DRUG USE IN RETINAL DISEASES

therapy.11,12 The primary outcome measure was the proportion of eyes with fewer than 15 letters (approximately 3 lines) of visual acuity loss at the month-24 examination. A benefit was found for the entire population, with 53% of the PDT-treated patients and 38% of the placebotreated patients. Subgroup analysis revealed that the benefit was largest in predominantly classic lesions (Table 43.1). In this lesion type, 59% of PDT-treated eyes compared with 31% of sham-treated eyes lost fewer than 15 letters. No statistically significant difference was noted for minimally classic lesions.11,12 Twenty-two per cent of eyes in the PDT group experienced a significant vision loss – defined as VA loss of more than 30 letters – compared to 36% in the sham group. An improvement in vision by 15 letters or more was seen in only 9% of treated patients at the 24 month visit (Figure 43.4).

The VIP study enrolled patients with subfoveal occult CNV with no classic lessions, presumed recent disease progression, larger lesion size (>4 disc areas (DA)), and a BCVA ≥ 20/50 in the affected eye.13,14 Patients were only eligible if recent disease progression – including vision loss by at least 1 line, new haemorrhage or an enlargement of the CNV by at least 10%, as seen by angiography – was documented. At 2 years, 45% of PDT-treated eyes compared to 32% of sham-treated eyes lost less than 15 letters. Subgroup analysis demonstrated that CNV with a lesion size < 4 DA or worse initial BCVA < 65 letters had a better outcome: 51% of PDT-treated eyes lost fewer than 15 letters versus 25% in the placebo group. A significant loss of 30 letters or more was observed in 29% of eyes in the PDT group versus 47% in the placebo group.

However, the VIO (Visudyne in Occult CNV) study recently demonstrated that, although PDT with Verteporfin was safe and well-tolerated in the treatment of occult with no classic CNV, the differences between PDT treated patients and the placebo group in the primary efficacy variables were not significant.14 The VIO study included patients with ≥50 years of age with lesion size ≤ 6 disc areas and BCVA of 20/4020/200. The primary outcome measures were loss of ≥15 and ≥30 letters of VA from baseline at 12 and 24 months. A total of 37% and 47% of verteporfin-treated patients versus 45% and 53% of placebo recipients lost ≥15 letters of VA at month 12 and month 24, respectively; 16% and 23% of verteporfin-treated patients versus 17% and 25% of placebo recipients lost ≥30 letters at month 12 and month 24, respectively.

These differences were not statistically significant. Therefore, PDT with Verteporfin may not be recommended for patients with subfoveal occult with no classic CNV.15

In summary, these studies demonstrated that, after PDT with verteporfin, the risk for a significant loss in vision is reduced to 50% compared to the spontaneous course of the disease in patients with neovascular AMD with predominantly classic CNV. The mean visual loss ranges between 2 and 4 lines and the proportion of patients showing improvement following verteporfin therapy is very limited. At 24 months, an improvement of ≥1 to <3 lines was seen in 8% and an increase of ≥3 to <6 lines was seen in 5% of patients.14

Later demonstration that CNV occlusion after PDT with verteporfin was associated with immediate massive exudation, followed by occlusive effects within the collateral choroid and an enhanced expression of vascular endothelial growth factor (VEGF), VEGFR-3, and pigment epithelium-derived factor, motivated the search for combination treatment strategies.16

Combination of PDT with verteporfin and intravitreal triamcinolone showed no visual benefit compared with PDT with verteporfin alone.17 Combination therapy, however, can reduce the number of treatments required by subjects who have predominantly classic CNV secondary to AMD. This reduced treatment quantity needs to be weighed against potential side effects, such as glaucoma and cataract formation.

Combination of PDT with verteporfin and anti-VEGF agents such as pegaptanib sodium or ranibizumab was safe and effective in predominantly classic lesions and reduced the need for retreatment.18 However, the prognosis in terms of vision maintenance and improvement appears to be worst in patients treated with PDT with Verteporfin in combination with intravitreal ranibizumab than in patients treated with ranibizumab alone.19

PATHOLOGIC MYOPIA

CNV represents the most important complication in pathologic myopia, occurring in a percentage ranging from 5% to 10% of cases, with a positive correlation between risk and degree of myopia.

≥3 lines. However, recurrence seriously affects long-term vision during follow-up after PDT.23 Further studies are needed to determine the efficacy of other treatments besides PDT.

CENTRAL SEROUS CHORIORETINOPATHY

PDT with half-dose verteporfin is effective in treating acute symptomatic central serous chorioretinopathy, resulting in a higher proportion of patients with absence of exudative macular detachment and better BCVA compared with placebo at 12 months.24

INTRAOCULAR VASOPROLIFERATIVE TUMORS

Exudative macular changes, such as exudative retinal detachment or cystoid macular edema, may occur in cases of vasoproliferative lesions and may lead to visual function impairment.

Combining PDT with the standard AMD protocol is an effective treatment for choroidal hemangioma in terms of resolution of exudative subretinal fluid and recovery of BCVA.25

In patients with idiopathic or secondary vasoproliferative retinal tumors, PDT with verteporfin is also a minimally invasive but effective method of treatment. Retinal tumors showed a marked shrinkage in height and resolution of leakage.26

PDT with verteporfin alone or in combination with intravitreal triamcinolone acetonide and/or intravitreal bevacizumab can also cause involution of retinal capillary hemangiomas with reduction in macular edema and improvement in BCVA.27

RETINAL ASTROCYTOMA

PDT with verteporfin can induce regression of progressive, vascularized, aggressive retinal astrocytomas and may prevent typical progression to total retinal detachment and enucleation, whether the astrocytoma is associated with tuberous sclerosis or not.28

CHOROIDAL OSTEOMA

PDT could be a therapeutic modality for CNV and induction of decalcification of extrafoveal osteoma to prevent tumor growth into the foveola.29