Light Targeted Occlusion (LTO)
The PhotoTarget system combines light-targeted drug delivery with a second targeting technology that uses light to activate photo-reactive drugs. The photo-reactive drugs act to destroy cells at the site of its activation. This second technology, known as Photodynamic Therapy or PDT, has been approved for use in certain cancers and for treatment of the predominately classic form of AMD. However, the tissue specificity of conventional PDT alone is less than ideal; it damages vital or normal tissue in addition to the targeted tissue. The PhotoTarget carriers allow for precise control of the time and location of drug release, as well as precise control of the time and location of drug activation. The result is significantly less errant tissue damage.
Studies have demonstrated the effectiveness of Light-Targeted Delivery using a photodynamic drug, aluminum phthalocyanin tetrasulfonate, acting on choroidal neovasculature (CNV). This method is termed "Light-Targeted Occlusion" or LTO. The method has the potential of minimizing the significant limitations of conventional systemic photodynamic therapy including photochemical damage to the RPE, the outer retina and choriocapillary vessels.
Light Targeted Angiogram AFTER Light Targeted Occlusion. LTO destroyed the CNV and left the choriocapillaries unaffected. Note that no dye is retained in the area of the CNV.
Key to the method's potential for selectivity is the variations in blood flow rates between different vascular structures in the eye. The AMD-causing choroidal neovasculature (CNV) has an abnormally slow blood flow relative to normal choriocapillaries and choroidal vessels. This is principally due to the small diameter of the CNV. Thus, when the photo-reactive drug is released from the liposome, the differences in flow rates allows the potentially damaging photodynamic drug to clear out of larger vessels before the light activation of the drug that remains in the target CNV. A typical result can be seen in the electron micrograph shown below.
Electron microscopy of a region immediately adjacent to a treated and occluded CNV. This region was within the area treated by LTO. Note the integrity of the RPE including the nucleus (arrowheads) and Bruch's membrane (white arrow) and the well perfused choriocapillaris (black arrow).
Light-Targeted Delivery of Other Drugs
Most therapies for "back-of-the-eye" diseases are administered through multiple intraocular injections. There are no effective, noninvasive, localized drug delivery mechanisms to meet this need. The PhotoTarget™ system has the potential to deliver a wide range of drugs that target the posterior chamber of the eye. PDT and angiographic dyes represent the first two compounds to show preclinical benefits from use of Light-Targeted Delivery of drugs. However, other drugs are being evaluated in the ophthalmic area and include angiogesis inhibitors and siRNA's.
In Detail
Benefits of LTO
There are numerous benefits of applications using Light-Targeted Occlusion. LTD using photodynamic drug for AMD offers advantages over current approaches and includes the following:
- Reduced photochemical and/or thermal damage to surrounding tissues such as normal choroidal vasculature, RPE and the neurosensory retina,
- Potential to affect more complete occlusion of CNV owing to reduced limitations posed by peripheral damage, and
- Potential to achieve improved outcomes in visual acuity and/or reduced need for multiple treatments owing to more complete occlusion.