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Preretinal lesions present after intravitreal antibiotics for suspected endophthalmitis
The patient underwent unremarkable cataract surgery 4 weeks before presentation.
It is important to identify rare complications of common procedures. The correct diagnosis allows for appropriate treatment and avoids unnecessary surgical interventions.
The case
A 66-year-old woman with a medical history of controlled essential hypertension and non-insulin-dependent diabetes mellitus presented from another hospital for presumed left eye endophthalmitis.
Per the patient, her ocular history was unremarkable except for cataract surgery in the left eye 4 weeks prior. She reported that the surgery was uncomplicated, but due to elevated IOP and corneal edema, she had not had functional vision since the surgery. No additional preoperative, intraoperative or postoperative information was available. The patient denied any additional intraocular treatments or surgeries and reported that since the cataract surgery, she received only topical treatment. At the time of examination at our institution, the patient was receiving bimatoprost, a combination of brimonidine and timolol, and prednisolone 1% drops. The presenting complaint was pain in the left eye.
Aleksandra V. Rachitskaya
Thomas A. Albini
On exam, the right eye was phakic with best corrected visual acuity of 20/25. Visual acuity in the left eye was count fingers, and IOP was 12 mm Hg. Diffuse keratic precipitates but no hypopyon were seen in the anterior chamber. Anterior chamber cell (2+) and flare (2+) were noted. A three-piece IOL was visualized in the capsular bag. A temporal white capsular opacity was documented. The detailed view of the fundus was compromised by vitreous haze (3+), but no retinal lesions, periphlebitis or retained lens fragments were observed.
The differential diagnosis included delayed-onset endophthalmitis or retained lens fragments. The patient underwent bedside vitreous tap and injection of vancomycin 1 mg/0.1 mL, ceftazidime 2.25 mg/0.1 mL and dexamethasone 0.4 mg/0.1 mL with three separate 30-gauge needles and three separate syringes. The patient was started on topical fortified vancomycin 50 mg/mL, prednisolone and gatifloxacin. The ultrasound showed dense vitreous opacities, moderately dense vitreous membranes and no evidence of retained lens fragments.
On the first day after the injection, the patient presented with multiple preretinal white lesions in her left eye (Figure 1a). Optical coherence tomography scan showed preretinal lesions (Figure 1b). The patient was referred to a subspecialty clinic for further evaluation and management.
Figure 1. Fundus photo of diffuse preretinal intravitreal vancomycin and ceftazidime aggregates in a patient with suspected endophthalmitis (a). Spectral-domain optical coherence tomography (Spectralis, Heidelberg Engineering) demonstrating preretinal aggregates of vancomycin and ceftazidime (b).
Images: Albini TA, Rachitskaya AV
Figure 2. Fundus photo demonstrating decreasing number and size of vancomycin and ceftazidime aggregates in a patient with suspected endophthalmitis after 2 weeks of observation.
The diagnosis
The differential diagnosis included worsening of the infection, onset of a separate uveitic process or aggregation of intravitreal antibiotics. Given that the lesions developed after the intravitreal injection, the diagnosis of aggregation of intravitreal antibiotics was established. The diagnosis was supported by the preretinal location of the lesions, as seen on OCT, with sparing of the vitreous or retina itself (Figure 1b). The fundus photos demonstrated that there was no obvious predilection for the retinal vessels. The patient was observed on topical therapy. No additional intravitreal injections or surgical interventions were performed. The intraocular cultures remained negative, and in the course of a month, the preretinal lesions decreased in size and number (Figure 2).
The patient’s clinical course was complicated by development of rhegmatogenous retinal detachment 2.5 months after the initial exam at our hospital. She underwent scleral buckle placement, pars plana vitrectomy with vitreous cultures, intravitreal injections of vancomycin 1 mg/0.1 mL and ceftazidime 2.25 mg/0.1 mL, and silicone oil infusion. The vitreous cultures remained negative. The patient subsequently underwent silicone oil removal with final best corrected visual acuity of 20/100 and no recurrence of preretinal lesions in her left eye.
Vancomycin and ceftazidime are routinely used in suspected cases of infectious endophthalmitis to provide broad gram-positive and gram-negative antibiotic coverage, respectively. In vitro, both antibiotics have been reported to precipitate on their own and to form aggregates when mixed. Preparation medium and its volume, temperature, pH and antibiotic concentrations have been implicated in formation of precipitates and aggregates. Of interest is an observation in one of the in vitro studies that, when mixed together, the aggregate and the supernatant retained significant antibacterial activity.
Aggregation of intravitreal ceftazidime and vancomycin has been reported clinically in cases of traumatic and post-intravitreal injection-presumed infectious endophthalmitis. The incidence is unknown, but given the isolated case reports, it appears to be low. The aggregates were seen in the preretinal location and in the vitreous along the needle tract in cases of intravitreal injections. They have also been reported on the globe surface in cases of subconjunctival injection. In all reported cases, the aggregates cleared without adverse sequelae. Although some authors recommend avoiding the combination of vancomycin and ceftazidime, this has not been the recommendation at our institution.
Patients with presumed antibiotic aggregates need to be observed closely to ensure that the aggregates clear and that patients improve clinically. The possibility that the deposits represent a manifestation of endophthalmitis must be kept in mind.