Initial experience with a new method of laser transscleral cyclophotocoagulation for ciliary ablation in severe glaucoma.
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Biomedical subjects
Publications and source records attributed to I P Pollack.
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We are just beginning to see the potential uses of laser energy to treat glaucoma. Each of the lasers described here has technical problems that make them less then perfect, but it is only a matter of time before we will be able to predictably alter the internal structures of the eye to better control any type of glaucoma.
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.
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.
We studied apraclonidine hydrochloride (aplonidine hydrochloride or ALO 2145), an alpha-agonist, for its effect on the intraocular pressure (IOP) rise following neodymium-YAG posterior capsulotomy (YPC). In a prospective multicentered double-masked study, 63 eyes were pretreated with one drop of either 1% apraclonidine hydrochloride or placebo one hour before performing YPC and again following the laser treatment. The greatest IOP rise in the placebo-treated eyes occurred in the third hour after YPC, when the mean (+/- SD) IOP rose from a baseline pressure of 16.4 +/- 3.7 to 20.8 +/- 6.8 mm Hg. In apraclonidine-treated eyes, the IOP fell from a mean of 15.6 +/- 3.8 to 12.8 +/- 6.0 mm Hg three hours postoperatively. There were five times as many eyes that had an IOP rise greater than 10 mm Hg in the placebo-treated group compared with those treated with apraclonidine. Apraclonidine proved to be highly effective in preventing the rise in IOP following YPC.
We performed a double-masked, cross-over, dose-response study of apraclonidine hydrochloride (formerly known as ALO 2145) in 20 patients with elevated intraocular pressure (IOP). We administered three concentrations of apraclonidine (0.125%, 0.25%, 0.5%) and vehicle alone bilaterally every 12 hours for one week. Patients were examined 2, 5, and 8 hours after the initial dose, and then on day 2 and day 8. We studied IOP, pupillary diameter, interpalpebral fissure width, blood pressure, and pulse. There was a two-week washout period after each one-week session. All concentrations of apraclonidine significantly lowered IOP. The 0.5% and 0.25% concentrations had equal maximal effects, lowering IOP in each patient by an average of 27% relative to vehicle alone. This corresponded to a mean decrease in IOP of 8.7 mm Hg, from a baseline of 24.9 mm Hg to 16.2 mm Hg. The 0.5% and 0.25% concentrations were significantly more effective than the 0.125% concentration at two and eight hours. Mean interpalpebral fissure width increased in a dose-dependent fashion; the pupillary effect was minimal. Blood pressure and pulse were unchanged. Thirty percent of subjects reported transient dry nose or dry mouth. These symptoms may be dose-dependent.
Neodymium:YAG (Nd:YAG) and argon laser iridotomies were compared in a prospective, randomized clinical trial of 43 patients with bilateral chronic pupillary-block glaucoma. All patients had one eye randomly assigned to argon and the fellow eye assigned to Nd:YAG laser treatment. Follow-up ranged from 20 to 42 months. Iridotomy closure was not observed in Nd:YAG-treated eyes, but nine (21%) argon iridotomies required retreatment. Visual loss due to progression of laser-induced lens or corneal damage was not observed in any eye. Nine (21%) argon-treated eyes and eight (19%) Nd:YAG-treated eyes required laser trabeculoplasty for further intraocular pressure (IOP) lowering after iridotomy. Five (12%) argon-treated and two (5%) Nd:YAG-treated eyes required intraocular filtration surgery for long-term IOP control, but this difference was not statistically significant. There were no significant long-term differences between these treatment modalities.
Seventy-nine eyes (61 patients) with open-angle glaucoma and uncontrolled intraocular pressure (IOP) of 23 mmHg or more despite maximal tolerated medical therapy and prior argon laser trabeculoplasty (75 eyes) were treated with neodymium: YAG (Nd: YAG) laser angle surgery and followed for at least 1 year. Ten pulses of 10 mJ were applied to the midtrabecular meshwork over 40 degrees in the most visible portion of the angle. The IOP was controlled successfully (less than or equal to 22 mmHg) in 60 eyes (76%) 1 month after treatment and in 36 of 78 eyes (46%) 1 year after treatment. Long-term complications included two eyes with advanced glaucoma that lost central fixation despite good IOP control after treatment.
Apraclonidine (para-aminoclonidine) is an alpha agonist that was studied for its effect on the IOP rise following YPC. In a prospective multicentered double-masked study 63 eyes were pretreated with one drop of either 1% apraclonidine or placebo 1 hour prior to performing YAG and again after the laser treatment. The greatest IOP rise in the placebo-treated eyes occurred in the third hour after YPC when the mean IOP rose from a baseline pressure of 16.4 +/- 3.7 mm Hg to 20.8 +/- 6.8 mm Hg (P less than .01). In apraclonidine-treated eyes the IOP fell from a mean of 15.6 +/- 3.8 mm Hg to 12.8 +/- 6.0 mm Hg 3 hours postoperatively (P less than .001). There were five times as many eyes that had a pressure rise greater than 10 mm Hg in the placebo-treated group compared to those treated with apraclonidine. Apraclonidine proved to be highly effective in preventing the rise in IOP following YPC.
A prospective, randomized, double-masked study compared topical 1% ALO 2145, an alpha 2-agonist, with placebo in therapy for immediate postoperative intraocular pressure (IOP) rise after argon laser trabeculoplasty. Seventy-three eyes (73 patients) underwent 360 degrees of treatment utilizing 80 spots of 800 to 1000 mW of power. Intraocular pressure rise was measured hourly for the first three hours after operation, at one week, and at one month. Eyes treated with ALO 2145 had both significantly lower mean IOPs and greater IOP decreases from baseline than placebo-treated eyes during the first three hours after operation. No eyes treated with ALO 2145 and six eyes (18%) treated with placebo experienced an IOP rise of 10 mm Hg or greater. Twenty eyes (59%) in the placebo group and eight eyes (21%) treated with ALO 2145 had an IOP elevation. No change was detected in the mean heart rate. ALO 2145 appears to be effective in eliminating large, acute IOP elevations after argon laser trabeculoplasty.
We prospectively evaluated the efficacy and safety of the twice-daily application of 1% ALO 2145 (p-aminoclonidine hydrochloride, a topical alpha 2-agonist) in 21 normal volunteers for one month. Criteria measured included intraocular pressure (IOP), basal tear secretion, pupillary size, corneal sensitivity, heart rate, and blood pressure; urinalysis and blood chemistry studies were also performed. The mean (+/- SD) IOP fell 38.7%, from 17.5 +/- 3.9 mm Hg to 10.7 +/- 3.4 mm Hg, in five hours. The mean IOP remained between 23% and 30% below the pretreatment level when checked 12 hours after the last drop's instillation from day 8 through day 28 of the study. No clinically significant changes in mean systolic blood pressure, blood chemistry values, urinalysis results, basal tear secretion, or corneal sensitivity were noted. The mean heart rate and diastolic blood pressure were each significantly decreased at only one of nine time intervals. Dry mouth was noted at some time in 52% of volunteers. ALO 2145 seems to be effective in lowering IOP in normal volunteers, without marked cardiovascular effects.
A prospective, randomized, double-masked pilot study compared topical 1% ALO 2145 (p-aminoclonidine hydrochloride, a topical alpha 2-agonist) with a placebo to determine its ability to minimize any acute postoperative intraocular pressure (IOP) increase after argon laser iridotomy. Twenty-eight eyes (21 patients) with chronic narrow angle glaucoma underwent argon laser iridotomy. Fourteen eyes were treated with ALO 2145; the remainder received a placebo. All eyes received one drop of the appropriate medication one hour before and following the iridotomy. Six eyes (43%) treated with the placebo and no eyes treated with ALO 2145 experienced an IOP increase greater than 10 mm Hg over baseline. The mean IOPs and mean IOP changes from baseline were significantly lower during the first three postoperative hours in the eyes treated with ALO 2145. No significant difference was noted in the ease of iridotomy formation, rate of iridotomy closure, visual acuity, anterior segment inflammation, or mean heart rate.
Four eyes that had undergone cataract extraction with intraocular lens implantation developed malignant glaucoma. Three eyes had posterior chamber lenses and one eye had an anterior chamber lens. Medical therapy was unsuccessful in each case. One eye was treated with Nd-YAG laser disruption of the anterior hyaloid face, but this did not reverse the glaucoma. In all four eyes pars plana vitrectomy reversed the glaucoma process. In the eyes with posterior chamber lenses, the vitrectomy included excision of a localized area of lens capsule and zonules. A pathway for the anterior flow of aqueous was created without dislocating the intraocular lens.
We conducted a short-term prospective clinical study to evaluate Q-switched neodymium-YAG laser iridotomy in 33 eyes with pupillary block glaucoma in which the argon laser was unable to create an iridotomy. These eyes had chronic angle closure glaucoma (11 eyes), acute angle closure glaucoma (five eyes), pseudophakic pupillary block (seven eyes), uveitic pupillary block (three eyes), and contralateral eyes (five eyes); also included were both eyes of a patient with a head tremor. In all eyes, a patent iridotomy was created in one treatment session, with a mean of 5 +/- 5 pulses and a mean total energy of 55 +/- 120 millijoules. Complications included iridotomy closure (two eyes with preexisting active uveitis), focal nonprogressive corneal opacities (six eyes), and minimal bleeding from the iridotomy margin (12 eyes). Q-switched neodymium-YAG laser iridotomy appears to be an effective next step in the management of pupillary block glaucoma prior to surgical iridectomy when argon laser iridotomy fails.
The creation of a posterior capsulotomy utilizing a neodymium:YAG (Nd:YAG) laser is often followed by an increase in the intraocular pressure (IOP). In order to study the cause of this pressure rise, six eyes of three cynomolgus monkeys underwent extracapsular cataract extraction followed 2 to 3 months later by Nd:YAG laser capsulotomy. Eyes were evaluated clinically and examined histopathologically at 1 hour, 3 hours, 1 day, 3 days, 1 week, and 1 month after laser treatment. Although IOP did not increase after laser capsulotomy, outflow facility was decreased 80% from baseline levels at 3 hours, at 3 hours, 1 day, and 3 days. After laser treatment, the anterior chamber and meshwork contained fibrin, lens material, inflammatory cells, pigmented macrophages, erythrocytes, and free pigment. Most of these elements had cleared the meshwork by 1 month.
Both Peritest perimetry and Goldmann visual field testing were performed on three groups of eyes. Eighty-one eyes had glaucoma with elevated intraocular pressures and abnormal visual fields determined by Goldmann perimetry. There were 47 eyes with suspected glaucoma, based on elevated IOPs and normal Goldmann visual fields. Nineteen eyes were normal. All visual fields were evaluated in masked fashion, and the results were compared. The Peritest had a high sensitivity in both glaucomatous (98.8%) and normal (94.7%) eyes. One half of the eyes with suspected glaucoma had abnormal Peritest results but normal Goldmann visual fields. These eyes were examined prospectively with color stereo discs and monochromatic nerve fiber layer photographs. One half of the eyes with suspected glaucoma and abnormal Peritest results also had photographic evidence suggesting optic nerve damage. Thus, early field defects detected by the Peritest perimeter in eyes with suspected glaucoma are likely to be representative of glaucomatous damage.
In a short-term pilot study, we evaluated Q-switched neodymium-YAG laser angle surgery in 25 eyes from 22 patients with medically uncontrolled open-angle glaucoma. All eyes had unacceptable intraocular pressures (IOPs), despite maximum tolerated medical therapy, argon laser trabeculoplasty, and prior intraocular filtration surgery (eight eyes). Using a pulse energy of 10 millijoules, ten spots were placed approximately 4 degrees apart in the mid-trabecular meshwork using an Nd-YAG laser (Coherent 9900). The mean preoperative and final postoperative IOPs were 30 +/- 6 mm Hg and 21 +/- 8 mm Hg, respectively. The mean follow-up time was five (+/- 3) months (range, two to 14 months). The final postoperative IOP was less than 22 mm Hg in 17 eyes (68%). Holes within the trabecular meshwork were visible in 14 eyes, and laser therapy was associated with the liberation of debris into the anterior chamber in all eyes. Complications included transient postoperative IOP elevation (eight eyes), angle bleeding (six eyes), and posterior displacement of the iris root (four eyes).
The histologic effects of various Neodymium:YAG laser energy levels were evaluated after iridotomy formation in cynomolgus monkey eyes. Scanning election microscopy of the corneal endothelium above the treated areas revealed no significant cell loss or pleomorphism when compared to the adjacent untreated areas. Light and phase contrast microscopy demonstrated closure of the iridotomies in most cases by a bridge of iris pigment epithelium. In several specimens, stromal tissue and pigment laden cells were present over the attenuated iris pigment epithelium. There were four lens opacities with rupture of the anterior lens capsule and anterior epithelial cell hyperplasia in one. No damage was apparent in the trabecular meshwork or retina with light microscopy or fluorescein angiography.