Photodynamic Therapy (PDT), introduced to ophthalmology in 2000[1], is a therapeutic procedure which utilizes the photosensitive intravenous drug, verteporfin (Visudyne) in combination with a low power, long duration infrared laser. In the eye, it is used to treat vascular issues in the retina and choroid. It was first indicated for neovascular age related macular degeneration (AMD), with large randomized clinical trials showed an improvement in visual acuity versus placebo. As new therapies have evolved, it is now typically used as an adjunctive treatment for certain types of neovascular AMD. PDT is now most often used to effectively treat cases of Central Serous Retinopathy (CSR) and have been shown to be efficacious by several published studies.
Drug/Laser Mechanism of Action
Verteporfin Drug Information
Verteporfin (marketed as Visudyne), also known as benzoporphyrin derivative, is commonly used as a photosensitizer in Photodynamic Therapy, Verteporfin was developed to treat wet AMD with an intensified long-wavelength absorption maxima at approximately 690 nm. It can be rapidly cleared from the body, minimizing patient photosensitivity to 1 to 2 days. Verteporfin has been approved for the treatment of wet AMD since 1999 by the FDA, having undergone Phase III clinical trials .[2]
Verteporfin Mechanism of Action
Photodynamic therapy with verteporfin causes release of free radicals when the verteporfin is activated by the laser energy. The reaction that ensues between the free radicals and blood vessel endothelial cell membranes lead to a series of events including vasoconstriction, thrombosis, increased vascular permeability, blood stasis and hypoxia.[3] In the case of neovascularization, this process serves to induce regression of these harmful blood vessels. After injected into the bloodstream, the Visudyne (6 mg/m2 dose) selectively collects in the abnormal blood vessels in the retina and choroid. Fifteen minutes after intravenous infusion, low power laser is applied (standard dose of 50 J/cm2, irradiance of 600 mW/cm2 of 689 nm light over 83 seconds[1]) which activates the phototoxic Visudyne to seal leaking blood vessels by generating these free radicals in areas of necessary treatment.
Indications
Age Related Macular Degeneration (Neovascular)
The wet form of AMD is characterized by the rapid growth of abnormal choroidal neovascular blood vessels under the macula. These new blood vessels often lack integrity and leak blood and fluid that harm the central retina; the damage to the retina causes eventual scarring and drastic vision loss over time.
AMD Trials
Central Serous Chorioretinopathy
Central serous chorioretinopathy (CSCR) is an eye disease in which choroidal leakage occurs, causing a serous pigment epithelial detachment and subretinal fluid. PDT was first used in 2003 to treat chronic form of CSCR in 20 eyes. This study showed that the use of PDT treatment was effective in reducing excess fluid in the retina and improving overall vision. Other studies demonstrated safety and efficacy of reduced dose PDT in chronic and recurrent forms of this disease. As the patophysiology underlying this disease is not completely understood there is still debate about treatment options in this disease.
Ocular Tumors
PDT has also shown promise in the treatment of various ocular tumors:
Choroidal Hemangiomas
Circumscribed choroidal hemangiomas (CCH) are non-malignant vascular tumors occurring as a circumscribed orange-red choroidal mass in the posterior pole of the eye. Leakage of fluid from the abnormal vessels of the tumor into the subretinal area causes retinal detachment and decreased vision. The efficacy of PDT in the treatment of this condition is shown in many case series. Although the tumor doesn’t completely disappear after treatment subretinal fluid resorbs and visual acuity increases in most cases. Repeated treatments may be necessary due to the persistence of the tumor.
Capillary hemangiomas
Retinal Capillary Hemangiomas (RCHs) are benign hamartomatous tumors characterized by dilated retinal capillaries. It may cause intraretinal and subretinal exudation that decrease visual acuity. PDT’s ability to treat RCH has been noted by several small case studies. In these studies many eyes demonstrated tumor regression or stabilization as well improvement in subretinal fluid (SRF) and lipid exudation; however, only some experienced an increase in visual acuity.
Combined Therapies
Combined therapy approaches in PDT have also been studied to maximize efficacy of treatments. Based on the results of several multicenterd studies, PDT has been found useful when used in combination with anti-VEGFs in a special type of AMD (Polypoidal choroidal angiopathy).
Risks/Side Effects
The primary effect of photodynamic therapy treatment is an increase in photosensitivity of the skin, attributed to the administration of verteporfin. For this reason, it is recommended that patients wear a wide-brimmed hat, clothes with full skin coverage, as well as sunglasses for 3-5 days after the treatment. It has been reported that a few patients could potentially suffer from an minimal allergic reaction to verteporfin, causing skin inflammation at the injection site. Other PDT side effects may also include:
1-4% have severe vision decrease, which is typically transient and is reduced with the reduced fluence treatment protocol
Procedure
Steps
Post-treatment
Patients are typically followed every 4-12 weeks, depending on the physician's preference. After an initial treatment period, fluorescein angiography and/or optical coherence tomography (OCT) may be needed to investigate the efficacy of the treatment. Further treatment with injections or additional PDT may be administered if deemed necessary
