Ophthalmological Abnormalities in Cases with Intracranial Aneurysms: A Retrospective Referral-Based Study

Abstract

Background

Intracranial aneurysms affect 2–3% of the population. Ophthalmological symptoms, such as ophthalmoplegia and visual field defects, can be symptoms of unruptured intracranial aneurysms. In this study, we reported the frequency of ophthalmological abnormalities and the relationship between these abnormalities and treatment and life prognosis.

Methods

One hundred forty-two patients who were referred from the Kyoto University Hospital Neurosurgery Department to the Ophthalmology Department between January 2011 and October 2022 were enrolled in this study. Age, sex, aneurysm location, visual field defects, ophthalmoplegia, presence of subarachnoid hemorrhage, treatment, and death during follow-up were retrospectively investigated.

Results

Of the 142 patients, internal carotid artery aneurysms were the most frequent (93 cases), followed by internal carotid-posterior communicating artery (IC-PC) aneurysms (20 cases). Cranial nerve III palsy was observed in 50% of cases with IC-PC aneurysms, and this frequency was higher compared to cases with other aneurysms (p=0.0095). Post-chiasmal visual field defects were present not only in patients with anterior circulation aneurysms (anterior communicating artery, 25%; internal carotid artery, 19%; and middle cerebral artery, 33%), but also in patients with posterior circulation aneurysms (basilar artery, 21%).

Conclusions

Cranial aneurysm not only causes III palsies but also causes visual field defects. Our findings support careful ophthalmologic assessment, including visual field testing when clinically feasible, especially when aneurysms are large or near the visual pathway, regardless of the anatomical position of the originating artery.

Introduction

Intracranial aneurysms affect 2–3% of the population.¹ Most unruptured intracranial aneurysms are incidentally found on brain imaging, including magnetic resonance imaging (MRI), and some are detected based on ophthalmological symptoms.¹ Unruptured intracranial aneurysms can cause ophthalmological abnormalities, including cranial nerve III palsy^1,2 and visual field defects.³ Internal carotid artery (ICA) aneurysms can cause uniocular visual field loss by compressing optic nerves, and can also cause lateral chiasmal syndrome.⁴ Large basilar artery aneurysms can cause chiasmal syndrome; however, basilar artery (BA) aneurysms were previously thought to rarely cause visual field defects.⁵ Internal carotid–posterior communicating artery (IC-PC) aneurysms cause cranial nerve III palsy owing to their proximity to this nerve.⁶

Accurate and prompt diagnosis of unruptured intracranial aneurysms is essential for appropriate preventive treatment.³ Clinical consensus regarding whether endovascular treatment or surgical clipping yields better results for aneurysm patients in terms of ophthalmologic symptoms remains lacking.^7,8 Although it has been reported that eye movement disorders and cranial nerve palsies occur with a certain frequency in both unruptured and ruptured cerebral aneurysms,^1,9 there have been few reports regarding visual field abnormalities, and most of them have been case studies.⁴ In a prospective study of unruptured intracranial aneurysms, the incidence of visual field defects was low, and the characteristics of each aneurysm were unclear.¹ In this study, we investigated our institutional cohort to further clarify the frequency of ophthalmological abnormalities and their impact on treatment selection and life prognosis.

Methods

Participants

One hundred forty-two patients who were referred from the Kyoto University Hospital Neurosurgery Department to the Ophthalmology Department between January 2011 and October 2022 were included in this study. There were no exclusion criteria.

Age, sex, aneurysm location, visual field defects, ophthalmoplegia, presence of subarachnoid hemorrhage (SAH), treatment, and aneurysm-related death during follow-up were retrospectively investigated. In this study, we considered BA, posterior cerebral artery (PCA), and vertebral artery (VA) aneurysms as posterior circulation aneurysms, and ICA, middle cerebral artery (MCA), IC-PC, and anterior communicating artery (A-com) aneurysms as anterior circulation aneurysms.

For patients with multiple aneurysms, the aneurysms eligible for the initial treatment were included.

Treatments were classified into three groups: observation (including pending treatments), endovascular treatment (coiling and flow diverters), and surgical treatment.

Ophthalmological Examinations

Visual field tests were conducted using a Humphrey Visual Field Analyzer (mainly the 30–2 SITA standard testing protocol) or Goldmann Perimeter according to clinical indications. Among Humphrey Visual Field tests, only reliable results (less than 20% fixation losses, 15% false-positive responses, and 15% false-negative responses) were included. Visual field defects were classified into two categories: pre-chiasmal (central scotoma, arcuate scotoma, or nonspecific visual field defects), which we assumed were more likely due to intraocular pathology, mainly glaucomatous optic neuropathy, or post-chiasmal (bitemporal, binasal, or homonymous hemianopia), which we assumed were caused by intracranial abnormalities. Ophthalmoplegia was diagnosed by a neuro-ophthalmologist based on quantitative eye position examinations, such as the alternate prism cover test.

Statistical Analysis

This study was exploratory in nature. The frequencies of cranial nerve palsy (III, IV, and VI) and visual field defects were compared using the Fisher’s exact test from Python SciPy package. P-values were computed for the two-sided tests. Statistical significance was defined as a p-value < 0.05.

Results

Between January 2011 and October 2022, 142 patients were included in this study, of which 80% were female. Eighty-five patients (60%) underwent endovascular treatment and 38 patients (27%) underwent surgical treatment (Table 1).

Table 1.

Participant Characteristics

		N=142
Age, years (mean ± standard deviation)		60.6 ± 13.3
Sex (male/female)	Male	28
	Female	114
Subarachnoid hemorrhage		18 (12%)
Treatment	Endovascular	85 (60%)
	Surgical	38 (27%)
	Observation	17 (12%)
Death		6 (4%)

Of 142 patients, four patients had A-com aneurysm, 93 patients had ICA aneurysms, 6 patients had MCA aneurysms, 20 patients had IC-PC aneurysms, 3 patients had PCA aneurysms, 14 patients had BA aneurysms, and 2 patients had VA aneurysms (Table 2 and Figure 1).

Table 2.

Aneurysm Locations and Ophthalmological Abnormalities

		Acom	ICA	MCA	IC-PC	PCA	BA	VA
Total		4	93	6	20	3	14	2
Visual field	Normal	0	23	1	3	3	2	0
	Pre-chiasmal	1	9	0	3	0	3	0
	Post-chiasmal	1 (25%)	18(19%)	2(33%)	2(10%)	0	3(21%)	0
	N/A	2	43	3	12	0	6	2
III palsy	Present, n (%)	1(25%)	19(20%)	0	10(50%)	1(33%)	4(29%)	0
IV palsy	Present, n (%)	0	2(2%)	0	0	0	2(14%)	0
VI palsy	Present, n (%)	0	11(12%)	1(17%)	1(5%)	0	1(7%)	0
SAH	Total	0	6(6%)	1(17%)	4(20%)	1(33%)	4(29%)	1(50%)
SAH onset	On arrival	0	3	1	3	1	0	1
	Follow-up	0	3	0	1	0	4	0
Death		0	2	0	1	0	3	0

Abbreviations: A-com, anterior communicating artery; ICA, internal carotid artery; MCA, middle cerebral artery; IC-PC, internal carotid–posterior communicating artery; PCA, posterior cerebral artery; BA, basilar artery; VA, vertebral artery; SAH, subarachnoid hemorrhage.

Figure 1.

Aneurysm locations in participants. ICA cases accounted for 65%.

Abbreviations: A-com, anterior communicating artery; ICA, internal carotid artery; MCA, middle cerebral artery; IC-PC, internal carotid-posterior communicating artery; PCA, posterior cerebral artery; BA, basilar artery; VA, vertebral artery; SAH, subarachnoid hemorrhage.

Post-chiasmal visual field defects were present not only in patients with anterior circulation aneurysms (A-com, 25%; ICA, 19%; and MCA, 33%), but also in patients with posterior circulation aneurysms (BA, 21%). Cranial nerve III palsy was observed in 50% of IC-PC aneurysm cases, and this frequency was higher compared to other aneurysms (Table 2; p=0.0095, odds ratio 95% confidence interval: [1.28, 11.6]). The frequency of cranial nerve III palsy was not high in patients with ICA aneurysm (20%). However, in the ICA group, patients with cavernous sinus aneurysms had a high rate of cranial nerve III palsy (Table S1). No ophthalmological abnormalities such as cranial nerve III palsy, cranial nerve IV palsy, cranial nerve VI palsy, or the presence of post-chiasmal visual field defects were predictive factors for death during follow-up (Table S2; p=0.64, p=0.16, p=1.0, p=0.12, respectively).

We also examined the treatments selected for the patients with cranial aneurysms (Table 3). Among the treated patients, endovascular treatment was used more frequently, regardless of the presence of visual field defects (Table 3). Additionally, those with ICA aneurysm were more frequently referred to ophthalmology department pre-operatively (83%), while other patients with aneurysm were more likely to be referred post-operatively (37%, p<0.001). The frequencies of cranial nerve palsies and post-chiasmal visual field defects were similar between pre-operative-and post-operative groups (Tables S3–S5).

Table 3.

Treatment Strategies for Patients with Cranial Aneurysm

		Observation	Endovascular	Surgical
Visual Field	Normal	2	25	5
	Pre-chiasmal	1	8	7
	Post-chiasmal	3	13	10
	N/A	11	39	16

In ICA aneurysm cases, cavernous sinus aneurysm cases accompanied cranial nerve III palsy more frequently (37%) compared with other ICA aneurysms (Table S1). Among ICA aneurysms, cranial nerve IV and VI palsies were only present in cavernous sinus aneurysm cases (Table S1).

Among the patients with BA aneurysm, three had post-chiasmal visual field defects. The causes of the post-chiasmal visual field defects were post-operative thalamic infarction, direct compression of the optic chiasm by a large BA aneurysm, and compression of the optic tract by an internal carotid artery and a BA aneurysm. Patients with BA aneurysm along with visual field defects commonly had large aneurysms (from 0.5 cm to 2 cm). The MRI and Goldmann perimetry results from the two patients with large BA aneurysms are shown in Figures 2 and S1. The frequency of SAH tended to be higher in patients with BA aneurysms, although the difference was not statistically significant (p=0.066, odds ratio 95% confidence interval: [0.70, 14.5]).

Figure 2.

Magnetic resonance imaging (MRI) and Goldmann perimetry results from patients with a giant basilar artery aneurysm. (A) Magnetic resonance angiography (MRA) showing an aneurysm originating from the basilar artery. (B and C) MRA showing a basilar artery aneurysm compressing the chiasma (arrow head) from the bottom. (D and E) Goldmann perimetry was obtained after the surgery, which revealed mild bitemporal hemianopia, consistent with MRI findings. (F and G) Goldmann perimetry obtained 2 years after the surgery revealed worsening bitemporal hemianopia. (F) left eye, (G) right eye.

In this cohort, one case of vitreous hemorrhage was observed; however, based on intraoperative findings, it was diagnosed as a rhegmatogenous retinal detachment, rather than Terson syndrome.

Discussion

Our results demonstrate that visual field defects are frequently observed not only in anterior circulation aneurysms, but also in posterior circulation aneurysms (BA), which were previously considered to rarely cause visual field defects.^5,10 This indicates the importance of vigorous screening for visual field defects in patients with cranial aneurysms, regardless of their anatomical position.

Aneurysm position in IC-PC was a strong risk factor predicting the presence of cranial nerve III palsy, which was observed in 50% of IC-PC cases. This relationship is in accordance with previous studies as well as the anatomical proximity of cranial nerves III and IC-PC.⁶ However, the frequency of 50% in this study was higher compared with 1/3 in a previous report.¹¹ This difference may represent a selection bias.

In our study, patients with ICA aneurysms were more likely to be referred to the Ophthalmology Department pre-operatively. Cavernous sinus aneurysms are a subtype of ICA aneurysms and are known to cause orbital symptoms, such as chemosis, blurred vision, and cranial nerve palsy.¹² However, they have a low rate of rupture, and the indication for treatment is decided based on symptoms and size.¹³ This may be one of the reasons for the higher rate of pre-operative ophthalmology screening in patients with ICAs.

The most important objective of cranial aneurysm treatment is to prevent death from aneurysms, which occurred in 4% of patients in our study. However, ophthalmological abnormalities were not correlated with the frequency of death. A possible cause of this is cavernous sinus aneurysm, which frequently exhibited cranial nerve palsies in our study, but is thought to have a more benign natural history than intracranial aneurysms in other territories with lower risk of rupture.¹³ Even if they rupture, they usually only cause carotid cavernous fistula and do not extend to the subarachnoid space, thus having a substantially lower rate of life-threatening SAH.¹⁴ In the present study, BA aneurysms tended to cause more SAHs. The diameter of BA aneurysms is a known risk factor for high-mortality rates.¹⁵ The patients with BA aneurysms who exhibited visual symptoms had relatively large aneurysms, which could be one of the reasons for the frequent occurrence of SAH.

Although both surgical clipping and endovascular treatment are effective for the management of intracranial aneurysms,¹⁶ currently, there is insufficient evidence for determining the preferred treatment for individual patients with intracranial aneurysms.¹⁷ Surgical clipping can immediately relieve the compressive effect of the aneurysm, which may be superior in terms of visual symptom recovery rate.^1,8,18,19 Recent studies have reported a good aneurysm occlusion rate with endovascular coiling and a lower post-operative visual field defect rate.^16,20 Flow-diverter stent implantation has recently been introduced. Flow diverters alter blood flow in the mother artery, facilitate aneurysm shrinkage,²¹ and have been reported to be effective not only for achieving aneurysm closure but also for resolving clinical symptoms.¹³ In this study, endovascular treatment was used more frequently than surgical treatment, regardless of the presence of visual field defects. Our results suggest the prevalence of endovascular treatment, even for aneurysms with mass effects; however, prospective and longitudinal follow-ups on ophthalmological examination and visual field testing would be necessary to establish its long-term effectiveness.

This study has some limitations. Although this study consisted of a relatively large number of cases, it is not a consecutive case series of patients with aneurysms, as the patients included in this study were limited to those with aneurysms who were referred to the ophthalmology department based on the decisions of neurosurgeons. Therefore, patients who were in medically critical situations and were unable to visit ophthalmology outpatient departments were not included. This also resulted in the low frequencies of SAH and death observed in this study, which may represent a selection bias and limit the interpretation of the mortality rate. As this research is a retrospective study, our results should be considered exploratory and lack formal power calculation. Among the participants of this study, ICA aneurysm patients were more frequent (65%) than those who were incidentally detected during screening (39%),²⁰ whereas cases with posterior circulation aneurysms were limited in this study. One reason for this difference is that the Neurosurgery Department at Kyoto University Hospital employs flow-diverter stents, which are mainly used for cavernous sinus (ICA) aneurysms, and more patients with ICA aneurysms are referred to our hospital. In this study, ophthalmological abnormalities detected at the first visit to the ophthalmology department were considered, and we did not track the effectiveness of each treatment in terms of ophthalmological symptoms. The small number of posterior circulation aneurysm cases limits our interpretation of their impacts on ophthalmological findings. Although pre-chiasmal visual field defects are thought to be caused by glaucomatous optic neuropathy, we did not perform formal glaucoma evaluations, such as gonioscopy or Goldmann tonometer measurements.

Conclusion

Visual field defects were observed in both anterior and posterior circulation aneurysms, highlighting the importance of careful screening for visual field defects in patients with cranial aneurysms, especially when aneurysms are large or near the visual pathway, regardless of the anatomical position of the originating artery. Although endovascular treatment is becoming increasingly prevalent even for aneurysms with mass effects, prospective and longitudinal follow-ups on ophthalmological examination and visual field testing would be necessary to establish its long-term effectiveness.

Funding Statement

This study was supported in part by a Grant-in-Aid for Scientific Research (No. [22K09812] [K.S.]) and a research funding from Alcon Japan Research Grants (KS). The funding organization had no role in the design or conduct of this study.

Data Sharing Statement

The data that support the findings of this study are not publicly available due to privacy and ethical restrictions imposed by the Institutional Review Board, but are available from the corresponding author upon reasonable request.

Statement of Ethics

This retrospective study adhered to the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board and Ethics Committee of the Kyoto University Graduate School of Medicine (approval number [R2652]). Written informed consent was waived because of the retrospective design of this study; instead, we publicly disclosed this retrospective research on neuromuscular and optic nerve diseases affecting visual function on our faculty’s website, also providing the participants with an opportunity to opt-out. The Institutional Review Board and Ethics Committee of Kyoto University Graduate School of Medicine waived the requirement for informed consent. Patient data were stored and handled safely to ensure confidentiality.

Disclosure

Dr Manabu Miyata reports grants or contracts from Kyoto University Foundation, Japan Society for the Promotion of Science, Santen Pharmaceutical, Chugai Pharmaceutical, Alcon Japan, Bayer Yakuhin; Honoraria from Amgen, Bayer Yakuhin, Chugai Pharmaceutical, Kowa Pharmaceutical, Otsuka Pharmaceutical, Santen Pharmaceutical, Senju Pharmaceutical, TBS television; Meeting/travel support from Santen Pharmaceutical, Bayer Yakuhin, outside the submitted work. No conflicting relationship exists for any other author.