Taking Ocular Surface Treatment to the Next Level
What’s working at our academic dry eye center
More than 25 million Americans suffer from dry eye, the disease state most frequently encountered by eyecare professionals, and they spend $3.8 billion annually on symptom relief.1 Some people have dry eye so chronic and/or so severe it adversely affects their daily lives. It’s not unheard of, as we see in Internet chat rooms for example, for it to cause people to contemplate suicide. We’ve been caring for dry eye patients for years at the Bascom Palmer Eye Institute in Miami, and we now have a facility in Plantation, Fla., where we’ve centered all of our ocular surface functions.
In Plantation, we see many patients for whom initial dry eye treatments, perhaps artificial tears, punctal occlusion, or warm compresses that work very well for others, simply haven’t been effective enough. Our approach for these patients begins with helping them to understand that dry eye is a chronic condition, and we aim to forge a supportive relationship to help them achieve the best outcomes. Thankfully, we have some newer treatments we can use to help us.
I’m a believer in omega dietary supplementation, and I recommend it for all of my dry eye patients. We do have unanswered questions about optimal omega supplementation, including what balance of omega-3 and omega-6 fatty acids is best, so further study is needed. But two recent clinical studies are notable.
A multicenter, randomized, prospective, controlled study by Sheppard, et al. compared the effects of HydroEye (ScienceBased Health) omega-GLA supplements with placebo in post-menopausal women.2 Only the supplements improved dry eye symptoms. In addition, the supplement group experienced no progression of ocular surface inflammation based upon conjunctival impression cytology T cell and HLA marker expression, while inflammation worsened in the placebo group. Corneal topographic smoothness was maintained with supplement use, but surface irregularity progressed in the patients taking placebo.
Kendall Donaldson, MD, MS
Bascom Palmer Eye Institute Plantation, Fla.
Another study, a multicenter, double-masked, randomized, placebo-controlled trial by Donnenfeld et al. compared placebo with supplementation with Dry Eye Omega Benefits (PRN), which contains 1,680 mg EPA and 580 mg DHA. By 12 weeks, the treatment was effective, resulting in statistically significant improvement in tear osmolarity, corneal staining, ocular surface disease index (OSDI) symptom scores, and omega-index levels.3 This study is continuing.
Certainly Restasis (cyclosporine, Allergan) can be considered as a first-line treatment for dry eye with an inflammatory component, which we can now better direct using MMP-9 point-of-care testing, and it’s also been shown to be effective in very complicated cases.
In a systematic review and meta-analysis by Zhou and Wei, even patients with systemic immune dysfunction exhibited statistically significant improvement in tear break-up time (TBUT) and Schirmer’s test scores with use of Restasis.4
There haven’t been many well-controlled appropriately randomized studies of serum tears, but last year a retrospective study of 50% concentration autologous serum tears by Hussain et al. found them to be safe and effective. Improvements in corneal fluorescein staining and Schirmer’s test scores were sustained with long-term use.5 I’m very interested in serum tears, and we’re having great success using them for our patients at Bascom Palmer. We’ve seen how this therapy can be life-changing for even the sickest of patients. We started out using primarily 20% serum tears and now we’re using 40% to 50% in many patients with very good results.
We’re in the process of running our own trial. As we’re looking at our data, we’re finding improvement in OSDI, corneal staining, TBUT, tear osmolarity, and Schirmer’s testing. Our objective biomicroscopic findings indicate that 26% have full resolution of signs, 42% have partial resolution, and in 32% we’re unable to distinguish an improvement.
When we asked our patients for their perspective on serum tears, 26% reported, “This has fully cured my problem.” These are patients who were refractory to all other treatments. In addition, the treatment isn’t covered by insurance, yet patients are motivated to spend $120 a month year after year to have it.
Cliradex for Demodex
As we now know, a substantial percentage of the dry eye cases we see are driven by eyelid and meibomian gland problems. One such problem that we’ve become more aware of is demodex. When these little mites multiply out of control, they contribute to a number of ocular surface-drying conditions, including blepharitis, meibomian gland dysfunction (MGD), and conjunctival inflammation.
Although tea tree oil is an effective treatment for demodex, it’s toxic to the ocular surface and eyelids. Our new demodex treatment of choice is Cliradex cleansing towelettes (Bio-Tissue). Cliradex towelettes contain the component of tea tree oil, 4-Terpineol, that has the greatest effectiveness at the lowest concentration. Therefore, when patients use these at home, they’re highly effective but don’t cause the reactions we would see with tea tree oil. Many of our staff members who don’t have demodex use Cliradex as part of their daily skin care regimen.
Meibomian Gland Therapies
We have a full lid clinic at our facility, where we perform all of our manual meibomian gland expression and MiBoFlo and Lipiflow (TearScience) treatments. MiBoFlo is relatively new to us, but we’re pleased with our results so far, and LipiFlow has been very successful for us. Somewhat unexpectedly, our patients who have benefitted the most from LipiFlow are those with the greatest degree of corneal staining, not necessarily those with the highest degree of MGD or most inflamed eyelids. Many of our patients return to our lid clinic for monthly or bimonthly manual expression and are choosing to return for MiBoFlo and LipiFlow treatments when necessary as well.
SHIRE’S PRODUCT PIPELINE
Currently, Shire’s ophthalmic unit is working to bring to market lifitegrast, a new dry eye product. Shire has completed its Phase 3 trial of the investigational drug, which is designed to treat the signs and symptoms of dry eye disease in adults.
In January, Shire announced it had resubmitted the New Drug Application (NDA) to the FDA for lifitegrast after receiving a request for an additional study in October 2015. To address the request, Shire included added data from OPUS-3, a Phase 3 efficacy and safety trial with a primary endpoint of patient-reported symptom improvement.
The FDA has granted Shire a Prescription Drug User Fee Act (PDUFA) date of July 22, 2016.
Scleral Contact Lens
The PROSE (prosthetic replacement of the ocular surface ecosystem) scleral contact lens (BostonSight) is a very important solution we offer to our severe dry eye patients. It’s designed for use in a variety of conditions, such as irregular astigmatism, corneal dystrophies, and scarring, but it has served as the missing link for many of our patients who are refractory to every other available ocular surface disease treatment.
Several different types of amniotic membrane are available and can be used to relieve the symptoms of chronic dry eye. The Prokera amniotic membrane (Bio-Tissue) is differentiated by the fact that it’s cryopreserved with a proprietary method that maintains the effectiveness of the components of the membrane that are necessary for regenerative healing. That means it does more than protect the surface of the eye — it rejuvenates it.
The newest version of Prokera, the Prokera Slim, is a game-changer due to its ease of use and enhanced tolerability for patients. In a case where a patient has trouble keeping the membrane in the eye, tape tarsorrhaphy is an easy, effective solution.
Utilizing novel, advanced treatments to help patients who weren’t able to find help elsewhere tends to turn challenging dry eye cases into some of the most rewarding. ■
1. Market Scope. 2013 Comprehensive Report on the Global Dry Eye Products Market.
2. Sheppard JD, Singh R, McClellan AJ, et al. Long-term supplementation with n-6 and n-3 PUFAs improves moderate-to-severe keratoconjunctivitis sicca: a randomized double-blind clinical trial. Cornea. 2013;32(10):1297-1304.
3. Donnenfeld ED, Holland EJ, Bucci FA, et al. Effect of oral re-esterified Omega-3 nutritional supplementation on dry-eye disease: double-masked randomized placebo-controlled study. Paper presented at the 2015 annual meeting of the American Society of Cataract and Refractive Surgery, San Diego, CA.
4. Zhou XQ, Wei RL. Topical cyclosporine A in the treatment of dry eye: a systematic review and meta-analysis. Cornea. 2014;33(7):760-7.
5. Hussain M, Shtein RM, Sugar A, et al. Long-term use of autologous serum 50% eye drops for the treatment of dry eye disease. Cornea. 2014;33(12):1245-51.