Cutaneous and Ocular Toxicology

ISSN: 1556-9527 (Print) 1556-9535 (Online) Journal homepage: http://www.tandfonline.com/loi/icot20

Effect of smoking on retina nerve fiber layer and ganglion cell-inner plexiform layer complex Mehmet Serdar Dervişoğulları, Yüksel Totan, Aylin Tenlik, Aslıhan Yüce & Emre Güler To cite this article: Mehmet Serdar Dervişoğulları, Yüksel Totan, Aylin Tenlik, Aslıhan Yüce & Emre Güler (2015) Effect of smoking on retina nerve fiber layer and ganglion cellinner plexiform layer complex, Cutaneous and Ocular Toxicology, 34:4, 282-285, DOI: 10.3109/15569527.2014.975240 To link to this article: http://dx.doi.org/10.3109/15569527.2014.975240

Published online: 03 Nov 2014.

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Date: 06 November 2015, At: 04:35

http://informahealthcare.com/cot ISSN: 1556-9527 (print), 1556-9535 (electronic) Cutan Ocul Toxicol, 2015; 34(4): 282–285 ! 2014 Informa Healthcare USA, Inc. DOI: 10.3109/15569527.2014.975240

RESEARCH ARTICLE

Effect of smoking on retina nerve fiber layer and ganglion cell-inner plexiform layer complex Mehmet Serdar Dervi¸sog˘ulları, Yu¨ksel Totan, Aylin Tenlik, Aslıhan Yu¨ce, and Emre Gu¨ler

Downloaded by [Australian National University] at 04:35 06 November 2015

¨ zal University, Ankara, Turkey Department of Ophthalmology, Medical School, Turgut O

Abstract

Keywords

Purpose: The aim of this study is to show the effects of smoking on retina layers, especially retina nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer complex (GCIPL). Materials and methods: Participants smoking for more than 10 years at least 1 pack of cigarettes a day and a control group, both including participants between ages of 20 and 50 years with no other systemic or ocular diseases were studied. After normality tests, an independent sample t test was used to analyze the differences in age, sex, spherical equivalent (SE), intraocular pressure (IOP), axial length (AL), GCIPL and RNFL values between the groups. Results: There were 44 participants in each group. There were 32 (62.5%) men and 12(37.5%) women in smokers and 36 (77.88%) men and 8 (22.22%) women in control group. Mean ages were 39.85 ± 8.41 and 38.66 ± 10.47 years, mean spherical equivalent (SE) values were 0.15 ± 0.4 and 0 ± 0.29 dioptries in smokers and control groups, respectively. The IOP, AXL, GCIPL and RNFL values were 17.58 ± 3.41 mmHg, 23.69 ± 0.56 mm, 84.3 ± 5.83 mm and 92.3 ± 3.51 mm in the smokers group and 18.5 ± 2.91 mmHg, 23.45 ± 0.72 mm, 86.11 ± 8.02 mm and 97.66 ± 8.23 mm in the control group. The inferior, superior, nasal and temporal values of RNFL quadrants were 123.18 ± 26.14, 117.05 ± 5.51, 64.95 ± 8.67 and 63.5 ± 6.88 mm in the smokers group and 130.81 ± 11.8, 123.55 ± 11.03, 72.44 ± 9.84 and 58.44 ± 7.48 mm in the control group. There were no significant difference of age, sex, SE, IOP, AXL and GCIPL values between the smokers and control groups (p40.05). The mean RNFL was significantly thinner in the smokers group compared to controls (p ¼ 0.03, independent t test). Inferior and superior quadrants of RNFL decreased in smokers group (p ¼ 0.01 and p ¼ 0.03, respectively) but temporal and nasal quadrants did not seem to be changed (p ¼ 0.96 and p ¼ 0.07, respectively). Discussion: Smoking may affect RNFL thickness but not GCIPL.

Ganglion cell, inner plexiform layer complex, retinal nerve fiber layer, smoking

Introduction Smoking affects nearly every organ of the body and is the number one cause of premature death among elderly in the world1,2. It is also proposed as a major risk factor for dementia, cognitive impairment and Alzheimer’s disease3,4. Smoking is also associated with many ocular conditions, mainly through ischemic or oxidative mechanisms. Smoking directly causes a decrease in orbital and ocular blood flow5. In addition, smoking causes high-oxidative stress, because tobacco smoke contains oxidizing agents that produce free radicals and may cause cell damage and even cell death by apoptosis6. Some common eye diseases such as cataract7, age-related macular degeneration8, retinal venous occlusion9, anterior ischemic optic neuropathy10, thyroid ophthalmopathy11 and primary open-angle glaucoma12 were found to be associated with cigarette smoking. Tobacco optic neuropathy (TON), a once common but now rare disease characterized by bilateral central visual disturbance, may occur as a result Address for correspondence: Dr. Mehmet Serdar Dervi¸sog˘ulları, ¨ zal Department of Ophthalmology, Medical School, Turgut O University, Ankara, Turkey. E-mail: [email protected]

History Received 27 June 2014 Revised 3 September 2014 Accepted 3 October 2014 Published online 30 October 2014

of direct toxic damage to the optic nerve particularly in heavy smokers13. A previous study found diffusely decreased retinal sensitivity and peripheral scotomata in the visual fields of healthy heavy cigarette smokers14. The peripapillary retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer complex (GCIPL) thickness, which are thinned in glaucomatous15 and non-glaucomatous optic neuropathies16 and central nervous system diseases17, can be successfully evaluated with high definition optical coherence tomography (HD-OCT) devices. However, no study has evaluated the effects of chronic smoking on these parameters in healthy subjects. The aim of this study was to evaluate the possible changes in RNFL and GCIPL on healthy but chronic heavy smokers.

Materials and methods In this prospective study, all participants were selected from the patients who came for eye examination, family members ¨ zal University of patients and hospital staff of Turgut O Hospital between May 2013 and September 2013. The study group consisted of 44 participants (32 men and 12 women)

Smoking and retina

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DOI: 10.3109/15569527.2014.975240

who were chronic, heavy smokers18 smoking more than 20 cigarettes per day for more than 10 years between ages of 20 and 50 years with no other systemic or ocular diseases. The standard pack year method was used to measure the incidence and degree of smoking. The control group consisted of age- and gender-matched (36 men and 8 women) healthy non-smokers who maintained adequate diet. This study was approved by the local ethics committee. The research adhered to the tenets of the Declaration of Helsinki, and a detailed written informed consent was taken before each individual’s participation in the study. In both groups, the subjects with a small refractive error (+1 to 1 D spherical equivalent) and with normal visual acuities in Snellen chart were enrolled in the study. The general physical examination together with biochemical laboratory data disclosed no evident systemic disease in all study and control subjects. Neurological diseases like Multiple Sclerosis and Alzheimer’s disease were excluded by history and examination. None of the subjects had any pathological findings such as cornea opacities, cataract, glaucoma, media opacities or optic neuropathy at the ophthalmologic examination. Subjects with high-refractive errors, under local or systemic medication, known to be exposed to any kind of neurotoxic substances or drugs, and with a history of eye or systemic diseases were excluded. Young, healthy and heavy smokers who maintained adequate diet and who had no alcohol consumption were chosen to rule out the effect of alcoholism and malnutrition. Only the right eyes were evaluated. The participants underwent full ophthalmological examination including measurement of the best corrected visual acuity (BCVA), mean spherical equivalent (SE) measurement by cycloplegic refraction, assessment of ocular motility and alignment, assessment of anterior segment and fundus. Intraocular pressures (IOP) were measured diurnally at 09:00, 11:00 and 14:00 with the Pascal Dynamic Contour Tonometer (Swiss Microtechnology AG, Port, Switzerland), and the average of three measurements was taken. Axial length (AL) was determined by Nidek AL-Scan optical biometer (Nidek Co Ltd. Gamagori, Japan). White-on-white standart automated perimetry was performed using a Humphrey Field AnalyzerÕ Model 750 (Carl Zeiss Meditec, Jena, Germany) and the C-30-2 SITA-standard strategy. OCT measurements Cirrus HD-OCT (Cirrus Version 6.0; Carl Zeiss Meditec, Dublin, CA) was used to obtain macular scan using the macular cube 200  200 scan protocols in each study eye. The prototype GCA algorithm, incorporated in Cirrus HD-OCT software Version 6, was used to measure the GCIPL thickness within a 14.13-mm2 elliptical annulus area centered on the fovea. The GCA algorithm segmented GCIPL within the outer boundary of RNFL and outer boundary of inner plexiform layer (IPL) at the macular region, thus the segmented layer led to the measurement of the GCIPL thickness. The average, minimum, and six sectorial (superotemporal, superior, superonasal, inferotemporal, inferior and inferonasal) GCIPL thicknesses were measured from the elliptical annulus centered on the fovea. RNFL measurements were also assessed

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with the 6 mm  6 mm data cube captured by the Optic Disc Cube 200  200 scan. The average and four sectorial (inferior, superior, nasal and temporal) RNFL thicknesses were measured. Internal fixation targets were used for proper alignment of the eye. All OCT scans were performed once by the same experienced operator. Each participant’s head was fixed on the sustainer with the eye focusing on the international fixation target without blinking and moving the eye while six radial retinal scans were performed. The scans were only accepted if they were completed, well centered, had signal strength of at least 6 and had no motion or blinking artifacts. Statistics Statistical analysis was performed using SPSS 20.0 for Windows (SPSS Inc., Chicago, IL). The Shapiro–Wilk test was performed first for normality, and the independent samples t test was performed after that. The p value less than 0.05 was considered to be significant.

Results There were 44 participants in each group. There were 32 (62.5%) men and 12 (37.5%) women in smokers and 36 (77.88%) men and 8 (22.22%) women in control group. The mean age was 39.85 ± 8.41 years in the smokers group. The SE, IOP, AL, GCIPL and RNFL values were 0.15 ± 0.4 dioptries (D), 17.58 ± 3.41 mmHg, 23.69 ± 0.56 mm, 84.3 ± 5.83 mm and 92.3 ± 3.51 mm in the smokers group. The mean age was 38.66 ± 10.47 years in the control group. The SE, IOP, AL, GCIPL and RNFL values were 0 ± 0.29 D, 18.5 ± 2.91 mmHg, 23.45 ± 0.72 mm, and 86.11 ± 8.02 and 97.66 ± 8.23 mm in the control group. Based on the Shapiro–Wilk test results, variables with a normal distribution were analyzed by independent samples t test. There were no significant differences of age, sex, SE, _ IOP, AL and GCIPL values between the smokers and control groups (p40.05) (Table 1). The mean RNFL was significantly thinner in the smokers group compared to controls (p ¼ 0.03, independent samples t test) (Table 2). The inferior, superior, nasal and temporal values of RNFL quadrants were 123.18 ± 26.14, 117.05 ± 5.51, 64.95 ± 8.67 and 63.5 ± 6.88 mm in the smokers group and 130.81 ± 11.8, 123.55 ± 11.03, 72.44 ± 9.84 and 58.44 ± 7.48 mm in the control group. Inferior and superior, nasal quadrants of RNFL were thinner in smokers group (p ¼ 0 and p ¼ 0.03, Table 1. Demographic and ocular characteristics of study participants.

Parameter Age (years) Sex Male Female SE (D) IOP (mmHg) AL (mm)

Smokers Mean (SD)

Controls Mean (SD)

p Value

39.85 (8.41)

38.66 (10.47)

0.32

32 12 0 (0.29) 17.58 (3.41) 23.69 (0.56)

36 8 0.15 (0.40) 18.5 (2.91) 23.45 (0.72)

0.47 0.13 0.72 0.11

SE, spherical equivalent; IOP, intraocular pressure; AL, axial length; SD, standard deviation; D, diopter.

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M. S. Dervi¸sog˘ulları et al.

Cutan Ocul Toxicol, 2015; 34(4): 282–285

Table 2. Mean GC-IPL and peripapillary RNFL thicknesses as measured by Cirrus HD-OCT for smokers and controls.

Parameter

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GC-IPL (mm) Average Superotemporal Superior Superonasal Inferotemporal Inferior Inferonasal RNFL (mm) Average Inferior Superior Nasal Temporal

Smokers Mean (SD)

Control Mean (SD)

84.3 84.30 84.65 84.30 85.40 83.40 84.25

(5.83) (6.05) (6.76) (7.72) (5.77) (6.19) (6.02)

86.11 86.77 87.55 86.05 86.11 86.33 85.94

92.3 123.18 117.05 64.95 63.5

(3.51) (26.14) (5.51) (8.676) (6.88)

97.66 130.81 123.55 72.44 85.44

p Value

(8.02) (8.26) (9.11) (8.07) (7.72) (8.51) (8.57)

0.94 0.72 0.69 0.98 0.76 0.71 0.83

(8.23) (11.8) (11.039 (9.84) (7.48)

0.0310.001 0.03 0.07 0.96

GC-IPL, ganglion cell inner plexiform layer complex; RNFL, retinal nerve fiber layer; SD, standard deviation; mm, micrometer.

respectively), but nasal and temporal quadrants did not show significant difference (p ¼ 0.07 and p ¼ 0.96, respectively). In visual field analysis, glaucoma hemifield test was normal, and there were no scotomas.

Discussion This study was performed to determine the effects of smoking on GCIPL and RNFL. Our results showed that RNFL was _ thinner in smokers but GCIPL was not affected (Table 2). Sectorial analyses showed that inferior and superior quadrants of RNFL were thinner in smokers, but temporal and nasal quadrants were not. Recent studies have evaluated the RNFL, ganglion cell layer and inner plexiform layer at macular regions and reported similar glaucoma discriminating performance compared with visual field sensitivity19. Optical coherence tomography (OCT) is a non-invasive and objective cross-sectional tissue imaging technique, which is now used widely to image the inner retinal layer, which includes the ganglion cell layer, RNFL and inner plexiform layer20. Hepsen et al. suggested that retinal sensitivity decreases in chronic, healthy heavy cigarette smokers, based on automated perimeter results14. However, no previous study evaluated the effect of chronic smoking on RNFL or GCIPL and in our study, RNFL was thinner in smokers but GCIPL was not affected. Regarding the sectorial analyses, all quadrants were thinner in smokers only the exception of the temporal quadrant as it is also known to be the most damage-resistant quadrant in glaucoma21. In our study, RNFL thickness decreased in chronic heavy smokers and to understand the mechanisms underlying this, one should overview the explanations about the origin of tobacco optic neuropathy (TON)13,22. The effect of smoking in the development of TON is thought to be related to the production of reactive oxygen species and reduced blood flow due to the vasoconstructive effect of nicotine23. In addition, cigarette contains cyanogen, precursor of cyanide neurotoxin that has been implicated as the cause of TON24. The papillomacular bundle and the macular retinal ganglion

cells are known to be preferentially involved in toxic exposition13. In our study, nasal and temporal sectors seem to be spared. This maybe because of the small size of the sample, and results could be influenced by the variability of RNFL measurement. A multifactorial etiology has been postulated to explain the decreased RNFL. In our study, the nutritional histories of healthy heavy smokers indicated that they were all well nourished and also free of neurologic or hematologic stigmata of nutritional deficiency and nutrition would not seem to be a likely explanation for the RNFL loss in our patients. It is also known that RNFL may significantly be influenced by age, sex and AL25. However, those parameters were not significantly different between smokers and controls in our study. The retinal ganglion cell layer is the first layer within the retina to be affected by early glaucoma26. Similar to RNFL, GCIPL may be significantly influenced by age, sex and axial length, while ethnicity seems to affect RNFL but not GCIPL27. It is well established from human and animal studies that there are large differences in retina ganglion cell (RGC) number between individuals. Because there is a direct relationship between the number of RGCs and the RGC layer thickness, a variation in GCIPL thickness reflects the real variation in the number of ganglion cells, as previously demonstrated in humans28. In our study, we did not observe any smoking-related changes in GCIPL thickness, but it is important to remember that it is still unknown whether axonal pathology precedes or follows RGC loss, like in glaucoma26. To the best of our knowledge, there are no studies to evaluate the effect of smoking on GCIPL and RNFL, but some other studies have demonstrated a reduction in retinal blood flow5,29, choroidal blood flow and choroidal thickness5,30 following smoking and decrease of retinal sensitivity in visual field tests of smokers14. A previous study suggested that smoking might be related to the elevation of IOP in middle aged subjects31. In our study, mean IOP values did not show any significant difference between smokers and controls. Major limitations of our study are the small sample size and the variability of RNFL measurements that could influence the results. In conclusion, our study results suggested that RNFL thickness decreases in chronic, healthy heavy cigarette smokers, whereas GCIPL thickness was not affected. Chronic nicotine toxicity by direct neurotoxic effect on the optic nerve and vascular effect or both seem to be reasonable causes of RNFL loss. To the best of our knowledge, our study is the first to evaluate the effect of smoking on GCIPL and RNFL thickness. However, further and detailed studies in larger samples including contrast sensitivity, pattern VEP and pattern ERG are needed to evaluate and distinguish early retinal and/or optic nerve dysfunctions in cigarette smokers.

Declaration of interest The authors declare no conflict of interest.

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Effect of smoking on retina nerve fiber layer and ganglion cell-inner plexiform layer complex.

The aim of this study is to show the effects of smoking on retina layers, especially retina nerve fiber layer (RNFL) and ganglion cell-inner plexiform...
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