Diameter and haemodynamics of internal carotid artery siphon and ophthalmic artery in patients with non-arteritic anterior ischaemic optic neuropathy

Purpose To compare the diameter and the haemodynamics of internal carotid artery siphon(ICAS) and ophthalmic artery (OA) in patients with unilateral non-arteritic anterior ischaemic optic neuropathy (NAION) with their contralateral sides and age-matched controls. Methods 30 patients clinically diagnosed with NAION (unilateral affected) and 30 age-matched controls participated in this study. By CTA, the diameter of ICAS and OA in both eyes were measured. By CDI, the blood flow velocity (Vm) and the blood flow volume of ICAS and OA in both eyes were measured or calculated. Measurements on the affected side of the patients were compared to the contralateral healthy side and the controls. Results Compared between the affected sides and the controls, the Vm, the diameter, and the blood flow volume in the ICAS were all significantly decreased (p<0.05), the Vm and the blood flow volume in the OA tended to be reduced (p=0.062, 0.055 respectively), while the difference of the diameter in the OA was insignificant (p=0.116). Compared between the affected sides and the unaffected healthy sides, the Vm, the diameter, and the blood flow volume in the ICAS were also significantly decreased (p<0.05), while no marked differences were detected in the OA, neither for the Vm, the diameter, or the blood flow volume(p=0.178, 0.151,0.173 respectively). . These findings might be potentially useful in the monitoring of NAION.


Introduction
Non-arteritic anterior ischaemic optic neuropathy (NAION) is a kind of serious ischaemic optic neuropathy, patients with NAION show a sudden, painless, decrease in vision accompanied with a visual field defect and optic disc edema [1][2][3][4]. It's believed that the pathogenesis of NAION is multifactorial [5,6], and the hypoperfusion of short posterior ciliary arteries (SPCAs)SPCAs was proved to be the major cause [7]. Previous research found that patients with NAION showed decreased velocities of blood cells in the capillaries of the optic nerve head by means of laser Doppler velocimetry [8]. Another study suggested that patients with NAION showed markedly different retrobulbar haemodynamics with reduced circulation velocity in the ophthalmic artery measured by colour Doppler imaging (CDI) [9]. As we have known, previous studies discovered a link between the pathogenesis of NAION and the intima-media thickness (IMT) IMT of carotid arteries and carotid diseases [9,10], but in our knowledge, there were few researches on the association of NAION and the diameter of ICAS so far. In fact, ICAS is a very special area from the anatomical point of view in patients with NAION [11], the narrowing of the vessel here might affect the lower reaches' hemodynamics directly.
The present study is, to our knowledge, the first of its kind to compare the diameter and the haemodynamics of ICAS and OA in patients with unilateral NAION with their contralateral sides and age-matched controls. Inclusion criteria for patients with NAION were as follows: 1) conformed to the diagnostic criteria of NAION [11], 2) unilateral optic disc swelling on ophthalmoscopy during the acute stage, 3)first time outbreak of NAION without previous treatment, and 4) completed all the examinations and follow-up visits.

Materials And Methods
Exclusion criteria were as follows: 1)any other ophthalmic diseases affecting the optic disc, including glaucoma, optic neuritis, uveitis, retinal or choroidal diseases, and trauma; and 4) any neurologic disease that may affect the optic nerve,such as multiple sclerosis, Alzheimer disease, and Parkinson disease.
The control group consisted of 30 age-matched subjects. The mean age of the 30 controls was The blood flow volume (A) of ICAS and OA was calculated using the following formula: A = πr 2 ×Vm r = 1/2 diameter All the measurements were performed by experienced operators unaware of the subject's condition.
The left side measurements were defined as the results of each control.
Heart rate and blood pressure (BP) were determined by sphygmomanometry in a sitting position after a rest of 5 min. Intraocular pressure (IOP) was measured before CDI examination using Goldmann applanation tonometry. Ocular perfusion pressure (OPP) was calculated using the following formula: Data were expressed as mean ± SEM. The Kolmogorov-Smirnov test was used to identify the normality of distribution. Differences in the parameters between the affected sides and the controls, and between the unaffected healthy sides and the affected sides were compared using the Mann-Whitney test, Wilcoxon test or t test. p value <0.05 was considered statistically significant. Statistical analysis was performed using the IBM SPSS software version 21.

Results
Concerned with the demographic and clinical data of the NAION patients and the controls, the age, IOP, systolic BP, diastolic BP, mean arterial pressure, heart rate and OPP showed no statistically significant difference between two groups p>0.05 (Table 1).
Compared between the affected sides of NAION and the controls, the diameter in the ICAS, the blood flow volume in the ICAS and the blood flow volume in the OA all significantly decreased (p<0.05), while the differences of the Vm in the ICAS, the Vm in the OA and the diameter in the OA were insignificant (p = 0.685, 0.062, 0.424 respectively) ( Table 2).
Compared between the affected sides and the unaffected healthy sides in the patients with NAION, the difference of the Vm in the ICAS was insignificant (p = 0.652), while the diameter and the blood flow volume in the ICAS significantly decreased (p<0.05), no marked differences were detected in the OA, neither for the Vm, the diameter, or the blood flow volume(p = 0.261, 0.197, 0.094 respectively) ( Table 3).

Discussion
NAION is a major nonglaucomatous optic neuropathy, the optic nerve impairment is caused by infarction of the laminar or retrolaminar portion of the optic nerve head which was supplied by SPCAs [6,12], the branches coming from the OA as it crosses the optic nerve. As we have known, the anatomy of SPCAs is highly variable between different individuals [13]. Since it is impossible to differentiate the individual paraoptic branches of the SPCAs and obtain the measurement data individually by using CDI [14][15][16], we took the hemodynamic in the OA as one of the subjects in the present study. Although the optic nerve head blood flow is only a minuscule fraction of ophthalmic artery flow [16], it is still valuable to measure the blood flow volume in the OA, for the latter could reflect the perfusion of SPCAs partly.
It's well known that small cup to disk ratio ("disk at risk") is a predisposing fator for NAION [17], furthermore, since almost all patients with acute NAION presented with papillary edema, the swelling of the nerve fibers crowded in the tight disk may compress capillaries and other small vessels among the nerve fibers [18], leading to the reduction of blood velocity of the ipsilateral central retinal artery(CRA) CRA. Therefore, CRA was not included in our study although there were studies found that the blood flow velocities of the CRA were considerably reduced in patients with acute NAION compared to healthy controls [15,19], since we didn't think the reduction of blood velocity of the ipsilateral CRA was the reason causing NAION.
ICAS was always an enigmatic region implicated in cephalic and ocular ischemic diseases. In previous studies, ICA was divided into seven segments according to BouthiIIier's classification [20],they were cervical segment, petrous segment, lacerum segment, cavenous segment, clinoidal segment, ophthalmic segment, and communicating segment. The tortuous, S-shaped course(include cavenous segment and clinoidal segment) has been defined as siphon. There is a close connection between the blood flow and the morphology of vessel: the vascular bending shape would have effects on shear force of vessel wall and cause the blood flow turbulence. The tortuous configuration of ICAS is crucial to the change of blood flow parameters, which influence circulatory dynamics of blood supply; The bending shape of ICAS is also very important for diseases related to turbulent circulation [21].Therefore, we assumed that there was some link between the vessel diameter of ICAS and NAION, we wanted to verify this association in means of observing the sequentially hemodynamic changes with the intention of exploring clinical significance of ICAS.
In our study, we found the diameter of ICAS distinctly narrowed in the patients suffering from NAION, no matter compared with the unaffected healthy side or with the controls. Also, we found that the blood flow volume in the ICAS in the patients with NAION significantly decreased accordingly, although the difference of the Vm in the ICAS was insignificant compared with the unaffected healthy side and with the controls (p = 0.652, 0.685respectively). As we know, the resolution of CDI is insufficient up to now to provide reliable volumetric flow measurements, however, according to the law of conservation of mass, the blood flow volume should be a fixed value as blood passing through a segment of vessel, so we could aquire the instantaneous blood flow volume through the measurement of the diameter and blood flow velocities. The narrowing of the diameter of ICAS led to the reduction of blood flow volume in the ICAS, and the latter definitely diminished the volume of blood supply to the downstream region in the patients with NAION. However, previous reports proved that the degree of ICA stenosis had no significant differences between the NAION group and the controls [22][23][24]. From above we concluded that it was siphon but not other segments of ICA which played more important role in the occurance of NAION.
In addition to these, we noticed that the difference of Vm in the NAION group was insignificant compared with the unaffected healthy sides or with the controls, no matter it was the Vm of ICAS or the Vm of OA. According to Bernoulli's equation, the flow velocity increases as a result of a constriction or narrowing in calibre [25]. We assumed that the reason arised from this discrepancy was as follows: blood is belonged to non-Newtonian fluid, the plasma viscosity or the elasticity of vascular wall could have influence on blood flow velocity. So we thought that the blood flow velocity alone wasn't a reliable parameter in the research of NAION, but the blood flow volume seemed to be more reliable. As we know, whether the narrowing in caliber or not, the instantaneous blood flow volume was constant when blood passing though the vessel, so this parameter could reflect the situation of blood perfusion precisely, the best evidence of which was the haemodynamics of OA. The difference of diameter and Vm in the OA were both insignificant between the NAION group and the controls, but the OA blood flow volume reduced significantly in the affected eyes compared to the controls. Another thing worth noting is that concerned with the blood flow volume in the OA, no marked differences were detected between the affected sides and the unaffected healthy sides in the patients with NAION (p = 0.094). We have known that almost 25-40% patients with unilateral NAION will suffer from onset of NAION in the fellow eye afterwards, so there is reason to hypothesis that as the progress of the lesion, the blood perfusion of lower reaches might reduce furtherly and lead to the hypoperfusion of SPCAs, all the hemodynamic changes would cause hypoperfusion of the optic disc, and such ischeamic insult to the optic disc could result in NAION in the end.
we concluded that the narrowing of the diameter of ICAS and the decreased blood flow volume in the ICAS and OA may be associated with NAION. These findings might be potentially useful in the    Head-and-neck CTA inspection. Showed the diameter of ICAS and OA.

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