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Laboratory Sciences |

Solid Hyaluronic Acid Film and the Prevention of Postoperative Fibrous Scar Formation in Experimental Animal Eyes FREE

Kimio Takeuchi, MD; Mitsuru Nakazawa, MD; Hitoshi Yamazaki, MD; Yasuhiro Miyagawa, MD; Tadashi Ito, MD; Futoshi Ishikawa, MD; Tomomi Metoki, MD
[+] Author Affiliations

Author Affiliations: Department of Ophthalmology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.


Arch Ophthalmol. 2009;127(4):460-464. doi:10.1001/archophthalmol.2009.70.
Text Size: A A A
Published online

Objective  To investigate the inhibitory effect of solid hyaluronic acid–carboxymethyl cellulose film (hyaluronic acid film) on the formation of postoperative wound adhesion on rabbit eyes.

Methods  We first created a conjunctival flap under which hyaluronic acid film was inserted. Then, we performed trabeculectomy on other rabbit eyes with hyaluronic acid film applied under and above the scleral flaps. Expression of proliferative cell nuclear antigen and α–smooth muscle actin (α-SMA) were histologically and immunohistochemically examined.

Results  Hyaluronic acid film significantly prevented adhesions after both kinds of surgery. Particularly, subconjunctival scar formation was significantly inhibited when the film was simply inserted under the wound. Furthermore, the adhesion around the scleral flap of trabeculectomy was less formed in eyes treated with hyaluronic acid film than in control eyes. Immunoreactivity to proliferative cell nuclear antigen almost disappeared after 28 days postoperatively in both treated and control groups. The α-SMA–positive cells appeared much less around the film-treated wound than the control eye.

Conclusion  The present results indicate that hyaluronic acid film can inhibit the formation of postoperative adhesion around the conjunctiva and sclera.

Clinical Relevance  The results of this study indicate that this substance has potential benefits for improving ophthalmic surgery, such as filtering surgery for glaucoma.

Figures in this Article

Both general surgeons and ophthalmologists are aware that adhesion formation after surgical operations sometimes causes serious problems. Ophthalmic surgeons sometimes have a hard time overcoming postoperative scar formation at the time of reoperation for strabismus, retinal detachment, or glaucoma, particularly filtering surgery.

A film consisting of solid hyaluronic acid and carboxymethyl cellulose (hyaluronic acid film, Seprafilm; Genzyme Corp, Cambridge, Massachusetts) has been reported to prevent the formation of adhesive tissues in surgical wounds in the fields of abdominal and respiratory surgery.15 Especially for glaucoma surgery, surgical prognosis after filtering surgery is well known to largely depend on wound adhesion. Various studies have suggested that the use of antimetabolic drugs, such as 5-fluorouracil and mitomycin C (MMC), is effective for maintaining the bleb.610 However, serious postoperative complications can arise from the antimetabolic effects of these agents, such as corneal erosion and infection from buttonholes of a thin filtering bleb.1116

In recent years, various new methods for maintaining a filtering bleb have been examined by other researchers. Surgery with implants has been reported to allow effective control of intraocular pressure as a means of maintaining the physical space.1720 In addition, as another approach, the CAT-152 Trabeculectomy Study Group21,22 attempted to use anti–transforming growth factor eye drops to restrain wound healing.

To the best of our knowledge, no basic research has yet been performed using hyaluronic acid film in ophthalmic surgery. This film mainly consists of hyaluronic acid, which has long been safely used for intraocular surgery. The present study evaluated and examined the effects of hyaluronic acid film on postoperative scar formation in rabbit ocular tissues to clarify the potential benefits of hyaluronic acid film in ophthalmic surgery.

MATERIALS AND SURGICAL TECHNIQUES

Hyaluronic acid film (Seprafilm, 80 μm thickness) was kindly provided by the manufacturer. All experimental procedures were designed to conform to both the ARVO Statement for the Use of Animals in Ophthalmic Vision Research and the guidelines of our own institution.

A total of 20 Japanese white rabbits (body weight, 1 kg) were used. For all procedures, rabbits were anesthetized using 25 mg/kg of body weight of pentobarbital sodium and all surgical manipulations described later were performed under additional topical anesthesia with 0.4% oxybuprocaine hydrochloride eye drops. All experimental procedures were carried out in duplicate.

EXPERIMENT 1: SIMPLE CONJUNCTIVAL INCISION

Eight rabbits were used for this experiment. Conjunctival incision was made along the corneal limbus at an angle of about 45° to expose the sclera. The wound was then sutured with 8-0 polyglactin with (film-treated eyes) and without (control eyes) subconjunctival insertion of hyaluronic acid film (Figure 1A). To examine the strength of adhesion, surgical wounds were reopened in 2 eyes of 2 rabbits in each group 60 days after initial surgery by the same surgical instruments used before, and also, 2 film-treated and 2 control eyes of 4 rabbits at 60 days after surgery were histologically prepared as described later in the “Histologic Preparation” subsection.

Place holder to copy figure label and caption
Figure 1.

Insertion of hyaluronic acid film and preparation for trabeculectomy. A, Insertion of the hyaluronic acid film (arrow) under the conjunctival wound in a rabbit eye. B, A scleral flap is made for trabeculectomy on a rabbit eye.

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EXPERIMENT 2: TRABECULECTOMY

We conducted trabeculectomy by means of ordinary methods in other rabbit eyes (12 eyes of 12 rabbits). After creating a fornix-based conjunctival incision, a limbal-based square scleral flap (3 × 3 mm) was made (Figure 1B). After trabeculectomy was performed, the scleral flap was closed by suturing with 10-0 nylon at 5 points. During the surgical procedure, sheets of hyaluronic acid film were inserted above (5 × 6 mm) and below (4 × 5 mm) the scleral flap. The conjunctival wound was then closed by suturing with both 8-0 polyglactin and 10-0 nylon. Histologic and immunohistologic examinations were performed at 7, 14, and 28 days after surgery, respectively.

HISTOLOGIC PREPARATION

Rabbit eyes were histopathologically studied to examine the effect of hyaluronic acid film on inhibition of postoperative fibrous scar formation. At 60 days after experiment 1 and at 7, 14, and 28 days after experiment 2, each rabbit was rapidly perfused through the auricular vein with a total of 250 mg of pentobarbital sodium. Eyeballs (2 eyes of 2 rabbits at each postoperative date) were then enucleated, fixed in 4% paraformaldehyde solution overnight, dissected at the equator, and embedded in paraffin. Anterior segments of eyes containing the cornea, sclera, and conjunctiva were cut vertically at 4 μm thickness, mounted on subbed slides, and dried.

MASSON TRICHROME STAINING

After deparaffinization with serially graded ethanol and xylene solutions, these sections were processed with Masson trichrome stain to evaluate the formation of fibrous tissues.

IMMUNOHISTOCHEMICAL EXAMINATION

To examine the proliferative activity of cells adjacent to the surgical wounds, we immunohistochemically measured the expressions of proliferative cell nuclear antigen (PCNA) and α–smooth muscle actin (α-SMA) after experiment 2. Tissue sections from eyes at 7, 14, and 28 days after surgery were blocked with 3% bovine serum albumin in phosphate-buffered saline for 1 hour and then incubated with either mouse antirabbit PCNA (1:20) or mouse antihuman α-SMA (1:100) monoclonal antibody as the primary antibody overnight at 4°C. Sections were then further incubated with horseradish peroxidase–conjugated rabbit antimouse IgG as the secondary antibody overnight at 4°C. Proliferative cell nuclear antigen and α-SMA were visualized by dinitro-amino bentizine. To semiquantitatively measure expression of PCNA in proliferating cells around the space in which hyaluronic acid film had been embedded, PCNA-positive cells were counted in 4 randomly selected square areas (400 m × 400 m) in the subconjunctival space and 3 rectangular areas (200 m × 400 m) under the scleral flap in each eye. Counted numbers were then compared statistically. The t test was used to calculate the level of statistical significance (P < .05). To examine the level of expression of α-SMA, we qualitatively observed immunohistologic sections of scleral flap areas.

HISTOPATHOLOGIC AND SURGICAL MICROSCOPIC FINDINGS

When hyaluronic acid film was not used in experiment 1, subconjunctival soft tissue was almost completely replaced by fibrous proliferation and scar tissue by 60 days after surgery (Figure 2A), whereas abundant subconjunctival soft tissue was preserved when hyaluronic acid film was embedded in the subconjunctival space (Figure 2B). These histopathologic differences were confirmed by reoperation. When the initial conjunctival wound was reopened, the conjunctival incision was much easier to make in film-treated eyes than in control eyes under a surgical microscope.

Place holder to copy figure label and caption
Figure 2.

Conjunctival wound at 60 days postoperatively with and without hyaluronic acid film. A, Conjunctival wound at 60 days postoperatively with insertion of hyaluronic acid film showing a space (arrow) between intact conjunctival tissue and the sclera. B, Conjunctival wound at 60 days postoperatively without hyaluronic acid film shows fibrous scar formation and disappearance of intact subconjunctival soft tissue. Bars in photographs indicate 100 μm (Masson trichrome).

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As for experiment 2, histopathologic examination revealed that spaces between the conjunctiva and scleral flap and between the scleral flap and scleral bed remained wide even 7 days after surgery in film-treated eyes (Figure 3A). At 14 days postoperatively, formation of subconjunctival fibrous scar appeared retarded in film-treated eyes compared with control eyes (Figure 3B and C). In addition, a conjunctival filtering bleblike space was observed in film-treated eyes but not in control eyes at 28 days postoperatively (Figure 3D and E). Under surgical microscopic examinations, diffuse but shallow conjunctival filtering blebs were maintained over the scleral flap in film-treated eyes at 7, 14, and 28 days after surgery, but no filtering bleblike tissue was observed in control eyes at any date after surgery.

Place holder to copy figure label and caption
Figure 3.

Postoperative trabeculectomy wounds. A, Trabeculectomy wound at 7 days after insertion of hyaluronic acid film shows spaces in tissues in the subconjunctiva (arrowhead) and subscleral flap (arrow). B, Trabeculectomy wound at 14 days after insertion of hyaluronic acid film showing intact subconjunctival tissue (arrowhead) and a space under the scleral flap (arrow). C, Trabeculectomy wound at 14 days postoperatively without insertion of hyaluronic acid film shows fibrous scar formation in the subconjunctival space (arrow) and under the scleral flap (arrowhead). D, Trabeculectomy wound at 28 days after surgery with insertion of hyaluronic acid film shows formation of a filtering space (arrow) in the subconjunctival space. E, Trabeculectomy wound 28 days after surgery without hyaluronic acid film shows no filtering space. Bars in photographs indicate 500 μm (Masson trichrome).

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IMMUNOHISTOCHEMICAL FINDINGS

Figure 4 shows the numbers of PCNA-positive cells per 1-mm2 area in the space under the conjunctival flap (Figure 4A) and under the scleral flap (Figure 4B). Results obtained in this study indicate that overall numbers and course of PCNA-positive cells show a similar tendency between film-treated and control eyes in both areas, although the peak of PCNA-positive cells was seen at 14 days postoperatively in film-treated eyes, compared with 7 days postoperatively in control eyes (P < .05). Figure 5 shows α-SMA–positive cells around a scleral flap at 7 and 28 days after surgery. In film-treated eyes, α-SMA–positive cells were observed in border areas between the film and scleral or subconjunctival tissues at 7 days after surgery (Figure 5A), and these positive cells disappeared and filtering spaces were formed over and under the scleral flap by 28 days after surgery (Figure 5B). In control eyes, multiple layers of densely α-SMA–positive cells were found in subscleral flap tissue as well as a border area between the sclera and subconjunctiva at 7 days after surgery (Figure 5C). Although these positive cells also disappeared by 28 days after surgery in a control eye, no filtering space was recognized both under and over the scleral flap (Figure 5D).

Place holder to copy figure label and caption
Figure 4.

Postoperative changes in the numbers of proliferative cell nuclear antigen (PCNA)–positive cells in the subconjunctival space (A) and subscleral flap (B) show overall similar tendency, irrespective of insertion of hyaluronic acid film. Error bars indicate standard deviations.

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Place holder to copy figure label and caption
Figure 5.

Postoperative expression of α–smooth muscle actin (α-SMA). A, Expression of α-SMA around the scleral flap of a film-treated eye 7 days after trabeculectomy. Myofibroblasts expressing α-SMA were found in border areas between the film and scleral tissue (arrows) and film and subconjunctival tissue (arrowhead). B, Film-treated eye 28 days after surgery. No α-SMA–positive cells were found. Filtering spaces were formed under (arrow) and over (arrowhead) the scleral flap. C, Control eye 7 days after trabeculectomy. Multiple layers of cells highly positive for α-SMA were seen under the scleral flap (arrow) and in the subconjunctival tissue (arrowhead). D, Control eye 28 days after surgery. Cells expressing α-SMA disappeared and filtering spaces were not recognized. Bars in photos indicate 200 μm (diaminobenzidine).

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In terms of physical characteristics, hyaluronic acid film changes from solid form into gel form within 24 to 48 hours in the tissue and stays within the tissue for about 7 to 14 days. This material functions as a barrier to contact between separated tissues by which the postoperative formation of adhesions is reduced and delayed. Furthermore, because the film comprises hyaluronic acid and sodium carboxymethylcellulose, no subsequent removal procedure is required, as the materials are eventually absorbed into the body. Burns et al23 reported that this film has no toxicity, at least according to the Ames mutagenicity test, rabbit pyrogen test, intracutaneous toxicity test, and intraperitoneal and systemic toxicity tests.

In the field of abdominal and obstetric surgeries, hyaluronic acid film has already been reported to effectively prevent postoperative scar formation in abdominal wounds and to remain safe for a long time.24 However, the possibility of infection must be considered as the film remains in gel form between tissues. Although we encountered no sign of infection in our present short-term study, such complications can be prevented by thorough sterilization beforehand.

Given the present results, we found that hyaluronic acid film was easily inserted into the conjunctival space. Ophthalmic surgeons are thus likely to be able to easily insert hyaluronic acid film under the scleral flap in glaucoma filtering surgery, into the subconjunctival space without interfering with the use of MMC, and around the extraocular muscles during ophthalmic surgeries.

Proliferative cell nuclear antigen–positive cells can be considered to mainly comprise fibroblasts. Generally, fibroblasts increase the most at 4 to 7 days postoperatively. Numbers subsequently decrease gradually until about 28 days postoperatively. This duration almost corresponds to the point at which hyaluronic acid film is completely absorbed into the body. The activity of fibroblasts has largely finished by 28 days postoperatively, also meaning that wound healing is almost completed. Figure 4 shows that PCNA-positive cells were almost equal between the 2 groups, indicating that hyaluronic acid film does not inhibit cellular reactions but delays the initiation of cellular proliferation to some extent. This result also suggests that hyaluronic acid film has no toxic effects on fibrous cells around surgical wounds and that the effects are due solely to physical separation of tissues. Figure 5 shows that expression of α-SMA in myofibroblasts was much less abundant in film-treated eyes than in control eyes. Because conversion of fibroblasts into myofibroblasts expressing α-SMA indicates enhancement of scar formation by contraction of the collagen matrix,25 these findings indicate that hyaluronic acid film inhibits fibrous contraction in the surgical wound.

The present results show that hyaluronic acid film effectively inhibits excessive scar formation after conjunctival incision in glaucoma filtering surgery (Figure 3B and D and Figure 5C). They also suggest that hyaluronic acid film can be used in combination with MMC treatment or even reduce the dosage of MMC. In addition, use of hyaluronic acid film may further provide easy preparation of subconjunctival tissues in the case of reoperation for pars plana vitrectomy and buckling surgery, allowing creation of a long-term effective filtering bleb after glaucoma surgery if necessary.

As for complications, rates of shallow anterior chamber and hypotensive maculopathy by overflow from the wound seem likely to decrease. Slow changes from solid to gel form can slowly decrease intraocular pressure, and postoperative management is easier.

We conclude that the use of hyaluronic acid film in the outer segments of the eye seems to offer a safe and effective means of inhibiting the formation of postoperative adhesions. Although further studies are warranted to clarify long-term safety and efficacy, this approach offers potential benefits to various types of ophthalmic surgery.

Correspondence: Mitsuru Nakazawa, MD, Department of Ophthalmology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan (mitsuru@cc.hirosaki-u.ac.jp).

Submitted for Publication: August 20, 2008; final revision received January 6, 2009; accepted February 4, 2009.

Financial Disclosure: None reported.

Bowers  DRaybon  RBWheeless  CR  Jr Hyaluronic acid-carboxymethylcellulose film and perianastomotic adhesions in previously irradiated rats. Am J Obstet Gynecol 1999;181 (6) 1335- 1337, discussion 1137-1138
PubMed Link to Article
Hellebrekers  BWTrimbos-Kemper  GCvan Blitterswijk  CABakkum  EATrimbos  JB Effects of five different barrier materials on postsurgical adhesion formation in the rat. Hum Reprod 2000;15 (6) 1358- 1363
PubMed Link to Article
Osada  HMinai  MTsunoda  IFujii  TKTsubata  KSatoh  K The effect of hyaluronic acid-carboxymethylcellulose in reducing adhesion reformation in rabbits. J Int Med Res 1999;27 (6) 292- 296
PubMed
van 't Riet  Mde Vos van Steenwijk  PJBonthuis  F  et al.  Prevention of adhesion to prosthetic mesh.  Ann Surg 2003;237 (1) 123- 128
PubMed Link to Article
Burns  JWColt  MJBurgees  LSSkinner  KC Preclinical evaluation of Seprafilm bioresorbable membrane. Eur J Surg Suppl 1997; (577) 40- 48
PubMed
 Three-year follow-up of the Fluorouracil Filtering Surgery Study. Am J Ophthalmol 1993;115 (1) 82- 92
PubMed
Kitazawa  YKawase  KMatsushita  HMinobe  M Trabeculectomy with mitomycin. Arch Ophthalmol 1991;109 (12) 1693- 1698
PubMed Link to Article
Palmer  SS Mitomycin as adjunct chemotherapy with trabeculectomy. Ophthalmology 1991;98 (3) 317- 321
PubMed Link to Article
Kitazawa  YSuemori-Matsushita  HYamamoto  TKawase  K Low-dose and high-dose mitomycin trabeculectomy as an initial surgery in primary open-angle glaucoma. Ophthalmology 1993;100 (11) 1624- 1628
PubMed Link to Article
Belyea  DADan  JALieberman  MFStamper  RL Midterm follow-up results of combined phacoemulsification, lens implantation, and mitomycin-C trabeculectomy procedure. J Glaucoma 1997;6 (2) 90- 98
PubMed Link to Article
Greenfield  DSParrish  RK  II Bleb rupture following filtering surgery with mitomycin C. Ophthalmic Surg Lasers 1996;27 (10) 876- 877
PubMed
Sihota  RDada  TGupta  SDSharma  SArora  RAgarwal  HC Conjunctival dysfunction and mitomycin C-induced hypotony. J Glaucoma 2000;9 (5) 392- 397
PubMed Link to Article
Belyea  DADan  JAStamper  RLLieberman  MFSpencer  WH Late onset of sequential multifocal bleb leaks after glaucoma filtration surgery with 5-fluorouracil and mitomycin C. Am J Ophthalmol 1997;124 (1) 40- 45
PubMed
Mochizuki  KJikihara  SAndo  YHori  NYamamoto  TKitazawa  Y Incidence of delayed onset infection after trabeculectomy with adjunctive mitomycin C or 5-fluorouracil treatment. Br J Ophthalmol 1997;81 (10) 877- 883
PubMed Link to Article
Solomon  ATicho  UFrucht-Pery  J Late onset, bleb associated endophthalmitis following glaucoma filtering surgery with or without antifibrotic agents. J Ocul Pharmacol Ther 1999;15 (4) 283- 293
PubMed Link to Article
Poulsen  EJAllingham  RR Characteristics and risk factors of infections after glaucoma filtering surgery. J Glaucoma 2000;9 (6) 438- 443
PubMed Link to Article
Molteno  ACStraughan  JLAncker  E Long tube implants in the management of glaucoma. S Afr Med J 1976;50 (27) 1062- 1066
PubMed
Lee  DShin  DHBirt  CM  et al.  The effect of adjunctive mitomycin C in Molteno implant surgery. Ophthalmology 1997;104 (12) 2126- 2135
PubMed Link to Article
Lloyd  MABaerveldt  GHeuer  DKMinckler  DSMartone  JF Initial clinical experience with the Baerveldt implant in complicated glaucomas. Ophthalmology 1994;101 (4) 640- 650
PubMed Link to Article
Tsai  JCJohnson  CCDietrich  MS The Ahmed shunt versus the Baerveldt shunt for refractory glaucoma. Ophthalmology 2003;110 (9) 1814- 1821
PubMed Link to Article
Grehn  FHolló  GKhaw  P  et al. CAT-152 Trabeculectomy Study Group, Factors affecting the outcome of trabeculectomy. Ophthalmology 2007;114 (10) 1831- 1838
PubMed Link to Article
Khaw  PGrehn  FHolló  G  et al. CAT-152 0102 Trabeculectomy Study Group, A phase III study of subconjunctival human anti-transforming growth factor beta(2) monoclonal antibody (CAT-152) to prevent scarring after first-time trabeculectomy. Ophthalmology 2007;114 (10) 1822- 1830
PubMed Link to Article
Burns  JWColt  MJBurgees  LSSkinner  KC Preclinical evaluation of Seprafilm bioresorbable membrane. Eur J Surg Suppl 1997; (577) 40- 48
PubMed
Erkek  ABRemzi  FHHammel  JPAkyuz  MFazio  VW Effect of small bowel obstruction on functional outcome and quality of life in patients with ileal pouch-anal anastomosis. J Gastroenterol Hepatol 2008;23 (1) 119- 125
PubMed Link to Article
Micera  APuxeddu  ILambiase  A  et al.  The pro-fibrogenic effect of nerve growth factor on conjunctival fibroblasts is mediated by transforming growth factor-beta. Clin Exp Allergy 2005;35 (5) 650- 656
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Insertion of hyaluronic acid film and preparation for trabeculectomy. A, Insertion of the hyaluronic acid film (arrow) under the conjunctival wound in a rabbit eye. B, A scleral flap is made for trabeculectomy on a rabbit eye.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Conjunctival wound at 60 days postoperatively with and without hyaluronic acid film. A, Conjunctival wound at 60 days postoperatively with insertion of hyaluronic acid film showing a space (arrow) between intact conjunctival tissue and the sclera. B, Conjunctival wound at 60 days postoperatively without hyaluronic acid film shows fibrous scar formation and disappearance of intact subconjunctival soft tissue. Bars in photographs indicate 100 μm (Masson trichrome).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Postoperative trabeculectomy wounds. A, Trabeculectomy wound at 7 days after insertion of hyaluronic acid film shows spaces in tissues in the subconjunctiva (arrowhead) and subscleral flap (arrow). B, Trabeculectomy wound at 14 days after insertion of hyaluronic acid film showing intact subconjunctival tissue (arrowhead) and a space under the scleral flap (arrow). C, Trabeculectomy wound at 14 days postoperatively without insertion of hyaluronic acid film shows fibrous scar formation in the subconjunctival space (arrow) and under the scleral flap (arrowhead). D, Trabeculectomy wound at 28 days after surgery with insertion of hyaluronic acid film shows formation of a filtering space (arrow) in the subconjunctival space. E, Trabeculectomy wound 28 days after surgery without hyaluronic acid film shows no filtering space. Bars in photographs indicate 500 μm (Masson trichrome).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.

Postoperative changes in the numbers of proliferative cell nuclear antigen (PCNA)–positive cells in the subconjunctival space (A) and subscleral flap (B) show overall similar tendency, irrespective of insertion of hyaluronic acid film. Error bars indicate standard deviations.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 5.

Postoperative expression of α–smooth muscle actin (α-SMA). A, Expression of α-SMA around the scleral flap of a film-treated eye 7 days after trabeculectomy. Myofibroblasts expressing α-SMA were found in border areas between the film and scleral tissue (arrows) and film and subconjunctival tissue (arrowhead). B, Film-treated eye 28 days after surgery. No α-SMA–positive cells were found. Filtering spaces were formed under (arrow) and over (arrowhead) the scleral flap. C, Control eye 7 days after trabeculectomy. Multiple layers of cells highly positive for α-SMA were seen under the scleral flap (arrow) and in the subconjunctival tissue (arrowhead). D, Control eye 28 days after surgery. Cells expressing α-SMA disappeared and filtering spaces were not recognized. Bars in photos indicate 200 μm (diaminobenzidine).

Graphic Jump Location

Tables

References

Bowers  DRaybon  RBWheeless  CR  Jr Hyaluronic acid-carboxymethylcellulose film and perianastomotic adhesions in previously irradiated rats. Am J Obstet Gynecol 1999;181 (6) 1335- 1337, discussion 1137-1138
PubMed Link to Article
Hellebrekers  BWTrimbos-Kemper  GCvan Blitterswijk  CABakkum  EATrimbos  JB Effects of five different barrier materials on postsurgical adhesion formation in the rat. Hum Reprod 2000;15 (6) 1358- 1363
PubMed Link to Article
Osada  HMinai  MTsunoda  IFujii  TKTsubata  KSatoh  K The effect of hyaluronic acid-carboxymethylcellulose in reducing adhesion reformation in rabbits. J Int Med Res 1999;27 (6) 292- 296
PubMed
van 't Riet  Mde Vos van Steenwijk  PJBonthuis  F  et al.  Prevention of adhesion to prosthetic mesh.  Ann Surg 2003;237 (1) 123- 128
PubMed Link to Article
Burns  JWColt  MJBurgees  LSSkinner  KC Preclinical evaluation of Seprafilm bioresorbable membrane. Eur J Surg Suppl 1997; (577) 40- 48
PubMed
 Three-year follow-up of the Fluorouracil Filtering Surgery Study. Am J Ophthalmol 1993;115 (1) 82- 92
PubMed
Kitazawa  YKawase  KMatsushita  HMinobe  M Trabeculectomy with mitomycin. Arch Ophthalmol 1991;109 (12) 1693- 1698
PubMed Link to Article
Palmer  SS Mitomycin as adjunct chemotherapy with trabeculectomy. Ophthalmology 1991;98 (3) 317- 321
PubMed Link to Article
Kitazawa  YSuemori-Matsushita  HYamamoto  TKawase  K Low-dose and high-dose mitomycin trabeculectomy as an initial surgery in primary open-angle glaucoma. Ophthalmology 1993;100 (11) 1624- 1628
PubMed Link to Article
Belyea  DADan  JALieberman  MFStamper  RL Midterm follow-up results of combined phacoemulsification, lens implantation, and mitomycin-C trabeculectomy procedure. J Glaucoma 1997;6 (2) 90- 98
PubMed Link to Article
Greenfield  DSParrish  RK  II Bleb rupture following filtering surgery with mitomycin C. Ophthalmic Surg Lasers 1996;27 (10) 876- 877
PubMed
Sihota  RDada  TGupta  SDSharma  SArora  RAgarwal  HC Conjunctival dysfunction and mitomycin C-induced hypotony. J Glaucoma 2000;9 (5) 392- 397
PubMed Link to Article
Belyea  DADan  JAStamper  RLLieberman  MFSpencer  WH Late onset of sequential multifocal bleb leaks after glaucoma filtration surgery with 5-fluorouracil and mitomycin C. Am J Ophthalmol 1997;124 (1) 40- 45
PubMed
Mochizuki  KJikihara  SAndo  YHori  NYamamoto  TKitazawa  Y Incidence of delayed onset infection after trabeculectomy with adjunctive mitomycin C or 5-fluorouracil treatment. Br J Ophthalmol 1997;81 (10) 877- 883
PubMed Link to Article
Solomon  ATicho  UFrucht-Pery  J Late onset, bleb associated endophthalmitis following glaucoma filtering surgery with or without antifibrotic agents. J Ocul Pharmacol Ther 1999;15 (4) 283- 293
PubMed Link to Article
Poulsen  EJAllingham  RR Characteristics and risk factors of infections after glaucoma filtering surgery. J Glaucoma 2000;9 (6) 438- 443
PubMed Link to Article
Molteno  ACStraughan  JLAncker  E Long tube implants in the management of glaucoma. S Afr Med J 1976;50 (27) 1062- 1066
PubMed
Lee  DShin  DHBirt  CM  et al.  The effect of adjunctive mitomycin C in Molteno implant surgery. Ophthalmology 1997;104 (12) 2126- 2135
PubMed Link to Article
Lloyd  MABaerveldt  GHeuer  DKMinckler  DSMartone  JF Initial clinical experience with the Baerveldt implant in complicated glaucomas. Ophthalmology 1994;101 (4) 640- 650
PubMed Link to Article
Tsai  JCJohnson  CCDietrich  MS The Ahmed shunt versus the Baerveldt shunt for refractory glaucoma. Ophthalmology 2003;110 (9) 1814- 1821
PubMed Link to Article
Grehn  FHolló  GKhaw  P  et al. CAT-152 Trabeculectomy Study Group, Factors affecting the outcome of trabeculectomy. Ophthalmology 2007;114 (10) 1831- 1838
PubMed Link to Article
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