Why Do Some People Not Respond to Eye Injections for Macular Degeneration?

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Although the advent of anti-VEGF therapy (explained below) has revolutionized the treatment of wet age-related macular degeneration (AMD), there are still a number of persons – although in the minority – who do not respond to treatment. It is these “non-responders” or “reduced responders” who continue to pose significant challenges to clinicians and researchers.

Recently, a team of Japanese researchers attempted to identify a number of factors that could (a) predict non-response to intravitreal [i.e., into the eye] injections of Lucentis for wet AMD and (b) establish criteria for non-responders in order to avoid inefficient treatment.

The study, entitled Predictive factors for non-response to intravitreal [i.e., injection into the eye] ranibizumab [i.e., Lucentis] treatment in age-related macular degeneration, has been published online ahead-of-print in the April 7, 2014 edition of the British Journal of Ophthalmology (BJO).

The authors are Misa Suzuki, Norihiro Nagai, Kanako Izumi-Nagai, Hajime Shinoda, Takashi Koto, Atsuro Uchida, Hiroshi Mochimaru, Kenya Yuki, Mariko Sasaki, Kazuo Tsubota, and Yoko Ozawa from the Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.

About Wet Age-Related Macular Degeneration (AMD)

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 new blood vessels that develop into a cluster under the macula, called choroidal neovascularization (neo = new; vascular = blood vessels).

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.

Anti-Angiogenic Drugs and Anti-VEGF Treatments

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 anti-angiogenic drug 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 and are administered by injection directly into the eye after the surface has been numbed.

At present, these anti-VEGF drugs (Lucentis, Avastin, and Eylea) require monthly injections or a pro re nata [meaning “as needed”] (PRN) regimen, with monthly controls and injections for recurrent or persistent macular bleeding.

More about the Study

From Report examines factors for non-response to AMD injections at Insidermedicine:

A new report published in the British Journal of Ophthalmology examines factors that may predict non-response to intravitreal injections for age-related macular degeneration.

Researchers studied 141 AMD patients who had received intravitreal injections with ranibizumab [Lucentis] for three months followed by pro re nata [meaning “as needed”] injections for nine months.

Results showed that initial fibrovascular pigment epithelial detachment and serous pigment epithelial detachment were linked with non-response, as was type 1 choroidal nevascularization as judged by fundus findings.

An Explanation of Terms

  • Pigment epithelial detachment: A pathological process in which the retinal pigment epithelium separates from the underlying Bruch’s membrane
  • Retinal pigment epithelium: A specialized retinal tissue that plays a crucial role in maintaining the equilibrium of all retinal processes. It is the pigmented layer of the retina, containing the deepest cells of the retina.
  • Bruch’s membrane: Innermost layer of the choroid, lying beneath the retinal pigment epithelium. The choroid is the part of the eye containing blood vessels that nourish the retina.
  • Fundus: The rear portion of the interior of the eyeball that the doctor sees when looking at the eye through an ophthalmoscope, an illuminated instrument for viewing the interior of the eye.
  • Type 1 choroidal neovascularization: Refers to new blood vessels that grow and multiply underneath the retinal pigment epithelium. Their growth sometimes causes the pigment epithelium to detach.
  • Fibrovascular pigment epithelial detachment: A form of type 1 choroidal neovascularization
  • Serous pigment epithelial detachment: Occurs when the retina detaches from the pigment epithelial layer due to inflammation, injury, or vascular abnormalities. “Serous” refers to fluid that accumulates in the space beneath the retina.

More from the British Journal of Ophthalmology

From the article abstract:

Methods: We reviewed the clinical records of 141 eyes in 141 AMD patients who received monthly [intravitreal Lucentis injections] for three months and thereafter pro re nata [i.e., “as needed”] injections for nine months as the first treatment for AMD.

Patients whose best corrected visual acuity worsened at month 12, and those with increased exudative [i.e., leaking fluid] fundus findings after [intravitreal Lucentis injections] or an increased central retinal thickness of more than 100 micrometers at month 12, were considered to be non-responders as judged by best-corrected visual acuity and fundus findings, respectively.

Results: 14.9% of eyes were non-responders as judged by best-corrected visual acuity, and 17.0% were non-responders as judged by fundus findings.

Initial fibrovascular pigment epithelial detachment and serous pigment epithelial detachment were associated with non-response as judged by best-corrected visual acuity.

Initial fibrovascular pigment epithelial detachment and type 1 choroidal neovascularization were associated with non-response, as judged by fundus findings.

Conclusions: Although most AMD responded to [intravitreal Lucentis injections] non-responders had initial clinical characteristics that might be informative for managing their treatment.

VisionAware will provide updates of this important research as they become available