Background:  Retinal artery occlusion (RAO) is a time-sensitive ophthalmic emergency that demands rapid diagnosis and intervention. Administration of intravenous tissue plasminogen activator (IVtPA) within 4.5 hours of symptom onset appears to be the most promising approach for improving visual outcomes, supported by multiple studies and meta-analyses.^1,2 Intra-arterial (IA) tPA has also shown benefit but is less well studied.^3,4  It’s important to note that the available studies have several limitations including single-center studies, very small sample sizes, etc. Moreover, there are multiple operational and patient-specific barriers rendering timely thrombolytic administration difficult.

Timely recognition of RAO is challenging. Because of its rarity (it affects just 2 in 100,000 people/year),⁵  the diagnosis may not be considered or may be delayed. This is compounded by limited access to diagnostic tools like fundoscopic photography and optical coherence tomography (OCT) and emergency ophthalmology consultants. Transferring patients for consultation can further delay vision-preserving treatment. Finally, most hospitals lack the necessary protocols and processes to coordinate the complex interdisciplinary care patients with RAO may require.

Paper: Lema GMC, De Leacy R, Fara MG, et al. A Remote Consult Retinal Artery Occlusion Diagnostic Protocol. Ophthalmology. 2023. PMID: 38349294

Clinical Question: Can a remote consult protocol using point-of-care OCT improve the time to diagnosis and treatment of retinal artery occlusions in patients presenting with painless monocular vision loss?

What They Did:

• Retrospective review of consecutive RAO cases managed as part of a remote ophthalmology consult protocol activated on May 1, 2021, at three stroke centers across a health system.
• The protocol involved collaboration between the ophthalmology service, ED, and stroke service, including neurology and neuroendovascular teams.
• Outside eye care providers could refer patients directly to the ED for expedited evaluation.
• Macular OCT scans of both eyes were acquired using an Optovue iScan OCT machine.
• OCT images were evaluated remotely by the retina service.
  • OCT findings indicative of RAO included inner retinal hyperreflectivity, loss of differentiation of inner retinal layers, inner retinal thickening, decreased signal transmission to outer retinal layers, and the “foveal glow.”
• Patients received intra-arterial recombinant tissue plasminogen activator (IA-tPA) delivered into the ophthalmic artery via a transfemoral arterial route.
• Doses were administered in 2 mg aliquots every 5 minutes until visual improvement, choroidal blush restoration on angiogram, or a maximum dose of 22 mg was reached.

Population:

Inclusion Criteria:

• Adult patients who presented with sudden painless monocular vision loss.
• Diagnosed with a nonarteritic retinal artery occlusion (RAO) based on OCT findings and follow-up examination.
• Patients whose last known well (LKW) time was within 24 hours of presentation.
• Patients eligible for treatment with intra-arterial tissue plasminogen activator (IA-tPA) within 12 hours of LKW.

Exclusion Criteria:

• Patients under 18 years of age.
• Treatment could not be performed within 12 hours of LKW.
• Medical comorbidities that precluded surgery.
• Concern for a non-embolic cause for the patient’s vision loss.
• Patients previously known to the stroke service who received tPA during a diagnostic cerebral angiogram.

Intervention:

Implementation of a remote consult protocol using point-of-care OCT for the diagnosis of retinal artery occlusion, followed by treatment with intra-arterial tissue plasminogen activator (IA-tPA) in eligible patients.

Outcomes:

Primary Outcome: Visual Acuity (VA) Improvement

• Measured using logarithm of the minimum angle of resolution (logMAR). 
• Documented at the following time points:
  • Before treatment.
  • Within 24 hours after treatment.
  • 1 week after treatment.
  • 1 month after treatment.

Secondary Outcomes:

• Time from Last Known Well (LKW) to Treatment:
  • The duration from when the patient last remembered seeing well to the administration of tPA.
• Time from Presentation to Treatment:
  • The duration from when the patient arrived at the ED and the stroke code was called to the administration of tPA.

Results:

Patient Evaluations:

• 59 patients were evaluated using the remote consult protocol.
• 25 patients (42%) had confirmed retinal artery occlusion (RAO).
• 10 patients met the criteria for treatment with intra-arterial tissue plasminogen activator (IA-tPA).
• 9 patients received IA-tPA treatment.

Visual Acuity (VA) Improvement:

• Mean VA improved from logMAR 2.14 (counting fingers/hand motions) to logMAR 0.7 (approximately 20/100) within 24 hours after treatment (P = 0.0001).
• Mean VA at 1 month after treatment was logMAR 1.04 (approximately 20/200) (P = 0.01).
• 66% of treated patients showed clinically significant improvement in VA within 24 hours.
• 56% of treated patients maintained clinically significant VA improvement at 1 month.

Time to Treatment:

• The mean time from LKW to IA-tPA treatment was 543 minutes (approximately 9 hours).
• The mean door-to-treatment time (time from presentation at the stroke center to the administration of IA-tPA) was 146 minutes (approximately 2.5 hours).

Safety Outcomes:

• There were no reports of intracranial bleeds or systemic complications following IA-tPA treatment.

Strengths:

• The study addressed a clinical question and diagnostic challenge that directly impacts patient outcomes.
• The primary outcome, visual acuity,  was patient-oriented, making the results highly relevant to clinical practice.
• The study introduced a novel, collaborative remote consult protocol that successfully reduced the time to diagnosis and treatment for RAOs by using point-of-care OCT and remote interpretation.
• The protocol was designed to align with existing stroke procedures, ensuring that it could be smoothly integrated into clinical workflows across multiple sites without causing significant disruptions.

Limitations:

• The study had a relatively small sample size, with only 59 patients evaluated and 9 patients receiving treatment, which may limit the generalizability of the findings.
• The study was conducted in a single country, which may limit the generalizability of its findings to other regions.
• The study only included cases captured through the protocol, introducing potential selection bias. 
• There is no discussion on the total number of patients screened or the reasons for exclusion, including the 1 patient who had RAO but was not treated. 
• The absence of a typical flow chart depicting patient inclusion and exclusion criteria further complicates the interpretation.
• The study does not provide demographic information, limiting the understanding of the study population and potential biases in patient selection.
• No information is provided about the sensitivity and specificity of the OCT device used, nor is there a comparison to a gold standard for RAO diagnosis. Without citing other efficacy data, it is unclear whether the OCT device might have missed cases of RAO.
• The study was retrospective, which can introduce biases and limit the ability to establish causality between the intervention and outcomes.
• There was no control group for comparison, making it difficult to determine how much of the observed improvements were due to the protocol itself versus other factors.
• Although the OCT machines were designed to be user-friendly, variability in image acquisition by different operators could affect the quality of the images and, consequently, the accuracy of remote diagnoses.
• The follow-up period was limited to one month, which is shorter than the typical three-month follow-up reported in thrombolytic studies. This shorter follow-up may not capture important longer-term outcomes or complications, potentially underestimating the full impact of the treatment.
• The protocol was implemented at sites with endovascular capabilities, which may limit its applicability to other settings without similar resources.

Discussion:

The Numbers: The improvements in visual acuity observed among the treated patients are impressive. Specifically, some patients experienced a dramatic improvement in visual acuity, from counting fingers or hand motions (logMAR 2.14) to 20/100 (logMAR 0.7) within 24 hours of treatment, and further stabilization at 20/200 (logMAR 1.04) after one month. However, these improvements must be viewed in the context of the challenges associated with identifying and treating RAO. The mean time from the LKW to presentation was approximately 9 hours (543 minutes), and the mean door-to-treatment time (from presentation to administration of tPA) was about 2.5 hours (146 minutes). These delays underscore the difficulty in recognizing and treating RAO promptly, even when robust education and processes exist. Any delays can potentially impact the effectiveness of thrombolytics. 

The Pitfalls: Several methodological considerations limit the broader applicability of the resulting data. Over 18 months across three centers, only nine patients received intra-arterial tPA, highlighting both the rarity of the condition and the difficulty in generalizing the results. Additionally, the study’s retrospective design can offer correlation but not causation. The lack of a control group further complicates the interpretation of the findings, and the observed outcomes could be due to chance alone. These limitations highlight the need for large, multicenter studies, across varied populations to confirm the findings.

The Protocol: The strength of this study lies in its innovative protocol. The investigators identified a critical gap in the recognition and treatment of patients with RAO and successfully developed a protocol that effectively utilized existing resources. By implementing the protocol at stroke centers with endovascular capabilities, they were able to leverage familiar stroke management processes, ensuring a smooth integration. Although no patients in this study met the criteria for intravenous tPA administration, the protocol closely mirrors stroke treatment approaches, including the use of remote OCT retinal image interpretation, similar to tele-neurology evaluations. As the protocol continues to be refined and clinical staff gain more experience, treatment administration times will likely further improve.

Authors Conclusion: “We report the successful implementation of a remote consult protocol to facilitate treatment of RAOs using point-of-care automated OCT. This novel paradigm demonstrates the potential utility of remote consult services for the diagnosis of time-sensitive ophthalmic emergencies.”

Clinical Bottom Line:

This novel approach highlights the potential for integrating remote consultation services and point-of-care imaging with existing stoke processes to address time-sensitive ophthalmic emergencies. Larger more robust randomized controlled trials are needed to fully inform our care for patients with RAO. As technology advances, ED providers may find themselves increasingly participating in coordinating care for ophthalmological emergencies.

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References:

1. Mac Grory B, Nackenoff A, Poli S, et al. Intravenous Fibrinolysis for Central Retinal Artery Occlusion: A Cohort Study and Updated Patient-Level Meta-Analysis. Stroke. 2020;51(7):2018-2025. PMID: 32568646
2. Wang X, Liu Y, Suo Y, et al. Intravenous Recombinant Tissue-Type Plasminogen Activator Thrombolysis for Acute Central Retinal Artery Occlusion. J Craniofac Surg. 2021;32(1):313-316. PMID: 33156166
3. Sobol EK, Sakai Y, Wheelwright D, et al. Intra-Arterial Tissue Plasminogen Activator for Central Retinal Artery Occlusion. Clin Ophthalmol. 2021;15:601-608. Published 2021 Feb 16. PMID: 33623361
4. Weber J, Remonda L, Mattle HP, et al. Selective intra-arterial fibrinolysis of acute central retinal artery occlusion. Stroke. 1998;29(10):2076-2079. PMID: 9756585
5. Leavitt JA, Larson TA, Hodge DO, Gullerud RE. The incidence of central retinal artery occlusion in Olmsted County, Minnesota. Am J Ophthalmol. 2011;152(5):820-3.e2. PMID: 21794842
6. Lema GMC, De Leacy R, Fara MG, et al. A Remote Consult Retinal Artery Occlusion Diagnostic Protocol. Ophthalmology. 2023. PMID: 38349294

Co-Authored By:

Jonathan Siegal MD FACEP
Chairperson
Department of Emergency Medicine
The Brooklyn Hospital Center
Assistant Professor of Clinical Emergency Medicine
Weill Cornell School of Medicine
Linkedin: jonathan-siegal

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter/X: @EMSwami)