The rate of structural change: the confocal scanning laser ophthalmoscopy ancillary study to the ocular hypertension treatment study.

PURPOSE: To compare rates of topographic change in ocular hypertensive eyes that develop primary open-angle glaucoma (POAG) compared to eyes that do not, and to identify factors that influence the rate of change. DESIGN: Longitudinal, randomized clinical trial. METHODS: Four hundred forty-one participants (832 eyes) in the Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study were included. POAG was defined as repeatable visual field, photography-based optic disc changes, or both. The rate of topographic change in the 52 participants (66 eyes) who developed POAG was compared with that of participants who did not develop POAG using multivariable mixed effects models. RESULTS: In both univariate and multivariate analyses, the rate of rim area loss was significantly faster in eyes in which POAG developed than in eyes in which it did not (univariate mean, -0.0131 mm(2)/year and -0.0026 mm(2)/year, respectively). The significantly faster rate of rim area loss in black persons found in the univariate analysis did not remain significant when baseline disc area was included in the model. In multivariate analyses, the rate of rim area loss and other topographic parameters also was significantly faster in eyes with worse baseline visual field pattern standard deviation and higher intraocular pressure during follow-up. Moreover, a significant rate of rim area loss was detected in eyes in which POAG did not develop (P < .0001). The rate of rim area loss in eyes with an optic disc POAG endpoint was significantly faster than in those with a visual field POAG endpoint. CONCLUSIONS: The rate of rim area loss is approximately 5 times faster in eyes in which POAG developed compared with eyes in which it did not. These results suggest that measuring the rate of structural change can provide important information for the clinical management of ocular hypertensive patients. Additional follow-up is needed to determine whether the statistically significant change in the eyes in which POAG did not develop represents normal aging or glaucomatous change not detected by conventional methods.

Predicting the onset of glaucoma: the confocal scanning laser ophthalmoscopy ancillary study to theOcular Hypertension Treatment Study.

OBJECTIVE: To evaluate the predictive ability of baseline confocal scanning laser ophthalmoscopy (CSLO) Glaucoma Probability Score (GPS) for the development of primary open-angle glaucoma (POAG) and to compare it with the Moorfields regression analysis (MRA) classification, other topographic optic disc parameters, and stereophotograph-based cup-to-disc ratio. DESIGN: Longitudinal, randomized clinical trial. PARTICIPANTS: We included 857 eyes of 438 participants in the CSLO Ancillary Study to the Ocular Hypertension Treatment Study (OHTS) with good quality baseline CSLO images. METHODS: The ability of baseline GPS, MRA, and optic disc parameters to predict the development of POAG was evaluated in univariate and multivariable proportional hazard ratio analyses. Likelihood ratios and positive and negative predictive values were compared. MAIN OUTCOME MEASURES: The POAG end point as determined by repeatable changes in the visual field or optic disc. RESULTS: Sixty-four eyes of 50 CSLO Ancillary Study participants developed POAG. Median time to reach a POAG end point was 72.3 months. The 93 eyes of 388 participants not reaching endpoint were followed for a median of 124.9 months. Baseline GPS identified many more eyes as outside normal limits than the MRA. In multivariable analyses, all regional and global baseline GPS indices were significantly associated with the development of POAG; hazard ratios (95% confidence interval) ranged from 2.92 to 3.74 for an outside normal limits result. The MRA indices were also significantly associated with the development of POAG in multivariable analyses. In addition, the predictive ability of baseline GPS, MRA and stereometric parameters were similar to the predictive ability of models using photograph-based horizontal cup-to-disc ratio. CONCLUSIONS: These results suggest that baseline GPS, MRA, and stereoparameters alone or when combined with baseline clinical and demographic factors can be used to predict the development of POAG end points in OHTS participants and are as effective as stereophotographs for estimating the risk of developing POAG in ocular hypertensive subjects.

Long-term survival of central visual field in end-stage glaucoma.

PURPOSE: To evaluate the long-term survival of visual field and visual acuity in treated glaucoma patients with end-stage glaucomatous visual field loss defined by a field constricted to a 10-degree radius or less. DESIGN: Retrospective chart review. PARTICIPANTS: Sixty-four patients with end-stage glaucoma. METHODS: Serial 10-2 Humphrey visual fields with size III stimulus were analyzed. The following data were recorded for each visual field: mean deviation (MD), pattern standard deviation, the largest horizontal and vertical diameters measured in degrees including only locations with thresholds of 10 decibels or more, and the number of points on the pattern deviation plot with a probability value of more than 5%. MAIN OUTCOME MEASURE: Change in visual acuity and visual field. RESULTS: Eighty-four eyes of 64 patients satisfied inclusion criteria with an average follow-up of 8.34+/-3.1 years. Seventy-eight percent of patients were black. During the study period, 14 eyes lost more than 3 lines of visual acuity. Of these 14, 8 eyes progressed to a visual acuity of 20/200 or worse. Seven eyes lost 3 decibels or more from the MD that could be reproduced over 2 visual fields. CONCLUSIONS: In this predominantly black population, most treated patients with end-stage glaucoma did not demonstrate a decline in visual acuity or progressive loss of the central visual field during long-term follow-up.

Central corneal thickness and corneal diameter in patients with childhood glaucoma.

PURPOSE: To determine and compare the central corneal thickness (CCT) and corneal diameter among groups of patients with childhood glaucomas and assess the relationship between CCT and corneal diameter in these patients. DESIGN: A multicenter observational case series using prospective and retrospective data. METHODS: Patients from the Scheie Eye Institute, Children's Hospital of Philadelphia, and Emory and Vanderbilt Medical Centers with childhood glaucomas were eligible to participate. Retrospective data on CCT and corneal diameter of these patients were collected when available; otherwise, patients were asked to return to the ophthalmology clinics for measurements. Patients with corneal edema or central corneal scarring were excluded. One hundred eighty four glaucomatous eyes from 109 patients (median age = 9.0 y; age range = 0 to 60 y) were included. RESULTS: The mean CCT (+/-SE) was 651.1+/-63.5 microm for aphakic, 528.7+/-38.5 microm for Axenfeld-Rieger, and 563.4+/-67.9 microm for 1 degrees infantile eyes. The mean corneal diameter in aphakic, Axenfeld-Rieger, and 1 degrees infantile glaucoma eyes were 11.2+/-1.0, 12.5+/-0.9, and 13.2+/-1.2 mm, respectively. There was a significant difference in CCT and in corneal diameter between aphakic and 1 degrees infantile glaucoma eyes, and between aphakic and Axenfeld-Rieger eyes (P < 0.0001). There was a negative correlation between CCT and corneal diameter in all eyes (r = -0.41, P < 0.0001). CONCLUSIONS: Patients with aphakic glaucoma are different from those with congenital glaucoma or Axenfeld-Rieger in CCT and corneal diameter. A patient with pediatric glaucoma and a larger corneal diameter was more likely to have a thinner CCT. Attention should be paid to the CCT of patients with childhood glaucomas for interpretation of intraocular pressure.

Detection and prognostic significance of optic disc hemorrhages during the Ocular Hypertension Treatment Study.

PURPOSE: To compare the rates of detection of optic disc hemorrhages by clinical examination and by review of optic disc photographs at the Optic Disc Reading Center (ODRC), to assess the incidence of and the predictive factors for disc hemorrhages in the annual disc photographs of the Ocular Hypertension Treatment Study (OHTS), and to determine whether optic disc hemorrhages predict the development of primary open-angle glaucoma (POAG) in the OHTS. DESIGN: Cohort study. PARTICIPANTS: Three thousand two hundred thirty-six eyes of 1618 participants. METHODS: Both eyes of participants were examined for optic disc hemorrhages every 6 months by clinical examination, with dilated fundus examinations every 12 months, and by annual review of stereoscopic disc photographs at the ODRC. MAIN OUTCOME MEASURES: Incidence of optic disc hemorrhages and POAG end points. RESULTS: Median follow-up was 96.3 months. Stereophotography-confirmed glaucomatous optic disc hemorrhages were detected in 128 eyes of 123 participants before the POAG end point. Twenty-one cases (16%) were detected by both clinical examination and review of photographs, and 107 cases (84%) were detected only by review of photographs (P<0.0001). Baseline factors associated with disc hemorrhages were older age, thinner corneas, larger vertical cup-to-disc ratio, larger pattern standard deviation index on perimetry, family history of glaucoma, and smoking status. The occurrence of a disc hemorrhage increased the risk of developing POAG 6-fold in a univariate analysis (P<0.001; 95% confidence interval, 3.6-10.1) and 3.7-fold in a multivariate analysis that included baseline factors predictive of POAG (P<0.001; 95% confidence interval, 2.1-6.6). The 96-month cumulative incidence of POAG in the eyes without optic disc hemorrhage was 5.2%, compared with 13.6% in the eyes with optic disc hemorrhage. In eyes with a disc hemorrhage in which a POAG end point developed, the median time between the 2 events was 13 months. CONCLUSIONS: Review of stereophotographs was more sensitive at detecting optic disc hemorrhage than clinical examination. The occurrence of an optic disc hemorrhage was associated with an increased risk of developing a POAG end point in participants in the OHTS. However, most eyes (86.7%) in which a disc hemorrhage developed have not experienced a POAG end point to date.

Cardiovascular risk factors and events in glaucoma patients with peripapillary focal arteriolar narrowing.

PURPOSE: To evaluate cardiovascular risk factors and events in glaucoma patients with and without peripapillary focal arteriolar narrowing of retinal vessels. METHODS: We examined the fundus photographs of 325 consecutive glaucoma patients for evidence of focal arteriolar narrowing of retinal vessels adjacent to the optic disc. Cases and controls were matched for age, race, sex and mean deviation on Humphrey visual field. Medical information regarding cardiovascular risk factors and events was collected from patients' primary care physicians, and this information was confirmed by questionnaires sent to the patients themselves. RESULTS: A total of 58 pairs of cases and controls were matched. The prevalence of hypertension and diabetes was exactly equal in both groups, 65.5% and 27.6%, respectively. Similarly, the prevalences of myocardial infarction, cardiac surgery, angioplasty, family history of heart disease and smoking were nearly identical in both groups. There was no significant difference in the prevalence of strokes or transient ischaemic attacks. The prevalence of hypercholesterolemia and mortality was greater in the case group (mean differences of 8.6, p = 0.42 and 5.2, p = 0.25, respectively), however, these differences were not statistically significant. CONCLUSION: There is no significant relationship between peripapillary focal arteriolar narrowing of retinal vessels and cardiovascular risk factors or events in patients with glaucoma. Proximal narrowing does not appear to be a marker of systemic vascular disease.

A multicenter, retrospective pilot study of resource use and costs associated with severity of disease in glaucoma.

OBJECTIVE: To examine resource consumption and the direct costs of treating glaucoma at different disease severity levels. DESIGN: Observational, retrospective cohort study based on medical record review. PARTICIPANTS: One hundred fifty-one records of patients with primary open-angle or normal-tension glaucoma, glaucoma suspect, or ocular hypertension (age > or =18 years) were randomly selected from 12 sites in the United States and stratified according to severity based on International Classification of Diseases, Ninth Revision, Clinical Modification codes. Patients had to have been followed up for a minimum of 5 years. Patients with concomitant ocular disease likely to affect glaucoma treatment-related resource consumption were excluded. METHODS: Glaucoma severity was assessed and assigned using a 6-stage glaucoma staging system, modified from the Bascom Palmer (Hodapp-Anderson-Parrish) system. Clinical and resource use data were collected from the medical record review. Resource consumption for low-vision care and vision rehabilitation was estimated for patients with end-stage disease based on specialist surveys. For each stage of disease, publicly available economic data were then applied to assign resource valuation and estimate patient-level direct costs from the payer perspective. MAIN OUTCOME MEASURES: Average annual resource use and estimated total annual direct cost of treatment were calculated at the patient level and stratified by stage of disease. Direct costs by specific resource types, including ophthalmology visits, glaucoma surgeries, medications, visual field examinations, and other glaucoma services, were also assessed. RESULTS: Direct ophthalmology-related resource use, including ophthalmology visits, glaucoma surgeries, and medication use, increased as disease severity worsened. Average direct cost of treatment ranged from $623 per patient per year for glaucoma suspects or patients with early-stage disease to $2511 per patient per year for patients with end-stage disease. Medication costs composed the largest proportion of total direct cost for all stages of disease (range, 24%-61%). CONCLUSIONS: The study results suggest that resource use and direct cost of glaucoma management increase with worsening disease severity. Based on these findings, a glaucoma treatment that delays the progression of disease could have the potential to significantly reduce the health economic burden of this chronic disease over many years.

Baseline topographic optic disc measurements are associated with the development of primary open-angle glaucoma: the Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study.

OBJECTIVE: To determine whether baseline confocal scanning laser ophthalmoscopy (CSLO) optic disc topographic measurements are associated with the development of primary open-angle glaucoma (POAG) in individuals with ocular hypertension. METHODS: Eight hundred sixty-five eyes from 438 participants in the CSLO Ancillary Study to the Ocular Hypertension Treatment Study with good-quality baseline CSLO images were included in this study. Each baseline CSLO parameter was assessed in univariate and multivariate proportional hazards models to determine its association with the development of POAG. RESULTS: Forty-one eyes from 36 CSLO Ancillary Study participants developed POAG. Several baseline topographic optic disc measurements were significantly associated with the development of POAG in both univariate and multivariate analyses, including larger cup-disc area ratio, mean cup depth, mean height contour, cup volume, reference plane height, and smaller rim area, rim area to disc area, and rim volume. In addition, classification as "outside normal limits" by the Heidelberg Retina Tomograph classification and the Moorfields Regression Analysis classifications (overall, global, temporal inferior, nasal inferior, and superior temporal regions) was significantly associated with the development of POAG. Within the follow-up period of this analysis, the positive predictive value of CSLO indexes ranged from 14% (Heidelberg Retina Tomograph classification and Moorfields Regression Analysis overall classification) to 40% for Moorfields Regression Analysis temporal superior classification. CONCLUSIONS: Several baseline topographic optic disc measurements alone or when combined with baseline clinical and demographic factors were significantly associated with the development of POAG among Ocular Hypertension Treatment Study participants. Longer follow-up is required to evaluate the true predictive accuracy of CSLO measures.

Intermittent headaches as the presenting sign of subacute angle-closure glaucoma.

Subacute angle closure causes intermittent episodes of transiently elevated intraocular pressure. Headache is often the chief complaint, which may lead to misdiagnosis. The authors examined headache characteristics and consequences of delayed diagnosis. Patients presenting with headaches have a substantial delay in diagnosis, contributing to permanent ocular damage and glaucoma. Patients with subacute angle closure misdiagnosed with migraine are older and have shorter-duration headaches than patients with typical migraine.

The confocal scanning laser ophthalmoscopy ancillary study to the ocular hypertension treatment study: study design and baseline factors.

PURPOSE: To describe the study design of the Confocal Scanning Laser Ophthalmoscopy (CSLO) Ancillary Study to the Ocular Hypertension Treatment Study (OHTS) and to examine the associations between optic disk topography, and baseline demographic, clinical, and ocular factors at study entry. DESIGN: A randomized clinical trial. METHODS: Participants in this ancillary study were recruited from seven of the 22 OHTS clinical centers. Each participant completed imaging annually using a CSLO, the Heidelberg Retina Tomograph (HRT). Associations between HRT topographic optic disk measurements and intraocular pressure (IOP), baseline photographic estimates of horizontal and vertical cup-to-disk diameter ratios by the OHTS Optic Disk Reading Center, baseline visual field indices, and demographic and clinical factors were assessed using linear mixed effects models. RESULTS: Four hundred thirty-nine participants had good quality images and were included in this baseline analysis. No associations between HRT topographic optic disk measurements and diabetes, systemic hypertension, cardiovascular disease, IOP, or visual function were found. The HRT topographic optic disk measurements were associated with baseline stereophotographic estimates of horizontal and vertical cup-to-disk diameter ratios. The strongest associations were found between stereophotographic assessment of horizontal and vertical cup-to-disk diameter ratios, and HRT cup-to-disk area ratio (r =.85 and.84, respectively), rim-to-disk area ratio (r = -.85 and -.84, respectively), mean cup depth (r =.84 and.83, respectively), and cup area (r =.83 and.80, respectively). After adjusting for optic disk area, all HRT topographic optic disk measurements remained associated with stereophotographic assessment of horizontal and vertical cup-to-disk diameter ratios. CONCLUSIONS: The CSLO ancillary study to the OHTS is the first multicenter clinical trial to use CSLO imaging to monitor changes in the optic disk. At study entry, HRT topographic measurements corresponded well with both horizontal and vertical stereophotographic-based estimates of cup-to-disk diameter ratio in ocular hypertensive participants.

Racial differences in optic disc topography: baseline results from the confocal scanning laser ophthalmoscopy ancillary study to the ocular hypertension treatment study.

OBJECTIVE: To examine racial differences in optic disc topography among ocular hypertensive participants in the Ocular Hypertension Treatment Study. METHODS: Four hundred thirty-nine participants from 7 Ocular Hypertension Treatment Study centers who had good-quality baseline images obtained using a quantitative 3-dimensional confocal scanning laser ophthalmoscope, the Heidelberg Retina Tomograph (Heidelberg Engineering, Dossenheim, Germany), were included in this study. The first 10 degrees- or 15 degrees-field of view mean topographic image acquired was included in all analyses. Differences in Heidelberg Retina Tomograph topographic optic disc parameter measurements by self-identified race were assessed using a mixed-effects linear model to control for confounders and for the use of both eyes in the model. RESULTS: By self-attribution, 74 (17%) of the 439 participants were of African origin, 329 (75%) were white, 24 (5%) were Hispanic, and 12 (3%) were Native American, Native Alaskan, Asian, Pacific Islander, or unknown. The African American participants had statistically significantly (P<.001) larger mean (SD) optic disc areas than the other participants, 2.17 (0.41) mm(2) vs 1.87 (0.38) mm(2), respectively. African American participants had a larger cup area, cup volume, cup depth, neuroretinal rim area, rim volume, and smaller rim-optic disc area ratios than the other participants. No difference between African American and the other participants was found for cup shape and retinal nerve fiber layer thickness. After controlling for optic disc area, none of the differences between African American and the other participants found in the univariate analysis remained statistically significant (P>.10). CONCLUSIONS: This study demonstrated in a large cohort of subjects with ocular hypertension, that African Americans have significantly larger optic discs, optic cups, neuroretinal rims, and cup-disc ratios than other racial groups. Furthermore, this study found that differences in topographic optic disc parameters between African Americans with ocular hypertension and other racial groups are largely explained by the larger optic disc area in the African Americans. These results highlight the need to consider race and optic disc size when evaluating the appearance of the optic disc in glaucoma.

Collaborative Initial Glaucoma Treatment Study: a summary of results to date.

PURPOSE OF REVIEW: This review summarizes the key findings from the Collaborative Initial Glaucoma Treatment Study (CIGTS), which was designed to evaluate whether medical therapy or trabeculectomy is the better initial treatment for patients with open-angle glaucoma (OAG). In addition to examining effects on visual field progression, intraocular pressure control, and visual acuity, the study also examined the effects of medical and surgical treatments on quality of life. RECENT FINDINGS: The 4+-year interim outcomes noted no significant difference in visual field loss between the medically and surgically treated patients. Patients assigned to trabeculectomy had lower intraocular pressures, but demonstrated a greater risk for significant loss of visual acuity and a threefold increased rate of cataract progression. Most quality-of-life measurements were similar in the two treatment arms, except local eye symptoms, which were reported more frequently by the surgically treated patients. SUMMARY: Results from CIGTS do not support altering current treatment practices in the initial management of patients with primary open-angle glaucoma.

An unusual case of uveitis-glaucoma-hyphema syndrome.

PURPOSE: To report a case of uveitis-glaucoma-hyphema (UGH) syndrome in which anterior chamber paracentesis led to the diagnosis of sickle cell trait. DESIGN: Observational case report. METHODS: A 43-year-old Cuban pseudophakic male was seen multiple times over a 3-year period complaining of floaters and blurry vision in his left eye. He was noted to have an inferotemporally displaced posterior chamber intraocular lens and recurrent microhyphemas with elevated intraocular pressure (IOP) readings between 29 and 46 mm Hg with each episode. He was diagnosed with UGH syndrome. Posterior chamber intraocular lens explantation and anterior chamber washout was performed. The aqueous fluid was submitted for cytopathologic examination. RESULTS: Postoperatively, the patient's symptoms resolved and he had no further hemorrhages or elevated IOP readings. Cytopathology of the aspirate revealed sickled red blood cells. CONCLUSIONS: Microscopic examination of aqueous fluid can be a valuable tool in diagnosing ophthalmic manifestations of systemic disease.

Visual field loss in patients with glaucoma who have asymmetric peripapillary focal arteriolar narrowing.

OBJECTIVE: To evaluate the relationship between peripapillary focal arteriolar narrowing and visual field defects. METHODS: From our institutional practice, we identified 31 patients with glaucoma who had peripapillary focal arteriolar narrowing in only one eye and compared visual field data between the two eyes. Mean deviation (MD) and corrected pattern standard deviation (CPSD) were recorded using Humphrey visual field testing at the time proximal narrowing was apparent on the fundus photograph. Visual field data from subsets of patients with mild and severe narrowing were also compared. RESULTS: The MD and CPSD were significantly worse in eyes with peripapillary focal arteriolar narrowing. The eyes with narrowing exhibited a mean MD of -8.77 +/- 8.27 dB and a mean CPSD of 5.01 +/- 3.42 dB. Eyes without narrowing displayed a mean MD of -4.52 +/- 6.64 dB and a mean CPSD of 3.01 +/- 2.68 dB (P =.003 for both). There was no significant difference in severity of the visual field defect between eyes with mild and severe arteriolar narrowing. CONCLUSION: To our knowledge, this is the first study to show that the presence of peripapillary focal arteriolar narrowing is related to the severity of visual field loss in patients with glaucoma.