3.10 Eye diseases

 

Last updated: May 2020 
Suggested citation:  Hurley, S, Purcell, K, Greenhalgh, EM & Winstanley, MH. 3.10 Eye diseases. In Greenhalgh, EM, Scollo, MM and Winstanley, MH [editors]. Tobacco in Australia: Facts and issues. Melbourne: Cancer Council Victoria; 2020. Available from http://www.tobaccoinaustralia.org.au/chapter-3-health-effects/3-10-eye-diseases 

 

Cataract and age-related macular degeneration (AMD) are the two leading causes in Australia of vision impairment not correctable by refraction (eye glasses). Cataract is responsible for 37% of such vision loss and AMD is responsible for 26%.1 AMD is responsible for 48% of blindness in Australia and cataract for 12%.1 Smoking increases the risk of both cataract2 and AMD.3, 4 Smoking may also be associated with the rare eye condition Graves’ ophthalmopathy, and recent studies suggest a link between smoking and ocular inflammation. 

3.10.1 Cataract

The ocular lens, which is behind the pupil, focuses light onto the retina. It is normally a transparent organ but with age tends to develop opaque areas, which impair vision. These opaque areas are called cataracts.

There are three main types of cataract, classified by their location within the lens structure: nuclear, cortical and posterior subcapsular. Nuclear cataract, which occurs in the centre of the lens, is the most common.5 Each type of cataract has its own distinct risk factors.2 Smoking is a cause of nuclear cataract.2 A study of almost 4000 Australians aged 49 years and older who were followed up for 10 years found that people who had smoked at some time (ever smokers) had a 40% higher risk of developing nuclear cataract than people who had never smoked.5 A 2018 meta-analysis  of 13 cohort studies, 12 case-control studies, and 18 cross-sectional studies also found an increased risk of cataract in smokers, particularly the nuclear type.6

A prospective cohort study of more than 44,000 men found that smoking intensity and cumulative dose of smoking are associated with an increased risk of requiring cataract surgery. Current smokers who smoked of more than 15 cigarettes per day had a 42% increased risk of cataract extraction compared with never smokers.7 Smoking cessation can decrease the risk of requiring surgery, but it takes many years for this risk to decline to that of an never smoker.  Even after more than 20 years of cessation, men who had smoked about 15 or more cigarettes per day still had a 21% increased risk of cataract extraction compared with never smokers. 7

Although the exact mechanism of causation is not known, many trace metals and other chemicals in cigarette smoke are capable of damaging the proteins in the eyes’ lens. Quitting smoking may reduce the risk of developing nuclear cataract and of progression of cataract.2

Smoking may also be associated with an increased risk for developing posterior subcapsular cataract (situated under the external membrane, usually behind the lens) but more research is required.2

3.10.2 Age-related macular degeneration

The macula is the central area of the retina. It contains the fovea, which is responsible for high-resolution vision. There are two main types of AMD: neovascular (or exudative) and atrophic. AMD usually affects older adults resulting in a loss of vision in the macula, the centre of the visual field.8  AMD is a leading cause of blindness in older people in many developed countries.9, 10

 Smoking is  the most important modifiable risk factor for the development of AMD and its  progression 11 An extensive review of the evidence undertaken for the  2014 US Surgeon General’s report including analysis of two major meta-analyses concluded that smoking causes both types of AMD.3, 12, 13  One of these  meta-analyses included large studies from the US, Netherlands, Australia, France and Japan and the pooled analysis found a four-fold increase in risk for neovascular AMD and a two- to three-fold increase in the risk of atrophic AMD associated with smoking.3 A large cohort study of males in Korea found that the risk of neovascular AMD among past/current male smokers was 50% higher compared with males who had never smoked. There was a dose dependent association between the incidence of neovascular AMD and the duration of smoking and daily cigarette consumption.10

Smokers also have a greater risk of developing AMD at a younger age.14-16 A 2019 study found that current smokers developed neovascular AMD an average of 5.5 years earlier compared with never smokers and 4.4 years younger than ex-smokers.15 Another study found that current smokers were 6.2 years younger than never smokers when they commenced treatment for  neurovascular AMD.16

Oxidative stress is believed to be the major mechanism for smoking-related damage to retinal structures: cigarette smoke is a strong oxidant that causes systemic oxidative stress.4 Smoking may also increase oxidative stress on the macula by removing its defences and reducing macular pigment and plasma levels of antioxidants. Inadequate peripheral blood flow might also contribute to the development of AMD.4

Smokers who develop AMD may also have poorer  clinical outcomes compared to never smokers.9, 16 A 2019 study of more than 900 patients with neurovascular AMD in four countries found 12-month visual outcomes in patients who continued to smoke while receiving therapy for neurovascular AMD were worse than those in ex-smokers or never smokers.16

Smoking cessation appears to reduce the risk of AMD,2, 10 but several decades after quitting smoking, the risk remains higher for former smokers than for never smokers.13 One meta-analysis found evidence of reversibility, with ex-smokers having a lower risk of AMD compared to continuing smokers. Furthermore in this analysis, in patients with neovascular AMD who were treated successfully, there was a higher recurrence rate in those who continued smoking compared with those who quit.3 However the conclusion by the US Surgeon General in 2014 was that the evidence was ‘suggestive but not sufficient to infer that smoking cessation reduced the risk of age-related macular degeneration.4

Australian researchers developed a model predicting the decline in risk of AMD after quitting smoking and used it to assess the cost-effectiveness of smoking cessation in relation to AMD. They found that because of the high cost of treating AMD, smoking cessation interventions are cost-effective in terms of their impact on AMD alone (see Section 17.4.1.3).17 

3.10.3 Glaucoma

Glaucoma is a disease involving damage to the optic nerve and subsequent vision loss or blindness. The condition is often associated with increased intraocular pressure (IOP) but may be present with normal or even below-normal eye pressure. Most cases of glaucoma are open-angle glaucoma (OAG), also called chronic glaucoma. The early stage OAG is usually characterised by a loss of peripheral vision, which may not be noticed at first. As permanent nerve damage occurs, the symptoms become more obvious.18

Data from the Australian Eye Health Survey estimated that around 198, 923 non-Indigenous Australians aged 50 years and over and 2,139 Indigenous Australians aged 40 years and over have glaucoma. When definite and probable cases of glaucoma were combined, the prevalence of glaucoma was estimated to be 3.4% in the non-indigenous population and 1.6% among Indigenous Australians. It appears that many people may not know they have glaucoma with only 52.4% of non-Indigenous Australians and 28.0% of Indigenous Australians with glaucoma in this study reporting a history of the disease.19

 The evidence regarding the association between smoking and glaucoma is mixed. The US Surgeon General’s report in 2004 deemed the evidence at that time to be ‘inadequate to infer the presence or absence of a causal relationship’. p29 A meta- analysis of six observational studies (three cohort and three case-control studies) in 2016  reported there may not be a  causal association between smoking and the development of POAG.20 However, a systematic review in 2016 that included nine case-control studies, five cohort studies and three cross-sectional in design reported that six of the case-control studies found a positive association between smoking and POAG, unlike the remaining studies.21 A large prospective study in 2017 also found a direct association between current smoking and the incidence of glaucoma, and that there was a dose response relationship.22 A US study found that only heavier smokers had an increased risk of glaucoma.23

3.10.4 Graves’ ophthalmopathy

Graves’ ophthalmopathy is a complication of Graves’ disease, a fairly rare autoimmune thyroid disease. The eye complications include protrusion of the eyeballs, double vision, inflammation of eye tissue and damage to the optic nerve.

A number of studies have observed an increased risk among smokers for developing the ocular complications of Graves’ disease.2, 24, 25 The risk appears to increase with the number of cigarettes smoked per day. 24 Smoking also appears to increase the risk of developing the more severe forms of Graves ophthalmopathy, influences the progression of GO and is related to a poorer response to treatment.26, 27

The exact mechanism by which smoking influences Graves’ opthalmopathy is not well understood and more research is needed.2 One study found that the Graves' orbital fibroblasts have an exaggerated response to cigarette smoke and show increased oxidative stress. 24

3.10.5 Ocular inflammatory disease

Ocular inflammatory disease is inflammation of one or more parts of the eye and encompasses uveitis (inflammation of the middle layer of the eye), scleritis (inflammation of the white outer coating) and inflammation of the ocular surface.

Two recent studies have suggested that smoking may be associated with ocular inflammation. One study found that smokers were twice as likely as never smokers to have uveitis.28 The second study found that ocular inflammation was more severe in patients who were smokers and recurred more quickly.29 Cigarette smoke has an inflammatory effect and this may be the mechanism of action.28

3.10.6 Other disorders of the eye

Smoking results in damage to the meibomian gland (oil glands along the edge of the eyelids where the eyelashes are found) which may be a risk factor for dry eye.30 Compared with never smokers, smokers may also have deficits in contrast sensitivity and impaired colour vision .31  Short-term withdrawal from nicotine also affects contrast sensitivity.32


Relevant news and research

For recent news items and research on this topic, click  here. ( Last updated March 2020)


 

References

1. Access Economics. Clear insight. The economic impact and cost of vision loss in Australia.: Eye Research Australia, 2004. Available from: https://www.cera.org.au/wp-content/uploads/2013/12/CERA_clearinsight_overview.pdf.

2. US Department of Health and Human Services. The health consequences of smoking: a report of the Surgeon General. Atlanta, Georgia: US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2004. Available from: https://www.cdc.gov/tobacco/data_statistics/sgr/2004/index.htm.

3. Thornton J, Edwards R, Mitchell P, Harrison R, Buchan I, et al. Smoking and age-related macular degeneration: a review of association. Eye, 2005; 19:935-44. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16151432

4. US Department of Health and Human Services. The Health Consequences of Smoking: 50 Years of Progress. A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014. Available from: https://www.cdc.gov/tobacco/data_statistics/sgr/50th-anniversary/index.htm.

5. Tan J, Wang J, Younan C, Cumming R, Rochtchina E, et al. Smoking and the long-term incidence of cataract: the Blue Mountains Eye Study. Ophthalmic Epidemiology, 2008; 15(3):155–61. Available from: https://www.ncbi.nlm.nih.gov/pubmed/18569810

6. Beltran-Zambrano E, Garcia-Lozada D, and Ibanez-Pinilla E. Risk of cataract in smokers: A meta-analysis of observational studies. Arch Soc Esp Oftalmol, 2018. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30528895

7. Lindblad BE, Hakansson N, and Wolk A. Smoking cessation and the risk of cataract: a prospective cohort study of cataract extraction among men. JAMA Ophthalmol, 2014; 132(3):253-7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24385206

8. Merl-Pham J, Gruhn F, and Hauck SM. Proteomic Profiling of Cigarette Smoke Induced Changes in Retinal Pigment Epithelium Cells. Advances in Experimental Medicine and Biology, 2016; 854:785-91. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26427490

9. Kamao H, Goto K, Mito Y, Miki A, and Kiryu J. Effects of Smoking on Outcomes of Antivascular Endothelial Growth Factor Therapy in Patients with Neovascular Age-Related Macular Degeneration Smoking and Anti-VEGF Therapy in nAMD. J Ophthalmol, 2018; 2018:2353428. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30538852

10. Rim TH, Cheng CY, Kim DW, Kim SS, and Wong TY. A nationwide cohort study of cigarette smoking and risk of neovascular age-related macular degeneration in East Asian men. British Journal of Ophthalmology, 2017. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28292774

11. Velilla S, Garcia-Medina JJ, Garcia-Layana A, Dolz-Marco R, Pons-Vazquez S, et al. Smoking and age-related macular degeneration: review and update. J Ophthalmol, 2013; 2013:895147. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24368940

12. Chakravarthy U, Wong TY, Fletcher A, Piault E, Evans C, et al. Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis. BMC Ophthalmology, 2010; 10:31. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21144031

13. Uslu S, Zubarioglu U, Sozeri S, Dursun M, Bulbul A, et al. Factors Affecting the Target Oxygen Saturation in the First Minutes of Life in Preterm Infants. Journal of Tropical Pediatrics, 2016. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28013253

14. Brandl C, Breinlich V, Stark KJ, Enzinger S, Assenmacher M, et al. Features of Age-Related Macular Degeneration in the General Adults and Their Dependency on Age, Sex, and Smoking: Results from the German KORA Study. PLoS ONE, 2016; 11(11):e0167181. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27893849

15. Detaram HD, Joachim N, Liew G, Vu KV, Burlutsky G, et al. Smoking and treatment outcomes of neovascular age-related macular degeneration over 12 months. British Journal of Ophthalmology, 2019. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31558491

16. Vittorio AF, Nguyen V, Barthelmes D, Arnold JJ, Cheung CMG, et al. Smoking Status and Treatment Outcomes of Vascular Endothelial Growth Factor Inhibitors for Neovascular Age-Related Macular Degeneration. Retina, 2019. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31613840

17. Hurley S, Matthews J, and Guymer R. Cost-effectiveness of smoking cessation to prevent age-related macular degeneration. Cost Effective Resource Allocation, 2008; 6(1):18. Available from: http://www.resource-allocation.com/content/pdf/1478-7547-6-18.pdf

18. Australian Institute of Health and Welfare. Vision Problems among Older Australians Bulletin 27, Canberra Australia: AIHW, 2004.

19. Keel S, Xie J, Foreman J, Lee PY, Alwan M, et al. Prevalence of glaucoma in the Australian National Eye Health Survey. British Journal of Ophthalmology, 2019; 103(2):191-195. Available from: https://bjo.bmj.com/content/bjophthalmol/103/2/191.full.pdf

20. Zhou Y, Zhu W, and Wang C. The effect of smoking on the risk of primary open-angle glaucoma: an updated meta-analysis of six observational studies. Public Health, 2016. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27527843

21. Jain V, Jain M, Abdull MM, and Bastawrous A. The association between cigarette smoking and primary open-angle glaucoma: a systematic review. International Ophthalmology, 2016. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27138591

22. Pérez-de-Arcelus M TE, Martínez-González MÁ, Martín-Calvo N, Fernández-Montero A, Moreno-Montañés J. . Smoking and incidence of glaucoma: The SUN Cohort. Medicine (Baltimore). 2017; 96(1).

23. Law SM, Lu X, Yu F, Tseng V, Law SK, et al. Cigarette smoking and glaucoma in the United States population. Eye (Lond), 2018. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29303150

24. Kau HC, Wu SB, Tsai CC, Liu CJ, and Wei YH. Cigarette Smoke Extract-Induced Oxidative Stress and Fibrosis-Related Genes Expression in Orbital Fibroblasts from Patients with Graves' Ophthalmopathy. Oxidative Medicine and Cellular Longevity, 2016; 2016:4676289. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27340508

25. Yuksel N, Yaman D, Tugce Pasaoglu O, and Pasaoglu H. The Effect of Smoking on Mitochondrial Biogenesis in Patients With Graves Ophthalmopathy. Ophthalmic Plast Reconstr Surg, 2019. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31789788

26. Bartalena L and Piantanida E. Cigarette smoking: number one enemy for Graves ophthalmopathy. Polskie Archiwum Medycyny Wewnetrznej, 2016; 126(10):725-726. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27872448

27. Czarnywojtek A, Komar-Rychlicka K, Zgorzalewicz-Stachowiak M, Sawicka-Gutaj N, Wolinski K, et al. Efficacy and safety of radioiodine therapy for mild Graves' ophthalmopathy in dependence on cigarette consumption - a half year of follow-up. Polskie Archiwum Medycyny Wewnetrznej, 2016. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27534827

28. Lin P, Loh A, Margolis T, and Acharya N. Cigarette smoking as a risk factor for uveitis. Ophthalmology, 2010; 117:585–90. Available from: http://www.ncbi.nlm.nih.gov/20036011

29. Galor A, Feuer W, Kempen J, Kacmaz R, Liesegang T, et al. Adverse effects of smoking on patients with ocular inflammation. British Journal of Ophthalmology, 2010; 94(7):848–53. Available from: http://bjo.bmj.com/content/94/7/848.long

30. Muhafiz E, Aslan Bayhan S, Bayhan HA, and Gurdal C. Effects of chronic smoking on the meibomian glands. International Ophthalmology, 2019. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31410634

31. Fernandes TP, Silverstein SM, Almeida NL, and Santos NA. Visual impairments in tobacco use disorder. Psychiatry Research, 2018; 271:60-67. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30469090

32. Fernandes TMP, Almeida NL, and Santos NAD. Effects of smoking and smoking abstinence on spatial vision in chronic heavy smokers. Sci Rep, 2017; 7(1):1690. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28490803