Two Cases of Persistent Epithelial Defect After Subconjunctival and

Intrastromal Bevacizumab Injection in Patients With Corneal

Neovascularization

Hyung Seok Cho, M.D., Jin Hyoung Kim, M.D., Ph.D., Doh Lee, M.D., Ph.D.

Department of Ophthalmology, Ilsan Paik Hospital, Inje University College of Medicine, Gyeonggi, Korea

The authors have no financial interest in the subject matter of this poster

INTRODUCTION Bevacizumab (AvastinⓇ; Roche, San Francisco, CA) : a recombinant humanized monoclonal immunoglobulin G1 antibody directed against VEGF : Anti VEGF therapy is effective on corneal neovascularization - widely accepted

Anti-VEGF in corneal epithelium• Bevacizumab Application Delays Epithelial Healing in Rabbit Cornea (Kim TI, Chung JL, Hong JP, Min K, Seo KY, Kim EK. Invest Ophthalmol Vis Sci. 2009

Oct;50(10):4653-9) VS• Bevacizumab Accelerates Corneal Wound Healing by Inhibiting TGF-

β2 Expression in Alkali-Burned Mouse Cornea (Lee SH, Leem HS, Jeong SM, Lee K. BMB Rep. 2009 Dec 31;42(12):800-5.)

PURPOSE

To report two cases of persistent epithelial defect after subconjunctival and intrastromal injection of bevacizumab to suppress corneal neovascularization.

METHOD (Case 1) A 45-year-old man with a history of penetrating

keratoplasty Admitted for corneal neovascularization Subconjunctival and intrastromal

bevacizumab(1.25mg/0.05cc) injection to suppress corneal neovascularization

Figure 1. Anterior segment photography of cornea (A). Neovascularization of the cornea was observed Stained with fluorescein (B) Stained with fluorescein ; arrows indicate vascularized area.

A B

METHOD (Case 2) A 40-year-old women with a history of deep lamellar

keratoplasty Admitted for corneal neovascularization Subconjunctival and intrastromal

bevacizumab(1.25mg/0.05cc) injection to suppress corneal neovascularization

Figure 2. Anterior segment photography of cornea. (A), (B) Neovascularization of the cornea was observed ; arrows indicate vascularized area.

A B

RESULT (Case 1)

Following subsequent four time injections, ocular pain and conjunctival injection was developed.

In slit-lamp examination, corneal NVs were regressed but epithelial defect corvering 14% of the whole cornea was detected.

Figure 3. Anterior segment photography of cornea (A) Neovascularized areas were regressed after treated with subconjunctival & intrastromal bevacizumab injection but epithelial defect was occurred. (B) Stained with fluorescein.

A B

RESULT (Case 1) The corneal epithelial defect was refractory to conservative

treatment. Amniotic membrane transplantation was performed. One month after surgery, corneal epithelial defect was

disappeared and cornea was stable.

Figure 4. Anterior segment photography of cornea. (A) AMT was performed. (B) Total re-epithelialization was achieved 1month later after AMT.

A B

RESULT (Case 2)

After the third injection, she complained ocular pain. In slit lamp examination, corneal epithelial defect occupying

6% of the cornea was observed.

Figure 5. Anterior segment photography of cornea (A). Stained with fluorescein (B). Neovascularized areas were regressed after treated with subconjunctival & intrastromal bevacizumab injection but epithelial defect was occurred.

A B

RESULT (Case 2)

Two months after conservative treatment, no epithelial defect was detected and the cornea was stable.

Figure 6. Anterior segment photography of cornea (A). Stained with fluorescein (B).Total re-epithelialization was achieved 2month later after conservative therapy.

A B

CONCLUSION

Bevacizumab may be effective to inhibit corneal neovascularization.

But, bevacizumab also may induces corneal epithelial defect.

Integrin : well-known adhesion molecules (key role of corneal wound healing) Bevacizumab may inhibits the expression of integrin.

A careful observation and management will be needed in patients with corneal neovascularization after bevacizumab injection.