Using laser therapy for diabetic maculopathy and AMD

November 15, 2007

The less is more approach has been successful when applied to treating retinal disease with lasers. The best example of this is a laser therapy (2RT – Retinal Regeneration Therapy, Ellex) that uses extremely short (3-nanosecond) pulses of laser energy to stimulate the retinal pigment epithelium (RPE) to create a sort of renewal process within the retina.

Key Points

A laser therapy (2RT – Retinal Regeneration Therapy, Ellex) that uses extremely short (3-nanosecond) pulses of laser energy to stimulate the retinal pigment epithelium (RPE) to create a sort of renewal process within the retina may represent the culmination of this experience. This therapy may lead to a reduction in disease progression, together with a loss of retinal changes, as well as preservation or improvement of functional vision.

Initial results of the first clinical study on the therapy were presented at the annual meeting of the American Academy of Ophthalmology (AAO) in New Orleans. In the study, a Q-switched 532-nm laser was used to treat 24 patients (38 eyes) with either newly diagnosed or previously treated diabetic maculopathy. Patients had diffuse maculopathy and were in need of treatment as defined by the Early Treatment of Diabetic Retinopathy Study (ETDRS) guidelines.

The preliminary results demonstrated that the majority of patients experienced improvement in visual acuity, as well as improvement in central macular thickness as measured by optical coherence tomography (OCT), as early as 6 weeks. Also, micro-perimetry did not reveal any evidence of laser damage to the photoreceptor cells. This was not the case with standard laser photocoagulation, where photoreceptor cells lose function in patients and typically do not show any improvement until 3 months after laser treatment.

How the therapy works

In the 1970s, when lasers first were used to treat ocular vascular diseases, it quickly became apparent that firing a laser forward of the new vessels worsened the disease. Trial and error led to the development of pan-retinal photocoagulation to treat diabetic retinopathy, with laser spots placed in the periphery, whereas for diabetic maculopathy and neovascular age-related macular degeneration (AMD), laser spots were placed directly over areas of pathology if they were not too close to the fovea.

In theory, if one is able to keep the laser energy within the RPE, then the function of the pigment epithelium and Bruch's membrane will be improved, allowing the transport mechanisms supplying the outer retina to return to a more normal and healthy function.

In previous studies using conventional lasers to improve macular function by firing at drusen, results were not very successful. In fact, the risk of neovascularization increased. This occurrence was not surprising considering that only a few laser spots (typically between 10 and 12) were made, and each one destroyed photoreceptor cells.

With the new retinal regeneration therapy, hundreds of spots can be placed to generate a large effect on both the RPE and underlying Bruch's membrane, with no visual effect, because the photoreceptors are not damaged.

Another difference between the new approach and previous retinal laser therapy is that other treatments were treating end-stage disease, whereas the retinal regeneration approach treats disease before significant damage occurs.

In diabetic maculopathy, in which fluid builds up in the retina, retinal regeneration allows for the clearing of Bruch's membrane and the reduction of fluid. In AMD, the treatment is performed before neovascularization occurs, in hopes that it will never occur.

In laboratory tests, we have been able to demonstrate that the retinal regeneration treatment causes the RPE to migrate and release matrix metalloproteinases, the enzymes that clean up Bruch's membrane. By measuring the transport of water and other chemicals, we have been able to show that the whole transport mechanism of the retina is rejuvenated.

The new laser therapy has the potential to change the way patients with diabetic retinopathy or AMD are treated because the disease is treated earlier, before vision has been significantly affected. Earlier treatment means that the occurrences of diabetic maculopathy likely would be reduced, whereas in AMD, the potential to stop disease progression exists. By doing so, patients should be able to maintain functional vision, a significant benefit over current retinal laser therapies.

John Marshall, PhD, is the Frost Professor of Ophthalmology and chairman of the Academic Department of Ophthalmology at St. Thomas' Hospital, London. From 1982 to 1991, he was Sembal Professor of Experimental Ophthalmology at the University College London Institute of Ophthalmology. He is an honorary fellow of the Royal College of Pathologists, the Royal College of Ophthalmologists, and the College of Optometry. He may be reached at marshall-eye@kcl.ac.uk.

Lucia Pelosini, MRCOphth, is a research fellow at St. Thomas' Hospital.

Peter Hamilton, FRCS, FRCOphth, is an honorary consultant at Moorfields Eye Hospital, London, and at St. Thomas' Hospital. He may be reached at eyehamilton@msn.com
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Robin Hamilton, MBBS, MRCOphth, is a fellow in medical retina at Moorfields Eye Hospital and an honorary fellow at St. Thomas' Hospital. Dr. Hamilton may be reached at rob.hamilton@tiscali.co.uk
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Dr. Marshall is a member of the board of directors at Ellex Medical Lasers Ltd. and chairman of the company's medical advisory board. The other authors have no financial interests related to the subject matter.