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Treatment of posterior uveitis with a fluocinolone acetonide implant: three-year clinical trial results.

OBJECTIVES To evaluate the safety and efficacy of 0.59-mg and 2.1-mg fluocinolone acetonide (FA) intravitreous implants in noninfectious posterior uveitis. DESIGN A 3-year, multicenter, randomized, historically controlled trial of the 0.59-mg FA intravitreous implant in 110 patients and the 2.1-mg FA intravitreous implant in 168 patients. MAIN OUTCOME MEASURES Recurrence rate, vision, and complications. RESULTS Uveitis recurrence was reduced in implanted eyes from 62% (during the 1-year preimplantation period) to 4%, 10%, and 20% during the 1-, 2-, and 3-year postimplantation periods, respectively, for the 0.59-mg dose group (P < .01) and from 58% to 7%, 17%, and 41%, respectively, for the 2.1-mg dose group (P < .01). More implanted eyes than nonimplanted eyes had improved visual acuity (P < .01). Implanted eyes had higher incidences of intraocular pressure elevation (> or = 10 mm Hg) than nonimplanted eyes (P < .01), and glaucoma surgery was required in 40% of implanted eyes vs 2% of nonimplanted eyes (P < .01). Cataracts were extracted in 93% of phakic implanted eyes vs 20% of phakic nonimplanted eyes (P < .01). CONCLUSIONS The FA implant significantly reduced uveitis recurrence and improved or stabilized visual acuity in subjects with noninfectious posterior uveitis. Most subjects required cataract extraction, and a significant proportion required intraocular pressure-lowering surgery. APPLICATION TO CLINICAL PRACTICE The FA implant provides an alternative therapy for prolonged control of inflammation in noninfectious posterior uveitis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00407082.

ATOVAQUONE FOR THE TREATMENT OF TOXOPLASMA RETINOCHOROIDITIS IN IMMUNOCOMPETENT PATIENTS

OBJECTIVE To report the results of a phase I trial to evaluate the safety and efficacy of atovaquone for the treatment of ocular toxoplasmosis in immunocompetent patients. DESIGN Open label, nonrandomized, prospective, clinical trial. PARTICIPANTS Seventeen immunocompetent patients between the ages of 18 and 75 years with clinical and serologic evidence of ocular toxoplasmosis participated. INTERVENTION Treatment of ocular toxoplasmosis with atovaquone tablets (750 mg four times a day) for 3 months. Prednisone (40 mg) tablets were added on day 3 of treatment and tapered as inflammation resolved. MAIN OUTCOME MEASURES Clinical response and patient tolerance to atovaquone therapy for ocular toxoplasmosis. RESULTS Average follow-up was 10 months. Most patients experienced no adverse treatment effects. When present, side effects were usually mild and included rash, pruritus, headache, and nausea. With the exception of one patient, who discontinued treatment at 6 weeks secondary to persistent epigastric discomfort, all patients completed the 12 weeks of therapy. All patients had a favorable response to treatment that began within 1 to 3 weeks. Visual acuity was stabilized or improved in all patients. Median initial visual acuity was 20/200 and median final visual acuity was 20/25. In general, atovaquone was well tolerated. CONCLUSIONS Atovaquone is better tolerated than conventional antitoxoplasmosis therapy and appears to be at least as effective. Atovaquone is a promising alternative for the treatment of ocular toxoplasmosis in immunocompetent patients.

An intravitreal device providing sustained release of cyclosporine and dexamethasone.

PURPOSE A device that releases cyclosporine and dexamethasone into the eye for extended periods of time might be beneficial in diseases such as proliferative vitreoretinopathy and uveitis. In this study we examine the pharmacokinetics and toxicity of cyclosporine and dexamethasone combined in an intravitreal sustained-release device and the toxicity of a similar device containing only dexamethasone in rabbits. METHODS Rabbits were divided into three groups for (1) evaluation of the drug tissue levels and device release kinetics following implantation of a device containing 100 micrograms of cyclosporine labeled with 2 microCi of 3H-cyclosporine and 2 mg of dexamethasone; (2) evaluation of the toxicity of this intravitreal device; and (3) evaluation of the toxicity of a similar device containing 2 mg of dexamethasone only. Cyclosporine was measured using a scintillation counter and dexamethasone was measured by high pressure liquid chromatography (HPLC). Toxicity was evaluated by electroretinography, clinical examination, and light microscopy. RESULTS Vitreous concentrations of cyclosporine (+/- standard deviation) averaged 0.06 (+/- 0.02) microgram/ml over 10 weeks. The average dexamethasone concentration over the 10 week period was 2.9 (+/- 0.9) micrograms/ml. Devices containing cyclosporine and dexamethasone released each drug at rates similar to devices containing cyclosporine or dexamethasone alone. Devices containing both cyclosporine and dexamethasone caused reversible depressions in the b-wave amplitude of photopic and scotopic electroretinograms (ERGs). There was no evidence of toxicity associated with the devices containing dexamethasone only. There was no drug-related toxicity evident on clinical or histopathologic examination of eyes with devices containing the combination of cyclosporine and dexamethasone or dexamethasone alone. CONCLUSIONS We conclude that the device maintains potentially therapeutic levels of both cyclosporine and dexamethasone in the vitreous. Reversible electroretinographic abnormalities are attributable to cyclosporine. A sustained-release device containing cyclosporine and dexamethasone may be useful for reducing inflammation in diseases such as proliferative vitreoretinopathy and uveitis.

Clearance and distribution of ciprofloxacin after intravitreal injection.

This study was designed to determine the drug concentration and clearance after intravitreal injection of ciprofloxacin. Ciprofloxacin (100 micrograms/0.1 cc) was injected into the vitreous of normal eyes and into eyes that had undergone lensectomy and vitrectomy. Drug concentration was determined using high-pressure liquid chromatography analysis 0.5, 2, 4, and 12 hours after injection. In normal eyes, the elimination half life was 2.2 hours with a distribution volume of 1.2 ml. In aphakic vitrectomized eyes, the half life was 1 hour and the distribution volume was 1.4 ml. The majority of the drug appears to leave via a transretinal route, but clearance was not inhibited by probenecid. Because of the relatively short half life, intravitreal administration of ciprofloxacin for the treatment of endophthalmitis would provide only short-term therapy and would need to be supplemented by other forms of treatment.

Cranial injury from unsuspected penetrating orbital trauma: a review of five cases

Penetrating orbital-cranial injury is potentially life threatening. The history of the trauma and ophthalmologic examination may be misleadingly innocent; serious injury may be overlooked. We present five cases of orbital injury in which the diagnosis of intracranial extension was not obvious at the time of initial examination. A thorough history and physical examination should be performed on all patients, even those with apparently trivial injuries. Intracranial extension should be considered in any case where the injury was caused by an instrument small enough to enter the orbit. The threshold for obtaining a coronal CT scan of the orbits should be lowered, since this is the best way to detect an orbital roof fracture.

Anterior chamber lens implantation after vitreous loss.

Vitreous loss is a serious complication of cataract surgery. Following vitreous loss it is common practice to perform a primary implantation of an anterior chamber lens (AC-IOL). We retrospectively analysed 642 consecutive cases of cataract extraction performed between 1983 and 1986 with special attention to those patients in whom vitreous loss occurred and an AC-IOL was placed. There were 27 such cases, and 24 of these were available for follow-up. Eighteen (75%) had visual acuity of 20/40 or better. All six patients (25%) who had a visual acuity of less than 20/40 in the operated eye had a functional visual acuity of 20/200 or less. Complications that occurred in this group are discussed. We are concerned that the complications associated with vitreous loss and with AC-IOLs may be acting in concert to cause visually disabling results.

The Relationship of Mean Defect to Corrected Loss Variance in Glaucoma and Ocular Hypertension

Statistical analysis of visual-field data is permitted by the quantitative techniques used in automated perimetry. The visual-field indices mean defect (MD) and corrected loss variance (CLV) provide an opportunity to analyze and follow visual fields mathematically. We investigated the relationship of MD to CLV in 32 glaucoma suspects and 17 patients with visual-field defects due to chronic open-angle glaucoma. In glaucoma patients with early and moderate disease (up to a MD of 18 dB), the CLV statistically covaried with the MD (R2 = 0.85). Beyond an MD of 18 dB, increases in the MD seemed to cause a decline in the CLV. These results differ from prior reports on the relationship of MD and CLV. Reasons for this and implications for the use of these statistics in the clinical management of the glaucoma patient are discussed. These results may be helpful in the understanding of the pathophysiologic basis of damage in glaucoma.

Optic nerve edema as a consequence of respiratory disease

Article abstract The authors describe a patient with bilateral papilledema, visual field abnormalities, poorly reactive pupils, meningeal enhancement on cranial MRI, and diffuse brain parenchymal hypervascularity. The opening pressure at the time of lumbar puncture was normal, and results of other CSF studies were normal. All abnormalities resolved with home oxygen therapy.