Individualizing glaucoma patient care
More tools needed to optimise therapeutic tailoring
Although guidelines from around the world provide general advice on glaucoma management for populations of patients, their recommendations are not geared for individualised decision-making for each patient, notes Fotis Topouzis, MD.
Speaking at the ESCRS/EGS Glaucoma Day meeting in Paris, France, Dr Topouzis discussed current approaches to matching therapeutic strategies to individual glaucoma patients and outlined a path for improving customised treatment in the future.
Reviewing prospective clinical trial data on progression rates associated with various treatment strategies, Dr Topouzis brought forth the drawbacks of following a standard approach to care, but also the limitations of the current approach to an individualised regimen based on target IOP.
“We saw in the Early Manifest Glaucoma Trial (EMGT) and in the United Kingdom Glaucoma Treatment Study (UKGTS) that a standard approach with less aggressive treatment would probably result in many patients being under-treated. Therefore, one would ask why not be on the safe side and treat everyone more aggressively?” said Dr Topouzis, Professor of Ophthalmology, Aristotle University of Thessaloniki, Greece.
“According to results from the Collaborative Initial Glaucoma Treatment Study, the answer to that question is that aggressive treatment would result in overtreatment for many glaucoma patients. In addition, data from the EMGT and UKGTS show strikingly that many glaucoma patients do not progress when left untreated.”
Dr Topouzis reminded clinicians that as stated in the EGS guidelines, the goal of glaucoma treatment is to maintain the patient’s visual function and quality of life at a sustainable cost. In addition, every treatment is associated with cost and side-effects that affect quality of life.
“Increasing treatment increases side-effects leading to an increased impact on quality of life. Therefore, we need to be balanced in our decisions at the individual level,” said Dr Topouzis.
For now, customised treatment depends on setting a target IOP and reaffirming its appropriateness through continued follow-up. Multiple factors are considered when establishing the target, including the stage of glaucoma damage, the patient’s life expectancy, the level of untreated IOP, additional risk factors (e.g., central corneal thickness, presence of pseudoexfoliation) and rate of progression. Rate of progression, however, cannot be used as a parameter when first initiating therapy.
There are also challenges for assessing progression in clinical practice and a need to better understand how different rates of progression impact individual patients.
Dr Topouzis explained that in patients who are slow progressors, a larger number of visual fields are needed to detect progression in a given time frame. As described in a paper by Chauhan et al. (Br J Ophthalmol. 2008;92(4):569-573), six visual field examinations should be performed in the first two years to rule out the presence of rapid progression (≥-2 dB/year) and establish a good baseline.
“Obtaining that many visual fields is difficult, but even if it was feasible, it seems inadequate for detecting slower rates of progression that would result in visual impairment or blindness during lifetime in the majority of patients,” said Dr Topouzis.
Explaining his comment, Dr Topouzis presented findings from a study conducted to provide information on the maximum tolerable rate of progression to avoid visual impairment and blindness in patients with open-angle glaucoma (Br J Ophthalmol. 2018;102:916-921). The analysis, which included data from participants in the cross-sectional, population-based Thessaloniki Eye Study, found that the maximum tolerable rate of glaucoma progression to avoid blindness was <-2 dB/year in 72.4% of patients. Therefore, currently our best tools, methods and proposed strategies aiming to detect fast progressors (-2dB/year or faster) seem inadequate to detect slower rates of progression that would result in visual impairment or blindness during lifetime in the majority of patients.
Needs for the future
To be able to individualise therapy based on rate of progression, there is a need for better understanding of the stage of visual field damage that has to be prevented.
“We need to know the stage that is tolerable because quality of life may be affected even at an earlier stage of damage,” Dr Topouzis explained.
Then strategies and tools for calculating tolerable rates of progression for the individual patient are needed, fast progressors need to be defined at the individual level according to their tolerable rate of progression, taking into account life expectancy, stage of damage and other factors, and next strategies and tools to identify fast progressors are needed.
Potential tools in the era of precision medicine include the identification of biomarkers for fast progression, risk alleles for glaucoma onset and progression and biomarkers for guiding angle-based surgery approaches and efficacy.
Reviewing the status of these, Dr Topouzis said there is limited knowledge regarding risk factors and biomarkers for fast progression. Genetics is a promising pathway for the future, and methodologies are being developed to evaluate aqueous humour dynamics to obtain information for planning and monitoring the response to surgery.
“Ideally, we need a calculator for glaucoma progression and fast progression similar to what we have for ocular hypertension and that potentially integrates genetic information,” he said.
Fotis Topouzis: firstname.lastname@example.org