Dry eye treatment enters the ‘age of plenty’



Disclosures: White reports that he is a consultant for Allergan, Bausch + Lomb, Bruder, EyePoint, Eyevance, Johnson & Johnson, Kala, Novartis, Ocular Therapeutix, Omeros, Rendia, Sight Sciences, Sun, and TearLab; is a speaker for Allergan, Eyevance, Kala, Novartis, Omeros and Sun; and owns Eye Sciences.

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Long ago, in a galaxy far, far away, the diagnosis and treatment of DED was a spartan affair undertaken by a small group of Jedi doctors who were pitied by their doctor brothers and sisters if they and their quest were recognized.

Actually, it was around 2008 in Cleveland, but this whole “galaxy far, far away” thing makes for a much better lede. Yet, as fanciful as it sounds, it describes the state of dry eye care when people first started talking about it. As barren as the DED landscape was in the late 1980s, if you go back to the 80s and 90s, it’s almost like studying those ancient tribes who were cut off from contact with the developing world; we were cut off from “modern” medicine. This was the time when a DED doctor could only direct patients to the pharmacy to purchase one of the lookalike and do-nothing tear products on the shelves.

Darrell E. White, MD

Darrell E. White

I described my early peers in the DED community as the red-haired stepchildren of ophthalmology, alone in a corner of the professional village telling anyone who would listen that DED was real and needed to be treated. What must it have been like for the true pioneers of our sub-specialty before people like Mark Milner, Marguerite McDonald and I arrived? It’s amazing to think what it must have been like for Mike Lemp who talked about tear osmolarity and its primacy in the DED process. Or Hank Perry, who posted on Demodex and Meibomian Gland Dysfunction (MGD) back when “best practice” in treating blepharitis insisted on Johnson’s baby shampoo, not a generic. Ken Kenyon reflected on commonalities in the pathophysiology of DED and other more serious inflammatory diseases such as graft versus host disease, anticipating the epiphany that inflammation is the driving force behind DED.

Thank God they did not despair and gave up their investigations.

Our landscape is so different now. Even the over-the-counter artificial tear market is a veritable cornucopia of good options broken down into classes (hypotonic, oil-based, gel-based, etc.). Heck, there’s a real cutting-edge artificial tear that requires you to know the difference between osmolarity and osmolality (extracellular proteins that affect extracellular fluid movement), Eyevance Pharmaceuticals’ Freshkote. Where once we had only one drug approved to treat chronic surface inflammation, Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan), the addition of Xiidra (lifitegrast ophthalmic solution 5%, Novartis) and Cequa (cyclosporine ophthalmic solution 0.09%, Sun Pharmaceutical) brings us to three immunomodulators. I have long criticized the way Lotemax (loteprednol etabonate ophthalmic suspension 0.5%, Bausch + Lomb) and its stable mates have been treated on the market, so I am grateful that there are two steroids – Eysuvis (loteprednol etabonate ophthalmic suspension 0.25%, Kala Pharmaceuticals) and Flarex (fluorometholone acetate ophthalmic suspension 0.1%, Eyevance Pharmaceuticals) – which have the treatment of DED signs on their labels ( and you can still use all Lotemax options as well).

And can I just say: in-office procedures! Wow? Even with all the hype around insurance coverage, can anyone using these technologies imagine a world in which we don’t use heat treatments with or without contiguous gland evacuation? Not me, man. Keep giving me more. And you know what? This is exactly what is happening in our world. From the spartan options of the 80s and 90s, we now live in an era of “more”. Just on the horizon, there are even more treatments that are about to be approved that will further expand our ability to treat all the different types of conditions that we, and our patients, call “dry eye.” . Let me highlight a few of the important new drugs that are upon us.

Anti-inflammatory treatments continue to be a central part of our therapeutic arsenal. Some newcomers will be familiar. For example, Ocular Therapeutix has launched a trial using Dextenza (intracanalicular dexamethasone) to treat the signs and symptoms of DED. Anyone using Dextenza for cataract surgery knows it works; the trial will provide “on-label” support for prescribers seeking insurance coverage. Ocular Therapeutix is ​​also initiating a trial of an intracanalicular insert of cyclosporin A (CsA), another well-known and proven drug.

In the more traditional way we think of drug delivery, Novaliq is currently in phase 3 trials with its version of CsA. CyclASol is a water-free formulation of 0.1% CsA, which has shown rapid onset of significant improvements in the signs and symptoms of DED. It was well tolerated in trials. The newcomer to this space is reproxalap from Aldeyra Therapeutics. It’s a new RASP inhibitor that shows promise in treating inflammation in a way that mimics steroids, but in a new way. Reproxalap can treat the underlying inflammation of DED and allergic conjunctivitis, something that would lessen the challenge we all face in teasing these co-conspirators so often present at the same time (thanks to Dr John Sheppard for his writings on those ).

Targeting the eyelids and eyelid diseases that cause DED and other inflammatory ocular surface diseases is where the really cool stuff happens, at least for me. We all know that evaporative DED, largely induced by MGD and related entities, constitutes the majority of DED in the United States. At this time, we have no approved treatment for this indication (AzaSite, Akorn’s azithromycin ophthalmic solution, is only approved to treat bacterial conjunctivitis). This is about to change. Bausch + Lomb announced that its novel molecule NOV03 (perfluorohexyloctane) demonstrated a significant effect in reducing symptoms and signs in its pivotal Phase 3 trial. If approved, NOV03 will be the first direct MGD treatment available. Competition may come from Azura Ophthalmics and AZR-MD-001, which have been shown to improve tear break-up time, meibum secretion, and quality. This drug, which is now entering phase 2 trials, appears to promote the breaking of disulfide bonds in keratin, stimulating the production of meibum (tip: Dr. Laura Periman).

I look forward to the arrival of TP-03, or whatever Tarsus Pharmaceuticals plans to call its breakthrough treatment for Demodex infestation of eyelash follicles. This incredibly common problem is a source of eyelid inflammation and resulting MGD. Phase 2b results show what adds to the essential erasure of Demodex in study subjects. After seeing these results, I immediately began having my DED and MGD patients look at the slit lamp so that I could assess for the presence of cylindrical dandruff, the pathognomonic sign of Demodex. I take names! If the phase 3 trials are as definitive as phase 2, and there is no reason to expect anything else, I will have a long list of patients awaiting treatment. It’s as exciting today as when we were waiting for the arrival of Restasis, our first SSO treatment.

We’re about to enter an “age of plenty,” something that was inconceivable as recently as 2008. Red-haired stepkids are now, in many ways, the coolest kids in the world. piece. The force is strong within us, my fellow Jedi Knights.

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