Risk Factors for Developing Glaucoma

Educational Objectives

The goal of this program is to improve prediction of development and progression of glaucoma. After hearing and assimilating this program, the clinician will be better able to:

1. Analyze impacts of intraocular pressure peak and variation on development of glaucoma.
2. Remark on diagnostic features which portend increased risk for progression of glaucoma.

Summary

Assessment of Risk for Glaucoma Development

Prevention of disc or early visual field changes: the Ocular Hypertension Treatment Study (OHTS; Kass et al [2002]) demonstrate that treatment of 100 low-risk or 14 moderate-risk individuals is needed to prevent development of optic disc changes or early visual field (VF) changes in one person

Predicting the onset of primary open-angle glaucoma (POAG): Gordon et al (2002) — demonstrated an annual risk for POAG of 4% to 6% in patients with decreased central cornea thickness (CCT), increased intraocular pressure (IOP), and modest cup-to-disc ratio (CDR); European Glaucoma Prevention Study (EGPS; Miglior et al [2005]) — validated a prediction model developed from the OHTS, using variables which include age, IOP, CCT, vertical CDR (VCDR), and pattern standard deviation (PSD); Ocular Hypertension Treatment Study Group et al (2007) — combined OHTS and EGPS data to create a risk calculator which can also be applied to patients with increased IOP already taking medication (consider medication discontinuation in patients deemed moderate to low risk); Singh et al (2024) — demonstrate improvement in prediction of onset of POAG through use of polygenic risk scores

Optic disc hemorrhage (ODH): Budenz et al (2017) demonstrated a 2-fold increased risk for development of POAG in patients with OHT and ODH, compared with patients without ODH; median time from ODH to POAG development was 36 mo; only 16% of ODHs were detected by clinicians in OHTS; ODHs commonly occur in the inferotemporal and superotemporal regions; Airaksinen et al (1981) and Law et al (2001) demonstrate tendency of ODHs to occur adjacent to preexisting neural rim notches

Assessment of Risk for Glaucoma Progression

Intraocular pressure: the Early Manifest Glaucoma Trial (EMGT; Leske et al [2007]) found that patients with IOP ≥21 mm Hg are 77% more likely to experience progression, compared with patients with normal IOP; higher IOPs during follow-up portend a poorer prognosis; the Canadian Glaucoma Study (Chauhan et al [2008]) found that patients in the lowest IOP tertile had less progression, compared with patients in the highest IOP tertile; in the Advanced Glaucoma Intervention Study (AGIS [2007]), very few patients with IOP <18 mm Hg had progression; predictive analysis demonstrated lower risk for progression among patients with average IOP <14 mm Hg among 6-mo, 12-mo, and 18-mo follow-up visits; IOP variation — analysis of AGIS data by Caprioli et al (2008) reveals that greater IOP variation (standard deviation [SD] of IOP) at 6-mo follow-up is a better predictor of progression than mean or baseline IOP among patients with low, but not high, IOP (average IOP 20-21 mm Hg); Musch et al (2011) found that maximum SD, but not mean IOP, was predictive of progression in the Collaborative Initial Glaucoma Treatment Study; peak IOP — de Moraes et al (2011) found that mean follow-up IOP, peak IOP, and IOP fluctuation all reliably predict progression; Kim et al (2019) discovered that peak IOP effectively predicts faster progression of POAG

Central cornea thickness: the EMGT demonstrates that thinner CCT predicts progression among patients with higher, but not lower, baseline IOP; de Moraes et al (2011) demonstrated increased risk for progression in patients with thinner vs thicker CCT

Pseudoexfoliation syndrome (PXF): EMGT demonstrates >2-fold increased likelihood for progression among patients with PXF; de Moraes et al (2011) reported ≈1.5-fold greater likelihood for progression; Kim et al (2019) also reported that PXF is associated with accelerated progression

Optic disc hemorrhage: the Collaborative Normal-Tension Glaucoma Study (Drance et al [2001]) found that patients with baseline ODH are ≈3-fold more likely to progress; the EMGT also demonstrates increased likelihood for progression; Marvasti et al (2013) found that visual field index (VFI) is worse among patients with ODH (management of ODH slows progression); de Moraes et al (2011) reported ≈2.5-fold higher likelihood of progression

β-zone parapapillary atrophy (βPPA): present in ≥50% of patients with POAG; various studies demonstrate that patients with βPPA are more likely to progress

Ocular perfusion pressure (OPP): the Baltimore Eye Survey (BES; Sommer et al [1991]) demonstrated increased risk for progression among patients with high vs low OPP (low systemic blood pressure [BP] increases risk for progression); the EMGT found that higher BP is protective and decreases risk by ≈46%

Age: elderly patients progress more than younger patients; the AGIS reported 29% more progression for every 5 yr; in EMGT, patients ≥68 yr of age were ≈50% more likely to progress; Kim et al (2019) found that increasing age is associated with VF decay

Family history and ethnicity: univariate analysis of OHTS results demonstrated higher risk for progression among Black and Hispanic individuals, though multivariate analysis with CCT and IOP did not demonstrate a significant role of ethnicity; the BES found that family history was significant among Black, but not White, individuals; the Nottingham Family Glaucoma Screening Study (Sung et al [2006]) demonstrated ≈20% increased risk for POAG by 70 yr of age among siblings of patients with POAG

Baseline VF defect: de Moraes et al (2009) demonstrated greater likelihood of progression in patients with baseline VF defect in both hemifields vs one hemifield

Physical activity: more physical activity slows VF loss

Prediction Models

OHTS-EGPS prediction model: estimates the 5-yr risk of developing POAG based on IOP (3 separate readings), CCT (3 separate readings), VCDR, and PSD (from 2 separate VFs); the precision may decrease when readings from only a single visit are used

Validated model for POAG progression: de Moraes et al (2012) validated a model that predicts progression over 25 yr

Readings

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. doi:10.1016/s0002-9394(00)00538-9; Budenz DL, Anderson DR, Feuer WJ, et al. Detection and prognostic significance of optic disc hemorrhages during the Ocular Hypertension Treatment Study. Ophthalmology. 2006;113(12):2137-43. doi:10.1016/j.ophtha.2006.06.022; Caprioli J, Coleman AL. Intraocular pressure fluctuation a risk factor for visual field progression at low intraocular pressures in the advanced glaucoma intervention study. Ophthalmology. 2008;115(7):1123-1129.e3. doi:10.1016/j.ophtha.2007.10.031; Chauhan BC, Mikelberg FS, Artes PH, et al. Canadian Glaucoma Study: 3. Impact of risk factors and intraocular pressure reduction on the rates of visual field change. Arch Ophthalmol. 2010 Oct;128(10):1249-55. doi: 10.1001/archophthalmol.2010.196. Epub 2010 Aug 9. Erratum in: Arch Ophthalmol. 2010 Dec;128(12):1633. PMID: 20696979; de Moraes CGV, Juthani VJ, Liebmann JM, et al. Risk factors for visual field progression in treated glaucoma. Arch Ophthalmol. 2011;129(5):562-568. doi:10.1001/archophthalmol.2011.72; Drance S, Anderson DR, Schulzer M, Collaborative Normal-Tension Glaucoma Study Group. Risk factors for progression of visual field abnormalities in normal-tension glaucoma. Am J Ophthalmol. 2001;131(6):699-708. doi:10.1016/s0002-9394(01)00964-3; Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):714-720; discussion 829-830. doi:10.1001/archopht.120.6.714; Kass MA, Heuer DK, Higginbotham EJ, et al. 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):701-13; discussion 829-30. doi:10.1001/archopht.120.6.701; Leske MC, Heijl A, Hyman L, et al. Predictors of long-term progression in the early manifest glaucoma trial. Ophthalmology. 2007;114(11):1965-1972. doi:10.1016/j.ophtha.2007.03.016; Marvasti AH, Tatham AJ, Zangwill LM, et al. The relationship between visual field index and estimated number of retinal ganglion cells in glaucoma. PLoS One. 2013;8(10):e76590. doi:10.1371/journal.pone.0076590; Musch DC, Gillespie BW, Niziol LM, et al. Intraocular pressure control and long-term visual field loss in the Collaborative Initial Glaucoma Treatment Study. Ophthalmology. 2011;118(9):1766-1773. doi:10.1016/j.ophtha.2011.01.047; Ocular Hypertension Treatment Study Group, European Glaucoma Prevention Study Group, Gordon MO, et al. Validated prediction model for the development of primary open-angle glaucoma in individuals with ocular hypertension. Ophthalmology. 2007;114(1):10-19. doi:10.1016/j.ophtha.2006.08.031; Sommer A, Tielsch JM, Katz J, et al. Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. The Baltimore Eye Survey. Arch Ophthalmol. 1991;109(8):1090-5. doi:10.1001/archopht.1991.01080080050026; Sung VCT, Koppens JM, Vernon SA, et al. Longitudinal glaucoma screening for siblings of patients with primary open angle glaucoma: the Nottingham Family Glaucoma Screening Study. Br J Ophthalmol. 2006;90(1):59-63. doi:10.1136/bjo.2005.072751; The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators. Am J Ophthalmol. 2000;130(4):429-440. doi:10.1016/s0002-9394(00)00538-9.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Heuer was recorded at the USC Department of Ophthalmology 48th Annual Symposium, held on June 15, 2024, in Los Angeles, CA, and presented by USC Gayle and Edward Roski Eye Institute and USC Office of Continuing Medical Education, Los Angeles, CA. For more information about upcoming CME activities from this presenter, please visit https://keckusc.cloud-cme.com. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.00 CE contact hours.

Lecture ID:

OP622201

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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