Doxycycline may be the greatest photosensitizer in this group, with minocycline being the least. However, even with minocycline, in susceptible patients significant ocular and periocular photosensitivity reactions may occur. Shah and De Cock (1999) described three cases of ocular and periocular photosensitivity, one occurring after only one exposure and another after 2 weeks of therapy. The latter was the most severe and had the clinical appearance of an arc-welding injury. This includes intense bilateral photophobia, blepharospasm, lid angioedema, marked papillary conjunctivitis and superficial punctate keratitis. This cleared within 2 days after stopping the drug. These drugs are secreted in a crystalline form in the tear film, often in therapeutic concentration. Therefore, oral intake may cause or increase ocular irritation in patients with sicca or contact lenses. Long-term therapy may allow the drug or its metabolites to mix with calcium concretions, which may take on characteristics of the drug, such as yellow color and fluorescence. Permanent discoloration of the cornea has been seen in infants whose mothers received high doses of tetracycline during pregnancy.

Fig. 7.1d  Marginal peripheral ulcerative keratitis (non-staining) from systemic filgrastim treatment.

References and Further Reading

Bradfield YS, Robertson DM, Salomao DR, et al: Minocycline-induced ocular pigmentation. Arch Ophthalmol 121: 114–145, 2003.

Brothers DM, Hidayat AA. Conjunctival pigmentation associated with tetracycline medication. Ophthalmology 88: 1212, 1981.

Chiu AM, Cheunkongkaew WL, Cornblath WT, et al. Minocycline treatment and pseudotumor cerebri syndrome. Am J Ophthalmol 126(1): 116–121, 1998.

Edwards TS. Transient myopia due to tetracycline. JAMA 186: 175–176, 1963. Fraunfelder FT, Randall JA. Minocycline-induced scleral pigmentation.

Ophthalmology 104(6): 936–938, 1997.

Friedman DI, Gordon LK, Egan RA, et al. Doxycycline and intracranial hypertension. Neurology 62: 2297–2298, 2004.

Gardner K, Cox T, Digre KB. Idiopathic intracranial hypertension associated with tetracycline use in fraternal twins: case reports and review. Neurology 45: 6–10, 1995; Am J Ophthalmol 119: 536, 1995.

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

Krejci L, Brettschneider I, Triska J. Eye changes due to systemic use of tetracycline in pregnancy. Ophthalmic Res 12: 73, 1980.

Messmer E, et al. Pigmented conjunctival cysts following tetracycline/minocycline therapy. Histochemical and electron microscopic observations. Ophthalmology 90: 1462, 1983.

Morrison VL, Herndier BG, Kikkawa DO. Tetracycline induced green conjunctival pigment deposits. Br J Ophthalmol 89: 1372–1373, 2005.

Salamon SM. Tetracycline in ophthalmology. Surv Ophthalmol 29: 265, 1985.

Shah W, De Cock R. Actinic keratoconjunctivitis and minocycline (letter). Eye 13(Pt 1): 119–120, 1999.

Tabbara KF, Cooper H. Minocycline levels in tears of patients with active trachoma. Arch Ophthalmol 107: 93–95, 1989.

Weese-mayer DE, Yang RJ, Mayer JR, Zaparackas Z. Minocycline and pseudotumor cerebri: the well-known but well-kept secret 108: 519–520, 2001.

Wilson FM III. Adverse external ocular effects of topical ophthalmic medications. Surv Ophthalmol 24: 57, 1979.

Ocular side effect

Systemic administration – intravenous

Possible

1. Non-specific ocular irritation

a.Hyperemia

b.Eye pain

c.Foreign body sensation 2. Cornea

a.Peripheral marginal subepithelial infiltrates

b.Ulceration without staining

3. Marginal peripheral ulcerative keratitis (non-staining) (Fig. 7.1d)

4. Photophobia

5. Anterior uveitis – mild

Clinical significance

There are two reports (Esmaeli et al 2002; Fraunfelder and Harrison 2006) in which 2–4 days after receiving IV filgrastim, bilateral marginal ulcerative keratitis occurred. There were ­subepithelial infiltrates similar to those connected to connective tissue disorders such as Wegener’s granulomatosus. This is associated with ocular hyperemia, foreign body sensation and significant ocular irritation. There are only two such reports for the many thousands of patients who have been exposed to this drug so this is a rare event or may not even be drug related. One case resolved with the only treatment being artificial tears after the drug was discontinued. In the other case the patient continued the drug and the eyes were treated with topical ocular steroids and the infiltrate cleared within 24 hours.

Generic name: Filgrastim.

Proprietary name: Neupogen.

Primary use

A 175 amino acid protein used to prevent infection in neutropenic patients who are receiving myelosuppresive therapy for non-myeloid malignancies.

References and Further Reading

Esmaeli B, et al. Marginal keratitis associated with administration of filgrastim­ and sargramostim in a healthy peripheral blood progenitor cell donor. Cornea 21: 621–622, 2002.

Fraunfelder FW, Harrison D. Peripheral ulcerative keratitis associated with filgrastim. Arch Ophthalmol. February 2006.

MS# OPH06-0177.