The number of people with glaucoma worldwide in 2010 and 2020.

AIM: To estimate the number of people with open angle (OAG) and angle closure glaucoma (ACG) in 2010 and 2020. METHODS: A review of published data with use of prevalence models. Data from population based studies of age specific prevalence of OAG and ACG that satisfied standard definitions were used to construct prevalence models for OAG and ACG by age, sex, and ethnicity, weighting data proportional to sample size of each study. Models were combined with UN world population projections for 2010 and 2020 to derive the estimated number with glaucoma. RESULTS: There will be 60.5 million people with OAG and ACG in 2010, increasing to 79.6 million by 2020, and of these, 74% will have OAG. Women will comprise 55% of OAG, 70% of ACG, and 59% of all glaucoma in 2010. Asians will represent 47% of those with glaucoma and 87% of those with ACG. Bilateral blindness will be present in 4.5 million people with OAG and 3.9 million people with ACG in 2010, rising to 5.9 and 5.3 million people in 2020, respectively. CONCLUSIONS: Glaucoma is the second leading cause of blindness worldwide, disproportionately affecting women and Asians.

Neuronal death in glaucoma.

Glaucoma is recognized to have its major detrimental effect upon the eye by killing retinal ganglion cells. The process of cell death appears to be initiated at the optic nerve head, though other sites of injury are possible but unsubstantiated. At present the injury at the nerve head seems related to the level of the eye pressure, but its detailed mechanism is as yet unexplained. There is a greater loss of ganglion cells from some areas of the eye, and this feature of glaucoma seems related to the regional structure of the supporting connective tissues of the optic nerve head. Larger retinal ganglion cells have been consistently shown to have somewhat greater susceptibility to injury in glaucoma, though all cells are injured, even early in the process. Ganglion cells die by apoptosis in human and experimental glaucoma, opening several potential areas for future therapies to protect them from dying. Neurotrophin deprivation is one possible cause of cell death and replacement therapy is a potential approach to treatment.

Undetected eye disease in a primary care clinic population.

BACKGROUND: Population-based data have indicated that a significant proportion of persons with undiagnosed ocular disease in the community are regular users of general medical services. This, combined with the high prevalence of chronic medical disorders known to be risk factors for ocular disease in such clinics, makes them an attractive site for screening. METHODS: The prevalence of ocular disease was estimated in a sample of 405 general medicine patients attending an adult primary care clinic in an urban teaching hospital. RESULTS: Overall, 205 (50.6%) of 405 patients were found to have clinically important ocular pathology. One third of those affected (n = 68) were unaware of their eye disease, and 26% (n = 18) of these 68 patients required immediate medical or surgical intervention. Patients 65 years or older (odds ratio [OR], 1.76), in fair or poor general health (OR, 1.78), with diabetes mellitus (OR, 2.07), or with self-reported fair or poor vision (OR, 3.03), were at increased risk for the presence of ocular disease. Among patients with eye disease, those who had no insurance coverage for eye care (OR, 3.45), those who had not had an eye examination during the previous 2 years (OR, 4.03), and those whose last eye examination was performed by an optometrist (OR, 7.25, reference ophthalmologist) were more likely to not be aware of their eye disease. CONCLUSIONS: Our results underscore the importance of screening for ocular disease in primary health care settings, especially for patients who are older than 65 years, are in poor health, report poor vision, have had infrequent eye examinations, or have inadequate insurance coverage for eye care.

Gap junctions between optic nerve head astrocytes.

Astrocytes of the primate and human optic nerve head are joined to each other by the gap junction type of intercellular membrane specialization. Although the precise function of these contacts is not fully determined, they may serve such diverse roles as adhesive bonding and intercellular electrical and chemical coupling.

Models of open-angle glaucoma prevalence and incidence in the United States.

PURPOSE: To estimate the prevalence and incidence of open-angle glaucoma among black and white persons in the United States and to characterize quantitatively their life experience with glaucoma using a life table approach to estimate disease duration. METHODS: Review of published data on glaucoma combined with statistical models to estimate prevalence and incidence. RESULTS: The association of open-angle glaucoma with age was examined separately for white and black persons. By the year 2000, the number of persons in the United States with primary open-angle glaucoma is estimated to be 2.47 million (1.84 million white and 619,000 black Americans). A model using derived incidence rates for open-angle glaucoma (OAG) and United States mortality data indicated that the average black American has OAG 27% longer than the average white American (16.3 years compared to 12.8 years). CONCLUSIONS: Meta-analysis to obtain pooled prevalence estimates for glaucoma provides useful information on length of disease and age distribution of those affected. It may assist in estimating treatment effects and associated costs to derive data that effect health care decisions.

Laser energy levels for trabecular meshwork damage in the primate eye.

The authors treated the trabecular meshwork of 17 primate eyes with the argon laser by a variety of protocols in an attempt to cause moderate, consistent intraocular pressure elevation. This was achieved most satisfactorily with deliveries of 0.5 to 1.0 seconds and a total energy of at least 50 joules. The method allows production of a satisfactory laser-induced model of chronic glaucoma with one treatment session in most eyes. This experience provides a measure of the upper limit of acceptable total laser energy for therapeutic procedures in humans with this instrument. Delivery durations longer than 0.1 sec should be used with caution in trabeculoplasty.

Chronic experimental glaucoma in primates. I. Production of elevated intraocular pressure by anterior chamber injection of autologous ghost red blood cells.

Chronic elevations of intraocular pressure (IOP) were produced in rabbit and monkey eyes by anterior chamber injection of autologous fixed red blood cells. The method confirms the possibility of secondary glaucoma due to trabecular obstruction by ghost cells in eyes with intraocular hemorrhage. In primates, decreased aqueous outflow may result from direct obstruction by free cells and macrophages as well as swelling of trabecular endothelium following phagocytosis of cellular debris. IOP elevations for from 2 days to greater than 1 month were produced in order to study the effects of elevated IOP on ocular tissues. The model has the advantages of producing IOP elevation easily and without associated intraocular inflammation. The extensive filling of the anterior chamber necessary to produce IOP rises in healthy animal eyes leads to the disadvantage of poor visibility of the optic disk. In rabbit eyes, chronic IOP elevation leads to corneal enlargement and ectasia, making IOP measurements difficult.

Chronic experimental glaucoma in primates. II. Effect of extended intraocular pressure elevation on optic nerve head and axonal transport.

Intraocular pressure (IOP) elevations lasting from 2 to 42 days were produced in 13 primate eyes by anterior chamber injections of autologous, fixed red blood cells. The retina, optic nerve head, and optic nerves were studied by electron microscopy, and ganglion cell rapid axonal transport was examined after IOP elevations for various durations. Transport of axonal material was blocked at the scleral lamina cribrosa by IOP elevations to 50 mm Hg. With IOP elevation for less than 1 week, return to normal IOP restored normal transport in some axons. However, in other axons IOP elevation for less than 1 week intiated ganglion cell degeneration. The process of cellular death involved a rapid ascending degeneration from nerve head to brain, followed 3 to 4 weeks later by descending degeneration of the ganglion cell body and its attached axon. Axons of the superior and inferior optic nerve head and nerve seem to be damaged more extensively than those in the nasal and temporal optic nerve. Two to four days after IOP elevation, axons of the superficial optic nerve head were swollen with accumulating axonal material, leading to histologic disk edema. In those eyes with IOP elevation longer than 1 week, the loss of anterior disk nerve fibers combined with posterior and lateral movement of the lamina cribrosa lead to an increase in optic disk cupping. Astrocytes and capillaries of the optic nerve head seem to tolerate elevated IOP well and were relatively spared.

Distribution of axonal transport blockade by acute intraocular pressure elevation in the primate optic nerve head.

We studied the degree of axonal transport blockade in various areas of the optic nerve head with acute intraocular pressure (IOP) elevation in 19 squirrel monkey eyes. When IOP was raised to 20 to 50 mm. Hg for 7 hr., mild axonal transport blockade occurred in each area of the disk, most prominently in nerve fiber bundles of the superior pole. With 7 hr. IOP elevations between 50 and 90 mm. Hg, a somewhat greater degree of transport blockade occurred throughout the nerve head, although again the superior and inferior poles were somewhat more affected. The distribution of short-term transport blockade over the entire nerve head corresponds to the diffuse damage of acute glaucoma, but the pattern hints at the preference for damage near the poles of the disk seen in chronic glaucoma. However, before these results can be fully evaluated, further information is needed on axonal pathways through the optic nerve head and on the relationship between transport obstruction and ganglion cell death.

Retinal ganglion cell loss is size dependent in experimental glaucoma.

Thirty-two areas located in the temporal midperipheral retina were evaluated in whole-mount preparations from four monkeys with monocular experimental glaucoma. Diameter frequency distributions of remaining ganglion cells in the glaucomatous eye were compared with corresponding areas in the normal fellow eye. Large cells were significantly more vulnerable at each stage of cell damage as determined by linear-regression analysis. The magnitude of size-dependent loss was moderate at an early stage (20% loss), peaked at 50% total cell loss, and decreased in advanced damage (70% loss). In glaucomatous eyes, the lower retina had significantly more large cell loss than the corresponding areas of the upper retina. In optic nerve zones that matched the retinal areas studied, large axons selectively were damaged first. Psychophysical testing aimed at functions subserved by larger ganglion cells is recommended for detection and follow-up of early glaucoma; however, assessment of functions unique to small cells is more appropriate for detecting change in advanced glaucoma.

Foveal ganglion cell loss is size dependent in experimental glaucoma.

PURPOSE: The purpose of this study was to study the pattern of foveal ganglion cell loss in experimental glaucoma. METHODS: Retinal ganglion cell size and number in the foveal region of seven monkey eyes with experimental glaucoma was determined and compared to normal monkey eyes. Serial sections of macular retina were studied in two regions: the plateau of peak density of ganglion cells (800-1100 microns from the fovea), and within 500 microns of the foveal center. RESULTS: In normal eyes, cell densities were 37,900 +/- 2700 in the foveal plateau and 17,200 +/- 1800 cells/mm2 in the foveal center. There was selective loss of larger ganglion cells in glaucoma eyes. The degree of foveal ganglion cell loss was significantly correlated to the degree of nerve fiber loss in the temporal optic nerve of the same eye. CONCLUSIONS: Detection of early, central visual function loss in glaucoma could be enhanced by testing functions subserved by larger retinal ganglion cells.

Repeatability of the Glaucoma Hemifield Test in automated perimetry.

PURPOSE: To examine the concordance of the Glaucoma Hemifield Test and other global visual field indexes between two consecutive automated visual field tests. METHODS: Normal subjects, subjects with ocular hypertension, and subjects with glaucoma had two automated visual field tests on the Humphrey Field Analyzer. The Glaucoma Hemifield Test results, mean deviation, and corrected pattern standard deviation of the two consecutive visual field tests were compared. RESULTS: Forty-one normal subjects were tested within 1 and 2 years of each other. Four hundred seven subjects with ocular hypertension and 95 subjects with glaucoma were tested 1 year apart. The proportion of normal subjects who met a criterion for abnormality on two consecutive tests was 2.4%. The proportion of subjects with glaucoma with normal results of two tests was 10.5%. The specificity of automated visual field testing was improved from 80.8% to 89.9%, with a modest loss of sensitivity if two rather than one abnormal test result was required for entry into a clinical trial enrolling patients with glaucomatous field loss. Similarly, specificity increased from 84.2% to 89.5% if two normal tests were required for entry into an ocular hypertensive clinical trial. Among subjects with more closely spaced tests, the agreement between consecutive tests was similar for tests spaced 4 versus 12 months apart. CONCLUSIONS: Although there is concordance of Glaucoma hemifield Test results on consecutive testing, there is enough disagreement to result in improved specificity from the use of a second test in a clinical trial setting.

The effect of biogenic monomines on rapid axonal transport in the rabbit optic nerve.

Since L-dopa and serotonin have been reported to increase the rate of axonal transport in rat sciatic nerve, we decided to study the effect of these monoamines on rapid orthograde transport in the rattit optic nerve. To do this, tritiated leucine was injected into the vitreous of both eyes of 56 albino rabbits, and arrival of radioactive labeled proteins at the superior colliculus was measured at various intervals by liquid scintillation counting. Rabbits were studied 24 hr after intraperitoneal injections of (1) Sinemet + L-dopa, (2) Sinemet + 5-hydroxytryptophan, or (3) pargyline. There were 14 rabbits in each group compared to 14 controls that received no monoamies. In the monoamine-treated groups, transported labeled proteins arrived at the superior colliculus earlier, and an increased amount of radioactivity accumulated during the next several hours. The maximum amount of radioactive proteins accumulating in drug-treated animals did not differ significantly from the maximum amount in control animals. As judged by autoradiographic densitometry, retinal ganglion cell synthesis was similar in control and drug-treated animals. We suspect that the rate of rapid axonal transport is increased by monoamines, although an increased rate of ganglion cell protein synthesis is another possibility.

Analysis of progressive change in automated visual fields in glaucoma.

PURPOSE: To detect and estimate the rate of progression of visual field loss in subjects with glaucoma who undergo long-term automated perimetric visual field testing. METHODS: Automated visual field data were obtained for subjects with glaucomatous visual field loss and a minimum of seven threshold field tests over at least 4.5 years. Univariate linear regression was performed with respect to mean deviation (MD), corrected pattern standard deviation (CPSD), mean thresholds of clusters corresponding to the Glaucoma Hemifield Test (GHT), and thresholds of 52 individual test locations. Subjects were classified as progressive or stable (unchanged or improved) based on the slope and statistical significance of these parameters. Adjusted P values were used to maintain the overall type 1 error at 5%. RESULTS: One hundred ninety-one subjects with a mean follow-up period of 7.1 years (range, 4.5 to 10.5 years) and a mean number of visual field tests of 9.5 (range, 7 to 16) were included. Twenty-four subjects (12.6%) showed progression in MD (mean slope [95% confidence interval], -1.26 [-1.50, -1.01] dB/year), and 27 (14.1%) showed progression in CPSD (mean slope [95% confidence interval], 0.71 [0.58, 0.84] dB/year). Thirty-five subjects (18.3%) had > or = 1 progressive GHT cluster. The mean slope in progressive clusters ranged from -1.51 [-1.82, -1.20] to -2.84 [-3.39, -2.29] dB/year. Thirty-six subjects (18.8%) had > or = 1 progressive individual test locations. Fifty-two subjects (27.2%) were classified as progressive based on progression of CPSD, > or = 1 cluster and/or > or = 1 point. CONCLUSIONS: Fewer than 1 in 3 subjects progressed by any one of the criteria for progression over an average of 7.1 years. Rates of progression that could be statistically confirmed were in the range of approximately 1 to 5 dB/year, depending on the number of fields, the variability over time, and the parameter assessed (global indices, GHT clusters, or individual points). No correlation between initial visual field status and the rate of progression was found. A minimum of approximately 5 years of follow-up with annual perimetry would be required to detect significant changes in the visual field by linear regression.

Selective effects of experimental glaucoma on axonal transport by retinal ganglion cells to the dorsal lateral geniculate nucleus.

Rapid-phase axonal transport to the dorsal lateral geniculate nucleus (dLGN) was determined autoradiographically in seven macaque monkey eyes with chronic intraocular pressure (IOP) elevation, in four eyes with an acute IOP elevation, and in three eyes with normal IOP. The monkeys with chronic IOP elevation showed a greater decrease in radioactive labeling of the magnocellular layers of the dLGN than the parvocellular layers by qualitative examination. Grain counts in selected specimens confirmed that transport to the magnocellular layers was less than to the parvocellular layers in monkeys with chronic IOP elevation. This selectivity was present in mildly damaged specimens and increased with greater ganglion cell loss. In monkeys with acute IOP elevation, qualitative evaluation suggested no consistent difference in transport among the dLGN layers; one animal in this group had less transport to the parvocellular than to the magnocellular layers by grain counts. Starting in early stages of the disease, chronic experimental glaucoma causes preferential damage to the ganglion cells that project to the magnocellular layers of the dLGN.

D-penicillamine and beta-aminopropionitrile effects on experimental filtering surgery.

We studied the effect of two compounds, beta-aminopropionitrile (BAPN) and D-penicillamine on the success of experimental glaucoma filtering surgery in cynomolgus monkeys. All animals had laser-induced glaucoma and underwent punch sclerectomy operations. Eyes treated with BAPN or D-penicillamine maintained successful filtration for at least 3 days longer than nondrug-treated controls. This effect, while statistically significant (P less than 0.05), was temporary. The lack of more substantial improvement in prolonging filtering patency may have resulted from an inadequate effective drug concentration. Alternatively, these drugs may have limited potency because their action on new collagen synthesis affects only a minor component of the healing process that causes filter failure.

The number and diameter distribution of axons in the monkey optic nerve.

Using an automated image analysis system, cross-sections from optic nerves of 17 normal cynomolgus monkeys were examined. The number of nerve fibers, their density, and the distribution of their diameters for whole nerves and for various regions of the nerve cross-section were estimated. The mean total number of fibers in the optic nerve was 1.2 million. The mean diameter of axons was 0.8 micron. The method of tissue fixation substantially affected the measurements. Histograms of fiber diameter suggested a trimodal distribution of fiber size with peaks at 0.5, 0.8, and 1.5 micron. The relative proportions of these fiber peaks differed significantly in different regions of the nerve. The highest proportion of large fibers was in the superior nerve periphery. The highest concentration of smallest fibers and the highest density of all fibers were located centrally in the infero-temporal quadrant. The observation that higher fiber density and smaller mean fiber diameter are skewed toward the inferior pole appears to coincide with the inferior position of the fovea with respect to the optic nerve head. This finding has importance for interpretation of pathologic changes in the optic disc.

Mobility performance in glaucoma.

PURPOSE: To determine whether glaucoma affects mobility performance and whether there is a relationship between mobility performance and stage of disease as estimated from vision-function measures. METHODS: The mobility performance of 47 glaucoma subjects was compared with that of 47 normal-vision subjects who were of similar age. Mobility performance was assessed by the time required to complete an established travel path and the number of mobility incidents. The subjective assessment of falling and fear of falling were also compared. Vision function was assessed by measures of visual acuity, contrast sensitivity, monocular automated threshold perimetry, and suprathreshold; binocular visual fields were assessed with the Esterman test. RESULTS: The glaucoma subjects walked on average 10% more slowly than did the normal-vision subjects. The number of people who experienced bumps, stumbles, or orientation problems was almost twice as high in the glaucoma group than the normal-vision group, but the difference did not reach statistical significance. The difference between groups also was not significant with respect to the number of people who reported falling in the past year (38% for the glaucoma group and 30% for the normal-vision group) or a fear of falling (28% for the glaucoma group and 23% for the normal-vision group). The visual fields assessed with a Humphrey 24-2 test were more highly correlated with walking speed in glaucoma than the visual fields scored by the Esterman scale or than visual acuity or contrast sensitivity. CONCLUSIONS: Glaucoma is associated with a modest decrease in mobility performance. Walking speed decreases with severity of the disease as estimated by threshold perimetry.

Descending optic nerve degeneration in primates.

We cut the optic nerve at the orbital apex in squirrel monkeys to study the descending degeneration of optic nerve axons and their ganglion cell bodies. We could not detect progressive disintegration of the axon from the site of injury back to the cell body. Instead, the entire length of individual axons seemed to degenerate simultaneously as early as 3 weeks and as late as 6 weeks after injury, as judged both by ultrastructural integrity and by continued slow axonal transport, a reflection of local physiologic function. We could not relate the time of degeneration to the distance of the injury from the cell body. Evidently there is a signal of injury to the cell body after axotomy, though the nature of the signal and the mechanism by which it leads to cell death are unknown.

Primary open-angle glaucoma is not associated with photoreceptor loss.

PURPOSE: To determine if photoreceptors die in primary open-angle glaucoma. METHODS: Retinas were examined in a masked fashion from nine standard locations of 14 eyes with documented open-angle glaucoma and from nine age-matched control eyes. The number and density of photoreceptors, as well as the area and height of the outer nuclear layer, were calculated with an automated image analysis system. The number of photoreceptors per 0.1 mm of retina was determined. RESULTS: No significant difference was seen between control and glaucomatous eyes in comparisons of photoreceptor density, outer nuclear layer height, or photoreceptors per 0.1 mm of retinal length in nine retinal zones. There was no detectable association between photoreceptor number and severity of glaucoma (defined as mild, moderate, or severe), visual field, and optic nerve fiber loss. In eyes in which damage predominated in the upper or lower visual field, no corresponding difference in photoreceptor number in upper compared to lower retinal zones was observed. CONCLUSION: Photoreceptors are not lost in substantial numbers in primary open-angle glaucoma.