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.

Metastatic potential of B16 melanoma cells after in vitro selection for organ-specific adherence.

Heterogeneous primary tumors contain subpopulations of cells that differ in ability to metastasize to specific host organs. We have used cryostat sections of host organs to select for metastatic variants of B16 melanoma cells with increased adhesion to specific syngeneic tissues. By repeating the selection procedure with lung tissue, a subpopulation of cells was isolated that demonstrated a specific increase in binding to cryostat sections of mouse lung. This altered binding was reflected by a sixfold increase in the frequency of lung metastasis 21 d after tail vein injection of the tumor cells. In contrast, B16 melanoma cells selected on cryostat sections of mouse brain showed no increase in adhesion to brain or lung tissue and the metastatic pattern in vivo was not significantly different compared with the parent cell line. When cells selected for increased adhesion to cryostat sections of lung were further examined in vitro, they showed altered morphology and increased motility but no change in growth rate. These results demonstrate that alterations in the adhesive interactions between metastatic tumor cells and a specific host tissue can directly affect the frequency of metastasis to that tissue in vivo.

Organ-specific adhesion of metastatic tumor cells in vitro.

Binding of tumor cells to cryostat sections of host organs was studied. B16-F10 melanoma cells and reticulum cell sarcoma cells demonstrated an organ specificity in their binding in vitro that reflected the organ specificity of their metastatic distribution 25 days after intravenous injection. These results provide evidence for specific binding of tumor cells to the tissues that they selectively colonize in vivo.

Color Doppler ultrasound measurements after topical and retrobulbar epinephrine in primate eyes.

PURPOSE: To determine the effects of topical epinephrine and retrobulbar anesthesia containing lidocaine with epinephrine on retrobulbar hemodynamic measurements in the primate eye, using color Doppler ultrasound. METHODS: Color Doppler ultrasound measurements were performed at baseline and 90 minutes after masked administration of topical 2% epinephrine or balanced salt solution to six cynomolgus monkeys. Measurements were also performed at baseline and 30 minutes after retrobulbar injection of 2% lidocaine, with or without 1:200,000 epinephrine. RESULTS: After topical epinephrine, color Doppler ultrasound measurements were not significantly different compared with baseline measurements in the central retinal artery, posterior ciliary arteries, and superior ophthalmic vein. There were decreased systolic and diastolic velocities in the ophthalmic artery (P < 0.03 and P < 0.02, respectively) after topical epinephrine; however, Pourcelot's ratio (resistive index) was not significantly different compared with that at baseline. In contrast, there were marked changes in the retrobulbar arterial circulation after retrobulbar injection of lidocaine with epinephrine. The systolic and diastolic velocities were decreased significantly in the central retinal artery (P < 0.02 and P < 0.01, respectively), temporal posterior ciliary artery (P < 0.05 and P < 0.03, respectively), and nasal posterior ciliary artery (P < 0.03 and P < 0.02, respectively). Pourcelot's ratio was significantly increased in the central retinal artery (P < 0.01), temporal posterior ciliary artery (P < 0.02), and nasal posterior ciliary artery (P < 0.02) after retrobulbar injection of lidocaine with epinephrine. CONCLUSIONS: These results indicate that one drop of topical epinephrine has little or no effect on the retrobulbar circulation, whereas retrobulbar injection of anesthetic solution containing lidocaine with epinephrine significantly alters retrobulbar hemodynamics in the monkey eye.

Elevated intraocular pressure secondary to rhegmatogenous retinal detachment.

Elevated intraocular pressure secondary to rhegmatogenous retinal detachment was described by Ariah Schwartz in 1972, an entity commonly known as Schwartz's syndrome. Photoreceptor outer segments identified in the aqueous of patients with this syndrome are thought to play a role in the elevation of the intraocular pressure. We present two patients with open angles and elevated intraocular pressure associated with retinal detachment. Retinal reattachment surgery resulted in normalization of the intraocular pressure. Electron microscopic examination of aqueous specimens from our patients demonstrated a predominance of photoreceptor outer segments in varying stages of degeneration. In these specimens, inflammatory cells, fibrin, and pigment granules were rarely observed or were absent. We review the literature regarding the epidemiology, clinical characteristics, and pathogenesis of Schwartz's syndrome.

Calcium channel blockers in the management of low-tension and open-angle glaucoma.

Fifty-six patients with either open-angle or low-tension glaucoma who were concurrently taking calcium channel blockers were compared to similar groups not taking such medications for a mean follow-up period of 3.4 years. Serial stereoscopic optic nerve photographs and visual fields of all patients were evaluated for evidence of glaucomatous progression. In patients with low-tension glaucoma, there was a significant difference in the progression of visual field defects, with only two of 18 eyes (11%) of patients taking calcium channel blockers, compared to ten of 18 eyes (56%) of controls showing new visual field defects. Similarly, low-tension glaucoma patients taking calcium channel blocker therapy demonstrated no evidence of progressive optic nerve damage, compared to eight of 18 control eyes (44%). In contrast, patients with open-angle glaucoma taking calcium channel blockers showed no marked difference in the progression of glaucoma, compared to controls. These findings suggest that calcium channel blockers may be useful in the management of low-tension glaucoma.

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.

Assessment of intraocular pressure by palpation.

PURPOSE/METHODS: Corneal specialists may assess the intraocular pressure by palpation although this technique has never been validated. We explored the reliability of a tactile assessment of the intraocular pressure in comparison to Goldmann tonometry. RESULTS/CONCLUSION: There was little correlation between tactile assessment of the intraocular pressure and tonometry. However, palpation was moderately successful in identifying most eyes (five of seven eyes) with an intraocular pressure greater than 30 mm Hg. Although palpation was generally inaccurate, it may serve as a warning for marked increases in intraocular pressure exceeding 30 mm Hg.

Cardiovascular effects of topical carteolol hydrochloride and timolol maleate in patients with ocular hypertension and primary open-angle glaucoma. Night Study Group.

PURPOSE: To compare the effects of topical timolol maleate 0.5% and carteolol hydrochloride 1% on pulse rate and blood pressure. METHODS: In a randomized, double-masked, parallel-design, multicenter clinical trial, we compared the effects of timolol and carteolol on pulse rate and blood pressure measured by 24-hour ambulatory blood pressure monitoring in 169 adult patients with either ocular hypertension or primary open-angle glaucoma. RESULTS: From noon to 8 PM, baseline mean pulse rate of 82 to 83 beats per minute (bpm) had decreased by 4 to 6 bpm in both groups after 4 weeks of therapy with timolol or carteolol. From midnight to 4 AM, the pulse rate in the carteolol group was significantly above baseline (P = .005), while the timolol group was significantly below baseline (P < .001). Four times as many patients became bradycardic (heart rate, < 60 bpm) on timolol (18.4%) as did patients on carteolol (4.5%) from midnight to 4 AM. More than twice as many patients exhibited a resolution of their bradycardia with carteolol (46.7%) as did patients treated with timolol (18.2%) from midnight to 4 AM. Overall cardiovascular adverse effects were reported significantly more frequently in the timolol than the carteolol group (P = .002). CONCLUSIONS: Timolol causes significantly lower mean heart rate during the nighttime and more nocturnal bradycardia than carteolol does in patients with ocular hypertension and primary open-angle glaucoma. These differences may be because of the intrinsic sympathomimetic activity of carteolol.

Color Doppler ultrasound analysis of ocular circulation after topical calcium channel blocker.

PURPOSE: To investigate the effect of topical administration of the calcium channel blocker verapamil on intraocular pressure and retrobulbar hemodynamics. METHODS: In this randomized, prospective, double-masked study, we examined the effects of single-dose topical administration of verapamil in ten normal human volunteers by using color Doppler ultrasound imaging to measure hemodynamic parameters. Limitations of this study include single-dose application of verapamil and relatively small sample size. RESULTS: No systemic effect on heart rate or blood pressure was detected after administration of topical verapamil. The intraocular pressure significantly decreased compared with baseline two hours after topical 0.125% and 0.25% verapamil (P = .015 and .040, respectively). Pourcelot's ratio, an index of vascular resistance, measured in the central retinal artery was significantly reduced after topical application of 0.125% verapamil (P = .008). The change in Pourcelot's ratio primarily resulted from an increased end diastolic velocity in the central retinal artery. No significant differences compared with baseline values were detected in the color Doppler ultrasound measurements of the posterior ciliary arteries and the central retinal vein two hours after topically administered verapamil. CONCLUSIONS: Topical administration of verapamil decreases intraocular pressure and alters ocular hemodynamics, reducing the vascular resistance index in the central retinal artery.

Efficacy of carteolol hydrochloride 1% vs timolol maleate 0.5% in patients with increased intraocular pressure. Nocturnal Investigation of Glaucoma Hemodynamics Trial Study Group.

PURPOSE: To evaluate the ocular hypotensive effect and safety of carteolol hydrochloride 1% vs timolol maleate 0.5%. METHODS: One hundred seventy-six patients with ocular hypertension or primary open-angle glaucoma were randomly assigned to receive either carteolol 1% twice a day or timolol maleate 0.5% solution twice a day in a randomized, double-masked, multicenter, parallel-group, active-control comparison trial during a 3-month period. RESULTS: After 12 weeks, carteolol 1% reduced the mean +/- SE intraocular pressure from 25.0 +/- 0.3 to 19.5 +/- 0.3 mm Hg; timolol maleate 0.5% reduced the mean intraocular pressure from 25.2 +/- 0.3 to 19.6 +/- 0.3 mm Hg. The mean difference in trough intraocular pressure between carteolol and timolol maleate of -0.14 mm Hg was not significantly (P = .745) different (95% confidence limits, -0.97 to 0.70 mm Hg). Trough pulse and blood pressure also showed no consistent statistically significant differences between groups. The 2-hour postdose pulse, however, demonstrated a greater decrease in the timolol maleate than in the carteolol group (P < .001). Systemic and ocular signs and symptoms were similar between the groups except that the number of treatment-emergent reports of bradycardia was greater in the timolol maleate group (P = .039), and the carteolol group reported fewer ocular symptoms than the timolol maleate group did (P < .01). CONCLUSIONS: Both carteolol 1% and timolol maleate 0.5% are highly effective in lowering intraocular pressure when measured at the end of the dosing interval. Carteolol 1% demonstrates an ocular hypotensive effect and safety profile similar to those of timolol maleate 0.5% solution.

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.

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.

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.

Intraoperative anaphylaxis after irrigation with bacitracin: case report.

We report a case of anaphylaxis caused by irrigation with a bacitracin solution during lumbar laminectomy. The patient had been exposed to bacitracin during a previous anterior cervical discectomy. We recommend avoiding the use of irrigation solutions containing bacitracin in patients with previous systemic exposure to this antibiotic.

Anthropometric measurements for Asian and Caucasian elderly.

While differences in height and weight were observed, the results of this study indicate that there are similarities between Caucasian and Asian-American elderly in skin-fold measurements and prevalence of obesity. These results illustrate the value of skinfold thickness as a more accurate measure of adiposity than indexes on the basis of weight for given height. In addition, our results provide evidence for ethnic similarities in the distribution of subcutaneous fat and the prevalence of obesity in elderly Caucasians and Asian-Americans.

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.

Optic nerve head circulation after topical calcium channel blocker.

PURPOSE: Our purpose was to investigate the effects of the calcium channel blocker verapamil on intraocular pressure and blood circulation in the human optic nerve head. METHODS: The effects of three different concentrations of topical verapamil (0.063%, 0.125%, and 0.25%) on intraocular pressure and optic nerve head capillary blood speed were measured in 12 healthy normal subjects. In a randomized, double-masked design, each subject received one drop of either verapamil or placebo in one eye and the opposite treatment in the fellow eye. Anterior optic nerve circulation was assessed at baseline and 90 min after instillation of the drops using the laser Doppler technique. RESULTS: The intraocular pressure was significantly reduced compared with baseline in both verapamil- and placebo-treated eyes at each concentration. The reductions of intraocular pressure were greater in verapamil-treated eyes (12-17%) than in placebo-treated eyes (9-12%). No systemic effect on heart rate or blood pressure was detected after administration of topical verapamil. The capillary blood speed in the optic nerve head was increased in both verapamil- and placebo-treated eyes at each concentration, although the only statistically significant increases were with the 0.25% concentration. The mean +/- SEM increase compared with baseline at the 0.25% concentration was 10.4 +/- 3.6% in verapamil-treated eyes (p = 0.017), and 11.6 +/- 4.4% in placebo-treated eyes (p = 0.026). CONCLUSIONS: These results indicate that topical administration of verapamil lowers the intraocular pressure and increases the capillary blood speed in the optic nerve head in normal subjects. Changes measured in verapamil-treated eyes were also observed in placebo-treated eyes, indicating a crossover effect.

Transcorneal erbium laser sclerostomy: towards a guarded laser sclerostomy technique.

PURPOSE: To attempt transcorneal laser sclerostomy with the erbium laser and to control the flow of aqueous through this sclerostomy with a suture ligature. METHODS: A contact erbium laser was used to create sclerostomies through small corneal incisions in both eyes of eight rabbits. Prior to surgery, a Merocel sponge soaked in mitomycin-C (0. 4 mg/cc) was applied to the conjunctiva at the operative site in one eye of each rabbit for 5 min. In the perfused human autopsy eye, following the creation of transcorneal erbium laser sclerostomy, a ligature suture was placed at the limbus around the sclerostomy opening to limit fluid flow. RESULTS: Using the erbium laser probe and the transcorneal approach, patent sclerostomies were created in all eyes. Intraocular pressures were significantly lower in mitomycin-C-treated eyes up to four months postoperatively (p = 0. 05). Eyes not treated with mitomycin-C demonstrated failure of filtering blebs by 1 month postoperatively (mean bleb survival = 9. 3 days). All mitomycin-C-treated eyes showed evidence of bleb formation up to 4 months postoperatively. Histologic examination of transcorneal sclerostomies in rabbit eyes showed patent sclerostomies at 1 day postoperatively with minimal adjacent thermal damage. In perfused human autopsy eyes, intraocular pressure was maintained near preoperative levels following placement of a ligature suture around the sclerostomy and decreased with release of the suture. CONCLUSIONS: These results demonstrate that functional filtering blebs can be created via small transcorneal incisions using the erbium laser. Transconjunctival mitomycin-C produces lower postoperative intraocular pressures and prolongs bleb survival. Aqueous flow through the sclerostomy was controlled with a suture ligature.

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.