Gregory L. Skuta

Wound healing in glaucoma filtering surgery

Successful glaucoma filtering surgery is characterized by the passage of aqueous humor from the anterior chamber to the subconjunctival space, which results in the formation of a filtering bleb. Aqueous in the subconjunctival space may then exit by multiple pathways. Bleb failure most often results from fibroblast proliferation and subconjunctival fibrosis. Factors associated with an increased risk of bleb failure include youth, aphakia, active anterior segment neovascularization, inflammation, previously failed glaucoma filtering surgery, and, possibly, race. Several surgical and pharmacologic techniques have recently been introduced to enhance success in eyes with poor surgical prognoses. To elucidate the scientific rationale of these methods, we summarize the process of wound healing after glaucoma filtering surgery and describe postoperative clinical and histopathologic features, factors which may affect success, and specific methods to improve surgical success.

Intraoperative Mitomycin versus Postoperative 5-Fluorouracil in High-risk Glaucoma Filtering Surgery

In a randomized clinical trial, the authors compared the use of postoperative subconjunctival injections of 5-fluorouracil (5-FU) in 19 eyes with a single intraoperative application of subconjunctival mitomycin (MMC) at the filtering site in 20 eyes at high risk for failure of glaucoma filtering surgery. Six months after surgery, intraocular pressures averaged 10.9 +/- 5.3 mmHg (mean +/- standard deviation) in the MMC-treated eyes versus 14.2 +/- 5.5 mmHg in the 5-FU-treated eyes (P = 0.08) and were less than or equal to 12 mmHg in 60.0% of MMC-treated eyes and 21.1% of 5-FU-treated eyes (P = 0.03). Mitomycin-treated eyes were receiving an average of 0.3 +/- 0.5 medications for intraocular pressure control, and 5-FU-treated eyes were receiving an average of 1.1 +/- 1.1 medications (P = 0.01). Drug-induced corneal epithelial defects were seen in nine 5-FU-treated eyes and in no MMC-treated eyes (P = 0.0004). These results suggest that intraoperative MMC may be a viable alternative to postoperative 5-FU, with lower overall intraocular pressures, decreased dependence on postoperative ocular antihypertensive medications, and decreased corneal toxicity.

Glaucoma Filtering Surgery with 5-Fluorouracil

A life-table analysis of surgical outcomes was performed on the first eye of 155 patients who were enrolled in a pilot study of glaucoma filtering surgery with postoperative subconjunctival 5-fluorouracil (5-FU) injections. The success rates at 1-, 2-, and 3-year intervals were 68, 63, and 63%, respectively, for 88 patients with non-neovascular glaucoma in aphakia; 82, 75, and 75% for 39 patients with non-neovascular glaucoma after unsuccessful filtering surgery; and 68% at each yearly interval for 28 patients with neovascular glaucoma. Complications which resulted from filtering surgery and the 5-FU injections included corneal epithelial defects (55.5%), conjunctival wound leaks (36.8%), suprachoroidal hemorrhage (5.8%), rhegmatogenous retinal detachment (2.6%), endophthalmitis and phthisis (1.9% each), and corneal scarring, late bleb leak, malignant glaucoma, and traction retinal detachment (1.3% each). A Cox Model regression analysis failed to demonstrate a correlation between surgical success and age, race, type of filtering procedure, or total dose of 5-FU received. Postoperative subconjunctival 5-FU may increase the operative success rate for selected patients with a high risk for failure after glaucoma filtering surgery.

Mitomycin C versus 5-Fluorouracil in High-risk Glaucoma Filtering Surgery: Extended Follow-up

Background: With the increased use of a hand-held indirect lens and slit-lamp biomicroscopy for stereoscopic viewing of the optic nerve, the authors believe that an acquired pit of the optic nerve is more common than was recognized previously. This increased recognition has led to the awareness that the central visual field was affected frequently in the presence of such an acquired pit. Methods: The authors retrieved the charts of a series of 97 patients who had an acquired pit of the optic nerve during an 18-month period and retrospectively reviewed the automated visual fields associated with these pits using the Humphrey Visual Field Analyzer Programs 30-2 and 10-2 and looked for involvement of the central visual field. Results: In 81.7% of the acquired pits of the optic nerves, one of the central-most test points (3° from fixation) in the appropriate hemifield on the 30-2 format was depressed severely by Statpac II ( P P = 0.03). Conclusion: The authors showed that the presence of an acquired pit in an optic nerve damaged by glaucoma frequently is associated with a threat to fixation.

Mitomycin C versus 5-Fluorouracil in High-risk Glaucoma Filtering Surgery

PURPOSE To compare the outcome of filtering surgery in high-risk patients using intraoperative mitomycin C (MMC) versus postoperative 5-fluorouracil (5-FU). METHODS In a randomized clinical trial, the use of postoperative subconjunctival injections of 5-FU in 19 eyes of 19 patients was compared with a single intraoperative application of MMC in 20 eyes of 20 patients. All eyes were at high risk for failure of glaucoma filtering surgery. RESULTS Follow-up ranged from 26 to 38 months (mean, 32.0 months). Three eyes in the MMC-treated group and two eyes in the 5-FU-treated group required subsequent surgery to control the IOP. Excluding these patients, intraocular pressure (IOP) averaged 9.0 +/- 4.9 mmHg in the MMC-treated eyes versus 16.3 +/- 4.6 mmHg in the 5-FU-treated eyes at the patients last visit (P = 0.0003). Of the MMC-treated eyes, 81.3% had IOPs less than or equal to 12 mmHg compared with 26.7% of eyes in the 5-FU group (P = 0.0023). In the MMC-treated group, the average number of medications for IOP control at last visit was 0.5 +/- 0.8 compared with 1.6 +/- 1.3 in the 5-FU-treated group (P = 0.01). Late postoperative complications (those occurring more than 3 months after surgery) were similar for the two groups, with the exception of formation of a Tenon cyst in three of the eyes treated with MMC compared with none of the 5-FU-treated eyes. CONCLUSIONS Eyes treated with MMC have lower IOP on fewer medications than eyes treated with 5-FU. Late postoperative complications are similar with the exception of an increased incidence of Tenon cyst formation in the MMC-treated eyes.

Intraocular Pressure Reduction in Normal-tension Glaucoma Patients

BACKGROUND In a collaborative study, patients with untreated normal-tension glaucoma were randomly assigned to a marked intraocular pressure reduction group or to a no therapy group. It was anticipated that medical therapy and laser trabeculoplasty would generally not achieve adequate pressure lowering and that fistulizing surgery would be required. This hypothesis was examined using current observations in the study. METHODS Patients randomized to the therapy group had a pressure reduction of at least 30% from their last prerandomization level. This was achieved within 6 months by means of fistulizing surgery or with pilocarpine and/or laser trabeculoplasty. Beta-blockers and adrenergic agonists were excluded from both eyes. RESULTS Of 30 patients with documented stable 30% pressure reduction, 17 (57%) achieved this with topical medication and/or laser trabeculoplasty: 8 with pilocarpine alone, 2 with laser trabeculoplasty alone, and 7 with laser trabeculoplasty after initial topical medication. The remaining 13 (43%) patients required a single fistulizing procedure. There was no statistically significant difference between the mean follow-up time for the nonfistulized group (533.8 +/- 437.6 days) and for the fistulized group (502.7 +/- 344.7 days). Both treatment groups had similar baseline profiles. CONCLUSION Marked pressure reduction can be achieved and maintained on a long-term basis by means other than fistulizing surgery in a large proportion of patients with untreated normal-tension glaucoma.

MK-507 versus Sezolamide: Comparative Efficacy of Two Topically Active Carbonic Anhydrase Inhibitors

Topical carbonic anhydrase inhibitors MK-507 and sezolamide hydrochloride (previously known as MK-417) were compared in a double-masked, randomized, placebo-controlled study in 82 patients with bilateral primary open-angle glaucoma or ocular hypertension. MK-507 was given every 8 or 12 hours, sezolamide every 8 hours, or placebo every 8 or 12 hours for 4 days. Both drugs lowered intraocular pressure (IOP) substantially. MK-507 was somewhat more active than sezolamide, with a peak mean IOP reduction of 26.2% for MK-507 versus 22.5% for sezolamide, although the difference between the treatments was not statistically significant. These drugs may have potential in the treatment of glaucoma.

Effects of PuPiliary Constriction on Automated Perimetry in Normal Eyes

The authors studied the effects of pupillary constriction (pilocarpine 2%) on automated static threshold perimetry in 20 normal subjects using the Humphrey Field Analyzer 30-2 and STATPAC programs. The mean defect (MD) worsened by an average of 0.67 decibels (dB) (standard deviation, 0.67 dB) in constricted fields compared with baseline visual fields (P less than or equal to 0.001). Independent comparisons of the unweighted means of threshold values for the central 30 degrees, 24 degrees, and 10 degrees were also done and showed significant reductions in sensitivity after constriction (P less than or equal to 0.001). These findings indicate that changes in pupillary diameter may produce significant declines in threshold sensitivities and support the importance of consistent pupillary diameters on serial automated visual field examinations.

Effects of Pupillary Dilation on Automated Perimetry in Normal Patients

The effects of pupillary dilation (tropicamide 1%) on automated static threshold perimetry were studied in 18 normal subjects using the Humphrey field analyzer 30-2 and STATPAC programs. The mean defect worsened by 0.83 decibels (standard deviation, 0.92 decibels) in dilated fields as compared with baseline visual fields (P = 0.001). These findings indicate that pupillary dilation in healthy subjects who are not receiving ocular medications produces statistically significant declines in threshold sensitivities. Valid comparison of results from serial visual field testing, therefore, depends on control of or adjustment for the effect of pupillary dilation.

Threshold Equivalence Between Perimeters

To determine equivalence between perimeters, 49 eyes of 35 subjects underwent static threshold testing of the central 30 degrees twice on each of three automated perimeters and twice by manual kinetic threshold testing with the Goldmann perimeter. The Octopus-Humphrey difference was 3.3 dB (2.3 dB in the upper two rows for programs 32 and 30-2). The Dicon-Octopus difference was 3.5 dB and the Dicon-Humphrey, 6.5 dB. The I4e stimulus of the Goldmann perimeter was equivalent to 17.1 dB, 13.6 dB, and 10.8 dB on the Humphrey, Octopus, and Dicon perimeters, respectively. The III4e stimulus of the Goldmann perimeter, used for visual impairment determination, was roughly equivalent to 7 to 10 dB, 4 to 7 dB, and 0 to 6 dB on the Humphrey, Octopus, and Dicon perimeters, respectively. The prediction when converting from one instrument to another was only 10% less reliable than the ability of a perimeter to predict the values on a second examination with the same perimeter. Validity of the conversion formulas was confirmed by the age-corrected normal values available for the Octopus, Humphrey, and Goldmann perimeters.