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Cited by 4,210Glaucoma and retinal disordersDrug-Induced Ocular ToxicityCorneal surgery and disorders

The Pathophysiology and Treatment of Glaucoma: A Review

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Weinreb, Robert N., Aung, Tin, Medeiros, Felipe A.·2014·JAMA
DOI 10.1001/jama.2014.3192PMC PMC4523637
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Abstract

IMPORTANCE: Glaucoma is a worldwide leading cause of irreversible vision loss. Because it may be asymptomatic until a relatively late stage, diagnosis is frequently delayed. A general understanding of the disease pathophysiology, diagnosis, and treatment may assist primary care physicians in referring high-risk patients for comprehensive ophthalmologic examination and in more actively participating in the care of patients affected by this condition. OBJECTIVE: To describe current evidence regarding the pathophysiology and treatment of open-angle glaucoma and angle-closure glaucoma. EVIDENCE REVIEW: A literature search was conducted using MEDLINE, the Cochrane Library, and manuscript references for studies published in English between January 2000 and September 2013 on the topics open-angle glaucoma and angle-closure glaucoma. From the 4334 abstracts screened, 210 articles were selected that contained information on pathophysiology and treatment with relevance to primary care physicians. FINDINGS: The glaucomas are a group of progressive optic neuropathies characterized by degeneration of retinal ganglion cells and resulting changes in the optic nerve head. Loss of ganglion cells is related to the level of intraocular pressure, but other factors may also play a role. Reduction of intraocular pressure is the only proven method to treat the disease. Although treatment is usually initiated with ocular hypotensive drops, laser trabeculoplasty and surgery may also be used to slow disease progression. CONCLUSIONS AND RELEVANCE: Primary care physicians can play an important role in the diagnosis of glaucoma by referring patients with positive family history or with suspicious optic nerve head findings for complete ophthalmologic examination. They can improve treatment outcomes by reinforcing the importance of medication adherence and persistence and by recognizing adverse reactions from glaucoma medications and surgeries.

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  • Lowering IOP is currently the only clinically approved therapeutic option for glaucoma patients.

    “Lowering the IOP is currently the only clinically approved therapeutic option for patients and is achieved through drugs and/or surgery that target the aqueous humor outflow pathways in the anterior segment of the eye (Lusthaus and Goldberg, 2019; Weinreb et al., 2014).”

    From Sustained Vision Recovery by OSK Gene Therapy in a Mouse Model of Glaucoma (2023) · cites this paper as Weinreb et al., 2014

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Research works printed but not linked: 62

  1. [1]Weinreb RN Khaw PT Primary open-angle glaucoma Lancet 2004 363 9422 1711 1720 15158634
  2. [2]Nickells RW Howell GR Soto I John SW Under pressure: cellular and molecular responses during glaucoma, a common neurodegeneration with axonopathy Annu Rev Neurosci 2012 35 153 179 22524788
  3. [3]Quigley HA Broman AT The number of people with glaucoma worldwide in 2010 and 2020 Br J Ophthalmol 2006 90 3 262 267 16488940 PMC1856963
  4. [4]Leite MT Sakata LM Medeiros FA Managing glaucoma in developing countries Arq Bras Oftalmol 2011 74 2 83 84 21779659 PMC3787827
  5. [5]Rotchford AP Kirwan JF Muller MA Johnson GJ Roux P Temba glaucoma study: a population-based cross-sectional survey in urban South Africa Ophthalmology 2003 110 2 376 382 12578784
  6. [6]Hennis A Wu SY Nemesure B Honkanen R Leske MC Barbados Eye Studies Group Awareness of incident open-angle glaucoma in a population study: the Barbados Eye Studies Ophthalmology 2007 114 10 1816 1821 17698198
  7. [7]Sathyamangalam RV Paul PG George R Determinants of glaucoma awareness and knowledge in urban Chennai Indian J Ophthalmol 2009 57 5 355 360 19700873 PMC2804123
  8. [8]Budenz DL Barton K Whiteside-de Vos J Tema Eye Survey Study Group Prevalence of glaucoma in an urban West African population: the Tema Eye Survey JAMA Ophthalmol 2013 131 5 651 658 23538512 PMC4139110
  9. [9]Friedman DS Wolfs RC O’Colmain BJ Eye Diseases Prevalence Research Group Prevalence of open-angle glaucoma among adults in the United States Arch Ophthalmol 2004 122 4 532 538 15078671 PMC2798086
  10. [10]Day AC Baio G Gazzard G The prevalence of primary angle closure glaucoma in European derived populations: a systematic review Br J Ophthalmol 2012 96 9 1162 1167 22653314
  11. [11]Hollands H Johnson D Hollands S Simel DL Jinapriya D Sharma S Do findings on routine examination identify patients at risk for primary open-angle glaucoma? JAMA 2013 309 19 2035 2042 23677315
  12. [12]Kersey JP Broadway DC Corticosteroid-induced glaucoma: a review of the literature Eye (Lond) 2006 20 4 407 416 15877093
  13. [13]Quigley HA Addicks EM Green WR Maumenee AE Optic nerve damage in human glaucoma, II: the site of injury and susceptibility to damage Arch Ophthalmol 1981 99 4 635 649 6164357
  14. [14]Fechtner RD Weinreb RN Mechanisms of optic nerve damage in primary open angle glaucoma Surv Ophthalmol 1994 39 1 23 42 7974188
  15. [15]Burgoyne CF Downs JC Bellezza AJ Suh JK Hart RT The optic nerve head as a biomechanical structure: a new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage Prog Retin Eye Res 2005 24 1 39 73 15555526
  16. [16]Quigley HA McKinnon SJ Zack DJ Retrograde axonal transport of BDNF in retinal ganglion cells is blocked by acute IOP elevation in rats Invest Ophthalmol Vis Sci 2000 41 11 3460 3466 11006239
  17. [17]Ju WK Kim KY Lindsey JD Intraocular pressure elevation induces mitochondrial fission and triggers OPA1 release in glaucomatous optic nerve Invest Ophthalmol Vis Sci 2008 49 11 4903 4911 18469184 PMC2688012
  18. [18]Wang N Xie X Yang D Orbital cerebrospinal fluid space in glaucoma: the Beijing Intracranial and Intraocular Pressure (iCOP) study Ophthalmology 2012 119 10 2065e1 2073e1 22749084
  19. [19]Ren R Jonas JB Tian G Cerebrospinal fluid pressure in glaucoma: a prospective study Ophthalmology 2010 117 2 259 266 19969367
  20. [20]Almasieh M Wilson AM Morquette B Cueva Vargas JL Di Polo A The molecular basis of retinal ganglion cell death in glaucoma Prog Retin Eye Res 2012 31 2 152 181 22155051
  21. [21]Stone EM Fingert JH Alward WL Identification of a gene that causes primary open angle glaucoma Science 1997 275 5300 668 670 9005853
  22. [22]Rezaie T Child A Hitchings R Adult-onset primary open-angle glaucoma caused by mutations in optineurin Science 2002 295 5557 1077 1079 11834836
  23. [23]Monemi S Spaeth G DaSilva A Identification of a novel adult-onset primary open-angle glaucoma (POAG) gene on 5q22.1 Hum Mol Genet 2005 14 6 725 733 15677485
  24. [24]Kwon YH Fingert JH Kuehn MH Alward WL Primary open-angle glaucoma N Engl J Med 2009 360 11 1113 1124 19279343 PMC3700399
  25. [25]Thorleifsson G Walters GB Hewitt AW Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma Nat Genet 2010 42 10 906 909 20835238 PMC3222888
  26. [26]Wiggs JL Yaspan BL Hauser MA Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma PLoS Genet 2012 8 4 e1002654 22570617 PMC3343074
  27. [27]Harwerth RS Wheat JL Fredette MJ Anderson DR Linking structure and function in glaucoma Prog Retin Eye Res 2010 29 4 249 271 20226873 PMC2878911
  28. [28]Medeiros FA Alencar LM Zangwill LM Bowd C Sample PA Weinreb RN Prediction of functional loss in glaucoma from progressive optic disc damage Arch Ophthalmol 2009 127 10 1250 1256 19822839 PMC2828324
  29. [29]Jampel HD Friedman D Quigley H Agreement among glaucoma specialists in assessing progressive disc changes from photographs in open-angle glaucoma patients Am J Ophthalmol 2009 147 1 39 e1 44 e1 18790472 PMC2730020
  30. [30]Medeiros FA Vizzeri G Zangwill LM Alencar LM Sample PA Weinreb RN Comparison of retinal nerve fiber layer and optic disc imaging for diagnosing glaucoma in patients suspected of having the disease Ophthalmology 2008 115 8 1340 1346 18207246 PMC2832850
  31. [31]Medeiros FA Zangwill LM Bowd C Weinreb RN Comparison of the GDx VCC scanning laser polarimeter, HRT II confocal scanning laser ophthalmoscope, and stratus OCT optical coherence tomograph for the detection of glaucoma Arch Ophthalmol 2004 122 6 827 837 15197057
  32. [32]Chauhan BC O’Leary N Almobarak FA Enhanced detection of open-angle glaucoma with an anatomically accurate optical coherence tomography-derived neuroretinal rim parameter Ophthalmology 2013 120 3 535 543 23265804 PMC3667974
  33. [33]Medeiros FA Zangwill LM Anderson DR Estimating the rate of retinal ganglion cell loss in glaucoma Am J Ophthalmol 2012 154 5 814e1 24e1 22840484 PMC3787830
  34. [34]Strouthidis NG Gardiner SK Sinapis C Burgoyne CF Garway-Heath DF The spatial pattern of neuroretinal rim loss in ocular hypertension Invest Ophthalmol Vis Sci 2009 50 8 3737 3742 19357354
  35. [35]McKean-Cowdin R Wang Y Wu J Impact of visual field loss on health-related quality of life in glaucoma: the Los Angeles Latino Eye Study Ophthalmology 2008 115 6 941e1 948e1 17997485 PMC4864605
  36. [36]Boland MV Ervin AM Friedman DS Comparative effectiveness of treatments for open-angle glaucoma: a systematic review for the US Preventive Services Task Force Ann Intern Med 2013 158 4 271 279 23420235
  37. [37]Kass MA Heuer DK Higginbotham EJ The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma Arch Ophthalmol 2002 120 6 701 713 12049574
  38. [38]Heijl A Leske MC Bengtsson B Hyman L Bengtsson B Hussein M Early Manifest Glaucoma Trial Group Reduction of intraocular pressure and glaucoma progression Arch Ophthalmol 2002 120 10 1268 1279 12365904
  39. [39]The AGIS Investigators The Advanced Glaucoma Intervention Study (AGIS), 7: the relationship between control of intraocular pressure and visual field deterioration Am J Ophthalmol 2000 130 4 429 440 11024415
  40. [40]Lichter PR Musch DC Gillespie BW CIGTS Study Group Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery Ophthalmology 2001 108 11 1943 1953 11713061
  41. [41]Collaborative Normal-Tension Glaucoma Study Group Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures Am J Ophthalmol 1998 126 4 487 497 9780093
  42. [43]Gaton DD Sagara T Lindsey JD Gabelt BT Kaufman PL Weinreb RN Increased matrix metalloproteinases 1, 2, and 3 in the monkey uveoscleral outflow pathway after topical prostaglandin F(2 alpha)-isopropyl ester treatment Arch Ophthalmol 2001 119 8 1165 1170 11483084
  43. [44]Stewart WC Konstas AG Nelson LA Kruft B Meta-analysis of 24-hour intraocular pressure studies evaluating the efficacy of glaucoma medicines Ophthalmology 2008 115 7 1117e1 1122e1 18082886
  44. [45]Liu JH Kripke DF Weinreb RN Comparison of the nocturnal effects of once-daily timolol and latanoprost on intraocular pressure Am J Ophthalmol 2004 138 3 389 395 15364220
  45. [46]Weinreb RN Kaufman PL Glaucoma research community and FDA look to the future, II: NEI/FDA Glaucoma Clinical Trial Design and Endpoints Symposium: measures of structural change and visual function Invest Ophthalmol Vis Sci 2011 52 11 7842 7851 21972262 PMC3207797
  46. [47]Mansouri K Medeiros FA Weinreb RN Global rates of glaucoma surgery Graefes Arch Clin Exp Ophthalmol 2013 251 11 2609 2615 24068439
  47. [48]Odberg T Sandvik L The medium and long-term efficacy of primary argon laser trabeculoplasty in avoiding topical medication in open angle glaucoma Acta Ophthalmol Scand 1999 77 2 176 181 10321534
  48. [49]Shingleton BJ Richter CU Dharma SK Long-term efficacy of argon laser trabeculoplasty: a 10-year follow-up study Ophthalmology 1993 100 9 1324 1329 8371919
  49. [50]Shingleton BJ Richter CU Bellows AR Hutchinson BT Glynn RJ Long-term efficacy of argon laser trabeculoplasty Ophthalmology 1987 94 12 1513 1518 3431820
  50. [51]Gedde SJ Schiffman JC Feuer WJ Treatment outcomes in the Tube Versus Trabeculectomy (TVT) study after five years of follow-up Am J Ophthalmol 2012 153 15 789e2 803e2 22245458 PMC4460598
  51. [52]Ayyala RS Chaudhry AL Okogbaa CB Zurakowski D Comparison of surgical outcomes between canaloplasty and trabeculectomy at 12 months’ follow-up Ophthalmology 2011 118 12 2427 2433 21856008
  52. [53]Rulli E Biagioli E Riva I Efficacy and safety of trabeculectomy vs nonpenetrating surgical procedures: a systematic review and meta-analysis JAMA Ophthalmol 2013 131 12 1573 1582 24158640
  53. [54]He M Foster PJ Johnson GJ Khaw PT Angle-closure glaucoma in East Asian and European people: different diseases? Eye (Lond) 2006 20 1 3 12 15688051
  54. [55]Sakai H Morine-Shinjyo S Shinzato M Nakamura Y Sakai M Sawaguchi S Uveal effusion in primary angle-closure glaucoma Ophthalmology 2005 112 3 413 419 15745767
  55. [56]Lavanya R Wong TY Friedman DS Determinants of angle closure in older Singaporeans Arch Ophthalmol 2008 126 5 686 691 18474780
  56. [57]Nongpiur ME Ku JY Aung T Angle closure glaucoma: a mechanistic review Curr Opin Ophthalmol 2011 22 2 96 101 21252671
  57. [58]Amerasinghe N Zhang J Thalamuthu A The heritability and sibling risk of angle closure in Asians Ophthalmology 2011 118 3 480 485 21035870
  58. [59]Vithana EN Khor CC Qiao C Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma Nat Genet 2012 44 10 1142 1146 22922875 PMC4333205
  59. [60]Sakata LM Lavanya R Friedman DS Comparison of gonioscopy and anterior segment ocular coherence tomography in detecting angle closure in different quadrants of the anterior chamber angle Ophthalmology 2008 115 5 769 774 17916377
  60. [61]Wong HT Lim MC Sakata LM High-definition optical coherence tomography imaging of the iridocorneal angle of the eye Arch Ophthalmol 2009 127 3 256 260 19273787
  61. [62]Alsagoff Z Aung T Ang LP Chew PT Long-term clinical course of primary angle-closure glaucoma in an Asian population Ophthalmology 2000 107 12 2300 2304 11097612
  62. [63]Aung T Ang LP Chan SP Chew PT Acute primary angle-closure: long-term intraocular pressure outcome in Asian eyes Am J Ophthalmol 2001 131 1 7 12 11162972

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Authors
Weinreb, R. N., Aung, T., & Medeiros, F. A.
Affiliations
  • University of California San Diego (US)
  • National University of Singapore (SG)
Corresponding author
Weinreb, Robert N.
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2014-05-14
Volume
311
Issue
18
Pages
1901
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2014.3192
PMC
PMC4523637
OpenAlex
W2034742711
Cited by
4,210
References
0
Citations by year
2026: 512 · 2025: 594 · 2024: 536 · 2023: 507 · 2022: 466 · 2021: 447 · 2020: 376 · 2019: 260 · 2018: 173 · 2017: 139 · 2016: 108 · 2015: 75 · 2014: 16 · 2013: 1
FWCI
105.98
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
National Eye Institute (R01EY021818, EY019692, EY021818, R01EY019692, P30EY022589)
Topics
  • Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
  • Health Sciences › Medicine › Ophthalmology › Drug-Induced Ocular Toxicity
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Corneal surgery and disorders
Keywords
glaucoma, open-angle glaucoma, angle-closure glaucoma, pathophysiology, intraocular pressure, retinal ganglion cell death, optic neuropathy, laser trabeculoplasty, glaucoma surgery, medication adherence, adverse drug reactions, primary care referral, vision loss
MeSH terms
Glaucoma, Open-Angle, Humans, Primary Health Care, Glaucoma, Angle-Closure

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