Intravitreal Injection Of Pegaptanib Sodium Research Articles

Long-term outcome of intravitreal pegaptanib sodium as maintenance therapy in Japanese patients with neovascular age-related macular degeneration.

To evaluate the results of a 3-year follow-up of intravitreal pegaptanib sodium injection as maintenance therapy for the treatment of neovascular age-related macular degeneration (AMD) in Japanese patients. In this prospective, uncontrolled interventional study, 20 eyes of 19 patients with treatment-naïve AMD who had received 3 consecutive monthly injections of 0.5 mg/0.05 mL ranibizumab as the induction treatment and had shown clinical/anatomical improvement were enrolled. An intravitreal injection of 0.3 mg/0.09 mL pegaptanib sodium was administered as the maintenance therapy every 6 weeks. Booster treatments using ranibizumab were allowed if clinical deterioration was judged to be present. The primary outcome measures were the best-corrected visual acuity (BCVA) and the central foveal thickness (CFT) as evaluated using spectral-domain optical coherence tomography. Sixteen of the 20 eyes (80 %) were assessed at the 3-year follow-up. The mean logMAR BCVA improved significantly from 0.56 ± 0.31 before the induction treatment to 0.24 ± 0.25 at baseline (P < 0.001) and was well maintained at 156 weeks (0.25 ± 0.28, P = 0.938). Moreover, the mean CFT also decreased significantly from 346 ± 111 μm before the induction treatment to 232 ± 54 μm at baseline (P < 0.001) and was well preserved at 156 weeks (210 ± 59 μm, P = 0.278). Thirteen eyes (81.3 %) received an unscheduled booster treatment, and no severe systemic or ocular side effects occurred during follow-up. Intravitreal pegaptanib sodium injection as the maintenance therapy was effective in stabilizing the vision of patients with AMD in whom induction treatment led to improved BCVA, as evaluated at the 3-year follow-up.

Lamellar macular hole following intravitreal pegaptanib sodium (Macugen) injection for diabetic macular edema

To report on a patient who developed a lamellar macular hole 1month after an intravitreal pegaptanib sodium injection. Interventional case report. A 66year old patient developed a lamellar macular hole 1month after an intravitreal pegaptanib sodium injection for diabetic macular edema (DME). The pathogenesis of the lamellar macular hole in our case can be attributed to the intravitreal injection that may have induced vitreous incarceration, causing vitreoretinal traction at the macula and development of a lamellar macular hole. Alternatively or in association, pegaptanib itself may have caused the lamellar macular hole by inducing sudden reduction of the DME and exacerbation of tangential traction of the posterior vitreous on the overlying macular retina. Lamellar macular hole seems to be a potential complication of pegaptanib injection even in patients without pretreatment clinically detectable vitreomacular traction.

Pegaptanib sodium for acute retinal necrosis‐induced macular oedema

35-year-old immunocompromisedwoman with umbilical cordblood transplantation for adult lym-phoma presented with a 2-week his-tory of redness and blurred vision inboth eyes following initial herpes zos-ter encephalitis. Examination revealedvitritis, retinal whitening (Fig. 1), vas-culitis and optic nerve head oedema.Best-corrected visual acuity (BCVA)was 20⁄40 right eye (OD) and 20⁄60left eye (OS). Optical coherencetomography (OCT) showed no cystoidmacular oedema (CMO).Polymerase chain reaction testing ofthe aqueous fluid revealed varicellazoster virus and the patient was diag-nosed with bilateral acute retinalnecrosis (ARN).The retinitis was controlled withoral valacyclovir and intravitrealfoscarnet (2.4 mg) every 3 days,followed 10 days later by pars-planavitrectomy and endolaser in both eyes.BCVA improved to 20⁄25 OD and20⁄20 OS with no signs of ocularinflammation.One month later, the clinical coursewas complicated by severe CMO inthe right eye with a central fovealthickness of 410 lm and a BCVA of20⁄60, with no signs of ocular inflam-mation.After discussion of periocularand⁄or intravitreal use of steroids, thepatient refused to have this treatmentbecause of his family history of glau-coma and the increased potential riskof cataract formation. After a lengthydiscussion of the potential risks andbenefits of off-label intravitreal bev-acizumab or intravitreal pegaptanibsodium use, the patient requestedintravitreal pegaptanib sodium.An intravitreal injection of pegap-tanib sodium (Macugen; Eyetech⁄Pfizer, New York, NY, USA) wasadministered in the right eye withoutcomplication. Two weeks after injec-tion, OCT demonstrated a markedimprovement of the macular oedema,with a central foveal thickness of 197lm and a BCVA of 20⁄25 in theright eye (Fig. 2). Three months aftertreatment, there was no ocularinflammation and the OCT revealedno CMO.Acute retinal necrosis (ARN) syn-drome is a distinct infectious retinitiscaused by members of the herpes virusfamily that can impair vision. Itoccurs mostly in adult patients,especially those severely immunocom-promised, in association with a reacti-vation of a herpes virus infection (Lauet al. 2007).Active vasculitis is characterized byvascular sheathing and perivascularintraretinal haemorrhages. Vesselobstruction affects the central retinalartery more often than the vein and isa contributing factor to severe visionloss (Chang & Young 2007). Retinalischaemia is the major trigger ofvascular endothelial growth factor(VEGF) over-expression; it can leadto chronic inflammation and thedevelopment of retinal neovasculari-zation (Nishijima et al. 2007).Active inflammation secondary toARN progresses despite antiviraltreatment. High-dose systemic cortico-steroid therapy improves intraocularinflammation and improves vitreousopacity (Chang & Young 2007).However, some patients have CMOthat is resistant or non-responsive tosteroids.Bevacizumab is an anti-VEGFmonoclonal antibody that blocksall VEGF isoforms. Intravitrealbevacizumab has been used success-fully for the treatment of uveitic-resistant CMO (Cordero Coma et al.2007) with short-term improvementin BCVA and decreased OCT retinalthickness in a considerable propor-tion of patients. However, VEGF-Ais a survival factor for retinal neu-rons and a critical neuroprotectantduring the adaptative response toischaemic injury (Nishijima et al.2007).Pegaptanib sodium is a selectiveRNA aptamer that inhibits VEGF-165, the VEGF isoform primarilyresponsible for pathological ocularneovascularization and vascular per-meability, while sparing the physiolog-ical isoform VEGF-121. Retrospectivedata suggest that pegaptanib may pro-vide therapeutic benefit for patientswith diabetic macular oedema, prolif-erative diabetic retinopathy and reti-nal vein occlusion (Ng & Adamis2006).

Foveal Geographic Atrophy following Intravitreal Pegaptanib Sodium (Macugen) for Drusenoid Pigment Epithelium Detachment

To describe a patient with nonexudative age-related macular degeneration (AMD) who underwent intravitreal pegaptanib sodium injection for drusenoid pigment epithelium detachment (PED). A 66-year-old woman, who underwent intravitreal pegaptanib sodium injection in her right eye (RE) for chronic serous drusenoid PED, was submitted to a complete ophthalmologic examination, including fundus biomicroscopy, fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT-3, Humphrey-Zeiss, San Leandro, CA), 3 days and 1 month after the treatment. Three days after the intravitreal pegaptanib sodium injection, best-corrected visual acuity (BCVA) was 20/32 in the RE. One month later, the patient's BCVA dropped to 20/200 in the RE. Interestingly, fundus biomicroscopy, FA, OCT, and ICGA revealed the development of foveal geographic atrophy. Fundus-related perimetry (MP-1 Micro Perimeter, Nidek Technologies, Padova, Italy) revealed an eccentric and unstable fixation within 2 degrees with central absolute scotoma and pericentral diffuse reduction of sensitivity. The rapid development of foveal geographic atrophy in our patient may be related to the antivascular endothelial growth factor treatment, in part because of the reduced neuroprotective effect, and in part because of the adjunctive decreased blood flow in an already imbalanced foveal choroidal circulation due to AMD complicated by chronic serous drusenoid PED.

Intravitreal injection of pegaptanib sodium for proliferative diabetic retinopathy

Background:To compare the efficacy of intravitreal pegaptanib (IVP) with panretinal laser photocoagulation (PRP) in the treatment of active proliferative diabetic retinopathy (PDR).Methods:A prospective, randomised, controlled, open-label, exploratory study. Twenty subjects...

685 Trou maculaire lamellaire après injection intravitréenne de pegaptanib sodium pour œdème maculaire diabétique

The benefit of immediate focal photocoagulation for diabetic macular edema was demonstrated in the Early Treatment Diabetic Retinopathy Study (ETDRS). Anti-vascular endothelial growth factor (VEGF) therapy have been focused as alternative or adjunct treatments. We report a case of a patient who developed lamellar macular hole, one month after intravitreal pegaptanib sodium injection for diabetic macular edema. Interventional case report. A 66 – year-old patient with type 2 diabetes presented in the right eye a cystoid diabetic macular edema, without clinically detectable vitreomacular traction. One injection of pegaptanib 0.05 ml/0.3 mg was administered without complication. One month after intravitreal pegaptanib sodium injection (0.05 ml/0.3 mg), the patient presented no visual acuity improvement and complained of newly developed metamorphopsia. Fundus biomicroscopy and OCT revealed deep reduction of the cystoid macular edema, with lamellar macular hole formation, characterized by visibly detached posterior hyaloid, roof of the cyst above the macula, and foveal photoreceptors layer intact below the area of foveal dehiscence. Despite a lamellar hole could result from the degenerative process associated with cystoid macular edema, the pathogenesis of lamellar macular hole can be attributed in our case to the intravitreal injection, which may have induced vitreous incarceration, causing a vitreoretinal traction at the macula and the development of a lamellar macular hole. Alternatively or in association, pegaptanib itself may have caused the lamellar macular hole by inducing a sudden reduction of the diabetic macular edema and hence, the exacerbation of tangential traction of the posterior vitreous on the overlying macular retina. On the other hand, in our patient, we were not able to detect any other potential causes, such as epiretinal membrane formation and/or contraction, after the intravitreal pegaptanib injection. Lamellar macular hole seems to be a potential complication of pegaptanib injection, even in patients without pre treatment clinically detectable vitreo-macular traction.

Streptococcus mitis Endophthalmitis Presenting as Frosted Branch Angiitis After Intravitreal Pegaptanib Sodium Injection

An 80-year-old woman presented with endophthalmitis and a frosted branch angiitis-like picture following intravitreal injection of pegaptanib sodium for age-related macular degeneration. After vitreous tap and injection of antibiotics, the patient underwent vitrectomy because her clinical condition worsened. Cultures grew Streptococcus mitis, and the patient's visual acuity stabilized at hand motions following unsuccessful repair of a retinal detachment complicated by proliferative vitreoretinopathy. Because S. mitis can cause an endophthalmitis that presents as frosted branch angiitis, it must be considered in the differential diagnosis of patients who present with frosted branch angiitis.

Comparative Evaluation of Apoptotic Activity in Photoreceptor Cells after Intravitreal Injection of Bevacizumab and Pegaptanib Sodium in Rabbits

To evaluate quantitatively the apoptotic activity after intravitreal injections of pegaptanib sodium and bevacizumab in the rabbit retina. Different doses of bevacizumab (0.25, 0.625, 1.25, and 2.5 mg) and pegaptanib sodium (0.15, 0.3, and 0.6 mg) were injected intravitreally in 48 rabbits. The eyes were enucleated at different times for early studies at day 14 and for late studies at 3 months after a single injection or at 3 months, with 1 injection in each of the 3 months (day 90). The time course and dose-response of photoreceptor cells in the rabbit retina after intravitreal injection of bevacizumab or pegaptanib sodium were examined by histologic analysis with hematoxylin and eosin (H&E) staining, caspase-3 and -9 immunostaining, and in situ terminal-deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) of DNA fragments of paraffin-embedded sections. No sign of retinal toxicity was seen in H&E stained histologic sections of eyes that had received bevacizumab or pegaptanib sodium. Nuclear DNA fragmentation in the outer retinal layers shown by the TUNEL method was evident in the high-dose groups (55.3% with 1.25 mg and 64.5% with 2.5 mg bevacizumab, and 48.5% with 0.6 mg pegaptanib sodium) at 14 days and also in the clinical dose groups (49.8% with three injections [1 each month] of 0.625 mg bevacizumab and 44.3% with 0.15 mg pegaptanib sodium) at 90 days. The ratios of TUNEL-positive cells in physiologic saline and the sham-control groups were 32.3% and 21%, respectively. Intravitreal injection of bevacizumab and pegaptanib sodium caused a significant increase in apoptotic activity in rabbit photoreceptor cells. However, although bevacizumab caused increasing apoptotic activity at higher doses, similar dose-dependent adverse effects were not evident for pegaptanib sodium.

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.

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.

Progression of Choroidal Neovascularization Following Injection of Pegaptanib Sodium (Macugen) in Two Eyes With Neovascular Age-related Macular Degeneration

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. Interventional case report. 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. 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. 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.

Retinal Pigment Epithelial Tear Following Intravitreal Pegaptanib Sodium

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. Observational case reports. 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. 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. 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.