Age-Related Macular Degeneration

Kiran Panesar, BPharmS (Hons), MRPharmS, RPh, CPh

Disclosures

US Pharmacist. 2015;40(6):22-26. 

In This Article

Treatment

Thermal laser photocoagulation was the treatment of choice for many years in the management of patients with wet ARMD. In this procedure, the laser is directed toward the CNV to destroy it. This procedure, however, has been associated with a high rate of recurrence.[30]

Various strategies for managing ARMD have been used or proposed, including laser photocoagulation for neovascular ARMD, submacular surgery, external beam irradiation, proton beam irradiation, focal radiation, intravitreal steroids (for their antiangiogenic properties), and transpupillary thermotherapy. These modalities demonstrated no efficacy, were associated with severe adverse effects, or were surpassed by more recent therapies.

Although statins were proposed to have a beneficial effect on ARMD, there is insufficient evidence to support the use of statins in the management of ARMD, whether for preventing or delaying onset.[3]

The prognosis for patients with neovascular ARMD has improved significantly with the development of verteporfin photodynamic therapy (PDT) and antiangiogenic therapy (i.e., intravitreal pegaptanib sodium, intravitreal bevacizumab, and intravitreal ranibizumab).[31]

PDT

This therapeutic modality takes advantage of certain unique properties of subretinal neovascular vessels and is based on the fact that neovascular tissue differs from normal blood vessels in terms of retaining dye. In PDT, which uses a combination of drugs and laser therapy, a verteporfin photosensitive compound that localizes to the target tissue is injected into a peripheral vein and excited with laser light of a specific wavelength.[3] Activated verteporfin forms free radicals, which coagulate the leaky subretinal vessel responsible for cellular injury.[3,5]

For administration, verteporfin (Visudyne, Bausch and Lomb) must be reconstituted with 7 mL of Sterile Water for Injection to provide 7.5 mL containing 2 mg/mL. The reconstituted solution is an opaque dark green in color and must be protected from light. Reconstituted Visudyne should be used within 4 hours and should be inspected visually for particulate matter and discoloration prior to administration. Reconstituted Visudyne should be diluted with 5% Dextrose for Injection. Since it precipitates in normal saline, it should not be diluted with normal saline or another parenteral solution. Visudyne should not be mixed in the same solution used for other drugs.[32]

Patients receiving PDT should be advised to avoid exposure to the sun and other sources of bright light. Some patients may complain of injection-site problems, photosensitivity, and infusion-related back pain during the first year of therapy.[5] Severe chest pain and vasovagal and hypersensitivity reactions have been reported in some patients following verteporfin administration.[32] The use of verteporfin is contraindicated in patients with porphyria or known hypersensitivity to any component of the preparation.[32]

VEGF Inhibition

Based on the angiogenic role of vascular endothelial growth factor (VEGF) in neovascularization, VEGF inhibition has become one of the targets of successful therapies for neovascular ARMD. It has been shown that visual improvements of +6.9 letters to +11.3 letters can be achieved by using bevacizumab (Avastin, Genentech/Roche), ranibizumab (Lucentis, Genentech), and aflibercept (Eylea, Regeneron) intravitreally in patients with CNV.[33]

Pegaptanib, an RNA-binding anti-VEGF165 aptamer, was the first antiangiogenic agent tested.[34] Its use has declined since the development of the more potent agents ranibizumab and bevacizumab, which are derived from the same monoclonal antibody precursor.[35,36] Bevacizumab has quickly become more popular than ranibizumab, and its wide off-label use is due to its low cost.[37] A single dose of ranibizumab costs 40 times more than a dose of bevacizumab.[38]

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