Acute bilateral endophthalmitis following bilateral intravitreal bevacizumab (avastin) injection.

The clinical presentation and management of two patients who presented with acute bilateral endophthalmitis following bilateral intravitreal bevacizumab injection. Both cases were diagnosed clinically and subsequent to a vitreous sample, intravitreal ceftazidime (2.25 mg/0.1 ml) and vancomycin (1 mg/0.1 ml) were injected. One patient had a significant improvement in signs and symptoms after intravitreal antibiotics. However, there were was no improvement in the other patient and pars plana vitrectomy was performed bilaterally. Vitreous cultures were positive in both cases for Staphylococcus epidermidis.

INTRODUCTION

Bevacizumab (Avastin; Genentech Inc., San Francisco, CA) is a monoclonal antibody against vascular endothelial growth factor (VEGF) which was approved by the United States Food and Drug Administration for the treatment of metastatic colorectal cancer.1 Ophthalmologists have used intravitreal injection of Avastin off-label, for a number of indications including age-related macular degeneration, diabetic macular edema, cystoid macular edema and retinal vascular accidents.2

Acute endophthalmitis is a rare but devastating complication of intravitreal bevacizumab (IVB) injection. The incidence of endophthalmitis varies in the literature from 1:1000 to 1:5233 per injection.3–5 Potentially, bilateral intravitreal injection of bevacizumab can lead to bilateral endophthalmitis. Our literature review during the research for this case report did not yield any reports of bilateral endophthalmitis following IVB injection. Here we describe the first two cases in peer review literature of bilateral endophthalmitis after IVB.

CASE REPORTS

Case 1

A 76-year-old female was referred to our emergency clinic with complaints of bilateral ocular pain and decreased vision 1 day after receiving bilateral IVB injection for diabetic macular edema.

On examination, her visual acuity was hand movement and light perception in right and left eyes, respectively. There was severe cellular reaction in anterior chamber and vitreous in the right eye. Significant anterior chamber reaction with a 0.7-mm hypopyon and severe vitritis were present in the left eye. The red reflex was absent bilaterally. B-scan ultrasonography revealed inflammatory cells in the vitreous of both eyes.

Due a high index of suspicion for bilateral postoperative endophthalmitis, the patient underwent diagnostic and therapeutic vitreous tap and intravitreal injection of 2.25 mg/0.1 ml ceftazidime and 1 mg/0.1 ml vancomycin. The vitreous sample was turbid. Two days after antibiotic injection, visual acuity improved to 20/400 in both eyes and there was a significant improvement in the symptoms and signs of inflammation. Cultures of the vitreous sample were positive for Staphylococcus epidermidis.

Case 2

A 52-year-old female with a history of bilateral IVB injection for diabetic macular edema, presented with bilateral ocular pain and photophobia 2 days after IVB injections. On examination, visual acuity was light perception in both eyes. There was significant anterior chamber inflammation and hypopyon in both eyes. There was 4+ cell in the vitreous. The retina was not visible due to media opacity.

B-scan ultrasonography showed diffuse vitreous opacity bilaterally. The patient underwent diagnostic and therapeutic vitreous tap and intravitreal injection of 2.25 mg/0.1 ml ceftazidime and 1 mg/0.1 ml vancomycin. Two days later despite intravitreal antibiotics therapy, the signs and symptoms progressed and pars plana vitrectomy and intravitreal antibiotic injection was performed in both eyes. During vitrectomy, the retina appeared necrotic, especially in the macular region. Five days after vitrectomy, the signs and symptoms of endophthalmitis resolved. However, there was no improvement in visual acuity due to the retinal necrosis. Vitreous culture inoculated onto blood agar was positive for S. epidermidis.

DISCUSSION

Postoperative endophthalmitis is a rare devastating complication observed after IVB injection. Similar to our cases, most reports of endophthalmitis document decreased vision, ocular pain and redness, soon after IVB injection.3–6 Recently, some standardization has been advocated to minimize the risk of postoperative endophthalmitis after IVB injection. These measures include preoperative cleansing of eyelids and conjunctiva with a 5% povidone-iodine solution, isolation of lids and lashes from the surgical field and treatment of high-risk patients with topical antibiotics.

Sterile and infectious endophthalmitis after intravitreal injection presents with similar sign and symptoms such as a rapid decrease in visual acuity. Hence, prompt diagnosis of infectious or noninfectious endophthalmitis is imperative. Signs of infectious endophthalmitis include, inflammation, pain, fibrin, sudden and significant loss of vision within days of IVB. S. epidermidis was isolated in both cases in the current paper. S. epidermidis is the most common pathogen isolated from the vitreous samples.78 The cause of infectious endophthalmitis after IVB remains contentious. Some studies have implicated the needle used during IVB as it contacts the ocular surface and inoculates the vitreous.8 Others suggest pharmacological compounding during preparation of bevacizumab for ophthalmic use as the cause of infection.9

Prophylactic measures are particularly important for bilateral procedures. In the current cases, both patients were diabetic and received bilateral IVB. We recommend performing IVB injection in diabetics or immunocompromised patients in separate sessions for each eye. Moreover, it is imperative to adhere to all prophylactic measures for each eye in all patients undergoing bilateral injection. We believe separate, surgical grade instruments (including speculum, drug vial and calipers) should be used for each eye in a bilateral procedure.