Biomedical subjects

Lisa R Grillone

Publications and source records attributed to Lisa R Grillone.

4 recordsLinked to original sources

PubMed2005

Pooled efficacy results from two multinational randomized controlled clinical trials of a single intravitreous injection of highly purified ovine hyaluronidase (Vitrase) for the management of vitreous hemorrhage.

PURPOSE: To evaluate the efficacy of intravitreous ovine hyaluronidase for the management of vitreous hemorrhage. DESIGN: Two prospective, randomized, placebo-controlled, double-masked studies. Safety data are presented in a companion article in The Journal. METHODS: Eligible patients with vitreous hemorrhage > or = 1 month duration; severe at entry with best corrected visual acuity (BCVA) worse than 20/200 were randomized to 55 IU or 75 IU ovine hyaluronidase or saline. Primary efficacy (clearance of hemorrhage sufficient to see the underlying pathology and completion of treatment when indicated) was measured at months 1, 2, and 3. Key secondary endpoints were: > or = 3-line improvement in BCVA; hemorrhage density reduction; and therapeutic utility assessment. RESULTS: The intent-to-treat population for common dose groups (55 IU, 75 IU, saline) consisted of 1125 patients. At baseline, 76.3% had diabetes, 90.4% were not able to read any letters on the eye chart, and mean hemorrhage duration was 120 days. Statistical significance was reached in the 55 IU dose group by months 1 and 2 for the primary efficacy endpoint based on an adjusted P-value. By months 1, 2, and 3, 13.2%, 25.5%, and 32.9% of patients (55 IU) reached primary efficacy compared with 5.5%, 16.2%, and 25.6% of saline-treated patients (P < .001; P = .002; P = .025, respectively). Key secondary endpoints confirmed the treatment effect at both doses and all timepoints (P < or = .01). CONCLUSIONS: Fifty-five IU ovine hyaluronidase showed statistically significant efficacy as early as months 1 and 2. These results were supported by outcomes for three key secondary endpoints. These results suggest a therapeutic utility of ovine hyaluronidase in the management of vitreous hemorrhage.

Diabetes Mellitus, Type 1↗

PubMed2005

Safety results of two phase III trials of an intravitreous injection of highly purified ovine hyaluronidase (Vitrase) for the management of vitreous hemorrhage.

PURPOSE: To evaluate the safety of intravitreous ovine hyaluronidase for the management of vitreous hemorrhage. DESIGN: Two prospective, randomized, placebo-controlled, double-masked studies. Pooled efficacy data are presented in a companion article in this issue of The Journal. METHODS: Subjects with vitreous hemorrhage > or = 1 month, severe at entry and best corrected visual acuity (BCVA) worse than 20/200 in the study eye were randomized to 7.5 IU, 55 IU, 75 IU ovine hyaluronidase, saline, or no injection. Assessments occurred on day 1, week 1, months 1, 2, 3, 6, and then every 6 months for as long as 32 months. Assessments included history, ocular symptoms, adverse events, BCVA, intraocular pressure, external eye examination, slit-lamp biomicroscopy, fundus examination, B-scan ultrasonography, and fundus photography. RESULTS: Of 1362 subjects in the safety population, 1344 received hyaluronidase or saline and 18 no treatment. Iritis was the most common ocular adverse event, occurring in 33.3%, 62.1%, 58.9%, and 62.1% of saline, 7.5 IU, 55 IU, and 75 IU-treated subjects. In eyes with more than mild iritis, a dose response was observed: 8.9%, 20.2%, 33.7%, and 39.7% of saline, 7.5 IU, 55 IU, and 75 IU-treated subjects, respectively, were noted to have moderate or severe iritis. Retinal detachments (RDs) were reported in 9.5% of study eyes: 26 (6.9%), 22 (11.1%), 35 (9.3%), and 45 (11.5%) in the saline, 7.5 IU, 55 IU, and 75 IU-treated subjects. Overall, 1.8% of study eyes had rhegmatogenous RD: 1.1%, 2.5%, 1.6%, and 2.3% of saline, 7.5, 55, and 75 IU treated subjects. Cataracts occurred similarly across treatment groups. No injection-related infectious endophthalmitis was reported. CONCLUSIONS: No serious safety issues were reported after a single intravitreous injection of ovine hyaluronidase. RD incidence was not statistically different between groups. Iritis manifesting as an acute self limited inflammation was the most common adverse event, occurred in a dose response fashion, but was not noted to result in a serious adverse event in any hyaluronidase treated eye.

Aged↗

PubMed2004

Evolving guidelines for intravitreous injections.

Intravitreous (i.v.t.) injection is increasingly being incorporated into the management of ocular diseases. While only fomivirsen sodium (Vitravene) is currently approved by the Food and Drug Administration as an i.v.t. injection, the number of approved i.v.t. injections indications is anticipated to grow on the basis of promising results from ongoing clinical studies. Despite the potential benefits that may be derived from intraocular injections of different agents, no guidelines have been published previously for i.v.t. injection. The purpose of this document is to identify specific strategies for the delivery of i.v.t. injection that may reduce risks and improve outcomes. Consensus was sought among a panel of investigators, surgeons experienced with this technique, and industry representatives. Objective evidence was sought for all guidelines, but consensus was accepted where evidence remains incomplete. In the absence of either evidence or consensus, the current manuscript identifies outstanding issues in need of further investigation. It is anticipated that more complete guidelines will evolve over time, potentially altering some of the guidelines included here, based on new applications of i.v.t. injection, additional clinical experience, and results of clinical trials.

Humans↗

PubMed2002

Fomivirsen: clinical pharmacology and potential drug interactions.

Fomivirsen sodium is a 21-base phosphorothioate oligodeoxynucleotide complementary to the messenger RNA of the major immediate-early region proteins of human cytomegalovirus, and is a potent and selective antiviral agent for cytomegalovirus retinitis. Following intravitreal administration, fomivirsen is slowly cleared from vitreous with a half-life of approximately 55 hours in humans. Preclinical studies show that fomivirsen distributes to retina and is slowly metabolised by exonuclease digestion. Clearance from retina was shown to be similarly slow following loading from the vitreous. The estimated half-life for clearance of fomivirsen from retina was 78 hours in monkeys following a 115-microg dose. Because of the low doses coupled with slow disposition from the eye, measurable concentrations of drug are not detected in the systemic circulation following intravitreal administration. Systemically administered phosphorothioate oligodeoxynucleotides are highly bound to albumin and alpha2-macroglobulin in blood plasma. Because fomivirsen does not compete for oxidative metabolic processes involved in clearance of many xenobiotics, the most likely mechanism for drug interactions may be altered protein binding of a coadministered drug. The extremely low systemic exposure to this oligodeoxynucleotide following intravitreal administration largely negates its potential ability to interact with systemically administered drugs. Even if fomivirsen were able to access the blood, protein binding assays indicate that drugs that are site I and site II binders of albumin (warfarin, ibuprofen, salicylic acid) are not displaced in the presence of phosphorothioate oligodeoxynucleotides of various sequences at concentrations orders of magnitude higher than that seen for fomivirsen. Administration of fomivirsen with numerous systemically administered antiretrovirals (for example zidovudine and zalcitabine) as well as systemically administered anticytomegalovirus agents such as foscarnet and ganciclovir has been reported to be well tolerated. The only reported warning is a recommendation against administration within 2 to 4 weeks of cidofovir treatment due to an increased risk of ocular inflammation.

Animals↗