Several mechanisms have been postulated to explain the optic nerve damage that occurs in primary open angle glaucoma (POAG). No single mechanism can adequately explain the great variations in ...susceptibility to damage and the patterns of damage seen in this syndrome. The etiology of POAG is likely to be multifactorial. Mechanical, vascular and other factors may influence individual susceptibility to optic nerve damage. An enhanced understanding of the nature of the optic nerve damage in POAG and improved methods of study may result in earlier diagnosis or may allow us to distinguish among different pathological processes all currently grouped under the diagnosis of POAG. As we gain a better understanding of the neuropharmacology and cellular biology of injury and repair of the visual system we will undoubtedly refine the concepts of glaucomatous optic neuropathy.
The early detection of glaucoma is important in order to enable appropriate monitoring and treatment, and to minimize the risk of irreversible visual field loss. Although advances in ocular imaging ...offer the potential for earlier diagnosis, the best method is likely to involve a combination of information from structural and functional tests. Recent studies have shown it is possible to estimate the number of retinal ganglion cells from optical coherence tomography and standard automated perimetry, and to then pool the results to produce a combined structure-function index (CSFI). The CSFI represents the estimated percentage of retinal ganglion cells lost compared to an age-matched healthy eye. Previous studies have suggested that the CSFI is better able to detect glaucoma than isolated measures of structure and function, and that it performs well even in preperimetric glaucoma. The purpose of this review is to describe new strategies, such as the CSFI, that have the potential to improve the early detection of glaucoma. We also describe how our ability to detect early glaucoma may be further enhanced by incorporating demographic risk factors, clinical examination findings, and imaging and functional test results into intuitive models that provide estimates of disease probability.
To compare short-wavelength automated perimetry, frequency-doubling technology perimetry, and motion-automated perimetry, each of which assesses different aspects of visual function, in eyes with ...glaucomatous optic neuropathy and ocular hypertension.
One hundred thirty-six eyes from 136 subjects were evaluated with all three tests as well as with standard automated perimetry. Fields were not used in the classification of study groups to prevent bias, because the major purpose of the study was to evaluate each field type relative to the others. Seventy-one of the 136 eyes had glaucomatous optic neuropathy, 37 had ocular hypertension, and 28 served as age-matched normal control eyes. Glaucomatous optic neuropathy was defined by assessment of stereophotographs. Criteria were asymmetrical cupping, the presence of rim thinning, notching, excavation, or nerve fiber layer defect. Ocular hypertensive eyes had intraocular pressure of 23 mm Hg or more on at least two occasions and normal-appearing optic disc stereophotographs. Criteria for abnormality on each visual field test were selected to approximate a specificity of 90% in the normal eyes. Thresholds for each of the four tests were compared, to determine the percentage that were abnormal within each patient group and to assess the agreement among test results for abnormality, location, and extent of visual field deficit.
Each test identified a subset of the eyes with glaucomatous optic neuropathy as abnormal: 46% with standard perimetry, 61% with short-wavelength automated perimetry, 70% with frequency-doubling perimetry, and 52% with motion-automated perimetry. In the ocular hypertensive eyes, standard perimetry was abnormal in 5%, short wavelength in 22%, frequency doubling in 46%, and motion in 30%. Fifty-four percent (38/71) of eyes with glaucomatous optic neuropathy were normal on standard fields. However, 90% were identified by at least one of the specific visual function tests. Combining tests improved sensitivity with slight reductions in specificity. The agreement in at least one quadrant, when a defect was present with more than one test, was very high at 92% to 97%. More extensive deficits were shown by frequency-doubling perimetry followed by short-wavelength automated perimetry, then motion-automated perimetry, and last, standard perimetry. However, there were significant individual differences in which test of any given pairing was more extensively affected. Only 30% (11/37) of the ocular hypertensive eyes showed no deficits at all compared with 71% (20/28) of the control eyes (P < 0.001).
For detection of functional loss standard visual field testing is not optimum; a combination of two or more tests may improve detection of functional loss in these eyes; in an individual, the same retinal location is damaged, regardless of visual function under test; glaucomatous optic neuropathy identified on stereophotographs may precede currently measurable function loss in some eyes; conversely, function loss with specific tests may precede detection of abnormality by stereophotograph review; and short-wavelength automated perimetry, frequency-doubling perimetry, and motion-automated perimetry continue to show promise as early indicators of function loss in glaucoma.
To describe the association between pattern electroretinogram (PERG) amplitude and spectral domain-optical coherence tomography (SD-OCT) macular thickness, retinal nerve fibre layer (RNFL) thickness ...and optic disc topography measurements.
Both eyes (n = 132) of 66 glaucoma patients (mean age = 67.9 years) enrolled in the University of California, San Diego, CA, USA, Diagnostic Innovations in Glaucoma Study (DIGS) were included. Eyes were tested with PERG (Glaid PERGLA, Lace Elettronica, Pisa, Italy), RTVue SD-OCT (Optovue Inc., Fremont, CA, USA) GCC, and NHM4 protocols on the same day. Of the 66 enrolled patients, 43 had glaucoma defined by repeated abnormal standard automated perimetry (SAP) results in at least one eye and 23 were glaucoma suspects defined by a glaucomatous-appearing optic disc by physicians' examination in at least one eye and normal SAP results in both eyes. Associations (R(2)) were determined between PERG amplitude (μV) and SD-OCT macular ganglion cell complex (GCC) thickness (μm), macular thickness (μm), macular outer retinal thickness (macular thickness minus GCC thickness) (μm), RNFL thickness (μm), neuroretinal rim area (mm(2)), and rim volume (mm(3)).
PERG amplitude was significantly associated with GCC thickness (R(2) = 0.179, P < 0.001), RNFL thickness (R(2) = 0.174, P < 0.001), and macular thickness (R(2) = 0.095, P<0.001). R(2) associations with other parameters were not significant (all P > 0.624). Significant associations remained for GCC and average RNFL thickness when age and intraocular pressure at the time of testing were included in multivariate models (both P ≤ 0.030).
PERG amplitude is significantly (but weakly) associated with macular GCC thickness, RNFL thickness, and macular thickness. The lack of association between PERG amplitude and macular outer retinal thickness supports previous results, possibly suggesting that that the PERG is driven primarily by retinal ganglion cell (inner retinal) responses.
To evaluate the correlations between office-hour intraocular pressures (IOP) and peak nocturnal IOP in healthy and glaucomatous eyes.
Retrospective review of laboratory records.
We reviewed 24-hour ...data of IOP collected from 33 younger healthy subjects (aged 18 to 25 years), 35 older healthy subjects (aged 40 to 74 years), and 35 untreated older glaucoma patients (aged 40 to 79 years) housed in a sleep laboratory. Measurements of IOP were taken every 2 hours using a pneumatonometer in the sitting and supine positions during the diurnal/wake period (7
am to 11
pm) and in the supine position during the nocturnal/sleep period. Correlations between average sitting or supine IOP in the right eye between 9:30
am and 3:30
pm (office hours) and peak right eye IOP during the nocturnal hours were analyzed.
The average values of supine IOP during office hours were found to have the strongest correlation with peak nocturnal IOP in older glaucoma subjects (
r = .713,
P < .001), whereas the correlation was less in older healthy subjects (
r = .523,
P < .01) and was absent in younger healthy subjects (
r = .224,
P = .21). The correlation between average sitting IOP values during office hours and peak nocturnal IOP was also strong in older glaucoma subjects (
r = .601,
P < .001) and moderate in older healthy subjects (
r = .412,
P < .05), but absent in younger healthy subjects (
r = −.077,
P = .672).
Using a modification of the diurnal IOP curve, the magnitude of peak nocturnal IOP in untreated glaucoma patients can be estimated during routine office visits. Supine IOP measurements estimate peak nocturnal IOP better than sitting measurements. This estimation may provide the clinician with valuable information regarding the nocturnal IOP peak in glaucoma patients.
To evaluate the sensitivity and specificity for discriminating between early to moderate glaucomatous and normal eyes using summary data reports from the Heidelberg Retina Tomograph (HRT), the GDx ...Nerve Fiber Analyzer (GDx), and the Optical Coherence Tomograph (OCT).
Comparative cross-sectional study
One eye each of 50 normal subjects and 39 glaucoma patients with early to moderate visual field damage (mean deviation, −5.04 ± 3.32 dB; range, −0.85 to −13.2 dB).
Three experienced graders masked to patient identity and diagnosis evaluated each summary data report from the HRT, GDx, and OCT independently.
Each summary report was classified as either normal or glaucomatous. Sensitivity and specificity are reported for each grader, and agreement between graders is reported.
For the HRT, sensitivity and specificity ranged from 64% to 75% and 68% to 80%, respectively. Agreement (κ ± standard error SE) between observers one and two, two and three, and one and three was 0.73 ± 0.07, 0.77 ± 0.07, and 0.67 ± 0.08, respectively. For the GDx, sensitivity and specificity ranged from 72% to 82% and 56% to 82%, respectively. Agreement (κ ± SE) between observers one and two, two and three, and one and three was 0.66 ± 0.08, 0.66 ± 0.08, and 0.50 ± 0.09, respectively. For the OCT, sensitivity and specificity ranged from 76% to 79% and 68% to 81%, respectively. Agreement (κ ± SE) between observers one and two, two and three, and one and three was 0.73 ± 0.07, 0.58 ± 0.08, and 0.51 ± 0.09, respectively.
When used alone, HRT, GDx, and OCT summary data reports can differentiate between normal and glaucomatous eyes with mild to moderate visual field loss. However, none of the instruments provided sensitivity and specificity that justify summary data reports being used as a screening tool for early to moderate glaucoma.
To describe a method for assessment and individualized compensation of anterior segment birefringence with scanning laser polarimetry.
A scanning laser polarimeter (GDx Nerve Fiber Analyzer; Laser ...Diagnostic Technologies, Inc., San Diego, CA) was modified to accommodate a variable compensator. The magnitude and axis of anterior segment birefringence of normal eyes were determined from a polarimetry image of the Henle fiber layer. The variable compensator was then adjusted to minimize anterior segment birefringence. Retinal nerve fiber layer (RNFL) and macular measurements were then obtained. Macular images with individualized compensation served to verify the effectiveness of the compensation. To demonstrate individualized compensation, two sets of three images each were obtained from four eyes of four normal subjects. One set was obtained with individualized compensation and another with fixed compensation, as used in the commercial polarimetry system.
In the tested eyes, the magnitude of anterior segment birefringence ranged from 21.7 to 86.3 nm, and the slow axis ranged from 5.7 degrees nasally upward to 54.3 degrees nasally downward. The maximum residual retardation resulting from compensation was 70 nm for fixed compensation and 11.5 nm for individualized compensation. The compensation residual directly affected the assessment of the RNFL by scanning laser polarimetry. RNFL images obtained with individualized compensation were more consistent with the expected anatomy of the eye. In the eyes measured, the range of RNFL thicknesses appeared to be narrower with the variable corneal and lens compensator (VCC) compared with the fixed corneal compensator (FCC).
In eyes with a normal macula, the magnitude and axis of anterior segment birefringence can be determined from a polarimetry image of the Henle fiber layer. Individualized anterior segment compensation can be achieved with the described method so that the measured birefringence largely reflects the RNFL birefringence. Whether and how macular diseases affect this method remain to be investigated.
Rising healthcare costs motivate continued cost-reduction efforts. To help lower costs associated with open-angle glaucoma (OAG), a prevalent, progressive disease with substantial direct and indirect ...costs, clinicians need to understand the cost-effectiveness of intraocular pressure (IOP)-lowering pharmacotherapies. There is little published information on clinicians' knowledge and attitudes about cost-effectiveness in glaucoma treatment.
This pilot focus group study aimed to explore clinician attitudes and perspectives around the costs and cost drivers of glaucoma therapy; the implementation of cost-effectiveness decisions; the clinical utility of cost-effectiveness studies; and the cost-effectiveness of available treatments.
Six US glaucoma specialists participated in two separate teleconferencing sessions (three participants each), managed by an independent, skilled moderator (also a glaucoma specialist) using a discussion guide. Participants reviewed recent publications (n=25) on health economics outcomes research in glaucoma prior to the sessions.
Participants demonstrated a clear understanding of the economic burden of glaucoma therapy and identified medications, diagnostics, office visits, and treatment changes as key cost drivers. They considered cost-effectiveness an appropriate component of treatment decision-making but identified the need for additional data to inform these decisions. Participants indicated that there were only a few recent studies on health economics outcomes in glaucoma which evaluate parameters important to patient care, such as quality of life and medication adherence, and that longitudinal data were scant. In addition to efficacy, participants felt patient adherence and side-effect profile should be included in economic evaluations of glaucoma pharmacotherapy. Recently approved medications were evaluated in this context.
Clinicians deem treatment decisions based on cost-effectiveness data as clinically appropriate. Newer IOP-lowering therapies with potentially greater efficacy and favorable side-effect and adherence profiles may help optimize cost-effectiveness. Future studies should include: clinicians' perspectives; lack of commercial bias; analysis of long-term outcomes/costs; more comprehensive parameters; real-world (including quality-of-life) data; and a robust Markov model.
PURPOSE:To examine the diurnal variation of static and dynamic anterior segment parameters in young, healthy eyes by comparing anterior segment optical coherence tomography (AS-OCT) measurements ...obtained in the morning and evening and also in the light and dark.
METHODS:Twenty-two subjects ranging from 19 to 47 years of age with no past ocular history were selected. Imaging was performed with the Tomey CASIA2 AS-OCT device in 2 fixed lighting environments, light and dark, between the hours of 08:30 to 10:00 and 17:30 to 19:00. Four AS-OCT images were analyzed per eye. Pupil diameter (PD), iris area (IA), iris curvature (IC), anterior chamber depth (ACD), lens vault (LV), anterior chamber width (ACW), anterior chamber area (ACA), angle opening distance (AOD), angle recess area (ARA), trabecular iris space area (TISA), and trabecular iris angle (TIA) were measured.
RESULTS:Pupil diameter was similar between the AM and PM groups in the light (P=0.89) and dark (P=0.51). There was no significant difference between AM and PM measurement values for any of the static or dynamic parameters in the light (P>0.39) and dark (P>0.31). Intraclass correlation coefficients (ICC) demonstrated excellent agreement between AM and PM measurement values in the light (ICC>0.81) and dark (ICC>0.93). In addition, there was no significant difference between AM and PM angle opening distance at 500 µm measurement values in the light (P>0.34) and dark (P>0.40) when each of 8 angle sectors was analyzed individually.
CONCLUSIONS:No significant diurnal variation of static or dynamic anterior segment parameter measurements was detected in the light and dark. Diurnal variation of these parameters does not regularly occur in young, healthy eyes.
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