The relationship between macular cell layer thickness and visual function in different stages of glaucoma.

PURPOSE: To determine whether there were differences in the structure-function relationship between early and advanced glaucoma, and study the association between thickness of discrete macular cell layers, the thickness of the retinal nerve fiber layer, and visual field sensitivity. METHODS: In all, 71 eyes of 50 subjects (28 glaucoma patients and 22 normal control subjects) were included. Thickness of macular retinal nerve fiber layer (mRNFL), macular inner retinal layer (mIRL), and macular outer retinal layer (mORL) were measured from Stratus optical coherence tomography macular scans, using our previously published segmentation algorithm. Visual sensitivity loss was determined by mean deviation (MD) using Humphrey Visual Field Analyzer. The mean thickness for each layer from the normal control subjects, early, and advanced glaucoma groups was compared. In addition, a mixed model analysis was used to explore the relationship between structure-function, allowing for possible interaction with glaucoma stage. RESULTS: The mean mRNFL thickness in early and advanced glaucoma patients was significantly less than measurements in normal subjects (P<0.01). The mean mIRL thickness in advanced glaucoma was significantly less than normal subjects (P=0.04). The mean mORL thickness in early and advanced glaucoma was not statistically significant different from that of normal subjects (P>0.8). There was no statistically significant difference in macular structure-function relationship between the two glaucoma groups (P>0.05). Mean mIRL thickness was significantly associated with MD (P=0.04). CONCLUSION: There was no significant difference in macular structure-function relationship between early and advanced glaucoma groups. Combined data from both glaucoma groups indicated that mIRL thickness was associated with visual sensitivity loss.

Recurrent hyphema in an aphakic child: Swan syndrome.

In 1973, Swan described 3 patients who developed hyphema months to years after uncomplicated cataract surgery. He noted focal vascularization from an ingrowth of episcleral vessels at the cataract wound site, resulting in recurrent intraocular bleeding. Swan syndrome has been reported following intracapsular cataract extraction, extracapsular cataract extraction (including clear corneal incisions), iridocyclectomy, and glaucoma filtering procedures. Patients typically present with sudden painless blurred vision, often upon awakening, which may or may not be preceded by physical strain or trauma. Other patients are asymptomatic and diagnosed with hyphema or anterior chamber red blood cells on routine examination. The hyphema often resolve spontaneously, making later diagnosis difficult. Gonioscopic visualization of the abnormal wound vessels is necessary for diagnosis. Without active bleeding, however, the fibrovascular tuft may be easily overlooked. We report a case of Swan syndrome in a 16-month-old boy after cataract extraction was performed. To our knowledge, Swan syndrome has not been reported in the pediatric population. Children represent a significant proportion of patients undergoing anterior segment surgery and Swan syndrome should be considered in the differential diagnosis of hyphema in this population.

Comparison of contrast sensitivity, visual acuity, and Humphrey visual field testing in patients with glaucoma.

PURPOSE: To investigate the relationship between large-letter contrast sensitivity, high-contrast visual acuity, and visual field defects in patients with glaucoma. METHODS: Patients with a diagnosis of glaucoma, glaucoma suspect, or ocular hypertension whose visual acuity was 20/40 (logMAR = 0.3) on better were included in the study. Visual acuity was measured using the Lighthouse visual acuity charts. Contrast sensitivity was measured using the Pell-Robson (PR) chart. The mean depression (MD) score from the most recent Humphrey visual field was used to quantify the visual field defect. RESULTS: A total of 120 eyes were studied. The PR contrast sensitivity score correlated more strongly with the MD of the visual field (r = .589, P < .001) than did the logMAR visual acuity (r = .193, P = .035). When just the eyes with open-angle glaucoma were considered (N = 54), the correlation was even greater for the PR score (r = .638). In ocular hypertensive eyes (N = 25), the correlations to PR and logMAR were not that different (r = .394 for PR, r = .303 for logMAR). Pseudophakic eyes did not show as strong a correlation (r = .335) as did phakic eyes (r = .591). CONCLUSION: For glaucomatous eyes with visual acuity of 20/40 or better, a decrease in the contrast sensitivity correlates with increased visual field loss. We speculate that this decrease in contrast sensitivity in glaucoma patients may account for their complaints of poor vision despite normal or near normal visual acuity.

3' deletions cause aniridia by preventing PAX6 gene expression.

Aniridia is a panocular human eye malformation caused by heterozygous null mutations within PAX6, a paired-box transcription factor, or cytogenetic deletions of chromosome 11p13 that encompass PAX6. Chromosomal rearrangements also have been described that disrupt 11p13 but spare the PAX6 transcription unit in two families with aniridia. These presumably cause a loss of gene expression, by removing positive cis regulatory elements or juxtaposing negative DNA sequences. We report two submicroscopic de novo deletions of 11p13 that cause aniridia but are located >11 kb from the 3' end of PAX6. The clinical manifestations are indistinguishable from cases with chain-terminating mutations in the coding region. Using human x mouse retinoblastoma somatic cell hybrids, we show that PAX6 is transcribed only from the normal allele but not from the deleted chromosome 11 homolog. Our findings suggest that remote 3' regulatory elements are required for initiation of PAX6 expression.

Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma.

PURPOSE: To study the risk associated with diurnal intraocular pressure (IOP) variations in patients with open-angle glaucoma. PATIENTS AND METHODS: Sixty-four patients (105 eyes) from the practices of two glaucoma specialists successfully performed home tonometry with a self-tonometer five times a day for 5 days. All patients had open-angle glaucoma and documented IOP below 25 mm Hg over a mean follow-up period of 5 years. Baseline status and time to progression of visual field loss were identified from the clinical charts. The level and variability of diurnal IOP obtained using home tonometry were characterized. Risk of progression was analyzed using a nonparametric time-to-event model, incorporating methods for correlated outcomes. RESULTS: Although mean home IOP and baseline office IOP were similar (16.4 +/- 3.6 mm Hg and 17.6 +/- 3.2 mm Hg, respectively), the average IOP range over the 5 days of home tonometry was 10.0 +/- 2.9 mm Hg. Baseline office IOP had no predictive value (relative hazard, 0.98). The diurnal IOP range and the IOP range over multiple days were significant risk factors for progression, even after adjusting for office IOP, age, race, gender, and visual field damage at baseline (relative hazards [95% confidence intervals], 5.69 [1.86, 17.35] and 5.76 [2.21, 14.98]). Eighty-eight percent of patients in the upper twenty-fifth percentile of IOP and 57% of patients in the lower twenty-fifth percentile progressed within 8 years. CONCLUSIONS: In patients with glaucoma with office IOP in the normal range, large fluctuations in diurnal IOP are a significant risk factor, independent of parameters obtained in the office. Fluctuations in IOP may be important in managing patients with glaucoma. Development of methods to control fluctuations in IOP may be warranted.

Cost considerations of medical therapy for glaucoma.

PURPOSE: To determine the calculated daily patient cost (cost minimization) of medical glaucoma therapy. METHODS: The actual volume of various glaucoma medications was determined for all commercially available sizes of the tested products. The drops per ml on the basis of the actual volume and the daily costs of the dosage schedules recommended by the manufacturers were compared. The cost of each bottle of medication was determined from the average wholesale price in the United States. RESULTS: The generic timolol products dosed twice daily and the once-daily gel-forming solutions (range, $0.30 to $0.46/day) were similar on a cost-per-day basis compared with the brand name metipranolol (Optipranolol; Bausch & Lomb Pharmaceuticals, Tampa, Florida, at $0.43/day) and timolol (Timoptic; Merck, West Point, Pennsylvania, at $0.46/day and Timoptic XE at $0.38/ day). Betaxolol (Betoptic S; Alcon Laboratories, Fort Worth, Texas, at $0.65/day), carteolol (Ocupress; CibaVision, Duluth, Georgia, at $0.57/day), levobunolol ($0.61/day), and brand name levobunolol (Betagan; Allergan, Irvine, California, at $0.81/day) all were dosed twice daily and were more costly on a per-day basis. The topical carbonic anhydrase inhibitors brinzolamide (Azopt; Alcon, at $0.96/day) and dorzolamide (Trusopt; Merck, at $1.02/day) were dosed three times daily and were similar on a cost-per-day basis. The combination product Cosopt (timolol 0.5% + dorzolamide 2.0%, Merck, at $1.12/day) was less costly than separate bottles of a topical carbonic anhydrase inhibitor (three times daily dosing) and a beta-blocker ($1.26 to $1.83/day), often even if the topical carbonic anhydrase inhibitor was dosed two times daily ($0.94 to $1.49). The selective alpha2-agonist brimonidine (Alphagan; Allergan, at $0.90/day) twice daily and the prostaglandin analog latanoprost (Xalatan; Pharmacia & Upjohn, Kalamazoo, Michigan, at $0.92/day) once daily were similarly priced. CONCLUSIONS: All generic timolol, Optipranolol, Timoptic, and Timoptic XE ranged between $0.30 and $0.46 per day. Betaxolol, Ocupress, generic levobunolol, and Betagan were more costly, ranging between $0.57 and $0.81 per day. Cosopt ($1.12/day) was less costly than separate bottles of a topical beta-blocker and a topical carbonic anhydrase inhibitor dosed three times daily ($1.26 to $1.83/day) and often twice daily ($0.94 to $1.49). Alphagan and Xalatan were similarly priced ($0.90/day and $0.92/day, respectively). This study is based on a best-case scenario for all medicines and does not account for wasted doses, the frequency of refills, or a medication's success or failure rate. New adjunctive glaucoma regimens exhibit similar costs per day compared with more traditional regimens.

The role of medical therapy in the rank order of glaucoma treatment.

There is no consensus as to how treatment of open-angle glaucoma should be initiated. Medical therapy, laser trabeculoplasty, and filtration surgery each have their advocates as the best modality for initial treatment. The advantages and disadvantages of these three options are discussed here. It is pointed out that there may not be a single answer as to how to begin treatment. Patient factors such as age, general health, and stage of glaucoma as well as various socioeconomic and technologic factors may lead to different recommendations for different patients. At present, most patients with open-angle glaucoma are started on medical therapy. beta-Blockers are used most commonly as the initial drug of choice, but latanoprost and brimonidine are now being recommended by many as alternate first-line therapy.

Ocular amyloidosis and secondary glaucoma.

OBJECTIVE: To report the clinical and histopathologic findings in two cases of secondary glaucoma associated with amyloidosis. DESIGN: Two case reports. METHODS: Retrospective review of clinical findings, course, and treatment of the two patients. The histopathologic findings from available biopsy material were also reviewed. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), visual field changes, and surgical outcome. RESULTS: The first case describes a 76-year-old woman with orbital amyloidosis who developed gradual unilateral elevation of IOP that was poorly responsive to medical therapy and underwent filtration surgery. Episcleral venous pressure was elevated on the affected side, and histopathologic analysis of the conjunctival tissue confirmed perivascular amyloid deposits, further suggesting raised episcleral venous pressure to be a possible mechanism of glaucoma. The second case describes a 47-year-old white woman with familial amyloid neuropathy with a transthyretin cys-114 mutation. The association of glaucoma with this mutation has not been described previously. Persisting elevation of IOP in one eye was initially responsive to topical antiglaucoma medications but eventually required filtration surgery. Amyloid particles were found in the aqueous and on the lens surface. Histopathologic analysis of the aqueous and sclerectomy specimens demonstrated amyloid, suggesting outflow obstruction as a possible mechanism of glaucoma. Conjunctival buttonholing complicated filtration surgery in both cases, and the leaks eventually resolved with good control of IOP. CONCLUSIONS: Amyloid associated with glaucoma may involve different pathophysiologic mechanisms. The elevated IOP may not respond well to medical therapy. Cautious surgical manipulation of the conjunctiva is warranted in these cases.

Latanoprost treatment for glaucoma: effects of treating for 1 year and of switching from timolol. United States Latanoprost Study Group.

PURPOSE: To determine the efficacy and safety of latanoprost treatment for 1 year in glaucoma patients, and to evaluate the effects of switching from timolol to latanoprost therapy. METHODS: Latanoprost 0.005% was topically applied once daily without masking for 6 months in 223 patients with elevated intraocular pressure after previous treatment with latanoprost once daily or 0.5% timolol twice daily for 6 months in a multicenter, randomized, double-masked, parallel group study. RESULTS: Compared with baseline values before treatment, a significant (P < .0001) diurnal reduction in intraocular pressure of 6 to 8 mm Hg was maintained with minimal fluctuation for the duration of treatment. When treatment was switched from timolol to latanoprost, intraocular pressure was reduced by 1.5 +/- 0.3 mm Hg (mean +/- SEM; 8% change in intraocular pressure; 31% of the intraocular pressure reduction produced by timolol; P < .001) compared with the change in intraocular pressure in patients remaining on latanoprost therapy. Of the patients initially enrolled, 95% successfully completed treatment. There was a slight overall increase in conjunctival hyperemia in patients who switched from timolol to latanoprost, but no change in those who continued latanoprost. The timolol-induced reduction of resting heart rate returned to baseline levels after switching to latanoprost. Of the 247 patients treated with latanoprost during the masked and/or open-label studies, 12 (5%) demonstrated a definite (n = 4) or possible (n = 8) increase in iris pigmentation. CONCLUSIONS: Latanoprost is a well-tolerated ocular hypotensive agent that appears to be more effective than timolol in reducing intraocular pressure. The increase in iris pigmentation appears to be harmless but requires further investigation.

Long-term follow-up of initially successful trabeculectomy.

OBJECTIVE: The purpose was to study the long-term outcomes of primary trabeculectomies that were successful at 1 year. DESIGN: A retrospective study of patients with various types of glaucoma who had trabeculectomies that were successful at 1 year and who had a follow-up of at least 10 years. PARTICIPANTS: There were 40 patients (40 eyes) who had primary trabeculectomies that were successful at 1 year and who had a follow-up range of 10 to 21 years. INTERVENTION: Control of intraocular pressure (IOP) and disease progression was evaluated at 5, 10, and 15 years and at the last obtainable follow-up. MAIN OUTCOME MEASURES: Successful control of IOP was defined as IOP less than 21 mmHg or a reduction of 33% if preoperative IOP was less than 21 mmHg. Successful control of disease progression was defined as stable cup-disc ratios determined by examination, or color photographs or both, as well as stable visual fields. RESULTS: If an eye was considered successful by IOP at 1 year, the probability of successful control of IOP was 82% at 5 years and 67% at 10 and 15 years. If an eye was considered successful by IOP at 1 year, the probability of successful control of disease progression at 5 years was 77%, at 10 years 61%, and at 15 years 48%. If an eye did not require further glaucoma surgery at 1 year, the probability that it still would not need further surgery at 5 years was 90%, at 10 years 75%, and at 15 years 67%. Forty percent of eyes had cataract extraction by the time of last follow-up examination. CONCLUSIONS: Loss of IOP control and progression of glaucomatous damage occurs over time despite initial success at 1 year.

The role of brimonidine in the treatment of open-angle glaucoma.

At present, medical therapy is the first line of attack against primary open-angle glaucoma. beta-blockers, miotics, sympathomimetics, carbonic anhydrase inhibitors, and prostaglandins have been used with varying degrees of success. The alpha 2-agonists, clonidine, apraclonidine, and now brimonidine are powerful inhibitors of aqueous humor production, thereby lowering intraocular pressure (IOP) in these patients. Brimonidine is emerging as a potential first-line therapy for primary open-angle glaucoma, with a peak IOP-lowering efficacy comparable to that of timolol, but without timolol's adverse cardiopulmonary side effects. Brimonidine promises to be an important new drug to help meet the therapeutic challenges faced by ophthalmologists in treating glaucoma.

Should patients with anatomically narrow angles have prophylactic iridectomy?

In this set of articles, the authors outline methods and criteria for determining which patients with anatomically narrow angles should have laser iridectomy to prevent acute angle-closure glaucoma.

Management of bleb leaks after glaucoma filtering surgery. Use of autologous fibrin tissue glue as an alternative.

PURPOSE: To study the nature of bleb leaks after contemporary glaucoma filtering surgery as well as to evaluate various treatment modalities, including autologous fibrin tissue glue (AFTG) prepared in a modified manner. METHODS: Patients who presented to a Glaucoma Service during a 1-year period with a postoperative bleb leak were studied. Evaluation of various treatment modalities, including AFTG, was performed. RESULTS: Thirty-five episodes of bleb leaks were encountered in 25 eyes of 22 patients in a 1-year period. There was no statistically significant association between late or early leaks and the age or the race of the patient, previous eye surgery, or the use of antimetabolites at the time of filtering surgery. Eleven (31.4%) of the leaks were refractory to nonsurgical treatment modalities, 8 or them being of the late type. Successful healing of the leaks was obtained in 9 of the 12 episodes in which AFTG was used. However, there were no statistically significant differences between AFTG and the other treatment modalities. CONCLUSION: Bleb leaks are a common complication of contemporary glaucoma filtering surgery. Various nonsurgical and surgical modalities can be used in the treatment. In early as well as late bleb leaks, AFTG offers an alternative nonsurgical treatment and is at least as efficacious and may, in some ways, be superior to other nonsurgical modalities of treatment.

Long-term results of trabeculectomy in eyes that were initially successful.

A number of published case series provide short-term and intermediate success rates for the surgical treatment of glaucoma with trabeculectomy. There is little information, however, regarding long-term outcomes that extend beyond 10 years. Therefore, we conducted a retrospective study to determine the long-term outcome of eyes that had successful trabeculectomy surgery at 1 year (IOP < 21 mmHg, or lowering by 33% if preoperative IOP was < 21 mm Hg) and had been followed up for at least 10 years. We found 40 such eyes. With respect to IOP control, 83% were still considered to be successful at 5 years, 73% at 10 years, but only 42% at 15 years. Ten percent required additional glaucoma surgery by 5 years, 25% by 10 years, and 58% by 15 years. Forty percent of the eyes had cataract surgery by the time of the last follow-up examination. It appears that there is a significant late failure rate of trabeculectomy in eyes that were initially successful.

Glaucoma after congenital cataract surgery.

OBJECTIVES: To study eyes that manifested glaucoma after congenital cataract surgery and to identify factors that might lead to better diagnosis and treatment of such glaucoma. DESIGN: A retrospective review of patients treated for glaucoma that developed after congenital cataract surgery. RESULTS: Sixty-four eyes of 38 patients were studied. Open-angle glaucoma was the more frequent type of glaucoma (51 eyes, 79.7%). Glaucoma was diagnosed a mean interval of 12.2 years after cataract surgery, but it could occur at any time from months to decades after the cataract surgery. Medications alone were successful in intraocular pressure control in 21 (63.6%) of 33 eyes, and additional surgical procedures resulted in successful intraocular pressure control in 11 of 14 eyes in which they were performed. CONCLUSION: The authors cannot predict in which eyes glaucoma will develop after surgery for congenital cataracts. Once detected, the glaucoma can be treated successfully in the majority of cases. Careful follow-up, including examinations with the patient sedated or anesthetized as needed, is required.

The effects of glaucoma filtering surgery on the variability of diurnal intraocular pressure.

The results of this study indicate that filtration surgery reduces the mean diurnal IOP, the range of diurnal variation, and the day-to-day variability. The effect on the range is proportionally greater than on the other two parameters. Further study will be required to determine whether this selective effect makes surgical reduction of IOP any more effective in the prevention of further glaucomatous visual field damage than other therapeutic methods that lower mean IOP to the same degree.

Can the concentration of timolol or the frequency of its administration be reduced?

BACKGROUND: There is evidence that the ocular hypotensive effect of topical beta-blockers persists for at least 24 hours once beta-blockade has been achieved. In previous studies, the highest concentration of drug generally has been used for this purpose. METHOD: Home tonometry was performed with a self-tonometer by 14 patients to study the intraocular pressure (IOP) reduction of 0.5% timolol administered once daily in the morning or in the evening and of 0.25% timolol administered in the morning. The study was masked and included washout periods before and between the different regimens. At the end of each treatment period, the IOP was monitored five times daily for 3 days. RESULTS: No significant difference in mean reduction of IOP was found between the morning instillation of once daily 0.5% timolol compared with evening instillation of 0.5% timolol. In addition, there was no statistically significant difference in the mean IOP reduction between once daily administration of 0.25% versus 0.5% timolol. CONCLUSION: This study indicates that a lower concentration of timolol maleate used once daily may achieve maximum IOP reduction. The time of the single administration appears not to make any difference.