Mark Saeger

Temperature-Controlled Retinal Photocoagulation - A Step Toward Automated Laser Treatment

PURPOSE Retinal laser photocoagulation carries the risk of overtreatment due to effect variation of identically applied lesions. The degree of coagulation depends on the induced temperature increase and on exposure time. We introduce temperature controlled photocoagulation (TCP), which uses optoacoustics to determine individually exposure times necessary to create reproducible lesions. METHODS Optoacoustic temperature measurement relies on pressure waves that are excited in the retinal tissue by repetitive low-energy laser pulses. Signal amplitudes correlate with tissue temperature and are detected by a transducer in the laser contact lens. We used a continuous wave (CW) photocoagulator for treatment irradiation and superimposed probe laser pulses for simultaneous temperature measurement. Optoacoustic data of 1500 lesions (rabbit) were evaluated to develop an algorithm that controls exposure times automatically in TCP. Lesion diameters of 156 TCP lesions were compared to 156 non-controlled lesions. Histology was performed after 1 hour, and 1 and 4 weeks. RESULTS TCP resulted in exposure times from 4 to 800 ms depending on laser power chosen. Ophthalmoscopic and histologic lesion diameters were independent of power between 14 and 200 mW. TCP lesions barely were visible with a mean diameter equal to the treatment beam (130 μm). In contrast, standard lesion diameters increased linearly and statistically significantly with power. Histology confirmed sparing of the ganglion and nerve fiber layers in TCP. CONCLUSIONS TCP facilitates uniform retinal lesions over a wide power range. In a clinical setting, it should generate soft and reproducible lesions independently of local tissue variation and improve safety, particularly at short exposure times.

Correlation with OCT and histology of photocoagulation lesions in patients and rabbits

Purpose: To examine spectral domain optical coherence tomographic (OCT) and histological images from comparable retinal photocoagulation lesions in rabbits, and to correlate these images with comparable OCT images from patients.

Correlation of temperature rise and optical coherence tomography characteristics in patient retinal photocoagulation.

We conducted a study to correlate the retinal temperature rise during photocoagulation to the afterward detected tissue effect in optical coherence tomography (OCT). 504 photocoagulation lesions were examined in 20 patients. The retinal temperature increase was determined in real-time during treatment based on thermoelastic tissue expansion which was probed by repetitively applied ns laser pulses. The tissue effect was examined on fundus images and OCT images of individualized lesions. We discerned seven characteristic morphological OCT lesion classes. Their validity was confirmed by increasing visibility and diameters. Mean peak temperatures at the end of irradiation ranged from approx. 60 °C to beyond 100 °C, depending on burn intensity.

Comprehensive Detection, Grading, and Growth Behavior Evaluation of Subthreshold and Low Intensity Photocoagulation Lesions by Optical Coherence Tomographic and Infrared Image Analysis

Purpose. To correlate the long-term clinical effect of photocoagulation lesions after 6 months, as measured by their retinal damage size, to exposure parameters. We used optical coherence tomographic (OCT)-based lesion classes in order to detect and assess clinically invisible and mild lesions. Methods. In this prospective study, 488 photocoagulation lesions were imaged in 20 patients. We varied irradiation diameters (100/300 µm), exposure-times (20–200 ms), and power. Intensities were classified in OCT images after one hour, and we evaluated OCT and infrared (IR) images over six months after exposure. Results. For six consecutive OCT-based lesion classes, the following parameters increased with the class: ophthalmoscopic, OCT and IR visibility rate, fundus and OCT diameter, and IR area, but not irradiation power. OCT diameters correlated with exposure-time, irradiation diameter, and OCT class. OCT classes discriminated the largest bandwidth of OCT diameters. Conclusion. OCT classes represent objective and valid endpoints of photocoagulation intensity even for “subthreshold” intensities. They are suitable to calculate the treated retinal area. As the area is critical for treatment efficacy, OCT classes are useful to define treatment intensity, calculate necessary lesion numbers, and universally categorize lesions in clinical studies.

Photocoagulation in rabbits: optical coherence tomographic lesion classification, wound healing reaction, and retinal temperatures.

The rabbit is the most common animal model to study retinal photocoagulation lesions. We present a classification of retinal lesions from rabbits, that is based on optical coherence tomographic (OCT) findings, temperature data, and OCT‐follow‐up data over 3 months.

Tocilizumab and steroid boli for treatment-resistant anterior necrotizing scleritis

(95% CI, 1.314–31.834) in PEX and PEX glaucoma, respectively. But Bonferroni-corrected p value was 0.192 and 0.216, respectively. Other SNPs were not associated with PEX syndrome (p > 0.05). The rs2151532 SNP which is closer to CTGF than rs928501 (linkage disequilibrium r = 0.046) was also associated with disease in total patients, especially associated with PEX glaucoma (p = 0.002, Bonferroni-corrected p = 0.024). Additional haplotype analyses were performed using significant SNPs and neighbouring SNPs (rs9399005-rs2151532-rs928501rs7768619). Haplotype ‘G-C-C-C’ was more frequent in cases (7.5%) than in controls (2.6%) (p = 0.040). Another haplotype ‘A-T-C-T’ also showed similar pattern (3.0% in cases and 0.5% in controls) (p = 0.069). The result showed no significant association after Bonferroni’s correction. There is limitation of small sample size in this study. Nevertheless, functional data of the ENCODE project provide diverse biochemical evidence that near the region of rs928501 are enriched protein binding, DNase I hypersensitivity and histone modification sites (http://www.regulomedb.org). Further expression quantitative loci analysis is essential to prove that the SNPs associated with PEX have an effect on the gene expression level of CTFG. Our findings might support the differentially expressed CTGF in PEX samples in previous studies and suggest the genetic basis of CTGF for the pathogenesis of PEX.