Algorithms for optoacoustically controlled selective retina therapy (SRT)

Abstract

Objectives: Selective Retina Therapy (SRT) uses microbubble formation (MBF) to target retinal pigment epithelium (RPE) cells selectively while sparing the neural retina and the choroid. Intra- and inter-individual variations of RPE pigmentation makes frequent radiant exposure adaption necessary. Since selective RPE cell disintegration is ophthalmoscopically non-visible, MBF detection techniques are useful to control adequate radiant exposures. It was the purpose of this study to evaluate optoacoustically based MBF detection algorithms.

Methods: Fifteen patients suffering from central serous chorioretinopathy and diabetic macula edema were treated with a SRT laser using a wavelength of 527 nm, a pulse duration of 1.7 µs and a pulse energy ramp (15 pulses, 100 Hz repetition rate). An ultrasonic transducer for MBF detection was embedded in a contact lens. RPE damage was verified with fluorescence angiography.

Results: An algorithm to detect MBF as an indicator for RPE cell damage was evaluated. Overall, 4646 irradiations were used for algorithm optimization and testing. The tested algorithms were superior to a baseline model. A sensitivity/specificity pair of 0.96/1 was achieved. The few false algorithmic decisions were caused by unevaluable signals.

Conclusions: The algorithm can be used for guidance or automatization of microbubble related treatments like SRT or selective laser trabeculoplasty (SLT).

Keywords: Algorithm; Feedback; Lasers in medicine; Ophthalmology; Optoacoustics; RPE; Retina therapy; SRT; Selectivity.

Fig. 1

Schematic of the clinical setup with (a) treatment laser and (b) irradiation unit.

Fig. 2

Processing steps of NL algorithm include offset removal, filtering, rectification, integration, normalization and an error check.

Fig. 3

Processing steps of BL algorithm include offset removal, rectification, summation, and an error check .

Fig. 4

Three diagnostic images of the same region. (a) FA image taken before irradiation, (b) Irradiation map pre treatment with spot location and additional information about applied pulse energy. (c) FA image taken 1 h after treatment. Circles and pointers identify selected irradiated regions (Spot 1, 12, and 30) in the three images. This includes a non-damaged region (spot 1), a FA-visible region (spot 12), and a region with ophthalmoscopically visible cell damage (spot 30).

Fig. 5

Examples of NL and BL values of a spot above and below the MBF threshold. The black horizontal line shows the threshold value for the algorithms. (a) Displays pressure transients without any signs of microbubble formation (red) and with signs of microbubble formation. (green). (b) Displays the corresponding NL and BL-values from the data of subfigure a. The BL algorithm does not exceed its threshold value in subfigure b. This is a false negative decision. (c) Displays pressure transients without any signs of microbubble formation. (d) Displays NL and BL values from the data of subfigure c. The BL algorithm exceeds its threshold. This is a false positive decision.

Fig. 6

Scatter plots of (a) training set and (b) Development set. Datapoints were labeled as OA negative or OA positive with respect to absence or presence of a nonlinear increase in pressure amplitude. The threshold of 1.15 leads to the highest Y in the development set. The threshold value of 1.23 leads to a specificity of 1 in the development set.

Fig. 7

(a) Scatter plot with cell damage labels. Datapoints were labeled as FA negative or FA positive with respect to the visibility of hyperfluorescent regions in FA images. (b) Scatter plot with microbubble classification labels. Datapoints were labeled as OA negative or OA positive with respect to absence or presence of a nonlinear increase in pressure amplitude. The threshold of 1.15 leads to the highest Y in the development set. The threshold value of 1.23 leads to a specificity of 1 in the development set.

Fig. 8

ROC Curve of Fig. 6b (NL algorithm, cv set) and Fig. 7a (NL algorithm, test set, FA labeling). The threshold of 1.15 is indicated with black markers 1.23 is indicated with blue markers. The dotted lines indicate the 95% confidence interval.