Abstract
BACKGROUND: Hypersensitivity reaction to hyaluronidase, though rare, can occur following regional anesthesia in ophthalmic surgery and may mimic serious conditions such as orbital cellulitis. Prompt recognition is critical to avoid misdiagnosis and unnecessary interventions. CASE PRESENTATION: We report two cases of hypersensitivity reaction following hyaluronidase-augmented peribulbar anesthesia for cataract surgery. Case 1: A 90-year-old female with no prior allergy history developed progressive periorbital edema extending to the ipsilateral face and neck within 7 hours after surgery. Infection and hemorrhage were excluded via ultrasound. The reaction resolved promptly with antihistamines and systemic corticosteroids. Case 2: A 69-year-old female developed progressive bilateral periorbital edema extending to the forehead, accompanied by moderate pain within 7 hours postoperatively. While her C-reactive protein (CRP) level was within normal limits on the day of surgery, it rose significantly to 33.92 mg/L on postoperative day 1. Given this clinical and laboratory progression, an empirical and prophylactic therapeutic protocol was initiated, including a short course of systemic antibiotics alongside intensified anti-inflammatory treatment. All bacterial and fungal cultures returned negative, confirming a non-infectious etiology. Both patients achieved complete resolution of symptoms with uneventful recoveries maintained at both the one-week and one-month postoperative follow-up visits. CONCLUSION: These cases illustrate that hyaluronidase hypersensitivity, though uncommon, should be considered in the differential diagnosis of acute postoperative periorbital inflammation. A combination of clinical vigilance, targeted imaging, and judicious use of laboratory tests is key to distinguishing this condition from infectious complications. Early diagnosis and a structured management approach are crucial to ensure patient safety and optimal outcomes.