symptoms.
Healthy meibomian glands produce meibum, a lipid-rich secretion that forms the tear film lipid layer and helps to maintain a healthy ocular surface. “When evaporation exceeds production of aqueous, often due to a deficiency of meibum, this results in loss of homeostasis, inflammation, desiccation stress, and subsequent tissue damage,” said Epitropoulos. “Miebo is a single-ingredient, water-free, preservative-free, and steroid-free prescription eye drop. It spreads quickly and comfortably and is designed to mimic a key function of natural meibum by reducing tear evaporation.”
The solution fills a significant pharmacological need to treat MGD, said Epitropoulos. “Excessive tear evaporation can result directly from lipid deficiency — this reduced quantity of lipid may be due to either poor quality meibum or plugging or obstruction of the glands. This results in breakdown of the tear film lipid layer and excessive tear evaporation, making MGD a leading cause of DED signs and symptoms,” she said. Perfluorohexyloctane mimics the natural meibum by inhibiting evaporation and reducing friction, which promotes healing of the ocular surface.
It remains to be seen whether continued use of perfluorohexyloctane will actually change the eyelid findings and pathophysiology of MGD. However, relieving corneal signs and the symptoms of MGD is an excellent start to tackling this condition, said Wirta. For MGD patients, Sheppard said he would prescribe an anti-inflammatory medication along with the perfluorohexyloctane eye drops.
Clinical Trial Results
The perfluorohexyloctane solution was evaluated in two randomized, multicenter, double-masked, saline-controlled trials (GOBI and MOJAVE). A total of 1,217 patients with a history of DED and clinical signs of MGD received either perfluorohexyloctane or hypotonic saline (0.6%).
“Across both phase III studies, perfluorohexyloctane delivered significant improvements over control in both primary endpoints,” said Epitropoulos, who was one of the MOJAVE investigators. Those endpoints were change from baseline at week 8 in total corneal fluorescein staining (tCFS) and eye dryness visual analog scale (VAS) score.
Secondary endpoints in the phase III studies were relief of signs and symptoms as early as day 15, at which timepoint statistically significant reductions in tCFS and VAS eye dryness scores favoring perfluorohexyloctane were observed. Patients treated with perfluorohexyloctane also experienced a 31% greater improvement from baseline in VAS burning/stinging over saline at day 57. Perfluorohexyloctane also delivered four times the improvement compared with saline in central corneal fluorescein staining.
In the clinical trials, perfluorohexyloctane was well tolerated. Discontinuations due to adverse events were low, with the discontinuation rate for perfluorohexyloctane comparable to control (0.2% vs 0.5%). Blurred vision and eye redness were the most common ocular adverse reactions and were reported in 1% to 3% of individuals.
“I anticipate similar responses in the real world,” said Sheppard. “There were no significant treatment-emergent events. The entire preparation is active and there is little risk. It’s a unique, highly sophisticated therapeutic molecule.”
Perfluorohexyloctane has shown to be effective in reducing symptoms and cornea staining in the dry eye population. “By reducing these signs and symptoms, the normal, healthy ocular surface environment would be given the chance to reestablish itself,” said Wirta. “There is often an immediate soothing effect to the drop instillation, and the drop has very high tolerability.”
The management of DED and MGD is multifactorial and should be individualized to address the needs of each patient. Every day, practitioners’ understanding of DED evolves as more findings and treatments develop in eye care. “Having a novel therapeutic such as Miebo that targets evaporation is a valuable asset to our arsenal for addressing DED,” said Epitropoulos.
Epitropoulos reports relationships with AimMax Therapeutics, Bausch + Lomb, Sylentis S.A., Allergan/AbbVie, Abbott Medical Optics/Johnson & Johnson, Bio-Tissue, Bruder Healthcare Company, Dompé, EyePoint Pharmaceuticals, Imprimis Pharmaceuticals, Kala Pharmaceuticals, Novartis, Ocular Therapeutix, OTX, Oyster Point Pharma, Sight Sciences, Sun Ophthalmics, Tarsus Pharmaceuticals, Visus Therapeutics, Zeiss International, Physician Recommended Nutriceuticals, and EpiGlare Tester (Hilco Vision).
Wirta disclosed grant support from Bausch + Lomb and Novaliq.
Sheppard disclosed relationships with 1-800-DOCTORS, AbbVie, Alcon, Aldeyra, Allergan, Alphaeon/Strathspey Crown, ArcScan, Avedro, Bausch + Lomb, Biolayer, BioTissue/TissueTech, Bruder Healthcare, Clearside, Clearview, Clementia Pharma, Dompé, Eleven, Eyedetec, EyeGate Research, EyeRx Research, Eyevance, Glaukos, Hovione, Imprimis Pharma, Inspire/Merck, InSite Vision, Ionis Pharmaceuticals, Johnson & Johnson/TearScience/Vistakon, Kala Pharmaceuticals, Kowa, LacriSciences, LayerBio, Lenstatin, Lux Biosciences, Lumenis, Mallinckrodt, Mati Therapeutics, MedEdicus, Mitotech, NeoMedix, Nicox, NovaBay, Novaliq, Novartis, Noveome Biotherapeutics/Stemnion, Talia Technology, OccuHub, OcuCure, Ocular Therapeutix, Oculis, Okogen, Omeros, Oyster Point, Parion, PentaVision, Pfizer, Portage, Quidel, Rapid Pathogen Screening, RuTech, Santen, Science Based Health, Senju, Shire, Sun Pharmaceuticals, Surrozen, Synedgen, Takeda, Talia Technology, TearLab, Tear Solutions, Topcon, Topivert, and Xoma/Servier.