Ординатура / Офтальмология / Английские материалы / Mechanisms of the Glaucomas_Shields, Tombran-Tink, Barnstable_2008

at shorter intervals, than with POAG patients. Any therapy should, however, aim to reduce both mean IOP and 24-h IOP fluctuations (76).

In one comparative trial, latanoprost and a fixed combination of timolol and dorzolamide had a comparable IOP effect in eyes with PEX glaucoma (77), whereas another study found that the IOP-lowering effect of dorzolamide/timolol fixed combination was significantly better than that of latanoprost or travoprost in PEX glaucoma patients (78). In a multicenter study, latanoprost was slightly more effective than timolol alone in lowering IOP in eyes with PEX glaucoma but provided significantly lower diurnal fluctuations and mean peak IOP (79). Latanoprost monotherapy has also been shown to normalize the concentrations of certain pathogenetic factors, including TGF- 1, MMP-2, and TIMP-2, in the aqueous humor of patients with PEX glaucoma, suggesting that it may confer a long-term beneficial effect on the abnormal matrix process of PEX besides lowering IOP (80).

In a prospective, three-center, crossover study of patients with PEX glaucoma, the mean diurnal IOP was significantly lower with bimatoprost than with latanoprost (81), whereas in another prospective crossover comparison, latanoprost and travoprost both significantly reduced the 24-h IOP in patients with PEX glaucoma, but travoprost had a greater hypotensive efficacy in the late afternoon (82), and a third prospective study of patients with PEX glaucoma receiving either latanoprost, travoprost, or bimatoprost therapy showed that the mean 24-h range of IOP was significantly lower with travoprost (83).

Unoprostone was also reported to provide a clinically significant IOP-lowering effect, equivalent to betaxolol but not as good as timolol, in patients with PEX glaucoma (84).

Despite good IOP-lowering effects of miotic agents (2), there are some hazards of miotic use in PEX patients: aggravation of blood–aqueous barrier breakdown, and reduced pupillary movement increasing the risk of posterior synechiae, as well as the risk of cataract formation, aggravation of lens opacities, and induction of pupillary or ciliary block angle-closure glaucoma in eyes with marked zonular instability may make these drugs relatively contraindicated. Aqueous suppressants result in decreased aqueous flow through the trabecular meshwork, which may conceivably lead to worsening of trabecular function and further compromise the degenerative ciliary epithelium (76) although this has yet to be clarified.

Laser Treatments

Argon laser trabeculoplasty (ALT) is reported to have an early pressure-lowering effect, in up to 80% of eyes with PEX glaucoma, due to increased laser absorption by the trabecular pigmentation. However, the success rates decrease with time, and by 3 years, there is a substantial failure rate averaging 50%, as is also seen in eyes with POAG (85,86).

Nevertheless, one study suggested that primary ALT seems to be a good first-line therapy in PEX glaucoma patients, as it can delay the use of medical therapy for up to 8 years in a significant proportion of these patients (86). Post-laser complications are more common in PEX eyes and include transient inflammatory reactions and IOP spikes (86), requiring careful follow-up together with anti-inflammatory therapy and pressure control in the early post-operative phase.

Selective laser trabeculoplasty (SLT) may be an effective and safe alternative to ALT in the treatment of PEX glaucoma although further study is needed (76).

Peripheral laser iridotomy is the procedure of choice for therapy of angle-closure glaucoma. A narrow angle associated with PEX syndrome may also represent an argument for prophylactic iridotomy.

Filtration Surgery

Because long-term effects of medical therapy and laser treatment are often unsatisfactory in patients with PEX glaucoma, filtering surgery may be required earlier and more frequently than in other forms of glaucoma. In cases of extremely high IOP fluctuations, a primary trabeculectomy may be considered (87). An alternative surgical approach involving aspiration of pigment and PEX material from the inner surface of the meshwork was specifically developed for treating PEX glaucoma (88). Although efficacious in decreasing IOP in the early course, the effect regressed with time, being often limited to a few weeks (89), possibly due to failure to reach the juxtacanalicular region where the bulk of PEX material is deposited. Other procedures described for PEX glaucoma include sclerocanalectomy (90) and nonpenetrating deep sclerectomy (91). Whatever filtration technique selected, antifibrotic agents may be helpful in limiting the risk of post-operative scarring. A drainage implant may also be indicated when one or more trabeculectomies have failed.

Filtration surgery combined with phacoemulsification does not seem to adversely influence the success rate (92). However, trabecular aspiration, as described above, combined with phacoemulsification was less effective in PEX glaucoma (93). Combined cataract and glaucoma surgery, as compared to cataract surgery alone, has been reported to reduce the frequency and magnitude of post-operative pressure elevation (94). The rate of intraand post-operative complications after combined trabeculectomy and phacoemulsification was the same in PEX patients as compared with non-PEX patients (95). Cataract extraction alone may also improve IOP control in hypertensive patients with PEX syndrome and appears to be more effective than in POAG and cataract patients (96,97).

Post-operative surgical complications, including inflammatory responses, fibrin reactions, formation of synechiae, and IOP spikes, are more common and more serious in PEX eyes than in eyes without PEX because of the exaggerated and prolonged breakdown of the blood–aqueous barrier and the anterior segment hypoxia (53,98). Pre-operative treatment with corticosteroids may therefore be beneficial along with more intensive and prolonged post-operative anti-inflammatory therapy and IOP control. The presence of abnormal iris vessels can lead to intraoperative hemorrhage during iridectomy, with post-operative hyphema. Weakened zonular support may allow vitreous loss, intraoperative lens movement, or even subluxation.

SUMMARY AND PERSPECTIVES

Open-angle glaucoma associated with PEX syndrome accounts for approximately 25% of all glaucomas and represents the most common identifiable cause of glaucomas overall. Because of high IOP levels and diurnal pressure fluctuations, PEX glaucoma

represents a relatively more severe and progressive type of glaucoma. The underlying disorder, PEX syndrome, is a generalized process of the extracellular matrix characterized by production and progressive accumulation of an abnormal extracellular material in intraand extraocular tissues. An emerging clinical spectrum of associations with cardiovascular and cerebrovascular diseases appears to elevate PEX syndrome/glaucoma to a condition of general medical importance. Recent data support the pathogenetic concept of PEX syndrome as a type of stress-induced elastic microfibrillopathy, with TGF- 1 and increased oxidative stress being key factors in the pathogenesis. Active involvement of the trabecular meshwork cells in local production of PEX material in the juxtacanalicular area may be the primary cause of outflow resistance and chronic pressure elevation. Additional pathogenetic factors contributing to pressure rise and glaucoma development include marked pigment dispersion, increased aqueous humor protein concentrations, vascular factors, and connective tissue alterations of the lamina cribrosa. Other mechanisms of glaucoma, including acute openangle glaucoma, due to sudden pigment liberation after diagnostic mydriasis, and angle-closure glaucoma, due to pupillary or ciliary block mechanisms in the presence of an instable zonular apparatus, are also seen in PEX patients.

The debate as to whether PEX is a coincidental finding or is actually the cause of open-angle glaucoma continues. Most studies suggest that the risk of developing glaucoma is cumulative and forms part of the natural course of the disease. However, in patients with clinically unilateral PEX syndrome, glaucoma may develop in the contralateral eyes before there are any clinical signs of PEX, and PEX syndrome may appear later in eyes that were first diagnosed as having POAG. It is not clear whether this reflects an inaccurate clinical diagnosis or coincidence of two different conditions. It is conceivable that an underlying defect in aqueous humor dynamics or additional involvement of a “glaucoma susceptibility gene” may predispose to glaucoma development in PEX eyes. This would also explain why some patients with PEX syndrome never develop ocular hypertension or glaucoma. Glaucoma development may further depend on interindividual differences in managing the metabolic disturbance in the outflow tissues or in the susceptibility to optic nerve damage. In any case, molecular genetic studies are needed to identify specific risk and genetic factors that would help further subclassify patients with PEX syndrome who are at risk for glaucoma development.

In relation to the clinical management of PEX glaucoma patients, early and accurate diagnosis, rigorous reduction and stabilization of mean and diurnal IOP, careful examinations at frequent intervals, expectations of a higher complication rate during surgery, and close attention to post-operative follow-up are all important in preserving the sight of these patients.

REFERENCES

1.Naumann, G.O.H., Schlötzer-Schrehardt, U., Küchle, M. (1998) Pseudoexfoliation syndrome for the comprehensive ophthalmologist. Intraocular and systemic manifestations.

Ophthalmology. 105, 951–968.

2.Ritch, R., Schlötzer-Schrehardt, U. (2001) Exfoliation syndrome. Surv. Ophthalmol. 45, 265–315.

3.Conway, R.M., Schlötzer-Schrehardt, U., Küchle, M., Naumann, G.O.H. (2004) Pseudoexfoliation syndrome: pathologic manifestations of relevance to intraocular surgery. Graefes Arch. Clin. Exp. Ophthalmol. 32, 199–210.

4.Schlötzer-Schrehardt, U., Naumann, G.O.H. (2006) Perspective – ocular and systemic pseudoexfoliation syndrome. Am. J. Ophthalmol. 141, 921–937.

5.Schlötzer-Schrehardt, U., Koca, M., Naumann, G.O.H., Volkholz, H. (1992) Pseudoexfoliation syndrome: ocular manifestation of a systemic disorder? Arch. Ophthalmol. 110, 752–756.

6.Streeten, B.W., Li, Z.Y., Wallace, R.N., Eagle, R.C.J., Keshgegian, A.A. (1992) Pseudoexfoliative fibrillopathy in visceral organs of a patient with pseudoexfoliation syndrome.

Arch. Ophthalmol. 110, 1757–1762.

7.Lindberg, J.G. (1989) Clinical investigations on depigmentation of the pupillary border and translucency of the iris. Acta Ophthalmol. 67(Suppl 190),1–96.

8.Vogt, A. (1925) Ein neues Spaltlampenbild des Pupillengebiets: Hellblauer Pupillensaumfilz mit Häutchenbildung auf der Linsenvorderkapsel. Klin. Monatsbl. Augenheilkd. 75, 1–12.

9.Ritch, R. (1996) Exfoliation syndrome – the most common identifiable cause of open-angle glaucoma. J. Glaucoma. 3, 176–178.

10.Ritch, R., Schlötzer-Schrehardt, U., Konstas, A.G.P. (2003) Why is glaucoma associated with exfoliation syndrome? Prog. Ret. Eye Res. 22, 253–275.

11.Bialasiewicz, A.A., Wali, U., Shenoy, R., Al-Saeidi, R. (2005) Patients with secondary open-angle glaucoma in pseudoexfoliation (PEX) syndrome among a population with high prevalence of PEX. Clinical findings and morphological and surgical characteristics.

Ophthalmology. 102, 1064–1068.

12.Damji, K.F., Bains, H.S., Stefansson, E., Loftsdottir, M., Sverrison, T., Thorgeirsson, E., Jonasson, F., Gottfredsdottir, M., Allingham, R. (1998) Is pseudoexfoliation syndrome inherited? A review of genetic and nongenetic factors and a new observation. Ophthalmic Genet. 19, 175–185.

13.Orr, A.C., Robitaille, J.M., Price, P.A., Hamilton, J.R., Falvey, D.M., De SaintSardos, A.G., Pasternak, S., Guernsey, D.L. (2001) Exfoliation syndrome: clinical and genetic features. Ophthalmic Genet. 22, 171–185.

14.Schlötzer-Schrehardt, U., Zenkel, M., Küchle, M., Sakai, L.Y., Naumann, G.O.H. (2001) Role of transforming growth factor- 1 and its latent form binding protein in pseudoexfoliation syndrome. Exp. Eye Res. 73, 765–780.

15.Zenkel, M., Pöschl, E., von der Mark, K., Hofmann-Rummelt, C., Naumann, G.O.H., Kruse, F.E., Schlötzer-Schrehardt, U. (2005) Differential gene expression in pseudoexfoliation syndrome. Invest. Ophthalmol. Vis. Sci. 46, 3742–3752.

16.Streeten, B.W. (1993) Aberrant synthesis and aggregation of elastic tissue components in pseudoexfoliative fibrillopathy: a unifying concept. New Trend. Ophthalmol. 8, 187–196.

16a. Ovodenko, B., Rostagno, A., Neubert, T.A., Shetty, V., Thomas, S., Yang, A., Liebmann, J., Ghiso, J., Ritch, R. (2007) Proteomic analysis of exfoliation deposits. Invest. Ophthalmol. Vis. Sci. 48, 1447–1457.

17.Gartaganis, S.P., Georgakopoulos, C.D., Exarchou, A.M., Mela, E.K., Lamari, F., Karamanos, N.K. (2001) Increased aqueous humor basic fibroblast growth factor and hyaluronan levels in relation to the exfoliation syndrome and exfoliative glaucoma. Acta Ophthalmol. Scand. 79, 572–575.

18.Hu, D.N., Ritch, R. (2001) Hepatocyte growth factor is increased in the aqueous humor of glaucomatous eyes. J. Glaucoma. 10, 152–157.

19.Ho, S.L., Dogar, G.F., Wang, J., Crean, J., Wu, Q.D., Oliver, N., Weitz, S., Murray, A., Cleary, P.E., O’Brien, C. (2005) Elevated aqueous humour tissue inhibitor of matrix metalloproteinase-1 and connective tissue growth factor in pseudoexfoliation syndrome.

Br. J. Ophthalmol. 89, 169–173.

20.Gartaganis, S.P., Georgakopoulos, C.D., Mela, E.K., Exarchou, A., Ziouti, N., Assouti, M., Vynios, D.H. (2002) Matrix metalloproteinases and their inhibitors in exfoliation syndrome. Ophthalmic Res. 34, 165–171.

21.Schlötzer-Schrehardt, U., Lommatzsch, J., Küchle, M., Konstas, A.G.P., Naumann, G.O.H. (2003) Matrix metalloproteinases and their inhibitors in aqueous humor of patients with pseudoexfoliation syndrome, pseudoexfoliation glaucoma, and primary open-angle glaucoma. Invest. Ophthalmol. Vis. Sci. 44, 1117–1125.

22.Koliakos, G.G., Konstas, A.G.P., Schlötzer-Schrehardt, U., Hollo, G., Katsimbris, I.E.,

Georgiadis, N., Ritch, R. (2003) 8-isoprostaglandin F2A and ascorbic acid concentration in the aqueous humour of patients with exfoliation syndrome. Br. J. Ophthalmol. 87, 353–356.

23.Koliakos, G.G., Konstas, A.G.P., Schlötzer-Schrehardt, U., Hollo, G., Mitova, D., Kovatchev, D., Maloutas, S., Georgiadis, N. (2004) Endothelin-1 concentration is increased in the aqueous humour of patients with exfoliation syndrome. Br. J. Ophthalmol. 88, 523–527.

24.Gartaganis, S.P., Patsoukis, N.E., Nikolopoulos, D.K., Georgiou, C.D. (2006) Evidence

for oxidative stress in lens epithelial cells in pseudoexfoliation syndrome. Eye (E-Pub ahead of print).

25. Yilmaz, A., Adigüzel, U., Tamer, L., Yildirim, Ö., Öz, Ö., Vatansever, H., Ercan, B., Degirmenci, U., Atik, U. (2005) Serum oxidant/antioxidant balance in exfoliation syndrome. Graefes Arch. Clin. Exp. Ophthalmol. 33, 63–66.

26.Yagci, R., Gürel, A., Ersöz, I., Keskin, U.C., Hepsen, I.F., Duman, S., Yigitoglu, R. (2006) Oxidative stress and protein oxidation in pseudoexfoliation syndrome. Curr. Eye Res. 31, 1029–1032.

27.Helbig, H., Schlötzer-Schrehardt, U., Noske, W., Kellner, U., Foerster, M.H., Naumann, G.O.H. (1994) Anterior chamber hypoxia and iris vasculopathy in pseudoexfoliation syndrome. Ger. J. Ophthalmol. 3, 148–153.

28.Yüksel, N., Karabas, L., Arslan, A., Demirci, A., Caglar, Y. (2001) Ocular hemodynamics in pseudoexfoliation syndrome and pseudoexfoliation glaucoma. Ophthalmology. 108, 1043–1049.

29.Harju, M., Vesti, E. (2001) Blood flow of the optic nerve head and peripapillary retina in exfoliation syndrome with unilateral glaucoma or ocular hypertension. Graefes Arch. Clin. Exp. Ophthalmol. 239, 271–277.

30.Ocakoglu, O., Koyluoglu, N., Kayiran, A., Tamcelik, N., Ozkan, S. (2004) Microvascular blood flow of the optic nerve head and peripapillary retina in unilateral exfoliation syndrome. Acta Ophthalmol. Scand. 82, 49–53.

31.Cursiefen, C., Händel, A., Schönherr, U., Naumann, G.O.H. (1997) Pseudoexfoliation syndrome in patients with branch and central retinal vein thrombosis. Klin. Monatsbl.

Augenheilkd. 211, 17–21.

32.Gillies, W.E., Brooks, A.M.V. (2002) Central retinal vein occlusion in pseudoexfoliation of the lens capsule. Graefes Arch. Clin. Exp. Ophthalmol. 30, 176–178.

33.Kotikoski, H., Moilanen, E., Vapaatalo, H., Aine, E. (2002) Biochemical markers of the L-arginine-nitric oxide pathway in the aqueous humour in glaucoma patients. Acta Ophthalmol. Scand. 80, 191–195.

34.Bleich, S., Roedl, J., von Ahsen, N., Schlötzer-Schrehardt, U., Reulbach, U., Beck, G., Kruse, F.E., Naumann, G.O.H., Kornhuber, J., Jünemann, A.G.M. (2004) Elevated homocysteine levels in aqueous humor of patients with pseudoexfoliation glaucoma. Am. J. Ophthalmol. 138, 162–164.

35.Forsius, H., Forsman, E., Fellman, J., Eriksson, A.W. (2002) Exfoliation syndrome: frequency, gender distribution and association with climatically induced alterations of the cornea and conjunctiva. Acta Ophthalmol. Scand. 80, 478–484.

36.Puska, P.M. (2002) Unilateral exfoliation syndrome: conversion to bilateral exfoliation and to glaucoma: a prospective 10-year follow-up study. J. Glaucoma. 11, 517–524.

37.Yarangümeli, A., Davutluoglu, B., Köz, Ö.G., Elhan, A.H., Yaylaci, M., Kural, G.K. (2006) Glaucomatous damage in normotensive fellow eyes of patients with unilateral hypertensive pseudoexfoliation glaucoma: normotensive pseudoexfoliation glaucoma?

Graefes Arch. Clin. Exp. Ophthalmol. 34, 15–19.

38.Konstas, A.G.P., Stewart, W.C., Stromann, G.A. (1997) Clinical presentation and initial treatment patterns in patients with exfoliation glaucoma versus primary open-angle glaucoma. Ophth. Surg. Lasers 28, 111–117.

39.Konstas, A.G.P., Mantziris, D.A., Stewart, W.C. (1997) Diurnal intraocular pressure in untreated exfoliation and primary open-angle glaucoma. Arch. Ophthalmol. 115, 182–185.

40.Leskea, M.C., Heijl, A., Hyman, L., Bengtsson, B., Komaroff, E. (2004) Factors for progression and glaucoma treatment: the Early Manifest Glaucoma Trial. Curr. Opin. Ophthalmol. 15, 102–106.

41.Linnér, E., Schwartz, B., Araujo, D. (1989) Optic disc pallor and visual field defect in exfoliative and non-exfoliative, untreated ocular hypertension. Int. Ophthalmol. 13, 21–24.

42.Jonas, J.B., Papastathopoulos, K.I. (1997) Optic disc appearance in pseudoexfoliation syndrome. Am. J. Ophthalmol. 123, 174–180.

43.Puska, P., Vesti, E., Tomita, G., Ishida, K., Raitta, C. (1999) Optic disc changes in normotensive persons with unilateral exfoliation syndrome: a 3-year follow-up study-

Graefes Arch. Clin. Exp. Ophthalmol. 237, 457–462.

44.Tezel, G., Tezel, T.H. (1993) The comparative analysis of optic disc damage in exfoliative glaucoma. Acta Ophthalmol. 71, 744–750.

45.Johnson, D.H., Brubaker, R.F. (1982) Dynamics of aqueous humor in the syndrome of exfoliation with glaucoma. Am. J. Ophthalmol. 93, 629–634.

46.Gharagozloo, N.Z., Baker, R.H., Brubaker, R.F. (1992) Aqueous dynamics in exfoliation syndrome. Am. J. Ophthalmol. 114, 473–478.

47.Richardson, T.M., Epstein, D.L. (1981) Exfoliation glaucoma. A quantitative perfusion and ultrastructural study. Ophthalmology. 88, 968–980.

48.Schlötzer-Schrehardt, U., Naumann, G.O.H. (1995) Trabecular meshwork in pseudoexfoliation syndrome with and without open-angle glaucoma. A morphometric, ultrastructural study. Invest. Ophthalmol. Vis. Sci. 36, 1750–1764.

49.Gottanka, J., Flügel-Koch, C., Martus, P. (1997) Correlation of pseudoexfoliative material and optic nerve damage in pseudoexfoliation syndrome. Invest. Ophthalmol. Vis. Sci. 38, 2435–2446.

50.Alvarado, J., Murphy, C., Juster, R. (1984) Trabecular meshwork cellularity in primary open-angle glaucoma and non-glaucomatous normals. Ophthalmology 91, 564–579.

51.Gottanka, J., Kuhlmann, A., Scholz, M., Johnson, D.H., Lütjen-Drecoll, E. (2005) Pathophysiologic changes in the optic nerves of eyes with primary open angle and pseudoexfoliation glaucoma. Invest. Ophthalmol. Vis. Sci. 46, 4170–4181.

52.Asano, N., Schlötzer-Schrehardt, U., Naumann, G.O.H. (1995) A histopathologic study of iris changes in pseudoexfoliation syndrome. Ophthalmology. 102, 1279–1290.

53.Küchle, M., Nguyen, N., Hannappel, E. (1995) The blood-aqueous barrier in eyes with pseudoexfoliation syndrome. Ophthalmic Res. 27(Suppl 1),136–142.

54.Schlötzer-Schrehardt, U., Küchle, M., Naumann, G.O.H. (1999) Mechanisms of glaucoma development in pseudoexfoliation syndrome, in Pathogenesis and Risk Factors of Glaucoma (Gramer, E. and Grehn, F., eds.), Springer, Heidelberg, pp. 34–49.

55.Schlötzer-Schrehardt, U., Naumann, G.O.H. (2004) Pseudoexfoliation glaucoma, in Essentials in Ophthalmology – Glaucoma (Grehn, F. and Stamper, R., eds.), Springer, Heidelberg, pp.157–176.

56.Cobb, C.J., Blanco, G., Spaeth, G.L. (2004) Exfoliation syndrome angle characteristics: a lack of correlation with amount of disc damage. Br. J. Ophthalmol. 88, 1002–1003.

57.Sampaolesi, R., Zarate, J., Croxato, O. (1988) The chamber angle in exfoliation syndrome: Clinical and pathological findings. Acta Ophthalmol. 66(Suppl 184), 48–53.

58.Zagórski, Z., Gossler, B., Naumann, G.O.H. (1989) Effect of low oxygen tension on the growth of bovine corneal endothelial cells in vitro. Ophthalmic Res. 21, 440–442.

59.Netland, P.A., Ye, H., Streeten, B.W., Hernandez, M.R. (1995) Elastosis of the lamina cribrosa in pseudoexfoliation syndrome with glaucoma. Ophthalmology. 102, 878–886.

60.Krause, U., Helve, J., Forsius, H. (1973) Pseudoexfoliation of the lens capsule and liberation of iris pigment. Acta Ophthalmol. 51, 39–46.

61.Gillies, W.E., Brooks, A.M. (1988) The presentation of acute glaucoma in pseudoexfoliation of the lens capsule. Aust. N. Z. J. Ophthalmol. 16, 101–106.

62.Lim, M.C., Doe, E.A., Vroman, D.T., Rosa, R.H., Parrish, R.K. (2001) Late onset lens particle glaucoma as a consequence of spontaneous dislocation of an intraocular lens in pseudoexfoliation syndrome. Am. J. Ophthalmol. 132, 261–263.

63.Bartholomew, R.S. (1981) Pseudoexfoliation and angle-closure glaucoma. Glaucoma. 3, 213–216.

64.Gross, F.J., Tingey, D., Epstein, D.L. (1994) Increased prevalence of occludable angles and angle-closure glaucoma in patients with pseudoexfoliation. Am. J. Ophthalmol. 117, 333–336.

65.Ritch, R. (1994) Exfoliation syndrome and occludable angles. Trans. Am. Ophthalmol. Soc. 92, 845–944.

66.Wishart, P.K., Spaeth, G.L., Poryzees, E.M. (1985) Anterior chamber angle in the exfoliation syndrome. Br. J. Ophthalmol. 69, 103–107.

67.Lanzl, I.M., Merté, R.L., Graham, A.D. (2000) Does head positioning influence anterior chamber depth in pseudoexfoliation syndrome? J. Glaucoma 9, 214–218.

68.Von der Lippe, I., Küchle, M., Naumann, G.O.H. (1993) Pseudoexfoliation syndrome as a risk factor for acute ciliary block angle closure glaucoma. Acta Ophthalmol. 71, 277–279.

69.Altintas, Ö., Yüksel, N., Karabas, V.L., Caglar, Y. (2004) Diurnal intraocular pressure variation in pseudoexfoliation syndrome. Eur. J. Ophthalmol. 14, 495–500.

70.Teus, M.A., Castejon, M.A., Calvo, M.A. (1998) Intraocular pressure as a risk factor for visual field loss in pseudoexfoliative and in primary open-angle glaucoma. Ophthalmology 105, 2225–2229.

71.Gumus, K., Bozkurt, B., Sonmez, B., Irkec, M., Orhan, M., Saracbasi, O. (2006) Diurnal variation of intraocular pressure and its correlation with retinal nerve fiber analysis in Turkish patients with exfoliation syndrome. Graefes Arch. Clin. Exp. Ophthalmol. 244, 170–176.

72.Bergea, B., Bodin, L., Svedbergh, B. (1999) Impact of intraocular pressure regulation on visual fields in open-angle glaucoma. Ophthalmology 106, 997–1004.

73.Konstas, A.G.P., Hollo, G., Astakhov, Y.S., Teus, M.A., Akopov, E.L., Jenkins, J.N., Stewart, W.C. (2004) Factors associated with long-term progression or stability in exfoliation glaucoma. Arch. Ophthalmol. 122, 29–33.

74.Inoue, K., Okugawa, K., Oshika, T., Amano, S. (2003) Morphological study of corneal endothelium and corneal thickness in pseudoexfoliation syndrome. Jpn. J. Ophthalmol. 47, 235–239.

75.Grodum, K., Heijl, A., Bengtsson, B. (2005) Risk of glaucoma in ocular hypertension with and without pseudoexfoliation. Ophthalmology 112, 386–390.

76.Konstas, A.G.P., Tsironi, S., Ritch, R. (2006) Current concepts in the pathogenesis and management of exfoliative syndrome and exfoliative glaucoma. Comp. Ophthalmol. Update. 7, 131–141.

77.Konstas, A.G.P., Kozobolis, V.P., Tersis, I., Leech, J., Stewart, W.C. (2003) The efficacy and safety of the timolol/dorzolamide fixed combination vs latanoprost in exfoliation glaucoma. Eye 17, 41–46.

78.Parmaksiz, S., Yüksel, N., Karabas, V.L., Özkan, B., Demirci, G., Caglar, Y. (2005) A comparison of travoprost, latanaoprost, and the fixed combination of dorzolamide and timolol in patients with pseudoexfoliation glaucoma. Eur. J. Ophthalmol. 16, 73–80.

79.Konstas, A.G.P., Mylopoulos, N., Karabatsas, C.H., Kozobolis, V.P., Diafas, S., Papapanos, P., Georgiadis, N., Stewart, W.C. (2004) Diurnal intraocular pressure reduction with latanoprost 0.005% compared to timolol maleate 0.5% as monotherapy in subjects with exfoliation glaucoma. Eye 18, 893–899.

80.Konstas, A.G.P., Koliakos, G.G., Liakos, P., Karabatsas, C.H., Liakos, P., SchlötzerSchrehardt, U., Georgiadis, N., Ritch, R. (2006) Latanoprost therapy reduces the levels of TGF beta 1 and gelatinases in the aqueous humor of patients with exfoliative glaucoma.

Exp. Eye Res. 82, 319–322.

81.Konstas, A.G.P., Hollo, G., Irkec, M., Tsironi, S., Durukan, I., Goldenfeld, M., Melamed, S. (2006) Diurnal IOP control with bimatoprost vs latanoprost in exfoliative glaucoma: a crossover observer-masked three-center study. Br. J. Ophthalmol. (E-Pub ahead of print).

82.Konstas, A.G.P., Kozobolis, V.P., Katsimpris, I.E., Boboridis, K., Koukoula, S., Jenkins, J.N., Stewart, W.C. (2007) Efficacy and safety of latanoprost versus travoprost in exfoliative glaucoma patients. Ophthalmology (E-Pub ahead of print).

83.Hepsen, I.F., Ozkaya, E. (2006) 24-h IOP control with latanoprost, travoprost, and bimatoprost in subjects with exfoliation syndrome and ocular hypertension. Eye (E-Pub ahead of print).

84.Nordmann, J.P., Mertz, B., Yannoulis, N.C., Schwenninger, C., Kapik, B., Shams, N., Unoprostone Monotherapy Study Group-EU (2002) A double-masked randomized comparison of the efficacy and safety of unoprostone with timolol and betaxolol in patients with primary open-angle glaucoma including pseudoexfoliation glaucoma or ocular hypertension. 6 month data. Am. J. Ophthalmol. 133, 1–10.

85.Threlkeld, A.B., Hertzmark, E., Sturm, R.T. (1996) Comparative study of the efficacy of argon laser trabeculoplasty for exfoliation and primary open-angle glaucoma. J. Glaucoma 5, 311–316.

86.Odberg, T., Sandvik, L. (1999) The medium and long-term efficacy of primary argon laser trabeculoplasty in avoiding topical medication in open-angle glaucoma. Acta Ophthalmol. Scand. 77, 176–181.

87.Popovic, V., Sjöstrand, J. (1999) Course of exfoliation and simplex glaucoma after primary trabeculectomy. Br. J. Ophthalmol. 83, 305–310.

88.Jacobi, P.C., Krieglstein, G.K. (1995) Trabecular aspiration: a new mode to treat pseudoexfoliation glaucoma. Invest. Ophthalmol. Vis. Sci. 36, 2271–2276.

89.Grüb, M., Mielke, J., Rohrbach, J.M., Schlote, T. (2002) Trabecular aspiration in pseudoexfoliative glaucoma-surgery to primarily reduce intraocular pressure. Klin. Monatsbl. Augenheilkd. 219, 353–357.

90.Pallas, G., Pajic, B. (2000) Sclerothalamectomy (STE): stable postoperative intraocular pressure regulation in primary open-angle and pseudoexfoliative glaucoma. Klin. Monatsbl. Augenheilkd. 216, 256–260.

91.Drolsum, L. (2003) Deep sclerectomy in patients with capsular glaucoma. Acta Ophthalmol. Scand. 81, 553–555.

92.Cillino, S., Pace, F.D., Casuccio, A., Calvaruso, L., Morreale, D., Vadala, M., Lodato, G. (2004) Deep sclerectomy versus punch trabeculectomy with or without phacoemulsification: a randomized clinical trial. J. Glaucoma. 13, 500–506.

93.Jacobi, P.C., Dietlein, T.S., Krieglstein, G.K. (2000) The risk profile of trabecular aspiration versus trabeculectomy in glaucoma triple procedure. Graefes Arch. Clin. Exp. Ophthalmol. 238, 545–551.

94.Krupin, T., Feitl, M.E., Bishop, K.I. (1989) Postoperative intraocular pressure rise in openangle glaucoma patients after cataract or combined cataract-filtration surgery. Ophthalmology 96, 579–584.

95.Landa, G., Pollack, A., Marcovich, A., Rachmiel, R., Bukelman, A., Zalish, M. (2005) Results of combined phacoemulsification and trabeculectomy with mitomycin C in pseudoexfoliation versus non-pseudoexfoliation glaucoma. Graefes Arch. Clin. Exp. Ophthalmol. 243, 1236–1240.

96.Merkur, A., Damji, K.F., Mintsioulis, G., Hodge, W.G. (2001) Intraocular pressure decrease after phacoemulsification in patients with pseudoexfoliation syndrome. J. Cataract Refract. Surg. 27, 528–532.

97.Damji, K.F., Konstas, A.G.P., Liebmann, J.M., Hodge, W.G., Ziakas, N.G., Giannikakis, S., Mintsioulis, G., Merkur, A., Pan, Y., Ritch, R. (2006) Intraocular pressure following phacoemulsification in patients with and without exfoliation syndrome: a 2 year prospective study. Br. J. Ophthalmol. 90, 1014–1018.

98.Nguyen, N.X., Küchle, M., Martus, P., Naumann, G.O.H. (1999) Quantification of bloodaqueous barrier breakdown after trabeculectomy: pseudoexfoliation versus primary openangle glaucoma. J. Glaucoma 8, 18–23.