Mechanisms of laser-tissue interactions in ocular surgery and therapy [electronic resource]
Keywords: Applied Physics.

Lasers enable precise, minimally-invasive interactions with ocular tissues for many ophthalmic applications, including vision correction surgery of the cornea, cataract surgery in the lens, treatment of trabecular meshwork in glaucoma, and retinal therapy for diseases such as diabetic retinopathy and age-related macular degeneration. Laser light is a versatile and powerful tool for medical treatment but, like a drug, overdose can have harmful consequences. The challenge then is to design and deliver the laser exposure to maximize efficacy while minimizing the safety risks to the target tissue and to adjacent areas, which may be inadvertently exposed. The rapid advancement of laser technology has made many wavelengths, a wide range of pulse durations, and ever higher peak powers accessible for use in ophthalmology. With a large parameter space available, a clear understanding of the mechanisms of laser-tissue interactions, which determine the potential safety and efficacy trade-offs, is essential for optimizing various treatments. In this work, the interaction between lasers and ocular tissue is evaluated for the treatment of two leading causes of vision impairment: retinal disorders, particularly those of the macula, and cataract, the clouding of the lens. Retinal laser therapy, based on heating of the retinal pigment epithelium and choroid, began as a treatment to selectively destroy parts of the peripheral retina to balance the metabolic supply and demand in diabetic patients and thereby spare central vision. Clinical reports of effective macular laser therapy suggested that laser-induced thermal stress could produce a therapeutic effect at lower temperatures, without the tissue destruction by photocoagulation. To test this hypothesis, a computational model of tissue response to laser heating was developed and used to define a protocol for delivering consistent amounts of sub-lethal thermal stress to the retina. In-vivo experiments in rabbits validated this delivery protocol as well as our model. Initial human case studies using this non-damaging approach to retinal laser therapy have shown promising results in chronic central serous chorioretinopathy and macular telangiectasia, while avoiding any destruction of retinal tissue. Micropulse modulation in retinal laser therapy is believed to increase the selectivity of laser treatment through the use of trains of sub-ms pulses rather than continuous-wave laser. Despite its widespread clinical adoption, the tradeoffs of modulated laser have not been carefully analyzed. To dispel misconceptions about micropulse modulation, we applied our computational model to analyze the effects of different modulation parameters. In-vivo experiments validated our modeling results and indicated that only micropulse modulation with sufficiently short envelope and duty cycle can increase the selectivity of damaging RPE treatment, and that micropulse modulation actually reduces the therapeutic window for non-damaging therapy by producing higher peak temperatures. To further optimize laser therapy, real-time tissue monitoring is needed to account for variation in pigmentation and transparency in the patient eye. Currently, laser cataract surgery uses near-infrared (NIR) femtosecond lasers, which are focused into the lens to produce optical breakdown and cavitation bubbles which rupture tissue in the desired pattern. While femtosecond laser cataract systems have been successfully translated into clinical practice, their adoption is limited by complexity and cost. In this dissertation, ultraviolet (UV) nanosecond lasers, which are far simpler and cheaper, are evaluated for their ability to dissect lens tissue compared to NIR and visible femtosecond lasers. Scanning electron microscopy was performed to analyze tissue cuts and showed that finer edges were possible with shorter wavelengths. Measurements of the laser-induced protein breakdown with UV, visible and NIR lasers, along with comparison of the dielectric breakdown thresholds, determined the relative contributions of photochemical vs. photomechanical interaction in dissection of transparent tissue. Finally, analysis of the hazards to ocular tissue outside the intended cut volume, including in-vivo experiments and thermal modeling, established the safety limits for cataract surgery with NIR and UV lasers.