Ординатура / Офтальмология / Английские материалы / Mechanisms of the Glaucomas_Shields, Tombran-Tink, Barnstable_2008
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this hypothesis, a pressure differential is created between the vitreous and aqueous compartments, and the iris–lens diaphragm and ciliary body are pushed anteriorly. As a consequence, there is diffuse shallowing of the anterior chamber and angle closure.
Initial medical therapy is directed at lowering the IOP with aqueous suppressants, shrinking the vitreous with hyperosmotic agents, and attempting backward displacement of the lens–iris diaphragm with cycloplegics. If unsuccessful after a few days, or if lens–cornea touch occurs, laser therapy may be attempted. As pupillary block is difficult to exclude, a patent iridotomy must first be verified or created. Immediate deepening of the anterior chamber and decrease in IOP after successful Nd : YAG laser disruption of the anterior vitreous face, with establishment of direct vitreous–aqueous communication, is perhaps the greatest support for the theory of aqueous misdirection (59–63). When laser hyaloidotomy is not possible or is unsuccessful, vitrectomy should be performed. Here again, support for the proposed mechanism is given by the observation that vitrectomy alone is less often successful compared with cases in which vitrectomy is combined with excision of at least part of the lens capsule or zonules, thereby establishing vitreo–aqueous communication (64–68).
The availability of UBM has led to the description of mechanisms that were previously indistinguishable from malignant glaucoma. In one such mechanism, the accumulation of supraciliary fluid leads to the detachment and anterior rotation of the ciliary body and consequent angle closure (see Fig. 8). It may be part of diffuse choroidal detachment observable with B-scan ultrasound (69) or it may be a more subtle finding observable only with UBM (70). These cases may respond more favorably to medical therapy alone, hence the importance of their identification.
Choroidal Effusion/Swelling and Ciliary Body Rotation/Detachment
Ciliary body swelling and/or anterior suprachoroidal effusion can be a manifestation of well-defined clinical conditions and infrequently lead to angle narrowing or closure.
Fig. 8. Angle closure caused by supraciliary fluid causing anterior rotation of the ciliary body. Asterisk indicates supraciliary effusion. AC, anterior chamber; C, cornea; CB, ciliary body; LC, lens capsule; I, iris; S, sclera.
Posterior Pushing Angle Closure |
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This has been described in posterior scleritis (71), central vein occlusion (72–74), and following panretinal photocoagulation (75).
Other Causes
Cases of bilateral anterior chamber shallowing and angle closure have been associated with idiosyncratic drug reactions and systemic inflammatory conditions (76–79). UBM has allowed the identification of ciliary body detachment as the underlying mechanism (80,81).
Angle Closure After Scleral Buckling Procedures
Angle closure has also been reported after scleral buckling (21,82). It has been proposed that when pupillary block is absent, the underlying mechanism is detachment and/or edema of the ciliary body resulting in anterior displacement and angle closure. If this condition is diagnosed in the early post-operative period, PAS and chronic angle closure can be prevented with ALPI (83).
Rarely, tumors in the posterior segment can present with angle closure (84,85). As in the case of other primary sources in the posterior segment for angle closure, a tumor should be suspected when the fellow eye has a wide open angle and the two eyes have similar refraction. If the posterior segment cannot be visualized, imaging with ultrasound is required.
ACKNOWLEDGMENTS
This study was supported in part by the Paul and Ellen Richman Research Fund of the New York Glaucoma Research Institute, New York, NY.
REFERENCES
1.Ritch R. Argon laser treatment for medically unresponsive attacks of angle-closure glaucoma. Am J Ophthalmol 1982;94:197.
2.Pavlin CJ, Ritch R, Foster FS. Ultrasound biomicroscopy in plateau iris syndrome. Am J Ophthalmol 1992;113:390–395.
3.Wand M, Grant WM, Simmons RJ, Hutchinson BT. Plateau iris syndrome. Trans Am Acad Ophthalmol Otolaryngol 1977;83:122–130.
4.Yeung BY, Ng PW, Chiu TY, et al. Prevalence and mechanism of appositional angle closure in acute primary angle closure after iridotomy. Clin Exp Ophthalmol 2005;33:478–482.
5.Ritch R, Liebmann JM, Tello C. A construct for understanding angle-closure glaucoma: the role of ultrasound biomicroscopy. Ophthalmol Clin N Amer 1995;8:281–293.
6.Tello CT, Ishikawa H, Rothman RF, Ritch R. Differential diagnosis of the angle-closure glaucomas. Ophthalmol Clin N Amer 2000;13:443–454.
7.Pavlin CJ, Foster FS. Plateau iris syndrome: changes in angle opening associated with dark, light, and pilocarpine administration. Am J Ophthalmol 1999;128:288–291.
8.Gazzard G, Foster PJ, Friedman DS, Khaw PT, Seah SKL. Light to dark physiological variation in irido-trabecular angle width. Br J Ophthalmol 2004; 88 video report. Available online: http://bio.bmjjournals.com/cgi/content/full/88/11/DC1/1.
9.Dorairaj SK, Tello C, Liebmann JM, Ritch R. Narrow angles and angle closure: anatomic reasons for earlier closure of the superior portion of the iridocorneal angle. Arch Ophthalmol 2007 Jun;125(6):734–9.
184 |
Barkana et al. |
10.Hoerauf H, Scholz C, Koch P, et al. Transscleral optical coherence tomography: a new imaging method for the anterior segment of the eye. Arch Ophthalmol 2002;120:816–819.
11.Radhakrishnan S, Goldsmith J, Huang D, et al. Comparison of optical coherence tomography and ultrasound biomicroscopy for detection of narrow anterior chamber angles. Arch Ophthalmol 2005;123:1053–1059.
12.Leung CKS, Chan W-M, Ko CY, et al. Visualization of anterior chamber angle dynamics using optical coherence tomography. Ophthalmology 2005;112:980–984.
13.Tornquist R. Angle-closure glaucoma in an eye with a plateau type of iris. Acta Ophthalmol 1958;36:413–420.
14.Ritch R. Plateau iris is caused by abnormally positioned ciliary processes. J Glaucoma 1992;1:23–26.
15.Tran HV, Ritch R, Liebmann JM. Iridociliary apposition in plateau iris syndrome persists after cataract extraction. Am J Ophthalmol 2003;135:40–44.
16.Lowe RF, Ritch R. Angle-closure glaucoma: Clinical types. In: Ritch R, Shields MB, Krupin T, editors. The Glaucomas. St. Louis: CV Mosby Co, 1989:839–853.
17.Godel V, Stein R, Feiler-Ofry V. Angle-closure glaucoma following peripheral iridectomy and mydriasis. Am J Ophthalmol 1968;65:555–560.
18.Lowe RF. Primary angle-closure glaucoma: postoperative acute glaucoma after phenylephrine eye-drops. Am J Ophthalmol 1968;65:552.
19.Lowe RF. Plateau iris. Aust J Ophthalmol 1981;9:71.
20.Ritch R, Chang BM, Liebmann JM. Angle closure in younger patients. Ophthalmology 2003;110:1880–1889.
21.Barkana Y, Shihadeh W, Oliveira C, et al. Angle closure in highly myopic eyes. Ophthalmology 2006;113:247–254.
22.Ritch R. Techniques of Argon Laser Iridectomy and Iridoplasty. Palo Alto: Coherent Medical Press, 1983.
23.Ritch R. Argon laser peripheral iridoplasty: an overview. J Glaucoma 1992;1:206–213.
24.Sassani JW, Ritch R, McCormick S, Liebmann JM, et al. Histopathology of argon laser peripheral iridoplasty. Ophthalmic Surg 1993;24:740–745.
25.Ritch R, Tham CCY, Lam DSC. Long-term success of argon laser peripheral iridoplasty in the management of plateau iris syndrome. Ophthalmology 2004;111:104–108.
26.Azuara-Blanco A, Spaeth GL, Araujo SV, Augsburger JJ, Terebuh AK. Plateau iris syndrome associated with multiple ciliary body cysts. Report of three cases. Arch Ophthalmol 1996;114:666–668.
27.Crowston JG, Medeiros FA, Mosaed S, Weinreb RN. Argon laser iridoplasty in the treatment of plateau-like iris configuration as result of numerous ciliary body cysts. Am J Ophthalmol 2005;139:381–383.
28.Ritch R. Exfoliation syndrome: clinical findings and occurrence in patients with occludable angles. Trans Am Ophthalmol Soc 1994;92:845–944.
29.Gross FJ, Tingey D, Epstein DL. Increased prevalence of occludable angles and angleclosure glaucoma in patients with pseudoexfoliation. Am J Ophthalmol 1994;117:333–336.
30.Ritch R, Wand M. Treatment of the Weill-Marchesani syndrome (editorial). Ann Ophthalmol 1981;13:665.
31.Ritch R, Solomon LD. Argon laser peripheral iridoplasty for angle-closure glaucoma in siblings with Weill-Marchesani syndrome. J Glaucoma 1992;1:243–247.
32.Kutner BN. Acute angle closure glaucoma in nonperforating blunt trauma. Arch Ophthalmol 1988;106:19–20.
33.Izquierdo NJ, Traboulsi EI, Enger C, Maumenee IH. Glaucoma in the Marfan syndrome. Trans Am Ophthalmol Soc 1992;90:111–117; discussion 118–122.
34.Tomey KF, Al-Rajhi AA. Neodymium:YAG laser iridotomy in the initial management of phacomorphic glaucoma. Ophthalmology 1992;99:660–665.
Posterior Pushing Angle Closure |
185 |
35.Ritch R, Liebmann J, Solomon IS. Laser iridectomy and iridoplasty. In: Ritch R, Shields MB, Krupin T, editors. The Glaucomas. St. Louis: CV Mosby Co, 1989:581–603.
36.Abramson DH, Coleman DJ, Forbes M, Franzen LA. Pilocarpine: effect on the anterior chamber and lens thickness. Arch Ophthalmol 1972;87:615–619.
37.Abramson DH, Chang S, Coleman J. Pilocarpine therapy in glaucoma: effects on anterior chamber depth and lens thickness in patients receiving long term therapy. Arch Ophthalmol 1976;94:914–918.
38.Rosenthal JW, Kloepfer HW. The spherophakia-brachymorphia syndrome. Arch Ophthalmol 1956;55:28.
39.Shapira TM. Micro-and spherophakia with glaucoma. Am J Ophthalmol 1934;17:726–735.
40.Ritch R, Solomon IS. Laser treatment of glaucoma, 3 ed. In: L’Esperance FAJ, editor. Ophthalmic Lasers. St Louis: CV Mosby Co, 1989:650–748.
41.Wishart PK, Atkinson PL. Extracapsular cataract extraction and posteror chamber lens implantation in patients with primary chronic angle-closure glaucoma: effect on intraocular pressure control. Eye 1989;3:706–712.
42.Greve EL. Primary angle closure glaucoma: extracapsular cataract extraction or filtering procedure? Int Ophthalmol 1988;12:157–62.
43.Acton J, Salmon JF, Scholtz R. Extracapsular cataract extraction with posterior chamber lens implantation in primary angle closure glaucoma. J Cataract Refract Surg 1997;23: 930–934.
44.Roberts TV, Francis IC, Lertusumitkul S, et al. Primary phacoemulsification for uncontrolled angle-closure glaucoma. J Cataract Refract Surg 2000;26:1012–1016.
45.Nonaka A, Kondo T, Kikuchi M, et al. Cataract surgery for residual angle closure after peripheral laser iridotomy. Ophthalmology 2005;112:974–979.
46.Nonaka A, Kondo T, Kikuchi M, et al. Angle widening and alteration of ciliary process configuration after cataract surgery for primary angle closure. Ophthalmology 2006;113:437–441.
47.Lai JSM, Tham CCY, Chan JCH. The clinical outcomes of cataract extraction by phacoemulsification in eyes with primary angle-closure glaucoma (primary angle-closure glaucoma) and co-existing cataract: a prospective case series. J Glaucoma 2006;15:47–52.
48.Gunning FP, Greve EL. Lens extraction for uncontrolled angle-closure glaucoma: long-term follow-up. J Cataract Refract Surg 1998;24:1347–1356.
49.Liu CJ, Cheng CY, Wu CW, et al. Factors predicting intraocular pressure control after phacoemulsification in angle-closure glaucoma. Arch Ophthalmol 2006;124:1390–1394.
50.Campbell DG, Vela A. Modern goniosynechialysis for the treatment of synechial angleclosure glaucoma. Ophthalmology 1984;91:1052–1060.
51.Tanihara H, Nishiwaki K, Nagata M. Surgical results and complications of goniosynechialysis. Graefes Arch Clin Exp Ophthalmol 1992;230:309–313.
52.Teekhasaenee C, Ritch R. Combined phacoemulsification and goniosynechialysis for uncontrolled chronic angle-closure glaucoma after acute angle-closure glaucoma. Ophthalmology 1999;106:669–675.
53.Harasymowycz PJ, Papamatheakis DG, Ahmed I, et al. Phacoemulsification and goniosynechialysis in the management of unresponsive primary angle closure. J Glaucoma 2005;14:186–189.
54.Tham CCY, Lai JSM, Poon ASY, et al. Immediate argon laser peripheral iridoplasty (ALPI) as initial treatment for acute phacomorphic angle-closure (phacomorphic glaucoma) before cataract extraction: a preliminary study. Eye 2005;19:778–783.
55.Jacobi PC, Dietlein TS, Luke C, Engels B, Kreiglstein GK. Primary phacoemulsification and intraocular lens implantation for acute angle-closure glaucoma. Ophthalmology 2002;109:1597–603.
56.Ming Zhi Z, Lim AS, T. YW. A pilot study of lens extraction in the management of acute primary angle-closure glaucoma. Am J Ophthalmol 2003;135:534–536.
186 |
Barkana et al. |
57.von Graefe A. Beiträge zur Pathologie und Therapie des Glaukoms. Arch f Ophthalmol 1869;15:228.
58.Shaffer RN. The role of vitreous detachment in aphakic and malignant glaucoma. Trans Am Acad Ophthalmol Otolaryngol 1954;58:217–231.
59.Epstein DL, Steinert RF, Puliafito CA. Neodymium-YAG laser therapy to the anterior hyaloid in aphakic malignant glaucoma. Am J Ophthalmol 1984;98:137.
60.Brown RH, Lynch MG, Tearse JE, Nunn RD. Neodymium-YAG vitreous surgery for phakic and pseudophakic malignant glaucoma. Arch Ophthalmol 1986;104:1464–1466.
61.Melamed S, Ashkenazi I, Blumenthal M. Nd-YAG laser hyaloidotomy for malignant glaucoma following one-piece 7 mm intraocular lens implantation. Br J Ophthalmol 1991;75:501.
62.Halkias A, Magauran DM, Joyce M. Ciliary block (malignant) glaucoma after cataract extraction with lens implant treated with YAG laser capsulotomy and anterior hyaloidotomy. Br J Ophthalmol 1992;76:569–570.
63.Little BC, Hitchings RA. Pseudophakic malignant glaucoma: Nd:YAG capsulotomy as a primary treatment. Eye 1993;7:102–104.
64.Weiss H, Shin DH, Kollarits CR. Vitrectomy for malignant (ciliary block) glaucomas. Int Ophthalmol Clin 1981;21:113–119.
65.Momoeda S, Hayashi H, Oshima K. Anterior pars plana vitrectomy for phakic malignant glaucoma. Jpn J Ophthamol 1983;27:73–79.
66.Lynch MG, Brown RH, Michels RG, Pollack IP, Stark WJ. Surgical vitrectomy for pseudophakic malignant glaucoma. Am J Ophthalmol 1986;102:149–153.
67.Byrnes GA, Leen MM, Wong TP, Benson WE. Vitrectomy for ciliary block (malignant) glaucoma. Ophthalmology 1995;102:1308–1311.
68.Tsai JC, Barton KA, Miller MH, Khaw PT, Hitchings RA. Surgical results in malignant glaucoma refractory to medical or laser therapy. Eye 1997;11:677–681.
69.Dugel PR, Heuer DK, Thach AB, et al. Annular peripheral choroidal detachment simulating aqueous misdirection after glaucoma surgery. Ophthalmology 1997;104:439–444.
70.Liebmann JM, Weinreb RN, Ritch R. Angle-closure glaucoma associated with occult annular ciliary body detachment. Arch Ophthalmol 1998;116:731–735.
71.Quinlan MP, Hitchings RA. Angle-closure glaucoma secondary to posterior scleritis. Br J Ophthalmol 1978;62:330–335.
72.Hyams SW, Neumann E. Transient angle closure glaucoma after retinal vein occlusion. Br J Ophthalmol 1972;56:353–355.
73.Bloome MA. Transient angle-closure glaucoma in central retinal vein occlusion. Ann Ophthalmol 1977;9:44.
74.Mendelsohn AD, Jampol LM, Schoch D. Secondary angle-closure glaucoma after central retinal vein occlusion. Am J Ophthalmol 1985;100:581–585.
75.Blondeau P, Pavan PR, Phelps CD. Acute pressure elevation following panretinal photoagulation. Arch Ophthalmol 1981;99:1239.
76.Mandelkorn RM, Zimmerman TJ. Nonsteroidal drugs and glaucoma. In: Ritch R, Shields MB, Krupin T, editors. The Glaucomas. St Louis: CV Mosby Co, 1996:1189–1204.
77.Wisotsky BJ, Magat-Gordon CB, Puklin JE. Angle-closure glaucoma as an initial presentation of systemic lupus erythematosus. Ophthalmology 1998;105:1170–1172.
78.Rathinam SR, Namperumalsamy P, Nozik RA, Cunningham ET, Jr. Angle closure glaucoma as a presenting sign of Vogt-Koyanagi-Harada syndrome. Br J Ophthalmol 1997;81: 608–609.
79.Rhee DJ, Goldberg MJ, Parrish RK. Bilateral angle-closure glaucoma and ciliary body swelling from topiramate. Arch Ophthalmol 2001;119:1723–1725.
80.Postel EA, Assalian A, Epstein DL. Drug-induced transient myopia and ACG associated with supraciliary choroidal effusion. Am J Ophthalmol 1996;122:110–112.
Posterior Pushing Angle Closure |
187 |
81.Kishi A, Nao-i N, Sawada A. Ultrasound biomicroscopic findings of acute angle-closure glaucoma in Vogt-Koyanagi-Harada syndrome. Am J Ophthalmol 1996;122:735–737.
82.Perez RN, Phelps CD, Burton TC. Angle-closure glaucoma following scleral buckling operations. Trans Am Acad Ophthamol Otolaryugol 1976;81:247–252.
83.Burton TC, Folk JC. Laser iris retraction for angle-closure glaucoma after retinal detachment surgery. Ophthalmology 1988;95:742–748.
84.Al-Torbak A, Karcioglu ZA, Abboud E, Netland PA. Phacomorphic glaucoma associated with choroidal melanoma. Ophthalmic Surg Lasers 1998;29:510–513.
85.Escalona-Benz E, Benz MS, Briggs JW, et al. Uveal melanoma presenting as acute angleclosure glaucoma: report of two cases. Am J Ophthalmol 2003;136:756–758.
III
GENETICS OF GLAUCOMA
INTRODUCTION
The vast majority of glaucoma phenotypes have a hereditary basis, with exceptions being primarily those that result from trauma, infection, or surgical intervention. In some cases, these inherited forms of glaucoma have a Mendelian autosomal-dominant or autosomal-recessive mode, whereas others are inherited as a complex multifactorial trait (1). The former tend to be early-onset forms of glaucoma, such as congenital glaucoma, developmental syndromes, and early-onset primary open-angle glaucoma (POAG). Specific gene mutations have been identified for some of these conditions, including the CYP1B1 gene for congenital glaucoma, PITX2, and FOXC1 for the Axenfeld–Rieger syndrome and other iridodysgenesis phenotypes, and MYOC for early-onset and adult-onset POAG. Most adult-onset forms of open-angle glaucoma tend to have more complex modes of inheritance. However, as a positive family history, especially in first-degree relatives, is a strong risk factor for these forms of glaucoma, it is likely that specific gene defects contribute to many of these disorders. Indeed, mutations in the OPTN gene have been associated with adult-onset open-angle glaucoma, especially the low-tension form, and WDR36 has been linked to other families with adult-onset POAG. There are many other early-onset and adult-onset forms of glaucoma for which gene associations have been supported by linkage studies. However, all of these genes only account for a small fraction of heritable cases. With the continued correlation of well-defined glaucoma phenotypes and their genotypes and the application of single nucleotide polymorphism-based technologies, it is likely that the list of genes associated with glaucoma will grow exponentially in the coming years, ultimately leading to a mutation database that can be used for diagnostic and prognostic testing (1).
REFERENCE
1. Wiggs JL. Genetic etiologies of glaucoma. Arch Ophthalmol 2007;125:30–37.
13
Genetics and Glaucoma Susceptibility
Karim F. Damji, md, frcsc, mba, and R. Rand Allingham, md
CONTENTS
Relevance of Genetics
Genetic Susceptibility and Progress in Gene Localization and
Identification
Collaboration Between Clinical and Basic Researchers
Conclusion
References
RELEVANCE OF GENETICS
The etiology of the most common types of glaucoma such as primary open-angle glaucoma (POAG) and primary angle-closure glaucoma is complex. It is likely that many inherited and environmental factors play a role in the development of these and other forms of glaucoma (1). In the past decade mutations and disease-associated variants in a number of genes have been identified, however, that are unequivocally associated with the development of various glaucomas.
The processes used to unravel the genetic underpinnings of glaucoma and other inherited disorders include genetic linkage analysis, case–control association studies, genome-wide scans, and candidate gene studies. These approaches are frequently combined with gene expression studies and proteomic approaches to unravel the fundamental biologic processes of complex inherited disorders like glaucoma (2).
This chapter provides an overview of genetic susceptibility for various types of glaucoma as well as advances that have furthered our understanding of the etiology and pathophysiology of these entities.
Much of the progress outlined in this and subsequent chapters could not have been accomplished without close collaboration between clinicians and scientists. The importance of this partnership to enable continued progress is highlighted.
From: Ophthalmology Research: Mechanisms of the Glaucomas
Edited by: J. Tombran-Tink, C. J. Barnstable, and M. B. Shields © Humana Press, Totowa, NJ
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GENETIC SUSCEPTIBILITY AND PROGRESS IN GENE LOCALIZATION AND IDENTIFICATION
Open-Angle Glaucomas
Primary Open-Angle Glaucoma
There is compelling evidence to indicate that susceptibility to POAG is inherited and that it is a highly heterogeneous disorder. Familial association in glaucoma was reported as early as 1842 by Benedict (3). Further evidence of a genetic background comes from studies indicating that the prevalence of POAG in first-degree relatives of affected patients is 7–10 times higher than the general population (4,5). There is a high concordance rate for POAG between monozygotic twins (6,7). It is also well known that patients with POAG or their family members have a much higher tendency toward a rise in intraocular pressure (IOP) with use of steroids, indicating a possible hereditary association between steroid response and glaucoma. In addition, the prevalence and severity of POAG, particularly in older age groups, is greater in black and Hispanic Americans compared to whites, which may indicate an increased genetic susceptibility to POAG in these populations (8–10).
The high prevalence of POAG, variability in age of onset, and variable penetrance (variable phenotypic expression of a disease despite carrying the genetic mutation) in some pedigrees that have been reported argue strongly that in most cases POAG is inherited as a “complex” trait that does not demonstrate simple Mendelian inheritance. It appears likely that there is interplay between various environmental and genetic factors, or between multiple genes, resulting in a high degree of variability in phenotypic expression and severity of disease.
To date, linkage studies on families with POAG provide strong evidence for genetic heterogeneity. At least, 11 loci and three genes (myocilin, optineurin, and WDR36) have been identified (see Table 1).
A number of studies have supported the role of multiple genetic loci in POAG. The three known genes for POAG appear to account for no more than 5–10 % of all POAG cases. Therefore, the majority of the genetic architecture of POAG remains to be determined. An analysis using methodology for complex diseases by Wiggs et al. have identified multiple loci for POAG (11). Subsequently, one locus was identified on chromosome 15, GLC1I, which is associated with the development of a mid-life form of POAG, with mean onset of disease in the fifth decade (12). Preliminary evidence supports the role of GLC1I in approximately one in five individuals with POAG including families of both Caucasian and African-American ancestry. The GLC1I locus has been corroborated in a second independent POAG family data set (13).
A recent study of Africans in Ghana using quantitative trait mapping for loci linked to IOP in affected sibling pairs revealed suggestive linkage on chromosome 5 (5q22) and chromosome 14 (14q22) (14). Interestingly, Wiggs et al. also found a locus for POAG on chromosome 14; whether these represent the same loci remains to be determined (11).
Additional evidence for genetic susceptibility comes from polymorphisms of genes that are suspected of playing a role in glaucoma. Polymorphisms in the genes coding for the beta-adrenergic receptors ADRB1 and ADRB2 expressed within the trabecular
Genetics and Glaucoma Susceptibility |
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Table 1 |
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Glaucoma Loci and Genes |
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Glaucoma type |
Locus symbol |
Locus/loci |
Gene |
|
|
|
|
Juvenile OAG |
GLC1A |
1q23-25 |
Myocilin/ TIGR |
|
|
6p25 |
FKHL7 |
|
|
10p15-14 |
OPTN |
|
|
9q22 |
|
|
|
20p12 |
|
Adult OAG (Note: |
GLC1A |
1q23-25 |
Myocilin/ TIGR |
OPTN and WDR36 are also |
GLC1B |
2cen-q13 |
|
associated with low- |
GLC1C |
3q21-24 |
|
tension glaucoma) |
GLC1D |
8q23 |
|
|
GLC1E |
10p15-14 |
OPTN |
|
GLC1G |
5q21.3-22.1 |
WDR36 |
|
GLC1F |
7q35-36 |
|
|
GLC1I |
15q11-13 |
|
|
GLC1J |
9q22 |
|
|
GLC1K |
20p12 |
|
Pseudoexfoliation syndrome |
|
15q24.1 |
LOXL1 |
Pigment dispersion |
GPDS1 |
7q35-36 |
|
|
GPDS2 |
18q11-21 |
|
Congenital glaucoma |
GLC3A |
2p22-21 |
CYP1B1 |
(Note: possible role for digenic |
GLC3B |
1p36.2-36.1 |
|
inheritance with CYP1B1 |
|
|
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and MYOC). |
|
|
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Anterior segment |
|
|
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dysgenesis |
RIEG1 |
4q25 |
PITX2 (solurshin) |
Rieger syndrome |
RIEG2 |
13q14 |
|
Axenfeld-Rieger |
IRID1 |
11p13 |
PAX 6 |
syndrome |
IRID2 |
6p25 |
FOXc1 (FKHL7) |
Iridogoniodysgenesis |
|
4q25 |
PITX2 |
Anterior segment |
|
10q25 |
PITX3 |
mesenchymal dysgenesis |
|
6p25 |
FOXC1 (FKHL7) |
Autosomal-dominant iris |
|
10q25 |
PITX3 |
hypoplasia |
|
4q25 |
PITX2 |
Nanophthalmos |
NNO1 |
11p |
?VMD2 |
|
NNO2 |
11q23.3 |
MFRP |
Aniridia |
AN2 |
11p13 |
PAX 6 |
Posterior polymorphous |
PPCD1 |
20p11.21- |
VSX 1 |
dystrophy |
PPCD2 |
q11.23 |
COL8A2 |
|
PPCD3 |
1p34.3-32.3 |
|
|
|
10p11.2 |
|
Peter’s anomaly |
|
11p13 |
PAX 6 |
|
|
4q25-q26 |
PITX2 |
|
|
2p22-p21 |
CYP1B1 |
|
|
6p25 |
FOXC1 |
Congenital microcoria |
|
13q31-32 |
|
Microphthalmos (AR) |
|
14q32 |
|
Ectopia Lentis (simple) |
|
15q21 |
FBN1 (Fibrillin) |
Wagner syndrome |
WGN1 |
5q13-14 |
|
References can be obtained from Online Mendelian Inheritance in Man: http://www.ncbi. nlm.nih.gov/entrez/query.fcgi?db=OMIM or Human Genome Database http://gdbwww.gdb.org/.