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G. Chidlow, J. P. M. Wood, R. J. Casson, M. Plunkett; Retinal Damage Profiles and Cellular Responses to Laser Treatment: Comparison Between a Novel, Non-Thermal Laser and a Conventional Photocoagulator. Invest. Ophthalmol. Vis. Sci. 2009;50(13):204.
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© ARVO (1962-2015); The Authors (2016-present)
Thermal lasers remain the gold standard for treatment of diabetic retinopathy; however, there are many associated clinical side-effects such as the inability to treat within the foveal region due to collateral retinal damage. Ongoing clinical trials indicate that a novel nanosecond pulse laser (2RT) reduces diabetic macular edema. In the current study we compared retinal damage and cellular responses resulting from laser treatment of rats with a conventional thermal photocoagulator laser and the 2RT laser at clinically relevant energy levels.
Pigmented Dark Agouti rats were treated with approximately 100 shots of either a conventional photocoagulator laser (532nm, CW laser, Ellex Integre with 0.1sec pulse duration) or a nanosecond pulse laser (532nm, Q-switched Retinal Regeneration Therapy laser prototype, Ellex 2RT with 3 nanosecond pulse duration). Laser settings were at visible lesion threshold for the CW laser and at visible lesion threshold and below for the 2RT laser. Rats were killed at various time points following the procedure. Samples were processed for histology, immunohistochemistry, in situ biochemical assays, real-time and conventional RT-PCR and Western blotting using standard methodologies.
The photocoagulator laser caused retinal lesions that were principally evident within the outer retina. These were associated with photoreceptor cell death, astrocyte and Müller cell activation, and infiltration of macrophages and neutrophils. In addition, upregulations of inflammatory cytokines, heat shock proteins, endogenous trophic factors, and matrix metalloproteinases were induced. In comparison, all of these changes were drastically attenuated when the 2RT laser was used, particularly at the sub-visual power setting, although RPE cell loss was still evident.
The photocoagulator laser produced marked retinal damage and cellular responses consistent with an inflammatory response to thermal injury. In contrast, the 2RT laser produced negligible retinal damage and cellular responses at clinically relevant energy levels, and only marginally greater effects at elevated energy levels. These results show that nanosecond pulses of the 2RT laser produce an isolated insult at the level of the RPE without causing collateral damage to the neuroretina, which is a normal clinical consequence of thermal photocoagulator laser procedures. These results may have important implications for the treatment of diabetic macular edema, proliferative diabetic retinopathy and early AMD.
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