Postoperative endophthalmitis is a devastating complication of intraocular surgery, particularly in the posttrauma setting, and as a result, many ophthalmologists have adopted the off-label practice of intracameral injection of either Food and Drug Administration (FDA)-approved topical-formulation moxifloxacin drugs or compounded moxifloxacin drug products for endophthalmitis prophylaxis at the conclusion of surgery. Multiple authors have endorsed the safety of intracameral moxifloxacin in routine cataract surgery, although the FDA, using the Adverse Event Reporting System database, identified 29 cases of toxic anterior segment syndrome (TASS) associated with intraocular administration of drugs containing moxifloxacin as of December 19, 2019.1–5 To our knowledge, there are no cases in the literature describing a potential association between TASS and the practice of using undiluted 0.5% topical-formulation moxifloxacin for intrastromal hydration of corneal wounds following intraocular surgery, particularly for traumatic ocular injuries. The use of compounded moxifloxacin 0.1% for intrastromal hydration of clear corneal incisions following routine cataract surgery has been reported in the literature, and these surgeons reported no complications observed with this practice.6,7 We report 2 consecutive cases in which the surgeon used undiluted 0.5% preservative-free topical-formulation moxifloxacin to perform intrastromal hydration of corneal wounds in addition to intracameral injection following anterior segment surgery. Both patients developed moxifloxacin-induced toxic anterior segment syndrome and corneal decompensation.
This case report adhered to the tenets of the Declaration of Helsinki and was compliant with the Health Insurance Portability and Accountability Act of 1996. Both patients provided written consent for the publishing of this case, including photographs and clinical and imaging details.
The first case involves a 42-year-old man who was struck in the right eye with a high-velocity 1 mm metallic foreign body while hammering with a brass chisel against steel 7 days prior to presentation. The cornea was clear on initial examination. The metallic foreign body was embedded into the anterior lens capsule with early traumatic cataract formation (Figure 1, A). Corrected distance visual acuity was 20/70 in the right eye. The corneal entry wound was found to be self-sealed, and the patient was taken to the operating room for removal of the foreign body and phacoemulsification with intraocular lens placement. Following a gentle mechanical synechiolysis with a 27-gauge cannula, a continuous curvilinear capsulorhexis was completed to encompass the foreign body. The foreign body was then removed using Dutch Ophthalmic Research Center 20-gauge serrated jaw forceps through the main keratome incision. Phacoemulsification proceeded in usual fashion using a stop-and-chop technique with minimal cumulative dispersed energy, followed by placement of a single-piece intraocular lens. At the conclusion of the case, approximately 0.2 mL of undiluted 0.5% preservative-free moxifloxacin was instilled into the anterior chamber for endophthalmitis prophylaxis, and approximately 0.1 mL was injected intrastromally to hydrate the clear corneal incisions until they were watertight (Figure 1, B). He returned on postoperative day 4 with severe, diffuse corneal edema (Figure 2). At his 1 month postoperative visit, his corrected distance visual acuity in the affected eye was 20/400 with a pachymetry of 1055 μm. He was managed conservatively with prednisolone acetate and hypertonic saline drops without improvement of the corneal edema. He underwent Descemet stripping automated endothelial keratoplasty 3 months from the time of cataract surgery, and 2 months later, his corrected distance visual acuity improved to 20/50 in the affected eye.
The second case involves a 60-year-old man who sustained an extensive corneoscleral laceration of the right eye after an angle grinder exploded in his face (Figure 3). The visual acuity at presentation was light perception. Computed tomography of the orbits revealed no intraocular foreign bodies. The laceration was adjacent to the limbus spanning 7 clock hours with uveal prolapse, and a total hyphema was present. Intraoperatively, the cornea was noted to be clear. The posterior limit of the laceration extended beyond the equator and was not closed to prevent posterior prolapse of the retina and vitreous. Following repositioning of the prolapsed uveal tissue and watertight closure of the laceration with 9-0 nylon sutures, approximately 0.2 mL of undiluted 0.5% preservative-free moxifloxacin was instilled into the anterior chamber between adjacent corneal sutures, and approximately 0.1 mL was injected intrastromally to hydrate a segment of the corneal laceration for endophthalmitis prophylaxis. On postoperative day 1, severe corneal edema with extensive Descemet folds was noted (Figure 4). B-scan ultrasonography revealed the presence of a tractional retinal detachment, and the patient was taken to the operating room on postoperative day 3 for attempted retinal detachment repair. The corneal decompensation, however, precluded an adequate view of the posterior segment for successful surgery.
Multiple authors have endorsed a low postoperative toxicity profile for intracameral moxifloxacin at varying concentrations for postoperative endophthalmitis prophylaxis.1–4 This safety profile is often attributed to the self-sterilizing properties of moxifloxacin, which negates the need for preservatives in solution. The use of preservative-free intracameral moxifloxacin is becoming increasingly popular because of its broader antimicrobial coverage against common culprits of postoperative endophthalmitis compared with cefuroxime and vancomycin. It also demonstrates substantial activity against atypical organisms.8
Commercially available Vigamox eyedrops (moxifloxacin 0.5%) are preservative free and isotonic, with a 6.8 pH and an osmolality of approximately 290 mOsm/kg, similar to those of aqueous (pH 7.4, osmolality 305 mOsm/kg). This suggests that undiluted topical-formulation moxifloxacin used intracamerally should pose minimal risk for ocular toxicity.9,10
Espiritu et al. reported that 0.5% intracameral Vigamox appeared to be nontoxic in terms of visual rehabilitation, anterior chamber reaction, pachymetry, and corneal endothelial cell density.11
Haripriya et al. reported a reduction in overall endophthalmitis rate by 3.5-fold in a retrospective study of over 600,000 patients with no adverse events attributed to 0.1 mL of intracameral 0.5% moxifloxacin at the conclusion of cataract surgery.12 Rathi et al. reported a 3.95-fold reduction in endophthalmitis rates in a prospective study in which 0.1 mL of intracameral 0.5% moxifloxacin was administered at the conclusion of cataract surgery in 24 534 eyes.13 They reported no cases of TASS associated with moxifloxacin. The only published clinical trial on the subject by Melega et al. found no study-related ocular adverse events with the use of 0.03 mL of intracameral 0.5% moxifloxacin for postcataract endophthalmitis prophylaxis.14
However, despite very low complication rates reported in the literature and encouraging safety data from the largest studies on the subject, the FDA, using the Adverse Event Reporting System database, identified 29 cases of TASS associated with intraocular administration of drugs containing moxifloxacin as of December 19, 2019.5 Among these 29 cases—19 cataract surgeries and 10 unspecified intraocular surgeries—several surgeons reported the use of up to 0.5 mL of 0.5% moxifloxacin, and several surgeons reported the use of Moxeza, which contains xanthan gum—a known endothelial toxin.5 The Intermountain Ocular Research Center in 2013 also reported 12 patients with TASS following intracameral 0.5% Moxeza, which contains inactive ingredients such as xanthan gum, sorbitol, and tyloxapol. The latter has both detergent and mucolytic properties.15 The FDA cautions against the use of intraocular administration of moxifloxacin drugs that contain more than 0.3 mL of 0.5% moxifloxacin and warns surgeons to be keenly aware of certain potentially harmful inactive ingredients, such as xanthan gum, in the drug product they select.
Our patient who underwent complex cataract extraction with intralenticular foreign-body removal ultimately required a Descemet stripping automated endothelial keratoplasty due to severe nonresolving corneal edema despite maximal topical therapy. Our other patient with ruptured globe repair declined surgical intervention for nonresolving corneal edema and retinal detachment due to the guarded prognosis of the injured eye. To our knowledge, there are no cases in the literature describing an association between the use of undiluted topical moxifloxacin for intrastromal hydration of corneal wounds and corneal decompensation and TASS following intraocular surgery.
In both of our patients, the correct drug product of intracameral moxifloxacin was used, but both surgeons reported intrastromal hydration of the corneal wounds with undiluted topical 0.5% moxifloxacin. Both surgeons estimated a total use of approximately 0.3 mL of 0.5% moxifloxacin delivered intracamerally and intrastromally, which is consistent with the maximum dose recommended by the FDA's public health advisory.5 We recognize, however, that this total dosage is 3-fold higher than the 0.1 mL dose of 0.5% moxifloxacin reported as safe by Harapriya et al. and Rathi et al.
We are aware that some surgeons recommend 0.1% preservative-free moxifloxacin produced by compounded pharmacies for endophthalmitis prophylaxis, both with instillation in the anterior chamber and with intrastromal hydration of the clear corneal incisions following routine cataract surgery.6,7 They report an excellent safety profile and reduction in endophthalmitis rates at their respective institutions.6 We hypothesize that intrastromal hydration of clear corneal incisions with 0.5% topical moxifloxacin, as opposed to 0.1% compounded moxifloxacin products reported by Shorstein et al., could lead to localized toxic concentrations of non-circulating drug product within the corneal stroma.6 Haruki et al. demonstrated in vitro that moxifloxacin at more than 500 mg/mL caused damage to the cell membranes of corneal endothelial cells and at even higher concentrations decreased cell viability.16 We postulate that intrastromal accumulation of the drug product could reach this toxic concentration, resulting in corneal endothelial dysfunction and the observed corneal decompensation in both of the cases in this report. We cannot exclude the potential effect of toxicity secondary to the presence of an unidentified metallic foreign body as in case 1, or severe globe trauma as in case 2, although both patients had clear corneas prior to and during surgery. In case 1, severe corneal edema was observed on the patient's first examination after surgery on postoperative day 4. In case 2, severe corneal edema was observed approximately 12 hours after surgery. Although it is not possible to determine whether the TASS and corneal decompensation events were solely due to moxifloxacin 0.5% injected intrastromally, we have not observed this complication at our institution despite the frequent use of intracameral prophylactic moxifloxacin. Instrastromal hydration with moxifloxacin, in these 2 cases, was believed to be the only deviation from the standard procedure.
Therefore, we encourage surgeons to avoid intrastromal injection of undiluted 0.5% topical moxifloxacin and recommend either using only 0.1% compounded formulations or avoiding intrastromal injection altogether. We understand that the concentration and volume of intrastromal and intracameral moxifloxacin injections used in our cases is above the maximum dose established by some of the largest studies on the subject. Intrastromal injection, concentration, and volume of the moxifloxacin preparation used in our cases are all factors that may have resulted in endothelial toxicity. In addition, corneal trauma, including metallic foreign-body toxicity in one of the cases, is a potentially confounding issue that may have contributed to corneal decompensation in these patients. However, as the practice of using intracameral moxifloxacin for postcataract endophthalmitis becomes more commonplace, we urge cataract surgeons to be conscientious of the moxifloxacin drug product, concentration, and volume that they use.
WHAT WAS KNOWN
- Many ophthalmologists have adopted the off-label practice of using either FDA-approved topical-formulation moxifloxacin drugs or compounded moxifloxacin drug products for intracameral endophthalmitis prophylaxis at the conclusion of surgery.
WHAT THIS PAPER ADDS
- Surgeons should avoid the use of undiluted 0.5% topical-formulation moxifloxacin drugs for intrastromal hydration of clear corneal incisions following intracameral administration to decrease the risk for corneal decompensation and toxic anterior segment syndrome. We recommend using only 0.1% compounded formulations for instrastromal and intracameral injection or avoiding intrastromal injection altogether.
1. Arshinoff SA, Modabber M. Dose and administration of intracameral moxifloxacin for prophylaxis of postoperative endophthalmitis. J Cataract Refract Surg 2016;42:1730–1741
2. Bowen RC, Zhou AX, Bondalapati S, Lawyer TW, Snow KB, Evans PR, Bardsley T, McFarland M, Kliethermes M, Shi D, Mamalis CA, Greene T, Rudnisky CJ, Ambati BK. Comparative analysis of the safety and efficacy of intracameral cefuroxime, moxifloxacin and vancomycin at the end of cataract surgery: a meta-analysis. Br J Ophthalmol 2018;102:1268–1276
3. Galvis V, Tello A, Sánchez MA, Camacho PA. Cohort study of intracameral moxifloxacin in postoperative endophthalmitis prophylaxis. Ophthalmol Eye Dis 2014;6:1–4
4. Grzybowski A, Brona P, Zeman L, Stewart MW. Commonly used intracameral antibiotics for endophthalmitis prophylaxis: a literature review. Surv Ophthalmol 2021;66:98–108
5. U.S. Food and Drug Administration. FDA Alerts Health Care Professionals of Risks Associated With Intraocular Use of Compounded Moxifloxacin: FDA Public Health Advisory. Silver Spring, MD: FDA; 2020
6. Shorstein NH, Myers WG. Drop-free approaches for cataract surgery. Curr Opin Ophthalmol 2020;31:67–73
7. Nguyen ET, Shorstein NH. Preparation of intracameral antibiotics for injection. J Cataract Refract Surg 2013;39:1778–1779
8. Barreau G, Mounier M, Marin B, Adenis JP, Robert PY. Intracameral cefuroxime injection at the end of cataract surgery to reduce the incidence of endophthalmitis: French study. J Cataract Refract Surg 2012;38:1370–1375
9. Arbisser LB. Safety of intracameral moxifloxacin for prophylaxis of endophthalmitis after cataract surgery. J Cataract Refract Surg 2008;34:1114–1120
10. O'Brien TP, Arshinoff SA, Mah FS. Perspectives on antibiotics for postoperative endophthalmitis prophylaxis: potential role of moxifloxacin. J Cataract Refract Surg 2007;33:1790–1800
11. Espiritu CR, Caparas VL, Bolinao JG. Safety of prophylactic intracameral moxifloxacin 0.5% ophthalmic solution in cataract surgery patients. J Cataract Refract Surg 2007;33:63–68
12. Haripriya A, Chang DF, Ravindran RD. Endophthalmitis reduction with intracameral moxifloxacin prophylaxis: analysis of 600 000 surgeries. Ophthalmology 2017;124:768–775
13. Rathi VM, Sharma S, Das T, Khanna RC. Endophthalmitis prophylaxis study. Report 1: intracameral cefuroxime and moxifloxacin prophylaxis for the prevention of postcataract endophthalmitis in rural India. Indian J Ophthalmol 2020;68:819–824
14. Melega MV, Alves M, Cavalcanti Lira RP, Cardoso da Silva I, Ferreira BG, Assis Filho HL, Pedreira Chaves FR, Martini AAF, Dias Freire LM, Reis RD, Leite Arieta CE. Safety and efficacy of intracameral moxifloxacin for prevention of post-cataract endophthalmitis: randomized controlled clinical trial. J Cataract Refract Surg 2019;45:343–350
15. Mamalis N. ASCRS alert: TASS associated with intracameral antibiotic injection. ASCRS This Week
, May 8, 2013
16. Haruki T, Miyazaki D, Matsuura K, Terasaka Y, Noguchi Y, Inoue Y, Yamagami S. Comparison of toxicities of moxifloxacin, cefuroxime, and levofloxacin to corneal endothelial cells in vitro. J Cataract Refract Surg 2014;40:1872–1878