Intraocular inflammation after intravitreal ranibizumab injections

Editor, Intravitreal injections with anti-VEGF agents such as bevacizumab and ranibizumab have been increasingly used for the treatment of retinal disorders over the past years. Although both drugs are often repeatedly injected in patients with choroidal neovascularizations, serious adverse events are rare. Here, we present a case of a patient with two episodes of a severe inflammation in a series of four injections with ranibizumab. A 76-year-old woman was diagnosed with an exudative AMD in her left eye. The first intravitreal ranibizumab injection was well tolerated. Twenty-four hours after the second ranibizumab injection, the patient complained of pain and vision loss. Visual acuity had dropped from 20/100 to 20/1000. A hypopyon (0.5 mm), anterior chamber cells (2+) and vitreous cells (2+) were present. There was no past history of uveitis. The patient was hospitalized and treated with local steroids and antibiotic eye drops as well as an intravitreal injection of ceftazidime and vancomycin. Intravenous ceftazidime and vancomycin were given for presumed infectious endophthalmitis for 10 days. An anterior chamber sample was sterile, and the eye resolved its inflammatory response with recovery of the visual acuity to 20/200. One month later, a third ranibizumab injection was given. One day after injection, the patient complained of pain. Again a hypopyon (0.5 mm), anterior chamber cells (2+) and some vitreous cells were seen but visual acuity remained stable at 20/200. Only local steroids were given, and the patient recovered quickly after treatment. The patient was referred to the department of dermatology in our hospital to rule out an allergy to either ranibizumab or bevacizumab. Prick test and patch testing (epicutane test) were negative for both medications. Another intravitreal injection followed because of new subretinal fluid. The fourth intravitreal injection was given with ranibizumab at the patient's explicit request. No signs of inflammation were seen this time. One possible complication of intravitreal ranibizumab or bevacizumab administration is an inflammatory response or sterile endophthalmitis. In a large clinical trial, intraocular inflammation was reported in 2.9% (cell/flare 2+ to 4+) of the patients after intravitreal injection of ranibizumab (Rosenfeld et al. 2006). However, Kiss et al. did not find an inflammatory response by flare meter following intravitreal bevacizumab in 61 consecutive patients (Kiss et al. 2006). So it seems that only a small group of patients responds to the drug administration with inflammation. It is usually painless. The clinical spectrum comprises iritis and vitritis. Patients often respond rapidly to treatment with steroids (Bakri et al. 2008; Georgopoulos et al. 2009). The main differential diagnosis of an inflammation is an infectious endophthalmitis requiring antibiotics immediately. Differentiating infection from inflammation is often difficult especially when patients complain of pain as reported in this case. Bakri et al. found silicone oil droplets after intravitreal injections without evidence of any adverse effects. They assume that the oil originated from the needles and syringes used for the injections (Bakri et al. 2009). We used uncoated syringes and have performed the same standardized injection procedures for all four reported injections. An allergic reaction to any of the components of the anti-VEGF medication was also excluded. Up to this point, the cause of inflammation in this case remains unclear. However, the patient responded well to steroids with good visual recovery.