Effects of beta-adrenergic blockers on retinal circulation

We evaluated the effects of 0.5% betaxolol hydrochloride and 0.5% timolol maleate on retinal blood flow. We measured the diameter of the retinal artery (Da) and vein (Dv), and retinal venous blood flow rate (V) in 8 healthy young volunteers by laser speckle velocimetry before and after the application of betaxolol or timolol topically to both eyes daily for one week. There were no any significant changes. Da before and after the application of betaxolol was 114.2 +/- 6.3 (mean +/- standard deviation) microns and 115.6 +/- 6.7 microns and before and after the application of timolol, 117.5 +/- 12.7 microns and 101.3 +/- 9.5 microns. Dv before and after the application of betaxolol was 149.5 +/- 11.1 microns and 148.4 +/- 13.3 microns, and before and after the application of timolol 148.5 +/- 9.2 microns and 146.2 +/- 10.3 microns. V before and after the application of timolol was 12.3 +/- 2.6 mm/s and 12.6 +/- 2.4 mm/s, and before and after the application of betaxolol, 11.6 +/- 1.5 mm/s and 11.4 +/- 2.1 mm/s. Thus one-week application of the beta-blockers, betaxolol and timolol did not change the retinal arterial or venous blood flow.     

A double-masked, randomized 1-year study comparing dorzolamide (Trusopt), timolol, and betaxolol. International Dorzolamide Study Group

OBJECTIVE: To investigate the safety profile and efficacy of 2.0% dorzolamide hydrochloride, when administered three times daily for up to 1 year, compared with that of 0.5% timolol maleate and 0.5% betaxolol hydrochloride, each administered twice daily. In addition, the effect of adding dorzolamide to the regimen of patients with inadequate ocular hypotensive efficacy while they were receiving one of the two beta-adrenoceptor antagonists and the effect of adding timolol to the regimen of patients receiving dorzolamide were also evaluated. DESIGN: A double-masked, randomized, parallel comparison. SETTING: Multinational study at 34 international sites. PATIENTS: Five hundred twenty-three patients with open-angle glaucoma or ocular hypertension, 17 to 85 years of age. Patients currently using ocular hypotensive medications were required to undergo a washout. INTERVENTION: Two percent dorzolamide three times a day, 0.5% timolol (Timoptic, Merck, Whitehouse Station, NJ) twice daily, and 0.5% betaxolol solution (Betoptic, Alcon, Fort Worth, Tex) twice daily. RESULTS: At 1 year, the mean percent reduction in intraocular pressure at peak of 2% dorzolamide, 0.5% timolol, and 0.5% betaxolol was approximately 23%, 25%, and 21%, respectively. At afternoon trough, the mean percent reduction in intraocular pressure was 17%, 20%, and 15% for dorzolamide, timolol, and betaxolol, respectively. CONCLUSIONS: The ocular hypotensive efficacy of 2.0% dorzolamide, given three times a day, is comparable with that of 0.5% betaxolol, given twice daily, for up to 1 year. In addition, long-term use of dorzolamide was not associated with clinically meaningful electrolyte disturbances or systemic side effects commonly observed with the use of oral carbonic anhydrase inhibitors.     

The favorable effect of topical betaxolol and timolol on glaucomatous visual fields: a 2-year follow-up study

BACKGROUND: It has been suggested that beta-adrenergic antagonists might have mechanisms of action other than ocular hypotensive effects affecting the visual function in glaucoma patients and that betaxolol might protect the visual field better than others. A randomized, double-blind study was conducted to compare the effects of betaxolol and timolol on visual fields of glaucoma patients. METHODS: Sixty-four glaucoma patients were treated with either 0.5% betaxolol or 0.25% timolol eyedrops twice daily. The Octopus visual field performance was followed up for 2 years and analyzed to find diffuse and localized changes. We analyzed the change in the mean sensitivity (MS) and performed a cluster analysis and clinical assessment of the visual fields in both treatment groups. RESULTS: The mean sensitivity (MS) improved significantly and equally in both treatment groups. There was a tendency towards more improved clusters in the betaxolol group than in the timolol group and more worsened cluster in the timolol group than in the betaxolol group, but the difference was not statistically significant. The clinical assessment also showed no statistically significant difference between the two groups. CONCLUSION: In the present study both betaxolol and timolol had a favorable effect on the visual fields of glaucoma patients. There was no statistically significant difference between betaxolol- and timolol-treated patients either in the change in mean retinal sensitivity or in the change in localized scotomatous areas.     

A double-masked, randomized, 1-year study comparing the corneal effects of dorzolamide, timolol, and betaxolol. Dorzolamide Corneal Effects Study Group

OBJECTIVE: To compare the long-term effects of dorzolamide hydrochloride (Trusopt, Merck and Co Inc, White-house Station, NJ), timolol maleate, and betaxolol hydrochloride on corneal endothelial cell density and corneal thickness. METHODS: This 1-year multicenter study was conducted in 298 patients with ocular hypertension or open-angle glaucoma who had a baseline central corneal endothelial cell density greater than 1500 cells/mm2 and central corneal thickness less than 0.68 mm in each eye. Patients were randomized to 0.5% betaxolol twice daily, 0.5% timolol twice daily, or 2.0% dorzolamide 3 times daily. Specular microscopy and ultrasonic pachymetry of the central cornea was performed at baseline and 6 and 12 months following institution of therapy. Endothelial cell densities were determined by a single masked observer. RESULTS: The mean percent changes from baseline for both outcome measures were similar in all 3 treatment groups at both 6 and 12 months. After 1 year of treatment, the mean percent loss in endothelial cell density from baseline was 3.6%, 4.5%, and 4.2% for the dorzolamide, timolol, and betaxolol groups, respectively. The mean percent change from baseline for corneal thickness was 0.47%, -0.25%, and 0.39% for the dorzolamide, timolol, and betaxolol groups, respectively. CONCLUSIONS: Dorzolamide is equivalent to timolol and betaxolol in terms of the change in central endothelial cell density and thickness after 1 year of therapy. All 3 treatments exhibit good long-term corneal tolerability in patients with normal corneas at baseline.     

Quantification of optic nerve blood flow changes using magnetic resonance imaging

PURPOSE: To evaluate the possibilities of magnetic resonance imaging (MRI) for quantification of pharmacologically induced changes in optic nerve microcirculation. METHOD: T2-weighted MRI sequences were used to image the eye, optic nerve, and frontal cortex in rats. Two sets of control images before and one set during Gd (DTPA) infusion were recorded. Blood flow values for two regions of the optic nerve (an anterior part, including the optic nerve head, and a more posterior part) and the frontal cortex were calculated by image analysis from the change in signal intensity, as already reported for cerebral blood flow. For each rat, a control experiment before drug administration and a second experiment 30 minutes after subcutaneous injection of either placebo (n = 7), timolol (n = 7), or SDZ GLC-756, a dopamine D-1 antagonist and D-2 agonist (n = 7), were carried out in a double-blind fashion. RESULTS: Mean basal blood flow values were found between 29.4 and 45.6 ml/100 g per minute in the anterior part of the optic nerve, 38.3 and 42.9 ml/100 g per minute in the posterior part of the optic nerve, and 68.0 and 75.0 ml/100 g per minute in the frontal cortex. Placebo and timolol did not cause significant changes. SDZ GLC-756 significantly increased blood flow by 238% +/- 65% in the anterior part and by 87% +/- 40% in the posterior part of the optic nerve. CONCLUSIONS: These results suggest that MRI provides quantification of optic nerve blood flow and that dopaminergic substances increase optic nerve blood flow.     

Efficacy and tolerability of 0.5% timolol maleate ophthalmic gel-forming solution QD compared with 0.5% levobunolol hydrochloride BID in patients with open-angle glaucoma or ocular hypertension

We compared the efficacy of timolol maleate ophthalmic gel-forming solution 0.5% QD with that of levobunolol hydrochloride 0.5% BID, as measured by change in intraocular pressure (IOP), effect on heart rate, and ocular tolerability. The study had a positive-controlled, double-masked, randomized, multicenter, 12-week, two-period (6 weeks each), crossover design. One hundred fifty-two patients with open-angle glaucoma or ocular hypertension were randomized to receive either timolol maleate gel-forming solution QD or levobunolol BID for 6 weeks, followed by a crossover to the alternate treatment. IOP and heart rate were measured at morning trough and peak during weeks 3, 6, 9, and 12. Timolol maleate gel-forming solution QD was comparable to levobunolol BID in reducing IOP at peak and trough. Although the effects on peak heart rate were similar between the two medications, the effect on trough heart rate of timolol maleate gel-forming solution QD was significantly less than that of levobunolol BID (P = 0.001). The incidence of ocular burning and stinging was comparable between the two treatments. Patients experienced significantly more blurred vision when using timolol maleate gel-forming solution than when using levobunolol (P = 0.013). Overall, more patients experienced at least one adverse event when using timolol maleate gel-forming solution. Timolol maleate gel-forming solution QD is as efficacious in reducing IOP as levobunolol BID.     

The effects of unoprostone isopropyl 0.12% and timolol maleate 0.5% on diurnal intraocular pressure

PURPOSE: To compare the effect of unoprostone isopropyl 0.12% to that of timolol maleate 0.5% solution given twice daily on the diurnal curve of intraocular pressure (IOP) in patients with primary open-angle glaucoma or ocular hypertension. METHODS: In this investigator-masked, single-center, parallel-group comparison, 36 patients with primary open-angle glaucoma or ocular hypertension were randomized in a 2:1 ratio to receive either unoprostone isopropyl 0.12% or placebo/timolol maleate 0.5% solution, respectively. A placebo-controlled diurnal curve on day 0 and active-controlled diurnal curves at weeks 2 and 4 were performed at 0, 2, 4, 6, 8, 10, 12, and 24 hours. At week 2, administration of unoprostone isopropyl twice daily was compared with administration of timolol maleate twice daily. At week 4, administration of unoprostone isopropyl three times daily was compared with administration of timolol maleate twice daily. RESULTS: At the 24-hour 8:00 AM trough at week 2, administration of unoprostone isopropyl twice daily decreased IOP from 23.4 +/- 2.0 mmHg at baseline to 19.3 +/- 4.4 mmHg, and timolol maleate reduced IOP from 24.4 +/- 2.6 mmHg to 17.5 +/- 2.9 mmHg. At the 8:00 AM trough at week 4, unoprostone isopropyl given three times daily produced an IOP of 19.6 +/- 3.3 mmHg and timolol maleate resulted in an IOP of 19.4 +/- 3.0 mmHg. No statistical differences between groups were observed at any time point during either diurnal curve. Safety was similar in the two treatment groups, with no differences between groups in conjunctival hyperemia, anterior segment inflammation, or iris color change. CONCLUSION: Results of this short-term pilot trial indicate that unoprostone isopropyl may be safe and effective in reducing IOP from baseline when given twice or three times daily.     

Optic disk vasculitis

A 44-year-old woman developed progressive loss of vision associated initially with a swollen optic disk, and later with optic atrophy and a diffuse retinal vasculopathy, which caused extensive retinal hemorrhagagic. Histopathologic examination showed hemorrhagagic infarction of the retina, as well as infarction of the anterior optic nerve. In the optic nerve, the central retinal vessels showed extensive phlebitis and occlusion of many small arterioles.     

A randomized trial in patients inadequately controlled with timolol alone comparing the dorzolamide-timolol combination to monotherapy with timolol or dorzolamide. Dorzolamide-Timolol Combination Study Group

OBJECTIVE: To compare the dorzolamide-timolol fixed combination twice daily to its components, timolol maleate and dorzolamide hydrochloride, given in their usual monotherapy regimens in patients whose intraocular pressure (IOP) was not controlled on timolol twice daily alone. DESIGN: Parallel, randomized, double-masked, and active-controlled study. PARTICIPANTS: Enrolled were 253 patients from 22 sites throughout the United States. INTERVENTION: After a 3-week run-in of timolol (TIMOPTIC; Merck & Co., Inc., Whitehouse Station, NJ) twice daily, eligible patients received either the combination (COSOPT; Merck & Co., Inc., Whitehouse Station, NJ) twice daily (plus placebo to ensure masking), timolol twice daily (plus placebo to ensure masking), or dorzolamide (TRUSOPT; Merck & Co. Inc., Whitehouse Station, NJ) three times daily for 3 months. MAIN OUTCOME MEASURES: Intraocular pressure taken at hours 0 (trough) and 2 (peak) after week 2 and months 1, 2, and 3 was compared to baseline within each treatment group and between the combination and each component group. The safety profile of the combination was compared to each component. RESULTS: The combination was numerically superior at all study timepoints and was statistically superior at all timepoints except for month 2, hour 0 for timolol, and month 2, hour 2 for dorzolamide. The safety profile of the combination reflected those of its two components. The number of patients reporting ocular or local adverse experiences was greater for the combination (45%) and dorzolamide (45%) than for timolol (27%), with burning and/or stinging eye being the most frequently reported. CONCLUSION: The dorzolamide-timolol combination provides additional IOP lowering compared to either of its individual components and generally is well-tolerated.     

Long-term epinephrine therapy of ocular hypertension

Nineteen patients with symmetrical ocular hypertension and symmetrical cupping of the optic nerves were made asymmetric with respect to intraocular pressure for one to five years by unilateral topical treatment with epinephrine hydrochloride. Development of glaucomatous visual field defects was observed in 32% of the untreated eyes and in none of the treated eyes (P less than .05). Progressive cupping of the optic nerve was noted in 53% of the untreated eyes and in 11% of the treated eyes (P less than .025). Evidence of glaucomatous damage was observed more frequently in subjects maintained on this regimen for longer periods and in subjects with initial horizontal cup/disc ratios greater than 0.4 (P less than .05). None of the eyes, either treated or untreated, with mean intraocular pressures less than 24 mm Hg developed glaucomatous damage during the period of this study.     

Alcohol and poor compliance as factors in Wernicke''s encephalopathy diagnosed 13 years after gastric bypass

OBJECTIVE: The aim was to study the relationship between aqueous humour betaxolol concentration and intraocular pressure (IOP). METHODS: In this double-blind, randomized study, we administered betaxolol (a) or placebo (b) ocularly to 131 patients scheduled for cataract surgery. The patients were randomly divided into ten groups. In groups 1a and 1b, the drug was scheduled to be instilled 1-2 h, in groups 2a and 2b 12 h, in groups 3a and 3b 24 h, and in groups 4a and 4b 48 h before surgery. The pupil was dilated in all eyes prior to surgery. The IOP was measured with Perkins' applanation tonometer before the instillation of the drug and just before the peribulbar block. Twenty microlitres of 0.5% betaxolol or placebo solution was instilled into the eye. IOP was also measured before instillation of the drug and after 1 2 h in undilated eyes of 20 patients, whose contralateral eye was to be operated on, to rule out the effect of pupil dilation on IOP (groups 5a and 5b). Aqueous humour betaxolol concentrations were analysed using a radioreceptor assay. RESULTS: Betaxolol did not decrease IOP significantly in eyes with pupillary dilation. Both betaxolol and placebo decreased IOP significantly in patients without pupillary dilation, the effect of betaxolol being slightly more pronounced. The betaxolol concentration in aqueous humour was 731 ng m-1 in group la, 2.4 h after drug instillation. Measurable concentrations of betaxolol were also detected in aqueous humour in group 4a 47.7 h after drug administration. CONCLUSION: No correlation between aqueous humour concentration of betaxolol and the effect on IOP was found in eyes where the pupil was dilated before surgery. A single betaxolol dose did not decrease IOP significantly in patients undergoing cataract surgery, but the IOP decreasing effect was, however, clearly seen in patients who did not receive mydriatic drugs. The routine use of topical betaxolol prior to cataract surgery to decrease IOP is not recommended.     

Evaluation of the retinal nerve fiber layer

In normal eyes, the retinal nerve fiber layer (RNFL) is usually best visible in the inferior temporal part of the fundus, followed by the superior temporal region, the nasal superior region and the nasal inferior region. This distribution correlates with the configuration of the neuroretinal rim, the diameter of the retinal arterioles, the location of the foveola, and the lamina cribrosa morphology. With increasing age, the RNFL visibility decreases diffusely without preferring special fundus regions and without the development of localized defects. With all optic nerve diseases, the visibility of the RNFL is decreased in addition to the age-related loss, in a diffuse and/or a localized manner. The localized defects are wedge-shaped and not spindle-like defects, running toward or touching the optic disk border. Typically occurring in about 20% of all glaucoma eyes, they can be found also in other ocular diseases, such as optic disk drusen, toxoplasmotic retinochoroidal scars, longstanding papilledema or optic neuritis due to multiple sclerosis. Since they are not present in normal eyes, they almost always signify an abnormality. RNFL evaluation is especially helpful for early glaucoma diagnosis and in glaucoma eyes with small optic disks. In advanced optic nerve atrophy, other examination techniques, such as perimetry, may be more helpful for following optic nerve damage. Considering its great importance in the assessment of optic nerve anomalies and diseases and taking into account the feasibility of its ophthalmoscopic evaluation using green light, the retinal nerve fiber layer should be examined during any routine ophthalmoscopy.     

Effects of topical nipradilol, a beta-blocking agent with alpha-blocking and nitroglycerin-like activities, on aqueous humor dynamics and fundus circulation

PURPOSE: To study the effects of nipradilol, a nonselective beta-blocker with alpha 1-blocking activity and nitroglycerin-like activity, on aqueous humor dynamics and optic nerve head (ONH) circulation in albino rabbits. METHODS: Experiments were carried out during the dark phase, in conscious rabbits conditioned to a schedule of alternating 12-hour periods of light and dark. The blood-aqueous barrier permeability and the aqueous flow rate were determined fluorophotometrically. The effect on outflow to general blood circulation and uveoscleral outflow were determined by using the fluorophotometric Diamox technique, and the effect on the uveoscleral outflow was further assessed by using the anterior chamber perfusion method. The ONH circulation was estimated by using the laser speckle method. RESULTS: Unilateral topical administration of 0.25% nipradilol solution lowered intraocular pressure (IOP) with relatively weak contralateral effects in a dose-dependent manner with a maximum reduction of 6 mm Hg and an effect duration of 6 hours. Twice-daily instillation for 14 days showed no attenuation of the effects. Single instillation of 0.25% nipradilol showed no significant effect on blood-aqueous barrier permeability and decreased aqueous flow rate in the treated eye (17%; P < 0.01) and in the contralateral eye (9%, P < 0.05). Nipradilol produced no significant effect on outflow facility to general blood circulation, whereas it substantially increased uveoscleral outflow. Twice-daily 0.25% nipradilol instillation increased ONH tissue blood velocity by 13% (P < 0.01), which was probably attributable to locally penetrating drug. CONCLUSIONS: Because of its ability to lower IOP and to increase uveoscleral outflow and optic nerve head circulation in rabbits, further studies are warranted to determine whether nipradilol has potential as an antiglaucoma agent in humans.     

Normal and aberrant functions of integrins in the adult central nervous system

Eighteen normal human eye-bank eyes (age: 18-81 years), five fetal eyes (16-24 weeks), 11 primary open-angle glaucoma (POAG) eyes (age: 76-89 years), and two Schnabel's cavernous optic atrophy eyes were examined using a biotinylated-hyaluronan binding protein to study the changes in the distribution of hyaluronic acid (HA) in the fetal, adult and glaucomatous optic nerve head. The vitreous body served as a positive control. Sections treated with Streptomyces hyaluronidase were used to confirm specificity. Monoclonal antibodies to myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) were used as additional controls. In fetal optic nerve, HA was localized in blood vessels, peripapillary sclera and the pial septae in the retrolaminar nerve. No staining was associated with axons. Staining for MBP was negative. In adults, HA was found surrounding the myelin sheaths in the retrolaminar nerve; staining decreased with age. In contrast, HA staining in myelinated peripheral nerves (e.g. ciliaries) remained unchanged with age. HA also was localized to the adventitia of arteries and veins throughout the posterior segment. Compared to age-matched normal eyes, HA staining was virtually absent around myelin sheaths of the retrolaminar nerve in POAG eyes. Similar changes were not found in other HA positive structures. In Schnabel's cavernous optic atrophy. HA was present in increased amount in the atrophic area, but virtually absent in the remaining retrolaminar nerve. HA staining was invariably positive in vitreous, and Streptomyces hyaluronidase treated sections were negative. In adults, staining of MBP was associated with the myelin sheath in the retrolaminar nerve. In contrast to HA, staining of MBP was unchanged with age and in POAG. In Schnabel's atrophy, MBP staining disappeared only in the atrophic area. HA in the retrolaminar optic nerve appears to be associate with the space-filling matrix between myelin sheaths. HA is not present in the axon bundles prior to myelination of the optic nerve. HA in the retrolaminar optic nerve appears to decrease with age and is further reduced in POAG; however, corresponding changes are not found in MBP or in peripheral nerves. Perhaps, decreased amounts of HA is related to a higher susceptibility to elevated intraocular pressure or to optic nerve atrophy. In Schnabel's cavernous optic atrophy, HA is present in increased amount only in the atrophic area while MBP is markedly decreased, suggesting in situ production of HA in areas of optic nerve atrophy.     

Elevation of intraocular glutamate levels in rats with partial lesion of the optic nerve

BACKGROUND: Acute partial lesion of the rat optic nerve, although not a model for glaucoma, mimics some of the features of the disease. OBJECTIVE: To learn whether degeneration of rat optic nerve fibers and death of their retinal ganglion cells induced by an acute partial lesion are associated with elevated levels of glutamate, known to occur in the eyes of humans and monkeys with glaucoma. MATERIALS AND METHODS: Rat optic nerve was subjected to a partial crush injury. Aqueous humor samples were aspirated from the anterior and posterior aqueous chambers at specified times and their amino acid contents were determined by means of high-performance liquid chromatography. RESULTS: Three and 7 days after injury, intraocular glutamate and aspartate levels were found to be significantly higher than in normal or sham-operated-on eyes, and returned to normal by day 14. CONCLUSIONS: Degeneration of the optic nerve, induced by a mechanical injury of the axons, leads to intraocular elevation of glutamate and aspartate levels. These results illustrate that the model of the partial optic nerve lesion exhibits another feature typical of a long-term optic neuropathy, such as glaucoma.     

Expanding role of alpha adrenoceptor blockade in the treatment of benign prostatic hyperplasia

PURPOSE: To evaluate the efficacy and safety of timolol hemihydrate once daily versus timolol maleate gel forming solution once daily in patients with primary open-angle glaucoma or ocular hypertension. METHODS: We prospectively randomized patients with primary open-angle glaucoma or ocular hypertension to receive either timolol hemihydrate 0.5% solution or timolol maleate gel forming solution 0.5% every morning. The primary efficacy variable was the 8:00 AM trough intraocular pressure (IOP) 24 hours after administration. RESULTS: Three months after initiation of therapy, baseline IOP had decreased from 23.6 +/- 1.9 mmHg to 18.3 +/- 2.8 mmHg in the group taking timolol hemihydrate (n = 22) and from 23.7 +/- 2.2 mmHg to 18.4 +/- 3.1 mmHg in the group receiving timolol maleate gel (n = 21) at the 24-hour trough level. This was not a significant difference between groups at 3 months. Also, no difference was observed between groups in the 2-hour post instillation IOP. Visual acuity was decreased in the group receiving timolol maleate gel compared with those receiving timolol hemihydrate one minute after instillation of study medicine at month 3. Otherwise, ocular and systemic safety were similar between groups. No differences between groups in cardiac pulse or systolic and diastolic blood pressure were observed. CONCLUSION: Timolol hemihydrate 0.5% solution given once a day appears to be as efficacious and safe in decreasing IOP as timolol maleate gel 0.5% given once a day.     

Muscarinic acetylcholine receptor antagonists inhibit chick scleral chondrocytes

PURPOSE: Muscarinic acetylcholine receptors (mAChRs) have been implicated in the control of myopia in humans and in animal models. This study was conducted to determine whether mAChRs influence the growth of the chick sclera and, if so, which mAChR subtypes are involved. METHODS: Sclera and scleral chondrocytes from normal and form-deprived eyes of 10- to 14-day-old chicks were treated with a total of seven ligands: two agonists, carbachol (nonselective) and McN-A-343 (selective for the M1 mAChR subtype); and five antagonists, atropine (nonselective), pirenzepine and telenzepine (M1), gallamine (M2), and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; M1 and M3). Incorporation of sulfate into glycosaminoglycans and of thymidine into DNA were quantified and normalized to sample DNA content. Possible toxicity of ligands at high doses was examined by analysis of cell number (by cell counting), viability (by trypan blue exclusion), and cellular metabolic activity (by dehydrogenase activity). RESULTS: Cellular proliferation and extracellular matrix production were inhibited by atropine in whole sclera and in its cartilaginous layer. Sulfate incorporation by chondrocytes from normal and form-deprived eyes was inhibited by mAChR antagonists with a rank order of potency (atropine > pirenzepine = 4-DAMP > gallamine) consistent with regulation by M1, rather than M3 or M2 mAChR subtypes. Pirenzepine inhibited sulfate incorporation by chondrocytes from form-deprived eyes more effectively than those from normal eyes. Chondrocyte cultures were not viable when grown in high doses of any of the ligands used except gallamine. CONCLUSIONS: In chick scleral chondrocytes, synthesis of DNA and glycosaminoglycans was inhibited by mAChR antagonists. This inhibition was probably mediated by the M1 subtype mAChR. Therefore in vivo the sclera may be a site of action for the mAChR antagonists previously used to influence myopia. Although at high concentrations mAChR antagonists tested seemed to be toxic to chondrocytes, at lower doses inhibition occurred without toxic effects.     

Cholinergic vasoconstrictor effects in the rabbit eye: vasomotor effects of pentobarbital anesthesia

Oculomotor nerve stimulation causes vasoconstriction in the anterior uvea, which is due partly to a muscarinic mechanism and partly to a non-sympathetic aminergic mechanism. The labelled microsphere method was used to analyze the effect of pentobarbital anesthesia on the resting cholinergic vasomotor tone in the anterior uvea and to determine the relationship between stimulation frequency and vasomotor response. An attempt was made also to ascertain whether the aminergic part of the vasoconstriction is caused by release of 5-hydroxytryptamine or norepinephrine. Induction of pentobarbital anesthesia caused a marked vasodilation in the iris and the ciliary processes and a subsequent muscarinic blockade had no effect on the blood flow. A similar result was obtained in the optic nerve. In the choroid plexus, heart muscle, pineal body and coecum, pentobarbital anesthesia caused vasodilation and a subsequent muscarinic blockade caused vasoconstriction. In the brain pentobarbital anesthesia caused a marked reduction in the blood flow of the grey matter and a moderate reduction in the white matter. After a muscarinic blockade there was some increase in the blood flow of the grey matter. Stimulation of the oculomotor nerve caused near maximum vasomotor responses at 10-20 Hz; maximum effect on the pupil size was obtained at 40-50 Hz. Depletion of 5-hydroxytryptamine with fenfluramine did not prevent the aminergic part of the vasoconstriction and a marked vasoconstriction was also observed after pretreatment with reserpine. The results indicate the pentobarbital anesthesia abolishes most of the spontaneous cholinergic vasoconstrictor tone of the anterior uvea and that the aminergic part of the oculomotor nerve induced vasoconstriction is caused by the stimulation of phentolamine-sensitive receptors by a mechanism probably not involving release of norepinephrine or 5-hydroxytryptamine.     

Optic disc morphology in eyes after nonarteritic anterior ischemic optic neuropathy

PURPOSE: Parapapillary chorioretinal atrophy, neuroretinal rim loss, and a decrease of retinal vessel diameter have been described to occur in glaucomatous eyes. This study was conducted to evaluate the frequency and degree of these signs in nonarteritic anterior ischemic optic neuropathy (AION). METHODS: We evaluated morphometrically and compared stereo color optic disc photographs of 17 patients after AION, 184 patients with primary open-angle glaucoma, and 98 normal subjects. RESULTS: The optic disc area and retinal vessel diameter were significantly smaller and the visibility of the retinal nerve fiber bundles was significantly reduced in patients after nonarteritic AION compared with that of the normal subjects. The optic disc shape, area, and form of zones alpha and beta of the parapapillary chorioretinal atrophy and the size and form of the neuroretinal rim did not differ significantly between these two groups. In the group of eyes with glaucoma, the neuroretinal rim was significantly smaller and the parapapillary chorioretinal atrophy was significantly larger than in the group of eyes with AION. Visibility of the retinal nerve fiber bundles and retinal vessel caliber did not differ statistically between the eyes with AION and those with glaucoma. CONCLUSIONS: These results indicate that the parapapillary chorioretinal atrophy is not larger in eyes after nonarteritic AION compared with normal eyes. They show that the area and shape of the neuroretinal rim, as determined planimetrically, may not markedly change after nonarteritic AION. They confirm previous reports on a small optic disc size as a risk factor for nonarteritic AION. They agree with findings of a reduced retinal vessel caliber in eyes with optic nerve damage, independently of the cause.     

The cupped disc. Who needs neuroimaging?

OBJECTIVE: To determine the incidence of positive neuroradiologic studies in consecutive patients with glaucoma associated with normal intraocular pressure and to compare the psychophysical and clinical characteristics of these eyes with eyes with disc cupping associated with intracranial masses. DESIGN: Retrospective case-controlled study. PARTICIPANTS: Fifty-two eyes of 29 patients with glaucoma associated with normal intraocular pressure and 44 eyes of 28 control patients with compressive lesions were reviewed. INTERVENTION: The medical records of consecutive glaucoma patients with normal intraocular pressure who underwent brain magnetic resonance imaging or computed tomography scanning as part of a diagnostic evaluation between January 1, 1985, and July 1, 1995, were reviewed. A masked reading of optic nerve photographs and visual fields was performed by one observer. A similar analysis was performed on a control group of consecutive patients with nonglaucomatous optic nerve cupping with known intracranial mass lesions. MAIN OUTCOME MEASURES: The neuroradiologic findings, clinical characteristics, optic nerve head appearance, and patterns of visual field loss were compared between groups. RESULTS: None of the patients diagnosed with glaucoma had neuroradiologic evidence of a mass lesion involving the anterior visual pathway. Compared to control subjects, patients with glaucoma were older (P = 0.0001), had better visual acuity (P = 0.002), greater vertical loss of neuroretinal rim tissue (P = 0.0001), more frequent optic disc hemorrhages (P = 0.01), less neuroretinal rim pallor (P = 0.0001), and more nerve fiber bundle visual field defects aligned at the horizontal midline (P = 0.0001). Visual acuity less than 20/40, vertically aligned visual field defects, optic nerve pallor in excess of cupping, and age younger than 50 years were 77%, 81%, 90%, and 93% specific for nonglaucomatous cupping associated with compressive lesions, respectively. CONCLUSIONS: Anterior visual pathway compression is an uncommon finding in the neuroradiologic evaluation of patients with a presumptive diagnosis of normal-tension glaucoma. Younger age, lower levels of visual acuity, vertically aligned visual field defects, and neuroretinal rim pallor may increase the likelihood of identifying an intracranial mass lesion.