Susan Vitale

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 twentyfifth 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.

Azithromycin in control of trachoma

The new Global Initiative by the World Health Organization has an ambitious goal of eliminating blinding trachoma by 2020, twenty years into the next millennium. GET 2020 consists of a four-pronged strategy to reduce active trachoma through community-based antibiotic distribution and health education on face washing and environmental sanitation, and to reduce vision loss from trichiasis through provision of appropriate surgical services. The SAFE strategy – Surgery, Antibiotics, Face-washing, Environmental change – is currently being implemented or planned for five pilot countries where the antibiotic component will be based on the drug azithromycin under a donation programme by Pfizer, Inc. Azithromycin represents a breakthrough for the community-based, antibiotic treatment of ocular Chlamydia trachomatis infection. Trachoma is a community disease, which clusters in neighbourhoods and within families, children having the highest rates of disease.1 Treatment of a few cases in such a setting guarantees re-infection from familial or neighbourhood sources, unless the treatment is more widespread. Moreover, re-infection from extra-ocular sites can occur if only topical treatment is used,2 and re-infection from other people can occur if treatment of members of the community is not carried out at the same time. Previously, topical agents, such as tetracycline, have been the agents of choice. This was done due to the absence of systemic side effects in children (seen with oral tetracycline) and the high cost and lack of availability of oral erythromycin in many of these remote communities. However, topical tetracycline must be used every day for four to six weeks to be effective. It also stings, is messy to use, and results in blurred vision because of its oily base. Compliance (regular use of the prescribed medicine) with topical agents is typically quite poor.

Lumboperitoneal shunt for the treatment of pseudotumor cerebri

We conducted a retrospective study of 27 patients with pseudotumor cerebri (PTC) treated with at least one lumboperitoneal shunt (LPS) to ascertain the efficacy of this treatment.The average duration of follow-up for this population was 77 months (median, 47 months), with a range of 21 to 278 months. A functioning LPS was successful in alleviating symptoms in all patients studied, and no patient with a functioning shunt complained of shunt-related symptoms, such as low-pressure headache or abdominal pain, within 2 months after the shunt was performed. Twelve patients (44%) required no revisions. The number of revisions among the 15 patients (56%) who required them ranged from 1 (5 patients) to 13 (1 patient). Three of these patients required 35 of the 66 total shunt revisions (53%). There were no major complications from LPS, other than failure of the shunt, even in patients who required multiple shunts. We conclude that placement of a lumboperitoneal shunt is satisfactory treatment for the majority of patients with PTC who require surgical therapy for the disorder, even though some patients ultimately require multiple shunt revisions. NEUROLOGY 1996;46: 1524-1530

Plasma antioxidants and risk of cortical and nuclear cataract.

We evaluated nutritional risk factors for cataract in 660 subjects enrolled in the Baltimore Longitudinal Study on Aging. As a part of a regular cycle of visits, nuclear and cortical lens photographs were taken over a 2-year period. Measurements of plasma antioxidants (beta-carotene, ascorbic acid, and alpha-tocopherol) were obtained in this cohort as part of the study protocol up to 4 years before lens photographs were taken. We found that plasma beta-carotene and ascorbic acid levels were not associated with risk of nuclear or cortical lens opacities. Higher levels of plasma alpha-tocopherol, however, were associated with a reduced risk of nuclear opacity [odds ratio (OR) for highest quartile vs lowest quartile = 0.52, 95% confidence interval (CI) = 0.27–0.98; OR for middle two quartiles vs lowest quartile = 0.55, 95% CI = 0.30–0.98], after adjusting for age, sex, and history of diabetes. Middle levels of alpha-tocopherol were associated with a reduced risk of cortical opacity (OR = 0.57, 95% CI = 0.32–1.02), but no such association was observed for high levels of alpha-tocopherol. We constructed an index of overall antioxidant status, which indicated that higher levels of plasma antioxidants were not associated with risk of nuclear or cortical opacities.

Clinical features and associated systemic diseases of HLA-B27 uveitis

PURPOSE To delineate the clinical features, course, complications, and associated systemic diseases in patients with HLA-B27-associated uveitis. METHODS We reviewed the records of 148 patients with HLA-B27-associated uveitis from two large uveitis practices. RESULTS There were 127 (86%) white and 21 (14%) nonwhite patients, and a male-to-female ratio of 1.5:1. The median age at onset of uveitis was 32 years; eight patients (5%) had their first attack after age 55 years. Acute anterior uveitis was noted in 129 patients (87%), and nonacute inflammation was noted in 19 (13%). Ocular involvement was categorized as unilateral or unilateral alternating in 138 patients (93%), but ten patients (7%) had bilateral, concurrent disease. The median duration of an attack was six weeks, and the median number of recurrences for patients with more than 12 months of follow-up was three. Cataracts were associated with posterior synechiae (P = .03), increased intraocular pressure (P = .003), and cystoid macular edema (P = .04). An HLA-B27-associated systemic disorder was present in 83 patients (58%), 30 of whom were women, and it was diagnosed in 43 of the 83 patients as a result of the ophthalmologic consultation. Thirty-four (30%) of 112 patients had a family history of a spondyloarthropathy. CONCLUSIONS Although HLA-B27-associated uveitis is usually described as a disease of young white men, women and nonwhites may also be affected. A subgroup of patients have severe disease and consequently more complications. Most patients have an associated systemic disease, including women, who appear to have more atypical spondyloarthropathies. The systemic diseases were frequently undiagnosed before the onset of the ocular disease and before the uveitis consultation.

Early Changes in Optic Disc Compliance and Surface Position in Experimental Glaucoma

PURPOSE To detect changes in the compliance and baseline position (position at the baseline time point of a compliance test) of the monkey optic disc after the onset of chronic experimental glaucoma. METHODS Sixty-six compliance tests were performed on 26 eyes of 13 monkeys. Longitudinal Study. In seven normal monkeys, compliance tests were performed three times in one eye (study eye) and once in the contralateral eye. In the study eye of five of these monkeys, chronic experimental glaucoma was then induced and compliance tests were performed at some or all of the following postglaucoma testing intervals: 1 to 2 weeks, 3 to 4 weeks, 5 to 8 weeks, 9 to 12 weeks, 13 to 18 weeks, and more than 18 weeks after the onset of elevated intraocular pressure (IOP). In the study eye of the remaining two monkeys, the optic nerve was transected, and compliance was tested at 5, 9, and 13 weeks after transection. An analysis of variance (ANOVA) was performed to detect an increase (hypercompliance) or decrease (rigidity) in the compliance of the glaucomatous eyes at each testing interval. A second ANOVA was performed to detect the onset of chronic posterior deformation of the baseline position of each disc. Cross-Sectional Study. In six additional monkeys with pre-existing experimental glaucoma, the glaucomatous study eye was compliance tested at one of the postglaucoma testing intervals used in the longitudinal study. The contralateral normal eye was compliance tested once. These data were then added to the data from the five longitudinally studied monkeys at the appropriate preglaucoma and postglaucoma testing intervals. A third ANOVA was done to compare the compliance of the expanded group of glaucomatous eyes at each postintervention testing interval with the compliance of the 13 normal contralateral eyes. RESULTS Compliance. In the longitudinally (Pr > F = 0.0005) and cross-sectionally (Pr > F = 0.0001) studied glaucomatous eyes, optic disc compliance increased significantly by 1 to 2 weeks and then returned to a level statistically indistinguishable from normal within 13 to 18 weeks after the onset of glaucoma. In the transection eyes, the optic discs were significantly less compliant (more rigid) at 5 and 9 weeks after transection compared with the discs in either the normal or the glaucomatous eyes (Pr > F < 0.05). Baseline Optic Disc Position. Chronic posterior deformation of the disc was detected in one of three eyes tested 1 to 2 weeks and three of four eyes tested 3 to 4 weeks after the onset of glaucoma (Pr > F < 0.05). Chronic posterior deformation was not detected in the discs of either of the transection eyes at any of the post-transection testing intervals. CONCLUSION Changes in optic disc compliance and surface position were detected by digitized image analysis within 2 to 4 weeks of the onset of experimental glaucoma in the monkey eye. These findings are unlikely to be due to axon loss alone, because they did not occur in optic nerve transection eyes (which constitute a model of axon loss in which intraocular pressures remain normal). The results suggest that IOP-related damage to the load-bearing connective tissues of the optic nerve head may occur early in the course of experimental glaucoma.

Diagnostic capabilities of frequency-doubling technology, scanning laser polarimetry, and nerve fiber layer photographs to distinguish glaucomatous damage

PURPOSE To investigate the ability of three diagnostic tests: frequency-doubling technology (FDT), scanning laser polarimetry (GDx), and nerve fiber layer (NFL) photographs to distinguish normal from glaucomatous eyes. METHODS Data were obtained in a cross-sectional, hospital clinic-based study, including one eye from each of 253 persons older than 40 years (68 normal, 94 glaucoma suspects and 91 glaucoma patients). We performed a comprehensive ocular examination, as well as static automated perimetry (Humphrey 24-2), screening FDT, GDx, optic nerve stereoscopic photographs and high-contrast NFL photographs. RESULTS The following were significantly different for glaucomatous patients compared with suspects and normals: mean values of mean deviation (MD, Humphrey 24-2) and corrected pattern standard deviation (CPSD), 11 GDx indices, mean FDT testing time and missed points, and NFL graded defects (ANOVA, Mantel-Haenszel test; p = 0.0001). Using Humphrey 24-2 test results and clinical assessment as the defining features of glaucoma, we found that the optimal mix of sensitivity and specificity values were 84% and 100% for FDT (presence of any defect); 62% and 96% for GDx (The Number, cut-off value of 27); and, 95% and 82% for NFL photographs (presence of any abnormality). FDT testing took the least time to be administered. CONCLUSIONS The FDT had the best diagnostic performance. Neural network analysis of GDx data outperformed other elements of its software.

A randomized trial of intraocular lens fixation techniques with penetrating keratoplasty

PURPOSE Pseudophakic corneal edema is the principal indication for penetrating keratoplasty in the United States. Currently, three techniques of intraocular lens (IOL) fixation during penetrating keratoplasty for this condition are commonly used--flexible anterior chamber IOL (AC IOL) implantation, iris suture fixation of a posterior chamber IOL (PC IOL), and transscleral suture fixation of a PC IOL. This study represents the first prospective, randomized comparison of these three techniques. METHODS One hundred seventy-six consecutive patients with pseudophakic corneal edema who underwent penetrating keratoplasty with IOL exchange were randomized to one of the three implantation techniques. Standardized evaluations were performed at baseline and at 6, 12, and 18 months postoperatively. Life-table analysis provided cumulative risk estimates for specific complications. RESULTS Randomization produced comparable groups at baseline. The cumulative risk of macular edema was significantly less for the iris fixation cohort than for either the AC IOL or scleral fixation group. A complications index was constructed based on the major adverse outcomes of glaucoma escalation, cystoid macular edema, IOL dislocation, and graft failure. A significantly lower risk of complication was found for iris compared with scleral fixation of PC IOLs. CONCLUSION The authors conclude that transscleral fixation of the PC IOL at the time of penetrating keratoplasty for pseudophakic corneal edema is associated with a greater risk of adverse outcome than iris fixation of a PC IOL.

Displacement of the Optic Nerve Head by Acute Changes in Intraocular Pressure in Monkey Eyes

The authors used the Humphrey Retinal Analyzer to study the effect of acute changes in intraocular pressure (IOP) on the topography of the optic nerve head in normotensive and hypertensive eyes of cynomolgus monkeys. Chronically elevated IOP was produced monocularly in monkeys by argon laser angle treatment. In 8 hypertensive eyes, the mean IOP of 51 mmHg was lowered acutely to 15 mmHg with a needle placed in the anterior chamber. In 12 normotensive eyes, the mean IOP of 16 mmHg was similarly increased to 45 mmHg. Simultaneous stereophotographs were taken both before and within 15 minutes after the IOP change. The surface of normotensive optic nerve heads moved posteriorly a mean of 17.8 microns after IOP elevation (P less than 0.02). The surface of hypertensive optic nerve heads moved anteriorly 47.4 microns after IOP lowering (P = 0.1); this change was significantly less in nerve heads with larger and deeper cups (P less than 0.02). Significant changes were not detected in disc diameter or vein diameter with acute changes in IOP. Measurable shifts in the position of the optic nerve head surface when IOP is altered may provide a future prognostic test for glaucomatous optic neuropathy.

Comparison Between Retinal Thickness Analyzer and Optical Coherence Tomography for Assessment of Foveal Thickness in Eyes With Macular Disease

PURPOSE To use the retinal thickness analyzer (RTA) and optical coherence tomography (OCT) scanners for quantitative measurement of retinal thickness in eyes with macular disease. DESIGN In a cross-sectional study, 44 patients (55 eyes) with macular disease and sufficient media clarity to visualize the fundus using clinical biomicroscopy underwent an ophthalmologic examination, fluorescein angiography, RTA, and OCT during the same visit. METHODS Foveal and foveal center (foveolar) retinal thickness measurements were obtained by RTA and by OCT. RESULTS Retinal thickness measurements were obtained by OCT in all 55 eyes and by RTA in 34 eyes (62%, primarily due to interference from media opacities). In the 34 eyes in which measurements were obtained by both instruments, mean foveal thickness was 291 and 269 microm for OCT and RTA, respectively; foveolar thickness was 277 and 265 microm, respectively. OCT and RTA measurements of foveal thickness were strongly correlated (intraclass correlation coefficient = 0.89), as were measurements of the foveolar thickness (intraclass correlation coefficient = 0.94). Topographic maps generated by the two techniques yielded qualitatively similar information. CONCLUSIONS Overall, there was excellent agreement between RTA and OCT measurements. Each technique has advantages that may make its use preferable in a particular subgroup of eyes or to describe a particular disease process. An important consideration is that media opacities create less interference for OCT than for RTA, so that in study populations with a moderate-to-high prevalence of media opacity, images can be obtained in a greater percentage of eyes by OCT than by RTA.