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Anti-vascular Endothelial Growth Factor (VEGF) Treatment in Neovascular Age-Related Macular Degeneration: Outcomes and Outcome Predictors

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Anti-Angiogenic Therapy in Ophthalmology

Part of the book series: Essentials in Ophthalmology ((ESSENTIALS))

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Abstract

Anti-vascular endothelial growth factor (VEGF) treatment maintains vision in most and improves vision in a considerable proportion of patients with neovascular age-related macular degeneration (nvAMD). Treatment outcomes in routine medical care seem to be best with a Treat & Extend regimen. However, overall results in routine medical care are lacking behind those achieved in highly standardized clinical phase III trials of monthly anti-VEGF treatment for a number of reasons, such as different patient populations and less intense treatment. Several clinical factors can predict anti-VEGF treatment outcomes. Those who present at a younger age, with better baseline vision and smaller CNV lesions are more likely to have a better final visual outcome, although individuals with better visual acuity at baseline stand to gain fewer letters due to a ceiling effect. Genetic factors, predominantly related to CFH and VEGF-A gene polymorphisms, may also be associated with anti-VEGF treatment outcomes. However, whilst genetic factors have been strongly associated with the development of nvAMD, their overall effect on anti-VEGF treatment outcome appears to be small. Clinical factors at presentation as well as intensity of treatment largely determine current anti-VEGF treatment outcomes. The most important factor is baseline visual acuity. Persons who present with better visual acuity will maintain better visual acuity with anti-VEGF treatment in the long term. This emphasizes the need to identify newly incident nvAMD rapidly and increase public awareness.

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Abbreviations

ABC:

Aflibercept (Eylea®)

ABC-Trial:

Bevacizumab for neovascular age-related macular degeneration—multicenter randomized double-masked study

AMD:

Age-related macular degeneration

ANCHOR:

Anti-VEGF antibody for the treatment of predominantly classic choroidal neovascularization in AMD—phase III clinical trial

APOE:

Apolipoprotein E

AREDS:

Age-Related Eye Disease study

ARMS2:

Age-related maculopathy susceptibility 2 gene

BCVA:

Best corrected visual acuity

BMES:

Blue Mountains Eye Study

BVZ:

Bevacizumab (Avastin®)

C2:

Complement factor 2

C3:

Complement factor 3

C5:

Complement factor 5

CATT:

Comparisons of Age-Related Macular Degeneration Treatments Trial

CFB:

Complement factor B

CFT:

Central foveal thickness

CFH:

Complement factor H

CFHR:

Complement factor H receptor

CI:

Confidence interval

CMT:

Central macular thickness

CNV:

Choroidal neovascularization

CRT:

Central retinal thickness

CSMT:

Central subfield macular thickness

ETDRS:

Early Treatment Diabetic Retinopathy Study

EXCITE:

Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration—phase IIIb clinical trial

EXTEND-I:

Long-term efficacy and safety of ranibizumab administered pro re nata in Japanese patients with neovascular age-related macular degeneration—open label phase I/II study

FA:

Fluorescein angiography

FLT1:

fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)

FOCUS:

Ranibizumab combined with verteporfin photodynamic therapy in neovascular age-related macular degeneration—phase I/II randomized-controlled trial

FT:

Foveal thickness

GEFAL:

Ranibizumab versus bevacizumab for neovascular age-related macular degeneration—a non-inferiority randomized trial

HELIOS:

Real-world variability in ranibizumab treatment and associated clinical quality of life and safety outcomes over 24 months—prospective, observation open-label study with arms based in Belgium and the Netherlands

HORIZON:

Open label extension trial of ranibizumab for choroidal neovascularization secondary to age-related macular degeneration

HTRA1:

High-temperature requirement A-1

IL:

Interleukin

IQR:

Inter-quartile range

IVAN:

Randomized-Controlled Trial of Alternative Treatments to Inhibit VEGF in Age-related Choroidal Neovascularization

LogMAR:

Logarithm of the minimum angle of resolution

LUMINOUS:

Safety of ranibizumab in routine clinical practice: 1-year retrospective pooled analysis of four European neovascular AMD registries.

MANTA:

A randomized double-masked trial comparing the visual outcome after treatment with ranibizumab or bevacizumab in patients with neovascular age-related macular degeneration

MARINA:

Minimally Classic/Occult Trial of Anti-VEGF antibody Ranibizumab—phase III clinical trial

MedDRA SOC:

Medical Dictionary for Regulatory Activities System Organ Classes

MT:

Macular thickness. In the context of this chapter, this encompasses a variety of anatomical measures, including CFT, CMT, CRT, CSMT, and FT

NR:

Not reported

nv:

Neovascular

OCT:

Optical coherence tomography

PCV:

Polypoidal choroidal vasculopathy

PDT:

Photodynamic therapy

PED:

Pigment epithelial detachment

PIER:

Randomized double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration

PLA2G12A:

Group 12 secretory phospholipase A2 gene

PRN:

Pro re nata, i.e., as required

PrONTO:

Prospective OCT Study with Lucentis for Neovascular AMD

RAP:

Retinal angiomatous proliferations

RBZ:

Ranibizumab (Lucentis®)

RCT:

Randomized-controlled trial

RPE:

Retinal pigment epithelium

SD:

Standard deviation

SAILOR:

A phase IIb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration

SE:

Standard error

SECURE:

Long-term safety of ranibizumab 0.5 mg in neovascular age-related macular degeneration—24-month phase IV extension study

SEVEN-UP:

Seven-year outcome in ranibizumab-treated patients in ANCHOR MARINA and HORIZON—a multicenter cohort study

SNP:

Single nucleotide polymorphisms

SUSTAIN:

Safety and efficacy of a flexible dosing regimen of ranibizumab in neovascular age-related macular degeneration—12-month phase III single arm study

UK:

United Kingdom

US:

United States

VA:

Visual acuity

VEGF:

Vascular endothelial growth factor

VIEW:

VEGF Trap-Eye: Investigation of efficacy and safety in wet AMD—non-inferiority trial comparing aflibercept with ranibizumab

WAVE:

Lucentis in wet AMD: Evaluation of visual acuity and quality of life—German noninterventional clinical practice study

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  1. Department of Ophthalmology, Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, East Melbourne, VIC, 3002, Australia

    Dujon Fuzzard, Robyn H. Guymer & Robert P. Finger

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Fuzzard, D., Guymer, R.H., Finger, R.P. (2016). Anti-vascular Endothelial Growth Factor (VEGF) Treatment in Neovascular Age-Related Macular Degeneration: Outcomes and Outcome Predictors. In: Stahl, A. (eds) Anti-Angiogenic Therapy in Ophthalmology. Essentials in Ophthalmology. Springer, Cham. https://doi.org/10.1007/978-3-319-24097-8_3

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