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

  • Johann RoiderEmail author
  • Shiao Hui Melissa Liew
  • Carsten Klatt
  • Hanno Elsner
  • Erk Poerksen
  • Jost Hillenkamp
  • Ralf Brinkmann
  • Reginald Birngruber
Retinal Disorders

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 ≥10 letters, while 16% of eyes lost more than 5 letters. There was no severe loss of vision (≥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).

Keywords

Diabetic macular edema Diabetes Laser Selective retina therapy SRT 

Notes

Acknowledgement

The authors wish to thank A.M. Peter Hamilton, John Marshall, Dirk Theisen-Kunde, Georg Schüle, Arnd Bunse, Horst Laqua, Bernhard Nölle, Badrul Hussain, and John Shilling for helpful discussions and Ron Lohrding for expert statistical advice.

References

  1. 1.
    Aiello LP, Gardner TW, King GL, Blankenship G, Cavallerano JD, Ferris FL III, Klein R (1998) Diabetic retinopathy. Diabetes Care 21:143–156PubMedGoogle Scholar
  2. 2.
    Ferris FL III, Patz A (1984) Macular edema. A complication of diabetic retinopathy. Surv Ophthalmol 28(Suppl):452–461CrossRefPubMedGoogle Scholar
  3. 3.
    Klein R, Klein BE, Moss SE, Davis MD, DeMets DL (1984) The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema. Ophthalmology 91:1464–1474PubMedGoogle Scholar
  4. 4.
    Klein R, Klein BE, Moss SE (1984) Visual impairment in diabetes. Ophthalmology 91:1–9PubMedGoogle Scholar
  5. 5.
    Resnikoff S, Pascolini D, Etya’ale D, Kocur I, Pararajasegaram R, Pokharel GP, Mariotti SP (2004) Global data on visual impairment in the year 2002. Bull World Health Organ 82:844–851PubMedGoogle Scholar
  6. 6.
    Early Treatment Diabetic Retinopathy Study research group (1985) Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol 103:1796–1806Google Scholar
  7. 7.
    Diabetic Retinopathy Clinical Research Network (2008) A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology 115:1447–1449CrossRefGoogle Scholar
  8. 8.
    Birngruber R, Gabel VP, Hillenkamp F (1983) Experimental studies of laser thermal retinal injury. Health Phys 44:519–531CrossRefPubMedGoogle Scholar
  9. 9.
    Roider J, Hillenkamp F, Flotte T, Birngruber R (1993) Microphotocoagulation: selective effects of repetitive short laser pulses. Proc Natl Acad Sci USA 90:8643–8647CrossRefPubMedGoogle Scholar
  10. 10.
    Pearson AR, Tanner V, Keightley SJ, Casswell AG (1998) What effect does laser photocoagulation have on driving visual fields in diabetics? Eye 12:64–68PubMedGoogle Scholar
  11. 11.
    Ulbig MR, Arden GB, Hamilton AM (1994) Color contrast sensitivity and pattern electroretinographic findings after diode and argon laser photocoagulation in diabetic retinopathy. Am J Ophthalmol 117:583–588PubMedGoogle Scholar
  12. 12.
    Whitelocke RA, Kearns M, Blach RK, Hamilton AM (1979) The diabetic maculopathies. Trans Ophthalmol Soc UK 99:314–320PubMedGoogle Scholar
  13. 13.
    Bresnick GH (1983) Diabetic maculopathy. A critical review highlighting diffuse macular edema. Ophthalmology 90:1301–1317PubMedGoogle Scholar
  14. 14.
    Ogata N, Tombran-Tink J, Jo N, Mrazek D, Matsumura M (2001) Upregulation of pigment epithelium-derived factor after laser photocoagulation. Am J Ophthalmol 132:427–429CrossRefPubMedGoogle Scholar
  15. 15.
    Stefansson E (2001) The therapeutic effects of retinal laser treatment and vitrectomy. A theory based on oxygen and vascular physiology. Acta Ophthalmol Scand 79:435–440CrossRefPubMedGoogle Scholar
  16. 16.
    Roider J, Michaud N, Flotte T, Birngruber R (1993) Histology of retinal lesions after continuous irradiation and selective micro-coagulation of the retinal pigment epithelium. Ophthalmologe 90:274–278PubMedGoogle Scholar
  17. 17.
    Brinkmann R, Roider J, Birngruber R (2006) Selective retina therapy (SRT): a review on methods, techniques, preclinical and first clinical results. Bull Soc Belge Ophtalmol 302:51–69PubMedGoogle Scholar
  18. 18.
    Brinkmann R, Huttmann G, Rogener J, Roider J, Birngruber R, Lin CP (2000) Origin of retinal pigment epithelium cell damage by pulsed laser irradiance in the nanosecond to microsecond time regimen. Lasers Surg Med 27:451–464CrossRefPubMedGoogle Scholar
  19. 19.
    Schuele G, Rumohr M, Huettmann G, Brinkmann R (2005) RPE damage thresholds and mechanisms for laser exposure in the microsecond-to-millisecond time regimen. Invest Ophthalmol Vis Sci 46:714–719CrossRefPubMedGoogle Scholar
  20. 20.
    Neumann J, Brinkmann R (2008) Self-limited growth of laser-induced vapor bubbles around single microabsorbers. Applied Physics Letters 93:033901Google Scholar
  21. 21.
    Roider J, Brinkmann R, Wirbelauer C, Laqua H, Birngruber R (1999) Retinal sparing by selective retinal pigment epithelial photocoagulation. Arch Ophthalmol 117:1028–1034PubMedGoogle Scholar
  22. 22.
    Schuele G, Elsner H, Framme C, Roider J, Birngruber R, Brinkmann R (2005) Optoacoustic real-time dosimetry for selective retina treatment. J Biomed Opt 10:064022CrossRefPubMedGoogle Scholar
  23. 23.
    The Diabetes Control and Complications Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977–986CrossRefGoogle Scholar
  24. 24.
    UK Prospective Diabetes Study (UKPDS) Group (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352:837–853CrossRefGoogle Scholar
  25. 25.
    Chew EY, Klein ML, Ferris FL III, Remaley NA, Murphy RP, Chantry K, Hoogwerf BJ, Miller D (1996) Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. Early Treatment Diabetic Retinopathy Study (ETDRS) Report 22. Arch Ophthalmol 114:1079–1084PubMedGoogle Scholar
  26. 26.
    Lund-Andersen H (2002) Mechanisms for monitoring changes in retinal status following therapeutic intervention in diabetic retinopathy. Surv Ophthalmol 47(Suppl 2):S270–S277CrossRefPubMedGoogle Scholar
  27. 27.
    Gardner TW, Antonetti DA, Barber AJ, LaNoue KF, Levison SW (2002) Diabetic retinopathy: more than meets the eye. Surv Ophthalmol 47(Suppl 2):S253–S262CrossRefPubMedGoogle Scholar
  28. 28.
    Gandorfer A, Messmer EM, Ulbig MW, Kampik A (2000) Resolution of diabetic macular edema after surgical removal of the posterior hyaloid and the inner limiting membrane. Retina 20:126–133CrossRefPubMedGoogle Scholar
  29. 29.
    Tachi N, Ogino N (1996) Vitrectomy for diffuse macular edema in cases of diabetic retinopathy. Am J Ophthalmol 122:258–260PubMedGoogle Scholar
  30. 30.
    Friberg TR, Venkatesh S (1995) Alteration of pulse configuration affects the pain response during diode laser photocoagulation. Lasers Surg Med 16:380–383CrossRefPubMedGoogle Scholar
  31. 31.
    Friberg TR (2001) Infrared micropulsed laser treatment for diabetic macular edema—subthreshold versus threshold lesions. Semin Ophthalmol 16:19–24CrossRefPubMedGoogle Scholar
  32. 32.
    Lewis H, Schachat AP, Haimann MH, Haller JA, Quinlan P, von Fricken MA, Fine SL, Murphy RP (1990) Choroidal neovascularization after laser photocoagulation for diabetic macular edema. Ophthalmology 97:503–510PubMedGoogle Scholar
  33. 33.
    Guyer DR, D’Amico DJ, Smith CW (1992) Subretinal fibrosis after laser photocoagulation for diabetic macular edema. Am J Ophthalmol 113:652–656PubMedGoogle Scholar
  34. 34.
    Del Priore LV, Glaser BM, Quigley HA, Green WR (1989) Response of pig retinal pigment epithelium to laser photocoagulation in organ culture. Arch Ophthalmol 107:119–122PubMedGoogle Scholar
  35. 35.
    Roider J, Michaud NA, Flotte TJ, Birngruber R (1992) Response of the retinal pigment epithelium to selective photocoagulation. Arch Ophthalmol 110:1786–1792PubMedGoogle Scholar
  36. 36.
    Marshall J (1981) Interactions between sensory cells, glial cells and the retinal pigment epithelium and their response to photocoagulation. Dev Ophthalmol 2:308–317PubMedGoogle Scholar
  37. 37.
    Berger JW (1997) Thermal modelling of micropulsed diode laser retinal photocoagulation. Lasers Surg Med 20:409–415CrossRefPubMedGoogle Scholar
  38. 38.
    Friberg TR, Karatza EC (1997) The treatment of macular disease using a micropulsed and continuous wave 810-nm diode laser. Ophthalmology 104:2030–2038PubMedGoogle Scholar
  39. 39.
    Laursen ML, Moeller F, Sander B, Sjoelie AK (2004) Subthreshold micropulse diode laser treatment in diabetic macular oedema. Br J Ophthalmol 88:1173–1179CrossRefPubMedGoogle Scholar
  40. 40.
    Luttrull JK, Musch DC, Mainster MA (2005) Subthreshold diode micropulse photocoagulation for the treatment of clinically significant diabetic macular oedema. Br J Ophthalmol 89:74–80CrossRefPubMedGoogle Scholar
  41. 41.
    Moorman CM, Hamilton AM (1999) Clinical applications of the MicroPulse diode laser. Eye 13(Pt 2):145–150PubMedGoogle Scholar
  42. 42.
    Stanga PE, Reck AC, Hamilton AM (1999) Micropulse laser in the treatment of diabetic macular edema. Semin Ophthalmol 14:210–213CrossRefPubMedGoogle Scholar
  43. 43.
    Roider J, Lindemann C, el-Hifnawi e, Laqua H, Birngruber R (1998) Therapeutic range of repetitive nanosecond laser exposures in selective RPE photocoagulation. Graefes Arch Clin Exp Ophthalmol 236:213–219CrossRefPubMedGoogle Scholar
  44. 44.
    Puliafito CA, Deutsch TF, Boll J, To K (1987) Semiconductor laser endophotocoagulation of the retina. Arch Ophthalmol 105:424–427PubMedGoogle Scholar
  45. 45.
    Massin P, Vicaut E, Haouchine B, Erginay A, Paques M, Gaudric A (2001) Reproducibility of retinal mapping using optical coherence tomography. Arch Ophthalmol 119:1135–1142PubMedGoogle Scholar
  46. 46.
    Massin P, Erginay A, Haouchine B, Mehidi AB, Paques M, Gaudric A (2002) Retinal thickness in healthy and diabetic subjects measured using optical coherence tomography mapping software. Eur J Ophthalmol 12:102–108PubMedGoogle Scholar
  47. 47.
    Browning DJ, Glassman AR, Aiello LP, Bressler NM, Bressler SB, Danis RP, Davis MD, Ferris FL, Huang SS, Kaiser PK, Kollman C, Sadda S, Scott IU, Qin H (2008) Optical coherence tomography measurements and analysis methods in optical coherence tomography studies of diabetic macular edema. Ophthalmology 115:1366–1371CrossRefPubMedGoogle Scholar
  48. 48.
    Estabrook EJ, Madhusudhana KC, Hannan SR, Newsom RS (2007) Can optical coherence tomography predict the outcome of laser photocoagulation for diabetic macular edema? Ophthalmic Surg Lasers Imaging 38:478–483PubMedGoogle Scholar
  49. 49.
    Olk RJ (1986) Modified grid argon (blue-green) laser photocoagulation for diffuse diabetic macular edema. Ophthalmology 93:938–950PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Johann Roider
    • 1
    Email author
  • Shiao Hui Melissa Liew
    • 3
  • Carsten Klatt
    • 1
  • Hanno Elsner
    • 1
    • 2
  • Erk Poerksen
    • 1
    • 2
  • Jost Hillenkamp
    • 1
  • Ralf Brinkmann
    • 4
  • Reginald Birngruber
    • 4
  1. 1.Department of OphthalmologyUniversity Medical Center Schleswig-Holstein, Campus KielKielGermany
  2. 2.Department of OphthalmologyUniversity Medical Center Schleswig-Holstein, Campus LübeckLübeckGermany
  3. 3.St. Thomas’ HospitalLondonUK
  4. 4.Medical Laser CenterLübeckGermany

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