RESUMO
Purpose: Subthreshold, nanosecond pulsed laser treatment shows promise as a treatment for age-related macular degeneration (AMD); however, the safety profile needs to be robustly examined. The aim of this study was to investigate the effects of laser treatment in humans and mice. Methods: Patients with AMD were treated with nanosecond pulsed laser at subthreshold (no visible retinal effect) energy doses (0.15-0.45 mJ) and retinal sensitivity was assessed with microperimetry. Adult C57BL6J mice were treated at subthreshold (0.065 mJ) and suprathreshold (photoreceptor loss, 0.5 mJ) energy settings. The retinal and vascular responses were analyzed by fundus imaging, histologic assessment, and quantitative PCR. Results: Microperimetry analysis showed laser treatment had no effect on retinal sensitivity under treated areas in patients 6 months to 7 years after treatment. In mice, subthreshold laser treatment induced RPE loss at 5 hours, and by 7 days the RPE had retiled. Fundus imaging showed reduced RPE pigmentation but no change in retinal thickness up to 3 months. Electron microscopy revealed changes in melanosomes in the RPE, but Bruch's membrane was intact across the laser regions. Histologic analysis showed normal vasculature and no neovascularization. Suprathreshold laser treatment did not induce changes in angiogenic genes associated with neovascularization. Instead pigment epithelium-derived factor, an antiangiogenic factor, was upregulated. Conclusions: In humans, low-energy, nanosecond pulsed laser treatment is not damaging to local retinal sensitivity. In mice, treatment does not damage Bruch's membrane or induce neovascularization, highlighting a reduced side effect profile of this nanosecond laser when used in a subthreshold manner.
Assuntos
Cegueira/prevenção & controle , Terapia com Luz de Baixa Intensidade , Degeneração Macular/radioterapia , Neovascularização Retiniana/prevenção & controle , Idoso , Animais , Cegueira/fisiopatologia , Proteínas do Olho/genética , Feminino , Angiofluoresceinografia , Humanos , Imuno-Histoquímica , Lasers de Estado Sólido/uso terapêutico , Degeneração Macular/fisiopatologia , Masculino , Melanossomas/ultraestrutura , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Pessoa de Meia-Idade , Fatores de Crescimento Neural/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Retina/fisiopatologia , Neovascularização Retiniana/fisiopatologia , Epitélio Pigmentado da Retina/fisiopatologia , Serpinas/genética , Fator A de Crescimento do Endotélio Vascular/genética , Acuidade Visual/fisiologia , Testes de Campo VisualRESUMO
Complete loss of vision is one of the most feared sequelae of retinal disease. Currently, there are few if any treatment options available to patients that may slow or prevent blindness in diseases caused by photoreceptor loss, such as retinitis pigmentosa and age-related macular degeneration. Electronic restoration of vision has emerged over recent years as a safe and viable option for those who have lost substantial numbers of photoreceptors and who are severely vision impaired. Indeed, there has been a dramatic increase in our understanding of what is required to restore vision using an electronic retinal prosthesis. Recent reports show that for some patients, restoration of vision to the point of reading large letters is possible. In this review, we examine the types of implants currently under investigation and the results these devices have achieved clinically. We then consider a range of engineering and biological factors that may need to be considered to improve the visual performance of newer-generation devices. With added research, it is hoped that the level of vision achieved with newer generation devices will steadily improve, resulting in enhanced quality of life for those with severe vision impairment.