Mechanism of Action

Ellex’s proprietary, patented 2RT™ technology features a speckled beam profile which exclusively targets selected, individual cells within the retinal pigment epithelium (RPE). All of the 2RT™ laser energy is designed to stay within the targeted RPE cells.

The application of 2RT™ to the RPE results in the formation of microbubbles around the melonasomes. These microbubbles expand and then coalesce, causing intracellular damage. It is important to note that the cell damage is confined within the targeted RPE cells and does not extend to the neighboring cells. A process of extracellular signaling occurs in response to the selected death of the targeted RPE cells, which causes the neighboring RPE cells to migrate and proliferate into the cell space vacated by these dead RPE cells.

This stimulates a process of cell division and growth, which improves permeability of Bruch’s membrane and thereby restores the transport of fluid across Bruch’s membrane. As a result, the RPE is rejuvenated – and without damage to the overlying neurosensory retina (specifically, no damage is caused to the photoreceptors and choroid.)

1. 2RT® selectively targets individual RPE cells
2. Microbubbles around melanosomes expand, coalesce and cause intracellular damage
3. Intracellular structure damaged, leading to individual RPE cell death
4. Extracellular signaling occurs from neighboring RPE cells: neighboring cells migrate and proliferate into vacant cell space and RPE cells divide to produce new RPE cell
5. Microglial processes extending towards lasered site without any classical signs of microglial activity (gliosis)
6. Permeability of Bruch’s membrane improved and transport of fluid across Bruch’s membrane restored

FIGURE 1: Mononuclear Cell Response of 2RT

Research conducted by Associate Professor Erica L. Fletcher MScOptom, PhD (Department of Anatomy and Neuroscience, The University of Melbourne, Australia) and colleagues has shown that 2RT® induces a mononuclear cell response, including the release of microglia. Microglia, the resident immune cell of the central nervous system is known to remove cellular debris and facilitate healing.(1)
In the image below, the retinal microglia are shown extending their processes through the outer nuclear layer toward the laser treatment site.

Treatment Characteristics

The 2RT™ laser is a specially designed Q-switched, green Nd:YAG with a wavelength of 532 nm. Its pulse duration is 3 nanoseconds with energy of approximately 200 μJ per pulse. This is one of the key differences of 2RT: instead of using millisecond or microsecond treatment times, 2RT™ utilizes extremely fast nanosecond pulses. 2RT™ also features a large 400 μm spot size, instead of the traditional top-hat or Gaussian-shaped laser beam and 50-μm spot size commonly used for retinal laser treatments.

2RT Versus Photocoagulation

Historically, retinal photocoagulation has been used to control the progress of neovascularisation by destroying ischemic retina. The trade-off is destruction of photoreceptor cells. As a result, treatment cannot commence too early, and cannot proceed too far without causing a significant risk to eyesight.

In contrast, 2RT™ targets the RPE and Bruch’s membrane to stimulate a process of intra-cellular micro-bubble formation, which helps to increase fluid and metabolite flow across Bruch’s membrane without causing damage to the retina.

Table 1. Treatment Parameters: 2RT Compared to Retinal Photocoagulation

2RT Photocoagulation* Ratio
Laser Pulse Duration 3 nanoseconds 0.1 seconds 1:33,333,333
Laser Fluence (average) 0.2J/cm2 160J/cm2 1:800
Retinal Spot Size 400 microns 100 microns 4:1
Laser Wavelength 532nm (green) 532nm (green) 1:1
Primary Tissue Interaction Intra-Cellular Micro-Bubble Formation Thermal Coagulation n/a

* Typical values for mild threshold macular treatment for DME using 532nm (green) CW laser photocoagulation

These images show the effect of 2RT™ once the neuro-retina has been peeled away from the RPE. The RPE cells have been killed within the area of the laser treatment area, but the cell structure remains normal and the photoreceptors undamaged.

Source: Wood J.P et al. Nanosecond Pulse lasers for Retinal Applications. Lasers in Surgery and Medicines. 43:499-510, 2011.

These images show the effect of conventional retinal photocoagulation once the neuro-retina has been peeled away from the RPE. The RPE cells are “welded” to the photoreceptors, ripping away from Bruch’s membrane i.e. coagulation has occurred.

Source: Wood J.P et al. Nanosecond Pulse lasers for Retinal Applications. Lasers in Surgery and Medicines. 43:499-510, 2011.

1. Jobling et al., “Nanosecond Laser Therapy Reverses Pathologic and Molecular Changes in Age-Related Macular Degeneration without Retinal Damage,” The FASEB Journal 29, no. 2 (February 1, 2015): 696–710, doi:10.1096/fj.14-262444.