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Specialists discuss dry eye’s new definition, recent advances, unmet needs
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Due to the aging of the population and multiple factors related to environmental and lifestyle changes, the prevalence of dry eye has escalated in recent years in the West, in Asia and in other developing nations. A condition that was considered a minor ailment has become an important focus for research and practice in ophthalmology, branching out to involve other specialties, such as neurology and immunology.
In spring 2017, 10 years after the first report, the second International Dry Eye WorkShop is expected to disclose results, providing an updated definition of dry eye disease, new data on epidemiology, and a critical assessment of current diagnostic means and therapies. Meanwhile, the Asian Dry Eye Society is about to publish in The Ocular Surface its own new definition and guidelines, 10 years after the previous, revised “Definition of and diagnostic criteria for dry eye.”
“One of the characteristics of this new definition is that we emphasize on tear film stability. We define dry eye as a multifactorial disease characterized by unstable tear film causing a variety of symptoms and/or visual impairment potentially accompanied by ocular surface damage,” Jun Shimazaki, MD, PhD, a Dry Eye Society board member, said.
This way of characterizing dry eye is meant to be “simple and practical” for the general ophthalmologist, who can formulate a diagnosis based on tear breakup time and symptoms.
“Our approach is different from the DEWS’s approach because we are making guidelines and recommendations based on high-level evidence, while the DEWS definition and criteria are based on the consensus of dry eye specialists,” Shimazaki said.
Pathogenesis of dry eye
In the last 10 years, research has gone deeper into the multiple and complex factors leading to dry eye disease. The key role of osmolarity and inflammation has been confirmed, but more has been discovered within their interaction mechanisms and cascade of events.
Among the interesting discoveries was that inflammation in dry eye disease affects not only the conjunctiva but also the cornea and involves the activation of lymphocytes (Th1 and Th17) in the lymph nodes.
“This highlights that we are not dealing with simple inflammation but with an immune reaction that involves the entire system of the ocular surface, including the cornea and the lymph nodes. It also gives us new insights into how dry eye becomes a chronic condition,” Stefano Barabino, MD, PhD, DEWS committee member, said.
Another recent focus of research has been the activation of corneal nerves. The studies of Carlos Belmonte, MD, PhD, showed that a dry ocular surface environment promotes the activation of nerve receptors, leading to nerve sensitization and chronic neuropathic pain.
“The neuropathic component of DED was only marginally taken into account by the previous DEWS because we did not have the data we have now. Belmonte’s research has opened a new, important chapter and has given us a new key to the understanding of ocular pain,” Barabino said.
Diagnostic challenges
A major challenge in the diagnosis of dry eye disease is the frequent discrepancy between clinical signs and subjective symptoms. Patients often complain of severe, persistent symptoms while the ocular surface presents no evident signs of alteration or, conversely, may present with severe ocular surface damage and have no symptoms at all.
One possible explanation is the imprecision of diagnostic tools, according to Shimazaki.
“We are using traditional methods to detect changes in the tears or ocular surface, but we may not be able to see very subtle changes,” he said.
“The other explanation is that we should focus more on patient sensitivity. Very severe symptoms without notable changes on the ocular surface might be related to damage in the corneal nervous system, to the brain or even to depression and anxiety.”
This is a new research area many dry eye specialists are interested in, Shimazaki said.
“Some of us are trying to look at the subtle changes in tear film with biomarkers, others are looking at changes in corneal nerves using new tools such as confocal microscopy, and others are doing research on the signaling changes between the ocular surface and brain. Many of us believe that inflammation is involved in producing chronic changes in the peripheral and central nervous system, leading to chronic dry eye symptoms,” he said.
According to Jimmy Lim Wei Kheong, MD, a cornea and refractive surgery consultant at Tan Tock Seng Hospital in Singapore, “We are now able to measure tear film osmolarity, lipid layer thickness, quantifying tear meniscus, and use of indexes, such as the surface regularity index and the surface asymmetry index, for the aid in diagnosis and monitoring treatment of dry eye. These tools have become available for the clinic, such as the osmolarity measurement system, anterior segment OCT to measure tear meniscus and interferometry to measure lipid layer thickness. We are aiming at increasingly precise diagnosis, based on multiple factors and the correlation between these factors, and at the same time, understanding more about dry eye with these new parameters.”
New treatment options
Xiidra (lifitegrast ophthalmic solution 5%, Shire) has recently entered the scene of dry eye treatment and promises to be an effective new way of combating inflammation by inhibiting the chronic cycle of immune T-cell activation. Approved by the FDA in the U.S. in July, lifitegrast is keenly awaited as a potentially safer alternative to steroids, acting faster than cyclosporine.
“Tear substitutes have also evolved to a new generation of products that do not simply aim at replacing the aqueous component of tears but interact with the system of the ocular surface. Some new interesting products are currently in the pipeline,” Barabino said.
Two new approaches come from Japan. One is diquafosol, which promotes the secretion of tears as well as mucin from the conjunctival epithelium.
“Unlike artificial tears, it stimulates secretion by the patients’ own cells,” Shimazaki said.
The other drug is rebamipide, which has been used for almost 30 years in the treatment of gastric ulcer.
“The mechanism is protection of mucous membranes, and the conjunctiva is one of the mucous membranes. It also increases the secretion of mucin, the number of goblet cells in the conjunctiva and, in some way that is not yet fully understood, it suppresses inflammation,” he said.
Lim uses a staged approach to treat dry eye disease.
“For mild to moderate dry eye, I give topical aqueous tear replacement or lipid-based eye drops, oral omega-3 supplements, and improving the lid condition. For moderate to severe dry eye, or very symptomatic dry eye, I add steroids in tandem with cyclosporine. As cyclosporine takes a while to have an effect, a short course of steroids helps relieve and reassure patients in the meantime, while minimizing side effects of long-term steroid use in a chronic condition like dry eye. For very severe dry eye patients, we must re-evaluate the possible causes, review patients’ daily habits, their use of other systemic medications and do systemic investigation. These patients may require a multidisciplinary approach with other specialists, for example in patients with Sjögren’s syndrome or patients on anti-androgen treatment. Surgical management may be an option in selected cases to improve the ocular surface,” Lim said.
Patient education is a crucial part of the treatment, he said. As in all chronic conditions, compliance to medications tends to be low and dissatisfaction rate, as a consequence, is high.
“Patients need to understand more about their condition and how to manage it on a chronic basis. I rely on the use of documentation of patients’ symptoms and more importantly photos of the ocular surface with the aid of stains to show them if there is improvement with increased compliance and encourage improved behavior,” he said.
Dry eye and refractive procedures
Cataract and corneal refractive surgeons are nowadays fully aware of the critical role of the ocular surface for the success of refractive procedures and of the way dry eye can affect IOL power calculations and visual outcomes.
“If there is dry eye, topography maps show missing keratometry data due to the irregular tear film. Keratometry values and axes will therefore not be reliable, and patients may end up with 1 D to 2 D of unexpected refractive surprise. With toric and multifocal IOLs, outcomes that miss the refractive target are very disappointing to the doctor and patient and may require a second surgical procedure, IOL exchange, piggybacking or a surface procedure,” Aylin Kiliç MD, OSN Europe Edition Board Member, said.
Patients who present with dry eye before lens surgery are asked to return after an intensive course of treatment and no contact lens wear for 2 to 3 weeks. If epithelial profile maps and topography maps still show irregularity, dry eye treatment is continued for a few more weeks. Only after surface regularity is confirmed, Kiliç makes a plan for surgery.
Postoperative dry eye is another critical point for clear vision. Even if there is no dry eye preoperatively, postsurgical dry eye after premium IOL insertion is possible as a consequence of pre-existing subclinical dryness, ocular surface irritation caused by topical anesthesia, preservatives in the eye drops used during surgery or disruption of corneal innervations from surgical incisions.
“A suboptimal tear film may lead to an increase in total and higher-order aberrations and reduction in retinal image quality. Patients sometimes do not complain of classical dry eye symptoms and the only problem they report may be vision,” Kiliç said.
LASIK is an even more classic cause of postoperative dry eye, due to the severing of corneal nerves. According to Kiliç, the most important step for prevention is detailed preoperative screening. Postoperatively, dry eye treatment should be administered as a precaution, even if patient tear production ordinarily is normal.
As a cornea and refractive specialist, Lim tends to be strict on his patient selection and excludes patients with significant dry eye from having cornea refractive surgery.
“Even though PRK may be a safer choice, we must also take into account that any form of refractive surgery in patients with pre-existing dry eye may not achieve the patient satisfaction you need. For lens-based surgery, there are inaccuracies in preoperative biometry in patients with pre-existing dry eye. Patients also have poorer image quality postoperatively secondary to increased total aberrations from poor ocular surface, so it is important to optimize and stabilize the ocular surface before biometry measurement and the use of monofocal lenses in patients with significant dry eye and counsel them on expected image quality,” he said.
Treating dry eye before refractive surgery is a good idea, but there is no guarantee that the treatment will sustain its efficacy postoperatively. Therefore, meticulous counseling of patients preoperatively is critical.
“The fundamental goal of refractive surgery is to provide patients with good and comfortable unaided vision. If we achieve good vision without comfort, or if we achieve comfort without good vision, that’s not exactly refractive surgery. Dry eye impacts on results, on satisfaction rate, and the surgery itself may worsen the dry eye condition,” Lim said. – by Michela Cimberle
- References:
- Barabino S, et al. Exp Eye Res. 2010;doi:10.1016/j.exer.2010.07.008.
- Barabino S, et al. Ocul Surf. 2016;doi:10.1016/j.jtos.2016.04.005.
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- Baudouin C, et al. Br J Ophthalmol. 2016;doi:10.1136/bjophthalmol-2015-307415.
- Belmonte C, et al. Curr Ophthalmol Rep. 2015;doi:10.1007/s40135-015-0073-9.
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- The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007;doi:10.1016/S1542-0124(12)70081-2.
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- For more information:
- Stefano Barabino, MD, PhD, is associate professor of ophthalmology at Genoa University, Italy. He can be reached at Università degli Studi di Genova, Cinica Oculistica, Viale Benedetto XV 5, 16135 Genova, Italy; email: stebarabi@gmail.com.
- Aylin Kiliç, MD, PhD, is senior consultant and director of the Refractive Surgery Department at Istanbul Eye Hospital, Istanbul, Turkey. She can be reached at email: aylinkilicdr@gmail.com.
- Jimmy Lim Wei Kheong, MD, is a consultant at Tan Tock Seng Hospital, Singapore. He can be reached at email: jimmy_lim@ttsh.com.sg.
- Jun Shimazaki, MD, PhD, is professor of ophthalmology at Tokyo Dental Hospital, Ichikawa General Hospital, Chiba. He can be reached at email: jun@eyebank.or.jp.
Disclosures: Barabino reports he is a consultant to TRB Chemedica, SIFI and Farmigea. Kiliç and Lim report no relevant financial disclosures. Shimazaki reports he is a consultant to Otsuka Pharmaceutical and Santen Pharmaceutical.
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