Local chemotherapeutic agents for the treatment of ocular malignancies

We critically analyze available peer-reviewed literature, including clinical trials and case reports, on local ocular cancer treatments. Recent innovations in many areas of ocular oncology have introduced promising new therapies, but, for the most part, the optimal treatment of ocular malignancies remains elusive.     

Desferrioxamine-related ocular toxicity: a case report

A 29-year-old lady receiving repeated blood transfusions for β thalassemia since childhood, presented with rapidly deteriorating symptoms of night blindness and peripheral visual field loss. She was recently commenced on high-dose intravenous desferrioxamine for reducing the systemic iron overload. Clinical and investigative findings were consistent with desferrioxamine-related pigmentary retinopathy and optic neuropathy. Recovery was partial following cessation of desferrioxamine. This report highlights the ocular side-effects of desferrioxamine mesylate and the need to be vigilant in patients on high doses of desferrioxamine.     

Eicosanoids as a new class of ocular hypotensive agents. 2. Comparison of the apparent mechanism of the ocular hypotensive effects of A and F type prostaglandins

It has recently been shown that derived prostaglandins (PGs) of the A and B types are much more potent ocular hypotensive agents than primary PGs of the E, F, or D type. The purpose of this study was to determine whether two representatives of these structurally different PGs, namely PGA2 and PGF2 alpha-1-isopropyl ester (PGF2 alpha IE), reduce intraocular pressure (IOP) of the feline eye by similar or dissimilar mechanisms. Aqueous humor flow rate was determined by a fluorophotometric technique, Schiotz electronic tonography was used to measure outflow facility and venomanometry was done to measure episcleral venous pressure. Although at the doses used, both PGF2 alpha IE (2.5 micrograms/eye) and PGA2 (5.0 micrograms/eye) caused significant IOP reduction within 2.5 hr after their topical application, neither caused a significant decrease in aqueous humor flow rate, a significant increase in outflow facility or a change in episcleral venous pressure. It was concluded, therefore, that both of these PGs reduce IOP by an apparently similar mechanism, presumably by increasing uveoscleral outflow.     

Fourth-generation fluoroquinolones: new topical agents in the war on ocular bacterial infections

PURPOSE OF REVIEW: The fourth-generation fluoroquinolones, moxifloxacin and gatifloxacin, were introduced in 2003 promising improved spectrum of activity and delayed development of resistance. Although these topical agents have recently been introduced in commercial form, there is already a growing body of evidence showing excellent potency in the war on ocular infections. The purpose of this review is to discuss the literature to date regarding these two agents. RECENT FINDINGS: Since their introduction in 1990 in the United States, fluoroquinolones have rapidly become the standard of care in the topical antibiotic arena. Unfortunately, recent evidence has shown the widespread use of fluoroquinolones, not only in eye care, but also in agriculture, and general medical and surgical use, has lead to decreasing susceptibilities of important ocular bacterial pathogens. Moxifloxacin and gatifloxacin have improved potency and are able to overcome resistant isolates. These agents also provide improved penetration into ocular tissues. SUMMARY: Moxifloxacin and gatifloxacin offer improved spectrum of activity, increased penetration into ocular tissues, and delayed propensity to the development of bacterial antibiotic resistance.     

Deferoxamine-related ocular toxicity: incidence and outcome in a pediatric population

PURPOSE: Deferoxamine (DFO) is a chelating agent used widely for the treatment of transfusional hemochromatosis. DFO-related ocular toxicity has been previously reported several times, and many institutions have adopted an ophthalmic screening protocol for patients treated with DFO despite little information regarding the rate of ocular toxicity. Our study aimed to determine the incidence of DFO toxicity at a major pediatric hospital that uses regular ophthalmic screening for all DFO-treated patients. METHODS: A retrospective case series of all patients treated with DFO for transfusional hemochromatosis at The Hospital for Sick Children (Toronto, Ontario, Canada) between 1995 and 2005 inclusive. RESULTS: A total of 84 patients received regular DFO treatment for transfusional hemochromatosis related to long-term hypertransfusion. A total of 421 ophthalmic screening examinations were performed (average, 5.0 examinations per patient). DFO-related ocular toxicity was found only in one patient (1.2%). This patient had central blurriness and retinal pigmentary changes shown by examination and decreased central responses shown by electroretinography, but these changes were all found to be completely reversible after a change from intravenous to subcutaneous therapy at a reduced dose. CONCLUSIONS: In this large pediatric center, DFO-related ocular toxicity has been a rare and mild finding. Regular ophthalmic screening should be carried out for patients receiving high-dose subcutaneous or intravenous therapy, because early detection of retinal toxicity may lead to optimization of the DFO dose and thus prevention of long-term visual sequelae.     

Effects of selected repeated intravitreal chemotherapeutic agents

The toxic effects of repeated intravitreal injections of selected chemotherapeutic agents were studied in female albino rabbits. Three groups of eyes participated in each therapeutic regimen. Agents studied were doxorubicin (dox), 3 and 5ug; 5-fluorouracil (5-FU), 0.375 and 1.0 mg; bleomycin (bleo), 15 ug; thiotepa (thio), 12 ug; etoposide (VP-16), 150 ug; and methotrexate (MTX), 600 ug. Toxicity was evaluated using electroretinography (ERG) in 66% and histopathology in 100% of eyes 5 weeks following the initial injection and at least 2 weeks after the final injection of each series. Eyes receiving 2 doses of dox 3 ug showed no toxicity. Eyes receiving 3 or more doses of dox 3 ug and those treated with 2 or more doses of dox 5 demonstrated toxicity proportional to the number of doses received.Eyes treated with 5-FU 0.375 or 1.0 mg showed no toxic reaction. Successive intravitreal injections of 5-FU, 0.375 mg and dox 5 ug, and 5-FU, dox, and bleo produced no toxicity. Eyes treated with successive intravitreal injections of 5-FU, dox, bleo, and thio displayed decreased ERG response. The addition of VP-16 and MTX resulted in further loss of ERG response and more severe histologic retinal changes.     

Pathology of practolol-induced ocular toxicity.

The ocular side-effects of prolonged practolol administration concern the cornea and conjunctiva and are related to deficient tear secretion and the formation of an autoantibody which has an affinity for the intercellular zones of squanmous epithelium. Histopathological study of six cases, including a review of the necropsy findings in two, showed destruction of lacrimal gland tissue, epidermalization of the conjunctival epithelium, with epitheliolysis and stromal ulceration of the cornea leading to perforation in two patients. Immunoperoxidase studies showed fixation of specific antibody in the corneal and conjunctival epithelium but, in the one case in which the tissue could be adequately studied, complement fixation could not be demonstrated. Possibly, therefore, the immune response in patients with practolol-induced ocular damage is secondary to the epithelial disturbance rather than its cause.     

载抗感染药物的眼内缓释给药系统的应用

眼内感染性疾病对视功能危害极大,常规治疗方法存在着许多局限性.缓释给药系统具有高效、低毒以及患者易于接受等优点,载抗感染药物的眼内缓释给药系统有可能成为治疗眼内感染性疾病的有效手段,已成为近年来眼科学相关领域的研究热点.     

Experimental studies with timolol: a new ocular hypotensive agent (author's transl)]

The present report reviews the animal pharmacology supporting the clinical use of timolol maleate ophthalmic solution in the therapy of glaucoma and elevated intraocular pressure (IOP). The studies have included the effects of timolol upon normal IOP of rabbits and upon elevated IOP in two models of experimental ocular hypertension. Comparisons are made between the latter actions of timolol and those of the reference adrenergic antiglaucoma agent, epinephrine. The interaction of timolol and the beta-adrenergic stimulant, isoproterenol, was also studied to assess the ability of timolol to block beta-adrenergic receptors in the eye. Additionally, the penetration and distribution of timolol in ocular and extraocular tissues and fluids following local application to the eyes of rabbits is described and a resume of the toxicological studies with timolol are presented.