The Effects of the Subconjunctival Injection of Bevacizumab (Avastin®) in Recurrrent Pterygium Cheil Eye Hospital Young Jeung Park, MD Jong Wook Lee, MD Kyoo Won Lee, MD @ Recurrent pterygium 환자에서 bevacizumab subconjunctival injection의 효과에 대해 알아보았습니다. (다음)

Background Vascular Endothelial Growth Factor (VEGF) - Mediator cytokine of pathological angiogenesis - Key transcriptional regulator of hypoxic responses Vascular endothelial growth factor는 pathologic angiogensis에 관여하는 cytokine으로 hypoxic response시에 key regulator로 작용합니다. 특히 ARMD, Diabetic retinopathy, Neovascular Glaucoma, Pterygium, Corneal neovascularization 과 같은 ocular angiogenesis에 key role로 작용합니다.

Angiogenesis in pterygium Angiogenic stimulators↑, inhibitors↓ : the formation and progression of pterygium Abundant expression of VEGF in pterygium tissue Application of anti-VEGF therapy Inducing regression of blood vessels in pterygium Pterygium에서 angiogenesis에 대해 보면 정상 결막조직보다 군날개에서 VEGF가 더 많이 관찰되었으며 군날개의 형성 및 진행에서 angigenic inhibitor는 감소되고, stimulator는 증가되어 있습니다. 이에 군날개 조직에서 VEGF가 많이 발현되어 있기에 anti-VEGF 치료시 vessel이 regression 될 것을 디자인 하였습니다. (다음)

Bevacizumab (Avastin®) Humanized recombinant Ab : binds all isoforms of VEGF Bevacizumab은 VEGF의 모든 isoform에 binding하는 antibody로 FDA에 metastatic colorectal cancer의 치료제로 승인되어있습니다.

Purpose the subconjunctival injection of Bevacizumab (Avastin®) To evaluate the effects of the subconjunctival injection of Bevacizumab (Avastin®) in recurrent pterygium. Recurrent pterygium 환자에서 bevacizumab subconjuncival injection 의 효과에 대해 알아보고자 하였습니다. (다음)

Materials and Methods From December 2006 to May 2007 20 eyes with recurrent pterygium Bevacizumab subconjunctival injection (0.2cc) Folllowed up at 1st week, 2nd week, 4th week, and every month thereafter. Evaluation - Clinical results (degree of conjunctival injection) - ICG angiography : at pre-injection and at 2 weeks post-injection) - Ocular and systemic complications 2006년 12월부터 2007년 5월까지 본원에서 치료받은 재발성군날개 환자 20안을 대상으로 하였습니다. Bevacizumab을 결막하로 0.25cc 주사하였으며 주사후 1주,2주 4주 그 후엔 매달 임상 경과를 관찰하였습니다. ICG 형광안저촬영은 주사전과 주사후 2주째 측정하였으며 그외 각막 및 결막등 눈의 합병증과 전신 부작용에 대해 관찰하였습니다. 관찰기간은 평균 17주입니다. (다음)

Method of subconjunctival Bevacizumab injection Bevacizumab (Avastin®) - Refrigerated before use - No more than 14 days Topical anesthesia 5% povidone/iodine and topical antibiotics 0.2cc (5.0mg) of Avastin® injected subconjuntivally with tuberculin syringe(30G) Topical antibiotics & steroid Bevacizumab의 결막하 주사방법에 대해 보시겠습니다.

The level of conjunctival injection Level 1 - Reached the rock-bottom after injection. Level 2 - Level between 1~3. Level 3 - Similar level before injection. Level 4 - Increase of conjunctival injection compared to the degree before Bevacizumab injection. Wilcoxon signed ranks test

Vessel thickness ICG ant. segment angiography with HRA II® - 10 eyes - Before and 2 weeks after the subconjunctival injection - Measured 5 vessels thickness per eye - Larger than 0.01mm (possible to measure the thickness) Paired t-test

Demography Patients No. 20 Sex (M / F) 6/14 Age (years) (Mean ± SD) Patients No. 20 Sex (M / F) 6/14 Age (years) 53.45 ± 18.32(38~72) Follow-up period (weeks) 17.10±8.22 Demography 보시겠습니다. 총 20명의 환자 중 남자는 6명 여자는 14명이었으며 평균 나이는 53.45세 였으며, 경과관찰기간은 17.1주 였습니다. (다음)

Clinical Results Before treatment 1 week after treatment

Progressive change in the level of conjunctival injection Pre-injection level * Wilcoxon signed ranks test

Changes in degree of conjunctival injection B. 2 weeks after D. 5 months after C. 2 months after A. Pre-injection

B. 2 weeks after D. 5 months after C. 2 months after A. Pre-injection

A. Pre-injection B. 2 weeks after C. 2 months after D. 5 months after

B. 2 weeks after D. 5 months after C. 2 months after A. Pre-injection

Ant. segment photographs and ICG angiopgaphy Pre-injection 2 weeks after 0.04mm 0.03mm 0.02mm

The change of conjunctival vessel thickness of recurrent pterygium * Paired T-test

Complications Subconjunctival hemorrhage - 4 cases  resolved within 1 week Rebound conjunctival injection - 2 cases  improved after reinjection Other ocular & systemic complication - none

Rebound conjunctival injection Case-1 A. before injection C. 2 months after B. 2 weeks after D. after reinjection

Rebound conjunctival injection Case-2 A. before injection C. 2 months after B. 2 weeks after D. after reinjection

Conclusions After injection, Conjunctival injection was decreased than before injection. The maximum effect of subconjunctival injection of pterygium lasted less than 1 month. In ICG, the thickness of conjunctival blood vessels decreased(30.14%). The subconjunctival injection of Bevacizumab 0.2cc was effective for recurrent pterygium

Additional research - timing of additional injection - the long term effect on the progress of recurrent pterygium.

Rebound phenomenon Matsumoto Y et al. Rebound macular edema following bevacizumab therapy for retinal venous occlusive disease. Retina 2007;27:426-31 Inhibition of the VEGF pathway by Bevacizumab → Upregulate VEGF receptors → An increase in VEGF receptors → the endothelial cells more sensitive to the VEGF

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