Medical Outcomes of Therapy for Glaucoma
Medical Outcomes of Therapy for Glaucoma
Objective: To evaluate the medical outcomes of patients treated for primary open angle glaucoma (POAG) or ocular hypertension.
Patients and Methods: Sixty-eight ophthalmologists selected at random from a national professional list in France were asked to report on disease progression in consecutive patients who they saw in their clinics and who had either POAG, normal tension glaucoma/ocular hypertension, and who were aged >18 years of age. Data on sociodemographics, general and ocular comorbidities, glaucoma risk factors, visual acuity (VA), optic nerve head (ONH) clinical data, and visual fields were collected. Disease progression was defined as a deterioration of ONH and/or visual field since initial diagnosis. Changes in treatment were also monitored. A treatment change was defined as adding a new drug or changing any of the current treatments. Time to treatment failure was compared using the Wilcoxon test applied to survival curves.
Results: Of 127 patients who were evaluated, 12 developed a disease progression after diagnosis (average follow-up 2.4 years). No statistically significant difference in the known confounding factors of disease progression was found between patients with or without disease progression. At 32 months, 2.6% of the patients with no changes in treatment had a DP, compared with 22.6% with one change in treatment and 46.2% with two or more changes in treatment (p < 0.03). Patients who experienced adverse effects (p < 0.008) and those who said they were unhappy with their treatment (p < 0.03) more often experienced disease progression.
Conclusion: An estimated 9.4% of a representative sample of patients with POAG or ocular hypertension experienced disease progression within 2.5 years of initial diagnosis. Patients with disease progression had more changes in treatment and adverse events; they were also more likely to have complained about being unhappy with their treatment.
Control of intraocular pressure (IOP) is one of the critical requirements for glaucoma treatment in those < 40 years of age. Several clinical strategies have been developed to achieve this control, including drugs, laser treatment and conventional surgery. Most of the studies evaluating these technologies considered control of IOP as a surrogate endpoint for visual field deterioration. Large long-term studies have been conducted aimed at measuring the long-term consequences of lowering IOP and at identifying predictive factors for clinical outcome.
Randomised clinical trial (RCT) results often differ from those obtained in normal clinical practice. Moreover, RCT results do not entirely satisfy the current demands of regulatory bodies that are in charge of resource allocation (pricing, formulary listing, reimbursement, etc). Observational studies are studies in which the investigator does not control the therapy, but observes and evaluates the results of ongoing medical care. The study designs that are used are those that do not involve randomisation, namely case reports, case series and cohort studies.
Several factors explain the differences between RCTs and observational studies. Patients included in an RCT know that they will be scrutinised by their ophthalmologist (observational bias); this might affect treatment compliance and might lead to an optimal control of IOP that would never have occurred in normal clinical practice. Stringent protocols control the way that the disease is managed (visit to clinic, time at IOP measure, definition of failure, when and how to switch treatment). Patients fulfilling the inclusion and exclusion criteria and willing to participate and investigators (generally experts in their field) are carefully selected (selection bias). Even in the very large RCTs (e.g. Collaborative Initial Treatment Study, Advanced Glaucoma Intervention Study, Early Manifest Glaucoma Trial, Ocular Hypertension Treatment Study), patients were managed differently from normal clinical practice, for example measures were more standardised, and visits to ophthalmologists were fixed by protocols. Therefore, although the internal validity (unbiased estimate of treatment difference) of RCTs is very strong due to randomisation and blinded assessment of outcomes, their external validity (ability to extrapolate results to the general targeted population) is open to discussion.
Some observational surveys, either prospective or retrospective, have been conducted with patients treated for ocular hypertension or primary open angle glaucoma (POAG), but these were generally driven by economic considerations. Disease progression was not documented. As a consequence, detailed information was given on the utilisation of medical resources, but very little information was provided on outcomes. At the most, IOP is reported as a surrogate endpoint of visual field status.
The aim of this pilot study was to develop a specific methodology that could attempt: (i) to estimate the medical outcomes of a representative sample of patients treated for POAG or ocular hypertension in a normal clinical setting, and (ii) to identify factors related to the outcomes.
Objective: To evaluate the medical outcomes of patients treated for primary open angle glaucoma (POAG) or ocular hypertension.
Patients and Methods: Sixty-eight ophthalmologists selected at random from a national professional list in France were asked to report on disease progression in consecutive patients who they saw in their clinics and who had either POAG, normal tension glaucoma/ocular hypertension, and who were aged >18 years of age. Data on sociodemographics, general and ocular comorbidities, glaucoma risk factors, visual acuity (VA), optic nerve head (ONH) clinical data, and visual fields were collected. Disease progression was defined as a deterioration of ONH and/or visual field since initial diagnosis. Changes in treatment were also monitored. A treatment change was defined as adding a new drug or changing any of the current treatments. Time to treatment failure was compared using the Wilcoxon test applied to survival curves.
Results: Of 127 patients who were evaluated, 12 developed a disease progression after diagnosis (average follow-up 2.4 years). No statistically significant difference in the known confounding factors of disease progression was found between patients with or without disease progression. At 32 months, 2.6% of the patients with no changes in treatment had a DP, compared with 22.6% with one change in treatment and 46.2% with two or more changes in treatment (p < 0.03). Patients who experienced adverse effects (p < 0.008) and those who said they were unhappy with their treatment (p < 0.03) more often experienced disease progression.
Conclusion: An estimated 9.4% of a representative sample of patients with POAG or ocular hypertension experienced disease progression within 2.5 years of initial diagnosis. Patients with disease progression had more changes in treatment and adverse events; they were also more likely to have complained about being unhappy with their treatment.
Control of intraocular pressure (IOP) is one of the critical requirements for glaucoma treatment in those < 40 years of age. Several clinical strategies have been developed to achieve this control, including drugs, laser treatment and conventional surgery. Most of the studies evaluating these technologies considered control of IOP as a surrogate endpoint for visual field deterioration. Large long-term studies have been conducted aimed at measuring the long-term consequences of lowering IOP and at identifying predictive factors for clinical outcome.
Randomised clinical trial (RCT) results often differ from those obtained in normal clinical practice. Moreover, RCT results do not entirely satisfy the current demands of regulatory bodies that are in charge of resource allocation (pricing, formulary listing, reimbursement, etc). Observational studies are studies in which the investigator does not control the therapy, but observes and evaluates the results of ongoing medical care. The study designs that are used are those that do not involve randomisation, namely case reports, case series and cohort studies.
Several factors explain the differences between RCTs and observational studies. Patients included in an RCT know that they will be scrutinised by their ophthalmologist (observational bias); this might affect treatment compliance and might lead to an optimal control of IOP that would never have occurred in normal clinical practice. Stringent protocols control the way that the disease is managed (visit to clinic, time at IOP measure, definition of failure, when and how to switch treatment). Patients fulfilling the inclusion and exclusion criteria and willing to participate and investigators (generally experts in their field) are carefully selected (selection bias). Even in the very large RCTs (e.g. Collaborative Initial Treatment Study, Advanced Glaucoma Intervention Study, Early Manifest Glaucoma Trial, Ocular Hypertension Treatment Study), patients were managed differently from normal clinical practice, for example measures were more standardised, and visits to ophthalmologists were fixed by protocols. Therefore, although the internal validity (unbiased estimate of treatment difference) of RCTs is very strong due to randomisation and blinded assessment of outcomes, their external validity (ability to extrapolate results to the general targeted population) is open to discussion.
Some observational surveys, either prospective or retrospective, have been conducted with patients treated for ocular hypertension or primary open angle glaucoma (POAG), but these were generally driven by economic considerations. Disease progression was not documented. As a consequence, detailed information was given on the utilisation of medical resources, but very little information was provided on outcomes. At the most, IOP is reported as a surrogate endpoint of visual field status.
The aim of this pilot study was to develop a specific methodology that could attempt: (i) to estimate the medical outcomes of a representative sample of patients treated for POAG or ocular hypertension in a normal clinical setting, and (ii) to identify factors related to the outcomes.
