FP1531 : Endophthalmitis After Intravitreal Anti Vegf and Steroid Injections.

Dr. Subhash PrasadP06836, Dr. Randhir Kumar, Dr.Satya Prakash Tiwary, Dr. Bandana Kumari

Endophthalmitis after intravitreal anti VEGF and steroid injections

Purpose:To report the incidence of endophthalmitis following intravitreal anti VEGF and steroid injections  in a private clinic setup

Methods:A retrospective study of  medical records of intravitreal anti VEGF  and steroid injections  between January 2008 to March 2016 was performed to select all cases who developed  endophthalmitis.

Results: A total of 12 out of 9124 cases (0.13%) were found to have presentations of endophthalmitis with complains of noticeable decrease in vision along with vitreous exudate and anterior segment inflammation within 4 days of injection.Out of 9124 injections,Bevacizumab(Avastin) was injected in 7512, Ranibizumab(Lucentis/Accentrix )in 1420, Triamcinolone in 150 and Ozurdex in 52.Only 4 patients were culture positive.While 5 patients recovered with intravitreal antibiotics,7 required pars plana vitrectomy.2 eyes went into phthisis.

Conclusion:Endophthalmitis after intravitreal anti VEGF  and steroid injections though rare,can result in devastating loss of vision

Introduction:

While the advent of molecular therapeutics targeting vascular endothelial growth factor (VEGF) has revolutionized the management and visual prognosis for patients with age-related macular degeneration, retinal vein occlusion, diabetic macular edema, and other diseases resulting in retinal vascular leakage or choroidal neovascularization, each injection of these agents carries a small associated risk of endophthalmitis. Similarly the intravitreal use of  steroids in various forms are not immune to the risk of endophthalmitis. Retrospective studies have suggested that the incidence of post-injection endophthalmitis ranges from 0.02 to 1.6 %, with several recent large-scale meta-analyses placing the incidence rates closer to 0.049 to 0.056 % [1-5]. Although the risk is low, the visual consequences can be devastating. A recent literature review highlighted the lack of current data regarding the most appropriate initial management of post-injection endophthalmitis [6].

Methods:

The medical   records of all patients treated with intravitreal injections of anti- VEGF and steroids at Divyadrishti eye centre, Patna   from January 2008 to March 2016 were reviewed and those developing signs and symptoms consistent with diagnosis of endophthalmitis were further analysed  in detail. We reviewed all cases of endophthalmitis during a 8-year period (January 2008 to March 2016 ) and then specifically investigated the microbial pathogens and clinical course of those cases which occurred following intravitreal injection of an anti-VEGF agents and steroids.All intraviteal injections were performed under strict aseptic condition. In all cases, lid speculums with lid guards   were used. All patients received topical 5 % Betadine prior to injection with a 30-gauge needle administered in the inferotemporal quadrant 3.5 or 4 mm posterior to the limbus for pseudophakic or phakic patients, respectively.

The diagnosis of endophthalmitis was made clinically. In all cases of endophthalmitis following anti-VEGF and steroids injection, aqueous or vitreous fluid was sent for microbial culture and culture results were reviewed. Regarding presentation of data, quantitative variables are expressed as the mean ± standard deviation and qualitative variables are expressed as percentages.

Results:

The medical records of 9124 cases were analysed. The indications for treatment included neovascular age-related macular degeneration, diabetic macular edema, macular edema related to  retinal vein occlusion. In 7512  patients, the drug administered was bevacizumab (Avastin; Genentech, Inc., South San Francisco, California, USA), in 1420 patients  ranibizumab (Lucentis; Genentech, Inc., South San Francisco, California, USA) was used while intravitreal triamcinolone and ozurdex were used in  150, and 52 patients respectively. A total of 12 out of 9124 (0.13%) cases were found to have presentations of endophthalmitis,10 cases in bevacizumab group (0.13%) and 2 in ranibizumab group (0.14%).

The most common presenting symptoms were decreased vision (12/12)  and pain(4/12) ; all cases exhibited conjunctival injection, anterior chamber cells, and vitreous cells and exudates. Visual acuity at presentation ranged from 6/24 to hand movement . The average time to presentation was 4.3 ± 3 days following injection (range 1–15 days). All but one patient underwent primary vitreous tap with intravitreal injection of antibiotics (vancomycin and ceftazidime). The patient who underwent primary vitrectomy had the longest duration between injection and presentation (15 days) and visual acuity immediately prior to vitrectomy was counting fingers (CF). Of those who underwent primary tap/inject, 6 of the 11 underwent subsequent pars plana vitrectomy, with the decision to proceed to surgery based on persistent vitritis.

Vitreous or anterior chamber cultures were positive in 4 of the 12 cases (33 % total; 3 cases with positive vitreous culture, 1 case with positive aqueous tap). The most commonly isolated organism in our series was Coagulase negative Staphylococcus (3/4, or 75 % of all culture positive cases). Culture positivity correlated with poorer visual acuity at presentation or recovery. The remaining one culture-positive case was Acenetbacter sp. Interestingly, the patient’s symptoms were mild with signs more confined to the posterior segment. Vitrectomy was performed 5 days after presentation in the setting of persistent dense vitritis. All but two  patients exhibited some  improvement in  vision at most recent follow-up. Two patients went into pthisis bulbi despite all these efforts.

Discussion:

As VEGF  inhibitors are  the mainstay of treatment for highly prevalent retinal diseases characterized by neovascularization and retinal vascular leakage such as neovascular AMD, diabetic macular edema, and retinal vein occlusions, it’s imperative to know  the associated risk of infectious endophthalmitis with intravitreal injection of these agents. Several large retrospective analyses have indicated that the rate of endophthalmitis is low (approximately 0.05 % or 5 in 10, 000), for any individual patient potentially receiving repeated monthly injections. The use of pre- and post-procedure topical antibiotics for prophylaxis has been debated and recent evidence argues against its utility in improving visual outcomes [2, 7, 8]. Widespread use of prophylactic antibiotics may also contribute to the emergence of antibiotic-resistant organisms and higher rates of antibiotic treatment failure.

Here, in our 8-year retrospective analysis at Divyadrishti eye centre,Patna, we report  an incidence of 0.13% (12 out of 9124) cases of endophthalmitis after   intravitreal injections of anti-VEGF  and steroids. Over these  8-year period, anti-VEGF treatment has become frequently performed procedure.All but one patient in our series underwent initial treatment with tap/inject, and six of them  required subsequent vitrectomy.Thus 7  out of 12 required vitectomy.

Of the 33 % of cases of endophthalmitis following intravitreal  injections, which were culture-positive, three out of four (3/4 ) grew coagulase-negative Staphylococcus as the causative agent, consistent with prior reports. However, in the remaining one  case, we identified Acenetobacter sp. Acinetobacter spp. are found in the environment, soil, and water and have the ability to colonize almost any surface including the skin, respiratory, and gastrointestinal tracts. There are few reports of post-operative and post-traumatic endophthalmitis caused by Acinetobacter spp., and endogenous endophthalmitis caused byAcinetobacter spp. (.9,10,11). To our knowledge, this is the first report of intraocular , Acenetobacter  sp. infection following intravitreal anti-VEGF injections.  There were several atypical features of this patient’s presentation compared with endophthalmitis caused by other organisms, including the minimal pain and the worst effect on visual acuity. This patient’s persistent vitritis following tap/inject also necessitated vitrectomy, and  this visual outcome was also unfavourable. Our data suggest that atypical organisms should be suspected in patients with dense non-clearing vitritis following tap/inject.

Falacy of our study is that it was a retrospective study,the  negative rate of vitreous aspirate cultures limited the attempts to identify all potential causative micro-organisms associated with endophthalmitis. However, the overall incidence of endophthalmitis following anti-VEGF injection is fortunately very low and such a prospective randomized clinical trial would likely not be feasible.

Conclusion:

Endophthalmitis following intravitreal injection of anti-VEGF agents represents an uncommon but serious complication of a very commonly done procedure and symtoms and signs are not so evident as in postoperative endophthalmitis,hence high index of suspicion must be observed during the early follow up after intravitreal antiVEGF and steroid injections.

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