Faculty Bibliography

Topical beta-blocking agents have been associated with adverse central nervous system (CNS) effects, including depression, emotional lability, and sexual dysfunction. Two studies were done to determine if patients who develop CNS effects while using timolol maleate would improve with betaxolol hydrochloride. In one study, 18 patients with CNS symptoms during timolol therapy were switched to betaxolol. Sixteen of the 18 patients noted symptomatic improvement with betaxolol. The second study involved seven patients with CNS symptoms during timolol therapy who were entered into a double-masked cross-over study. In two patients CNS symptoms resolved with betaxolol; in three patients symptoms improved; and in one patient symptoms worsened with betaxolol. Although factors influencing beta-blocker activity in the CNS are not well understood, there may be some advantage to a selective agent.

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.

An automated trephine (trabecuphine) was used to perform an internal sclerectomy in seven glaucoma patients who were aphakic or had undergone previous filtering surgery that had failed or both. A patent fistula was achieved intraoperatively in all seven eyes. Postoperatively, six patients received subconjunctival injection of 5-fluorouracil (5-FI) once daily for an average of 8 days. Five of seven patients have retained a functional bleb and a controlled intraocular pressure (IOP) after surgery (follow-up, 4-24 months). The only intraoperative complication was hemorrhage from the sclerectomy site in a patient with aniridia that resulted in a 20% hyphema. The hyphema cleared quickly, and the bleb has remained functional with a pressure of 12 mmHg for 9 months. The trabecuphine makes it possible to perform a glaucoma filtering operation safely from within the anterior chamber. This technique minimizes conjunctival trauma in the filtration area. The absence of a conjunctival incision overlying the fistula simplifies the adjunctive use of antimetabolites such as 5-FU.

Automated detection of subtle changes in sequential images requires development of procedures that ensure true subtraction of two images by proper registration and normalization of illumination. The difference image can then be further processed to analyze the spectral components and the gray level variations. An innovative and generalized approach to accurate image subtraction incorporating illumination normalization and correction for translation, rotation, and scale difference in two sequential images is considered. The entire procedure yielding true image subtraction has been implemented in a PC-based image processing system and can be executed by menu-driven operations. The effectiveness of this approach is illustrated through subtraction of registered sequential fundus images and analysis of the spectral and gray-level variations of the difference images.

The effect of an alpha adrenergic agonist, ALO 2145 (para-amino-clonidine [PAC]), was examined in a double-masked, multicenter study on the postoperative intraocular pressure (IOP) elevation after laser surgery in 165 patients (83 trabeculoplasty, 36 iridotomy, and 46 capsulotomy). One drop of 1.0% ALO 2145 or vehicle was instilled 1 hour before and immediately after laser surgery. The mean IOP increase in the ALO 2145-treated group was lower (P less than 0.05) than in the placebo group at each of the first three postoperative hours. Overall, 18% of placebo-treated eyes experienced IOP increases greater than or equal to 10 mmHg as compared with 4% of ALO 2145-treated eyes (P less than 0.003). Ocular and systemic side effects were minimal and did not differ between the treatment groups. ALO 2145 safely and effectively reduced the incidence and magnitude of potentially harmful IOP elevations after anterior segment laser surgery.

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.

The OCTOPUS 2000 perimeter and a central 30 degrees program were used to study consecutively 27 patients with glaucoma who had either a relative afferent pupillary defect (APD) or asymmetric optic nerve cupping without an APD. The mean difference in visual field sensitivity between fellow eyes was 48.2% (range, 13% to 93%) for the APD group and 5.5% (range, 0% to 9.0%) for the non-APD group. The mean difference in cup-disc ratio was 0.43 (range, 0.2 to 0.6) for the APD group and 0.24 (range, 0.2 to 0.3) for the non-APD group. The APD depth was quantitated with neutral density filters and correlated with visual field asymmetry but not with cup-disc ratio asymmetry. There was no overlap between the APD and non-APD groups in the amount of visual field asymmetry: Every patient with a sensitivity difference of 13% or greater had an APD. The presence of an APD indicates that a threshold of asymmetric optic nerve damage has been exceeded. With automated perimetry, this threshold can be quantitated and may improve the assessment of patients with glaucoma.

We studied the effect of reducing eye drop size on the efficacy and systemic absorption of topical 2.5% phenylephrine hydrochloride in neonates and infants. Eleven neonates received an 8-microL drop volume in one eye and a 30-microL drop volume (commercial size) in the fellow eye. Mean pupillary dilation at 60 minutes was equivalent (4.86 mm vs 4.57 mm) for both eyes, respectively. The plasma phenylephrine level was determined for the two drop sizes in a second group of infants. Eight infants received an 8-microL drop volume in both eyes, while nine infants received a 30-microL drop volume in both eyes. The mean phenylephrine level at ten minutes was 0.9 ng/mL for the 8-microL drop group and 1.9 ng/mL for the 30 microL drop group. In neonates and infants, reducing the drop volume of topical phenylephrine may improve the risk-benefit ratio.