New medical treatments for glaucoma.
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Adrenergic alpha-Agonists↗
Biomedical subjects
A L Robin
Publications and source records attributed to A L Robin.
Confocal laser scanning ophthalmoscope. Reproducibility of optic nerve head topographic measurements with the confocal laser scanning ophthalmoscope.
BACKGROUND: Glaucoma is an optic neuropathy in which changes in the appearance of both the optic nerve head and the surrounding tissues are important in both diagnosing its presence and progression. Accurate methods to objectively document the appearance of the optic nerve are necessary. The confocal laser scanning ophthalmoscope (Zeiss) is a new prototype instrument that may have the capability to accurately perform this function. METHODS: The authors performed a prospective pilot study evaluating the ability of the confocal laser scanning ophthalmoscope to reproduce three-dimensional optic nerve images. Each retinal image contained 600,000 bytes of information. Thirty discrete images of the right optic nerves of 19 visually normal volunteers were obtained. Depth measurements were compared from the same 100 x 100 micron areas (neighborhoods). RESULTS: Image comparisons found the variability of depth measurements for the entire image were within 102 microns (95% confidence interval). Sixty percent of the depth measurements were reproducible within 100 microns. Variability of the depth measurements was greatest where the neuroretinal rim sloped at the edge of the optic cup and lowest in the peripapillary area. CONCLUSION: The confocal laser scanning ophthalmoscope has the potential to be a safe, rapid, and reproducible method of imaging ocular structures.
Adult↗
Reformulation and drop size of apraclonidine hydrochloride.
We performed a prospective, double-masked, placebo-controlled, six-period, cross-over study in which normal subjects were randomly assigned to treatment and compared three different formulations of apraclonidine hydrochloride (the present commercially available formulation, and formulations with hydroxypropylmethylcellulose or lysolecithin). We also evaluated the efficacy of a 16-microliters and 30-microliters drop size. The magnitude and duration of decrease in intraocular pressure was comparable for all formulations. Most subjects tolerated all formulations well with only a few reporting any side effects. The best-tolerated formulation was 0.5% apraclonidine hydrochloride delivered with a 16-microliters drop size. Dry mouth developed frequently with the commercially available 1% apraclonidine solution. Blurred vision complicated the use of the formulation containing hydroxypropylmethylcellulose. Both dry mouth (P less than .05) and blurred vision (P = .004) were statistically significant side effects.
Adrenergic alpha-Agonists↗
Once-daily versus twice-daily levobunolol (0.5%) therapy. A crossover study.
The authors executed a two-period, randomized, double-masked, crossover study comparing once-daily to twice-daily levobunolol hydrochloride (0.5%) in 20 patients with elevated intraocular pressure (IOP). Modified diurnal curves were performed at four times for each study arm: baseline, day 1, day 14, and day 28. The mean diurnal corrected decrease in IOP from baseline ranged from 16% +/- 11% to 22% +/- 9% when the subjects were treated twice daily, and from 14% +/- 10% to 18% +/- 8% when the same subjects were treated once daily. At day 1, patients had a significantly greater IOP lowering after twice-daily therapy than after once-daily therapy (P less than 0.05). At 14 and 28 days, there was no clinically significant difference between the two treatment regimens. The results of our crossover study suggest that once-daily treatment with levobunolol (0.5%) is as effective as twice-daily treatment.
Adult↗
The influence of iris pigmentation on the miotic effect of thymoxamine.
We performed a randomly assigned, double-masked, placebo-controlled study in 78 patients with varied iris pigmentation to evaluate the influence of iris pigmentation on the ability of 0.1% thymoxamine to reverse mydriasis produced by 2.5% phenylephrine. Patients were chosen so that a 1.6:1 ratio of dark to light irides was obtained. Within one-half hour after medication, thymoxamine-treated nonbrown irides constricted significantly compared to their fellow placebo-treated irides (P less than .001). Thymoxamine-treated pupils of nonbrown irides were 1.0 to 3.1 mm smaller than placebo-treated fellow eyes. Thymoxamine-treated light brown irides constricted less (0.6 to 2.0 mm) and more slowly compared to fellow placebo-treated irides. Thymoxamine did not reverse the mydriasis in eyes of patients with dark brown irides. Thymoxamine appears similar to other adrenergic agents that bind to melanin, delaying onset and strength of action. Its efficacy as presently formulated may be limited, in part, by iris color.
Adolescent↗
Clinically detectable nerve fiber atrophy precedes the onset of glaucomatous field loss.
Standardized perimetry and nerve fiber layer and color fundus photography were performed annually on 1344 eyes with elevated intraocular pressures. In 83 eyes, glaucomatous field defects developed that met rigid criteria on manual kinetic and suprathreshold static perimetry. Individual nerve fiber layer photographs were read by two masked observers. The more sensitive of the two identified nerve fiber layer defects in 88% of readable photographs at the time field loss first occurred; 60% (6/10) of eyes already had nerve fiber layer defects 6 years before field loss. In contrast, the nerve fiber layer was considered abnormal in only 11% (3/27) of normal eyes and 26% (84/327) of hypertensive eyes. The location of nerve fiber layer and field defects closely corresponded, but nerve fiber layer loss was generally more widespread. Examiner experience and severity of optic nerve damage influenced results. Mild focal defects were more readily recognized than more severe diffuse atrophy. Nerve fiber layer defects expanded with time, often by the development and coalescence of adjacent areas of damage.
Adult↗
Effects of topical flurbiprofen on the intraocular pressure lowering effects of apraclonidine and timolol.
We performed a prospective study that evaluated whether pretreatment with topical flurbiprofen alters the intraocular pressure (IOP) lowering effects of either topical 1% apraclonidine hydrochloride or 0.5% timolol maleate. Eighteen normal volunteers participated in this six-armed, randomized, double-masked, crossover study. All subjects received the first study medication, either bilateral 0.3% flurbiprofen or placebo (its vehicle), every 30 minutes for four applications. They next received the second study medication: either 0.5% timolol maleate (Timoptic), 1% apraclonidine hydrochloride, or placebo in both eyes. We measured IOP before the instillation of the first study medication and the second study medication (baseline), and then at 1, 3, and 6 hours later. All subjects underwent all six treatment arms. Flurbiprofen alone had no effect on IOP. Maximum IOP lowering occurred between 3 and 6 hours after timolol and apraclonidine administration. There was no difference in IOP lowering between timolol- and apraclonidine-treated eyes. Pretreatment with flurbiprofen did not affect the IOP lowering that was obtained with timolol or apraclonidine administration.
Administration, Topical↗
Extracapsular cataract extraction in Nepal. 2-year outcome.
We evaluated the 2-year outcome of extracapsular cataract surgery with posterior chamber intraocular lens insertion by a single fellowship-trained surgeon in Kathmandu, Nepal. Six hundred ten eyes were followed up for 2 years. Patients underwent manual irrigation and aspiration with the insertion of a modified J loop posterior chamber intraocular lens. Almost half of the patients had uncorrected visual acuities of 20/50 or better after surgery. Sight-threatening complications in seven eyes (1.2%) included retinal detachment, corneal decompensation, and endophthalmitis. Although this rate is comparable to that in developed countries, 21% of patients had posterior capsular opacification at follow-up. Extracapsular cataract surgery with intraocular lens insertion may be an alternative to intracapsular cataract surgery in developing nations, where aphakic spectacles are expensive, not easily obtainable, or difficult to replace.
Aged↗
New developments in the drug treatment of glaucoma.
This article reviews standard treatment modalities for patients with glaucoma and describes 3 classes of drugs which are undergoing development: apraclonidine (aplonidine, ALO 2145), an alpha 2-adrenergic agonist which has been released for clinical use; topical carbonic anhydrase inhibitors, a modification of the systemic carbonic anhydrase inhibitors currently in use; and prostaglandins (PGs), a new class of drugs with topical ocular hypotensive activity. Standard treatment modalities include parasympathomimetic agents such as pilocarpine, carbachol, and phospholine iodide, which lower intraocular pressure (IOP) by increasing aqueous outflow through the trabecular meshwork. A newer form of pilocarpine as a gel produces a longer action. Adrenergic agonist medications, such as epinephrine (adrenaline) and its prodrug dipivefrine (dipivalyl epinephrine), function by increasing uveoscleral outflow and trabecular outflow facility. A decrease in aqueous formation by the ciliary processes is thought to be the mechanism of action of beta-adrenoceptor antagonists, but the physiological basis for this action has not been clearly demonstrated. A newer beta-blocker, betaxolol, has relatively selective beta 1-blocking activity. Carbonic anhydrase inhibitors are nonbacteriostatic sulphonamide derivatives which decrease aqueous formation by the ciliary body. Almost 50% of patients taking these medications are unable to tolerate them because of their adverse effects, and there is thus much interest in the development of a topical carbonic anhydrase inhibitor with the potential for fewer adverse effects. MK 507 is the most recent and most potent compound in the series of topically active carbonic anhydrase inhibitors. Apraclonidine hydrochloride is a derivative of clonidine hydrochloride, an alpha 2-adrenergic agonist. Clonidine has previously been shown to lower IOP significantly, but has the potential to produce marked lowering of both systolic and diastolic blood pressures. Its major ocular effect appears to be a decrease in aqueous production. The structural modification to apraclonidine decreases corneal absorption and the drug's ability to cross the blood-brain barrier, minimising the risk of centrally mediated cardiovascular side effects. Apraclonidine may also influence secondary avenues of aqueous outflow, such as uveoscleral outflow, and may also affect conjunctival and episcleral vascular flow. It produces a mean decrease in IOP of 25% for as long as 12 hours. Adverse effects include blanching of the conjunctiva, minimal mydriasis and eyelid retraction. This drug has been approved in the US for use in prevention of elevated IOP after argon laser trabeculoplasty and iridotomy, and has potential uses in preventing an IOP rise after YAG laser posterior capsulotomy and cataract surgery in patients already on other antiglaucomatous medications.(ABSTRACT TRUNCATED AT 400 WORDS)
Adrenergic alpha-Agonists↗
Long-term results of extracapsular cataract extraction and posterior chamber intraocular lens insertion in Nepal.
We performed a prospective study evaluating the 2-year success rate of extracapsular cataract surgery and posterior chamber IOL insertion performed in 610 eyes by an experienced surgeon in the Nepal Eye Hospital, Kathmandu, Nepal. All patients were followed for 2 years. All eyes underwent manual irrigation and aspiration of cortical materials with the insertion of a modified J-loop posterior chamber IOL. Almost one half of eyes had final uncorrected visual acuities of 20/50 or better. Devastating complications, including retinal detachment, corneal decompensation, and endophthalmitis, occurred in 7 (1.2%) eyes. Extracapsular cataract surgery with IOL implantation appears to be a possible alternative in underdeveloped nations where the prevalence of cataract is high and aphakic spectacles are not easily obtained by poor patients and may be lost or broken. The procedure may improve the quality of vision, and therefore the quality of life, in those patients able to obtain pseudophakic vision.
Aged↗
Social acceptability of methylphenidate and behavior modification for treating attention deficit hyperactivity disorder.
The social acceptability of methylphenidate, behavior modification, and methylphenidate plus behavior modification was evaluated. Fifty mothers of children with attention deficit hyperactivity disorder (ADHD) and 50 control mothers, along with 21 children with ADHD and 20 control children, read a case vignette of an 8-year-old boy with ADHD and descriptions of the three treatment conditions. Subjects then rated the acceptability of each treatment. The mothers of children with ADHD were reassessed 3.5 months later, after experience with interventions for their children. Both ADHD and control families rated behavior modification as the most acceptable, methylphenidate as least acceptable, and the combined condition intermediate between the other two. At follow-up, there was a significant improvement in the acceptability of methylphenidate and the combined condition. The increased acceptability of methylphenidate at follow-up was related to increases in parents' knowledge about ADHD but not to the significant improvements that occurred in the children's hyperactive behavior.
Adult↗
Argon laser trabeculoplasty medical therapy to prevent the intraocular pressure rise associated with argon laser trabeculoplasty.
A prospective, randomized, investigator-masked, parallel study compared the capability of five different intraocular pressure (IOP) lowering agents to prevent acute IOP elevations following argon laser trabeculoplasty. Two hundred sixty eyes (patients) received either apraclonidine 1% (125 eyes), pilocarpine hydrochloride 4% (37 eyes), timolol maleate 0.5% (35 eyes), dipivefrin 0.1% (32 eyes), or acetazolamide 250 mg (31 eyes) both 1 hour before and immediately following 360-degree argon laser trabeculoplasty. Apraclonidine was the only medication that significantly decreased mean IOP from baseline. Only 4 (3%) of the apraclonidine-treated eyes had IOP rises greater than 5 mm Hg. This frequency was significantly lower than that found in eyes treated with acetazolamide (39%), dipivefrin (38%), pilocarpine (33%), or timolol (32%).
Adult↗
Cardiovascular and intraocular pressure effects and plasma concentrations of apraclonidine.
We performed a double-masked, crossover study comparing the cardiovascular and intraocular pressure effects of 0.5% and 0.25% topical apraclonidine hydrochloride and 0.5% timolol maleate in 20 healthy female volunteers. The contralateral effects of unilateral apraclonidine and the plasma concentrations of apraclonidine were also assessed. All measurements were done 2, 5, and 8 hours after drop instillation. A 15-minute treadmill test was performed after the 2-hour measurements. All three active medications lowered intraocular pressure comparably. There was no significant contralateral intraocular pressure effect seen with apraclonidine. The apraclonidine plasma concentrations were variable and unrelated to the amount of intraocular pressure lowering and cardiovascular parameters measured. Apraclonidine did not affect blood pressure or heart rate any differently than placebo. Timolol, however, blunted exercise-induced tachycardia. There were no significant differences in pupillary diameters or interpalpebral fissure widths among treatment groups.
Administration, Topical↗
Medical management of acute postoperative intraocular pressure rises associated with anterior segment ophthalmic laser surgery.
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Anterior Eye Segment↗
Apraclonidine hydrochloride: an evaluation of plasma concentrations, and a comparison of its intraocular pressure lowering and cardiovascular effects to timolol maleate.
We performed a prospective, placebo-controlled, cross-over study in 20 young healthy female volunteers. We evaluated both the cardiovascular and IOP effects of both timolol maleate and apraclonidine hydrochloride. In addition, we evaluated the plasma levels of various apraclonidine concentrations. We utilized 0.5% timolol and both the 0.25% and 0.50% concentrations of apraclonidine. Both timolol and apraclonidine lowered IOP comparably. Timolol lowered the resting pulse rate and blunted exercise-induced tachycardia. Apraclonidine did not affect blood pressure or heart rate any differently than placebo. We detected plasma levels of apraclonidine in many individuals for up to 8 hours. These serum levels were variable and did not appear to relate to the quantity of IOP lowering.
Adrenergic alpha-Agonists↗
Behavioral assessment and treatment of parent-adolescent conflict.
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Adolescent↗
A limited comparison of apraclonidine's dose response in subjects with normal or increased intraocular pressure.
We performed a multicentered, placebo-controlled, randomized, crossover study comparing the efficacy of 0.5% and 1.0% apraclonidine hydrochloride in 15 normal volunteers and 17 subjects with increased intraocular pressure. Apraclonidine 1% produced a maximum 30.4% +/- 14.0% (4.7 +/- 2.4 mm Hg) decrease in mean intraocular pressure in normal eyes and a 31.3% +/- 16.5% (7.6 +/- 4.2 mm Hg) decrease in eyes with increased pressure. Apraclonidine 0.5% produced a maximum 25.8% +/- 9.7% (4.0 +/- 1.7 mm Hg) decrease in mean intraocular pressure in normal eyes and a 27.4% +/- 16.0% (6.8 +/- 4.5 mm Hg) decrease in eyes with increased pressure. There was no statistically significant difference in mean percent intraocular pressure lowering effect between the 0.5% and 1.0% apraclonidine concentrations. Most subjects treated with apraclonidine had a greater than or equal to 20% reduction in intraocular pressure from baseline. Twelve hours after instillation of apraclonidine, nine of the normal volunteers had an intraocular pressure of 10 mm Hg or less. Apraclonidine produced the same percent intraocular pressure decrease regardless of the initial level of intraocular pressure.
Adult↗
Adjunctive glaucoma therapy. A comparison of apraclonidine to dipivefrin when added to timolol maleate.
The authors compared the additive intraocular pressure (IOP)-lowering effects of two different topical medications, apraclonidine hydrochloride and dipivefrin hydrochloride, when used in conjunction with timolol maleate. Eighteen patients with elevated IOPs entered a randomized, double-masked, cross-over study. Each used apraclonidine 1.0%, dipivefrin 0.1%, or placebo, twice daily for 3 weeks each, in addition to timolol 0.5% twice daily. Only apraclonidine produced a significant additional IOP lowering over timolol treatment alone at all time intervals (P less than 0.001). Its additive effect was significantly greater than that seen with dipivefrin at all time intervals (P less than 0.01), with the exception of day 22 (P = 0.061). No significant change in pulse rate or blood pressure was seen during apraclonidine administration. Apraclonidine may be a useful adjunctive agent in patients with poorly controlled glaucoma.
Adult↗