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5-fluorouracil and glaucoma filtering surgery: I. An animal model.

Failure of a glaucoma filtering procedure commonly results from scarring at the surgical site. Fibroblasts play an important role in the scarring process. 5-fluorouracil is an antimetabolite capable of inhibiting fibroblast proliferation. We tested the ability of 5-fluorouracil to inhibit cicatrization at the filtering site in an experimental model. Posterior lip sclerectomies were performed in each eye of ten normal owl monkeys. Postoperatively, one eye of each animal received subconjunctival injections of fluorouracil and the fellow eye received saline injections in a randomized, masked fashion. Two animals died of undetermined causes. None of the control eyes developed blebs, but six of the eight treated eyes in surviving animals developed blebs. The difference between intraocular pressures in fluorouracil-treated and control eyes was statistically significant (P less than 0.05). Signs of ocular toxicity included persistent corneal epithelial defects and delayed healing of the conjunctival incision. These results are considerably more favorable than those previously reported with experimental filtering procedures in non-human primates. Pharmacologic modulation of wound healing may decrease the risk of failure of filtering operations.

Animals

Bleb rupture following filtering surgery with mitomycin-C: clinicopathologic correlations.

A 91-year-old woman with a complete rupture of her mitomycin-C filtration bleb associated with eye rubbing while crying was examined. An 18mm soft contact lens was placed preoperatively to re-form the anterior chamber and the patient underwent a conjunctival advancement. Histopathology of the free conjunctival specimen revealed a stratified squamous epithelium with marked attentuation of the subepithelial tissue in the area treated with mitomycin-C. Bleb rupture may be associated with minimal physical trauma following guarded filtration surgery. Successful visual rehabilitation is possible with conjunctival advancement, yet long-term survival of the bleb is poor.

Aged

Preoperative mitomycin-C subconjunctival injection and glaucoma filtering surgery.

Intraoperative mitomycin-C application has been well accepted recently as a useful adjunctive procedure to enhance the filtering effect in glaucoma surgery. However, the exact dose of mitomycin-C left after such a procedure in the ocular tissue is variable and unclear. It is important to determine such residual because of potential long-term toxicity of mitomycin-C to the eye. Based on previous successful experience using preoperative mitomycin-C subconjunctival injection in the THC-YAG laser sclerostomy on rabbits, the effect of intraocular pressure (IOP) control and its clinical observation was studied in six eyes of six refractory and high risk glaucoma patients by subconjunctival 1.2 micrograms to 3.6 micrograms mitomycin-C injection 24 to 72 hours prior to classic, routine, limbal-based trabeculectomy surgery. After 18 months of satisfactory clinical observation of the first eye for IOP, functioning bleb appearance and smooth clinical course, the same procedure was used on an additional five eyes, with a follow-up period of more than five months. Average IOP was reduced from 27.8 mm Hg (range 24 to 34 mm Hg) preoperatively to 9.5 mm Hg (range 5 to 14 mm Hg) postoperatively, with a smooth clinical course. The advantages of such preoperative subconjunctival mitomycin-C injection are emphasized here.

Adolescent

The effects of glaucoma filtering surgery on the variability of diurnal intraocular pressure.

The results of this study indicate that filtration surgery reduces the mean diurnal IOP, the range of diurnal variation, and the day-to-day variability. The effect on the range is proportionally greater than on the other two parameters. Further study will be required to determine whether this selective effect makes surgical reduction of IOP any more effective in the prevention of further glaucomatous visual field damage than other therapeutic methods that lower mean IOP to the same degree.

Circadian Rhythm

Internal sclerectomy for glaucoma filtering surgery with an automated trephine.

A technique is described for performing full-thickness glaucoma filtering operation from within the anterior chamber. The procedure utilizes an automated trephine, designated the "trabecuphine," that is capable of simultaneous cutting and irrigation. The trabecuphine is brought into the anterior chamber through a limbal incision 180 degrees away from the planned filter site. The trephine is passed across the anterior chamber, above the iris, and into the angle to perform the sclerotomy. This procedure was performed successfully in 13 eyes of seven cynomolgus monkeys. Complications included two small hyphemas that cleared completely. Other complications such as flat anterior chamber, corneal damage, iridodialysis, conjunctival buttonhole, and cataract formation did not occur. Internal scleral trephination may offer another alternative in the surgical management of patients with intractable glaucoma.

Animals

Temporary visual loss with ciliary body detachment and hypotony after attempted YAG laser repair of failed filtering surgery.

Ciliary body detachment, hypotony, and visual loss developed within one month after an attempt to reopen a closed filtering bleb with YAG laser treatment. The patient was a 68-year-old black woman who had a previously functioning thermal sclerostomy. YAG laser energy delivered to the sclerosed filtering site ab interno was unsuccessful in restoring patency to the filtering site as judged by clinical examination. Because of hypotony, all glaucoma medications were discontinued. Resolution of the ciliary body detachment with return of vision and stable intraocular pressures occurred after three weeks of intensive topical and systemic corticosteroid treatment.

Aged

Recurrent choroidal detachment following timolol therapy in previously filtered eye. Choroidal detachment post filtering surgery.

A 64-year-old patient with open-angle glaucoma was treated with timolol following two unsuccessful filtering procedures. While on timolol therapy, she developed three episodes of choroidal detachment, hypotony and shallow anterior chamber. These findings resolved upon cessation of timolol and reappeared on 3 occasions shortly after reinstitution of the beta blocker therapy.

Choroid Diseases

Reducing corneal toxicity of 5-fluorouracil in the early postoperative period following glaucoma filtering surgery.

To gain a better understanding of the relationship between postoperative 5-fluorouracil administration and corneal complications associated with its use, we analysed 43 consecutive filtering procedures in which it had been employed. Nine of the 43 eyes had corneal complications during that period. At the end of the three-month period, these corneal complications had all resolved. There was no correlation between postoperative intraocular pressure lowering and incidence of corneal complications. A low dose of 5-fluorouracil, and early recognition and treatment of corneal toxicity associated with its use may reduce corneal complications while maintaining filtration in eyes with poor surgical prognosis.

Aged

[Intraocular pressure after filtering operation or combined filter-cataract operation].

BACKGROUND: The prevalence of glaucoma is 2% and of cataract 25% in patients at the age of 65 to 75 years. To this moment the discussion is open about the optimal therapy when there is simultaneous cataract and glaucoma. We evaluated and compared the intraocular pressure and the visual acuity in patients with filtering-surgery and combined surgery (= filtering surgery plus simultaneous cataract surgery). METHOD: In a retrospective study 56 eyes of 45 patients operated by filtering surgery and 46 eyes of 40 patients operated by combined surgery were examined. RESULTS: Patients with combined surgery showed significant higher frequency of fibrin in the anterior chamber compared to patients with filtering-surgery. After 12 months there was no significant difference in intraocular pressure between both groups. The IOP of the last examination was 16 +/- 4 mm Hg in eyes with combined surgery and 14 +/- 4 mm Hg in eyes with filtering surgery. Eyes with combined surgery showed an increase of visual acuity from 0.2 +/- 0.2 to 0.4 +/- 0.3, eyes with filtering surgery a decrease of visual acuity from 0.7 +/- 0.3 to 0.6 +/- 0.3. CONCLUSION: Combined surgery is perioperatively associated with a higher frequency of complications, but showed 12 months postoperatively equal values of regulated intraocular pressure.

Aged

[Initial experience with the use of mitomycin C in anti-glaucoma filtering surgery].

The authors report on their initial experience with the use of peroperative administration of mitomycin C (0.5 mg/ml for a period of 5 mins.) in complicated cases of glaucoma. In 14 eyes of 15 with a mean observation period of 8 months compensation of the intraocular pressure was achieved. In one eye 5 months after a filtering operation transplantation of the cornea was performed with secondary implantation of the posterior-chamber intraocular lens, decompensation of the intraocular pressure was treated 11 months after the filtering operation by cyclocryotherapy. Mitomycin C is a promising substance which improves substantially the prognosis of complicated cases of glaucoma.

Adult

Filtering surgery in children: barriers to success.

The use of trabeculectomy in advanced pediatric glaucoma is reviewed. Intraocular pressure was controlled in only 50% of the patients, and the best visual results was 20/200. Complications of vitreous loss, scleral collapse, ectasia, retinal detachment, and endophthalmitis were encountered. No evidence was found to support the claim that in the seriously compromised buphthalmic eyes, trabeculectomy is safer than other filtering operations since it filters under a scleral flap.

Adolescent

Topical fluorouracil. II. Postoperative administration in an animal model of glaucoma filtering surgery.

Unilateral posterior lip sclerectomies were performed in ten owl monkeys. Five milligrams of fluorouracil was injected subconjunctivally in each operated eye immediately after surgery. Three drops (approximately 2.4 mg/drop) of fluorouracil were instilled ten minutes apart in each operated eye twice daily on postoperative days 1 through 7 and once daily on postoperative days 8 through 15, 17, 19, and 21. One monkey died on the seventh postoperative day; its death could not be attributed to systemic fluorouracil toxicity. All of the operated eyes had filtering blebs after the full course of fluorouracil, but seven also had corneal epithelial defects. By the seventh postoperative week, two of the operated eyes manifested moderately severe corneal opacification. Ten weeks postoperatively, the electroretinographic a- and b-wave amplitudes averaged 17% and 12% less, respectively, in the seven operated eyes without clinically significant corneal opacification than in the unoperated fellow eyes. Only two eyes had blebs after the 12th postoperative week. Histopathologic examination was performed on five eyes, of which only two revealed patent sclerostomies. Although topical fluorouracil appears to delay bleb scarring, the corneal findings suggest that it may be more toxic than subconjunctival fluorouracil.

Administration, Topical

Complications of subconjunctival 5-fluorouracil following glaucoma filtering surgery.

The antimetabolite 5-fluorouracil (5-FU) has been used to inhibit fibroblastic growth to increase the success rate in glaucoma filtration surgery. Subconjunctival 5-FU can have adverse side effects. This paper describes two cases in detail of the ocular side effects of 5-FU. The first case is representative of the ocular surface problems. The second case deals with bleb leaks. Relative contraindications to 5-FU treatment are pre-existing ocular surface problems, early postoperative bleb leaks and fornix-based conjunctival flaps in filtering procedures. New drug delivery methods are presently being investigated to help decrease the adverse side effects and increase the efficacy of 5-FU.

Aged