Anti-vascular endothelial growth factor for neovascular age-related macular degeneration

Solomon, Sharon D.; Lindsley, Kristina; Vedula, Satyanarayana S; Krzystolik, Magdalena G.; Hawkins, Barbara S.

doi:10.1002/14651858.cd005139.pub3

Cited by 352 publications

(332 citation statements)

References 133 publications

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“…Similar reviews have shown increased visual acuity with continued AMD intravitreal treatment and a low incidence of adverse side effects. 74,75 While some patients respond to intravitreal injection with sustained elevation of IOP, most do not even after multiple injections. [76][77][78][79][80][81][82] In our study, we performed intravitreal injection of drug-loaded NS once and observed IOPlowering effects out to 32 days (Fig.…”

Section: Discussionmentioning

confidence: 99%

Nanosponge-Mediated Drug Delivery Lowers Intraocular Pressure

Lambert

Carlson

Ende

et al. 2015

Trans. Vis. Sci. Tech.

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Purpose: We examined the efficacy of an extended-release drug delivery system, nanosponge (NS) encapsulated compounds, administered intravitreally to lower intraocular pressure (IOP) in mice.Methods: Bilateral ocular hypertension was induced in mice by injecting microbeads into the anterior chamber. Hypertensive mice received NS loaded with ocular hypotensive drugs via intravitreal injection and IOP was monitored. Retinal deposition and retinal ganglion cell (RGC) uptake of Neuro-DiO were examined following intravitreal injection of Neuro-DiO-NS using confocal microscopy.Results: Brimonidine-loaded NS lowered IOP 12% to 30% for up to 6 days (P , 0.02), whereas travoprost-NS lowered IOP 19% to 29% for up to 4 days (P , 0.02) compared to saline injection. Three bimatoprost NS were tested: a 400-nm NS and two 700-nm NS with amorphous (A-NS) or amorphous/crystalline (AC-NS) crosslinkers. A single injection of 400 nm NS lowered IOP 24% to 33% for up to 17 days compared to saline, while A-NS and AC-NS lowered IOP 22% to 32% and 18% to 26%, respectively, for up to 32 days (P , 0.046). Over time retinal deposition of Neuro-DiO increased from 19% to 71%; Neuro-DiO released from NS was internalized by RGCs.Conclusions: A single injection of NS can effectively deliver ocular hypotensive drugs in a linear and continuous manner for up to 32 days. Also, NS may be effective at targeting RGCs, the neurons that degenerate in glaucoma.Translational Relevance: Patient compliance is a major issue in glaucoma. The use of NS to deliver a controlled, sustained release of therapeutics could drastically reduce the number of patients that progress to vision loss in this disease.

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Section: Discussionmentioning

confidence: 99%

Nanosponge-Mediated Drug Delivery Lowers Intraocular Pressure

Lambert

Carlson

Ende

et al. 2015

Trans. Vis. Sci. Tech.

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“…2 Humanized antibodies that inhibit vascular endothelial growth factor have been widely used clinically over the past decade after several randomized controlled trials demonstrated their benefit in improving visual outcomes in patients with neovascular agerelated macular degeneration (nAMD). 3 However, there are several different treatment regimens for nAMD, including fixed dosing, pro re nata (PRN), and treat-and-extend.…”

mentioning

confidence: 99%

Metaanalysis of Real-World Outcomes of Intravitreal Ranibizumab for the Treatment of Neovascular Age-Related Macular Degeneration

Kim

Mehta

Barthelmes

et al. 2016

Retina

157

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PURPOSE: To report the efficacy and safety of intravitreal ranibizumab for neovascular agerelated macular degeneration (nAMD) in real-world practice. METHODS: Metaanalysis of 26,360 patients from 42 real-world observational studies reporting outcomes of intravitreal ranibizumab for nAMD published between 2007 and 2015. Baseline demographics, lesion type, and visual acuity (VA) were recorded. The weighted mean was calculated for change in VA and frequency of injections and visits during year 1, year 2, and 3 years. Local and systemic adverse events were recorded. RESULTS: The mean change in VA for patients receiving a treat-and-extend regimen was +8.8 (95% confidence interval [CI]: 5.8 to 11.8), +6.7 (95% CI: 3.2 to 10.1), and +5.4 (95% CI: -4.1 to 14.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 1 year (n = 1,539), 2 years (n = 2,521), and 3 years (n = 1,298), in comparison with +3.5 (95% CI: 2.0 to 5.0), +1.3 (95% CI: -1.6 to 4.2), and -1.9 (95% CI: -9.8 to 6.0) ETDRS letters for pro re nata at 1 year (n = 20,247), 2 years (n = 14,408), and 3 years (n = 11,714). Treat-and-extend patients received on average more injections (6.9 vs. 4.7) but had fewer visits (7.6 vs. 9.2) in the first year. Baseline characteristics were similar between the regimens. The reported rate of endophthalmitis was 17 of 66,176 intravitreal injections (0.026%). CONCLUSION: Intravitreal ranibizumab for nAMD prevents severe visual loss in real-world practice. Patients can achieve visual gain from baseline, but the extent to which these are maintained in the long term may depend on the frequency of injections. Methods: Metaanalysis of 26,360 patients from 42 real-world observational studies reporting outcomes of intravitreal ranibizumab for nAMD published between 2007 and 2015. Baseline demographics, lesion type, and visual acuity (VA) were recorded. The weighted mean was calculated for change in VA and frequency of injections and visits during year 1, year 2, and $3 years. Local and systemic adverse events were recorded.Results: The mean change in VA for patients receiving a treat-and-extend regimen was +8.8 (95% confidence interval [CI]: 5.8 to 11.8), +6.7 (95% CI: 3.2 to 10.1), and +5.4 (95% CI: 24.1 to 14.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 1 year (n = 1,539), 2 years (n = 2,521), and $3 years (n = 1,298), in comparison with +3.5 (95% CI: 2.0 to 5.0), +1.3 (95% CI: 21.6 to 4.2), and 21.9 (95% CI: 29.8 to 6.0) ETDRS letters for pro re nata at 1 year (n = 20,247), 2 years (n = 14,408), and $3 years (n = 11,714). Treat-andextend patients received on average more injections (6.9 vs. 4.7) but had fewer visits (7.6 vs. 9.2) in the first year. Baseline characteristics were similar between the regimens. The reported rate of endophthalmitis was 17 of 66,176 intravitreal injections (0.026%).Conclusion: Intravitreal ranibizumab for nAMD prevents severe visual loss in real-world practice. Patients can achieve visual gain from baseline, but the extent to which these are maintained in the long...

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“…The CATT study found monthly treatments of bevacizumab not inferior to monthly ranibizumab, although ranibizumab had a greater mean decrease in central retinal thickness and bevacizumab had more serious systemic adverse events (CATT Research Group et al 2011). A Cochrane Review including 12 randomized controlled trials including 5,496 patients for AMD found no difference in mean visual acuity outcomes between ranibizumab and bevacizumab, no difference in adverse events, and a statistically significant but clinically insignificant increase in reduction in central retinal thickness (À14 μm) with ranibizumab compared to bevacizumab (Solomon et al 2014). Some disagreement also exists whether a difference in safety of bevacizumab and ranibizumab exists .…”

Section: Rvomentioning

confidence: 99%