Risk Factors for Development of Glaucoma

European Ophthalmic Review, 2007:10-2 DOI: http://doi.org/10.17925/EOR.2007.00.00.10
Received: January 17, 2011 Accepted January 17, 2011 Citation European Ophthalmic Review, 2007:10-2 DOI: http://doi.org/10.17925/EOR.2007.00.00.10

In recent years, our knowledge of risk factors relating to open-angle glaucoma (OAG) has improved substantially. A number of studies have evaluated the cross-sectional association betwen risk factors and OAG, whereas only a few have investigated the risk factors for glaucoma development.1 Prospective data provide better evidence on which to base inferences on causation because of ascertainment of temporality, which is one of the major causative criteria and has always been an inherent problem in studying a disease with low incidence. The first requirement in assessing glaucoma onset is to study a cohort of individuals or patients over a period of time that is long enough to allow the development of the disease. The second requirement is an adequate definition of progressive change for the development of new cases of OAG. The third requirement is the collection of all of the possible clinical and non-clinical information from each study participant at baseline and, whenever possible, at different times during the follow-up, until the end of the investigation. These three requirements allow all the factors that were noted before the occurrence of the end-point to be weighed, thus elucidating and emphasising the potential relationship between each single risk or protective factor and the studied outcome.

In OAG, the following study designs, which meet all three requirements, are most often used: longitudinal population-based studies (PBS), randomised controlled clinical trials (RCTs) and cohort studies. Few major differences exist between these three study designs. PBS are usually designed to assess the incidence of OAG in a sample of the population of a well-defined geographical area, and are generally based on two examinations taken at least four years apart. This design usually takes into account the factors that were collected at the first examination and the factors that could be retrieved during the follow-up time before the second examination. This allows precise information to be collected only at baseline, as the indirectly acquired follow-up data cannot be matched precisely with the time of occurrence of progression. RCTs are designed to evaluate the efficacy of treatments, using an untreated group or a standard-treated group as control. Information is collected at baseline and at all the observation time-points until the end of the study. This design allows a very precise temporal relationship to be assessed (as the information is collected before the occurrence of the outcome), but is always restricted to a clinically very well-defined population – those with ocular hypertension (OHT), pseudoexfoliation (PEX), etc. This limits the potential for the results to be generalised, which differs from the PBS. Moreover, the intervention interferes with the results. Cohort studies tend to have the same pros and cons as RCTs, differing only in that single hypothetical factors are the targets of the investigation, and the results may provide information concerning only those individuals affected by the studied condition.

An important issue to be outlined is the different relative importance in terms of ‘causality’ that should be attributed to the various factors. Indeed, there are factors that may precede the progression – such as disc haemorrhage or high cup-to-disc (C/D) ratio – that are often strongly associated with the outcome. These cannot be interpreted as ‘causal factors’ of the progression, but simply as predictive factors that can be clinically observed. Furthermore, there are other factors, such as high intraocular pressure (IOP), for which a more relevant causal effect has been established. This review will therefore focus only on those longitudinal studies in which OAG onset was documented by the clinical detection of visual field (VF) and/or optic disc progressive changes. The data will be summarised and discussed in the context of each study design.

References:
  1. Boland MV, Quigley HA, Risk factors and open-angle glaucoma: classification and application, J Glaucoma, 2007;16:406–18.
  2. Rothman K, Greenland S, Modern Epidemiology, 2nd edn, Philadelphia, Lippincott-Raven, 1998;23–8.
  3. Leske MC, Wu SY, Hennis A, et al., Risk factors for incident open-angle glaucoma. The Barbados Eye Studies, Ophthalmology, e-pub, July 2007.
  4. Le A, Mukesh BN, McCarty CA, Taylor HR, Risk factors asociated with the incidence of open-angle glaucoma: the Visual Impairment Project, Invest Ophthalmol Vis Sci, 2003;44:3783–9.
  5. De Voogd S, Ikram MK, Wolfs RCW, et al., Is diabetes mellitus a risk factor for open-angle glaucoma? The Rotterdam Eye Study, Ophthalmology, 2006;113:1827–31.
  6. Muskens RPHM, de Voogd S, Wolfs RCW, et al., Systemic antihypertensive medication and incident open-angle glaucoma, Ophthalmology, e-pub, June 2007.
  7. Kass MA, Heuer DK, Higginbotham EJ, et al., The Ocular Hypertension Treatment Study. A randomized trial determines that topical hypotensive medication delays or prevents the onset of primary open-angle glaucoma, Arch Ophthalmol, 2002;120:701–13.
  8. The European Glaucoma Prevention Study Group. Results of the European Glaucoma Prevention Study, Ophthalmology, 2005;112:366–75.
  9. 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;120:714–20.
  10. The European Glaucoma Prevention Study Group, Predictive factors for open-angle glaucoma among patients with ocular hypertension in the European Glaucoma Prevention Study, Ophthalmology, 2007;114:3–9.
  11. Levine RA, Demirel S, Fan J, et al., for the Ocular Hypertension Treatment Study Group. Asymmetries and visual field summaries as predictors of glaucoma in the Ocular Hypertension Treatment Study, Invest Ophthalmol Vis Sci, 2006;47:3896–3903.
  12. Budenz DL, Anderson DR, Feuer WJ, et al., for the Ocular Hypertension Treatment Study Group. Detection and prognostic significance of optic disc hemorrhages during the Ocular Hypertension Treatment Study, Ophthalmology, 2007;113: 1603–12.
  13. Miglior S, Torri V, Zeyen T, et al., for the European Glaucoma Prevention Study Group. Inter-current factors associated with the development of open-angle glaucoma in the European Glaucoma Prevention Study, Am J Ophthalmol, 2007;144:266–75.
  14. A long-term prospective study of risk factors for glaucomatous visual field loss in patients with ocular hypertension, J Glaucoma, 2005;14:135–8.
  15. Coleman A, Gordon MO, Beiser J, et al., for the Ocular Hypertension Treatment Study Group. Baseline risk factors for the development of primary open-angle glaucoma in the Ocular Hypertension Treatment Study, Am J Ophthalmol, 2004;138: 684–5.
  16. Zangwill LM, Weinreb RN, Beiser JA, et al., for the Ocular Hypertension Treatment Study Group. Baseline topograhic optic disc measurements are associated with the development of primary open-angle glaucoma, Arch Ophthalmol, 2005;123:1188–97.
  17. Bengtsson B, Heijl A, Diurnal IOP fluctuation: not an independent risk factor for glaucomatous visual field loss in high-risk ocular hypertension, Graefe’s Arch Clin Exo Ophthalmol, 2005;243:513–18.
  18. Gordon MO, Torri V, Miglior S, et al., Validated prediction model for the development of primary open-angle glaucoma in individuals with ocular hypertension, Ophthalmology, 2007;114:10–19.
  19. Kymes SM, Kass MA, Anderson DR, et al., Management of ocular hypertension: a cost-effectiveness approach from the Ocular Hypertension Treatment Study, Am J Ophthalmol, 2006;141:997–1008.
  20. Mansberger SL, A risk calculator to determine the probability of glaucoma, J Glaucoma, 2004;13:345–7.
  21. Medeiros FA, Weinreb RN, Sample PA, et al., Validation of a predictive model to estimate the risk of conversion from ocular hypertension to glaucoma, Arch Ophthalmol, 2005;123:1351–60.