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Photo Dynamic Therapy(PDT) :

 

Photodynamic therapy is a new technique to tumor or neovascularisation destruction by vaso occlusive effect using photosensitisation.

Mechanism of action: Photodynamic therapy involves two steps: The administration of a photosensitizing agent that localizes in the target tissue, followed by the application of low-intensity light to the target tissue to produce localized tissue damage. The photosensitizer may be administered by various methods, including topical, local, or systemically. For example, photosensitizers are often given topically for dermatologic disorders.  In ophthalmology, these agents are typically administered intravenously to reach the retinal or choroidal circulation. These photosensitizers delivered and preferentially concentrated in the target tissue than adjacent normal tissues. Certain photosensitizers have affinity to neovascular or tumor tissue. Verteporfin, is a photosensitizer which has absorbtion band of 689nm, used in ophthalmology. After the drug has reached the desired tissue, low-energy nonthermal 689 nm light, which is supplied by a laser source, is applied directly to the area of interest. The interaction of the photosensitizer with light of a specific wavelength induces a photochemical reaction that liberates by-products that are toxic to the target tissue. In photochemical reaction the photosensitizing agent is activated by the delivered light energy, the agent is transformed from its ground state to a higher energy singlet activated molecule. For the more efficient photosensitizers, the higher energy state decays into a lower energy, more stable molecule referred to as a triplet sensitizer. This triplet sensitizer can undergo either a Type I or Type II reaction. The Type I reaction generates superoxide anions, whereas Type II reactions result in production of singlet oxygen.9 These by-products are believed to be responsible for the localized tissue damage produced by PDT. Neither the drug nor the light alone (at the irradiance in the range used to PDT) appears to have any significant biological effect. It is the combination of these factors, utilizing light of a specific wavelength to activate the photosensitizer drug, which creates the photochemical reaction. Sequestering of the photosensitizing agent in the target tissue and direct application of low-energy, focused light by a contact lens to activate the photosensitizer within the lesion are the main features that limit induced damage to the surrounding tissue.

Indications: Photodynamic therapy is the first line treatment for Polypoidal Choroidal Vasculopathy, and subfoveal Choroidal neovascular membrane. Earlier, laser was the only treatment option for subfoveal CNVM but laser treatment of subfoveal CNV produces immediate and permanent central visual loss due to full-thickness retinal destruction induced by thermal photocoagulation. Laser photocoagulation is also unsatisfactory as long-term therapy for CNV in any location owing to the high recurrence rate of CNV leakage and the full-thickness neurosensory retinal destruction that it produces.

TECHNIQUE OF PDT: Subfoveal CNVM due to any cause and PCV are the two main indication for PDT. Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study and Verteporfin Therapy of Subfoveal Choroidal Neovascularization in Age-Related Macular Degeneration (VIP) Study has provided the guidelines for administration of PDT. Before going for Verteporfin-PDT, FFA and ICG angiogram is studied again for the determination of the percentage composition of type of CNVM and great linear dimension (GLD) of the lesion across the longest diameter of leakage in angiogram. The size of the area to be treated using the nonthermal 689 nm light should have a 500 ?m border around the CNV, so a total of 1,000 ?m should be added to the greatest diameter (or GLD) of CNV. The treatment area should extend no closer than 200 ?m to the optic nerve, as recommended by the TAP studies.

Verteporfin, which is stored as a dry powder, is reconstituted with sterile water and diluted with 5% dextrose solution immediately before use. This solution is infused intravenously over 10 minutes, preferably through a large cubital or cephalic vein. Constant monitoring during the entire infusion is imperative to avoid photosensitizer extravasation, which can have serious dermatological consequences. The calculated dose of verteporfin is 6.0 mg/m2 body surface area; thus, the accurate weight of the patient should be obtained before treatment. The 689-nm diode laser light treatment begins 15 minutes after commencing the verteporfin infusion. The laser treatment is delivered at the slit lamp through a diode-coated contact lens. Laser treatment is applied for 83 seconds, which produces a total energy dose of 50 J/cm2.

In case of the bilateral PDT in same sitting the size of treatment area and laser setting of both eye is determined, then the eye with more aggressive disease should be treated first at the standard 15-minute post-injection time. Treatment for the fellow eye should commence no later than 20 minutes after commencement of verteporfin infusion.

Post-treatment precautions include avoidance of direct sunlight or bright indoor lights. A wide-brimmed hat, gloves, long pants, long sleeves, and protection of the eyes and face from direct sunlight are required for travel immediately after PDT. Complete avoidance of direct sunlight is strictly prescribed for 7 days following verteporfin-PDT. Watching television is also restricted for 7 days. These are to prevent potentially serious skin burns and photosensitivity that may occur from residual, circulating photosensitizer after PDT.

Clinical effects: PDT causes Choroidal neovascular occlusion and produces choroidal hypofluorescence in FFA within few days of PDT treatment. It corresponds to the Choroidal hypoperfusion in ICG angiography. This hypoperfusion of the underlying choroidal vasculature is most pronounced within the first week after PDT. The vascular occlusive effect of PDT is not permanent whether low or high energy used, and reperfusion of the choroidal vessels typically recurs between 4 and 12 weeks after PDT. By 12 weeks after PDT, approximately two thirds of CNV lesions had recurred.  This led to the concept of repeating PDT treatments to reinduce or maintain occlusion within CNV.

COMPLICATIONS ASSOCIATED WITH PDT: Adverse effects associated with PDT using Vertepofin are usually rare. Injection site event like extravasation, hypersensitivity and pain can occur.  There is possibility of photosensitive reactions like mild to moderate sunburn occurring within 24 hours of PDT. Infusion related back pain has been reported to occur on successive infusions of verteporfin probably due to neutrophil margination from vascular wall during infusion.  Infusion related pain is not limited to back, it can occur at leg, groin, chest, buttock, arm, and shoulder also but the episode subsides with cessation of infusion.

CONTRAINDICATIONS: Contraindications to PDT include porphyria, severe liver disease, pregnancy, or a known hypersensitivity to a photosensitizing agent.

 

 

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