we administered intravitreal bevacizumab injection to eight eyes of eight patients of various etiologies ranging from retinal vein occlusion to diabetic retinopathy , age related macular degeneration amd , and choroidal neovascular membrane cnvm . the best corrected visual acuity of seven out of eight patients was poor and ranged from 20/120 to finger counting . the details of the procedure , complications were discussed with the patients , and written consent taken . injection bevacizumab was procured by a patient five days prior to the date of appointment and stored under recommended conditions ( i.e. , below 4c ) . on the day of injection , under aseptic precautions , the vial was opened in operation theatres , hood was not used due to its nonavailability . the syringe was then capped with a 30-gauge needle and kept on a sterile tray . best corrected visual acuity of patients and indication for intravitreal injection the eye of each patient was prepared following standard aseptic procedures ( i.e. , lids cleaned sequentially first with spirit and then with 10% povidone - iodine ) . fornices were flushed with normal saline and 1 drop of 10% povidone - iodine was instilled 2 min before the procedure . intravitreal bevacizumab injection was administered into the superotemporal quadrant , 4 mm from the limbus . different needles were used each time after cleaning the surface of vial with spirit , thereby administering multiple pricks in the vial . all of them were asked to come next week for follow - up or earlier if patient experienced severe discomfort . four of the eight patients reported to the hospital on the 3rd day after injection with complaints of pain , watering , and diminution of vision . two patients who did not report by the 4th day were contacted and recalled for an examination . six out of eight patients had absent fundal glow along with presence of cells and flares [ table 2 ] . clinical findings in patients following intravitreal injection of bevacizumab these six patients were clinically diagnosed to have endophthalmitis and were administered intravitreal antibiotics ( injection ceftazidime 2.25 mg in 0.1 ml and injection vancomycin 1 mg in 0.1 ml ) on the same day of presentation . vitreous samples and drug vial were sent for culture sensitivity in two different laboratories which turned out to be sterile . intravitreal antibiotics were repeated after 48 h. all patients were closely followed up and remaining drug was discarded . while pegaptanib and ranibizumab are labeled for intravitreal use , bevacizumab is labeled for use in cancer therapy and is currently being used  off - label  for the treatment of ocular neovascular diseases . because of its  off - label  use , bevacizumab is supplied in much larger volumes than those needed for single intravitreal injection . thus , hospitals and compounding pharmacies must divide the larger volume of bevacizumab into smaller units suitable for single - use , individual doses . contaminants could possibly be introduced during the compounding process and compromise the sterility of the aliquoted drug . multiple pricks ( procedure common in india ) were made in vial to prepare administrating dose for eight patients . an alternative protocol suggested is that small aliquot of drug should be prepared using single prick technique , i.e. , 0.5 in . 26 gauge needle should be inserted into rubber cap of vial and drug should be drawn into different 1 ml syringes , every time changing only the syringe , leaving the needle in place . next group should be administered injection after one week , i.e. , after the first follow - up of the previous batch . in this way , we would be able to minimize incidence of cluster endophthalmitis and detect possible contamination in the compounded aliquoted drug before it is administered to the next batch . if required , each eye should be injected using drug from different lots under sterile conditions . six out of eight patients had endophthalmitis , remaining two patients though belonging to different age groups ( 50 and 72 years ) , did not develop endophthalmitis . the possible reason for this could be the inherent immunity against the causative organism or the quantity of causative organism in the inoculums could have been below the threshold required for endophthalmitis . presentation of cases with signs and symptoms of endophthalmitis and response with intravitreal injection of antibiotics led us to assume infective pathology despite the negative culture report . the possibility of tass syndrome in these patients was considered , but review of literature suggests that series of patients , who developed tass syndrome in canada , had reported as early as 24 h. the final visual outcome was poor even with aggressive treatment . all patients had worse visual acuity at the end of follow - up than on injection day . four patients in our study presented on day 3 , while two patients reported on day 4 , after intravitreal injection . three out six patients with endophthalmitis showed improvement in visual acuity with intravitreal antibiotic therapy , as compared to pretreatment level . visual acuity remained same in two cases , while it deteriorated drastically in one case even after aggressive treatment [ table 3 ] . as the approval of intravitreal use of bevacizumab and its subsequent availability in the market in single dose ( 0.05 ml ampoules ) is still awaited , using the single - dose vial and aliquoting into smaller doses for multiple uses , is the call of the day . however , the present incident highlights the risks of microbial contamination and the need to stay vigilant against preexisting contamination within the vial or its access to the drug via multiple pricks . the alternative protocol , as described previously , is recommended to increase the safety margin of the intravitreal injection of bevacizumab .
the risk of endophthalmitis is always a concern when an intraocular procedure is performed . 
 intravitreal injection is a frequently used method for therapeutic management of many diseases , affecting the posterior segment of the eye . 
 hence , it is important to assess the risk of complications , especially endophthalmitis . 
 most studies conducted concentrate on risk assessment from single use from single drug vial . 
 the present article reports the occurrence of cluster endophthalmitis following multiple intravitreal bevacizumab injections from a single vial . 
 intravitreal injection of bevacizumab was administered to eight eyes of eight patients . 
 administered dose was prepared from single 4-ml vial of bevacizumab and was injected in the eye , after patient preparation and under aseptic conditions . 
 the procedure was repeated for the remaining patients , thereby imparting multiple pricks in the same vial . 
 four of the eight patients reported to the hospital on the 3rd day after injection with complaints of pain , watering , and diminution of vision . 
 two patients reported the following day with similar complaints . 
 two patients who did not report by the 4th day were contacted and recalled for an examination . 
 all the patients were thoroughly examined using slit lamp biomicroscopy and indirect ophthalmoscopy . 
 six out of eight were clinically diagnosed to have endophthalmitis and were administered intravitreal antibiotics . 
 the present report highlights possibility of microbial contamination of the drug vial or during compounding process . 
 however , from the present incident , we are encouraged to stay vigilant and wary of contamination