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Biomedical subjects

Donald J D'Amico

Publications and source records attributed to Donald J D'Amico.

At least 19 recordsLinked to original sources
PubMed2006

Pegaptanib sodium for neovascular age-related macular degeneration: two-year safety results of the two prospective, multicenter, controlled clinical trials.

OBJECTIVE: To evaluate the safety of pegaptanib sodium injection, a specific vascular endothelial growth factor (VEGF) antagonist, in the treatment of neovascular age-related macular degeneration (AMD) during 2 years of therapy. DESIGN: Two concurrent, prospective, randomized, multicenter, double-masked, sham-controlled studies. METHODS: Patients with all angiographic choroidal neovascularization lesion compositions of AMD received either intravitreous pegaptanib sodium (0.3 mg, 1 mg, 3 mg) or sham injections every 6 weeks for 54 weeks. Those initially assigned to pegaptanib were re-randomized (1:1) to continue or discontinue therapy for 48 more weeks; sham-treated patients were re-randomized (1:1:1:1:1) to continue sham, discontinue, or receive one of the pegaptanib doses. MAIN OUTCOME MEASURES: All reported adverse events, serious adverse events, and deaths. PARTICIPANTS: In year 1, 1190 subjects received at least one study treatment (0.3 mg, n = 295; 1 mg, n = 301; 3 mg, n = 296; sham, n = 298); 7545 intravitreous injections of pegaptanib were administered. In year 2, 425 subjects (0.3 mg, n = 128; 1 mg, n = 126; 3 mg, n = 120; sham, n = 51) continued the same masked treatment as in year 1 and received at least one study treatment in year 2; 2663 intravitreous injections of pegaptanib were administered in these subjects. RESULTS: All doses of pegaptanib were well tolerated. The most common ocular adverse events were transient, mild to moderate in intensity, and attributed to the injection preparation and procedure. There was no evidence of an increase in deaths, in events associated with systemic VEGF inhibition (e.g., hypertension, thromboembolic events, serious hemorrhagic events), or in severe ocular inflammation, cataract progression, or glaucoma in pegaptanib-treated patients relative to sham-treated patients. In year 1, serious injection-related complications included endophthalmitis (12 events, 0.16%/injection), retinal detachment (RD) (6 events [4 rhegmatogenous, 2 exudative], 0.08%/injection), and traumatic cataract (5 events, 0.07%/injection). Most cases of endophthalmitis followed violations of the injection preparation protocol. In patients receiving pegaptanib for >1 year, there were no reports of endophthalmitis or traumatic cataract in year 2; RD was reported in 4 patients (all rhegmatogenous, 0.15%/injection). CONCLUSION: The 2-year safety profile of pegaptanib sodium is favorable in patients with exudative AMD.

Aged↗
PubMed2006

In vivo redirection of retinal blood flow into borosilicate micro-cannulas in rabbits.

BACKGROUND: Microvascular manipulation is one application in the emerging field of retinal vascular surgery that could lead to new therapeutic approaches for retinal disease. Research in this field has largely focused on vessel cannulation and injection of vasoactive substances. This study expands on applications for retinal vessel manipulation by demonstrating that redirection of retinal blood flow in vivo can be achieved through retinal vessel cannulation in a rabbit model. METHODS: Dutch-belted rabbits were anesthetized, and a sectoral peritomy and sclerotomy 1 mm from the superotemporal limbus were performed. Borosilicate glass microtips with external diameters of 10-20 mum were introduced into the vitreous through the sclerotomy site. Using an operating microscope and a direct contact lens for visualization, we cannulated the rabbits' retinal vessels, and blood flow was redirected through the microtips. RESULTS: Retinal vessels approximately 30-60 mum in size were cannulated, and controlled blood flow through the microcannula was demonstrated with minimal or no vitreous hemorrhage. Though still achievable, flow after arterial cannulation was more difficult to demonstrate. CONCLUSIONS: This study demonstrates that partial diversion of blood flow from a native vessel lumen could be successfully accomplished by retinal vessel cannulation. This early work indicates that more advanced retinal vascular procedures, such as vessel bypass around a thrombus or shunting blood towards an area of ischemic retina, may be feasible in the future.

Anastomosis, Surgical↗
PubMed2006

Predictors of visual outcome and choroidal neovascular membrane formation after traumatic choroidal rupture.

OBJECTIVE: To determine predictors of choroidal neovascularization (CNV) and visual outcome after traumatic choroidal rupture. METHODS: A retrospective review of patients with traumatic choroidal rupture diagnosed in the Retina Service, Massachusetts Eye and Ear Infirmary, Boston, between January 1993 and August 2001 was performed. Parametric and nonparametric statistical methods were used to evaluate visual prognosis, CNV, and retinal detachment after traumatic choroidal rupture. RESULTS: One hundred eleven cases were identified and reviewed. Visual acuity (VA) changes were recorded in all of the cases. Thirty-eight (34%) of the 111 patients recovered driving vision (VA > or =20/40). Rupture location was recorded in 107 cases. Recovery of driving vision was seen in 20 (59%) of 34 eyes with peripheral choroidal ruptures, 17 (22%) of 73 eyes with macular choroidal ruptures, 38 (38%) of 99 eyes without CNV, 1 (8%) of 12 eyes with CNV, 38 (40%) of 96 eyes without retinal detachment, and 1 (7%) of 15 eyes with retinal detachment. Older age and location of rupture within the arcades were positively associated with CNV formation (P = .04 and .03, respectively). Foveal location of rupture, multiple ruptures, and poor baseline VA were associated with failure to recover driving vision in univariate regression analyses. In multivariate analysis, rupture location and baseline VA were independently associated with visual outcome. Of 12 patients diagnosed with CNV, 5 were not treated, 4 were treated with argon laser photocoagulation, 1 was treated with surgery, 1 was treated with argon laser photocoagulation followed by surgery, and 1 was treated with verteporfin photodynamic therapy. CONCLUSIONS: Most patients with traumatic choroidal rupture do not achieve final VA of 20/40 or better. Poor visual outcome was most highly associated with a macular rupture and baseline VA of less than 20/40. The formation of CNV was most strongly associated with older age and macular choroidal rupture.

Adolescent↗
PubMed2006

Lamina puncture for central retinal vein occlusion: results of a pilot trial.

OBJECTIVE: To evaluate the effect of treatment by lamina puncture, a novel procedure to create a perivascular opening within the optic nerve head by a transvitreal approach, on visual acuity after central retinal vein occlusion (CRVO) in older patients. METHODS: The patients comprised a nonrandomized, consecutive, interventional case series of older patients being seen with CRVO. Patients 65 years or older with CRVO and a visual acuity of 20/200 or worse were treated with vitrectomy and lamina puncture of the optic disc. Preoperative visual acuity, clinical examination results, and fluorescein angiography results were compared with postoperative results. RESULTS: Twenty patients (12 men and 8 women), an average age of 72 years, were enrolled. The mean duration of CRVO was 5.4 months; 14 eyes had nonischemic CRVO when first seen, while 6 had substantial ischemia. The mean preoperative visual acuity was in the counting fingers range, and the mean postoperative visual acuity was also in the counting fingers range. Complications included 5 eyes with iris neovascularization, of which 4 progressed to neovascular glaucoma; also, preoperative ischemia seemed to predispose to neovascular complications. CONCLUSION: Lamina puncture does not restore visual acuity in older patients with CRVO.

Aged↗
PubMed2006

Pegaptanib (Macugen): treating neovascular age-related macular degeneration and current role in clinical practice.

Repeated Macugen intravitreal injections, well tolerated and safe when performed according to protocol, is the first successful pharmacotherapy for wet AMD. Macugen has already had a significant impact on neovascular AMD management, in regard to both individual patients with AMD lesions that would become amenable to treatment, and in its effects on visual function and its preservation in the aging United States population. Although results and delivery method are not optimal, the positive outcomes indicate the beginning, and not the limit, of pharmacotherapy for AMD. The benefits of Macugen therapy for AMD strongly outweigh the risks. It is pointed out by some that the overall magnitude of the efficacy results is very similar to the PDT trials and question why there is so much enthusiasm about a treatment that entails intravitreal injections every 6 weeks instead of PDT every 12 weeks. In all fairness, PDT is not equally efficacious across the lesion subtypes and sizes, whereas Macugen has effect with all lesion subtypes. In addition, these studies widen the armamentarium and open up the possibility of combination therapy in attacking neovascularization through multiple ways.

Aptamers, Nucleotide↗
PubMed2005

Anecortave acetate (15 milligrams) versus photodynamic therapy for treatment of subfoveal neovascularization in age-related macular degeneration.

PURPOSE: To compare 1-year safety and efficacy of anecortave acetate 15 mg with photodynamic therapy (PDT) with verteporfin in patients eligible for initial PDT treatment. DESIGN: Prospective, masked, randomized, multicenter, parallel group, active control, noninferiority clinical trial. PARTICIPANTS: Five hundred thirty patients with predominantly classic subfoveal choroidal neovascularization secondary to age-related macular degeneration were randomized to treatment with either anecortave acetate 15 mg or PDT. METHODS: In the anecortave acetate group, the drug was administered under the Tenon's capsule as a periocular posterior juxtascleral depot (PJD) at the beginning of the study and at month 6. Before the first administration of anecortave acetate, patients in this treatment group received a sham PDT treatment, and sham PDT treatments were repeated every 3 months if there was evidence of leakage on fluorescein angiography (FA). Patients assigned to PDT received up to 4 PDT treatments at 3-month intervals, as needed based upon FA, and a sham PJD procedure at the beginning of the study and at month 6. Best-corrected visual acuity was determined at baseline and all follow-up visits. Safety data were regularly reviewed by an independent safety committee. MAIN OUTCOME MEASURE: Percent responders (patients losing <3 lines of vision) at month 12. RESULTS: Percent responders in the anecortave acetate and PDT groups were 45% and 49%, respectively (not statistically different, P = 0.43). The confidence interval (CI) for the difference ranged from -13.2% favoring PDT to +5.6% favoring anecortave acetate. The month 12 clinical outcome for anecortave acetate was improved in patients for whom reflux was controlled and who were treated within the 6-month treatment window (57% vs. 49%; 95% CI, -4.3% favoring PDT to +21.7% favoring anecortave acetate). No serious adverse events related to the study drug were reported in either treatment group. CONCLUSIONS: The safety and efficacy outcomes in this study demonstrate that the benefits of anecortave acetate for the treatment of choroidal neovascularization outweigh the risks associated with either the drug or the PJD administration procedure.

Aged↗
PubMed2005

Successful treatment of Fusarium endophthalmitis with voriconazole and Aspergillus endophthalmitis with voriconazole plus caspofungin.

PURPOSE: To report successful treatment of exogenous Fusarium and Aspergillus endophthalmitis with new antifungal agents. DESIGN: Interventional case report. METHODS: Treatment of two cases is reviewed. RESULTS: A 64-year-old man developed post-cataract Fusarium moniliforme endophthalmitis. Infection persisted despite removal of the intraocular lens, three vitrectomies, and five intravitreal injections of amphotericin. Inflammation resolved and vision improved from 20/80 to 20/40 on 6 months of oral voriconazole. A 55-year-old man developed post-cataract intraocular inflammation. After three vitrectomies and removal of the intraocular lens, Aspergillus fumigatus endophthalmitis was diagnosed. Intravitreal amphotericin and systemic voriconazole were given, but one week later there were early signs of recurrence. Intravenous caspofungin was added and the eye improved. Caspofungin was continued for 6 weeks and voriconazole for 6 months. Vision improved from counting fingers to 20/80 at 6 months and 20/25 at 23 months. CONCLUSION: Voriconazole is a promising new therapy for Fusarium and Aspergillus endophthalmitis. Caspofungin may act synergistically with voriconazole in treating Aspergillus endophthalmitis.

Anti-Bacterial Agents↗
PubMed2005

A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema.

OBJECTIVE: To evaluate the safety and efficacy of pegaptanib sodium injection (pegaptanib) in the treatment of diabetic macular edema (DME). DESIGN: Randomized, double-masked, multicenter, dose-ranging, controlled trial. PARTICIPANTS: Individuals with a best-corrected visual acuity (VA) between 20/50 and 20/320 in the study eye and DME involving the center of the macula for whom the investigator judged photocoagulation could be safely withheld for 16 weeks. INTERVENTION: Intravitreous pegaptanib (0.3 mg, 1 mg, 3 mg) or sham injections at study entry, week 6, and week 12 with additional injections and/or focal photocoagulation as needed for another 18 weeks. Final assessments were conducted at week 36. MAIN OUTCOME MEASURES: Best-corrected VA, central retinal thickness at the center point of the central subfield as assessed by optical coherence tomography measurement, and additional therapy with photocoagulation between weeks 12 and 36. RESULTS: One hundred seventy-two patients appeared balanced for baseline demographic and ocular characteristics. Median VA was better at week 36 with 0.3 mg (20/50), as compared with sham (20/63) (P = 0.04). A larger proportion of those receiving 0.3 mg gained VAs of > or =10 letters (approximately 2 lines) (34% vs. 10%, P = 0.003) and > or =15 letters (18% vs. 7%, P = 0.12). Mean central retinal thickness decreased by 68 microm with 0.3 mg, versus an increase of 4 microm with sham (P = 0.02). Larger proportions of those receiving 0.3 mg had an absolute decrease of both > or =100 microm (42% vs. 16%, P = 0.02) and > or =75 microm (49% vs. 19%, P = 0.008). Photocoagulation was deemed necessary in fewer subjects in each pegaptanib arm (0.3 mg vs. sham, 25% vs. 48%; P = 0.04). All pegaptanib doses were well tolerated. Endophthalmitis occurred in 1 of 652 injections (0.15%/injection; i.e., 1/130 [0.8%] pegaptanib subjects) and was not associated with severe visual loss. CONCLUSIONS: In this phase II trial, subjects assigned to pegaptanib had better VA outcomes, were more likely to show reduction in central retinal thickness, and were deemed less likely to need additional therapy with photocoagulation at follow-up.

Adult↗
PubMed2004

Safety of posterior juxtascleral depot administration of the angiostatic cortisene anecortave acetate for treatment of subfoveal choroidal neovascularization in patients with age-related macular degeneration.

BACKGROUND: Anecortave acetate is a synthetic derivative of cortisol, but very specific and irreversible chemical modifications to the cortisol structure have resulted in the creation of a potent inhibitor of blood vessel growth with no evidence non-clinically or clinically of glucocorticoid receptor-mediated bioactivity. The clinical safety of Anecortave Acetate administered as a posterior juxtascleral depot every 6 months for up to 4 years is reviewed in this manuscript. METHODS: Clinical safety and efficacy of the novel angiostatic agent Anecortave Acetate for Depot Suspension was evaluated in patients with subfoveal exudative age-related macular degeneration (AMD) in a masked, randomized, dose-duration clinical trial completed in June 2003. This safety and efficacy study enrolled and treated 128 patients at 18 clinical sites in the US and EU. This was the first clinical trial of Anecortave Acetate for Depot Suspension administered as a posterior juxtascleral depot. Assessments of clinical safety were made with general physical examinations including electrocardiograms and hematology/serum chemistry/urinalysis, detailed ophthalmic evaluations with fluorescein/indocyanine green angiography and assessments of best-corrected logMAR visual acuity. All safety reports have been reviewed periodically by an Independent Safety Committee responsible for overseeing these activities. RESULTS: No clinically relevant safety issues related to either Anecortave Acetate for Depot Suspension or the administration procedure have been identified by an Independent Safety Committee. The most frequent safety issues reported were cataractous changes, decreased visual acuity, ptosis, ocular pain, abnormal vision and subconjunctival hemorrhage, but the majority of these were assessed as unrelated to treatment. CONCLUSIONS: Anecortave Acetate for Depot Suspension (3, 15 and 30 mg) is clinically safe following administration and re-administration at 6-month intervals as a posterior juxtascleral depot using a specially designed curved cannula.

Angiogenesis Inhibitors↗
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↗
PubMed2004

In vivo rabbit eyecup preparation for use in retinal research.

PURPOSE: To develop an in vivo rabbit eyecup preparation that preserves neuronal and vascular connections with normal posterior segment contour, permitting direct access to the retina and facilitating retinal microsurgical and neuroscience research. METHODS: Cyanoacrylate glue was applied to the anterior sclera of six Dutch-belted rabbits before open-sky vitrectomy. The glue was used to harden the compliant scleral wall and to fix it to the surrounding periorbital tissues. RESULTS: A normal contour of the posterior segment was retained in all cases. Vitrectomy under air was successfully accomplished and an extensive removal of the vitreous gel was achieved. Fluorescein angiography revealed normal vascular patency of the retinal vessels after vitrectomy. CONCLUSIONS: The proposed modification of the rabbit eyecup retains the normal neurovascular connections and configuration of the retina, making it suitable for retinal microsurgical maneuvers or any procedures in which easy access to anatomically undisturbed retina is required.

Animals↗