Clinical landscape of neovascular AMD is changing

June 1, 2005

In the world of eye care, therapy for age-related macular degeneration (AMD) presents as an urgent medical need both now and for future generations. Neovascular AMD accounts for 20% of total AMD cases, but 90% of the severe loss of vision that is associated with the disease, and there are more than 200,000 new cases of neovascular AMD each year.

It is important for eye-care professionals to be familiar with the signs and symptoms of AMD to aid in early diagnosis. Although AMD can progress slowly in its initial stages, once choroidal neovascularization (CNV) develops, loss of vision can be sudden, severe, and irreversible. A better understanding of CNV disease pathways and the associated lesion subtypes will help put the available treatment options into perspective.

CNV lesion subtypes CNV is characterized by the abnormal proliferation of blood vessels. CNV vessels leak blood and/or fluid into and beneath the retina, distorting or destroying vision most prominently within the macula. CNV lesions are characterized as either classic or occult based on their appearance on fluorescein angiographic images. Fluorescein angiography documents the circulation of fluorescein dye within normal and abnormal blood vessels over time. CNV lesions can be characterized as having either classic or occult components, or may contain both types of leakage patterns.2

Occult CNV displays less bright and discrete hyperfluorescence in early views and is characterized as either late leakage from an undetermined source (where minimal to no leakage is seen in early views) or irregular elevation of the RPE-a pigment epithelial detachment (PED). Late leakage appears as speckled hyperfluorescence in the subretinal space.3

There are various subclassifications of CNV lesions manifested as retinal vascular abnormalities. The characteristics of these subtypes may be difficult to discern because they often present in combination with other subtypes, which can lead to overlapping classification.

Another clinical tool used to delineate AMD damage is optical coherence tomography (OCT), which provides high-resolution, three-dimensional images. OCT can assist in identifying macular elevation and localized retinal pathology. The detailed, cross-sectional images can detect aspects of CNV lesions that cannot always be seen by other tests. However, it is not an easy task to distinguish between lesions within the deep retinal layers and subretinal space. Future advancements in imaging technology will improve our ability to identify the specifics of lesion subtypes.

Based on data from the Macular Photocoagulation Study (MPS), patients with classic CNV lesions are less likely to retain visual acuity after 3 years if the lesions are left untreated. On the other hand, patients who present with occult-only lesions have more variable outcomes. In some cases vision may remain stable for years without any vision loss while others may experience loss similar in severity to that of patients with purely classic CNV.2 A clearer understanding of lesion development is needed in order to classify better how the different subtypes respond to presently available treatments as well as those that are under development. It is also important to recognize lesion pathologies in the context of patient population when reviewing data from various studies.

Clinical trials subsequent to the MPS have classified lesions into the categories of predominantly classic (at least 50% of the entire lesion contains classic CNV), minimally classic (greater than 0% but less than 50% of the entire lesion is classic), and occult with no classic. These categories are used to analyze results and as a basis for enrolling patients. Additional lesion characteristics such as age from diagnosis, size, and pathology will be increasingly important to recognize because they all influence severity of vision loss and the general rate of progression of the disease.