Pegaptanib Research Articles

Are intravitreal bevacizumab and ranibizumab effective in a rat model of choroidal neovascularization?

Vascular endothelial growth factor (VEGF) is an important stimulator of choroidal neovascularization (CNV). Bevacizumab (Avastin), ranibizumab (Lucentis) and pegaptanib sodium (Macugen) are anti-VEGF medications that have been used in the treatment of CNV. The purpose of our study is to evaluate the efficacy and safety of intravitreal injections of bevacizumab, ranibizumab and pegaptanib sodium in the treatment of CNV in a rat model. Multiple CNV lesions were induced by laser photocoagulation of the retina in Brown-Norway rats. After 3 weeks, 17 rats were divided into three groups and received intravitreal injections of bevacizumab, ranibizumab or pegaptanib sodium in different dosages. The lesions were evaluated by fluorescein angiography 1, 7, 14, and 28 days later to assess the efficacy of these medications. Different doses of bevacizumab did not show any effect on stopping the leakage on fluorescein angiography on days 1, 7, 14, and 28. Ranibizumab and pegaptanib sodium did not stop the leakage of CNV either. No angiographic or histopathologic toxicity was observed. These three anti-VEGF agents did not show any therapeutic effect on stopping CNV leakage in rats. Previous experiments with ranibizumab in monkeys resulted in a significant decrease in leakage of CNV. The difference may be due to the fact that both ranibizumab and bevacizumab are humanized and species-specific. There are several studies evaluating the effect of bevacizumab in non-primates. Since bevacizumab is humanized, the results of studies on non-primates may not be similar to humans and non-human primates.

Efficacy of pegaptanib sodium in occult or minimally classic

Abstract Purpose Recent studies have highlighted the efficacy of Pegatanib sodium in sub‐epithelial, occult, CNV seen in the early stages of the disease. Methods This was a prospective study with a follow‐up of 24 months. Patients underwent a complete examination including ETDRS visual acuity measurements, fundus photographs, FA and ICG‐A and OCT, as well as treatment by intra‐vitreous injection every 6 weeks. Results 24 patients (16 women) presenting with exudative ARMD were chosen. The mean age was 76 years. 8 eyes had a sub‐epithelial occult without classic neovascular lesion, or minimally classic. 8 eyes had a neovascular lesion of pre‐epithelial type, predominantly classic. 4 eyes had a neovascular lesion of chorio‐retinal anastomosis (CRA) associated with a PED. 4 lesions were fibro‐vascular in type. At the end of the study, 100% of pure, occult type or « minimally classic » lesions presented with a loss of less than 15 letters of VA and in 25% of cases there was an improvement of 15 letters or more. Six out of eight treated patients did not lose any letter and five patients had an improvement of at least one letter. These patients had an initial VA of 20/100 or more. FA did not demonstrate any leakage in six cases, and OCT demonstrated an absence of intra‐retinal edema in all cases. Out of the 16 patients who presented with a « predominantly classic » or with CRA or with fibro‐vascular type lesion, only 3 had an improvement of at least one letter compared with 10 who had the loss of more than 15 letters of VA. Patients in younger age brackets had the better functional results. Conclusion Treatment with Pegaptanib sodium is indicated preferentially for occult or minimally classic type lesions, which are recent and small.

Injection intravitréenne : évaluation rétrospective de la technique et des complications d’une série de 2028 injections

To observe the tolerance of repeated intravitreous injections over the short and long term and to analyze their complications. The clinical records of consecutive patients having one or several intravitreous injections between 2002 and 2007 were evaluated, for all indications except the treatment of endophthalmitis. 2028 intravitreous injections were performed, mainly for age-related macular degeneration (n=1 192) or macular edema secondary to diabetes mellitus or retinal vein occlusion (n=41). The injected drug was triamcinolone acetonide 4 mg (339 injections), pegaptanib sodium 0.3 mg (1179 injections), and ranibizumab 0.3 (497 injections). The patients received 1-27 intravitreous injections per eye. The main complications were endophthalmitis (two after triamcinolone, 0.1% of the total group), pseudoendophthalmitis (two after triamcinolone, 0.1% of the total group), hypertony (7.69% of the total group, 13.78% after triamcinolone, 3.56% after pegaptanib, 1.21% after ranibizumab), including five cases of acute hypertony with transient light perception loss after ranibizumab, cataract (0.44% of total group), and macular hole (one patient after triamcinolone). No case of retinal detachment nor systemic complication was observed. Most of the complications were observed with the use of nonfiltered triamcinolone. The incidence of endophtalmitis was considerably lower with increased experience and the use of a dedicated room for the injections. Repeated injections were locally well tolerated. With the strict respect of asepsis rules, intravitreous injection seems well tolerated over the short and long term.

Intravitreal pegaptanib sodium (Macugen) for diabetic macular edema

Abstract Purpose To report the functional and anatomic outcomes resulting from the use of intravitreal pegaptanib sodium as primary therapy in patients with diabetic macular edema (DME). Methods We conducted a retrospective outcome analysis, by optical coherence tomography (OCT) and best‐corrected visual acuity (BCVA), of eyes with DME treated with primary intravitreal pegaptanib sodium (Macugen). Moreover, we evaluated the foveal transverse photoreceptor (PR) band integrity in the OCT images, at the time of the last follow‐up visit. Results Sixty‐three eyes of 48 patients with a minimum of 6 months’ follow‐up (FU) were included for analysis. Intravitreal pegaptanib was found to produce significant improvements in mean BCVA (p = 0.019) and reductions in mean central macular thickness (CMT) (p <0.001), as soon as the 6‐weeks FU. Most eyes (60/63) required a mean of 3 repeated treatments, over a mean FU period of 6.7 +/‐ 1.2 months, to achieve significant improvements in mean BCVA (p <0.001) and mean CMT (p <0.001). In our series, the lower visual acuities tended to congregate in the group with the less‐defined PR band (p <0.001), and the lower CMT tended to congregate in the group with the best‐defined PR band (p=0.04), even though the higher CMT did not tend to congregate in the group with the less‐defined PR band. Conclusion Our findings demonstrate that selective inhibition by intravitreal pegaptanib sodium of VEGF165 may produce a clinically meaningful and statistically significant benefit in the treatment of DME.

Intravitreal pegaptanib sodium (Macugen®) for radiation retinopathy following episcleral plaque radiotherapy

Editor, A 63-year-old woman was referred to our department with a best-corrected visual acuity (BCVA) of 20/25 in her right eye and 20/20 in her left eye. She presented with a posterior uveal mass of her right eye; this was diagnosed as choroidal melanoma, involving the superonasal quadrant. The tumour sizes were 12.54 mm (base) and 4 mm (height). The patient underwent episcleral plaque radiotherapy with a notched Ruthenium 106 plaque. Fourteen months after plaque treatment, the patient developed early radiation retinopathy involving the fovea – consisting of capillary changes, retinal haemorrhages and retinal exudation (non-proliferative radiation retinopathy) – and was therefore offered sector laser photocoagulation to prevent progression of radiation retinopathy (Finger 1997). Three months later, the patient developed disc neovascularization (proliferative radiation retinopathy) and massive retinal exudation involving the fovea, as evaluated by fundus biomicroscopy, fluorescein angiography (FA) (Fig. 1A) and optical coherence tomography (OCT-3; Humphrey-Zeiss, San Leandro, California, USA) (Fig. 1B); BCVA dropped to 20/200. After discussing adjunctive treatment options and being presented with the option of intravitreal pegaptanib sodium [Macugen®; (OSI) Eyetech and Pfizer Inc., Melville, New York, USA], the patient requested that the treatment be given. Intravitreal pegaptanib sodium 0.3 mg was administered without complication. At the 1-month follow-up, BCVA improved to 20/40; fundus biomicroscopy, FA and OCT revealed almost total resolution of the retinal and macular exudation and partial regression of disc neovascularization. At the time of writing, 6 months after the injection, the patient’s BCVA remained 20/40, with no recurrence of retinal and macular exudation as well as partial regression of disc neovascularization, as evaluated by fundus biomicroscopy, FA (Fig. 1C) and OCT (Fig. 1D). Fluorescein angiography frame (A) and OCT-3 scan (B) of the right eye showing disc neovascularization and massive retinal exudation involving the fovea 3 months after sector scatter laser photocoagulation. Fluorescein angiography frame (C) and OCT-3 scan (D) of the right eye showing partial regression of disc neovascularization and resolution of the retinal and macular exudation 6 months after intravitreal injection of pegaptanib sodium. Closure of blood vessels is the central effect of ionizing radiation. FA after radiation therapy of choroidal melanomas reveals closure of blood vessels within and around the tumour (the tissues surrounding the targeted zone). The histopathology of radiation-induced ischaemic vasculopathy shows the destruction of the endothelial cells and pericytes that maintain blood-vessel walls (Archer et al. 1991). These changes, induced by hypoxia, alter blood flow patterns and produce alternative channels with thickened and fenestrated walls (Archer et al. 1991). Vascular endothelial growth factor (VEGF) is induced by hypoxia and it has been implicated in the development of iris and retinal neovascularization in ischaemic retinopathies. In addition or in association with its role in inducing neovascularization, VEGF may contribute to blood–retinal barrier breakdown in a variety of ocular disorders, and blockage of VEGF signalling may help to reduce some types of macular oedema. Pegaptanib sodium is an anti-VEGF, developed to bind and block the activity of extracellular VEGF (aptamer), specifically the 165-amino-acid isoform (VEGF 165); it is used effectively in the treatment of neovascular age-related macular degeneration (Gragoudas et al. 2004). Given that blockage of VEGF signalling may help to reduce some types of macular oedema (Vinores et al. 1997) and seems to induce short-term reduction of fluorescein leakage from persistent active retinal new vessels (Jorge et al. 2006), we decided to inject 0.3 mg of pegaptanib sodium into the vitreous cavity of our patient. One month after the intravitreal injection of pegaptanib sodium, BCVA improved to 20/40; fundus biomicroscopy, FA and OCT revealed almost total resolution of the retinal and macular exudation and partial regression of disc neovascularization. In addition, there has been no recurrence and no complications from the intravitreal injection of pegaptanib sodium, even at the 6-month follow-up. Similar results have been reported recently using intravitreal bevacizumab, a non-specific anti-VEGF (Finger & Chin 2007). Based on our findings, intravitreal pegaptanib sodium associated with sector scatter laser photocoagulation seems to induce short-term regression of retinal and macular exudation and partial regression of disc neovascularization, with improvement of visual acuity. Further investigations are required to confirm our results. Given that recurrences could be possible and should require additional therapy, we believe that not only more treated cases but also a longer follow-up are needed.

Intravitreal ranibizumab (Lucentis) for choroidal neovascularization associated with vitelliform macular dystrophy

Editor, C horoidal neovascularization (CNV) is a rare complication of Best’s disease (Miller et al. 1976; Noble et al. 1978). Ranibizumab (Lucentis , Genentech, Inc., San Francisco, CA, USA) is a recombinant, humanized, monoclonal antibody antigen-binding fragment (Fab) that neutralizes all biologically active forms of vascular endothelial growth factor (VEGF) and is effectively used in the treatment of neovascular agerelated macular degeneration (AMD) (Brown et al. 2006; Rosenfeld et al. 2006). We present an interventional case report describing a young patient affected with retrofoveolar CNV associated with Best’s vitelliform macular dystrophy, who underwent treatment with intravitreal ranibizumab. A 13-year-old boy was referred to our department for a sudden decrease in vision in his left eye (LE). Three years before, the patient had been diagnosed with extrafoveal CNV in the right eye (RE) occurring as a complication of bilateral vitelliform macular dystrophy, which had been treated by argon laser photocoagulation. The parents of the young patient signed a comprehensive consent form before proceeding with any examinations or treatments. The subject’s best corrected visual acuity (BCVA) was 20 ⁄32 RE and 20 ⁄ 126 LE. On fundus biomicroscopy, the macula of the LE showed a subfoveal greenish-grey lesion, and a subretinal haemorrhage inferonasal to the fovea associated with a serous detachment, within the egg-yolk lesion area. Fluorescein angiography (FA) in the LE showed blocking hypofluorescence caused by subretinal haemorrhage, and hyperfluorescence resulting from CNV leakage into the subretinal space at the superior border of the fovea (Fig. 1A). Indocyanine green angiography (ICGA) late frames showed focal hyperfluorescence in the area corresponding with the CNV (Fig. 1B). Optical coherence tomography (OCT3; Humphrey-Zeiss, San Leandro, CA, USA) confirmed the presence of a subfoveal CNV, characterized by a moderately reflective mass protruding from the retinal pigment epithelium, associated with neurosensory retina elevation in the macular area (Fig. 1C). After discussing treatment options, including that of intravitreal ranibizumab, the parents of the young patient requested that intravitreal ranibizumab be given. Intravitreal ranibizumab 0.05 ml ⁄ 0.5 mg was administered with no complications. At the 1-month follow-up, BCVA in the LE had improved to 20 ⁄ 40, fundus biomicroscopy revealed resolution of the subretinal haemorrhage, FA and ICGA revealed the CNV closure, and OCT revealed total resolution of the associated serous retinal detachment as a result of the CNV closure. Three months after the injection, BCVA remained at 20 ⁄ 40, with no recurrence as evaluated by fundus biomicroscopy, FA (Fig. 2A), ICGA (Fig. 2B) and OCT (Fig. 2C). Moreover, at the time of writing, 6 months after the injection, we documented the absence of recurrence by high-definition spectral domain OCT (HD-OCT) (OCT 4000 Cirrus; Humphrey-Zeiss) (Fig. 2D–G). In this patient we performed intravitreal ranibizumab because of the subfoveal localization of the CNV. One month after the injection, BCVA had improved to 20 ⁄ 40, and fundus biomicroscopy, FA, ICGA and OCT revealed total regression of the CNV. No subsequent recurrence and no complications from the intravitreal injection of ranibizumab have arisen during follow-up (6 months). A B

Pegaptanib sodium for occult choroidal neovascularization in neovascular age-related macular degeneration: a prospective case series

To assess the effects of pegaptanib in the treatment of subfoveal occult choroidal neovascularisation (CNV) associated with neovascular age-related macular degeneration (NV-AMD) in a compassionate use program in France. Pegaptanib was authorized for patients with CNV-associated visual impairment and in whom usual care (thermal laser photocoagulation or photodynamic therapy with verteporfin) was not appropriate. Patients with occult CNV lesions received intravitreous pegaptanib (0.3 mg every 6 weeks) and were followed with repeated fluorescein angiography, scanning laser ophthalmoscopy-infracyanine green angiography, and ocular coherence tomography through 52 weeks. Of 56 patients (predominantly occult, N=22; purely occult, N=8; occult with chorioretinal anastomosis, N=12; occult with pigment epithelial detachment, N=14), 30% had earlier treatment. All received eight pegaptanib injections. At week 52, 79% were responders (lost <15 letters of visual acuity), 43% gained >or=0 letters, and 9% gained >or=15 letters. The best functional results were obtained in the predominantly and pure occult subgroups (responders, 86 and 75%; gained >or=0 letters, 50 and 50%). Maximum visual outcomes that correlated with morphologic improvements on each diagnostic imaging tool were seen after at least three injections. No significant ocular or systemic adverse events occurred. Treatment with pegaptanib was associated with objective functional improvements that can be correlated with objective clinical improvements on routine diagnostic imaging tools in patients with occult NV-AMD. Optimum treatment results appear after at least 4 months of therapy in the majority of cases.

Comparing Pegaptanib and Triamcinolone Efficacy in the Rat Choroidal Neovascularization Model

To evaluate the prophylactic effect of intravitreal pegaptanib sodium on choroidal neovascularization membrane (CNVM) development and compare its performance with that of triamcinolone acetonide. In drug-treated and control groups, CNVMs were induced by laser trauma. Immediately after undergoing the laser procedure, animals received intravitreal injections of pegaptanib sodium, 8 or 17 mug; triamcinolone acetonide, 200 mug; or a vehicle solution. After 21 days, fluorescein angiography was performed. The CNVM mean diameters and radial thicknesses were measured histologically. Mean CNVM diameters were 10% to 13% smaller in pegaptanib-treated eyes and 43% smaller in triamcinolone-treated eyes compared with laser-only control eyes. Late-stage fluorescein angiography leakage scores, on a scale of 0 to 3, suggested a statistical difference between triamcinolone- (0.6) and pegaptanib(8 microg)-treated (1.5) groups compared with the laser-only control group (2.0). The CNVM mean thicknesses were greater in the pegaptanib(8 microg)- (79 microm) and pegaptanib(17 microg)-treated (71 microm) groups and significantly smaller in the triamcinolone-treated group (26 microm) compared with the laser-only control group (67 microm). In this animal model of choroidal neovascularization, intravitreal pegaptanib exhibited marginal or no effect on CNVM development; whereas intravitreal triamcinolone evoked robust inhibition of CNVMs. Clinical Relevance Pegaptanib treatment may be insufficient to prevent CNVM formation.

Pegaptanib sodium for neovascular age-related macular degeneration: third-year safety results of the VEGF Inhibition Study in Ocular Neovascularisation (VISION) trial

Aims:To evaluate the safety of up to 3 years of pegaptanib sodium therapy in the treatment of neovascular age-related macular degeneration (NV-AMD).Methods:Two concurrent, prospective, multicentre, double-masked studies randomised subjects with...

Cost-Effectiveness Model for Neovascular Age-Related Macular Degeneration: Comparing Early and Late Treatment with Pegaptanib Sodium Based on Visual Acuity

Objective To compare the cost-effectiveness of pegaptanib and usual care within three distinct cohorts of subfoveal neovascular age-related macular degeneration (NV-AMD) patients, that is, those with early, moderate, and late disease, using a comprehensive economic model. Methods A Markov framework was used to model lifetime movement of a subfoveal NV-AMD cohort through health states based on visual acuity. The model takes a US payer perspective of patients over the age of 65 years. Clinical efficacy was based on published results for the 0.3 mg pegaptanib and usual care groups. Expert interviews were conducted to determine adverse event treatment patterns and vision rehabilitation resource use. Incidence and costs of comorbidities such as depression and fractures associated with the effects of declining visual acuity were based on our previously published analysis of Medicare data. Transition probabilities were derived from published clinical trial data for each 3-month cycle. Utilities were derived from published sources. Three runs of the model were conducted with cohorts of newly diagnosed patients. Patients were classified as having early, moderate, or late NV-AMD defined as visual acuity in the better-seeing eye of 20/40 to more than 20/80, 20/80 to more than 20/200, and 20/200 to more than 20/400, respectively. Costs and outcomes were discounted 3.0% per annum. Results Incremental costs per vision-year gained and per quality-adjusted life-year (QALY) gained for early NV-AMD patients were approximately one-third those of patients with late disease ($15,279 vs. $57,230 and $36,282 vs. $132,381, respectively). On average, patients treated early with either pegaptanib or usual care incurred lower lifetime total direct costs than those treated later. Sensitivity analysis showed that base-case incremental costs per QALY gained for pegaptanib versus usual care were relatively robust. Conclusions For patients with subfoveal NV-AMD, treatment with pegaptanib should be started as early as possible to maximize the clinical and economic benefits.

Pegaptanib sodium treatment in neovascular age-related macular degeneration: clinical experience in Germany

The VEGF Inhibition Study In Ocular Neovascularisation (VISION) reported the efficacy of intravitreal (ITV) vascular endothelial growth factor (VEGF) inhibition with pegaptanib sodium (Macugen((R))) 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. 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 mum at baseline to 251.63 mum 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.

Pegaptanib sodium for neovascular age-related macular degeneration: clinical experience in the UK

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 VEGF(165) (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.

Role of pegaptanib sodium in the treatment of neovascular age-related macular degeneration

Age-related macular degeneration (AMD) is responsible for more than half the blind registration in the United Kingdom. Retinal manifestations of AMD can be categorized as either atrophic or neovascular. The hallmark of AMD is the development of choroidal neovascularization (CNV). Until recently, there have been few, limited treatment modalities (eg, photodynamic therapy [PDT]) for this condition and the mainstay of treatment has comprised social and lifestyle support. However, increased understanding of the molecular processes at work in neovascular AMD and CNV in recent years has led to the introduction of new anti-angiogenic agents that target vascular endothelial growth factor (VEGF). These agents either inhibit a selected VEGF isoform (eg, VEGF(165) inhibition by pegaptanib sodium) or inhibit all forms of the VEGF isoform (eg, non-selective VEGF blockade by ranibizumab). The trial data suggest that non-selective inhibition of VEGF offers better treatment outcomes in neovascular AMD. As a result, agents that inhibit all VEGF isoforms are now widely used as first-line therapy for this condition. However, it is known that VEGF plays an important role in maintaining the intergrity of the cardiovascular system and, particularly as the age of patients with AMD places them at an elevated risk of thromboembolic events, long-term post-marketing surveillance data are essential to determining whether non-selective VEGF blockade confers any increased risk. Theoretically, selective VEGF inhibition may reduce any risk associated with pan-VEGF blockade, yet on the basis of initial trials, their use remains more limited at this time. However, clinical practice suggests that initial trials may have under-estimated the efficacy of selective-VEGF inhibition. Observational studies also indicate that better treatment outcomes may be possible by combining VEGF inhibitors sequentially with each other, or with existing therapies (eg, photodynamic therapy [PDT]). The optimum role and indications of anti-VEGF agents will come through careful consideration of the available efficacy and safety data, from the outcomes of long-term follow-up studies, and through assessment of the relative merits of the two approaches to VEGF inhibition in clinical practice. At this time, further head-to-head trials, and economic evaluations, comparing the treatment alternatives are needed.

Update on treatments for diabetic macular edema

Due to modest outcomes with macular laser, other treatment modalities for diabetic macular edema have been evaluated. Intravitreal triamcinolone acetonide, pars plana vitrectomy, oral protein kinase C inhibitors and, from more recently, anti-vascular endothelial growth factor therapy are reviewed. Intravitreal triamcinolone acetonide may be more effective than laser. Intravitreal triamcinolone acetonide followed by laser may be more effective than intravitreal triamcinolone acetonide alone. Ruboxistaurin, a selective protein kinase C betainhibitor, reduced retinal vascular leakage in patients with diabetic macular edema and reduced the rate of sustained moderate visual loss in those with moderately severe to very severe non proliferative diabetic retinopathy. Several anti-vascular endothelial growth factor agents are under evaluation. Intravitreal pegaptanib sodium (0.3 mg) improved vision and reduced central retinal thickness compared to sham. Data on the other anti-vascular endothelial growth factor agents is limited, but there are promising results, with ranibizumab (0.5 mg) and bevacizumab reducing foveal thickness and improving visual acuity in some patients with diabetic macular edema. There remains no proven intervention that consistently prevents or reverses visual loss from diabetic macular edema in all patients. A variety of promising new medical and surgical therapies are under investigation, but further research is required to determine their role alone or in combination.

Intravitreal pegaptanib sodium for refractory pseudophakic macular oedema

Evaluate the efficacy of intravitreal pegaptanib sodium (Macugen) in refractory pseudophakic cystoid macular oedema (CME). Prospective, nonrandomized, interventional case series. Four eyes of four patients with refractory pseudophakic CME to pars plana vitrectomy and intravitreal bevacizumab and triamcinolone, were treated with pegaptanib sodium, with a mean follow up of 4 months. Pre- and postinfection examinations included assessment of best-corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study chart (ETDRS), fluorescein angiography (FA), and optical coherence tomography (OCT). Visual acuity increased in all patients after intravitreal pegaptanib sodium. OCT showed improvement of the retinal thickness in the macular area. Intravitreal pegaptanib sodium (Macugen) is a promising treatment for pseudophakic cystoid macular oedema resistant to other medical treatment strategies. However, further study is needed to assess the treatment's long term efficacy and the need for retreatment.

TREATMENT OF VASCULARLY ACTIVE FAMILIAL EXUDATIVE VITREORETINOPATHY WITH PEGAPTANIB SODIUM (MACUGEN)

To report results of treatment of vascularly active familial exudative vitreoretinopathy (FEVR) with pegaptanib sodium (Macugen; Eyetech Pharmaceuticals, New York, NY) injection. In a retrospective case series, four patients with vascularly active FEVR, as demonstrated by increasing subretinal exudation despite photocoagulation, cryotherapy, and/or intravitreal steroid injection, received a single intravitreal injection of pegaptanib sodium. Preinjection and postinjection fundus photography, fluorescein angiography, and optical coherence tomography were performed to evaluate the changes in visual acuity, vascular activity, and amount of exudation. The mean follow-up period was 11.2 months (range, 8.1-15.5 months) after the first intravitreal injection. All four patients had a decrease in exudation after treatment with pegaptanib sodium documented by a decrease in subretinal exudate by fundus photography and decreased leakage by fluorescein angiography. After reduction of exudation, two patients required vitrectomy to relieve vitreoretinal traction. Visual acuity improved in two patients, stabilized in one patient, and worsened in one patient secondary to tractional retinal detachment. No injection-associated systemic or ocular complications were observed in any of the treated patients. Intravitreal injection of pegaptanib sodium is a potential treatment option for patients with FEVR and worsening exudation despite treatment with standard therapy. Vitreoretinal traction may develop with rapid resolution of subretinal exudates, requiring surgical intervention. However, visual acuity can improve after retinal traction is released. Further studies using anti-vascular endothelial growth factor agents are needed to better understand treatment of FEVR.

Simultaneous but Not Prior Inhibition of VEGF165 Enhances the Efficacy of Photodynamic Therapy in Multiple Models of Ocular Neovascularization

To investigate the effect of the combined treatment of photodynamic therapy and specific VEGF165 inhibition with pegaptanib sodium (Macugen; Eyetech Pharmaceuticals, Lexington, MA) on ocular neovascularization. Photodynamic therapy's (PDT's) effects on the integrity of pegaptanib sodium were analyzed by HPLC, a VEGF165-binding assay, and a VEGF165-induced tissue factor gene expression assay. The effects of mono- or combined treatment on vessel growth and regression were determined in a murine corneal neovascularization model. The effects of combined treatment on vessel growth were also determined in a murine choroidal neovascularization model. PDT did not affect the chemical composition of pegaptanib sodium nor the efficacy of pegaptanib sodium in the inhibition of VEGF165 binding to Flt-1 and VEGF165-induced gene expression. In an animal model of effects on existing ocular neovascular lesions (corneal neovascularization), PDT monotherapy yielded an initial regression of these vessels, but there followed a rapid regrowth. In contrast, pegaptanib sodium monotherapy yielded little regression but potently abrogated further vessel growth. The combination of pegaptanib sodium and PDT resulted in the regression of the neovascular lesions, as observed with PDT alone, but also prevented significant vessel regrowth, leading to a significantly greater reduction in lesion size than did each monotherapy. In addition, there was a significantly greater effect of the combination of pegaptanib sodium and PDT on lesion size in choroidal neovascularization than with each monotherapy. Pretreatment with pegaptanib sodium appeared to decrease the efficacy of PDT-induced vessel regression in corneal neovascularization, and as such the enhanced efficacy over monotherapy when the agents were delivered simultaneously was not observed. Although the combined simultaneous treatment of ocular neovascularization with PDT and pegaptanib sodium may provide a more effective approach for the regression and overall treatment of CNV associated with AMD, the order of addition of these treatments may play a role in achieving optimal efficacy.

Pegaptanib sodium for the treatment of age-related macular degeneration

Background: Pegaptanib sodium, the first aptamer therapeutic approved for use and the first antiangiogenic agent used to treat ocular neovascular disease, acts by inhibiting the 165 isoform of vascular endothelial growth factor believed primarily responsible for pathologic ocular neovascularization and vascular permeability. Objective: To briefly present the pharmacology, clinical efficacy and safety, and role of pegaptanib in treating ocular neovascular diseases. Methods: A systematic literature review and synopsis. Results/conclusion: After more than 10 years in development, clinical trials have shown pegaptanib efficacy in treating choroidal neovascularization of age-related macular degeneration. Its excellent ocular and systemic safety profiles have been confirmed in up to 3 years of experience. Early phase, well-controlled studies also suggest therapeutic benefit in diabetic retinopathy and retinal vein occlusion.

Treatment of Neovascular Age-Related Macular Degeneration with Pegaptanib and Boosting with Bevacizumab or Ranibizumab as Needed

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. 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. 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. 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.

Intravitreal Pegaptanib Sodium for Irvine-Gass Syndrome

To report the novel use of intravitreal pegaptanib sodium for the treatment of refractory cystoid macular edema (CME) following cataract extraction. A 72-year-old man presented with decreased visual acuity in his right eye 8 months after uncomplicated phacoemulsification cataract extraction and intraocular lens implantation. His bestcorrected visual acuity (BCVA) was 20/125 in the affected eye, and fundus examination revealed CME despite 6 months of oral and topical indomethacin therapy. Fluorescein angiography (FA) showed leakage in the central region with no signs of neovascularization, and optical coherence tomography (OCT) confirmed the diagnosis with thickening of the fovea. Because of his history of glaucoma, the patient chose to be treated with intravitreal pegaptanib sodium 0.3 mg. At the 1-week follow-up, BCVA was 20/25, and the FA and OCT revealed almost total resolution of the CME with no adverse sequelae. Six months postinjection, the patient's BCVA remained 20/25 with no recurrence of CME. Perimetry revealed a stable fixation within 4 degrees with slight reduction of sensitivity. Vascular endothelial growth factor inhibition with intravitreal pegaptanib sodium appears to be of benefit in the treatment of chronic refractory CME with improvement of visual acuity. Studies evaluating pegaptanib''s use in this setting with long-term follow-up are warranted to confirm its efficacy and safety.