effects side ocular induced-Drug • 7 Part

primarily in infants and young children, periocular injections or topical ocular steroids in high dosages can cause severe systemic reactions of hypertension, Cushing’s syndrome, hypertensive encephalopathy and death.

The recent popularity of subconjunctival injections of steroids has been accompanied by additional ocular drug reactions. Sub­ conjunctival injections of steroids placed over a diseased cornea or sclera can cause a thinning, and possibly a rupture, at the site of the injection. Zamir et al (2002) and Albini et al (2005) have shown that subconjunctival steroids in non-necrotizing anterior scleritis appear to be safe. Periocular injections may produce sclerosing lipogranuloma (Abel et al 2003). Posterior sub-tenon injections may cause ptosis associated with orbital fat prolapse (Dal Canto et al 2005), cutaneous hypopigmentation (Gallando and Johnson 2004), or retinal or choroidal vascular occlusion (Moshfeghi et al 2002). Feldman-Billard et al (2006) reported on a series of 25 patients with type-2 diabetes receiving subconjunctival or peribulbar injections of dexamethasone and found that this may induce a median doubling from baseline fol­ lowed by a decrease in their blood glucose around 6 hours post injection. Intractable glaucoma can occur after subconjunctival depo-injections of steroids. The surgical removal of the steroids may be required to normalize the ocular pressure. Inadvertent intraocular steroid injections have caused blindness. This is probably due to the drug vehicle. Inadvertent intraocular depot injections are numerous and include a significant toxicity vehi­ cle and the prolonged release of the steroid. While triamcinolone acetonide appears to be the least toxic of the steroid medica­ tions with inadvertent vitreous injections, often vitrectomy is required to remove the depot steroid, prevent tract bands and examine the penetration site. Pendergast et al (1995) reported a case of inadvertent depot betamethasone acetate and metha­ sone sodium phosphate preserved with benzalkonium chloride that caused severe intraocular damage. The preservative, they feel, was the reason for the ocular changes. Most feel removal of deposteroids accidentally injected into the vitreous may be con­ sidered an emergency procedure. Keeping the patient prone be­ fore surgery to prevent the material from coming into contact with the macula is important. To date, all commercial deposter­ oids contain components that are toxic to the retina.

Multiple authors (Bouzas et al 1993; Haimovici et al 1997) have implicated corticosteroids as a causative factor in pa­ tients with central serous chorioretinopathy. This may occur for oral, intranasal sprays (Haimovici et al 1997), intrajoint or epidural injections (Iida et al 2001). Carvalho-Recchia et al (2002) did a prospective case-controlled study which identified corticosteroids as a significant risk factor for the development of acute exudative macular manifestation. Systemic steroids have been implicated in causing central serous chorioretin­ opathy (DeNijs et al 2003; Levy et al 2004) when injected intravenously or by epidural injection (Pizzimenti and Daniel 2005). Steroids effect changes in almost all ocular structures. This has been reconfirmed by showing that steroids can cause microcysts of the iris pigment epithelium and of the ciliary body non-pigment epithelium. The time required for onset of a major adverse effect from topical ocular steroids varies greatly. Effects to enhance epithelial herpes simplex may be days, while it may take years for posterior subcapsular cataracts to develop. Taravella et al (1994) have shown that the topical ocular phosphate preparations can cause a corneal band keratopathy, especially in patients with sicca. Huige et al (1991) stated that topical ocular beta blockers enhance superficial stromal deposits of the phosphated forms of steroid eye drops.

References And Further Reading

Abel AD, Carlson A, Bakri S, et al. Sclerosing lipogranuloma of the orbit after periocular steroid injection. Ophthalmology 110: 1841–1845, 2003.

Agrawal S, Agrawal J, Agrawal TP. Conjunctival ulceration following triam­ cinolone injection. Am J Ophthalmol 136: 538–540, 2003.

Albini TA, Zami E, Read RW, et al. Evaluation of subconjunctival triam­ cinolone for nonnecrotizing anterior scleritis. Ophthalmology 112: 1814–1820, 2005.

Batton DG, Roberts C, Trese M, Maisels MJ. Severe retinopathy of prematu­ rity and steroid exposure. Pediatrics 90(4): 534–536, 1992.

Bouzas EA, Scott MH, Mastorakos G, et al. Central serous chorioretinopa­ thy in endogenous hypercortisolism. Arch Ophthalmol 111: 1229–1233, 1993.

Bowie EM, Folk JC, Barnes CH. Corticosteroids, central serous chorio­ retinopathy, and neurocysticercosis. Arch Ophthalmol 122: 281–283, 2004.

Carvalho-Recchia CA, Yannuzzi LA, Negrão S, et al. Corticosteroids and central serous chorioretinopathy. Ophthalmology 109: 1834–1837, 2002.

Çekiç O, Chang S, Tseng JJ, et al. Cataract progression after intravitreal triamcinolone injection. Am J Ophthalmol 139: 993–998, 2005.

Chaine G, Haouat M, Menard-Molcard C, et al. Central serous chorio­ retinopathy and systemic steroid therapy. J Fr Opthalmol 24: 139– 146, 2001.

Chen SDM, Lochhead J, McDonald B, et al. Pseudohypopyon after intravit­ real triamcinolone injection for the treatment of pseudophakic cystoid macular oedema. Br J Ophthalmol 88: 843–844, 2004.

Cohen BA, et al. Steroid exophthalmos. J Comput Assist Tomogr 5: 907, 1981.

Dal Canto AJ, Downs-Kelly E, Perry JD. Ptosis and orbital fat prolapse after posterior sub-tenon’s capsule triamcinolone injection. Ophthalmology 112: 1092–1097, 2005.

De Nijs E, Brabant P, De Laey JJ. The adverse effects of corticosteroids in central serous chorioretinopathy. Bull Soc Belge Ophtalmol 35: 35–41, 2003.

Ehrenkranz RA. Steroids, chronic lung disease, and retinopathy of prematu­ rity. Pediatrics 90(4): 646–647, 1992.

Feldman-Billard S, Du Pasquier-Frediaevsky L, Héron E. Hyperglycemia after repeated periocular dexamethasone injections in patients with diabetes. Ophthalmology 113: 1720–1723, 2006.

Fischer R, Henkind P, Gartner S. Microcysts of the human iris pigment epithelium. Br J Ophthalmol 63: 750, 1979.

Fraunfelder FT, Meyer SM. Posterior subcapsular cataracts associated with nasal or inhalation corticosteroids. Am J Ophthalmol 109(4): 489–490, 1990.

Gallardo MJ, Johnson DA. Cutaneous hypopigmentation following a posterior sub-tenon triamcinolone injection. Am J Ophthalmol 137: 780–799, 2004.

Garbe E, Suissa S, Lelorier J. Association of inhaled corticosteroid use with cataract extraction in elderly patients. JAMA 280: 539–544, 1998.

Giangiacomo J, Dueker DK, Adelstein EH. Histopathology of triamcinolone in the subconjunctiva. Ophthalmology 94: 149, 1987.

Gilles MC, Simpson JM, Billson FA, et al. Safety of an intravitreal injection of triamcinolone. Arch Ophthalmol 122: 336–340, 2004.

Gilles MC, Kuzniarz M, Craig J, et al. Intravitreal triamcinoloneinduced­ elevated intraocular pressure is associated with the development of posterior subcapsular cataract. Ophthalmology 112: 139–143, 2005.

Gupta V, Sharma SC, Gupta A. Retinal and choroidal microvascular emboli­ zation with methylprednisolone 22: 382–385, 2002.

Gupta OP, Boynton JR, Sabini P, et al. Proptosis after retrobulbar corticos­ teroid injections. Ophthalmology 110: 443–447, 2003.

Haimovici R, Gragoudas ES, Duker JS, et al. Central serous chorioretinopa­ thy associated with inhaled or intranasal corticosteroids. Ophthalmol­ ogy 104(10): 1653–1660, 1997.

Henderson RP, Lander R. Scleral discoloration associated with long-term prednisone administration. Cutis 34: 76, 1984.

Huige WM, Beekhuis WH, Rijneveld WJ, Schrage N. Unusual deposits in the superficial corneal stroma following combined use of

topical corticosteroid and beta-blocking medication. Doc Ophthalmol 78(3-4): 169–175, 1991.

Iida T, Spaide RF, Negrao SG, et al. Central serous chorioretinopathy after epidural corticosteroid injection. Am J Ophthalmol 132: 423–425, 2001.

Jick SS, Vasilakis-Scaramozza C, Maier WC. The risk of cataract among users of inhaled steroids. Epidemiology 12: 229–234, 2001.

Jonas JB, Degenring RF, Kreissig I, et al. Intraocular pressure elevation after

intravitreal triamcinolone acetonide injection. Ophthalmology 112: 593–598, 2005.

Jordan DR, Brownstein S, Lee-wing MW, et al. Orbital mass following injection with depot corticosteroids. Can J Ophthalmol 36: 153–155, 2001.

Kass MA, et al. Corticosteroid-induced iridocyclitis in a family. Am J Ophthalmol 93: 268, 1982.

Kaushik S, Gupta V, Gupta A, et al. Intractable glaucoma following intravitreal triamcinolone in central retinal vein occlusion. Am J Ophthalmol 137: 758–760, 2004.

Leibowitz HM, Bartlett JD, Rich R, et al. Intraocular pressure-raising poten­ tial of 1.0% rimexolone in patients responding to corticosteroids. Arch Ophthalmol 114: 933–937, 1996.

Levy J, Tessler Z, Klemperer I, et al. Acute intractable glaucoma after a single low-dose sub-Tenon’s corticosteroid injection for macular edema. Can J Ophthalmol 39: 672–673, 2004.

Levy J, Marcus M, Belfair N, et al. Central serous chorioretinopathy in patients receiving systemic corticosteroid therapy. Can J Ophthalmol 40: 217–221, 2005.

Lipworth BJ. Systemic adverse effects of inhaled corticosteroid therapy. Arch Intern Med 159: 941–955, 1999.

Liu GT, Kay MD, Bienfang DC, Schatz NJ. Pseudotumor cerebri associated with corticosteroid withdrawal in inflammatory bowel disease. Am J Ophthalmol 117(3): 352–357, 1994.

Mabry RL. Visual loss after intranasal corticosteroid injection. Incidence, causes, and prevention. Arch Otolaryngol 107: 484, 1981.

Meyer CH, Mennel S, Schmidt JC. Intravitreal triamcinolone acetonide may increase the intraocular pressure even in vitrectomized eyes after more than 3 months. Am J Ophthalmol 140: 766–767, 2005.

Mills DW, Siebert LF, Climenhaga DB. Depot triamcinolone-induced glaucoma­ . Can J Ophthalmol 21: 150, 1986.

Mitchell P, Cumming RG, Mackey DA. Inhaled corticosteroids, family history, and risk of glaucoma. Ophthalmology 106: 2301–2306, 1999.

Moshfeghi DM, Lowder CY, Roth DB. Retinal and choroidal vascular occlusion after posterior sub-tenon triamcinolone injection. Am J Ophthalmol 134: 132–134, 2002.

Moshfeghi AA, Scott IU, Flynn HW. Pseudohypopyon after intravitreal triamcinolone acetonide injection for cystoid macular edema. Am J Ophthalmol 138: 489–492, 2004.

Parke DW. Intravitreal triamcinolone and endophthalmitis. Am J Ophthalmol 136: 918–919, 2003.

Pendergast SD, Eliott D, Machemer R. Retinal toxic effects following inadvertent intraocular injection of Celestone Soluspan. Arch Ophthalmol 113(10): 1230–1231, 1995.

Piccolino FC, Pandolfo A, Polizzi A, et al. Retinal toxicity from accidental intraocular injection of depo-medrol. Retina 22:

117–119, 2002.

Pizzimenti JJ, Daniel KP. Central serous chorioretinopathy after epidural steroid injection. Pharmacotherapy 25: 1141–1146, 2005.

Quiram PA, Gonzales CR, Schwartz SD. Severe steroid-induced glaucoma following intravitreal injection of triamcinolone acetonide. Am J ­Ophthalmol 141: 580–582, 2006.

Ramanathan R, Siassi B, deLemos RA. Severe retinopathy of prematurity in extremely low birth weight infants after short-term dexamethasone therapy. J Perinatology 15(3): 178–182, 1995.

Romano PE. Fluorinated ocular/periocular corticosteroids have caused death as well as glaucoma in children. Clin Experiment Ophthalmol 31: 278–279, 2002.

Romano PE, Traisman HS, Green OC. Fluorinated corticosteroid toxicity in infants. Am J Ophthalmol 84: 247–250, 1977.

Roth DB, Chieh J, Spirn MJ, et al. Noninfectious endophthalmitis associ­ ated with intravitreal triamcinolone injection. Arch Ophthalmol 121: 1279–1282, 2003.

Ruiz-Moreno JM, Montero JA, Artola A, et al. Anterior chamber tansit of tiramcinolone after intravitreal injection. Arch Ophthalmol 123: 129–130, 2005.

Sahni D, Darley CR, Hawk JLM. Glaucoma induced by periorbital steroid use – a rare complication. Clin Exp Dermatol 29: 617–619, 2004.

Singh IP, Ahmad SI, Yeh D, et al. Early rapid rise in intraocular pressure after intravitreal triamcinolone acetonide injection. Am J Ophthalmol 138: 286–287, 2004.

Smeeth L, Boulis M, Hubbard R, et al. A population based case-control study of cataract and inhaled corticosteroids. Br J Ophthalmol 87: 1247–1251, 2003.

Smithen LM, Ober MD, Maranan L, et al. Intravitreal triamcinolone aceto­ nide and intraocular pressure. Am J Ophthalmol 138: 740–743, 2004.

Srinivasan S, Prasad S. Conjunctival necrosis following intravitreal injection of triamcinolone acetonide. Cornea 24: 1027–1028, 2005.

Taravella MJ, et al. Calcific band keratopathy associated with the use of topical steroid-phosphate preparations. Arch Ophthalmol 112: 608–613, 1994.

Thompson JT. Cataract formation and other complications of intravitreal triamcinolone for macular edema. Am J Ophthalmol 141: 629–637, 2006.

Tognetto D, Zenoni S, Sanguinetti G, et al. Staining of the internal limit­ ing membrane with intravitreal triamcinolone acetonide. Retina 25: 462–467, 2005.

Tsuchiya T, Ayaki M, Onishi T, et al. Three-year prospective randomized study of incidence of posterior capsule opacification in eyes treated with topical diclofenac and betamethasone. Ophthalmic Res 35: 67–70, 2003.

Zamir E, Read RW, Smith RE, et al. A prospective evaluation of subconjunc­ tival injection of tiramcinolone acetonide for resistant anterior scleritis. Ophthalmology 109: 798–807, 2002.

Class: Androgens

Generic name: Danazol.

Proprietary name: Generic only.

Primary use

This synthetic androgen is used to treat pelvic endometriosis, fibrocystic breast disease and hereditary angioneurotic edema.

Ocular side effects

Systemic administration

Certain

1. Decreased vision

2. Eyelids or conjunctiva

a.Erythema

b.Edema

c.Photosensitivity

d.Urticaria

e.Purpura

f.Loss of eyelashes or eyebrows

Possible

1. Eyelids or conjunctiva – Stevens-Johnson syndrome

Conditional/Unclassified

1. Diplopia

2. Optic nerve

a.Papilledema secondary to intracranial hypertension

b.Pallor

c.Atrophy

3. Visual field defects

4. Cataracts

Clinical significance

Decreased vision, usually associated with headaches, is the most frequent ocular side effect reported secondary to danazol. This is reversible and may resolve while continuing to take the drug. There are at least 14 cases of intracranial hypertension with papilledema associated with this drug that were either published or reported to the National Registry. Intracranial hypertension may occur while taking this medication or shortly after stopping it. While intracranial hypertension was documented in at least half of the cases, only papilledema was mentioned in the rest. Causation is unknown, but may be due to danazol-induced weight gain, fluid retention or cerebral venous thrombosis. There are not

mechanisms hormonal affecting agents and Hormones • 7 Section