­require over a month. Systemic absorption from topical ocular application is minimal with normal anterior segments, however with ulcerated corneas or with fortified solutions, absorption can occur. There is a case report by Kella and Kozart (1997) of exacerbation of myasthenia gravis by topical ocular tobramycin, betoxal and dexamethasone. There are two cases in the National Registry where topical ocular tobramycin alone or in a steroid combination was implicated in causing or enhancing myasthenia gravis. Both patients had chronic renal disease. One of these cases, at an academic center, resulted in a lawsuit. A case of anaphylaxis after topical ocular combination of tobramycin, steroid and Naplicon A has been reported to the National Registry.

Systemic absorption and local toxicity significantly increases in collagen-soaked tobramycin shields. Grazozi et al (1999) reported a case of inadvertent tobramycin ophthalmic ointment entering the anterior chamber through a microperforation after radial keratocomy. This was followed by three attacks of uveitis and glaucoma. The endothelial cell count was a third less and the iris texture was slightly atrophic compared to the fellow eye. Animal studies confirm the toxicity of tobramycin to the corneal endothelial cell. Retinal degeneration and optic atrophy have followed inadvertent intraocular injection of tobramycin (Balian 1983). Intraocular complications have possibly occurred from subconjunctival injection, with the drug entering the eye through the cataract wound (Judson 1989). Campo­ chiaro and Conway (1991) reported three cases of macular infarctions after subconjunctival injections or tobramycin.

References and Further Reading

American Academy of Ophthalmology. Corneal toxicity with antibiotic/ steroid-soaked collagen shields. Clinical Alert 11: 1, 1990.

Balian JV. Accidental intraocular tobramycin injection: a case report. ­Ophthalmic Surg 14: 353, 1983.

Campochiaro PA, Conway BP. Aminoglycoside toxicity – a survey of retinal specialists. Arch Ophthalmol 109: 946–950, 1991.

Caraffini S, Assalve D, Stingeni L, et al. Allergic contact conjunctivitis and blepharitis from tobramycin. Contact Dermatitis 32(3): 186–187, 1995.

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

Garzozi HJ, Muallem MS, Harris A. Recurrent anterior uveitis and glaucoma associated with inadvertent entry of ointment into the anterior chamber after radial keratotomy. J Cataract Refract Surg 25: 1685– 1687, 1999.

Judson PH. Aminoglycoside macular toxicity after subconjunctival injection. Arch Ophthalmol 107: 1282–1283, 1989.

Kaeser HE. Drug-induced myasthenic syndromes. Acta Neurol Scand 70(Suppl 100): 39, 1984.

Khella SL, Kozart D. Unmasking and exacerbation of myasthenia gravis by ophthalmic solutions: betoxolol, tobramycin, and desamethasone. A case report (letter). Muscle & Nerve 20(5): 631, 1997.

McCartney CF, Hatley LH, Kessler JM. Possible tobramycin delirium. JAMA 247: 1319, 1982.

Pflugfelder SC, Murchison JF. Corneal toxicity with an antibiotic/ steroid-soaked collagen shield (letter). Arch Ophthalmol 111(1): 18, 1993.

Wilhelmus KR, Gilbert ML, Osato MS. Tobramycin in ophthalmology. Surv Ophthalmol 32(2): 111–122, 1987.

Class: Antifungal Agents

Generic name: Amphotericin B.

Proprietary names: Abelcet, AmBisome, Amphotec, Fungizone.

Primary use

This polyene fungistatic agent is effective against Blasto­ myces, Histoplasma, Cryptococcus, Coccidioides, Candida and ­Aspergillus.

Ocular side effects

Systemic administration

Probable

1. Decreased vision – transitory

Possible

1. Subconjunctival or retinal hemorrhages secondary to drug-induced anemia

Conditional/Unclassified

1. Paresis of extraocular muscles

2. Retinal exudates

3. Diplopia

4. Blindness (IV)

Local ophthalmic use or exposure – topical application or subconjunctival injection

Certain

1. Irritation

a.Ocular pain

b.Burning sensation 2. Punctate keratitis

3. Eyelids or conjunctiva

a.Allergic reactions

b.Ulceration

c.Conjunctivitis – follicular

d.Necrosis – subconjunctival injection

e.Nodules – subconjunctival injection

f.Yellow discoloration – subconjunctival injection 4. Overgrowth of non-susceptible organisms

5. Uveitis

6. Hyphema

7. Delayed wound healing

Local ophthalmic use or exposure – intracameral injection

Certain

1. Uveitis

2. Corneal edema

3. Lens damage

Clinical significance

Seldom are significant ocular side effects seen from systemic administration of amphotericin B, except with intrathecal injections. In general, transitory blurred vision is the most common ocular side effect. Allergic reactions are so rare that initially it was felt they did not even occur. Li and Lai (1989) reported that after IV amphotericin B, a patient with previously bilateral normal vision went to irreversible light perception within 10 hours and optic atrophy within 10 weeks.

Topical ocular administration of amphotericin B can produce significant conjunctival and corneal irritative responses. This agent can affect cell membranes and allow increased ­penetration of other drugs through the cornea. There have been rare reports of marked iridocyclitis with small hyphemas occurring after each exposure of topical ocular amphotericin B. The formation of salmon-colored raised nodules can occur secondary to subconjunctival injection, especially if the dosage exceeds 5 mg (Bell and Ritchey 1973). These regress somewhat

nfectivesi -Anti ectiS • 1on