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Continuing Medical Education

Technical Specification Overview Comparing Photocoagulation and PDT

Wavelength Choice versus One Wavelength

Parameters being used in photocoagulation differ considerably from those in PDT when treating CNV. Table 1 gives an overview of the major differences. In photocoagulation, the laser wavelengths used for treatment usually are green, yellow, or red. However, results from MPS trials do not show a large difference in treatment benefits between wavelengths (MPS Group 1994). This result is probably due to little difference of treatment effect on ocular tissue occurs at the high intensities used for photocoagulation of CNV. As the laser wavelength in PDT must match an absorption peak of the photosensitizer, only 689 nm (a red wavelength) can be used for Visudyne therapy.

Treatment Parameters
According to MPS criteria, intense treatment of the entire area of the CNV lesion was required in order to decrease the chance of recurrence with less intense treatment or inadequate coverage. The desired end point is a gray-white burn (MPS Group 1991). To achieve that effect, multiple, overlapping laser spots at approximately 200 µm spot size at 200 – 500 ms pulse duration were placed, covering the entire lesion. The chosen power, depending on ocular conditions and wavelength chosen, usually ranges between 150 and 500 mW (MPS Group 1991). To contrast, in PDT only one spot covering the entire lesion is exposed at a duration of 83 seconds. In trials on PDT with Visudyne, treatable CNV lesions could have a greatest linear dimension as large as 5400 µm on the retina. To ensure that the entire lesion is covered, a safety margin of 500 µm must be added to either side of the greatest linear dimension (1000 µm total) to obtain the proper spot size used in the trials that showed benefit. Contrary to photocoagulation, multiple overlapping spots must not be applied as the overlapping areas would receive more than the required light dose.

In PDT, basically one variable determines the photodynamic effect: fluence (also known as light dose).

The laser irradiance (also known as intensity or power density) determines the exposure time. The exposure time is a direct function of fluence and irradiance.

Phase I/II clinical trials determined that a fluence of 50 J/cm2 and an irradiance of 600 mW/cm2 could achieve a safe, potentially beneficial effect on the CNV. Higher irradiances shorten the exposure time but can lead to thermal photocoagulation effects. Of note, irradiances used in photocoagulation are higher by a factor of at least 500, if assuming standard parameters for macular photocoagulation (see Table 1).

Laser Specification	Photocoagulation	PDT
Wavelength	Green, yellow, red	Red (689 nm)
Number of laser spots	Multiple, overlapping laser spots to treat the lesion	One laser spot covering the entire lesion
Spot size	100-500 µm	500-6400µm (retinal spot size
Time	Pulse duration 0.1 to 0.5 seconds/pulse	Exposure time (fluence divided by irradiance) 83 seconds
Power	Usually 150 to 500 mW	Max. 200 mW, depends on fluence, irradince nad spot size
Fluence (light dose)	Not common terminology in photocoagulation _300,000 mW/cm²	50 J/cm²
Irradiance (power density, intensity)	(assuming 100 mW power, 200 µm spot)	600 mW/cm²
Table 1: Comparison of laser parameters between photocoagulation and PDT used in the treatment of CNV in AMD.

USING THE VISULAS 690S IN PDT THERAPY
The first step towards a successful introduction of PDT into clinical practice was taken with the availability of a semiconductor-based, software-controlled diode laser, providing a sufficiently high output power at the required wavelength (689 nm, red). The VISULAS 690s was introduced in the summer of 1997 for use in phase III clinical trials. This laser has been used since that time at the Wilmer Ophthalmological Institute (Johns Hopkins University,* Baltimore, Maryland USA) and other major centers participating in the TAP Investigation. The VISULAS 690s presented a totally new handling concept customized for the needs of PDT with Visudyne and phase III trials, simplifying input of laser parameter settings for the treating ophthalmologist. During the entire phase III clinical trials, the Zeiss laser proved its clinical effectiveness and reliability.

Figure 3A: The first VISULAS 690s menu that appears when the laser console is turned on shows fluence, exposure time, irradiance, drug timer settings, and contact lens magnification. Only the contact lens magnification needs to be entered by the treating ophthalmologist on this menu. The second menu can be viewed by pressing the continuation button.

Figure 3B: The second VISULAS 690s menu can show the actual treatment in progress as the remaining time elapses and the fluence delivered increases up to 50 J/cm2. In this menu, the treating ophthalmologist needs only to enter the retinal spot size. The doctor may adjust the aiming beam and switch the laser to ready mode as well. By pressing the Reset button, the doctor is returned to the first menu (Figure 3A).

When the laser is activated, the fluence and irradiance are preset to the values required by Visudyne, as shown in Figure 3A. Only two parameters need to be entered onto the laser console by the treating ophthalmologist: the magnification of the contact lens used in the procedure and the desired retinal spot size for the therapy (Figure 3A,B).

The required output power, or irradiance, is automatically calculated by the software based on the laser intensity (600mW/cm2), contact lens magnification, and the selected spot size. A drug timer counting the time between the start of the infusion and the beginning of laser application (15 minutes) as well as a timer that counts down time of light application from 83 seconds to zero is available for convenience of the treating ophthalmologist. All the settings required to begin the procedure can be performed by setting two parameters.

Locating the CNV and Determining Its Composition
After thorough examination of the fluorescein angiogram and determination of the lesion size by measuring the greatest linear dimension, landmarks (for example retinal vessels, areas of blood, pigment or lipid) are selected to help find the lesion with slit lamp biomiscroscopy and location of the treatment spot (with the aiming beam which is the same size as the treatment spot) relative to these landmarks so that the lesion will be covered in its entirety with the treatment spot. Treatment is facilitated when the physician has a clear stereoscopic view without any obstruction by media opacities. Since the laser adapter to the slit lamp has a clear physician safety filter integrated, a clear image can be obtained from the fundus. If needed, a green filter can be swiveled into place to enhance contrast on the fundus.

Precision Handling of Instrumentation
The equipment used in PDT is optimally designed to minimize effort in selecting treatment parameters. With the VISULAS 690s, only two parameters (contact lens magnification and spot size) must be set prior to treatment. All the other treatment parameters (such as light dose, exposure time, power density, and dye timer) are preset. The required output power is immediately calculated by the software after selecting the contact lens magnification and spot size. After initiating light application, the delivered dose and remaining time also are calculated and displayed. The software controlled power output is monitored by two internal sensors, which recognize power fluctuations.

Controlling Treatment Variables
In order to avoid preactivation of the drug, the physician should use the flow setting on the voltage selector, after Visudyne is administered to the patient. The Zeiss slit lamp provides a low illumination setting with a specific filter coating in the beam splitter located within the slit lamp, that eliminates the risk of activating the drug prior to the actual laser treatment.²

Other safety features include the following:

Foot pedal laser activation engages the laser only while the physician depresses the pedal switch to the on position. This ensures the patient and the physician that the laser will not be activated at random, and it will only be activated when the treating ophthalmologist wants to deliver light. Interruption of light can be quicker, requiring only a release of the pedal rather than active re-depression of the pedal.
User friendly interface consists of two text driven menus with pressure-sensitive push button panel.
Power output sensor ensures laser light is uninterrupted.
Hermetically sealed diode cooling fan allows the diode to cool, extending its life and decreasing the risk of laser malfunction.
Slit lamp adapter filter gives the physician extra eye protection from laser light during the procedure.

The use of photocoagulation lasers for the activation of Visudyne is not possible for several reasons: 1) The laser has to emit the absorption wavelength of the photosensitizer as exact and as constant as possible; 2) The maximal intensity must not induce any coagulation effect in ocular tissue; 3) The exposure time is within the range of minutes; 4) Spot sizes should vary within the range of 500 to 6400 µm.

SUMMARY
Photodynamic therapy (PDT) with Visudyne, activated by the VISULAS 690s laser can reduce the risk of vision loss in patients with age-related macular degeneration who present with a predominantly classic choroidal neovascular lesion that extends under the center of the foveal avascular zone (TAP Group Study 1999)

Macular Photocoagulation Study Group. 1993.
Laser photocoagulation of subfoveal neovascular lesions of age-related macular degeneration. Updated findings from two clinical trials. Arch Ophthalmol 111:1200-9 Kahn HA, Leibowitz HM, Ganley JP, Kini MM, Colton T, Nickerson RS, Dawber TR. July 1997.
The Framingham Eye Study: I. Outline and major prevalence findings. Am J Epidemiol 106:17-32. Macular Photocoagulation Study Group. 1991. Subfoveal neovascular lesions in age-related macular degeneration: guidelines for evaluation and treatment in the Macular Photocoagulation Study. Arch Ophthalmol 109:1232-1241.
Macular Photocoagulation Study Group. 1994. Evaluation of argon green versus krypton red laser for photocoagulation of subfoveal choroidal neovascularization in the macular photocoagulation study. Arch Ophthalmol 112:1176-1184.
Treatment of Age-related Macular Degeneration With Photodynamic Therapy (TAP) Study Group. 1999. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin, One year results of two randomized clinical trials-TAP Report 1. Arch Ophthalmol 117:1329-1402.
Visudyne is a trademark of CIBA Vision, a division of Novartis AG. VISULAS 690s is a trademark of Carl Zeiss.

* Laboratory testing has shown that the total power in the low intensity position of the slit illumination intensity is limited to 1/1000 of the laser intensity.

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