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Exudative (Wet) Age-Related Macular Degeneration (AMD)

Sections Exudative (Wet) Age-Related Macular Degeneration (AMD)
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Medication

Medication Summary

Intravitreal injections with vascular endothelial growth factors (VEGF) inhibitors (eg, aflibercept, ranibizumab, brolucizumab, faricimab) are used to reduce the progression of exudative AMD.

Complement inhibitors, such as pegcetacoplan intravitreal (Syfovre) and avacincaptad pegol intravitreal (Izervay), are indicated for geographic atrophy (GA) secondary to age-related macular degeneration.

Class Summary

These agents are used for PDT in cases of subfoveal, predominantly classic CNV membranes.

Verteporfin (Visudyne)

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Benzoporphyrin derivative monoacid (BPD-MA), consisting of equally active isomers BPD-MAC and BPD-MAD, which can be activated by low-intensity, nonthermal light of 689-nm wavelength. After activation and with oxygen, forms cytotoxic oxygen free radicals and singlet oxygen, which damages biologic structures in range of diffusion, leading to local vascular occlusion, cell damage and cell death.

Phase III data from the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy Study Group showed that 61% of 402 eyes treated lost < 15 letters of visual acuity at 12 months vs 46% of 207 eyes receiving placebo (P< .001). In subgroup analysis, visual-acuity benefit persisted (67% vs 37%, P< .001) when CNV membrane was predominantly classic (50% or more of area of entire complex). Visual acuity not significantly different when the area of classic CNV membranes < 50% entire complex. Patients needed mean of about 3 treatments in first y. At most recent follow-up, patients needed mean of 5 treatments in first 2 y.

Class Summary

This treatment reduces the risk of visual loss similar to that seen with PDT.

Aflibercept intravitreal (Eylea, Eylea HD)

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Binds and prevents activation of vascular endothelial growth factors (all forms of VEGF-A) and placental growth factor (PIGF). Indicated for neovascular (wet) age-related macular degeneration (AMD). Initial injection frequency is every 4 weeks for 3 months. After 3 once-monthly loading doses, maintenance doses are administered. Frequency of maintenance doses is dependent on which product is being administered (ie, original formulation or high-dose).

Brolucizumab intravitreal (Beovu, brolucizumab-dbll)

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Human VEGF inhibitor; binds to the 3 major VEGF-A isoforms (eg, VEGF110, VEGF121, VEGF165), thereby preventing interaction with receptors VEGFR-1 and VEGFR-2. By inhibiting VEGF-A, brolucizumab suppresses endothelial cell proliferation, neovascularization, and vascular permeability. Indicated for adults with nAMD.

Ranibizumab intravitreal injection (Lucentis, Byooviz, Cimerli)

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Recombinant humanized IgG1-kappa isotype monoclonal antibody fragment designed for intraocular use. Indicated for neovascular (wet) AMD. In clinical trials, about one third of patients had improved vision at 12 months that was maintained by monthly injections. Binds to VEGF-A, including biologically active, cleaved form (ie, VEGF110). VEGF-A has been shown to cause neovascularization and leakage in ocular angiogenesis models and is thought to contribute to AMD disease progression. Binding VEGF-A prevents interaction with its receptors (ie, VEGFR1, VEGFR2) on surface of endothelial cells, thereby reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation. After 3 once-monthly loading doses, maintenance doses may be administered every 1 month.

Ranibizumab intravitreal implant (Susvimo)

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Indicated for treatment of neovascular (wet) AMD in patients who have previously responded to at least 2 intravitreal injections of a VEGF inhibitor.

Faricimab (Vabysmo)

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Bispecific antibody for treatment of adults with neovascular (wet) age-related macular degeneration. Faricimab targets 2 distinct pathways – angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A). By inhibiting VEGF-A, faricimab suppresses endothelial cell proliferation, neovascularization and vascular permeability. By inhibiting Ang-2, faricimab promotes vascular stability and desensitize blood vessels to the effects of VEGF-A.

Class Summary

Indicated for geographic atrophy (GA) secondary to age-related macular degeneration.

Pegcetacoplan intravitreal (Syfovre)

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Binds to complement protein C3 and its activation fragment C3b, thereby regulating cleavage of C3 and the generation of downstream effectors of complement activation.

Avacincaptad pegol intravitreal (Izervay)

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Pegylated oligonucleotide that binds to and inhibits complement protein C5. Inhibiting C5 may prevent its cleavage to C5a and C5b thus decreasing membrane attack complex (MAC) formation.

Questions

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Media Gallery

Age-related macular degeneration (AMD), exudative.
Age-related macular degeneration (AMD), exudative.
Color photograph of the fundus shows nonexudative age-related macular degeneration (AMD) with geographic atrophy of the retinal pigment epithelium (RPE) and drusen. Absolute atrophy of the RPE occupies the foveal region in this case of nonexudative AMD. The central atrophic region causes a corresponding central scotoma. Note the large choroidal vessels, which are visible through the RPE defect. Drusen surround the region of geographic atrophy. Photo by Tim Steffens.

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Author

F Ryan Prall, MD Assistant Professor of Ophthalmology, Indiana University School of Medicine

F Ryan Prall, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Coauthor(s)

Thomas A Ciulla, MD, MBA Clinical Professor (Volunteer) of Ophthalmology, Indiana University School of Medicine; Ophthalmologist, Vitreoretinal Medicine and Surgery, Midwest Eye Institute

Thomas A Ciulla, MD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American Society of Gene and Cell Therapy, American Society of Retina Specialists, Association for Research in Vision and Ophthalmology, Indiana Academy of Ophthalmology, International Society for Genetic Eye Diseases and Retinoblastoma, Macula Society, Retina Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Ophthotech Corp.; Spark Therapeutics; Clearside Biomedical<br/>Received income in an amount equal to or greater than $250 from: Ophthotech Corp.; Spark Therapeutics; Clearside Biomedical.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Steve Charles, MD Founder and CEO of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine

Disclosure: Received royalty and consulting fees for: Alcon Laboratories.

Chief Editor

Andrew A Dahl, MD, FACS Assistant Professor of Surgery (Ophthalmology), New York College of Medicine (NYCOM); Director of Residency Ophthalmology Training, The Institute for Family Health and Mid-Hudson Family Practice Residency Program; Staff Ophthalmologist, Telluride Medical Center

Andrew A Dahl, MD, FACS is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, American Intraocular Lens Society, American Medical Association, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Medical Society of the State of New York, New York State Ophthalmological Society, Outpatient Ophthalmic Surgery Society

Disclosure: Nothing to disclose.

Additional Contributors

Brian A Phillpotts, MD Ophthalmologist, St Luke's Cataract and Laser Institute

Brian A Phillpotts, MD is a member of the following medical societies: American Academy of Ophthalmology, American Diabetes Association, American Society of Retina Specialists, Association for Research in Vision and Ophthalmology, Association of University Professors of Ophthalmology

Disclosure: Nothing to disclose.

Mark H Criswell, PhD Adjunct Assistant Research Professor, Department of Ophthalmology, Indiana University School of Medicine

Mark H Criswell, PhD is a member of the following medical societies: Association for Research in Vision and Ophthalmology

Disclosure: Nothing to disclose.

Alon Harris, PhD Lois Letzter Professor, Director of Glaucoma Research and Diagnostic Center, Department of Ophthalmology, Indiana University School of Medicine

Alon Harris, PhD is a member of the following medical societies: American College of Sports Medicine, American Physiological Society, American Society for Laser Medicine and Surgery, New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Grant M Comer, MD, to the development and writing of this article.

Sections Exudative (Wet) Age-Related Macular Degeneration (AMD)
Overview
Presentation
- History
- Physical
- Causes
- Show All
DDx
Workup
Treatment
Medication
Questions & Answers
Media Gallery
References

Exudative (Wet) Age-Related Macular Degeneration (AMD) Medication

Medication Summary

Phototherapy Agents

Class Summary

Verteporfin (Visudyne)

Verteporfin (Visudyne)

Anti-VEGF Therapy

Class Summary

Aflibercept intravitreal (Eylea, Eylea HD)

Aflibercept intravitreal (Eylea, Eylea HD)

Brolucizumab intravitreal (Beovu, brolucizumab-dbll)

Brolucizumab intravitreal (Beovu, brolucizumab-dbll)

Ranibizumab intravitreal injection (Lucentis, Byooviz, Cimerli)

Ranibizumab intravitreal injection (Lucentis, Byooviz, Cimerli)

Ranibizumab intravitreal implant (Susvimo)

Ranibizumab intravitreal implant (Susvimo)

Faricimab (Vabysmo)

Faricimab (Vabysmo)

Ophthalmics, Complement Inhibitors

Class Summary

Pegcetacoplan intravitreal (Syfovre)

Pegcetacoplan intravitreal (Syfovre)

Avacincaptad pegol intravitreal (Izervay)

Avacincaptad pegol intravitreal (Izervay)

Exudative (Wet) Age-Related Macular Degeneration (AMD) Medication

Medication Summary

Phototherapy Agents

Class Summary

Verteporfin (Visudyne)

Anti-VEGF Therapy

Class Summary

Aflibercept intravitreal (Eylea, Eylea HD)

Brolucizumab intravitreal (Beovu, brolucizumab-dbll)

Ranibizumab intravitreal injection (Lucentis, Byooviz, Cimerli)

Ranibizumab intravitreal implant (Susvimo)

Faricimab (Vabysmo)

Ophthalmics, Complement Inhibitors

Class Summary

Pegcetacoplan intravitreal (Syfovre)

Avacincaptad pegol intravitreal (Izervay)

References

Tables

Contributor Information and Disclosures

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