Patients receiving anti-VEGF injection for retinal disease often require repeated doses for long period of time that increases bacterial resistance. Repeated use of prophylactic antibiotics changes the type of normal flora as well as pathogenic bacteria.
The mean age of patients in our study was 59.62 years.The minimum age being 19 years /and the maximum age 91 years. 264 were right eye and 239 were left eye. Similar to the study done by Afarid M et al where the mean age ( ± SD) of the patients was 61.48 (± 11.21) years. Out of 141 patients, (39.3%) were men and 218 (60.7%) were women in contrast to our study. There were 308 males and 195 females in our study. Greater number of male patients had sterile conjunctiva than females and conjunctiva of old people were found to be increasingly more colonized than young [1].
The indications of intravitreal injection in our study were diabetic macular edema, CRVO with macular edema, BRVO with macular edema, choroidal neovascular membrane, central serous retinopathy and uveitic macular edema which was similar to study done by Mohammad et al [7].
Halachmi-Eyal et al. concluded that endophthalmitis prophylaxis with pre injection of antibiotics does not reduce the endophthalmitis rate, neither it decreases the bacterial count any more than the use of Povidone iodine alone. According to Bhavsar et al [6] the benefit of pre injection of topical antibiotics is not demonstrated.
The profile of resistance to the three fluoroquinolones (levofloxacin, ofloxacin and moxifloxacin) was correlated with the number of injections, indicating that resistance increased with this number. In contrast to Povidone iodine application, administration of antibiotics before intravitreal injection did not reduce the number of recolonizations with new bacteria. Antibiotic prophylaxis with ofloxacin did not reduce the number of positive cultures as opposed to PVI application.[2]
The results of a large meta-analysis study by MF Bande et al established that the prophylactic use of antibiotics for intravitreal anti-VEGF injections is associated with a higher incidence of endophthalmitis. This finding could potentially eliminate an unnecessary intervention that is likely harmful to patients. [3]
Fluoroquinolones are the most commonly used post-injection prophylactic antibiotics in patients due to their broad spectrum and high penetration. Several studies have demonstrated substantial levels of resistance to third- and fourth-generation fluoroquinolones, as well as multi-drug resistance in patients treated with topical antibiotics after multiple intravitreal injection [7,8]
Despite the absence of data to support the reduction of endophthalmitis through the use of antibiotics after intravitreal injections, many ophthalmologists continue to recommend a multiday course of topical antibiotic use before and after intravitreal injection. Repeated use of antibiotic prophylaxis due to monthly intravitreal injections, promotes resistance and virulence of conjunctival flora even on short duration with low doses. Strict rules of asepsis remain the only evidence-based support for prophylaxis of endophthalmitis. Therefore, antibiotics should be prescribed only in exceptional cases such as immunosuppression or fragile conjunctiva. International guidelines surrounding the use of antibiotics in intravitreal injections should be generated.[4]
Povidone Iodine. Ophthalmic or “half strength” povidone-iodine is routinely used in ophthalmic surgery due to its broad spectrum antimicrobial activity, low incidence of microorganism resistance, cost-effectiveness, and wide availability [9]. As endophthalmitis is hypothesized to occur due to inoculation or ingress of microorganisms into the globe during injection, sterilizing of the ocular surface is of paramount importance and the central evidence-based recommendation of any injection protocol. In a study reported by Diabetic Retinopathy Clinical Research Network (DRCR.net), 3123 eyes received 28,786 intravitreous injections, usually with povidone-iodine preparation. However, a total of 13 injections in 2 participants were administered without antiseptic and both participants developed endophthalmitis in 1 eye each. This was 15% risk of endophthalmitis per injection. 100% of the risk subjects developed endophthalmitis during the short duration of the treatment[10] The omission of topical antiseptic is associated with significantly higher rates of endophthalmitis.
The rate of endophthalmitis without the use of pre and post injection antibiotics in our study was very low ie 0.0019%. Similarly another study by Benoist showed the incidence of endophthalmitis with antibiotic use was 0.052% versus 0.048% without antibiotic use [4]. Muhammad et al showed in their study that the use of antibiotics after intravitreal Bevacizumab injection does not make any difference for the prevention of postoperative endophthalmitis. Out of 620 injections given in 480 eyes, 310 were control group without any post-injection medicine and 310 were cases who were given post-injection medicine. No case of proven or suspected endophthalmitis was identified, corresponding to a risk of 0% per injection [11]. Bhatt et al in their study found the rate of endophthalmitis post injection antibiotics were 0.22% versus not receiving antibiotics were 0.20% The rate of endophthalmitis after intravitreal injections administered in a clinical practice setting when aseptic technique is used is similar with or without the use of post-injection antibiotics [12].
In Endophthalmitis Vitrectomy Study, diabetic patients showed more virulent microorganisms and a higher proportion of Gram negatives and less probability of presenting negative cultures 19 [6]. The risk factors for endophthalmitis in diabetes melllitus are Insulin Dependent Diabetes Mellitus, old age, immunosuppression and most infections arouse from own flora [11]. Although no large-scale study has looked exclusively at subjects with diabetes and endophthalmitis, analysis of the subgroup of patients with diabetes in studies comprising both (patients with diabetes and patients without) suggest that virulence is worse in the former group, growth of organisms is faster and a more aggressive treatment bares a better result [13]. Therefore uncontrolled diabetes and old age are a high risk factor for endophhalmitis in our study rather than not using antibiotics.
The standardized Diabetic Retinopathy Clinical Research Network (DRCR.net) intra vitreous injection protocol requires the application of topical anesthetic, the use of a sterile eyelid speculum, and the application of topical povidone-iodine to the conjunctiva. The protocol does not require but allows topical antibiotics prior to, on the day of, or after the injection. The results of DCCR.net study by Bhavsar et al were that the rates of endophthalmitis by antibiotic use were 0.11% versus 0.03% without antibiotic use [6].
PET. Lau et al examined the factors that can be used to reduce or prevent post-intravitreal injection-related endophthalmitis. The authors believe there is evidence to recommend (in order of strength of evidence): povidone iodine antisepsis (aqueous chlorhexidine where this is not
possible), eyelid retraction with speculum, prevention of droplet spread via masks, adhesive drapes and reduced talking, and subconjunctival anesthetic with lidocaine base agent. The omission of prophylactic topical antibiotics seems justified by the existing literature; however
Prospective trials are lacking [5].
Recent studies have indicated that the use of topical antibiotics could increase resistance to some antibiotics like fluoroquinolones by affecting the conjunctival and nasopharyngeal flora. Moreover, increasing the proportion of resistant bacteria on the ocular surface increases the risk of developing antibiotic-resistant infections that are difficult to treat. Ocular surface preparation for intravitreal injection using povidone-iodine 5% alone in the absence of post injection topical antibiotics does not appear to promote bacterial resistance or a discernible change in conjunctival flora. [14]
Grzybowski et al recommended expert consensus on intravitreal injections. The topical administration of 5% povidone-iodine over at least 30 second into the conjunctival sac is recommended. It doesn’t recommend the use of perioperative antibiotics for intravitreal injection as in our study[15].
Recommendation from 2014 expert panel came to the consensus that the most important aspects of the antiseptic technique include the use of conjunctival 5% povidone-iodine, avoiding lash or lid touch to the site of injection following the povidone-iodine, and the use of surgical masks or decreased talking during the procedure. It doesn’t recommend the use of antibiotics for intravitreal injection [16] which strongly supports our study.