Nanosecond pulse lasers for retinal applications†
Corresponding Author
John P.M. Wood DPhil
South Australian Institute of Ophthalmology, Ophthalmic Research Laboratories, Level 2 Hanson Institute, IMVS, Adelaide, South Australia, Australia
University of Adelaide, School of Medical Sciences, Adelaide, South Australia, Australia
Frome Road, Adelaide, South Australia SA 5000, Australia.Search for more papers by this authorMalcolm Plunkett
Ellex R&D Pty Ltd, Adelaide, South Australia, Australia
Search for more papers by this authorVictor Previn BEng
Ellex R&D Pty Ltd, Adelaide, South Australia, Australia
Search for more papers by this authorGlyn Chidlow DPhil
South Australian Institute of Ophthalmology, Ophthalmic Research Laboratories, Level 2 Hanson Institute, IMVS, Adelaide, South Australia, Australia
University of Adelaide, School of Medical Sciences, Adelaide, South Australia, Australia
Search for more papers by this authorRobert J. Casson DPhil, FRANZCO
South Australian Institute of Ophthalmology, Ophthalmic Research Laboratories, Level 2 Hanson Institute, IMVS, Adelaide, South Australia, Australia
University of Adelaide, School of Medical Sciences, Adelaide, South Australia, Australia
Search for more papers by this authorCorresponding Author
John P.M. Wood DPhil
South Australian Institute of Ophthalmology, Ophthalmic Research Laboratories, Level 2 Hanson Institute, IMVS, Adelaide, South Australia, Australia
University of Adelaide, School of Medical Sciences, Adelaide, South Australia, Australia
Frome Road, Adelaide, South Australia SA 5000, Australia.Search for more papers by this authorMalcolm Plunkett
Ellex R&D Pty Ltd, Adelaide, South Australia, Australia
Search for more papers by this authorVictor Previn BEng
Ellex R&D Pty Ltd, Adelaide, South Australia, Australia
Search for more papers by this authorGlyn Chidlow DPhil
South Australian Institute of Ophthalmology, Ophthalmic Research Laboratories, Level 2 Hanson Institute, IMVS, Adelaide, South Australia, Australia
University of Adelaide, School of Medical Sciences, Adelaide, South Australia, Australia
Search for more papers by this authorRobert J. Casson DPhil, FRANZCO
South Australian Institute of Ophthalmology, Ophthalmic Research Laboratories, Level 2 Hanson Institute, IMVS, Adelaide, South Australia, Australia
University of Adelaide, School of Medical Sciences, Adelaide, South Australia, Australia
Search for more papers by this authorCommercial relationships: John P. M. Wood, Glyn Chidlow, and Robert J. Casson—none; Malcolm Plunkett and Victor Previn—Ellex R&D Pty Ltd.
Abstract
Background and Objectives
Thermal lasers are routinely used to treat certain retinal disorders although they cause collateral damage to photoreceptors. The current study evaluated a confined, non-conductive thermal, 3-nanosecond pulse laser in order to determine how to produce the greatest therapeutic range without causing collateral damage. Data were compared with that obtained from a standard thermal laser.
Materials and Methods
Porcine ocular explants were used; apposed neuroretina was also in place for actual laser treatment. After treatment, the retina was removed and a calcein-AM assay was used to assess retinal pigmented epithelium (RPE) cell viability in the explants. Histological methods were also employed to examine lased transverse explant sections. Three nanoseconds pulse lasers with either speckle- or gaussian-beam profile were employed in the study. Comparisons were made with a 100 milliseconds continuous wave (CW) 532 nm laser. The therapeutic energy range ratio was defined as the minimum visible effect threshold (VET) versus the minimum detectable RPE kill threshold.
Results
The 3-nanosecond lasers produced markedly lower minimum RPE kill threshold levels than the CW laser (e.g., 36 mJ/cm2 for speckle-beam and 89 mJ/cm2 for gaussian-beam profile nanosecond lasers vs. 7,958 mJ/cm2 for CW laser). VET values were also correspondingly lower for the nanosecond lasers (130 mJ/cm2 for 3 nanoseconds speckle-beam and 219 mJ/cm2 for gaussian-beam profile vs. 1,0346 mJ/cm2 for CW laser). Thus, the therapeutic range ratios obtained with the nanosecond lasers were much more favorable than that obtained by the CW laser: 3.6:1 for the speckle-beam and 2.5:1 for the gaussian-beam profile 3-nanosecond lasers versus 1.3:1 for the CW laser.
Conclusions
Nanosecond lasers, particularly with a speckle-beam profile, provide a much wider therapeutic range of energies over which RPE treatment can be performed, without damage to the apposed retina, as compared with conventional CW lasers. These results may have important implications for the treatment of retinal disease. Lasers Surg. Med. 43:499–510, 2011. © 2011 Wiley-Liss, Inc.
REFERENCES
- 1 Dorin G. Evolution of retinal laser therapy: Minimum intensity photocoagulation (MIP). Can the laser heal the retina without harming it? Semin Ophthalmol 2004; 19: 62–68.
- 2 Akduman L, Olk RJ. Laser photocoagulation of diabetic macular edema. Ophthalmic Surg Lasers 1997; 28: 387–408.
- 3 Group ETDRSR. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report number 1. Early Treatment Diabetic Retinopathy Study Research Group. Arch Ophthalmol 1985; 103: 1796–1806.
- 4 Group TETDRSR. Photocoagulation for diabetic macular edema: Early Treatment Diabetic Retinopathy Study Report no. 4. The Early Treatment Diabetic Retinopathy Study Research Group. Int Ophthalmol Clin 1987; 27: 265–272.
- 5 Graham CE, Binz N, Shen WY, Constable IJ, Rakoczy EP. Laser photocoagulation: Ocular research and therapy in diabetic retinopathy. Adv Exp Med Biol 2006; 572: 195–200.
- 6 Ben-Shlomo G, Belokopytov M, Rosner M, Dubinsky G, Belkin M, Epstein Y, Ofri R. Functional deficits resulting from laser-induced damage in the rat retina. Lasers Surg Med 2006; 38: 689–694.
- 7 Behar-Cohen F, Benezra D, Soubrane G, Jonet L, Jeanny JC. Krypton laser photocoagulation induces retinal vascular remodeling rather than choroidal neovascularization. Exp Eye Res 2006; 83: 263–275.
- 8 Tackenberg MA, Tucker BA, Swift JS, Jiang C, Redenti S, Greenberg KP, Flannery JG, Reichenbach A, Young MJ. Muller cell activation, proliferation and migration following laser injury. Mol Vis 2009; 15: 1886–1896.
- 9 Paulus YM, Jain A, Gariano RF, Stanzel BV, Marmor M, Blumenkranz MS, Palanker D. Healing of retinal photocoagulation lesions. Invest Ophthalmol Vis Sci 2008; 49: 5540–5545.
- 10 Jennings PE, MacEwen CJ, Fallon TJ, Scott N, Haining WM, Belch JJ. Oxidative effects of laser photocoagulation. Free Radic Biol Med 1991; 11: 327–330.
- 11 Sanchez MC, Luna JD, Barcelona PF, Gramajo AL, Juarez PC, Riera CM, Chiabrando GA. Effect of retinal laser photocoagulation on the activity of metalloproteinases and the alpha(2)-macroglobulin proteolytic state in the vitreous of eyes with proliferative diabetic retinopathy. Exp Eye Res 2007; 85: 644–650.
- 12 Spranger J, Osterhoff M, Reimann M, Mohlig M, Ristow M, Francis MK, Cristofalo V, Hammes HP, Smith G, Boulton M, Pfeiffer AF. Loss of the antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye disease. Diabetes 2001; 50: 2641–2645.
- 13 Spranger J, Hammes HP, Preissner KT, Schatz H, Pfeiffer AF. Release of the angiogenesis inhibitor angiostatin in patients with proliferative diabetic retinopathy: Association with retinal photocoagulation. Diabetologia 2000; 43: 1404–1407.
- 14 Yoshimura N, Matsumoto M, Shimizu H, Mandai M, Hata Y, Ishibashi T. Photocoagulated human retinal pigment epithelial cells produce an inhibitor of vascular endothelial cell proliferation. Invest Ophthalmol Vis Sci 1995; 36: 1686–1691.
- 15 Matsumoto M, Yoshimura N, Honda Y. Increased production of transforming growth factor-beta 2 from cultured human retinal pigment epithelial cells by photocoagulation. Invest Ophthalmol Vis Sci 1994; 35: 4245–4252.
- 16 Ahmadi MA, Lim JI. Update on laser treatment of diabetic macular edema. Int Ophthalmol Clin 2009; 49: 87–94.
- 17 Starita C, Hussain AA, Marshall J. Decreasing hydraulic conductivity of Bruch's membrane: Relevance to photoreceptor survival and lipofuscinoses. Am J Med Genet 1995; 57: 235–237.
- 18 Starita C, Hussain AA, Pagliarini S, Marshall J. Hydrodynamics of ageing Bruch's membrane: Implications for macular disease. Exp Eye Res 1996; 62: 565–572.
- 19 Guo L, Hussain AA, Limb GA, Marshall J. Age-dependent variation in metalloproteinase activity of isolated human Bruch's membrane and choroid. Invest Ophthalmol Vis Sci 1999; 40: 2676–2682.
- 20 Antcliff RJ, Hussain AA, Marshall J. Hydraulic conductivity of fixed retinal tissue after sequential excimer laser ablation: Barriers limiting fluid distribution and implications for cystoid macular edema. Arch Ophthalmol 2001; 119: 539–544.
- 21 Marshall J, Hamilton AM, Bird AC. Histopathology of ruby and argon laser lesions in monkey and human retina. A comparative study. Br J Ophthalmol 1975; 59: 610–630.
- 22 Bowbyes J, Hamilton AM, Kohner EM, Marshall J. The effect of the argon laser on the retina. J Physiol 1973; 231: 70P.
- 23 Bowbyes JA, Hamilton AM, Bird AC, Blach RK, Marshall J, Kohner EM. The argon laser-the effect on retinal tissues its clinical applications. Trans Ophthalmol Soc UK 1973; 93: 439–453.
- 24 Flaxel C, Bradle J, Acott T, Samples JR. Retinal pigment epithelium produces matrix metalloproteinases after laser treatment. Retina 2007; 27: 629–634.
- 25 Rosner M, Solberg Y, Turetz J, Belkin M. Neuroprotective therapy for argon-laser induced retinal injury. Exp Eye Res 1997; 65: 485–495.
- 26 Ansell PL, Marshall J. Laser induced phagocytosis in the pigment epithelium of the Hunter dystrophic rat. Br J Ophthalmol 1976; 60: 819–828.
- 27 Hussain AA, Starita C, Hodgetts A, Marshall J. Macromolecular diffusion characteristics of ageing human Bruch's membrane: Implications for age-related macular degeneration (AMD). Exp Eye Res 90: 703–710.
- 28 Ahir A, Guo L, Hussain AA, Marshall J. Expression of metalloproteinases from human retinal pigment epithelial cells and their effects on the hydraulic conductivity of Bruch's membrane. Invest Ophthalmol Vis Sci 2002; 43: 458–465.
- 29 Jain A, Blumenkranz MS, Paulus Y, Wiltberger MW, Andersen DE, Huie P, Palanker D. Effect of pulse duration on size and character of the lesion in retinal photocoagulation. Arch Ophthalmol 2008; 126: 78–85.
- 30 Nagpal M, Marlecha S, Nagpal K. Comparison of laser photocoagulation for diabetic retinopathy using 532-nm standard laser versus multispot pattern scan laser. Retina 2010; 30: 452–458.
- 31 Anderson RR, Parrish JA. Selective photothermolysis: Precise microsurgery by selective absorption of pulsed radiation. Science 1983; 220: 524–527.
- 32 Roider J, Michaud NA, Flotte TJ, Birngruber R. Response of the retinal pigment epithelium to selective photocoagulation. Arch Ophthalmol 1992; 110: 1786–1792.
- 33 Roider J, Hillenkamp F, Flotte T, Birngruber R. Microphotocoagulation: Selective effects of repetitive short laser pulses. Proc Natl Acad Sci USA 1993; 90: 8643–8647.
- 34 Roider J, Lindemann C, El-Hifnawi ES, Laqua H, Birngruber R. Therapeutic range of repetitive nanosecond laser exposures in selective RPE photocoagulation. Graefes Arch Clin Exp Ophthalmol 1998; 236: 213–219.
- 35
Roider J,
El Hifnawi ES,
Birngruber R.
Bubble formation as primary interaction mechanism in retinal laser exposure with 200-ns laser pulses.
Lasers Surg Med
1998;
22:
240–248.
10.1002/(SICI)1096-9101(1998)22:4<240::AID-LSM9>3.0.CO;2-P CAS PubMed Web of Science® Google Scholar
- 36 Roider J, Brinkmann R, Wirbelauer C, Laqua H, Birngruber R. Retinal sparing by selective retinal pigment epithelial photocoagulation. Arch Ophthalmol 1999; 117: 1028–1034.
- 37 Brinkmann R, Roider J, Birngruber R. Selective retina therapy (SRT): A review on methods, techniques, preclinical and first clinical results. Bull Soc Belge Ophtalmol 2006; 302: 51–69.
- 38 Hansen WP, Fine S. Melanin granule models for pulsed laser induced retinal injury. Appl Opt 1968; 7: 155–159.
- 39 Kelly MW, Lin CP. Microcavitation and cell injury in RPE cells following short-pulsed laser irradiation. SPIE Proc 1997; 2975: 174–179.
- 40 Rockwell BA, Hammer DX, Hopkins RA, Payne DJ, Toth CA, Roach WP, Druessel JJ, Kennedy PK, Amnotte RE, Eilert B, Phillips S, Noojin GD, Stolarski DJ, Cain C. Ultrashort laser pulse bioeffects and safety. J Laser Appl 1999; 11: 42–44.
- 41
King SA,
Johnson MA,
Wilcox M,
Snellman EA.
Effects of nanosecond pulsed laser light on porcine retinal pigment epithelium.
Bios
2006;
77:
13–19.
10.1893/0005-3155(2006)77[13:RAEONP]2.0.CO;2 Google Scholar
- 42 Thompson CR, Gerstman BS, Jacques SL, Rogers ME. Melanin granule model for laser-induced thermal damage in the retina. Bull Math Biol 1996; 58: 513–553.
- 43 Schuele G, Rumohr M, Huettmann G, Brinkmann R. RPE damage thresholds and mechanisms for laser exposure in the microsecond-to-millisecond time regimen. Invest Ophthalmol Vis Sci 2005; 46: 714–719.
- 44 Gerstman BS, Thompson CR, Jacques SL, Rogers ME. Laser induced bubble formation in the retina. Lasers Surg Med 1996; 18: 10–21.
- 45 Brinkmann R, Huttmann G, Rogener J, Roider J, Birngruber R, Lin CP. Origin of retinal pigment epithelium cell damage by pulsed laser irradiance in the nanosecond to microsecond time regimen. Lasers Surg Med 2000; 27: 451–464.
- 46 Framme C, Schuele G, Kobuch K, Flucke B, Birngruber R, Brinkmann R. Investigation of selective retina treatment (SRT) by means of 8 ns laser pulses in a rabbit model. Lasers Surg Med 2008; 40: 20–27.
- 47 Marshall J. Thermal and mechanical mechanisms in laser damage to the retina. Invest Ophthalmol 1970; 9: 97–115.
- 48 Wilson AS, Hobbs BG, Shen WY, Speed TP, Schmidt U, Begley CG, Rakoczy PE. Argon laser photocoagulation-induced modification of gene expression in the retina. Invest Ophthalmol Vis Sci 2003; 44: 1426–1434.
- 49 Prahs P, Walter A, Regler R, Theisen-Kunde D, Birngruber R, Brinkmann R, Framme C. Selective retina therapy (SRT) in patients with geographic atrophy due to age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 2010; 248: 651–658.
- 50 Casson RJ, Raymond G, Newland HS, Gilhotra J, Gray T, Runciman J, Jaross N, Plunkett M. A pilot, prospective, randomised clinical trial of a new nanopulse retinal laser versus conventional photocoagulation for the treatment of diabetic macular edema. Invest Ophthalmol Vis Sci 2010; 51: 5843.
- 51 Zinn KM, Benjamin-Henkind JV. Anatomy of the human retinal pigment epithelium. In: KM Zinn, MF Marmor, editors. The retinal pigment epithelium. Cambridge, Mattachusetts: Harvard University Press; 1979. pp 3–31.
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