Selektive Retina-Therapie (SRT)

Abb.1

Die selektive Retina-Therapie (SRT) wurde am Medizinischen Laserzentrum Lübeck entwickelt und wird zurzeit als neue, schonende Laser-Behandlungs­methode für verschiedene Erkrankungen des Augenhintergrunds evaluiert, die mit einer reduzierten Funktion des Retinalen Pigmentepithels (RPE) assoziiert werden. Das RPE ist ein monozelluläres hexagonales Zelllayer (Abb. 1) auf der Bruchschen Membran, das die Photorezeptoren von der versorgenden Aderhaut trennt. Das RPE regelt den Metabolismus der Netzhaut.

Abb.2A+2B

Mit der SRT wird das RPE im bestrahlten Areal selektiv durch Mikrosekunden-Laserpulse behandelt. Durch Mikrovaporisation an den Melaningranula der Zelle (Abb. 2A) kommt es zur Photodisruption der bestrahlten Zellen, wobei die angrenzende neurosensorische Netzhaut mit den Photorezeptoren und die unter dem RPE liegende Aderhaut nicht geschädigt wird (Abb 1: dunkle Zellen selektiv geschädigt, grüne vital; Abb. 2 A gelb markierte Zellen). Die Therapie führt idealerweise zu einer Regeneration des RPEs und der Bruchschen Membran (Abb. 2B) und einem gesteigerten Metabolismus am chorioretinalen Übergang.

Im Gegensatz zur etablierten Laserphotokoagulation (Abb. 3A), bei der die bestrahlten und umgebenden Areale der Netzhaut verödet werden, bleiben bei der SRT Skotome vollständig aus (Abb. 3B). Hierdurch sind die Lasereffekte allerdings für den behandelnden Arzt während der Therapie nicht sichtbar und nur durch spätere Fluoreszenzangiographie der Schrankendefekt an den bestrahlten Arealen demarkierbar (Abb. 3C).

Abb.3 A-C

Aktuelle Forschungsthemen umfassen:

  • Optimierung der Bestrahlung
  • Echtzeitvisualisierung und Dynamik der Mikrovaporisation
  • Automatische Therapiekontrolle und Dosierung
  • Klinische Studien zu verschiedenen Erkrankungen

Publikationen

2015

  • Kim, H. D. and Han, J. W. and Ohn, Y. H. and Brinkmann, R. and Park, T. K.: Functional evaluation using multifocal electroretinogram after selective retina therapy with a microsecond-pulsed laser. Invest Ophthalmol Vis Sci, no. 56, pp. 122-31, 2015
    BibTeX Link
    @article{Kim2015,
       author = {Kim, H. D. and Han, J. W. and Ohn, Y. H. and Brinkmann, R. and Park, T. K.},
       title = {Functional evaluation using multifocal electroretinogram after selective retina therapy with a microsecond-pulsed laser},
       journal = {Invest Ophthalmol Vis Sci},
       volume = {56},
       number = {1},
       pages = {122-31},
       note = {1552-5783
    Kim, Hoon Dong
    Han, Jung Woo
    Ohn, Young-Hoon
    Brinkmann, Ralf
    Park, Tae Kwann
    Journal Article
    United States
    Invest Ophthalmol Vis Sci. 2014 Dec 11;56(1):122-31. doi: 10.1167/iovs.14-15132.},
       abstract = {PURPOSE: To evaluate the changes of retinal function with multifocal electroretinogram (mfERG), and estimate the association between functional and structural changes after selective retina therapy (SRT) with microsecond-pulsed laser in comparison to continuous wave laser photocoagulation (cwPC). METHODS: Selective retina therapy and cwPC were applied with 10 x 10 shots and 1/2 lesion-width on the retina in the right and left eyes of 20 healthy Chinchilla Bastard rabbits, respectively. Optical coherence tomography (OCT), fundus fluorescein angiography (FFA), and mfERG were performed before, and on days 1, 7, and 30 after both laser treatments. The mean ratios of amplitudes and implicit times of N1 and P1 from eight hexagons covering laser-treated retinal lesions/total retina were measured. Histology was obtained after killing three rabbits at each time period to observe the anatomic changes after both laser treatments. RESULTS: The mean ratios of amplitudes of N1 and P1 in SRT lesions did not change significantly for 30 days after laser treatment. Only subtle reductions of the mean ratios of N1 and P1 amplitudes on day 1, thereafter the amplitudes showed the trend to recover toward baseline values. Histology and OCT revealed temporary and reversible morphologic changes after SRT, which restored to normal within 1 month. However, the mean ratios of N1 amplitudes on days 7 and 30 (P = 0.010, P < 0.001, respectively), and P1 amplitudes on days 7 and 30 (P < 0.001, P < 0.001, respectively) declined significantly in cwPC lesions compared with baseline. Disorganization and atrophic changes were identified on histology and OCT after cwPC. CONCLUSIONS: The results suggest that SRT preserved retinal function as well as anatomical structure after treatment.},
       keywords = {continuous wave laser photocoagulation (cwPC)
    multifocal electroretinogram (mfERG)
    selective retina therapy (SRT)},
       ISSN = {0146-0404},
       DOI = {10.1167/iovs.14-15132},
       year = {2015},
       type = {Journal Article}
    }
    

2011

  • Klatt, C. and Saeger, M. and Oppermann, T. and Porksen, E. and Treumer, F. and Hillenkamp, J. and Fritzer, E. and Brinkmann, R. and Birngruber, R. and Roider, J.: Selective retina therapy for acute central serous chorioretinopathy. Br J Ophthalmol, no. 95, pp. 83-8, 2011
    BibTeX
    @article{Klatt,
       author = {Klatt, C. and Saeger, M. and Oppermann, T. and Porksen, E. and Treumer, F. and Hillenkamp, J. and Fritzer, E. and Brinkmann, R. and Birngruber, R. and Roider, J.},
       title = {Selective retina therapy for acute central serous chorioretinopathy},
       journal = {Br J Ophthalmol},
       volume = {95},
       number = {1},
       pages = {83-8},
       note = {Using Smart Source Parsing
    Jan; Epub 2010 Jun 15},
       abstract = {AIMS: To evaluate selective retina therapy (SRT) as a treatment of acute central serous chorioretinopathy. METHODS: 30 eyes of 30 patients with central serous chorioretinopathy of at least a 3 months' duration were recruited. 14 eyes were randomised to an SRT group (Q-switched neodymium-doped yttrium lithium fluoride (Nd:YLF) laser, wavelength 527 nm, t=1.7 mus, energy 100-370 muJ, spot diameter 200 mum, pulse repetition rate 100 Hz,) and 16 eyes to a control group. After 3 months of follow-up, patients in the control group with persistence of subretinal fluid (SRF) were allocated to a cross-over group, treated with SRT and followed up for further 3 months. The main outcome measures were change of best-corrected Early Treatment Diabetic Retinopathy Study visual acuity (BCVA) and SRF. RESULTS: At 3 months of follow-up, the mean (SD) improvement of BCVA was significantly greater after SRT than in the control group: 12.7 (7.2) versus 6.3 (8.9) letters (p=0.04). SRF had decreased significantly more after SRT as compared with that the control group: 203 (136) mum versus 41 (150) mum (p=0.005). In eight eyes allocated to the cross-over group, the mean BCVA had increased during 3 months of follow up before SRT by 1.4 (5.2) letters and continued to increase during 3 months following SRT by 7.4 (6.3) letters, while SRF increased by 39.5 (160.2) mum before SRT and decreased by 151.5 (204.9) mum after SRT. In six of the eight eyes, SRF had completely resolved 3 months after SRT. CONCLUSIONS: SRT appears to expedite functional recovery and the re-absorption of SRF as compared with that in untreated controls. A larger prospective, randomised phase 3 confirmative patient study is warranted. TRIAL REGISTRATION NUMBER: NCT00987077.},
       year = {2011}
    }

2010

  • Roider, J. and Liew, S. H. and Klatt, C. and Elsner, H. and Poerksen, E. and Hillenkamp, J. and Brinkmann, R. and Birngruber, R.: Selective retina therapy (SRT) for clinically significant diabetic macular edema. Graefes Arch Clin Exp Ophthalmol, no. 248, pp. 1263-72, 2010
    BibTeX
    @article{Roider,
       author = {Roider, J. and Liew, S. H. and Klatt, C. and Elsner, H. and Poerksen, E. and Hillenkamp, J. and Brinkmann, R. and Birngruber, R.},
       title = {Selective retina therapy (SRT) for clinically significant diabetic macular edema},
       journal = {Graefes Arch Clin Exp Ophthalmol},
       volume = {248},
       number = {9},
       pages = {1263-72},
       note = {Using Smart Source Parsing
    Sep},
       abstract = {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).},
       year = {2010}
    }
    

2007

  • Framme, C. and Alt, C. and Schnell, S. and Sherwood, M. and Brinkmann, R. and Lin, C. P.: Selective targeting of the retinal pigment epithelium in rabbit eyes with a scanning laser beam. Invest Ophthalmol Vis Sci, no. 48, pp. 1782-92, 2007
    BibTeX
    @article{Framme,
       author = {Framme, C. and Alt, C. and Schnell, S. and Sherwood, M. and Brinkmann, R. and Lin, C. P.},
       title = {Selective targeting of the retinal pigment epithelium in rabbit eyes with a scanning laser beam},
       journal = {Invest Ophthalmol Vis Sci},
       volume = {48},
       number = {4},
       pages = {1782-92},
       note = {0146-0404 (Print)
    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't},
       abstract = {PURPOSE: Selective targeting of the retinal pigment epithelium (RPE) with repetitive laser pulses that minimize thermal damage to the adjacent photoreceptors is a promising new therapeutic modality for RPE-related retinal diseases. The selectivity of an alternative, more versatile scanning approach was examined in vivo by using a broad range of scanning parameters. METHODS: Acousto-optic deflectors repeatedly scanned the focus of a continuous wave (cw)-laser across the retina of Dutch belted rabbits, producing microsecond irradiation at each RPE cell. Two irradiation patterns forming separated lines (SEP) or interlaced lines (INT), different dwell times (2.5-75 micros), and repetition numbers (10 and 100 scans with 100-Hz repetition rate) were tested. Thresholds were evaluated by fundus imaging and angiography. Histology was performed for selected parameters. RESULTS: Selective RPE cell damage was obtained with moderate laser power. The angiographic threshold power decreased with pulse duration, number of exposures, and applying the INT pattern. Ophthalmoscopic thresholds, indicating onset of thermal coagulation, were higher than twice the angiographic threshold for most tested parameters. Histology confirmed selective RPE cell damage for SEP irradiation with 7.5 and 15 micros; slower scan speeds or closed lines caused photoreceptor damage. CONCLUSIONS: A cw-laser scanner can be set up as a highly compact and versatile device. Selective RPE damage is feasible with dwell times up to 15 micros. Greatest selectivity is achieved with short exposure times and separated scan lines. Interlaced lines and long exposure times facilitate heat conduction into photoreceptors. A scanner is an attractive alternative for pulsed selective targeting, because both selective targeting and thermal photocoagulation can be realized.},
       keywords = {Animals
    Eye Injuries/diagnosis
    Fluorescein Angiography
    Laser Coagulation/adverse effects/instrumentation/*methods
    Ophthalmoscopy
    Photoreceptors, Vertebrate/pathology
    Pigment Epithelium of Eye/injuries/pathology/*surgery
    Rabbits
    Retina/injuries/pathology},
       year = {2007}
    }

2006

  • Klatt, C. and Elsner, H. and Porksen, E. and Brinkmann, R. and Bunse, A. and Birngruber, R. and Roider, J.: Selektive Retina-Therapie bei Retinopathia centralis serosa mit Pigmentepithelabhebung. Ophthalmologe, no. 103, pp. 850-855, Aug, 2006
    BibTeX
    @article{Klatt,
       author = {Klatt, C. and Elsner, H. and Porksen, E. and Brinkmann, R. and Bunse, A. and Birngruber, R. and Roider, J.},
       title = {Selektive Retina-Therapie bei Retinopathia centralis serosa mit Pigmentepithelabhebung},
       journal = {Ophthalmologe},
       volume = {103},
       number = {10},
       pages = {850-855},
       note = {0941-293X (Print)
    Clinical Trial
    English Abstract
    Journal Article},
       month = {Aug},
       abstract = {Selective Retina Therapy (SRT) is a new laser treatment that selectively targets the retinal pigmen epithelium (RPE). In this study, we treated 39 patients presenting with nonischemic, focal and focal-diffuse diabetic maculopathy with SRT. In the main. the results indicate that SRT had stabilizing effects on visual acuity, angiographic leakage, lipid exudation, and foveal retinal thickness. SRT is safe and is especially useful for treating pathologies that are located close to the fovea, which cannot be treated with conventional argon laser photocoagulation.},
       keywords = {Aged
    Diabetic Retinopathy/*surgery
    Female
    Humans
    Laser Surgery/*methods
    Lasers/*therapeutic use
    Macular Degeneration/*surgery
    Male
    Ophthalmologic Surgical Procedures/*methods
    Preoperative Care/methods
    Treatment Outcome},
       year = {2006}
    }