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Case Report Acute bacterial endophthalmitis after intravitreal bevacizumab injection: Case report and literature review Saba Al Rashaed, MD ; Abdulaziz Rushood, MD Abstract A case report of a 52 year old male who received intravitreal bevacizumab and developed culture positive endophthalmitis. Vit- reous culture indicated that endophthalmitis was caused by Staphylococcus epidermidis. The patient was initially managed with intravitreal injection of ceftazidime and vancomycin, followed by pars plana lensectomy, pars plana vitrectomy with intravitreal injection of 1 mg/0.1 ml vancomycin, 2.25 mg/0.1 ml ceftazidime, 5 mg/0.1 ml fortified amphotericin-B and 4 mg/0.1 ml dexa- methasone. Postoperatively the patient improved significantly. However, vision improved from hand motion to counting fingers secondary to severe retinal ischemia. Acute endophthalmitis can develop after intravitreal bevacizumab injections and cause pro- found visual loss. A review of literature was also performed for similar cases. Keywords: Endophthalmitis, Bevacizumab, Staphylococcus, Pars plana vitrectomy, Visual loss, Infection Ó 2012 Saudi Ophthalmological Society, King Saud University. All rights reserved. http://dx.doi.org/10.1016/j.sjopt.2012.04.002 Introduction The introduction of vascular endothelial growth factor antagonists has lead to a dramatic increase in intravitreal injections worldwide. Currently the most common intravitreal injections are performed with triamcinolone acetonide, bev- acizumab (Avastin Ò ; Genentech Inc., San Francisco, CA, USA) and ranibizumab (Lucentis Ò ; Genentech Inc., San Fran- cisco, CA, USA) for a variety of conditions including exudative age related macular degeneration (AMD) and macular ede- ma of various etiologies. 1–5 Complications after intravitreal injection include infectious and sterile endophthalmitis, rhegmatogenous retinal detach- ment, a transient increase in intraocular pressure and iatro- genic injury to the eye. 1–5 Infectious endophthalmitis is a rare complication of intravitreal injection, but is relevant due to the increased frequency and number of injections being performed. Clinically, endophthalmitis can cause pro- found loss of vision, which may be permanent despite prompt and appropriate management. In this case report we present a case of acute endophthal- mitis after intravitreal injection of bevacizumab for prolifera- tive diabetic retinopathy with macular edema that resulted in with poor vision despite prompt management. We also performed a literature review of similar cases of endophthalmitis. Case report A 52 years old insulin dependent male diabetic was pre- sented to the emergency room with loss of vision, pain, and redness in his left eye. Three days prior to presentation, the patient received an intravitreal injection of bevacizumab elsewhere for diabetic macular edema. Ophthalmic examination revealed visual acuity was 20/80 in the right eye and hand motion in the left eye. There were no significant Peer review under responsibility of Saudi Ophthalmological Society, King Saud University Production and hosting by Elsevier Access this article online: www.saudiophthaljournal.com www.sciencedirect.com Received 5 March 2012; received in revised form 26 March 2012; accepted 16 April 2012; available online 28 April 2012. From Vitreoretinal Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia q The authors have no proprietary interests in the materials presents in this paper. Corresponding author. Address: King Khaled Eye Specialist Hospital, P.O. Box 7191, Riyadh 11462, Saudi Arabia. Tel./fax: +966 1 482 1234x1908. e-mail address: [email protected] (S.A. Rashaed). Saudi Journal of Ophthalmology (2013) 27, 55–57
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Saudi Journal of Ophthalmology (2013) 27, 55–57

Case Report

Acute bacterial endophthalmitis after intravitreal bevacizumabinjection: Case report and literature review

Saba Al Rashaed, MD ⇑; Abdulaziz Rushood, MD

Abstract

A case report of a 52 year old male who received intravitreal bevacizumab and developed culture positive endophthalmitis. Vit-reous culture indicated that endophthalmitis was caused by Staphylococcus epidermidis. The patient was initially managed withintravitreal injection of ceftazidime and vancomycin, followed by pars plana lensectomy, pars plana vitrectomy with intravitrealinjection of 1 mg/0.1 ml vancomycin, 2.25 mg/0.1 ml ceftazidime, 5 mg/0.1 ml fortified amphotericin-B and 4 mg/0.1 ml dexa-methasone. Postoperatively the patient improved significantly. However, vision improved from hand motion to counting fingerssecondary to severe retinal ischemia. Acute endophthalmitis can develop after intravitreal bevacizumab injections and cause pro-found visual loss. A review of literature was also performed for similar cases.

Keywords: Endophthalmitis, Bevacizumab, Staphylococcus, Pars plana vitrectomy, Visual loss, Infection

� 2012 Saudi Ophthalmological Society, King Saud University. All rights reserved.http://dx.doi.org/10.1016/j.sjopt.2012.04.002

Introduction

The introduction of vascular endothelial growth factorantagonists has lead to a dramatic increase in intravitrealinjections worldwide. Currently the most common intravitrealinjections are performed with triamcinolone acetonide, bev-acizumab (Avastin�; Genentech Inc., San Francisco, CA,USA) and ranibizumab (Lucentis�; Genentech Inc., San Fran-cisco, CA, USA) for a variety of conditions including exudativeage related macular degeneration (AMD) and macular ede-ma of various etiologies.1–5

Complications after intravitreal injection include infectiousand sterile endophthalmitis, rhegmatogenous retinal detach-ment, a transient increase in intraocular pressure and iatro-genic injury to the eye.1–5 Infectious endophthalmitis is arare complication of intravitreal injection, but is relevantdue to the increased frequency and number of injectionsbeing performed. Clinically, endophthalmitis can cause pro-

Peer review under responsibilityof Saudi Ophthalmological Society,King Saud University

Received 5 March 2012; received in revised form 26 March 2012; accepted 16

From Vitreoretinal Division, King Khaled Eye Specialist Hospital, Riyadh, Saudq The authors have no proprietary interests in the materials presents in this paper.

⇑ Corresponding author. Address: King Khaled Eye Specialist Hospital, P.O.e-mail address: [email protected] (S.A. Rashaed).

found loss of vision, which may be permanent despiteprompt and appropriate management.

In this case report we present a case of acute endophthal-mitis after intravitreal injection of bevacizumab for prolifera-tive diabetic retinopathy with macular edema that resultedin with poor vision despite prompt management. We alsoperformed a literature review of similar cases ofendophthalmitis.

Case report

A 52 years old insulin dependent male diabetic was pre-sented to the emergency room with loss of vision, pain,and redness in his left eye. Three days prior to presentation,the patient received an intravitreal injection of bevacizumabelsewhere for diabetic macular edema. Ophthalmicexamination revealed visual acuity was 20/80 in the righteye and hand motion in the left eye. There were no significant

Production and hosting by Elsevier

Access this article online:www.saudiophthaljournal.comwww.sciencedirect.com

April 2012; available online 28 April 2012.

i Arabia

Box 7191, Riyadh 11462, Saudi Arabia. Tel./fax: +966 1 482 1234x1908.

Figure 1. Progress of an eye that underwent intravitreal bevacizumab injection and subsequently developed culture positive endophthalmitis. (A) Atpresentation, 48 h after intravitreal injection showed no improvement with ciliary vessel injection, hypopyon and absence of a red reflex. (B) Three daysafter the surgery. Note the disorganized hypopyon with corneal edema. (C) Two weeks after surgery showed a quiet eye and remnants of a disorganizedhypopyon. (D) Two months follow up showed central corneal haze with a quiet eye and resolution of the hypopyon.

56 S.A. Rashaed, A. Rushood

findings in the right eye other than severe non-proliferativediabetic retinopathy. The left eye had marked lid edema withciliary injection, corneal edema with a 3 ml hypopyon, poster-ior synechia and a white fundus reflex.

B-scan showed marked vitreal and subvitreal opacitieswith diffuse retino-choroidal layers. The patient was diag-nosed with acute endophthalmitis after intravitreal bev-acizumab. An urgent vitreous tap was performed alongwith intravitreal injection of vancomycin and ceftazidime.The patient was placed on oral moxifloxacin once a dayand instructed to instill topical fortified cephalexin and ceft-azidime drops hourly. Two days later, there was no clinicalimprovement. The patient underwent synechiolysis, parsplana lensectomy, pars plana vitrectomy with intravitrealinjection of 1 mg/0.1 ml vancomycin, 2.25 mg/0.1 ml ceftazi-dime, 5 mg/0.1 ml amphotericin-B and 4 mg/0.1 ml dexa-methasone. Postoperatively there was significant clinicalimprovement. However, the vision improved from hand mo-tion to counting by fingers secondary to severe retinal ische-mia caused by the disease process. Fig. 1 presents theprogress of the eye from presentation onward. A culturefrom the vitreous sample was positive for Staphylococcusepidermis.

Discussion

Bevacizumab (Avastin�) is a recombinant humanized fulllength monoclonal antibody which binds to all biologicallyactive isoforms of a key mediator of angiogenesis – vascularendothelial growth factor A (VEGF A). Bevacizumab has beenused off label to treat neovascular age related maculardegeneration (AMD) since 2005.3,6–9 Several groups have re-ported the use of intravitreal bevacizumab for a number ofposterior segment conditions including central retinal veinocclusion in proliferative diabetic retinopathy,10–19 pseud-

ophakic cystoid macular edema,20 iris neovascularization,neovascular glaucoma and diabetic macular edema.21–27

The incidence of (sterile or infectious) endophthalmitis re-ported in most studies remains rare. For example, Funget al.28 analyzed 7113 cases of intravitreal bevacizumabworldwide and found 1 case (0.01%) of endophthalmitis.However Fung et al. did not differentiate between sterileand infectious endophthalmitis. We believe the outcomesfrom Fung et al’s28 and similar studies may underestimate ad-verse events due to survey design, specifically the self report-ing of complications.

The development of infectious endophthalmitis after anintravitreal bevacizumab injection has been previously re-ported. Fintak et al.1 reported an incidence of 0.02% forinfectious endophthalmitis following 12,585 cases of intravi-treal bevacizumab. Two of the cases were caused by Strepto-coccus viridans and one by S. epidermidis.1 All cases in Fintaket al’s1 study ended with hand motion vision.1 The incidenceof endophthalmitis following intravitreal bevacizumab injec-tion in a large case series ranges from 0.019% to0.099%.1,29–31 The organism isolated in one study was Serra-tia marcescens in two cases with a final visual outcome of nolight perception.29 However in30,31 two separate series,reporting on cases of Haemophilus influenzae, or S. epide-rmidis (2 cases) the patients had a final visual acuity of 20/400 vision. Our case resulted in a final visual outcome of 4/200.

In a report32 of 5 cases of severe acute intraocular inflam-mation from 1278 cases that received intravitreal bev-acizumab, 2 cases of Propionibacterium acnes, 1 case ofcoagulase-negative Staphylococcus and 2 cases with nomicrobial growth were detected from the vitreous aspirate.In our case, Staphylococcus epidermidis was identified.

The risk of infectious endophthalmitis is always a concernwith any intraocular procedure. The most common sources

Acute bacterial endophthalmitis after intravitreal bevacizumab 57

of bacteria are from patient’s flora originating from the lids,lashes, and conjunctiva.33 Hence, thorough, standardizedcleansing techniques should help mitigate the incidence ofinfectious endophthalmitis. Precautions against infectiontend to vary between studies and practitioners. The onlystandard prophylactic measure is the use of preoperativepovidone–iodine drops and the use of a lid speculum. Preop-erative povidone–iodine is recommended due to a previousreport of a significant reduction in endophthalmitis after pre-operative use of povidone–iodine for intraocular surgery.34,35

The importance of a lid speculum, was determined by theVISION36 trial that found two thirds of the 12 cases ofendophthalmitis were associated with protocol violations,the most common being the lack of a lid speculum. The lidspeculum retracts the lid margin and lashes away from theinjection site, the general consensus is that lid speculumuse is an important step in reducing the risk of endophthalmi-tis. Other prophylactic measures include instillation of topicalantibiotic postoperatively, wearing sterile gloves, and wear-ing a mask during the procedure. In conclusion, although pre-vious studies report a low incidence rate of endophthalmitisafter intravitreal injection of bevacizumab, it is still a concerndue to the potential for profound visual loss as our and pre-vious reported cases have demonstrated. Informed consentshould incorporate the possibility of profound visual lossafter the procedure.

References

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