J Korean Ophthalmol Soc.  2008 Sep;49(9):1515-1524.

The Effect of Photodynamic Therapy with Verteporfin Retreatment on Corneal Neovascularization in Rabbits

• Jun EJ
• Rho YJ
• Kim YH
• Chung SK

Abstract

PURPOSE
This study evaluated the effect and safety of photodynamic therapy (PDT) with verteporfin retreatment on patients with corneal neovascularization.
METHODS
Corneal neovascularization was induced with a silk suture of the corneal stroma in 24 white rabbits (48 eyes). Four rabbits were examined histologically before performing PDT. Ten rabbits were chosen randomly, one eye from each rabbit was treated with PDT at 50 J/cm2, and the other eye was used as a control. Both eyes of the remaining 10 rabbits were treated with PDT at 150 J/cm2. One week later, one eye was further retreated with PDT at the same intensity. The area of corneal neovascularization was measured and evaluated histologically using light and electron microscopies.
RESULTS
The least neovascularized area was observed in the retreated group (P=0.04). The histologic examination revealed fewer new corneal vessels in the retreated group, but the corneal epithelium, stroma, and endothelium showed a normal appearance. Results from electron microscopic examination demonstrated thrombi as well as destruction and nuclear fragmentation of the vascular endothelial cells. However, there were no other changes in the cornea except for vascular endothelial cells, even in the retreated group.
CONCLUSIONS
In conclusion, these results suggest that PDT with verteporfin retreatment appears to be safe and significantly more effective in patients with regression of corneal neovascularization.

Keyword

Cornea; Neovascularization; Photodynamic therapy (PDT); Retreatment; Verteporfin

MeSH Terms

Cornea
Corneal Neovascularization
Corneal Stroma
Electrons
Endothelial Cells
Endothelium
Epithelium, Corneal
Eye
Humans
Light
Microscopy
Photochemotherapy
Porphyrins
Rabbits
Retreatment
Silk
Sutures
Triazenes
Porphyrins
Silk
Triazenes

Figure

• 

  Figure 1. Microscopic examination of the neovascularized area in the cornea after photodynamic therapy (PDT). Initially induced corneal neovascularization was observed before performing PDT (A, B, C). One week after PDT, the neovascularized area of the cornea was smaller in the 150 J/cm2 group (E, F) than in the 50 J/cm2 group (D). The same finding was observed in the corneas two weeks after PDT (G, H, I). The neovascularized area was smaller in the 150 J/cm2 group (H) than in the 50 J/cm2 group (G), and the smallest level of neovascularization was observed in the retreated group (I).

• 

  Figure 2. Comparison of the mean neovascular area in each group after PDT. The corneal neovascular area was standardized to the neovascularized corneal area before performing PDT. (A) One week after PDT, the area of neovascularization was significantly lower in the 50 J/cm2 group ( ) than in the control group ( ) and neovascularization was much lower in the 150 J/cm2 group ( ) than in the 50 J/cm2 group. B. Two weeks after PDT, the area of neovascularization was significantly decreased by the PDT, and the lowest level was observed in the retreated group ( ). (* P<0.05)

• 

  Figure 3. Light microscopic examination of a cornea with hematoxylin-eosin staining. New vessels in the cornea were induced experimentally in each group, followed by PDT. New stromal vessels in the cornea could be seen before performing PDT (A, B, C). One week after PDT, the new vessels of the corneal stroma were more regressed in the 150 J/cm2 group (E, F) than in the 50 J/cm2 group (D). The same finding was observed in the 2 -week PDT sections. The new vessels of the corneal stroma were more regressed in the 150 J/cm2 group (H-a) than in the 50 J/cm2 group (G), and they were markedly regressed in the retreated group (arrows, I-a, I-b) compared with the 150 J/cm2 group (arrows, H-a, H-b). H-b and I-b show the magnification view of the boxed area of H-a and I-a, respectively.

• 

  Figure 4. Electron microphotographs showing endothelial cellular changes in the new corneal vessels after PDT. (A) Before performing PDT, new vessels in the corneal stroma with a normal vascular endothelial cell structure (nl), vessel wall lining (w) and discoid red blood cells (rbc) were noted. (B) and (C) One week after PDT, condensed chromatin (arrow head) was observed adjacent to the nuclear envelope and an electron dense clump (arrow) was observed. There was no vessel wall lining (dotted arrow). The cytoplasm was vacuolized (v), and there were irregular red blood cells (i-rbc) suggesting thrombosis. (D) Two weeks after PDT, the nucleus of a vascular endothelial cell was fragmented (open arrow).

Reference

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