Abstract

Background: Visual field defect and visual impairment are important but poorly characterized complications after flow-diverter (FD) stent placement for internal carotid artery (ICA) aneurysms.

Methods: We retrospectively analyzed 31 consecutive patients with 32 ICA aneurysms treated by FD stent implantation between October 2015 and April 2021. Aneurysms were classified into two groups those with visual symptoms before and after FD stenting (symptomatic group) and those without (asymptomatic group). We analyzed patients’ background characteristics, treatment details, and imaging findings.

Results: Visual symptoms were present in 25% (8/32) of aneurysms and worsened after treatment in 9.4% (3/32). Aneurysm enlargement was more common in the symptomatic group than the asymptomatic group (50% vs. 4.1%; odds ratio 23.0, 95% confidence interval [CI] 2.0–262.6, P = 0.0086). Poor visualization of the ophthalmic artery after procedure was observed in 50% versus 12.5% (odds ratio 7.0, 95% confidence interval 1.1–44.1, P = 0.047). No central retinal artery occlusion or cerebral ischemic events were observed. All three deteriorating cases improved after high dose steroids: one required additional FD stenting.

Conclusion: In this single-center retrospective cohort, visual symptoms after FD stenting were relatively common but were usually reversible. Aneurysm enlargement and early loss of ophthalmic-artery flow identify patients at higher visual risk. Early steroid therapy and, when necessary, further endovascular treatment may mitigate visual deterioration.

Keywords: Aneurysm, Flow diverter stent, Ophthalmic artery, Optic nerve, Visual symptom

INTRODUCTION

Patients with internal carotid artery (ICA) aneurysms in the paraclinoid and cavernous segments sometimes develop cranial nerve symptoms, including visual symptoms such as visual field and visual acuity deficits. Overall, 1.4–1.9%[ 6 , 14 ] of all patients with aneurysms develop visual symptoms. The primary treatment methods for ICA aneurysms include clipping or trapping with bypass (direct approach) and coil embolization or parent artery occlusion (endovascular approach). However, conventional treatment methods have been associated with low cure rates and postoperative worsening of cerebral neurological symptoms.

In 2015, the use of flow diverter (FD) stent placement for aneurysms was approved. Notably, aneurysms in the cavernous and paraclinoid segments, which are large aneurysms that typically have less favorable outcomes after conventional treatment, have been successfully treated using FD stents. Worsening visual symptoms, which can occur with conventional treatment methods, have been reported with FD stent placement; however, those reports are limited, and the exact frequency of post-procedural visual worsening, its underlying mechanisms, and modifiable risk factors remain poorly defined. Therefore, this study assessed the frequency and details of visual symptoms (i.e., visual field deficit and visual acuity deficit) associated with FD stent placement at our institution and evaluated the mechanisms related to these symptoms.

MATERIALS AND METHODS

Subjects

We retrospectively identified patients with intracranial ICA aneurysms treated with FD stent placement between October 2015 and April 2021. There were 31 consecutive patients with 32 aneurysms. One patient had both left and right aneurysms (Observation period: 323-1923 days, median: 797 days.). Ethics Committee of our institution approved this retrospective study (approval no. 21-156-B).

Ophthalmic artery collateral vessel evaluation using the balloon occlusion test (BOT)

Visual symptoms were defined as symptoms caused by disorders of the optic nerve, such as visual field deficit and visual acuity deficit, with ocular movement disorders and diplopia being excluded. Patients with preoperative visual symptoms and patients with poor collateral vessel development (e.g., anterior and posterior communicating arteries on MRA) underwent the BOT. First, the cervical ICA ipsilateral to the aneurysm was occluded with a 5-Fr Selecon MPC Catheter II (Terumo, Tokyo, Japan) or Scepter XC catheter (MicroVention, Aliso Viejo, California, USA). Then, ipsilateral common carotid artery angiography was performed to confirm the presence of retrograde blood flow in the ophthalmic artery from the external carotid artery.

Endovascular treatment

More than 14 days before treatment, aspirin (100 mg/day) and clopidogrel (75 mg/day) were first administered. Then, 2 days before treatment, the platelet function was checked using the VerifyNow system (Werfen, Barcelona, Spain). Clopidogrel was stopped if the P2Y12 reaction unit value was more than 230 and a 20-mg loading dose of Prasugrel was administered instead; this was continued at 3.75 mg/day. Furthermore, the initial clopidogrel dose was reduced to 50 mg if the P2Y12 reaction unit value was <150. Finally, if the aspirin reaction unit value was more than 500, then 200 mg of cilostazol was added to the regimen.

Patients were administered systemic heparin and monitored during the procedure based on the activated clotting time. First, an 8-Fr guiding catheter or 6-Fr guiding sheath was placed in the ICA, and a MARKSMAN (Medtronic) or Headway Plus (MicroVention, Aliso Viejo, California, USA) microcatheter was guided to the distal part of the aneurysm using a 5-Fr NAVIEN (Medtronic) or SOFIA Flow Plus/ SOFIA Flow (MicroVention) support device. Finally, a Pipeline Flex or FRED (MicroVention) stent was deployed. The risk of subarachnoid hemorrhage was considered high for intradural aneurysms larger than 10 mm. Coil embolization was performed in addition to FD placement in such cases. Postoperative internal carotid angiography was performed to confirm the ophthalmic artery contrast findings.

Postoperative evaluation

Magnetic resonance imaging (MRI) and computed tomography (CT) were performed on the day after treatment to identify any hemorrhagic and ischemic complications. The maximum aneurysm diameter was measured by time-of-flight or fluid attenuated inversion recovery axial MRI at 1, 3, and 6 months after treatment; postoperative enlargement was defined as an increase in diameter of 10% or more from the preoperative level.

Visual follow-up was conducted by assessing patients daily for any visual symptoms whilst in hospital, followed by reviews at the first outpatient clinic appointment (within two weeks) and again at the one-month follow-up visit after discharge. Patients were also instructed to return immediately if they experienced any new or worsening visual symptoms. In addition, visual field and visual acuity disturbances were evaluated by ophthalmology examinations, including visual acuity, fundus, and visual field tests when patients reported symptoms; routine screening was not undertaken. Follow-up angiography was performed at 6–12 months after treatment.

Analysis groups

We divided the aneurysms into two groups, the symptomatic group and the asymptomatic group, based on the presence or absence of visual symptoms before and after treatment. In the symptomatic group, we compared the postoperative courses with symptom progression or appearance and those with stable or improving symptoms.

We collected data regarding the location (Fisher classification) and maximum diameter of the aneurysms, the presence or absence of collateral blood flow to the ophthalmic artery during the BOT, the presence or absence of concomitant coiling, and the O’Kelly Marotta (OKM) scale grade[ 8 ] of the aneurysms according to angiography immediately after and 6–12 months after treatment. Furthermore, we evaluated the ophthalmic artery during internal carotid angiography after FD stent placement.

A univariate analysis was conducted using Fisher’s exact test for dichotomous variables and the Mann–Whitney U-test for continuous and independent variables. Given the small sample size, no multivariate analysis was performed, and all statistics are reported as unadjusted values. Odds ratios with 95 % confidence intervals were calculated from 2 × 2 tables; P < 0.05 was considered significant. All data were statistically analyzed using SAS version 9.4 (SAS Institute, Cary, North Carolina, USA).

RESULTS

Patient and aneurysm characteristics

The mean patient’s age was 54.9 years, and 28 (90.3%) were female. The Pipeline Flex stent was used for 17 aneurysms. The FRED stent was used for 15 aneurysms. We treated one patient with bilateral aneurysms: and one patient had visual symptoms in the right eye and no symptoms in the left eye.

Eight patients experienced visual symptoms caused by optic neuropathies before or after treatment (symptomatic group), and 24 aneurysms were asymptomatic (asymptomatic group) [ Table 1 ]. Of the eight patients in the symptomatic group, improvement was noted in two patients, no change was noted in three patients, and the condition worsened after the treatment in three patients. Seven patients had visual symptoms before treatment and one developed symptoms after treatment. Furthermore, seven patients reported visual field deficits, and three reported visual acuity deficits. The mean maximum diameter of the aneurysm was 14.1 mm in the symptomatic group and 10.3 mm in the asymptomatic group. (P = 0.13). The frequency of ICophthalmic aneurysms was 25.0% in the symptomatic group and 29.2% in the asymptomatic group, respectively, with no significant differences noted (P = 1.0). A total of 15 patients (six in the symptomatic group and nine in the asymptomatic group) underwent BOT, and retrograde blood flow in the ophthalmic artery was observed in all cases at the time of ICA occlusion [ Table 1 ].

Table 1:

Patient characteristics.

Endovascular treatment

The Details of endovascular treatment are summarised in Table 2 . Coils were used for 5 (62.5%) and 7 (29.2%) aneurysms in the symptomatic group and the asymptomatic group, respectively. (P = 0.11) In such cases, coil embolization was performed for approximately five coils (average length: 173 cm).

Table 2:

Treatment and results summary.

There were no differences in the aneurysm size and location and use of coils between the two groups; however, aneurysm enlargement was more frequent in symptomatic cases (50% vs. 4.1%; OR 23.0, 95% confidence interval [CI] 2.0–262.6, P = 0.0086). All three aneurysms in patients with worsening symptoms after treatment enlarged.

Twenty-three patients underwent angiography at 6–12 months after treatment; of these, 20 (83.3%) had favorable embolization results according to the OKM scale (grade C or D).

In the symptomatic group, 4 (50%) patients had poor (i.e., no or delayed) ophthalmic artery visualization after FD stent implantation, and 3(12.5%) patients in the asymptomatic group (OR 7.0, 95% CI 1.1–44.1, P = 0.047). Blood flow progressively recovered during the chronic phase (6–12 months after treatment). However, another patient in the asymptomatic group had poor visualization after follow-up.

Prognosis of visual symptoms

Three patients experienced worsening or new visual symptoms after treatment and progressive worsening of the visual field and visual acuity deficits on postoperative days 3, 19, and 25. In all the patients, no evidence of cerebral infarction on MRI and findings of retinal ischemia were noted. In two of these patients, the aneurysms were thrombosed with a high T1 signal; furthermore, the aneurysms were obviously larger than they were before the treatment. 1In one patient, an ICA–ophthalmic artery aneurysm extended into an enlarged optic canal, with the ophthalmic artery arising near the dome apex. Both the coil and the thrombosed aneurysm were compressing the optic nerve. Compressive optic neuropathy caused by edema and inflammation were suspected; therefore, steroid pulse therapy was administered (1000 mg/day of methylprednisolone succinate sodium) for 3 days, followed by gradual tapering of prednisolone. In one patient, the aneurysm remained and enlarged again, and another FD stent was placed on postoperative day 133. Visual acuity returned to the preoperative level in two patients, but mild visual field deficit remained. Visual acuity and the visual field deficit improved marginally in the third patient.

Representative case

A C2 aneurysm with a maximum diameter of 15 mm was identified in a 57-year-old woman presenting with visual field deficit [ Figure 1 ]; the aneurysm was treated using FRED4*32/26 with coil embolization (5 coils, 190 cm, FRED 4.0*32/26) [ Figure 2 ]. On postoperative day 25, she noticed worsening of her visual field disturbances deficit and vision loss visual acuity deficit. The retinal examination results were normal, but MRI showed optic nerve compression. Therefore, steroid pulse therapy was administered twice; however, no improvement occurred. Angiography showed a residual and enlarged aneurysm; therefore, another FRED (3.5*17/11) was placed on postoperative day 133 [ Figure 2 ]. After retreatment, the aneurysm thrombosed, thus improving the visual acuity and visual field impairment [ Figure 3 ]. Angiography during the chronic phase suggested the residual neck of the aneurysm (OKM scale C), and the ophthalmic artery visualization progressively improved.

Figure 1:

The pre-treatment examination results of a 57-year-old woman with a C2 aneurysm. (a) Axial T2 MRI identified an aneurysm compressing the optic chiasma to the left. (b) Angiography showed a large internal carotid artery paraclinoid aneurysm.

Figure 2:

Treatment progressions. digital subtraction angiography images (a) before (3D image) and (b) after the initial treatment. (c) Cone-beam computed tomography after the second treatment. (d-f) OA visualization (arrowhead) in ICA arteriography. (d) before treatment, (e) after the first treatment, and (f) chronic phase. (ICA: Internal carotid artery)

Figure 3:

(a-c) Right eye visual field tests. (d-f) Coronal MRI T1 image. When the symptoms worsened, the aneurysm thrombosed and compressed the left optic nerve. When the symptoms improved, the high T1 signal within the aneurysm disappeared.

DISCUSSION

In this retrospective cohort, visual symptoms appeared in 25 % of intracranial ICA aneurysms treated with a FD stent, and 9 % worsened post-procedure. Worsening correlated with aneurysm enlargement and poor ophthalmi-cartery visualization on the completion angiogram, whereas no retinal or cerebral ischemic events were documented.

Large series and meta-analyses describe optic-nerve dysfunction in 21–38 % of paraclinoid ICA aneurysms and postoperative worsening in 5–11% after clipping, coiling or FD placement.[ 6 , 8 , 13 ] A pooled set of 2,458 aneurysms reported visual improvement in 58% of clipping cases, 49% of coiling cases and 71% of FD cases.[ 10 ] Our improvement rate of 75% and deterioration rate of 9% fall within these figures. Because an FD diverts flow at the neck, dense coil packing is unnecessary; many sacs are left uncoiled or receive only a few coils. The smaller implant volume reduces acute pressure on the optic nerve and probably underlies the generally favorable visual outcomes noted here and elsewhere.[ 9 , 10 ]

Three principal pathways may cause visual deterioration: (1) retinal ischemia due to centralretinal artery occlusion, (2) cerebral infarction in the posterior-cerebral territory, and (3) compressive optic neuropathy produced by thrombus-related sac enlargement and inflammation.[ 2 , 5 , 12 ] Our worsening cases developed 3–25 days after treatment, lacked retinal or cortical infarcts and showed aneurysm enlargement on MRI, supporting the compression mechanism. High-dose steroids alleviated symptoms in all three patients, consistent with previous reports that timely anti-inflammatory treatment can relieve edema-related optic neuropathy.[ 11 ]

Poor ophthalmic-artery visualization occurred in 29% of aneurysms and was associated with symptoms (odds ratio 7.0). Flow recovered within 6–12 months, paralleling the gradual resolution of thrombus-related edema. During periods of reduced antegrade flow, retrograde collaterals from the external carotid system – particularly the middle meningeal artery – appear to sustain retinal circulation.[ 3 , 4 , 9 ] BOTs demonstrate retrograde flow in 86–93 % of cases;[ 1 , 7 ] in our own series, BOT was performed in 15 patients and showed retrograde filling in every instance, making true ophthalmic-artery thrombosis unlikely.

When visual symptoms due to thrombosis of aneurysm arise, early steroid therapy and, if persistent sac filling is confirmed, placement of an additional FD stent should be considered to limit further deterioration.

Study limitations include the single-center, retrospective design, and small cohort, which limit statistical power. Visual symptoms were mainly self-reported, and systematic ophthalmological testing was not routine. Quantitative ophthalmic-artery flow studies and BOT were performed in only some patients and follow-up imaging schedules varied. Potential confounding from adjunctive coil uses or changes in antiplatelet therapy cannot be excluded. Prospective multicenter studies employing uniform visual-function protocols are warranted.

CONCLUSION

In patients with ICA aneurysms treated with FD stents, visual symptoms occurred in 25% of cases, and 9.4% experienced postoperative worsening. Aneurysmal enlargement and poor ophthalmic artery visualization were associated factors. Early intervention with steroids and repeat stenting may improve outcomes.

Ethical approval:

The study was approved by the Institutional Review Board of Showa Medical University, Tokyo, Japan (Approval No. 21-156-B) and dated March 15, 2022.

Declaration of patient consent:

Patient’s consent was not required as there are no patients in this study.

Financial support and sponsorship:

Nil.

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that they have used artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript or image creations.

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.

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