A Potential Eye Drop Treatment for Wet and Dry Macular Degeneration

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Researchers have identified a possible topical [i.e., eye drop] treatment for age-related macular degeneration (AMD) that is capable of inhibiting the characteristic symptoms of both the dry and wet forms of AMD.

This “proof of concept” research is in its earliest stages and has been conducted only with laboratory mice. Nevertheless, the concept of a possible topical treatment shows promise for persons with AMD.

The study, entitled Topical Application of PPADS Inhibits Complement Activation and Choroidal Neovascularization in a Model of Age-Related Macular Degeneration, has been published in PLoS ONE, an international, peer-reviewed, open-access online journal, published monthly by the Public Library of Science (PLoS). The PLoS is a non-profit organization of scientists and physicians who are committed to making the world’s scientific and medical literature a freely available public resource.

The authors are Kerstin Birke, Erion Lipo, Marco T. Birke, and Rajendra Kumar-Singh from the Department of Ophthalmology, Tufts University School of Medicine, Boston, Massachusetts.

About the Research

From Tufts researchers identify potential topical treatment for macular degeneration, via YottaFire.com:

The team of researchers, led by Rajendra Kumar-Singh, Ph.D., reported in their “proof of concept” study that topical application of … a compound called PPADS inhibits damage to the tissues in the eye that impacts the individual’s ability to see color and fine detail, as well as reduces the growth of extraneous blood vessels in the back of the eye related to advanced AMD.

The development of a topical eye-drop treatment that works in both dry and wet AMD could increase treatment adherence and reduce patient discomfort by reducing or removing the need for direct injections.

“An ideal therapy would be one that can be self-administered daily by patients. Further studies are needed to determine safety, dosage, and other factors before advancement of this therapy towards clinical trials, but our study suggests that there’s significant promise for the development of self-administered topical treatments for age-related macular degeneration in humans,” said Kumar-Singh.

Dry Macular Degeneration

The dry (also called atrophic) type of AMD affects approximately 80-90% of individuals with AMD. Its cause is unknown, it tends to progress more slowly than the wet type, and there is not – as of yet – an approved treatment or cure; however, there are clinical trials underway.

In dry age-related macular degeneration, small white or yellowish deposits, called drusen, form on the retina, in the macula – the small sensitive area in the center of the retina that provides clear central vision – causing it to deteriorate or degenerate over time.

Photograph of a retina with drusen

A retina with drusen

Drusen are the hallmark of dry AMD. These small yellow deposits beneath the retina are a buildup of waste materials, composed of cholesterol, protein, and fats. Typically, when drusen first form, they do not cause vision loss. However, they are a risk factor for progressing to vision loss.

Wet Macular Degeneration

In wet, or exudative, macular degeneration (AMD), the choroid (a part of the eye containing blood vessels that nourish the retina) begins to sprout abnormal blood vessels that develop into a cluster under the macula (called choroidal neovascularization).

The macula is the part of the retina that provides the clearest central vision. Because these new blood vessels are abnormal, they tend to break, bleed, and leak fluid under the macula, causing it to lift up and pull away from its base. This damages the fragile photoreceptor cells, which sense and receive light, resulting in a rapid and severe loss of central vision.

Current Treatments for Wet Macular Degeneration

Angiogenesis is a term used to describe the growth of new blood vessels and plays a crucial role in the normal development of body organs and tissue. Sometimes, however, excessive and abnormal blood vessel development can occur in diseases such as cancer (tumor growth) and AMD (retinal and macular bleeding).

Substances that stop the growth of these excessive blood vessels are called anti-angiogenic (anti=against; angio=vessel; genic=development), and anti-neovascular (anti=against; neo=new; vascular=blood vessels).

The focus of current treatments for wet AMD is to reduce the level of a particular protein (vascular endothelial growth factor, or VEGF) that stimulates abnormal blood vessel growth in the retina and macula; thus, these drugs are classified as anti-VEGF treatments. At present, these drugs (Lucentis, Avastin, and Eylea) are administered by injection directly into the eye after the surface has been numbed.

More about the Study from PLoS

From the article Discussion:

Our studies were motivated primarily by the current limitations in the treatment procedure utilized for wet AMD patients, which requires intraocular injection every 4 to 12 weeks under local anesthesia. Such injections have significant side effects including retinal detachment, an increase in intraocular pressure, endophthalmitis [i.e., an inflammation of the internal parts of the eye] etc. and lead to a large bolus [i.e., an increased concentration] of drug in the intraocular compartment immediately after the injection that dissipates over time.

Given that VEGF plays significant roles in maintenance of the retina, these large ‘pulses’ of anti-VEGF molecules are detrimental to tissue homeostasis [i.e., a stable equilibrium]. Since intravitreal injections are outpatient procedures, the cost to the healthcare system is substantial given the very high prevalence of wet AMD. An alternative mode of drug delivery such as self-administered topical drops is hence potentially very attractive.

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