Retina Today - Continuous-wave and Micropulse 577 nm Yellow Laser Photocoagulation: A Laser for All Reasons (April 2010)

摘要

Retinal photocoagulation is effective, but it is also destructive. In the past, the prevailing view was that to be useful, laser therapy had to destroy oxygen-consuming rods and cones or retinal pigment epithelium (RPE) cells that produce angiogenic mediators. That perspective has been disproven now by numerous clinical trials and better understanding of the cellular and molecular changes induced by laser exposures. PHOTOCOAGULATIONa??S BIOLOGICAL EFFECTSPhotocoagulation upregulates inhibitors and downregulates inducers of VEGF-related angiogenesis, as shown by microarray and quantitative polymerase chain reaction techniques.1-3 It downregulates matrix metalloproteinases, which degrade extracellular matrix, and it upregulates their tissue inhibitors, thereby inhibiting initiation and maintenance of angiogenesis.4 It induces bone marrowderived stem cells to migrate to exposure sites, where they can differentiate into and replace dysfunctional or injured cells.5-7 It also induces RPE apoptosis and choroidal heat shock proteins.8,9 Additionally, it upregulates pigment epithelium-derived factor (PEDF), a powerful inhibitor of angiogenesis.10 MICROPULSE PHOTOCOAGULATIONRandomized prospective clinical trials demonstrate that subthreshold micropulse photocoagulation is as effective a treatment for diabetic macular edema as conventional, more damaging laser therapy.11,12 Moreover, a recent study documents that it can improve visual sensitivity, whereas standard suprathreshold ETDRS-type photocoagulation decreases sensitivity.13 The bottom line is that subthreshold micropulse photocoagulation can be constructive without being destructive, whereas conventional suprathreshold photocoagulation causes permanent rod, cone, and retinal ganglion photoreceptor damage, with corresponding losses in scotopic, mesopic, and circadian photoreception.17,20 Micropulse photocoagulation can decrease retinal damage by: 1) using subvisible or barely visible treatment endpoints; 2) localizing laser effects with exposures 100 times shorter than those available with manual or automatedpattern conventional photocoagulators; and 3) optimizing laser wavelength.14 SUBTHRESHOLD ENDPOINTSPhotocoagulation occurs when laser radiation is absorbed primarily by melanin in the RPE and the choroid.14-17 Light absorption in pigmented tissues converts laser energy into heat, increasing the temperature of the pigmented tissue targets. Heat conduction then spreads this temperature rise from laser-irradiated pigmented tissue to overlying neural or collateral retina. Overlying retina damaged by heat conduction loses its transparency and scatters white slit lamp light back at the observer. Retinal whitening is the optical signature of a chorioretinal burn. More damage means less transparency and a whiter lesion.14,17 There are many a??thresholdsa?? for retinal laser exposures. Hemorrhages occur at roughly three times the exposure needed to produce ophthalmoscopically apparent lesions. Invisible lesions that are angiographically apparent occur at approximately half the laser exposure needed for a visible lesion. Maximum permissible exposure (MPE) levels established by international laser safety standards represent roughly one-tenth the laser exposure needed to produce a retinal effect.14,17,18 In clinical terms, a??subthresholda?? means a??invisible.a?? Smaller retinal irradiances (power density in W/cm2) produce therapeutic effects with lower retinal temperature rises that cause less or no retinal damage.14,17 LOCALIZING RETINAL EFFECTSFigure 1 shows retinal temperature increase in the neural retina, the RPE, and the choroid for a 200-micron diameter retina spot, and laser exposures ranging in duration from 1 microsecond to 0.1 second.15,16 For very short microsecond exposures, retinal temperature increases only in the RPE and choroid, where light is directly absorbed. For lengthier exposures, heat conduct