To evaluate the safety of up to 3 years of pegaptanib sodium therapy in the treatment of neovascular age-related macular degeneration (NV-AMD).
Two concurrent, prospective, multicentre, double-masked studies randomised subjects with all angiographic lesion compositions of NV-AMD to receive intravitreous pegaptanib sodium (0.3, 1 and 3 mg) or sham injections every 6 weeks for 54 weeks. Those initially assigned to pegaptanib were rerandomised to continue or discontinue therapy for 48 more weeks; sham-treated subjects continued sham, discontinued or received pegaptanib. At 102 weeks, subjects receiving pegaptanib 0.3 mg or 1 mg in years 1 or 2 continued; those receiving pegaptanib 3 mg or who did not receive treatment in years 1 and 2 were rerandomised to 0.3 mg or 1 mg for year 3.
As in years 1 and 2, pegaptanib was well tolerated in year 3. Adverse events were mainly ocular in nature, mild, transient and injection-related. Serious adverse events were rare. No evidence of systemic safety signals attributed to vascular endothelial growth factor inhibition arose in year 3. There were no findings in relation to vital signs or electrocardiogram results suggesting a relationship to pegaptanib treatment.
The 3-year safety profile of pegaptanib sodium was favourable in patients with NV-AMD.
The VEGF Inhibition Study In Ocular Neovascularisation (VISION) reported the efficacy of intravitreal (ITV) vascular endothelial growth factor (VEGF) inhibition with pegaptanib sodium (Macugen®) for the treatment of neovascular age-related macular degeneration (AMD). This paper reports clinical experience with pegaptanib sodium for the treatment of occult or minimally classic choroidal neovascularization (CNV) due to AMD.
Material and methods
The study included 50 eyes (in 49 patients) with either occult CNV or minimally classic CNV secondary to neovascular AMD who were not eligible for photodynamic therapy (PDT). Study data were analyzed retrospectively. During the 6-month study, patients were administered an average 2.74 injections of 0.3 mg ITV pegaptanib sodium. Angiography and optical coherence tomography (OCT) examinations were carried out and intraocular pressure (IOP) and visual acuity (VA) were measured at baseline, at 3 months and at 6 months. An eye examination was performed and VA was measured the 2 days following treatment and then again at weeks 4–6, and at 3 and 6 months. OCT, VA, and IOP were also assessed at 1 month.
ITV pegaptanib sodium was well tolerated and no treatment complications arose. Mean VA was measured as: 0.37 ± 0.24 at baseline; 0.37 ± 0.25 at 1 month; 0.37 ± 0.25 at 3 months and 0.40 ± 0.26 at 6 months. VA was stabilized in approximately 90% of eyes treated with pegaptanib sodium. OCT examination showed a minimal change in central retinal thickness (CRT) during the course of the study, from 251.19 μm at baseline to 251.63 μm at 6 months. No elevation in IOP was measured during treatment at 4–6 months in patients receiving pegaptanib sodium.
ITV therapy with pegaptanib sodium for occult and minimally classic CNV secondary to neovascular AMD offered good efficacy with a favorable adverse events profile. The majority of patients showed stabilization in all assessed parameters. In clinical practice, careful consideration should be given to the use of nonselective VEGF inhibition in patients with a high cardiovascular risk profile or in those with a history of thromboembolic events.
Intravitreal (ITV) injection; age-related macular degeneration (AMD); choroidal neovascularization (CNV); anti-VEGF therapy; pegaptanib sodium
To assess the clinical effectiveness of pegaptanib sodium and ranibizumab for neovascular age‐related macular degeneration (AMD).
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.
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.
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.
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-naïve subjects with newly diagnosed NV-AMD and to gain insight into characteristics of lesions treated in community-based practices.
From seven private US practices, charts were retrospectively reviewed on 73 subjects with previously untreated subfoveal choroidal NV-AMD treated with their first dose of pegaptanib monotherapy on/after 4/1/2005 through 6/5/2006, receiving ≥4 treatments at 6-week intervals over 21 weeks. Primary endpoint: mean visual acuity (VA) change from baseline to month 6.
75% of lesions were occult, and 82% were subfoveal. From baseline to month 6, mean VA change was -0.68 lines; 58% and 16% gained ≥0 and ≥3 lines of VA, and 70% were responders (<3 lines lost). In 35 subjects with early disease, 80% were responders with a mean gain of 0.46 lines.
Pegaptanib is effective in real-world patients with treatment-naïve NV-AMD in uncontrolled community-based retina practices.
Purpose. To report the outcomes after primary intravitreal pegaptanib sodium in patients with diabetic macular edema (DME).
Methods. We conduced a retrospective analysis of eyes with DME treated with primary intravitreal pegaptanib sodium (Macugen) (intravitreal pegaptanib group). The results were compared with the ones of eyes treated with intravitreal pegaptanib sodium associated with macular laser photocoagulation (combined treatment group), and the ones of eyes treated with primary macular laser photocoagulation (macular laser photocoagulation group).
Results. For the intravitreal pegaptanib group (13 eyes), we found significant changes in mean best-corrected visual acuity (BCVA) and reductions in mean central macular thickness (CMT) at the last follow-up visit (P = .0014
and P = .0001). For the macular laser photocoagulation group (15 eyes), we found no statistically significant changes in mean BCVA and CMT at the last follow-up visit (P > .05). For the combined treatment group (12 eyes), we found no significant changes in mean BCVA at the last follow-up visit (P > .05) despite significant reductions in mean CMT (P = .0188).
Conclusion. Intravitreal pegaptanib treatment alone may be superior to macular laser photocoagulation alone and to combined intravitreal pegaptanib treatment associated with macular laser photocoagulation in patients with DME.
Pegaptanib sodium (MacugenTM) 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.
Age-related macular degeneration; aptamer; diabetic macular edema; pegaptanib; vascular endothelial growth factor
To determine the safety of a surgeon’s initial consecutive intravitreal injections using a specific protocol and to review the complications that may be attributed to the injection procedure.
A retrospective chart review.
Fifty-nine patients (30 females, 29 males) received intravitreal injections of pegaptanib, bevacizumab, or ranibizumab as part of their treatment for neovascular age-related macular degeneration. The average patient age was 80 years. Twenty-two patients were diagnosed with or suspected of having glaucoma. Each patient received an average of 5.8 injections.
The charts of 59 patients who received a total of 345 intravitreal injections (104 pegaptanib, 74 bevacizumab, 167 ranibizumab) were reviewed. All injections were performed in an office-based setting. Povidone–iodine, topical antibiotics, and eye speculum were used as part of the pre injection procedure. Vision and intraocular pressure were evaluated immediately following each injection.
Main outcome measures
Incidence of post injection complications, including but not limited to endophthalmitis, retinal detachment, traumatic cataract, and vitreous hemorrhage.
There were no cases of endophthalmitis, toxic reactions, traumatic cataracts, retinal detachment, or vitreous hemorrhage. There was one case each of lid swelling, transient floaters, retinal pigment epithelial tear, corneal edema, and corneal abrasion. There were five cases of transient no light perception following pegaptanib injections.
The incidence of serious complications was very low for the intravitreal injections given. A surgeon’s initial intravitreal injections may be performed with a very high degree of safety using this protocol.
intravitreal injection; post injection complications; intraocular disease; age-related macular degeneration; bevacizumab; endophthalmitis; pegaptanib; ranibizumab
Age-related macular degeneration (AMD) is a major cause of severe visual loss worldwide. Neovascular (wet) AMD accounts for 90% of the visual loss associated with the disorder and vascular endothelial growth factor (VEGF) has been shown to play a major role in neovascularization and vascular permeability, the major causes of visual loss in AMD, making it an ideal target for therapeutic intervention. To utilize this strategy, pegaptanib, an aptamer that specifically binds to and blocks VEGF165, the VEGF isoform primarily responsible for abnormal vascular growth and permeability in AMD, was developed. Following encouraging preclinical trials, clinical trials showed that pegaptanib stabilized vision and reduced the risk of severe visual loss in the majority of patients with AMD, with some patients showing visual improvement. Pegaptanib has maintained a good safety profile with only occasional adverse effects. Even greater success was achieved when pegaptanib was used in combination with another therapeutic strategy, such as photodynamic therapy or bevacizumab, a pan isoform VEGF inhibitor. Further investigation of pegaptanib for the therapy of wet AMD, particularly in combination with other modes of therapy, should be encouraged.
age-related macular degeneration; pegaptanib; vascular endothelial growth factor; choroidal neovascularization; macular edema
To assess the efficacy of intravitreal Pegaptanib sodium (Macugen®) injection in the management of refractory macular edema secondary to branch retinal vein occlusion.
This is a prospective, nonrandomized, interventional case series. Five eyes of five patients with macular edema refractory to either bevacizumab or triamcinolone were treated with intravitreal injection of Pegaptanib sodium.
After three months follow-up, both visual acuity and macular edema, measured by optical coherence tomography and fluorescence angiography, dramatically improved.
Pegaptanib sodium is a safe and efficacy treatment for macular edema secondary to branch retinal vein occlusion.
Macugen®; BRVO; BCVA; pegaptanib sodium
To compare the effect of pegaptanib versus ranibizumab on exudative age-related macular degeneration (AMD) with small lesion size.
This is a retrospective study of 81 eyes from 78 patients with exudative AMD treated and followed up over 12 months. Patients with baseline best corrected visual acuity (BCVA) under 20/400 and with a greatest linear dimension of lesion over 4500 μm were excluded from the study. Twenty-six eyes from 25 patients were treated with three consecutive intravitreal injections of pegaptanib (IVP group) and 55 eyes from 54 patients were treated with three consecutive ranibizumab injections (IVR group). Each therapy was repeated as needed. The alteration in BCVA was evaluated in the IVP and IVR groups.
No differences were detected in baseline parameters between the IVP and IVR groups. The mean BCVA (logMAR) at month 1, 3, 6 and 12 after the initial treatment was improved from baseline in the IVP group (−0.095, −0.17, −0.18 and −0.18, respectively) and in the IVR group (−0.077, −0.15, −0.17 and −0.11, respectively), which was statistically significant. There was no difference in the change in mean BCVA between IVP and IVR groups at the same time periods.
The visual outcome of IVP was equivalent with IVR in exudative AMD with small lesion size.
pegaptanib; ranibizumab; age-related macular degeneration; small lesion size
To assess the efficacy of pegaptanib as maintenance therapy in neovascular age-related macular degeneration (NV-AMD) patients after induction therapy.
A phase IV, prospective, open-label, uncontrolled exploratory study including subjects with subfoveal NV-AMD who had had one to three induction treatments 30–120 days before entry and showed investigator-determined clinical/anatomical NV-AMD improvement. Lesions in the study eye were: any subtype, 12 or fewer disc areas; postinduction centre point thickness (CPT) 275 μm or less or thinning of 100 μm or more (optical coherence tomography); visual acuity (VA) 20/20–20/400. Intravitreal pegaptanib 0.3 mg was administered as maintenance every 6 weeks for 48 weeks with follow-up to week 54. Booster treatment additional unscheduled treatment for wet age-related macular degeneration, was allowed in the study eye at the investigators' discretion for clinical deterioration.
Of 568 enrolled subjects, 86% completed 1 year of pegaptanib. Mean VA improvement during induction (49.6 to 65.5 letters) was well preserved (54-week mean 61.8 letters). Mean CPT was relatively stable during maintenance (20 μm increase during the study). Fifty per cent did not receive unscheduled booster treatment to week 54; 46% did have one such booster (mean 147 days after maintenance initiation).
An induction-maintenance strategy, using non-selective then selective vascular endothelial growth factor (VEGF) inhibitors, could be considered for NV-AMD. This approach may have particular relevance for patients with systemic comorbidities who require long-term anti-VEGF therapy for NV-AMD.
Macula; macular degeneration; pegaptanib sodium; vascular endothelial growth factor A
Diabetic retinopathy is the leading cause of blindness among individuals of working age in industrialized nations, with most of the vision loss resulting from diabetic macular edema (DME). The formation of DME depends on the action of several growth factors and inflammatory mediators, but vascular endothelial growth factor (VEGF) appears to be critical for breaking down the blood-retinal barrier and promoting the accumulation of macular edema. Laser photocoagulation has been the standard-of-care for three decades, and although it stabilizes vision, significant gains in visual acuity after treatment are unusual. Several VEGF inhibitors (pegaptanib, aflibercept, and ranibizumab) have been initially developed and tested for the treatment of age-related macular degeneration and subsequently for DME. In Phase I, II, and III trials for DME, ranibizumab has been shown to be superior to macular laser photocoagulation and intraocular triamcinolone acetonide injections for improving visual acuity and drying the macula. As a result, ranibizumab is the only anti-VEGF drug that has been approved by the United States Food and Drug Administration for the treatment of DME. Most experts now consider intravitreal anti-VEGF therapy to be standard-of-care for DME involving the fovea.
aflibercept; bevacizumab; diabetic macular edema; diabetic retinopathy; ranibizumab; vascular endothelial growth factor
To compare the efficacies of subconjunctival bevacizumab, ranibizumab, and pegaptanib sodium injections for the inhibition of corneal neovascularization in an experimental rat model.
Sixteen corneas of 16 rats were chemically cauterized and randomized into four groups: bevacizumab group that treated with 0.05mL/1.25mg bevacizumab, ranibizumab group that treated with 0.05mL/0.5mg ranibizumab, pegaptanib group that treated with 0.05mL/0.15mg pegaptanib sodium, and control group that treated with 0.05mL saline solution. Digital photographs of the corneas were taken and analyzed using an image analysis software program. All corneas were excised and examined histologically on the 15th day.
Each treatment group had significantly less neovascularized corneal areas and fewer blood vessels than the control group (all P<0.05). In addition, bevacizumab group had significantly less neovascularized corneal areas and fewer blood vessels than ranibizumab and pegaptanib groups (both P<0.05). However, there was no significant difference between the ranibizumab and pegaptanib groups regarding percentage of neovascularized corneal areas and number of blood vessels (both P>0.05).
Subconjunctival bevacizumab, ranibizumab, and pegaptanib sodium were effective with no corneal epitheliopathy for inhibiting corneal neovascularization after corneal burn in rats. Bevacizumab was more effective than ranibizumab and pegaptanib sodium.
corneal neovascularization; bevacizumab; ranibizumab; pegaptanib; subconjunctival injection
To determine longitudinal rates of ocular complications after anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (AMD) in a nationally representative longitudinal sample.
retrospective, longitudinal case-control study.
Using the Medicare 5% claims database, diagnoses of neovascular AMD and anti-VEGF injections of ranibizumab, bevacizumab, or pegaptanib were identified from International Classification of Diseases (ICD-9-CM) and Current Procedural Terminology (CPT) procedure codes. 6,154 individuals undergoing anti-VEGF treatment for neovascular AMD (total of 40,903 injections) were compared with 6,154 matched controls with neovascular AMD who did not undergo anti-VEGF treatment. Propensity score matching was used to match individuals receiving anti-VEGF injections with controls. Rates of post-injection adverse outcomes (endophthalmitis, rhegmatogenous retinal detachment, retinal tear, uveitis, and vitreous hemorrhage) were analyzed by cumulative incidence and Cox proportional hazards model to control for demographic factors and ocular comorbidities.
At 2-year follow-up, the rates of endophthalmitis per injection (0.09%; p<0.01), uveitis (0.11%; p<0.01), and vitreous hemorrhage per injection (0.23%; p<0.01) were significantly higher in the anti-VEGF treatment group. With Cox proportional hazards modeling, the anti-VEGF treatment group had an 102% higher risk of severe ocular complications overall, and a 4% increased risk per injection, both of which were statistically significant (p<0.01)
Rates of endophthalmitis, uveitis, and vitreous hemorrhage were higher in the group treated with anti-VEGF injection than in the control group, though nevertheless rare in both groups. The overall risk of severe ocular complications was significantly higher in the anti-VEGF treatment group.
The pathogenesis of age-related macular degeneration (AMD) is unclear, but it can take either a neovascular/exudative/wet form, characterized by choroidal neovascularization (CNV), or a dry form. No treatments are available for the dry form, but there are a number of pharmacological interventions that inhibit vascular endothelial growth factor (VEGF), which is central to the pathogenesis of CNV and neovascular AMD. Available anti-VEGF agents either target all active VEGF isoforms (eg, ranibizumab), or take a more selective approach and inhibit only VEGF165 (eg, pegaptantib sodium). Current guidance on their use is equivocal and restrictive at best, resulting in associated difficulties in securing adequate, timely funding for treatment. The Moorfields Eye Hospital undertook an audit of 70 patients receiving intravitreal (ITV) pegaptanib sodium on a pro re nata (prn) dosing schedule. Despite initial funding delays, the audit recorded superior treatment outcomes compared with those reported in the VISION trials at 12 weeks: 88% of audit patients maintained stable vision, 29% gained vision and 6% experienced severe vision loss compared with 70%, ≥6% and ≤10% of patients in VISION at 54 weeks, respectively. The audit indicates a positive correlation between patients with better baseline visual acuity (VA) and improved therapeutic benefits, including a greater likelihood of both vision gain and vision preservation. Experience at Moorfields also suggests that pegaptanib sodium is more useful in occult lesions than minimally classic lesions, and clinical experience suggests that combination therapies may offer the best approach with anti-VEGF therapies. Further randomized clinical trials will help better determine the optimal treatment strategies with pegaptanib sodium in neovascular AMD.
age-related macular degeneration; choroidal neovascularization; vascular endothelial growth factor; pegaptanib sodium; visual outcomes; funding
Evaluation of 1-year safety profile of intravitreal ranibizumab 0.5 mg in neovascular age-related macular degeneration (NV-AMD) within routine clinical practice.
The LUMINOUS programme comprises a prospective observational study assessing ranibizumab ‘real-world’ safety and clinical effectiveness across licensed indications worldwide and an annual retrospective pooled safety analysis from completed NV-AMD ranibizumab registries. 1-year data from four European registries are available. This retrospective pooled safety analysis assessed 1-year incidence rates for safety events of particular interest (key ocular or systemic events possibly related to the injection procedure or vascular endothelial growth factor inhibition) together with treatment exposure. Patients were treated according to local protocols within the ranibizumab licence.
Data of 4444 patients from registries in Germany (n=3470), the Netherlands (n=243), Belgium (n=260) and Sweden (n=471) were retrospectively pooled. Between 70.4% and 84.4% of enrolled patients completed 1 year of follow-up. Most frequent overall ocular events of particular interest were retinal pigment epithelial tears (27 patients; <1%) and intraocular pressure-related events (12 patients; <0.3%). Most frequent non-ocular event of particular interest was stroke (19 patients; 0.4%); annual incidence of stroke was low across all registries (0.0–0.5%).
Ranibizumab demonstrated favourable 1-year safety profile for NV-AMD in this routine clinical practice sample, consistent with previous reported trial data. Additional data from a larger patient population are needed to better describe the long-term safety profile of ranibizumab in routine clinical practice and further evaluate risk for infrequent but serious events in ‘real-life’ settings. The 5-year LUMINOUS prospective observational study will address this need.
Degeneration; Macula; Treatment Medical
We describe the role of intravitreal anti-vascular endothelial growth factor (VEGF) agents in Coats' disease in children. In a prospective, interventional, non-randomized case series, three patients (three eyes) aged 16, seven and two years were diagnosed to have Coats' disease. In Case 1 (16 yr/ male) with macular edema, previous laser photocoagulation being unsuccessful, intravitreal pegaptanib sodium (Macugen™) was tried. Case 2 (seven yr/ male) and Case 3 (two yr/ female) were diagnosed to have Stage 4 Coats' and underwent external needle drainage, laser photocoagulation, SF6 gas injection and intravitreal injection of bevacizumab (Avastin™). Reduction of exudation and attached posterior pole (Cases 2 and 3) was seen at a follow-up of six months and two months respectively. Intravitreal anti-VEGF agents may be successfully used as adjunct treatment in select cases of Coats' disease in childhood.
Coats' disease; vascular endothelial growth factor
Age-related macular degeneration (AMD) is the leading cause of severe visual loss and blindness over the age of 50 in developed countries. Vascular endothelial growth factor (VEGF) is considered as a critical molecule in the pathogenesis of choroidal neovascularization (CNV), which characterizes the neovascular AMD. Anti-VEGF agents are considered the most promising way of effectively inhibition of the neovascular AMD process. VEGF is a heparin-binding glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells. Two anti-VEGF agents have been approved by the US Food and Drug Administration (FDA) for the treatment of neovascular AMD. Pegaptanib sodium, which is an aptamer and ranibizumab, which is a monoclonal antibody fragment. Another humanized monoclonal antibody is currently off-label used, bevacizumab. This paper aims to discuss in details the effectiveness, the efficacy and safety of these three anti-VEGF agents. New anti-VEGF compounds which are recently investigated for their clinical usage (VEGF-trap, small interfering RNA) are also discussed for their promising outcomes.
Objective. To estimate the net health benefits of pegaptanib and ranibizumab by considering the impact of visual acuity and unintended effects (cardiovascular and hemorrhagic events) on quality-of-life among persons with neovascular age-related macular degeneration. Methods. We designed a probabilistic decision-analytic model using published data. It employed 17 visual health states and three for unintended effects. We calculated incremental net health benefits by subtracting the harms of each medication from the benefit using the quality-adjusted life year (QALY). Results. In a hypothetical cohort of 1,000 75-year olds with new-onset bilateral age-related macular degeneration followed for ten years, the mean QALYs per patient is 3.7 for usual care, 4.2 for pegaptanib, and 4.3 for ranibizumab. Net benefits decline with increasing baseline rates of unintended effects. Interpretation. Net health benefits present a quantitative, potentially useful tool to assist patients and ophthalmologists in balancing the benefits and harms of interventions for age-related macular degeneration.
Evaluate the efficacy of pegaptanib, a selective anti-vascular endothelial growth factor (VEGF) agent, and bevacizumab, a nonselective anti-VEGF agent, for retinal pigment epithelial detachment (PED) associated with occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).
Prospective, comparative, nonrandomized pilot study included patients with PED comprising >50% of total lesion in subfoveal location with visual acuity (VA) 20/40–20/400 and lesions either previously untreated or treated only with photodynamic therapy/verteporfin. Seven patients received pegaptanib 0.3 mg intravitreally (IVT); eight received IVT bevacizumab 1.25 mg. Follow-up occurred every 4–6 weeks for 6 months. Reinjection of initial medication occurred if there was intra- or subretinal fluid observed by optical coherence tomography (OCT) or increased PED. Endpoints were mean changes from baseline to month 6 in VA (ETDRS) and foveal thickness.
At baseline, mean VA was lower, and mean foveal thickness was greater in pegaptanib versus bevacizumab-treated patients (36.1 vs 49.5 letters; 470.4 vs 321.1 μm). Mean improvements to month 6 in VA and foveal thickness were greater for pegaptanib (VA: +9.1 vs +7.2 letters; foveal thickness: −88.2 vs −52.9 μm). On average, pegaptanib-treated patients had slower but more sustained improvement in VA and foveal thickness; bevacizumab-treated patients showed rapid improvement with a slow return towards baseline. Both agents were well tolerated.
Intravitreal injections of pegaptanib or bevacizumab are both efficacious and safe treatments for PED associated with occult CNV secondary to AMD.
bevacizumab; pegaptanib; retinal pigment epithelial detachment
Pegaptanib sodium (Macugen®) blocks the extracellular vascular endothelial growth factor (VEGF) isoform VEGF165, whose elevated levels are associated with the development of choroidal neovascularization (CNV). This selective inhibition prevents binding to the VEGF receptors and the development of the increased vascular permeability and the CNV associated with neovascular age-related degeneration (AMD). The VEGF Inhibition Study In Ocular Neovascularization (VISION) demonstrated that pegaptanib sodium confers clinically meaningful benefit in the treatment of all angiographic subtypes of neovascular AMD. It also has a favorable safety profile after 1 and 2 years of continuous treatment, and recent data suggest that the agent has a disease-modifying effect. Post hoc analysis of VISION suggests that treatment benefit may be greatest in patients with early lesions, in whom 80% achieved the primary endpoint of <15 letters lost, 47% maintained visual acuity (VA), and 20% gained ≥15 letters of vision. Similarly, our own clinical experience indicates that pegaptanib sodium achieves better outcomes in early lesions than in established lesions, particularly in patients with previously untreated minimally classic and occult lesions in whom VA improvement and lesion size stabilization has been recorded. Observations indicate that pegaptanib sodium has a slower mode of action than unselective VEGF inhibitors, resulting in an average of 3–4 injections being required to stabilize VA and lesion size. Pegaptanib sodium has good efficacy and safety profiles and represents a good treatment option for patients with early CNV membranes associated with neovascular AMD.
vascular endothelial growth factor (VEGF); choroidal neovasularization (CNV); age-related macular degeneration (AMD); pegaptanib sodium; early lesions; visual acuity (VA)
Vascular endothelial growth factor (VEGF) inhibitor medications such as ranibizumab, pegaptanib and bevacizumab are in use for the treatment of neovascular age-related macular degeneration (AMD) and other retinal conditions, although only ranibizumab and pegaptanib are approved for these conditions. In contrast, bevacizumab was developed for the intravenous systemic treatment of colorectal cancer and is not formulated for intravitreal use, but is commonly used off-label in ophthalmology. European Union legislation permits the use of drugs outside the terms of their licence (‘off-label’) only under certain circumstances, such as during clinical trials, compassionate/named patient use in the absence of a licensed alternative, emergency scenarios (e.g., pandemics) or at the discretion of a treating physician. In such cases, patients should be fully informed regarding their treatment and any potential risks involved. Off-label drug use can be an important tool to provide patients with treatment in cases of unmet medical need. However, the use of an unlicensed medicinal product, when a suitable licensed alternative is available, puts prescribing physicians at risk of liability if safety issues arise. Emerging clinical evidence suggests safety differences exist between ranibizumab and bevacizumab.
Medication safety; Off-label prescribing; Ranibizumab; Bevacizumab; Age-related macular degeneration
Age-related macular degeneration (ARMD) is the most common cause for visual impairment in the elderly in western countries. Recently several anti-vascular endothelial growth factor (VEGF) drugs like pegaptanib sodium (Macugen), ranibizumab (Lucentis) and bevacizumab (Avastin) are available for use in the management of wet ARMD. A major limitation of these drugs is that they require multiple intravitreal injections, every 4 to 6 weeks interval for a period of 2 years. Moreover, most of these drugs are too expensive for the general masses to afford in developing nations. Avastin, though used "off-label", offers a comparable result at affordable cost, however, long term results are awaited. The drug industry should review the entire pricing policy of these drugs in developing countries like India, and develop affordable alternative compounds. The article reviews the economic burden and affordability issues of these Anti-VEGF drugs in ARMD.
Age-related macular degeneration; avastin; lucentis; macugen
Diabetic Macular Edema (DME) is a common cause of impaired vision and blindness amongst diabetics. If not detected and treated early, the resulting vision loss can lead to considerable health costs and decreased health-related quality of life (HRQoL). The aim of this study was to provide evidence of the psychometric properties of the National Eye Institute - Visual Functioning Questionnaire (VFQ-25) for use in a cohort of DME patients who participated in a clinical efficacy and safety trial of pegaptinib sodium (Macugen).
A phase 2/3 randomised, double masked trial evaluated pegaptanib injection versus sham injection in patients with DME. The analysis was conducted using baseline HRQoL data of the VFQ-25 and the EQ-5D, on a modified intent-to-treat sample of 235 patients. These measures were administered by a trained interviewer by telephone in all but one of the study countries, where face-to-face interviews were conducted in the clinic. The measures were completed in the week prior to baseline, and after 54 weeks of treatment. Distance visual acuity, measured according to the Early Treatment Diabetic Retinopathy Study (ETDRS), was assessed at all time points. Psychometric properties of the VFQ-25 assessed included domain structure, reliability, concurrent and construct validity, responsiveness.
The VFQ-25 was found to consist of 11 domains slightly different than those proposed. Nevertheless, none of the eight established multi-item scales met the criterion for further splitting and the VFQ-25 was scored as in the developers’ instructions. Internal consistency reliability was demonstrated for six out of the eight original multi-item scales, with Cronbach's alpha ranging from 0.58 (Distance Activities) to 0.85 (Vision Specific: Dependency). The VFQ-25 domains generally showed a low to moderate correlation with EQ-5D visual analogue scale (range 0.16-0.43) and with the visual acuity score (range 0.10-0.41). Construct validity was upheld with higher VFQ-25 scores for patients who saw more letters according to the ETDRS. Almost all scales were shown to be responsive with Guyatt's statistic ranging from 0.10 to 0.56 at 54 weeks.
The VFQ-25 has evidence to support its validity and reliability for measuring HRQoL in DME. However, some operating characteristics of the instrument need further consideration and discussion in the case of DME patients. Further research is therefore warranted in this indication.
Diabetic macular edema; Visual functioning questionnaire; Psychometric analyses
The aim of this systematic review is to appraise the evidence for the use of anti-VEGF drugs and steroids in diabetic macular oedema (DMO) as assessed by change in best corrected visual acuity (BCVA), central macular thickness and adverse events
MEDLINE, EMBASE, Web of Science with Conference Proceedings and the Cochrane Library (inception to July 2012). Certain conference abstracts and drug regulatory web sites were also searched.
Study eligibility criteria, participants and interventions
Randomised controlled trials were used to assess clinical effectiveness and observational trials were used for safety. Trials which assessed triamcinolone, dexamethasone, fluocinolone, bevacizumab, ranibizumab, pegaptanib or aflibercept in patients with DMO were included.
Study appraisal and synthesis methods
Risk of bias was assessed using the Cochrane risk of bias tool. Study results are narratively described and, where appropriate, data were pooled using random effects meta-analysis.
Anti-VEGF drugs are effective compared to both laser and placebo and seem to be more effective than steroids in improving BCVA. They have been shown to be safe in the short term but require frequent injections. Studies assessing steroids (triamcinolone, dexamethasone and fluocinolone) have reported mixed results when compared with laser or placebo. Steroids have been associated with increased incidence of cataracts and intraocular pressure rise but require fewer injections, especially when steroid implants are used.
The quality of included studies varied considerably. Five of 14 meta-analyses had moderate or high statistical heterogeneity.
Conclusions and implications of key findings
The anti-VEGFs ranibizumab and bevacizumab have consistently shown good clinical effectiveness without major unwanted side effects. Steroid results have been mixed and are usually associated with cataract formation and intraocular pressure increase. Despite the current wider spectrum of treatments for DMO, only a small proportion of patients recover good vision (≥20/40), and thus the search for new therapies needs to continue.