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open-angle glaucoma (OAG)

Etiology: - genetic forms - calcium channel blockers increase risk (RR=1.4) [39] - dyslipidemia is a risk factor [43] - air pollution; particulate matter < 2.5 microns [46] Epidemiology: 1) most common form of glaucoma in adults (90%) [40] 2) affects 3 million people in USA (2002) - 1/2 of those affected are unaware 3) 6 times more common in African Americans [4] 4) accounts for 9-12% of blindness in the U.S. & 19% of blindness among African Americans 5) 200% increase in cases by 2050 predicted [40] 6) lower socioeconomic status associated with increased risk Physiology: - intraocular pressure varies throughout the diurnal & nocturnal periods & according to body posture - elevated intraocular pressure occurs from midnight until 10 AM - maximal intraocular pressure is at 4 AM [18] - intraocular pressure variable during the course of the day - maximum pressure in late afternoon in some cases Pathology: 1) a major cause of blindness 2) optic nerve degeneration 3) decreased flow of aqueous humor 4) normal irido-corneal angle 5) calcium channel blockers diminish the macular ganglion cell complex thickness - macular retinal nerve fiber layer thickness - macular ganglion cell-inner plexiform layer thickness [39] 6) calcium channel blockers do not increase intraocular pressure [39] Genetics: 1) autosomal dominant form 2) mutations in optineurin gene in 17% (autosomal dominant, chromosome 10) 3) mutations in GLC1A (myocilin, MYOC) on chromosome 1q juvenile & adult-onset 4) mutations in GLC1B on chromosome 2 5) mutations in GLC1C on chromosome 3 6) mutations in GLC1D on chromosome 8q 7) mutations in GLC1F chromosome 7q 8) defects in WDR36 (type 1G) [6] 9) defects in NTF4 (type 10) [7] Clinical manifestations: 1) intraocular pressure is generally increased, but may be normal (10-21 mm Hg) 2) visual field loss - visual field change over 25 years in most treated patients similar to healthy persons [35] 3) insidious onset: - generally asymptomatic until significant visual loss occurs [40] - contrast sensitivity may be noted - loss of night vision may be noted [10] 4) blurred vision often attributed to needing new glasses Special laboratory: - tonometry (measurement of intraocular pressure) - 24 hour contact lens sensor measuring intraocular pressure [23] - visual field testing (perimetry) - blacks may show increased visual field variability compared with whites, resulting in delayed detection of progression [21] - macular optical coherence tomography & 10-2 visual field with detection of diffuse macular damage is associated with diminished facial recognition & contrast sensitivity [28] - optical coherence tomography angiography monitoring provides complementary information to visual field in monitoring patients with glaucoma [33] - optical coherence tomography measurement of macular ganglion cell complex thickness correlates with central visual field change in glaucoma [36] Complications: - unilateral or bilateral blindness - 26.5% & 5.5%, respectively, after 10 years - 38.1% & 13.5% at 20 years [13] - risk factors [14] - higher intraocular pressure & worse visual field status at baseline were important risk factors - older age at death - not associated with significant risk of comorbidities before development of visual impairment [15] - normotensive glaucoma associated with increased risk of cognitive impairment - 14.8% of patients with normotensive glaucoma met criteria for cognitive impairment vs 5.4% of patients with high-tension glaucoma [29] - otherwise, no association between either prevalent or incident glaucoma & cognitive impairment [37] - increased risks for Alzheimer's disease (RR=1.3), vascular dementia (RR=1.6), & all-cause dementia, when diagnosed with glaucoma at age >= 70 years [48] - risks are not elevated with glaucoma diagnosis < 60 years - visual field deficits in older adults with glaucoma associated with decline in walking speeds [30] Differential diagnosis: - macular degeneration - central scotoma, loss of fine central vision, drusen - cataracts - lenticular opacities, blurry vision, glare sensitivity, contrast sensitivity - diabetic retinopathy - cotton wool spots, microaneurysms, neovascularization (proliferative stage) Management: 1) focuses on lowering intraocular pressure a) suppression of aqueous humor production - beta blockers - timolol maleate (Timoptic) 1 drop BID - alpha-2 adrenergic agonists - brimonidine ophthalmic - may increase neurotrophic factor & inhibit glutamate toxicity [47] - evidence is limited, not confirmatory in humans [47] - carbonic anhydrase inhibitors - dorzolamide ophthalmic 1 drop TID - brinzolamide ophthalmic 1 drop TID - acetazolamide (Diamox) 250 mg PO QD-QID b) improving aqueous humor outflow - parasympathomimetics - pilocarpine (Pilocar) 1 drop OU 6 times/day - epinephrine (Epifrin) 1-2 drops OU QD/BID (adjunctive therapy) Cautions: [1] gonioscopy required before initiation of treatment; [2] do not use in closed-angle glaucoma - prostaglandin analogs increase outflow - prostaglandin analogs are the most effective monotherapy [38] - best systemic safety profile [38] - latanoprost (Xalatan) 1 drop QHS: reduces of intraocular pressure (25-35%, 4 mm Hg); reduces risk of visual field deterioration (15% vs 26% for placebo) [17] - bimatoprost (Lumigan) 1 drop QHS - latanoprostene BUNOD (Vyzulta) 1 drop QHS: dual action; may be more effective than latanoprost - netarsudil (Rhopressa) & latanoprost/netarsudil (Rocklatan) c) hyperosmotic agents (isosorbide dinitrate, mannitol, glycerin) [41] d) combination of improving aqueous humor outflow with suppression of aqueous humor production, for example: latanoprost + dorzolamide may be more effective than either agent alone 2) topical agents have systemic side effects [2] 3) consider discontinuation of calcium channel blocker if glaucoma progression despite optimal therapy, especially amlodipine [39] - amlodipine has the largest association with glaucoma [39] - calcium channel blockers not associated with increase intraocular pressure 4) laser trabeculoplasty a) useful in the elderly - unable to instill eyedrops [10] - unfit for surgery or anesthesia b) long term benefits questionable c) 50% success rate in lowering intraocular pressure for 3-5 years [10] 5) surgery a) create new pathways for aqueous outflow - laser surgery increases aqueous humor drainage through the eye's trabecular meshwork - micropulse transscleral laser treatment - safer than continuous-wave transscleral cyclophotocoagulation - can lower IOP for 12 months [43] - conventional surgery (filtering microsurgery) creates a drainage hole with the use of a small surgical tool (trabeculectomy) - surgery can be repeated several times without substantial risk b) if all else fails, destruction of the ciliary body to obliterate aqueous humor production 6) glaucoma drainage device - outcomes similar to trabeculectomy at 5 years [27] - mean intraocular pressure 12.6 vs 14.4 mm Hg for trabeculectomy - mean ancillary ophthalmics 1.2 vs 1.5 for trabeculectomy - probability of failure 29.8% vs 46.9% for trabeculectomy - reoperation rate 9% vs 29% for trabeculectomy [7] - Baerveldt aqueous shunt implant - associated with poorer quality of life than medical therapy, trabeculoplasty or surgery [] - adverse effects of trabeculectomy & glaucoma drainage device smilar - bleeding, inflammation, infection, cataract formation, corneal swelling, hypotony, persistent IOP elevation due to scar tissue limiting outflow, 7) microinvasive glaucoma surgeries - dilates, cleaves open, or bypasses abnormally resistant tissue obstructing aqueous outflow, or inserts a device into an outflow structure to enhance aqueous drainage - can be performed with concomitant cataract surgery [27] - cataract surgery itself of benefit [31] - Hydrus marginally superior to iStent [31] - intracameral implant (iDose TR) with 75 mcg of travoprost [42] - inserted into a corneal incision on the temple side of the eye - reductions in IOP of 6.6 to 8.4 mm Hg for 3 months [42] * 8) marijuana is reported to lower intraocular pressure [5] 9) estrogen in hormone replacement therapy may reduce risk [12] 10) yoga breathing practices but not yoga postures improve IOP 11) prevention - exercise may reduce risk [19] - omega-3 fatty acids EPA & DHA may reduce risk [20] - statins reported to reduce risk conferred by high cholesterol, but article retracted citing errors in both benefit of statins & risk associated with elevated cholesterol [24] 12) screening: a) USPSTF concludes evidence insufficient to recommend for or against screening [8] b) screening recommended every 1-2 years after age 50 [10] * $14,000/implant Clinical trials: - oral nicotinamide (1000-3000 mg) & pyruvate (1500 -3000 mg)/day may improve visual function & provide neuroprotection for patients with glaucoma [32]

Related

intraocular pressure (IOP) optineurin; optic neuropathy-inducing protein; E3-14.7K-interacting protein; FIP-2; huntingtin-interacting protein L; huntingtin yeast partner L; huntingtin-interacting protein 7; HIP-7; NEMO-related protein; transcription factor IIIA-interacting protein; TFIIIA-intP (OPTN, FIP2, GLC1E, HIP7, HYPL, NRP)

Specific

glaucomatocyclitic crisis (Posner-Schlossman Syndrome)

General

primary glaucoma genetic disease of the eye

Database Correlations

OMIM correlations

References

  1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 66-67
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 18. American College of Physicians, Philadelphia 1998, 2009, 2012, 2018.
  3. Journal Watch 22(6):50, 2002 Rezaie et al, Science 295:1077, 2002
  4. Mangione CM. In: UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  5. Green K. Marijuana smoking vs cannabinoids for glaucoma therapy Arch Ophthalmology 1998, 116:1433 PMID: 9823341
  6. OMIM :accession 609887
  7. OMIM :accession 613100
  8. Moyer VA et al Screening for Glaucoma: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. Published online 9 July 2013 PMID: 23836133 http://annals.org/article.aspx?articleid=1707740 - US Preventive Services Task Force Screening for Primary Open-Angle GlaucomaUS Preventive Services Task Force Recommendation Statement. JAMA. 2022;327(20):1992-1997. May 24/31 PMID: 35608574 https://jamanetwork.com/journals/jama/fullarticle/2792609 - Chou R, Selph S, Blazina I et al Screening for Glaucoma in Adults. Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2022;327(20):1998-2012 May 24/31 PMID: 35608575 https://jamanetwork.com/journals/jama/fullarticle/2792610 - Jampel HD, Shukla AG Screening for Glaucoma. JAMA. 2022;327(20):1961-1962 PMID: 35608599 https://jamanetwork.com/journals/jama/fullarticle/2792640
  9. Weinreb RN, Khaw PT. Primary open-angle glaucoma. Lancet. 2004 May 22;363(9422):1711-20. Review. PMID: 15158634
  10. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
  11. Peeters A, Webers CA, Prins MH, et al Quantifying the effect of intraocular pressure reduction on the occurrence of glaucoma. Acta Ophthalmol. 2010 Feb;88(1):5-11 PMID: 19432875
  12. Newman-Casey PA et al. The potential association between postmenopausal hormone use and primary open-angle glaucoma. JAMA Ophthalmol 2014 Jan 30; PMID: 24481323
  13. Peters D, Bengtsson B, Heijl A. Lifetime risk of blindness in open-angle glaucoma. Am J Ophthalmol. 2013 Oct;156(4):724-30. PMID: 23932216
  14. Peters D, Bengtsson B, Heijl A Factors associated with lifetime risk of open-angle glaucoma blindness. Acta Ophthalmol. 2013 Jul 10. PMID: 23837818
  15. Kymes SM, Plotzke MR, Li JZ, Nichol MB, Wu J, Fain J. The increased cost of medical services for people diagnosed with primary open-angle glaucoma: a decision analytic approach. Am J Ophthalmol. 2010 Jul;150(1):74-81 PMID: 20493465
  16. Yumori JW, Cadogan MP. Primary open-angle glaucoma: clinical update. J Gerontol Nurs. 2011 Mar;37(3):10-5 PMID: 21366162
  17. Garway-Heath DF et al Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial. Lancet. Dec 19, 2014 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2962111-5/abstract
  18. Mansouri K, Shaarawy T. Continuous intraocular pressure monitoring with a wireless ocular telemetry sensor: initial clinical experience in patients with open angle glaucoma. Br J Ophthalmol. 2011 May;95(5):627-9. PMID: 21216796
  19. Bankhead C AAO Poster Rounds: Cataract Surgery Reduces Falls; Lasers for Floaters; Exercise and Glaucoma Selected studies from poster sessions at the ophthalmology meeting. MedPage Today. November 15, 2017 https://www.medpagetoday.com/meetingcoverage/aaoposterrounds/69314 - Tseng VL, et al. Exercise intensity and risk of glaucoma in the National Health and Nutrition Examination Survey. American Academy of Ophthalmology (AAO) 2017. Abstract PO344.
  20. Bankhead C. Mixed Data for Fatty Acid Intake and Glaucoma. Lower risk with higher EPA, DHA intake but not total PUFA. MedPage Today. December 24, 2017 - Wang YE, Tseng VL, Yu F, Caprioli J, Coleman AL. Association of dietary fatty acid intake with glaucoma in the United States. JAMA Ophthalmol. 2017 Dec 21 PMID: 29270632 https://www.medpagetoday.com/ophthalmology/glaucoma/70093
  21. Gracitelli CPB, Zangwill LM, Diniz-Filho A et al Detection of Glaucoma Progression in Individuals of African Descent Compared With Those of European Descent. JAMA Ophthalmol. Published online Feb 15, 2018. PMID: 29450497 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2672743
  22. Harrison P. Glaucoma Drainage Devices Linked to Lower QOL Timely diagnosis and preoperative discussions about potential psychosocial effects are key. MedPage Today. February 24, 2018 https://www.medpagetoday.com/ophthalmology/glaucoma/71361 - Khanna CL, Leske DA, Holmes JM. Factors associated with health-related quality of life in medically and surgically treated patients with glaucoma. JAMA Ophthalmol 2018 PMID: 29470573
  23. De Moraes CG, Mansouri K, Liebmann JM et al Association Between 24-Hour Intraocular Pressure Monitored With Contact Lens Sensor and Visual Field Progression in Older Adults With Glaucoma. JAMA Ophthalmol. Published online May 24, 2018. PMID: 29800011 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2681469
  24. Kang JH, Boumenna T, Stein JD et al Association of Statin Use and High Serum Cholesterol Levels With Risk of Primary Open-Angle Glaucoma. JAMA Ophthalmol. Published online May 2, 2019. PMID: 31046067 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2732293 - Liu Y, Klein BE The Role of Statins and Cholesterol in the Primary Prevention of Primary Open-Angle Glaucoma. JAMA Ophthalmol. Published online May 2, 2019 PMID: 31046110 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2732286 - Notice of Retraction and Replacement. Kang et al. Association of statin use and high serum cholesterol levels with risk of primary open-angle glaucoma. JAMA Ophthalmol. 2019;137(7):756-765 JAMA Ophthalmol. Published online March 12, 2020.
  25. Fan BJ, Bailey JC, Igo RP Jr et al Association of a Primary Open-Angle Glaucoma Genetic Risk Score With Earlier Age at Diagnosis. JAMA Ophthalmol. 2019;137(10):1190-1194 PMID: 31436842 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2748604 - Xu BY, Varma R. Surgical Management of Primary Angle-Closure Disease - Why Less Is More. JAMA Ophthalmol. 2019;137(10):1113-1114 PMID: 31294767 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2737861
  26. Salazar D, Morales E, Rabiolo A et al Pointwise Methods to Measure Long-term Visual Field Progression in Glaucoma. JAMA Ophthalmol. Published online April 2, 2020. PMID: 32239185 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2763869
  27. Stein JD, Khawaja AP, Weizer JS Glaucoma in Adults - Screening, Diagnosis, and ManagementA Review. JAMA. 2021;325(2):164-174. Jan 12 PMID: 33433580 https://jamanetwork.com/journals/jama/fullarticle/2774838
  28. Khan SS, Hirji SH, Hood DC et al Association of Macular Optical Coherence Tomography Measures and Deficits in Facial Recognition in Patients With Glaucoma. JAMA Ophthalmol. Published online March 11, 2021 PMID: 33151275 PMCID: PMC7645734 Free PMC article https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2777496
  29. Bankhead C. Eyes Offer Window Into Cognitive Impairment. Glaucoma study provides more evidence of common neurodegenerative pathway. https://www.medpagetoday.com/ophthalmology/glaucoma/91857 - Mullany S, Xiao L, Qassim A et al Normal-tension glaucoma is associated with cognitive impairment. Br J Ophthalmol Published Online First: 29 March 2021 PMID: 33781990 Free article https://bjo.bmj.com/content/early/2021/02/25/bjophthalmol-2020-317461
  30. E JY, Mihailovic A, Garzon C et al Association Between Visual Field Damage and Gait Dysfunction in Patients With Glaucoma. JAMA Ophthalmol. 2021;139(10):1053-1060 PMID: 34292297 PMCID: PMC8299359 (available on 2022-07-22) https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2782066 - Medeiros FA Severe Glaucoma Associated With Changes in Gait Over Time JAMA Ophthalmol. 2021;139(10):1060-1061 PMID: 34292307 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2782068
  31. Bicket AK, Le JT, Azuara-Blanco A et al Minimally Invasive Glaucoma Surgical Techniques for Open-Angle Glaucoma. An Overview of Cochrane Systematic Reviews and Network Meta-analysis. JAMA Ophthalmol. 2021;139(9):983-989 PMID: 34264292 PMCID: PMC8283665 (available on 2022-07-15) https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2781900
  32. Gustavo De Moraes C, John SWM, Williams PA et al Nicotinamide and Pyruvate for Neuroenhancement in Open-Angle Glaucoma. A Phase 2 Randomized Clinical Trial. JAMA Ophthalmol. 2022;140(1):11-18 PMID: 34792559 PMCID: PMC8603231 (available on 2022-11-18) https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2786482
  33. Nishida T, Moghimi S, Wu JH et al Association of Initial Optical Coherence Tomography Angiography Vessel Density Loss With Faster Visual Field Loss in Glaucoma. JAMA Ophthalmol. Published online February 24, 2022 PMID: 35201270 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2789470 - Chopra V. Association of Rates of Optical Coherence Tomography Angiography Vessel Density Loss on Initial Visits With Future Visual Field Progression. JAMA Ophthalmol. Published online February 24, 2022 PMID: 35201259 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2789473
  34. Lawlor M, Quartilho A, Bunce C et al. Patients with normal tension glaucoma have relative sparing of the relative afferent pupillary defect compared to those with open angle glaucoma and elevated intraocular pressure. Invest Ophthalmol Vis Sci. 2017;58(12):5237-5241 PMID: 29049724 Free article https://iovs.arvojournals.org/article.aspx?articleid=2657596
  35. Giammaria S, Hutchison DM, Rafuse PE et al Rates of Visual Field Change in Patients With Glaucoma and Healthy Individuals. Findings From a Median 25-Year Follow-up. JAMA Ophthalmol. 2022;140(5):504-511. PMID: 35389449 PMCID: PMC8990362 (available on 2023-04-07) https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2790660
  36. Nishida T, Moghimi S, Mohammadzadeh V et al Association Between Ganglion Cell Complex Thinning and Vision-Related Quality of Life in Glaucoma. JAMA Ophthalmol. 2022;140(8):800-806 PMID: 35771529 PMCID: PMC9247856 (available on 2023-06-30) https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2793763 - Palmberg PF Making Better-Informed Decisions in Glaucoma JAMA Ophthalmol. 2022;140(8):807-808 PMID: 35771536 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2793764
  37. Kolli A, Kabeto M, McCammon R et al Glaucoma and cognitive function trajectories in a population-based study: Findings from the health and retirement study. J Am Geriatr Soc 2022. Oct;70(10):2827-2837. Epub 2022 Jun 22 PMID: 35730426 https://agsjournals.onlinelibrary.wiley.com/doi/full/10.1111/jgs.17903
  38. NEJM Knowledge+ Ophthalmology
  39. Kastner A, Stuart KV, Montesano G et al Calcium Channel Blocker Use and Associated Glaucoma and Related Traits Among UK Biobank Participants. JAMA Ophthalmol. 2023;141(10):956-964. Sept 7 PMID: 37676684 PMCID: PMC10485742 (available on 2024-09-07) https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2809275
  40. Kalter L Glaucoma: A Hidden Threat to Vision Health Rising Swiftly. Medscape: Sept 20, 2023 https://www.medscape.com/s/viewarticle/996638
  41. Biggerstaff KS et al Primary Open-Angle Glaucoma (POAG) Medscape. 2024. Jan 9. https://emedicine.medscape.com/article/1206147-overview
  42. Kirkner M FDA Approves Implant for Glaucoma Medscape. December 15, 2023 https://www.medscape.com/viewarticle/fda-approves-implant-glaucoma-2023a1000vmb
  43. Patel S Rapid Review Quiz: Glaucoma Medscape: Sept 26, 2023 https://reference.medscape.com/viewarticle/996790_2
  44. Chetry D, Singh J, Chhetri A et al Effect of yoga on intra-ocular pressure in patients with glaucoma: A systematic review and meta-analysis. Indian J Ophthalmol. 2023 May;71(5):1757-1765. PMID: 37203026 PMCID: PMC10391478 Free PMC article. Review.
  45. Huang G, Wang J, Li L et al Meta-Analysis of Dyslipidemia and Blood Lipid Parameters on the Risk of Primary Open-Angle Glaucoma. Comput Math Methods Med. 2022 Sep 21;2022:1122994. PMID: 36188106 PMCID: PMC9519322 Free PMC article.
  46. Grant A, Leung G, Freeman EE et al Ambient Air Pollution and Age-Related Eye Disease: A Systematic Review and Meta-Analysis. Invest Ophthalmol Vis Sci. 2022 Aug 2;63(9):17. PMID: 35960515 PMCID: PMC9396677 Free PMC article.
  47. Mohan N, Chakrabarti A, Nazm N, Mehta R, Edward DP. Newer advances in medical management of glaucoma. Indian J Ophthalmol. 2022 Jun;70(6):1920-1930. PMID: 35647957 PMCID: PMC9359258 Free PMC article. Review. - Skopinski P et al New perspectives of immunomodulation and neuroprotection in glaucoma. Cent Eur J Immunol. 2021;46(1):105-110 PMID: 33897291 PMCID: PMC8056344 Free PMC article. Review. - Saylor M, McLoon LK, Harrison AR, Lee MS. Experimental and clinical evidence for brimonidine as an optic nerve and retinal neuroprotective agent: an evidence-based review. Arch Ophthalmol. 2009 Apr;127(4):402-6. PMID: 19365015 Review.
  48. Crump C, Sundquist J, Sieh W, Sundquist K. et al Risk of Alzheimer's Disease and Related Dementias in Persons with Glaucoma. A National Cohort Study. Ophthalmology. 2024 Mar;131(3):302-309. ePub: 2023. Oct. 13 PMID: 37839560 https://www.aaojournal.org/article/S0161-6420(23)00756-X/fulltext
  49. Glaucoma Research Foundation: Glaucoma Surgery http://www.glaucoma.org/treatment/surgery-overview.php