Selective retina therapy (SRT) for clinically significant diabetic macular edema.

PURPOSE: To test selective retina therapy (SRT) as a treatment of clinically significant diabetic macular edema (DME). METHODS: Prospective two-center interventional uncontrolled phase II pilot study. Thirty-nine eyes of 39 patients with previously untreated non-ischemic DME were treated with focal laser treatment using a Q-switched frequency doubled Nd:YLF laser which selectively affects the retinal pigment epithelium while sparing the photoreceptor layer. Optoacoustic measurements, fundus fluorescein angiography (FFA), and funduscopy were used to determine the individual threshold of RPE damage of each patient. The pulse energy was adjusted to apply angiographically visible but funduscopically invisible effects. Optoacoustic measurements were correlated with funduscopy and FFA. Follow-up examinations at 3 and 6 months post-treatment included best-corrected ETDRS visual acuity (BCVA), FFA, fundus photography, and retinal thickness measured by optical coherence tomography. The primary outcome measure was change of BCVA. Other outcome measures were change of retinal thickness, presence of hard exudates, leakage in FFA, accuracy of optoacoustic measurements, and correlation of BCVA with change of anatomical and systemic parameters. RESULTS: Mean BCVA improved from 43.7 letters (standard deviation, SD=9.1) at baseline to 46.1 letters (SD=10.5) at the 6-month follow-up (p=0.02). BCVA improved (>5 letters) or remained stable (+/-5 letters) in 84% of eyes. Thirteen percent of eyes improved by > or =10 letters, while 16% of eyes lost more than 5 letters. There was no severe loss of vision (> or =15 letters). Overall, retinal thickness, hard exudates, and leakage in FFA did not change significantly (p> 0.05), while improvement of BCVA correlated with a reduction of hard exudates (p=0.01) and central retinal thickness (p=0.01). Specificity and sensitivity of detecting the angiographic visible threshold of RPE damage by optoacoustic measurements were 86% and 70% respectively. No adverse effects or pain were noted during or after treatment. Conclusions Functional and anatomical improvement or stabilization was observed in most patients. SRT appears to be safe. Optoacoustic measurements accurately detect the individual threshold of RPE damage. A randomized trial is required to further test efficacy and safety of SRT as a treatment of clinically significant diabetic macular edema (DME).

Selective retina therapy (SRT) of chronic subfoveal fluid after surgery of rhegmatogenous retinal detachment: three case reports.

BACKGROUND: Shallow subfoveal fluid accumulation after successful surgery for retinal detachment can be the reason for compromised visual acuity. To date, therapeutical options to tackle this problem have not been established. Selective retina therapy (SRT) is a new laser technology that uses a train of mus-laser pulses to selectively damage retinal pigment epithelial (RPE) cells while sparing retinal structures. METHODS: We treated three patients with chronic subfoveal fluid accumulation after retinal detachment surgery. The median period between retinal surgery and SRT treatment was 7 months. For SRT, we used a prototype frequency-doubled, Q-switched Nd:YLF laser (lambda = 527 nm). Each laser exposition contained 30 pulses (t = 1,7 micros, 100 Hz, E = 100-400 microJ). Two of the three patients were treated subfoveally. OCT III (optical coherence tomography) examinations were performed to evaluate changes in subretinal fluid accumulation. RESULTS: In all three patients, we observed complete resolution of subfoveal fluid within 1-5 months. Follow-up has been 16 months to 2 years. Visual acuity improved in all patients. In one patient, cystoid macular edema developed 3 months after treatment. Additional SRT treatments were not necessary. CONCLUSION: SRT is a safe treatment. Visual acuity improved after SRT, even in subfoveal irradiations. SRT is an option to support subretinal fluid reabsorption. In this situation where no other therapeutical options are established, SRT may be a beneficial treatment for chronic subfoveal fluid accumulation after retinal detachment surgery.

Noninvasive optoacoustic online retinal temperature determination during continuous-wave laser irradiation.

The therapeutic effect of most retinal laser treatments is initiated by a transient temperature increase. Although crucial to the effectiveness of the treatment, the temperature course is not exactly known due to individually different tissue properties. We develop an optoacoustic method to determine the retinal temperature increase in real time during continuous-wave (cw) laser irradiation, and perform temperature calculations to interpret the results exemplary for transpupillary thermotherapy (TTT). Porcine globes ex vivo and rabbit eyes in vivo are irradiated with a diode laser (lambda=810 nm, P< or =3 W, phi=2 mm) for 60 s. Simultaneously, pulses from a N2-laser pumped dye laser (lambda=500 nm, tau=3.5 ns, E approximately 5 microJ) are applied on the retina. Following its absorption, an ultrasonic pressure wave is emitted, which is detected by a transducer embedded in a contact lens. Using the previously measured temperature-dependent Gruneisen coefficient of chorioretinal tissue, a temperature raise in porcine eyes of 5.8 degrees C(Wcm2) after 60 s is observed and confirmed by simultaneous measurements with an inserted thermocouple. In a rabbit, we find 1.4 degrees C(Wcm2) with, and 2.2 degrees C(Wcm2) without perfusion at the same location. Coagulation of the rabbit's retina occurs at DeltaT=21 degrees C after 40 s. In conclusion, this optoacoustic method seems feasible for an in vivo real-time determination of temperature, opening the possibility for feedback control retinal laser treatments.

Optoacoustic real-time dosimetry for selective retina treatment.

The selective retina treatment (SRT) targets retinal diseases associated with disorders in the retinal pigment epithelium (RPE). Due to the ophthalmoscopic invisibility of the laser-induced RPE effects, we investigate a noninvasive optoacoustic real-time dosimetry system. In vitro porcine RPE is irradiated with a Nd:YLF laser (527 nm, 1.7-micros pulse duration, 5 to 40 microJ, 30 pulses, 100-Hz repetition rate). Generated acoustic transients are measured with a piezoelectric transducer. During 27 patient treatments, the acoustic transients are measured with a transducer embedded in an ophthalmic contact lens. After treatment, RPE damage is visualized by fluorescein angiographic leakage. Below the RPE damage threshold, the optoacoustic transients show no pulse-to-pulse fluctuations within a laser pulse train. Above threshold, fluctuations of the individual transients among each other are observed. If optoacoustic pulse-to-pulse fluctuations are present, RPE leakage is observed in fluorescein angiography. In 96% of the irradiated areas, RPE leakage correlated with the optoacoustic defined threshold value. A noninvasive optoacoustic real-time dosimetry for SRT is developed and proved in vitro and during patient treatment. It detects the ophthalmoscopically invisible laser-induced damage of RPE cells and overcomes practical limitations of SRT for use in private practice.