Comorbidities and risk factors
The relationship between glaucoma, comorbidities,
and other risk factors
Glaucoma prevalence can be influenced by age, ethnicity, and additional factors such as family history and gender1,2
Glaucoma is a leading cause of irreversible blindness worldwide, with 76 million people aged 40–80 years old that were estimated to be living with glaucoma in 2020.*,**2,3
POAG is the most common type of glaucoma, accounting for at least 90% of all glaucoma cases.4
* Estimated using data from population-based studies.2
** (95% CrI), 51.9–111.7.3
Ethnicity1
A 2014 systematic review and meta-analysis found the prevalence of POAG highest in Africa (4.20%; 95% CrI, 2.08–7.35), followed by Latin America and the Caribbean (3.65%; 95% CrI, 1.90–6.54), North America (3.29%; 95% CrI, 1.83–5.53) and Asia (2.31%; 95% CrI, 1.44–3.44).1,2
Relative risk of developing POAG based on ethnicity (OR, 95% CrI)*,2
* Age and gender adjusted. Results of a systematic review and meta-analysis of data from 50 population-based studies published up to March 2013 and included 3770 POAG cases among 140,496 examined individuals aged 40–80 years.2
Age
A systematic review and meta-analysis found that the relative risk of developing POAG increased 1.75* times for each decade lived over the age of 40 years.*,5
* Age and gender adjusted. Results of a systematic review and meta-analysis of data from 50 population-based studies published up to March 2013 and included 3,770 POAG cases among 140,496 examined individuals aged 40–80 years.5
Estimated prevalence of POAG based on ethnicity and age in men and women combined*,**,6
Adapted from Kapetanakis VV et al. 2016.6
POAG, primary open-angle glaucoma.
* Based on a 2016 systematic review and meta-analysis of population-based studies evaluating the relationship between POAG and demographic factoring. A total of 81 studies were included with 216,214 participants (5,266 POAG cases) from 37 countries.6
** Estimates obtained by extrapolation from the fitted model.6
Additional factors
Gender
Men were shown to be 1.36* times more likely to develop POAG than women.**,2
* OR (95% CrI): 1.36 (1.23–1.52).2
** Age and gender adjusted. Results of a systematic review and meta-analysis of data from 50 population-based studies published up to March 2013 and included 3,770 POAG cases among 140,496 examined individuals aged 40–80 years.2
Family history5
A family history of glaucoma increases the risk of developing OAG by 2.1 times.7
The relative importance of family history may vary according to the closeness of relationship of a patient to an affected family member (1st, 2nd, or 3rd third degree).7
It is important that patients are asked about their family history at ophthalmologic appointments to determine whether they may be at an increased risk of developing glaucoma or other ocular conditions.8
Glaucoma and diabetes
In 2021, there were an estimated 529 million people living with diabetes worldwide.9 Vision loss from diabetic retinopathy is the leading cause of blindness in working age adults. Glaucoma is another vision-threatening ocular complication that has been associated with diabetes.10
One of the mechanisms thought to explain this possible association is the link between hyperglycemia and glycation of lipids and abnormalities of lipid metabolism which may increase oxidative stress and promote cellular apoptosis – the same mechanism by which retinal ganglion cell loss occurs in glaucoma.10
A 2015 meta-analysis of 47 studies from 16 countries reported a pooled relative risk of glaucoma of 1.48 (95% CI, 1.29–1.71) in patients with diabetes compared to those without.11
Furthermore, diabetic patients had a pooled average increase in IOP of 0.09 mmHg for every 10 mg/dL increase in fasting glucose.10
Change in IOP associated with a 10 mg/dL increase in fasting serum glucose12
Adapted from Zhao D et al. Supplementary appendix. 2015.12
The American Diabetes Association currently recommends that all patients with diabetes undergo annual dilated funduscopic examinations to evaluate for the presence of retinopathy, although eye examinations may be performed:13,14
• every 2 years at the discretion of the eye care provider if no retinopathy is present
• for newly diagnosed patients with type 1 diabetes mellitus, an initial eye examination is recommended within 5 years after diagnosis
• for type 2 diabetes mellitus, eye examinations are recommended at the time of diagnosis
Glaucoma and obesity
In 2022, 2.5 billion adults (18 years and older) worldwide were overweight. Of these, 890 million were living with obesity.15 The correlation between obesity and POAG has not yet been fully established, but studies have been carried out to investigate this relationship.16
A two-sample Mendelian randomization* study showed that BMI (an index to evaluate general obesity) has a positive effect on the risk of POAG, with 1 SD increase in BMI; the risk of POAG increases by approximately 90.9% (OR=1.909; 95% CI 1.225–2.975; p=0.0042).16
* Mendelian randomization is an epidemiological approach for investigating whether a causal effect exists between exposures and outcomes by using genetic variants as instrumental variables.16
The pathophysiological explanation for the association between obesity and glaucoma is not yet fully understood, but there are two suggested theories:17
Mechanically, obesity has been suggested to exert an effect on IOP by causing excessive intraorbital adipose tissue, increased blood viscosity, increased episcleral venous pressure, and impairment of aqueous outflow facility17
Vascularly, obesity has been shown to cause vascular endothelial dysfunction, which can impair vascular supply to the optic nerve head, leaving eyes more susceptible to damage by both normal and elevated IOP17
Iatrogenic diseases and glaucoma
Cataracts
Cataract formation is a well-known complication of trabeculectomy.18
The Advanced Glaucoma Intervention Study (AGIS) has reported an increased risk of cataract formation with first trabeculectomy, whether as the first or second AGIS intervention, by 78% after adjustment for age and diabetes (RR=1.78, p<0.001).*,18
* The AGIS followed 789 eyes in 591 patients with medically uncontrolled open-angle glaucoma between 1988–1992. The eyes were randomized to either an ALT-trabeculectomy-trabeculectomy treatment sequence or a trabeculectomy-ALT-trabeculectomy sequence.
The pathogenesis of cataract formation following trabeculectomy is likely due to multiple factors:18,19
Surgical peripheral iridectomy with trabeculectomy may increase post-operative inflammation, which has been associated with increased risk of cataract formation18,19
Flat anterior following trabeculectomy may be an additional risk factor18
Predictors of cataract extraction include:20
Patient factors such as older age, myopia, pseudoexfoliative glaucoma, and diabetes19
Cataract surgery may be performed in combination with glaucoma surgery in patients presenting with both glaucoma and cataracts.21,5
Retinal detachment surgery
Glaucoma can occur as a secondary complication from retinal detachment procedures, and may be related to pre-operative conditions.22
Glaucoma after scleral buckling procedures:
The incidence of angle-closure glaucoma after scleral buckling procedures has been reported to range from 1.4%–4.4% in several studies ranging from 817–1558 eyes22
A variety of factors can affect the incidence and extent of angle-closure glaucoma including:22
Pre-existing narrow angles
Use of an encircling band
Placement of an encircling band anterior to the equator
High myopia
Older patient age
Post-operative ciliochoroidal detachment
Pathogenesis:22
• Data suggests that angle-closure glaucoma is produced by impaired venous drainage from the vortex veins by the scleral buckle
• Blood from the ciliary body drains into the vortex veins, so their obstruction leads to congestion and swelling of the ciliary body
• As the ciliary body swells, it rotates anteriorly and shifts the lens-iris diaphragm forward causing secondary ACG
Subscribe to newsletter
Contact us
Material
References and abbreviations
1. European Glaucoma Society. Terminology and Guidelines for Glaucoma. 5th edition. EGS. 2021.
2. Tham YC, Li, Wong et al. Global Prevalence of Glaucoma and Projections of Glaucoma Burden through 2040. Am Acad Ophthalmol 2014; 121(11): 2081–2089.
3. World Health Organization. World Report on Vision. WHO 2019. Available at: https://www.who.int/publications/i/item/world-report-on-vision. Accessed: July 2024.
4. Munteanu G, Munteanu Z V I, Roiu et al. Aspects of Tertiary Prevention in Patients with Primary Open Angle Glaucoma. J Pers Med 2021; 11(9): 830.
5. European Glaucoma Society. Terminology and Guidelines for Glaucoma. 5th edition. EGS. 2020.
6. Kapetanakis VV, Chan, Foster et al. Global variations and time trends in the prevalence of primary open angle glaucoma (POAG): a systematic review and meta-analysis. Br J Ophthalmol 2016; 100: 86–93.
7. McMonnies C. J. Glaucoma history and risk factors. Optom 2017; 10(2): 71–78.
8. Takusewanya M. How to take a complete eye history. Community Eye Health 2019; 32(107). 44–45.
9. GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet 2023; 402(10397): 203–234.
10. Song B, Aiello, Pasquale. Presence and Risk Factors for Glaucoma in Patients with Diabetes. Curr Diab Rep 2016; 16: 124.
11. Zhao D, Cho, Kim et al. Diabetes, fasting glucose, and the risk of glaucoma: a meta-analysis. Ophthalmology 2015; 122(1): 72–78.
12. Zhao D et al. Diabetes, fasting glucose, and the risk of glaucoma: a meta-analysis. Ophthalmology 2015; 122(1): 72–78. Supplementary Appendix.
13. ElSayed N, Aleppo, Aroda et al. 12. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes-2023. Diabetes Care 2023; 46(Suppl. 1): S203–S215.
14. American Diabetes Association. What Can You Do to Protect Your Eyes? Available at:https://diabetes.org/health-wellness/eye-health/what-can-you-do-protect-your-eyes#:~:text=The%20American%20Diabetes%20Association%20recommends,within%20five%20years%20of%20diagnosis. Accessed June 2024.
15. World Health Organization. Factsheet: Obesity and overweight. 2021. Available at: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Accessed May 2024.
16. Lin Y, Zhu, Luo et al. The Causal Association Between Obesity and Primary Open-Angle Glaucoma: A Two-Sample Mendelian Randomization Study. Front Genet 2022; 13(835524).
17. Cheung N and Wong T. Obesity and eye diseases. Surv Ophthalmol 2007; 52(2): 180–195.
18. The AGIS Investigators. The Advanced Glaucoma Intervention Study: 8. Risk of cataract formation after trabeculectomy. Arch Ophthalmol 2001; 119: 1771–1780.
19. De Barros DSM, Da Silva, Siam et al. Should an iridectomy be routinely performed as a part of trabeculectomy? two surgeons' clinical experience Eye (Lond.) 2007; 23(2): 362–367.
20. Musch D, Gillespie, Niziol et al. Cataract Extraction in the Collaborative Initial Glaucoma Treatment StudyIncidence, Risk Factors, and the Effect of Cataract Progression and Extraction on Clinical and Quality-of-Life Outcomes. Arch Ophthalmol 2006; 124: 1694–1700.
21. Kyari F. Managing cataract surgery in patients with glaucoma. Community Eye Health 2019; 31(104): 88–90.
22. Gedde S. Management of glaucoma after retinal detachment surgery. Curr Opin Ophthalmol 2002; 13(2): 103–109.
ACG, angle closure glaucoma; CrI, credible interval; OAG, open-angle glaucoma; OR, odds ratio; POAG, primary open-angle glaucoma;
IOP, intraocular pressure; OAG, open-angle glaucoma; BMI, body mass index; CI, confidence interval; SD, standard deviation.
ALT, argon laser trabeculoplasty; RR, relative risk.
SE-OPHTHG-240008 v. 1.0 July 2024
