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A comparative study of the chemical stability of various mitomycin C solutions used in glaucoma filtering surgery.

OBJECTIVE: To determine the chemical stability of various mitomycin C (MMC) solutions used in glaucoma filtering surgery. METHODS: A survey of the MMC solutions currently in use in 21 hospitals (11 in Canada, 10 in the United States) was conducted. A comparative study of the chemical stability of five different representative solutions was performed. The effects of buffer and storage variables on the chemical breakdown of MMC in the solutions were studied by means of high-performance liquid chromatography (HPLC). RESULTS: The survey revealed 33 different variations (including recipes and storage conditions) in the preparation of MMC solutions. Although the majority of the hospitals (15 of 21; 72%) were preparing stable solutions, six of the hospitals (28%) were preparing potentially unstable solutions. The stability of the solutions varied in a nonuniform manner when stored at different temperatures in different buffers. CONCLUSION: The lack of standardization and quality control of MMC solutions used in filtering surgery allows for the possibility of hospitals preparing unstable solutions.

Buffers↗

Dexamethasone, D-penicillamine, and glaucoma filter surgery in rabbits.

A study was made in rabbits of the effect of topical dexamethasone ointment, .05%, and either subconjunctival or intraperitoneal D-penicillamine on the duration of function of glaucoma filtering surgery. The drugs were tested alone and in combination. Intraperitoneal D-penicillamine was not effective, either alone or combined with topical dexamethasone. Topical dexamethasone ointment alone and subconjunctival D-penicillamine alone significantly prolonged the duration of function of the filter surgery; however, when combined, no additional effect was observed. It was concluded that the institution of therapy with both drugs immediately after glaucoma filtering surgery was not the optimal temporal sequence for combining the two modes of therapy.

Administration, Topical↗

Filtering surgery with 5-fluorouracil subsequent to Molteno implant.

In cases of refractory glaucoma, when Molteno shunt implantation has been performed and resulted in failure, the best surgical option has not yet been established. Filtering surgery with 5-fluorouracil (5-FU) as one option for the above was performed in four non-neovascular glaucomatous eyes (four patients) after failure of Molteno shunt implantation. Injections of 5 mg 5-FU were administered once daily for 9-14 days. After follow-up of 6-18 months in 3 eyes, intraocular pressure ranged from 10 to 16 mm Hg. In the fourth eye, in which bleb scarring ensued, a second filtering surgery with 5-FU was performed after 4 months, and resulted in a successful outcome as recorded 26 months later. These preliminary results suggest that filtering surgery with 5-FU might be an acceptable surgical option in non-neovascular refractory glaucoma subsequent to failure of Molteno shunt implantation.

Adolescent↗

5-fluorouracil and glaucoma filtering surgery. II. A pilot study.

5-Fluorouracil (5-FU) was injected subconjunctivally after glaucoma filtering surgery in a pilot study of eyes with poor surgical prognoses. Twenty-seven (79%) of the 34 aphakic eyes with glaucoma achieved an intraocular pressure (IOP) of less than or equal to 21 mmHg (range of follow-up on nonreoperated eyes, 91 -468 days). Nine (69%) of 13 eyes with neovascular glaucoma achieved an IOP of less than or equal to 21 mmHg (range of follow-up on nonreoperated eyes, 120-379 days). Eight (89%) of nine phakic eyes with glaucoma following unsuccessful filtering procedures achieved an IOP of less than or equal to 21 mmHg (range of follow-up on nonreoperated eyes, 134-394 days). Visual acuities remained within one line of their preoperative levels or improved in 32 (94%) of the 34 aphakic eyes with glaucoma, eight (62%) of the 13 eyes with neovascular glaucoma, and six (67%) of the nine phakic eyes with glaucoma following unsuccessful filtering procedures. Postoperative corneal epithelial defects occurred in 45% of the cases. Conjunctival wound and conjunctival needle tract leaks were observed in 41% of the cases, but only one eye required wound revision. No other serious side effects that we attributed to 5-FU were observed. It seems that postoperative subconjunctival 5-FU increases the likelihood of achieving IOP control following filtering surgery in eyes with poor surgical prognoses; however, a randomized clinical trial is necessary to confirm this.

Adolescent↗

Late-onset bleb leaks after glaucoma filtering surgery.

OBJECTIVE: To determine the incidence of focal, late-onset, conjunctival bleb leaks after glaucoma filtering surgery. DESIGN: Prospective, cross-sectional analysis. SETTING: Tertiary care outpatient referral center. PATIENTS: Consecutive patients who underwent glaucoma filtering surgery prior to June 1996 presenting for evaluation from September 2,1996, through November 15,1996. Five hundred twenty-five eyes of 525 consecutive patients were enrolled in the study. INTERVENTION: Bleb height (elevated or flat), area (diffuse or localized), and wall thickness (thin, thick, or encapsulated) were classified. Each bleb was tested for focal leakage using a moistened fluorescein strip, cobalt blue illumination, and slit-lamp biomicroscopy. Diffuse transconjunctival aqueous flow did not qualify as a focal leak. MAIN OUTCOME MEASURE: Seidel-positive aqueous leakage. RESULTS: Bleb leakage occurred in 14 eyes following trabeculectomy (mitomycin C treatment, 10 eyes; 5-fluorouracil treatment, 3 eyes; no antifibrosis agent, 1 eye) and in 1 eye following combined cataract and glaucoma surgery with adjunctive mitomycin C therapy. Bleb leakage occurred more frequently in eyes that received mitomycin C (10 [3.7%] of 273 eyes) than 5-fluorouracil (3 [1.4%] of 213 eyes) or no antifibrosis agent (1 [2.6%] of 39 eyes), using Kaplan-Meier estimates (P=.008, log-rank test). Conjunctival blebs were significantly thinner after trabeculectomy with mitomycin C than with 5-fluorouracil (P=.001). Bleb wall thickness was greater following combined cataract and glaucoma surgery than following trabeculectomy alone (P=.008). Age (P=.84), sex (P=.68), race (P=.77), duration of mitomycin C exposure (P=.62), number of antiglaucoma medications (P=.16), and total 5-fluorouracil dose (P=.85) were not associated with late-onset leaks. CONCLUSIONS: The risk of late-onset focal bleb leakage increases following trabeculectomy with mitomycin C therapy. Late leakage after combined cataract and glaucoma surgery is infrequent.

Adolescent↗

[Wound healing after glaucoma filtering surgery--a review].

Wound healing after glaucoma filtering surgery is characterized by a complex sequence of molecular and cellular events. Results of recent investigations have shown that the activation, migration, proliferation and differentiation of Tenon's capsule fibroblasts represents the central element of the wound healing response. An exaggerated wound healing will result in the closure of the artificial fistula between the anterior chamber and the subconjunctival space, leading to an increase in intraocular pressure. The present review summarizes the current knowledge regarding the most important cellular and molecular mechanisms, which regulate the postsurgical wound healing response in the subconjunctival space. Special emphasis will be put on the specific role of cytokines during the wound healing response. An extensive understanding of these mechanisms appears pivotal for the development of specific therapeutic strategies to inhibit the events which lead to fibrogenesis and scarring in the wound region after glaucoma filtration surgery. The databank was Medline.

Animals↗

[An analysis of causes of post-operative shallow anterior chamber in glaucoma filtering surgery].

131 eyes of 103 cases having undertaken glaucoma filtering surgeries were randomly selected to analyze retrospectively the causes of the post-operative shallow anterior chamber. The causes are choroidal detachment accounting for 75.6%, excessive filtration 13.3% and malignant glaucoma 11.1%. As the rate of discovery of the choroidal detachment under a direct ophthalmoscope was quite low, the definite diagnosis depended primarily on B-ultrasonography. It is discovered that in the analysis of the possible factors leading to choroidal detachment, the plasma level of fibronectin is correlated to the development of the post-operative choroidal detachment of a glaucoma filtering operation, suggesting the impairment of microcirculatory function be investigated to approach the causes of the choroidal detachment following anti-glaucoma and other intraocular surgeries.

Adult↗

Alpha-tocopherol derivatives and wound healing in an experimental model of filtering surgery.

OBJECTIVE: To describe the effect of alpha-tocopherol derivatives (acetate and acid-succinate) on the histopathological characteristics of the surgical fistula in an experimental model of filtering surgery. MATERIALS AND METHODS: Thirty pigmented rabbits were divided into 3 groups. Twenty-four hours before surgery the animals were injected subconjunctivally with 0.5 mL of solution that depended on the group of treatment: Group 1 (n = 10) 0.75% ethanol in balanced salt solution (BSS); Group 2 (n = 10) 100 microg alph-tocopherol-acetate in 0.75% ethanol in BSS; Group 3 (n = 10) 100 microg alpha-tocopheryl-acid-succinate in 0.75% ethanol in BSS. Histological findings were evaluated 30 days after surgery. RESULTS: The groups treated with alpha-tocopherol derivatives showed a higher percentage of persistence of the fistula and better intraocular pressure (IOP) control. CONCLUSIONS: Alpha-tocopherol derivatives showed antiproliferative properties in this experimental model of filtering surgery.

Animals↗

The incidence of sickle trait in Blacks requiring filtering surgery.

Open-angle glaucoma in the blacks is generally thought to be a more malignant disease than in whites in terms of response to therapy and subsequent visual loss. An increased incidence of unsuspected sickle trait and undetected sickling may have contributed to these patients' optic nerve ischemia, progressive field loss and need for surgery. A homoglobin electrophoresis was done on 40 black patients who required filtering surgery for uncontrolled open-angle glaucoma. Only 2 of the 40 patients (5%) had sickle trait as determined by the hemoglobin electrophoresis. In a matched group of 40 controls, only 3 patients (7.5%) had sickle trait. Therefore, there does not appear to be an increased incidence of sickle trait in black patients requireing filtering surgery.

Adult↗

Effects of daunomycin implants on filtering surgery outcomes in rabbits.

PURPOSE: To evaluate the effects of a novel daunomycin (DM) implant on intraocular pressure (IOP), bleb survival, and anterior segment complications when administered during filtering surgery on New Zealand White rabbits. METHODS: Implants were prepared by covalent coupling of DM to a high molecular weight hyaluronic acid (HA) and fabricated into solid implants containing 250, 65, and 25 microg of DM. Full thickness sclerostomies were performed, and rabbits received no implant (control), placebo implant containing HA, or an implant containing HA-DM conjugate at the time of surgery. Rabbits were then followed for 30 days to assess change in IOP, bleb survival, and anterior segment associated complications. RESULTS: In vitro, the release of DM from the implants was a first order process with a half-life of 51 h. In control rabbits, rabbits receiving placebo implant, and rabbits receiving HADM (250 microg) implants, the mean IOPs on day 3 were 11.1 +/-1.6, 10.8 +/- 2.7, and 14 +/- 0.98 mm of Hg, respectively. On days 5 through 9, IOP in the control and placebo-implanted groups returned to preoperative levels. However, in rabbits receiving 250 microg of conjugated DM, mean IOP on day 7 was reduced from preoperative levels by 11.8 +/- 3.2 mm of Hg (P < 0.05). This reduction in IOP was significantly different (P < 0.05) from both control and placebo implant groups, and IOPs remained at these levels until studies were terminated on day 30. In control and placebo-implanted rabbits, bleb size started decreasing on day 1, and by day 7, no blebs were observed. In rabbits receiving 250 microg HA-DM implants, mean bleb survival time was greater than 30 days. The DM-induced reduction in IOP and enhanced bleb survival was dose-dependent. In rabbits receiving 65 microg of conjugated DM, lOPs were significantly reduced through day 30; however, at times beyond day 19 there was a gradual rise in mean IOP as filtering procedures in individual animals began to fail. Mean bleb survival time was greater than 30 days for implants containing 65 microg of conjugated DM. In rabbits receiving HA-DM implant containing 25 microg of DM, IOPs were not significantly different from preoperative levels beyond day 9, and no significant enhancement in bleb survival was observed in these animals. Comparison of HA-DM conjugated implants to those containing equal doses of free DM demonstrated that the mean IOP change at 30 days were similar; however, there was a reduction in anterior segment complications associated with the use of HA-DM conjugated implants. CONCLUSIONS: This study provides evidence that the controlled release of DM when conjugated to HA can significantly improve the success of filtering procedures. The maintenance of ocular hypotension and bleb survival along with the reduction in anterior segment complications supports the idea that HA-DM conjugate will be more efficacious than the use of free DM in improving the success rate of filtering surgery.

Animals↗

Late-onset Moraxella catarrhalis endophthalmitis after filtering surgery.

We describe a young man in whom endophthalmitis caused by Moraxella catarrhalis developed 5 years after glaucoma filtering surgery. The infection responded to treatment with broad-spectrum antibiotics, and 2 months after presentation the visual acuity had returned to 20/50. To our knowledge this is the first report of late-onset endophthalmitis due to M. catarrhalis complicating glaucoma filtering surgery.

Adult↗

Effect of gamma-interferon on fibroblast proliferation and collagen synthesis after glaucoma filtering surgery in white rabbits.

Failure of a glaucoma filtering operation mainly results from scarring at the filtering wound, and postoperative proliferation and migration of fibroblasts play an important role histologically in the formation of scar tissue. As an inhibitory agent for fibroblast proliferation, gamma-interferon has been introduced, and the application of gamma-interferon following filtering surgery is now being made on a trial basis. We studied the effect of gamma-interferon histologically on the fibroblast proliferation and collagen synthesis occurring at the filtering site by comparing the effect of gamma-interferon on the experimental group with that of 5-fluorouracil on the control group, using 10 rabbits (20 eyes) after posterior lip sclerectomy. Both groups showed similar flat and diffused bleb grossly and also showed a similar inhibitory effect on fibroblast proliferation and collagen fiber synthesis histologically. Our findings seem to justify the clinical use of gamma-interferon. Further studies on adequate dosage, method of administration, and local and systemic complications would be desired.

Animals↗

Quantification of intraoperative administration of mitomycin-C in filtering surgery with surgical sponge material.

PURPOSE: To determine the absorption and release of mitomycin-C 0.4 and 0.2 mg/mL from sponge-like specimens of Spongostan film (Ferrosan, Copenhagen, Denmark) and the scleral and conjunctival impregnation in an experimental model of filtering surgery. METHODS: The maximum amount of mitomycin per volume unit that Spongostan is able to absorb was determined physically as the difference between dry weight and soaked weight. Mitomycin-C activity in known volumes of Spongostan after mitomycin-C release in vitro also was determined at 0, 1, 10, and 30 seconds and 1, 3, 5, 10, 15, and 30 minutes. Antibiotic activity of the specimens was evaluated by means of bioassay. Millimeters of inhibition of bacterial growth were related to microg of mitomycin activity according to a reference curve obtained from known amounts of mitomycin-C. Finally, 10 eyes of 10 rabbits underwent filtering surgery with intraoperative application of mitomycin by means of the Spongostan film. The Spongostan implants then were removed and tested for mitomycin activity. Scleral and conjunctival specimens were obtained for bioassay. RESULTS: The maximum capacity of 25 mm2 x 0.5 mm thick Spongostan films saturated in 0.4 and 0.2 mg/mL solutions of mitomycin-C were 8.49 microg and 4.23 microg, respectively. Biologic activity (bioassay determination) was 8.24 microg and 4.19 microg of mitomycin-C, respectively. In vitro release of mitomycin was gradual until 30 minutes. In vivo mitomycin release from Spongostan after 5 minutes was 6.91 microg. Impregnation with the antimitotic was better in conjunctiva than sclera. CONCLUSION: Bioassay permits quantification of mitomycin-C activity. The release from sponge specimens is gradual, and impregnation was better in conjunctiva than sclera.

Absorption↗

Role of 5 fluorouracil in the management of failed glaucoma surgery.

Filtering surgery for glaucoma usually controls the intraocular pressure adequately. However, in glaucoma patients with aphakia, neovascularisation of iris, previous failed filtering surgeries and relatively young patients, results of surgery leave much scope for improvement. Most failures of filtering surgery are related to extra-ocular factors. Histopathological studies of eyes after failed filtering operations have suggested that proliferation of fibroblasts and deposition of collagen constitute a barrier to filteration. There is also a positive correlation between success of filtering surgery and inhibition of fibroblast growth by the patients aqueous humour. Thus agents inhibiting fibroblast proliferation should play an important role in increasing the success rate of filtering surgery. 5 Fluorouracil is a pyrimidine analogue which has been utilised for over 15 years as an antimetabolite in cancer therapy. Its efficiency in inhibiting fibroblast proliferation in vitro and in rabbit eyes has been proved beyond doubt. We undertook a pilot project to estimate the efficiency of the subconjunctival 5 FU to increase the changes of success in problematic cases of glaucoma in pigmented eyes.

Adolescent↗

The comparative benefits of glaucoma filtering surgery with an electric-pulse targeted drug delivery system demonstrated in an animal model.

PURPOSE: To evaluate the safety and effectiveness of glaucoma filtering surgery performed with the adjunctive use of bleomycin administered in conjunction with electric pulses (EP). DESIGN: Experimental study in rabbits. CONTROLS AND METHODS: Trabeculectomies were performed on pigmented rabbits (2 to 2.5 kg) using the following adjunctive treatments: 5 microM of topical bleomycin and EP (5V, 50 msec, 8 pulses) (group A: B+E+, n=15); bleomycin but no EP (group B: B+E-, n=15); 5 ,uM mitomycin C (MMC) and EP (group C: M+E+, n= 10); MMC but no EP (group D: M+E-, n=10); EP alone (group E: E+, n=10); and no adjunctive treatment (group F: E-, negative control, n=10). MAIN OUTCOME MEASURES: Intraocular pressure (IOP) was measured regularly for 60 days after the operation. Bleb formation and the condition of the conjunctiva, cornea, and retina were also regularly evaluated. Histologic studies were performed by light microscopy, and retinal functions were evaluated by electroretinography. RESULTS: Postoperative IOP was significantly lower than the preoperative level in all the animals until day 7. However, in groups E and F (the negative control) it returned to the preoperative level after day 7, and in groups B, C, and D after 15 days. The IOP of group A remained lower even on day 40. The average amount IOP was lowered or increased on day 20 was -6.4 mmHg (P < 0.05) in group A; -0.2 mmHg in group B; +1.2 mmHg in group C; and -3.25 mmHg in group D. The survival rate of the filtering blebs on day 20 was significantly higher in group A than in the other groups. Clinical and histologic studies uncovered no pathologic findings in any intra- or paraocular tissues. Electroretinographic evaluation of retinal function in group A showed no apparent change over the 60 days of the study. CONCLUSION: Glaucoma filtering surgery in rabbits with the adjunctive use of bleomycin in conjunction with EP significantly lowered IOP for up to 40 days without clinically, morphologically, or functionally harming intraocular tissues.

Animals↗

Shell tamponade in filtering surgery for glaucoma.

The glaucoma shell tamponade technique in filtering surgery for glaucoma is a technique for (1) decreasing the incidence of flat anterior chamber and choroidal separation postoperatively, (2) promoting the development of a low diffuse filtration area, and (3) increasing the possibility of achieving very low resulting postoperative pressure. The glaucoma shell technique is applicable to all types of filtration procedures, including conventional filtering procedures utilizing no scleral flap and those utilizing a scleral flap, such as trabeculectomy. It can be used at surgery or can be applied in the postoperative period to deal with flat or shallow anterior chambers immediately at the time of onset. The shell tamponade technique can be utilized to aid in the management of some cases of leaking bleb in the early postoperative period or in the late postoperative period. The technique for operative and postoperative use of the glaucoma shell tamponade technique and its closely related pressure dressing is a demanding and exacting art. Because the technique increases the possibility of very low resulting tensions, its use should be considered especially for cases in which very low pressures are desired, such as some cases of extremely advanced cupping and field loss and low-tension glaucoma.

Anterior Chamber↗

Scleritis after glaucoma filtering surgery with mitomycin C.

BACKGROUND: Adjunctive intraoperative mitomycin C increases the success of glaucoma filtering surgery, but also the postoperative complications. This is the first report of scleritis after its use. PATIENTS: In five patients, scleritis developed 3 to 24 weeks after inferior trabeculectomy with mitomycin C. The onset was characterized by acute pain, redness of the eye, and decreased vision. Three patients had anterior scleritis and two had posterior scleritis. Infection or bleb leakage was not seen in any patient. RESULTS: All patients responded to a course of topical steroids and oral ibuprofen or prednisone. CONCLUSION: Anterior and posterior scleritis may complicate the use of topical mitomycin C during trabeculectomy, Prompt diagnosis and treatment reverses the inflammation, maintaining the success of the surgical procedure.

Administration, Oral↗

Improved suture for fornix-based conjunctival flap in filtering surgery.

Major problems in the early postoperative phase in filtering surgery are hypotony, flattening of the anterior chamber and choroidal detachment. We describe a new suture technique for the closure of the conjunctiva in goniotrephination with a fornix-based conjunctival flap which is helpful in reducing these complications. After dissecting the conjunctiva from the limbus, a shallow groove is cut directly behind the former conjunctival insertion. At the end of the operation the conjunctiva is sutured into this groove using a running 10.0 nylon suture in a meander-like fashion. A very tight wound closure results. We used this technique in 104 consecutive goniotrephinations. We found a low incidence of only mild external fistulation, hypotony, flattening of the anterior chamber and choroidal detachment. Astigmatism induced by the operation was -1.2 +/- 1.2 D, usually with the rule.

Aged↗