Downloaded from http://bjo.bmj.com/ on December 11, 2014 - Published by group.bmj.com
BJO Online First, published on November 13, 2013 as 10.1136/bjophthalmol-2013-304044 Clinical science
The effect of nicotine on choroidal thickness Mehmet Ozgur Zengin, Esat Cinar, Cem Kucukerdonmez Department of Ophtalmology, Izmir University Faculty of Medicine, Izmir, Turkey Correspondence to Dr Cem Kucukerdonmez, Gursel Aksel Bulvarı, No. 14 35350, Uckuyular, Izmir, Turkey; [email protected] Received 20 July 2013 Revised 23 October 2013 Accepted 24 October 2013
ABSTRACT Purpose To investigate the effect of nicotine on choroidal thickness using optical coherence tomography (OCT). Design Prospective, case–control study. Methods Sixteen young, healthy subjects and 16 age and gender matched control cases were included in this study; 4 mg nicotine gum was given to the study group and placebo gum to the control group. All participants underwent OCT scanning with a high-speed and resolution spectral-domain OCT device (3D OCT 2000, Topcon, Japan) at baseline, and 1 h following nicotine or placebo administration. The measurements were taken in the morning (10:00–12:00 hours) to avoid diurnal fluctuation. Results The median foveal choroidal thickness at baseline was 337.00 μm (IQR 84.50), which decreased to 311.00 μm (IQR 78.00) at 1 h following oral nicotine intake ( p=0.001). The median choroidal thickness was also significantly decreased at five other extrafoveal points ( p0.05). Tne baseline choroidal thickness measurements of the study and control groups showed no significant difference (table 1). The median choroidal thickness measurements of nicotine users at baseline, and at 1 h following nicotine gum are shown in table 2. At the fovea, choroidal thickness, which was 337.00 μm (IQR 84.50) (median (IQR)) at baseline, decreased to 311.00 μm (IQR 78.00) at 1 h following nicotine intake. ( p=0.001). Nicotine caused a significant reduction in choroidal thickness, compared with baseline, at all six measurement points. However, the choroidal thicknesses of the control group revealed no significant difference at all points when comparing measurements at baseline with 1 h after placebo intake (table 3). Figures 1A,B and 2A,B illustrate the change in choroidal thickness at each study interval for an individual in the nicotine user and control groups, respectively. 2
Table 1 The median choroidal thickness measurements of the study and control groups at baseline
T3 T2 T1 F N1 N2
Median (IQR) (μm) Nicotine
Median (IQR) (μm) Controls
p Value
267.50 (99.75) 295.00 (90.00) 315.50 (83.50) 337.00 (84.50) 305.50 (109.50) 295:00 (104.50)
274.00 296.50 305.50 330.50 310.50 289.50
0.678 0.850 0.610 0.650 0.940 0.678
(92.75) (100.25) (106.00) (104.25) (133.50) (112.50)
F, choroidal thickness at fovea; N1, choroidal thickness at 500 μm nasal to the fovea; N2, choroidal thickness at 1000 μm nasal to the fovea; T1, choroidal thickness at 500 μm temporal to the fovea; T2, choroidal thickness at 1000 μm temporal to the fovea; T3, choroidal thickness at 1500 μm temporal to the fovea.
Side effects of the nicotine gum such as throat irritation, mild dyspepsia, cough and a cold feeling were reported, in the study cases, but these were minor.
DISCUSSION As a highly vascular ocular structure, the choroid is directly influenced by intraocular and perfusion pressure; therefore, real time high-definition images of the choroid are more likely to demonstrate the real time vascular status of this tissue in vivo.18 It is suggested that even histology cannot demonstrate the thickness of the living choroid. Moreover, OCT is shown to be superior to histology to reflect accurate choroidal thickness.19 However, there is still debate on the relationship of choroidal thickness with choroidal blood flow. Many recent studies have reported ocular disorders associated with altered abnormal choroidal thickness.20–23 Also, there are recent data on the haemodynamic effect of chemicals—sildenafil and cigarettes— on the choroid, obtained by OCT.7 14 It has been reported that sildenafil citrate increases choroidal thickness due to a vasodilatory effect of sildenafil citrate on the choroidal circulation.14 This relationship was further investigated by Kim et al24 using swept-scan high-frequency digital ultrasound to measure the ocular blood flow. Moreover, in a recent study by Ulaş et al,25 significant choroidal thinning was reported in chronic renal failure patients after haemodialysis. In another recent study on this topic by Rishi et al,26 the choroidal thickness in eyes with polypoidal choroidal vasculopathy was found to be higher than normal. The authors hypothesised that the high mean ocular perfusion pressure could possibly play a
Table 2 The median choroidal thickness measurements of the study group at baseline, and one following oral nicotine intake
T3 T2 T1 F N1 N2
Median (IQR) (μm) Baseline
Median (IQR) (μm) 1 h after nicotine intake
p Value
267.50 295.00 315.50 337.00 305.50 295.00
263.50 (75.00) 284.50 (71.50) 278.50 (89.25) 311.00 (78.00) 283.00 (92.00) 262.50 (109.00)
0.024 0.008 0.026 0.001 0.004 0.010
(99.75) (90.00) (83.50) (84.50) (109.50) (104.50)
F, choroidal thickness at fovea; N1, choroidal thickness at 500 μm nasal to the fovea; N2, choroidal thickness at 1000 μm nasal to the fovea; T1, choroidal thickness at 500 μm temporal to the fovea; T2, choroidal thickness at 1000 μm temporal to the fovea; T3, choroidal thickness at 1500 μm temporal to the fovea.
Zengin MO, et al. Br J Ophthalmol 2013;0:1–5. doi:10.1136/bjophthalmol-2013-304044
Downloaded from http://bjo.bmj.com/ on December 11, 2014 - Published by group.bmj.com
Clinical science Table 3 The median choroidal thickness measurements of the control group at baseline, and 1 h following oral placebo intake
T3 T2 T1 F N1 N2
Median (IQR) (μm) Baseline
Median (IQR) (μm) 1 h after placebo intake
p Value
274.00 (92.75) 296.50 (100.25) 305.50 (106.00) 330.50 (104.25) 310.50 (133.50) 289.50 (112.50)
276.50 296.00 306.50 332.00 311.00 290.00
0.158 0.887 0.379 0.271 0.222 0.678
(99.25) (82.50) (97.50) (103.75) (127.00) (111.75)
F, choroidal thickness at fovea; N1, choroidal thickness at 500 μm nasal to the fovea; N2, choroidal thickness at 1000 μm nasal to the fovea; T1, choroidal thickness at 500 μm temporal to the fovea; T2, choroidal thickness at 1000 μm temporal to the fovea; T3, choroidal thickness at 1500 μm temporal to the fovea.
role in the aetiology of the disease. All of the above-mentioned studies give strong evidence that choroidal thickness reflects choroidal blood flow. According to the results of our study, chewing 4 mg of nicotine gum decreased choroidal thickness compared with placebo. Rojanapongpun and Drance6 studied the effect of nicotine on the ophthalmic artery flow velocity using transcranial Doppler ultrasound. They observed that small doses of nicotine (nicotine gum) increased blood flow velocities in the ophthalmic artery while finger blood flow was significantly decreased when comparing the nicotine-tested glaucoma group with the placebotested group. Steigerwalt et al9 found a reduction in blood flow velocity in the posterior ciliary artery following smoking, which the authors suggested was a good indicator of peripapillary choroidal blood flow, with colour duplex scanning. They
proposed that this decrease was due to the increase in the vascular resistance of the vessels. In another study using the laser speckle method, Tamaki et al27 reported a decrease in choroidal blood flow 30 min after smoking. Although choroidal blood flow was not measured directly in the current study, when previous reports about nicotine and ocular blood flow changes are considered, our results support the hypothesis of the relationship between choroidal thickness and ocular blood flow. Moreover, cigarette smoking has been shown to be related to choroidal thickness decrease in otherwise healthy subjects.7 In our opinion, our study findings give further evidence that choroidal thickness correlates directly with choroidal blood flow. There are several limitations to our study. One is that we have no quantification of nicotine levels for our subjects. Ideally, we would be able to measure blood serum nicotine levels to quantify the amount of nicotine being absorbed through the gum. Without this information, we cannot definitively identify when nicotine concentrations reached their maximum. However, based on the investigation reported by Russell and colleagues28 on blood nicotine levels after cigarette smoking and nicotine gum, we can estimate when nicotine might reach the maximum level. Their study revealed maximum blood plasma nicotine levels 1 h after the consumption of 4 mg nicotine gum, which was comparable to that of smoking one cigarette.28 In addition, the study by Sizmaz et al,7 which showed significant choroidal thickness reduction at 1 h after smoking, supports these findings. Other limitations of the current study are the limited number of cases and the potential interobserver and intraobserver bias while measuring choroidal thickness manually. However, this bias is an issue to be solved in all studies regarding choroidal thickness measurements. To include more than one
Figure 1 Choroidal thickness measurements of a participant in the study group at baseline (A) and at 1 h (B) after oral nicotine intake.
Zengin MO, et al. Br J Ophthalmol 2013;0:1–5. doi:10.1136/bjophthalmol-2013-304044
3
Downloaded from http://bjo.bmj.com/ on December 11, 2014 - Published by group.bmj.com
Clinical science Figure 2 Choroidal thickness measurements of a participant in the control group at baseline (A) and at 1 h (B) after oral placebo intake.
measurement point and to use two independent observer may partly overcome this problem. The relatively small sample size may also result in type 1 error; however, the design of the study with age and sex-matched control groups makes the results more valuable. Besides these limitations, to the best of our knowledge this is the first study to investigate the isolated effects of nicotine on choroidal thickness. As there is growing evidence in the literature on the relationship between choroidal thickness and choroidal blood flow, the findings of this preliminary study may be of clinical importance. We believe that the results of this preliminary study will be useful in future studies about this topic. Contributors Conception and design: MOZ and CK; acquisition of data: MOZ; analysis and interpretation of data: MOZ, CK and EC; article drafting and revising: CK; final approval: CK. Competing interests None.
3
4 5
6
7
8
9 10
Patient consent Obtained. Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
11
Ethics approval The study protocol was approved by Izmir University Institutional Review Board and Ethics Committee, and the research adhered to the tenets of the Declaration of Helsinki.
12
Provenance and peer review Not commissioned; externally peer reviewed.
13 14
REFERENCES 1
2
4
Dean JD, Matthews SB, Dolben J, et al. Cholesterol rich apo B containing lipoproteins and smoking are independently associated with macrovascular disease in normotensive NIDDM patients. Diabet Med 1994;11:740–7. Bloom RJ, Stevick CA, Lennon S. Patient perspectives on smoking and peripheral vascular disease. A veteran population survey. Am Surg 1990;56:535–9.
15 16
Riefkohl R, Wolfe JA, Cox EB, et al. Association between cutaneous occlusive vascular disease, cigarette smoking, and skin slough after rhytidectomy. Plast Reconstr Surg 1986;77:592–5. Robinson F, Petrig BL, Riva CE. The acute effect of cigarette smoking on macular capillary blood flow in humans. Invest Ophthalmol Vis Sci 1985;26:609–13. Morgado PB, Chen HC, Patel V, et al. The acute effect of smoking on retinal blood flow in subjects with and without diabetes. Ophthalmology 1994;101:1220–6. Rojanapongpun P, Drance SM. The effects of nicotine on the blood flow of the ophthalmic artery and the finger circulation. Graefes Arch Clin Exp Ophthalmol 1993;231:371–4. Sizmaz S, Küçükerdönmez C, Pinarci EY, et al. The effect of smoking on choroidal thickness measured by optical coherence tomography. Br J Ophthalmol 2013;97:601–4. Wimpissinger B, Resch H, Berisha F, et al. Response of choroidal blood flow to carbogen breathing in smokers and non-smokers. Br J Ophtalmol 2004;88:776–81. Steigerwalt RD Jr, Laurora G, Incandela L, et al. Ocular and orbital blood flow in cigarette smokers. Retina 2000;20:394–7. Bill A. Circulation in the eye. In: Renkin EM, Michel Cc, eds. Handbook in physiology. Microcirculation, Part 2. The American Physiological Society 1984: 1001–35. Manjunath V, Taha M, Fujimoto JG, et al. Choroidal thickness in normal eyes measured using Cirrus-HD optical coherence tomography. Am J Ophthalmol 2010;150:325–9. Drexler W, Fujimoto JG. State-of-the-art retinal optical coherence tomography. Prog Retin Eye Res 2008;27:45–88. Sander B, Larsen M, Thrane L, et al. Enhanced optical coherence tomography imaging by multiple scan averaging. Br J Ophthalmol 2005;89:207–12. Vance SK, Imamura Y, Freund KB. The effects of sildenafil citrate on choroidal thickness as determined by enhanced depth imaging optical coherence tomography. Retina 2011;31:332–5. Rabinoff M, Caskey N, Rissling A, et al. Pharmacological and chemical effects of cigarette additives. Am J Public Health 2007;97:1981–91. Benowitz NL, Hukkanen J, Jacob P III. Nicotine chemistry, metabolism, kinetics and biomarkers. Handb Exp Pharmacol 2009:29–60. doi:10.1007/978-3-54069248-5_2
Zengin MO, et al. Br J Ophthalmol 2013;0:1–5. doi:10.1136/bjophthalmol-2013-304044
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19
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West R, Hajek P, Foulds J, et al. A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray and inhaler. Psychopharmacology 2000;149:198–202. Manjunath V, Goren J, Fujimoto JG, et al. Analysis of choroidal thickness in age-related macular degeneration using spectral-domain optical coherence tomography. Am J Ophthalmol 2011;152:663–8. Maul EA, Friedman DS, Chang DS, et al. Choroidal thickness measured by spectral domain optical coherence tomography: factors affecting thickness in glaucoma patients. Ophthalmology 2011;118:1571–9. Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol 2008;146:496–500. Maruko I, Iida T, Sugano Y, et al. Subfoveal choroidal thickness after treatment of central serous chorioretinopathy. Ophthalmology 2010;117:1792–9. Maruko I, Iida T, Sugano Y, et al. Subfoveal choroidal thickness after treatment of Vogt–Koyanagi–Harada disease. Retina 2011;31:510–17.
Zengin MO, et al. Br J Ophthalmol 2013;0:1–5. doi:10.1136/bjophthalmol-2013-304044
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26
27
28
Fujiwara T, Imamura Y, Margolis R, et al. Enhanced depth imaging optical coherence tomography of the choroid in highly myopic eyes. Am J Ophthalmol 2009;148:445–50. Kim DY, Silverman RH, Chan RVP, et al. Measurement of choroidal perfusion and thickness following systemic sildenafil (Viagra). Acta Ophthalmol 2013;91:183–8. Ulaş F, Doğan U, Keleş A, et al. Evaluation of choroidal and retinal thickness measurements using optical coherence tomography in non-diabetic haemodialysis patients. Int Ophthalmol 2013;33:533–9. Rishi P, Rishi E, Mathur G, et al. Ocular perfusion pressure and choroidal thickness in eyes with polypoidal choroidal vasculopathy, wet-age-related macular degeneration, and normals. Eye 2013;27:1038–43. Tamaki Y, Araie M, Nagahara M, et al. The acute effects of cigarette smoking on human optic nerve head and posterior fundus circulation in light smokers. Eye 2000;14:67–72. Russell MA, Feyerabend C, Cole PV. Plasma nicotine levels after cigarette smoking and chewing nicotine gum. BMJ 1976;1:1043–6.
5
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The effect of nicotine on choroidal thickness Mehmet Ozgur Zengin, Esat Cinar and Cem Kucukerdonmez Br J Ophthalmol published online November 13, 2013
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BJO Online First, published on November 13, 2013 as 10.1136/bjophthalmol-2013-304044 Clinical science
The effect of nicotine on choroidal thickness Mehmet Ozgur Zengin, Esat Cinar, Cem Kucukerdonmez Department of Ophtalmology, Izmir University Faculty of Medicine, Izmir, Turkey Correspondence to Dr Cem Kucukerdonmez, Gursel Aksel Bulvarı, No. 14 35350, Uckuyular, Izmir, Turkey; [email protected] Received 20 July 2013 Revised 23 October 2013 Accepted 24 October 2013
ABSTRACT Purpose To investigate the effect of nicotine on choroidal thickness using optical coherence tomography (OCT). Design Prospective, case–control study. Methods Sixteen young, healthy subjects and 16 age and gender matched control cases were included in this study; 4 mg nicotine gum was given to the study group and placebo gum to the control group. All participants underwent OCT scanning with a high-speed and resolution spectral-domain OCT device (3D OCT 2000, Topcon, Japan) at baseline, and 1 h following nicotine or placebo administration. The measurements were taken in the morning (10:00–12:00 hours) to avoid diurnal fluctuation. Results The median foveal choroidal thickness at baseline was 337.00 μm (IQR 84.50), which decreased to 311.00 μm (IQR 78.00) at 1 h following oral nicotine intake ( p=0.001). The median choroidal thickness was also significantly decreased at five other extrafoveal points ( p0.05). Tne baseline choroidal thickness measurements of the study and control groups showed no significant difference (table 1). The median choroidal thickness measurements of nicotine users at baseline, and at 1 h following nicotine gum are shown in table 2. At the fovea, choroidal thickness, which was 337.00 μm (IQR 84.50) (median (IQR)) at baseline, decreased to 311.00 μm (IQR 78.00) at 1 h following nicotine intake. ( p=0.001). Nicotine caused a significant reduction in choroidal thickness, compared with baseline, at all six measurement points. However, the choroidal thicknesses of the control group revealed no significant difference at all points when comparing measurements at baseline with 1 h after placebo intake (table 3). Figures 1A,B and 2A,B illustrate the change in choroidal thickness at each study interval for an individual in the nicotine user and control groups, respectively. 2
Table 1 The median choroidal thickness measurements of the study and control groups at baseline
T3 T2 T1 F N1 N2
Median (IQR) (μm) Nicotine
Median (IQR) (μm) Controls
p Value
267.50 (99.75) 295.00 (90.00) 315.50 (83.50) 337.00 (84.50) 305.50 (109.50) 295:00 (104.50)
274.00 296.50 305.50 330.50 310.50 289.50
0.678 0.850 0.610 0.650 0.940 0.678
(92.75) (100.25) (106.00) (104.25) (133.50) (112.50)
F, choroidal thickness at fovea; N1, choroidal thickness at 500 μm nasal to the fovea; N2, choroidal thickness at 1000 μm nasal to the fovea; T1, choroidal thickness at 500 μm temporal to the fovea; T2, choroidal thickness at 1000 μm temporal to the fovea; T3, choroidal thickness at 1500 μm temporal to the fovea.
Side effects of the nicotine gum such as throat irritation, mild dyspepsia, cough and a cold feeling were reported, in the study cases, but these were minor.
DISCUSSION As a highly vascular ocular structure, the choroid is directly influenced by intraocular and perfusion pressure; therefore, real time high-definition images of the choroid are more likely to demonstrate the real time vascular status of this tissue in vivo.18 It is suggested that even histology cannot demonstrate the thickness of the living choroid. Moreover, OCT is shown to be superior to histology to reflect accurate choroidal thickness.19 However, there is still debate on the relationship of choroidal thickness with choroidal blood flow. Many recent studies have reported ocular disorders associated with altered abnormal choroidal thickness.20–23 Also, there are recent data on the haemodynamic effect of chemicals—sildenafil and cigarettes— on the choroid, obtained by OCT.7 14 It has been reported that sildenafil citrate increases choroidal thickness due to a vasodilatory effect of sildenafil citrate on the choroidal circulation.14 This relationship was further investigated by Kim et al24 using swept-scan high-frequency digital ultrasound to measure the ocular blood flow. Moreover, in a recent study by Ulaş et al,25 significant choroidal thinning was reported in chronic renal failure patients after haemodialysis. In another recent study on this topic by Rishi et al,26 the choroidal thickness in eyes with polypoidal choroidal vasculopathy was found to be higher than normal. The authors hypothesised that the high mean ocular perfusion pressure could possibly play a
Table 2 The median choroidal thickness measurements of the study group at baseline, and one following oral nicotine intake
T3 T2 T1 F N1 N2
Median (IQR) (μm) Baseline
Median (IQR) (μm) 1 h after nicotine intake
p Value
267.50 295.00 315.50 337.00 305.50 295.00
263.50 (75.00) 284.50 (71.50) 278.50 (89.25) 311.00 (78.00) 283.00 (92.00) 262.50 (109.00)
0.024 0.008 0.026 0.001 0.004 0.010
(99.75) (90.00) (83.50) (84.50) (109.50) (104.50)
F, choroidal thickness at fovea; N1, choroidal thickness at 500 μm nasal to the fovea; N2, choroidal thickness at 1000 μm nasal to the fovea; T1, choroidal thickness at 500 μm temporal to the fovea; T2, choroidal thickness at 1000 μm temporal to the fovea; T3, choroidal thickness at 1500 μm temporal to the fovea.
Zengin MO, et al. Br J Ophthalmol 2013;0:1–5. doi:10.1136/bjophthalmol-2013-304044
Downloaded from http://bjo.bmj.com/ on December 11, 2014 - Published by group.bmj.com
Clinical science Table 3 The median choroidal thickness measurements of the control group at baseline, and 1 h following oral placebo intake
T3 T2 T1 F N1 N2
Median (IQR) (μm) Baseline
Median (IQR) (μm) 1 h after placebo intake
p Value
274.00 (92.75) 296.50 (100.25) 305.50 (106.00) 330.50 (104.25) 310.50 (133.50) 289.50 (112.50)
276.50 296.00 306.50 332.00 311.00 290.00
0.158 0.887 0.379 0.271 0.222 0.678
(99.25) (82.50) (97.50) (103.75) (127.00) (111.75)
F, choroidal thickness at fovea; N1, choroidal thickness at 500 μm nasal to the fovea; N2, choroidal thickness at 1000 μm nasal to the fovea; T1, choroidal thickness at 500 μm temporal to the fovea; T2, choroidal thickness at 1000 μm temporal to the fovea; T3, choroidal thickness at 1500 μm temporal to the fovea.
role in the aetiology of the disease. All of the above-mentioned studies give strong evidence that choroidal thickness reflects choroidal blood flow. According to the results of our study, chewing 4 mg of nicotine gum decreased choroidal thickness compared with placebo. Rojanapongpun and Drance6 studied the effect of nicotine on the ophthalmic artery flow velocity using transcranial Doppler ultrasound. They observed that small doses of nicotine (nicotine gum) increased blood flow velocities in the ophthalmic artery while finger blood flow was significantly decreased when comparing the nicotine-tested glaucoma group with the placebotested group. Steigerwalt et al9 found a reduction in blood flow velocity in the posterior ciliary artery following smoking, which the authors suggested was a good indicator of peripapillary choroidal blood flow, with colour duplex scanning. They
proposed that this decrease was due to the increase in the vascular resistance of the vessels. In another study using the laser speckle method, Tamaki et al27 reported a decrease in choroidal blood flow 30 min after smoking. Although choroidal blood flow was not measured directly in the current study, when previous reports about nicotine and ocular blood flow changes are considered, our results support the hypothesis of the relationship between choroidal thickness and ocular blood flow. Moreover, cigarette smoking has been shown to be related to choroidal thickness decrease in otherwise healthy subjects.7 In our opinion, our study findings give further evidence that choroidal thickness correlates directly with choroidal blood flow. There are several limitations to our study. One is that we have no quantification of nicotine levels for our subjects. Ideally, we would be able to measure blood serum nicotine levels to quantify the amount of nicotine being absorbed through the gum. Without this information, we cannot definitively identify when nicotine concentrations reached their maximum. However, based on the investigation reported by Russell and colleagues28 on blood nicotine levels after cigarette smoking and nicotine gum, we can estimate when nicotine might reach the maximum level. Their study revealed maximum blood plasma nicotine levels 1 h after the consumption of 4 mg nicotine gum, which was comparable to that of smoking one cigarette.28 In addition, the study by Sizmaz et al,7 which showed significant choroidal thickness reduction at 1 h after smoking, supports these findings. Other limitations of the current study are the limited number of cases and the potential interobserver and intraobserver bias while measuring choroidal thickness manually. However, this bias is an issue to be solved in all studies regarding choroidal thickness measurements. To include more than one
Figure 1 Choroidal thickness measurements of a participant in the study group at baseline (A) and at 1 h (B) after oral nicotine intake.
Zengin MO, et al. Br J Ophthalmol 2013;0:1–5. doi:10.1136/bjophthalmol-2013-304044
3
Downloaded from http://bjo.bmj.com/ on December 11, 2014 - Published by group.bmj.com
Clinical science Figure 2 Choroidal thickness measurements of a participant in the control group at baseline (A) and at 1 h (B) after oral placebo intake.
measurement point and to use two independent observer may partly overcome this problem. The relatively small sample size may also result in type 1 error; however, the design of the study with age and sex-matched control groups makes the results more valuable. Besides these limitations, to the best of our knowledge this is the first study to investigate the isolated effects of nicotine on choroidal thickness. As there is growing evidence in the literature on the relationship between choroidal thickness and choroidal blood flow, the findings of this preliminary study may be of clinical importance. We believe that the results of this preliminary study will be useful in future studies about this topic. Contributors Conception and design: MOZ and CK; acquisition of data: MOZ; analysis and interpretation of data: MOZ, CK and EC; article drafting and revising: CK; final approval: CK. Competing interests None.
3
4 5
6
7
8
9 10
Patient consent Obtained. Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
11
Ethics approval The study protocol was approved by Izmir University Institutional Review Board and Ethics Committee, and the research adhered to the tenets of the Declaration of Helsinki.
12
Provenance and peer review Not commissioned; externally peer reviewed.
13 14
REFERENCES 1
2
4
Dean JD, Matthews SB, Dolben J, et al. Cholesterol rich apo B containing lipoproteins and smoking are independently associated with macrovascular disease in normotensive NIDDM patients. Diabet Med 1994;11:740–7. Bloom RJ, Stevick CA, Lennon S. Patient perspectives on smoking and peripheral vascular disease. A veteran population survey. Am Surg 1990;56:535–9.
15 16
Riefkohl R, Wolfe JA, Cox EB, et al. Association between cutaneous occlusive vascular disease, cigarette smoking, and skin slough after rhytidectomy. Plast Reconstr Surg 1986;77:592–5. Robinson F, Petrig BL, Riva CE. The acute effect of cigarette smoking on macular capillary blood flow in humans. Invest Ophthalmol Vis Sci 1985;26:609–13. Morgado PB, Chen HC, Patel V, et al. The acute effect of smoking on retinal blood flow in subjects with and without diabetes. Ophthalmology 1994;101:1220–6. Rojanapongpun P, Drance SM. The effects of nicotine on the blood flow of the ophthalmic artery and the finger circulation. Graefes Arch Clin Exp Ophthalmol 1993;231:371–4. Sizmaz S, Küçükerdönmez C, Pinarci EY, et al. The effect of smoking on choroidal thickness measured by optical coherence tomography. Br J Ophthalmol 2013;97:601–4. Wimpissinger B, Resch H, Berisha F, et al. Response of choroidal blood flow to carbogen breathing in smokers and non-smokers. Br J Ophtalmol 2004;88:776–81. Steigerwalt RD Jr, Laurora G, Incandela L, et al. Ocular and orbital blood flow in cigarette smokers. Retina 2000;20:394–7. Bill A. Circulation in the eye. In: Renkin EM, Michel Cc, eds. Handbook in physiology. Microcirculation, Part 2. The American Physiological Society 1984: 1001–35. Manjunath V, Taha M, Fujimoto JG, et al. Choroidal thickness in normal eyes measured using Cirrus-HD optical coherence tomography. Am J Ophthalmol 2010;150:325–9. Drexler W, Fujimoto JG. State-of-the-art retinal optical coherence tomography. Prog Retin Eye Res 2008;27:45–88. Sander B, Larsen M, Thrane L, et al. Enhanced optical coherence tomography imaging by multiple scan averaging. Br J Ophthalmol 2005;89:207–12. Vance SK, Imamura Y, Freund KB. The effects of sildenafil citrate on choroidal thickness as determined by enhanced depth imaging optical coherence tomography. Retina 2011;31:332–5. Rabinoff M, Caskey N, Rissling A, et al. Pharmacological and chemical effects of cigarette additives. Am J Public Health 2007;97:1981–91. Benowitz NL, Hukkanen J, Jacob P III. Nicotine chemistry, metabolism, kinetics and biomarkers. Handb Exp Pharmacol 2009:29–60. doi:10.1007/978-3-54069248-5_2
Zengin MO, et al. Br J Ophthalmol 2013;0:1–5. doi:10.1136/bjophthalmol-2013-304044
Downloaded from http://bjo.bmj.com/ on December 11, 2014 - Published by group.bmj.com
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The effect of nicotine on choroidal thickness Mehmet Ozgur Zengin, Esat Cinar and Cem Kucukerdonmez Br J Ophthalmol published online November 13, 2013
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