Ординатура / Офтальмология / Английские материалы / Shields Textbook of Glaucoma, 6th edition_Allingham, Damji, Freedman_2010

the same response each time (112).

COAG populations have more individuals with a high IOP response to topical corticosteroids. The actual reported percentage of high responders, however, varies according to the criteria used to define this group. Reports also differ as to whether patients with ocular hypertension do or do not have a greater incidence of high response than the general population (113, 114). The topical corticosteroid response, however, has not been found to be a useful prognostic indicator for COAG (115, 116). Inheritance of the topical corticosteroid response and how this may relate to COAG have been matters of particular controversy. Becker postulated an autosomal recessive mode for the corticosteroid response and suggested that the gene is closely related or identical to that for COAG, which he thought had an autosomal recessive inheritance (108, 117). Armaly agreed that the two conditions might be genetically related but proposed a polygenetic inheritance for COAG, with the gene for the topical corticosteroid response being one of the genes involved (110). Results of additional studies were consistent with a genetic basis for the topical corticosteroid response but could confirm neither the recessive mode nor even a relationship to glaucoma (114, 118). Still other investigators could not even substantiate that the corticosteroid response was entirely genetic. A twin-heritability study of monozygotic and like-sex dizygotic twins revealed a low estimate of heritability that did not support a predominant role of inheritance in the response to corticosteroids and suggested that nongenetic factors play the major role (111, 119, 120 and 121). A study that further confuses the role of steroids in COAG found that eyes with unilateral angle-closure glaucoma or angle recession also respond to topical corticosteroids with a higher pressure rise in the involved eye than in the fellow eye, which had not had angle closure or trauma (122, 123). These observations suggest that topical corticosteroid responsiveness is multifactorial.

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Relationship of Intraocular Pressure to Corticosteroid Sensitivity

Investigators have tried to explain if or why patients with COAG are unusually sensitive to corticosteroids.

Hypothalamic-Pituitary-Adrenal Axis Theory

An abnormal response of the hypothalamic-pituitary-adrenal axis in patients with COAG, and possibly in other forms of glaucoma, may be related to alterations in aqueous humor dynamics in response to corticosteroids (124, 125).

Cyclic-Adenosine Monophosphate Theory

It may be that corticosteroids influence the IOP by altering cyclic-adenosine monophosphate. Corticosteroids have a permissive effect on the ß-a drenergic stimulation of adenyl cyclase, the enzyme responsible for the synthesis of cyclic-adenosine monophosphate (126). How this relates to aqueous humor dynamics is uncertain, although patients with COAG and high topical steroid responders appear to be unusually sensitive to cyclic-adenosine monophosphate.

Glycosaminoglycans Theory

It has also been proposed that IOP elevation associated with corticosteroid sensitivity may be related to glycosaminoglycans in the trabecular meshwork (127). When polymerized, glycosaminoglycans become hydrated, swell, and obstruct aqueous outflow. Catabolic enzymes, released from lysosomes in the trabecular cells, depolymerize the glycosaminoglycans. Cortico — steroids stabilize the lysosome membrane, preventing release of these enzymes and thereby increasing the polymerized form of glycosaminoglycans and the resistance to aqueous outflow.

Phagocytosis Theory

The effect of steroids on IOP may be related to the phagocytic activity of endothelial cells lining the trabecular meshwork. These cells are normally phagocytic, and they may function to “clean” the aqueous of debris before it reaches the inner wall endothelium of the Schlemm canal. Failure to do so might result in a buildup of material that could account for the amorphous layer in the juxtacanalicular connective tissue (as previously described). Corticosteroids suppress phagocytosis, and it may be that the trabecular endothelium in patients with COAG is unusually sensitive, even to endogenous corticosteroids (128).

Mechanism of Optic Neuropathy Histopathologic Observations

Axon loss in eyes with COAG has been reported to be associated with increasing connective tissue in the septa and surrounding the central retinal vessels, including increased amounts of types IV and VI collagen (129). The total number of capillaries and the density of capillaries decreased with loss of axons. Arteriosclerotic changes were more common in glaucomatous eyes than in age-matched control eyes.

Immunologic Studies

A number of reports suggest an immunoregulatory mechanism in the pathogenesis of COAG, at the level of the meshwork, ganglion cell bodies and optic nerve axons, retinal vessels, and lamina cribrosa. The roles of the immune system in glaucoma have been described as either neuroprotective or neurodestructive. It has been proposed that a critical balance between beneficial protective immunity and harmful sequelae of autoimmune neurodegenerative injury (such as heat-shock proteins) determines the ultimate fate of retinal ganglion cells in response to various stressors in patients with glaucoma. The Canadian Glaucoma Study reported that an elevated anticardiolipin antibody is associated with progression of COAG (130). Anticardiolipin antibody is one of the antiphospholipid antibodies found in elevated levels in patients with acquired thrombotic syndromes (131, 132).

Blood Flow

Abnormalities of blood flow to the posterior segment of the eye in COAG have been shown by using color Doppler imaging, fluorescein angiography, laser Doppler flowmetry, and pulsatile ocular blood flow measurements (133, 134, 135, 136, 137, 138, 139, 140 and 141). Rheological studies have also demonstrated differences in red cell aggregability, increased plasma viscosity, and activation of the clotting system in patients with COAG compared with controls (65, 142, 143). Altered autoregulation of blood flow in the optic nerve and retinal circulation has also been demonstrated (144, 145).

Changes in the retrobulbar hemodynamics also appear to occur with age. Color Doppler imaging analysis of the ophthalmic, central retinal, and nasal and temporal posterior ciliary arteries in healthy men and women demonstrated age-related alterations in hemodynamics, similar to those seen in patients with glaucoma, suggesting that these age-related changes may contribute to an increased risk for glaucoma (146).

There is also evidence that the choroidal circulation is compromised in COAG (147, 148), which is supported by electroretinographic data demonstrating outer retinal damage in eyes with glaucoma (149). Apoptotic Susceptibility of Ganglion Cells

Ganglion cells appear to die by apoptosis in experimental glaucoma (150). This may relate to a multiplicity of factors (Fig. 11.1). Clinically, some evidence is related to excitotoxic cell death from accumulation of glutamate and an imbalance of proteases that modulate the extracellular matrix milieu in the retina (151, 152).

Possible Infectious Susceptibility

In a study of 32 patients with COAG, 9 with exfoliative glaucoma, and 30 age-matched control patients with anemia, upper gastrointestinal endoscopy was performed to evaluate macroscopic abnormalities and gastric mucosal biopsy specimens were analyzed for the presence of Helicobacter pylori infection (153). Approximately 88% of the patients with COAG and exfoliative glaucoma had histologically confirmed H. pylori infection, compared with 47% among controls. Patients with

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glaucoma also exhibited abnormal gastric mucosa, antral gastritis, and peptic ulcer disease. Not all studies have found this correlation (154).

Figure 11.1 Diverse insults can lead to retinal ganglion cell death. These include IOP-related and non- IOP-related factors. (Reproduced from Libby RT et al. Complex genetics of glaucoma susceptibility. Annu Rev Genomics Hum Genet. 2005;6:15-44, with permission).

Cerebrospinal Fluid Pressure

The lamina cribrosa is located between two pressurized compartments, intraocular space and the subarachnoid space posteriorly (see Chapter 4). The pressure difference between these two spaces has been termed the “translaminar pressure.” In this co ntext, a reduced cerebrospinal fluid (CSF) pressure would exert the same effect as an increase in IOP. Emerging evidence suggests that the translaminar pressure may play an important role in glaucomatous optic neuropathy (155, 156 and 157). In these studies, the measured CSF pressure was significantly lower in participants with COAG compared with controls. In addition, CSF pressure was lower in participants with NTG, compared with those who had COAG associated with elevated IOP. These data, although preliminary, suggest that the dynamic interplay between these fluid spaces may play a role in glaucoma and may help explain why some individuals with normal IOP may develop glaucoma and others with elevated IOP may not. MANAGEMENT

General Principles of Management

The principles of when and how to treat patients with COAG are discussed in Chapter 27. In brief, it is important to establish a target IOP range for both eyes of the patient—that is, an IOP range in which there will presumably be no further anticipated optic nerve damage. This begins with a detailed history, complete examination, and appropriate testing, after which the target IOP is set on the basis of stage of glaucomatous damage and risk factors for progression (as discussed here). The target is a dynamic concept that needs to be reevaluated at each visit. Once the target IOP range is set, it is achieved with topical medication in most cases. If the target IOP range cannot be achieved despite maximum tolerable medical therapy, argon or selective laser trabeculoplasty is usually indicated, followed by glaucoma filtering surgery or other therapeutic maneuvers as deemed necessary. If optic nerve or visual field progression occurs despite achieving the target IOP range, it may be necessary to revise the target IOP downward and to consider IOP-independent mechanisms of the optic neuropathy.

Throughout the treatment course, the expense, inconvenience, and side effects of therapy should be considered and an effective treatment plan that includes patient education, efficacy and toxicity of therapy, and patient adherence should be established. A regimen of the least medication to achieve the desired therapeutic response should be chosen for each eye of the patient. Follow-up evaluation should be guided by the severity of the disease.

Treatment of Normal-Tension Glaucoma

Although damage to the optic nerve head and visual field may progress even at low-normal pressures in NTG, compelling evidence shows that IOP reduction from baseline values is effective. In the CNTGS, 57% of the patients achieved a 30% IOP reduction with topical medication, laser trabeculoplasty, or both (158). The remaining 43% required filtering surgery. Although filtering surgery did not help in one reported series (156), other surgeons have found that it may prevent progressive damage (159, 160, 161 and 162), and the CNTGS has confirmed the benefit of aggressive IOP reduction in these patients. Despite the proven value of IOP reduction, some patients with NTG may have IOP-independent mechanisms of glaucomatous optic neuropathy, and this must especially be considered when damage is progressing with pressures in the single digits. An additional aspect of managing the patient with NTG may be the treatment of any cardiovascular abnormality, such as anemia, hypotension, congestive heart failure, transient ischemic attacks, and cardiac arrhythmias, to ensure maximum perfusion of the optic nerve head (163).

Ultimately, the treatment of choice may prove to be therapy that directly protects and improves the function of ganglion

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cells and the optic nerve head. A placebo-controlled 3-year study of the calcium-channel blocker nilvadipine on visual field and ocular circulation in 33 patients with NTG suggested that blood flow to the optic nerve and fovea was increased in the treated group. Furthermore, the mean negative slope in mean deviation of the visual field over time was also less in the treated group (164). Other studies involving patients with NTG receiving concurrent calcium-channel blocker therapy have demonstrated a significant reduction in the rate of disc and field progression, compared with similar NTG groups who were not receiving the concomitant therapy (165, 166).

KEY POINTS

COAG is the most common form of glaucoma worldwide. It has a familial tendency and is more prevalent with increasing age, black race, myopia, and certain systemic diseases, such as diabetes mellitus and cardiovascular abnormalities.

COAG is typically asymptomatic until advanced visual field loss occurs and is characterized by an open, normal-appearing anterior chamber angle.

A clinical subset of COAG, NTG, has similar disc and field changes but pressures that remain in the normal range without treatment. However, IOP is a contributing risk factor in both conditions, with an increasing influence of IOP-independent factors in NTG. NTG is a diagnosis of exclusion, and it is important to ensure that no atypical clinical features suggest nonglaucomatous causes of optic nerve cupping.

The precise mechanism of increased resistance to aqueous outflow and to optic nerve damage in COAG remains unclear, although continued research, especially in molecular biology, is beginning to reveal answers to these complex processes.

REFERENCES

1.American Academy of Ophthalmology (AAO). Primary Open-Angle Glaucoma, Preferred Practice Pattern. San Francisco, CA: AAO; 2005. Available at: http://www.aao.org/ppp.

2.Kolker AE, Becker B. ‘Ocular hypertension’ vs op en-angle glaucoma: a different view. Arch Ophthalmol. 1977;95(4):586-587.

3.Phelps CD. Ocular hypertension: to treat or not to treat. Arch Ophthalmol. 1977;95(4):588-589.

4.Chandler PA, Grant WM. ‘Ocular hypertension’ vs open-angle glaucoma. Arch Ophthalmol. 1977;95 (4):585-586.

5.Shaffer R. ‘Glaucoma suspect’ or ‘ocular hyperte nsion’. Arch Ophthalmol. 1977;95(4):588.

6.Lee BL, Bathija R, Weinreb RN. The definition of normal-tension glaucoma. J Glaucoma. 1998;7 (6):366-371.

7.Shields MB. Normal-tension glaucoma: is it different from primary open-angle glaucoma? Curr Opin Ophthalmol. 2008;19(2):85-88.

8.O'Brien C, Schwartz B, Takamoto T, et al. Intraocular pressure and the rate of visual field loss in chronic open-angle glaucoma. Am J Ophthalmol. 1991;111(4):491-500.

9.Weber J, Koll W, Krieglstein GK. Intraocular pressure and visual field decay in chronic glaucoma. Ger J Ophthalmol. 1993;2(3):165-169.

10.Chauhan BC, Drance SM. The relationship between intraocular pressure and visual field progression in glaucoma. Graefes Arch Clin Exp Ophthalmol. 1992;230(6):521-526.

11.Cedrone C, Mancino R, Cerulli A, et al. Epidemiology of primary glaucoma: prevalence, incidence, and blinding effects [review]. Prog Brain Res. 2008;173:3-14.

12. Leske MC. Open-angle glaucoma—an epidemiologic overview [review]. Ophthalmic Epidemiol. 2007;14(4):166-172.

13.Hollows FC, Graham PA. Intraocular pressure, glaucoma, and glaucoma suspects in a defined population. Br J Ophthalmol. 1966;50(10):570-586.

14.Shiose Y, Kitazawa Y, Tsukahara S, et al. Epidemiology of glaucoma in Japan—a nationwide glaucoma survey. Jpn J Ophthalmol. 1991; 35(2):133-155.

15.Leydhecker W. On the distribution of glaucoma simplex in apparently healthy population not treated by ophthalmologists [in German]. Doc Ophthalmol. 1959;13:359-388.

16.Lichter PR, Shaffer RN. Ocular hypertension and glaucoma. Trans Pac Coast Otoophthalmol Soc. 1973;54:63-75.

17.Jay JL, Murdoch JR. The rate of visual field loss in untreated primary open angle glaucoma. Br J Ophthalmol. 1993;77(3):176-178.

18.Harbin TS Jr, Podos SM, Kolker AE, et al. Visual field progression in open-angle glaucoma patients presenting with monocular field loss. Trans Sect Ophthalmol Am Acad Ophthalmol Otolaryngol. 1976;81(2): 253-257.

19.Grant WM, Burke JF Jr. Why do some people go blind from glaucoma? Ophthalmology. 1982;89 (9):991-998.

20.Ekstrom C, Haglund B. Chronic open-angle glaucoma and advanced visual field defects in a defined population. Acta Ophthalmol. 1991; 69(5):574-580.

21.Anderson DR, Drance SM, Schulzer M. Natural history of normal-tension glaucoma. Ophthalmology. 2001;108(2):247-253.

22.Leske MC, Heijl A, Hyman L, et al. Predictors of long-term progression in the early manifest glaucoma trial. Ophthalmology. 2007;114(11): 1965-1972.

23.Behki R, Damji KF, Crichton A. Canadian perspectives in glaucoma management: the role of central corneal thickness [review]. Can J Ophthalmol. 2007;42(1):66-74.

24.Kimura R, Levene RZ. Gonioscopic differences between primary openangle glaucoma and normal subjects over 40 years of age. Am J Ophthalmol. 1975;80(1):56-61.

25.Campbell DG, Boys-Smith JW, Woods WD. Variation of pigmentation and segmentation of pigmentation in primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 1984;25(suppl):122.

26.Sommer A, Miller NR, Pollack I, et al. The nerve fiber layer in the diagnosis of glaucoma. Arch Ophthalmol. 1977;95(12):2149-2156.

27.Kass MA, Kolker AE, Becker B. Prognostic factors in glaucomatous visual field loss. Arch Ophthalmol. 1976;94(8):1274-1276.

28.Susanna R, Drance SM, Douglas GR. The visual prognosis of the fellow eye in uniocular chronic open-angle glaucoma. Br J Ophthalmol. 1978;62(5):327-329.

29.Iester M, Mikelberg FS. Optic nerve head morphologic characteristics in high-tension and normaltension glaucoma. Arch Ophthalmol. 1999; 117(8):1010-1013.

30.Kim DM, Seo JH, Kim SH, et al. Comparison of localized retinal nerve fiber layer defects between a low-teen intraocular pressure group and a high-teen intraocular pressure group in normal-tension glaucoma patients. J Glaucoma. 2007;16(3):293-296.

31.Yamazaki Y, Koide C, Miyazawa T, et al. Comparison of retinal nervefiber layer in highand

normal-tension glaucoma. Graefes Arch Clin Exp Ophthalmol. 1991;229(6):517-520.

32.Kubota T, Khalil AK, Honda M, et al. Comparative study of retinal nerve fiber layer damage in Japanese patients with normaland high-tension glaucoma. J Glaucoma. 1999;8(6):363-366.

33.Gramer E, Althaus G, Leydhecker W. Site and depth of glaucomatous visual field defects in relation to the size of the neuroretinal edge zone of the optic disk in glaucoma without hypertension, simple glaucoma, pigmentary glaucoma. A clinical study with the Octopus perimeter 201 and the optic nerve head analyzer [in German]. Klin Monatsbl Augenheilkd. 1986;189(3):190-198.

34.Gliklich RE, Steinmann WC, Spaeth GL. Visual field change in low-tension glaucoma over a fiveyear follow-up. Ophthalmology. 1989; 96(3):316-320.

35.Gramer E, Althaus G. Quantification and progression of the visual field defect in glaucoma without hypertension, glaucoma simplex and pigmentary glaucoma. A clinical study with the Delta Program of the 201 Octopus perimeter [in German]. Klin Monatsbl Augenheilkd. 1987; 191(3):184-198.

36.Gramer E, Leydhecker W. Glaucoma without ocular hypertension. A clinical study [in German]. Klin Monatsbl Augenheilkd. 1985;186(4):262-267.

37.Araie M, Sekine M, Suzuki Y, et al. Factors contributing to the progression of visual field damage in eyes with normal-tension glaucoma. Ophthalmology. 1994;101(8):1440-1444.

P.186

38.Jonas JB, Grundler AE, Gonzales-Cortes J. Pressure-dependent neuroretinal rim loss in normalpressure glaucoma. Am J Ophthalmol. 1998;125(2):137-144.

39.Noureddin BN, Poinoosawmy D, Fietzke FW, et al. Regression analysis of visual field progression in low tension glaucoma. Br J Ophthalmol. 1991;75(8):493-495.

40.Cartwright MJ, Anderson DR. Correlation of asymmetric damage with asymmetric intraocular pressure in normal-tension glaucoma (low-tension glaucoma). Arch Ophthalmol. 1988;106(7):898-900.

41.Crichton A, Drance SM, Douglas GR, et al. Unequal intraocular pressure and its relation to asymmetric visual field defects in low-tension glaucoma. Ophthalmology. 1989;96(9):1312-1314.

42.Greenfield DS, Liebmann JM, Ritch R, et al. Visual field and intraocular pressure asymmetry in the low-pressure glaucoma treatment study. Ophthalmology. 2007;114(3):460-465.

43.Ido T, Tomita G, Kitazawa Y. Diurnal variation of intraocular pressure of normal-tension glaucoma. Influence of sleep and arousal. Ophthalmology. 1991;98(3):296-300.

44.Larsson LI, Rettig ES, Sheridan PT, et al. Aqueous humor dynamics in low-tension glaucoma. Am J Ophthalmol. 1993;116(5):590-593.

45.Weinreb RN, Liu JH. Nocturnal rhythms of intraocular pressure. Arch Ophthalmol. 2006;124 (2):269-270.

46.Drance SM, Sweeney VP, Morgan RW, et al. Studies of factors involved in the production of low tension glaucoma. Arch Ophthalmol. 1973;89(6):457-465.

47.Drance SM, Morgan RW, Sweeney VP. Shock-induced optic neuropathy: a cause of nonprogressive glaucoma. N Engl J Med. 1973;288(8): 392-395.

48.Goldberg I, Hollows FC, Kass MA, et al. Systemic factors in patients with low-tension glaucoma. Br J Ophthalmol. 1981;65(1):56-62.

49.James CB, Smith SE. Pulsatile ocular blood flow in patients with low tension glaucoma. Br J Ophthalmol. 1991;75(8):466-470.

50.Hashimoto M, Ohtsuka K, Ohtsuka H, et al. Normal-tension glaucoma with reversed ophthalmic artery flow. Am J Ophthalmol. 2000;130(5): 670-672.

51.Rader J, Feuer WJ, Anderson DR. Peripapillary vasoconstriction in the glaucomas and the anterior ischemic optic neuropathies. Am J Ophthalmol. 1994;117(1):72-80.

52.Kondo Y, Niwa Y, Yamamoto T, et al. Retrobulbar hemodynamics in normal-tension glaucoma with asymmetric visual field change and asymmetric ocular perfusion pressure. Am J Ophthalmol. 2000;130 (4): 454-460.

53.Meyer JH, Brandi-Dohrn J, Funk J. Twenty four hour blood pressure monitoring in normal tension glaucoma. Br J Ophthalmol. 1996; 80(10):864-867.

54.Hulsman CA, Vingerling JR, Hofman A, et al. Blood pressure, arterial stiffness, and open-angle glaucoma: the Rotterdam study. Arch Ophthalmol. 2007;125(6):805-812.

55.Waldmann E, Gasser P, Dubler B, et al. Silent myocardial ischemia in glaucoma and cataract patients. Graefes Arch Clin Exp Ophthalmol. 1996;234(10):595-598.

56.Pillunat LE, Stodtmeister R, Wilmanns I. Pressure compliance of the optic nerve head in low tension glaucoma. Br J Ophthalmol. 1987;71(3): 181-187.

57.Phelps CD, Corbett JJ. Migraine and low-tension glaucoma. A case-control study. Invest Ophthalmol Vis Sci. 1985;26(8): 1105-1108.

58.Usui T, Iwata K, Shirakashi M, et al. Prevalence of migraine in low-tension glaucoma and primary open-angle glaucoma in Japanese. Br J Ophthalmol. 1991;75(4):224-226.

59.Orgul S, Flammer J. Headache in normal-tension glaucoma patients. J Glaucoma. 1994;3(4):292-

60.Drance SM, Douglas GR, Wijsman K, et al. Response of blood flow to warm and cold in normal and low-tension glaucoma patients. Am J Ophthalmol. 1988;105(1):35-39.

61.Gasser P, Flammer J. Blood-cell velocity in the nailfold capillaries of patients with normal-tension and high-tension glaucoma. Am J Ophthalmol. 1991;111(5):585-588.

62.Schulzer M, Drance SM, Carter CJ, et al. Biostatistical evidence for two distinct chronic open angle glaucoma populations. Br J Ophthalmol. 1990;74(4):196-200.

63.Henry E, Newby DE, Webb DJ, et al. Peripheral endothelial dysfunction in normal pressure glaucoma. Invest Ophthalmol Vis Sci. 1999;40(8): 1710-1714.

64.Kim SH, Kim JY, Kim DM, et al. Investigations on the association between normal tension glaucoma and single nucleotide polymorphisms of the endothelin-1 and endothelin receptor genes. Mol Vis. 2006; 12:1016-1021.

65.Klaver JH, Greve EL, Goslinga H, et al. Blood and plasma viscosity measurements in patients with glaucoma. Br J Ophthalmol. 1985; 69(10):765-770.

66.Joist JH, Lichtenfeld P, Mandell AI, et al. Platelet function, blood coagulability, and fibrinolysis in patients with low tension glaucoma. Arch Ophthalmol. 1976;94(11):1893-1895.

67.Carter CJ, Brooks DE, Doyle DL, et al. Investigations into a vascular etiology for low-tension glaucoma. Ophthalmology. 1990;97(1): 49-55.

68.Winder AF. Circulating lipoprotein and blood glucose levels in association with low-tension and chronic simple glaucoma. Br J Ophthalmol. 1977;61(10):641-645.

69.Stroman GA, Stewart WC, Golnik KC, et al. Magnetic resonance imaging in patients with lowtension glaucoma. Arch Ophthalmol. 1995;113(2): 168-172.

70.Ong K, Farinelli A, Billson F, et al. Comparative study of brain magnetic resonance imaging findings in patients with low-tension glaucoma and control subjects. Ophthalmology. 1995;102 (11):1632-1638.

71.Cartwright MJ, Grajewski AL, Friedberg ML, et al. Immune-related disease and normal-tension glaucoma. A case-control study. Arch Ophthalmol. 1992;110(4):500-502.

72.Wax MB, Barrett DA, Pestronk A. Increased incidence of paraproteinemia and autoantibodies in patients with normal-pressure glaucoma. Am J Ophthalmol. 1994;117(5):561-568.

73.Romano C, Barrett DA, Li Z, et al. Anti-rhodopsin antibodies in sera from patients with normalpressure glaucoma. Invest Ophthalmol Vis Sci. 1995;36(10):1968-1975.

74.Yang J, Tezel G, Patil RV, et al. Serum autoantibody against glutathione S-transferase in patients with glaucoma. Invest Ophthalmol Vis Sci. 2001;42(6):1273-1276.

75.Wax MB, Tezel G, Saito I, et al. Anti-Ro/SS-A positivity and heat shock protein antibodies in patients with normal-pressure glaucoma. Am J Ophthalmol. 1998;125(2):145-157.

76.Ritch R. Nonprogressive low-tension glaucoma with pigmentary dispersion. Am J Ophthalmol. 1982;94(2):190-196.

77.Tamm ER, Fuchshofer R. What increases outflow resistance in primary open-angle glaucoma? Surv Ophthalmol. 2007;52(suppl 2):S101-S104.

78.Grant WM. Further studies on facility of flow through the trabecular meshwork. Arch Ophthalmol.

1958;60(4 pt 1):523-533.

79.Johnson M. What controls aqueous humour outflow resistance? Exp Eye Res. 2006;82(4):545-557.

80.Johnson DH. Myocilin and glaucoma: A TIGR by the tail? Arch Ophthalmol. 2000;118(7):974-978.

81.Lutjen-Drecoll E, May CA, Polansky JR, et al. Localization of the stress proteins alpha B-crystallin and trabecular meshwork inducible glucocorticoid response protein in normal and glaucomatous trabecular meshwork. Invest Ophthalmol Vis Sci. 1998;39(3):517-525.

82.Zatulina NI. Electron microscopy of trabecular tissue in the advanced stage of simple open-angle glaucoma [in Russian]. Oftalmol Zh. 1973;28(2):115-118.

83.Alvarado J, Murphy C, Juster R. Trabecular meshwork cellularity in primary open-angle glaucoma and nonglaucomatous normals. Ophthalmology. 1984;91(6):564-579.

84.Tripathi RC, Tripathi BJ. Contractile protein alteration in trabecular endothelium in primary openangle glaucoma. Exp Eye Res. 1980;31(6): 721-724.

85.Clark AF, Miggans ST, Wilson K, et al. Cytoskeletal changes in cultured human glaucoma trabecular meshwork cells. J Glaucoma. 1995;4(3): 183-188.

86.Finkelstein I, Trope GE, Basu PK, et al. Quantitative analysis of collagen content and amino acids in trabecular meshwork. Br J Ophthalmol. 1990;74(5):280-282.

87.Li Y, Yi YZ. Histochemical and electron microscopic studies of the trabecular meshwork in primary open-angle glaucoma [in Chinese]. Yan Ke Xue Bao. 1985;1(1):17-22.

88.Armaly MF, Wang Y. Demonstration of acid mucopolysaccharides in the trabecular meshwork of the Rhesus monkey. Invest Ophthalmol. 1975;14(7):507-516.

89.Knepper PA, Covici S, Fadel JR, et al. Surface-tension properties of hyaluronic Acid. J Glaucoma. 1995;4(3):194-199.

90.de Kater AW, Melamed S, Epstein DL. Patterns of aqueous humor outflow in glaucomatous and nonglaucomatous human eyes. A tracer study using cationized ferritin. Arch Ophthalmol. 1989;107 (4):572-576.

P.187

91.Alvarado JA, Yun AJ, Murphy CG. Juxtacanalicular tissue in primary open angle glaucoma and in nonglaucomatous normals. Arch Ophthalmol. 1986;104(10):1517-1528.

92.Rodrigues MM, Spaeth GL, Sivalingam E, et al. Value of trabeculectomy specimens in glaucoma. Ophthalmic Surg. 1978;9(2):29-38.

93.Segawa K. Electron microscopic changes of the trabecular tissue in primary open-angle glaucoma. Ann Ophthalmol. 1979;11(1):49-54.

94.Rohen JW. Presence of matrix vesicles in the trabecular meshwork of glaucomatous eyes. Graefes Arch Clin Exp Ophthalmol. 1982;218(4): 171-176.

95.Rohen JW. Why is intraocular pressure elevated in chronic simple glaucoma? Anatomical considerations. Ophthalmology. 1983;90(7):758-765.

96.Babizhayev MA, Brodskaya MW. Fibronectin detection in drainage outflow system of human eyes in ageing and progression of open-angle glaucoma. Mech Ageing Dev. 1989;47(2):145-157.

97.Umihira J, Nagata S, Nohara M, et al. Localization of elastin in the normal and glaucomatous human trabecular meshwork. Invest Ophthalmol Vis Sci. 1994;35(2):486-494.

98.Worthen DM, Cleveland PH, Slight JR, et al. Selective binding affinity of human plasma fibronectin for the collagens I-IV. Invest Ophthalmol Vis Sci. 1985;26(12):1740-1744.

99.Knepper PA, Goossens W, Palmberg PF. Glycosaminoglycan stratification of the juxtacanalicular tissue in normal and primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 1996;37(12):2414-2425.

100.Allingham RR, de Kater AW, Ethier CR, et al. The relationship between pore density and outflow facility in human eyes. Invest Ophthalmol Vis Sci. 1992;33(5):1661-1669.

101.Alvarado JA, Murphy CG. Outflow obstruction in pigmentary and primary open angle glaucoma. Arch Ophthalmol. 1992;110(12): 1769-1778.

102.Gottanka J, Johnson DH, Martus P, et al. Severity of optic nerve damage in eyes with POAG is correlated with changes in the trabecular meshwork. J Glaucoma. 1997;6(2):123-132.

103.Johnson MC, Kamm RD. The role of Schlemm's canal in aqueous outflow from the human eye. Invest Ophthalmol Vis Sci. 1983;24(3): 320-325.

104.Buller C, Johnson D. Segmental variability of the trabecular meshwork in normal and glaucomatous eyes. Invest Ophthalmol Vis Sci. 1994; 35(11):3841-3851.

105.Ashton N. The exit pathway of the aqueous. Trans Ophthalmol Soc U K. 1960;80:397-421.

106.Krasnov MM. Symposium: microsurgery of the outflow channels. Sinusotomy. Foundations, results, prospects. Trans Am Acad Ophthalmol Otolaryngol. 1972;76(2):368-374.

107.Nesterov AP, Batmanov YE. Trabecular wall of Schlemm's canal in the early stage of primary open-angle glaucoma. Am J Ophthalmol. 1974;78(4):639-647.

108.Becker B, Hahn KA. Topical corticosteroids and heredity in primary open-angle glaucoma. Am J Ophthalmol. 1964;57:543-551.

109.Armaly MF. The heritable nature of dexamethasone-induced ocular hypertension. Arch Ophthalmol. 1966;75(1):32-35.

110.Armaly MF. Inheritance of dexamethasone hypertension and glaucoma. Arch Ophthalmol. 1967;77 (6):747-751.

111.Schwartz JT, Reuling FH, Feinleib M, et al. Twin study on ocular pressure after topical dexamethasone. 1. Frequency distribution of pressure response. Am J Ophthalmol. 1973;76(1):126-136.

112.Palmberg PF, Mandell A, Wilensky JT, et al. The reproducibility of the intraocular pressure response to dexamethasone. Am J Ophthalmol. 1975;80(5):844-856.

113.Dean GO Jr, Deutsch AR, Hiatt RL. The effect of dexamethasone on borderline ocular hypertension. Ann Ophthalmol. 1975;7(2):193-198.

114.Levene R, Wigdor A, Edelstein A, et al. Topical corticosteroid in normal patients and glaucoma suspects. Arch Ophthalmol. 1967;77(5):593-597.

115.Lewis JM, Priddy T, Judd J, et al. Intraocular pressure response to topical dexamethasone as a predictor for the development of primary openangle glaucoma. Am J Ophthalmol. 1988;106(5):607-612.

116.Klemetti A. The dexamethasone provocative test: a predictive tool for glaucoma? Acta Ophthalmol. 1990;68(1):29-33.

117.Becker B. The genetic problem of chronic simple glaucoma. Ann Ophthalmol. 1971;3(4):351-354.

118.Francois J, Heintz-de Bree CH, Tripathi RC. The cortisone test and the heredity of primary openangle glaucoma. Am J Ophthalmol. 1966; 62(5):844-852.

119.Schwartz JT, Reuling FH, Feinleib M, et al. Twin heritability study of the effect of corticosteroids on intraocular pressure. J Med Genet. 1972; 9(2):137-143.

120.Schwartz JT, Reuling FH Jr, Feinleib M, et al. Twin heritability study of the corticosteroid response. Trans Am Acad Ophthalmol Otolaryngol. 1973;77(2):OP126-OP136.

121.Schwartz JT, Reuling FH, Feinleib M, et al. Twin study on ocular pressure following topically applied dexamethasone. II. Inheritance of variation in pressure response. Arch Ophthalmol. 1973;90 (4):281-286.

122.Akingbehin AO. Corticosteroid-induced ocular hypertension. II. An acquired form. Br J Ophthalmol. 1982;66(8):541-545.

123.Spaeth GL. Traumatic hyphema, angle recession, dexamethasone hypertension, and glaucoma. Arch Ophthalmol. 1967;78(6):714-721.

124.Schwartz B. The hypothalamo-hypophyseal-adrenal gland system and steroid glaucoma [in German]. Klin Monatsbl Augenheilkd. 1972; 161(3):280-287.

125.Schwartz B, Golden MA, Wiznia RA, et al. Differences of adrenal stress control mechanisms in subjects with glaucoma and normal subjects. Effect of vasopressin and pyrogen. Arch Ophthalmol. 1981;99(10):1770-1777.

126.Kass MA, Shin DH, Cooper DG, et al. The ocular hypotensive effect of epinephrine in high and low corticosteroid responders. Invest Ophthalmol Vis Sci. 1977;16(6):530-531.

127.Francois F, Victoria-Troncoso V. Mucopolysaccharides and pathogenesis of cortisone glaucoma [in German]. Klin Monatsbl Augenheilkd. 1974;165(1):5-10.

128.Bill A. The drainage of aqueous humor [editorial]. Invest Ophthalmol. 1975;14(1):1-3.

129.Gottanka J, Kuhlmann A, Scholz M, et al. Pathophysiologic changes in the optic nerves of eyes with primary open angle and exfoliation glaucoma. Invest Ophthalmol Vis Sci. 2005;46(11):4170-4181.

130.Chauhan BC, Mikelberg FS, Balaszi AG, et al. Canadian Glaucoma Study: 2. Risk factors for the progression of open-angle glaucoma. Arch Ophthalmol. 2008;126(8):1030-1036.

131.Grus FH, Joachim SC, Wuenschig D, et al. Autoimmunity and glaucoma [review]. J Glaucoma. 2008;17(1):79-84.

132.Wax MB, Tezel G. Immunoregulation of retinal ganglion cell fate in glaucoma [review]. Exp Eye Res. 2009;88(4):825-830.

133.Rankin SJ, Walman BE, Buckley AR, et al. Color Doppler imaging and spectral analysis of the optic nerve vasculature in glaucoma. Am J Ophthalmol. 1995;119(6):685-693.

134.Rankin SJ, Drance SM. Peripapillary focal retinal arteriolar narrowing in open angle glaucoma. J Glaucoma. 1996;5(1):22-28.

135.Nicolela MT, Walman BE, Buckley AR, et al. Ocular hypertension and primary open-angle glaucoma: a comparative study of their retrobulbar blood flow velocity. J Glaucoma. 1996;5(5):308-310.

136.Butt Z, O'Brien C, McKillop G, et al. Color Doppler imaging in untreated highand normalpressure open-angle glaucoma. Invest Ophthalmol Vis Sci. 1997;38(3):690-696.

137.Kerr J, Nelson P, O'Brien C. A comparison of ocular blood flow in untreated primary open-angle glaucoma and ocular hypertension. Am J Ophthalmol. 1998;126(1):42-51.

138.Schwartz B, Rieser JC, Fishbein SL. Fluorescein angiographic defects of the optic disc in glaucoma. Arch Ophthalmol. 1977;95(11):1961-1974.

139.Michelson G, Langhans MJ, Groh MJ. Perfusion of the juxtapapillary retina and the neuroretinal rim area in primary open angle glaucoma. J Glaucoma. 1996;5(2):91-98.

140.Findl O, Rainer G, Dallinger S, et al. Assessment of optic disk blood flow in patients with openangle glaucoma. Am J Ophthalmol. 2000;130(5): 589-596.

141.Trew DR, Smith SE. Postural studies in pulsatile ocular blood flow: II. Chronic open angle glaucoma. Br J Ophthalmol. 1991;75(2):71-75.

142.Hamard P, Hamard H, Dufaux J, et al. Optic nerve head blood flow using a laser Doppler velocimeter and haemorheology in primary open angle glaucoma and normal pressure glaucoma. Br J Ophthalmol. 1994; 78(6):449-453.

143.O'Brien C, Butt Z, Ludlam C, et al. Activation of the coagulation cascade in untreated primary open-angle glaucoma. Ophthalmology. 1997; 104(4):725-729, discussion 9-30.

144.Pillunat LE, Stodtmeister R, Wilmanns I, et al. Autoregulation of ocular blood flow during changes in intraocular pressure. Preliminary results. Graefes Arch Clin Exp Ophthalmol. 1985;223(4):219-223.

145.Grunwald JE, Riva CE, Stone RA, et al. Retinal autoregulation in openangle glaucoma. Ophthalmology. 1984;91(12):1690-1694.

146.Harris A, Harris M, Biller J, et al. Aging affects the retrobulbar circulation differently in women and men. Arch Ophthalmol. 2000;118(8):1076-1080.

147.Hayreh SS. Blood supply of the optic nerve head and its role in optic atrophy, glaucoma, and oedema of the optic disc. Br J Ophthalmol. 1969;53(11):721-748.

P.188

148.Hayreh SS. Pathogenesis of visual field defects. Role of the ciliary circulation. Br J Ophthalmol. 1970;54(5):289-311.

149.Vaegan BL. The locus of outer retinal change in glaucoma using Sutter multifocal flash and pattern ERG field tests. Aust NZ J Ophthalmol. 1996;24:28.

150.Quigley HA. Neuronal death in glaucoma. Prog Retin Eye Res. 1999; 18(1):39-57.

151.Chintala SK. The emerging role of proteases in retinal ganglion cell death. Exp Eye Res. 2006;82 (1):5-12.

152.Dreyer EB, Zurakowski D, Schumer RA, et al. Elevated glutamate levels in the vitreous body of humans and monkeys with glaucoma. Arch Ophthalmol. 1996;114(3):299-305.

153.Kountouras J, Mylopoulos N, Boura P, et al. Relationship between Helicobacter pylori infection