Published in Retina

Rates and Risk Factors for Submacular Hemorrhage in nAMD Following Anti-VEGF Injections

Rishi P. Singh, MD, FASRS

Matthew Starr, MD

This is editorially independent content

3 min read

Join Drs. Singh and Starr as they discuss the rates and risk factors of submacular hemorrhage in neovascular AMD patients undergoing anti-VEGF treatment.

In this episode of Evidence Based Retina, Rishi Singh, MD, FASRS, and Matt Starr, MD, Associate Professor of Ophthalmology and Program Director of the residency program at the Mayo Clinic, engage in a discussion about Dr. Starr’s research on the rates and risk factors associated with submacular hemorrhage (SMH) in neovascular age-related macular degeneration (nAMD) following anti-VEGF injections.

Rates of SMH in nAMD patients undergoing anti-VEGF injections

The study conducted by Kaufmann et al. was a retrospective cohort analysis using data from a nationwide aggregated electronic healthcare database called Vestrum Health. It involved all eyes diagnosed with nAMD and SMH recorded in the Vestrum database between January 2015 and November 2023.¹

The analysis assessed patient characteristics, specific anti-VEGF agents, known risk factors (such as anti-platelet and anti-coagulant use), injection volume and timing, injection frequency, and disease duration, as well as age and basic demographic risk factors.¹

Key findings

Age and SMH Risk: Younger patients showed a higher likelihood of associations with hemorrhages compared to older patients.¹
Risk Factors: Patients on blood thinners and anti-coagulants had a higher hemorrhagic risk.¹
Agent Efficacy: Faricimab (VABYSMO, Genentech, a member of Roche) was a significant outlier, as eyes treated with it had a lower risk of submacular hemorrhage.¹ Dr. Starr comments that this lower risk might be due to its dual inhibition of Ang-2 and VEGF-A, which may provide "protective or anti-fibrotic effects" by using Tie-2 blockage to stabilize neovascular complexes and membranes.
Frequency and Timing: The frequency of injections and the timing from the last injection were not associated with hemorrhagic risk.¹
Time to Hemorrhage: The faricimab group had a shorter time to hemorrhage than other agents, such as bevacizumab, ranibizumab, or aflibercept.¹
Post-Hemorrhage Outcomes: Most eyes in the study did well after the hemorrhage developed.¹
- Out of about 3,000 eyes in the study, only a few hundred underwent surgical intervention.
- All cohorts that underwent vitrectomy showed improvement in their vision afterward.
- The faricimab group saw one of the largest improvements, potentially because they "had the most to gain."

Relevance to clinical practice and outcomes

Because faricimab may offer better protection than other anti-VEGF injections against SMH in patients with nAMD, Dr. Starr currently shifts patients with significant or recurrent hemorrhages to faricimab.

References

Kaufmann GT, Boucher N, Sharma C, Aggarwal N, Starr MR. Submacular Hemorrhage Rates Following Anti-Vascular Endothelial Growth Factor Injections for Exudative Age-Related Macular Degeneration. Am J Ophthalmol. 2025;270:172-182. doi:10.1016/j.ajo.2024.10.017

About Rishi P. Singh, MD, FASRS

Rishi P. Singh, MD, FASRS, is the Chair of the Department of Ophthalmology at Mass General Brigham, overseeing ophthalmology across Massachusetts Eye and Ear, Massachusetts General Hospital, Brigham and Women’s Hospital, and affiliated sites. He is also a Professor of Ophthalmology at Harvard Medical School.

Previously, Dr. Singh served as Vice President and Chief Medical Officer at Cleveland Clinic Martin Health in Stuart, Florida, and as a staff surgeon at the Cleveland Clinic, where he was also Professor of Ophthalmology at the Cleveland Clinic Lerner College of Medicine in Cleveland, Ohio. He received both his undergraduate degree in medical science and his medical degree from Boston University, completing his internship at Tufts University. Dr. Singh went on to complete his ophthalmology residency at the Massachusetts Eye and Ear Infirmary/Harvard Medical School and a medical and surgical vitreoretinal fellowship at the Cole Eye Institute at the Cleveland Clinic.

Dr. Singh specializes in the management of complex retinal diseases, including diabetic retinopathy, retinal vein occlusions, retinal detachment, and age-related macular degeneration. He has authored over 300 peer-reviewed publications, books, and book chapters and serves as Principal Investigator for numerous national and international clinical trials aimed at improving outcomes for patients with retinal diseases.

He is the founder and past president of the Retina World Congress, chairs some of the largest continuing medical education meetings in retina, and serves on editorial boards and review panels for major ophthalmology journals. His leadership has extended into digital innovation, having helped lead enterprise-wide implementation of clinical technologies including Epic modules, digital informed consent, and patient-facing kiosks.

Dr. Singh has received multiple accolades for his contributions to ophthalmic research and innovation, including the Alpha Omega Alpha Research Award, the American Society of Retina Specialists Young Investigator Award, and the J. Donald Gass Beacon of Sight Award. He also leads The Center for Ophthalmic Bioinformatics, a research initiative focused on leveraging big data and artificial intelligence to advance understanding and treatment of retinal disease.

More by Rishi P. Singh, MD, FASRS

About Matthew Starr, MD

Dr. Starr is an Assistant Professor of Neurology, the Associate Director of the UPMC Stroke Institute, Director of the Vascular Neurology Fellowship, and Stroke Neurologist at UPMC who is actively involved in student, resident, and fellow education, as well as research.

He is the director of the Thrombectomy Stroke Centers at UPMC Mercy, and Primary Stroke Center at Shadyside, working with large multidisciplinary groups to provide quality stroke care for patients with ischemic and hemorrhagic stroke.

His clinical and research focus is on ischemic and hemorrhagic stroke, focusing on cryptogenic stroke. The goal of his clinical practice is to identify the etiology of patients’ strokes and direct secondary prevention.

Dr. Starr earned his Medical Degree from the University of New Mexico School of Medicine and pursued a residency in Neurology at the University of Pittsburgh Medical Center. Subsequently, he completed a fellowship in Vascular Neurology at the University of Pittsburgh Medical Center.

More by Matthew Starr, MD

💙 Evidence Based Retina

Jobs

Events