Combined Treatment with Bevacizumab and 5-Fluorouracil Attenuates the Postoperative Scarring Response after Experimental Glaucoma Filtration Surgery

How, Alicia C.; Chua, Jocelyn; Charlton, Amanda; Su, Roseline; Lim, Marcus; Kumar, Rajesh S.; Crowston, Jonathan G; Wong, Tina

doi:10.1167/iovs.09-3949

Cited by 63 publications

(47 citation statements)

References 33 publications

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“…The rabbit has been considered as a useful model for evaluating histopathology or clinical outcome in glaucoma surgery. [20][21][22][23]27,28 In addition, it has been known that there are little difference in protein distribution between human and rabbit aqueous humor. 29 Therefore, we believe that our findings may apply to humans to a certain extent.…”

Section: Discussionmentioning

confidence: 99%

Foreign Body Reaction in Glaucoma Drainage Implant Surgery

Jung

Lee

Kim

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To investigate the histopathology of the foreign body reaction (FBR) and the effect of aqueous humor on it in glaucoma drainage implant surgery. METHODS.A glaucoma drainage device was implanted into 20 New Zealand white rabbits. We monitored the histopathology of blebs at microscopic levels from 3 days to 8 weeks postoperatively. Hematoxylin and eosin staining, Masson's trichrome staining, anti-actin and a-smooth muscle immunofluorescence staining, and antiproliferating cell nuclear antigen immunohistochemistry were performed. To observe effects of aqueous humor on FBR, we designed two implant models. One group received a plate with a tube placed in the anterior chamber (experimental group), whereas the other received the plate cut from the tube (control group).RESULTS. Foreign body giant cells were found along the inner border of blebs, and the innermost layer of blebs demonstrated a densely packed collagenous stratum in both groups. The number of foreign body giant cells was suppressed in the experimental group compared with the control group (P < 0.001). Fibroblast division was more active in the experimental group than that in the control group. Masson's trichrome staining demonstrated that the innermost avascular collagenous layer was much thicker in the experimental group than that in the control group (P ¼ 0.021). The extent of a-SMA staining was greater in the experimental group than that in the control group.CONCLUSIONS. In the aqueous humor environment, wound healing around a glaucoma drainage implant revealed a unique FBR with the relatively small number of foreign body giant cells and reinforced fibrotic encapsulation.

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Section: Discussionmentioning

confidence: 99%

Foreign Body Reaction in Glaucoma Drainage Implant Surgery

Jung

Lee

Kim

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…In bevacizumab treated group (Group B and Group D), the rabbits maintained a low IOP for a longer time and a relative long filtering bleb survival function comparing to the BSS and PECE groups, and post-operative inflammatory infiltration is mild, and no toxic effects were observed on the tissue tested. Furthermore, the following 1-2 weeks afterwards GFS is the critical period of scar tissue generated in the conjunctival tissues and filtering aisle [40][41][42]. We observed that PECE hydrogel was slowly degraded after injecting into the anterior chamber of a rabbit eye model and thoroughly degraded in the third week.…”

Section: Discussionmentioning

confidence: 99%

Effects of bevacizumab loaded PEG-PCL-PEG hydrogel intracameral application on intraocular pressure after glaucoma filtration surgery

Han

Wang

et al. 2015

J Mater Sci: Mater Med

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PEG-PCL-PEG (PECE) hydrogel for intracameral injection as a sustained delivery system can get a stable release of the medication and achieve an effective local concentration. The injectable PECE hydrogel is thermosensitive nano-material which is flowing sol at low temperature and can shift to nonflowing gel at body temperature. This study evaluated the intracameral injection of bevacizumab combined with a PECE hydrogel drug release system on postoperative scarring and bleb survival after experimental glaucoma filtration surgery. The best result was achieved in the bevacizumab loaded PECE hydrogels group, which presented the lowest IOP values after surgery. And the blebs were significantly more persistent in this group. Histology, Massion trichrome staining and immunohistochemistry further demonstrated that glaucoma filtration surgery in combination with bevacizumab loaded PECE hydrogel resulted in good bleb survival due to scar formation inhibition. In conclusions, this study demonstrated that bevacizumab-loaded PECE hydrogel for intracameral injection as a sustained delivery system provide a great opportunity to increase the therapeutic efficacy of glaucoma filtration surgery.

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“…How с включением дополнительной группы кроликов для оценки синергизма беваци-зумаба и 5-фторурацила. Наилучшие результаты были отмечены именно в этой группе [34].…”

Section: применение ингибиторов Vegf после фистулизирующих антиглаукоunclassified

VEGF inhibitors in glaucoma surgery

Mamikonyan¹,

Petrov²,

Сафонова³

2016

Ophthalmology Reports

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Vascular endothelial growth factor (VEGF) is a signaling protein, that controls vasculogenesis, angiogenesis, vascular support and stimulates permeability of small blood vessels. The following isoforms are presently known: VEGF-A, VEGF-B, VEGF-C, VEGF-В and PGF. VEGF-A, that regulates neoangiogenesis and fibroblast formation, is thought to play the most important role in human organism. Increased expression of VEGF may lead to development and aggravation of pathological conditions including oncology. The article presents a review of preclinical and clinical studies of the main VEGF-inhibitors - bevacizumab and ranibizumab, as well as a brief account on other existing medications of this group. It describes ophthalmological indications for the use of antiangiogenetic agents, as well as the ways of their possible off-label use. The review presents investigations of intravitreal and intracameral injections of VEGF-inhibitors in patients with retinal, chorioidal, iris, and anterior chamber angle neovascularization. It gives examples of successful anti-VEGF use before Ahmed glaucoma valve drainage device implantation and in cases of neovascular glaucoma, induced by radiation therapy for intraocular tumors. Tenon’s capsule’s fibroblasts take part in the process of postoperative wound healing and scarring. According to the latest research, this process could be modulated by angiogenesis inhibitors. This review also recounts the use of anti-angiogenic agents to inhibit postoperative fibroblast proliferation, when used as monotherapy, or as an adjuvant to mitomycin С or 5-fluorouracil. It reviews the research on VEGF-inibitors use in combination with postoperative needling.

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Combined Treatment with Bevacizumab and 5-Fluorouracil Attenuates the Postoperative Scarring Response after Experimental Glaucoma Filtration Surgery

Abstract: The results provide compelling evidence that combined bevacizumab and 5-FU offers superior antifibrotic effect over monotherapy in a model of glaucoma filtration surgery, while prolonging bleb survival at the same time. A synergistic effect is suggested to be present.

Cited by 63 publications

References 33 publications

Foreign Body Reaction in Glaucoma Drainage Implant Surgery

Foreign Body Reaction in Glaucoma Drainage Implant Surgery

Effects of bevacizumab loaded PEG-PCL-PEG hydrogel intracameral application on intraocular pressure after glaucoma filtration surgery

VEGF inhibitors in glaucoma surgery

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