Abstract
Purpose: :
Minimally traumatic, sub-visible and sub-lethal laser therapies have been successfully applied to treat diabetic macular edema and other retinal diseases. Proper dosimetry is a key factor in decreasing the side effects while retaining the therapeutic benefits. A multimodal imaging and structural correlation study was conducted to verify and calibrate a computational model-based algorithm for laser dosimetry.
Methods: :
A computational model of retinal photothermal therapy was used to specify power and duration variation in a titration algorithm for visible and sub-visible photocoagulation. Experimental verification of the model was conducted using PASCAL Streamline 577 (TMLS) in Dutch Belted rabbits. Power was first titrated to produce a lesion barely visible within 3 seconds following a 20 ms pulse. Retinal responses to pulse energies ranging from 30 to 170% of the titration level were then imaged at 1 hour, 1, 3, 7, 30 and 60 days. In-vivo multimodal imaging included infrared and blue reflectance, fluorescein angiography (FA) and spectral domain OCT (SD-OCT). After 2 months eyes were enucleated and fixed for light (LM) and scanning electron microscopy (SEM).
Results: :
Power and pulse duration at each energy level was determined by tying linear changes in energy to exponential changes in Arrhenius integral of retinal thermal damage. 170% and 120% energy burns corresponded to moderate and light clinical grades, respectively. 75% lesions were clinically sub-visible, detectable with FA and OCT. 50 and 30% lesions were typically invisible with all in-vivo imaging modalities. SEM showed minimal RPE damage down to 30% energy levels. Restoration of the photoreceptor layer in barely visible and sub-visible burns was observed by SD-OCT as reestablishment of inner-outer segment junction layer over time, and confirmed by LM.
Conclusions: :
Proper dosimetry of laser treatment can help optimize therapeutic benefit and minimize collateral damage. Titration algorithms based on computational modeling of retinal photocoagulation provide a reliable method for achieving different clinical endpoints, including sub-visible and sub-lethal regimes. Efficacy and safety of restorative retinal phototherapy utilizing minimally-damaging visible lesions, as well as sub-visible and sub-lethal settings based on this titration method should be confirmed in clinical trials.
Keywords: laser • retinal pigment epithelium • wound healing