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Retinal nerve fibre layer, ganglion cell layer and choroid thinning in migraine with aura
© Ekinci et al.; licensee BioMed Central Ltd. 2014
Received: 13 November 2013
Accepted: 20 May 2014
Published: 31 May 2014
The aim of this study was to investigate the thickness of the retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), and choroid thickness (CT) in patients who have migraines, with and without aura, using spectral optical coherence tomography (OCT).
Forty-five patients who had migraines without aura (Group 1), 45 patients who had migraines with aura (Group 2), and 30 healthy participants (control group) were included in the study. Spectral OCT was used to measure the RNFL, GCL and CT values for all patients.
The mean age of Group 1, Group 2, and the control group was 34.6 ± 4.3, 32.8 ± 4.9, and 31.8 ± 4.6 years, respectively. The mean attack frequency was 3.6/month in Group 1 and 3.7/month in Group 2. The mean age among the groups (p = 0.27) and number of attacks in migraine patients (p = 0.73) were not significantly different. There was significant thinning in the RNFL and GCL in Group 2 (p < 0.05, p < 0.001 respectively), while there were no significant differences in RNFL and GCL measurements between Group 1 and the control group (p > 0.05). All groups were significantly different from one another with respect to CT, with the most thinning observed in Group 2 (p < 0.001). When all migraine patients (without grouping) were compared with the control group, there were significant differences on all parameters: RNFL thickness, GCC thickness and CT (p < 0.05).
RNFL and GCL were significantly thinner in the migraine patients with aura as compared with both the migraine patients without aura and the control subjects. In migraine, both with aura and without aura, patients’ choroid thinning should be considered when evaluating ophthalmological findings.
Migraine is a disease presenting with an episodic headache capable of causing significant dysfunction, together with neurological, gastrointestinal, and autonomic changes, its pathogenesis is still unclear [1, 2]. There are two syndrome definitions related to migraine, namely with aura and without aura . The migraine aura is a mixture of focal neurological symptoms that are seen prior to an attack, accompanying an attack, and rarely after an attack. Most auras develop within 5–20 minutes, and generally last for less than 60 minutes. They may present as visual, sensory, and motor phenomena, and sometimes may affect tongue and brain stem functions. Various vascular, neurovascular, hypoxic, cellular, hormonal, and genetic hypotheses have been debated with respect to migraine pathogenesis . Importantly, vasospasm in the occipital hemisphere in patients who have migraine with aura, and the subsequent reduction in the blood flow, is a major hypothesis in the explanation of visual aura and headache. In certain patients, vasospasm has been shown to occur in the tissues outside the brain, especially in the retina layer, concurrent with a reduction in brain blood flow [5, 6]. There are various studies on the effects of vascular anomalies related to vasospasm and ischemia on the retina and optic nerve head . Owing to technological advances in recent years, the new-generation spectral domain OCT instruments that use improved scanning speed and special software techniques (EDI) enable the acquisition of high-resolution images OCT , which can perform reproducible, non-invasive in vivo evaluations, has come into clinical use as an imaging method for evaluating the thickness of the optic nerve head, peripapillary RNFL, GCL, and choroid layers in various neuroophthalmologic diseases [9, 10].
Although some studies have investigated the RNFL thickness in patients who have migraine with and without aura by using OCT and scanning laser polarimetry [1, 2, 11], there are no studies on the GCL and CT in these patients. The aim of the present study was to investigate potential differences in RNFL, GCL, and CT between patients who have migraine with aura and patients who have migraine without aura.
This observational, cross-sectional and multicenter study adhered to the tenets of the Declaration of Helsinki. It was approved by the local ethical committee (Kafkas University, Human Ethics Committee, Meeting: 2011/5, Document No:28, Kars, Turkey) and written informed consent was obtained from all patients before they had been recruited into the study. A total of 90 patients (30 males and 60 females with a similar mean age) who were followed in the Neurology Department; were divided into 2 groups (Group 1: Migraine without aura; Group 2: Migraine with aura). Each group consisted of 15 males and 30 females. Thirty non-smoking hospital employee participants (10 males and 20 females) were included in the control group. The right eye of each participant was included in the study. The diagnosis of migraine with and without aura was made according to the 2004 guidelines of the International Headache Society . Patients’ detailed histories were recorded, and information about the frequency of migraine attacks, pain localization, age at onset, duration, and the presence of aura was obtained. The type of migraine was determined, and systemic comorbidities, presence of migraine in the family, and history of glaucoma were noted. All measurements involving migraine patients were performed during both pain- and attack-free periods.
One hundred and thirty-seven migraine patients were evaluated. Volunteers who had full vision (1.0 with or without correction) and who had normal ocular findings were included in the study. Forty-seven patients with myopia, central serous chorioretinopathy, retinitis pigmentosa, angioid streaks, primary angle-closure glaucoma, choroidal neovascularization, and those who had previous eye surgery for disorders such as scleral buckling, diabetes mellitus and chronic hypertension (untreated or on Ht medication), patients who had been diagnosed with Multiple Sclerosis, Parkinson’s disease, or Alzheimer’s disease and patients who smoked tobacco were excluded from the study.
The normal distribution of the data was checked using the Kolmogorov-Smirnov test. The non-parametric Kruskal-Wallis test for continuous data was used to compare the three groups.. Non-parametric post-hoc tests with Bonferroni correction were performed on data that had reached significance with the Kruskal-Wallis Test. Comparisons between the two experimental groups were performed with a Mann Whitney U test. IBM SPSS for Windows Ver. 20.0 was used for the statistical analysis, and a p value <0.01 was considered significant.
Demographic results of the three groups
Migraine diagnosed (months)
Mean attack frequency
Mean ± SD
Mean ± SD
34.6 ± 4.3
88.8 ± 12.5
32.8 ± 4.9
85.3 ± 11.9
31.8 ± 4.6
. p = 0.27
p = 0.53
p = 0.73
All patients in Group 2 reported visual symptoms such as light flashes, light refraction, and black dots in the visual area.
Median OCT analysis results of the three groups
RNFL thickness (μm)
GCL thickness (μm)
When the groups were evaluated according to their median GCC thickness, there were significant differences between Group 1 and Group 2 regarding both superior and inferior faces (p = 0.02, p = 0.003, respectively). While there were no significant differences between Group 1 and the control group (p = 0.36, p = 0.75; respectively), there were significant differences between Group 2 and the control group regarding both faces (p < 0.001 for both) (Table 2).
There were significant differences among all groups with respect to median CT values (p < 0.001 for all) (Table 2).
Median OCT analysis results of the migraine and control groups
RNFL thickness (μm)
GCL thickness (μm)
(n = 90)
(n = 30)
p = 0.001
p = 0.001
p = 0.001
p = 0.001
p = 0.001
p = 0.002
p = 0.003
p < 0.001
We investigated the correlations among RNLF, GCL, and CT values and migraine. When we collapsed the two migraine conditions and compared those patients to the control group, we found significant thinning of the RNLF, GCL and choroid in the migraine patients. When the patients were evaluated as subgroups of migraine with aura, without aura and a control group, there was a significant thinning of the RNLF, GCL and choroid in migraine patients with aura, but no significant differences in RNLF and GCL measurements between migraine patients without aura and healthy subjects.
As far as we know, this is the first study to investigate the relationship between GCL, CT values and migraine.
Migraine is a chronic, progressive neurological disorder with unknown etiology, and progresses with episodic headache attacks . The most common known event in migraine pathogenesis is vascular dysregulation (vasospastic diathesis) . The neurovascular system is the most affected system in this pathology. Studies have detected an increased risk for ischemic stroke in patients who had migraine with aura [14, 15]. Vasospasm emerging prior to or during the pain has been considered to occur concurrently in tissues located outside the brain, and local infarctions, by extension, have been considered to lead to histopathological and functional disorders at the tissue level. Various studies related to the vascular theory have been carried out in recent years to demonstrate changes in the retinal layer [5, 6]. Killer et al. demonstrated a reduction in blood flow in the lower temporal artery in a patient who had a visual area defect in the left eye during a migraine attack . According to another hypothesis, the vasoconstrictive metabolites that join the systemic circulation during a migraine attack affect the retina as a result of retrobulbar flow, thus reducing local blood flow . Kara et al. used colored Doppler ultrasonography and found a reduction in blood flow at the level of the central retinal artery and posterior ciliary artery in migraine patients, compared to healthy individuals .
Tan et al.  measured RNFL thickness in 15 patients who had migraine with aura and 24 patients who had migraine without aura using a scanning laser polarimetry instrument, and detected that there was no reduction in RNFL thickness in migraine patients compared to healthy individuals. On the other hand, although the method for measuring the retinal nerve fiber layer (RNFL) was different (Scanning Laser Polarimetry), Martinez et al.’s study results suggest a significantly difference between the migraine patients with aura and those without aura . Another of their another studies, Martinez et al.  used OCT to measure the RNFL, and determined that the mean RNFL thickness in migraine patients was similar to that of healthy individuals, while only the thickness of the temporal quadrant RNFL was reduced in patients compared to the control group. Gippono et al.  found no difference in the foveal thickness and macular volume in female migraine patients compared to healthy women, but determined that there was a significant thinning in the RNFL thickness in the upper quadrant in the female migraine patients. In the present study, the thinning of the RNFL and GCL was detected only in patients who had migraine with aura. It is possible that Tan et al. obtained different results because they used a scanning laser polarimetry instrument to measure the RNFL thickness. On the other hand, Gipponi et al. may have obtained different results because they did not classify the patients according to the presence of aura. Several studies have emphasized that cerebral hypoperfusion, which occurs most commonly in the posterior region of one hemisphere during the aura period , and the risk of ischemic stroke, cardiac diseases, intracerebral hemorrhage and mortality, increases in migraine patients with aura ; the pathogenic mechanism might be endothelial and vascular smooth muscle dysfunction and hypercoagulability . Different studies have shown that neurodegenerative changes occur secondary to the subclinical ischemic lesions that form after hypoperfusion [14, 15] . Moreover, some studies have reported a thinning in RNFL measurements in neurodegenerative diseases such as multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease [20–22]. In light of our findings in the present study, we propose that the thinning of the RNFL is a secondary event to the neurodegenerative changes in the central nervous system after ischemia in the migraine patients with aura.
The choroid is the vascular compartment of the eye. It supplies oxygen and nutrients to the outer retina. The major blood supply to the retina is the choroid, especially in darkness, where 90% of the oxygen comes from choroidal circulation . In the literature, Bourke et al. defined the correlation between untreated systemic hypertension and choroidopathy , Regatieri et al. defined CT in diabetic retinopathy and suggested that CT was associated with retinal tissue hypoxia , and Steigerwalt et al. and Sızmaz et al. reported a decrease in CT in patients who smoked cigarettes, due to the increase in vascular resistance of the vessels [26, 27]. According to the before-mentioned studies, migraine is known to be a neurovascular disease, and is known to reduce the blood flow at the level of the central retinal artery and posterior ciliary artery; the thinning of the choroid layer is an expected clinical outcome in migraine patients. Similarly, we found choroidal thinning in patients who had migraine both with aura and without aura.
Our study had some limitations. First, we did not grade migraine severity as was done in the Martinez et al. study. Second, we did not have access to brain MRIs to support our theory and to show ischemic changes in migraine with aura, because ethical committee disallowed this procedure.
Overall, a structurally and functionally normal retinal and choroidal vasculature is essential for the function of the retina: abnormal choroidal blood volume and/or compromised flow can result in photoreceptor dysfunction and death . Changes in retinal and choroidal blood flow may be important in retinal and choroideal pathologies.
We report the correlations among RNLF, GCL, and CT values and migraine with aura. Further investigation with a larger number of cases might provide more information about the relationship between retinal-choroidal pathologies and migraine with aura.
We thank Barbara Reid for editing our manuscript as a native speaker. She had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
No commercial relationship exists for any of this article’s authors in the form of financial support or personal financial interest.
- Martinez A, Proupim N, Sanchez M: Retinal nerve fibre layer thickness measurements using optical coherence tomography in migraine patients. Br J Ophthalmol. 2008, 92: 1069-1075. 10.1136/bjo.2008.137471.View ArticlePubMedGoogle Scholar
- Tan FU, Akarsu C, Güllü R: Retinal nerve fiber layer thickness is unaffected in migraine patients. Acta Neurol Scand. 2005, 112: 19-23.View ArticlePubMedGoogle Scholar
- Marror MF, Zrenner E: Standard for clinical electroretinograpy 1994 update. Doc Ophtalmol. 1995, 89: 199-210. 10.1007/BF01203373.View ArticleGoogle Scholar
- Totan Y, Çekiç O: Görme ile ilgili elektrofizyolojik testler ve klinik uygulamaları. (Vision-related Electrophysiological tests and their clinical applications. MN Oftalmol. 1996, 3: 195-198.Google Scholar
- Beversdof D, Stommel E, Allen C, Stevens R, Lessel S: Recurrent branch retinal infarcts in association with migraine. Headache. 1997, 37: 396-399. 10.1046/j.1526-4610.1997.3706396.x.View ArticleGoogle Scholar
- Killer HE, Forrer A, Flammer J: Retinal vasospasm during an attack of migraine. Retina. 2003, 23: 253-254. 10.1097/00006982-200304000-00023.View ArticlePubMedGoogle Scholar
- Solomon S, Grosberg BM, Friedman DI, Lipton RBJ: Retinal migraine. J Neuroophthalmol. 2007, 27: 243-244. 10.1097/WNO.0b013e31814a6243.View ArticlePubMedGoogle Scholar
- Manjunath V, Taha M, Fujimoto JG, Duker JS: Choroidal thickness in normal eyes measured using Cirrus-HD optical coherence tomography. Am J Ophthalmol. 2010, 150: 325-329. 10.1016/j.ajo.2010.04.018.View ArticlePubMedPubMed CentralGoogle Scholar
- Christiensen GS, Kylstra JA: A comparative study of the predicted postoperative visual acuity using the PAM and the Heine retinometer. ARVO Abstract Book. 1993Google Scholar
- Xu W, Yao K, Shentu X: The comprasion of two methods to predict the postoperative visual acuity of cataractous patients. Zhonghua Yan Ke Za Zhi. 2001, 37: 121-124.PubMedGoogle Scholar
- Martinez A, Proupim N, Sanchez M: Scanning laser polarimetry with variable corneal compensation in migraine patients. Acta Ophthalmol. 2009, 87: 746-753. 10.1111/j.1755-3768.2008.01356.x.View ArticlePubMedGoogle Scholar
- The Headache Classification Subcommittee of the International HeadacheSociety: The International classification of headache disorders (2nd edn). Cephalalgia. 2004, 24 (Suppl 1): 1-160S.Google Scholar
- Wang JJ, Mitchell P, Smith W: Is there an association between migraine headache and open-angle glaucoma? Findings from the blue mountains eye study. Ophthalmology. 1997, 104: 714-719.View ArticleGoogle Scholar
- Kurth T, Slomke MA, Kase CS, Cook NR, Lee IM, Gaziano JM, Diener HC, Buring JE: Migraine, headache, and the risk of stroke in women: a prospective study. Neurology. 2005, 64: 1020-1026. 10.1212/01.WNL.0000154528.21485.3A.View ArticlePubMedGoogle Scholar
- Sacco S, Ricci S, Carolei A: Migraine and vascular diseases: a review of the evidence and potential implications for management. Cephalalgia. 2012, 32: 785-795. 10.1177/0333102412451361.View ArticlePubMedGoogle Scholar
- Sorkhabi R, Mostafaei S, Ahoor M, Talebi M: Evaluation of retinal nerve fiber layer thickness in migraine. Iran J Neurol. 2013, 12: 51-55.PubMedPubMed CentralGoogle Scholar
- Kara SA, Erdemoğlu AK, Karadeniz MY, Altinok D: Color Doppler sonography of orbital and vertebral arteries in migraineurs without aura. J Clin Ultrasound. 2003, 31: 308-314. 10.1002/jcu.10181.View ArticlePubMedGoogle Scholar
- Gipponi S, Scaroni N, Venturelli E, Forbice E, Rao R, Liberini P, Padovani A, Semeraro F: Reduction in retinal nerve fiber layer thickness in migraine patients. Neurol Sci. 2013, 34 (6): 841-845. 10.1007/s10072-012-1103-0.View ArticlePubMedGoogle Scholar
- Larrosa-Campo D, Ramón-Carbajo C, Para-Prieto M, Calleja-Puerta S, Cernuda-Morollón E, Pascual J: Migraine as a vascular risk factor. Rev Neurol. 2012, 55: 349-358.PubMedGoogle Scholar
- Galetta KM, Calabresi PA, Frohman EM, Balcer LJ: Optical coherence tomography (OCT): imaging the visual pathway as a model for neurodegeneration. Neurotherapeutics. 2011, 8: 117-132. 10.1007/s13311-010-0005-1.View ArticlePubMedPubMed CentralGoogle Scholar
- Kirbas S, Turkyilmaz K, Anlar O, Tufekci A, Durmus M: Retinal nerve fiber layer thickness in Alzheimer disease. J Neuroophthalmol. 2013, 33: 58-61. 10.1097/WNO.0b013e318267fd5f.View ArticlePubMedGoogle Scholar
- Kirbas S, Turkyilmaz K, Tufekci A, Durmus M: Retinal nerve fiber layer thickness in Parkinson disease. J Neuroophthalmol. 2013, 33: 62-65. 10.1097/WNO.0b013e3182701745.View ArticlePubMedGoogle Scholar
- Linsenmeier RA, Braun RD: Oxygen distribution and consumption in the cat retina during normoxia and hypoxia. J Gen Physiol. 1992, 99: 177-197. 10.1085/jgp.99.2.177.View ArticlePubMedGoogle Scholar
- Bourke K, Patel MR, Prisant LM, Marcus DM: Hypertensive choroidopathy. J Clin Hypertens (Greenwich). 2004, 6: 471-472. 10.1111/j.1524-6175.2004.3749.x.View ArticleGoogle Scholar
- Regatieri CV, Branchini L, Carmody J, Fujimoto JG, Duker JS: Choroidal thickness in patients with diabetic retinopathy analyzed by spectral-domain optical coherence tomography. Retina. 2012, 32: 563-568.View ArticlePubMedPubMed CentralGoogle Scholar
- Steigerwalt RD, Laurora G, Incandela L, Cesarone MR, Belcaro GV, De Sanctis MT: Ocular and orbital blood flow in cigarette smokers. Retina. 2000, 20: 394-397. 10.1097/00006982-200007000-00013.View ArticlePubMedGoogle Scholar
- Tamaki Y, Araie M, Nagahara M, Tomita K, Matsubara M: The acute effects of cigarette smoking on human optic nerve head and posterior fundus circulation in light smokers. Eye (Lond). 2000, 14: 67-72. 10.1038/eye.2000.15.View ArticleGoogle Scholar
- Shiragami C, Shiraga F, Matsuo T, Tsuchida Y, Ohtsuki H: Risk factors for diabetic choroidopathy in patients with diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 2002, 240: 436-442. 10.1007/s00417-002-0451-5.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2415/14/75/prepub
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