Sub-Internal Limiting Membrane Hemorrhage: Molecular Microenvironment and Review of Treatment Modalities

Sub-internal limiting membrane (sub-ILM) hemorrhage is a distinct preretinal bleeding entity in which blood accumulates between the ILM and the retinal nerve fiber layer (RNFL), forming a sharply confined compartment. The ILM’s low permeability and lack of immune cell access create a stagnant microenvironment in which erythrocyte lysis leads to the accumulation of hemoglobin, heme, and iron, promoting the generation of reactive oxygen species. This oxidative burden poses a direct risk to retinal ganglion cells and Müller cell endfeet. Spectral-domain optical coherence tomography (SD-OCT) enables precise identification of sub-ILM blood through its characteristic dome-shaped elevation and hyperreflective contents, distinguishing it from subhyaloid and vitreous hemorrhage. Management options include observation, neodymium-doped yttrium–aluminum–garnet (Nd: YAG) laser membranotomy, pneumatic displacement, and pars plana vitrectomy (PPV). While small, extrafoveal hemorrhages may resolve spontaneously, prolonged blood entrapment is associated with increased retinal toxicity, tractional changes, and proliferative vitreoretinopathy (PVR). Early intervention generally results in faster clearance and improved visual outcomes, particularly for dense or foveal bleeding. Major gaps remain regarding cellular stress responses, biomarkers that predict irreversible damage, and the optimal timing of intervention. Standardized imaging criteria and evidence-based management algorithms are needed to guide individualized treatment.