Skip to main content

Advertisement

SpringerLink
Log in

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

  • Basic Science
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

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

  2. 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 24:389–394

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  7. 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 81:877–883

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  9. 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 118:453–458

    Article  PubMed  Google Scholar 

  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 110:345–352

    Article  PubMed  Google Scholar 

  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 90:175–180

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  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 110:2192–2197

    Article  PubMed  Google Scholar 

  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 18:301–314

    Article  PubMed  Google Scholar 

  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 27:1797–1802

    Article  PubMed  CAS  Google Scholar 

  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 18:220–226

    Article  PubMed  Google Scholar 

  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 82:1489–1493

    Article  PubMed  Google Scholar 

  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 112:1979–1986

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  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 120:941–949

    PubMed  CAS  Google Scholar 

  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 109:1725–1730

    Article  PubMed  CAS  Google Scholar 

  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 100:367–372

    PubMed  CAS  Google Scholar 

  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 26:37–43

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  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 24:985–988

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  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 15:552–558

    Article  PubMed  Google Scholar 

  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 62:792–799

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Koichi Tsuneyama, MD, PhD, for technical assistance and helpful discussion of the histology experiments. This work was supported by the New Energy and Industrial Technology Development Organization, Japan and a grant-in-aid for scientific research from the Japan Society for the Promotion of Science (Grant 22791652).

Conflict of interest

Tetsuhiko Okuda, Tomomi Higashide, Yukako Fukuhira, Hiroaki Kaneko and Kazuhisa Sugiyama are inventors of the honeycomb-patterned film which is under patent application in Japan. Yukako Fukuhira and Hiroaki Kaneko are employees of Teijin limited.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan

    Tetsuhiko Okuda, Tomomi Higashide & Kazuhisa Sugiyama

  2. Research Laboratories III, Integrative Technology Research Institute, New Business Development Group, Teijin Limited, Tokyo, Japan

    Yukako Fukuhira & Hiroaki Kaneko

  3. Institute of Multidisciplinary Research for Advance Materials, Tohoku University, Sendai, Japan

    Masatsugu Shimomura

  4. Department of Ophthalmology and Visual Science, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, Ishikawa Prefecture, 920-8641, Japan

    Tetsuhiko Okuda

Authors
  1. Tetsuhiko Okuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tomomi Higashide
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yukako Fukuhira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiroaki Kaneko
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Masatsugu Shimomura
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kazuhisa Sugiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tetsuhiko Okuda.

Additional information

The authors have no financial relationship with the sponsoring foundation. The authors have full control of all primary data, and they agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review their data if requested. Clinical trials must be registered.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Okuda, T., Higashide, T., Fukuhira, Y. et al. Suppression of avascular bleb formation by a thin biodegradable film in a rabbit filtration surgery with mitomycin C. Graefes Arch Clin Exp Ophthalmol 250, 1441–1451 (2012). https://doi.org/10.1007/s00417-012-2068-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-012-2068-7

Keywords

Search

Navigation