Exudative Age-Related Macular Degeneration Treatment

Age related macular degeneration (AMD) is the gradual deterioration of the central retina – responsible for central vision – as we age. It may occur as a result of protein deposits called drusen under the retina or due to thinning.

Macular degeneration cannot currently be effectively treated; however, dietary supplements containing lutein and zeaxanthin may help slow its progress.

1. Intravitreal Anti-VEGF Injections

Vascular Endothelial Growth Factor (VEGF) is a protein that stimulates the formation of new blood vessels. While normally beneficial, VEGF may become toxic in certain eye conditions such as diabetic macular edema (DME) and proliferative vitreoretinopathy (PVR). Anti-VEGF injections block this action to stop abnormal vessel growth that results in vision loss due to wet age-related macular degeneration.

Numerous studies have proven the efficacy of anti-VEGF injections to stabilize and improve vision in wet AMD patients with neovascular disease, but such treatments come with risks including cataract formation and glaucoma.

Multiple strategies are currently under development to enhance the long-term outcomes of anti-VEGF therapy, including personalized OCT-guided dosing regimens and innovative delivery methods. Unfortunately, however, it remains uncertain whether such measures can significantly surpass even the modest visual gains seen during clinical trials.

Many patients are either unwilling or unable to comply with the required injection frequency in order to achieve good results, including some who suffer severe side effects that make treatment impossible; geographic attrition; or do not respond at all – factors which likely contribute to lower outcomes observed in real world clinical practice compared with trials.

Researchers are investigating molecular mechanisms behind neovascularization to develop more effective therapies, with one promising approach being the use of Ro5-3335, a compound which blocks RUNX1 function as well as inhibiting VEGF production; Ro5-3335, when tested in CNV mouse models was shown to significantly decrease development of leaky cells and retinal scars.

Care should be taken when injecting, to avoid reflux and subconjunctival haemorrhage. For maximum patient comfort, injection should take place under topical anaesthetic and the drug injected via a tiny needle placed just under the crystalline lens. After each injection it is important to closely monitor eye as signs of increased discomfort or decreased vision should prompt you to contact their ophthalmologist immediately.

2. Anti-VEGF Trap-Eye

Vascular endothelial growth factor (VEGF), an endogenous protein produced in our bodies naturally, triggers the creation of new blood vessels to support tissue and organ development. When present in eye tissue, VEGF can cause abnormally rapid macular blood vessel growth characterized by excessive permeability and fluid leakage leading to retinal cell swelling and scarring, leading to scarring edema and scarring – thus contributing to age-related macular degeneration as well as other ocular diseases caused by vascular neovascularization. Anti-VEGF therapies have revolutionized treatment of age-related macular degeneration as well as diseases caused by vascular neovascularization.

Aflibercept (Eylea), an innovative new agent with a unique binding mechanism, has shown great promise in treating exudative AMD. In two trials called the VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW 1) and VIEW 2, monthly injections of Aflibercept were found to be noninferior to monthly Ranibizumab in terms of maintaining visual acuity while improving angiographical features.

As opposed to conventional anti-VEGF agents, which work by blocking interactions between VEGF and its receptors, Aflibercept works differently by interfering with binding of VEGF proteins with those that promote migration and proliferation within the eye – leading to reduced dosage requirements, reduced injection frequency and quicker stabilization of vision over time. This unique inhibition mechanism could result in lower drug dosages with faster stabilization over time.

Regeneron and Bayer HealthCare have joined forces in the COPERNICUS study, testing aflibercept in macular edema due to central retinal vein occlusion – one of the leading causes of blindness. Six-month results published in February 2010 demonstrated significant improvements in visual acuity within this patient population after taking this medication.

Aflibercept is also being studied as part of the Phase 3 DA VINCI study to treat polypoidal choroidal vasculopathy, another form of exudative AMD. Initial one-year results for this trial are anticipated in early 2011; bimonthly injections following a three-month loading dose will be evaluated against monthly dosing in treatment-naive PCV patients using ICG angiography; this trial aims to enroll approximately 1,400 subjects.

3. Photodynamic Therapy

Age-related macular degeneration (ARMD) is one of the leading causes of irreversible blindness among adults aged 50 or above, and occurs when light-sensing cells in the retina called macula break down and cease functioning normally, rendering fine details unreadable while reading and driving difficult or impossible. Over time, patients may notice blurriness, dark areas or distortion of straight lines as their central vision decreases slowly but eventually leads to total blindness despite remaining peripheral (outer) vision remaining functional.

Eighty-five to ninety percent of ARMD cases fall into the dry, nonexudative form where deposits called drusen slowly build up behind the macula, gradually damaging it over time. About 10-15 percent are more severe neovascular (wet) forms where abnormal blood vessels grow beneath the retina and leak blood and fluid into the macula; these forms account for up to 90% of cases that cause severe vision loss.

Photodynamic Therapy (PDT) is an anti-neovascularization laser treatment used to address wet age-related macular degeneration. PDT relies on photosensitizers that, when activated by light, produce reactive oxygen species that destroy neovascularization and stop blood vessel growth; as an additional benefit this appears to help reduce macular fluid leaking from abnormal vessels.

An initial step to diagnosing macular degeneration involves conducting a comprehensive eye exam, consisting of visual acuity tests and an Amsler grid to detect any distortion in straight lines of patterns. An optical coherence tomography (OCT) scan uses laser technology to scan retina and allows doctors to assess its structure as well as detect fluid in macular area. Another test called fluorescein angiography uses dye injection into arm, then photographing retina after it absorbs it to detect abnormal blood vessels that leak fluid into macular area.

4. Intravitreal Aflibercept

Macular degeneration is the deterioration of the central part of your retina known as the macula, responsible for central vision. This area allows you to clearly see details when performing daily tasks like driving and threading a needle, while macular degeneration may cause blurriness, dark areas or distortion to your central vision. Macular degeneration does not impact peripheral (peripheral) vision so you still remain able to see everything around you; however, certain activities, like reading or driving may become difficult.

Exudative age-related macular degeneration is a more severe form of the disease characterized by abnormal blood vessels that form beneath areas weakened by drusen and atrophy, and leak serum and fluid, leading to scar tissue formation that reduces your central vision severely and eventually legal blindness in those over 50. Furthermore, its progression often necessitates loss of independence and assistance with daily activities requiring assistance.

Aflibercept is a fully human, recombinant fusion protein which acts as a decoy receptor to block signalling of vascular endothelial growth factor family members and their receptors, such as VEGF-A and VEGF-B, with high affinity. This decoy receptor binds tightly with all isoforms of both proteins for maximum impactful binding in vitreous fluid and inhibits downstream signalling pathways in vitreous fluid. Available under its brand name Eylea, numerous clinical trials including GALILEO and COPERNICUS have also demonstrated its efficacy.

Aflibercept injection helps restore vision loss by blocking new blood vessel growth and decreasing fluid leakage from those suffering from neovascular AMD or retinal vein occlusion macular edema. Studies conducted over two years have demonstrated its ability to significantly increase best corrected visual acuity compared to sham treatments (GALILEO and COPERNICUS). Furthermore, Aflibercept is the first therapy proven to slow progression of nonproliferative diabetic retinopathy without center-involved macular edema in clinical trials conducted over two years (GALILEO and COPERNICUS). Therefore it should initially be administered monthly, gradually increasing until eventually reaching every 8 weeks or sooner if required.