Romero-Aroca et al are already approved in some territories, and intravitreal implants are already under consideration. However, this increase in the number of intravitreal injections has also meant an increase in the number of complications, such as post-intravitreal injection endophthalmitis, over the past few years.2 Despite the existence of guidelines3 and a degree of con- formity in procedures for intravitreal injection, differences between institutions and physicians4 have resulted in some variation in the rate of endophthalmitis; however, the most studies report rates in the range of 0.02%–0.3%.5–9 Prophylaxis for postoperative endophthalmitis after cataract surgery has improved in recent years with the postoperative administration of eye drops (such as fourth- generation quinolones) or intracameral cephalosporin injection at the end of surgery.10–15 Conversely, informa- tion is lacking on postoperative endophthalmitis prophy- laxis after intravitreal injections.16,17 Endophthalmitis is a relatively rare complication of intravitreal injection and so controlled clinical trials require large patient samples to provide definitive conclusions. At present, one approach for prophylaxis consists of instillation of povidone iodine into the conjunctival sac prior to injection, plus subsequent administration of antibiotic eye drops.18 The aim of this study was to evaluate the prophylactic effect of azithro- mycin versus ofloxacin eye drops against endophthalmitis after intravitreal injection. Materials and methods This prospective, observational study was conducted in five hospitals in Spain. The study population included all patients undergoing intravitreal injections of triamcinolone, bevacizumab, ranibizumab, or pegaptanib from January 2010 to December 2010. Patients undergoing ocular surgery or those allergic to quinolones or macrolides were excluded. Prophylactic treatment The prophylactic protocol consisted of topical povidone iodine 10% on the skin of the periorbital region plus 5% on the conjunctiva and eyelashes for a minimum of one minute. The periorbital region and eyelashes were draped and a sterile lid speculum, topical anesthetic, and sterile gloves were used. Patients were randomized to receive azithro- mycin 15 mg/g eye drops (twice daily on the day prior to injection and for 2 days post-injection) or ofloxacin 3 mg/g eye drops (every 6 hours on the day prior to injection and for another 7 days). 1596 submit your manuscript | www.dovepress.com Dovepress Dovepress Standard operation procedures After prophylactic measures, the injection was made at the temporal inferior quadrant 4 mm from the limbus. All patients were examined the day before injection. Assessments A total of eight follow-up visits every 6 weeks were scheduled. A complete ophthalmologic examination was performed at each visit. Vitreous samples were obtained by manual vir- trectomy before intravitreal antibiotics in patients showing signs of acute endophthalmitis. Definition of acute postoperative endophthalmitis A diagnosis of presumed acute endophthalmitis was made by the ophthalmologist according to Endophthalmitis Vitrectomy Study criteria.19 All suspected cases had swollen eye lids, pain and an opaque vitreous.20 If a positive culture of vitreous sample was obtained, the case was confirmed as acute endophthalmitis. The diagnosis of pseudoendophthalmitis secondary to intravitreal triamcinolone injection was based on decreased visual acuity, without pain and with minimal red eye that appeared 1–3 days after the injection, with hyalitis and a fibrinous reaction in the anterior chamber. Microbiological methods Vitreous samples obtained by the ophthalmologist were processed immediately. A Gram stain was performed and the sample cultivated in Petri dishes. Antibiogram susceptibil- ity testing was performed according to MENSURA (Mesa Española de Normalización de la Sensibilidad y Resistencia a los Antimicrobianos) criteria.21,22 Statistical analyses Statistical analyses were performed using SPSS statistical software version 17.0 (SPSS Inc, Chicago, IL). Values are expressed as the mean ± standard deviation, and statistical analysis was determined using the Mann–Whitney U test. Results A total of 1383 patients were included. The mean patient age was 69.8 ± 7.55 (53–89) years in the azithromycin group and 68.17 ± 7.83 (53–90) years in the ofloxacin group (P = 0.372). Females accounted for 58% of patients in both groups. There were no statistically significant differences between the groups. The drugs injected in each group are shown in Table 1. Again, there were no statistically significant differences between the groups. In the azithromycin group, there were a total of Clinical Ophthalmology 2012:6