When Should Anti-Vascular Endothelial Growth Factor Treatment Be Stopped in Age-Related Macular Degeneration? (original) (raw)
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Investigative Opthalmology & Visual Science, 2007
PURPOSE. Photodynamic therapy (PDT) and the administration of compounds acting against vascular endothelial growth factor (anti-VEGF) are approved for the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Experimental evidence that the combined use of both treatment options may improve therapeutic outcome is presented. METHODS. Fertilized chick eggs were incubated until day 12 of embryo development (EDD12) and were treated by PDT using two different photosensitizing agents (liposomal formulation of BPD-MA; m-THPP encapsulated in polymeric nanoparticles) and were visualized using an epifluorescence microscope. Vascular occlusion of the treated zones of the chorioallantoic membrane (CAM) was assessed by fluorescence angiography 24 and 48 hours after treatment. Alternatively, PDT-treated areas were exposed to a soluble VEGF receptor antagonist (sFlt-1) 6 hours after treatment and were analyzed. RESULTS. Vascular occlusion in the PDT-treated areas was observed with both photosensitizers 24 hours after treatment. Reperfusion of preexisting blood vessels and first signs of revascularization were visible 48 hours after PDT. Topical administration of sFlt-1 to the treated areas augmented occlusion and limited subsequent angiogenesis in a dose-dependent manner. CONCLUSIONS. The combined use of PDT and of agents targeting angiogenic cytokines may synergistically improve therapeutic outcome after combined treatment in patients with CNV secondary to AMD.
Anti-VEGF therapy for choroidal neovascularisation previously treated with photodynamic therapy
Eye, 2009
Purpose This interventional, noncomparative case series assessed the outcome of intravitreal pan-anti-vascular endothelial growth factor (VEGF) agents in eyes with persistent or reactivated choroidal neovascularisation (CNV) following previous treatment with photodynamic therapy (PDT). Methods Baseline assessments including best-corrected visual acuity, fluorescein angiography (FFA), and optical coherent tomography (OCT) were performed. Intravitreal ranibizumab and/ or bevacizumab were administered on a PRN basis, guided by changes in visual outcome and OCT findings. The follow-up period was at least 6 months. Results Twenty-five subjects with predominantly classic CNV, previously treated with PDT (mean 1.84 PDT sessions) showed reactivation or persistent CNV. The mean interval between PDT and intravitreal anti-VEGF treatment was 18.32 months (1-48 months); and patients received an average of 3.2 injections over a 6-month period. The mean change of visual acuity following PDT was À10.12 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (54.36 ± 15.79-44.24 ± 17.32 letters). Following anti-VEGF therapy, the mean change in visual acuity at 3 and 6 months were þ 1.76 and þ 0.72, respectively. The proportion of subjects with stable vision (loss of p15 letters) was 96% at 3 months and 88% at 6 months; the proportion of subjects who showed improved vision (X15 letters) was 8% at 3 months and 4% at 6 months. Conclusions Anti-VEGF agents stabilised the visual outcomes of eyes previously treated with PDT. However, the proportion of patients who showed improved vision in this group was smaller than the proportion reported in subjects with treatment-naive lesions.
Retina, 2008
Purpose: To evaluate the 12-month visual outcome of photodynamic therapy with verteporfin (PDT-V) for patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration and to verify the predictive role of visual and angiographic factors. Methods: This retrospective, interventional, consecutive case series study included subjects with different forms of subfoveal CNV. All patients received PDT-V according to Treatment of Age-Related Macular Degeneration With Photodynamic Therapy/Visudyne in Photodynamic Therapy guidelines. A review of medical and angiographic records was performed. Results: Two hundred sixteen patients were divided into 4 study groups: group I, 60 eyes with classic CNV; group II, 56 eyes with predominantly classic CNV; group III, 42 eyes with minimally classic CNV; and group IV, 58 eyes with occult CNV. In groups I and II, best-corrected visual acuity (BCVA) was moderately decreased, without reaching a statistically noticeable level during the entire follow-up; lesion size reduction only reached significance in group I. Groups III and IV showed evident worsening of BCVA (P Ͻ 0.05), despite concomitant reduction in CNV size (statistically remarkable only for occult CNV). All study groups exhibited a significant correlation between higher baseline BCVA and better final visual outcome. In groups II and IV, smaller baseline CNV sizes also favorably influenced final BCVA. Conclusions: Standardized PDT-V minimizes deterioration of central vision only in patients with classic and predominantly classic CNV. Irrespective of the CNV type, better BCVA at presentation represents a good predictive sign. In predominantly classic and occult lesions, minor initial CNV dimension is also a positive prognostic element.
Ophthalmology, 2009
The 2-year, phase III trial designated Anti-vascular endothelial growth factor (VEGF) Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization (CNV) in Age-related Macular Degeneration (ANCHOR) compared ranibizumab with verteporfin photodynamic therapy (PDT) in treating predominantly classic CNV. Design: Multicenter, international, randomized, double-masked, active-treatment-controlled clinical trial. Participants: Patients with predominantly classic, subfoveal CNV not previously treated with PDT or antiangiogenic drugs. Intervention: Patients were randomized 1:1:1 to verteporfin PDT plus monthly sham intraocular injection or to sham verteporfin PDT plus monthly intravitreal ranibizumab (0.3 mg or 0.5 mg) injection. The need for PDT (active or sham) retreatment was evaluated every 3 months using fluorescein angiography (FA). Main Outcome Measures: The primary, intent-to-treat efficacy analysis was at 12 months, with continued measurements to month 24. Key measures included the percentage losing Ͻ15 letters from baseline visual acuity (VA) score (month 12 primary efficacy outcome measure), percentage gaining Ն15 letters from baseline, and mean change over time in VA score and FA-assessed lesion characteristics. Adverse events were monitored. Results: Of 423 patients (143 PDT, 140 each in the 2 ranibizumab groups), the majority (Ն77% in each group) completed the 2-year study. Consistent with results at month 12, at month 24 the VA benefit from ranibizumab was statistically significant (PϽ0.0001 vs. PDT) and clinically meaningful: 89.9% to 90.0% of ranibizumab-treated patients had lost Ͻ15 letters from baseline (vs. 65.7% of PDT patients); 34% to 41.0% had gained Ն15 letters (vs. 6.3% of PDT group); and, on average, VA was improved from baseline by 8.1 to 10.7 letters (vs. a mean decline of 9.8 letters in PDT group). Changes in lesion anatomic characteristics on FA also favored ranibizumab (all comparisons PϽ0.0001 vs. PDT). Overall, there was no imbalance among groups in rates of serious ocular and nonocular adverse events. In the pooled ranibizumab groups, 3 of 277 (1.1%) patients developed presumed endophthalmitis in the study eye (rate per injection ϭ 3/5921 [0.05%]). Conclusions: In this 2-year study, ranibizumab provided greater clinical benefit than verteporfin PDT in patients with age-related macular degeneration with new-onset, predominantly classic CNV. Rates of serious adverse events were low. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.
Singapore medical journal, 2011
In Asian countries, age-related macular degeneration (AMD), specifically wet AMD or choroidal neovascularisation (CNV), is an important cause of blindness and visual handicap. Vascular endothelial growth factors (VEGF) play an integral role in the development of CNV and thus provide an important therapeutic target. Current treatment paradigms for neovascular AMD recognise the place of photodynamic therapy (PDT) in the management of this condition. However, combination therapy targeting different pathways to produce a synergistic effect may result in improved visual outcomes and reduced duration of treatment. Anti-VEGF therapy has greatly improved treatment outcomes in patients with CNV, and a growing body of evidence supports the role of these agents as monotherapy or in combination with PDT. In particular, anti-VEGF may be a first-line treatment option in certain types of subfoveal myopic CNV as well as for classic and occult juxtafoveal and subfoveal CNV. The implementation of evi...
Clinical Ophthalmology, 2014
Purpose: To examine the potential long-term benefit of an anti-VEGF/photodynamic therapy (PDT) combination on patients treated for wet age-related macular degeneration (AMD). Methods: A retrospective chart review was conducted on 29 eyes (subjects) from 26 patients (eight male and 18 female) that showed sustained, positive response to combination therapy for exudative AMD for a minimum of 1 year. Collected data included: visual acuity, central retinal thickness, intraocular pressure and history of glaucoma, wet AMD onset and treatment history, concomitant use of anticoagulants and past history or development of cerebrovascular or cardiovascular disease while receiving combination therapy. Results: Subjects underwent an average of five injections and two PDT treatments in total over 16 months before the choroidal neovascular membrane (CNVM) stabilized and became inactive for at least 1 year. Prior to the effective anti-VEGF/PDT combination therapy the median Snellen visual acuity ranged from 20/200 to 20/250 and presented at no worse than 20/200 at 1 year after treatment. Some subjects were followed for up to 5 years and remained inactive. Conclusion: Combination therapy can cause long-lasting closure of the CNVM, even with advanced disease resistant to anti-VEGF monotherapy.