Research and Future Directions

  • Fernanda Hidemi Sakamoto
  • Richard Rox Anderson


In retrospect, it is interesting to realize the way technology and new developments are sometimes so obvious and simple. Looking back over the history of laser surgery, laser tissue ablation (removal) was developed over 40 years. It became popular in the 1980s and 1990s especially because of skin resurfacing, but faded at the end of 1990s due to side effects, and almost vanished from most clinical practices. In 2004, with the introduction of new fractionated methods of skin resurfacing, the same old lasers developed decades ago became popular again, by delivering their beams in microscopic patterns. The technology to make arrays of microscopic laser beams has been available for 40 years, but not used this way in dermatology. The limiting factor is not the technology, but the way we look at it.


Optical Coherence Tomography Confocal Laser Scanning Microscopy Photodynamic Therapy Actinic Keratosis Human Amniotic Membrane 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Acknowledgements The authors would like to thank Prof. Irene Kochevar, PhD, Min Yao, MD, PhD (Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA) and Dr. Sandy Tsao, MD (Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA), for providing the photograph and discussion about photochemical tissue bonding; Prof. Michael Hamblin, PhD and Aaron C-H Chen (Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA) for discussion about low-level light therapy; Prof. B. Hyle Park, PhD (Department of Bioengineering, University of California Riverside, CA) and Prof. Johannes F. de Boer, PhD (Vrije University, Amsterdam, Netherlands) for providing the photograph about optical coherence tomography.


  1. 1.
    Manstein D, Herron GS, et al. Fractional photothermolysis: a new concept for cutaneous remodeling using microscopic patterns of thermal injury. Lasers Surg Med. 2004;34(5):426-438.PubMedCrossRefGoogle Scholar
  2. 2.
    Rahman Z, MacFalls H, et al. Fractional deep dermal ablation induces tissue tightening. Lasers Surg Med. 2009;41(2):78-86.PubMedCrossRefGoogle Scholar
  3. 3.
    Sukal SA, Chapas AM, et al. Eyelid tightening and improved eyelid aperture through nonablative fractional resurfacing. Dermatol Surg. 2008;34(11):1454-1458.PubMedCrossRefGoogle Scholar
  4. 4.
    Ruiz-Rodriguez R, Lopez L, et al. Enhanced efficacy of photodynamic therapy after fractional resurfacing: fractional photodynamic rejuvenation. J Drugs Dermatol. 2007;6(8):818-820.PubMedGoogle Scholar
  5. 5.
    Henry FP, Goyal NA, et al. Improving electrophysiologic and histologic outcomes by photochemically sealing amnion to the peripheral nerve repair site. Surgery. 2009;145(3):313-321.PubMedCrossRefGoogle Scholar
  6. 6.
    Mulroy L, Kim J, et al. Photochemical keratodesmos for repair of lamellar corneal incisions. Invest Ophthalmol Vis Sci. 2000;41(11):3335-3340.PubMedGoogle Scholar
  7. 7.
    Proano CE, Azar DT, et al. Photochemical keratodesmos as an adjunct to sutures for bonding penetrating keratoplasty corneal incisions. J Cataract Refract Surg. 2004;30(11):2420-2424.PubMedCrossRefGoogle Scholar
  8. 8.
    Proano CE, Mulroy L, et al. Photochemical keratodesmos for bonding corneal incisions. Invest Ophthalmol Vis Sci. 2004;45(7):2177-2181.PubMedCrossRefGoogle Scholar
  9. 9.
    Chan BP, Kochevar IE, et al. Enhancement of porcine skin graft adherence using a light-activated process. J Surg Res. 2002;108(1):77-84.PubMedCrossRefGoogle Scholar
  10. 10.
    Kamegaya Y, Farinelli WA, et al. Evaluation of photochemical tissue bonding for closure of skin incisions and excisions. Lasers Surg Med. 2005;37(4):264-270.PubMedCrossRefGoogle Scholar
  11. 11.
    Solban N, Rizvi I, et al. Targeted photodynamic therapy. Lasers Surg Med. 2006;38(5):522-531.PubMedCrossRefGoogle Scholar
  12. 12.
    Lange N. Pharmaceutical and biological considerations in 5-aminolevulinic acid in PDT. In: Hamblin MR, Mroz P, eds. Advances in Photodynamic Therapy. Basic, Translational, and Clinical. 1st ed. Norwood: Artech House; 2008:59-91.Google Scholar
  13. 13.
    Chen B, Pogue BW, et al. Liposomal delivery of photosensitizing agents. Expert Opin Drug Deliv. 2005;2(3):477-487.PubMedCrossRefGoogle Scholar
  14. 14.
    Konan YN, Gurny R, et al. State of the art in the delivery of photosensitizers for photodynamic therapy. J Photochem Photobiol B. 2002;66(2):89-106.PubMedCrossRefGoogle Scholar
  15. 15.
    Malik Z, Kostenich G, et al. Topical application of 5-aminolevulinic acid, DMSO and EDTA: protoporphyrin IX accumulation in skin and tumours of mice. J Photochem Photobiol B. 1995;28(3):213-218.PubMedCrossRefGoogle Scholar
  16. 16.
    Steluti R, De Rosa FS, et al. Topical glycerol monooleate/propylene glycol formulations enhance 5-aminolevulinic acid in vitro skin delivery and in vivo protoporphyrin IX accumulation in hairless mouse skin. Eur J Pharm Biopharm. 2005;60(3):439-444.PubMedCrossRefGoogle Scholar
  17. 17.
    Rhodes LE, Tsoukas MM, et al. Iontophoretic delivery of ALA provides a quantitative model for ALA pharmacokinetics and PpIX phototoxicity in human skin. J Invest Dermatol. 1997;108(1):87-91.PubMedCrossRefGoogle Scholar
  18. 18.
    van den Akker JT, Iani V, et al. Topical application of 5-aminolevulinic acid hexyl ester and 5-aminolevulinic acid to normal nude mouse skin: differences in protoporphyrin IX fluorescence kinetics and the role of the stratum corneum. Photochem Photobiol. 2000;72(5):681-689.PubMedCrossRefGoogle Scholar
  19. 19.
    Sakamoto FH, Doukas A, et al. Skin temperature can control ALA-Photodynamic therapy. American Society for Laser Medicine and Surgery, Twenty-Seventh Annual Meeting; 2007; Grapevine. Wiley-Liss, A Wiley Company.Google Scholar
  20. 20.
    Joe EK, Anderson RR, et al. Spatial confinement of 5-aminolevulinic acid-based photodynamic therapy by thermal and chemical inhibition. Fourth International Investigative Dermatology Meeting; 2003; Miami Beach.Google Scholar
  21. 21.
    Katz BE, Truong S, et al. Efficacy of microdermabrasion preceding ALA application in reducing the incubation time of ALA in laser PDT. J Drugs Dermatol. 2007;6(2):140-142.PubMedGoogle Scholar
  22. 22.
    Sitnik TM, Hampton JA, et al. Reduction of tumour oxygenation during and after photodynamic therapy in vivo: effects of fluence rate. Br J Cancer. 1998;77(9):1386-1394.PubMedCrossRefGoogle Scholar
  23. 23.
    Li G, Szewczuk MR, et al. Effect of mammalian cell differentiation on response to exogenous 5-aminolevulinic acid. Photochem Photobiol. 1999;69(2):231-235.PubMedCrossRefGoogle Scholar
  24. 24.
    Ortel B, Chen N, et al. Differentiation-specific increase in ALA-induced protoporphyrin IX accumulation in primary mouse keratinocytes. Br J Cancer. 1998;77(11):1744-1751.PubMedCrossRefGoogle Scholar
  25. 25.
    Ortel B, Sharlin D, et al. Differentiation enhances aminolevulinic acid-dependent photodynamic treatment of LNCaP prostate cancer cells. Br J Cancer. 2002;87(11):1321-1327.PubMedCrossRefGoogle Scholar
  26. 26.
    Sakamoto FH, Tannous Z, et al. Porphyrin distribution after topical aminolevulinic acid in a novel porcine model of sebaceous skin. Lasers Surg Med. 2009;41(2):154-160.PubMedCrossRefGoogle Scholar
  27. 27.
    Oseroff AR, Ohuoha D, et al. Antibody-targeted photolysis: selective photodestruction of human T-cell leukemia cells using monoclonal antibody-chlorin e6 conjugates. Proc Natl Acad Sci USA. 1986;83(22):8744-8748.PubMedCrossRefGoogle Scholar
  28. 28.
    Huang Y-Y, Chen A C-H, et al. Advances in low intensity laser and phototherapy. In: Tuchin VV, editor. Advanced Biophotonics. Taylor and Francis Books Inc, Boca Raton FL. 2010. ISBN 978-1-4398-0628-9.Google Scholar
  29. 29.
    Karu TI, Kolyakov SF. Exact action spectra for cellular responses relevant to phototherapy. Photomed Laser Surg. 2005;23(4):355-361.PubMedCrossRefGoogle Scholar
  30. 30.
    Passarella S, Casamassima E, et al. Increase of proton electrochemical potential and ATP synthesis in rat liver mitochondria irradiated in vitro by helium-neon laser. FEBS Lett. 1984;175(1):95-99.PubMedCrossRefGoogle Scholar
  31. 31.
    Passarella S, Ostuni A, et al. Increase in the ADP/ATP exchange in rat liver mitochondria irradiated in vitro by helium-neon laser. Biochem Biophys Res Commun. 1988;156(2):978-986.PubMedCrossRefGoogle Scholar
  32. 32.
    Gordon MW. The correlation between in vivo mitochondrial changes and tryptophan pyrrolase activity. Arch Biochem Biophys. 1960;91:75-82.PubMedCrossRefGoogle Scholar
  33. 33.
    Yu W, Naim JO, et al. Photomodulation of oxidative metabolism and electron chain enzymes in rat liver mitochondria. Photochem Photobiol. 1997;66(6):866-871.PubMedCrossRefGoogle Scholar
  34. 34.
    Plaetzer K, Kiesslich T, et al. Characterization of the cell death modes and the associated changes in cellular energy supply in response to AlPcS4-PDT. Photochem Photobiol Sci. 2002;1(3):172-177.PubMedCrossRefGoogle Scholar
  35. 35.
    Eichler M, Lavi R, et al. Flavins are source of visible-light-induced free radical formation in cells. Lasers Surg Med. 2005;37(4):314-319.PubMedCrossRefGoogle Scholar
  36. 36.
    Borutaite V, Budriunaite A, et al. Reversal of nitric oxide-, peroxynitrite- and S-nitrosothiol-induced inhibition of mitochondrial respiration or complex I activity by light and thiols. Biochim Biophys Acta. 2000;1459(2–3):405-412.PubMedGoogle Scholar
  37. 37.
    Rajadhyaksha M, Gonzalez S, et al. In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology. J Invest Dermatol. 1999;113(3):293-303.PubMedCrossRefGoogle Scholar
  38. 38.
    Rajadhyaksha M, Grossman M, et al. In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast. J Invest Dermatol. 1995;104(6):946-952.PubMedCrossRefGoogle Scholar
  39. 39.
    Langley RG, Rajadhyaksha M, et al. Confocal scanning laser microscopy of benign and malignant melanocytic skin lesions in vivo. J Am Acad Dermatol. 2001;45(3):365-376.PubMedCrossRefGoogle Scholar
  40. 40.
    Busam KJ, Charles C, et al. Morphologic features of melanocytes, pigmented keratinocytes, and melanophages by in vivo confocal scanning laser microscopy. Mod Pathol. 2001;14(9):862-868.PubMedCrossRefGoogle Scholar
  41. 41.
    Busam KJ, Hester K, et al. Detection of clinically amelanotic malignant melanoma and assessment of its margins by in vivo confocal scanning laser microscopy. Arch Dermatol. 2001;137(7):923-929.PubMedGoogle Scholar
  42. 42.
    Koehler MJ, Konig K, et al. In vivo assessment of human skin aging by multiphoton laser scanning tomography. Opt Lett. 2006;31(19):2879-2881.PubMedCrossRefGoogle Scholar
  43. 43.
    Konig K. Multiphoton microscopy in life sciences. J Microsc. 2000;200(2):83-104.PubMedCrossRefGoogle Scholar
  44. 44.
    Konig K, Riemann I. High-resolution multiphoton tomography of human skin with subcellular spatial resolution and picosecond time resolution. J Biomed Opt. 2003;8(3):432-439.PubMedCrossRefGoogle Scholar
  45. 45.
    de Boer JF, Milner TE, et al. Determination of the depth-resolved stokes parameters of light backscattered from turbid media by use of polarization-sensitive optical coherence tomography. Opt Lett. 1999;24(5):300-302.PubMedCrossRefGoogle Scholar
  46. 46.
    Park BH, Saxer C, et al. In vivo burn depth determination by high-speed fiber-based polarization sensitive optical coherence tomography. J Biomed Opt. 2001;6(4):474-479.PubMedCrossRefGoogle Scholar
  47. 47.
    Pierce MC, Sheridan RL, et al. Collagen denaturation can be quantified in burned human skin using polarization-sensitive optical coherence tomography. Burns. 2004;30(6):511-517.PubMedCrossRefGoogle Scholar
  48. 48.
    Pierce MC, Strasswimmer J, et al. Birefringence measurements in human skin using polarization-sensitive optical coherence tomography. J Biomed Opt. 2004;9(2):287-291.PubMedCrossRefGoogle Scholar
  49. 49.
    Pierce MC, Strasswimmer J, et al. Advances in optical coherence tomography imaging for dermatology. J Invest Dermatol. 2004;123(3):458-463.PubMedCrossRefGoogle Scholar
  50. 50.
    Tannous Z, Al-Arashi M, et al. Delineating melanoma using multimodal polarized light imaging. Lasers Surg Med. 2009;41(1):10-16.PubMedCrossRefGoogle Scholar
  51. 51.
    Yaroslavsky AN, Barbosa J, et al. Combining multispectral polarized light imaging and confocal microscopy for localization of nonmelanoma skin cancer. J Biomed Opt. 2005;10(1):14011.PubMedCrossRefGoogle Scholar
  52. 52.
    Yaroslavsky AN, Neel V, et al. Demarcation of nonmelanoma skin cancer margins in thick excisions using multispectral polarized light imaging. J Invest Dermatol. 2003;121(2):259-266.PubMedCrossRefGoogle Scholar
  53. 53.
    Jacques SL, Ramella-Roman JC, et al. Imaging skin pathology with polarized light. J Biomed Opt. 2002;7(3):329-340.PubMedCrossRefGoogle Scholar
  54. 54.
    Sterenborg NJ, Thomsen S, et al. In vivo fluorescence spectroscopy and imaging of human skin tumors. Dermatol Surg. 1995;21(9):821-822.PubMedGoogle Scholar

Copyright information

© Springer-Verlag London Limited 2011

Authors and Affiliations

  • Fernanda Hidemi Sakamoto
    • 2
  • Richard Rox Anderson
    • 1
  1. 1.Department of Dermatology, Harvard Medical SchoolMassachusetts General HospitalBostonUSA
  2. 2.Department of Dermatology, Wellman Center for Photomedicine, Harvard Medical SchoolMassachusetts General HospitalBostonUSA

Personalised recommendations