Local tolerance and systemic safety of pegaptanib sodium in the dog and rabbit.

PURPOSE: To evaluate the local tolerance, systemic toxicity, and toxicokinetics in dogs and rabbits of pegaptanib sodium, an aptamer that targets vascular endothelial growth factor (VEGF(165)). METHODS: Dogs received biweekly, bilateral, intravitreous (IVT) injections of pegaptanib sodium for 9 months at doses of 0.3 (n = 10), 1 (n = 10), or 3 mg (n = 14); 14 control dogs received phosphate-buffered saline (PBS). In rabbits, pegaptanib sodium was administered by IVT injection biweekly for 6 months at doses of 0.2 (n = 14), 0.67 (n = 14), or 2 mg (n = 18); 18 rabbits received PBS. The systemic and ocular safety of pegaptanib sodium was assessed. Assessments in both dogs and rabbits included complete ophthalmologic examinations, serum chemistry, hematology, urinalysis, and coagulation assessments, as well as gross and microscopic pathologic examination. In addition, dogs were assessed by electroretinography and electrocardiography. In a cardiovascular safety study, loading intravenous boluses and maintenance infusions of pegaptanib sodium or PBS were administered to dogs (n = 4) in an ascending dose design, with each dose level separated by 2-3 days. The pegaptanib dosing regimens were designed to achieve pegaptanib plasma concentrations of approximately 90, 270, or 900 ng/mL. RESULTS: There were no pegaptanib sodium-associated clinical, ophthalmologic, pathologic, or cardiovascular abnormalities at doses of pegaptanib that achieved systemic and ocular exposure levels in excess of those associated with the recommended pegaptanib IVT dosing regimen of 0.3 mg per study eye in patients with age-related macular degeneration. CONCLUSION: These studies, together with data from clinical trials, provide strong evidence that inhibition of VEGF(165) by pegaptanib in the eye is a safe therapy for the treatment of ocular neovascular disease.     

Treatment of neovascular age-related macular degeneration with pegaptanib and boosting with bevacizumab or ranibizumab as needed

BACKGROUND AND OBJECTIVE: Neovascular age-related macular degeneration presents a therapeutic challenge. The efficacy of pegaptanib sodium, a selective inhibitor of vascular endothelial growth factor 165, was examined as a therapeutic mainstay combined with "as needed" boosts of nonselective vascular endothelial growth factor blockade with bevacizumab or ranibizumab. PATIENTS AND METHODS: A retrospective chart review of outcomes of patients treated with pegaptanib and later boosted with bevacizumab or ranibizumab was conducted. Visual acuity, optical coherence tomography, and fluorescein angiography findings were recorded and assessed. RESULTS: During a mean follow-up of 12.1 months, an average of 7.8 injections of pegaptanib 0.3 mg, 1.4 injections of bevacizumab 1.25 mg, and 0.9 injections of ranibizumab 0.5 mg were administered to 17 eyes. In all, 47% of eyes gained 3 or more lines of visual acuity and 76% gained 0 or more lines. CONCLUSION: Pegaptanib as a mainstay of neovascular age-related macular degeneration therapy with an occasional boost of bevacizumab or ranibizumab appears to be an effective treatment option.     

Pegaptanib sodium one-year treatment study for neovascular age-related macular degeneration

PURPOSE: To evaluate the safety and efficacy of intravitreal administration of pegaptanib sodium in Japanese patients with age-related macular degeneration associated with subfoveal choroidal neovascularization. METHODS: Ninety-five male and female patients (mean age 72.5 years.) were assigned randomly in a double-masked manner to receive 0.3 or 1 mg of pegaptanib sodium every 6 weeks over a 48-week period. Efficacy was assessed by visual acuity change from baseline as the proportion of patients who lost fewer than 15 letters at week 54 using the Early Treatment Diabetic Retinopathy Study chart. RESULTS: The group that received 0.3 mg pegaptanib experienced a mean loss of 3.8 letters; 78.7% (37/47) of patients lost fewer than 15 letters. The 1 mg group had a change of -4.3 letters and the proportion that lost 15 letters was 72.9% (35/48). The proportion of patients whose visual acuity was unchanged or improved was 46.8% (22/47) and 43.8% (21/48) in the 0.3 and 1 mg groups, respectively. The majority of adverse events with possible, probable, or unknown relationship to pegaptanib were related to the intravitreal injection, such as mild conjunctival hemorrhage (0.3 mg: 76.6%, 1 mg: 77.1%) and superficial punctuate keratitis by sterilization (0.3 mg: 29.8%, 1 mg: 39.6%) at the injection site. Compliance with the study treatment of 9 intravitre al injections was as high as 87.2% and 85.4% for patients receiving 0.3 and 1 mg, respectively. CONCLUSION: Intravitreal injection of sodium pegaptanib every 6 weeks produced clinically significant stabilization of visual acuity for one year in more than 70% of patients with age-related macular degeneration, with good treatment compliance.     

Long-term efficacy and safety profile of pegaptanib sodium for age-related macular degeneration with choroidal neovascularization--evaluation of extended phase II clinical trial

Long-term efficacy and safety profile of pegaptanib was evaluated for age-related macular degeneration (AMD) with choroidal neovascularization. Sixty-one AMD patients from phase II clinical trial were entered into an extended trial and followed up for more than 2 years. Pegaptanib sodium 0.3 mg was administered once every six weeks. Changes in visual acuity were evaluated using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The number of responders and adverse events were monitored. The mean change in visual acuity decreased by 10.3 letters for up to 199 weeks (62-199 weeks; mean 140 weeks) during follow-up. There were 77.4% responders at the beginning (54 weeks since the beginning of phase II trial) and 56.6% at the end of the extended trial. Adverse events were found in 57 of 61 patients (93.4%); 36 of the events (59.0%) were due to a preparation procedure, while 12 adverse events (19.7%), including retinal hemorrhage (3 events; 4.9%), anterior chamber inflammation (2 events; 3.3%), macular degeneration, floaters, photopsia, retinal vessel aneurysm, vitreous hemorrhage, ocular hypertension, arteriosclerosis obliterans and hypertension (1 event; 1.6%, respectively) were associated with pegaptanib sodium. Thus, the majority of adverse events was at least in part a result of the preparation procedure for injection. Based on the long-term efficacy and tolerability data of this trial, pegaptanib sodium appears to be beneficial for preventing the worsening of visual acuity caused by age-related macular degeneration with choroidal neovascularization.     

Safety and efficacy of intravitreal bevacizumab followed by pegaptanib maintenance as a treatment regimen for age-related macular degeneration.

BACKGROUND AND OBJECTIVE: Vascular endothelial growth factor (VEGF)-A, both necessary and sufficient in promoting ocular neovascularization, is an attractive therapeutic target. Combining nonselective and selective VEGF blockade may provide clinical benefit with minimal risks in the treatment of neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: Twenty patients with all subtypes of neovascular AMD and a broad range of baseline vision were treated with intravitreal bevacizumab followed by pegaptanib sodium for 54 weeks. Visual acuity measurements, biomicroscopy, funduscopy, fluorescein angiography, optical coherence tomography, and adverse event assessments were performed. RESULTS: Mean visual acuity improved from approximately 20/200 at baseline to 20/80. All patients experienced an improvement in retinal thickness, ranging from -47 to -297 microns. Adverse events were limited to transient irritation or redness. No significant elevation in intraocular pressure occurred following either bevacizumab or pegaptanib injections. CONCLUSIONS: Nonselective VEGF blockade with bevacizumab induction and selective VEGF165 blockade with pegaptanib as maintenance therapies may offer clinically meaningful outcomes with acceptable safety profiles in patients with AMD.     

Systemic and ocular safety of intravitreal anti-VEGF therapies for ocular neovascular disease

The treatment of ocular neovascular diseases is being revolutionized by intravitreal therapies targeting vascular endothelial growth factor (VEGF). Two agents are approved for treating neovascular age-related macular degeneration and are being evaluated for other retinal conditions: the RNA aptamer pegaptanib and the monoclonal antibody antigen-binding fragment ranibizumab. Bevacizumab, a related antibody, is being used similarly, although its use is off-label. Pegaptanib selectively binds to a VEGF isoform identified as being especially pathogenic in the eye and spares other isoforms, whereas the other two agents nonselectively bind all VEGF isoforms. Because VEGF is involved in a wide variety of physiologic processes, the ocular and systemic safety of anti-VEGF agents is of paramount concern. I provide an overview of safety data for intravitreal anti-VEGF therapies, focusing primarily on randomized, controlled trials. For pegaptanib, an accumulation of data from pivotal trials and a dedicated systemic safety study have revealed no ocular or systemic safety concerns. For ranibizumab, the principal ocular adverse event detected in clinical trials was a low frequency of ocular inflammation, and systemic adverse events included a slightly elevated risk of nonocular hemorrhage and stroke. Safety data from properly designed randomized controlled trials for bevacizumab are not available.     

Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for neovascular age-related macular degeneration.

To determine whether intravitreal bevacizumab could improve optical coherence tomography and visual acuity outcomes in a patient with neovascular age-related macular degeneration who was responding poorly to pegaptanib therapy, an intravitreal injection of bevacizumab (1.0 mg) was given. Within 1 week, optical coherence tomography revealed resolution of the subretinal fluid, resulting in a normal-appearing macular contour. The improved macular appearance was maintained for at least 4 weeks, and visual acuity remained stable. No inflammation was observed. An intravitreal injection of bevacizumab may provide an effective, safe, and inexpensive option for patients with age-related macular degeneration who are losing vision secondary to macular neovascularization.     

Targeting angiogenesis, the underlying disorder in neovascular age-related macular degeneration

Angiogenesis has a causal role in many diseases, including neovascular age-related macular degeneration (AMD). Identification of key regulators of angiogenesis, including vascular endothelial growth factor (VEGF), fibroblast growth factor 2, pigment epithelium-derived growth factor, angiopoietins and extracellular matrix molecules, has facilitated the development of novel therapeutic agents that target the underlying pathological angiogenic process. Among these, VEGF serves as a "master switch" for many ocular neovascular conditions through its promotion of endothelial cell proliferation and survival, vascular permeability and ocular inflammation. Two anti-VEGF agents are now clinically available: bevacizumab, an antibody for metastatic colorectal cancer, and pegaptanib sodium, an aptamer for neovascular AMD. Unlike bevacizumab, which binds all VEGF isoforms, pegaptanib targets only VEGF165, the isoform responsible for pathological ocular neovascularization and thus an ideal target for treatment of AMD. Although other therapies targeting angiogenesis in AMD are in clinical development, to date, pegaptanib is the only therapy approved by the Food and Drug Administration of the United States for the treatment of all neovascular AMD and represents a valuable addition to the hitherto limited options available for patients.     

Pegaptanib and ranibizumab for neovascular age-related macular degeneration: a systematic review

AIMS: To assess the clinical effectiveness of pegaptanib sodium and ranibizumab for neovascular age-related macular degeneration (AMD). METHODS: A systematic review of randomised controlled trials (RCTs) identified through searching 12 electronic databases, bibliographies and consultation with experts and manufacturers. RCTs were eligible if they assessed the effects of pegaptanib or ranibizumab with best supportive care, sham injection or photodynamic therapy (PDT) on patients with subfoveal choroidal neovascularisation associated with wet AMD and examined outcomes including visual acuity and adverse events. RESULTS: Three RCTs of ranibizumab (MARINA, ANCHOR, FOCUS) and two of pegaptanib (VISION study) met the inclusion criteria. The RCTs included patients with different lesion types. The studies showed statistically significant benefit on different measures of visual acuity for patients receiving pegaptanib, ranibizumab or ranibizumab with PDT compared to control (sham injection, PDT or sham injection with PDT) after 12 months. These differences appeared to be clinically significant. Although adverse events were common among those receiving pegaptanib or ranibizumab, they were considered mild to moderate in nature. Meta-analysis of ranibizumab trials and indirect comparison of the two drugs were not possible due to differences in the study populations' lesion types. However, results from the RCTs of ranibizumab tended to show a greater effect on visual acuity than results from the RCT of pegaptanib. CONCLUSIONS: Pegaptanib and ranibizumab appear to slow or stop the progression of neovascular AMD. Uncertainty remains over the relative benefits of pegaptanib compared with ranibizumab and other unlicensed drugs (eg, Avastin), due to the nature of the evidence. Head-to-head RCTs and economic evaluations comparing these alternatives are needed.     

Progression of choroidal neovascularization following injection of pegaptanib sodium (macugen) in two eyes with neovascular age-related macular degeneration

PURPOSE: To describe two cases of neovascular age-related macular degeneration (AMD) that progressed despite a single intravitreal injection of pegaptanib sodium (Macugen) six weeks earlier. DESIGN: Interventional case report. METHODS: A 62-year-old man and a 76-year-old woman with occult and minimally classic lesions, respectively, each received a single injection of intravitreal pegaptanib. RESULTS: Within six weeks of an intravitreal pegaptanib injection, the choroidal neovascularization (CNV) progressed. In one eye, the chronic occult lesion developed subfoveal classic CNV. In the other eye, the classic component of the minimally classic lesion tripled in size. CONCLUSIONS: A single dose of intravitreal pegaptanib was not effective in these two patients at six weeks. This report reminds the ophthalmologist to consider obtaining a fluorescein angiogram during follow-up after an intravitreal pegaptanib injection to monitor CNV lesion characteristics, particularly if the visual acuity decreases.     

Optical coherence tomography findings during pegaptanib therapy for neovascular age-related macular degeneration

BACKGROUND: To evaluate macular thickness measured by optical coherence tomography (OCT) during pegaptanib therapy for neovascular age-related macular degeneration (AMD). METHODS: For this prospective, nonrandomized, observational case series, 41 eyes from 41 patients with neovascular AMD received intravitreous pegaptanib (1 mg) injections repeated every 6 weeks. The primary outcome measure was central foveal thickness measured by OCT. Secondary outcomes were fluorescein angiographic leakage and visual acuity. RESULTS: Mean thickness of the central area on OCT decreased from 340 +/- 24 microm to 299 +/- 14 microm after 12 weeks of pegaptanib injections. This represents a reduction in thickening of 32%. Fluorescein angiograms with definite leakage decreased from 100% to 81%, and mean visual acuity decreased from 20/116 to 20/120. CONCLUSIONS: Intravitreal injections of pegaptanib at 6-week intervals result in a moderate reduction of central foveal thickness in eyes with subfoveal neovascular AMD. This presents a modest effect relative to that reported with other anti-angiogenic agents.     

Pegaptanib for the treatment of age-related macular degeneration

Although neovascular (wet) age-related macular degeneration (AMD) only accounts for 10-20% of all AMD, the majority (about 90%) of severe vision loss associated with AMD is due to this form. Results from recent studies have implied that vascular endothelial growth factor (VEGF), particularly VEGF(165), plays a predominant role in the development of ocular neovascularization and vascular leakage secondary to AMD. Thus VEGF is an important therapeutic target in neovascular AMD. Pegaptanib, an anti-VEGF aptamer, can selectively bind with VEGF(165) and inhibit both the growth of blood vessels and vascular leakage, and was approved by the Food and Drug Administration in the United States as the therapy for the treatment of all subtypes of neovascular AMD in December 2004. This review summaries the mechanism, preclinical and clinical studies, and adverse events of pegaptanib treatment.     

Complications of intravitreal injections--own experience

PURPOSE: Authors present complications associated with intravitreal injection perfomed in Ophthalmic Clinic CMKP MATERIAL AND METHODS: retrospective study, between January 2006 and July 2009 we performed intravitreal injections with triamcinolone acetonide (Kenalog, 4 mg), ranibizumab (Lucentis, 0.5 mg), bevacizumab (Avastin, 1.25 mg) and pegaptanib (Macugen, 0.3 mg). We treated eyes with age-related macular degeneration, diabetic macular edema, after retinal venous occlusion, with uveitis, Irvine-Gass syndrome, idiopathic juxtafoveolar teleangiectasia and central serous retinopathy. RESULTS: 943 eyes received intravitreal injections. The most common ocular complication was subconjunctival hemorrhage which was seen in 36% cases. Temporary elevated intraocular pressure above 21 mmHg was noticed in 18 eyes (5%) after anti-VEGF agents injections and in 30 eyes (23.4%) after Kenalog injection. Anterior uveitis developed in sixteen cases (1.7%) from the Avastin (5 eyes) and Lucentis (3 eyes) group. Anterior-posterior inflammation occurred in 8 eyes (0.8%), including four eyes (0.4%) with sterile endophthalmitis (3 following bevacizumab and 1 following ranibizumab injection), one eye (0.1%) with pseudoendophthalmitis (after triamcinolone). There were three cases of suspected endophthalmitis (2 following bevacizumab and 1 following triamcinolone injection). The infectious endophthalmitis after triamcinolone injection was culture-proven and revealed Staphylococcus epidermidis. Cataract formation or progression was noted in 34 eyes totally. In Kenalog group progression of cataract was seen in 23.4% of eyes (30 cases) during 2-years of follow-up and in anti-VEGF agents group--in two cases (0.6%) and 2 cases of iatrogenic cataract. Three diabetic patients suffered systemic adverse events: one patient developed renal insufficiency, one patient developed cerebrovascular accidents and one suffered a myocardial infarction resulting in death. Conclusions: Intravitreal injections are associated with a low incidence of serious adverse events. The most common ocular complication was subconjunctival hemorrhage. There was one case of serious complication--the culture-proven infectious endophthalmitis after Kenalog injection. Cataract formation and increase of intraocular pressure were more often observed following intravitreal triamcinolone injection.     

康柏西普在眼部新生血管性疾病中的应用进展

康柏西普是中国自主研发的一种抗血管内皮生长因子新药。自从2013年被中国国家食品药品管理总局批准用于临床,康柏西普在治疗湿性年龄相关性黄斑变性、脉络膜新生血管、黄斑水肿等眼部新生血管性疾病过程中显示出可靠的安全性和疗效。针对不同的疾病,康柏西普的治疗策略有所不同。本文就近年来康柏西普在湿性年龄相关性黄斑变性、糖尿病性黄斑水肿、病理性近视脉络新生血管、新生血管性青光眼、未成熟儿视网膜病变、角膜新生血管等眼部新生血管性疾病中的应用进展进行综述,总结探讨康柏西普的用药适应证、给药方案和治疗效果。期待康柏西普的用药适应证会更广,给药方案会更多,为眼部新生血管性疾病的治疗带来新的思路。     

Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration

PURPOSE: To evaluate the safety and efficacy of intravitreal bevacizumab (Avastin, Genentech Inc.) for the treatment of neovascular age-related macular degeneration (ARMD). METHODS: A retrospective review was performed on consented patients with neovascular ARMD receiving intravitreal bevacizumab therapy. All patients received intravitreal bevacizumab at baseline with additional monthly injections given at the discretion of the treating physician. At each visit, a routine Snellen visual acuity assessment was performed followed by an ophthalmic examination and optical coherence tomography (OCT) imaging. RESULTS: Fifty-three eyes of 50 patients received an intravitreal bevacizumab injection between May and August 2005. Including the month 3 visit, the average number of injections was 2.3 out of a maximum of 4 injections. No serious drug-related ocular or systemic adverse events were identified. Improvements in visual acuity and central retinal thickness measurements were evident by week 1 and continued through month 3. At month 3, the mean visual acuity improved from 20/160 to 20/125 (P < 0.001) and the mean central retinal thickness decreased by 99.6 microm (P < 0.001). CONCLUSION: Off-label intravitreal bevacizumab therapy for neovascular ARMD was well tolerated over 3 months with improvements in visual acuity and OCT central retinal thickness measurements. While the long-term safety and efficacy of intravitreal bevacizumab remain unknown, these short-term results suggest that intravitreal bevacizumab may be the most cost effective therapy for the treatment of neovascular ARMD.     

Retinal pigment epithelial tear following intravitreal pegaptanib sodium

PURPOSE: To report two cases of a retinal pigment epithelial tear after intravitreal injection of pegaptanib sodium. To our knowledge, this is the first report of this finding after intraocular antivascular endothelial growth factor therapy. DESIGN: Observational case reports. METHODS: Two patients presented with occult choroidal neovascularization and associated serous pigment epithelial detachment that was a result of age-related macular degeneration. Both patients were treated with an intravitreal injection of pegaptanib sodium. RESULTS: One patient developed a retinal pigment epithelium tear one week after the intravitreal injection. The second patient developed a retinal pigment epithelium tear eight weeks after treatment. CONCLUSIONS: Although these cases may represent natural history, there should be a high index of suspicion for retinal pigment epithelium tears in patients who report significant visual deterioration after intravitreal injection of pegaptanib sodium. Further studies are needed to determine whether angiographic subtypes of choroidal neovascular membranes are more susceptible to developing retinal pigment epithelium tears after treatment with antivascular endothelial growth factor agents.     

Pegaptanib sodium for ocular vascular disease

Pegaptanib sodium (Macugen) is a selective RNA aptamer that inhibits vascular endothelial growth factor (VEGF) 165 , the VEGF isoform primarily responsible for pathologic ocular neovascularization and vascular permeability, while sparing the physiological isoform VEGF 121 . After more than 10 years in development and preclinical study, pegaptanib was shown in clinical trials to be effective in treating choroidal neovascularization associated with age-related macular degeneration. Its excellent ocular and systemic safety profile has also been confirmed in patients receiving up to three years of therapy. Early, well-controlled studies further suggest that pegaptanib may provide therapeutic benefit for patients with diabetic macular edema, proliferative diabetic retinopathy and retinal vein occlusion. Notably, pegaptanib was the first available aptamer approved for therapeutic use in humans and the first VEGF inhibitor available for the treatment of ocular vascular diseases.     

Quality of life in patients with age-related macular degeneration: results from the VISION study

PURPOSE: To assess the impact of treatment with pegaptanib sodium vsusual care on vision-related quality of life (VRQoL) in patients with age-related macular degeneration (AMD). METHODS: VRQoL was a secondary end point in the trial, a prospective, randomized, double-masked, multicentre, dose-ranging study. Three doses of pegaptanib (0.3, 1, and 3 mg) were compared with usual care with respect to changes in VRQoL as indicated by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ 25), administered at baseline and weeks 30 and 54. Four of the NEI-VFQ 25 domains were prospectively designated as primary: near vision, distance vision, role limitations, and dependency. Between-group differences were assessed using an analysis of covariance model with age, gender, and baseline score as covariates. RESULTS: NEI-VFQ 25 data were available for 569 subjects. At week 54, improvements in the distance vision and role limitations domains were greater in pegaptanib than usual care arms. No substantial increase in ocular pain was noted in pegaptanib-treated patients. No clear superiority of any particular dosage strength of pegaptanib was demonstrated, and no significant differences or trends favoured usual care on any domain score or the NEI-VFQ 25 composite score. The greatest VRQoL benefit was seen in responders (lost<3 lines) to treatment. CONCLUSION: The VISION trial provided evidence of trends in quality-of-life benefit associated with effective treatment of AMD using pegaptanib. Treatment with pegaptanib is expected to contribute significantly to VRQoL improvement for responder patients.     

Newly diagnosed exudative age-related macular degeneration treated with pegaptanib sodium monotherapy in US community-based practices: medical chart review study

Background  

Studies have shown that early detection and treatment of neovascular age-related macular degeneration (NV-AMD) can delay vision loss and blindness. The objective of this study was to evaluate the efficacy/safety of intravitreal pegaptanib sodium monotherapy in treatment-na?ve subjects with newly diagnosed NV-AMD and to gain insight into characteristics of lesions treated in community-based practices.     

Enhanced efficacy associated with early treatment of neovascular age-related macular degeneration with pegaptanib sodium: an exploratory analysis

PURPOSE: To assess the vision benefit of treating early subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD) with pegaptanib sodium. METHODS: Exploratory analyses of week 54 vision outcomes (VEGF Inhibition Study in Ocular Neovascularization study) of subject subgroups with early disease who received 0.3 mg of pegaptanib (Groups 1 [n = 34] and 2 [n = 30]) or sham injections (usual care). Two sets of clinical characteristics typical of early disease defined the subgroups. RESULTS: Baseline characteristics were generally well balanced between treatment arms. Pegaptanib responder rates (loss of <15 letters of visual acuity) were 76% and 80% in treatment Groups 1 and 2 versus 50% and 57% for usual care Groups 1 and 2 (P = 0.03 and P = 0.05), respectively. Compared with subjects assigned to pegaptanib, those in Groups 1 and 2 receiving usual care on average lost 11.1 letters and 12.7 letters more of visual acuity (P < 0.01 and P < 0.006), respectively. Subjects assigned to usual care were approximately 10 times more likely to have severe vision loss than were those treated with pegaptanib (Group 1, 29% vs. 3%, respectively; P < 0.01). In Group 1, 12% of pegaptanib-treated subjects gained > or =15 letters of visual acuity versus 4% receiving usual care; 20% of Group 2 pegaptanib-treated subjects gained > or =15 letters of visual acuity versus none of the usual care subjects. CONCLUSION: Early detection and treatment with pegaptanib may result in superior vision outcomes in patients with neovascular AMD.