Editorial
Safety of bilateral intravitreal injections delivered in a teaching institution Daniel L Chao, Ninel Z Gregori†, Joyce Khandji & Raquel Goldhardt †
Expert Opin. Drug Deliv. Downloaded from informahealthcare.com by Gazi Univ. on 08/20/14 For personal use only.
Bascom Palmer Eye Institute, Miami Veterans Affairs Medical Center, Miami, FL, USA
Intravitreal injection is one of the most common in-office procedures performed in ophthalmic practices. In teaching institutions such as the Veterans Affairs (VA) Hospitals, patient care is delivered by physicians-in-training, while mastering intravitreal injection technique. Infectious endophthalmitis and visual loss are the most feared complications of intravitreal injections, especially in the context of recent outbreaks caused by contaminated compounded medications. Ophthalmologists and ophthalmic educators increasingly face the dilemma of timing as well as balancing the risks and benefits of bilateral treatments required by many patients. In this editorial, we discuss published reports of bilateral injections, summarize our experience with bilateral intravitreal injections in a teaching setting at the Miami VA Hospital and list our recommendations for minimizing the risk of infectious endophthalmitis. Keywords: aflibercept, anti-VEGF, bevacizumab, bilateral intravitreal injection, ophthalmology resident, ranibizumab, teaching institution, Veterans Affairs hospital Expert Opin. Drug Deliv. (2014) 11(7):991-993
Intravitreal injections of anti-VEGF agents are the current first-line treatment for neovascular age-related macular degeneration (AMD), retinal venous occlusive disease, diabetic macular edema and non-AMD-related choroidal neovascularization. As many patients have active disease in both eyes, ophthalmologists increasingly face the dilemma of timing and balancing risks and benefits of bilateral treatments. Bilateral same-day intravitreal injections improve cost-effectiveness and are more convenient for the patient; however, many physicians are hesitant to treat both eyes on the same day for fear of bilateral endophthalmitis and vision loss [1,2]. A 2010 survey revealed that only 46% of retina specialists in the US were performing bilateral simultaneous intravitreal injections [3]. A meta-analysis of endophthalmitis cases after anti-VEGF injections between 2005 and 2009 reported a rate of 0.049% [4]. Recent endophthalmitis outbreaks due to contaminated compounded bevacizumab have heightened physicians’ fears of this devastating complication [5,6]. Should bilateral injections be administered? How safe are bilateral injections delivered by ophthalmology residents and fellows learning intravitreal injection technique? Several studies have reported on the safety of bilateral same-day injections. In a cohort from the University of Iowa, 102 patients received 452 injections, with no cases of endophthalmitis or retinal detachment [7]. In a cohort from Bascom Palmer Eye Institute, 127 patients received 1322 bilateral same-day injections and developed no serious ocular or systemic adverse events [8]. In a cohort from Korea, 135 patients received 574 bilateral bevacizumab, ranibizumab or triamcinolone injections drawn from the same vial and reported no cases of endophthalmitis or retinal detachment [9]. In a cohort from New York City, 367 patients who received 1552 injections had two cases of culture proven unilateral endophthalmitis 10.1517/17425247.2014.909806 © 2014 Informa UK, Ltd. ISSN 1742-5247, e-ISSN 1744-7593 All rights reserved: reproduction in whole or in part not permitted
991
Expert Opin. Drug Deliv. Downloaded from informahealthcare.com by Gazi Univ. on 08/20/14 For personal use only.
D. L. Chao et al.
(0.065%), and one incidence of unilateral ocular inflammation (0.033%) [10]. In a cohort from Mayo Clinic, 35 patients who received 208 bilateral injections had one case of unilateral culture-negative endophthalmitis [11]. Two publications from the Middle East reported bilateral endophthalmitis after bilateral intravitreal bevacizumab injections. One publication reported two patients with bilateral Staphylococcus epidermidis endophthalmitis [1], and the other listed one patient with bilateral culture-negative endophthalmitis [2]. We commonly deliver bilateral injections in our teaching retina clinics at the Miami Veterans Affairs (VA) Hospital. Our retina clinics are conducted by retina specialists (n = 2) with first-year residents (n = 7 per year) and retina fellows (n = 4 per year). All injections are delivered by the physicians-in-training under direct supervision of the retina specialists. The physicians-in-training are taught a standard aseptic technique for drawing up and administering the medications. All anesthetic preparations are performed by trained technicians (n = 7) according to a standard protocol. Between October 2007 and May 2013, a total of 660 same-day bilateral and 3570 unilateral anti-VEGF injections were delivered, for a grand total of 4230 injections. The two eyes were prepared and injected sequentially on the same day without reusing any instruments or medications. Mean follow-up was 26 months (range, 1 -- 66 months). Bilateral injections were 282 bevacizumab, 281 ranibizumab and 97 aflibercept. The mean number of bilateral injections was 8.4 per patient and 4.2 per eye (range, 1 -- 31 per eye). Out of 282 bilateral bevacizumab injections, 134 doses were purchased from a compounding pharmacy prior to September 2011. After this date, according to the VA policy all bevacizumab injections were drawn up by the physicians from a new commercially available bevacizumab vial for each eye immediately prior to the injection. Of the 660 bilateral injections, 438 were delivered without the use of topical antibiotics, which have not been used in our clinics since August 2011. No infectious endophthalmitis cases were encountered with either compounded or non-compounded bevacizumab. There were no cases of endophthalmitis, uveitis or retinal detachment in unilateral or bilateral patients. The only ocular complications encountered were two corneal abrasions in the right eye of two bilateral patients. These data were collected after obtaining Miami VA Institutional Review Board approval. Recent well-publicized infectious outbreaks from compounded ophthalmic and non-ophthalmic medications, including bevacizumab, methylprednisolone and betamethasone, have resulted in significant morbidity and mortality to patients [5,6,12]. As a result, compounding pharmacies have come under intense scrutiny, and in September 2011 VA Hospitals discontinued the use of compounded bevacizumab. If a compounding pharmacy is used, providers need to ensure that the pharmacy adheres to the US Pharmacopeia, chapter 797 sterile preparation guidelines and performs sterility testing (which is actually not required by the USP 797 but is the last line of defense against contamination) [5]. It is also 992
prudent to use vials from different medication lots for each eye, in order to mitigate the risk of giving potentially contaminated vials or aliquots in both eyes. Another crucial factor in assuring patient safety is utilization of meticulous technique for ocular antisepsis, anesthesia and injection of medication. It is prudent to establish a detailed intravitreal injection protocol, which is followed by all individuals who prepare the eye and administer the injections. Our technicians’ competency is certified and maintained via periodic checks, and the residents and fellows are educated and observed by the retina specialists. We recommend performing bilateral injections sequentially, treating each eye as belonging to a separate patient, and not reusing any equipment or medications. Povidoneiodine 5% is applied to the ocular surface and the skin and lashes, always prior to anesthetic gel [13]. Sterile speculum and sterile caliper are used, although a drape and sterile gloves are not, in line with common practices by retina specialists in the US [3]. Topical antibiotics are not used since multiple publications have shown an increase in microorganism resistance rates, changes in commensal ocular flora and the same or higher endophthalmitis rates with the use of antibiotics [14,15]. It is also important to consider and manage other patient factors, such as the presence of nasolacrimal duct obstruction, significant blepharitis and active infectious or inflammatory surface disease, prior to the injection. In conclusion, published reports show that bilateral sameday injections can be delivered without major safety signals. In our VAs Hospital clinics, the injections are well tolerated by patients and resulted in no serious ocular complications, specifically no bilateral infectious or noninfectious endophthalmitis or retinal detachment. Therefore, we suggest that bilateral intravitreal injections can be delivered safely on the same day by physicians-in-training with support of ancillary personnel and supervision from retina specialists via a standard aseptic protocol. Our practice may provide a practical template for instituting bilateral intravitreal injection protocols within the VA Healthcare system or other teaching institutions.
Expert opinion Retrospective nature and relatively small number of injections are the main limitations of published literature and our experience. The goal of research in the area of intravitreal drug delivery is to assure patient comfort and safety, especially in a teaching setting. For informed consent purposes, it is helpful to know the complication rates of injections delivered by experienced ophthalmologists versus those in training. While patient safety is at the forefront of patient care in any institution, it is especially imperative to assure excellent patient care in a teaching setting. Therefore, additional quality surveillance should be performed demonstrating that with proper direction and supervision of trainees, safe unilateral or bilateral intravitreal treatments can be delivered. Of course, the
Expert Opin. Drug Deliv. (2014) 11(7)
Safety of bilateral intravitreal injections delivered in a teaching institution
Expert Opin. Drug Deliv. Downloaded from informahealthcare.com by Gazi Univ. on 08/20/14 For personal use only.
main challenge of showing bilateral injection safety is the mere number of injections needed to study. Reported mean rate of endophthalmitis is 0.049%, that is, 5 in 10,000 with unilateral injections [4]. If the two eyes are not correlated at all, the chance of both eyes getting endophthalmitis is 5/10,000 times 5/10,000, which is 5 in 100 million. If the two eyes are perfectly correlated, then the chance of both eyes getting it is 5 in 10,000. If there is some correlation, the chance of both eyes getting it is somewhere between 5 in 10,000 and 5 in 100 million. Pulling data from multiple teaching institutions would allow generating injection numbers required by these power calculations. Further studies in the area of ophthalmic education are needed to assure
adequate training of future providers without compromise of patient safety and quality of eye care delivered by the ophthalmic trainees.
Declaration of interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. This manuscript has not been presented at any meeting.
Bibliography 1.
Tabatabaii A, Ahmadraji A, Khodabande A, Mansouri M. Acute bilateral endophthalmitis following bilateral intravitreal bevacizumab (avastin) injection. Middle East Afr J Ophthalmol 2013;20(1):87-8
2.
Falavarjani KG, Modarres M, Hashemi M, et al. Incidence of acute endophthalmitis after intravitreal bevacizumab injection in a single clinical center. Retina 2013;33(5):971-4
3.
Green-Simms AE, Ekdawi NS, Bakri SJ. Survey of intravitreal injection techniques among retinal specialists in the United States. Am J Ophthalmol 2011;151(2):329-32
4.
5.
6.
McCannel CA. Meta-analysis of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents: causative organisms and possible prevention strategies. Retina 2011;31(4):654-61 Gonzalez S, Rosenfeld PJ, Stewart MW, et al. Avastin doesn’t blind people, people blind people. Am J Ophthalmol 2012;153(2):196-203; e191 Goldberg RA, Flynn HW Jr, Miller D, et al. Streptococcus endophthalmitis outbreak after intravitreal injection of bevacizumab: one-year outcomes and investigative results. Ophthalmology 2013;120(7):1448-53
7.
Mahajan VB, Elkins KA, Russell SR, et al. Bilateral intravitreal injection of antivascular endothelial growth factor therapy. Retina 2011;31(1):31-5
8.
Davis RP, Schefler AC, Murray TG. Concomitant bilateral intravitreal anti-vegf injections for the treatment of exudative age-related macular degeneration. Clin Ophthalmol 2010;4:703-7
9.
Woo SJ, Han JM, Ahn J, et al. Bilateral same-day intravitreal injections using a single vial and molecular bacterial screening for safety surveillance. Retina 2012;32(4):667-71
10.
Lima LH, Zweifel SA, Engelbert M, et al. Evaluation of safety for bilateral same-day intravitreal injections of antivascular endothelial growth factor therapy. Retina 2009;29(9):1213-17
11.
Bakri SJ, Risco M, Edwards AO, Pulido JS. Bilateral simultaneous intravitreal injections in the office setting. Am J Ophthalmol 2009;148(1):66-9; e61
12.
Gudeman J, Jozwiakowski M, Chollet J, Randell M. Potential risks of pharmacy compounding. Drugs R D 2013;13(1):1-8
13.
Wykoff CC, Flynn HW Jr, Rosenfeld PJ. Prophylaxis for endophthalmitis following intravitreal injection: antisepsis and antibiotics. Am J Ophthalmol 2011;152(5):717-19; e712
Expert Opin. Drug Deliv. (2014) 11(7)
14.
Bhavsar AR, Stockdale CR, Ferris FL III, et al. Update on risk of endophthalmitis after intravitreal drug injections and potential impact of elimination of topical antibiotics. Arch Ophthalmol 2012;130(6):809-10
15.
Cheung CS, Wong AW, Lui A, et al. Incidence of endophthalmitis and use of antibiotic prophylaxis after intravitreal injections. Ophthalmology 2012;119(8):1609-14
Affiliation Daniel L Chao1,2 MD PhD, Ninel Z Gregori†1,2,3 MD, Joyce Khandji4 BA & Raquel Goldhardt1,2 MD † Author for correspondence 1 Miami Veterans Affairs Medical Center, Miami, FL, USA 2 University of Miami Miller School of Medicine, Bascom Palmer Eye Institute, 900 NW 17th St, Miami, FL 33136, USA 3 Bascom Palmer Eye Institute, Miami Veterans Affairs Hospital, 900 NW 17th St, Miami, FL 33136, USA Tel: +1 305 326 6000; Fax: +1 305 326 6417; E-mail: [email protected] 4 Medical student, MD Candidate, Columbia University College of Physicians and Surgeons (JK), 630 W 168th St, New York, NY 10032, USA
993
Safety of bilateral intravitreal injections delivered in a teaching institution Daniel L Chao, Ninel Z Gregori†, Joyce Khandji & Raquel Goldhardt †
Expert Opin. Drug Deliv. Downloaded from informahealthcare.com by Gazi Univ. on 08/20/14 For personal use only.
Bascom Palmer Eye Institute, Miami Veterans Affairs Medical Center, Miami, FL, USA
Intravitreal injection is one of the most common in-office procedures performed in ophthalmic practices. In teaching institutions such as the Veterans Affairs (VA) Hospitals, patient care is delivered by physicians-in-training, while mastering intravitreal injection technique. Infectious endophthalmitis and visual loss are the most feared complications of intravitreal injections, especially in the context of recent outbreaks caused by contaminated compounded medications. Ophthalmologists and ophthalmic educators increasingly face the dilemma of timing as well as balancing the risks and benefits of bilateral treatments required by many patients. In this editorial, we discuss published reports of bilateral injections, summarize our experience with bilateral intravitreal injections in a teaching setting at the Miami VA Hospital and list our recommendations for minimizing the risk of infectious endophthalmitis. Keywords: aflibercept, anti-VEGF, bevacizumab, bilateral intravitreal injection, ophthalmology resident, ranibizumab, teaching institution, Veterans Affairs hospital Expert Opin. Drug Deliv. (2014) 11(7):991-993
Intravitreal injections of anti-VEGF agents are the current first-line treatment for neovascular age-related macular degeneration (AMD), retinal venous occlusive disease, diabetic macular edema and non-AMD-related choroidal neovascularization. As many patients have active disease in both eyes, ophthalmologists increasingly face the dilemma of timing and balancing risks and benefits of bilateral treatments. Bilateral same-day intravitreal injections improve cost-effectiveness and are more convenient for the patient; however, many physicians are hesitant to treat both eyes on the same day for fear of bilateral endophthalmitis and vision loss [1,2]. A 2010 survey revealed that only 46% of retina specialists in the US were performing bilateral simultaneous intravitreal injections [3]. A meta-analysis of endophthalmitis cases after anti-VEGF injections between 2005 and 2009 reported a rate of 0.049% [4]. Recent endophthalmitis outbreaks due to contaminated compounded bevacizumab have heightened physicians’ fears of this devastating complication [5,6]. Should bilateral injections be administered? How safe are bilateral injections delivered by ophthalmology residents and fellows learning intravitreal injection technique? Several studies have reported on the safety of bilateral same-day injections. In a cohort from the University of Iowa, 102 patients received 452 injections, with no cases of endophthalmitis or retinal detachment [7]. In a cohort from Bascom Palmer Eye Institute, 127 patients received 1322 bilateral same-day injections and developed no serious ocular or systemic adverse events [8]. In a cohort from Korea, 135 patients received 574 bilateral bevacizumab, ranibizumab or triamcinolone injections drawn from the same vial and reported no cases of endophthalmitis or retinal detachment [9]. In a cohort from New York City, 367 patients who received 1552 injections had two cases of culture proven unilateral endophthalmitis 10.1517/17425247.2014.909806 © 2014 Informa UK, Ltd. ISSN 1742-5247, e-ISSN 1744-7593 All rights reserved: reproduction in whole or in part not permitted
991
Expert Opin. Drug Deliv. Downloaded from informahealthcare.com by Gazi Univ. on 08/20/14 For personal use only.
D. L. Chao et al.
(0.065%), and one incidence of unilateral ocular inflammation (0.033%) [10]. In a cohort from Mayo Clinic, 35 patients who received 208 bilateral injections had one case of unilateral culture-negative endophthalmitis [11]. Two publications from the Middle East reported bilateral endophthalmitis after bilateral intravitreal bevacizumab injections. One publication reported two patients with bilateral Staphylococcus epidermidis endophthalmitis [1], and the other listed one patient with bilateral culture-negative endophthalmitis [2]. We commonly deliver bilateral injections in our teaching retina clinics at the Miami Veterans Affairs (VA) Hospital. Our retina clinics are conducted by retina specialists (n = 2) with first-year residents (n = 7 per year) and retina fellows (n = 4 per year). All injections are delivered by the physicians-in-training under direct supervision of the retina specialists. The physicians-in-training are taught a standard aseptic technique for drawing up and administering the medications. All anesthetic preparations are performed by trained technicians (n = 7) according to a standard protocol. Between October 2007 and May 2013, a total of 660 same-day bilateral and 3570 unilateral anti-VEGF injections were delivered, for a grand total of 4230 injections. The two eyes were prepared and injected sequentially on the same day without reusing any instruments or medications. Mean follow-up was 26 months (range, 1 -- 66 months). Bilateral injections were 282 bevacizumab, 281 ranibizumab and 97 aflibercept. The mean number of bilateral injections was 8.4 per patient and 4.2 per eye (range, 1 -- 31 per eye). Out of 282 bilateral bevacizumab injections, 134 doses were purchased from a compounding pharmacy prior to September 2011. After this date, according to the VA policy all bevacizumab injections were drawn up by the physicians from a new commercially available bevacizumab vial for each eye immediately prior to the injection. Of the 660 bilateral injections, 438 were delivered without the use of topical antibiotics, which have not been used in our clinics since August 2011. No infectious endophthalmitis cases were encountered with either compounded or non-compounded bevacizumab. There were no cases of endophthalmitis, uveitis or retinal detachment in unilateral or bilateral patients. The only ocular complications encountered were two corneal abrasions in the right eye of two bilateral patients. These data were collected after obtaining Miami VA Institutional Review Board approval. Recent well-publicized infectious outbreaks from compounded ophthalmic and non-ophthalmic medications, including bevacizumab, methylprednisolone and betamethasone, have resulted in significant morbidity and mortality to patients [5,6,12]. As a result, compounding pharmacies have come under intense scrutiny, and in September 2011 VA Hospitals discontinued the use of compounded bevacizumab. If a compounding pharmacy is used, providers need to ensure that the pharmacy adheres to the US Pharmacopeia, chapter 797 sterile preparation guidelines and performs sterility testing (which is actually not required by the USP 797 but is the last line of defense against contamination) [5]. It is also 992
prudent to use vials from different medication lots for each eye, in order to mitigate the risk of giving potentially contaminated vials or aliquots in both eyes. Another crucial factor in assuring patient safety is utilization of meticulous technique for ocular antisepsis, anesthesia and injection of medication. It is prudent to establish a detailed intravitreal injection protocol, which is followed by all individuals who prepare the eye and administer the injections. Our technicians’ competency is certified and maintained via periodic checks, and the residents and fellows are educated and observed by the retina specialists. We recommend performing bilateral injections sequentially, treating each eye as belonging to a separate patient, and not reusing any equipment or medications. Povidoneiodine 5% is applied to the ocular surface and the skin and lashes, always prior to anesthetic gel [13]. Sterile speculum and sterile caliper are used, although a drape and sterile gloves are not, in line with common practices by retina specialists in the US [3]. Topical antibiotics are not used since multiple publications have shown an increase in microorganism resistance rates, changes in commensal ocular flora and the same or higher endophthalmitis rates with the use of antibiotics [14,15]. It is also important to consider and manage other patient factors, such as the presence of nasolacrimal duct obstruction, significant blepharitis and active infectious or inflammatory surface disease, prior to the injection. In conclusion, published reports show that bilateral sameday injections can be delivered without major safety signals. In our VAs Hospital clinics, the injections are well tolerated by patients and resulted in no serious ocular complications, specifically no bilateral infectious or noninfectious endophthalmitis or retinal detachment. Therefore, we suggest that bilateral intravitreal injections can be delivered safely on the same day by physicians-in-training with support of ancillary personnel and supervision from retina specialists via a standard aseptic protocol. Our practice may provide a practical template for instituting bilateral intravitreal injection protocols within the VA Healthcare system or other teaching institutions.
Expert opinion Retrospective nature and relatively small number of injections are the main limitations of published literature and our experience. The goal of research in the area of intravitreal drug delivery is to assure patient comfort and safety, especially in a teaching setting. For informed consent purposes, it is helpful to know the complication rates of injections delivered by experienced ophthalmologists versus those in training. While patient safety is at the forefront of patient care in any institution, it is especially imperative to assure excellent patient care in a teaching setting. Therefore, additional quality surveillance should be performed demonstrating that with proper direction and supervision of trainees, safe unilateral or bilateral intravitreal treatments can be delivered. Of course, the
Expert Opin. Drug Deliv. (2014) 11(7)
Safety of bilateral intravitreal injections delivered in a teaching institution
Expert Opin. Drug Deliv. Downloaded from informahealthcare.com by Gazi Univ. on 08/20/14 For personal use only.
main challenge of showing bilateral injection safety is the mere number of injections needed to study. Reported mean rate of endophthalmitis is 0.049%, that is, 5 in 10,000 with unilateral injections [4]. If the two eyes are not correlated at all, the chance of both eyes getting endophthalmitis is 5/10,000 times 5/10,000, which is 5 in 100 million. If the two eyes are perfectly correlated, then the chance of both eyes getting it is 5 in 10,000. If there is some correlation, the chance of both eyes getting it is somewhere between 5 in 10,000 and 5 in 100 million. Pulling data from multiple teaching institutions would allow generating injection numbers required by these power calculations. Further studies in the area of ophthalmic education are needed to assure
adequate training of future providers without compromise of patient safety and quality of eye care delivered by the ophthalmic trainees.
Declaration of interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. This manuscript has not been presented at any meeting.
Bibliography 1.
Tabatabaii A, Ahmadraji A, Khodabande A, Mansouri M. Acute bilateral endophthalmitis following bilateral intravitreal bevacizumab (avastin) injection. Middle East Afr J Ophthalmol 2013;20(1):87-8
2.
Falavarjani KG, Modarres M, Hashemi M, et al. Incidence of acute endophthalmitis after intravitreal bevacizumab injection in a single clinical center. Retina 2013;33(5):971-4
3.
Green-Simms AE, Ekdawi NS, Bakri SJ. Survey of intravitreal injection techniques among retinal specialists in the United States. Am J Ophthalmol 2011;151(2):329-32
4.
5.
6.
McCannel CA. Meta-analysis of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents: causative organisms and possible prevention strategies. Retina 2011;31(4):654-61 Gonzalez S, Rosenfeld PJ, Stewart MW, et al. Avastin doesn’t blind people, people blind people. Am J Ophthalmol 2012;153(2):196-203; e191 Goldberg RA, Flynn HW Jr, Miller D, et al. Streptococcus endophthalmitis outbreak after intravitreal injection of bevacizumab: one-year outcomes and investigative results. Ophthalmology 2013;120(7):1448-53
7.
Mahajan VB, Elkins KA, Russell SR, et al. Bilateral intravitreal injection of antivascular endothelial growth factor therapy. Retina 2011;31(1):31-5
8.
Davis RP, Schefler AC, Murray TG. Concomitant bilateral intravitreal anti-vegf injections for the treatment of exudative age-related macular degeneration. Clin Ophthalmol 2010;4:703-7
9.
Woo SJ, Han JM, Ahn J, et al. Bilateral same-day intravitreal injections using a single vial and molecular bacterial screening for safety surveillance. Retina 2012;32(4):667-71
10.
Lima LH, Zweifel SA, Engelbert M, et al. Evaluation of safety for bilateral same-day intravitreal injections of antivascular endothelial growth factor therapy. Retina 2009;29(9):1213-17
11.
Bakri SJ, Risco M, Edwards AO, Pulido JS. Bilateral simultaneous intravitreal injections in the office setting. Am J Ophthalmol 2009;148(1):66-9; e61
12.
Gudeman J, Jozwiakowski M, Chollet J, Randell M. Potential risks of pharmacy compounding. Drugs R D 2013;13(1):1-8
13.
Wykoff CC, Flynn HW Jr, Rosenfeld PJ. Prophylaxis for endophthalmitis following intravitreal injection: antisepsis and antibiotics. Am J Ophthalmol 2011;152(5):717-19; e712
Expert Opin. Drug Deliv. (2014) 11(7)
14.
Bhavsar AR, Stockdale CR, Ferris FL III, et al. Update on risk of endophthalmitis after intravitreal drug injections and potential impact of elimination of topical antibiotics. Arch Ophthalmol 2012;130(6):809-10
15.
Cheung CS, Wong AW, Lui A, et al. Incidence of endophthalmitis and use of antibiotic prophylaxis after intravitreal injections. Ophthalmology 2012;119(8):1609-14
Affiliation Daniel L Chao1,2 MD PhD, Ninel Z Gregori†1,2,3 MD, Joyce Khandji4 BA & Raquel Goldhardt1,2 MD † Author for correspondence 1 Miami Veterans Affairs Medical Center, Miami, FL, USA 2 University of Miami Miller School of Medicine, Bascom Palmer Eye Institute, 900 NW 17th St, Miami, FL 33136, USA 3 Bascom Palmer Eye Institute, Miami Veterans Affairs Hospital, 900 NW 17th St, Miami, FL 33136, USA Tel: +1 305 326 6000; Fax: +1 305 326 6417; E-mail: [email protected] 4 Medical student, MD Candidate, Columbia University College of Physicians and Surgeons (JK), 630 W 168th St, New York, NY 10032, USA
993
