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The cumulative experience of more than 20 years of treating retinal diseases with a variety of lasers has taught clinicians and researchers one very important lesson: less is more.

A laser therapy [Retinal Regeneration Therapy (2RT); 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 could lead to a reduction in disease progression, together with a loss of retinal changes, as well as preservation or improvement of functional vision.

What do the studies tell us?

Key points to note

Patients underwent laser treatment using a standard recommended ETDRS grid pattern; the number of spots used depended on the size of the clinically significant macular oedema. All patients were seen at three weeks, six weeks and three months following laser treatment.

The preliminary results demonstrated that the majority of patients experienced improvement in visual acuity, as well as improvement in central macular thickness (CMT) as measured by optical coherence tomography (OCT), as early as six weeks. Sixteen patients (55%) experienced a decrease in CMT of >5% and CMT remained within ±5% in seven patients (24%).

Furthermore, microperimetry 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 three months after laser treatment.

 
Laser treatment as it used to be

In the 1970s, when lasers were first used to treat ocular vascular diseases, it quickly became apparent that firing a laser in front of the new vessels worsened the disease. Trial and error led to the development of panretinal 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 retrospect, the major element of therapeutic benefit derived from retinal laser therapy was the triggering of changes within the RPE. In attempting to deliver sufficient laser energy to the RPE, however, too much energy was used, causing the entire thickness of the retina to be destroyed. In short, the treatment killed the very cells that were intended to be preserved.

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.

 
How is this better?

Figure 1*

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 (Figure 2: Optical coherence tomography shows a patient before (left) and after (right) laser treatment. Note that the intraretinal fluid has almost completely resolved). In AMD, the treatment is performed before neovascularization occurs, in the hope that it will never occur.

Figure 2*

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.

Let's sum up

 
Authors

Dr Marshall is a member of the board of directors at Ellex Medical Lasers and chairman of the company's medical advisory board. The other authors have no financial interests related to the subject matter.

* Figures courtesy of Robin Hamilton, MBBS, MRCOphth