There are several previous studies regarding the histopathological findings after PDT, mostly from surgically excised CNV membranes. The report using a postmortem eye showed occluded vascular channels and PTAH‐positive thrombi in vessels in the CNV 2 weeks after PDT.10
In our current study, the vascular channels were patent in both specimens, and no thrombi were noted within the vessels at 3 months (case 1) and 17 months (case 2) after a single treatment of PDT. A report regarding the histopathological findings of surgically excised CNV 4 months after PDT revealed that there were patent vascular channels.2
A clinicopathological study with eight submacular choroidal neovascular membranes obtained from 3 days to 152 days after PDT demonstrated that the CNV obtained 3 days after PDT showed partial vascular occlusion, which was not present in specimens obtained at longer intervals after PDT (29–152 days).7
Ultrastructural examination revealed evidence of vascular damage in all the specimens obtained at longer intervals after PDT, and all the specimens had patent CNV. Considering this reopening or regrowth of vascular channels in CNV after PDT, the current retreatment interval of 3 months seems appropriate.
Transient choroidal ischaemia after PDT with verteporfin in AMD has been observed previously in human and animal studies.13,14,15
Tzekov and colleagues demonstrated histopathological changes in monkeys 9 months after a single session of PDT. They included fibrovascular proliferation in the choriocapillaris associated with closure, and RPE degeneration and necrosis.16
Another study showed perfusion defects in the choroid in patients receiving a single PDT. The defects started at 1 day and were still present at 3 months after PDT.17
In our study, there were no light‐microscopic abnormalities in the choroid (figs 1B and 2C), but the cellular and subcellular effects as well as the functional effects of long‐term PDT cannot be completely ruled out. The clinical effect of the multiple sessions of PDT on the choroid warrants further histopathological evaluation.
Patent blood vessels were present in the CNV in our cases after a single session of PDT. CNV growth is a dynamic process over time, with initiation, inflammatory active, and involutional or inflammatory inactive stages.12,18
RPE cells and macrophages interact with each other during the initiation stage of CNV by increased production of monocyte chemotactic protein by RPE.18
Macrophages and RPE express VEGF in the active inflammatory stage, thus stimulating angiogenesis. This is followed by an inactive inflammatory (involutional) stage with decreased production of cytokine, especially VEGF, and increased amount of fibrosis as CNV matures.18
A recent study showed that VEGF expression was significantly increased in RPE in CNV treated with PDT, shortly after the treatment.19
The balance between VEGF and pigment epithelium derived factor (PEDF) was disturbed in the CNV membranes following PDT, resulting in an increased VEGF to PEDF ratio in the RPE and stroma.20
This situation favours angiogenesis in the CNV. These findings are compatible with the persistence of patent blood vessels in the CNV after PDT in our cases, by recanalisation and/or angiogenesis.
The median size of surgically excised CNV was 1980×325 µm in patients with AMD enrolled in the Submacular Surgery Trials (SST), and 1800×395 µm in patients with predominantly haemorrhagic lesions attributed to AMD.9
The CNV from our current cases 1 and 2 measured 400×70 µm and 700×170 µm, respectively, thus exhibiting a smaller size compared with the results from SST. Even though PDT does not result in the permanent closure of vascular channels in CNV, it appears to shorten the active stage of the CNV growth, thus accelerating the involutional stage.12
This corresponds to a smaller CNV size and preservation of photoreceptors. Limitations of our study included the limited number of the cases (2 eyes), the lack of detailed clinical information of the patients and lack of ultrastructural information.
Our first case received a single intravitreal injection of triamcinolone with the PDT. High doses of intravitreal triamcinolone (more than 4 mg) have been shown to cause structural changes such as destruction of photoreceptor outer segments and migration of macrophage‐like cells in the subretinal spaces in rabbits.21
For the purposes of our study, the dose of 4 mg in the vitreous of a human eye is equivalent to 0.5 or 1 mg in the rabbit eyes, so it is assumed that the triamcinolone had no tissue effect by light microscopy.
In summary, although involution with fibrous tissue proliferation occurred, PDT did not result in permanent occlusion of vascular channels in CNV. However, PDT does appear to limit the size of CNV and accelerates CNV involution.