Subretinal hemorrhage (SRH) refers to the accumulation of blood between the neurosensory retina and the retinal pigment epithelium (RPE). When hemorrhage exceeds 3 to 4 disc diameters (DD), it is classified as massive (mSRH) and carries a particularly poor visual prognosis, with presenting acuity often ranging from 20/200 to hand motion depending on hemorrhage size, location, and etiology.^1,2 The most common etiology is neovascular age-related macular degeneration (nAMD), though other etiologies include retinal arterial macroaneurysms, polypoidal choroidal vasculopathy (PCV), and choroidal or retinal masses.^1,3

Management of mSRH remains challenging, with no universally accepted standard of care. Available treatment strategies include anti-VEGF injections, pars plana vitrectomy (PPV) with tissue plasminogen activator (tPA), and pneumatic displacement with gas tamponade. Herein, we describe 2 patients with mSRH, one secondary to wet AMD and one secondary to peripheral exudative hemorrhagic chorioretinopathy (PEHCR), who were successfully managed with anti-VEGF monotherapy and followed long term with serial optical coherence tomography (OCT) imaging over 10 years.

Case Descriptions

Case 1 involved a 71-year-old White female with a history of dry AMD in the right eye and wet AMD in the left eye, who presented with blurred vision in the left eye for a week. Best-corrected visual acuity (BCVA) was 20/40 in the right eye and 5/200 in the left eye; the right eye was dry at presentation. Fundus examination of the left eye demonstrated a mSRH extending from the superior arcade to the inferior arcade with elevation of the retina involving the macula (Figure 1A). The OCT of the left eye showed a hemorrhage in the subretinal space without any visible sub-RPE hemorrhage on OCT (Figure 1B). This patient received monthly ranibizumab injections (Lucentis; Genentech) for 4 months, after which she was lost to follow-up for 6 months and did not receive additional injections during that interval. Repeat examination showed that the mSRH had cleared, leaving early pigmentary changes (Figure 1C, 1D). The patient subsequently followed for more than 10 years without additional injections. At last follow-up, BCVA was 20/200 in the left eye, with localized RPE atrophy and subretinal fibrosis on OCT (Figure 1E, 1F).

Case 2 involved a 60-year-old White female who presented with blurred vision in the right eye for 5 days. Her BCVA was 20/200 in the right eye and 20/20 in the left eye. Fundus examination showed an mSRH temporal to the macula extending to the inferior midperiphery, with a mass-like elevation temporal to the macula (Figure 2A). Fluorescein angiography demonstrated intact arteriovenous retinal circulation with leakage from a polypoidal lesion consistent with PEHCR (Figure 2B). The patient subsequently underwent monthly bevacizumab injections (Avastin; Genentech) for 5 months. Follow-up fundus examinations showed resolution of the hemorrhage with residual subretinal pigment temporally and drusen (Figure 2C). OCT was otherwise unremarkable, demonstrating a flat macula without subretinal hemorrhage (Figure 2D). The patient has now been followed for 20 years. At last follow-up, BCVA was 20/25 in the right eye, with stable subretinal pigment temporal to the macula and persistent macular drusen (Figure 2E, 2F).

Discussion

Massive subretinal hemorrhages have traditionally been considered a poor prognostic sign, because large amounts of blood may lead to irreversible photoreceptor damage through multiple mechanisms, including iron toxicity from hemoglobin breakdown, a physical barrier effect between the RPE and photoreceptors, and fibrin contraction involving photoreceptors and RPE.^4-6 These effects may occur within hours of hemorrhage onset.⁴ Prompt treatment may therefore help improve current vision and preserve visual potential.

Intravitreal anti-VEGF therapy has emerged as a major treatment strategy, given VEGF’s central role in vascular leakage across retinal diseases, including wet AMD and diabetic retinopathy. Multiple studies have reported good efficacy and favorable safety profiles with anti-VEGF monotherapy. In a large comparative study of 236 patients with SRH, Mun et al reported no significant difference in mean 12-month BCVA among observation, anti-VEGF monotherapy, pneumatic displacement, and vitrectomy groups (P=.204) after controlling for age, baseline BCVA, hemorrhage size, and prior anti-VEGF treatment.⁷ Notably, the anti-VEGF monotherapy group achieved significantly better mean BCVA at 3 months (P<.001), potentially indicating a faster early visual recovery trajectory.⁷

A 2025 meta-analysis by Shaheen et al analyzed 43 observational studies and reported that anti-VEGF monotherapy produced visual acuity gains comparable to surgical intervention.⁸ Anti-VEGF monotherapy also carried a significantly lower complication rate, including reduced rates of retinal detachment (0.1% vs 10.6%), cataract formation (0% vs 4.6%), and proliferative vitreoretinopathy (0.1% vs 2.0%).⁸

Most SRHs are related to nAMD or PCV, although other etiologies, such as PEHCR, also occur. Anti-VEGF monotherapy has demonstrated statistically significant clinical resolution in PEHCR as well. In the largest published series of 35 eyes, Safir et al reported that 88.9% of eyes achieved resolution with bevacizumab monotherapy.⁹ In a systematic review of PEHCR, Gowda et al concluded that anti-VEGF therapy demonstrated efficacy, particularly in cases in which exudative involvement threatened the macula.¹⁰

For mSRH specifically, defined as greater than 3 DD, Miyazato et al analyzed 31 eyes and compared anti-VEGF monotherapy with vitrectomy, reporting no significant difference in BCVA outcomes between the 2 groups at 12 months.¹¹ In a 2015 study of 49 eyes with mSRH, defined as greater than 5 DD, Kim et al reported significant visual improvement with anti-VEGF monotherapy at 12 months; BCVA improved from approximately 20/276 to 20/132 (P=.002), and 49% of eyes gained 3 or more lines of vision.¹²

Additional treatment modalities, including pneumatic displacement, PPV, and recombinant tissue plasminogen activator (r-tPA), have demonstrated meaningful but variable visual outcomes. Notably, these interventions are frequently paired with anti-VEGF therapy, underscoring its central role in SRH management. However, long-term visual outcomes have not differed significantly between anti-VEGF monotherapy and surgical approaches.¹³

To date, no single anti-VEGF agent has demonstrated superiority in the treatment of SRH. In a 2023 retrospective study of 62 treatment-naïve eyes comparing aflibercept (Eylea; Regeneron) and brolucizumab (Beovu; Novartis), Maruyama-Inoue et al reported no significant difference in 12-month visual acuity between agents, with meaningful improvement observed primarily in eyes without breakthrough hemorrhage.¹⁴

Conclusion

These 2 cases illustrate that massive subretinal hemorrhage, even when extensive at presentation, does not necessarily portend irreversible severe vision loss. The patient with nAMD achieved stable vision over 10 years despite residual RPE atrophy and subretinal fibrosis, while the patient with PEHCR maintained 20/25 BCVA.

Collectively, the available evidence continues to support anti-VEGF monotherapy as an effective first-line treatment strategy, particularly in small to moderate SRH or in patients who are poor surgical candidates. Massive subretinal hemorrhage secondary to PEHCR and nAMD may therefore achieve meaningful visual recovery with anti-VEGF therapy, even when hemorrhage is extensive at presentation. Consistent follow-up, however, remains important for optimizing visual outcomes. RP

Michael Y. Zhao, MD, is an ophthalmology resident at Bascom Palmer Eye Institute, University of Miami Health System, in Miami. He reports no disclosures.

Harry W. Flynn Jr., MD, is the J. Donald M. Gass Distinguished Chair in Ophthalmology at the University of Miami’s Miller School of Medicine, and a professor of ophthalmology at Bascom Palmer Eye Institute. He reports no relevant disclosures. Reach him at hflynn@med.miami.edu. The authors report that this work was supported in part by Research to Prevent Blindness Unrestricted Grant GR004596-1.

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