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Erica L Fletcher, Samuel A Mills, Kirstan Vessey, Ursula Greferath, Chi D Luu, Kate Brassington, Khin Zaw Aung, Malcolm J Plunkett, Robyn H Guymer, Andrew Ian Jobling; Treatment with a nanosecond laser reduces drusen and thins Bruch’s membrane: evidence from human and animal model studies. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6347.
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Treatments that reduce drusen may have the potential to limit the progression of age-related macular degeneration (AMD). Here, we evaluated a nanosecond laser in patients with intermediate stages of AMD and investigated the retinal response and mechanism of action in a mouse model of thickened Bruch’s membrane.
Patients (N=51) with intermediate AMD (bilateral drusen >125um) received treatment to one eye with a 532nm nanosecond (2RT laser; Ellex Pty Ltd) Q-switched YAG laser. Drusen area in each eye was graded at baseline, 12 and 24 months later. Changes in drusen area in the treated eyes were compared with a natural history AMD cohort (N=58) of similar age range and clinical AMD severity. In order to better understand the mechanism of action, human and mouse retinae were examined to assess the acute effect (1 hour to 7 days) of the laser, while long lasting effects (4 months) were evaluated in aged C57Bl6J and ApoEnull mice. Retinae and RPE were assessed for structural integrity (Nissl; phalloidin, ultrastructure), cell death (TUNEL), gliosis (GFAP), and microgliosis (IBA-1). PCR microarrays and qPCR were used to characterise the changes in expression of extracellular matrix genes.
Nanosecond laser treatment reduced drusen area in 35-40% of eyes following twelve and 24 months (compared to 5-11% of eyes in a natural history cohort; p<0.001). The laser-treated human and mouse eyes exhibited similar acute structural changes such as selective lesions of the RPE and microglial invasion of the lasered area without overt photoreceptor death or retinal injury. Aged control and ApoEnull mice showed a thinning of Bruch’s membrane 4 months after a single laser treatment, that coincided with a change in the RPE expression of select extracellular matrix genes.
Nanosecond laser treatment thins Bruch’s membrane via mechanisms involving altered extracellular matrix turnover. Similar mechanisms may also explain the reduction in drusen area observed in patients with intermediate AMD following nanosecond laser treatment.
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