Combined Pharmacological and Pneumatic Displacement Therapy for Sub-Macular Haemorrhage Secondary to Age-Related Macular Degeneration: A Case Series and Review of the Literature<b></b>

Purpose: To present the clinical outcomes of a combined pharmacological and gas-assisted treatment approach for sub-macular haemorrhage secondary to neovascular age-related macular degeneration (nAMD). Methods: A retrospective analysis was conducted on ten patients with sub-macular haemorrhage secondary to nAMD treated between 2024 and 2025. Each patient received a single intravitreal injection of tissue plasminogen activator (tPA; alteplase, Actylise 10, Boehringer Ingelheim, Int.) and perfluoropropane (C₃F₈, Micromed) gas. This treatment was administered within 3 weeks of symptom onset (range 7-60 days). Subsequently, all patients received anti-VEGF injections of aflibercept (Eylea 2mg, or Eylea 8 mg, Bayer) using a treat-and-extend (T&Ex) regimen, started 7–14 days after the tPA + gas injection. Clinical evaluation included best-corrected visual acuity (BCVA), fundus photography, optical coherence tomography (OCT), and OCT- angiography angio-OCT at baseline and at 7 -14 days, 1 month, 3 months, and 6 months after the initial tPA + gas injection. Results: All patients showed rapid anatomical improvement of the haemorrhage. Visual acuity improved in the majority of cases, with an average gain of three ETDRS lines at four weeks, an additional three lines at three months, and over four lines at six months. No major adverse events were reported. One patient developed a transient intraocular-pressure rise, which was easily controlled with medication. Conclusion: Prompt combined therapy using intravitreal alteplase with C₃F₈ gas, followed by anti-VEGF treatment, may offer a safe and minimally invasive alternative to surgery for sub-macular haemorrhage due to nAMD, providing promising visual and anatomical outcomes.