Blood Thinners Tied to Risk of Eye Hemorrhage in Wet Macular Degeneration

 

• Prior research has suggested that 7% to 8% of patients with AMD develop hemorrhagic complications.
• In this study, the use of anticoagulants or antiplatelets was linked to a higher risk of intraocular hemorrhage requiring vitrectomy in patients with exudative AMD.
• The highest risk was observed with the combined use of anticoagulants and antiplatelets, and higher medication adherence was tied to increased odds of hemorrhage.

The use of anticoagulants or antiplatelets was linked to a higher risk of intraocular hemorrhage requiring vitrectomy in patients with exudative, or "wet," age-related macular degeneration (AMD), according to a study from South Korea.

Using a retrospective, longitudinal cohort study design, anticoagulant or antiplatelet exposure was associated with a higher risk of intraocular hemorrhage requiring vitrectomy (adjusted HR 1.15, 95% CI 1.02-1.29, P=0.03), reported Se Joon Woo, MD, PhD, of Seoul National University Bundang Hospital in Seongnam, and colleagues in JAMA Network Openopens in a new tab or window.

When using a cross-sectional case-control study design, intraocular hemorrhage requiring vitrectomy was associated with the use of anticoagulants (adjusted OR 1.88, 95% CI 1.45-2.44, P<0.001) and antiplatelets (aOR 1.37, 95% CI 1.19-1.57, P<0.001).

The highest risk was observed with the combined use of anticoagulants and antiplatelets (aOR 2.28, 95% CI 1.65-3.15), and higher medication adherence was tied to increased odds of hemorrhage (aOR 1.69, 95% CI 1.45-1.97).

Prior research has suggested that 6.7% to 8% of patients with AMD develop hemorrhagic complications, including vitreous hemorrhage and retinal hemorrhage, Woo and team noted, and those with the polypoidal choroidal vasculopathy (PCV) subtype are especially vulnerable, with rates of 12.4% to 19.9%.

Hemorrhage "is one of the more feared complications of wet AMD because it can be associated with significant vision loss," Bobeck Sam Modjtahedi, MD, of Kaiser Permanente in Pasadena, California, told MedPage Today. "The severity of vision loss can vary depending on the size and location of the hemorrhage."

"Patients with larger and more central macular hemorrhages are likely to have severe vision loss," he added. "Although attempts can be made to displace the hemorrhage while concurrently treating with anti-VEGF therapy, the prognosis often remains poor."

The researchers launched the study to gain more insight into antithrombotics and ocular hemorrhage in light of small, largely underpowered studies with mixed results, Woo told MedPage Today.

He noted that the absolute risk of hemorrhage severe enough to need vitrectomy in the retrospective cohort was low, at 1.7%. Still, "because this hemorrhage is usually sight-threatening and leads to irreversible blindness, even a modest relative increase deserves attention, especially in patients on dual therapy or with high adherence."

The likely explanation for the higher risk is the fact that the drugs make bleeding more likely, he said. "Antithrombotics reduce clotting thresholds, and neovascular membranes in AMD are inherently fragile. We adjusted for major cardiovascular comorbidities, and the association persisted, suggesting the drugs themselves likely contribute. However, causality can't be proven in observational data."

Woo emphasized that "we are not advocating routine discontinuation of antithrombotics that are indicated for cardiovascular or cerebrovascular protection." Instead, he highlighted the following strategies that "address risk without compromising systemic safety":

• "Shared decision-making with cardiology/primary care to avoid unnecessary dual therapy and to ensure dosing/INR [international normalized ratio] targets are appropriate"
• "Closer ophthalmic surveillance, e.g., tighter follow-up intervals when disease is active and rapid access if new floaters/dark curtain occur"
• "Aggressive control of exudation with timely anti-VEGF treatment when indicated"

Modjtahedi noted that "we know there is a heightened risk of bleeding in general when patients take these drugs. Additionally, patients can have macular hemorrhages with or without antithrombotics, but it is foreseeable that the medication causes any bleed to be larger and more severe than it would have been otherwise."

He agreed with Woo that "these medications play an important role in reducing morbidity and mortality, so we wouldn't want patients or physicians to stop these medications prematurely."

Still, he said, "it is important to discuss the risks with patients and view these risks on a case-by-case basis."

Modjtahedi also highlighted the study's inability to distinguish cases of the PCV subtype, "which is more common in East Asia and tends to be associated with more severe hemorrhages."

Future research, he said, could offer insight into whether "physicians should take a different approach in their management of patients -- including selection of anti-VEGF agent, utilization of secondary treatment like PDT [photodynamic therapy], or modification of treatment interval -- depending on the use of antithrombotic and risk of macular hemorrhage."

For this study, Woo and team used the Korean Health Insurance Review and Assessment Service database, and identified 149,620 patients with exudative AMD older than 40 from May 2014 through April 2023. A total of 94,449 patients were included in the retrospective cohort study (mean age 71.8, 59% men), and 8,110 patients were included in the case-control study (mean age 70.2, 62.8% men).

The authors noted limitations to their study, such as limited claims data, lack of detail about anti-VEGF agents and AMD subtypes, changes in prothrombin time, and potential confounders.

Disclosures

The study was supported by the National Research Foundation of Korea and the Korean ARPA-H Project.

Woo disclosed relationships with Alteogen, AbbVie, Alcon, Bayer, Boehringer Ingelheim, Curacle, Janssen, Novartis, Novelty Nobility, Roche, Kyowa Kirin, Samil, Samsung, Bioepis, Sometech, Zeiss, and RetiMark.

Modjtahedi disclosed a relationship with Genentech.

Primary Source

JAMA Network Open

Source Reference: Kim MS, et al "Antithrombotic medications and intraocular hemorrhage risk in exudative age-related macular degeneration" JAMA Netw Open 2025; DOI: 10.1001/jamanetworkopen.2025.31366.

https://www.medpagetoday.com/ophthalmology/generalophthalmology/117433