Jenny Wang1, Yi Quan2, Roopa Dalal2, Daniel Palanker2,3. 1. Department of Applied Physics, Stanford University, Stanford, California, United States. 2. Department of Ophthalmology, Stanford University, Stanford, California, United States. 3. Hansen Experimental Physics Laboratory, Stanford University, Stanford, California, United States.
Abstract
Purpose: Recent progress in retinal laser therapy has centered upon using thermal stress below damage threshold or selective destruction of targeted tissue layers as a stimulus for retinal repair. Temporal modulation, including micropulse, is thought to increase the selectivity of laser treatment, but has not been carefully analyzed. We measure and model the tissue response to continuous-wave (CW) and micropulse laser to evaluate the advantages and drawbacks of temporal modulation. Methods: Thresholds of ophthalmoscopic visibility, which indicates damage to photoreceptors, and fluorescein angiography (FA), indicating damage to retinal pigment epithelium (RPE), were measured with 577-nm laser in rabbits for duty cycles ranging from 3% to 100% (CW) and pulse envelopes of 20 and 200 ms. Heat shock protein (HSP) expression was measured in rats. Thresholds were compared to a computational model of tissue response based on the Arrhenius integral. Results: Damage to photoreceptors was defined by average power, regardless of the duty cycle, as predicted by the model. The average power for FA threshold was lower with 5% duty cycle than with CW laser by 22 ± 15% for 200-ms and 35 ± 21.5% for 20-ms envelopes, demonstrating some heat localization to RPE. The ratio of RPE damage threshold to HSP expression threshold was 1.30 ± 0.15 and 1.39 ± 0.11 for 20 ms at 5% duty cycle and CW, respectively. Conclusions: Micropulse modulation with sufficiently short envelope and duty cycle can help reduce the spread of heat from the light-absorbing RPE and choroid. However, this localization does not benefit nondamaging retinal laser therapy, which is intended to avoid any cell death.
Purpose: Recent progress in retinal laser therapy has centered upon using thermal stress below damage threshold or selective destruction of targeted tissue layers as a stimulus for retinal repair. Temporal modulation, including micropulse, is thought to increase the selectivity of laser treatment, but has not been carefully analyzed. We measure and model the tissue response to continuous-wave (CW) and micropulse laser to evaluate the advantages and drawbacks of temporal modulation. Methods: Thresholds of ophthalmoscopic visibility, which indicates damage to photoreceptors, and fluorescein angiography (FA), indicating damage to retinal pigment epithelium (RPE), were measured with 577-nm laser in rabbits for duty cycles ranging from 3% to 100% (CW) and pulse envelopes of 20 and 200 ms. Heat shock protein (HSP) expression was measured in rats. Thresholds were compared to a computational model of tissue response based on the Arrhenius integral. Results: Damage to photoreceptors was defined by average power, regardless of the duty cycle, as predicted by the model. The average power for FA threshold was lower with 5% duty cycle than with CW laser by 22 ± 15% for 200-ms and 35 ± 21.5% for 20-ms envelopes, demonstrating some heat localization to RPE. The ratio of RPE damage threshold to HSP expression threshold was 1.30 ± 0.15 and 1.39 ± 0.11 for 20 ms at 5% duty cycle and CW, respectively. Conclusions: Micropulse modulation with sufficiently short envelope and duty cycle can help reduce the spread of heat from the light-absorbing RPE and choroid. However, this localization does not benefit nondamaging retinal laser therapy, which is intended to avoid any cell death.
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