What are the risks and complications associated with intravitreal injection?

Risks and Complications of Intravitreal Injection

Intravitreal injections are generally safe procedures with serious complications occurring rarely, but patients must be counseled about both vision-threatening ocular complications and potential systemic risks before proceeding.

Ocular Complications

Serious Vision-Threatening Complications (Uncommon)

The most critical complications that require immediate intervention include:

• Infectious endophthalmitis: Cumulative incidence ≤1.0% over 1-2 years 1, with real-world data showing rates as low as 0.02% (27 cases in 123,373 injections) 2 to 0.16% per injection 1. This is the most feared complication requiring emergent treatment.

• Retinal detachment: Both rhegmatogenous (0.02%) and tractional (0.16%) types can occur 1

• Retinal vasculitis: Particularly associated with brolucizumab and newer agents, can cause severe vision loss 3, 4. This drug-specific complication represents an emerging safety concern with certain anti-VEGF agents.

• Cataract formation: Can develop with repeated injections, especially with corticosteroid agents 5

• Elevated intraocular pressure (IOP): Occurs acutely post-injection and chronically, particularly common with intravitreal corticosteroids 5

Common Minor Complications (Frequent but Self-Limited)

Most patients experience benign complications that resolve spontaneously:

• Subconjunctival hemorrhage: One of the most common events (4-284 cases in large series) 6, 7
• Irritation/foreign body sensation: Reported by 18% of patients 6
• Seeing air bubbles: 17% of patients 6
• Ocular itching: 12% of patients 6
• Eye redness: 11% of patients 6
• Corneal abrasion: Most common serious complication requiring intervention (46 cases in one series) 6
• Vitreous hemorrhage: 0.16% incidence 1, 7

Inflammatory Complications

Noninfectious inflammation can mimic endophthalmitis and requires careful differentiation:

• Sterile intraocular inflammation/uveitis: 0.09-31 cases depending on series 1, 3, 6
• Anterior uveitis and vitritis: Variable presentation depending on agent used 3
• Occlusive retinal vasculitis: Particularly with brolucizumab, can cause significant vision loss 3, 4

Systemic Adverse Events

The evidence regarding systemic complications remains inconclusive but warrants discussion:

• Arterial thromboembolic events: Anti-VEGF therapy carries theoretical risks, but meta-analyses show no evidence of increased arterial thromboembolic events 5. However, CATT study showed higher rates of serious systemic events with bevacizumab versus ranibizumab (24% vs 19%, P=0.04) 1.

• Venous thrombotic events: No statistically significant differences found between agents in major trials 1

• Death: No significant differences in mortality rates between anti-VEGF agents 1

• Gastrointestinal disorders: Including hemorrhage, more common with bevacizumab 1

Risk Factors and Clinical Pearls

Patient-specific factors influence complication rates:

• Gender, age, number of previous injections, and provider experience significantly affect patient-reported complication rates 6
• Male patients report severe post-injection pain less frequently 2
• No injection protocol parameters (anesthesia type, preparation method, post-injection medications) increase complication risk 6
• Bilateral same-day injections do not increase endophthalmitis risk 2

Critical Safety Measures

To minimize complications, adhere to these evidence-based practices:

• Use topical povidone-iodine before all injections (strongly recommended) 5
• Do NOT use routine prophylactic antibiotic eye drops (not recommended) 5
• Face mask use by both patient and physician may decrease culture-positive endophthalmitis 4

Patient Counseling Considerations

More than 10% of patients report complaints the day after injection 6, 2, and nearly 2% consider treatment discontinuation due to discomfort 2. Proper pre-procedure counseling about expected minor symptoms can improve treatment adherence and prevent unnecessary emergency visits.

Overall complication rates in routine clinical practice (1.9% of all injections) are substantially lower than those reported in clinical trials 6, providing reassurance about the safety profile of this procedure when performed with appropriate technique and sterile precautions.