Richard K. Parrish

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.

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.

A comparison of latanoprost, bimatoprost, and travoprost in patients with elevated intraocular pressure:

PURPOSE To Internet Advance publication at ajo.com Feb 13, 2003. compare the intraocular pressure (IOP)-lowering effect and safety of latanoprost, bimatoprost, and travoprost in patients with open-angle glaucoma (OAG) or ocular hypertension (OH). DESIGN Interventional study. METHODS This 12-week, randomized, parallel-group study was conducted at 45 US sites. Previously treated patients with OAG or OH and an IOP > or =23 mm Hg in one or both eyes after washout received either latanoprost 0.005%, bimatoprost 0.03%, or travoprost 0.004% once daily in the evening. At baseline and after 6 and 12 weeks of therapy, masked evaluators measured IOP in triplicate at 8:00 AM, 12 noon, 4:00 PM, and 8:00 PM, and masked investigators graded conjunctival hyperemia before the 8:00 AM IOP measurement. The primary efficacy outcome measure was change between baseline and Week 12 in the 8:00 AM IOP (time of peak drug effect). RESULTS In all, 410 of 411 randomized patients were included in intent-to-treat analyses (latanoprost, 136; bimatoprost, 136; travoprost, 138). Baseline mean 8:00 AM IOP levels were similar (P =.772); by week 12, reductions were observed in all 3 groups (P <.001 for each). Adjusted (ANCOVA) reductions in mean IOP at 8:00 AM were similar (P =.128) as were those at 12 noon, 4:00 PM, and 8:00 PM. Fewer latanoprost-treated patients reported ocular adverse events (P <.001, latanoprost vs bimatoprost), fewer reported hyperemia (P =.001, latanoprost vs bimatoprost), and average hyperemia scores were lower at week 12 (P =.001, latanoprost vs bimatoprost). CONCLUSIONS Latanoprost, bimatoprost, and travoprost were comparable in their ability to reduce IOP in OAG and OH patients. Latanoprost exhibited greater ocular tolerability.

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.

Trabeculectomy in Young Patients

The results of 117 trabeculectomies performed on 98 patients under the age of 50 years were reviewed. The success rate in primary glaucomas (29/39, 74%) was considerably higher than in secondary glaucomas (24/50, 48%) or in developmental glaucomas (6/17, 35%). Only one (9%) of 11 trabeculectomies performed for neovascular glaucoma was successful. Trabeculectomies for secondary glaucomas were significantly more often successful in eyes that had not undergone previous surgery. None of the six trabeculectomies performed on patients under the age of ten years controlled the intraocular pressure. Of the 45 trabeculectomies performed on patients aged 10 to 29 years, 17 (38%) were successful. Of the 66 trabeculectomies performed on patients aged 30 to 49 years, 43 (65%) were successful. The success rates among black, white, and hispanic patients were similar. The ability to identify patients at high risk for failure of trabeculectomy may be of value in guiding the surgical management of glaucoma.

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.

2002 Survey of the American Glaucoma Society: Practice Preferences for Glaucoma Surgery and Antifibrotic Use

Purpose:To determine the preference of members of the American Glaucoma Society for the use of antifibrotic agents (mitomycin C or 5-fluorouracil or both) and glaucoma drainage devices in ten clinical settings. Materials and Methods:Voluntary written survey of the American Glaucoma Society. Results:American Glaucoma Society (AGS) members continue to report preference for mitomycin C use in ten clinical settings. The percent usage for glaucoma drainage devices has increased in poor prognosis scenarios including the following: neovascular glaucoma, previous failed trabeculectomy, previous ECCE/ICCE, previous PKP, previous scleral buckling surgery, and uveitic glaucoma. However, trabeculectomy and MMC continue to be more likely employed for surgical management. Conclusion:Despite the long-term complications of bleb-related infections, no statistically significant shift in preference away from MMC use or reduction in the concentration of drug delivery was observed since the 1996 survey.

Trabeculectomy in Aphakic Eyes

One hundred twenty-seven trabeculectomies performed on aphakic eyes at the Bascom Palmer Eye Institute (BPEI) between 1972 and 1982 were reviewed. Forty-five cases were excluded from data analysis: 28 in eyes with confounding conditions, such as neovascular glaucoma; ten with follow-up of less than six months; and seven that were the second or third trabeculectomy performed at the BPEI in six eyes. Of the remaining 82 trabeculectomies in 82 eyes: 32 (39%) were categorized as successes (eyes that achieved an intraocular pressure of less than or equal to 21 mmHg with medication or less than or equal to 25 mmHg without medication); eight (10%) were categorized as qualified failures (eyes that had an intraocular pressure of greater than 21 mmHg despite medication or greater than 25 mmHg without medication); and 42 (51%) were categorized as complete failures (eyes that underwent further glaucoma surgery, had further glaucoma surgery recommended, or lost light perception). In the 20 eyes of the patients younger than 50 years of age, only one (5%) was categorized as a success; while in the 62 eyes of the patients 50 years of age or older, 31 (50%) were categorized as successes.

Use of antifibrosis agents and glaucoma drainage devices in the American and Japanese Glaucoma Societies.

PURPOSE To investigate practice patterns among glaucoma subspecialists in the American Glaucoma Society (AGS) and the Japanese Glaucoma Society (JGS), regarding use of antifibrosis agents and glaucoma drainage devices. METHODS An anonymous survey incorporating 10 clinical situations was mailed to all AGS and JGS members in December 1995. RESULTS Half of the AGS (105 of 210), and JGS (25 of 50) members returned surveys. Most respondents (51-87%) preferred trabeculectomy with adjunctive mitomycin for all 10 clinical situations. Mitomycin concentrations varied from 0.1 to 0.8 mg/ml (range of means for 10 situations 0.31-0.39 mg/ml) and intraoperative application times ranged from 5 s to 7 min (range of means for 10 situations 2.5-4.6 min). Preferences for either no antifibrosis agent (up to 39%) or 5-fluorouracil (up to 29%) were highest in primary trabeculectomy. Thirty-seven percent to 64% of AGS members used glaucoma drainage devices, especially after complicated postsurgical glaucomas (after penetrating keratoplasty, scleral buckling, or pars plana vitrectomy) and in neovascular glaucoma, but few JGS members used them. Large differences between university- and private practice-based AGS members were found only in mitomycin use for primary trabeculectomy (33% vs. 52%, respectively; p = 0.07) and for complicated postsurgical glaucomas (46% vs. 70%, respectively; p = 0.03). CONCLUSIONS Trabeculectomy with mitomycin was the preferred surgical procedure among AGS and JGS members in the clinical situations surveyed. Mitomycin concentration and time of application varied widely. Many respondents used 5-fluorouracil or no antimetabolite in primary trabeculectomy. Glaucoma drainage devices were widely used for complicated glaucomas in the United States.

Neovascular Glaucoma Following Central Retinal Vein Obstruction

The results of a prospective clinical and fluorescein angiographic study of 155 patients with central retinal vein obstruction (CRVO) were analyzed to identify risk factors contributing to the subsequent development of iris neovascularization (NVI) and neovascular glaucoma (NVG). Of 144 untreated eyes, 20% developed NVG. The eyes were classified as having either an ischemic or a hyperpermeable type of CRVO according to the extent of retinal capillary nonperfusion demonstrated by the initial fluorescein angiogram. The risk of developing NVG was found to be approximately 60% in those eyes with extensive retinal ischemia. None of the 22 eyes with an ischemic CRVO treated with panretinal photocoagulation (PRP) prior to the onset of NVI developed NVG.