Abstract
Purpose :
Subthreshold retinal laser therapies (SLT) have vast clinical evidence in the treatment of various retinal disorders, including diabetic macular edema and central serous chorioretinopathy, and also early evidence for age-related macular degeneration. SLTs aim to trigger the heat shock response (HSR), a cellular response to combat stress, in the retinal pigment epithelium (RPE) through laser-induced hyperthermia without causing cell death. However, the therapeutic temperature window for triggering HSR but avoiding apoptosis is narrow, and the same laser exposure produces differing temperature elevations in different patients. Hence, SLT protocols without thermal dosimetry may lead to suboptimal treatment efficacy or safety profile. Here we present a focal electroretinogram (fERG) based method to provide thermal dosimetry for long-pulse SLT to enable personalized treatments.
Methods :
Thirty-six laser treatments were delivered to 8 eyes in 4 anaesthetized pigs with 5 mm laser spot diameter and 60 s laser pulse duration. Each treatment was preceded by a laser power calibration protocol, where retinal temperature elevation per unit laser power was determined with a fERG-based method. The obtained value was used to estimate the laser power needed to reach a target temperature between 43.6 and 48.6°C. The treated areas were investigated for visible lesions with fundus imaging and fluorescein angiography. The threshold temperature for lesion generation and the accuracy of the thermal dosimetry were determined by fitting a probit model between the target temperature and damage classification data.
Results :
The kinetics of the fERG response was found to accelerate linearly with temperature up to 43°C. At temperatures above 45°C the kinetics of the fERG signal started to decelerate accompanied by a drop in signal amplitude. The fERG-based thermal dosimetry method produced a standard relative error of 7% of the laser-induced temperature elevation. The steady-state threshold temperature for generating a lesion was determined to be 48.0°C for 60 second laser exposures.
Conclusions :
fERG responses can be used to estimate laser-induced changes in retinal temperature and to estimate the laser power needed to reach a desired retinal temperature with high accuracy. We conclude that fERG-based retinal temperature determination can enhance the safety and efficacy of SLT with large spot size and long pulse duration.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.