Acupuncture: A Dry-Eye Therapy?

Humans are a visual species. When daily activities are disrupted by impaired vision, patients are confronted with the reality of how important their eyes are to them, and how often they take good visual function for granted. This fundamental importance of visual health in everyday life distinguishes ophthalmology from other medical specialties. Many of our patients may come to us with the apprehension that stems from a disruption of something that is central to their day-to-day living: their eyesight.

Dry eye is one disease that can have a significant impact on visual function. The burning, the blurring of vision and the inability to sustain simple activities like reading or driving can be the cause of great frustration for patients with dry eye. Without truly efficacious treatments, we are left to provide a combination of eye drops, plugs, humidifiers and an assortment of palliative approaches that often only mitigate the symptoms of the disease. Due to the constant impact of the disease on their lives, patients with dry eye, particularly those suffering with the most severe forms, are motivated to try any and all remedies, treatments or procedures that promise substantial relief. One such non-traditional approach is acupuncture, the ancient Chinese method of physiologic manipulation using fine needles targeting specific points on the body.Kaptchuk TJ. Acupuncture: Theory, effi cacy, and practice. Ann Intern Med 2002;136:374-383.,Yang ES, Li P-W, Nilius B, Li G. Ancient chinese medicine and mechanistic evidence of acupuncture physiology. Pfl ugers Arch – Eur J Physiol 2011;462:645–653. Now, more than 40 years after its “introduction” to Western medicine, acupuncture is generally accepted as an alternative anti-nociceptive and anti-emetic therapy. Despite this, its use for treating other conditions, such as dry eye, is generally considered more speculative.

As alternative medical techniques such as acupuncture move into the mainstream, there is a growing need for evidence-based studies that allow us to assess them relative to other therapeutic interventions. In recent years randomized clinical trials of acupuncture for a number of ocular indications including dry eye have been conducted, and several are currently under way. In our June column, we discussed the importance of applying principles of evidence-based medicine to herbal and other nontraditional therapies; this month, we’ll examine the data from clinical studies of acupuncture, with a particular focus on its use as a treatment modality for dry eye.

Acupuncture’s Origins

The exact history of acupuncture isn’t known, but there is evidence of wooden and bone needles suitable for acupuncture in Chinese ruins dating back to before 1000 B.C.,,Zhao ZQ. Neural mechanism underlying acupuncture analgesia. Prog Neurobiol 2008;85:355-75. The most often-cited early written reference to acupuncture as an established therapy is the Nei Jing, a manual of Chinese medicine that dates to the first century B.C., and describes the bodily paths of energy flow (sometimes referred to as a wind), or Qi (pronounced “chee”), that are a primary target of acupuncture. It’s likely that the method is much older than this ancient text, as various forms of the technique were well-established in both Japan and Korea around the time of the Nei Jing. In addition, there is evidence that a frozen Neolithic man found in the Swiss Alps may have been part of a Stone-Age society that practiced a well-developed form of acupuncture.Dorfer L, Moser M, Bahr F, Spindler K, Egarter-Vigl E, Giulle´n S, et al. A medical report from the stone age? Lancet 1999;354:1023-5. That finding pushes the origins of the technique back by several thousand years, and also brings into question the dogma of a Chinese origin. It’s not likely that a man from central Europe circa 3000 B.C. made weekend trips to Beijing to see his acupuncturist.

Acupuncture mapAcupuncture maps areas of therapy as meridians (appearing as lines on the model above) and acupoints (the alphanumerically labeled points).

From the earliest records, the goal of acupuncture treatments has been described as a means to restore balance, and therefore health, by manipulation of the flow of Qi through invisible tracts running from head to toe. These pathways, commonly referred to as meridians, are distinct from anatomical networks such as nerves or blood vessels. The rationale for acupuncture rests heavily on concepts of duality, of the yin and yang, central to eastern philosophies; in the body, the duality is represented by blood and Qi. Earliest records referred to bloodletting and acupuncture as parallel means of balance restoration. Treatments often include needle manipulation at a dozen or more acupoints, the precisely mapped points used for needle insertion.

There are several hundred acupoints in most manuals of acupuncture, and treatments often involve a combination of sites surrounding the symptomatic areas together with more distant acupoints. For example, trials of acupuncture therapy for dry eye typically employ 13 to 19 needle sites, and include those near the orbits as well as sites in the hand and in the foot.Shin MS, Kim JI, Lee MS, et al. Acupuncture for treating dry eye: A randomized, placebo-controlled trial. Acta Ophthalmol 2010;88:8. Despite skepticism about a technique based upon an invisible network of wind energy, it’s clear from both history and recent scientific studies that there is more to this than smoke, mirrors or needles.

In recent years there has been a significant research effort focused on identifying the physiological basis of acupuncture, and much of this work has yielded clear mechanistic details for some of the effects of the method. The earliest of these studies showed a link between the anti-nociceptive action of acupuncture and the release of endogenous endorphins.Mayer DJ Price DD Raffi i A. Antagonism of acupuncture analgesia in man by the narcotic antagonist naloxine. Brain Res 1977;121:368-372. A key part of this work was the demonstration that pain relief provided by acupuncture could be prevented by the narcotic antagonist naloxine. Other studies in animals and in humans have linked acupuncture-mediated pain relief with needle-evoked release of adenosine and adenosine triphosphate. Goldman N, Chen M, Fujita T, et al. Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nature Neurosci 2010;13:883-888.,Takano T, Chen X, Luo F, et al. Traditional acupuncture triggers a local increase in adenosine in human subjects. J Pain 2012;13:1215-23. Local accumulations of these transmitters can lead to adenosine receptor activation on nearby afferent nerves, and this is likely to be responsible for acupuncture-elicited local analgesia. These effects can be replicated with direct adenosine injections, and do not occur in mice lacking the adenosine A1 receptor. Another finding of this work, replicated in many other studies, is the importance of needle manipulation. While descriptions of acupuncture tend to focus on the specifi c locations of the acupoints, it’s also equally important to note that duration of treatment and the amount of needle manipulation are also integral parts of the method.

Acupuncture orbital acupoints for dry eye therapyAcupuncture orbital acupoints (sites designated as BL2, GB14 and TE23). Among those points used for dry-eye therapy are points surrounding the orbit.

In addition to the traditional methods that rely on needle manipulation, other variations combine use of acupuncture with heat application (moxibustion), or focus on specific body regions (e.g., auricular acupuncture). However, there are few controlled studies examining the efficacy of these methods, and even fewer focusing on potential ocular indications.

Part of the interest and demand for alternative treatments such as acupuncture comes from a growing patient population that seeks alternatives to mainstream pharmaco therapies that they view as inherently dangerous. In contrast, it is common to find descriptions of acupuncture as a therapy “without adverse effects.” Fortunately, even some of the most vocal proponents of the technique are quick to point out that although it is an exceptionally safe treatment modality, it is not without risk: For example, inappropriate use of acupuncture needles can result in the puncturing of vital organs. A consideration of the potential risks of acupuncture treatment has to be part of the therapeutic decision-making process for both patient and practitioner.Ernst E. Acupuncture—a treatment to die for? J R Soc Med 2010;103:384-385.

Acupuncture in the Clinic

Since its re-introduction into western medicine in the 1970s, there has been a sustained effort to assess the clinical efficacy of acupuncture in a controlled, empirical fashion. By the late 1990s, acupuncture had become more accepted as a viable treatment for alleviation of pain and/or nausea, and since then has been generally acknowledged as an effective therapeutic option for these indications. In addition, acupuncture has been used for a number of ophthalmic disorders, including ocular allergy, glaucoma and dry eye. While there is no consensus as to the effectiveness of acupuncture for these indications, there is a growing body of evidence-based data that clinicians can use to make an informed appraisal.

Clinical trials involving acupuncture- based treatments face the same difficulties that other procedural therapies, such as surgery, encounter, including the need for valid placebo groups and for appropriate treatment masking. Many studies have used sham needles placed at positions other than the acupoints designated in study protocols. This approach has revealed a significant placebo effect in many acupuncture trials, while at the same time providing an appropriate comparator with which to judge acupuncture effi cacy.Vickers AJ, Cronin AM, Maschino AC, et al. Acupuncture for chronic pain: Individual patient data meta-analysis. Arch Intern Med 2012;172:1444-53.,Coeytaux RR, Park JJ. Acupuncture research in the era of comparative effectiveness research. Ann Intern Med 2013;158:4:287-8. Some of the best data has come from studies using both sham needle placebos and active comparators (drug) that allow for both a direct assessment of the relative efficacy of acupuncture, and a measure of the technique’s utility as adjunct therapy.

Use of acupuncture for allergic and inflammatory diseases including asthma, rhinitis and allergic conjunctivitis is common among traditional practitioners. Several small-scale (n=24 to 30) randomized trials compared standard and sham acupuncture effects on either signs and symptoms of seasonal allergic diseaseXue CC, English R, Zhang JJ, Da Costa C, Li CG. Effect of acupuncture in the treatment of seasonal allergic rhinitis: A randomized controlled clinical trial. Am J Chin Med 2002;30:1-11. or on circulating IgE levels in allergic patientsMagnuson A, Svensson RE, Leirvik C, Gunnarsson RK. The effect of acupuncture on allergic rhinitis: A randomized controlled clinical trial. Amer J Chinese Med 2004;32:105-115. and were unable to demonstrate a significant clinical effect. More recently, a larger trial (n=422) was able to show a statistically significant improvement in Rhinitis Quality of Life Questionnaire scores in the acupuncture-treated group compared with either sham acupuncture or oral cetirizine alone (all patients were provided medication). Brinkhaus B, Ortiz M, Witt CM, Roll S, Linde K, Pfab F, Niggemann B, Hummelsberger J, Treszl A, Ring J, Zuberbier T, Wegscheider K, Willich SN. Acupuncture in patients with seasonal allergic rhinitis: A randomized trial. Ann Intern Med 2013;158:4:225-34. In addition, those receiving acupuncture treatments (but not sham treatments) reduced their cetirizine intake by between 10 to 15 mg per day. These improvements were transient, however, and did not reach a clinically significant level.

There are also studies of acupuncture treatments for primary open angle glaucoma patients, including a recent study that examined the effect of acupuncture on intraocular pressure and ocular hemodynamics.Takayama S, Seki T, Nakazawa T, et al. Short-term effects of acupuncture on open-angle glaucoma in retrobulbar circulation: Additional therapy to standard medication. Evid Based Complement Alternat Med 2011;2011:157090. This study had a small sample size (20 eyes) and no true placebo group, but it was able to show a decrease in IOP following acupuncture, and also reported Doppler imaging-based increases in ocular blood fl ow following treatment. The value of acupuncture, as with any other treatment approaches for the disease, will be measured in future studies that evaluate the ability of the technique to slow or reverse the retinal damage associated with POAG.

Acupuncture for Dry Eye

In contrast to glaucoma, dry eye is a condition with significant unmet therapeutic need, and so would seem to be an appropriate condition for acupuncture therapy. The chronic nature of dry eye further supports an examination of acupuncture treatment efficacy. A number of early studies were designed to test mechanistic actions of acupuncture on tear-film physiology; in one study, periorbital acupuncture was shown to cause a 0.44 C decrease in ocular surface temperature, an effect that would be expected to reduce evaporative tear loss.Nepp J, Tsubota K, Goto E, Schauersberger J, Schild G, Jandrasits K, Abela C, Wedrich A. The effect of acupuncture on the temperature of the ocular surface in conjunctivitis sicca measured by non-contact thermography: Preliminary results. Adv Exp Med Biol 2002;506(Pt A):723-6. A small-scale trial of acupuncture showed positive effects on subjective, patient-reported symptoms, but this early study lacked randomization and control groups necessary for objective assessment. Grönlund MA, Stenevi U, Lundeberg T. Acupuncture treatment in patients with keratoconjunctivitis sicca: A pilot study. Acta Ophthalmol Scand 2004;82:283-90. Another, more recent pilot study compared acupuncture and sham acupuncture treatments, (Shaw KS, IOVS 2011;52:ARVO E-abstract 3839) but found no significant differences between the two groups. In general, early trials of acupuncture, both for dry eye and for other conditions, suffered from a lack of rigorous controls, masking and other study features necessary for evidence-based assessments.

Studies conducted in the past three to five years have addressed these issues and so provide a growing dataset from which to draw clear conclusions. Two studies conducted in Korea have employed a specific set of acupoints together with more clearly defined treatment and control criteria, including parallel sham acupoints.,Kim T-H, Kang JW, Kim KH, Kang K-W, Shin M-S, et al. Acupuncture for the treatment of dry eye: A multicenter, randomised, controlled trial with active comparison intervention (artifi cial teardrops). PLoS ONE 2012;7:5:e36638. Acupuncture efficacy was measured using score reduction in questionnaires including the Ocular Surface Disease Index, the Visual Acuity Scale and quality-of-life scales of subjective symptomology. Both groups also examined endpoints including tear-film breakup time and Schirmer’s scores with anesthesia. One study involved a four-week course of acupuncture treatments, and although researchers found no significant differences between groups at the end of the treatment period, re-examination at eight weeks showed statistically significant improvements in both subjective scores and in TFBUT for the acupuncture treatment group.18 The study’s use of artificial tears for the control group further strengthens these findings.

Sham-needle controls provide the best means to assess the placebo effect of needle treatments in order to clearly define the therapeutic benefit of acupuncture. In one study, three weeks of nine different treatments were compared with the same number of sham treatments. Both groups demonstrated significant improvements in OSDI and VAS scores, and TFBUT scores were improved. However, sham treatments also improved signs and symptoms, again suggesting a significant placebo effect. The one exception to this was the TFBUT measures, for which only the acupuncture group showed significant improvement (3.29 ±1.01 to 4.24 ±1.26 sec.). While not an overwhelming endorsement for acupuncture as a treatment approach, it does suggest that additional studies, including those with objective endpoints such as corneal staining or reduced use of artificial tears, may be warranted.

Sham-needle controls provide the best means to assess the placebo effect of needle treatments in order to clearly define the therapeutic benefit of acupuncture.

 

The verdict is still out on acupuncture’s use as a treatment for dry eye; while we are not ready to adopt a policy of referring dry-eye sufferers for acupuncture treatments just yet, the whiff of possible effectiveness is intriguing nonetheless. As long as drugs with proven efficacy are unavailable, people suffering with symptoms that disturb their everyday visual function will undoubtedly fi ll the void with alternative therapies. It is essential that we continue to seek evidence regarding whether any possible treatments, including those such as acupuncture, have a potential place in the armamentarium available to treat patients with dry eye.

Dr. Abelson is a clinical professor of ophthalmology at Harvard Medical School. Dr. McLaughlin is a medical writer at Ora Inc.