E. Michael Van Buskirk

Plasma Timolol in glaucoma Patients

Plasma timolol levels were measured in our timolol-treated glaucoma patients employing three protocols: (1) measurements in ten patients over age 60 on chronic timolol therapy before, one hour, and three hours after receiving one drop of 0.5% timolol, (2) measurements in nine adult patients, with and without punctal occlusion, and (3) random measurement of plasma timolol in children on chronic timolol therapy while under general anesthesia. In the ten patients over age 60 years, baseline mean plasma timolol was 0.34 ng/ml, increasing to a mean of 1.34 ng/ml one hour after receiving drops. When punctal occlusion was applied, the mean one-hour plasma timolol diminished to 0.9 ng/ml, approximately 40% less than that observed without punctal occlusion. The plasma timolol levels examined in nine determinations in five children ranged from a low 3.5 ng/ml in a five-year-old child to 34 ng/ml in a three-week-old infant.

Argon laser trabeculoplasty. Studies of mechanism of action

The effects of argon laser trabeculoplasty (LTP) on outflow facility, Schlemms canal morphology, trabecular cellularity, and trabecular glycosaminoglycan composition were determined in 33 pairs of eye-bank human eyes. At two levels of intraocular pressure, measured outflow facility did not immediately drop in response to LTP. Schlemms canal distention was observed only at 40 mmHg intraocular pressure, where the canal normally tends to collapse. Trabecular cell density was reduced by about 40% in the eyes receiving laser treatment. The organ cultured trabecular meshworks in response to LTP altered their incorporation of 35S-sulfate, compared to controls, suggesting a change in the synthesis or turnover of the extracellular matrix of the trabeculum after trabeculoplasty. At least three potential mechanisms were identified in response to laser trabeculoplasty, including some mechanical distortion of the trabeculum at high intraocular pressures. We also hypothesize that laser trabeculoplasty dislodges some trabecular cells and may stimulate the remaining cells to renew more active synthesis and/or turnover of the trabecular extracellular matrix.

Cysts of Tenon's Capsule Following Filtration Surgery

Hypertrophy of Tenons capsule resembling a cyst and recurrence of increased intraocular pressures occurred shortly after glaucoma filtration surgery in eight patients on whom a variety of surgical techniques had been used. Preoperatively, the patients generally had secondary glaucomas with intraocular pressures exceeding 40 mm Hg. The cysts of Tenons capsule were uniformly localized to the filtration site and were dome-shaped and hard. They were associated with intraocular pressures near the preoperative levels. Three patients were successfully treated with corticosteroids and massage. The others required surgical intervention to restore adequate filtration. Prompt recognition of a Tenons capsule cyst and appropriate management can restore function to an otherwise failing filtration bleb.

Ciliary Vasoconstriction After Topical Adrenergic Drugs

Rabbits underwent the single-dose or long-term therapeutic administration of the adrenergic drugs phenylephrine hydrochloride, timolol maleate, and betaxolol hydrochloride. After a single dose, all three drugs caused substantial, localized constriction in the arterioles that supply the ciliary processes but did not affect the downstream bore of the same vessels. After seven weeks of a daily dose, tolerance reduced the response to betaxolol to insignificant levels and that to phenylephrine substantially, whereas timolol maleate continued to produce identical levels of vasoconstriction to those seen with single-dose administration. In addition to the consequent lowering of perfusion of the ciliary processes and presumptive impact on aqueous humor production, vasoconstriction also reinforces concerns about impaired vascular perfusion of eyes undergoing long-term ocular therapy.

The anatomy of the limbus

The limbus forms the border between the transparent cornea and opaque sclera, contains the pathways of aqueous humour outflow, and is the site of surgical incisions for cataract and glaucoma. Externally the epithelial cell border between conjunctiva and cornea possesses multipotential cells important for differentiation of the respective cell types. By the same token, the internal limbal border zone between corneal endothelium and anterior trabeculum appears to contain specialised cells some of which are activated to migrate and repopulate the trabecular meshwork after trabecular injury.The oblique interface between corneal and scleral stroma determines the appearance of the surgical limbus whose landmarks vary around the circumference of the globe but predictably correlate with structures of the anterior chamber angle. The vasculature of the limbus derives in primates primarily from the anterior ciliary arteries.Their superficial branches form arcades to supply the limbal conjunctiva and peripheral cornea. Perforating branches contribute to the vascular supplies of the deep limbal structures and the anterior uvea.The limbus forms the border between the transparent cornea and opaque sclera, contains the pathways of aqueous humour outflow, and is the site of surgical incisions for cataract and glaucoma. Externally the epithelial cell border between conjunctiva and cornea possesses multipotential cells important for differentiation of the respective cell types. By the same token, the internal limbal border zone between corneal endothelium and anterior trabeculum appears to contain specialised cells some of which are activated to migrate and repopulate the trabecular meshwork after trabecular injury.The oblique interface between corneal and scleral stroma determines the appearance of the surgical limbus whose landmarks vary around the circumference of the globe but predictably correlate with structures of the anterior chamber angle. The vasculature of the limbus derives in primates primarily from the anterior ciliary arteries.Their superficial branches form arcades to supply the limbal conjunctiva and peripheral cornea. Perforating branches contribute to the vascular supplies of the deep limbal structures and the anterior uvea.

Pigmentary Glaucoma Associated with Posterior Chamber Intraocular Lenses

Six cases of glaucoma associated with pigment dispersion syndrome occurred after the implantation of posterior chamber intraocular lenses. All six patients had iris transillumination defects associated with the intraocular lens haptics, increased intraocular pressure, and pigment deposition in the trabecular meshwork and the anterior chamber. Medication controlled the glaucoma and none of the patients required further surgery.

Exercise Conditioning and Intraocular Pressure

We studied the intraocular pressure response to short-term maximal aerobic exertion before and after exercise conditioning in ten healthy sedentary volunteers. Before exercise conditioning, mean intraocular pressure +/- S.E.M. decreased by 5.9 +/- 0.6 mm Hg after short-term maximal aerobic exercise, returning to baseline in a mean of 37 +/- 4 minutes. After four months of exercise conditioning, this ocular hypotensive response was significantly dampened, with a mean intraocular pressure reduction of only 1.6 +/- 0.4 mm Hg after short-term maximal aerobic exercise (P less than .01). Additionally, a significant reduction in baseline intraocular pressure occurred, with a mean intraocular pressure of 14.3 +/- 0.7 mm Hg before exercise conditioning, declining to a mean intraocular pressure of 13 +/- 0.9 mm Hg (P less than .02) after four months of physical training. Exercise conditioning may significantly reduce baseline intraocular pressure and attenuate the hypotensive response to short-term maximal aerobic exercise.

Pathophysiology of laser trabeculoplasty

Abstract The precise effect of argon laser trabeculoplasty on the trabecular meshwork is only partially understood. Its intraocular pressure lowering effect through enhancement of aqueous outflow is well documented. Clinically, this effect seems non-specific for laser characteristics, including wave form, wave length, burn location, clock hours treated, and even to some degree, laser power. The response is delayed in onset, diminishes over time, and in some cases can be renewed with retreatment. Laser photocoagulation of the trabecular meshwork focally destroys, but diffusely stimulates trabecular meshwork cells. Shape alterations in the trabecular meshwork after laser are likely to contribute to outflow enhancement only at very high levels of intraocular pressure. More likely, cellular stimulation activates a molecular biologic chain of events, perhaps within the trabecular extracellular matrix, that permits improved facility of aqueous outflow.

Pupillary Block After Intraocular Lens Implantation

Seventeen patients, ranging in age from 40 to 86 years, developed pupillary block detected one week to three years after intraocular lens implantation. Sixteen of the implants were anterior chamber intraocular lenses and one was a posterior chamber intraocular lens. Despite iris bombe that closed the anterior chamber angle, many cases were asymptomatic and were discovered fortuitously during routine postoperative examinations. Laser iridotomy or iridectomy eliminated the pupillary block in all 17 cases, but permanent synechial closure of a portion of the anterior chamber angle persisted in most cases and sometimes required medication or further surgery. One eye eventually lost all light perception.

Three-year Efficacy of Argon Laser Trabeculoplasty

The authors report on the effect of argon laser trabeculoplasty on intraocular pressure (IOP) over a 3-year period with a mean follow-up period of 1.8 years in patients with uncontrolled primary open-angle glaucoma who had not undergone prior surgery. An analysis of the effect of laser trabeculoplasty using the criteria for success of an IOP of 22 mmHg or less with no further laser trabeculoplasty or glaucoma surgery, showed a cumulative success of 79% (112 eyes) at 1 year, 69% (85 eyes) at 2 years, and 59% (58 eyes) at 3 years. Similar results are presented for 22 eyes from patients with pseudoexfoliation glaucoma. The authors conclude that although the initial success rate of laser trabeculoplasty is high, it diminishes progressively over time.