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Cold Laser

By Dr. Shantan Reddy

Photodynamic therapy (PDT) with verteporfin (Visudyne ®) (vPDT) emerged as a welcome alternative to thermal laser for the treatment of CNV. This technique employs intravenous administration of a pharmacological photosensitizer (e.g. verteporfin) followed by physical activation of the substance using a 689nm laser light. Excitation of the photosensitizer initiates a photochemical reaction involving singlet oxygen and reactive oxygen intermediates, which damage endothelial cells lining the CNV and can lead to selective occlusion of the CNV with less severe effects on the retina and underlying choroid. Because a non-thermal light intensity is used to induce the photochemical oxidation within the vascular endothelium, thermal tissue damage does not theoretically occur but vaso-occlusion with concomitant thrombosis of the normal choriocapillaris has been documented. Moreover, the thrombotic effect induces a hypoxia which locally increases the expression of VEGF. The Treatment of Age Related Macular Degeneration with Photodynamic Therapy (TAP) study found a benefit to treatment after one and two years. Subjects with subfoveal lesions (containing any proportion of a classic component) of up to 5400 microns in the greatest linear diameter were enrolled in these trials, and pre-randomization visual acuity ranged from an approximate Snellen equivalent of 20/40 to 20/200. A benefit was found for the entire population, with 53% of the vPDT-treated subjects and 38% of the sham-treated subjects losing fewer than 15 letters in visual acuity at 2 years (p<0,001).  Sub-group analysis by angiographic classification revealed that the benefit was largest in predominantly classic lesions (in which the area of classic CNV is greater than 50% of the entire lesion). In this type of lesion, 59% of vPDT-treated eyes compared with 31% of sham-treated eyes lost fewer than 15 letters. An improvement in vision by 15 letters or more was seen in only 9% of treated subjects (including predominantly and minimally classic lesions) at the 24 month visit.

The Verteporfin in Photodynamic therapy (VIP) trial enrolled subjects with subfoveal CNV lesions composed of angiographically occult lesion sub- type only, and with a presumed recent disease progression (vision loss by at least one line, new hemorrhage, or an enlargement of the CNV by at least 10% seen by angiography). At two years, 45% of vPDT-treated eyes compared to 32% of sham-treated eyes lost fewer than 15 letters and an improvement in vision by at least 15 letters was seen in 5% of treated subjects. Loss  of 30 letters or more was observed in 29% of eyes in the vPDT group versus 47% of eyes in the placebo group. Sub-group analysis revealed that CNV with relatively small size (less than 4 MPS disc areas) or relatively low visual acuity (< 65 letters) had better outcomes. In this sub-group, 51% of the vPDT-treated eyes lost less than 15 letters versus 25% of placebo-treated eyes. The benefit or stabilization achieved during the first two years was often maintained for at least the following three years.

The ocular and systemic safety of verteporfin therapy was confirmed in the TAP and VIP trials. Acute severe visual loss (loss of more than 20 letters or four lines of vision within seven days of verteporfin therapy) was noted however (0.7% in the TAP investigation and 4.9% in the VIP trial) and was more often seen in the treatment of large occult lesions with better initial visual acuity.
Participants in the TAP study received on average five treatments over the two years and the risk ratio of losing three or more lines and six or more lines of visual acuity was 0.77 (95% confidence interval 0.69 to 0.87) and 0.62 (95% confidence interval 0.50 to 0.76), respectively. The frequency of re-treatments decreased from an average of 3.4 in the first year, to 2.2 in the second year, to 0.4 by the fourth year (TAP Study Group 2005). An analysis of treatment outcomes by lesion size following vPDT from the TAP and VIP studies suggested that therapy might reduce the risk of visual loss in small, minimally classic lesions.

In summary, the TAP and VIP studies provided evidence of the efficacy and safety of the verteporfin therapy. This therapy reduces the risk of further loss in vision by 50%; however, an improvement in vision was still a rare event. Predominantly classic or purely occult lesions smaller than four disc diameters that showed recent progression were shown to have better outcomes. Considering the durability and need for fewer repeated treatments, in the pre- anti-VEGF era, vPDT was an appropriate therapy for subfoveal CNV, new or recurrent, where the classic component is greater than 50% of the entire lesion (≤5400µm; or in an occult CNV when the visual acuity is worse than 20/50 or greater than 20/50 with a lesion size less than a disc diameter).

Topics and Subtopics: Eye Care

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