Editorial Spotlight | Jul/Aug 2016

Factors Influencing Adoption: Intracameral Antibiotics and Steroids

Practice patterns for intracameral drug delivery vary from country to country.

Cataract surgery is the most commonly performed surgical procedure in the world, estimated at more than 20 to 25 million in number annually.1 With the aging of the population, the volume will continue to rise.2 Although there have been advances in technology, techniques, and training to increase the safety and efficacy of cataract surgery, there has not been a commensurate evolution in the prophylaxis of infectious postoperative endophthalmitis and the treatment of postoperative inflammation.


• Interest in and acceptance of intracameral, transzonular, and pars plana alternatives to topical drops has grown, but adoption has been slow in some areas.

• Concerns with use of intracameral antibiotics and steroids are mitigated in some regions by national regulatory and professional society support of alternative routes of drug delivery.

The incidence of infectious postoperative endophthalmitis is low, ranging from 0.04% to 0.36%,3,4 but, because of its devastating sight-threatening potential, constant vigilance and motivation are needed to further minimize its occurrence. Additionally, postoperative cystoid macular edema (CME) persists as a significant cause of suboptimal visual recovery, and this is particularly important given the increasing population of diabetic patients.5

Globally, there has been growing interest in and acceptance of intracameral, transzonular, and pars plana alternatives to topical drops in the treatment of postoperative cataract patients.6,7 However, adoption of these so-called dropless approaches has been slow in some areas. This article reviews the roadblocks to the acceptance of intracameral antibiotics and steroids in the cataract surgery setting.


Practice patterns for antibiotic prophylaxis vary from country to country. In the United States, the most common method of infectious postoperative endophthalmitis prophylaxis is perioperative topical antibiotics, usually consisting of a fourth-generation fluoroquinolone prescribed 1 to 3 days preoperatively and resumed immediately postoperatively for at least 1 week.3,6

Practitioners in the United States, Canada, Europe, Latin America, South America, Mexico, Australia, Asia, and Africa responded to a 2014 American Society of Cataract and Refractive Surgery (ASCRS) member survey. Fifteen percent of ASCRS members (n=1,147) responded. The survey found that, at the conclusion of surgery, 69% of respondents reported instilling a topical antibiotic, and 36% said they were injecting an intracameral antibiotic, up from 14% in the 2007 ASCRS member survey. The percentages totaled more than 100% because some surgeons used multiple methods of drug delivery. Among US respondents only, 30% said they were injecting an intracameral antibiotic at the end of surgery, in contrast with 70% of European respondents.6

One factor that may help explain this difference is the availability of intracameral cefuroxime powder 50 mg (Aprokam/Aprok/Prokam; Théa), which was approved by the European Medicines Agency in 2012 and is available in 24 European countries and Canada but not the United States. This single-dose unit of cefuroxime powder is reconstituted in 5 mL of sodium chloride 0.9%; 0.1 mL (cefuroxime 1.0 mg) is injected into the anterior chamber at the end of surgery.

Among US respondents only, 53% said they believe the US FDA should approve Aprokam based on European clinical trials and usage. In 2014, 75% of respondents stated that it was important to have a commercially available antibiotic approved for intracameral use, compared with 54% in 2007; 50% of those not using this route expressed concern about the risks of non–commercially prepared antibiotics, including the risks of mixing or compounding errors leading to toxic anterior segment syndrome (TASS) and contamination.


The question of how best to deliver perioperative medications has become increasingly relevant, as there is more strong evidence supporting direct intracameral antibiotic injections than any other method of antibiotic prophylaxis.3,8-11 More than 1.3 million units of Aprokam have been used worldwide without significant incidence of reported adverse events.6 Globally, there appears to be consensus on the importance of direct intracameral antibiotics, but the major barrier to its use, particularly in the United States, is the lack of a commercially available formulation.

Although topical antibiotics can reach intraocular therapeutic levels when frequently applied, only intracameral antibiotics achieve suprathreshold antibiotic levels for an extended period.12 Intracameral antibiotics reach concentrations several times higher than the concentration needed to kill 90% of most bacterial isolates.13-16 This is in contrast to subconjunctival and topical antibiotics, which may not produce high enough aqueous concentrations to kill the most common causative organisms, coagulase-negative staphylococci.11,13 Additionally, intracameral injection achieves an instantaneously high concentration of antibiotic in the anterior chamber.

The strong evidence in support of direct intracameral antibiotic at the conclusion of surgery8,10 also raises the question of whether perioperative topical antibiotics can be eliminated. Both the landmark 2007 European Society of Cataract and Refractive Surgeons (ESCRS)10 endophthalmitis study and a 2013 Kaiser Permanente study17 found borderline additional effectiveness when topical antibiotics were combined with intracameral antibiotics at the conclusion of surgery.

The 2007 ESCRS study10 found that the use of direct intracameral cefuroxime at the conclusion of surgery reduced the risk of infectious postoperative endophthalmitis fivefold (from 0.34% to 0.07%). The results were so striking that recruitment of additional patients was stopped, as the study’s data monitoring committee advised that it would be unethical to withhold the use of prophylactic intracameral cefuroxime. To date, this is the only large (16,603 patients) prospective, multicenter, randomized controlled trial to evaluate direct intracameral antibiotic injection. This study determined that the use of topical antibiotics perioperatively did not have a significant impact on the rate of infectious postoperative endophthalmitis when intracameral cefuroxime was used.

Comparable results were found in a similarly large study by Shorstein et al17 in 2013. Shorstein’s group at Kaiser Permanente in Northern California reviewed 16,624 cataract surgeries over three time periods based on increasing adoption of intracameral injections at the end of surgery. (Cefuroxime was the first-line choice; if the patient was allergic to this agent, then moxifloxacin or vancomycin was used.) This retrospective time-trend study from 2007 through 2011 found a 22-fold decline in infectious postoperative endophthalmitis with the increasing use, from 11% to 100%, of intracameral antibiotics. The authors also documented a low incidence of endophthalmitis (0.049%) with use of intracameral antibiotics alone in the absence of preoperative or postoperative antibiotic drops.8 This was similar to the 0.045% rate reported in a study in Sweden, in which 95% of 225,471 patients received intracameral cefuroxime without a postoperative topical antibiotic.17

A study in Utah18 found that intracameral moxifloxacin without postoperative topical antibiotics after cataract surgery was safe and effective. Out of 222 eyes, 131 received a topical antibiotic and 91 received an intracameral antibiotic only. No case of endophthalmitis occurred in either group.

Most recently, Herrinton et al19 and the Kaiser Permanente group published a large retrospective, observational, longitudinal cohort study to examine the effects of topical and intracameral antibiotics on the risk of infectious postoperative endophthalmitis. They identified 215 cases of infectious postoperative endophthalmitis out of 315,246 procedures (0.07%) from 2005 to 2012. In this study, intracameral antibiotics (cefuroxime or moxifloxacin) were more effective than topical antibiotics alone (0.04% vs 0.07%), and topical antibiotics were not shown to add to the effectiveness of an intracameral regimen. Because of this, the authors are considering the exclusive use of intracameral antibiotic and elimination of topical antibiotics.

On top of minimizing the incidence of infectious postoperative endophthalmitis, intracameral antibiotic use may be advantageous in other ways: reduced eye drop burden on the patient, leading to quality of life improvement and reduction of self-inflicted contamination and injury; decreased cost for postoperative eye drops; decreased antibiotic resistance resulting from improper usage; and decreased ocular surface toxicity.


Although intracameral cefuroxime is commercially available in Europe and recommended by the ESCRS and by French, Scottish, and Canadian practice guidelines, practice patterns still vary throughout Europe.20 A 2013 survey of 479 surgeons in the United Kingdom, Spain, Sweden, Italy, Germany, Netherlands, Belgium, France, and Poland found no uniformity of antibiotic product use prior to, during, or after surgery and no standardization in regard to antiinflammatory drugs and antisepsis immediately prior to incision.21

Sweden has the longest experience with intracameral cefuroxime; use of intracameral without additional perioperative topical antibiotic has become standard practice there.22 Similarly, Spain now almost universally uses intracameral cefuroxime.21 In contrast, in Germany intracameral cefuroxime is injected in less than half of cases, and in the Netherlands its use is reserved for high-risk patients such as those with diabetes or history of eye infection.20,21 Although the limits of this study included its survey method and its sponsorship by Théa (the manufacturer of Aprokam), it still provides valuable information on attitudes and highlights the variability of practice patterns among countries, even those with access to a European Medicines Agency–approved, single-use intracameral agent.

According to a 2009 member survey of the United Kingdom and Ireland Society of Cataract and Refractive Surgeons (UKISCRS), 55% of respondents used intracameral cefuroxime. Almost half of these injecting surgeons reported switching to this method in response to the landmark ESCRS 2007 study.23 Like the American Academy of Ophthalmology (AAO), the Royal College of Ophthalmologists (RCO) leaves details of antibiotic use to the surgeon’s discretion.24

A 2007 Australian survey found just 1% of surgeons using intracameral antibiotics; 80% used preoperative topical antibiotics and 95% postoperative topical antibiotics.25 By 2012, with a commercial preparation of intracameral cefazolin available, a massive change in practice pattern occurred, with 84.4% of surveyed surgeons reporting use of intracameral antibiotics.26


Geographic differences in microorganism distributions and priorities of antibiotic prophylaxis can also affect surgeon practices. In 2013, a retrospective survey cohort study of 19 clinics in Japan showed that intracameral moxifloxacin decreased the risk of infectious postoperative endophthalmitis threefold, and, in more than 18,000 cases, a dose of 500 µg/mL or less did not result in severe complications such as TASS or corneal endothelial cell loss.27 Prior to this study, in a 2012 survey, only 1% of surgeons in Japan used intracameral administration of antibiotic.28 Moxifloxacin was of particular interest in Japan because of its effectiveness against Enterococcus faecalis, which is associated with a poor prognosis and accounts for about 20% of cases of infectious postoperative endophthalmitis in Japan. This is in contrast to the United States and Europe, where coagulase-negative staphylococci are most prevalent.18

US surgeons frequently use fourth-generation fluoroquinolones for prophylaxis, whereas, in France, these are reserved for the treatment of known severe infection.20 In a similar way, the US Centers for Disease Control and the AAO discourage the prophylactic use of vancomycin, in order to preserve its effectiveness against methicillin-resistant Staphylococcus aureus.

Commercial cefuroxime is largely unavailable outside Europe. Aravind Eye Hospital has an affiliated pharmaceutical company, Aurolab, which manufactures unit packages of 0.1 mL moxifloxacin 0.5% (Promox). In addition to Aurolab, since 2013, surgeons in India have had access to 4 Quin PFS (Entod Pharmaceuticals), a commercially available formulation of intracameral moxifloxacin (0.5 mL prefilled moxifloxacin 0.5% syringe).


In the United States, the absence of commercially available intracameral cefuroxime favors the use of moxifloxacin 0.5% ophthalmic solution (Vigamox; Alcon), as this commercially available topical agent does not require dilution or compounding; it is supplied as a sterile isotonic solution, with pH near 6.8 and osmolality of 290 mOsm/kg, making it compatible with intraocular tissues.29 Moxifloxacin is also self-preserved, containing no benzalkonium chloride or other preservatives known to have toxic effects on the corneal epithelium. Although Vigamox can be safely used straight out of the bottle for intracameral delivery, accidental substitution of Vigamox with Moxeza (moxifloxacin 0.5% ophthalmic solution; Alcon) has been associated with TASS due to differences in inactive ingredients.30

Recent problems have increased concerns about use of compounded products. In Florida, an outbreak of endophthalmitis occurred among patients who had injections of intravitreal bevacizumab prepared in a compounding pharmacy.31 A Turkish hospital had eight cases of Fusarium endophthalmitis following use of intracameral cefuroxime prepared in the operating room.32 Another Turkish study found 17 patients with TASS linked to cefuroxime; all patients responded to intensive topical corticosteroids.33

An incorrect dilution at a Finnish hospital resulted in a series of 16 patients receiving intracameral cefuroxime at 50 to 100 times the recommended dose of 1 mg/0.1 mL. Eight of the 16 eyes experienced severe, permanent visual loss.34 There are two case reports of anaphylactic reaction following the administration of intracameral cefuroxime during cataract surgery.35,36 Both patients had a known penicillin allergy, and cross-reactivity with the cephalosporin cefuroxime occurred.

Wong et al37 reported an intracameral cefuroxime compounding error, in which 9 mg of cefuroxime was administered to 13 eyes of 11 patients. This resulted in acute macular edema in six eyes, which resolved within 1 week without further adverse consequences.

Recently, there was a report of 11 eyes with hemorrhagic occlusive retinal vasculitis possibly associated with intracameral vancomycin use after cataract surgery.38 Nicholson et al39 were the first to report four eyes in two patients with severe bilateral ischemic retinal vasculitis after rapidly sequential and otherwise uneventful phacoemulsfication. Authors of both papers suggested that a delayed immune reaction to vancomycin was the cause. The ASCRS Cataract Clinical Committee and the American Society of Retina Specialists (ASRS) have developed a joint task force and registry to further explore this rare but potentially devastating condition.

Arguments that resistance can be bred by the routine prophylactic use of intracameral cefuroxime or moxifloxacin may be countered by noting that a single dose of highly concentrated drug is delivered into a confined space. By contrast, with topical therapy, there are the variables of corneal absorption, aqueous concentration, and less reliable dosing of topical antibiotics in the hands of patients.40 Intracameral vancomycin is currently reserved for about 1% of patients who are allergic to penicillin, cephalosporin, and a fluoroquinolone.19,41

The preferred antibiotic for intracameral use tends to vary according to geographic region and perspective, as described earlier. The Kaiser Permanente group uses compounded cefuroxime as its first-line agent, followed by moxifloxacin and vancomycin to accommodate patient allergy contraindications. This group did not find a difference in effectiveness between cefuroxime and moxifloxacin in 315,246 cases.19

The anterior chamber is able to clear some microorganisms, but, when they move posteriorly, they tend to grow in the vitreous, which may provide a protective matrix; a more posterior delivery of antibiotic might address this. One concern with the transzonular injection approach is the possibility of disrupting the anterior hyaloid face, with resulting retinal tears or detachments. From the patient’s perspective, intracameral delivery of a corticosteroid suspension, such as triamcinolone, can cause a few days to weeks of blurring and floaters from the deposits, but advances in formulation are addressing this. With the pars plana approach, there is a track record of safety and efficacy for the treatment of macular degeneration, infectious postoperative endophthalmitis, and other diseases. Intracameral, transzonular, and pars plana approaches to prophylaxis are now available with formulations provided by compounding companies such as Imprimis Pharmaceuticals and Ocular Science; these warrant further clinical study.


Intracameral delivery of corticosteroids in cataract surgery is not new. In 2005, Gills and Gills42 analyzed 608 eyes and reported using up to 3 mg of intracameral triamcinolone with safety and success in the reduction of postoperative inflammation. This approach obviated the need for postoperative corticosteroid drops for patients receiving a dose of 2.8 mg or more. At doses of 1.8 mg or higher, no CME occurred. These practitioners delivered the triamcinolone through the anterior chamber but facilitated flow through the zonules by aiming the cannula posteriorly.42

In 2009, Chang et al43 reported that 0.4 mg intracameral dexamethasone was safe and efficacious when given at the end of surgery in conjunction with standard postoperative corticosteroid drops; this retrospective study included 91 patients with and without glaucoma who were undergoing phacoemulsification. The authors did not find a significant increase in postoperative IOP in dexamethasone-treated glaucoma patients.

When injected into the anterior chamber, neither dexamethasone nor triamcinolone acetonide has been associated with ocular hypertension.43,44 This is likely due to the rapid turnover of aqueous volume and the short half-life of intraocular dexamethasone. By contrast, ocular hypertension has been noted when triamcinolone acetonide is injected sub–Tenon capsule or intravitreally, yielding a sustained duration of action.43,45,46 Studies in pediatric cataract surgery patients have not shown an increased risk for glaucoma with the use of intracameral dexamethasone or triamcinolone acetonide.47-49


Major concerns with the use of intracameral drug delivery for cataract surgery remain include the lack of a commercially available and approved antibiotic for intracameral use in some markets; the lack of national regulatory and professional society support of alternative routes of drug delivery; reports of delayed adverse sequelae, such as hemorrhagic occlusive retinal vasculitis, possibly associated with intracameral vancomycin; the risk of disrupting the anterior hyaloid face, with resultant retinal tears and or detachments; and ocular hypertension resulting from direct injection of a steroid. Additionally, the potential for blur and floaters from steroid deposits after surgery is concerning in these times of high patient expectations. These concerns are mitigated in some regions by national regulatory and professional society support of alternative routes of drug delivery.

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21. Behndig A, Cochener-Lamard B, Güell J, et al. Surgical, antiseptic, and antibiotic practice in cataract surgery: results from the European Observatory in 2013. J Cataract Refract Surg. 2015;41:2635-2643.

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23. Gore DM, Angunawela RI, Little BC. United Kingdom survey of antibiotic prophylaxis practice after publication of the ESCRS Endophthalmitis Study. J Cataract Refract Surg. 2009;35:770-773.

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27. Matsuura K, Miyoshi T, Suto C, et al. Efficacy and safety of prophylactic intracameral moxifloxacin injection in Japan. J Cataract Refract Surg. 2013;39:1702-1706.

28. Matsuura K, Suto C, Inoue Y, et al. A Japanese survey of perioperative antibiotic prophlyaxis in cataract surgery. Asia Pac J Ophthalmol. 2012;1:283-286.

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31. Goldberg RA, Flynn HW Jr, Isom RF, et al. An outbreak of streptococcus endophthalmitis after intravitreal injection of bevacizumab. Am J Ophthalmol. 2012;153:204-208.

32. Cakir M, Imamoglu S, Cekic O, et al. An outbreak of early-onset endophthalmitis caused by Fusarium species following cataract surgery. Curr Eye Res. 2009;34:988-995.

33. Cakir B, Celik E, Aksoy NÖ, et al. Toxic anterior segment syndrome after uncomplicated cataract surgery possibly associated with intracameral use of cefuroxime. Clin Ophthalmol. 2015;9:493-497.

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38. Witkin AJ, Shah AR, Engstrom RE, et al. Postoperative hemorrhagic occlusive retinal vasculitis: expanding the clinical spectrum and possible association with vancomycin. Ophthalmology. 2015;122:1438-1451.

39. Nicholson LB, Kim BT, Jardón J, et al. Severe bilateral ischemic retinal vasculitis following cataract surgery. Ophthalmic Surg Lasers Imaging Retina. 2014;45:338-342.

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42. Gills JP, Gills P. Effect of intracameral triamcinolone to control inflammation following cataract surgery. J Cataract Refract Surg. 2005(31):1670-1671.

43. Chang DT, Herceg MC, Bilonick RA, et al. Intracameral dexamethasone reduces inflammation on the first postoperative day after cataract surgery in eyes with and without glaucoma. Clin Ophthalmol. 2009;3:345-355.

44. Karalezli A, Borazan M, Akova YA. Intracameral triamcinolone acetonide to control postoperative inflammation following cataract surgery with phacoemulsification. Acta Ophthalmol. 2008;86:183-187.

45. Paganelli F, Cardillo JA, Melo LA Jr, et al. A single intraoperative sub-Tenon’s capsule triamcinolone injection for the treatment of post-cataract surgery inflammation. Ophthalmology. 2004;111:2102-2108.

46. Kiddee W, Trope GE, Sheng L, et al. Intraocular pressure monitoring post intravitreal steroids: a systematic review. Surv Ophthalmol. 2013;58:291-310.

47. Dixit NV, Shah SK, Vasavada V, et al. Outcomes of cataract surgery and intraocular lens implantation with and without intracameral triamcinolone in pediatric eyes. J Cataract Refract Surg. 2010;36:1494-1498.

48. Mataftsi A, Dabbagh A, Moore W, et al. Evaluation of whether intracameral dexamethasone predisposes to glaucoma after pediatric cataract surgery. J Cataract Refract Surg. 2012;38:1719-1723.

49. Cleary CA, Lanigan B, O’Keeffe M. Intracameral triamcinolone acetonide after pediatric cataract surgery.J Cataract Refract Surg. 2010;36:1676-1681.

Francis S. Mah, MD
• Director of Cornea and External Disease and Codirector of Refractive Surgery, Scripps Clinic Medical Group, La Jolla, California
• Financial disclosure: Alcon, Allergan, Bausch + Lomb, Ocular Science, Ocular Therapeutix, PolyActiva, Shire

Michelle K. Rhee, MD
• Assistant Professor of Ophthalmology and Codirector, Refractive Surgery Service, Icahn School of Medicine, Mount Sinai, New York
• Financial interest: None acknowledged