Elsevier

Survey of Ophthalmology

Volume 55, Issue 6, November–December 2010, Pages 516-530
Survey of Ophthalmology

Major Review
Micropulsed Diode Laser Therapy: Evolution and Clinical Applications

https://doi.org/10.1016/j.survophthal.2010.02.005Get rights and content

Abstract

Many clinical trials have demonstrated the clinical efficacy of laser photocoagulation in the treatment of retinal vascular diseases, including diabetic retinopathy. There is, however, collateral iatrogenic retinal damage and functional loss after conventional laser treatment. Such side effects may occur even when the treatment is appropriately performed because of morphological damage caused by the visible endpoint, typically a whitening burn. The development of the diode laser with micropulsed emission has allowed subthreshold therapy without a visible burn endpoint. This greatly reduces the risk of structural and functional retinal damage, while retaining the therapeutic efficacy of conventional laser treatment. Studies using subthreshold micropulse laser protocols have reported successful outcomes for diabetic macular edema, central serous chorioretinopathy, macular edema secondary to retinal vein occlusion, and primary open angle glaucoma. The report includes the rationale and basic principles underlying micropulse diode laser therapy, together with a review of its current clinical applications.

Section snippets

I. Introduction

Therapeutic retinal photocoagulation has been practiced for more than 50 years. Since the initial experiments carried out by Meyer-Schwickerath in the late 1940s, laser treatment has gradually become more refined, effective, and safe. With conventional continuous-wave laser therapy, energy is absorbed mostly by the retinal pigment epithelium (RPE). However, heat is also conducted to neighboring structures, including the neural retina and the choroid, which can result in collateral thermal

II. Laser Parameters

Laser light has three important characteristics: it is non-divergent (collimated or parallel), monochromatic, and coherent (in phase). Because laser light is highly directional, it can be focused into a small spot size with high irradiance (laser power per unit area, W/cm2).41, 51 Increasing the spot size spreads power over a larger area and decreases irradiance intensity. The minimal spot size into which a laser beam can be focused is proportional to its wavelength and the focal length of the

III. Laser–Tissue Interaction

When the laser energy is emitted in the visible and near infrared spectrum, a rise in the initial temperature occurs where ocular chromophores absorb the laser energy and convert it into heat. These chromophores consist mainly of the melanin in the RPE cells and choroidal melanocytes. After approximately 1 msec, heat spreads toward adjacent locations where there is no light absorption.46, 47, 48 As the heat wave spreads, it releases energy and the temperature of the wave gradually decreases

IV. Mechanism of Action of Laser

Although the mechanism of action of laser photocoagulation remains poorly understood and subject to numerous theories, full-thickness retinal damage may not be needed to obtain beneficial effects.35 A recent hypothesis suggests that the benefits of laser photocoagulation may be derived from the up-and-down regulation of factors mediated by the biological reaction of RPE cells. This is more likely to occur in RPE cells that have been only sub-lethally injured by a lower thermal elevation than at

V. Complications Associated with the Use of Conventional Lasers

Undoubtedly, laser photocoagulation is the first line of treatment for many chorioretinal disorders, validated by many clinical studies.16, 19 Conventional laser treatment with an ophthalmoscopically visible endpoint, however, causes iatrogenic anatomic and functional chorioretinal damage.

VI. Limiting Retinal Damage

Although conventional photocoagulation is practiced as a destructive procedure, chorioretinal damage can be minimized by modifying laser parameters and clinical endpoints. Mainster summarized the optical and thermodynamic principles that can be applied to minimize retinal damage.49 We now discuss these principles in detail.

VII. Micropulse Operating Mode and Terminology

Dorin has provided a summary of the micropulse operating mode and terminology.17, 18 In continuous wave mode, the laser energy is delivered as a single pulse, with a “width” typically in the range of 0.1–0.5 sec that constitutes the exposure duration. In micropulse mode, the laser energy is delivered with a train of repetitive short pulses (typically 100–300 μsec in duration each) within an “envelope” whose width is typically in the range of 0.1–0.5 sec, and this envelope duration constitutes

VIII. Biophysical Basics and Mechanism of Action of Minimal Intensity Photocoagulation

Subthreshold minimal intensity photocoagulation (MIP) protocols are intended to minimize the laser-induced chorioretinal damage and spare the neurosensory retina.8 They are designed to avoid intra- and postoperatively visible burn endpoints. These protocols produce only sub-lethal thermal elevations, with effects that are invisible during treatment and remain so thereafter. The treatments adhere to the following biophysical criteria:17

  • axial confinement of the thermal gradient (rise in

IX. Axial Confinement of the Thermal Gradient during Laser Exposure

In retinal photocoagulation, the temperature first increases at the RPE. From the RPE, it spreads by conduction to re-equilibrate with adjacent cooler tissues. In MIP, the inner retinal temperature must remain below the threshold of irreversible damage. Any increase in temperature at the RPE must be axially confined, which can be achieved by making the heat production time (the laser exposure duration) shorter than the thermal relaxation time for the space between the RPE and the neural retina.

X. Control of the Thermal Gradient in the Retinal Pigment Epithelium

Even when the rise in temperature is successfully confined around the RPE during laser exposure, unavoidable thermal equilibration could still damage the neurosensory retina.81 This can occur when the temperature at the RPE creates a heat wave that reaches the inner retina at lethal temperature levels. This post-operative inner retinal damage must be avoided by limiting the temperature rise at the RPE by adjusting the laser “irradiance” (power density in W/cm2). In order to deliver the needed

XI. Clinical Applications of Subthreshold Micropulse Diode-laser Photocoagulation

Subthreshold micropulse diode-laser (MPD) protocols using a micropulse 810 nm diode laser were originally pioneered by Friberg24 and Hamilton57 and are now gaining the interest of retinal surgeons worldwide. Emerging evidence indicates that subthreshold MIP protocols with a micropulse 810 nm laser can be as effective as the more destructive conventional photocoagulation with visible endpoint in several chorioretinal diseases.9

XII. Problems with Micropulse Diode-laser Laser Treatment

The greatest limitation of MPD laser procedures is the difficulty of titrating the treatment without the feedback of an ophthalmoscopically visible endpoint. Conversely, minimizing chorioretinal laser damage permits confluent therapy and re-treatment of the same areas, which may be needed in macular edema. Re-treatment is feasible after MPD because MPD does not produce chorioretinal scars that could expand or increase the risk of choroidal neovascularization.

The treatment protocol is not yet

XIII. Summary

The introduction of the infrared diode laser and its proven efficacy in treating diabetic macular edema has provided a valuable insight into the mechanism of action of retinal laser therapy. Direct closure of microvascular abnormalities with a relatively heavy burn is not necessary to achieve the desired clinical therapeutic endpoint. Micropulsed diode laser therapy has lent further weight to this concept, with an increasing body of clinical evidence suggesting that resolution of retinal

XIV. Method of Literature Search

Searches were done on Medline/Ovid/Embase in addition to a manual search from 1975 to the present. Search words used alone or in combination included micropulse, laser, diabetic macular edema, selective laser, diode laser, central serous chorioretinopathy, vein occlusions, glaucoma. Additional sources were articles cited in the reference lists of retrieved articles. All articles relevant to the field were considered for the review. Non-English literature was reviewed with the help of

References (88)

  • N. Ogata et al.

    Upregulation of pigment epithelium-derived factor after laser photocoagulation

    Am J Ophthalmol

    (2001)
  • M.R. Ulbig et al.

    Color contrast sensitivity and pattern electroretinographic findings after diode and argon laser photocoagulation in diabetic retinopathy

    Am J Ophthalmol

    (1994)
  • M.S. Wang et al.

    Retinal atrophy in idiopathic central serous chorioretinopathy

    Am J Ophthalmol

    (2002)
  • L. Akduman et al.

    Subthreshold (invisible) modified grid diode laser photocoagulation in diffuse diabetic macular edema (DDME)

    Ophthalmic Surg Lasers

    (1999)
  • M.W. Balles et al.

    Exposure time dependent variation in diode laser energy required for retinal photocoagulation [ARVO abstract no. 1276]

    Invest Ophthalmol Vis Sci

    (1993)
  • F. Bandello et al.

    Light panretinal photocoagulation (LPRP) versus classic panretinal photocoagulation (CPRP) in proliferative diabetic retinopathy

    Semin Ophthalmol

    (2001)
  • J. Birch et al.

    Xenon arc and argon laser photocoagulation in the treatment of diabetic disc neovascularization. Part 2

    Effect on colour vision. Trans Ophthalmol Soc UK

    (1981)
  • M.S. Blumenkranz et al.

    Semiautomated patterned scanning laser for retinal photocoagulation

    Retina

    (2006)
  • R. Brancato et al.

    Histopathology of diode and argon lasers in rabbit retina

    Invest Ophthalmol Vis Sci

    (1989)
  • R. Brancato et al.

    Applications of diode lasers in Ophthalmology

    Lasers Light Ophthalmol

    (1987)
  • J.A. Cardillo et al.

    Comparison of the modified ETDRS and normal or high density subthreshold infrared micropulsed laser photocoagulation strategies for diabetic macular edema

    Invest Ophthalmolmol Vis Sci

    (2008)
  • P.F. Cardillo et al.

    Photodynamic therapy for chronic central serous chorioretinopathy

    Retina

    (2003)
  • W.M. Chan et al.

    Choroidal vascular remodelling in central serous chorioretinopathy after indocyanine green guided photodynamic therapy with verteporfin: a novel treatment at the primary disease level

    Br J Ophthalmol

    (2003)
  • G.M. Clover

    The effects of argon and krypton photocoagulation on the retina: implication for the inner and outer blood retinal barriers

  • M. Detry-Morel et al.

    Micropulse diode laser (810 nm) versus argon laser trabeculoplasty in the treatment of primary open-angle glaucoma: comparative short-term safety and efficacy profile

    Bull Soc Belge Ophthalmol

    (2008)
  • Preliminary report on effects of photocoagulation therapy

    Am J Ophthalmol

    (1976)
  • G. Dorin

    Evolution of retinal laser therapy: minimum intensity photocoagulation (MIP). Can the laser heal the retina without harming it?

    Semin Ophthalmol

    (2004)
  • G. Dorin

    Subthreshold and micropulse diode laser photocoagulation

    Semin Ophthalmol

    (2003)
  • Early photocoagulation for diabetic retinopathy: ETRDS report number 9

    Ophthalmology

    (1991)
  • Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report Number 1

    Arch Ophthalmol

    (1985)
  • A.M. Fea et al.

    Micropulse diode laser trabeculoplasty (MDLT): A phase II clinical study with 12 months follow-up

    Clin Ophthalmol

    (2008)
  • C. Figueira et al.

    Prospective randomized controlled trial comparing subthreshold micropulse diode laser photocoagulation and conventional green laser for clinically significant diabetic macular oedema

    Br J Ophthalmol

    (2009)
  • C. Framme et al.

    Online autofluorescence measurements during selective RPE laser treatment

    Graefes Arch Clin Exp Ophthalmol

    (2004)
  • S.J. Fudemberg et al.

    Trabecular meshwork tissue examination with scanning electron microscopy: a comparison of micropulse diode laser (MLT), selective laser (SLT), and argon laser (ALT) trabeculoplasty in human cadaver tissue

    Invest Ophthalmol Vis Sci

    (2008)
  • W. Goebel et al.

    Patient discomfort during laser treatment, a comparison between diode and argon laser [ARVO abstract]

    Invest Ophthalmol Vis Sci

    (1994)
  • G.A. Greiss et al.

    Multiple-pulse laser retinal damage thresholds

    Am Ind Hyg Assoc J

    (1981)
  • W.T. Ham et al.

    Evaluation of retinal exposures from repetitively pulsed and scanning lasers

    Health Phys

    (1988)
  • L.O. Hattenbach et al.

    Pigment-epithelium-derived factor is upregulated in photocoagulated human retinal pigment epithelial cells

    Ophthalmic Res

    (2005)
  • F.G. Iliusi et al.

    The adaptometry study in patients with diabetic retinopathy

    Oftalmologia

    (2004)
  • A. Jain et al.

    Effect of pulse duration on size and character of the lesion in retinal photocoagulation

    Arch Ophthalmol

    (2008)
  • P.K. Khosla et al.

    Contrast sensitivity in diabetic retinopathy after panretinal photocoagulation

    Ophthalmic Surg

    (1994)
  • S.Y. Kim et al.

    The selective effect of micropulse diode laser upon the retina [ARVO abstract no. 3584]

    Invest Ophthalmol Vis Sci

    (1996)
  • P. Lanzetta et al.

    Theoretical bases of non-ophthalmoscopically visible endpoint photocoagulation

    Semin Ophthalmol

    (2001)
  • P. Lanzetta et al.

    Nonvisible subthreshold micropulse diode laser (810 nm) treatment of central serous chorioretinopathy. A pilot study

    Eur J Ophthalmol

    (2008)
  • Cited by (0)

    Giorgio Dorin is an employee of Iridex Corporation. The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article.

    View full text