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PubMed2005

Effect of mitomycin C on ciliary body and intraocular pressure with various application depths: an experimental study.

BACKGROUND: To evaluate the effects of mitomycin C (MMC) on intraocular pressure (IOP) and ciliary body via transmission electron microscopy when applied under conjunctiva or different depths of sclera, without performing any filtering surgery. METHODS: Thirty-six eyes of 36 New Zealand albino rabbits were used in this study. MMC was prepared in a concentration of 0.4 mg/mL and 0.05 cc (20 microg) was soaked in preprepared sterile surgical sponges. Six groups each consisting of six eyes were formed and IOP was measured preoperatively. Group 1 was the control group: the superior conjunctiva was opened and only irrigated with balanced salt solution (BSS). In group 2, MMC soaked sponges were applied under the conjunctiva. In groups 3 and 4, a scleral flap of approximately 1/3 scleral thickness was prepared and in groups 5 and 6, and a scleral flap of approximately 2/3 scleral thickness was prepared, all with a standard size of 4 x 4 mm. MMC soaked sponges were applied under these areas for 5 min in eyes in groups 3 and 5 followed by an irrigation of the relevant areas with 10 cc BSS, whereas only irrigation with BSS was done in groups 4 and 6 as control groups. No filtering procedure was performed in any of the eyes. Eyes were enucleated on the 30th day following measurement of IOP and the ciliary body regions were evaluated using transmission electron microscopy. Kruskal-Wallis test was used for the statistical assessment of IOP between groups. RESULTS: The deep scleral flap group (group 5) showed statistically significantly more IOP reduction than both the superficial scleral flap group (group 3; P = 0.004) and the subconjunctival group (group 2; P = 0.002) on postoperative day 30. Electron microscopic evaluation of the surgical groups revealed a wide range of different histopathological effects due to different MMC application methods. The histopathological changes were more evident in the group 5, where MMC was applied under deep scleral flap. CONCLUSIONS: Subscleral application of MMC seems to provide greater IOP decrease than subconjunctival application, possibly caused by a more significant ciliary body toxicity. This may be the beginning of a non-penetrating, easy to perform and safe method to decrease IOP in glaucoma patients, which the authors call 'toxic ciliary ablation surgery'. However, the long-term results and complications must be assessed with further studies.

Animals↗

PubMed2006

Sustained release of nanosized complexes of polyethylenimine and anti-TGF-beta 2 oligonucleotide improves the outcome of glaucoma surgery.

The purpose of this study was to design microspheres combining sustained delivery and enhanced intracellular penetration for ocular administration of antisense oligonucleotides. Nanosized complexes of antisense TGF-beta2 phosphorothioate oligonucleotides (PS-ODN) with polyethylenimine (PEI), and naked PS-ODN were encapsulated into poly(lactide-co-glycolide) microspheres prepared by the double-emulsion solvent evaporation method. The PS-ODN was introduced either naked or complexed in the inner aqueous phase of the first emulsion. We observed a marked influence of microsphere composition on porosity, size distribution and PS-ODN encapsulation efficiency. Mainly, the presence of PEI induced the formation of large pores observed onto microsphere surface. Introduction of NaCl in the outer aqueous phase increased the encapsulation efficiency and reduced microsphere porosity. In vitro release kinetic of PS-ODN was also investigated. Clearly, the higher the porosity, the faster was the release and the higher was the burst effect. Using an analytical solution of Fick's second law of diffusion, it was shown that the early phase of PS-ODN and PS-ODN-PEI complex release was primarily controlled by pure diffusion, irrespectively of the type of microsphere. Finally, microspheres containing antisense TGF-beta2 nanosized complexes were shown, after subconjunctival administration to rabbit, to significantly increase intracellular penetration of ODN in conjunctival cells and subsequently to improve bleb survival in a rabbit experimental model of filtering surgery. These results open up interesting prospective for the local controlled delivery of genetic material into the eye.

Animals↗

PubMed1997

Mitomycin-C supplemented trabeculectomy, phacoemulsification, and foldable lens implantation.

PURPOSE: To evaluate the outcome of combined mitomycin-C filtering surgery, phacoemulsification, and foldable intraocular lens (IOL) implantation. SETTING: Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. METHODS: This retrospective study evaluated 182 eyes of 174 patients who had combined mitomycin-C trabeculectomy, phacoemulsification, and insertion of a foldable IOL through a 3.5 mm incision. Success of the combined procedure was defined as intraocular pressure (IOP) below 21 mm Hg, with or without medications, and no serious complication. Success rates were calculated using the Kaplan-Meier actuarial method. RESULTS: Mean follow-up was 16.7 months +/- 5.4 (SD). The probability of success at 6, 12, 18, and 24 months was 98.3, 95.6, 90.6, and 88.0%, respectively. When compared with preoperatively, visual acuity improved one or more lines in 148 eyes (81.3%) and worsened one or more lines in 15 (8.2%); 111 eyes (61.0%) achieved visual acuity of 20/40 or better. The most frequent complication was posterior capsule opacification requiring capsulotomy, which occurred in 22 cases (12.0%). CONCLUSION: The 1 year and 2 year IOP control rate of combined mitomycin-C filtering procedures and phacoemulsification in glaucoma patients was high.

Aged↗

PubMedDate not supplied

A comparative study of small incision trabeculectomy avoiding tenon's capsule with conventional trabeculectomy.

BACKGROUND AND OBJECTIVE: The purpose of this study was to compare the results of small incision trabeculectomy (SIT) avoiding Tenon's capsule vis-à-vis conventional trabeculectomy, and find a safe, effective alternative to conventional trabeculectomy with or without pharmacological wound modulation. PATIENTS AND METHODS: A controlled prospective study was conducted on 80 consecutive open-angle glaucoma patients requiring glaucoma filtration surgery. They were divided into two groups: Group I (n = 40): patients undergoing conventional trabeculectomy; and Group II (n = 40): patients undergoing limbal approach SIT. Patients were followed up serially for a minimum of 12 months and their intraocular pressure was monitored. Success of the procedure was defined as an intraocular pressure (IOP) <22 mm Hg with no additional antiglaucoma medication or surgery, and achieving at least a 30% reduction from the initial IOP at which optic disc cupping and/or visual field changes occurred. RESULTS: A significant fall (P <0.0001) in the final mean IOP was present in both groups at all time intervals in comparison to their preoperative values. The final mean intraocular pressure achieved with conventional trabeculectomy was 18.90 +/- 4.86 mm Hg versus 16.60 +/- 5.93 mm Hg with SIT. The final success rate of 90% was obtained with SIT vs 80% with conventional trabeculectomy. No major complications were encountered with either procedure although complications such as shallow anterior chamber and progression of cataractogenesis were seen more often in patients undergoing conventional trabeculectomy. CONCLUSION: Small incision trabeculectomy avoiding Tenon's capsule is a low-cost and safe alternative to conventional trabeculectomy that effectively reduces IOP in 90% of cases. The use of a small 2.5 mm limbal incision, which obviates the dissection of Tenon's capsule and absence of any major complication, suggests that this procedure be used more often in glaucomatous eyes needing filtering surgery.

Adult↗

PubMed2002

Surgical management of epiretinal membrane in young patients.

PURPOSE: To report the outcome of epiretinal membrane (ERM) surgery in young patients. DESIGN: Interventional case series study. METHOD: A retrospective review of 20 young patients who had undergone vitrectomy and epiretinal membrane removal. All patients had a preoperative examination, including fundus biomicroscopy, red free photographs, and fluorescein angiography. RESULTS: Nine patients were males and 11 females (age: 7-26 years; mean: 16.3 years). Follow up ranged from 4-96 months (mean: 21.2 months). The 20 patients comprised 13 cases of idiopathic ERM, six cases in which ERM was associated with ocular inflammation and one case of combined hamartoma of the retina and retinal pigment epithelium (RPE). In 13 cases, the ERM was especially white, thick, and opaque, with localized constriction and severe retinal distortion. Final best-corrected visual acuity (VA) was significantly better than preoperatively (20/50 vs. 20/112), (P = 0.0002). Mean improvement in VA was 4.25 lines and 17 patients gained two or more lines. This improvement was better in secondary than idiopathic ERM (6 lines vs. 3.3). During follow up, five cases of recurrence were observed (25%). In another case, postoperative persistent ocular hypertension required filtering surgery. CONCLUSION: The characteristics of ERM in young patients are quite different in many cases from those in adults in terms of thickness and adherence. Removal of ERM in young patients is feasible and safe although the membrane may focally adhere strongly to retinal vessels. VA usually improves significantly after surgery, but recurrences are more frequent than in adults.

Adolescent↗

PubMed2000

[Frequency and risk factors of intraocular pressure increase after penetrating keratoplasty].

PURPOSE: The aim of this study was to evaluate the incidence, risk factors and management of glaucoma following penetrating keratoplasty (PK) and to check for possible correlations with the indication for PK. PATIENTS AND METHODS: 534 eyes of 483 patients (age 54.7 +/- 19.8 years), that had undergone PK from 1989 to 1999 were retrospectively analyzed. The mean follow-up was 2.7 +/- 1.8 years. According to the type of surgical procedure patients were classified in 5 groups: group 1) PK only (n = 291); group 2) PK combined with extracapsular cataract extraction and intraocular lens (IOL) implantation (n = 124); group 3) PK combined with secundary IOL-implantation or IOL-change (n = 32); group 4) PK only after previous cataract surgery (n = 55) and group 5) Cataract surgery after PK (n = 32). The trephination was performed from the epithelial side in donor and recipient either by nonmechanical trephination with the 193 nm excimer laser (n = 444) or mechanical trephination (n = 90). An iridotomy was performed routinely during PK. The postoperative treatment with topical steroids was standardized. RESULTS: Preoperatively, glaucoma was diagnosed in 3.2% for all patients with groups 3 und 4 showing a significantly larger number of glaucomatous eyes (15.6% and 18.9%). Most of the mild early intraocular pressure elevations in group 1 (3.4%) and group 2 (3.0%) were controlled after 6 months (0.5% and 1.1%). Groups 3 and 4 showed most frequently increased intraocular pressure and/or antiglaucomatous treatment (21.4% and 18.7%) six weeks postoperatively. Patients in all groups showed no higher prevalence of persistent glaucoma from six months postoperatively than preoperatively throughout the follow-up period. Again groups 3 and 4 presented the largest number of persistent glaucoma. In most eyes the IOP was controlled by topical antiglaucomatous treatment. Serious forms seen in 2 patients with anterior synechiae caused by anterior chamber lens required several filtering surgeries or pars plicata diathermy, respectively. One patient with pseudoexfoliation syndrome required laser trabeculoplasty. The so-called "Urrets-Zavalia syndrome" was seen in none of the patients. CONCLUSION: The development of increased intraocular pressure after PK varied with the indication for keratoplasty. Postkeratoplasty glaucoma seems to be strongly associated with preexisting anterior synechiae and/or simultaneous anterior chamber lens implant removal. Intraoperative iridotomy can prevent the development of acute angle closure glaucoma after keratoplasty.

Adult↗

PubMed2005

The tube versus trabeculectomy study: design and baseline characteristics of study patients.

PURPOSE: The Tube Versus Trabeculectomy (TVT) Study will compare the safety and efficacy of nonvalved tube shunt surgery to trabeculectomy with mitomycin C in patients with previous intraocular surgery. DESIGN: Multicenter randomized clinical trial. METHODS SETTING: 17 Clinical Centers. STUDY POPULATION: Patients 18 to 85 years of age who have undergone previous trabeculectomy, cataract extraction with intraocular lens implantation, or both and have inadequately controlled glaucoma with intraocular pressure (IOP) >or=18 mm Hg and <or=40 mm Hg on tolerated medical therapy. INTERVENTIONS: Study patients were randomized to undergo placement of a 350-mm(2) Baerveldt glaucoma implant or trabeculectomy with mitomycin C (0.4 mg/ml for 4 minutes). MAIN OUTCOME MEASURES: IOP, complication rates, visual acuity, visual field, quality of life, reoperations for glaucoma, and need for supplemental medical therapy. RESULTS: A total of 212 patients were enrolled between October 1999 and April 2004. The age of the study population was 71.0 +/- 10.4 years (mean +/- SD), and 53% were women. The baseline IOP was 25.3 +/- 5.3 mm Hg (mean +/- SD). There were no significant differences in the demographic and ocular characteristics between the 2 treatment groups. CONCLUSIONS: Practice patterns vary in the surgical management of glaucoma, and there are differing opinions among glaucoma surgeons regarding the preferred surgical approach in patients who have undergone previous cataract extraction and/or failed filtering surgery. Forthcoming data from the TVT Study should provide valuable information comparing two surgical procedures commonly used in this patient population.

Adult↗

PubMed2005

Intraocular pressure control after clear corneal phacoemulsification in eyes with previous trabeculectomy: a controlled study.

PURPOSE: To compare intraocular pressure (IOP) control in eyes with or without clear corneal phacoemulsification following trabeculectomy. METHODS: The study group included 30 eyes that underwent uneventful clear corneal phacoemulsification and foldable intraocular lens implantation following trabeculectomy without antimetabolites. Thirty eyes that had undergone filtering surgery without cataract extraction were selected as controls. Case and control groups were matched with respect to age, gender, IOP, number of glaucoma medications, glaucoma type (primary open-angle glaucoma/pseudoexfoliative glaucoma), trabeculectomy time and follow-up. Comparisons between the study and control groups (intergroup) and within the same group at different time-points (intragroup) were performed for IOP, glaucoma medications and bleb morphology. Success rates were investigated by Kaplan-Meier survival analysis and the factors influencing final success by logistic regression. RESULTS: Intraocular pressure (p = 0.04) and glaucoma medications (p = 0.001) increased during an average follow-up of 26.1 +/- 9.9 months in both groups. Intragroup differences became statistically significant after the 6-month visit, but intergroup differences remained insignificant. Bleb height decreased significantly following phacoemulsification in the study group (p = 0.017). Success rates decreased with time in both groups, with no intergroup difference (p = 0.46). The final success rate was negatively correlated with IOP and number of glaucoma medications used at the study entry, while there was a positive correlation between the baseline and final success rates. CONCLUSION: Trabeculectomy success decreased in a time-dependent manner in eyes with and without subsequent phacoemulsification. Uncomplicated clear corneal phacoemulsification was not found to have any additional unfavorable influence on IOP control in eyes with filtering blebs.

Aged↗

PubMed2001

Effect of latanoprost and timolol on the histopathology of the rabbit conjunctiva.

PURPOSE: Long-term medical treatment of glaucoma has an effect on the conjunctiva, possibly affecting the outcome of subsequent filtering surgery. The type and extent of these tissue changes caused by frequently used medications is important. An animal study using rabbits was performed to assess the tissue changes caused by timolol, latanoprost, and a combination of both substances. METHODS: Rabbits were treated with timolol, latanoprost, or a combination of these drugs for 18 months. Conjunctival specimens were examined by light microscopy, quantitative transmission electron microscopy, and immunohistochemistry with antibodies against matrix metalloproteinase (MMP)-3 and tissue inhibitors of metalloproteinase (TIMP)-2. RESULTS: By electron microscopy, the area of subepithelial collagen was significantly larger (P: < 0.03; Mann-Whitney test) in timolol-treated eyes (71.6%) than in control (52.7%) and latanoprost-treated eyes (57.7%). An increase of amorphous material was present in timolol-treated eyes (25.6% versus 7.6% in the controls) as well as a smaller area of empty spaces (2.5% versus 39.4% in control eyes). Latanoprost-treated eyes had no significant increase of empty spaces but showed a marked staining for MMP-3 in the conjunctiva. This staining was not present in control or timolol-treated eyes. Morphologically, degenerative changes of fibrocytes were seen in timolol-treated eyes only. CONCLUSIONS: A significant increase of subepithelial collagen density was present in timolol-treated eyes, whereas this finding was not apparent in latanoprost-treated eyes. Latanoprost-treated eyes showed an upregulation of MMP-3, which may be the reason for reduced extracellular matrix accumulation in such eyes. The morphologic feature of increased subepithelial collagen density and extracellular matrix changes may relate to failure of filtering blebs.

Animals↗

PubMed2006

Contractility as a prerequisite for TGF-beta-induced myofibroblast transdifferentiation in human tenon fibroblasts.

PURPOSE: To assess the significance of Rho-kinase-dependent contractility in TGF-beta-induced myofibroblast transdifferentiation of human tenon fibroblasts to characterize possible pharmacological targets for the inhibition of postoperative scarring after glaucoma surgery. METHODS: Human tenon fibroblasts (HTFs) were grown in culture and stimulated with TGF-beta1. The effect of TGF-beta on Rho-GTPase activity was assessed by GST-rhotekin binding domain pulldown assay and detected by Western blot analysis. Contractility was evaluated in a silicone substrate wrinkling assay and in fibroblast-populated collagen gels. The actin cytoskeleton and focal adhesions were visualized by immunofluorescence microscopy. alpha-SMA transcripts were measured by real-time RT-PCR. TGF-beta-induced Smad- and p38-activation and expression of alpha-SMA were detected by Western blot analysis. Nuclear translocation of Smad2/3 was determined by confocal immunofluorescence microscopy. The influence of Rho-dependent kinase (ROCK) and myosin light chain kinase (MLCK) were studied by using specific kinase inhibitors (Y-27632, HA-1077, H-1152, and ML-7). RESULTS: Within 10 minutes of stimulation, TGF-beta induced Rho activation that was associated with an increase in cell tension and followed by actin stress fiber enhancement. ROCK inhibitors released cell tension and averted TGF-beta-induced cytoskeletal changes, p38 activation and subsequent alpha-SMA expression, whereas Smad2-phosphorylation and nuclear translocation were preserved. MLCK inhibition also blocked alpha-SMA expression. In fibroblast-populated collagen lattices, ROCK inhibitors prevented TGF-beta-induced stress fiber assembly and contraction. CONCLUSIONS: TGF-beta induces a rapid contractile response in HTFs that precedes myofibroblast transdifferentiation. ROCK inhibitors release this contraction and block subsequent TGF-beta-induced myofibroblast transdifferentiation and may therefore serve to modulate postoperative scarring after glaucoma filtering surgery.

Actins↗

PubMed1985

Topical fluorouracil. Pharmacokinetics in normal rabbit eyes.

Postoperative subconjunctival fluorouracil injections may be a useful adjunct to standard glaucoma filtering surgery in eyes that are at high risk of failure. Topical administration would be preferable to subconjunctival administration; however, there are no data on the ocular penetration of topically applied fluorouracil. Consequently, we investigated the pharmacokinetics of topically administered fluorouracil labeled with carbon 14 in normal rabbit eyes. One drop (approximately 2.4 mg) of fluorouracil resulted in the following concentrations at 0.5 and six hours, respectively: 17.3 and 0.9 micrograms/g of conjunctiva; 24.3 and 1.3 micrograms/g of cornea; 14.6 and 0.2 micrograms/mL of aqueous; 0.8 and 0.5 microgram/g of lens; 1.1 and 0.3 microgram/g of vitreous; and 0.2 and less than 0.1 microgram/mL of serum. Three drops (approximately 7.2 mg) of fluorouracil resulted in the following concentrations at 0.5 and eight hours, respectively: 589.8 and 1.3 micrograms/g of conjunctiva; 502.9 and 1.8 micrograms/g of cornea; 199.6 and 0.8 micrograms/mL of aqueous; 6.2 and 0.5 micrograms/g of lens; 6.8 and 0.5 micrograms/g of vitreous; and 1.3 and 0.2 microgram/mL of serum. Since a fluorouracil concentration of 0.2 microgram/mL inhibits rabbit conjunctival fibroblast proliferation in cell culture by 50%, these data suggest that topically applied fluorouracil achieves sufficient levels in the ocular compartments and tissues to have potential therapeutic applications.

Administration, Topical↗

PubMed1987

Central retinal vein occlusion and malignant glaucoma.

Malignant (ciliary block) glaucoma developed in three patients with primary open angle glaucoma with preexisting central retinal vein occlusion following trabeculectomy. Two of the three patients had 360 degrees open angles prior to surgical trabeculectomy. Although the relationship may be coincidental, we propose that central retinal vein occlusion may be a risk factor for the development of malignant glaucoma following filtering surgery.

Aged↗

PubMed1988

Surgical results in iridocorneal endothelial syndrome.

The charts of 83 patients with iridocorneal endothelial (ICE) syndrome were retrospectively reviewed. Forty-two eyes of 42 patients had had filtering surgery, 37 of whom had had a trabeculectomy to reduce uncontrolled intraocular pressure. Twenty-four of these trabeculectomy patients required a second surgery, and 8 required a third surgery. The results are presented using a survival analysis. The success rates at one year of follow-up for the first, second, and third trabeculectomies were 64%, 79%, and 63%, respectively. Patients subclassified as having Chandler's syndrome, essential iris atrophy, and Cogan-Reese syndrome responded with approximately the same success rates within the first two years following their first surgery. The success rates for repeated surgeries are comparable with those of initial surgery in patients with primary open angle glaucoma. On the basis of this study, further surgery is recommended despite initial failure in this group of difficult patients.

Endothelium, Corneal↗

PubMed1988

Extracapsular cataract extraction using a temporal limbal approach after filtering operations.

We reviewed the charts of 29 patients who underwent extracapsular cataract extraction after filtering surgery. Seven of these patients also had simultaneous implantation of a posterior chamber intraocular lens. All eyes were operated on using a temporal limbal approach. The median postoperative follow-up was 13 months. There was no statistically significant difference between the preoperative and postoperative intraocular pressures, but there tended to be an increase in the number of antiglaucoma medications administered postoperatively. None of these patients, however, required further surgery for intraocular pressure control.

Adult↗

PubMed1988

The effect of fluorouracil on the corneal endothelium.

The utility of the antiproliferative agent fluorouracil has been demonstrated recently in glaucoma-filtering surgery and in the management of proliferative vitreoretinopathy after vitrectomy. Because of the potential for contact with the corneal endothelium, its toxicity to the endothelium is an important consideration. The effect of fluorouracil on corneal endothelial integrity in an in vitro animal model was studied. Freshly excised sheep corneal buttons were exposed to increasing concentrations of fluorouracil for four hours and were subsequently evaluated microscopically using vital staining with alizarin red and trypan blue. Exposure to normal saline and chlorhexidine gluconate was used to establish negative- and positive-staining controls. Corneal buttons exposed to normal saline or to 1.0 mg/mL or less of fluorouracil had intact endothelial monolayers that completely excluded trypan blue. Corneal buttons exposed to chlorhexidine gluconate or to 10 mg/mL of fluorouracil, however, had severely or totally disrupted endothelial monolayers in which the remaining cells, if any, all had blue-staining nuclei. These results suggest that the threshold concentration for fluorouracil toxicity to corneal endothelium lies between 1 and 10 mg/mL when exposure time is four hours.

Animals↗

PubMed1993

Prolonged localized tissue effects from 5-minute exposures to fluorouracil and mitomycin C.

Rabbits undergoing full-thickness glaucoma filtering surgery were exposed for 5 minutes to one of three intraoperative treatments: (1) distilled water; (2) fluorouracil, 50 mg/mL; or (3) mitomycin C, 0.4 mg/mL. Tissue samples were taken from the subconjunctival and scleral tissues at the treated area and 90 degrees and 180 degrees from the center of the treated area and the adjacent cornea 2 mm from the limbus, 1 hour, 5 days, and 30 days postoperatively. The biopsy specimens were then placed in tissue culture media and the fibroblast outgrowths measured. Five-minute intraoperative treatments with fluorouracil resulted in a reversible delay of fibroblast outgrowths from treated subconjunctival and scleral tissues of just over 1 week in this model, whereas treatment with mitomycin C, 0.4 mg/mL, resulted in prolonged inhibition of at least 30 days. These effects were localized to the area treated. The many clinical implications of these findings are discussed.

Animals↗

PubMed1997

Transconjunctival application of mitomycin C in combination with laser sclerostomy ab interno: a long-term morphological study of the postoperative healing process.

The precise mechanism whereby mitomycin C enhances IOP reduction in glaucoma filtering surgery still eludes us. Ten rabbits received full-thickness Nd:YAG laser sclerostomy ab interno and adjunctive intraoperative treatment with mitomycin C (MMC) applied topically over the intact conjunctiva (0.5 mg ml-1 for 5 min). A systematic ultrastructural analysis of the fistulas and surrounding tissue was then conducted in conjunction with clinical observations, over the ensuing 10 weeks. In order to investigate also the extent to which MMC impedes fistula occlusion in the absence of percolating aqueous humour, we created non-perforating ('half-thickness') sclerostomies ab interno in three additional rabbits, one with and two without MMC therapy. Transconjunctival MMC application resulted in no serious complications. Eight of the ten full-thickness fistulas remained patent throughout the study, maintaining significant IOP reduction; the other two sclerostomies were compromised by iris incarceration. The MMC-treated, half-thickness canal remained as a tissue-free cul de sac; the two non-treated ones became completely occluded within one week without having recourse to extraocular cell populations. MMC suppressed the migration and proliferation of fibroblasts, macrophages and clump cells from the episclera, sclera, ciliary body and iris root. Repolymerization of heat-damaged collagen was abortive; neosynthesis was not observed. Myofibroblasts were encountered in the vicinity of the sclerostomy canals, and, after the fifth week, these cells were also found to be deployed as a canal-lining layer, delimiting the lumen from the surrounding stroma along most of the fistula length. Towards the external ostium, this layer of myofibroblasts was incomplete or absent. Near the internal ostium, lining cells were derived from the corneal endothelium. The transconjunctival mode of applying MMC appears to be efficient. This antifibrotic drug exerts its inhibitory influence by suppressing not only cell migration and proliferation, but also phagocytic and synthetic activities. However, exposed tissues are not acellular, and amongst the populations present, myofibroblasts are found to dominate the scene. The canal-delimiting cellular lining may play a role in maintaining fistula patency in MMC-treated eyes.

Administration, Topical↗

PubMed1998

Growth inhibition of cultured human Tenon's fibroblastic cells by targeting the E2F transcription factor.

The transcription factor E2F regulates the expression of several genes concerned with cell growth. The ability to inhibit transcription by blocking E2F expression has great potential in the treatment of proliferative disorders. The effect of double-stranded phosphorothioate oligonucleotides containing E2F transcription factor cis element, a so called 'decoy' has examined on the growth of cultured human Tenon's fibroblastic cells. Human Tenon's fibroblastic cells were cultured and challenged by E2F decoy coated with the Hemagglutinating virus of Japan (HVJ) cationic liposomes (HVJ-CL). The outcome was evaluated using fluorescence microscopy, RT-PCR and growth assays. HVJ-CL facilitated the transfer of external oligonucleotides to cultured human Tenon's fibroblastic cells. The E2F decoy, transferred by HVJ-CL, inhibited simultaneously the expression of the mRNAs of several cell cycle related genes such as c-myc, cdc2, proliferative cell nuclear antigen, and dehydrofolate reductase. Entry into S phase was also reduced to 42.7% of the positive control by the E2F decoy. The total increase of DNA at four days was reduced to 59.7% of the positive control by 5 microM and 29.9% by 15 microM of E2F decoy. It is concluded that gene therapy using the E2F transcription factor offers a potential therapeutic modality for the treatment of proliferative disorders such as proliferative vitreoretinopathy and fibrosis following filtering surgery.

Carrier Proteins↗