Physiological and Toxicological Effects of Cefuroxime on the Albino Rabbit Retina

Shahar, Jonathan; Zemel, Esther; Perlman, Ido; Loewenstein, Anat

doi:10.1167/iovs.11-8053

Cited by 35 publications

(30 citation statements)

References 24 publications

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“…While doses as low as 10 mg injected into the vitreous in rabbits have induced structural changes to the retina, 14 no reports as yet show deleterious clinical effects in humans at this dose. This is the first report, to our knowledge, of the effects on the human eye of intracameral injection of cefuroxime sodium at a dose of 9 mg.…”

Section: Discussionmentioning

confidence: 99%

Transient Macular Edema After Intracameral Injection of a Moderately Elevated Dose of Cefuroxime During Phacoemulsification Surgery

et al. 2015

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efuroxime sodium (1 mg/0.1 mL) appears to be effective in preventing endophthalmitis. 1,2 Kaiser Permanente surgeons began injecting intracameral cefuroxime in 2007, with resulting declining rates of infection. 3,4 Cefuroxime is available in Europe as Aprokam, a manufactured product for intracameral injection. In the United States, no intracameral antibiotic preparation is approved to prevent endophthalmitis, thus creating a need for compounding for each surgical case. Reports have shown a long-term deleterious effect on the retina and cornea of injecting cefuroxime sodium at concentrations greater than 50 mg, 5,6 while no adverse effect has been observed at 3 mg. 7 We describe transient macular edema from injection of 9 mg of cefuroxime sodium. MethodsFollowing Kaiser Permanente Institutional Review Board approval, we reviewed medical records of 11 patients (13 eyes) who underwent cataract surgery by a single surgeon (D.C.W.) on a single day. In this article, exposed eye refers to an eye that underwent surgery and was injected with cefuroxime sodium at a dose of 9 mg/ 0.1 mL on that day. Reduced vision refers to Snellen visual acuity of 20/70 or worse on postoperative day 1 following uncomplicated clear-cornea cataract surgery. Data were collected and analyzed between June 2014 and January 2015. Informed consent was not required owing to the retrospective nature of the study.All patients were prescribed topical prednisolone acetate, 1%, diclofenac, 0.1%, and ofloxacin, 0.3%, 4 times daily in the eye undergoing surgery beginning 3 days prior to surgery. Two of the 11 patients underwent bilateral same-day surgery. Ordinarily, 750 mg of cefuroxime sodium injectable powder is reconstituted with 7.5 mL of preservative-free normal saline (sodium chloride, 0.9%). Three milliliters (300 mg) of the resulting solution is then injected into an empty 30-mL sterile interior vial. To this, 27 mL of preservative-free normal saline is added, resulting in a final cefuroxime sodium concentration of 1 mg/0.1 mL. 8 At each procedure's conclusion, 0.1 mL of compounded cefuroxime sodium solution was injected through the paracentesis. However, on this day, the final concentration was 9 mg/0.1 mL. Results Postoperative Day 1On the first postoperative day, 6 of 13 eyes (46%; 95% CI, 19%-75%) had reduced vision with uncorrected distance visual acu-IMPORTANCE Intracameral injection of cefuroxime sodium (1 mg/0.1 mL) has been reported to reduce the risk of endophthalmitis following cataract surgery. In the United States it must be compounded, which is subject to dilution error. We describe a series of 13 eyes that received intracameral injection of cefuroxime sodium, 9 mg/0.1 mL, intraoperatively.OBSERVATIONS On postoperative day 1, 6 of 13 eyes (46%; 95% CI, 19%-75%) had visual acuity of 20/70 or worse and macular edema. Spectral-domain optical coherence tomography of 2 eyes revealed central subfield thicknesses of 909 and 873 μm. On postoperative day 4, the mean (SD) central subfield thickness was 309 (78) μm in the 6 eyes with diagnosed...

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Section: Discussionmentioning

confidence: 99%

Transient Macular Edema After Intracameral Injection of a Moderately Elevated Dose of Cefuroxime During Phacoemulsification Surgery

et al. 2015

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“…Astrocytes present in the central nervous system, retina, and optic nerve head were previously thought to be bystander cells, but clearly in the past few years various studies have indicated that they play important roles such as regulation of ionic balance, neurotransmission, synaptic plasticity, and neurodegeneration (39). GFAP is an intermediate filament that is normally expressed in astrocytes but not Müller cells in the retina (34,40). However, in a variety of retinal injuries such as retinal detachment (41), ischemia (42), and increased intraocular pressure (43), GFAP expression in retinal Müller cells became evident (34).…”

Section: Discussionmentioning

confidence: 99%

“…GFAP is an intermediate filament that is normally expressed in astrocytes but not Müller cells in the retina (34,40). However, in a variety of retinal injuries such as retinal detachment (41), ischemia (42), and increased intraocular pressure (43), GFAP expression in retinal Müller cells became evident (34). Because of this, GFAP expression in Muller cells has been widely used as a molecular indicator of retinal stress.…”

Section: Discussionmentioning

confidence: 99%

“…Because of this, GFAP expression in Muller cells has been widely used as a molecular indicator of retinal stress. It has also been suggested that GFAP immunostaining is a more sensitive tool for detecting retinal stress than ERG (34). Reactive glial cells also express various inflammatory cytokines such as TNF-α, interleukin-1b, and endothelin-1 that lead to death of retinal ganglion cells (39).…”

Section: Discussionmentioning

confidence: 99%

“…1. Fundoscopic images before and after intravitreal injection of NA3 glycan: a rabbit 1, day 0, before injection; b rabbit 1, day 1 after 100 nM NA3 glycan injection; c rabbit 2, day 0, before injection; and d rabbit 2, day 14 after 100 nM NA3 glycan injection GFAP and TUNEL Staining GFAP expression in Muller cells is a widely used, highly sensitive molecular indicator of retinal stress (34). As shown in Fig.…”

Section: Slit Lamp Biomicroscopymentioning

confidence: 99%

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Novel Endogenous Glycan Therapy for Retinal Diseases: Safety, In Vitro Stability, Ocular Pharmacokinetic Modeling, and Biodistribution

Swaminathan

Palamoor

et al. 2014

AAPS J

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Abstract. Asialo, tri-antennary oligosaccharide (NA3 glycan) is an endogenous compound, which supports proper folding of outer segment membranes, promotes normal ultrastructure, and maintains protein expression patterns of photoreceptors and Müller cells in the absence of retinal pigment epithelium support. It is a potential new therapeutic for atrophic age-related macular degeneration (AMD) and other retinal degenerative disorders. Herein, we evaluate the safety, in vitro stability, ocular pharmacokinetics and biodistribution of NA3. NA3 was injected into the vitreous of New Zealand white rabbits at two concentrations viz. 1 nM (minimum effective concentration (MEC)) and 100 nM (100XMEC) at three time points. Safety was evaluated using routine clinical and laboratory tests. Ocular pharmacokinetics and biodistribution of [ 3 H]NA3 were estimated using scintillation counting in various parts of the eye, multiple peripheral organs, and plasma. Pharmacokinetic parameters were estimated by non-compartmental modeling. A 2-aminobenzamide labeling and hydrophilic interaction liquid interaction chromatography were used to assess plasma and vitreous stability. NA3 was well tolerated by the eye. The concentration of NA3 in eye tissues was in the order: vitreous>retina>sclera/choroid> aqueous humor>cornea>lens. Area under the curve (0 to infinity) (AUC∞) was the highest in the vitreous thereby providing a positive concentration gradient for NA3 to reach the retina. Half-lives in critical eye tissues ranged between 40 and 60 h. NA3 concentrations were negligible in peripheral organs. Radioactivity from [ 3 H]NA3 was excreted via urine and feces. NA3 was stable at 37°C in vitreous over a minimum of 6 days, while it degraded rapidly in plasma. Collectively, these results document that NA3 shows a good safety profile and favorable ocular pharmacokinetics.

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Effectiveness and Safety of an Intracameral Injection of Cefuroxime for the Prevention of Endophthalmitis After Cataract Surgery With or Without Perioperative Capsular Rupture

et al. 2016

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Physiological and Toxicological Effects of Cefuroxime on the Albino Rabbit Retina

Cited by 35 publications

References 24 publications

Transient Macular Edema After Intracameral Injection of a Moderately Elevated Dose of Cefuroxime During Phacoemulsification Surgery

Transient Macular Edema After Intracameral Injection of a Moderately Elevated Dose of Cefuroxime During Phacoemulsification Surgery

Novel Endogenous Glycan Therapy for Retinal Diseases: Safety, In Vitro Stability, Ocular Pharmacokinetic Modeling, and Biodistribution

Effectiveness and Safety of an Intracameral Injection of Cefuroxime for the Prevention of Endophthalmitis After Cataract Surgery With or Without Perioperative Capsular Rupture

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