Drug-induced ocular disorders.

While beneficial therapeutically, almost all medications have untoward effects on various body tissues and functions, including the eye in which organ toxic reactions are readily detectable. Every part of the eye and all ocular functions could be affected adversely. In this review, we describe the most commonly recognized drug-induced ocular disorders, their specific clinical features, the medications that can cause the problem, the differential diagnosis and possible mechanisms of action, as well as guidelines for the management of the adverse reactions. The eyelids are most frequently involved in drug toxicity that commonly manifests as inflammation, hypersensitivity reaction or dermatitis. Drug-induced keratoconjunctival disorders present mainly as conjunctival hyperaemia (red eye), with or without superficial corneal involvement. Frequently, drug preservatives in topical ocular medications induce these adverse effects. Treatment of blepharospasm with Botox may lead to drooping of the eyelids and corneal exposure. Intraoperative floppy iris syndrome is a drug-induced reaction in patients treated with tamsulosin and who undergo cataract surgery. Certain sulfa-based drugs can cause swelling of the ciliary body and lead to the development of angle-closure glaucoma. In addition, adrenergic agents, certain beta(2)-adrenergic agonists and anticholinergic agents may induce pupillary dilation and precipitate angle-closure glaucoma in susceptible patients. Glucocorticoids administered systemically, topically or intravitreally are known to increase intraocular pressure, which can lead to the development of open-angle glaucoma in susceptible patients. This painless form of glaucoma has also been associated with the use of the anticancer agents docetaxel and paclitaxel. The toxic effects of systemic and topically applied drugs may manifest as cloudiness of the lens. Long-term use of glucocorticoids produces a characteristic posterior subcapsular cataract and, although the opacities may remain stationary or progress, they rarely regress upon drug withdrawal. Systemic administration of phenothiazines or busulfan induce cataractous changes in the anterior or posterior cortex, respectively. Many systemic drugs reach the retina through the vascular supply. Aminoquinolines induce a characteristic bull's eye maculopathy. Phenothiazines bind to melanin granules and can cause a severe phototoxic retinopathy. Typical tamoxifen retinopathy manifests as crystalline deposits in the inner retina. Some patients treated with retinoids have decreased night vision and abnormal dark-adaptation. Patients on long-term treatment with linezolid may develop an optic neuropathy (swollen or pale optic disc), symmetric painless decrease of visual acuity and colour vision, and bilateral visual field defects. A probable link exists between amiodarone and a bilateral optic neuropathy that is very similar to nonarteritic ischaemic optic neuropathy (NAION). The most common adverse effects of cGMP-specific phosphodiesterase type 5 inhibitors (erectile dysfunction drugs) are changes in colour perception, blurry vision and increased light sensitivity; recently these drugs have been also implicated in the development of NAION. A bilateral, retrobulbar optic neuropathy that manifests as loss of visual acuity or colour vision and visual field defect is associated with the use of ethambutol. Many different kinds of medications can cause similar ocular adverse reactions. Conversely, a single medication may affect more than one ocular structure and cause multiple, clinically recognizable disorders. Clinicians should be mindful of drug-induced ocular disorders, whether or not listed in product package inserts, and, if in doubt, consult with an ophthalmologist.

Effects of interleukin-1beta and dexamethasone on the expression of matrix metalloprotease mRNA by trabecular cells exposed to elevated hydrostatic pressure.

PURPOSE: We investigated the effects of interleukin-1beta (Il-1beta) and dexamethasone (Dex) on the expression of matrix metalloprotease-1, -2, -3 and -14 (membrane type-1 MMP-MT1-MMP) as well as tissue inhibitors of matrix metalloproteases (TIMP-1 and -2) mRNA by trabecular cells exposed not only to normal, but also to elevated levels of hydrostatic pressure. METHODS: Confluent primary cultures of porcine trabecular cells were incubated in a serum-free medium (SFM) as controls, or in SFM containing either 10 ng/ml Il-1beta or 10 nm Dex and exposed to pressures of 15 mmHg or 50 mmHg (corresponding to normal and high intraocular pressure, respectively) in specially designed pressure chambers. After 72 hours, total RNA was extracted from the harvested cells, reverse transcribed and amplified using primers specific to MMP-1, -2, -3 and -14, and TIMP-1 and -2. RESULTS: The most significant changes were detected in the levels of MMP-3 mRNA in control cells (2.4-fold increase), of TIMP-1 and -2 mRNA in cells treated with Il-1beta (2.6-fold increase) and of MMP-3 mRNA in cells treated with Dex (3.5-fold increase) exposed to 50 mmHg pressure. CONCLUSION: Because MMP-3 (stromelysin) mRNA showed the highest upregulation, our findings suggest that trabecular cells preferentially degrade and turn over the proteoglycan components of the extracellular matrix in response to short-term exposure to increased hydrostatic pressure with and without Dex as a homeostatic mechanism.

Trabecular cell expression of fibronectin and MMP-3 is modulated by aqueous humor growth factors.

We investigated the mRNA and protein expression of fibronectin and stromelysin-1 (matrix metalloproteinase-3, MMP-3) by trabecular cells treated with growth factors present in primary and secondary aqueous humors. Serum-deprived trabecular cells were incubated for 48 hr or 7 days in medium containing either primary or secondary aqueous humor growth factors or in serum-free medium. We extracted total RNA, performed reverse transcription-polymerase chain reaction using primer pairs for fibronectin, stromelysin-1 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and quantified the products. We utilized Western blotting to detect and quantify fibronectin and stromelysin-1 protein. Compared to controls, expression of fibronectin mRNA by trabecular cells was increased by 50 and 100% after incubation in primary aqueous humor growth factors for 48 hr or 7 days, respectively, and 50 and 130% after incubation in secondary aqueous humor growth factors. Stromelysin-1 mRNA expression was decreased by 25 and 50% after incubation in primary aqueous humor growth factors for 48 hr or 7 days, respectively, and 80 and 85% after incubation for 48 hr or 7 days, respectively, in secondary aqueous humor growth factors. Fibronectin protein increased 3.5-fold and 6-fold after incubation for 48 hr with primary or secondary aqueous humor growth factors, respectively; after 7 days, the level increased 4- and 7-folds, respectively. Stromelysin-1 protein was not detectable by western blotting. The up-regulation of fibronectin mRNA by trabecular cells exposed to growth factors present in secondary aqueous humor augmented by the down-regulation of stromelysin-1 mRNA contributed to the accumulation of fibronectin. Our findings open the possibility that induction of stromelysin-1 gene expression in the trabecular meshwork of glaucomatous eyes could effectively reduce buildup of fibronectin in the aqueous outflow pathway to decrease outflow resistance in glaucomatous states of the eye.

Drug-induced glaucomas: mechanism and management.

Glaucoma comprises a heterogeneous group of diseases that have in common a characteristic optic neuropathy and visual field defects, for which elevated intraocular pressure is the major risk factor. The level of intraocular pressure within the eye depends on the steady state of formation and drainage of the clear watery fluid, called the aqueous humour, in the anterior chamber of the eye. An obstruction in the circulatory pathway of aqueous humour causes an elevation in intraocular pressure. Because intraocular pressure is the most modifiable parameter, therapeutic measures (medical and surgical) are aimed at reducing the pressure to protect against optic nerve damage. Glaucomatous optic neuropathy results from degeneration of the axonal nerve fibres in the optic nerve and death of their cell bodies, the retinal ganglion cells. Clinical examination of the optic nerve head or disc and the peripapillary nerve fibre layer of the retina reveals specific changes, and the resulting visual field defects can be documented by perimetry. Glaucoma can be classified into four main groups: primary open-angle glaucoma; angle-closure glaucoma; secondary glaucoma; and developmental glaucoma. Drug-induced glaucoma should be considered as a form of secondary glaucoma because it is brought about by specific systemic or topical medications. Although there is a high prevalence of glaucoma worldwide, the incidence of drug-induced glaucoma is uncertain. Drugs that cause or exacerbate open-angle glaucoma are mostly glucocorticoids. Several classes of drugs, including adrenergic agonists, cholinergics, anticholinergics, sulpha-based drugs, selective serotonin reuptake inhibitors, tricyclic and tetracyclic antidepressants, anticoagulants and histamine H(1) and H(2) receptor antagonists, have been reported to induce or precipitate acute angle-closure glaucoma, especially in individuals predisposed with narrow angles of the anterior chamber. In some instances, bilateral involvement and even blindness have occurred. In this article, the mechanism and management of drug-induced glaucomatous disease of the eye are emphasised. Although the product package insert may mention glaucoma as a contraindication or as an adverse effect, the type of glaucoma is usually not specified. Clinicians should be mindful of the possibility of drug-induced glaucoma, whether or not it is listed as a contraindication and, if in doubt, consult an ophthalmologist.

Pars plana modified Baerveldt implant versus neodymium:YAG cyclophotocoagulation in the management of neovascular glaucoma.

OBJECTIVE: To determine the relative effectiveness of neodymium:YAG cyclophotocoagulation (NCYC) and pars plana modified Baerveldt implant (PPBI) surgery on intraocular pressure (IOP) control in eyes with neovascular glaucoma (NVG). PARTICIPANTS: In this retrospective comparative group study, 30 patients with NVG treated with contact NCYC were compared with 18 patients who underwent PPBI. Patients groups were not statistically dissimilar with respect to the underlying disorder-causing angle and iris neovascularization, intraocular pressure, and patient's age. RESULTS: During a follow up of 6 months, an IOP control of > or = 6 and < or = 21 mm Hg was achieved in 23 eyes (76.6%) treated with NCYC compared with 17 eyes (94.4%) receiving PPBI (P = 0.13). Among eyes that had unsuccessful outcome in both groups, the proportions with persistently high IOP or hypotony were greater in the NCYC group than in the PPBI group. Based on our criteria, the cumulative proportion of failure in the NCYC group was 23.3% at 6 months as compared to 5.6% in the PPBI group. Seven eyes (23.3%) in the NCYC group lost light perception versus 1 eye (5.6%) in the PPBI group. The incidence of postoperative choroidal effusion (36%) was higher in the PPBI group. CONCLUSIONS: This study suggests that in the management of NVG, PPBI surgery more frequently controls IOP in a medically acceptable range with less hypotony and greater preservation of visual acuity than NCYC.