Large two-centre UK experience with good long-term stability and safety profile in the flow diversion of carotid-ophthalmic aneurysms

Introduction

Carotid-ophthalmic artery aneurysms represent 5–10% of all intracranial aneurysms (1). These are sidewall paraclinoid aneurysms, often wide-neck, located between the distal dural internal carotid artery (ICA) ring to the origin of the posterior communicating artery (2).

Open surgical intervention is technically difficult, due to the narrow surgical corridor which contains perforating arteries, the cavernous sinus, oculomotor nerve and the optic apparatus (3). Furthermore, open techniques are associated with a higher rate morbidity and visual complications.

With the development of less-invasive endovascular techniques, some of these difficulties may be circumvented with a lower risk of complications. However, classical treatment consisting of simple or balloon assisted coiling in side-wall aneurysms poses the risk of lower rates of complete occlusion and cure with more frequent aneurysm recurrences. New treatment modalities including flow diverter stents (FDS) have shown promising results (4). On the other hand, the longevity and efficacy provided by treatment with stent assisted coiling and flow diversion may be associated with a higher risk of embolic complications. Currently, there is no consensus regarding the optimal management of carotid-ophthalmic aneurysms.

In our study we aim to present a large United Kingdom experience and series of carotid-ophthalmic segment aneurysms treated with flow diversion. We present this article in accordance with the STROBE reporting checklist (available at https://jni.amegroups.com/article/view/10.21037/jni-25-38/rc).

Methods

This is a retrospective analysis at two large tertiary neurosurgical centres in the United Kingdom (Leeds General Infirmary, Leeds, UK and Hull Royal Infirmary, Hull, UK) in the treatment of carotid-ophthalmic artery aneurysms with a flow diverter. All patients treated for carotid-ophthalmic aneurysms with a flow diverter were included. Data collected included: (I) demographics; (II) aneurysm characteristics: laterality, dimensions and pre-intervention thrombosis status; (III) treatment modality; (IV) follow-up; (V) efficacy (occlusion rates) and (VI) complications (morbidity and mortality). Incomplete data were excluded from the analysis.

Continuous variables were expressed as means with standard deviations or medians with interquartile ranges, depending on data distribution. Categorical variables were expressed as frequencies and percentages. Microsoft Excel was used for data collection and simple analysis.

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study did not require local ethical approval due to the retrospective nature of the data collection and individual consent for this retrospective analysis was waived.

Procedural data

All patients were pre-loaded with dual antiplatelets prior to endovascular treatment. The use of specific antiplatelets was heterogeneous. One centre relied mostly on Clopidogrel and Aspirin, whilst the other centre used Ticagrelor and Aspirin. All patients were continued on dual antiplatelets for 5–6 months, then carried on with a lifelong single antiplatelet.

All procedures were performed under general anaesthetic in biplane angiography suites. A transfemoral approach was used. Patients received heparin intravenously after successful common femoral puncture with the aim of achieving an activated clotting time of 1.5–2 times the baseline. The use of triaxial or biaxial systems was decided before the procedure to ensure stable navigation and deployment of the microcatheters required and the flow diverter. This choice was dependent on assessment of the patient’s vascular anatomy on pre-operative imaging [computed tomography angiography (CTA) or magnetic resonance angiography (MRA)]. On navigation into the target vessel, initial biplane and 3D rotational angiograms were obtained for planning and aneurysm measurement.

Our cohort did not have a strict measurement cut-off for adjunctive complete or partial coiling. Complete coiling was defined as O’Kelly Marotta scoring (OKM) score D on the final run angiogram appearance. Generally, we would perform coiling through a jailed microcatheter in the aneurysm in the following circumstances:

• Aneurysm size >8 mm;
• Irregular aneurysm morphology;
• Recurrence of previously ruptured aneurysm;
• Compressive aneurysm causing visual symptoms.

The patients were discharged home the next day if there were no immediate complications.

Radiological results

The immediate occlusion rates were categorised according to OKM. The aim is to observe a degree of contrast stagnation in the aneurysm. Complete or partial occlusion is not necessary at the time of implantation. If stagnation is not observed, then the process involves checking for correct device placement, coverage of the aneurysm neck and ensuring there is no endo-leak along the proximal or distal end of the flow diverter.

Routine imaging follow-up was routinely performed at 6- and 24-month post-procedure. MRA, CTA and digital subtraction angiography (DSA) were the primary modalities of choice for angiographic follow-up. The Raymond-Roy occlusion criteria (RROC) was used to characterise occlusion rates.

The outcomes were defined as complete occlusion (modified Raymond-Roy criteria 1) and adequate occlusion (modified Raymond-Roy criteria 1 and modified Raymond-Roy criteria 2) at 6-month and 2-year posttreatment.

Clinical outcome and complications

Functional outcome was assessed at the end of hospital stay and 6 months post-discharge. Visual complications were self-reported by patients, with no formal pre- or post-operative ophthalmological testing. Procedural complications including thromboembolic events and vascular injury were recorded.

The primary safety outcome was the rate of device-related adverse events. Secondary safety outcomes included time to discharge and functional outcome [modified Rankin score (mRS)] at 6-month follow-up.

Statistical analysis

Statistical analyses were performed using SPSS V29. Continuous variables were defined according to mean, median and range. Categorical data were described with frequency statistics.

Results

Baseline characteristics

Baseline characteristics are shown in Table 1.

In our cohort, 102 patients with carotid-ophthalmic aneurysms were treated with a flow diverter from January 2015 to December 2021.

All 102 patients were elective cases. The indication for treatment were: definitive treatment of aneurysm recurrence in 7 patients (6.9%), visual deficits in 6 patients (5.8%), embolic event from partially thrombosed aneurysm in 1 patient (1.0%) and incidental finding of the aneurysm in 88 patients (86.3%).

The mean age of the patients was 56 (range, 29–78) years. The average aneurysm neck diameter was 4.53 mm (1.4–9.46 mm), average dome width was 7.58 mm (1.5–25.8 mm), average dome height was 7.25 mm (2–27.7 mm) and the dome-to-neck ratio (DNR) was 1.67 (0.64–4.82). Eleven aneurysms were partially thrombosed (10.78%).

Endovascular treatment

The treatment paradigm is demonstrated in Table 2. In total, 70/102 (68.6%) patients were treated with a flow diverter alone, partial coiling was performed in 25 (24.5%) and complete coiling in 7 (6.9%). The flow diverters used were operator and centre dependent and are detailed in table 2.

Radiological follow-up and anatomical results

A total of 88 aneurysms (87.1%, out of 101; immediate angiographic imaging not available for 1 patient) demonstrated a form of contrast stagnation (A2: 46, A3: 10, B2: 20, B3: 8, C2: 3, C3: 1). Nine aneurysms (8.9%) demonstrated complete aneurysm occlusion, which included 7 aneurysms that were complete coiled. Four aneurysms (4%) showed no contrast stagnation on immediate post flow diverter deployment. No further flow diverters were placed for these aneurysms as the device was fully open with good wall and aneurysm neck apposition.

The median radiological follow-up was 2 years. One hundred patients underwent 6-month follow-up. Two patients did not have follow-up: 1 patient died from an unrelated cause, and 1 patient was non-compliant with imaging follow-up. Complete aneurysm occlusion (RROC1) was achieved in 80 patients (80%) and neck residuum (RROC2) in 12 patients (12%). A residual aneurysm (RROC 3) was observed in 8 patients (8%). The adequate occlusion rate (RROC 1 + RROC 2) at 6 months was 92/100 (92%). Figure 1 demonstrates an example of flow diversion without coiling with complete aneurysm occlusion on magnetic resonance imaging (MRI) follow-up.

Figure 1 Example case demonstrating complete aneurysm occlusion of a flow diverter treated carotid-ophthalmic aneurysm. (A) DSA demonstrating a complex wide-neck right ICA in the paraophthalmic segment. (B) Native DSA image demonstrating deployment of a Pipeline flow diverter from the right M1 segment to the ICA below the aneurysm. (C) T2 MRI sequence demonstrating thrombosis and significant reduction in the size of the paraophthalmic aneurysm seen in figure (A). The arrow points to the thrombosed shrunken aneurysm. (D) TOF MRA demonstrates complete occlusion of the aneurysm with no residuum. DSA, digital subtraction angiography; ICA, internal carotid artery; MRA, magnetic resonance angiography; MRI, magnetic resonance imaging; TOF, time of flight.

One patient underwent deployment of a further flow diversion after demonstration of a residual aneurysm at 6-month follow-up. This resulted in complete aneurysm occlusion on further interval follow-up.

At the last angiographic follow-up, the adequate occlusion rate was 100%. The results demonstrated 91 aneurysms (91%) with complete occlusion and 9 aneurysms (9%) with a small residual neck.

Table 3 breaks down the follow-up periods achieved for our cohort. Figure 2 demonstrates an example case of coiling and flow diversion of a carotid-ophthalmic aneurysm with complete occlusion on DSA follow-up.

Figure 2 A DSA demonstrating coiling and flow diversion treatment of a large carotid-ophthalmic aneurysm with follow-up. (A) DSA image of an irregular wide-neck asymptomatic large carotid ophthalmic aneurysm. (B,C) Demonstration of immediate post-operative DSA imaging of the treated aneurysm with subtotal coiling and flow diversion. (D) Demonstration of 6-month DSA follow-up of the aneurysm with complete occlusion (no residual or recurrence). DSA, digital subtraction angiography.

Safety outcomes and complications

Table 4 demonstrates a breakdown of the post-operative complications. Two patients (1.9%) had complications resulting in a significant permanent neurological deficit (mRS >1). One patient had slightly poor apposition of the flow diverter (Surpass Evolve; Stryker) in a segment of stenosis along the ICA. An attempt to improve the apposition was made with a balloon (Hyperglide 4×15, Medtronic), which did not improve the appearances. A further attempt was made with the balloon, which caused a rupture of the ICA. The balloon was quickly reinflated to stop the bleeding. Subsequently, an angiogram of the right ICA demonstrated good cross-flow via the anterior communicating artery (ACOM) into the left hemisphere, therefore decision was made to coil the ICA and rupture point, which was successful. The patient required an extra-ventricular drain (EVD). A prolonged inpatient rehabilitation was required and was discharged home at 228 days, walking independently with a stick (mRS 2).

The second patient was treated for a left sided carotico-ophthalmic aneurysm with FRED (Microvention) after being preloaded with Aspirin and Ticagrelor. There was incomplete opening of the proximal aspect of the flow diverter, which resulted in build-up of thrombus. This was treated with placement of a laser-cut stent (Solitaire AB, Medtronic). The patient woke up with right sided weakness, agitation and dysphasia. A post-op MRI showed left parietal and frontal infarction. The patient had residual weakness and speech difficulty at 6-month follow-up (mRS 3).

Ten patients developed transient ischaemic symptoms in the postprocedural period. All of these patients fully recovered prior to discharge and all were independent (mRS 0) at 6-month follow-up. Six patients developed a puncture site haematoma, with three patients requiring treatment (thrombin injection).

The median length of post-operative stay in hospital was 1 day (average 5.06 days; range, 1–228 days). Three patients had prolonged hospital admission. In one patient, this was due the intracranial haemorrhage from ICA rupture as described above. In another patient, hospital stay was 38 days due to prolonged recovery from pre-treatment embolic stroke. In the third patient, prolonged stay of 10 days was required due to recovery from a brachial artery pseudoaneurysm, which occurred from arterial line insertion for invasive blood pressure monitoring. Overall, 95 patients were discharged within 7 days of admission.

Six patients presented with visual field defects. No patient reported a deterioration in vision following endovascular treatment.

Discussion

Aneurysms of the carotid-ophthalmic segment can present due to symptoms of headache or visual field defects due to compression of the optic apparatus and subsequently require treatment (5). Additionally, they can be incidentally detected and undergo treatment due to the inherent risk of future subarachnoid haemorrhage as per PHASES and ISUIA (6).

The aim of treatment is to achieve aneurysm decompression, minimise risk of future haemorrhage and recurrence. Classically, open surgical clipping of ophthalmic and hypophyseal segment aneurysms presents a durable treatment option. However, owing to the complexity of the local anatomy and narrow surgical corridor, morbidity rates can be high. The particular risk is of intraprocedural rupture as well as incidence or worsening of visual field defect. A study by Kamide et al. of the largest reported population of surgically treated carotid-ophthalmic aneurysms demonstrated a complete occlusion rate of 91%, but this was associated with a 10.5% risk of new or worsening visual field defects (7). Multiple potential mechanisms have been hypothesised: thermal injury from high-speed drilling of the optic canal; direct optic nerve compression or ischaemic change of the optic tract. Lower visual morbidity has been reported with flow diverter stent treatment. One meta-analysis including 913 ophthalmic artery segment aneurysms treated with FDS found a 3% rate of visual complications, however there this was limited by a moderate-high heterogeneity of the included studies (8).

In our cohort, none of the six patients that presented with visual deficits suffered a deterioration of vision on routine clinical testing however formal ophthalmology assessment was not undertaken for these patients in the postoperative period.

Simple or balloon assisted coiling of side-wall aneurysms such as carotid-ophthalmic aneurysms would be considered lower risk than flow diversion for thrombo-embolic phenomena as there is no parent artery metal component. Due to the anatomy and difficulty achieving a high packing density, there is a high risk of recurrence causing increased risk of future haemorrhage or worsening compression related visual field defects (9). Flow diversion demonstrates favourable results in this regard with very high complete aneurysm occlusion rates above 90%.

Recently, novel endovascular techniques including flow diverter systems have gained traction as alternative modalities for the treatment of these aneurysms. Flow diversion systems were initially designed to treat aneurysms with challenging morphology, i.e. those with wide necks and overall large dimensions. Flow diverting stents can stimulate aneurysm occlusion through cessation of intrasaccular flow and subsequent aneurysm thrombosis and may be robust over time. In one study, 101 carotid-ophthalmic aneurysms treated with flow diversion demonstrated a total or near-total occlusion rate of 92% in a follow-up period 6–18 months following treatment (10). In our cohort, 99% of patients had at least 1-year radiological follow-up with excellent occlusion rates.

Partially thrombosed aneurysms are well-known for difficult treatment as well as high recurrence and rebleeding risk, with as high as 75% risk of recurrence in cases of simple coiling or intrasaccular devices (11). Our cohort had a significant percentage of partially thrombosed carotid-ophthalmic aneurysms at approximately 11%, which were all completely occluded within 6 months of treatment.

There has been a significant improvement and technological advancement in the world of flow diversion. The stent structures have been developed to provide better deliverability, navigability and apposition, whilst maintaining the flexibility for difficult tortuous anatomy and the degree of desired flow diversion. The development of newer devices with Nitinol and anti-thrombotic coating, has led to the improvement of these properties, whilst reducing the risk of thromboembolic complications and need for long-term antiplatelet therapy (12). There was a decrease of complications during the second half of our cohort (although not statistically significant), which could be attributed, although has not been directly analysed nor associated in our study.

Accurate sizing of a flow diverters length and diameter is essential. Oversizing of a device risks unintentionally jailing side-branches or bifurcations, as well as suboptimal flow diverter deployment such as fish-mouthing or a ledge at the proximal or distal end of the stent along tortuous anatomy, which would increase the risk of thromboembolic complications. On the other hand, under-sizing in length or diameter might risk an endo-leak. A significant endoleak might require further flow diverter deployment or the use of techniques such as deployment of an intracranial stent to pin the device to the parent vessel or balloon angioplasty, both of which carry an increased risk of rupture or thrombosis. Both of our serious complications were associated with incorrect sizing, which resulted in significant morbidity and mortality.

New technology such as SimandSize and Presize have created platforms for 3D reconstruction of the vessel and accurate sizing and deployment of intracranial stent and flow diverters (13,14). This would benefit the operator with increased confidence of flow diverter sizing as well as predict and troubleshoot any issues in the sizing of flow diverters in advance. Moreover, accurate planning of the procedure and flow diverter required would reduce the potential costs, including flow diverter wastage.

Thromboembolic phenomena are a documented risk from endovascular treatment. One of the potential pitfalls of flow diversion may be the occlusion of branching arteries. However, this has been shown to be a rare complication in the anterior choroidal artery orophthalmic artery, particularly when it is a well-sized artery, or required to maintain flow if there is no collateral supply. Flow diverter stent thrombosis is rare. As previously demonstrated, clear indication for treatment and accurate deployment reduces the risk significantly. Adequate use of intra-operative heparin and peri-operative antiplatelet treatment further reduces the risk. The use of pre-operative antiplatelet testing remains variable world-wide, however is increasing in use and frequency. Multiple studies involving the use of clopidogrel in cardiovascular literature have demonstrated that 25% of the population show resistance to clopidogrel with a significant associated risk of thromboembolic complications (15). Moreover, the risk of resistance is markedly higher in Asian population at 50–60% and would warrant consideration of different antiplatelet regimens such as Prasugrel and Ticagrelor (16). The use of a specific antiplatelet was heterogeneous in our cohort and we have started pre-operative VerifyNow testing since this data was collected and analysed (17).

Post-operative aneurysm rupture after flow diverter treatment has been a well-described complication. Multiple studies have subsequently suggested that aneurysms larger than 10mm treated with flow diversion, with no adjunctive coiling are at higher risk (18). Our cohort underwent adjunctive coiling with flow diversion for aneurysms larger than 10mm with no post-operative haemorrhage recorded in this aneurysm cohort.

This study has some important limitations. The retrospective design has implications for bias in reporting. Although none of our patients developed a deterioration in vision on crude testing, formal ophthalmology assessment was not undertaken and therefore subtle field deficits may be underestimated.

The interpretation of the outcomes is limited as the variations in treatment (coiling vs. no coiling and models of flow diverters) were pooled in the analysis.

Conclusions

FDS for the treatment of carotid-ophthalmic aneurysms was demonstrated to be safe and effective in the follow-up period studied with a complete occlusion rate of 91% and adequate occlusion rate of 100%. Further study is required to corroborate these findings and particularly investigation of routine antiplatelet testing and optimisation of device sizing as methods to reduce the risk of thromboembolic complications. Additionally, the favourable outcomes compared to other endovascular means and open surgical clipping calls for comparative randomised trials of flow diversion vs. clipping of carotid-ophthalmic aneurysms.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jni.amegroups.com/article/view/10.21037/jni-25-38/rc

Data Sharing Statement: Available at https://jni.amegroups.com/article/view/10.21037/jni-25-38/dss

Peer Review File: Available at https://jni.amegroups.com/article/view/10.21037/jni-25-38/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jni.amegroups.com/article/view/10.21037/jni-25-38/coif). T.P. serves as an unpaid editorial board member of Journal of Neurointervention from November 2024 to December 2026. T.P. is also a consultant for Medtronic, Styker and BALT. F.I.I. is a consultant for Medtronic and Stryker; received payment for presentation on NEQSTENT at QUINS, London, 2025; received support to attend QUINS from Medtronic. A.S. has proctor/teaching contracts with Microvention, WallabyPhenox; and teaching contract with Penumbra. N.S. received funding support for attending ESMINT conference in September 2024 from Medtronic. H.N. acts as a clinical consultant for Phenox and Penumbra and received financial support from Stryker, J and J MedTech and Terumo Neuro to attend educational events and conferences. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study did not require local ethical approval due to the retrospective nature of the data collection and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Drake CG, Vanderlinden RG, Amacher AL. Carotid-ophthalmic aneurysms. J Neurosurg 1968;29:24-31. [Crossref] [PubMed]
2. Day AL. Aneurysms of the ophthalmic segment. A clinical and anatomical analysis. J Neurosurg 1990;72:677-91.
3. Tamaki N, Kim S, Ehara K, et al. Giant carotid-ophthalmic artery aneurysms: direct clipping utilizing the “trapping-evacuation” technique. J Neurosurg 1991;74:567-72. [Crossref] [PubMed]
4. Becske T, Kallmes DF, Saatci I, et al. Pipeline for uncoilable or failed aneurysms: results from a multicenter clinical trial. Radiology 2013;267:858-68. [Crossref] [PubMed]
5. Greving JP, Wermer MJ, Brown RD Jr, et al. Development of the PHASES score for prediction of risk of rupture of intracranial aneurysms: a pooled analysis of six prospective cohort studies. Lancet Neurol 2014;13:59-66. [Crossref] [PubMed]
6. Wiebers DO, Whisnant JP, Huston J 3rd, et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 2003;362:103-10. [Crossref] [PubMed]
7. Kamide T, Tabani H, Safaee MM, et al. Microsurgical clipping of ophthalmic artery aneurysms: surgical results and visual outcomes with 208 aneurysms. J Neurosurg 2018;129:1511-21. [Crossref] [PubMed]
8. Touzé R, Gravellier B, Rolla-Bigliani C, et al. Occlusion Rate and Visual Complications With Flow-Diverter Stent Placed Across the Ophthalmic Artery’s Origin for Carotid-Ophthalmic Aneurysms: A Meta-Analysis. Neurosurgery 2020;86:455-63. [Crossref] [PubMed]
9. Tian Z, Liu J, Zhang Y, et al. Risk Factors of Angiographic Recurrence After Endovascular Coil Embolization of Intracranial Saccular Aneurysms: A Retrospective Study Using a Multicenter Database. Front Neurol 2020;11:1026. [Crossref] [PubMed]
10. Griessenauer CJ, Piske RL, Baccin CE, et al. Flow Diverters for Treatment of 160 Ophthalmic Segment Aneurysms: Evaluation of Safety and Efficacy in a Multicenter Cohort. Neurosurgery 2017;80:726-32. [Crossref] [PubMed]
11. Ferns SP, van Rooij WJ, Sluzewski M, et al. Partially thrombosed intracranial aneurysms presenting with mass effect: long-term clinical and imaging follow-up after endovascular treatment. AJNR Am J Neuroradiol 2010;31:1197-205. [Crossref] [PubMed]
12. Chen Y, Howe C, Lee Y, et al. Microstructured Thin Film Nitinol for a Neurovascular Flow-Diverter. Sci Rep 2016;6:23698. [Crossref] [PubMed]
13. Mantilla D, Ferreira-Prada CA, Galvis M, et al. Clinical impact of Sim & Size® simulation software in the treatment of patients with cerebral aneurysms with flow-diverter Pipeline stents. Interv Neuroradiol 2023;29:47-55. [Crossref] [PubMed]
14. Patankar T, Madigan J, Downer J, et al. How precise is PreSize Neurovascular? Accuracy evaluation of flow diverter deployed-length prediction. J Neurosurg 2022;137:1072-80.
15. Wiviott SD, Antman EM. Clopidogrel resistance: a new chapter in a fast-moving story. Circulation 2004;109:3064-7. [Crossref] [PubMed]
16. Hasan MS, Basri HB, Hin LP, et al. Genetic polymorphisms and drug interactions leading to clopidogrel resistance: why the Asian population requires special attention. Int J Neurosci 2013;123:143-54. [Crossref] [PubMed]
17. Neyens R, Donaldson C, Andrews C, et al. Platelet Function Testing with a VerifyNow-Directed Personalized Antiplatelet Strategy and Associated Rates of Thromboembolic Complications After Pipeline Embolization for Complex Cerebral Aneurysms. World Neurosurg 2020;138:e674-82. [Crossref] [PubMed]
18. Darsaut TE, Rayner-Hartley E, Makoyeva A, et al. Aneurysm rupture after endovascular flow diversion: the possible role of persistent flows through the transition zone associated with device deformation. Interv Neuroradiol 2013;19:180-5. [Crossref] [PubMed]