The use of intraoperative intracameral antibiotics for endophthalmitis prevention has increased in popularity since recent studies have demonstrated both the efficacy1–5 and safety6–9 of such use. Indeed, a survey of American Society of Cataract and Refractive Surgery (ASCRS) members in 2014 showed that 50% of respondents were using intracameral antibiotics10 versus 30% in a previous ASCRS survey from 2007,11 with vancomycin, moxifloxacin, and cefuroxime being the most common agents of choice. The use of intracameral moxifloxacin specifically resulted in a 3.5-fold reduction in rates of endophthalmitis post-cataract surgery in a recent large retrospective study12 without any reported adverse events. Overall, fluoroquinolones have been shown to have excellent ocular safety, although some ocular toxicities have been reported, including phototoxicity and neurotoxicity.7–9,13
Over the past decade, numerous descriptions of a new clinical entity, bilateral acute iris transillumination (BAIT) have been reported.14–21 This entity is characterized by acute, diffuse bilateral iris transillumination defects, pigment dispersion, and variable pupillary sphincter paralysis. The underlying etiology is unclear, but an association with systemic moxifloxacin use and/or viral illness has been proposed. To our knowledge, however, this condition has never been reported after local intracameral injection of moxifloxacin or any other antibiotic, and it has only been observed in the setting of oral or intravenous moxifloxacin therapy. Here, we report the first known case of a unilateral BAIT-like syndrome postintracameral moxifloxacin injection for endophthalmitis prevention during intraocular surgery.
A 45-year-old man with past ocular history of moderate myopia, symptomatic vitreous syneresis in both eyes, and an uneventful pars plana vitrectomy (PPV) in the left eye had an elective PPV in the right eye for ongoing symptomatic floaters. After an uneventful procedure, intracameral moxifloxacin (0.5 mg/0.1 mL) was administered into the anterior chamber for endophthalmitis prophylaxis. The initial postoperative course was unremarkable. However, 3 weeks after the surgery, the patient presented with sudden worsening of vision and mild pain in the right eye. The corrected distance visual acuity was reduced from 20/25 to 20/70, and the intraocular pressure (IOP) was elevated to 52 mm Hg in that eye. An examination of the right eye showed significant flare and circulating pigment in the anterior chamber without inflammatory cells. Diffuse 360-degree iris transillumination defects (Figure 1, A), significant iris surface pigment deposition (Figure 1, B), and dense pigment accumulation in all quadrants of the angle on gonioscopy were also noted. No posterior bowing of iris was noted. The pupils were equal and reactive bilaterally. An examination of the left eye was unremarkable (Figure 1, C). The postoperative topical steroids were discontinued, topical nonsteroidal antiinflammatory drops were continued, and the patient was started on a topical carbonic anhydrase inhibitor, β-blocker and α-agonist, as well as an oral carbonic anhydrase inhibitor. A follow-up examination 5 days later revealed persistent IOP elevation, continued pigment circulating in the anterior chamber, and transillumination defects. The patient's medical history was carefully reviewed and was unremarkable for any medical problems. His only medication use was for topical drops after vitrectomy, which included topical fluoroquinolone and steroid and nonsteroidal antiinflammatory drops. A review of systems was negative. He denied any symptoms typically associated with viral illness in the previous 3 months, specifically, no fatigue, malaise, nausea, vomiting, anorexia, unexplained weight loss, joint pain, or skin rash.
An anterior chamber paracentesis was performed to obtain aqueous fluid, and herpes simplex virus, varicella zoster virus, and cytomegalovirus polymerase chain reaction (PCR) diagnostic tests were all negative. The patient was placed on a 10-day course of oral acyclovir prophylactically. The anterior chamber washout was performed with the intent of removing the recently deposited pigment from the trabecular meshwork. Because of the persistently elevated IOP (>40 mm Hg), the patient underwent goniotomy with a Kahook dual blade (New World Medical, Inc.) combined with cataract extraction and an intraocular lens placement. Five days later, his IOP remained elevated despite maximum medical therapy; therefore, a trabeculectomy was performed. This resulted in normalization of the IOP with no further IOP-lowering medications required. Of note, the patient's left eye never developed pigmentary, iris, or IOP changes after the PPV performed 2 years prior, which did not include intracameral moxifloxacin.
Herein we present the first known case of unilateral BAIT-like iris transillumination and pigment-associated ocular hypertension after intraoperative injection of moxifloxacin into the anterior chamber. It is prudent to consider other known etiologies of iris transillumination and pigment dispersion before concluding that this patient's presentation was indeed associated with exposure to intracameral moxifloxacin.
Although herpetic etiology cannot be entirely excluded by this patient's negative aqueous humor PCR, given the reported test sensitivity of only 91.3%,22 there are several features of this case that differ from typical herpetic uveitis. Specifically, this patient did not have keratic precipitates and sectoral iris atrophy causing pupil distortion typical of herpetic anterior uveitis.23 He also had significant pigment deposition in the angle on gonioscopic examination not typical of herpetic disease.
Pigment dispersion syndrome (PDS) often presents in myopic males in the fourth and fifth decades of life, which is descriptive of our patient. Patients who have PDS frequently develop glaucoma, but the onset is usually insidious and generally asymptomatic. Furthermore, in PDS, iris transillumination defects develop slowly and demonstrate a midperipheral spoke-like pattern.24 In our case, the IOP rise was acute and the patient was symptomatic. Similarly, the pigment dispersion was sudden and involved the entire iris. Other differentiating characteristics include the lack of posterior iris bowing as well as resolution of circulating pigment cells in the anterior chamber and stabilization of the iris appearance within 2 months of onset.
Thus, we believe that our patient's presentation is most likely reflective of his intracameral moxifloxacin exposure. Although by no means definitive, the lack of symptom development in the patient's contralateral eye after undergoing an identical intraocular procedure without intracameral antibiotic exposure 2 years prior is suggestive of a possible association with moxifloxacin in this case.
The clinical entity described in the literature that most closely resembles our patient's case is bilateral acute iris transillumination (BAIT). Systemic moxifloxacin exposure has been frequently cited as a possible association with the condition. However, a 26-case series by Tugal-Tutkun et al.20 called this into question, noting only 35% of their patients had received moxifloxacin exposure and suggesting viral etiology might be more likely. We could not identify any history of antecedent viral or bacterial syndrome in our patient in the weeks or months before the ocular surgery. There is some recent evidence that topical moxifloxacin might cause subclinical iris melanocyte toxicity in vivo,25 although to date, no studies have assessed direct iris pigment epithelium toxicity with moxifloxacin exposure in vitro.
Notable and uncharacteristic of classic BAIT, is our patient's unilateral presentation, which we ascribe to the use of intracameral moxifloxacin in the symptomatic eye only. In published reports of BAIT,14,18 rare unilateral or asymmetric cases have been noted; however, in these cases, systemic moxifloxacin exposure was reported rather than unilateral intracameral injection. A series of 12 cases reported by Kreps et al.14 demonstrated one such asymmetric case, with markedly less transillumination noted in the patient's only pseudophakic eye. Indeed, the vast majority of BAIT cases appear limited to phakic eyes. It is worth noting that our patient remained phakic after the original PPV. This might explain why no cases have yet been reported in the context of cataract extraction surgery despite the recent surge in the use of anterior chamber moxifloxacin prophylaxis during these procedures. Knape et al.17 hypothesized that phakic eyes might demonstrate impaired posterior-to-anterior clearance with trapping of drugs in the posterior chamber by synechiae between the lens and iris, resulting in prolonged exposure of the iris pigment epithelium.17 The corollary of this reduced anterior-to-posterior drug diffusion has been shown in phakic patients with topical moxifloxacin administration,26 which could raise the question of the extent of posterior iris exposure with anterior drug delivery. However, an in vivo animal study27 showed significant vitreous penetration after anterior chamber moxifloxacin injection, implying that posterior chamber concentration and thus iris pigment epithelium exposure are likely substantial with this route of administration.
To our knowledge, no cases of acute iris transillumination have yet been reported in the context of intracameral moxifloxacin injection. We report just such a case here. As the use of intracameral moxifloxacin for endophthalmitis prophylaxis during intraocular surgery becomes a widely-accepted practice, it is prudent to recognize acute iris transillumination and pigment-related ocular hypertension as a possible adverse effect, in particular in procedures where the native lens is left intact. Further studies to investigate the direct effects of moxifloxacin and other fluoroquinolones on iris pigment epithelium are warranted and might help to further establish whether a true association between these agents and BAIT-like clinical entities exists. As intracameral moxifloxacin use increases in intraocular surgery in the United States, we anticipate that further cases similar to ours will be reported.
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