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

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

Effect of Bevacizumab

and Ranibizumab Injection on Corneal Neovascularization

Authors have no relevant financial interests pertaining to this research

What’s the difference?

• Increase its affinity for binding and inhibiting the growth factor

• Higher and fasterretinal penetration ability(smaller molecular size)

• Longer duration of action(larger molecular size)

Anti VEGF therapy of NV in ocular surface disease

•Anti VEGF therapy is also effective on corneal neovascularization : widely acceptedmost studies, using Bevacizumab

PURPOSE

To evaluate and compare the short term effect of

subconjunctival and/or intrastromal Bevacizumab and

Ranibizumab injection on corneal neovascularization(CNV)

in various ocular surface disorders in terms of regression

METHODS

Pateint selection• Longstanding CNV more than 6months without other corneal disease• Prospective randomized study

Injection method • Subconjunctival or intrastromal adjacent corneal NV Group I Bevacizumab (Avastin): 1.25 mg/0.05cc 0.1ml injection

Group II Ranibizumab (Lucentis): 0.5 mg/0.05cc 0.1ml injection

• Patients were followed up at 1, 7, 30 days after treatment.

Analysis of NV regressionPhotographs taken at 1:1.8 magnification using digital camera (x 4.0

zoom up, x10 magnification) under slit lamp examination

Image J software (image processing and analysis in Java, NIH) used to analyze the vascularized corneal area

S : subconjunctival injection I : Intrastromal injectionS/A : Same as above

Demographics of patients

Results

Avastin only Age Gender Etiology of NV Route of injection1 43 F Lipid keratopathy S & I

2 44 M Post LT rejection (chemical burn) S & I

3 82 M r/o Phemphigoid S & I

4 S/A S/A S/A S/A

5 70 M Post LT (rec. pterygium) S

6 60 M Post Lamellar KP S & I

7 39 M post herpetic keratitis S & I

8 49 F Cicatrization d/t Sjogren synd. S

Total : 8 eyes(7pts)

Lucentis Age Gender Etiology of NV Route of Injection

9 72 F Post herpetic keratitis S & I

10 62 F Post Lamellar KP S

11 S/A S/A S/A S/A

12 40 F Post KP (chemical burn) S & I

13 21 F Lipid keratopathy I

14 45 M Post KP (chemical burn) S

15 S/A S/A S/A S/A

16 43 M post herpetic keratitis S & I

17 37 M post herpetic keratitis S & I

Total : 9eyes(7pts)

Group I : 8 eyes of 7 patients+8 eyes of 6 patients =16 eyes of 13 patientsGroup II : 9 eyes of 7 patients

No effective regressionNo effective regressionafter 1monthafter 1month: additional Avastin injection: additional Avastin injection after 2monthsafter 2months

Bevacizumab Case No. 1Lipid keratopathy

Results

Pre injection POD # 7D

Ranibizumab Case No. 9Post herpetic CNV with corneal opacity

Results

POD # 7DPre injection

Case No.

EtiologyDecreased

%

Group I(Avastin)

12 Post KP(chemical burn) 33.8

9 Post herpetic keratitis 19.5

17 post herpetic keratitis 26.4

7 Post herpetic keratitis 33.9

6 Post Lamellar KP 26.9Mean±SD : 28.1±6.009

Group II(Lucentis)

12 Post KP(chemical burn 12.72

9 Post herpetic keratitis -10.1

17 post herpetic keratitis -12.8

10 Post Lamellar KP 2.13

13 Lipid keratopathy 20.5Mean±SD :

5.636±14.414

ResultsComparison of % of NV area reductionNumber of Available case for analysis using Image J software Group I: 5 eyes, Group II: 5 eyes

P=0.016 (Mann-Whithney test)

ResultsComparison of NV area at pre& postinjection

*

*P=0.043, Wilcoxon signed ranks test

P=0.043, Wilcoxon signed ranks test

* P=0.022, Friedman test P=0.4, Friedman test

Bevacizumab injection showed more effective to reduce CNV than Bevacizumab injection showed more effective to reduce CNV than Ranibizumab injection.Ranibizumab injection.

Why? hypothesis

- Ranibizumab : because of low MW, higher clearance rate than Bevacizumab

( half life: 4.32 days Vs 2.88days in animal study via intravitreal injection)

- Subconjunctival space :abundant subconjunctival vessel and lymphatics

much faster clearance than intravitreal cavity

- Fc portion of Bevacizumab: active transport to NV of Bevacizumab ??

mediated by NK cell, Neutrophils ,Macrophage, or mast cells

- Higher effective dosage than in intravitreal use

: especially in case of low MW Ranibizumab

DiscussionVEG

F

Limitation of this study• The improvement of NV measurement technique is needed• Too small cases & short term F/U

• Subconjunctival and intrastromal Bevacizumab

injection is effective to regress CNV induced by various causes during short term follow-up, whereas there is no significant effect for reduction of CNV after Ranibizumab injection.

• Evaluation of potential duration time, side effects and minimal effective dose of Bevacizumab including larger volume of cases in Corneal NV treatment will be needed.

• Further research for the delivery mechanism of subconjunctival Bevacizumab and Ranibizumab will be needed.

Conclusion