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• We conducted a randomized, double-masked, long-term clinical trial to determine whether topical timolol therapy was effective in delaying or preventing the onset of glaucomatous damage in moderate-risk ocular hypertensive subjects. In 62 patients, one eye was chosen randomly to receive timolol therapy twice daily while the fellow eye received placebo. During the course of the study, the mean ± SD difference in intraocular pressure between the timolol-treated and the placebo-treated eyes was 2.3 ± 2.6 mm Hg. Reproducible visual field loss developed in 4 timolol-treated eyes and 10 placebo-treated eyes. Progressive optic disc cupping was noted in 4 timolol-treated and 8 placebotreated eyes. Using a computerized image analysis system, the mean ± SD increase in optic disc pallor during the course of the study was 0.86% ± 2.4% in the timolol-treated eyes as opposed to 1.80% ± 3.6% in the placebo-treated eyes. This study provides evidence that lowering intraocular pressure by medical treatment reduces the incidence of glaucomatous damage in ocular-hypertensive individuals.

• Topical 0.125% and 0.25% clonidine hydrochloride were compared with 2% pilocarpine hydrochloride and a placebo in a double-masked crossover study. Both strengths of clonidine had an ocular hypotensive effect similar in magnitude and duration to pilocarpine. Clonidine in both concentrations also significantly lowered systemic blood pressure. Further studies will be needed to establish the value and safety of clonidine in the treatment of glaucoma.

• A prospective collaborative study was conducted in five centers during a 13-year period to identify factors that influence the development of visual-field defects (GVFDs) of open angle glaucoma. In 5,000 subjects, GVFDs developed in only 1.7% of eyes. Statistical analysis of 26 factors at first examination identified five that were significantly related to the development of GVFDs—outflow facility, age, applanation pressure, cup-disc ratio, and pressure change after water drinking. Their absolute initial value, and not its change with time, was the important predictor. Multivariate analysis showed their collective predictive power to be undesirably poor, indicating that other factors must play an important role in the development of GVFDs. Mortality-table analysis indicated that during a period of five years, 98.54% of eyes with initial pressure less than 20 mm Hg continued to be free from GVFDs as compared with 93.34% of those with pressure 20 mm Hg or greater.

OBJECTIVE: To determine whether parapapillary chorioretinal atrophy in patients with ocular hypertension remained stationary or progressed along with glaucomatous optic nerve damage. METHODS: The morphometric parameters and progression of parapapillary atrophy were retrospectively investigated, using serial photographs, in 350 eyes of 175 patients with ocular hypertension. The association of parapapillary atrophy progression with subsequent glaucomatous conversion and with other baseline patientand eye-specific characteristics was analyzed. RESULTS: Progression in the area and extension of parapapillary atrophy before noticeable optic disc or visual field changes was observed in 48 (49.0%) of 98 eyes that converted to glaucoma, while parapapillary atrophy progression was noted in 25 (9.9%) of 252 ocular hypertensive eyes that did not develop glaucomatous damage (P<.001). The predictive sensitivity and specificity of this observation were 49% and 90%, respectively. In a logistic multiple regression model, the progression of parapapillary atrophy was associated with a family history of glaucoma (odds ratio, 2.7) and the initial size of zone β (odds ratio, 1.64, for an increase of 0.10 of the zone β area—disc area ratio). CONCLUSION: The progression of parapapillary chorioretinal atrophy may be an early glaucomatous finding in some patients with ocular hypertension.

OBJECTIVE: To determine whether parapapillary chorioretinal atrophy is a risk factor for the development of glaucomatous optic disc or visual field damage. METHODS: The initial morphometric parameters of the optic disc and parapapillary atrophy were retrospectively investigated in 350 eyes of 175 patients with ocular hypertension. The prognostic value of parapapillary atrophy at the baseline examination and its relationship with known risk factors for the development of glaucomatous damage were analyzed by multivariate analysis. RESULTS: Visual field loss, optic disc damage, or both were detected in 98 eyes of 53 patients during the follow-up period of at least 10 years. By univariate analysis, the presence of parapapillary atrophy, as well as higher parapapillary atrophy area—disc area, zone β area—disc area, and parapapillary atrophy length—disc circumference ratios, at the baseline examination was associated with the conversion to glaucoma. In addition, higher intraocular pressure, larger vertical cupdisc ratio, and smaller neural rim area—disc area ratio at the baseline examination were associated with subsequent glaucomatous optic nerve damage. In a multivariate regression model adjusted for other factors, intraocular pressure (relative risk, 1.19), neural rim area—disc area ratio (relative risk, 0.72), and zone β area—disc area ratio (relative risk, 1.32) were found to be associated with the development of optic disc damage, visual field damage, or both. CONCLUSION: The presence and the size of parapapillary atrophy are related to the development of subsequent optic disc or visual field damage in patients with ocular hypertension.

OBJECTIVE: To determine whether the use of releasable scleral-flap sutures affects the success rate and the incidence of complications following trabeculectomy. DESIGN: A retrospective chart review of a consecutive series of trabeculectomies. SETTING: A university-based referral practice. PATIENTS: Two hundred fifty-eight consecutive patients (274 eyes) undergoing trabeculectomy because of uncontrolled glaucoma. INTERVENTION: During the first year, 124 patients (128 eyes) underwent trabeculectomies with permanent scleral-flap sutures. During the second year, 134 patients (146 eyes) underwent trabeculectomies with releasable scleral-flap sutures. MAIN OUTCOME MEASURES: Incidence of flat and shallow anterior chamber, incidence of operations to drain choroidal detachment and to re-form anterior chamber, and long-term control of intraocular pressure. RESULTS: In the group with permanent sutures, 42 eyes (32.8%) had clinically detectable shallowing of the anterior chamber in the early postoperative period. In contrast, a shallow anterior chamber was noted in 21 eyes (14.4%) in the group with releasable sutures (P=.0003). Flat anterior chamber, defined as iridocorneal apposition to the pupil margin, occurred in 11 eyes with permanent sutures (8.6%) but in only two eyes (1.4%) with releasable sutures (P=.0078). Surgical intervention to drain suprachoroidal fluid and re-form the anterior chamber was required in eight eyes with permanent sutures (6.2%) but in only one eye with releasable sutures (0.7%) (P=.014). At 1-year follow-up, the two groups were similar in terms of intraocular pressure and the need for ocular hypotensive medications. CONCLUSIONS: Releasable scleral-flap sutures reduce the incidence of shallow and flat anterior chamber after trabeculectomy without compromising long-term control of intraocular pressure.

Following orogastric intubation, varying volumes of tap water from 50 ml to 200 ml were administered to normal rabbits and the offspring of glaucomatous rabbits. Tonography was performed 15, 30, and 60 minutes following water loading. Significant elevation of the intraocular pressure and decrease in the outflow facility occurred 15 minutes after water loading, and were still present after 30 minutes. These changes in pressure and outflow facility were considerably decreased after one hour. The offspring of two glaucomatous parents showed a greater pressure elevation and fall in the outflow facility than did the normal rabbits or offspring of one glaucomatous rabbit. This was correlated with a lower initial facility of outflow in these animals.

A high prevalence of elevated intraocular pressures in the diabetic population is less striking in those with proliferative diabetic retinopathy than in those without proliferative changes. In both adult and juvenile groups without proliferative retinopathy, there is a significantly higher prevalence of elevated intraocular pressure after application of topical corticosteroids than in the nondiabetic population. In contrast, the distribution of corticosteroid response in the group of diabetics with proliferative retinopathy resembles more closely that in the nondiabetic volunteer population and differs significantly from that in diabetics without proliferative changes. Speculations concerning the relationship of intraocular pressure and corticosteroid responsiveness to the development of proliferative diabetic retinopathy are presented.

The clinical features of a maculopathy related to the use of topical epinephrine in 22 eyes of 15 patients are presented. Visual loss varied from 20/40 to less than 20/400, and was reversible in all but one instance when the drug was withdrawn. All patients, except one, were aphakic. In the one phakic case the lens was completely dislocated into the vitreous. The incidence of the maculopathy appears to be at least 20% to 30% in aphakic eyes treated with epinephrine. It varies with the concentration of epinephrine used, may appear within a few weeks or many months after epinephrine therapy is begun, and is reproducible on administration of topical epinephrine to the same patient.

Isosorbide is an effective hyperosmotic agent which can be administered orally without gastrointestinal irritation. It is absorbed quantitatively and more than 95% of the administered dose is excreted unchanged in the urine. Oral administration of a 50% solution to rabbits or man results in prompt increases in osmolarity of the serum and profound decreases in intraocular pressure. The drug proves useful in acute primary and secondary glaucomas, and as preoperative medication for various surgical procedures including cataract extraction, retinal detachment, corneal transplant, and glaucoma operations.

INTRODUCTION Patients with glaucoma who have progressive loss of visual field usually demonstrate elevations of intraocular pressure. The pressure susceptibility to the loss of field varies greatly from individual to individual. In some instances it may be related to the level of systemic blood pressure.1,2 Attempts have been made to produce rapid changes in intraocular pressure by pressure or suction applied to the globe and to estimate the pressure level at which field defects occur.2-5 Such approaches have stimulated considerable interest in the posterior segment aspects of glaucoma but have been difficult to standardize or duplicate because of ocular distention, vascular effects, and the lack of steady state conditions.Recently it has been demonstrated that topical corticosteroids decrease outflow facility and elevate intraocular pressure when applied to the eyes of patients with primary open-angle glaucoma, of glaucoma suspects, and of some volunteers.6 The pressure can be raised

The effect of low doses of epinephrine hydrochloride on intraocular pressure was evaluated. Concentrations of ⅛%, ¼%, ½% and 1% epinephrine were administered to one eye of a patient over a four-week period. An interval of four weeks was allowed before the successive higher concentration was applied. The fellow eye was left untreated and served as a control. The results indicate that epinephrine lowers intraocular pressure at the concentrations tested with significantly greater effectiveness at the higher dose levels.

• A family history of glaucoma was found in 50% of patients with primary open-angle glaucoma (POAG) and 43% of patients with ocular hypertension (OH). Positive family history was twice as prevalent in those with OH and either HLA-B7 or B12 antigens than in OH with neither antigen (P <.01). Although POAG occurred equally in men and women, the prevalence of a positive family history of glaucoma on the maternal side of the family in POAG patients was six to seven times greater than on the paternal side (P <.0005). However, in patients with OH, but no glaucomatous field loss, there was no difference in prevalence of maternal and paternal family history. Even in OH with HLA-B7 or B12 antigens, there was no predominance of maternal family history. The implication that offspring were more likely to develop POAG when their mother's side of the family rather than their father's side had the disease has provided an additional potentially useful risk factor in patients with OH. In addition, it has raised interesting questions as to possible maternal cytoplasmic factors in the transmission and pathogenesis of POAG.(Arch Ophthalmol 95:598-600, 1977)

• Platelet function in vitro and in vivo and certain measurements of blood coagulability and fibrinolysis were examined in 12 patients with low tension glaucoma and the results were compared with those obtained in 12 normal subjects matched for age, race, and sex. The data obtained seem to indicate that patients with low tension glaucoma cannot be readily distinguished from individuals of similar age and sex not afflicted with this disorder by measuring these variables. Thus, a "hypercoagulable state," ie, a thrombotic tendency, does not appear to be of major importance in the pathogenesis of this disorder.

• A retrospective review was conducted of 31 patients with bilateral elevations of intraocular pressure and unilateral glaucomatous visual field loss. Nine (29%) of the fellow eyes developed visual field loss during a three- to seven-year follow-up period. Of the 13 fellow eyes that had an initial intraocular pressure greater than 26 mm Hg, eight (62%) developed visual field loss, as opposed to one (6%) of the 18 eyes that had lower intraocular pressures. Of the 11 fellow eyes whose intraocular pressures exceeded 24 mm Hg, either treated or untreated, on more than 50% of the measurements, seven (64%) lost visual field, whereas in the 20 eyes whose intraocular pressures were lower, only two (10%) lost visual field.

• The initial topical administration of 1 drop of 0.25% timolol maleate in 25 nontreated ocular hypertensive patients resulted in a significant reduction of mean intraocular pressure one hour later, from a baseline of 28.1 ± 5.3 (mean ± SD) mm Hg to 18.5 ± 4.5 mm Hg. Two patients (8%) failed to show at least a 10% decrease in IOP one hour after the initial administration. After three to four weeks of twice a day unilateral therapy with 0.25% timolol, mean IOP increased to 21.1 ± 4.2 mm Hg. At this time seven patients (28%) failed to obtain a 10% decrease in IOP from topical timolol administration. Changing to 0.5% timolol for three to four weeks did not cause an additional significant lowering of IOP (20.4 ± 3.5 mm Hg). At this time five patients (20%) had less than a 10% reduction in IOP. The one-hour response failed to predict future IOP nonresponsiveness.

• Twelve patients who had previously demonstrated an intolerance to topically applied epinephrine received dipivefrin 0.1% in one eye and epinephrine 2% in the other eye. An adverse reaction occurred in only one eye (8%) receiving dipivefrin, but in ten (83%) on epinephrine. Topical dipivefrin 0.1% proved useful for lowering intraocular pressure in patients intolerant to topically applied epinephrine.(Arch Ophthalmol 95:2157-2158, 1977)

• The safety and success rates of trabeculectomy using fornix-based or limbus-based conjunctival flaps were investigated in a randomized, prospective study. Patients with phakic eyes and uncontrolled primary open-angle glaucoma had a trabeculectomy with either a standard limbus-based conjunctival flap (18 eyes) or a fornix-based conjunctival flap (19 eyes). Filtration surgery was equally successful (intraocular pressure, ≤21 mm Hg) in both groups independent of the type of conjunctival flap: 17 (94%) of 18 eyes with a limbus-based flap (three eyes with additional medical therapy) and 17 (89%) of 19 eyes with a fornix-based flap (three eyes with additional medical therapy). Four eyes in the fornix-based group showed positive Seidel tests in the early postoperative period. Aqueous leakage was from the suture sites at the lateral margins of the flap and resolved spontaneously without surgical intervention. The fornix-based conjunctival flap was easier to perform, provided better surgical exposure, and was easier to close than the limbus-based flap.

After reviewing the preceding editorial prior to publication, we find that we must disagree with much of the pessimistic thesis and many of the conclusions of the authors. We agree with the authors' definition of ocular hypertension as a "condition where the angle is open, and the disc and visual field are normal, but the tension is above the normal range." It is important to realize, however, that the "normal range" is purely a statistical definition—its relationship to glaucoma is based on the fact that the vast majority of patients with open-angle glaucoma have elevated intraocular pressures. In addition, the elevated intraocular pressure usually precedes glaucomatous damage to the optic nerve by a variable period of time. The fact that most patients with glaucoma have elevated intraocular pressure does not logically mean, however, that most patients with elevated intraocular pressure have glaucomatous optic nerve damage, or will, in fact, ever

• 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 <.05). Progressive cupping of the optic nerve was noted in 53% of the untreated eyes and in 11 % of the treated eyes (P <.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 <.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.

CATARACT formation with resultant reduction of vision is a frequent occurrence in patients receiving miotic therapy for glaucoma. This is especially true when using cholinesterase inhibitors which produce such intense miosis that the visual impairment from even minimal lens changes is greatly magnified. The development of proliferations of the pigment epithelium of the iris may cause further reduction of the pupillary opening in patients using these agents. In addition, individuals subjected to prolonged use of anticholinesterase drugs may develop central anterior subcapsular vacuoles and opacities. The necessity for cataract surgery, therefore, often arises in the long-term follow-up of glaucoma patients.Since the glaucoma patient will often require miotics postoperatively, it is advisable to create a permanent large pupillary opening at the time of cataract surgery. The advantages of the larger opening are twofold. First, during the operative procedure, the delivery of the lens is facilitated. Second, postoperatively, the fundus can

TO THE EDITOR. —I was interested to see the recent article by Tilden et al1 reporting 13 cases of bilateral anterior uveitis caused by systemic use of sulfonamides. It was surprising to learn that, as mentioned in the article, only one case of this cause-effect relationship had been previously reported.2 It reminded me of a patient I saw in 1974 whom I believed had two episodes of medication-induced anterior uveitis; the first as a response to methenamine hippurate, and the second caused by sulfamethoxazole and trimethoprim. REPORT OF A CASE. —On November 26, 1974, a 28-year-old black woman presented with a symmetric, moderately severe, bilateral, anterior uveitis and presumed trabeculitis 2 days after beginning methenamine hippurate for a bladder infection. She had a history of congenital bladder problems that resulted in frequent bladder infections requiring antibiotic treatment. On presentation she had elevated intraocular pressure (27 mm Hg

IN REPLY Drs Cohen and Osher describe a useful technique to minimize complications associated with exposed removable sutures. When using this technique, a small epithelial defect results when the suture is removed, but this is usually of negligible consequence. Two additional problems that may be avoided by using this technique include retraction of the suture into the corneal stroma and movement of the free end under fornix-based conjunctival flaps; in both cases, the suture may become inaccessible for removal.Finally, the figure from Burchfield et al was included to illustrate the "windshield-wiper effect" and does not represent the patient described. We apologize for any confusion.

Epinephrine hydrochloride—Adrin, Glaucon, Adrenaline chloride, Epifrin, Mistura E.In Reply.—Drance and Anderson raise important questions about the details of our epinephrine hydrochloride studies. They note that the 1966 series excluded patients with a family history of glaucoma and did not require high corticosteroid responsiveness. They failed to note, however, that the 1966 series did not require ocular hypertension but only borderline intraocular pressure (more than one third of the patients included were normotensive throughout the study). It must also be pointed out that the follow-up period was only four to five years in 1966 as compared with five to ten years in 1976. In addition, Drance and Anderson did not have available the epinephrine testing (24 hours or seven days) for the 1966 study. Instead, they used the reported mean intraocular pressure values during the entire six- to 60-month period of treatment.When the criteria of the 1976

Releasable sutures are used in glaucoma filtering surgery to titrate the degree of aqueous humor outflow to avoid early postoperative hypotony and its associated complications.1 The technique involves externalizing scleral flap sutures through the peripheral cornea, which allows for their removal at a later time when increased aqueous humor outflow is desired. We report, to our knowledge, the first case of postoperative endophthalmitis following trabeculectomy with releasable sutures. REPORT OF A CASE. A 67-year-old white man with primary openangle glaucoma had a trabeculectomy with intraoperative application of mitomycin C (0.3 mg/mL, 3-minute exposure) in the right eye. The scleral flap was secured with 2 releasable sutures that were externalized through the cornea, per the technique of Cohen and Osher.2 The free corneal ends of the sutures were buried so that only a small loop of suture remained exposed. Postoperatively, the intraocular pressure stabilized at 4 to 8 mm