Joan L. Jefferys

Outcomes and Bleb-Related Complications of Trabeculectomy

PURPOSE To determine rates of success and complications of trabeculectomy surgery. DESIGN Case series. PARTICIPANTS Consecutive patients undergoing trabeculectomy by 2 surgeons between May 2000 and October 2008. INTERVENTION By using the Wilmer Institutes billing database, we identified all patients at least 12 years of age coded as having undergone trabeculectomy between May 2000 and October 2008 by 1 of 2 glaucoma surgeons and whose surgery was not combined with another operation. From the chart, we abstracted demographic information on the patients and clinical characteristics of the eyes. The Kaplan-Meier product-limit method and Cox proportional hazard models were used to look at success rates and characteristics associated with inadequate intraocular pressure (IOP) reduction. Complications were tabulated. MAIN OUTCOME MEASURES (1) Success rate of trabeculectomy, as determined by the achievement of each of 4 different IOP goals, with or without IOP-lowering medications; and (2) incidence of surgical complications. RESULTS During the study period, 797 eyes of 634 persons underwent trabeculectomy without concurrent surgery. The success rates 4 years after surgery, with or without the use of IOP-lowering eye drops, were 70%, 72%, 60%, and 44%, for achievement of target IOP, ≤18 mmHg and ≥20% IOP reduction, ≤15 mmHg and ≥25% reduction, and ≤12 mmHg and ≥30% reduction, respectively. Increased chance of success was associated with European-derived race; use of mitomycin C (MMC); higher concentrations of MMC, when used; and higher preoperative IOP. Age and previous intraocular surgery were not associated with surgical success. Complications included worsening lens opacity in 242 of 443 phakic eyes (55%), loss of ≥3 lines of acuity (Snellen) in 161 eyes (21%), surgery for bleb-related problems in 70 eyes (8.8%), and infection occurring >6 weeks after surgery in 27 eyes (3.4%). A total of 101 eyes of 94 patients had at least 1 subsequent operation for inadequate IOP control. CONCLUSIONS Trabeculectomy surgery performed by 2 experienced glaucoma specialists achieved target IOP at 4 years in 70% of those operated and was associated with progressive cataract and small risks of bleb-related complications. These results are comparable to those reported in smaller series.

The Choroid Is Thicker in Angle Closure than in Open Angle and Control Eyes

PURPOSE To study factors associated with choroidal thickness (CT) and to compare CT in angle closure (AC), open angle (OA), and normal eyes. METHODS Forty controls, 106 OA, and 79 AC subjects underwent measurements of posterior CT by spectral domain-optical coherence tomography, and of intraocular pressure (IOP), blood pressure, axial length (AL), and central corneal thickness (CCT). RESULTS CT was significantly greater in AC than in OA and normal eyes (HSD test, P ≤ 0.05), but there was no significant difference between OA and normal CT; mean CT was 234, 235, and 318 μm in the normal, OA, and AC groups, respectively. With multivariable analysis among all participants, thinner CT was associated with older age, longer AL, higher IOP, and thicker CCT (all P ≤ 0.03, R(2) = 0.45). Adjusting for other relevant variables, the AC group had a significantly greater CT than either the normal or the OA group (P = 0.003 and 0.03, respectively). In multivariable analysis including only OA and AC patients, neither cup-to-disc ratio nor visual field mean deviation were significantly associated with CT. Multivariable analysis for CT among normal eyes found longer AL to be associated with thinner CT (P = 0.04). CONCLUSIONS AC eyes had significantly thicker CT than OA and normal eyes, even after adjusting for the shorter AL in AC eyes, supporting hypotheses that choroidal expansion contributes to the development of AC disease. Age, AL, CCT, and IOP were also significantly associated with CT, while severity of glaucoma damage was not.

Evaluation of minimum clinically meaningful changes in scores on the National Eye Institute Visual Function Questionnaire (NEI-VFQ) SST report number 19

Purpose: To evaluate responsiveness of the National Eye Institute Visual Function Questionnaire (NEI-VFQ) to changes in visual acuity and to provide estimates of minimum clinically meaningful changes in NEI-VFQ scores. Methods: Data were combined from three clinical trials of submacular surgery for subfoveal choroidal neovascularization. Patients who completed NEI-VFQ interviews and visual acuity measurements at baseline and 2 years later contributed data for analysis. Data were analyzed using anchor-based (relating 2-year change in NEI-VFQ to 2-year change in visual acuity using correlation and linear regression) and distribution-based (standardized response mean) methods. Results: Of 1,015 patients enrolled, 828 patients completed NEI-VFQ interviews and had visual acuity measurements at baseline and 2 years later. Median age of patients was 75 years (range 18 to 94); all patients had subfoveal choroidal neovascularization in at least one eye. Median overall NEI-VFQ score at baseline was 69.9 (mean, 66.5). Based on anchor-based methods, a 2-line change in visual acuity of the better-seeing eye translated to a 3.4-point change in the overall NEI-VFQ score and from 2.4-point to 7.0-point changes in most subscale scores. The NEI-VFQ was sensitive to both gains and losses in visual acuity; the standardized response mean for the overall NEI-VFQ score in patients with a 2-line gain was 0.6 and for patients with 2-line loss was −0.3. In the subgroup of patients with a 2-line loss of visual acuity in the better-seeing eye, patients who had overall NEI-VFQ scores at baseline greater than the median (59.8) had an standardized response mean of −0.9 for the overall NEI-VFQ score and patients who had overall NEI-VFQ scores at baseline at or below the median had a standardized response mean of 0.2 for the overall NEI-VFQ score. A 4-point change in the overall NEI-VFQ and a 5-point change in individual subscale scores corresponded to a small clinically meaningful change. Conclusions: The NEI-VFQ was responsive to 2-year changes in visual acuity but was less responsive to changes among patients with poorer NEI-VFQ scores at baseline. Based on this analysis, a 4-point change in the overall NEI-VFQ and a 5-point change in individual subscale scores may be considered minimum clinically meaningful within-person changes in NEI-VFQ scores.

Comparison of Limbus-Based and Fornix-Based Trabeculectomy: Success, Bleb-Related Complications, and Bleb Morphology

PURPOSE To compare the success and complications of trabeculectomy performed with limbus-based and fornix-based conjunctival approaches. DESIGN Retrospective case series with some prospective data collection. PARTICIPANTS Consecutive patients undergoing trabeculectomy by 2 surgeons between May 2000 and October 2008. INTERVENTION We performed limbus-based operations during the first 4 years and fornix-based operations during the last 4 years. We collected data by chart review and by examination at the most recent visit. For each follow-up visit, we defined success as undergoing no further glaucoma procedure and achieving one of our intraocular pressure (IOP) criteria. We used Kaplan-Meier survival analysis, Cox proportional hazards models, and generalized estimating equation (GEE) analysis. During 2009, 439 trabeculectomy sites of 347 patients were quantitatively assessed by the Indiana bleb grading system. MAIN OUTCOME MEASURES (1) Success rate of trabeculectomy, as determined by the achievement of each of our different IOP goals, with or without IOP-lowering medications; and (2) incidence of surgical complications. RESULTS During the 4 years after surgery, the success rates of limbus-based and fornix-based trabeculectomy were not statistically different for any of our IOP criteria. Blebs after limbus-based surgery were more likely to be graded as higher and to be avascular (GEE model, both P < 0.0001). Four percent of eyes experienced late-onset bleb leaks within 4 years after both limbus- and fornix-based operations; however, limbus-based cases developed bleb leaks significantly later than did fornix-based cases (2.1 vs. 1.0 years; P=0.002, GEE model). Late bleb-associated infection during the first 4 years after surgery occurred more often in limbus-based operations, although statistical significance was borderline (P=0.054, Cox model). Symptomatic hypotony during all available follow-up was more common with fornix-based operations (P=0.01, GEE model). Eyes undergoing the fornix-based operation had a greater risk of cataract surgery in the 4-year period after surgery (P=0.02, Cox model), and fornix-based cases requiring cataract surgery had the operation earlier than limbus-based cases (P=0.002, GEE model). CONCLUSIONS Success rates are similar between limbus-based and fornix-based trabeculectomy. Limbus-based procedures produce higher, more avascular blebs, with a greater risk of infection. Fornix-based procedures have more symptomatic hypotony and more and earlier cataract development.

Studies of Scleral Biomechanical Behavior Related to Susceptibility for Retinal Ganglion Cell Loss in Experimental Mouse Glaucoma

PURPOSE To study anatomical changes and mechanical behavior of the sclera in mice with experimental glaucoma by comparing CD1 to B6 mice. METHODS Chronic experimental glaucoma for 6 weeks was produced in 2- to 4-month-old CD1 (43 eyes) and B6 mice (42 eyes) using polystyrene bead injection into the anterior chamber with 126 control CD1 and 128 control B6 eyes. Intraocular pressure (IOP) measurements were made with the TonoLab at baseline and after bead injection. Axial length and scleral thickness were measured after sacrifice in the CD1 and B6 animals and compared to length data from 78 eyes of DBA/2J mice. Inflation testing of posterior sclera was conducted, and circumferential and meridional strain components were determined from the displacement response. RESULTS Experimental glaucoma led to increases in axial length and width by comparison to fellow eyes (6% in CD1 and 10% in B6; all P < 0.03). While the peripapillary sclera became thinner in both mouse types with glaucoma, the remainder of the sclera uniformly thinned in CD1, but thickened in B6. Peripapillary sclera in CD1 controls had significantly greater temporal meridional strain than B6 and had differences in the ratios of meridional to effective circumferential strain from B6 mice. In both CD1 and B6 mice, exposure to chronic IOP elevation resulted in stiffer pressure-strain responses for both the effective circumferential and meridional strains (multivariable regression model, P = 0.01-0.03). CONCLUSIONS Longer eyes, greater scleral strain in some directions at baseline, and generalized scleral thinning after glaucoma were characteristic of CD1 mice that have greater tendency to retinal ganglion cell damage than B6 mice. Increased scleral stiffness after glaucoma exposure in mice mimics findings in monkey and human glaucoma eyes.

Detection of New-Onset Choroidal Neovascularization Using Optical Coherence Tomography: The AMD DOC Study

PURPOSE To determine the sensitivity of time domain optical coherence tomography (OCT) in detecting conversion to neovascular age-related macular degeneration (AMD) in eyes at high risk for choroidal neovascularization (CNV), compared with detection using fluorescein angiography (FA) as the gold standard. DESIGN Prospective, multicenter, observational study. PARTICIPANTS Individuals aged ≥50 years with nonneovascular AMD at high risk of progressing to CNV in the study eye and evidence of neovascular AMD in the fellow eye. METHODS At study entry and every 3 months through 2 years, participants underwent best-corrected visual acuity, supervised Amsler grid testing, preferential hyperacuity perimetry (PHP) testing, stereoscopic digital fundus photographs with FA, and OCT imaging. A central Reading Center graded all images. MAIN OUTCOMES MEASURES The sensitivity of OCT in detecting conversion to neovascular AMD by 2 years, using FA as the reference standard. Secondary outcomes included comparison of sensitivity, specificity, positive predictive value, and negative predictive value of OCT, PHP, and supervised Amsler grid relative to FA for detecting incident CNV. RESULTS A total of 98 participants were enrolled; 87 (89%) of these individuals either completed the 24-month visit or exited the study after developing CNV. Fifteen (17%) study eyes had incident CNV confirmed on FA by the Reading Center. The sensitivity of each modality for detecting CNV was: OCT 0.40 (95% confidence interval [CI], 0.16-0.68), supervised Amsler grid 0.42 (95% CI, 0.15-0.72), and PHP 0.50 (95% CI, 0.23-0.77). Treatment for incident CNV was recommended by the study investigator in 13 study eyes. Sensitivity of the testing modalities for detection of CNV in these 13 eyes was 0.69 (95% CI, 0.39-0.91) for OCT, 0.50 (95% CI, 0.19-0.81) for supervised Amsler grid, and 0.70 (95% CI, 0.35-0.93) for PHP. Specificity of the OCT was higher than that of the Amsler grid and PHP. CONCLUSIONS Time-domain OCT, supervised Amsler grid, and PHP have low to moderate sensitivity for detection of new-onset CNV compared with FA. Optical coherence tomography has greater specificity than Amsler grid or PHP. Among fellow eyes of individuals with unilateral CNV, FA remains the best method to detect new-onset CNV.

Difficulty with Out-Loud and Silent Reading in Glaucoma

PURPOSE We evaluated the impact of glaucoma on out-loud and silent reading. METHODS. Glaucoma patients with bilateral visual field (VF) loss and normally-sighted controls had the following parameters measured: speed reading an International Reading Speed Text (IReST) passage out loud, maximum out-loud MNRead chart reading speed, sustained (30 minutes) silent reading speed, and change in reading speed during sustained silent reading. RESULTS Glaucoma subjects read slower than controls on the IReST (147 vs. 163 words per minute [wpm], P < 0.001), MNRead (172 vs. 186 wpm, P < 0.001), and sustained silent (179 vs. 218 wpm, P < 0.001) tests. In multivariable analyses adjusting for age, race, sex, education, employment, and cognition, IReST and MNRead reading speeds were 12 wpm (6%-7%) slower among glaucoma subjects compared to controls (P < 0.01 for both), while sustained silent reading speed was 16% slower (95% confidence interval [CI] = -24 to -6%, P = 0.002). Each 5 decibel (dB) decrement in better-eye VF mean deviation was associated with 6 wpm slower IReST reading (95% CI = -9 to -3%, P < 0.001), 5 wpm slower MNRead reading (95% CI = -7 to -2%, P < 0.001), and 9% slower sustained silent reading (95% CI = -13 to -6%, P < 0.001). A reading speed decline of 0.5 wpm/min or more over the sustained silent reading period was more common among glaucoma subjects than controls (odds ratio [OR] = 2.2, 95% CI = 1.0-4.9, P < 0.05). CONCLUSIONS Reading speed is slower among glaucoma patients with bilateral VF loss, with the greatest impact present during sustained silent reading. Persons with glaucoma fatigue during silent reading, resulting in slower reading over time.

Progression of Age-Related Macular Degeneration After Cataract Surgery

OBJECTIVE To document age-related macular degeneration (AMD) progression after cataract surgery. METHODS Surgeons prospectively enrolled patients with nonneovascular AMD who were awaiting cataract surgery. Fluorescein angiography was performed preoperatively and at the postoperative week 1, month 3, and month 12 visits. Incidence of neovascular AMD development within 12 months after operation was the primary outcome measure. RESULTS A total of 108 subjects were enrolled. Of 86 eyes with preoperatively photographically confirmed nonneovascular AMD, 71 had gradable images by month 12. Neovascular AMD was observed in 9 of 71 eyes (12.7%; 95% confidence interval, 6.0%-22.7%). The progression rate between week 1 and month 12 decreased to 3 of 65 eyes (4.6%; 95% confidence interval, 1.0%-12.9%) after excluding 5 neovascular events identified on the postoperative week 1 visit and 1 case with missing photographs at this visit. CONCLUSION The low incidence rate of neovascular AMD development between 1 week and 1 year after cataract surgery did not support the hypothesis that cataract surgery increases the risk of AMD progression. Several eyes appeared to have disease progression on postsurgery week 1 fluorescein angiograms, suggesting that many cases of presumed progression to neovascular AMD following cataract surgery may have been present prior to cataract surgery, but not recognized owing to lens opacity.

Change in choroidal thickness and axial length with change in intraocular pressure after trabeculectomy

Background/aims We studied the change in choroidal thickness (CT) and axial length (AL) after intraocular (IOP) changes produced by trabeculectomy. Methods Twenty-one eyes of 20 patients were studied preoperatively, and then postoperatively at 1 week, 1, 3, and 6 months. Variables measured included IOP, AL, keratometry, refractive error, central corneal thickness, and average CT in the posterior 6 mm centred on the fovea using enhanced depth imaging spectral domain optical coherence tomography (OCT). Results OCT images in 17 eyes (58 images, preoperatively and postoperatively) were of sufficient quality to determine CT. In every patient, CT increased with IOP lowering postoperatively. For each 1 mm Hg decrease in IOP, there was a mean increase of 3.4 µm in CT (p<0.0001; univariate regression, 95% CI 2.5 to 4.3). This represented a CT increase of 1.7% per mm Hg decrease (p<0.0001; 95% CI 1.3 to 2.0%). AL decreased by 6.8 µm per mm Hg decrease in IOP (p<0.0001, univariate regression, 95% CI 4.9 to 8.6). Conclusions The dynamic relationship between change in IOP and the state of sclera and choroid was confirmed by sequential measurements in postoperative trabeculectomy patients, providing estimates of the magnitude of choroidal swelling and scleral volume decrease with IOP lowering.

Recruitment in the Hypertension Prevention Trial

Abstract The Hypertension Prevention Trial (HPT) was a randomized, controlled, multicenter (four clinics, four resource centers) trial designed to test the feasibility of achieving and sustaining dietary changes in the intake of calories, sodium, and potassium and to assess the effect of those changes on blood pressure in a normotensive population. The trial involved 841 men and women (plus a test cohort of 78) who, at the first baseline (BL) examination were in the age range of 25–49 years and had diastolic blood pressure (DBP) ≥ 76 but This chapter describes the process of recruiting participants for the trial. Methods used to identify and contact study participants are presented. Details of the steps involved in the recruitment process and strategies for reducing costs are discussed.