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March 2011

 
Clinical Update: Uveitis
The Smoking Connection: Encouraging Cessation in Uveitis Patients
By Marianne Doran, Contributing Writer
Interviewing Nisha R. Acharya, MD, Emmett T. Cunningham Jr., MD, PHD, MPH, Phoebe Lin, MD, PHD, and Jennifer E. Thorne, MD, PHD
 
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Uveitis is challenging enough to treat without adding cigarette smoking to the mix. Recent studies, in fact, indicate that smoking is itself a significant risk factor for uveitis and makes bilateral disease and compromised vision at presentation more likely. Evidence suggests that smoking both prolongs the time required to control the inflammation and shortens the duration of that control.

Long Suspected, Finally Indicted?

Cigarette smoking has been a suspected risk factor in uveitis for many years, said Nisha R. Acharya, MD, an associate professor of ophthalmology at the University of California, San Francisco. But the potential connection was not rigorously examined until recently, in a study reported by Dr. Acharya and colleagues in Ophthalmology.1 “We had a clinical hunch, but the relationship had never been formally addressed,” noted Dr. Acharya, senior author of the study and director of the uveitis clinic at the Francis I. Proctor Foundation at UCSF. “A lot of uveitis specialists had noticed that their patients seemed more likely to smoke compared with other ophthalmology patients or in comparison to the general population. That stimulated us to address the question because we weren’t able to definitely tell patients that smoking was a risk factor for their inflammation.”

All types of uveitis implicated. In the retrospective case-control study, the researchers reviewed the records of 564 patients with ocular inflammation who were seen in the uveitis clinic between 2002 and 2009. They compared them with the records of 564 randomly selected patients examined in the comprehensive eye clinic during the same time frame. Their primary finding was that smokers were 2.2-fold more likely to have ocular inflammation than were people who had never smoked.

But the extent of smoking’s deleterious impact was surprising. “We found that smoking is associated with all types of uveitis, not just a certain anatomic subtype,” said first author Phoebe Lin, MD, PhD, a vitreoretinal surgical fellow at Duke University. “Especially interesting was our finding that infectious uveitis is also associated with smoking.” The researchers speculated that the pro-inflammatory components of tobacco smoke that trigger vascular inflammation not only provide organisms access to intraocular tissue but also may increase the inflammatory response.

Dr. Lin noted that the odds ratios for smoking and uveitis are equal to or higher than the associations between smoking and macular degeneration found in major studies like the Beaver Dam Eye Study.

Dr. Acharya added, “Our findings are very strong in support of an association between cigarette smoke exposure and eye inflammation. The findings held up with all types of eye inflammation—infectious, noninfectious, all anatomical subtypes—and the odds ratios approached an eightfold increase in some subgroups. It was a very robust association across many groups of patients, even after accounting for possible confounders.”

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How Smoking Compromises Treatment

A study reported last year in the British Journal of Ophthalmology2 provides more evidence to indict smoking in the development and persistence of uveitis.

Jennifer E. Thorne, MD, PhD, an associate professor of ophthalmology and epidemiology and director of the division of ocular immunology at the Wilmer Eye Institute, noted that the exact mechanisms behind smoking’s effects on the eye are not known. “A number of compounds present in cigarettes could potentially be toxic to ocular tissue,” she said. “Tobacco also might decrease the effectiveness of anti-inflammatory medications or somehow alter the immune response. Some of the components of cigarettes may contribute to the disease directly.”

Dr. Thorne added that some researchers have speculated that the cigarette smoke may cause irritation to the ocular surface or that there may be differences in terms of treatment adherence or in showing up for appointments among smokers vs. nonsmokers.

Dr. Thorne noted that smoking-associated comorbidities, such as damage to small blood vessels, have been reported. “Some of these comorbidities may actually be at the heart of why ocular inflammation is more common in smokers,” she said, “or why the disease is more difficult to control and the recurrence rate is higher.” In a previous study, her group found that smokers with intermediate uveitis were more likely to develop cystoid macular edema.3

Elaborate inflammatory response. In an editorial accompanying the British Journal of Ophthalmology paper,4 Emmett T. Cunningham Jr., MD, PhD, MPH, director of the uveitis service at California Pacific Medical Center in San Francisco and adjunct clinical professor of ophthalmology at Stanford University, noted strong research support for the role of antigen-activated T lymphocytes in the initiation and maintenance of uveitis.

Dr. Cunningham added that other potential contributing factors, depending on the clinical situation, are B lymphocytes and antibodies, circulating pro-inflammatory cytokines, components of the innate immune system (primarily complement) and pattern recognition receptors.

Dr. Cunningham also cited evidence that external or environmental triggers, such as psychological stress, infection, trauma and immune-mediated food intolerance, may trigger uveitis and that genetic predisposition appears to play a role in some patients.

But he pointed out that patient noncompliance may be the most important exogenous factor in controlling the disease. That includes lack of adherence to medication regimens and the substitution of alternative therapies and persistence in smoking despite being counseled to stop.

Dr. Cunningham said, “We now have pretty solid cumulative evidence that smoking is bad for the eye and particularly bad for patients with uveitis. But lifestyle interventions are always difficult, particularly the addicting lifestyles. We always counsel patients to stop smoking, but in practice few of them do.”

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Educating Patients

“Ophthalmologists should ask their patients whether they smoke, but I don’t think many ask,” Dr. Acharya said. “Eye inflammation is yet another reason to encourage a patient who smokes to quit—and patients with uveitis may be more motivated to stop if you can actually tell them that smoking makes their disease worse and puts them at greater risk. Now we have evidence to support that.”

Dr. Acharya encourages ophthalmologists to point their at-risk patients toward a smoking cessation program, ask them about their cessation efforts at every visit and try to motivate them. These efforts may be especially important in younger uveitis patients who are otherwise healthy and may not have given much thought to the many dangers of smoking, she said.

Gentle persistence is key. Dr. Acharya’s advice: Never give up. “I bring up the importance of smoking cessation at every visit. I acknowledge that stopping smoking is going to be one of the hardest things they’ve ever done and tell patients that it’s not just for their eyes—it’s for their whole body and their life. Sometimes patients relapse, but I don’t give up, and I don’t make them feel bad. We just try to remain positive and try again because I don’t want them to get discouraged.” She acknowledged that this counseling does take time out of an appointment and may be hard for some ophthalmologists to do, but she believes it’s worth taking one or two minutes to discuss it.

Two years ago she helped start a uveitis support group at UCSF to provide an outlet for patients to meet each other and talk about their stressors. The patient-run group meets every month, is open to any uveitis patient and includes an online support group. Speakers are brought in a few times a year to provide information on topics ranging from new research to meditation and relaxation techniques. Dr. Acharya noted that most people with uveitis have never met anyone else with the disease, and a support group can be an important source of encouragement and motivation.

“The results of our study definitely made me change the way I counsel patients,” she added. “If patients come in with uveitis and I know they smoke, our study, along with other recent studies, gives me more ammunition to tell them to stop.”

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Tools to Help Smokers Quit

The looming challenges for ophthalmologists who would like to help patients break their tobacco dependency are time and resources.

The Agency for Healthcare Research and Quality (AHRQ) has published Treating Tobacco Use and Dependence: 2008 Update—Clinical Practice Guideline, which offers concise, practical, data-driven advice and strategies for overcoming tobacco dependence. (The document can be found online at www.ahrq.gov/path/tobacco.htm#clinicians.)

There is help everywhere you look. The guideline emphasizes that there is an increasing availability of smoking cessation programs. These are provided (or reimbursed) by managed health care plans, state Medicaid programs, the Veterans Health Administration, the U.S. Military and, increasingly, private health insurers. State-sponsored telephone “quitlines” also have proven effective in providing broad access to evidence-based smoking-cessation counseling.

Moreover, seven FDA-approved medications are on the market to help patients quit.

Three particular combinations of these medications have proved especially effective in many patients, including:

  • Long-term use (at least 14 weeks or more) of a nicotine patch plus another nicotine replacement therapy (such as a nicotine gum or spray);
     
  • The nicotine patch plus the nicotine inhaler;
     
  • The nicotine patch plus buproprion.

    Another AHRQ report called Helping Smokers Quit: A Guide for Clinicians offers physicians a straightforward, efficient and evidenced-based approach to counseling patients (also available at www.ahrq.gov/path/tobacco.
    htm#clinicians
    ). In this simplified approach, physicians are directed to “Ask, Advise, Assess, Assist and Arrange:” 

  • Ask about cigarettes each visit.
     
  • Advise users to quit, using clear, strong and personalized language.
     
  • Assess the readiness to quit. This involves providing resources and assistance to those who are ready to quit or, for those who are not ready, discussing reasons to quit in a supportive, encouraging manner.
     
  • Assist with a plan. This includes discussing the importance of setting a quit date, removing tobacco products from the home, enlisting the support of family and friends, anticipating challenges, reviewing past attempts at quitting and identifying reasons for quitting.sp;
     
  • Arrange follow-up visits.

    Counseling patients about smoking cessation can be discouraging and time consuming. But repetition of the message and referring patients to the available resources may pay off over time, Dr. Acharya said.

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1 Lin, P. et al. Ophthalmology 2010;117:585–590.
2 Galor, A. et al. Br J Ophthalmol 2010;94:848–853.
3 Thorne, J. E. et al. Am J Ophthalmol 2008;145:841–846.
4 Cunningham, E. T. Br J Ophthalmol 2010;94:813–814.
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None of the physicians interviewed report related financial interests.

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