Assessment of PAX6 alleles in 66 families with aniridia.

We report on PAX6 alleles associated with a clinical diagnosis of classical aniridia in 81 affected individuals representing 66 families. Allelic variants expected to affect PAX6 function were identified in 61 families (76 individuals). Ten cases of sporadic aniridia (10 families) had complete (8 cases) or partial (2 cases) deletion of the PAX6 gene. Sequence changes that introduced a premature termination codon into the open reading frame of PAX6 occurred in 47 families (62 individuals). Three individuals with sporadic aniridia (three families) had sequence changes (one deletion, two run-on mutations) expected to result in a C-terminal extension. An intronic deletion of unknown functional significance was detected in one case of sporadic aniridia (one family), but not in unaffected relatives. Within these 61 families, single nucleotide substitutions accounted for 30/61 (49%), indels for 23/61 (38%), and complete deletion of the PAX6 locus for 8/61 (13%). In five cases of sporadic aniridia (five families), no disease-causing mutation in the coding region was detected. In total, 23 unique variants were identified that have not been reported in the Leiden Open Variation Database (LOVD) database. Within the group assessed, 92% had sequence changes expected to reduce PAX6 function, confirming the primacy of PAX6 haploinsufficiency as causal for aniridia.

Cyclophotocoagulation: a report by the American Academy of Ophthalmology.

OBJECTIVE: This document describes cyclophotocoagulation procedures for glaucoma and examines the evidence to answer key questions about patient selection, and efficacy of transscleral and endoscopic techniques. METHODS: A literature search conducted for the years 1968 to 2000 retrieved 130 citations. The author reviewed 34 of these articles and selected 19 for the panel methodologist to review and rate according to the strength of evidence. A Level I rating is assigned to properly conducted, well-designed, randomized clinical trials; a Level II rating is assigned to well-designed cohort and case-control studies; and a Level III rating is assigned to case series and poorly designed prospective and retrospective studies, including case-control studies. RESULTS: The predominant problem with all studies on cyclophotocoagulation is the lack of a uniform definition of success, which makes comparisons difficult. One randomized controlled trial (Level I evidence) compared the efficacy of transscleral cyclophotocoagulation with noncontact Nd:YAG and semiconductor diode laser. It found no significant difference between the two, although a significant problem was the variability allowed with laser parameters. Most of the literature consists of noncomparative case series that provide evidence that is limited and often not convincing. CONCLUSION: Cyclophotocoagulation is indicated for patients with refractory glaucoma who have failed trabeculectomy or tube shunt procedures, patients with minimal useful vision and elevated intraocular pressure, and patients who have no visual potential and need pain relief (based on Level III evidence). It may be useful for patients whose general medical condition precludes invasive surgery or who refuse more aggressive surgery (i.e., filter or tube). It is also useful in emergent situations, such as the acute onset of neovascular glaucoma. There is insufficient evidence to definitively compare the relative efficacy of the cyclophotocoagulation procedures for glaucoma. It is the panel's opinion, however, that semiconductor diode systems appear to possess the best combination of effectiveness (based on Level III evidence), portability, expense, and ease of use at this time.

Travoprost compared with latanoprost and timolol in patients with open-angle glaucoma or ocular hypertension.

PURPOSE: This study evaluated the safety and intraocular pressure-lowering efficacy of two concentrations of travoprost (0.0015% and 0.004%) compared with latanoprost 0.005% and timolol 0.5% in patients with open-angle glaucoma or ocular hypertension. METHODS: Eight hundred one patients with open-angle glaucoma or ocular hypertension were randomly assigned to travoprost 0.0015%, travoprost 0.004%, latanoprost 0.005%, or timolol 0.5%. The efficacy and safety of travoprost (0.0015% and 0.004%) daily was compared with latanoprost daily and timolol twice daily for a period of 12 months. RESULTS: Travoprost was equal or superior to latanoprost and superior to timolol with mean intraocular pressure over visits and time of day ranging from 17.9 to 19.1 mm Hg (travoprost 0.0015%), 17.7 to 19.1 mm Hg (travoprost 0.004%), 18.5 to 19.2 mm Hg (latanoprost), and 19.4 to 20.3 mm Hg (timolol). For all visits pooled, the mean intraocular pressure at 4 PM for travoprost was 0.7 mm Hg (0.0015%, P =.0502) and 0.8 mm Hg (0.004%, P =.0191) lower than for latanoprost. Travoprost 0.004% was more effective than latanoprost and timolol in reducing intraocular pressure in black patients by up to 2.4 mm Hg (versus latanoprost) and 4.6 mm Hg (versus timolol). Based on a criterion of 30% or greater intraocular pressure reduction from diurnal baseline or intraocular pressure 17 mm Hg or less, travoprost 0.0015% and 0.004% had an overall response to treatment of 49.3% and 54.7%, respectively, compared with 49.6% for latanoprost and 39.0% for timolol. Iris pigmentation change was observed in 10 of 201 of patients (5.0%) receiving travoprost 0.0015%, six of 196 of patients (3.1%) receiving travoprost 0.004%, 10 of 194 of patients (5.2%) receiving latanoprost, and none of the patients receiving timolol (0 of 196). The average ocular hyperemia score was less than 1 on a scale of 0 to 3, indicating that on average patients experienced between none/trace and mild for all treatment groups. There were no serious, unexpected, related adverse events reported for any therapy. CONCLUSIONS: Travoprost (0.0015% and 0.004%), a highly selective, potent prostaglandin F (FP) receptor agonist, is equal or superior to latanoprost and superior to timolol in lowering intraocular pressure in patients with open-angle glaucoma or ocular hypertension. In addition, travoprost 0.004% is significantly better than either latanoprost or timolol in lowering intraocular pressure in black patients. Travoprost is safe and generally well tolerated in the studied patient population.

Nonpenetrating glaucoma surgery.

OBJECTIVE: The purpose of this document is to describe nonpenetrating glaucoma surgery and to examine the available evidence to assess the efficacy and complications following the procedures. METHODS: A literature search that was conducted in February 2000 and repeated in September 2000 for the years 1968 to 2000 retrieved over 100 citations that matched the search criteria. Thirty three articles were selected as relevant to the assessment, and they were each evaluated by the panel methodologist for the quality of the evidence presented. RESULTS: One randomized controlled trial comparing nonpenetrating deep sclerectomy to trabeculectomy has been reported. The majority of the published literature contains information from case series, which are not randomized and lack a control group. The two major variations of nonpenetrating glaucoma surgery described in the literature are nonpenetrating deep sclerectomy and viscocanalostomy. The procedures are not familiar to many ophthalmologists, and reports often describe a difficult learning period. These procedures appear to lower intraocular pressure, usually to the mid to high teens, although follow-up is limited in most published reports. Postoperative complications due to overfiltration and hypotony are uncommon in the literature. There is no strong evidence indicating the mechanism of action, reports on bleb formation are lacking, and clinical correlation and gonioscopic findings have been minimal. CONCLUSIONS: Nonpenetrating glaucoma surgery has the potential to reduce intraocular pressure while minimizing the risk of postoperative relative hypotony and the complications associated with hypotony. Randomized clinical trials are needed to assess these procedures and to determine their role in the clinical management of glaucoma patients.

Switching patients with glaucoma or ocular hypertension from dual therapy to monotherapy: evaluation of brimonidine as a model.

A multicenter open-label study investigated the clinical effectiveness and economic feasibility of switching 142 patients from dual therapy to twice-daily monotherapy with brimonidine for glaucoma or ocular hypertension. Evaluations were performed at baseline and 2 (visit 2) and 8 (visit 3) weeks after the switch. Patients completed a questionnaire that rated medication-related visual function and satisfaction (comfort, convenience, vision, ease of remembering to use drops) at each visit. At visit 3, investigators, taking into account IOP measurements, safety, and responses on the questionnaire, recommended whether the patient should remain on brimonidine. A pharmacoeconomic analysis, including the number of visits, cost of medication, and success rates, compared the cost of dual therapy with that of switching to brimonidine monotherapy. Of the 131 patients who completed the study, 77 (59%) had no change or a decrease in IOP from baseline, and 53 (41%) had an increase. Investigators recommended that 77% of the study completers continue to take brimonidine monotherapy. Extending treatment with brimonidine for 12 months would achieve a significant cost savings of 16%. Brimonidine monotherapy is an efficacious and cost-effective alternative to dual therapy for glaucoma and ocular hypertension. Appropriate monotherapy may be as effective as dual therapy for many patients, and a clinically relevant trial such as this may be economically advantageous for testing a switch.

Emedastine ophthalmic solution 0.05% versus levocabastine ophthalmic suspension 0.05% in the treatment of allergic conjunctivitis using the conjunctival allergen challenge model.

PURPOSE: To compare a new ocular antihistamine, emedastine difumarate (Emadine Ophthalmic Solution 0.05%; Alcon Laboratories, Fort Worth, Texas), with the marketed ocular antihistamine, levocabastine hydrochloride (Livostin Ophthalmic Suspension 0.05%; CIBA Vision, Atlanta, Georgia), in the treatment of allergic conjunctivitis after conjunctival allergen challenge. METHODS: We performed a prospective, double-masked, randomized, contralateral eye study comparing emedastine 0.05% in one eye with levocabastine 0. 05% or emedastine vehicle (placebo) in the contralateral eye. Efficacy was determined 10 minutes and 2 hours after administration of study medications. Ocular itching and redness scores were recorded 3, 5, and 10 minutes after conjunctival allergen challenge. RESULTS: A total of 97 subjects with a history of allergic conjunctivitis and a positive response to a diagnostic test were evaluable for safety analysis, and 91 subjects were evaluable for the efficacy analysis. Emadastine 0.05% was statistically significantly more effective than levocabastine 0.05% in reducing ocular itching after conjunctival allergen challenge in both the 10-minute and the 2-hour challenge (P <.05). Emedastine 0.05% and levocabastine 0.05% were statistically equivalent in reducing conjunctival redness after conjunctival allergen challenge, although emedastine tended to be more efficacious than levocabastine at every observation time point. CONCLUSIONS: After conjunctival allergen challenge, emadastine 0.05% is significantly more effective than levocabastine 0.05% in reducing ocular itching associated with allergic conjunctivitis. The two compounds are equivalent in controlling the conjunctival redness associated with allergic conjunctivitis.

Effect of calcium channel blockers alone and in combination with antiglaucoma medications on intraocular pressure in the primate eye.

PURPOSE: To determine the effect of representative members from six classes of calcium channel blockers on intraocular pressure in the primate eye. Other antiglaucoma medications were administered with verapamil to determine their combined effect on intraocular pressure. METHODS: Six healthy cynomolgus monkeys were anesthetized, and baseline intraocular pressure was measured. Drug-containing solution (50 microL) was instilled in one eye and intraocular pressure was measured in both eyes 90 minutes later. RESULTS: All classes of calcium channel blockers significantly lowered intraocular pressure in the treated eye. The percent reduction in intraocular pressure compared with the baseline pressure was 10% for verapamil (P < 0.002), 18% for nifedipine (P < 0.001), 15% for diltiazem (P < 0.001), 17% for flunarizine (P < 0.001), 19% for prenylamine (P < 0.001), and 6% for perhexiline (P < 0.01). In the fellow eye, a significant reduction in intraocular pressure was also seen with all calcium channel blockers except perhexiline, which suggested a crossover effect. In contrast, neither vehicle treated nor contralateral eyes showed a lowering of intraocular pressure when tested under the same conditions. In the treated eye, 0.5% timolol (P < 0.01) and 0.05% clonidine (P < 0.02) combined with 0.25% verapamil each appeared to produce an additive effect, with a significantly greater pressure-lowering effect than either agent alone. In addition, 0.005% pilocarpine (P < 0.001) and 0.00125% demecarium (P < 0.01) combined with 0.25% verapamil each appeared to produce a synergistic effect, with a significantly greater reduction in intraocular pressure than both agents combined. CONCLUSIONS: Topical calcium channel blockers and combinations of verapamil with antiglaucoma medications may provide a useful alternative for reducing intraocular pressure in patients with ocular hypertension or primary open-angle glaucoma.

Management of uveitic glaucoma with Ahmed glaucoma valve implantation.

OBJECTIVE: To evaluate the safety and efficacy of Ahmed glaucoma valve implantation for the management of glaucoma associated with chronic uveitis. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Nineteen patients (21 eyes) with chronic uveitis underwent Ahmed glaucoma valve implantation for uncontrolled glaucoma between 1995 and 1998. INTERVENTION: All patients had their uveitis controlled before surgery via immunomodulatory therapy. Ahmed glaucoma valve implantation was performed. Immunosuppression was continued in the early postoperative period for strict control of inflammation. MAIN OUTCOME MEASURES: Control of intraocular pressure (IOP). A secondary outcome measure was the number of antiglaucoma medications required to achieve the desired IOP. Visual acuity and complications associated with the surgery were monitored. RESULTS: The postoperative follow-up averaged 24.5 months. At the most recent visit, all 21 eyes had IOPs between 5 and 18 mmHg. The average pressure reduction after Ahmed glaucoma valve implantation was 23.7 mmHg. The average number of antiglaucoma medicines required to achieve the desired IOP was reduced from 3.5 before surgery to 0.6 after surgery. No eye lost even a single line of Snellen acuity at the most recent postoperative visit. Two eyes developed hypotony in the course of follow-up. One resolved without specific intervention, and the other eye required two autologous blood injections and tube ligature to correct the hypotony. One eye underwent Ahmed glaucoma valve replacement for abrupt valve failure. Two eyes underwent penetrating keratoplasty for reasons believed to be unrelated to the glaucoma surgery. Kaplan-Meier life-table analysis showed a cumulative probability of success after Ahmed glaucoma valve implantation of 94% at 1 year. CONCLUSIONS: Ahmed glaucoma valve implantation can be an effective and safe method in the management of uveitic glaucoma. The authors hypothesize that control of the patients' uveitis, through preoperative and long-term postoperative immunomodulatory therapy, may have contributed to the success rate reported herein.

Traumatic anterior lens dislocation: a case report.

A 45-year-old man presented to the emergency department complaining of decreased vision and pain in the left eye after blunt trauma to the eye. On evaluation, the vision was limited to detecting hand motions, and the intraocular pressure was 37 mmHg. Secondary acute angle-closure glaucoma, with pupillary block due to anterior dislocation of the lens, was diagnosed. The intraocular pressure remained elevated after medical therapy, and the patient underwent intracapsular cataract extraction and anterior vitrectomy. The possibility of elevated intraocular pressure due to lens dislocation or other types of secondary glaucoma should be considered after blunt ocular trauma.

Diversity of response of optic nerve head circulation to timolol maleate in gel-forming solution.

PURPOSE: This randomized, double-masked, placebo-controlled, two-period crossover study was conducted to investigate the effects of 0.5% timolol maleate in gel-forming solution on intraocular pressure (IOP) and blood circulation in the optic nerve head in patients with untreated ocular hypertension. METHODS: The effects of 0.5% timolol in gel-forming solution on IOP and optic nerve head capillary blood speed were studied in 12 patients with untreated ocular hypertension. Optic nerve capillary blood speed was measured using the laser Doppler technique before and at the end of each treatment period. RESULTS: In each patient, IOP decreased after treatment with timolol (mean decrease 16.8% versus placebo). Systemic blood pressure and pulse rate did not differ significantly after treatment with topical timolol from values after placebo. The mean change from baseline in Doppler broadening was 10.6% greater after treatment with timolol than after placebo. There was no significant change in mean Doppler broadening from baseline after treatment with either timolol or placebo. However, optic nerve head capillary blood speed increased in six patients, and was within the range of placebo response in six patients after treatment with timolol. Spearman correlation analysis of the baseline with Doppler broadening measurements after treatment showed a correlation for placebo but not for timolol. The percent change in Doppler broadening after timolol treatment was correlated with iris color. CONCLUSION: These results indicate that administration of timolol for 4 weeks reduces IOP in patients with ocular hypertension and generally does not change the blood circulation in the optic nerve head. Individual patients, however, showed variable changes in optic nerve head circulation after topical administration of timolol. Although the sample size was small, these changes in optic nerve head circulation were correlated with iris color.

Intermediate-term clinical experience with the Ahmed Glaucoma Valve implant.

PURPOSE: We studied the intermediate-term clinical experience with the Ahmed Glaucoma Valve implant (New World Medical, Inc, Rancho Cucamonga, California). METHODS: In this multicenter, retrospective case series, we studied 159 eyes (144 patients) treated with the Ahmed Glaucoma Valve with a mean +/- SEM (standard error of mean) follow-up of 13.4 +/- 0.7 months (range, 4 to 44 months). The mean +/- SEM age was 60.9 +/- 1.9 years (range, 0.1 to 103 years). Surgical success was defined as intraocular pressure less than 22 mm Hg and greater than 5 mm Hg without additional glaucoma surgery and without loss of light perception. Postoperative use of antiglaucoma medications was not a criterion for success or failure. The definition of hypotony was intraocular pressure of 5 mm Hg or less in two consecutive visits. RESULTS: Intraocular pressure was reduced from a mean of 32.7 +/- 0.8 mm Hg before surgery to 15.9 +/- 0.6 mm Hg (P < .0001) at the most recent follow-up after surgery. The number of antiglaucoma medications was decreased from 2.7 +/- 0.1 before surgery to 1.1 +/- 0.1 after surgery (P < .0001). The cumulative probability of success was 87% at 1 year and 75% at 2 years after surgery (Kaplan-Meier life-table analysis). Postoperatively, 24 (15%) of 159 eyes had intraocular pressure greater than or equal to 22 mm Hg. The visual acuity was improved or within one Snellen line in 131 eyes (82%). Complications occurred in 75 eyes (47%), the majority of which did not affect surgical outcome. The most common complication was obstruction of the tube, which was observed in 17 eyes (11%). Transient postoperative hypotony was found in 13 eyes (8%). CONCLUSIONS: The Ahmed Glaucoma Valve implant is effective in lowering intraocular pressure, and postoperative hypotony is not commonly associated with this implant.

Inhibition of Tenon's fibroblast proliferation and enhancement of filtration surgery in rabbits with cytosine arabinoside.

Our purpose was to study the antiproliferative effect of cytosine arabinoside (Ara-C) on rabbit Tenon's fibroblasts and the efficacy of Ara-C as an adjunctive antifibrosis treatment for glaucoma filtration surgery in the rabbit eye. Rabbit Tenon's fibroblasts were exposed to 1 microg/ml of Ara-C for various time intervals, then cell number and viability was assessed at different time points. Following posterior lip sclerectomy, rabbit eyes were treated with 10 mg subconjunctival Ara-C daily for 7 days, then every other day for 7 days. Rabbit fibroblasts exposed to 1 microg/ml Ara-C for 1 hour showed no significant decrease in cell number compared with control. Continuous or 24-hour incubation of fibroblasts with Ara-C was lethal to the cells. Exposure of cells to Ara-C for 3-, 6-, and 9-hour intervals caused significant reduction of cell proliferation. Pulsed treatment of cells with 6 hour exposure to 1 microg/ml Ara-C every 3 days caused prolonged suppression of cell proliferation. Following posterior lip sclerectomy in rabbits, topical instillation of Ara-C drops at varying concentrations and dosing intervals did not cause any significant lowering of intraocular pressure compared with control eyes, although bleb survival was prolonged in eyes treated with Ara-C (P < 0.01). In rabbit eyes treated postoperatively with subconjunctival injections of 10 mg Ara-C every other day for two weeks, the mean intraocular pressure was significantly decreased and the bleb survival time was significantly prolonged (P < 0.0067) compared with control eyes. In conclusion, Ara-C inhibits rabbit Tenon's fibroblast proliferation in vitro. Postoperative subconjunctival injection of Ara-C results in improved bleb function after filtration surgery in the rabbit.

Topical verapamil and episcleral venous pressure.

OBJECTIVE: To investigate the effect of a single-dose and 2-week administration of topical 0.25% verapamil on episcleral venous pressure (EVP) and intraocular pressure (IOP). DESIGN: A prospective, randomized, double-masked, crossover, and placebo-controlled study. PARTICIPANTS: One eye of each of 20 normal subjects received topical verapamil or placebo. INTERVENTION: The EVP was measured using a pressure chamber episcleral venomanometer. The IOP, EVP, heart rate (HR), and blood pressure (BP) were measured at baseline, 1.5 hours after a single drop, and after 2-week, three-times-a-day topical administration of 0.25% verapamil or placebo to one eye. After a 4-week washout period, the treatment to the study eye was reversed, and measurements of EVP, IOP, HR, and BP were repeated. MAIN OUTCOME MEASURES: The EVP, IOP, HR, and BP were measured. RESULTS: Ninety minutes after a single drop, the EVP in the verapamil-treated eyes was reduced by 4.8% (P = <0.001) and in the untreated fellow eyes by 2.4% (P = 0.032). After 2-week topical administration, the EVP was reduced by 9.5% (P = <0.0001) in the verapamil-treated eyes and by 4.8% (P = 0.001) in the fellow eyes. The EVP was unchanged in the treated and fellow eyes after a single drop or after a 2-week treatment with placebo. Ninety minutes after topical administration of 0.25% verapamil, the IOP decreased by 7.7% (P = <0.0001) in the treated eyes and decreased by 3.6% (P = 0.03) in the fellow eyes. After a 2-week administration of topical verapamil, the IOP decreased by 12% (P = 0.0001) in the treated eyes and by 7.2% (P = 0.0289) in the fellow eyes. The changes of IOP in the placebo-treated and fellow eyes were not statistically significant after a single-dose and 2-week administration. After topical administration of verapamil, a contralateral effect on IOP and EVP was observed in the fellow, untreated eye. No systemic effect on HR or BP was detected after a single-dose administration of topical verapamil. There were, however, significant reductions in HR and BP after a 2-week treatment with topical 0.25% verapamil. CONCLUSION: These results indicate that a single drop and a 2-week administration of topical 0.25% verapamil decrease IOP and EVP significantly, with more pronounced reduction after a 2-week treatment than after a single-dose treatment.

A clinical study of the Ahmed glaucoma valve implant in advanced glaucoma.

OBJECTIVE: To assess clinical outcomes and establish the incidence and management of a hypertensive phase (HP) (defined as intraocular pressure [IOP] > 21 mmHg in the first 6 postoperative months) in patients with Ahmed glaucoma valve implant. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: A total of 85 patients were included in the current study, including consecutive patients who had intractable glaucoma and underwent Ahmed valve implant insertion at the University Glaucoma Center, Tampa, Florida (DWR and WEL) and the Massachusetts Eye and Ear Infirmary (PAN) between January 1993 and June 1997. Only patients with a minimum of 6 months' follow-up were included. INTERVENTION: Ahmed glaucoma valve implant insertion to control intractable glaucoma was performed. MAIN OUTCOME MEASURES: Success was defined as IOP less than 22 mmHg and greater than 4 mmHg on the last two visits, a decrease of no more than two lines in the visual acuity and no additional surgical interventions to control IOP. RESULTS: The cumulative probability of success at 12 months was 77%. A total of 26 patients (30.6%) failed during the study period, and 70 patients (82%) exhibited HP. Hypertensive phase peaked at 1 month after the operation and stabilized at 6 months. There were 34 patients (48%) with HP who were controlled with additional medications: 14 (20%) with needling and 5-fluorouracil injections and 20 (28%) who needed secondary surgical intervention. There were 8 patients (9.4%) who exhibited hypotony (< 5 mmHg) on postoperative day 1 and 3 (3.5%) at 3 months. Visual acuity returned to baseline between 3 and 6 months after the operation. The major complications associated with the valve were hyphema in 14 cases (16.5%), suprachoroidal hemorrhage in 4 cases (4.7%), end-plate exposure in 10 cases (11.7%), tube exposure in 6 cases (7%), tube block in 4 cases (4.7%), loss of vision in 5 cases (5.8%), and corneal graft failure in 4 (30%) of 13 cases with clear grafts. CONCLUSIONS: The overall success rate is comparable to that of prior studies using different implants. The majority of the patients exhibit an HP that peaks at 1 month, with gradual stabilization over 6 months. One third of the patients needed secondary surgical intervention to control the HP. The incidence of postoperative hypotony and flat or shallow anterior chambers is very low after Ahmed glaucoma valve insertion.

Five-year results of a randomized, prospective, clinical trial of diode vs argon laser trabeculoplasty for open-angle glaucoma.

PURPOSE: To evaluate the safety and efficacy of laser trabeculoplasty (LTP) with a semiconductor diode laser (810 nm, [DLT]) vs an argon blue-green laser (488 to 514 nm, [ALT]). METHODS: In a prospective, randomized clinical trial, 50 eyes of 46 patients with uncontrolled open-angle glaucoma on maximally tolerated medical therapy were treated and followed at regular intervals for 5 years. Fifty laser spots were applied over 180 degrees using either maximal laser power or sufficient power to produce blanching or a small bubble (570 to 850 mW, DLT; 400 to 1,100 mW, ALT). We performed DLT using a 100-microm spot size, a 0.5-second exposure, and a Ritch lens; we conducted ALT with a 50-microm spot, a 0.1-second exposure, and a Goldmann lens. Patients in the study were followed until trabeculectomy was required. RESULTS: The mean follow-up times +/- SD for all eyes were 38.6 +/- 5.4 months, DLT (n = 22; range, 1 to 68 months) and 35.5 +/- 4.8 months, ALT (n = 28; range, 1 to 66 months). Those in the diode laser group (n = 16) who had more than 1 year of follow-up were tracked for 49.4 months, and those in the argon laser group (n = 21) were tracked for 45.8 months. There were no significant differences in the mean pretreatment intraocular pressures (IOPs): 21.2 mm Hg, DLT (n = 22) and 21.5, ALT 21.5 mm Hg (n = 28); P = .81] or in mean final IOPs (15.7 mm Hg, DLT and 17.1 mm Hg, ALT; P = .19). Time to surgical failure showed no significant differences, with 50% of the DLT eyes and 58% of the ALT eyes surviving at 5 years (P = .59). CONCLUSION: In eyes with open-angle glaucoma and unsatisfactory IOP control on maximally tolerated medical therapy, DLT and ALT are equally effective in lowering IOP over a 5-year period.

Comparison of mitomycin C trabeculectomy, glaucoma drainage device implantation, and laser neodymium:YAG cyclophotocoagulation in the management of intractable glaucoma after penetrating keratoplasty.

PURPOSE: This study aimed to compare the surgical outcomes of mitomycin C trabeculectomy glaucoma drainage device (GDD) surgery and laser neodymium:YAG (Nd:YAG) cyclophotocoagulation (CPC) in the management of intractable glaucoma after penetrating keratoplasty (PKP) in a retrospective study. DESIGN: Interventional case series. PARTICIPANTS/METHODS: The medical charts of consecutive patients who had pre-existing glaucoma or who developed glaucoma after PKP and underwent a surgical procedure to control the glaucoma at the University Eye Associates of Boston University Medical Center, New England Eye Center, and Massachusetts Eye and Ear Infirmary between January 1991 and July 1995 were reviewed. Follow-up ranged from 6 months to 4 years after the glaucoma procedure. A total of 38 patients were included consisting of 17 patients who underwent mitomycin C, 10 patients who underwent GDD surgery, and 11 patients who had CPC. INTERVENTION: Mitomycin C trabeculectomy, GDDs, or Nd:YAG CPC to control glaucoma after PKP was performed, MAIN OUTCOME MEASURES: Graft status, postoperative intraocular pressure (IOP), and visual acuity were the main outcome measures. RESULTS: There were no differences among the three groups with respect to the follow-up time after the corneal graft operation (P = 0.15) or after the glaucoma operation (P = 0.98). At the final follow-up, the average decrease in the IOP was 17 mmHg (P < 0.001) after mitomycin C, 15 mmHg (P = 0.003) after GDD surgery, and 14.4 mmHg (P = 0.001) after CPC. There were no differences in the proportion of patients who developed postoperative IOP above 20 mmHg (P = 0.50) and in the proportion who developed hypotony (P = 0.10) among the three groups. Two grafts failed after mitomycin C and one failed after CPC. Among the three procedures, there were no differences in the proportion of patients who experienced either an improvement (P = 0.14) or a decrease (P = 0.22) in the visual acuity by more than one line after the glaucoma procedure. One patient each in the GDD group and the CPC group lost light perception after the procedure. The risk of graft failure was almost three times higher for each additional PKP (odds ratio = 2.80, P = 0.02). CONCLUSIONS: No differences were found among the three glaucoma procedures with respect to controlling IOP and graft failure. There was a trend for patients treated with CPC to have a higher incidence of graft failure, glaucoma failure, hypotony, and visual loss by more than one line, although this was not statistically significant. The number of PKPs was associated with graft failure, independent of the surgical procedure.

Phacomorphic glaucoma associated with choroidal melanoma.

Patients with phacomorphic glaucoma present with mature cataract, shallowing of the anterior chamber, and angle-closure glaucoma. The opaque ocular media due to cataract formation usually precludes visualization of the posterior segment of the affected eyes. The authors describe a 65-year-old man who presented with reduced vision and clinical findings typical of phacomorphic glaucoma. Preoperative ultrasonography revealed an intraocular tumor, and magnetic resonance imaging showed a high signal intensity in T1-weighted images and a low signal intensity in T2-weighted images consistent with choroidal melanoma. Histopathologic examination of the tumor after enucleation confirmed the diagnosis. The clinical findings characteristic of phacomorphic glaucoma may be associated with choroidal melanoma. Ultrasonography or other imaging studies should be performed on eyes with phacomorphic glaucoma and opaque ocular media to allow timely detection of any mass lesion and to guide appropriate surgical management.

Distribution of verapamil and norverapamil in the eye and systemic circulation after topical administration of verapamil in rabbits.

Our purpose was to determine the pharmacokinetics of verapamil and its active metabolite norverapamil after topical administration of verapamil in rabbits. New Zealand white albino rabbits were given 50 microl of verapamil ophthalmic formulation topically in each eye. Samples obtained at various time points were analyzed with high performance liquid chromatography and tandem mass spectrometry. The elimination half-life of verapamil after treatment with 0.5% verapamil was 0.76 hour for aqueous, 4.34 hours for vitreous, and 1.82 hours for serum. The peak concentrations for aqueous, vitreous, and serum were 2.34 x 10(-6) M by 0.5 hour, 1.57 x 10(-7) M at 2 hours, and 3.39 x 10(-8) M by 0.5 hour following instillation of one drop of 0.5% verapamil; and 1.41 x 10(-6) M by 0.5 hour, 5.48 x 10(-8) M at 4 hours, and 1.20 x 10(-8) M by 0.5 hour following 0.25% verapamil, respectively. The metabolite norverapamil was found at peak concentrations of 8.65 x 10-(8) M by 0.5 hour in aqueous, 1.65 x 10(-8) M at 2 hours in vitreous, and 1.30 x 10(-9) M by 0.5 hr in serum following administration of 0.5% verapamil. The elimination half-life of norverapamil for aqueous, vitreous, and serum following treatment with 0.5% verapamil was 0.91 hour, 1.43 hours, and 3.60 hours, respectively. We conclude that topical verapamil, administered to the rabbit eye, is rapidly absorbed in the aqueous, vitreous, and blood. Norverapamil, which is an active metabolite of verapamil, can be detected in the aqueous and vitreous of the rabbit eye after topical administration, suggesting enzymatic degradation of verapamil within the eye.

Glaucoma associated with keratoprosthesis.

OBJECTIVE: This study aimed to review the authors clinical experience with glaucoma associated with keratoprosthesis in patients with severe corneal disease. DESIGN: The study design was a retrospective review of case series. PARTICIPANTS: The authors studied 55 eyes in 52 patients with keratoprostheses with follow-up of 21 +/- 16 months (range, 3-77 months). INTERVENTION: Glaucoma drainage devices were implanted in 36 eyes (35 Ahmed valves, 1 Krupin valve) with 21 +/- 15 months' follow-up (range, 3-64 months). MAIN OUTCOME MEASURES: Clinical outcome assessment included vision, intraocular pressure (IOP), visual fields, optic disc appearance, and identification of complications. RESULTS: Glaucoma was found in the majority (64%) of eyes treated with keratoprostheses, identified in 20 eyes (36%) before surgery and an additional 15 eyes (28%) after surgery. Of the 36 eyes treated with glaucoma drainage devices, IOP was controlled in 29 eyes (81%), with 9 eyes (25%) requiring additional medications. Continued progression of glaucoma occurred in 5 (14%) of 36 eyes with keratoprostheses and glaucoma drainage implants (4 of these eyes had advanced glaucomatous optic nerve damage before surgery). There were nine nonvision-threatening complications due to drainage implants. Compared with the preoperative visual acuity, vision was markedly improved in 63%, unchanged in 17%, and worse in 20% of eyes after keratoprosthesis surgery. CONCLUSION: Elevation of IOP is common in patients with keratoprosthesis, and prevention or treatment with glaucoma drainage implants is effective.