Darrell WuDunn

Morphologic classification of filtering blebs after glaucoma filtration surgery: The Indiana Bleb Appearance Grading Scale

PurposeTo establish a new classification system for filtering blebs according to clinical morphologic parameters. The purpose of this classification system is to provide a uniform and objective assessment of bleb appearance and establish a framework system through which outcomes of filtration surgery may be better correlated to clinical morphology. Materials and MethodsThe Indiana Bleb Appearance Grading Scale contains a set of photographic standards illustrating a range of filtering bleb morphology selected from the slide library of the Glaucoma Service at the Indiana University Department of Ophthalmology. These standards consist of slit lamp images for grading bleb height, extent, vascularity, and leakage with the Seidel test. For grading, the morphologic appearance of the filtration bleb is assessed relative to the standard images for the 4 parameters and scored accordingly. Fifty-one clinical bleb photographs were evaluated and scored by 3 glaucoma subspecialists in a masked fashion according to the scale. ResultsFor all of the grading scales, high interobserver agreement was found using the scale to classify the appearance of filtering blebs (height +0.76; extent +0.78; vascularity +0.90, interclass correlation coefficient for consistency using a 2-way mixed effect model). ConclusionThe Indiana Bleb Appearance Grading Scale is a simple, reproducible, yet comprehensive system for classifying the morphologic slit lamp appearance of filtration blebs.

Long-term Outcomes of Intraoperative 5-Fluorouracil versus Intraoperative Mitomycin C in Primary Trabeculectomy Surgery

OBJECTIVE To compare the long-term efficacy of intraoperative 5-fluorouracil (5-FU) and mitomycin C (MMC) in primary trabeculectomy. DESIGN Comparative case series and extension of a prospective, randomized controlled trial. PARTICIPANTS One hundred fifteen eyes of 103 subjects undergoing primary trabeculectomy with either intraoperative 5-FU or MMC. METHODS This study is an extension of a 12-month, prospective, double-masked, randomized trial that previously was reported. Subjects were randomized to receive either intraoperative 5-FU (50 mg/ml for 5 minutes) or MMC (0.2 mg/ml for 2 minutes) during primary trabeculectomy. Follow-up data were collected from patient medical records after informed consent was obtained from the study patient. Attempts were made to contact subjects who had been lost to follow-up, and some consented to reexamination. MAIN OUTCOME MEASURES The primary measure was Kaplan-Meier survival function, with failure defined as intraocular pressure (IOP) of more than 21 mmHg or less than 6 mmHg on 2 consecutive visits, less than 20% reduction from baseline IOP, loss of light perception vision, or additional glaucoma surgery to lower IOP (except bleb revision). Secondary measures included IOP, number of glaucoma medications, visual acuity, additional surgeries, and number and type of complications. RESULTS Mean follow up was 53.4+/-31.4 months (interquartile range, 34-82 months) in the 5-FU group and 45.3+/-28.0 months (interquartile range, 19-70 months) in the MMC group (P = 0.15, t test). Kaplan-Meier success was 0.83 at 3 years and 0.76 at 5 years in the 5-FU group and 0.79 at 3 years and 0.66 at 5 years in the MMC group (P = 0.18, log-rank test). Bleb leakage was the most common complication in each group and developed in approximately 4% of subjects in each group per year (P = 0.33, log-rank test). CONCLUSIONS There were no significant differences between topical 5-FU and topical MMC in reducing IOP of eyes undergoing primary trabeculectomy. Both antifibrosis agents may contribute to the development of bleb leakage. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Dysfunctional regulation of ocular blood flow: A risk factor for glaucoma?

Primary open angle glaucoma (OAG) is a multifactorial optic neuropathy characterized by progressive retinal ganglion cell death and associated visual field loss. OAG is an emerging disease with increasing costs and negative outcomes, yet its fundamental pathophysiology remains largely undetermined. A major treatable risk factor for glaucoma is elevated intraocular pressure (IOP). Despite the medical lowering of IOP, however, some glaucoma patients continue to experience disease progression and subsequent irreversible vision loss. The scientific community continues to accrue evidence suggesting that alterations in ocular blood flow play a prominent role in OAG disease processes. This article develops the thesis that dysfunctional regulation of ocular blood flow may contribute to glaucomatous optic neuropathy. Evidence suggests that impaired vascular autoregulation renders the optic nerve head susceptible to decreases in ocular perfusion pressure, increases in IOP, and/or increased local metabolic demands. Ischemic damage, which likely contributes to further impairment in autoregulation, results in changes to the optic nerve head consistent with glaucoma. Included in this review are discussions of conditions thought to contribute to vascular regulatory dysfunction in OAG, including atherosclerosis, vasospasm, and endothelial dysfunction.

A prospective randomized trial comparing intraoperative 5-fluorouracil vs mitomycin C in primary trabeculectomy.

PURPOSE To compare the safety and efficacy of intraoperative 5-fluorouracil (5-FU) or Intraoperative mitomycin C (MMC) in eyes undergoing primary trabeculectomy. DESIGN Prospective double-masked randomized clinical trial. METHODS One hundred fifteen eyes of 103 patients with uncontrolled intraocular pressure (IOP) despite maximally tolerated medical therapy or laser were prospectively randomized in a double-masked fashion to one of two treatment groups in a single institution setting. Subjects eyes underwent primary trabeculectomy with either topical 5-FU (50 mg/ml for 5 minutes) or topical MMC (0.2 mg/ml for 2 minutes). Primary outcome measures included the number of eyes achieving target pressures of 21, 18, 15, and 12 mm Hg at 6 and 12 months postoperatively. Secondary outcome measures included IOP, best-corrected visual acuity, complications, and interventions. RESULTS Of the 115 eyes, 57 received 5-FU while 58 received MMC. A target IOP of 21 mm Hg at 6 months was achieved in 53 of 56 (95%) eyes in the 5-FU group and 54 of 57 (95%) eyes in the MMC group (P = 1.00). At 12 months, 45 of 48 (94%) eyes in the 5-FU group met a target IOP of 21 mm Hg while 48 of 54 (89%) eyes in the MMC group did (P =.49). The most common complications in each group were persistent choroidal effusions and bleb leak. CONCLUSION Our study suggests that intraoperative topical 5-FU is at least as effective as intraoperative topical MMC in reducing IOP of eyes undergoing primary trabeculectomy.

Delayed suprachoroidal hemorrhage after glaucoma filtration procedures

OBJECTIVES To determine the incidence of, risk factors for, and outcomes of delayed suprachoroidal hemorrhage (DSCH) after glaucoma filtration surgery. DESIGN Retrospective case-control study. PARTICIPANTS All patients undergoing glaucoma filtration procedures between 1986 and 2000 at Indiana University who were diagnosed postoperatively with suprachoroidal hemorrhage. A total of 66 patients with DSCH were identified. These were compared with a randomly selected group of patients who underwent similar procedures but did not have suprachoroidal hemorrhage. METHODS Total cases of DSCH were initially compared with the total number of glaucoma surgeries to determine the overall incidence and the incidence in the different procedures. Subsequently, a case-control study was performed comparing the group with hemorrhage to the control group to identify risk factors. Finally, outcomes and prognostic factors were determined by comparing vision preoperatively and postoperatively and parameters of patients with good and poor outcomes. MAIN OUTCOME MEASURES Incidence of DSCH, risk factors associated with its occurrence, visual outcomes, and factors important for prognosis. RESULTS Of a total of 2285 glaucoma filtration procedures, 66 (2.9%) cases of DSCH were identified. It developed in 9 of 615 (1.5%) trabeculectomies without antimetabolite, 30 of 1248 (2.4%) trabeculectomies with antimetabolite, 2 of 72 (2.8%) valved tube shunt implantations, and 25 of 350 (7.1%) nonvalved tube shunt implantations. The increased incidence of DSCH after tube shunts compared with trabeculectomy-associated DSCH was significant (P < 0.0001) with an odds ratio of 3.2. The risk factors for DSCH after glaucoma surgery include white race (P = 0.012), anticoagulation (P = 0.034), severe postoperative hypotony (P = 0.033), and aphakia/anterior chamber intraocular lens (P = 0.002). The visual outcomes of patients with hemorrhage were poor, with a decrease in logarithm of the minimum angle of resolution visual acuity from 0.72 to 1.36, which was statistically significant compared with the controls (P < 0.009). CONCLUSIONS Delayed suprachoroidal hemorrhage occurs more frequently after tube shunt implantation than after trabeculectomy. Caution should be exercised when operating on patients with known risk factors, because the visual outcomes after DSCH are poor.

Conjunctival advancement versus nonincisional treatment for late-onset glaucoma filtering bleb leaks

OBJECTIVE To compare the outcomes of conjunctival advancement and nonincisional management of late-onset glaucoma filtering bleb leak. DESIGN Retrospective, nonrandomized, comparative interventional trial. PARTICIPANTS Fifty-one eyes of 48 persons who underwent management of late-onset glaucoma filtering bleb leak from December 1986 through December 1999 were included. Thirty-seven eyes were included in the nonincisional treatment group (aqueous suppression with lubrication or patching, bandage contact lenses, cyanoacrylate glue, autologous blood injection, or a combination thereof) and 34 eyes were included in the surgical revision group (conjunctival advancement with preservation of the preexisting bleb). Twenty eyes underwent nonincisional treatment before surgical revision and were included in each treatment group. METHODS Retrospective chart review of bleb leaks occurring at least 2 months after trabeculectomy. Successful treatment was defined as the resolution of the bleb leak, a final intraocular pressure (IOP) of 21 mmHg or less, and no significant complications such as blebitis, endophthalmitis, or bleb dysesthesia requiring a bleb revision. MAIN OUTCOME MEASURES Cumulative success of closure of the filtering bleb leak, complications resulting from the intervention, IOP before and after treatment, and number of glaucoma medications before and after treatment. RESULTS The Kaplan-Meier cumulative probability of success at 12 and 24 months were 0.45 and 0.42, respectively, for the nonincisional treatment group and 0.80 and 0.80, respectively, for the surgical revision group. The overall difference between the cumulative success of surgical and nonincisional treatment was statistically significant (P = 0.0001, log-rank test). In the nonincisional treatment group, only 20 of 37 eyes (54%) achieved initial sealing of the bleb leak after the treatment, and of those, almost half (8/20) eventually failed. Reasons for failure included persistent or recurrent leak (n = 21), blebitis or endophthalmitis (n = 6, including 4 with persistent leak), and bleb dysesthesia (n = 2). All eyes in the surgical group achieved closure of the leak, however 7 eventually failed because of leak recurrence (n = 2), elevated IOP (n = 3), or bleb dysesthesia (n = 2), and 11 required additional glaucoma medications. CONCLUSIONS Patients with late bleb leaks managed with conjunctival advancement were more likely to have successful outcomes and less likely to have serious intraocular infections than those managed more conservatively.

Efficacy of the Ahmed S2 glaucoma valve compared with the Baerveldt 250-mm2 glaucoma implant.

OBJECTIVE To compare the efficacy of the Ahmed S2 Glaucoma Valve with the Baerveldt 250-mm(2) Glaucoma Implant in the treatment of adult glaucoma. DESIGN Comparative case series. PARTICIPANTS Fifty-nine eyes of 59 patients who received the Ahmed S2 Glaucoma Valve and 133 eyes of 133 patients who received the Baerveldt 250-mm(2) Glaucoma Implant by the Indiana University Glaucoma Service from 1996 to 2003. METHODS Eyes that had previous drainage implant procedures were excluded from both groups. If both eyes of a single patient received an implant, the second eye to undergo implantation was excluded from the study. MAIN OUTCOME MEASURES Kaplan-Meier survival with success defined as intraocular pressure (IOP) > 5 mmHg and < 22 mmHg and at least 20% reduction from preoperative IOP (with or without antiglaucoma medications) and without loss of light perception. Secondary outcome measures included intraocular pressure, visual acuity, number of glaucoma medications, and surgical complications. RESULTS The 2 groups were similar with regards to age, gender, race, neovascular glaucoma diagnosis, number of prior ocular surgeries, preoperative IOP, and number of preoperative glaucoma medications. Mean durations of follow-up were 20.0 months for Ahmed eyes and 22.9 months for Baerveldt eyes. Cumulative successes in the Ahmed group were 0.73 at 1 year and 0.62 at 2 years, whereas cumulative successes in the Baerveldt group were 0.92 at 1 year and 0.85 at 2 years (Kaplan-Meier survival functions: P = 0.03, log rank test). Male gender, African descent, neovascular glaucoma, and Ahmed implantation were found to be significant predictors of failure. At last follow-up visit, eyes in the Ahmed group had a significantly higher mean IOP (19.8+/-9.5 vs. 15.8+/-7.9 mmHg, P = 0.003, t test) and more antiglaucoma medications (1.4+/-1.2 vs. 0.9+/-1.1 medications, P = 0.008, Mann-Whitney test) than eyes in the Baerveldt group. Two methods for avoiding hypotony after Baerveldt 250-mm(2) implantation had similar outcomes. CONCLUSIONS Our study suggests that the Ahmed S2 Glaucoma Valve may be less effective at lowering IOP than the Baerveldt 250-mm(2) Glaucoma Implant.

The effect of mechanical strain on matrix metalloproteinase production by bovine trabecular meshwork cells

Purpose. To evaluate the effects of mechanical stretching of trabecular meshwork cells on matrix metalloproteinase activity. Methods. Cultured bovine trabecular meshwork cells grown on collagen-coated elastomer were subjected to 10% biaxial mechanical stretching. After various time intervals, culture medium was collected from stretched and non-stretched control cells. Matrix metalloproteinase activity was studied by zymography and levels of inhibitors were determined by immunoblotting or immunoassay of the collected medium. Results. Trabecular meshwork cells subjected to mechanical strain showed increased stromelysin and gelatinase A activity at 24 to 72 hours after initial stretching compared to control cells. By 72 hours of strain, stromelysin activity increased to up to 73% (p < 0.01) whereas gelatinase A activity increased by 31% (p < 0.05). The increased metalloproteinase activity was reversible with relaxation of mechanical stretch. Levels of tissue inhibitor of matrix metalloproteinase-1 and -2 remained unchanged during 72 hours of stretch. Conclusions. Changes in mechanical strain on the trabecular meshwork, which may occur in vivo during changes in intraocular pressure, induce changes in matrix metalloproteinase activity. The resultant alterations in the extracellular matrix may affect outflow resistance through the trabecular meshwork in response to alterations in intraocular pressure.

Intraocular pressure-lowering efficacy of bimatoprost 0.03% and travoprost 0.004% in patients with glaucoma or ocular hypertension

Aim: To evaluate the efficacies of bimatoprost and travoprost for lowering of intraocular pressure (IOP) for the treatment of glaucoma and ocular hypertension. Methods: Prospective, randomised, investigator-blinded, parallel-group clinical trial. After completing a washout of all glaucoma drugs, patients (n = 157) were randomised to bimatoprost or travoprost for 6 months. Visits were at baseline, 1 week, and 1, 3 and 6 months. IOP was measured at 09:00 h at each visit and also at 13:00 and 16:00 h at baseline and at 3 and 6 months. Results: No significant between-group differences were observed in IOP at baseline, at 09:00, 13:00 or 16:00 h (p⩾0.741). After 6 months, both drugs significantly reduced IOP at every time point (p⩽0.001). After 6 months, mean IOP reduction at 09:00 h was 7.1 mm Hg (27.9%) with bimatoprost (n = 76) and 5.7 mm Hg (23.3%) with travoprost (n = 81; p = 0.014). At 13:00 h, mean IOP reduction was 5.9 mm Hg with bimatoprost (25.3%) and 5.2 mm Hg (22.4%) with travoprost (p = 0.213). At 16:00 h, the mean IOP reduction was 5.3 mm Hg (22.5%) with bimatoprost and 4.5 mm Hg (18.9%; p = 0.207) with travoprost. Both study drugs were well tolerated, with ocular redness the most commonly reported adverse event in both treatment groups. Conclusions: Bimatoprost provided greater mean IOP reductions than travoprost.

Mechanobiology of trabecular meshwork cells

Trabecular meshwork (TM) cells likely play a key role in regulating outflow facility and hence intraocular pressure. They function in a dynamic environment subjected to variations in mechanical and fluid shear forces. Because the extent of mechanical stress on the trabecular meshwork is dependent on the intraocular pressure, the behavior of TM cells under mechanical strain may suggest mechanisms for how outflow facility is regulated. Studies have demonstrated that TM cells respond in a variety of ways to mechanical loads, including increased extracellular matrix turnover, altered gene expression, cytokine release, and altered signal transduction. This review highlights some of the considerations and limitations of studying the mechanobiology of TM cells.