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What is 2RT treatment
2RT (Retinal Rejuvenation Therapy) is the name of the innovative laser treatment used to counteract the progression of atrophic age-related macular degeneration (AMD), one of the main causes of vision loss and legal blindness in the industrialized world.
Features of the 2RT laser
The 2RT laser has very high precision and extremely low energy. These features allow you to perform a highly selective and controlled treatment only on certain cells of the retina, avoiding involving the photoreceptors. This allows for protect rods and cones from thermal damage, the most feared and dangerous side effect of conventional laser photocoagulation treatment.
The 2RT laser owes its characteristics to cutting-edge technology, capable of generating a beam of light with an extremely short emission, equal to 3 nanoseconds, or 3 billionths of a second. The emission time thus reduced ensures that the laser energy is always below the threshold considered dangerous for the retinal tissue. For this reason, when we refer to 2RT therapy we are talking about nanosecond laser need subthreshold laser.
How 2RT works
In 2RT treatment, the laser is applied in a selective and controlled way to certain cells of theretinal pigment epithelium and Bruch's membrane to stimulate the renewal of these tissues, which have an essential role for the vitality of the photoreceptors as they mediate the transport of oxygen and nutrients from the blood vessels of the choroid and allow it disposal of waste metabolites produced by the photoreceptors themselves.
Aging and loss of efficiency of the retinal pigment epithelium and Bruch's membrane are among the main factors causing AMD. The 2RT treatment stimulates a natural reparative biological response that promotes retinal tissue regeneration and slowing the progression of the disease towards the advanced stage, characterized by a high risk of loss of central vision.
Who is the 2RT for?
2RT treatment is indicated for people with AMD of atrophic type in the initial or intermediate stage and which they do not present reticular pseudodrusen. The research and clinical studies carried out for this treatment have shown that the nanosecond laser is able to induce an improvement in macular morphology and function in correctly selected patients, in total absence of side effects.
In particular, the LEAD multicenter clinical trial (Laser Intervention in the Early Stages of AMD) demonstrated that in appropriately selected patients, 2RT treatment is able to delay the degenerative processes associated with atrophic AMD by 76%. Given the risks associated with the advanced stage of the disease (geographical atrophy and wet AMD), these results represent a very important finding.
How the treatment takes place
The 2RT treatment is a non-invasive procedure that can be performed in outpatient mode after preparing the patient by instilling a few drops of midiatric and anesthetic eye drops starting 20-30 minutes before treatment. The application of the laser itself takes a couple of minutes, during which the patient must remain motionless and gaze at a fixation light.
Immediately after the treatment, the patient feels a dazzling sensation due partly to the midiatric eye drops and partly to the fixation light, for this reason it is advisable for the patient to wait about twenty minutes in the waiting room before returning home. In general, the presence of a companion is advisable to prevent vision discomfort from causing a fall or the risk of an accident while driving the car.
What results can be expected
In properly selected patients with early- to mid-stage AMD, treatment can promote regeneration of retinal tissue, with restoration of retinal pigment epithelial, Bruch's membrane, and photoreceptor cell function. This leads to a slowing of the progression of the disease but not to an improvement in vision or the recovery of any vision lost.
Absence of risks and side effects
In conventional laser photocoagulation, the therapeutic process is almost always accompanied by thermal damage which determines the death of the photoreceptors, with consequent loss of the architecture of the retinal tissue and the appearance of scotomas. Thanks to its advanced technology, however, the 2RT treatment is free from side effects and does not cause any damage to the retina and cells adjacent to the treatment area.
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Guymer RH, Wu Z, Hodgson LAB, Caruso E, Brassington KH, Tindill N, Aung KZ, McGuinness MB, Fletcher EL, Chen FK, Chakravarthy U, Arnold JJ, Heriot WJ, Durkin SR, Lek JJ, Harper CA, Wickremasinghe SS , Sandhu SS, Baglin EK, Sharangan P, Braat S, Luu CD; Laser Intervention in Early Stages of Age-Related Macular Degeneration Study Group. Subthreshold Nanosecond Laser Intervention in Age-Related Macular Degeneration: The LEAD Randomized Controlled Clinical Trial. Ophthalmology. 2019 Jun;126(6):829-838.
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Chidlow G, Plunkett M, Casson RJ, Wood JP. Investigations into localized re-treatment of the retina with a 3-nanosecond laser. Lasers Surg Med. 2016 Aug;48(6):602-15.
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Guymer RH, Brassington KH, Dimitrov P, Makeyeva G, Plunkett M, Xia W, Chauhan D, Vingrys A, Luu CD. Nanosecond-laser application in intermediate AMD: 12-month results of fundus appearance and macular function. Clin Exp Ophthalmol. 2014 Jul;42(5):466-79.
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Ferris FL 3rd, Wilkinson CP, Bird A, Chakravarthy U, Chew E, Csaky K, Sadda SR; Beckman Initiative for Macular Research Classification Committee. Clinical classification of age-related macular degeneration. Ophthalmology. 2013 Apr;120(4):844-51.
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Chidlow G, Shibeeb O, Plunkett M, Casson RJ, Wood JP. Glial cell and inflammatory responses to retinal laser treatment: comparison of a conventional photocoagulator and a novel, 3-nanosecond pulse laser. Invest Ophthalmol Vis Sci. 2013 Mar 28;54(3):2319-32.
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Wood JP, Shibeeb O, Plunkett M, Casson RJ, Chidlow G. Retinal damage profiles and neuronal effects of laser treatment: comparison of a conventional photocoagulator and a novel 3-nanosecond pulse laser. Invest Ophthalmol Vis Sci. 2013 Mar 28;54(3):2305-18.
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Pelosini L, Hamilton R, Mohamed M, Hamilton AM, Marshall J. Retina rejuvenation therapy for diabetic macular edema: a pilot study. Retina. 2013 Mar;33(3):548-58.
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Casson RJ, Raymond G, Newland HS, Gilhotra JS, Gray TL. Pilot randomized trial of a nanopulse retinal laser versus conventional photocoagulation for the treatment of diabetic macular oedema. Clin Exp Ophthalmol. 2012 Aug;40(6):604-10.
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Zhang JJ, Sun Y, Hussain AA, Marshall J. Laser-mediated activation of human retinal pigment epithelial cells and concomitant release of matrix metalloproteinases. Invest Ophthalmol Vis Sci. 2012 May 17;53(6):2928-37.
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Ferris FL, Davis MD, Clemons TE, Lee LY, Chew EY, Lindblad AS, Milton RC, Bressler SB, Klein R; Age-Related Eye Disease Study (AREDS) Research Group. A simplified severity scale for age-related macular degeneration: AREDS Report No. 18. Arch Ophthalmol. 2005 Nov;123(11):1570-4.
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Cusumano A, Falsini B, Giardina E, Cascella R, Sebastiani J, Marshall J. Doyne honeycomb retinal dystrophy - functional improvement following subthreshold nanopulse laser treatment: a case report. J Med Case Rep. 2019 Jan 10;13(1):5. doi: 10.1186/s13256-018-1935-1. PMID: 30626431; PMCID: PMC6327555.
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Cusumano A, Falsini B, D'Ambrosio M, D'Apolito F, Sebastiani J, Levialdi Ghiron JH, Giardina E, Cascella R. Long-Term Structural and Functional Assessment of Doyne Honeycomb Retinal Dystrophy following Nanosecond 2RT Laser Treatment: A Case Series . Case Rep Ophthalmol. 2023 Nov 23;14(1):626-639. doi: 10.1159/000534579. PMID: 38023612; PMCID: PMC10666958.
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Age-related macular degeneration
La age-related macular degeneration (AMD, from English Age-Related Macular Degeneration), commonly known as maculopathy, and the leading cause of loss of central vision and legal blindness in the population over 60. In the industrialized world, where life expectancy has increased significantly, cases of AMD have increased significantly, with an important impact on the social and health system.
AMD determines the anatomical and functional alterations at the level of the macula, the central part of the retina that allows us to see clearly the objects and people around us. There are two forms of AMD: the Atrophic AMD (o not neovascular) and the Wet AMD (o neovascular). Both, albeit with different pathogenic mechanisms, can cause a dramatic reduction in visual function, with loss of central vision.
La Atrophic AMD it is characterized by the presence of yellowish deposits, denominated friendly, in the macula. The initial stage of the pathology may be asymptomatic, but as the disease progresses a process of atrophy of the retinal pigment epithelium (EPR) which leads to the progressive loss of photoreceptors (cones e rods) and to the concomitant reduction of central vision. in terminal stage of the disease, Named geographical atrophy (AG, from English Ggeographic Atrophy), patients lose the ability to read, recognize faces, perform precision work, drive, etc.
To date, there is still no resolutive treatment for atrophic AMD, however the dietary supplementation with high doses of antioxidants, lutein e zeaxanthin it has proved effective in slowing its progression towards the evolved stage. The need for a therapy capable of blocking or at least containing the progression of atrophic AMD towards the advanced stage, which implies a high risk of serious vision complications, has prompted the development of new lasers with characteristics suitable for treating the retinal tissue in no thermal damage.
Among them, the nanosecond pulsed laser, developed in Australia, has been tested in a major randomized multicenter clinical trial (LEAD study) lasting 3 years, with results published in September 2018 and December 2021 in the scientific journal Ophthalmology Retina, who demonstrated that nanosecond laser treatment can significantly slow disease progression in patients with appropriately selected early- and intermediate-stage atrophic AMD.
Unlike the laser used in the traditional laser photocoagulation (PRP), which has pulses lasting between 100 and 200 milliseconds (thousandths of a second), the nanosecond pulsed laser has a duration of 3 nanoseconds (billionths of a second), which limits heat loss outside the RPE , protecting the neural retina from the risk of thermal damage. In fact, conventional laser photocoagulation generates thermal energy due to the absorption of the laser by the melanosomes present in the cells of the RPE, energy which is propagated to the adjacent retinal structures. Since the PRP pulse duration is around 100 milliseconds, a time interval that allows heat to travel well beyond the pigment epithelium, this procedure has the potential to cause significant damage to the surrounding retina, Bruch's membrane and choroid. The nanosecond pulsed laser presents no risk of thermal damage due to the extremely short duration of the pulse and the type of emission, called speckled, with a spot of 400 microns in diameter and a wavelength of 532 nm. This type of emission creates an ablation of the RPE in the area within 400 microns and limited to a percentage of cells between 10% and 40%. (Figure 1).
The nanosecond pulsed laser is selectively applied to the RPE, where it is exclusively absorbed by intracellular melanosomes, avoiding thermal damage to the underlying Bruch's membrane and photoreceptors. Laser radiation produces intracellular damage that remains confined only to target cells (RPE), which undergo cell death (Figure 2). The space left empty by these cells is filled by adjacent cells, induced to migrate and proliferate thanks to a process of "signalling” extracellular resulting from tissue damage.
The process of cell division and growth induced by the laser treatment is associated with the release of biochemical factors in the extracellular matrix and seems to lead to a thinning of Bruch's membrane and an improvement of its hydraulic conductivity, with the restoration of the fluid transport capacity, migration of metabolites from the choroid-choriocapillary and removal of catabolites deriving from turn over retinal cell. In particular, the biological mechanisms of tissue repair described above are mediated by the release of metalloproteases, mainly MMP2 and MMP9, capable of restoring retinal functions slowed down or compromised due to ageing. At the end of this process, the retinal pigment epithelium appears "rejuvenated" in the absence of damage to the photoreceptors or the choroid.
In a study vitro, the nanosecond laser induced a migration of RPE and an increase of matrix metalloproteinases (MMPs) involved in extracellular matrix (ECM) turnover. In an animal model with a thickened Bruch's membrane, the application of this laser led to a significant reduction in the thickness of Bruch's membrane and an increase in the expression of genes involved in ECM turnover. The same results were highlighted in two eyes treated with the nanosecond laser and which were subsequently enucleated for tumor pathologies and examined from a morphological and immunohistochemical point of view. Ultimately, treatment with the nanosecond laser maintains the therapeutic effect of conventional lasers while eliminating the associated thermal tissue damage. This new method seems to be able to stimulate a natural biological healing response in the eye which leads to a tissue renewal process capable of preserving or improving retinal function, reducing the progression of the disease towards its advanced stage, of which the drusen represent a marker biological.
FAQ
Il 2RT lasers is indicated for the treatment of Atrophic AMD early or intermediate stage
absence of pseudodrusen, as indicated by the results of the AREDS multi-center clinical study.
Il 2RT lasers has an energy 500 times lower than that of conventional laser photocoagulation, this allows to stimulate the regeneration of the retinal tissue in no thermal damage and therefore of side effects such as the appearance of scotomas and choroidal neovascularization.
The laser treatment itself lasts few minutes, the preparation – with mydriatic and anesthetic drops – can instead last from about 15 to 30 minutes, depending on the patient's pupillary dilation time.
The treated patient can immediately return to his normal daily activities, the only limit being represented by the blurred vision and the sense of dazzle caused by the mydriatic drops and by the fixation light, which the patient must watch during the treatment.
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