Leslie M. Niziol

Visual Field Progression in the Collaborative Initial Glaucoma Treatment Study: The Impact of Treatment and Other Baseline Factors

PURPOSE To evaluate factors associated with visual field (VF) progression, using all available follow-up through 9 years after treatment initiation, in the Collaborative Initial Glaucoma Treatment Study (CIGTS). DESIGN Longitudinal follow-up of participants enrolled in a randomized clinical trial. PARTICIPANTS Six hundred seven newly diagnosed glaucoma patients. METHODS In a randomized clinical trial, 607 subjects with newly diagnosed open-angle glaucoma initially were treated with either medication or trabeculectomy. After treatment initiation and early follow-up, subjects were evaluated clinically at 6-month intervals. Study participants in both arms of the CIGTS were treated aggressively in an effort to reduce intraocular pressure (IOP) to a level at or below a predetermined, eye-specific target pressure. Visual field progression was analyzed using repeated measures models. MAIN OUTCOME MEASURES Visual field progression, measured by Humphrey 24-2 full-threshold testing and assessed by the change in the mean deviation (MD), and an indicator of substantial worsening of the VF (MD decrease of > or =3 dB from baseline), assessed at each follow-up visit. RESULTS Follow-up indicated minimal change from baseline in each initial treatment groups average MD. However, at the 8-year follow-up examination, substantial worsening (> or =3 dB) of MD from baseline was found in 21.3% and 25.5% of the initial surgery and initial medicine groups, respectively. The effect of initial treatment on subsequent VF loss was modified by time (P<0.0001), baseline MD (P = 0.03), and diabetes (P = 0.01). Initial surgery led to less VF progression than initial medicine in subjects with advanced VF loss at baseline, whereas subjects with diabetes had more VF loss over time if treated initially with surgery. CONCLUSIONS The CIGTS intervention protocol led to a lowering of IOP that persisted over time in both treatment groups. Progression in VF loss was seen in a subset, increasing to more than 20% of the subjects. The findings regarding initial surgery being beneficial for subjects with more advanced VF loss at presentation, but detrimental for patients with diabetes, are noteworthy and warrant independent confirmation. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Intraocular pressure control and long-term visual field loss in the collaborative initial glaucoma treatment study

OBJECTIVE To evaluate the impact of measures of intraocular pressure (IOP) control on progression of visual field (VF) loss during long-term treatment for open-angle glaucoma (OAG). DESIGN Longitudinal, randomized clinical trial. PARTICIPANTS We included 607 participants with newly diagnosed OAG. METHODS Study participants were randomly assigned to initial treatment with medications or trabeculectomy, and underwent examination at 6-month intervals. Standardized testing included Goldmann applanation tonometry and Humphrey 24-2 full threshold VFs. Summary measures of IOP control during follow-up included the maximum, mean, standard deviation (SD), range, proportion less than 16, 18, 20, or 22 mmHg, and whether all IOP values were less than each of these 4 cutpoints. Predictive models for VF outcomes were based on the mean deviation (MD) from VF testing, and were adjusted for age, gender, race, baseline VF loss, treatment, and time. Each summary IOP measure was included as a cumulative, time-dependent variable, and its association with subsequent VF loss was assessed from 3 to 9 years postrandomization. Both linear mixed models, to detect shifts in MD levels, and logistic models, to detect elevated odds of substantial worsening (≥3 dB), were used. MAIN OUTCOME MEASURES We measured the MD from Humphrey 24-2 full threshold VF tests. RESULTS The effect of the summary IOP measures differed between the medicine and surgery groups in models that addressed the continuous MD outcome. After adjustment for baseline risk factors, in the medicine group larger values of 3 IOP control measures-maximum IOP (P = 0.0003), SD of IOP (P = 0.0056), and range of IOP (P<0.0001)-were significantly associated with lower (worse) MD over the 3- to 9-year period. No IOP summary measure was significantly associated with MD over time in the surgery group. The same 3 IOP summary measures were also significantly associated with substantial worsening of MD; however, the effects were similar in both treatment groups. In models predicting inadequate IOP control, consistently significant predictors of higher maximum, SD, and range of IOP included black race, higher baseline IOP, and clinical center. CONCLUSIONS These results support considering more aggressive treatment when undue elevation or variation in IOP measures is observed.

Incidence of, risk factors for, and combined mechanism of late-onset open-angle glaucoma after vitrectomy.

Purpose: To estimate the incidence of and identify the risk factors for late-onset open-angle glaucoma (OAG) after uncomplicated pars plana vitrectomy (PPV). Methods: All patients who underwent PPV at the Edward Harkness Eye Institute between January 1998 and January 2004 had at least 6 months of follow-up and did not have preexisting glaucoma or reason for secondary development of glaucoma were included. Retrospective cohort and matched case–control study designs were used. Results: Of 285 vitrectomized eyes that met enrollment criteria, 11.6% (n = 33) developed glaucoma after vitrectomy. In the matched case–control analysis, the only variable that had a statistically significant association with the development of OAG was cataract extraction (CE), as compared with phakic status at the last follow-up (odds ratio = 16.4; 95% confidence interval, 2.1–127.4; P = 0.007). There was no difference in OAG development between eyes that had CE before or at the time of PPV and those that had it after PPV. The overall incidence of OAG development after PPV among all eyes, phakic eyes, and nonphakic eyes was 11.6%, 1.4%, and 15.0%, respectively. The difference in incidence between phakic and nonphakic eyes was statistically significant (P = 0.001). Conclusion: Lens extraction is a strong risk factor for the development of late-onset OAG after uncomplicated PPV. While the overall incidence of OAG development after PPV is substantial, it is more so among eyes that have had CE. The absence of substantial OAG incidence in phakic patients points toward a combined mechanism for late-onset post-PPV OAG involving PPV and CE at any time. Preoperative PPV counseling should include the risk of glaucoma development in addition to cataract development and the connection between the two. Patients who have undergone PPV, and especially those who also had CE in the same eye, should be carefully monitored for glaucoma.

Clinical phenotypes and prognostic full-field electroretinographic findings in Stargardt disease.

PURPOSE To investigate the relationships between clinical and full-field electroretinographic (ERG) findings and progressive loss of visual function in Stargardt disease. DESIGN Retrospective cohort study. METHODS We performed a retrospective review of data from 198 patients with Stargardt disease. Measures of visual function over time, including visual acuity, quantified Goldmann visual fields, and full-field ERG data were recorded. Data were analyzed using SAS statistical software. Subgroup analyses were performed on 148 patients with ERG phenotypic data, 46 patients with longitudinal visual field data, and 92 patients with identified ABCA4 mutations (46 with 1 mutation, and 47 with 2 or more mutations). RESULTS Of 46 patients with longitudinal visual field data, 8 patients with faster central scotoma progression rates had significantly worse scotopic B-wave amplitudes at their initial assessment than 20 patients with stable scotomata (P = .014) and were more likely to have atrophy beyond the arcades (P = .047). Overall, 47.3% of patients exhibited abnormal ERG results, with rod-cone dysfunction in 14.2% of patients, cone-rod dysfunction in 17.6% of patients, and isolated cone dysfunction in 15.5% of patients. Abnormal values in certain ERG parameters were associated significantly with (maximum-stimulation A- and B-wave amplitudes) or tended toward (photopic and scotopic B-wave amplitudes) a higher mean rate of central scotoma progression compared with those patients with normal ERG values. Scotoma size and ERG parameters differed significantly between those with a single mutation versus those with multiple mutations. CONCLUSIONS Full-field ERG examination provides clinically relevant information regarding the severity of Stargardt disease, likelihood of central scotoma expansion, and visual acuity deterioration. Patients also may exhibit an isolated cone dystrophy on ERG examination.

Longitudinal Trends in Resource Use in an Incident Cohort of Open-Angle Glaucoma Patients: Resource Use in Open-Angle Glaucoma

PURPOSE To characterize the costs of caring for patients with open-angle glaucoma (OAG) in the United States over time and to identify factors that influence these costs. DESIGN Longitudinal cohort study. METHODS Claims data from 19 927 newly diagnosed OAG patients enrolled in a large United States managed care network were reviewed to identify glaucoma-related charges for all incident OAG patients from 2001 through 2009. Average glaucoma-related charges for enrollees with OAG were characterized in 6-month blocks from the date of initial OAG diagnosis through the ensuing 5 years. Factors associated with being an enrollee in the costliest 5% for glaucoma-related charges (accruing

Visual Field Improvement in the Collaborative Initial Glaucoma Treatment Study

5810 or more in charges in the first 2 years) were identified using logistic regression. RESULTS The costliest 5% of enrollees were responsible for

Peripapillary Dark Choroid Ring as a Helpful Diagnostic Sign in Advanced Stargardt Disease

10 202 871 (24%) of all glaucoma-related charges. By comparison, those whose costs fell within the lower 50% of the cost distribution collectively amassed only

Incidence of diffuse lamellar keratitis after LASIK with 15 KHz, 30 KHz, and 60 KHz femtosecond laser flap creation.

7 986 582 (19%) of all glaucoma-related charges. A spike in glaucoma-related charges occurred in the 6-month period around the time of OAG diagnosis, stabilized by 1 year after diagnosis, and remained relatively constant over time. Risk factors associated with being in the costliest 5% for glaucoma-related care included younger age, Northeastern United States state residence, undergoing cataract surgery, and possessing ocular comorbidities (P < .006 for all comparisons). CONCLUSIONS A small subset of enrollees account for a large proportion of all glaucoma-related charges. Understanding the characteristics of these individuals and finding ways to reduce disease burden and costs associated with their care can result in substantial cost savings.

The Effect of Trabeculectomy on Intraocular Pressure of the Untreated Fellow Eye in the Collaborative Initial Glaucoma Treatment Study

PURPOSE To evaluate critically visual field (VF) improvement in participants in the Collaborative Initial Glaucoma Treatment Study (CIGTS). DESIGN Prospective, comparative case series from a randomized clinical trial comparing trabeculectomy and topical medications in treating open-angle glaucoma (OAG). METHODS A total of 607 subjects with newly diagnosed OAG were identified for study. Baseline and follow-up VF tests were obtained and mean deviation (MD) change from baseline over follow-up was analyzed. Clinically substantial change (loss or improvement) was defined as change from baseline of ≥ 3 decibels in MD. Baseline factors were inspected to determine their association with VF improvement in repeated measures regression models. RESULTS The percentage of participants showing substantial VF improvement over time was similar to that showing VF loss through 5 years after initial treatment, after which VF loss became more frequent. Measures of better intraocular pressure (IOP) control during treatment were significantly predictive of VF improvement, including a lower mean IOP, a lower minimum IOP, and lower sustained levels of IOP over follow-up. Other predictive factors included female sex (odds ratio [OR] = 1.73), visits 1 year prior to cataract extraction (OR = 0.11), and an interaction between treatment and baseline MD wherein surgically treated subjects with worse baseline VF loss were more likely to show VF improvement. CONCLUSIONS In the CIGTS, substantial VF loss and improvement were comparable through 5 years of follow-up, after which VF loss became more frequent. Predictive factors for VF improvement included several indicators of better IOP control, which supports the postulate that VF improvement was real.

Safety and Feasibility of Quantitative Multiplexed Cytokine Analysis From Office-Based Vitreous Aspiration.

PURPOSE To investigate the prevalence of a peripapillary dark choroid ring on fluorescein angiography (FA) and the associated clinical features in patients with Stargardt disease. DESIGN Retrospective review of 135 patients with Stargardt disease. METHODS The presence or absence of a peripapillary dark choroid ring on FA was noted and was compared with patient demographics and clinical features. RESULTS Thirty-seven percent (50/135) had a peripapillary dark choroid ring on FA. When evaluated in subgroups, this sign was present in 41% (9/22) of patients with 2 causative ABCA4 mutations, in 28% (5/18) of patients with 1 causative ABCA4 mutation and a clinical diagnosis of Stargardt disease, and in 38% (36/95) of patients with a clinical diagnosis of Stargardt disease pending mutational analysis. Ninety-four percent (44/47) of patients for whom mutational testing confirmed the presence of ABCA4 mutations demonstrated a dark choroid sign. The peripapillary dark choroid ring sign was associated with diffuse flecks (P < .001), worse logarithm of the minimal angle of resolution visual acuity (P = .03), larger central scotoma size (P = .0146), and the presence of complete macular atrophy (P = .0017) compared with patients without this sign. CONCLUSIONS The presence of a peripapillary dark choroid ring on FA should prompt further evaluation for Stargardt disease by examination of peripheral retinal FA images for a dark choroid sign, followed by subsequent ABCA4 mutation screening.