Normal response to pilocarpine and phenylephrine.

Fifty-eight eyes from 58 patients in which there was no evidence of glaucoma were provoked with pilocarpine and phenylephrine drops. The result was a significant reduction in intraocular pressure and a significant increase in outflow facility. The 58 eyes were randomised and 19 submitted to a 'dummy' provocative test. There was no significant change in either pressure or outflow facility. The effect of the pilocarpine/phenylephrine provocative test in normal eyes is to produce a response that is the opposite of a positive provocative test in eyes at risk of developing closed-angle glaucoma.     

One model of outflow damage.

The intraocular pressure, facilities of outflow, and Po/C ratios of 3 groups of eyes were compared. Group 1 consisted of 20 eyes at risk to the development of acute closed-angle glaucoma that had been treated with prophylactic pilocarpine for at least 8 years. Group 2 consisted of 20 eyes at risk that had received no treatment and had been followed up for at least 4 years. Group 3 comprised 20 eyes in which there was no evidence of glaucoma. There were highly significant differences between the 3 groups. The 60 eyes were then provoked with pilocarpine and phenylephrine; 90% of Group 1, 75% of Group 2, and none of Group 3 developed significant gonioscopic angle closure. These results suggest that asymptomatic partial angle closure was the cause of the observed changes and provide a naturally occurring model of one mechanism that can produce outflow damage without clinical symptoms.     

Outflow changes in positive provocative tests.

The outflow changes in 26 eyes were measured during the course of a positive provocative test with pilocarpine and phenylephrine. Three separate patterns of response occurred: (1) One dose of pilocarpine and phenylephrine produced an acute attack with a large reduction in outflow. (2) The first dose of pilocarpine and phenylephrine produced a fall in pressure and increase in outflow. The second dose reversed this effect and closed the angle. (3) The first dose of pilocarpine and phenylephrine increased pressure by an insignificant amount and decreased outflow. The second dose accentuated this response and produced an acute attack.     

Pharmacological testing in the laser-induced monkey glaucoma model

Glaucoma was induced in cynomolgus monkeys by photocoagulating the trabecular meshwork with the argon laser. Repeat treatments were often necessary and wide intraocular pressure fluctuations were characteristic. Baseline intraocular pressure was measured with a calibrated pneumatonometer hourly for six hours. On a succeeding day a baseline measurement was made, 50 microliter of the drug to be tested applied, and six hourly measurements of intraocular pressure repeated. The effects on intraocular pressure of timolol, epinephrine, pilocarpine, vanadate, prostaglandin F2 alpha (PGF2 alpha), forskolin, and corynanthine were tested in at least eight eyes. Significant (p less than 0.05) reductions of intraocular pressure were produced by 0.5% timolol, 2% epinephrine, 4% pilocarpine, 1% vanadate, 500 micrograms of PGF2 alpha and 1% forskolin. Five per cent corynanthine produced no significant lowering of intraocular pressure. Tonography revealed an increased outflow facility associated with the reduction of intraocular pressure 2 hours after the administration of 4% pilocarpine. This glaucoma animal model may be useful in investigating agents that lower intraocular pressure by a variety of mechanisms.     

Dilating dangerous pupils.

Altogether 85 eyes from patients at risk to the development of closed-angle glaucoma were dilated with either parasympatholytic or sympathomimetic drugs. Of 21 eyes dilated with cyclopentolate 1/2%, 9 developed angle closure and a significantly raised pressure at some stage during dilatation and subsequent miosis. Of 58 eyes dilated with tropicamide 1/2%, 19 developed angle closure and a significantly raised pressure during dilatation. Treatment with intravenous acetazolamide and pilocarpine rapidly returned pressure to normal levels. Six eyes that had previously had a positive provocative test with simultaneous pilocarpine and phenylephrine were safely dilated with phenylephrine alone. Subsequent miosis with pilocarpine produced closed-angle glaucoma in all eyes. The significance of these observations is explained and discussed, and it is suggested that high-risk eyes should never be dilated with cyclopentolate. Tropicamide is safe if elementary precautions are observed. Safest of all, however, is phenylephrine-induced mydriasis and subsequent miosis with thymoxamine drops 1/2%.     

Phenylephrine provocative testing in the pigmentary dispersion syndrome

Forty-nine patients with bilateral pigmentary dispersion syndrome (abnormal accumulation of pigment in the anterior chamber, principally from the posterior layers of the iris), including 31 patients with pigmentary glaucoma, underwent 10% phenylephrine testing in one eye for evaluation of liberation of pigment floaters into the anterior chamber and the influence of phenylephrine on the intraocular pressure. Ten patients with pigmentary glaucoma developed a 3+ to 4+ pigment response, but only two demonstrated a pressure rise greater than 2 mm Hg. The highest pressure rise observed was 7 mm Hg. Nine patients with pigmentary dispersion syndrome but without glaucoma also developed a 3+ to 4+ pigment response, but none of these had a pressure rise. The incidence of pigment liberation was higher in older patients and in pigmentary glaucoma patients receiving topical antiglaucoma therapy at the time of testing. The extent of iris transillumination did not correlate with the grade of phenylephrine-induced pigment liberation. Two pigmentary glaucoma patients, who did not liberate pigment or have a pressure rise when tested with phenylephrine, did exhibit spontaneous or exercise-induced liberations of pigment into the anterior chamber, with marked rises of intraocular pressure and obstruction of aqueous outflow.     

Outflow changes in normal eyes after closed-angle glaucoma.

Twenty-four patients with spontaneous acute closed-angle glaucoma in one eye were selected for study. All 24 eyes had a peripheral iridectomy, were normotensive, and had no gonioscopically visible peripheral anterior synechiae. Of the 24 contralateral eyes 14 gave a positive response to provocative tests and had peripheral iridectomy. The remaining 10 eyes did not give positive responses to the tests and were on no treatment. The 24 pairs of eyes were provoked with pilocarpine and phenylephrine. Tonography was performed at the start of the test, 1 1/2 hours later, and at its termination. At the start of the test the 24 eyes that had had spontaneous closed-angle glaucoma showed a higher pressure and lower outflow facility than the 24 contralateral eyes. This difference disappeared as the test progressed. It is concluded that apparently normal eyes--after an acute attack--do none the less show a significant degree of damage to the outflow system. Ten pairs of eyes from 10 normal persons were provoked in a similar fashion and at no point did a significant difference appear between right and left eyes.     

Partial angle closure.

During the course of negative provocative test for closed-angle glaucoma using pilocarpine and phenylephrine 60% of eyes develop significant reductions in outflow facility at some stage during the test. It is shown that these reductions can be explained by postulating the presence of partial-angle closure since: (1) A random sample (6) of 53 eyes showing an abnormal response subsequently had a peripheral iridectomy. On reprovoking they then behaved as normal eyes with a uniform increase in outflow. (2) Fifty-eight eyes that had a peripheral iridectomy for closed-angle glaucoma (spontaneous or induced) responded to provocative testing as do normal eyes.     

Effects of jogging exercise on patients with the pigmentary dispersion syndrome and pigmentary glaucoma.

BACKGROUND: Exercise-induced anterior chamber pigment dispersion with intraocular pressure (IOP) elevation has been reported in patients with the pigmentary dispersion syndrome. Marked pigment dispersion with or without elevation of IOP could predispose these patients to visual field loss. The authors designed this study to evaluate the effects of jogging exercise on anterior chamber pigment and IOP in a group of patients with the pigmentary dispersion syndrome or pigmentary glaucoma. METHODS: Fourteen subjects with the pigmentary dispersion syndrome, 10 subjects with pigmentary glaucoma, and 10 control subjects underwent a 45-minute protocol of jogging exercise. Anterior chamber pigment was graded and IOP was measured before and up to 3 hours after completion of the exercise protocol. RESULTS: Eyes of experimental subjects were significantly more likely to develop exercise-induced pigment dispersion than were eyes of control subjects. In experimental subjects, eyes treated with pilocarpine at the time of the study were significantly less likely to develop exercise-induced pigment dispersion than eyes not treated with pilocarpine. In two experimental subjects, pre-exercise treatment with pilocarpine appeared to inhibit exercise-induced pigment dispersion. CONCLUSIONS: The authors do not believe that all patients with the pigmentary dispersion syndrome or pigmentary glaucoma need to avoid exercise. However, for patients with these disorders who regularly engage in jogging or more strenuous or more jarring types of exercise, they suggest an evaluation before and after the type of exercise in question. If marked exercise-induced pigment dispersion occurs, pilocarpine therapy may be an alternative to avoidance of the exercise.     

The long-term hypotensive effect of timolol maleate compared with the effect of pilocarpine in simple and capsular glaucoma.

The long-term intraocular pressure (IOP) lowering effect of a beta-adrenergic blocking agent, timolol maleate, in topical administration was compared with the effect of pilocarpine on simple and capsular glaucoma by means of diurnal pressure curves during a six-month follow-up. In simple glaucoma timolol was more effective than pilocarpine in lowering IOP. In the follow-up a significant but not marked increase of the IOP was observed. In capsular glaucoma timolol was not effective enough, but when it was co-administered with miotics the IOP lowering effect was better than with either substance alone. Timolol induced no accomodative myopia, miosis, reduction of tear flow or other side effects. It increased the outflow facility in simple glaucoma but not in capsular glaucoma. During the trial, the anterior chamber depth increased while the corneal thickness remained unchanged. Four out of the six eyes included in a previous report of secondary glaucoma due to chronic uveitis are still, after one year of therapy, controlled with timolol.     

Potential mechanism for the additivity of pilocarpine and latanoprost

PURPOSE: To determine the ocular hypotensive mechanism underlying the additivity of latanoprost and pilocarpine. METHODS: This randomized, double-masked study included 30 patients with ocular hypertension on no ocular medications for at least 3 weeks. On each of six visits to the clinic, measurements were taken of aqueous flow and outflow facility by fluorophotometry, intraocular pressure by tonometry, and episcleral venous pressure by venomanometry. Uveoscleral outflow was calculated. Clinic visits were scheduled on baseline day; on day 8 of four times daily pilocarpine (2%) to one eye and vehicle to the other; on day 8 of continued pilocarpine/vehicle treatment plus latanoprost (0.005%) once daily to both eyes; after a 3-week washout period; on day 8 of once-daily latanoprost to one eye and vehicle to the other; and on day 8 of continued latanoprost/vehicle treatment plus pilocarpine four times a day to both eyes. Drug-treated eyes were compared with contralateral vehicle-treated eyes and with baseline day by paired t tests. Combined pilocarpine and latanoprost-treated eyes were compared with individual drug-treated eyes and with baseline day using the Bonferroni test. RESULTS: Compared with baseline, pilocarpine reduced intraocular pressure from 18.9 to 16.2 mm Hg (P =.001) and increased outflow facility from 0.18 to 0.23 microl per minute per mm Hg (P =.03). No other parameters were affected. Adding latanoprost further reduced intraocular pressure to 13.7 mm Hg (P <.001) and increased uveoscleral outflow from 0.82 to 1.36 microl per minute (P =.02). Latanoprost alone reduced intraocular pressure from 17.6 to 14.3 mm Hg (P <.0001) and increased uveoscleral outflow from 0.89 to 1.25 microl per minute (P =.05). Adding pilocarpine to the latanoprost treatment further reduced intraocular pressure to 12.7 mm Hg (P <.001) and increased outflow facility from 0.21 to 0.30 microl per minute per mm Hg (P =.03). CONCLUSIONS: Latanoprost and pilocarpine predominantly increase uveoscleral outflow and outflow facility, respectively, when given alone. These drugs are additive because pilocarpine does not inhibit the uveoscleral outflow increase induced by latanoprost.     

Effect of pilocarpine in treatment of intraocular pressure elevation following neodymium: YAG laser posterior capsulotomy

A prospective study was conducted in 30 eyes of 30 patients to determine if pilocarpine would prevent increased intraocular pressure following Q-switched neodymium (Nd):YAG laser posterior capsulotomy. Fifteen eyes were given pilocarpine 4%, immediately following laser therapy and every hour until bedtime. Fifteen eyes served as untreated controls. Our results show that without prophylactic therapy, 10 of 15 eyes (67%) had a post-laser intraocular pressure (IOP) elevation of greater than 10 mmHg, while only one of 15 (6.6%) of the pilocarpine-treated eyes had a rise of that magnitude. The facility of outflow was reduced by 42% in the untreated eyes in contrast to an increase of 3% in those eyes treated with pilocarpine. Thus, pilocarpine 4% is effective in reducing the incidence and magnitude of elevated IOP following Nd:YAG posterior capsulotomy.     

Mechanisms in open-angle glaucoma.

One hundred and nineteen eyes from 68 patients with open-angle glaucoma were provoked by means of a pilocarpine phenylephrine provocative test. In 22% the response was the same as that seen in normal eyes. In 78% the response was the same as that seen in contralateral eyes at risk to the development of closed-angle glaucoma, which do not develop a positive provocative test. The 68 patients were randomised and 34 submitted to a "dummy" provocative test. No significant change in pressure or outflow occurred. Fifty-two of the 93 eyes with an abnormal provocative test were selected for a peripheral iridectomy and reprovoked at least 6 months after operation. The results were significantly different from those obtained before operation. It was concluded that partial-angle closure could be demonstrated in some eyes with apparent open-angle glaucoma. The mechanisms involved in the production of partial-angle closure in eyes with apparent open-angle glaucoma are discussed.     

H-7 effect on outflow facility after trabecular obstruction following long-term echothiophate treatment in monkeys

PURPOSE: To determine whether H-7 can enhance outflow facility after trabecular meshwork obstruction by extracellular material that accumulates after long-term treatment of monkeys with the cholinesterase inhibitor echothiophate iodide (ECHO). METHODS: Cynomolgus monkeys were treated topically with 150 microg ECHO in one (n = 4 eyes) or both (n = 8 eyes) eyes for up to 48 weeks. Accommodation response to topical pilocarpine was monitored periodically. Outflow facility response to H-7 was measured by two-level constant pressure perfusion on three or four different occasions after intraocular pressure was elevated for 12 to 18 weeks. RESULTS: Long-term treatment with ECHO decreased the accommodative response to pilocarpine and increased intraocular pressure, as has been reported. Baseline outflow facility was decreased by 46% +/- 7% (n = 12, P < 0.001). H-7 partially restored baseline outflow facility measured during subsequent perfusions while ECHO treatment was continued. Concurrent H-7 enhanced outflow facility by 73% +/- 18% (n = 12, P < 0.005) beyond the same-day baseline in ECHO-treated eyes. Cessation of ECHO treatment further restored baseline outflow facility, and the outflow facility response to H-7. CONCLUSIONS: H-7 can enhance OF in the presence of trabecular obstruction produced by long-term ECHO treatment. This suggests that H-7 may be useful in treating glaucoma, even in the presence of accumulated plaque material that has been described previously.     

Management of increased intraocular pressure after cataract extraction

We measured the change in intraocular pressure prospectively after extracapsular cataract extraction in 80 eyes after treatment with either pilocarpine gel, pilocarpine 4% solution, timolol 0.5% solution, or placebo. Intraocular pressure, pupil size, and anterior chamber cellular reaction were measured in a masked fashion on the first day after surgery. A significant increase in intraocular pressure was found in all groups postoperatively when compared with baseline values (P less than .001). Eyes treated with pilocarpine gel had an average intraocular pressure increase of 4.2 +/- 2.1 mm Hg (mean +/- 1 S.E.), eyes treated with pilocarpine 4% eyedrops had an average increase of 9.8 +/- 2.8 mm Hg, and eyes treated with timolol demonstrated an intraocular pressure increase of 8.25 +/- 3.19. The intraocular pressure in untreated eyes (controls) increased by an average of 12.9 +/- 2.7 mm Hg. Only the difference in intraocular pressure change between the eyes treated with pilocarpine gel and control eyes was statistically significant (P = .025). Postsurgical intraocular pressure exceeding 25 mm Hg was observed in three of 20 pilocarpine gel treated eyes (15%) and 11 of 20 control eyes (55%). Pilocarpine treatment was not associated with noticeable changes in intraocular inflammatory response, nor were significant ocular or systemic adverse reactions observed. A single administration of pilocarpine gel is effective in reducing increased intraocular pressure for the first 24 hours after extracapsular cataract extraction.     

The effect of low concentrations of pilocarpine with phenylephrine on intraocular pressure in glaucoma (author's transl)]

Orientating preliminary trials showed that the reducing action of pilocarpine on intraocular pressure is considerably enhanced by adding the alpha-receptor stimulant phenylephrine. Pilocarpine eyedrops 1% and pilocarpine drops 1% with phenylephrine 0.25% were compared in two double-blind crossover studies. Pressure reduction was more pronounced after administering the combination, the width of the pupil remaining unchanged. Attention is drawn to the advantages of pressure reduction without narrowing of the pupils in the treatment of all types of open-angle glaucoma. Miosis is of therapeutical advantage only in angle-closure glaucoma; hence, for reasons of safety, administration of phenylephrine should be avoided.     

Double-masked cross-over comparison of Ganda 1.02 (guanethidine 1% and adrenaline 0.2% mixture) with gutt. adrenaline 1% (Simplene 1%) and with pilocarpine 1% (Sno-Pilo 1%).

A trial of the efficacy of low-concentration nonmiotic therapy was carried out, the aim being to minimise the side effects produced by 1% adrenaline or pilocarpine. A total of 77 eyes with open-angle glaucoma were studied in both parts of the trial. Thirty-nine eyes had a base-line pressure of over 28 mmHg and 28 eyes a pressure of 30 mmHg or over. In the comparison between Ganda 1.02 and adrenaline 1% (Simplene) the mean lowering of intraocular pressure was 8.6 mmHg with Ganda and 7.69 mmHg with Simplene. In the comparison between Ganda 1.02 and pilocarpine 1% (Sno-Pilo) the mean decrease was 6.34 mmHg with Ganda and 6.13 mmHg with Sno-Pilo. The resulting falls in intraocular pressure were highly significant statistically, but the differences between the effects of the 3 drugs were not significant. No significant side effects were reported with Ganda 1.02, and in particular no ptosis or superficial punctate staining of the cornea was noted.     

Argon Laser Trabeculoplasty in the Presurgical Glaucoma Patient

The trabecular meshwork in 334 eyes of 260 patients with medically uncontrolled primary and secondary open-angle glaucoma was treated with the argon laser. The average intraocular pressure reduction obtained was 7.1 mm Hg. Tonographic data showed significant increase in the facility of outflow. Glaucoma surgical intervention was avoided in 87.5% of phakic eyes and in 62.1% of aphakic eyes. Laser trabeculoplasty was found to be effective in primary open-angle glaucoma, pseudoexfoliation glaucoma, pigmentary glaucoma, angle recession glaucoma, glaucoma secondary to uveitis, and in eyes with failed glaucoma surgical procedures. The length of follow-up in this series ranged from one week to 21 months, with an average of five months. The major complication noted was a rise in intraocular pressure following treatment. In one eye, a small central island of vision was lost due to this intraocular pressure elevation. Treating one-half of the angle in each of two treatment sessions separated by a few weeks reduces the degree of this pressure elevation. The glaucoma status of 3% eyes was made worse after treatment with trabeculoplasty.     

Aqueous humor dynamics following total iridectomy in the cynomolgus monkey.

Twenty-two cynomolgus monkeys underwent unilateral total iridectomy in vivo. Several weeks to several months postoperatively, intraocular pressure (IOP) was determined bilaterally by manometry under pentobarbital anesthesia (15 monkeys), by a minified Goldmann applanation tonometer under CI-744 anesthesia (16 monkeys), and by a minified Draeger applanation tonometer under light phencyclidine catalepsia (4 monkeys). Mean IOP in aniridic eyes was about 0.3 mm Hg, or about 3%, lower than in opposite eyes. IOPs of aniridic and opposite eyes of the individual monkeys were highly correlated in all groups. In 11 monkeys, resting total outflow facility and the facility response to intravenous pilocarpine were determined 6 to 9 weeks postoperatively by two-level constant-pressure perfusion under pentobarbital anesthesia. There were no significant differences between mean resting facility, postpilocarpine facility, or facility response to pilocarpine of aniridic and opposite eyes. Resting facility, postpilocarpine facility, and facility response to pilocarpine in aniridic and opposite eyes of the individual monkeys were each highly correlated. Total iridectomy in the cynomolgus monkey apparently has little, if any, effect on IOP, outflow facility, or facility response to intravenous pilocarpine, and the iris plays little, if any, role in mediating the facility response to intravenous pilocarpine.     

Does the pilocarpine phenylephrine provocative test help in the management of acute and subacute angle closure glaucoma?

The pilocarpine phenylephrine provocative test (PPPT) has been described as a highly sensitive method to identify eyes suffering from or at risk of angle closure glaucoma (ACG). This paper reports on average 10 years follow-up of the outcome of cases of primary acute ACG and subacute ACG in which the management was determined by the result of the PPPT--a positive result indicating the need for a peripheral iridectomy, a negative result conservative treatment. In spite of a negative PPPT the fellow eyes of cases of acute ACG treated conservatively had a high rate (40%) of development of ACG. Similarly, in eyes with a history of subacute ACG with a negative PPPT, ACG developed at some stage during the follow-up in 60%. Peripheral iridectomy alone resulted in normal intraocular pressure in 63% of eyes that had suffered an attack of acute ACG. In hypertensive eyes that presented with subacute ACG, however, only one eye became normotensive following peripheral iridectomy alone. In the subacute ACG group a positive PPPT was closely related to the presence of glaucomatous optic disc damage. These results indicate that the PPPT lacks sensitivity in detecting eyes at risk of angle closure glaucoma, and a positive result is likely in eyes with damaged outflow that will not respond to peripheral iridectomy.