Transpupillary thermotherapy for age-related macular degeneration: long-pulse photocoagulation, apoptosis, and heat shock proteins

Ophthalmic Surg Lasers. Sep-Oct 2000;31(5):359-73.


Objective: To provide a biophysical foundation for using transpupillary thermotherapy (TTT) to manage choroidal neovascularization in age-related macular degeneration (ARMD).

Methods: Retinal temperature rise in laser therapy is proportional to retinal irradiance (laser power/area) for a particular spot size, exposure duration, and wavelength. TTT is a low irradiance, large spot size, prolonged exposure (long-pulse), infrared laser photocoagulation protocol. Results from an experimentally confirmed, finite element model of retinal light absorption and heat conduction are used to analyze laser parameter selection and its consequences. Results from apoptosis, heat shock protein and hyperthermia research are used to examine how chorioretinal damage from clinical procedures might be reduced.

Results: Chorioretinal thermal equilibration occurs during long-pulse TTT photocoagulation. Retinal temperature increases are similar in the RPE where laser radiation absorption is significant and in the adjacent neural retina where there is negligible radiation absorption. For parameters used to treat occult choroidal neovascularization in lightly-pigmented fundi (800-mW, 810-nm, 3-mm retinal spot diameter, 60-sec exposure duration), the maximum chorioretinal temperature elevation is calculated to be roughly 10 degrees C, significantly lower than the 20 degrees C temperature elevations measured in threshold, conventional short-pulse retinal photocoagulation.

Conclusions: To achieve a preselected temperature rise, TTT laser power must be increased or decreased in proportion to the diameter rather than the area of the laser spot. Clinical power settings should be adjusted for fundus pigmentation and media clarity because both of these factors affect absorbed retinal irradiance and thus retinal temperature rise. Noninvasive thermal dosimetry currently is unavailable for clinical retinal photocoagulation, but potential thermometric techniques include MRI, liposomal-encapsulated dyes, multispectral imaging or reflectometry, and subretinal or episcleral thermometry. TTT may be useful not only as independent therapy, but also as an adjunct to PDT, antiangiogenic drugs and ionizing radiation therapy in the management of neovascular ARMD. Low temperature, long-pulse photocoagulation is a potential strategy for decreasing neural retinal damage in subsequent TTT or short-pulse photocoagulation and perhaps even for treating glaucoma or retinal degenerations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis*
  • Body Temperature
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Hyperthermia, Induced*
  • Laser Coagulation / methods*
  • Macular Degeneration / metabolism
  • Macular Degeneration / pathology
  • Macular Degeneration / therapy*
  • Prognosis
  • Pupil
  • Retina / metabolism
  • Retina / pathology*


  • Heat-Shock Proteins