Histological findings of surgically excised choroidal neovascular membranes after photodynamic therapy

Abstract

Aim-To investigate eVects of photodynamic therapy (PDT) on human choroidal neovascularisation (CNV).Methods-Two patients with recurrences after PDT with verteporfin underwent surgical extraction of the CNV. Immediately after surgical excision the subfoveal neovascular membranes were divided for light microscopic and for electron microscopic processing. For light microscopy tissues were embedded in paraYn. Sections were stained with haematoxylin and eosin, and the periodic acid SchiV (PAS) reaction was performed to determine histological diagnosis and to ensure tissue quality. For electron microscopy the specimens were fixed in glutaraldehyde and embedded in epoxy resin. Semithin sections were stained with uranyl acetate and lead citrate and examined with a transmission electron microscope. Results-Light microscopy showed thick fibrovascular membranes in both cases. On the outer surface remnants of retinal pigment epithelial cells resting on thickened inner aspect of Bruch's membrane were found. On the retinal side some outer segments were found. The membrane showed areas with irregularly shaped vessels. Electron photomicrographs showed occluded vessels within the CNV containing thrombotic masses and/or ultrastructural damage of the neovascular endothelium. Most of the vessels presented regressive changes with vacuolisation and fragmentation of the neovascular endothelium accompanied by disintegration of the endothelial cell layer. Extravasation of red blood cells was observed. Occasionally, vessels with normal endothelium containing intact red blood cells were observed. Some vessels contained immature endothelial cells. At some locations the retinal pigment epithelium cells (RPE) were metaplastic showing highly vacuolised cytoplasm. Conclusions-These findings suggest that the evidence of fluorescein leakage from the CNV and enlargement of the neovascular complex following PDT could be related to new vessel growth and recanalisation of occluded vessels. Additionally, RPE disturbances were observed in the specimens. This finding may be related to the original pathology or could indicate that PDT treatment may result in RPE atrophy. Age related macular degeneration (AMD) is the leading cause of new blindness in the elderly, and choroidal neovascularisation (CNV) is responsible for 80% of severe visual loss in patients with AMD.

Potential long-term inhibition of ocular neovascularisation by recombinant adeno-associated virus-mediated secretion gene therapy

“…31 However, all these approaches do not address the underlying stimuli of NV and recurrences are a significant problem. [32][33][34] Therefore, new therapies aimed at blocking the underlying stimuli for new vessel growth are necessary to achieve better treatment for these patients. Treatment with sFlt-1, a naturally-occurring truncated and secreted form of VEGF receptor Flt-1, has been shown to inhibit angiogenesis in a variety of disease models.…”

Long-term outcome of intravitreal ranibizumab treatment, compared with photodynamic therapy, in patients with polypoidal choroidal vasculopathy

“…Similar to this study, the long-term outcomes of AMD after PDT have indicated several serious problems. For example, long-term influences of PDT, such as damage to the retinal pigment epithelium after PDT 21 and choroidal hypoperfusion (which is correlated with chorioretinal atrophy), 22 have been reported.…”

Effect of photodynamic therapy on the function of the outer blood-retinal barrier in an in vitro model

“…Histological and electron microscopic examination of subretinal membranes removed after PDT revealed metaplastic changes in RPE [35]. Evaluation of the transient, PDT-induced neurosensory detachment showed that its size correlated more closely to the diameter of the laser treatment spot than to that of the CNV, suggesting that non-thermal laser may result in an outer BRB dysfunction causing transient retinal elevation [20].…”