AMD: innovation in the fast lane

It is now an acknowledged fact that vascular endothelial growth factor (VEGF) therapy is efficacious in preventing progressive visual loss in neovascular or wet AMD; evidence suggests that the angiogenic factor plays a significant role in the development and maintenance of choroidal neovascularization (CNV). Consequently, a great deal of research and development has focused on developing therapies that act to inhibit VEGF.

Today, the standard of care in the treatment of wet AMD includes the use of anti-VEGF therapies ranibizumab (Lucentis; Novartis/Genentech), pegaptanib (Macugen; Pfizer/OSI), and bevacizumab (off-label Avastin), as well as verteporfin (Visudyne; Novartis) photodynamic therapy (PDT), and intravitreal triamcinolone (Kenalog; Bristol Myers Squibb). Research, however, continues to unveil many other interesting avenues for potential AMD intervention, and it won't be long before more new and exciting therapeutics and combination treatments are added to a retina specialist's list of options.

Earlier this year, Ophthalmology Times Europe convened a meeting with a group of experts in the field of AMD therapy to discuss this issue. The outcomes of the meeting were published for the first time in May of this year and the second instalment of the highlights from this meeting is included as a supplement to this month's issue. Please read "Practice management in the era of anti-VEGF therapy" to find out how the panel of experts have prepared their clinics to cope with the rising demand on their time and resources. A copy of the first supplement from this meeting is available on http://www.oteurope.com/

Elsewhere, the field of retina imaging and diagnostics is yielding technologies that now allow specialists to see the retina in ways that was never previously possible. The speed, clarity and reliability of the new generation of imaging software is proving to be an invaluable tool for assessing the stage of disease and treatment monitoring.

All-in-all, the pace of research and development in AMD diagnosis, treatment and monitoring is showing no signs of slowing and the purpose of this feature section is to give you a flavour of what is out there and what is on the horizon.

It is always difficult to provide a full picture of everything that is going on in the world of AMD research and development, however, we hope that this will prove to be a useful guide for you in your quest to delve deeper into this exciting area of ophthalmology.

Other developments

Although the majority of new developments in the treatment of AMD have concentrated on therapeutic interventions, several other recent events have also caught specialists' attention.

The Implantable Miniature Telescope (IMT), created by VisionCare Ophthalmic Technologies in association with Dr Issac Lipshitz, is a quartz glass telescope prosthesis that is awaiting FDA approval for the treatment of end-stage AMD. It is implanted monocularly, to give one eye improved central vision, while the other eye is left alone to continue to provide peripheral vision for orientation and mobility. The device provides higher resolution images to the central retina and its telephoto effect also allows more to be seen in the central visual field, as the scotoma size is reduced relative to the objects the patient is viewing in their central field.

Two-year results indicate that the device improves visual acuity and quality of life in patients with end-stage AMD. However, the device is not recommended for use in all AMD patients and assessment of realistic patient expectations as well as a willingness of patients to participate in post-implantation rehabilitation is essential to the success of the procedure.

Other developments that have been hitting the headlines include the discovery of a gene that is thought to play an important role in the pathogenesis of AMD. John R.W Yates and colleagues from the Genetic Factors in AMD Study Group, tested for associations between AMD and 13 single-nucleotide polymorphisms spanning the complement genes C3 and C5. They found that the common functional polymorphism rs2230199 in the complement C3 gene, corresponding to the electrophoretic variants C3S (slow) and C3F (fast), are strongly associated with AMD.

Elsewhere, a pioneering project has been launched by University College London and Moorfields Eye Hospital, UK, which aims to use stem cells to cure blindness resulting from AMD. The procedure involves generating replacement retinal pigment epithelial cells from stem cells in the laboratory. Surgeons will then inject a small patch of new cells back into the eye. The project has been made possible by a donation of £4 million (almost €6 million) by an anonymous US donor who is frustrated by the US curb on stem cell research. It is hoped that the first test patients will receive the treatment in just five years time.

Imaging and diagnostics

The new generation of optical coherence tomography (OCT) technology is set to revolutionize how surgeons will examine and treat their patients. The devices, called spectral- or fourier-domain OCT, use spectrometers with up to 2,048 pixels to collect much more data than time-domain systems were ever capable of. Whereas time-domain OCT is able to peform approximately 44 A-scans per second, the spectral systems yield more than 20,000 A-scans per second.

This vastly improved system of data collection delivers higher-resolution images and the rapid image capture improves image clarity.

Examples of this new breed include the Spectralis HRA+OCT (Heidelberg Engineering), which was the world's first commercial spectral domain OCT combined with laser angiography. It is able to detect previously unrecognized structures, combining high-resolution cross-sectional images of the retina with any of four imaging modalities: autofluorescence, infrared, fluorescein angiography, or ICG angiography. The new device scans the retina 100 times faster than older, existing time domain OCT. Spectralis HRA+OCT scans the retina at 40,000 scans per second, creating highly detailed images of the structure of the retina.

Because the OCT and HRA images are captured simultaneously, the clinician can be assured of the exact location of the area of interest and can correlate the outer visible retina structure with the internal structure.

Another recent release is the Cirrus HD-OCT (Carl Zeiss Meditec), which offers precise algorithms and high quality live fundus images, presenting, according to the firm, a unique view of anatomical details of the human retina in high definition. The system uses advanced spectral domain OCT technology to perform high-resolution B-scans and densely sampled macular cube scans. The three parallel acquisition channels: the Iris Viewer, Line Scanning Ophthalmoscope (LSO) and OCT, contribute to the system's speed and accuracy.

Other available, next-generation Spectral OCT technologies include 3D OCT-1000 (Topcon), RTVue-100 (Optovue), Spectral OCT/SLO (OTI), and Copernicus (Optopol). Please go to "Impact of spectral OCT on clinical retinology" for a thorough account of a surgeon's experience with this technology.

Marketed

Visudyne (Novartis) Photodynamic therapy

Visudyne (verteporfin for injection) is a light-activated drug used in photodynamic therapy (PDT). PDT is a two-step outpatient procedure involving the intravenous administration of Visudyne, followed by irradiation by a non-thermal laser to activate the photosensitizer drug molecules. Free radicals and singlet oxygen molecules are produced, resulting in disruption of cellular structures and, ultimately, vessel thrombosis and vascular occlusion.

Visudyne therapy was the first pharmacologic treatment shown to have long-term safety and efficacy for many patients with subfoveal wet AMD in randomized clinical trials. It was subsequently approved for the treatment of predominantly classic subfoveal choroidal neovascularization (CNV) and is now also approved for occult with no classic CNV in the European Union and many other countries outside the US.