scholarly journals Effects of Regorafenib, a Multi-Kinase Inhibitor, on Conjunctival Scarring in a Canine Filtration Surgery Model in Comparison with Mitomycin-C

2019 ◽  
Vol 21 (1) ◽  
pp. 63
Author(s):  
Emika Nemoto ◽  
Shota Kojima ◽  
Tetsuya Sugiyama ◽  
Denan Jin ◽  
Shinji Takai ◽  
...  

Regorafenib eye drops were developed for treating age-related macular degeneration. This study aimed to investigate the effects of this multi-kinase inhibitor on intraocular pressure (IOP), bleb formation, and conjunctival changes in a canine filtration surgery model. Glaucoma filtration surgery models were created in 24 eyes of 24 beagles. In experiment 1 (Ex 1), regorafenib eye drops (regorafenib group: n = 6) or a vehicle (control group, n = 6) were instilled twice daily for 4 weeks postoperatively. In experiment 2 (Ex 2), regorafenib eye drops were instilled as in Ex 1 (regorafenib group: n = 6) for 12 weeks while conventional intraoperative mitomycin-C (MMC) was utilized (MMC group: n = 6), In Ex 1, only the regorafenib group showed significant IOP reduction with a significantly higher bleb score. Subconjunctival area, collagen density, vessels, and cells showing proliferation and differentiation were lower in subconjunctival tissue in the regorafenib group. In Ex 2, no significant difference was found in IOP reduction and bleb formation between the regorafenib and MMC groups; bleb walls were significantly thicker and collagen density and vessels were higher in the regorafenib group; and no differences were observed in the above-mentioned cells. Thus, regorafenib might be a better alternative to MMC for creating thicker and less ischemic blebs in glaucoma filtration surgery.

2020 ◽  
Vol 17 (1) ◽  
pp. 128-131
Author(s):  
Keith Ong ◽  
Leonard Ong

Purpose: Subconjunctival fibrosis is one of the main causes of failure of glaucoma filtration surgery. It can result in absence of a filtration bleb, a small scarred bleb, or a cystic bleb. 5-Fluorouracil (5-FU), mitomycin C (MMC), and topical steroids have been used to suppress subconjunctival fibrosis. Method: A study was done analyzing the number of postoperative subconjunctival 5-FU injections for trabeculectomy on pseudophakic eyes prior to and following the change to a BAK-free regimen. The cohort consisted of 16 consecutive cases undergoing primary trabeculectomy without intraoperative MMC or 5-FU. The trabeculectomy surgery included a groove sclerectomy procedure. Group A were 8 eyes of patients who had the author’s standard Chlorsig, Maxidex, and Prednefrin Forte eye drops tds. Group B were 8 eyes who had Chlorsig-dexamethasone and Optive-dexamethasone tds eye drops postoperatively. Results: Group B (BAK-free) patients required fewer postoperative 5-FU subconjunctival injections (average: 2.9, range: 1-5 injections) compared to Group A (BAK) patients (average: 7.3, range: 4-18 injections). This difference was statistically significant (P = 0.02, unpaired t-test). All patients had functioning blebs and did not require glaucoma medications to maintain target intraocular pressure. The Group B (BAK-free) patients had more diffuse blebs than the Group A (BAK) patients. Conclusion: The results demonstrated that when BAK was eliminated from postoperative eye drops in trabeculectomy, the number of postoperative 5-FU injections was reduced.


Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4422
Author(s):  
Wen-Sheng Cheng ◽  
Ching-Long Chen ◽  
Jiann-Torng Chen ◽  
Le-Tien Lin ◽  
Shu-I Pao ◽  
...  

Scar formation can cause the failure of glaucoma filtration surgery. We investigated the effect of AR12286, a selective Rho-associated kinase inhibitor, on myofibroblast transdifferentiation and intraocular pressure assessment in rabbit glaucoma filtration surgery models. Cell migration and collagen contraction were used to demonstrate the functionality of AR12286-modulated human conjunctival fibroblasts (HConFs). Polymerase chain reaction quantitative analysis was used to determine the effect of AR12286 on the production of collagen Type 1A1 and fibronectin 1. Cell migration and collagen contraction in HConFs were activated by TGF-β1. However, compared with the control group, rabbit models treated with AR12286 exhibited higher reduction in intraocular pressure after filtration surgery, and decreased collagen levels at the wound site in vivo. Therefore, increased α-SMA expression in HConFs induced by TGF-β1 could be inhibited by AR12286, and the production of Type 1A1 collagen and fibronectin 1 in TGF-β1-treated HConFs was inhibited by AR12286. Overall, the stimulation of HConFs by TGF-β1 was alleviated by AR12286, and this effect was mediated by the downregulation of TGF-β receptor-related SMAD signaling pathways. In vivo results indicated that AR12286 thus improves the outcome of filtration surgery as a result of its antifibrotic action in the bleb tissue because AR12286 inhibited the TGF-β receptor-related signaling pathway, suppressing several downstream reactions in myofibroblast transdifferentiation.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yuji Yamamoto ◽  
Atsushi Mukai ◽  
Toru Ikushima ◽  
Yasuo Urata ◽  
Shigeru Kinoshita ◽  
...  

AbstractInhibition of fibrosis is indispensable for maintaining filtering blebs after glaucoma filtration surgery (GFS). The purpose of this study was to investigate the ability of a pluripotent epigenetic regulator OBP-801 (OBP) to ameliorate extracellular matrix formation in a rabbit model of GFS. Rabbits that underwent GFS were treated with OBP. The gene expression profiles and intraocular pressure (IOP) were monitored until 30 postoperative days. The bleb tissues were evaluated for tissue fibrosis at 30 postoperative days. In in vitro models, OBP interfered the functions of diverse genes during the wound-healing process. In in vivo GFS models, the expressions of TGF-β3, MMP-2, TIMP-2 and 3, LOX, COL1A and SERPINH1 were significantly inhibited at 30 postoperative days in the OBP group compared with those in the vehicle control group. OBP treatment involving subconjunctival injection or eye drops showed no adverse effects, and reduced levels of α-SMA and collagen deposition at the surgical wound site. OBP maintained the long-lived bleb without scar formation, and IOP was lower at 30 postoperative days compared with the vehicle control group. These findings suggest that OBP is an effective and useful candidate low-molecular-weight agent for improving wound healing and surgical outcomes in a rabbit model of GFS.


2021 ◽  
Vol 10 (10) ◽  
pp. 2054
Author(s):  
Gerasimos Kopsinis ◽  
Dimitrios Tsoukanas ◽  
Dimitra Kopsini ◽  
Theodoros Filippopoulos

Conjunctival wound healing determines success after filtration surgery and the quest for better antifibrotic agents remains active. This study compares intracameral bevacizumab to sub-Tenon’s mitomycin C (MMC) in trabeculectomy. Primary open-angle or exfoliative glaucoma patients were randomized to either bevacizumab (n = 50 eyes) or MMC (n = 50 eyes). The primary outcome measure was complete success, defined as Intraocular Pressure (IOP) > 5 mmHg and ≤ 21 mmHg with a minimum 20% reduction from baseline without medications. Average IOP and glaucoma medications decreased significantly in both groups at all follow-up points compared to baseline (p < 0.001), without significant difference between groups at 3 years (IOP: bevacizumab group from 29 ± 9.4 to 15 ± 3.4 mmHg, MMC group from 28.3 ± 8.7 to 15.4 ± 3.8 mmHg, p = 0.60; Medications: bevacizumab group from 3.5 ± 0.9 to 0.5 ± 1, MMC group from 3.6 ± 0.7 to 0.6 ± 1.1, p = 0.70). Complete success, although similar between groups at 3 years (66% vs. 64%), was significantly higher for bevacizumab at months 6 and 12 (96% vs. 82%, p = 0.03; 88% vs. 72%, p = 0.04, respectively) with fewer patients requiring medications at months 6, 9 and 12 (4% vs. 18%, p = 0.03; 6% vs. 20%, p = 0.04; 8% vs. 24%, p = 0.03, respectively). Complication rates were similar between groups. In conclusion, intracameral bevacizumab appears to provide similar long-term efficacy and safety results as sub-Tenon’s MMC after trabeculectomy.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaochen Wang ◽  
Guiqiu Zhao ◽  
Jing Lin ◽  
Nan Jiang ◽  
Qian Wang ◽  
...  

Aims. The aim of this study was to assess the efficacy and safety of timolol in the treatment of myopic regression after laser in situ keratomileusis (LASIK).Methods. We searched MEDLINE, CENTRAL, EMBASE, China National Knowledge Infrastructure (CNKI), and Chinese Biological Medicine (CBM) from the inception to July 2015 for relevant randomized controlled trials that examined timolol therapy for myopic regression. The methodological quality of the studies included was assessed using the Revman 5.3 software.Results. We included six clinical trials involving 483 eyes in this review, including 246 eyes in treated group and 237 eyes in controlled group. We observed statistically significant improvements on the postoperative SE in the 3 months. However, the change of CCT was not statistically different between the control group and the experimental group. There were fewer cases of IOP, UDVA, and CDVA in treated group having significant difference from the controlled group.Conclusions. Topical timolol could be an effective treatment for reduction of myopic regression especially the spherical errors after myopic LASIK. Further RCTs with larger sample sizes for these trials are warranted to determine the efficacy and limitation for myopic regression after LASIK.


2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Jarno E.J. Wolters ◽  
Ralph J.S. van Mechelen ◽  
Rana Al Majidi ◽  
Leonard Pinchuk ◽  
Carroll A.B. Webers ◽  
...  

Vision ◽  
2020 ◽  
Vol 4 (2) ◽  
pp. 24
Author(s):  
Syed Naqib Ahmed ◽  
Syed Mohammed Shahid ◽  
Mayank A. Nanavaty

Purpose: To present a case of delayed onset scleromalacia and conjunctival bleb formation one year after conjunctival melanoma excision with intraoperative use of mitomycin-C (MMC) and double-freeze-thaw technique. Methods: Case report. Results: A 69-year-old woman had a conjunctival melanoma excised by the ‘no touch technique’ with intraoperative application of 0.02% MMC for 3 min on bare sclera, freeze-thaw cryotherapy and amniotic membrane transplant performed elsewhere. Three months later, she presented to us with a red, sore and painful right eye. Examination revealed severe scleritis. She was treated with lubricants and oral steroids for 6 weeks. She settled well with no recurrence of melanoma. At one year, she developed scleromalacia and conjunctival blebs in the inferonasal quadrant of right eye. She remains under closer observation as she is at high risk of perforation. Conclusion: Caution should be exercised with intraoperative use of MMC on bare sclera during excision and cryotherapy of conjunctival melanoma. As published in the literature, when using MMC, it is recommended to use the lowest dose topically in the form of eye drops in the postoperative period for the shortest time to avoid any sight-threatening complications.


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