FLORetina 2025: Navigating antithrombotic therapy in wet AMD

Sharon Fekrat, MD, FACS, FASRS, presented "Oral antithrombotics in eyes with submacular hemorrhage from wet AMD" during the 2025 FLORetina meeting and International Congress on OCT Angiography, En Face OCT, and Advances in OCT (ICOOR), held from 4 to 7 December in Florence, Italy.

In an interview, she shared some key takeaways from her presentation.

Editor's note: The following conversation has been lightly edited for clarity.

Modern Retina: What is the current protocol on antithrombotic use in wet AMD? If there is no consensus protocol, why not?

Sharon Fekrat, MD, FACS, FASRS: At present there is no formal consensus protocol specific to antithrombotic (anticoagulant or antiplatelet) use in the setting of neovascular age-related macular degeneration (AMD).

There are several reasons for this: first, the evidence base is largely retrospective and observational rather than prospective randomized trials, meaning that robust guideline-level recommendations cannot be determined. For example, we report an association between oral antithrombotic use and improved visual outcomes in eyes with submacular hemorrhage due to wet AMD but cannot establish causality or standardized management algorithms.

Second, patients with wet AMD often have significant systemic comorbidities that necessitate individualized antithrombotic decisions, making a retina-only standardized protocol difficult to safely implement.

Third, intraocular bleeding risk and systemic thrombotic risk must be balanced, and the heterogeneity of clinical presentations further complicates devising a standard protocol that would apply in all cases. Thus, current practice tends to rely on a case-by-case determination that includes multidisciplinary decision-making rather than following universal guidelines.

MR: What is the evidence in favour of more widespread usage versus discontinuing its use in these patients?

Fekrat: In recent years, many more older patients are taking an antiplatelet agent and/or an anticoagulant, especially since anticoagulant medication options have increased over recent years with a better overall safety profile compared to warfarin. Concurrently, ophthalmologists and retina specialists are less commonly pausing these medications perioperatively or in eyes with intraocular bleeding.

The Early Treatment Diabetic Retinopathy Study (ETDRS) previously reported that high-dose aspirin (650 mg/day) did not worsen diabetic retinopathy or increase the risk of vitreous hemorrhage. Thus, patients with diabetes no longer discontinue their aspirin if they were at risk for or had a vitreous hemorrhage.

In individuals with wet AMD, large population-based studies suggest that use of antiplatelet or anticoagulant therapy may be associated with a higher risk of hemorrhage requiring vitrectomy. However, visual acuity outcomes in those studies may be confounded by baseline differences, and thus causality has not been established.

Our study found that among eyes with submacular hemorrhage due to wet AMD, patients on oral anticoagulants had significantly better long-term visual acuity outcomes than those not on antithrombotics, after adjusting for lesion size and thickness.

We hypothesized that anticoagulant use at the time of the hemorrhage may reduce fibrin formation, thereby minimizing traction/shearing forces on photoreceptors overlying the hemorrhage. Thus, there may be some visual benefit of antithrombotic use at the time of hemorrhage in wet AMD, but there is also a non-trivial risk of bleeding in eyes with wet AMD; thus, the net balance remains uncertain.

MR: How do you balance systemic risk versus ocular outcomes?

Fekrat: Balancing systemic risk versus visual outcomes requires a nuanced, multidisciplinary approach.

First, assess the indication for antithrombotic therapy and the patient’s risk of a systemic thromboembolic event if therapy is withheld or modified. Second, evaluate the retinal status, including history of prior submacular hemorrhage, characteristics of the neovascular lesion, current anti-VEGF treatment status, and visual potential. Third, communicate clearly with the patient regarding the risks of intraocular bleeding and adverse systemic events, engaging in shared decision-making. Fourth, coordinate with the cardiologist to optimize antithrombotic therapy, ensure dosing and INR control, and consider shorter intervals between intravitreal injections in individuals who remain on antithrombotic agents.

The decision must be individualized, balancing life-threatening systemic risks against vision-threatening submacular hemorrhage.

MR: Are there guidelines for managing these patients perioperatively? 

Fekrat: Currently, there are no comprehensive, retina-specific published guidelines that dictate how to manage antithrombotic therapy in patients with wet AMD treated with anti-VEGF therapy or perioperatively. Available literature does not specify standardized peri-injection or perioperative management of antithrombotic medications.

Clinicians typically rely on individualized protocols developed within institutions or practices, incorporating input from cardiology colleagues. Key considerations include assessing systemic and ocular risk, determining agent-specific factors, planning the timing of hold and resumption, taking precautions intraoperatively to minimize bleeding risk, and closer postoperative monitoring. These decisions often rely on expert opinion and center-specific practice rather than high-level evidence, highlighting a gap and opportunity for future consensus guideline development.

MR: What aspects of this treatment protocol are frequently misunderstood or under-researched?

Fekrat: Several key areas in antithrombotic management of wet AMD are misunderstood or under-researched.

One misunderstanding is conflating association with causation. Our study demonstrated improved VA outcomes in patients already on antithrombotic therapy, but initiating therapy universally does not guarantee benefit. Mechanistic understanding of how systemic antithrombotics influence submacular hemorrhage, clot formation, fibrinolysis, and photoreceptor protection is limited.

Agent-specific granular data, long-term outcomes, antithrombotic management strategies in persons with wet AMD, and validated decision tools, including retinal imaging biomarkers to understand who is at increased risk of submacular hemorrhage, remain understudied. Addressing these areas would help strengthen evidence-based practice and may improve both systemic and visual outcomes.

MR: At this year’s FLORetina meeting, what topics are you most excited to address with your peers?

Fekrat: The FLORetina-ICOOR 2025 Congress agenda is very exciting, with speakers from all over the world sharing the latest up-to-date information and knowledge.

The Live Surgery session with insightful moderation is always a highlight. There is a buzz surrounding gene therapy, which is on deck to impact intravitreal pharmacotherapy protocols. Understanding how multimodal retinal imaging can identify systemic diseases, particularly neurocognitive conditions, has piqued interest into how it may be incorporated into clinical decision-making one day. Robotics, AI models, and home-based imaging will give us glimpses into how our practices may evolve in the not-so-distant future and prepare us for what is barreling down the pike.