Prophylaxis of Endophthalmitis Associated with Intravitreal Injections
Endophthalmitis remains a rare but potentially vision-threatening complication of intravitreal injections. The reported rates of endophthalmitis following a single intravitreal injection vary widely in the literature but are generally in the range of 0.02% to 0.2%,1 which is roughly comparable to the reported rates of endophthalmitis reported after cataract surgery.2 This is notable because, while cataract surgery is generally performed only once per eye, most patients with neovascular age-related macular degeneration (AMD) receive a series of injections so the cumulative per-patient rate of endophthalmitis is substantially higher. For example, the rate of endophthalmitis in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) was 0.93% per patient.3
It is probably impracticable to reduce the rate of endophthalmitis to zero.4 There are no major published randomized clinical trials (RCTs) that specifically address the question of endophthalmitis prophylaxis associated with intravitreal injections, although an expert committee published guidelines in 20045 and revised them in 2014.6 These guidelines include deferring injections in patients with active external infections, the use of topical povidone-iodine, and reducing exposure to aerosolized droplets containing oral contaminants. However, many questions remain unanswered, including the roles of eyelid speculums, face masks, and topical antibiotics. Practice patterns are highly variable, within and outside the United States.7
Eyelid speculums have been used traditionally but there is a growing subset of ophthalmologists achieving good outcomes without them. For example, one series of 10,164 consecutive injections performed without lid speculums reported an endophthalmitis rate of 0.03%.8 The use of face masks is logical but there are no validated clinical series reporting a reduction in endophthalmitis rates associated with their use. The use of topical antibiotics may seem intuitive, but there is very little evidence in support of their use. Most series (including CATT) that have compared antibiotic-treated and non-antibiotic-treated eyes have reported no significant differences in endophthalmitis rates.9,10 In fact, there is evidence suggesting that antibiotics may increase the endophthalmitis rates, perhaps by unfavorably altering conjunctival flora.
The approaches to prophylaxis with respect to endophthalmitis associated with intravitreal injections continue to evolve. Topical antibiotics and eyelid speculums are used less commonly, but the use of povidone iodine is important. It appears unlikely that RCTs will be conducted in the future to answer all questions related to potential endophthalmitis risk factors. Continued clinical experience with intravitreal injections may lead to further consensus.
1. Fileta JB, Scott IU, Flynn HW Jr. Meta-analysis of infectious endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. Ophthalmic Surg Lasers Imaging Retina. 2014;45(2):143-149.
2. Vaziri K, Schwartz SG, Kishor K, Flynn HW Jr. Endophthalmitis: state of the art. Clin Ophthalmol. 2015;9:95-108.
3. Meredith TA, McCannel CA, Barr C, et al. Postinjection endophthalmitis in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Ophthalmology. 2015;122(4):817-821.
4. Schachat AP, Rosenfeld PJ, Liesegang TJ, Stewart MW. Endophthalmitis is not a “never event.” Ophthalmology. 2012;119(8):1507-1508.
5. Aiello LP, Brucker AJ, Chang S, et al. Evolving guidelines for intravitreous injections. Retina. 2004;24(5 Suppl):S3-S19.
6. Avery RL, Bakri SJ, Blumenkranz MS, et al. Intravitreal injection technique and monitoring: updated guidelines of an expert panel. Retina. 2014;34(Suppl 12):S1-S18.
7. Schwartz SG, Grzybowski A, Flynn HW Jr. Antibiotic prophylaxis: different practice patterns within and outside the United States. Clin Ophthalmol. 2016;10:251-256.
8. Fineman MS, Hsu J, Spirn MJ, Kaiser RS. Bimanual assisted eyelid retraction technique for intravitreal injections. Retina. 2013;33(9):1968-1970.
9. Schwartz SG, Flynn HW, Grzybowski A. Controversies in topical antibiotics use with intravitreal injections. Curr Pharm Des. 2015;21(32):4703-4706.
10. Gregori NZ, Flynn HW Jr, Schwartz SG, et al. Current infectious endophthalmitis rates after intravitreal injections of anti-vascular endothelial growth factor agents and outcomes of treatment. Ophthalmic Surg Lasers Imaging Retina. 2015;46(6):643-648.
About our author(s):
Stephen G. Schwartz, MD, MBA, Associate Professor of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, and Medical Director, Bascom Palmer Eye Institute at Naples, Naples, FL
Harry W. Flynn Jr., MD, Professor of Ophthalmology, The J. Donald M. Gass Distinguished Chair in Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami