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ROLE OF PHOTODYNAMIC THERAPY IN THE MANAGEMENT OF AGE-RELATED MACULAR DEGENERATION
RAJENDRA S APTE, EYAL MARGALIT
Retinal Vascular Centre, The Wilmer Ophthalmological Institute, The Johns Hopkins University School of Medicine.
The advent of photodynamic therapy with verteporfin revolutionized the treatment of subfoveal CNVM. The review will summarize the results of the treatment of age-related macular degeneration with photodynamic therapy (TAP) investigation and the verteporfin in photodynamic therapy (VIP) trial. The TAP study showed that verteporfin therapy reduced risk to moderate vision loss in predominantly classic lesions. The VIP study showed the verteporfin therapy reduced the risk of moderate to severe vision loss in cases of occult with no classic CNVM.
Age-related macular degeneration (AMD) is a degenerative condition of the retina and choroid which predominantly affects individuals over 50 years of age.[1]Involvement of the macula in the neovascular or non-neovascular forms of AMD can lead to severe central vision loss. AMD is the leading cause of blindness in the population over 65 years of age in North America and Europe.[1,2] Neovascular AMD is characterised by choroidal neovascularization (CNV).[3] Until recently, the only treatment available for extrafoveal (EF), juxtafoveal (JF), and selected subfoveal (SF) forms of CNV was thermal laser photocoagulation (LPC).[4-6] In addition, LPC of SF CNV lesions leads to an immediate decrease in central vision and an irreversible destruction of the overlying retinal tissue.[6,7]
The advent of photodynamic therapy with verteporfin revolutionized the treatment of SF CNV in AMD.[8]Nonetheless, there was no preventive treatment available to retard the progression and severity of the disease process in AMD. The recently published age-related eye disease study (AREDS) results suggest that zinc and certain antioxidants in high doses may reduce the progression of AMD and might protect against moderate visual loss in a sub-group of patients with AMD.[9] This review will summarize the impact of PDT on our therapeutic options in the treatment of AMD.
Although AREDS has shown some benefit as a preventive treatment for neovascular AMD, many patients develop subfoveal CNV. As discussed earlier in this review, LPC is a viable treatment option for EF and JF CNV in AMD. However, photodynamic therapy with verteporfin is now available as another treatment option for subset of patients with SF CNV in AMD. The results of the treatment of age-related macular degeneration with photodynamic therapy (TAP) investigation and verteporfin in photodynamic therapy (VIP) trial will be reviewed here.[10-12] The TAP study showed that verteporfin therapy reduced the risk of moderate (>- 30 letters) vision loss in patients with predominantly (more than 50% of the lesion area) classic lesions, with or without an occult component at 12 and 24 months followup.[10,11]The placebo treated lesions were almost twice as likely to be >- 6 disc areas (DA) in size and 2.5 times as likely to be >- 9 DA as compared to the verteporfin treated lesions at 24 months.[11] The mean number of contrast sensitivity letters lost was 1.3 and 1.3 in the verteporfin group and 4.5 and 5.2 in the placebo group at 12 and 24 months respectively. There was no evidence of a significantly higher risk of ocular or systemic adverse events with verteporfin therapy at 24 months. Most of the visual acuity loss in both the verteporfin and placebo groups occurred during the first year of treatment, especially during the first 3 to 6 months of therapy. Average number of verteporfin applications were 3.4 in the first 12 months and 2.2 in the next 12 months. Table 1 outlines the visual outcomes at months 12 and 24 for the verteporfin and placebo groups in the TAP study. One of the findings in the study was that fluorescein angiographic outcomes did not always correlate with visual acuity.[11]
There was a small subgroup of patients in the TAP study with occult (without classic) CNV as determined at the Reading Centre, who showed a potential treatment benefit with verteporfin therapy. The number of patients was too small for conclusive evidence and these patients should originally not have been enrolled in the TAP study which was designed to address the treatment benefit for participants with predominantly classic CNV. The AMD arm of the verteporfin in photodynamic therapy (VIP) trial was designed to assess the treatment benefit of verteporfin in cases with occult (no classic) CNV.[12] The results showed that verteporfin therapy compared to placebo reduced the risk of moderate to severe vision loss in cases of occult with no classic CNV and presumed recent disease progression. Recent disease progression was defined as a visual (>- 5 letter loss) or anatomic (increase in the greatest linear dimension of the lesion by >- 10%) deterioration within last 3 months or evidence of haemorrhage from CNV. Participants with smaller lesions (<- 4 DA in size) or lower levels of visual acuity (<- 20/50-1) benefited the most from verteporfin therapy. Cautious interpretation was recommended with larger lesions (>- 4 DA) associated with better vision (>- 20/50) where verteporfin may not be beneficial.[12] These data from the AMD arm of the VIP study are summarized in Table 2.
Outcomes in the TAP investigation at 12 months and 24 monthsOutcomes Visual Acuity Gain All participants >=15 letters
24
9
4Visual Acuity Loss All participants >-15 letters
24
47
62>-30 letters
24
18
30<-20/200 Predominantly classic CNV
± occult CNV
>-15 letters
24
41
69>-30 letters
24
15
36<-20/200 Predominantly classic CNV
(Without occult )>-15 letters
24
-
->-30 letters
24
-
-Predominantly classic CNV
(With occult )>-15 letters
24
-
->-30 letters
24
17
36Minimally classic CNV >-15 letters >-30 letters Progression of classic CNV Absense of angiographic leakage from classic CNV
Outcomes in the AMD arm of the VIP studyOutcomes Visual Acuity Gain All occult with no classic CNV >-15 letters
24
55
68>-30 letters
24
29
47Occult with no classic CNV and baseline visual acuity <- 20/50-1 or lesion size <- 4 DA >-15 letters >-30 letters Occult with no classic CNV and baseline visual acuity >- 20/50 or lesion size >- 4 DA >-15 letters >-30 letters Fluorescein Angiographic Outcomes Progression of occult CNV
24
46
52Absence of leakage from occult CNV
24
42
29Absence of leakage from occult and classic CNV
24
35
14
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