Inflammation is the Prime Therapeutic Target in Dry Eye

Inflammation is the prime therapeutic target in Dry Eye. In the diagnosis and management of dry eye, we’ve reached a new level. We have a new generation of diagonostic tests for assessing specific signs of the disease, which we can then address with both new and familiar targeted treatments.

We can evaluate meibomian gland structure and function, detect markers of inflammation, assess tear film stability, and match the findings with the pertinent short and long term therapies. All of this is great news for the millions of dry eye patients whose vision and quality of life aren’t what they could be because of dry eye.

Inflammation – a major causative factor in both aqueous-deficient and evaporative dry eye – has been and will continue to be a target of therapy.

restasis multidose

restasis multidose

Restasis (cyclosporine ophthalmic emulsion 0,05%, Allergan) alone and with Lotemax (loteprednol etabonate ophthalmic suspension 0,5%, Bausch + Lomb) as recommended by the Asclepius Panel is a mainstay in dry eye treatment because it reduces inflammation. Restasis is the only therapeutic ocular medication for dry eye disease that acts on all three layers of the tear film, supporting the lipid layer with castor oil, increasing the acqueous laye, and increasing globet cell density in the mucin layer by 191%. Azithromycin or doxycycline are also frequently prescribed for dry eye patients when mitigating the signs and symptoms of meibomian gland dysfunction is the goal.

Recently approved option to treat dry eye inflammation now available

 

xiidra for dry eyes

xiidra for dry eyes

The newest prescription medication for dry eye, Xiidra (lifitegrast ophthalmic solution 5%, Shire), is a small-molecule integrin antagonist that reduces inflammation by blocking the interaction of integrin lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1), thereby disrupting T-cell activation and migration. Xiidra is FDA (and now Health Canada) approved for treatment of the signs and symptoms of dry eye disease. It was evaluated in four placebo -controlled 12 weeks trials. Each of the four studies assessed the effect of Xiidra on both the signs and symptoms of dry eye disease at baseline and weeks 2, 6 and 12. Assessment of symptoms was based on change from baseline in patient reported eye dryness score (EDS), and assessment of signs was based on the inferior corneal staining score (ICSS). In all four studies, a larger reduction in eye dryness score was observed with Xiidra at 6 and 12 weeks.

In two of the four studies, an improvement in eye dryness score was seen with Xiidra at 2 weeks. At week 12, a larger reduction in ICSS favoring Xiidra was observed in three of the four studies. Xiidra just recently became available to clinics, so time will tell how it best fits into treatment protocols.

Dry Eye related inflammation

HydroEye Dry Eye Relief

HydroEye Dry Eye Relief

We can also address dry eye related inflammation with neutraceuticals that contain omega fatty acids. We have many products to choose from, but it makes sense to recommend that our patients use an option that’s backed by solid data. A study that evaluated an omega-3 / omega-6 (gamma linoleic acid, GLA) combination, HydroEye Support for Dry Eyes (ScienceBased Health), in 38 postmenopausal women with moderate to severe dry eye. Patients received either four HydroEye softgels daily or placebo and were evaluated at baseline, 4, 12, and 24 weeks. By the end of the study, patients taking the supplements had significantly improved symptom scores compared with baseline and placebo.

HydroEye was found to dampen inflammation and maintain corneal smoothness, while these parameters worsened for those taking the placebo. A distinguishing feature of HydroEye is that it contains the unique Omega-6 fatty acid GLA. While omega-6s are often thought of as counter-productive in decreasing inflammation, GLA actually has a potent positive effect that is site-specific for the lacrimal gland and ocular surface.

Amniotic membrane treatment for Dry Eye

The last inflammation-targeting treatment that is important to mention in the context of dry eye is amniotic membrane, Prokera Slim (BioTissue), in particular. Amniotic membrane treatment has traditionnaly been used in the OR and for immediately vision-threatening conditions, such as corneal melts and infectious keratitis, but because of the attributes of Prokera Slim, it is being used more frequently in the clinic as part of dry eye therapy, as well as chemical burns, corneal abrasions, and so on.

Because the membrane used in Prokera is cryopreserved rather than dehydrated, it retains its full biologic capability to reduce inflammation and rejuvenate the ocular surface. Its ease of use and tolerability – it is placed on the eye in-office and is self-retaining – are aslo significant contributors to its increased use for dry eye. A large survey of dry eye patients treated with Prokera Slim showed that 93% felt better and 81% would request Prokera Slim if their symptoms returned.

Additional dry eye inflammation fighters on the way

While we continue to address all aspects of dry eye for our patients, we can also expect more treatments that target inflammation to become available. Many, including the immunomodulating JAK inhibitor tofacitinib (Pfizer), the small-molecule nerve growth factor MIM-D3 (Mimetogen), the interleukin-1 blockers EBI-005 (Eleven Biotherapeutics) and Anakinra (Amgen), the amino acid analog rebamipide (Otsuka Pharmaceuticals), and the chemokine thymosin beta-4 (RegeneRX), are currently in development.

By Walter O. Whitley, OD, MBA, FAAO

Dr. Whitley is director of optometric services at Virginia Eye Consultants, an optometry/ophthalmology tertiary referral center with five locations throughout the state. He is also residency program supervisor for the Salus University Pennsylvania College of Optometry.

Source: Optometric Management January 2017, p. 12-13

 


 

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