|Year : 2016 | Volume
| Issue : 1 | Page : 60-63
Incidence of endophthalmitis after intravitreal Anti-vascular endothelial growth factor: Experience in Saudi Arabia
Saba Al-Rashaed1, Sulaiman M Alsulaiman1, Abdulaziz Adel Alrushood1, Jluwi Almasaud1, J Fernando Arevalo2
1 Vitreoretinal Division, King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia
2 Vitreoretinal Division, King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia; Retina Division, Wilmer Eye Institute, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA
|Date of Web Publication||4-Jan-2016|
Vitreoretinal Division, King Khaled Eye Specialist Hospital, P.O. Box: 7191, Riyadh 11462
Kingdom of Saudi Arabia
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Purpose: To report the incidence of endophthalmitis, the clinical and microbiological aspects, after intravitreal (IVT) injection of anti-vascular endothelial growth factor.
Methods: A chart review was performed of patients diagnosed with endophthalmitis after receiving IVT injections of bevacizumab (Avastin) and ranibizumab (Lucentis) presenting to King Khaled Eye Specialist Hospital (KKESH) from May 2006 to December 2012. Endophthalmitis was diagnosed clinically as an intraocular infection with vitreous involvement that required treatment with IVT antibiotics or had undergone pars plana vitrectomy (PPV) to remove the suspected microorganism. Main outcome measures were the incidence of endophthalmitis and the clinical and microbiological features.
Results: Seven cases of endophthalmitis were identified, there was 1 (0.004%) case of endophthalmitis of 22674 IVT injections performed at KKESH. All cases were after IVT bevacizumab. Three (42.85%) cases were culture-positive and caused by Staphylococcus epidermidis. The initial management was vitreous tap and IVT injection of antibiotics followed by PPV in 6 (85.7%) cases. One (14.3%) case underwent evisceration. Visual acuity improved at last visit in only 2 (28.6%) cases. The rate of endophthalmitis was 0.0004% for bevacizumab.
Conclusions: The rate of endophthalmitis after IVT bevacizumab and ranibizumab was very low. We recommend following a standardized injection protocol, adherence to sterile techniques, and proper patient follow.up are determinant factors for low incidence rates. In addition, endophthalmitis after IVT bevacizumab and ranibizumab have poor visual outcomes despite prompt treatment.
Keywords: Anti-vascular Endothelial Growth Factor, Bevacizumab, Endophthalmitis, Gulf States, Intravitreal Injection, Ranibizumab, Saudi Arabia
|How to cite this article:|
Al-Rashaed S, Alsulaiman SM, Alrushood AA, Almasaud J, Arevalo J F. Incidence of endophthalmitis after intravitreal Anti-vascular endothelial growth factor: Experience in Saudi Arabia. Middle East Afr J Ophthalmol 2016;23:60-3
|How to cite this URL:|
Al-Rashaed S, Alsulaiman SM, Alrushood AA, Almasaud J, Arevalo J F. Incidence of endophthalmitis after intravitreal Anti-vascular endothelial growth factor: Experience in Saudi Arabia. Middle East Afr J Ophthalmol [serial online] 2016 [cited 2021 Sep 18];23:60-3. Available from: http://www.meajo.org/text.asp?2016/23/1/60/171756
| Introduction|| |
Over the last decade, the use of intravitreal (IVT) injections of bevacizumab (Avastin ®; Genentech, South San Francisco, CA) and ranibizumab (Lucentis ®; Genentech, South San Francisco, CA) have increased exponentially in retina practices worldwide. Conventional treatment modalities have been replaced due to the success of bevacizumab and ranibizumab as effective pharmacologic therapy to treat macular edema and choroidal neovascularization with minimal complications. However, the increased frequency of use can also increase the potential risk of intraocular infection.
Although rare endophthalmitis, after IVT injection of bevacizumab and ranibizumab, is a serious complication, which can be irreversible in spite of prompt and appropriate management., However, better injection technique, patient education, and use of broad-spectrum antimicrobial solutions for sterilizing the surgical field have controlled the incidence of endophthalmitis.
This study evaluates the incidence and outcomes, and the clinical and microbiological features of endophthalmitis after IVT injection of anti-vascular endothelial growth factors (VEGF).
| Methods|| |
This study was approved by the Institutional Review Board and Ethics Committee at the King Khaled Eye Specialist Hospital (KKESH). Oral informed consent was obtained from all patients. This study adhered to the tenets of the Declaration of Helsinki. None of the participants received a stipend for this study.
A retrospective chart review was performed for all patients with endophthalmitis after undergoing IVT injections of the anti-VEGFs, bevacizumab (Avastin), and ranibizumab (Lucentis) including cases referred to KKESH from May 2006 to December 2012. Endophthalmitis cases were diagnosed clinically as an intraocular infection with vitreous involvement and receiving treatment with IVT antibiotics or had undergone pars plana vitrectomy (PPV) to remove the suspected microorganism. The total number of IVT injections of bevacizumab and ranibizumab at KKESH was calculated using the KKESH pharmacy coding system.
Standard injection protocols were followed for all IVT injections in this study. A trained nurse who followed the standard preinjection protocol for the KKESH retina clinic prepared the injection. Preparation involved instilling a few drops of 5% povidone-iodine and 4% lidocaine drops from single-use dispensers into the conjunctiva. Then, the eyelid skin and lashes were cleansed with 10% povidone-iodine swabs. Topical antibiotics were not used prior to or after the injection. A sterile wire lid speculum was inserted and lashes directed away from the eye. Povidone-iodine and lidocaine drops were instilled in three alternating cycles to the inferior fornix and conjunctiva. Depending on the surgeon's preference, either a lidocaine-soaked cotton-tipped applicator was applied with gentle pressure or xylocaine gel applied at the injection site at least 5 min before the injection. The injection was performed with the physician wearing sterile gloves. For the last 3 years, the physician has been asked to wear a mask as well. The medication was administered through a pars plana approach, followed by instilling 5% povidone-iodine drops. After the injection, retinal artery perfusion was assessed by indirect ophthalmoscopy and visual acuity was checked to the count fingers level. The patients were educated on the visual symptoms and potential risk of endophthalmitis, and to present to the emergency room if necessary. A follow-up visit was scheduled. From May 2006 to May 2008, topical antibiotics were prescribed after the injections routinely; however, this practice has been abandoned for the last 4 years.
Preparation of bevacizumab
Bevacizumab was prepared under laminar airflow hoods by pharmacists following standardized KKESH policies and procedures (infection control policy, pharmacy). Briefly, the pharmacist used a disposable hair cover, yellow isolation gown, and mask, all jewelry including watches were removed, nails must be acceptable length (<1/4 length), and nail polish is prohibited. The hands, nails, and forearm up to elbow should be meticulously washed for at least 30 s with antibacterial soap in addition to using a nailbrush.
The bevacizumab is withdrawn by syringe from the vial ready for 25 syringes (1.25 mg/0.005 ml plus 0.07 ml overfill) into a 1 ml tuberculin syringe cap. The syringes and needles should be disposable. Finally, two syringes are randomly chosen for a sample culture to ensure no bacterial contamination. Each syringe is labeled with the following instructions: Do not filter; do not shake; do not freeze; protect from light; refrigerate; and expired after 14 days.
| Results|| |
Seven cases with a diagnosis of endophthalmitis were identified, and all occurred after IVT bevacizumab injections [Table 1]. There was 1 (0.004%) case of endophthalmitis out of 22,674 (21,387 bevacizumab injections and 1287 ranibizumab) IVT injections performed at KKESH. This case presented within 3 days of IVT bevacizumab. The case was culture-positive for Staphylococcus epidermidis. The rate of endophthalmitis after bevacizumab was 0.004% and 0% after ranibizumab injections.
|Table 1: Clinical features, indications, management, and outcome of endophthalmitis cases after intravitreal injection of anti-vascular endothelial growth factor*|
Click here to view
[Table 1] demonstrates the clinical features, indications, management, and outcomes of the seven patients with endophthalmitis after IVT injection of anti-VEGFs. The mean age of the patients with endophthalmitis was 55.4 years old. In all the cases, endophthalmitis was secondary to IVT injection of bevacizumab, and the indication for therapy was complications associated with diabetic retinopathy. Three (42.85%) cases were culture-positive and caused by S. epidermidis. The initial management was vitreous tap and IVT injection of vancomycin and ceftazidime followed by PPV in 6 (85.7%) cases. One (14.3%) case underwent evisceration. Visual acuity improved in 2 (28.6%) cases at the last visit.
| Discussion|| |
The reported incidence of endophthalmitis after anti-VEGF IVT injection ranges from 0.02% to 0.08%., A small study reported an incidence of 0.26%. However, in the current study, we found a very low incidence of endophthalmitis (0.004%) compared to some reports. This difference might be related to our standard protocol for preinjection preparation. Our results are consistent with a recent retrospective study by Shimada et al. that reported a 0% incidence of endophthalmitis. Shimada et al. evaluated a total of 15,144 injections comprising 548 injections of pegaptanib sodium, 846 injections of bevacizumab, and 13,750 injections of ranibizumab. They  recommended a protocol that included wearing surgical masks by operating room personnel (surgeons and nurses), draping patient's face, and irrigating the conjunctiva with 0.25% povidone-iodine prior to performing IVT injection.
Our study concurs with previous reports that prove that reduction of bacteria in the operative field is an important factor in preventing endophthalmitis. The use of povidone-iodine,, donning a surgical mask,, and silence when a surgical mask is not used , have been shown to be effective measures to achieve ocular surface antisepsis. However, use of a lid speculum, conjunctival displacement, injection site (inferior hemisphere or superior hemisphere) location, and type of anti-VEGF agent (bevacizumab or ranibizumab), have no significant association with the risk of endophthalmitis.
The value of topical antibiotic before or after IVT injections is uncertain, previous reports showed that the onset of the bactericidal effect of topical antibiotics was longer (approximately 60 min) than povidone-iodine (approximately 60 s). Hence, instillation of topical antibiotics immediately prior to an IVT injection is likely insufficient for adequate bactericidal effect. Therefore, installation of topical antibiotics either before the day of injection or immediately prior to injection is not generally recommended. A recent prospective study found that topical moxifloxacin 0.5% had no additional effect on reducing conjunctival bacterial counts beyond the effect of 5% povidone-iodine alone. Bhatt et al., showed that the incidence of endophthalmitis after IVT injections is similar with and without postinjection prophylactic antibiotics. In addition, Cheung et al., found a higher rate of endophthalmitis after the administration of topical antibiotics given immediately or for 5 days after the injection, compared with no antibiotics. In our hospital, the use of postinjection antibiotics was discontinued 4 years ago, and the one case of endophthalmitis occurred during period when we routinely used postinjection antibiotics. Our outcomes also support the findings that topical antibiotics after anti-VEGF injections are not required. Reports in literature indicate that in a nonsterile environment for IVT injection, bacteria are inoculated into the vitreous, and topical antibiotics after IVT injections do not adequately penetrate the vitreous.
The initial management for our patients (except one who underwent an evisceration because of a perforated globe) was vitreous tap, and IVT injection of antibiotics followed by PPV due to increasing severity of the condition. The value of a vitreous tap versus PPV as initial management remains uncertain. A recent study, did not draw any conclusions with regard to the benefit of PPV as a superior management to vitreous tap, and the latter was recommended as a viable primary intervention for endophthalmitis after anti-VEGF injection. In our study, only 2 (28.6%) patients had an improvement in visual acuity (20/80). The poor visual outcome might be attributed to the severity of the infection and, possibly, that the infection may have accelerated the underlying retinal pathology which in our series was proliferative diabetic retinopathy and diabetic macular edema.
The limitations of our study include that it was a retrospective, single-center consecutive case series, and uncontrolled study. Therefore, it is not possible to delineate which factors help prevent endophthalmitis after anti-VEGF IVT injections. However, our study shows that a low incidence of endophthalmitis can be achieved by following a standardized protocol that includes instilling 5% povidone-iodine in the conjunctiva and fornix, cleaning the eyelid skin and lashes with 10% povidone-iodine, a sterile wire lid speculum, wearing sterile gloves, and surgical masks. Another limitation of our study is that we did not have an adequate number of patients to detect an appropriately selected safety outcome rate for ranibizumab (0%). However, we can be reasonably confident (95%) that the true rate of endophthalmitis after IVT ranibizumab is <3/1287, or 0.002%.
In summary, in this series, a very low rate of endophthalmitis was observed after IVT injections of bevacizumab (0.0004%) and ranibizumab (0%) in an outpatient setting. We believe that following a standardized injection protocol, adherence to sterile techniques, and proper patient follow-up are determinant factors for low incidence rates. This series also showed that endophthalmitis after IVT injections of bevacizumab and ranibizumab have poor visual outcomes despite prompt treatment.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Peyman GA, Lad EM, Moshfeghi DM. Intravitreal injection of therapeutic agents. Retina 2009;29:875-912.
Sampat KM, Garg SJ. Complications of intravitreal injections. Curr Opin Ophthalmol 2010;21:178-83.
Jager RD, Aiello LP, Patel SC, Cunningham ET Jr. Risks of intravitreous injection: A comprehensive review. Retina 2004;24:676-98.
Shah CP, Garg SJ, Vander JF, Brown GC, Kaiser RS, Haller JA, et al
. Outcomes and risk factors associated with endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. Ophthalmology 2011;118:2028-34.
Pilli S, Kotsolis A, Spaide RF, Slakter J, Freund KB, Sorenson J, et al.
Endophthalmitis associated with intravitreal anti-vascular endothelial growth factor therapy injections in an office setting. Am J Ophthalmol 2008;145:879-82.
Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, et al.
Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 2006;355:1432-44.
Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, et al.
Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006;355:1419-31.
Fintak DR, Shah GK, Blinder KJ, Regillo CD, Pollack J, Heier JS, et al.
Incidence of endophthalmitis related to intravitreal injection of bevacizumab and ranibizumab. Retina 2008;28:1395-9.
Fong DS, Custis P, Howes J, Hsu JW. Intravitreal bevacizumab and ranibizumab for age-related macular degeneration: A multi-center retrospective study. Ophthalmology 2010;30:485-90.
Shimada H, Hattori T, Mori R, Nakashizuka H, Fujita K, Yuzawa M. Minimizing the endophthalmitis rate following intravitreal injections using 0.25% povidone-iodine irrigation and surgical mask. Graefes Arch Clin Exp Ophthalmol 2013;251:1885-90.
Doshi RR, Leng T, Fung AE. Reducing oral flora contamination of intravitreal injections with face mask or silence. Retina 2012;32:473-6.
Doshi RR, Leng T, Fung AE. Povidone-iodine before lidocaine gel anesthesia achieves surface antisepsis. Ophthalmic Surg Lasers Imaging 2011;42:346-9.
Wen JC, McCannel CA, Mochon AB, Garner OB. Bacterial dispersal associated with speech in the setting of intravitreous injections. Arch Ophthalmol 2011;129:1551-4.
Hyon JY, Eser I, O'Brien TP. Kill rates of preserved and preservative-free topical 8-methoxy fluoroquinolones against various strains of Staphylococcus
. J Cataract Refract Surg 2009;35:1609-13.
Wykoff CC, Flynn HW Jr, Rosenfeld PJ. Prophylaxis for endophthalmitis following intravitreal injection: Antisepsis and antibiotics. Am J Ophthalmol 2011;152:717-9.
Halachmi-Eyal O, Lang Y, Keness Y, Miron D. Preoperative topical moxifloxacin 0.5% and povidone-iodine 5.0% versus povidone-iodine 5.0% alone to reduce bacterial colonization in the conjunctival sac. J Cataract Refract Surg 2009;35:2109-14.
Bhatt SS, Stepien KE, Joshi K. Prophylactic antibiotic use after intravitreal injection: Effect on endophthalmitis rate. Retina 2011;31:2032-6.
Cheung CS, Wong AW, Lui A, Kertes PJ, Devenyi RG, Lam WC. Incidence of endophthalmitis and use of antibiotic prophylaxis after intravitreal injections. Ophthalmology 2012;119:1609-14.
Costello P, Bakri SJ, Beer PM, Singh RJ, Falk NS, Peters GB, et al.
Vitreous penetration of topical moxifloxacin and gatifloxacin in humans. Retina 2006;26:191-5.
Chaudhary KM, Romero JM, Ezon I, Fastenberg DM, Deramo VA. Pars plana vitrectomy in the management of patients diagnosed with endophthalmitis following intravitreal anti-vascular endothelial growth factor injection. Retina 2013;33:1407-16.
Hanley JA, Lippman-Hand A. If nothing goes wrong, is everything all right? Interpreting zero numerators. JAMA 1983;249:1743-5.