Caffeine May Relieve Dry Eye Syndrome

Yael Waknine

April 25, 2012

April 25, 2012 — Caffeine intake boosts a person's ability to make tears and may help overcome dry eye syndrome, according to a small Japanese study published online February 15 in Ophthalmology.

Dry eye, also known as keratoconjuctivitis sicca, is prevalent in older adults and involves malfunction of the rate and quality of tear production, as well as the rate of eye surface evaporation.

Although symptoms such as gritty, scratching, or burning sensations; excessive tearing; and production of stringy mucus are mostly inconvenient, the condition can escalate into vision loss.

Reiko Arita, MD, PhD, and colleagues at the University of Tokyo's School of Medicine found a statistically significant increase in tear volume after caffeine intake in 78 healthy adults, particularly among those with polymorphisms to the adenosine A2a receptor gene ADORA2A and the hepatic cytochrome P 450 enzyme 1A2 (CYP1A2), which affect caffeine metabolism and response, respectively.

"This study was started because a 58-year-old male patient with dry eye told me that his eyes were more comfortable when he had a cup of coffee after lunch," Dr. Arita told Medscape Medical News in an email interview.

The findings were supported by earlier research showing that caffeine users had a 13% risk for dry eye compared with 16.6% of nonusers, according to a news release from the American Academy of Ophthalmology. Researchers were also aware that caffeine was likely to stimulate tear production, as occurs with other exocrine secretions, such as saliva and digestive juices. They also knew of genetic variations in caffeine metabolism.

"The study was basically good and very clever — it's so simple, but the idea of looking at caffeine to increase secretion should have been thought of long ago in the scientific community," Ivan Schwab, MD, professor of ophthalmology and corneal specialist at the University of California Davis School of Medicine, told Medscape Medical News in an interview.

"[The study] was pretty vigorous and although the numbers were small I think it looks very promising as an idea and [reflects] sound science and sound biologic mechanism," Dr. Schwab said, adding, "It will change what I do for my dry eye patients."

Dr. Schwab is a clinical correspondent with the American Academy of Ophthalmology.

Caffeine Intake Boosts Tear Production in Healthy Adults

For the double-blinded, crossover study, researchers recruited 78 healthy volunteers (41 men, 37 women; mean age, 33.6 years [range, 20 - 54 years]), none of whom had dry eye, eye allergies, or other ocular conditions that would interfere with tear film production or function.

In 2 sessions separated by 6 or more days, participants received a capsule containing 5 mg/kg to 7 mg/kg caffeine or a placebo capsule containing dextrose. All sessions were held between 10 am and noon, when tear production is usually stable; all participants had avoided use of recreational drugs or caffeine for 6 or more days.

Results at 45 minutes showed that caffeine intake significantly increased lower tear meniscus height (TMH) by about 30% from baseline relative to placebo (change, 0.08 mm; 95% confidence interval [CI], 0.05 - 0.10 mm; P < .0001).

"Although an 0.08 mm increase in TMH was slightly less than the definition of clinically significant used in the power calculation [it] seems to serve as a clinically significant increase," the authors write.

Dr. Schwab still finds the concept worth considering in patients with no medical or religious contraindications to caffeine.

"You might not have to increase [tear production] much to help dry eye symptoms — even a little bit extra may be significant to patients," said Dr. Schwab.

Adults With Certain Polymorphisms Respond More Vigorously to Caffeine Therapy

Researchers also found that a statistically significant increase in TMH among participants heterozygous or minor homozygous for ADORA2A rs5751876 compared with participants who were major homozygous for the gene (change, 0.07 mm; 95% CI, 0.03 - 0.11 mm; P < .001).

Findings for ADORA2A rs2298383 were similar, but no significant association was found with ADORA2A rs2236624.

"Interestingly, both polymorphisms at ADORA2A rs5751876 and rs2298383 are associated with caffeine-induced anxiety and panic disorder," the authors write.

With respect to CYP1A2, the net TMH increase in major homozygous participants was greater than minor homozygous participants (change, 0.06 mm; 95% CI, 0.00 - 0.11 mm; P = .039).

TMH increased by 50% or more only in those 30 participants (38%) with the genetic variations, the authors note.

Researchers also found that the net increase in TMH significantly increased with daily caffeine intake (0.02 mm; 95% CI, 0.00 - 0.04 mm; P = .021) and every 10-year increase in age (0.07 mm; 95% CI, 0.02 - 0.12 mm; P = .006). The increase among participants who felt awake after daily caffeine intake was likewise significantly higher than that in participants who remained sleepy (change, 0.08 mm; 95% CI, 0.03 - 0.12 mm; P = .001).

More Studies Needed to Explore Caffeine Benefits in Patients With Dry Eye

Additional studies are needed to explore caffeine benefits in patients with dry eye, particularly those older than age 50, who are at highest risk for the condition. Tear glands gradually deteriorate with age, and the prevalence of arrhythmias and other medical conditions that would be a "relative contraindication" to caffeine therapy increases, Dr. Schwab points out.

In addition, caffeine therapy may not work for all patients.

"While I'm very willing to try anything for patients frustrated by dry eye syndrome, those with severe dry eye often have damaged tear duct glands and abnormal secretory mechanisms, so even if you can stimulate the secretion, there is nothing there to secrete — it's like trying to get blood out of a turnip," Dr. Schwab said.

Dr. Schwab also noted the small and homogenous nature of the study population, saying that that although the genetic polymorphism aspect makes sense, it is possible that other genetic factors play a role — a key point that can be addressed in larger, more heterogenous studies.

Future studies may also exclude participants with certain levels of caffeine or nicotine intake; caffeine tolerance and withdrawal may affect results, and smoking reduces the half-life of caffeine.

"If confirmed by other studies, our findings on caffeine should be useful in treating dry eye syndrome," said Dr. Arita in the news release. "At this point, though, we would advise using it selectively for patients who are most sensitive to caffeine's stimulating effects."

Alternative therapies include wetting drops or artificial tears, lubricating ointments, hot compresses, and prescription drugs that increase tear production.

The authors and Dr. Schwab have disclosed no relevant financial relationships.

Ophthalmology. Published online February 15, 2012. Abstract