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PubMed1993

Incidence of complications following 5-fluorouracil with trabeculectomies.

To investigate the incidence of complications reportedly caused by the use of 5-fluorouracil (5-FU) in glaucoma filtering surgery, we performed trabeculectomy with 5-FU on 57 eyes of 56 patients with advanced glaucoma. The mean preoperative intraocular pressure was 34.8 mm Hg. The most frequent complication encountered was superficial punctate keratopathy (26%), followed by shallowing of the anterior chamber (12%), choroidal detachment (9%), and flap retraction (7%). We, however, did not encounter any cases of confluent corneal epithelial defect, subepithelial scarring, or striate melanokeratosis which are usually described with the use of 5-FU. With a mean follow-up of 7.1 months, an intraocular pressure less than 16 mm Hg without hypotensive therapy were achieved in 73.7% of cases, and less than 21 mm Hg without hypotensive therapy in 86%. Considering the low incidence of complications and the high success rate, we recommend the use of 5-FU in routine glaucoma filtering surgery.

Combined Modality Therapy↗
PubMed1987

The effect of beta irradiation on monkey Tenon's capsule fibroblasts in tissue culture.

Fibroblast proliferation with subsequent bleb scarring is a major cause of filtering surgery failure. To investigate possible antiproliferative effects of beta radiation, owl monkey Tenon's capsule fibroblasts in tissue culture were irradiated to doses of 30, 100, 300, 1,000, and 3,000 rads with a linear accelerator and to doses of 95,285, and 950 rads with a Strontium-90 applicator. The irradiated cell proliferation expressed as the percentage of the non-irradiated control growth on the third and seventh days, respectively, after beta irradiation was: 97% and 96% after 30 rads; 72% and 90% after 100 rads; 48% and 44% after 300 rads; 39% and 14% after 1,000 rads; and 39% and 14% after 3,000 rads. Similar effects on cell proliferation were observed with the Strontium-90 applicator. The inhibitory effect of beta irradiation on fibroblast proliferation in tissue culture suggests that beta irradiation after filtering surgery may reduce postoperative bleb scarring.

Animals↗
PubMed2000

Outcome of trabeculectomy with mitomycin-C in the iridocorneal endothelial syndrome.

PURPOSE: Eyes with iridocorneal endothelial (ICE) syndrome have a high risk of failure in glaucoma filtering surgery failing. We investigated the efficacy of trabeculectomy with intraoperative mitomycin-C application in these patients. DESIGN: Retrospective nonrandomized comparative trial with historical controls. PARTICIPANTS AND CONTROLS: Ten patients with unilateral iridocorneal endothelial (ICE) syndrome were reviewed. Their intraocular pressures could not be controlled medically. In five eyes, this was the primary surgery performed. Five of the patients had undergone prior intraocular pressure-(IOP) lowering surgery that had failed at the time enrolled. Results were compared with previously published case series of similar patients treated with trabeculectomy alone or trabeculectomy and subconjunctival 5-fluorouracil injections. INTERVENTION: Intervention consisted of trabeculectomy with a limbus-based conjunctival flap and mitomycin-C application. The dosage of mitomycin-C was 0.4 mg/ml for 1 to 4 minutes (mean, 1.9 min). MAIN OUTCOME MEASURES: Adequate control of IOP (without medication lower than 21 mm Hg). RESULTS: In eight eyes the IOP remained well controlled (mean IOP, 12.1 mm Hg) over the entire length of available of follow-up (mean, 14.9 months). Two eyes required implantation of an aqueous tube shunt at 4 and 11 months, respectively, after trabeculectomy with mitomycin-C. One eye experienced visual loss of 3 Snellen lines because of hypotony maculopathy. CONCLUSIONS: Trabeculectomy with mitomycin-C application offers a reasonable intermediate-term success rate in ICE patients, who are otherwise at high risk for failure of filtering surgery.

Adult↗
PubMed1996

A novel MMC-loaded pHEMA drainage device for the treatment of glaucoma: in vitro and in vivo studies.

Administration of subconjunctival 5-fluorouracil (5-FU) and topical mitomycin-C (MMC) has been shown to improve the success rate of glaucoma-filtering surgery. However, corneal toxicity and administrative problems remain. To overcome this limitation, drainage devices for the sustained release of 5-FU and MMC were designed and tested in vitro and in vivo. This paper presents only the results of our studies which were carried out on MMC-loaded devices. Here, the drainage devices were prepared from MMC-loaded poly(hydroxyethyl methacrylate) (pHEMA) matrices in different cross-linking ratios and in different drug loading capacities, i.e. 0.2, 0.5, and 2.0 mg MMC per device. These devices released MMC at approximately 6.0-90.0 micrograms day-1 for over 2 months depending on cross-linking density and initial drug loading. The diffusional release of MMC from glassy and swollen copolymers showed that diffusion mechanism is Fickian in both cases. The usability of the pHEMA implants were investigated by in vivo experiments which were done on eight dog's eye. In the treatment eyes, intraocular pressures remained significantly lower than the control eyes throughout the experimental period (4 months). Subconjunctival implantations revealed no clinical and histological evidence for toxicity. The results of in vitro and in vivo studies indicate that an implantable release system delivering MMC for over 2 months can improve the prognosis for filtering surgery by preventing postoperative fibrosis.

Administration, Topical↗
PubMed1997

In vitro effects of doxorubicin and mitomycin C on human Tenon's capsule fibroblasts.

Doxorubicin is an antiproliferative agent, that also inhibits prolyl 4-hydroxylase in vitro. We evaluated the effects of doxorubicin and mitomycin C (MMC) on the proliferation of human Tenon's capsule fibroblasts and the secretion of type I collagen in these cells to explore the potential use of doxorubicin as an antifibrotic agent after glaucoma filtering surgery. Standard immunoassays were used to determine the concentrations of type I procollagen COOH-terminal peptide (PIP), laminin and vitronectin receptor in conditioned media and cell lysates in the presence or absence of doxorubicin or MMC. The mitotic activity and viability of these cells were also determined. Cellular ultrastructure was evaluated by transmission electron microscopy. Doxorubicin and MMC decreased the cellular viability, the mitotic activity, and the production of the peptides measured. The inhibition of PIP secretion into the culture medium was higher in doxorubicin-treated cultures than in MMC-treated cultures at the tested concentrations (5-100 microM). The decrease in PIP levels in cell lysates was less in doxorubicin-treated culture (25 microM) than in MMC-treated culture (25 microM), suggesting that procollagen synthesis and secretion might be attenuated by doxorubicin. Ultrastructural studies revealed increased numbers of lysosomes in the cytoplasm of doxorubicin-treated cells relative to MMC-treated cells. Doxorubicin and MMC reduced cell viability and inhibited the proliferation and synthesis of PIP, laminin, and vitronectin receptor peptide. Inhibitory effects of doxorubicin on PIP secretion were more potent than those of MMC. Doxorubicin may be useful for inhibiting the fibrotic response at the site of ocular filtering surgery.

Adult↗
PubMed1994

Transcriptional control of human Tenon's capsule fibroblast collagen synthesis in vitro by gamma-interferon.

PURPOSE: Gamma-interferon (gamma-IFN) has been shown to be a potent inhibitor of collagenous protein production independent of its effects on noncollagenous protein production and cell proliferation in vitro. To understand further the processes controlling tissue fibrosis and the potential use of gamma-IFN as an antifibrotic treatment after glaucoma filtering surgery, the in vitro effects of recombinant gamma-IFN on procollagen mRNA production were studied. METHODS: Subconfluent human Tenon's capsule fibroblast cultures were exposed to 10, 50, 500, and 1000 U/ml of human recombinant gamma-IFN for 48 hours and to 500 U/ml for 12, 24, and 72 hours. After the incubation period, polyA+ mRNAs were isolated by oligo (dT) cellulose columns, separated according to size by electrophoresis through a denaturing agarose gel, and transferred to an activated nylon membrane for Northern blot analysis. The levels of type III (alpha 1) procollagen, type I (alpha 1) procollagen, and fibronectin (noncollagenous protein) mRNA were determined by hybridization with radiolabeled cDNA probes specific for these components followed by autoradiography. RESULTS: Densitometric analysis showed gamma-IFN selectively inhibited type III and type I procollagen mRNA synthesis from 24% (10 U/ml) to 99% (1000 U/ml) while leaving fibronectin mRNA synthesis unaffected. The degree of inhibition was also time dependent; more inhibition occurred with increasing incubation time. CONCLUSIONS: These results indicate that gamma-IFN is able to regulate collagen synthesis at the transcriptional level and that its inhibition is relatively specific. Gamma-interferon's specific inhibitory effects may offer advantages over current therapies in modulating the fibrotic response after glaucoma filtering surgery.

Cell Line↗
PubMed2002

Antiproliferative effect of mycophenolate mofetil on cultured human Tenon fibroblasts.

BACKGROUND: Wound healing after glaucoma filtering surgery is often complicated by exaggerated scarring of the subconjunctival Tenon's layer. Therefore, antiproliferatives are commonly employed. The immunosuppressive drug mycophenolate mofetil (MMF) is used to prevent graft rejection after kidney or liver transplantation. The effect is mediated by inhibition of lymphocyte proliferation. In this study we investigated the effect of MMF on human Tenon fibroblast proliferation in cell culture. METHODS: Human Tenon fibroblasts (HTF) were cultivated with 10% fetal calf serum. Cells were incubated with MMF concentrations of 0.1 microM to 3000 microM for up to 20 days. In a second set of experiments HTF were incubated for 10 min only in MMF solutions. Cell counts were performed to evaluate the proliferation rate. The proliferation was also assessed by Ki67 staining. Morphological changes were documented by vimentin staining. RESULTS: Growth inhibition of HTF by MMF was concentration dependent. IC(50) was 0.85+/-0.05 microM for 6 days of incubation. Brief exposure to MMF leads to a reversible growth arrest for up to 14 days with concentrations of 1000 microM or higher. Ki67 staining confirmed the concentration dependent proliferation rate. CONCLUSION: MMF has a concentration-dependent antiproliferative effect on HTF without any detected cytotoxicity in the applied concentration range. Brief incubation also leads to a growth arrest; therefore, intraoperative MMF application might prevent exaggerated scarring after glaucoma filtering surgery.

Aged↗
PubMed1996

Immunolocalization of prolyl 4-hydroxylase in fibroblasts cultured from Tenon's capsule of humans.

BACKGROUND: The excessive accumulation of extracellular matrix (ECM) with the repopulation of fibroblasts may lead to an unsuccessful outcome of glaucoma filtering surgery. We examined the immunolocalization of ECM components and prolyl 4-hydroxylase, an enzyme involved in collagen biosynthesis, in cultured Tenon's capsule fibroblasts (TCFs) of humans to evaluate the production of ECM in the cells. METHODS: We used light microscopy to evaluate the immunolocalization of prolyl 4-hydroxylase and ECM components, collagen types I, III, and IV, cellular fibronectin, and laminin in TCFs. Ultrastructural localization of the enzyme was also evaluated by electron microscopy. RESULTS: Immunoreactivity with monoclonal antibodies against the alpha and beta subunits of the enzyme or with the polyclonal antibody against it was detected in the cytoplasm of the cells in a fine granular pattern, indicating its localization in the endoplasmic reticulum (ER). Immunoreactivity for the enzyme was detected in the cisternae of the ER on electron microscopy. Types I and III collagen reactivities were also observed in the cytoplasm in a fine granular pattern. Type IV collagen reactivity was present diffusely on the cell surface. The distribution of laminin reactivity in the cytoplasm resembled that of types I and III collagen. Cellular fibronectin reactivity was observed in the ECM in a reticular pattern. CONCLUSION: Prolyl 4-hydroxylase was located in the cisternae of the ER. TCFs produced a variety of ECM components in vitro. The results provide insight into the fibrotic process during scar formation at the site of a bleb following filtering surgery.

Aged↗
PubMed1999

An experimental study on homoharringtonine liposome and glaucoma filtration surgery.

PURPOSE: To observe the inhibitory action of homoharringtonine liposome during the healing process of wounds in the filtering sites. METHODS: Posterior sclerectomies were performed in 14 rabbits. Postoperatively one eye of each rabbit received subconjunctival injections of HH liposome and fellow eye received saline injection in a randomized masked fashion. RESULTS: Fourteen days after operation the IOP of experimental eyes reduced significantly (P < 0.01) as compared with the controlled eyes, and the number of remaining filtering blebs increased noticeably (P < 0.05). Pathohistological examination revealed that the number of fibroblasts per square micron in the filtering sites and the thickness of the scars in the center of the filtering sites of the experimental eyes were less than those of the controlled eyes. No serious ocular toxic and side effects were found. CONCLUSION: This experiment suggest that homoharringtonine liposome can markedly inhibit the scar formation of filtering sites after glaucoma filtering surgery, promote the formation of filtering blebs, and provide an experimental evidence for its clinical use in future.

Animals↗
PubMed1994

Modulation of human fibroblast activity by selected angiogenesis inhibitors.

Tenon's fibroblast (TF) bleb encapsulation is a common cause of filtering surgery failure. Various pharmacologic agents have been used in an attempt to inhibit this response. The effects of three angiogenesis inhibitors were studied. AGM-1470, a fumagillin analog and hydrocortisone 21-phosphate (HC21P) complexed with heparin or with the heparin analog beta-cyclodextrin tetradecasulfate (BCD-TDS) in modulating human tenon's fibroblasts in cell culture. It has been clinically demonstrated that well vascularized blebs are associated with a poorer prognosis. In addition to reducing bleb neovascularization, angiogenesis inhibitors may have an additional therapeutic role in decreasing fibroblast activity. Drug effects were assessed by studying cell growth rates by cell Coulter counting and rate of wound closure. TF's were grown in DMEM with 10% FBS and 1% PCN-strep with fungizone. Angiogenesis inhibitors were added to growth medium in varying concentrations: AGM-1470 alone, HC21P complexed with heparin and HC21P complexed with BCD-TDS. Controls were grown in control medium alone, medium with added ethanol, or with added BCD-TDS, heparin or HC21P. We found a dose related inhibition of cell growth with all of the angiogenesis inhibitor combinations, which was not seen in the control groups. Tenon's fibroblast proliferation was significantly inhibited by AGM-1470 as seen in the four higher concentrations (P < 0.05) with insignificant inhibition at the lowest concentration of AGM-1470 (P = 0.38). The heparin:HC21P and heparin:BCD-TDS combinations demonstrated significant inhibition at all concentrations (P < 0.05). Wound closure was significantly inhibited by all the added agents, except AGM-1470 and the controls. The rate of wound closure was significantly reduced by the highest concentrations of the heparin:HC21P and heparin:BCD-TDS combinations (P < 0.05), although it was not significantly affected by lower concentrations (P > 0.05). Rank order of potencies of these agents for inhibition of TF proliferation was AGM-1470, BCD-TDS:HC21P, heparin:HC21P, HC21P, while the rank order of potencies for these agents for inhibition of wound closure was HC21P, heparin:HC21P, BCD-TDS:HC21P, AGM-1470. These selected angiogenesis inhibitors appear to have marked inhibitory effects on TF proliferation and migration, which may have a potential clinical role in modulating wound healing associated with glaucoma filtering surgery.

Cell Division↗
PubMed2001

The use of antimetabolites with trabeculectomy: a critical appraisal.

PURPOSE: To examine why most ophthalmologists routinely use mitomycin C or 5-fluorouracil (antimetabolites) in association with filtering surgery for glaucoma. METHODS: Critical analysis of seven medical, social and economic trends. RESULTS: The rapid acceptance of the adjunctive use of antimetabolites at the time of filtration surgery may be explained by reasons other than anticipated increase in the "success" of glaucoma surgery. CONCLUSION: The use of antimetabolites in conjuction with filtering glaucoma surgery may be at least partially a consequence of changing medical-social-economic factors, rather than solely a desire on the part of physicians to improve the "success" of glaucoma surgery. This may indicate a need to reevaluate the proper place of antimetabolites in association with filtration surgery.

Antimetabolites↗
PubMed2000

Ultrasound biomicroscopic patterns after glaucoma surgery in congenital glaucoma.

OBJECTIVE: This study aimed to demonstrate specific morphologic patterns in congenital glaucoma after various surgical procedures by means of ultrasound biomicroscopy (UBM) and to investigate correlations between UBM morphology and the effectiveness of glaucoma surgery in reducing intraocular pressure. DESIGN: Observational case series. PARTICIPANTS AND INTERVENTIONS: Thirty four eyes of 18 consecutive patients, not older than 18 years, with congenital glaucoma and with a history of previous antiglaucomatous surgery underwent UBM examination of the anterior chamber angle in the treatment area and in an untreated region. MAIN OUTCOME MEASURES: The morphology of the anterior chamber angle region and the tissue reflectivity were analyzed. RESULTS: Specific UBM patterns of the anterior chamber angle in congenital glaucoma were observed after goniotomy, trabeculotomy, trabeculectomy, deep sclerectomy, and cyclodialysis. In the first months after surgery, a limited correlation was found between morphology and the success of filtering surgery. Adhesions of the iris or the ciliary processes to the trabeculectomy cleft were detected in 19 of 25 eyes after filtering procedures. CONCLUSIONS: In cases of cloudy cornea and unknown previous glaucoma surgery, UBM can be used to identify the type and localization of previous surgery in congenital glaucoma, thus assisting surgical planning for subsequent glaucoma management. The correlation between UBM morphology and the effectiveness of filtering surgery is less convincing than previously demonstrated in adults, possibly underlining the importance of individual nonsurgical factors for prognosis in congenital glaucoma.

Adolescent↗
PubMed1998

[Modulation of wound healing in glaucoma filtration surgery].

Authors evaluate application of mitomycin C (0.2-0.4 mg/ml) on the sclera during glaucoma filtering surgery. Mean follow up was 19.5 months in the group of 67 patients (75 eyes). The most serious complication was an early endophthalmitis in 2 cases with the loss of residual visual field and vision, 1x hemophthalmus followed with development of traction retinal detachment, 1x hypotonic maculopathy, 1x traction retinal detachment for progression of diabetic proliferative vitreoretinopathy of neovascular glaucoma. Higher rate of complications was noted in the group of mitomycin C 0.4 mg/ml. Visual acuity was better one line Snellen optotypes in 3 cases, and worse in 26 cases. Intraocular pressure compensation up to 20 mmHg was reached in 32 cases without therapy (45.1%), in 28 cases therapy (39.6%), Intraocular pressure above 20 mm Hg was in 11 cases (15.4) and the data are not known in 4 cases (5.4%). Intraocular pressure was compensated after mitomycin C application in 84.7%.

Administration, Topical↗
PubMedDate not supplied

[Encapsulated filtering blebs--incidence and methods of treatment].

Encapsulation of the filtering bleb occurs as a complication of glaucoma filtering surgery in 8.3-28% of all eyes filtered, often between 2-4 weeks after surgery. It has a characteristic clinical appearance--highly elevated localized bleb, prominent surface vessels and patent sclerostomies on gonioscopy. This study retrospectively reviewed the results of 100 filtering operations, performed in the Prof. Dr. I. Stankovitsh Eye Department, focused on the incidence, possible risk factors and management of encapsulated filtering blebs. Trabeculectomy was done in all patients with limbus-based conjunctival flap, rectangular scleral flap 4 x 4 mm, and sclerostomy 2 x 2 mm. Two or three interrupted 10-0 nylon sutures were used to tether the flap, the conjunctiva with Tenon's capsule was closed with a running suture. All eyes received topical dexamethasone drops, mydriatics-homatropin or tropicamide and antibiotic ointment for three weeks. Possible risk factors were considered: sex, age, other eye or systemic disease, type of glaucoma, previous ocular procedure and antiglaucoma medical therapy, early postoperative complications, postoperative and final intraocular pressure (IOP). All eycs with encapsulated filtering bleb were given topical beta-blocker initially and carbonic anhydrase inhibitor, and if IOP continued to be uncontrolled incisional surgical management was performed. Success was defined as IOP maintained at less than 22 mmHg, with or without medication. An encapsulated filtering bleb developed in 9% of eyes. Previous argon laser trabeculoplasty was associated with an increased frequency of bleb encapsulation. The mean postoperative IOP was 11.30 +/- 1.90. Encapsulation of filtering bleb was developing at mean time of 19.9 +/- 3.0 after surgery. Six eyes returned to IOP below 21 (mean IOP was 20.17 +/- 0.90) within 4 weeks, and 4 of them continued on a topical beta-blocker. Four eyes required incisional surgery. A week after surgery mean IOP was 18 mmHg. Haemophthalmus occurred after one incision performed in a patient suffering from diabetes mellitus. Late scarring of the filtering bleb was developed in 2 eyes. Seven months and 2 years after filtration surgery mean IOP was 21.30 +/- 4.00 mmHg. The cause of bleb encapsulation is not known. Male patients, surgical glove powder, topical corticosteroids, previous argon laser trabeculoplasty and beta-blockers are some of potential risk factors for the development of encapsulated filtering bleb. This study suggests the association between development of encapsulated bleb and previous argon laser trabeculoplasty--40% in the eyes with encapsulation and 18% in the eyes without encapsulation. The optimal management of bleb encapsulation has not been defined. In this study topical antiglaucoma therapy achieved IOP control and cyst's remodeling in 60% of cases. Forty percent of all cysts required incisional surgical management. Encapsulation of the filtering bleb is not an uncommon complication of glaucoma filtration surgery. It is important to examine postoperative eyes frequently during the first 2 months to detect this complication. Fortunately, most eyes have their IOPs controlled with antiglaucoma therapy.

Adrenergic beta-Antagonists↗
PubMed1998

Classification of filtering blebs in trabeculectomy: biomicroscopy and functionality.

The long-term success of filtering surgery is not dependent on surgical technique alone. The development of the filtering bleb in the postoperative period, in particular with regard to wound healing and subconjunctival scarring, is equally important. Morphologic changes of the developing filtering bleb after trabeculectomy can predict early failure even if the intraocular pressure is still normal. A basic understanding of wound healing processes and histologic changes of the developing filtering bleb are mandatory to interpret correctly the morphologic appearance of the developing filtering bleb. In clinical practice, follow-up of the filtering bleb according to a standardized morphologic classification may help to predict outcome and provide clues for the necessity and timing of further treatment.

Aqueous Humor↗