Allen D. Beck

The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration

Abstract PURPOSE: To investigate the association between control of intraocular pressure after surgical intervention for glaucoma and visual field deterioration. METHODS: In the Advanced Glaucoma Intervention Study, eyes were randomly assigned to one of two sequences of glaucoma surgery, one beginning with argon laser trabeculoplasty and the other trabeculectomy. In the present article we examine the relationship between intraocular pressure and progression of visual field damage over 6 or more years of follow-up. In the first analysis, designated Predictive Analysis, we categorize 738 eyes into three groups based on intraocular pressure determinations over the first three 6-month follow-up visits. In the second analysis, designated Associative Analysis, we categorize 586 eyes into four groups based on the percent of 6-month visits over the first 6 follow-up years in which eyes presented with intraocular pressure less than 18 mm Hg. The outcome measure in both analyses is change from baseline in follow-up visual field defect score (range, 0 to 20 units). RESULTS: In the Predictive Analysis, eyes with early average intraocular pressure greater than 17.5 mm Hg had an estimated worsening during subsequent follow-up that was 1 unit of visual field defect score greater than eyes with average intraocular pressure less than 14 mm Hg (P = .002). This amount of worsening was greater at 7 years (1.89 units; P CONCLUSIONS: In both analyses low intraocular pressure is associated with reduced progression of visual field defect, supporting evidence from earlier studies of a protective role for low intraocular pressure in visual field deterioration.

Trabeculectomy with adjunctive mitomycin C in pediatric glaucoma

PURPOSE To determine the safety and efficacy of trabeculectomy with adjunctive mitomycin C in patients 17 years of age or younger, and to identify risk factors for failure of this surgical technique. METHODS Retrospective review of consecutive cases of pediatric glaucoma that underwent mitomycin C augmented trabeculectomy between January 1991 and December 1995. Forty-nine patients (60 eyes) with a mean age of 7.6 years (range, 6 weeks to 17.6 years) were identified and followed up until repeat glaucoma surgery, or after a minimum of 6 months. Success was defined as intraocular pressure control of 22 mm Hg or less with or without topical glaucoma control medication, no evidence of glaucoma progression, no further glaucoma surgery necessary, and no visually devastating complication. RESULTS Cumulative probabilities of success +/- SD for 49 eyes (one eye per patient) were 67% +/- 13% at 12 months and 59% +/- 15% at 24 months. Multivariate regression analysis yielded the following characteristics as significantly increased risk for failure: age of less than 1 year at time of surgery (risk ratio, 5.6; confidence interval, 2.1 to 14.7; P = .0005), and aphakia (risk ratio, 2.7; confidence interval, 1.1 to 6.9; P = .0364). Shallow anterior chamber (17 [28%] of 60 eyes) and serous choroidal detachment (13 [22%] of 60 eyes) were the most common complications. Four (11%) of 38 eyes with obtainable Snellen acuity were noted to have a decrease in best-corrected visual acuity of more than 2 Snellen lines or loss of light perception. In 5 (8%) of 60 eyes bleb-related endophthalmitis was noted. CONCLUSIONS Trabeculectomy with adjunctive mitomycin C is generally effective for the treatment of pediatric glaucoma, especially in phakic children over 1 year of age. However, late-onset bleb-related endophthalmitis is a substantial risk in this patient population.

Blebitis, Early EndophthalmitS, and Late Endophthalmitis after Glaucoma-filtering Surgery

PURPOSE The differentiating characteristics in blebitis and early and late endophthalmitis after glaucoma filtration surgery are reviewed. METHODS All admission records and operative reports, as well as available office notes, on patients with blebitis or bleb-associated endophthalmitis admitted to a large referral eye center from 1985 to 1995 were reviewed retrospectively. RESULTS Ten cases of blebitis and 33 cases of bleb-associated endophthalmitis were identified. One patient with blebitis progressed to culture-positive endophthalmitis. Of the 33 cases of bleb-associated endophthalmitis, there were 6 cases of early endophthalmitis (before postoperative week 6) and 27 cases of late endophthalmitis. In early endophthalmitis, Staphylococcus epidermidis was isolated on vitreous culture in 4 (67%) of 6 cases, whereas in late endophthalmitis, this organism was isolated in only 1 (4%) of 27 cases. In the 27 late cases, Streptococcus species and gram-negative organisms comprised 48% of isolates; of 33 cases of endophthalmitis, 15 (45%) demonstrated no growth on vitreous culture. Patients with endophthalmitis fared more poorly than those with blebitis in terms of visual outcome. CONCLUSIONS Because blebitis may be prodromal to endophthalmitis, aggressive antimicrobial therapy, perhaps with oral quinolones, is warranted. In addition, patients with blebitis should be observed closely to identify extension into the vitreous cavity so that intravitreous antibiotics can be administered in a timely fashion. Finally, clinicians should not extrapolate the results of the Endophthalmitis Vitrectomy Study to the postfiltration surgery endophthalmitis given the differing pathogenesis and unique spectrum of organisms.

Aqueous shunt devices compared with trabeculectomy with Mitomycin-C for children in the first two years of life☆

PURPOSE To compare the outcomes of children 24 months of age or younger treated with aqueous shunt devices or with mitomycin-C (MMC) trabeculectomy. DESIGN Retrospective, age-matched, comparative case series. METHODS Forty-six eyes of 32 patients with mean age of 7.0 +/- 5.1 month (range, 1 to 22 months) and uncontrolled glaucoma, which received an aqueous shunt device (Ahmed glaucoma valve or Baerveldt implant), compared with 24 eyes of 19 patients with mean age of 5.3 +/- 4.8 months (range, 0.5 to 24 months), which received an MMC trabeculectomy. Surgical success was defined as intraocular pressure < 23 mm Hg on maximal glaucoma medication, no further glaucoma surgery performed or recommended, no devastating complication, and stable ocular dimensions (axial length and corneal diameter). RESULTS Cumulative probabilities of success were 87% +/- 5.0% for the aqueous shunt group compared with 36% +/- 8.0% success in the trabeculectomy group at 12 months and 53% +/- 12% in the aqueous shunt group compared with 19% +/- 7% in the trabeculectomy group at 72 months (chi(2) of 23.5, P <.0001). Aqueous shunt implantation was associated with significantly more postoperative complications requiring a return to the operating room (21 of 46 eyes, 45.7%) compared with trabeculectomy with MMC (3 of 24 eyes, 12.5%, P =.0074). The most common postoperative procedure in the aqueous shunt group was tube repositioning, performed in 16 of 46 eyes (34.8%). CONCLUSIONS Aqueous shunt implantation offers a significantly greater chance of successful glaucoma control in the first 2 years of life, compared with trabeculectomy with MMC. However, the enhanced success with aqueous shunt devices is associated with a higher likelihood of postoperative complications requiring surgical revision, most commonly tube repositioning.

The Infant Aphakia Treatment Study: Design and Clinical Measures at Enrollment

OBJECTIVE To compare the use of contact lenses and intraocular lenses (IOLs) for the optical correction of unilateral aphakia during infancy. METHODS In a randomized, multicenter (12 sites) clinical trial, 114 infants with unilateral congenital cataracts were assigned to undergo cataract surgery with or without IOL implantation. Children randomized to IOL treatment had their residual refractive error corrected with spectacles. Children randomized to no IOL treatment had their aphakia treated with a contact lens. MAIN OUTCOME MEASURES Grating acuity at 12 months of age and HOTV visual acuity at 4 1/2 years of age. APPLICATION TO CLINICAL PRACTICE This study should determine whether either treatment for an infant with a visually significant unilateral congenital cataract results in a better visual outcome. RESULTS Enrollment began December 23, 2004, and was completed January 16, 2009. The median age at the time of cataract surgery was 1.8 months. Fifty patients were 4 to 6 weeks of age at the time of enrollment; 32, 7 weeks to 3 months of age; and the remaining 32, more than 3 to less than 7 months of age. Fifty-seven children were randomized to each treatment group. Eyes with cataracts had shorter axial lengths and steeper corneas on average than the fellow eyes. CONCLUSIONS The optimal optical treatment of aphakia in infants is unknown. However, the Infant Aphakia Treatment Study was designed to provide empirical evidence of whether optical treatment with an IOL or a contact lens after unilateral cataract surgery during infancy is associated with a better visual outcome.

Trabeculectomy with antiproliferative agents in uveitic glaucoma.

PurposeTo evaluate the outcome of trabeculectomy with antiproliferative agents in patients with uveitic glaucoma MethodsA retrospective chart review of 44 eyes of 44 patients with uveitic glaucoma who underwent trabeculectomy with mitomycin C or 5-fluorouracil. The authors defined complete success as an intraocular pressure of 21 mm Hg or lower without pressure-lowering medications, qualified success as an intraocular pressure of 21 mm Hg or lower with medications, and failure as an intraocular pressure of more than 21 mm Hg with medications, loss of light perception, or the need for reoperation. ResultsThe cumulative probability of complete or qualified success was 78% at 1 year and 62% at 2 years. At 2 years, success rates were 39% in males and 71% in females (P = 0.02), 74% in white patients and 55% in black patients (P = 0.58), and 45% in patients with idiopathic uveitis and 74% in patients with sarcoid uveitis (P = 0.17). Sixteen of 31 (51.6%) phakic patients developed new cataracts or had progression of existing cataracts and required cataract extraction. Four of 16 eyes (25%) lost intraocular pressure control and needed repeat trabeculectomy after undergoing cataract surgery. ConclusionsPatients with uveitic glaucoma can have good outcomes after trabeculectomy with antiproliferative agents. Male gender was the only statistically significant risk factor for trabeculectomy failure. Cataract management in the presence of a filtering bleb poses a treatment dilemma between improvement of visual acuity and loss of intraocular pressure control.

DIAGNOSIS AND MANAGEMENT OF PEDIATRIC GLAUCOMA

Appropriate diagnosis of pediatric glaucoma in toddlers and school-aged children is aided by an understanding of the signs and symptoms of infantile-onset glaucoma, along with its associated conditions. Unlike adults with glaucoma, the management of pediatric glaucoma is frequently surgical, with medical therapy playing an adjunctive role. The ultimate goal of pediatric glaucoma management is not control of IOP but preservation of vision. The visual prognosis in children with glaucoma is correlated with the severity of the associated ocular pathology. Primary congenital glaucoma has the best visual prognosis, with 52% to 79% having visual acuity of 20/50 or better. Glaucomas associated with congenital ocular anomalies and secondary glaucomas have a worse visual prognosis, with 30% to 50% of eyes noted to be 20/50 or better. Amblyopia and uncontrolled glaucoma are the two main factors associated with reduction in vision. Control of the glaucoma by medical and surgical means and treatment of amblyopia during susceptible ages are the essential factors in the management of pediatric glaucoma.

An exploratory study of factors influencing glaucoma treatment adherence.

PurposeTo understand the factors that influence glaucoma treatment adherence with medication taking, prescription refills, and appointment keeping to develop an intervention for a specific population. Patients and MethodsIn-depth interviews were conducted with 80 individuals diagnosed with open-angle glaucoma, glaucoma suspect, or ocular hypertension. Additional eligibility requirements were that all participants were: between the ages of 18 to 80; white or African American; spoke and understood English; and were taking daily doses of topical glaucoma treatments for at least the past year. Cross-tabulations and χ2 tests were conducted to compare adherent and nonadherent individuals, classified as such based on self-report and medical chart/pharmacy data. ResultsCompared with adherent participants, nonadherent participants were less likely to: believe their eye doctors spent sufficient time with them; ask their eye doctor if they had any questions; know of benefits to taking their glaucoma medication regularly; and have someone help them take their glaucoma medications or drive them to eye appointments. Conversely, compared with adherent individuals, nonadherent participants were more likely to have difficulty remembering to take their medications and to believe their glaucoma would affect their eye sight in the future. ConclusionsNonadherent glaucoma patients struggle with a variety of issues related to consistent use of glaucoma medicine and routine eye care. Interventions are needed to address these modifiable factors related to glaucoma treatment adherence.

Glaucoma-Related Adverse Events in the Infant Aphakia Treatment Study: 1-Year Results

OBJECTIVES To report the incidence of glaucoma and glaucoma suspects in the IATS, and to evaluate risk factors for the development of a glaucoma-related adverse event in patients in the IATS in the first year of follow-up. METHODS A total of 114 infants between 1 and 6 months of age with a unilateral congenital cataract were assigned to undergo cataract surgery either with or without an intraocular lens implant. Standardized definitions of glaucoma and glaucoma suspect were created and used in the IATS. RESULTS Of these 114 patients, 10 (9%) developed glaucoma and 4 (4%) had glaucoma suspect, for a total of 14 patients (12%) with a glaucoma-related adverse event in the treated eye through the first year of follow-up. Of the 57 patients who underwent lensectomy and anterior vitrectomy, 5 (9%) developed a glaucoma-related adverse event; of the 57 patients who underwent an intraocular lens implant, 9 (16%) developed a glaucoma-related adverse event. The odds of developing a glaucoma-related adverse event were 3.1 times higher for a child with persistent fetal vasculature and 1.6 times higher for each month of age younger at cataract surgery. CONCLUSIONS Modern surgical techniques do not eliminate the early development of glaucoma following congenital cataract surgery with or without an intraocular lens implant. Younger patients with or without persistent fetal vasculature seem more likely to develop a glaucoma-related adverse event in the first year of follow-up. Vigilance for the early development of glaucoma is needed following congenital cataract surgery, especially when surgery is performed during early infancy or for a child with persistent fetal vasculature. Five-year follow-up data for the IATS will likely reveal more glaucoma-related adverse events. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00212134.

Glaucoma-related adverse events in the first 5 years after unilateral cataract removal in the infant aphakia treatment study

IMPORTANCE Glaucoma-related adverse events constitute major sight-threatening complications of cataract removal in infancy, yet their relationship to aphakia vs primary intraocular lens (IOL) implantation remains unsettled. OBJECTIVE To identify and characterize cases of glaucoma and glaucoma-related adverse events (glaucoma + glaucoma suspect) among children in the Infant Aphakia Treatment Study by the age of 5 years. DESIGN, SETTING, AND PARTICIPANTS A multicenter randomized clinical trial of 114 infants with unilateral congenital cataract in referral centers who were between ages 1 and 6 months at surgery. Mean follow-up was 4.8 years. This secondary analysis was conducted from December 23, 2004, to November 13, 2013. INTERVENTIONS Participants were randomized at cataract surgery to either primary IOL or no IOL implantation (contact lens). Standardized definitions of glaucoma and glaucoma suspect were created for the Infant Aphakia Treatment Study and applied for surveillance and diagnosis. MAIN OUTCOMES AND MEASURES Development of glaucoma and glaucoma + glaucoma suspect in operated on eyes for children up to age 5 years, plus intraocular pressure, visual acuity, and axial length at age 5 years. RESULTS Product limit estimates of the risk for glaucoma and glaucoma + glaucoma suspect at 4.8 years after surgery were 17% (95% CI, 11%-25%) and 31% (95% CI, 24%-41%), respectively. The contact lens and IOL groups were not significantly different for either outcome: glaucoma (hazard ratio [HR], 0.8; 95% CI, 0.3-2.0; P = .62) and glaucoma + glaucoma suspect (HR, 1.3; 95% CI, 0.6-2.5; P = .58). Younger (vs older) age at surgery conferred an increased risk for glaucoma (26% vs 9%, respectively) at 4.8 years after surgery (HR, 3.2; 95% CI, 1.2-8.3), and smaller (vs larger) corneal diameter showed an increased risk for glaucoma + glaucoma suspect (HR, 2.5; 95% CI, 1.3-5.0). Age and corneal diameter were significantly positively correlated. Glaucoma was predominantly open angle (19 of 20 cases, 95%), most eyes received medication (19 of 20, 95%), and 8 of 20 eyes (40%) underwent surgery. CONCLUSIONS AND RELEVANCE These results suggest that glaucoma-related adverse events are common and increase between ages 1 and 5 years in infants after unilateral cataract removal at 1 to 6 months of age; primary IOL placement does not mitigate their risk but surgery at a younger age increases the risk. Longer follow-up of these children may further characterize risk factors, long-term outcomes, potential differences between eyes having primary IOL vs aphakia, and optimal timing of unilateral congenital cataract removal. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00212134.