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Graefe's Archive for Clinical and Experimental Ophthalmology

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01-10-2012 | Basic Science

Suppression of avascular bleb formation by a thin biodegradable film in a rabbit filtration surgery with mitomycin C

Authors: Tetsuhiko Okuda, Tomomi Higashide, Yukako Fukuhira, Hiroaki Kaneko, Masatsugu Shimomura, Kazuhisa Sugiyama

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 10/2012

Abstract

Background

Avascularity of the bleb is regarded as a risk of bleb infection, which is the most serious complication after filtration surgery with mitomycin C (MMC). There is no perfect way to prevent avascular bleb formation. We hypothesized that keeping the conjunctiva away from direct exposure to aqueous filtration may suppress avascular bleb formation after filtration surgery with MMC. In order to prove our hypothesis, we investigated whether a thin biodegradable, honeycomb-patterned film (HPF) can reduce bleb avascularity in a rabbit model of filtration surgery with mitomycin C (MMC).

Methods

A fornix-based full-thickness filtration surgery was performed in one eye of each of five rabbits (control group). The same surgery with intraoperative MMC treatment was done in both eyes of six rabbits, with one eye receiving a 14-μm-thick HPF made from poly(L-lactide-co-ε-caprolactone), which was placed subconjunctivally over the filtration site with the honeycomb surface facing up. Intraocular pressure (IOP) measurements, bleb evaluations using ultrasound biomicroscopy (UBM), and in vivo confocal microscopy (IVCM) were performed periodically for 4 weeks postoperatively followed by histological examination.

Results

The postoperative IOP decrease and bleb survival were significantly greater in MMC-treated eyes than in control eyes, and were similar between MMC-only and MMC + HPF eyes. The avascular area in the bleb persisted for 4 weeks in MMC-only eyes. Postoperative IVCM showed morphological changes of the conjunctival epithelial cells (i.e., enlarged and variable in size and shape) and epithelial defects in MMC-only eyes, and significantly lower density of connective tissue and vascularity in the subepithelial space in MMC-only eyes compared to the control eyes. These IVCM findings agreed with those by UBM and histology. Bleb avascularity shown by clinical bleb appearance, IVCM and histology, conjunctival epithelial damage shown by IVCM and histology, and loose subepithelial connective tissue shown by UBM, IVCM, and histology were all reduced in MMC + HPF eyes compared to MMC-only eyes.

Conclusions

IVCM successfully showed the characteristic conjunctival damage in MMC-treated blebs. The concomitant use of a thin biodegradable HPF reduced avascularity and conjunctival damage in blebs, without compromising filtration in rabbits following filtration surgery with MMC.

Wilkins M, Indar A, Wormald R (2001) Intra-operative mitomycin C for glaucoma surgery. Cochrane Database Syst Rev: CD002897

Costa VP, Wilson RP, Moster MR, Schmidt CM, Gandham S (1993) Hypotony maculopathy following the use of topical mitomycin C in glaucoma filtration surgery. Ophthalmic Surg 24:389–394PubMed

Dreyer EB, Chaturvedi N, Zurakowski D (1995) Effect of mitomycin C and fluorouracil-supplemented trabeculectomies on the anterior segment. Arch Ophthalmol 113:578–580PubMedCrossRef

Greenfield DS, Suner IJ, Miller MP, Kangas TA, Palmberg PF, Flynn HW Jr (1996) Endophthalmitis after filtering surgery with mitomycin. Arch Ophthalmol 114:943–949PubMedCrossRef

Higginbotham EJ, Stevens RK, Musch DC, Karp KO, Lichter PR (1996) Bleb-related endophthalmitis after trabeculectomy with mitomycin C. Ophthalmology 103:650–656PubMed

Budenz DL, Hoffman K, Zacchei A (2001) Glaucoma filtering bleb dysesthesia. Am J Ophthalmol 131:626–630PubMedCrossRef

Mochizuki K, Jikihara S, Ando Y, Hori N, Yamamoto T, Kitazawa Y (1997) Incidence of delayed onset infection after trabeculectomy with adjunctive mitomycin C or 5-fluorouracil treatment. Br J Ophthalmol 81:877–883PubMedCrossRef

Soltau JB, Rothman RF, Budenz DL, Greenfield DS, Feuer W, Liebmann JM, Ritch R (2000) Risk factors for glaucoma filtering bleb infections. Arch Ophthalmol 118:338–342PubMed

Yamamoto T, Kuwayama Y (2011) Collaborative Bleb-related Infection Incidence and Treatment Study Group. Interim clinical outcomes in the collaborative bleb-related infection incidence and treatment study. Ophthalmology 118:453–458PubMedCrossRef

10.

Hu CY, Matsuo H, Tomita G, Suzuki Y, Araie M, Shirato S, Tanaka S (2003) Clinical characteristics and leakage of functioning blebs after trabeculectomy with mitomycin-C in primary glaucoma patients. Ophthalmology 110:345–352PubMedCrossRef

11.

Anand N, Arora S, Clowes M (2006) Mitomycin C augmented glaucoma surgery: evolution of filtering bleb avascularity, transconjunctival oozing, and leaks. Br J Ophthalmol 90:175–180PubMedCrossRef

12.

Agbeja AM, Dutton GN (1987) Conjunctival incision for trabeculectomy and their relationship to the type of bleb formation—a preliminary study. Eye 1:738–743PubMedCrossRef

13.

Wells AP, Cordeiro MF, Bunce C, Khaw PT (2003) Cystic bleb formation and related complications in limbus- versus fornix-based conjunctival flaps in pediatric and young adult trabeculectomy with mitomycin C. Ophthalmology 110:2192–2197PubMedCrossRef

14.

Hirooka K, Mizote M, Baba T, Takagishi M, Shiraga F (2009) Risk factors for developing avascular filtering bleb after fornix-based trabeculectomy with mitomycin C. J Glaucoma 18:301–314PubMedCrossRef

15.

Fukuhira Y, Kitazono E, Hayashi T, Kaneko H, Tanaka M, Shimomura M, Sumi Y (2006) Biodegradable honeycomb-patterned film composed of poly(lactic acid) and dioleoylphosphatidylethanolamine. Biomaterials 27:1797–1802PubMedCrossRef

16.

Okuda T, Higashide T, Fukuhira Y, Sumi Y, Shimomura M, Sugiyama K (2009) A thin honeycomb-patterned film as an adhesion barrier in an animal model of glaucoma filtration surgery. J Glaucoma 18:220–226PubMedCrossRef

17.

Narita Y, Fukuhira Y, Kagami H, Kitazono E, Kaneko H, Sumi Y, Usui A, Ueda M, Ueda Y (2006) Development of a novel temporary epicardial pacing wire with biodegradable film. Ann Thorac Surg 82:1489–1493PubMedCrossRef

18.

Morita K, Gao Y, Saito Y, Higashide T, Kobayashi A, Ohkubo S, Sugiyama K (2011) In vivo confocal microscopy and ultrasound biomicroscopy study of filtering blebs after trabeculectomy: limbus-based versus fornix-based conjunctival flaps. J Glaucoma Mar 16. [doi:10.1097/IJG.0b013e3182120a08, PMID: 21423030]

19.

Labbé A, Dupas B, Hamard P, Baudouin C (2005) In vivo confocal microscopy study of blebs after filtering surgery. Ophthalmology 112:1979–1986PubMedCrossRef

20.

Messmer EM, Zapp DM, Mackert MJ, Kampik A (2006) In vivo confocal microscopy of filtering blebs after trabeculectomy. Arch Ophthalmol 124:1095–1103PubMedCrossRef

21.

Perkins TW, Faha B, Ni M, Kiland JA, Poulsen GL, Antelman D, Atencio I, Shinoda J, Sinha D, Brumback L, Maneval D, Kaufman PL, Nickells RW (2002) Adenovirus-mediated gene therapy using human p21WAF-1/Cip-1 to prevent wound healing in a rabbit model of glaucoma filtration surgery. Arch Ophthalmol 120:941–949PubMed

22.

Bergstrom TJ, Wilkinson WS, Skuta GL, Watnick RL, Elner VM (1991) The effects of subconjunctival mitomycin-C on glaucoma filtration surgery in rabbits. Arch Ophthalmol 109:1725–1730PubMedCrossRef

23.

Khaw PT, Doyle JW, Sherwood MB, Smith MF, McGorray S (1993) Effects of intraoperative 5-fluorouracil or mitomycin C on glaucoma filtration surgery in the rabbit. Ophthalmology 100:367–372PubMed

24.

Akman A, Bilezikçi B, Küçükerdönmez C, Demirhan B, Aydin P (2003) Suramin modulates wound healing of rabbit conjunctiva after trabeculectomy: comparison with mitomycin C. Curr Eye Res 26:37–43PubMedCrossRef

25.

Hutchinson AK, Grossniklaus HE, Brown RH, McManus PE, Bradley CK (1994) Clinicopathologic features of excised mitomycin filtering blebs. Arch Ophthalmol 112:74–79PubMedCrossRef

26.

Wong TT, Mead AL, Khaw PT (2005) Prolonged antiscarring effects of ilomastat and MMC after experimental glaucoma filtration surgery. Invest Ophthalmol Vis Sci 46:2018–2022PubMedCrossRef

27.

Kobayashi A, Yoshita T, Sugiyama K (2005) In vivo findings of the bulbar/palpebral conjunctiva and presumed meibomian glands by laser scanning confocal microscopy. Cornea 24:985–988PubMedCrossRef

28.

Messmer EM, Mackert MJ, Zapp DM, Kampik A (2006) In vivo confocal microscopy of normal conjunctiva and conjunctivitis. Cornea 25:781–788PubMedCrossRef

29.

Efron N, Al-Dossari M, Pritchard N (2009) In vivo confocal microscopy of the bulbar conjunctiva. Clin Experiment Ophthalmol 37:335–344PubMedCrossRef

30.

Guthoff R, Klink T, Schlunck G, Grehn F (2006) In vivo confocal microscopy of failing and functioning filtering blebs: results and clinical correlations. J Glaucoma 15:552–558PubMedCrossRef

31.

Abdel-Khalek LM, Williamson J, Lee WR (1978) Morphological changes in the human conjunctival epithelium I. In the normal elderly population. Br J Ophthalmol 62:792–799PubMedCrossRef

32.

Geggel HS, Friend J, Thoft RA (1984) Conjunctival epithelial wound healing. Invest Ophthalmol Vis Sci 25:860–863PubMed

33.

Kim JW (1997) Conjunctival impression cytology of the filtering bleb. Korean J Ophthalmol 11:25–31PubMed

Title: Suppression of avascular bleb formation by a thin biodegradable film in a rabbit filtration surgery with mitomycin C
Authors: Tetsuhiko Okuda
Tomomi Higashide
Yukako Fukuhira
Hiroaki Kaneko
Masatsugu Shimomura
Kazuhisa Sugiyama
Publication date: 01-10-2012
Publisher: Springer-Verlag
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 10/2012
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-012-2068-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Suppression of avascular bleb formation by a thin biodegradable film in a rabbit filtration surgery with mitomycin C

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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