Vitreous Hemorrhage

Common Causes (Adults)

• Proliferative diabetic retinopathy (PDR): The single most common cause in adults, accounting for 31–54% of cases globally. Chronic retinal ischaemia drives neovascularisation (NVD/NVE); the resulting fragile new vessels rupture spontaneously or with minimal provocation (Valsalva, REM sleep, minor Valsalva equivalent). In Singapore, PDR is the leading cause of VH given the high local diabetes burden.
• Posterior vitreous detachment (PVD): The second most frequent cause (~12–17%). As the vitreous liquefies and separates from the retina, vitreoretinal traction can avulse a bridging retinal vessel or precipitate a full-thickness retinal tear, causing haemorrhage. VH from PVD is associated with a concurrent retinal tear in up to 70% of cases — making it the highest-risk VH aetiology for retinal detachment.
• Retinal vein occlusion (BRVO/CRVO): Venous stasis, retinal ischaemia, and VEGF-driven neovascularisation can rupture new vessels weeks to months after the original occlusive event. Together, RVO-related cases account for approximately 8–12% of VH.
• Retinal tear or rhegmatogenous detachment: Direct vessel avulsion at the tear margin. Every VH should be considered to have an underlying retinal tear until excluded by B-scan ultrasound or dilated examination.
• Retinal arterial macroaneurysm (RAM): Acquired, focal aneurysmal dilation of a first-to-third-order retinal artery. Spontaneous rupture — typically in hypertensive, elderly women — can produce dramatic sub-hyaloid or intravitreal haemorrhage. The classic "three-level" haemorrhage (sub-retinal, intra-retinal, pre-retinal) is pathognomonic.
• Ocular trauma: Most common cause in young patients. Blunt trauma compresses the globe, causing sudden IOP spike that ruptures retinal and vitreous vessels. Penetrating injuries cause direct vessel disruption and may introduce intraocular foreign bodies. Always consider non-accidental injury in children.
• Sickle cell retinopathy: Peripheral vascular occlusion in HbSS and HbSC disease leads to sea-fan neovascularisation (Goldberg stage IV PSR), which bleeds spontaneously. The HbSC phenotype paradoxically carries higher retinal risk. Relevant in Singapore's South Asian and Malay populations with haemoglobinopathy.

Less Common but Clinically Critical Causes

• Terson syndrome: Intracranial haemorrhage (most commonly aneurysmal subarachnoid) causes sudden elevation of ICP transmitted via the optic nerve sheath, rupturing preretinal and retinal vessels. Found in 13–40% of subarachnoid haemorrhage patients; bilateral in 50% of Terson cases. Bilateral VH in a patient with neurological symptoms is a medical emergency.
• Valsalva retinopathy: Sudden rise in intrathoracic pressure (weightlifting, violent coughing, straining at stool, childbirth, brass instrument playing) ruptures superficial perifoveal capillaries, producing sub-hyaloid haemorrhage that may break into the vitreous.
• Choroidal neovascularisation (CNV) breakthrough: Subretinal neovascular membranes in neovascular (wet) AMD, pathologic myopia (lacquer cracks), or ocular histoplasmosis can rupture and bleed superiorly through the retina into the vitreous cavity.
• Eales disease: Idiopathic obliterative retinal vasculitis, predominantly affecting young adult males in South and Southeast Asia. Progressive bilateral peripheral phlebitis leads to neovascularisation and recurrent VH.
• Blood dyscrasias and anticoagulation: Thrombocytopenia, leukaemia, haemophilia, and anticoagulant therapy (warfarin, NOACs) reduce haemostatic capacity, amplifying any minor vascular insult.
• Intraocular tumours: Choroidal melanoma, retinoblastoma (in children — leukocoria plus VH is a red flag), iris neovascularisation associated with tumour mass effect. Must be excluded by B-scan in any atypical or refractory VH.
• Ocular ischaemic syndrome: Carotid artery stenosis causing chronic retinal ischaemia, anterior segment neovascularisation, and secondary NV elsewhere.

1. Rupture of Pathological Neovascularisation

In ischaemic retinopathies (PDR, RVO, sickle cell, ocular ischaemic syndrome), sustained retinal hypoxia upregulates vascular endothelial growth factor (VEGF) and other angiogenic cytokines. VEGF drives sprouting angiogenesis from retinal venules, forming immature neovascular fronds that grow along the posterior hyaloid face or into the vitreous scaffold. These vessels lack tight junctions, adequate pericyte coverage, and the structural integrity of normal retinal vasculature. They rupture under physiological IOP fluctuations, Valsalva manoeuvres, nocturnal IOP reduction (REM sleep ocular movements), or minor trauma. Once ruptured, blood tracks rapidly along vitreous fibre planes and disperses throughout the cavity.

2. Vitreoretinal Traction During PVD

With age (accelerated in myopia, aphakia, and following trauma), the vitreous undergoes progressive syneresis — central liquefaction of the gel with condensation of peripheral collagen fibrils. Eventual collapse of the central gel exerts traction on the posterior hyaloid attachment to the retina. When the posterior hyaloid separates abruptly (acute PVD), it may avulse a bridging retinal vessel — particularly at sites of firm vitreoretinal adhesion: the optic disc rim, major retinal vessels, lattice degeneration, and paravascular adhesions. A full-thickness retinal tear at the adhesion site allows blood entry into the vitreous and creates the substrate for subsequent rhegmatogenous retinal detachment.

3. Direct Vascular Disruption

Traumatic globe deformation, sudden IOP elevation (Valsalva), or spontaneous aneurysmal rupture (RAM, Terson) causes direct vessel wall failure without underlying retinal ischaemia. Arterial haemorrhages accumulate rapidly and are often denser than venous bleeds. In RAM, the haemorrhage may be tri-layered: sub-retinal (earliest), intra-retinal, and pre-retinal/sub-hyaloid.

4. Breakthrough Haemorrhage

Blood originating in the subretinal or sub-RPE space — from CNV membranes in neovascular AMD, pathologic myopia, or from large RAM — can track anteriorly through Bruch's membrane, the RPE, and sensory retina to enter the vitreous cavity. This breakthrough mechanism is responsible for the most visually devastating presentations of wet AMD-related VH.

Clearance Mechanisms and Chronic Sequelae

Blood in the vitreous undergoes progressive haemolysis. Red blood cells release haemoglobin, which is progressively oxidised to methaemoglobin and ultimately to haemosiderin. Macrophages and Müller cells phagocytose erythrocytes and breakdown products over weeks to months, gradually clearing the vitreous. However, several pathological consequences may arise from chronic blood exposure:

• Ghost cells: Degenerated erythrocytes become rigid, spherical, khaki-coloured cells that can migrate anteriorly and obstruct the trabecular meshwork (ghost cell glaucoma).
• Haemolytic products: Free haemoglobin and haemoglobin-laden macrophages can independently obstruct trabecular outflow (haemolytic glaucoma).
• Haemosiderin: Iron released from haemoglobin precipitates as haemosiderin in retinal tissue, trabecular meshwork, lens, and ciliary body. Chronic iron exposure is directly toxic to photoreceptors (haemosiderosis bulbi) and accelerates optic nerve damage.
• Fibrovascular proliferation: Blood products stimulate fibrovascular membrane formation on the retinal surface, producing tractional retinal detachment as the membranes contract — most pronounced in PDR.

By Anatomical Location

By Severity — Spraul & Grossniklaus Grading

CF = counting fingers; HM = hand movements; LP = light perception; NLP = no light perception

By Aetiology

• Spontaneous: PDR, RVO, PVD, RAM, sickle cell, CNV breakthrough
• Traumatic: Blunt or penetrating ocular trauma (most common in patients under 40 years)
• Iatrogenic: Post-intravitreal injection haemorrhage, post-vitrectomy rebleeding, laser complication
• Systemic-mediated: Terson syndrome, coagulopathy, blood dyscrasias, anticoagulation

External & Slit-Lamp Signs

• Reduced or absent red reflex: The hallmark finding. Proportional to haemorrhage density. Grade 1 VH may show a faint, abnormally red-tinged reflex; Grade 3–4 VH produces a dark, near-absent, or completely absent reflex on direct ophthalmoscopy or retinoscopy. Compare with the fellow eye.
• Tobacco dust sign (Shafer's sign): Brown–orange pigment granules suspended in the anterior vitreous on slit-lamp biomicroscopy, representing retinal pigment epithelial cells liberated through a full-thickness retinal break. Highly specific for concurrent retinal tear — a critical finding demanding same-day ophthalmology referral regardless of VH severity.
• Vitreous red blood cells: Fine erythrocytes visible on slit-lamp in the anterior vitreous; may appear as diffuse red haze, discrete clumps, or a layered inferior pooling. Distinguished from inflammatory cells by their red colour and sedimentation pattern.
• Elevated IOP: Secondary ghost cell glaucoma or haemolytic glaucoma — consider when IOP is raised in the setting of confirmed or suspected VH. Normal to low IOP in a trauma setting may indicate open globe injury.
• Rubeosis iridis (anterior segment neovascularisation): Fine new vessels on the iris surface or at the pupillary margin, indicating advanced PDR, ischaemic CRVO, or ocular ischaemic syndrome. A critical high-risk sign.
• Hyphaema: Blood in the anterior chamber may coexist with VH in traumatic cases or in severe neovascular disease. Assess the AC angle for blood in the trabecular meshwork.

Fundoscopic Signs (When Fundal View Permits)

• Boat-shaped preretinal haemorrhage: Sub-hyaloid blood with a horizontal fluid level (gravity-dependent layering). Typical of Valsalva retinopathy, NVD rupture, and Terson syndrome.
• Neovascularisation of the disc (NVD) or elsewhere (NVE): Frond-like neovascular tufts at the disc or along the retinal vascular arcades, often identifiable as the source of haemorrhage in PDR.
• Fibrovascular proliferation: White traction bands extending from the disc surface into the vitreous in advanced PDR — hallmark of tractional disease requiring PPV consideration.
• Retinal tear: A U-shaped, horseshoe, or operculated tear in the peripheral retina at a site of vitreoretinal avulsion. May be visible in mild, localised VH; requires urgent laser if seen.
• Retinal detachment: Bullous, convex retinal elevation. May be concurrent with VH; B-scan is mandatory to detect this when the fundus is obscured.

Acute Complications

• Retinal detachment: The most immediately sight-threatening complication, present concurrently in 10–30% of VH cases. Rhegmatogenous (from a tear), tractional (from fibrovascular PDR membranes), or combined. A detached macula confers a significantly worse visual prognosis. Mandates emergent PPV.
• Acute secondary IOP elevation: Erythrocyte fragments and inflammatory products can acutely obstruct the trabecular meshwork, causing IOP spikes requiring immediate medical management. Suspect in any VH eye where IOP is >25 mmHg.

Subacute and Chronic Complications

• Ghost cell glaucoma: Degenerated erythrocytes (ghost cells) become spherical, rigid, khaki-brown cells over 1–3 months. These cells migrate anteriorly and obstruct the trabecular meshwork, causing sustained IOP elevation. The AC may show a characteristic khaki-coloured pseudohypopyon. Medical management; refractory cases require surgical washout.
• Haemolytic glaucoma: Haemoglobin released from lysed red cells, and haemoglobin-laden macrophages, independently obstruct trabecular outflow. Clinically similar to ghost cell glaucoma but occurs earlier (days to weeks). Treatment: IOP-lowering agents; anterior chamber lavage in refractory cases.
• Haemosiderosis bulbi: Chronic iron deposition from haemosiderin into retinal tissue, trabecular meshwork, lens epithelium, and ciliary body. Progressive photoreceptor degeneration (ring scotoma, ERG changes), heterochromia iridis, mydriasis, secondary glaucoma, and cataract. Irreversible once established; PPV indicated to remove the source of ongoing iron release.
• Proliferative vitreoretinopathy (PVR): Chronic VH stimulates fibrovascular membrane proliferation on the inner and outer retinal surfaces and in the vitreous base. Membrane contracture causes tractional retinal detachment — the most common cause of PPV failure. Risk is highest in eyes with prolonged (months) unresolved VH.
• Synchysis scintillans: Accumulation of golden-yellow cholesterol crystals in a liquefied vitreous following long-standing haemorrhage. Dense, gravity-dependent crystals that shower through the vitreous with eye movement. A marker of chronic pathology.
• Cataract: Haemosiderin deposition into the anterior lens capsule and subcapsular epithelium accelerates lens opacity formation, particularly in chronic VH.
• Amblyopia: In paediatric VH, prolonged visual deprivation during the critical developmental period causes irreversible amblyopia if not treated promptly. Any VH in a child <8 years requires urgent referral.

History

• Onset and rate of progression (minutes: acute vascular event; hours–days: gradual bleed)
• Prior similar episodes — recurrent VH strongly implies a neovascular source
• Known diabetes: duration, HbA1c trend, last diabetic eye review, whether PDR was previously diagnosed
• History of retinal vein occlusion, retinal detachment, or previous laser / intravitreal injection treatment
• Trauma history: direct ocular trauma, head injury, heavy Valsalva activity
• Current systemic medications: anticoagulants, antiplatelet agents, NSAIDs
• Systemic conditions: hypertension, sickle cell, haematological disorders, recent intracranial event
• Family history of retinal disease or haemoglobinopathy
• Flashes and floaters — onset, character, duration, any associated visual field defect

Clinical Assessment (Optometry)

• Best-corrected visual acuity: Establish baseline using the Snellen or ETDRS chart. Record both presenting and pinhole VA. A pinhole improvement suggests a refractive component; unchanged VA with pinhole confirms media opacity.
• Red reflex assessment (direct ophthalmoscope): Assess at arm's length in a darkened room. Reduced, asymmetric, or absent red reflex in one eye is a primary sign of VH. Weiss ring (annular floater) suggests PVD without haemorrhage.
• Intraocular pressure (non-contact tonometry or Goldmann applanation): Critical in all VH cases. Elevated IOP suggests ghost cell or haemolytic glaucoma. Low IOP in a traumatic eye may indicate open globe — never apply contact tonometry to a suspected open globe.
• Slit-lamp biomicroscopy: Examine the anterior vitreous for erythrocytes, Shafer's sign (tobacco dust — pigment granules indicating retinal tear), and ghost cells. Assess iris for rubeosis. Note any anterior segment trauma signs (hyphaema, lens subluxation, corneal laceration).
• B-scan ultrasonography — mandatory when fundus is not visible: The single most important investigation when VH obscures the fundal view. B-scan assesses: (1) presence / absence of retinal detachment — a tethered, highly reflective mobile membrane; (2) posterior vitreous detachment status; (3) echogenicity and distribution of haemorrhage; (4) intraocular foreign body (trauma); (5) choroidal or retinal mass lesion (tumour). Scan with probe over the closed upper lid with coupling gel in axial and transverse planes.
• Non-mydriatic fundus photography: Where media clarity permits, captures visible posterior segment findings for baseline documentation and teleophthalmology triage (SiDRP pathway in Singapore). Does not substitute for dilated examination.
• Blood pressure measurement: In-clinic BP must be obtained in all patients with unexplained VH. Hypertensive urgency or emergency must be identified and acted upon.

Ophthalmology-Level Investigations

• Dilated slit-lamp biomicroscopy and indirect ophthalmoscopy with scleral depression: Gold-standard retinal assessment performed after pharmacological dilation by the ophthalmologist. Identifies the source of haemorrhage, retinal tears, NV fronds, and detachment extent.
• OCT and OCT-Angiography: Posterior segment OCT to assess macular integrity, epiretinal membrane, and vitreoretinal traction once media clarity improves. OCTA delineates NV activity and flow without intravenous dye.
• Fundus fluorescein angiography (FFA): Defines NV extent, capillary non-perfusion zones, and guides PRP planning. Performed once haemorrhage clears sufficiently for adequate retinal imaging.

Systemic Investigations (Order or Refer)

• Fasting blood glucose and HbA1c — all new unexplained VH
• Full blood count (FBC) — thrombocytopenia, leukaemia screen, anaemia
• Coagulation screen (PT/INR, APTT) — if on anticoagulants or bleeding history
• Haemoglobin electrophoresis — if sickle cell haemoglobinopathy suspected
• Fasting lipid profile — dyslipidaemia in vascular occlusion workup
• CT brain (urgent) — if bilateral VH, neurological symptoms, or Terson syndrome suspected

Conservative / Supportive Measures

• Head elevation (30–45°): Elevating the head of bed during sleep encourages gravity-dependent settling of blood inferiorly, allowing partial clearing of the superior visual axis and facilitating better fundal visualisation at follow-up. Counsel patients to maintain this position throughout the acute phase.
• Activity restriction: Avoid strenuous exercise, heavy lifting, bending, or any Valsalva manoeuvre during the acute phase. Physical activity increases IOP transiently and vitreous movement, both of which risk rebleeding.
• Avoid NSAIDs: Reduce antiplatelet effect in the acute phase where clinically safe.
• Anticoagulant review (with medical consultation only): The decision to temporarily modify anticoagulation must be made collaboratively with the prescribing physician. Never unilaterally withhold anticoagulants for systemic indications (e.g., mechanical heart valve, atrial fibrillation with high CHA₂DS₂-VASc score, recent VTE).
• Systemic disease optimisation: Urgent glycaemic control (HbA1c target <7%), blood pressure management, and lipid control should be initiated or reinforced in parallel with ocular management.
• Patient education: Explain the gravity-dependent nature of symptoms, activity restrictions, the expected timeline of partial or full clearance, and the critical importance of reporting any worsening visual loss, new flashes, or the appearance of a dark curtain (retinal detachment symptoms).

Ophthalmology-Directed Treatment

• Intravitreal anti-VEGF injections (ranibizumab, bevacizumab, aflibercept): First-line treatment for NV-related VH from PDR or ischaemic RVO. Reduces neovascular activity and vessel fragility, promotes faster VH clearance, and decreases the rate of rebleeding. Serial injections are typically required; response guides transition to PRP.
• Panretinal photocoagulation (PRP): Ablation of ischaemic peripheral retina to reduce VEGF drive and induce NV regression. Applicable once sufficient media clarity permits laser delivery. Considered the definitive treatment for PDR-related NV; reduces long-term VH recurrence risk. Frequently combined with anti-VEGF therapy for synergistic effect.
• Barrier laser photocoagulation: Demarcation laser applied circumferentially around retinal tears to prevent rhegmatogenous retinal detachment. Must be performed urgently (same day) if a tear is identified on dilated examination.
• Pars plana vitrectomy (PPV): Surgical removal of the vitreous gel and blood — the definitive intervention for VH not responding to conservative management. Indications include:
  • Dense VH not clearing after 1–3 months of conservative management
  • VH with concurrent tractional or rhegmatogenous retinal detachment
  • Bilateral VH (to restore vision in at least one eye)
  • VH in a monocular patient (sole seeing eye)
  • Terson syndrome with visually significant haemorrhage
  • Ghost cell or haemolytic glaucoma unresponsive to medical IOP-lowering therapy
  • Suspected intraocular tumour requiring diagnostic vitrectomy
• Nd:YAG laser hyaloidotomy: For confined sub-hyaloid or sub-ILM haemorrhage (Valsalva retinopathy, Terson syndrome) — YAG puncture of the posterior hyaloid releases trapped blood into the vitreous cavity, where it disperses and clears more rapidly. An office-based, minimally invasive procedure.
• IOP management: Ghost cell and haemolytic glaucoma are managed with topical and systemic IOP-lowering agents (beta-blockers, carbonic anhydrase inhibitors, alpha-agonists). Refractory cases may require anterior chamber washout or trabecular aspiration.