RERF Report No. 17-12

Paper published in Investigative Ophthalmology and Visual Science§“Is the Association between Smoking and the Retinal Venular Diameter Reversible
following Smoking Cessation?”
Masahide Yanagi, Munechika Misumi, Ryo Kawasaki, Ikuno Takahashi, Katsumasa Itakura,
Saeko Fujiwara, Masazumi Akahoshi, Kazuo Neriishi, Tien Yin Wong, Yoshiaki Kiuchi
Invest Ophthalmol Vis Sci 2014 (January); 55(1):405–11 (doi:10.1167/iovs.13-12512)
Study Findings
After adjustment for such related factors as age, sex, blood pressure, body mass index(BMI), lipid profile, and radiation dose, this analysis of female A-bomb survivors showed that(1) the caliber of veins in the retina increases with the number of cigarettes smoked, and that(2) vein (venular) caliber differences between former smokers and those who never smokeddiminished, until 10 years after quitting smoking their calibers were nearly identical.
Explanation
Smoking has long been considered a risk factor for circulatory diseases (hypertension,
myocardial infarction, and stroke), and it may have harmful effects on the structure of bloodvessels. Retinal vessel caliber, measured from digital images of the fundus, is considered a good
indicator of blood vessel structure, and such changes have been reported to be associated withsmoking in various epidemiological studies. However, there has been little or no data regardingwhether the association increases with the number of cigarettes smoked, and whether there also
are changes in retinal vessel caliber among people who have stopped smoking. Thisepidemiological study addresses those gaps in our knowledge about smoking and blood vesselcaliber.
1. Objectives
To elucidate the association between habitual smoking or smoking cessation and retinal
vessel caliber changes among A-bomb survivors in Hiroshima and Nagasaki who have been
followed by the Radiation Effects Research Foundation through biennial health examinations(Adult Health Study: AHS).
2. Methods
Digital images of the fundus/retina were made for 1,664 participants in AHS
ophthalmological examinations from 2006 to 2008. To observe retinal vessel caliber, standard
indices, called the central retinal artery and vein equivalents (CRAE and CRVE), werecalculated using image analysis software. To assess smoking habits, current smoking status wasconfirmed based on AHS medical history records, and the average number of cigarettes smoked
per day was calculated. Information about smoking cessation was confirmed based on past AHS
medical history records and mail survey information, and the number of years of smoking

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cessation was calculated. Allowing for related factors such as age, sex, blood pressure, BMI,
lipid profile, diabetes, C-reactive protein, white blood cell count, and radiation dose, theassociation between habitual smoking or smoking cessation and changes in retinal vessel(artery/vein) caliber was evaluated.
3. Results(1) CRAE: No significant association was observed between habitual smoking or the number ofyears of smoking cessation and retinal artery caliber in either males or females.
(2) CRVE: Retinal venular caliber was positively associated with the number of cigarettes
smoked per day among female smokers. Compared with non-smokers, CRVE was increased
by about 5% on average for those who smoked 10 or more cigarettes per day (trend p = 0.001).
Among females, while the retinal venular caliber of those who had stopped smoking for lessthan 10 years was significantly larger than that of non-smokers, the venular caliber for neversmokers and those who had stopped smoking for 10 or more years was indistinguishable (p =0.99). No significant associations of either retinal artery or venular calibers were observed
among males for smoking frequency or the number of years of smoking cessation.
4. Discussion
1) The results of this study, which find that retinal venular caliber is significantly
associated with habitual smoking and the number of years of smoking cessation, are similar to
those of several other epidemiological studies, such as the Rotterdam Study and theSingapore/Malay Study. Increased venular caliber is generally believed to be associated withcirculatory diseases (e.g., cerebral ischemia). Smoking is known to accelerate bothinflammation and vascular endothelial dysfunction. Yet in this study an analysis adjusting forthe effects of typical inflammation markers (white blood cell count and C-reactive protein) still
showed an association between smoking and retinal venular caliber, which suggests there may
be non-inflammation-mediated effects on blood vessels as a result of smoking.
2) Generally, aging effects on the blood vessels appear earlier in males than in females. In
this study, smoking effects were not observed in males. A possible reason for this is that men
tend to experience accelerated effects of aging on the blood vessels, such as hardening of vessel
walls, which may have masked smoking effects on the vessels among our study cohort at thetime of examination (average age: 73.8).
3) The results of this study suggest that among Japanese females smoking cessation for asufficient period of time may reverse the effects of smoking on retinal venular caliber. Theseresults also shed some mechanistic light on the various reports that 10 or more years of smoking
cessation decrease the risk of mortality from myocardial infarction and cerebral infarction.
The Radiation Effects Research Foundation has studied A-bomb survivors and their offspring in
Hiroshima and Nagasaki for more than 60 years. RERF’s research achievements are considered the2RERF Report No. 17-12

principal scientific basis for radiation risk assessment by the United Nations Scientific Committee on
the Effects of Atomic Radiation (UNSCEAR) and for recommendations regarding radiation
protection standards by the International Commission on Radiological Protection (ICRP). RERF
expresses its profound gratitude to the A-bomb survivors and survivors’ offspring for theircooperation in our studies.

§Investigative Ophthalmology and Visual Science (IOVS), published online several times a month,is an official journal of the Association for Research in Vision and Ophthalmology (ARVO), aninternational organization whose purposes are to encourage and assist research, training, publication,and dissemination of knowledge in vision and ophthalmology. Included are original contributions
that emphasize clinical and laboratory hypothesis-based research with statistically good results thatclearly advance the fields of ophthalmic and vision research. (2012 impact factor for IOVS: 3.441)

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