effects side ocular induced-Drug  • PART7  

Intraocular gentamicin has caused severe retinal ischemia, rubeosis, iritis, neovascular glaucoma, optic atrophy and blindness. A number of cases of inadvertent intraocular injections have been reported in the literature and to the National Registry. The degree of ocular damage is primarily dependent on trauma of the injection, volume of the injection, location of the injection and toxicity of the drug. Injections into the anterior chamber are rarely devastating, in part due to early recognition, small volume and immediate irrigation. Inadvertent posterior injection may result in elevated intraocular pressure with secondary vascular occlusions. The trauma of the injection itself may in addition cause intraocular bleeding and retinal detachment.

While there are prior publications outlining posterior gentamicin toxicity from intravitreal injections, Campochiaro and Lim (1994), along with the follow-up Letter to the Editor by Grizzard (1995), give the most complete picture. In essence, even 0.1 mg of gentamicin may cause significant changes since gravity allows the drug to concentrate in a dependent area for an indefinite period of time. If this dependent area is in the fovea, permanent visual changes have occurred. Fluorescein angiograms show discrete geographic involvement with the nonperfusion not corresponding to the vascular pattern. The topography and the abrupt ‘cookie cutter’ margins, Campochiaro, Lim and Grizzard point out, suggest an event mediated by the drug in contact with the retinal surface. These findings show that a localized infarct is the end result of the gentamicin toxicity. Visual acuity loss has included cases of blindness. Additional findings have included retinal opacities, retinal hemorrhages and edema, neovascular glaucoma, retinal pigmentary degeneration, and ­optic atrophy.

References and Further Reading

Awan KJ. Mydriasis and conjunctival paresthesia from local gentamicin. Am J Ophthalmol 99: 723, 1985.

Bullard SR, O’Day DM. Pseudomembranous conjunctivitis following topical gentamicin therapy. Arch Ophthalmol 115: 1591–1592, 1997.

Campochiaro PA. Aminoglycoside toxicity in the treatment of endophthalmitis­ (letter). Arch 113: 262–263, 1995.

Campochiaro PA, Lim JI. Aminoglycoside toxicity in the treatment of ­endophthalmitis. Arch Ophthalmol 112: 48–53, 1994.

Chapman JM, Abdelatif OMA, Cheeks L, Green K. Subconjunctival gentamicin induction of extraocular toxic muscle myopathy. Ophthalmic Res 24: 189–196, 1992.

Conway BP, Campochiaro PA. Macular infarction after endophthalmitis treated with vitrectomy and intravitreal gentamicin. Arch Ophthalmol 104: 367, 1986.

D’Amico DJ, Kenyon KP. Drug-induced lipidoses of the cornea and conjunctiva. Int Ophthalmol 4: 67–76, 1981.

Davison CR, Tuft SJ, Dart JKG. Conjunctival necrosis after administration of topical fortified aminoglycosides. Am J Ophthalmol 111: 690–693, 1991.

De Maio R, Oliver GL. Recovery of useful vision after presumed retinal and choroidal toxic effects from gentamicin administration. Arch Ophthalmol 112(6): 736–738, 1994.

Grizzard WS. Aminoglycoside toxicity in the treatment of endophthalmitis (letter). Arch Ophthalmol 113: 262–263, 1995.

Libert J, Ketelbant-Balasse PE, et al: Cellular toxicity of gentamicin. Am J Ophthalmol 87(405): 411, 1979.

Lowenstein A, Esther Z, Yafa V, et al: Retinal toxicity of gentamicin after subconjunctival injection performed adjacent to thinned sclera. Ophthalmology 108: 759–764, 2001.

Marra TR, Reynolds NC Jr., Stoddard JJ. Subjective oscillopsia (‘Jiggling vision’) presumably due to aminoglycoside ototixicity. J Clin Neuro­ ophthalmol 8: 3538, 1988.

Minor LB. Gentamicin-induced bilateral vestibular hypofunction. JAMA 279(7): 541–544, 1998.

Nauheim R, Nauheim J, Merrick NY. Bulbar conjunctival defects associated with gentamicin. Arch Ophthalmol 105: 1321, 1987.

Schatz H, McDonald HR. Acute ischemic retinopathy due to gentamicin injection. JAMA 256: 1725, 1986.

Stern GA, et al: Effect of topical antibiotic solutions on corneal epithelial wound healing. Arch Ophthalmol 101: 644, 1983.

Waltz K. Intraocular gentamicin toxicity. Arch Ophthalmol 109: 911, 1991.

Generic name: Kanamycin sulfate.

Proprietary name: Kantrex.

Primary use

This aminoglycoside is effective against Gram-negative organisms and in drug-resistant staphylococcus.

Ocular side effects

Systemic administration

Certain

1. Decreased vision

2. Eyelids or conjunctiva – allergic reactions

Probable

1. Myasthenia gravis (aggravates)

a.Diplopia

b.Ptosis

c.Paresis of extraocular muscles

Possible

1. Eyelids or conjunctiva - Lyell’s syndrome

Conditional/Unclassified

1. Optic neuritis

Local ophthalmic use or exposure – subconjunctival injection

Certain

1. Irritation

2. Eyelids or conjunctiva – allergic reactions

3. Overgrowth of non-susceptible organisms

Clinical significance

Systemic and ocular side effects due to kanamycin are quite rare, partially due to its poor gastrointestinal absorption. Myasthenia gravis occurs more frequently if kanamycin is given in combination with other antibiotics, such as neomycin, gentamicin, polymyxin B, colistin or streptomycin. Allergic reactions with cross-sensitivity have been reported for gentomycin but not for neomycin (Sanchez-Perez et al 2001). Adverse ocular reactions to this agent are reversible, transitory and seldom have residual complications. While optic neuritis has been reported to be associated with this drug, it has not been proven.

References and Further Reading

D’Amico DJ, et al: Comparative toxicity of intravitreal aminoglycoside antibiotics. Am J Ophthalmol 100: 264, 1985.

Finegold SM. Kanamycin. Arch Intern Med 104: 15, 1959.

Finegold SM. Toxicity of kanamycin in adults. Ann NY Acad Sci 132: 942, 1966.

Freemon FR, Parker RL Jr., Greer M. Unusual neurotoxicity of kanamycin. JAMA 200: 410, 1967.

Kaeser HE. Drug-induced myasthenic syndromes. Acta Neurol Scand 70(Suppl 100): 9, 1984.