What are the next steps for a patient who received an anti-VEGF (Vascular Endothelial Growth Factor) injection 4 days ago for central retinal vein occlusion (RVO) and now presents with painless bleeding of the eye and upper gum numbness on one side?

Urgent Neurological and Vascular Emergency Requiring Immediate Evaluation

This patient requires immediate emergency department evaluation for possible giant cell arteritis (GCA) or stroke, as the combination of recent retinal vein occlusion, new ocular bleeding, and unilateral upper gum numbness suggests arteritic disease or concurrent cerebrovascular ischemia that could lead to bilateral blindness or stroke. 1

Immediate Actions Required

Emergency Referral

• Send the patient immediately to an emergency department affiliated with a stroke center, as acute retinal vascular occlusions are considered stroke equivalents requiring urgent evaluation 1
• The combination of central RVO with new bleeding and neurological symptoms (gum numbness) raises critical concern for:
  • Giant cell arteritis causing arteritic RVO 1
  • Concurrent cerebrovascular ischemia (up to 40% of retinal arterial occlusions have concurrent cerebral infarction) 1
  • Possible retinal artery occlusion complicating the existing RVO 2

Critical Diagnostic Workup in ED

• Obtain emergent ESR and CRP to evaluate for GCA, as elevated inflammatory markers support this diagnosis (though normal values do not exclude it) 1
• Assess for GCA symptoms: jaw claudication, temporal headache, scalp tenderness, constitutional symptoms, and polymyalgia rheumatica symptoms 1
• Neurological assessment with NIH Stroke Scale to evaluate for concurrent cerebral ischemia 1
• Brain MRI with diffusion-weighted imaging to identify concurrent cerebral infarction 1

Understanding the Clinical Presentation

The Painless Eye Bleeding

• The new ocular bleeding 4 days post-injection likely represents:
  • Vitreous hemorrhage from neovascularization (common complication of CRVO requiring anti-VEGF therapy) 3
  • Subconjunctival hemorrhage (most common ocular adverse event from intravitreal injections) 4
  • Less likely but possible: retinal artery occlusion complicating the RVO (rare but reported complication of anti-VEGF therapy) 2

The Upper Gum Numbness - Critical Red Flag

• Unilateral upper gum numbness is a neurological symptom that cannot be attributed to the intravitreal injection itself and suggests:
  • Maxillary nerve (V2 branch of trigeminal nerve) involvement
  • Possible GCA with cranial nerve involvement 1
  • Cerebrovascular ischemia affecting sensory pathways 1
  • This symptom transforms this from a routine post-injection complication to a neurological emergency

Management Algorithm

If GCA is Confirmed or Highly Suspected

• Start high-dose corticosteroids immediately, even before temporal artery biopsy, if clinical suspicion is high to prevent bilateral blindness 1
• This takes precedence over all other considerations given the devastating consequences of untreated GCA 1

If Non-Arteritic RVO with Vitreous Hemorrhage

• Continue anti-VEGF therapy as first-line treatment for vitreous hemorrhage and macular edema in non-arteritic RVO 1
• Anti-VEGF agents may be helpful to optimize visualization when vitreous hemorrhage limits visibility for panretinal photocoagulation 3
• Monitor for anterior segment neovascularization, which requires prompt panretinal photocoagulation 3

Cardiovascular Risk Stratification

• Immediate referral to internal medicine for optimization of hypertension, hyperlipidemia, and diabetes, as patients with RVO have significantly elevated risk of stroke and cardiovascular events 1
• Patients with RVO require aggressive secondary prevention given their elevated cardiovascular risk 1

Common Pitfalls to Avoid

• Do not attribute neurological symptoms to the intravitreal injection: The injection itself does not cause gum numbness; this requires systemic evaluation 1
• Do not delay evaluation for GCA in patients over 50: GCA can cause bilateral blindness if untreated, and treatment should begin before biopsy confirmation if suspicion is high 1
• Do not assume the bleeding is a benign post-injection complication when accompanied by new neurological symptoms 1
• Severe adverse effects of intravitreal injections (endophthalmitis, retinal detachment) are uncommon, but arterial occlusions have been reported after anti-VEGF therapy in RVO patients 2, 4

Follow-Up After Emergency Evaluation

If Emergency Workup is Negative

• Return to ophthalmology within 24-48 hours for:
  • Dilated fundus examination to characterize the bleeding source 3
  • OCT imaging to assess macular edema response 5
  • Fluorescein angiography to detect ischemic retinal areas requiring laser treatment 5
  • Gonioscopy for iris neovascularization if intraocular pressure is elevated 3

Ongoing CRVO Management

• Monthly monitoring for the first 6 months is essential to detect complications 6
• Continue anti-VEGF therapy as preferred first-line treatment for macular edema, with treatment decisions based on OCT findings rather than visual acuity alone 3, 5
• Early targeted laser coagulation of ischemic retina may reduce injection frequency and improve edema response 5