Smoking: The universal risk factor

Smoking is a risk factor for numerous ocular diseases. Studies have shown a strong association with cataract and AMD.

Issue: July 15, 2004

ByJeanne Gonzalez

Smoking is not only a cause of diseases of the heart and lungs, it is also a trigger for the development of age-related macular degeneration and cataract and is associated with increased risk for other major ocular diseases, many clinicians agree.

Although the exact mechanisms of damage are unknown, it is thought that smoking may increase the number of free radicals in the blood, molecules that are capable of corroding tissue in the macula and elsewhere throughout the body, said Lylas Mogk, MD, chairwoman of the Visual Rehabilitation Committee for the American Academy of Ophthalmology. It may also induce an immune system response, causing ocular irritation, inflammation and nuclear opacification, and it may affect ocular circulation.

Evidence exists for correlations between smoking and both AMD and cataract, but studies have also associated smoking with an increased risk for glaucoma, diabetic retinopathy, Graves’ ophthalmopathy and other ocular conditions including uveal melanoma, conjunctival intraepithelial neoplasia, strabismus, ocular sarcoidosis and retinal detachment. The risk of disease may depend on how much a person has smoked and for how long, and the risk may be reduced by smoking cessation but not brought down to zero, Dr. Mogk told Ocular Surgery News.

Although the risk for developing these diseases is greater for smokers in general, the mechanisms of the pathologies for certain conditions are still unknown. Much research is being conducted into the mechanisms linking smoking to so many ocular and systemic diseases.

People who smoke may develop dry eye syndrome because of lipid layer deterioration. Interferometry imaging of the lipid layer shows changes from before smoking (top left) to immediately after smoking (top right). Bottom image is after 10 years of heavy smoking.

Images: Akova YA

Setting free radicals

Smoking fits as a causative agent in some of the current theories of the disease pathology of AMD, Dr. Mogk said. It is thought that levels of free radicals are elevated in people with AMD. Conversely, these people have decreased levels of antioxidants, which would work to neutralize free radicals, she said.

“Free radicals are highly active molecules that are byproducts of oxygen metabolism. … They are electrically unstable and have to have a partner to neutralize them as soon as they’re produced. If they don’t have an appropriate one, they will attach to the tissue in which they are produced, react with it and damage it,” Dr. Mogk said.

The level of free radicals can be indirectly measured by analyzing the level of antioxidants in a patient’s serum. Increased levels of free radicals and decreased production of antioxidants are associated with the development of ocular diseases including AMD, cataract and Graves’ ophthalmopathy.

In an article that reviews existing research on smoking and eye disease, Arthur Cheng, MD, and colleagues outlined the “strong association between smoking and a number of common eye diseases,”including cataract, AMD, glaucoma and Graves’ disease.

“Despite the multifactorial etiology of these ocular syndrome, smoking is an independent risk factor that has dose-response effects,” Dr. Cheng and co-authors said. “It causes morphological and functional changes to the lens and retina due to its atherosclerotic and thrombotic effects on the ocular capillaries. Smoking also enhances the generation of free radicals and decreases the levels of antioxidants in the blood circulation, aqueous humor and ocular tissue. Thus, the eyes are more at risk of having free-radical and oxidation attacks in smokers.”

Other theories on smoking’s role in AMD include the potential to catalyze the growth of subretinal vessels, cause hypoxic damage and increase oxidative stress on the retina.

Smoking and cataracts

Increased free radical production is also thought to have an effect on the development of cataract, Dr. Mogk said.

There is an association between heavy smoking and the development of nuclear cataract but not cortical or subcapsular cataract, Dr. Cheng and colleagues said. The risk appears to be dose-dependent. Pipe smoking has been linked with higher prevalence of nuclear cataracts, the authors said.

“It is possible that this excess smoke causes more harm to the lens, either by direct entry of the combustion and condensation products of tobacco into the eyes, or by continually raising the temperature of the lens,” they said.

Graves’ disease

There is a growing body of evidence showing smoking’s effect on the immune system and its inflammatory response, Dr. Mogk said.

“That’s apparently the connection with Graves’ thyroiditis, because that’s an immune system problem,” she said.

A dose-dependent relationship to smoking has also been seen in Graves’ ophthalmopathy, Dr. Cheng and colleagues found in their literature review.

Smoking can affect the immune system by decreasing T-suppressor lymphocyte activity and immunosuppression, the authors said. Smoking also affects the clones of T-helper cells, which contributes to their ability to fight thyroid and orbital antigens.

Another study showed that smoking appears to affect the elasticity of ocular muscle fibers in Graves ophthalmopathy.

Ocular ischemia is known to cause ophthalmoplegia, said Michael Belkin, MA, MD, and colleagues in another review of the literature on smoking and ocular disorders.

Dry eye and irritation

Smoking can also change the tear break-up time in patients with dry eye, resulting in more severe symptoms, said Yonca A. Akova, MD, in a study presented at the American Society of Cataract and Refractive Surgery meeting.

Dr. Belkin and colleagues review also noted studies showing that the chemicals in cigarettes cause conjunctival redness and increased tearing.

Blocking circulation

Smoking-related atherosclerosis is a suspected cause of circulation problems that may lead to retinal disorders and a secondary cause for increased IOP and the development of glaucoma, Dr. Mogk said.

“There’s no firm evidence, but a lingering suspicion, that there’s something to do with circulation with macular degeneration and circulation of the retina,” Dr. Mogk said.

The correlation between smoking and the development of glaucoma is weak, Dr. Cheng and colleagues said. However, because it is associated with an increased risk for hypertension and diabetes mellitus, two conditions that raise IOP, smoking is considered a secondary risk factor for IOP. More studies are necessary to confirm this theory, the authors said.

Stopping

The effect of smoking on the body’s chemistry and immune system are reason enough to suggest smoking cessation to reduce the risk of ocular diseases, those interviewed said.

“Quitting smoking is the first step,” Dr. Cheng said in an interview.

Smoking is a modifiable risk factor, and patients should be made aware of the effect of their choice, several physicians said.

In some cases, smoking cessation reduces a patient’s level of risk to that of a nonsmoker, Dr. Akova said. In other cases, depending on the disease, the risk may be reduced, but the damage from past smoking has already been done, she said.

Smoking and other ocular disorders

Smoking is associated with increased risk or increased severity of numerous ocular disorders. The ones most often cited are cataract and age-related macular degeneration, but smoking is a risk factor for other less-often-discussed diseases as well.

Michael Belkin, MD, and co-authors reviewed the literature on smoking and eye diseases for an article in Survey of Ophthalmology.

Dr. Belkin and colleagues note that smoking is a risk factor for the development of conjunctival intraepithelial neoplasia, as shown by Napora et al. It is also a risk factor for strabismus in children whose mothers smoked during pregnancy, as reported by Chew et al. Merritt and Ballard investigated possible environmental factors in the development of ocular sarcoidosis and found that women in the tobacco industry were at increased risk for the condition. Smoking seemed to influence the severity of Leber’s hereditary optic neuropathy in a review by Berninger et al.

For Your Information:

Lylas Mogk, MD, can be reached at the Visual Rehabilitation and Research Center, 29200 Schoolcraft, Levonia, MI 48150; 313-824-4800; fax: 734-523-1080; e-mail: lmogk@aol.com.

Arthur Cheng, MD, can be reached at the Univ Eye Clinic, The Chinese University of Hong Kong, 3/F Hong Kong; 852-2632-2878; fax: 852-2715-9490; e-mail: arthurcheng@cuhk.edu.hk.

Michael Belkin, MD, can be reached at Ophth Tech Lab, Eye Res Inst, Tel Aviv Univ, Tel Hashomer Israel; 972-3-530-2956; fax: 973-3-535-0388; e-mail: belkin@netvision.net.il.

Yonca A. Akova, MD, can be reached at Bahçelievler 06490, Ankara, Turkey, 90-312-215-03-49; fax: 90-312-223-73-33; e-mail: yoncaakova@yahoo.com.

References:

Cheng, ACK, Pang, CP, et al. The association between cigarette smoking and ocular diseases. HKMJ. 2000;6(2):195-202.

Belkin, M, Rosner, M, et al. The association between cigarette smoking and ocular diseases. Surv Ophthalmol. 1998;42:535-547.