This is a great review on the benefit of Diurnal Curve.
Diurnal Tension Curves for Assessing the Development or Progression of Glaucoma
Executive Summary
Clinical Need: Condition and Target Population
Diurnal Curves for Intraocular Pressure Measurement
Diurnal Curve
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The role of a diurnal tension curves is to assess IOP in relationship to either a risk factor for the development or progression of glaucoma or achievement of a target pressure which may direct a therapeutic change.
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Candidates for a diurnal curve are usually limited to glaucoma suspects (based on optic disc changes or less commonly visual field changes) to assess the risk for development of glaucoma or in patients with progressive glaucoma despite normal single office IOP measurements.
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Clinically diurnal tension curves are used to determine the peak IOP and range.
Single IOP Measurements
Objective
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To determine whether the use of a diurnal tension curve (multiple IOP measurements over a minimum 8 hour duration) is more effective than not using a diurnal tension curve (single IOP measurements) to assess IOP fluctuation as a risk factor for the development or progression of glaucoma.
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To determine whether the use of a diurnal tension curve is beneficial for glaucoma suspects or patients with progressive glaucoma despite normal single office IOP measurements and leads to a more effective disease management strategy.
Research Methods
Literature Search
Search Strategy
Inclusion Criteria
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Open angle glaucoma (established or OHT high risk) in an adult population
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IOP measurement by Goldmann applanation tonometry (the gold standard)
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Number and timing of IOP measurements explicitly reported (e.g., 5 measurements a day for 5 visits to generate a diurnal curve or 1 measurement a day [no diurnal curve] every 3 months for 2 years)
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IOP parameters include fluctuation (range [peak minus trough] or standard deviation) and mean
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Outcome measure = progression or development of glaucoma
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Study reports results for ≥ 20 eyes
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Most recent publication if there are multiple publications based on the same study
Exclusion Criteria
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Angle closure glaucoma or pediatric glaucoma
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Case reports
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IOP measured by a technique other than GAT (the gold standard)
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Number and timing of IOP measurements not explicitly reported
Outcomes of Interest
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Progression or development of glaucoma
Conclusion
Background
Clinical Need and Target Population
Description of Glaucoma
Diagnosis and Treatment of Glaucoma
Intraocular Pressure Measurement
Diurnal Curve
IOP peak | Highest IOP recorded in a stated time period |
IOP trough: | Lowest IOP recorded in a stated time period |
Short-term IOP fluctuation: | IOP peak minus trough measured in a stated time period, understood to be 24 hours or less (intravisit, using diurnal curve) |
Long-term IOP fluctuation: | IOP peak minus IOP trough measured in a stated time period, understood to be on separate days (intervisit, using or not using diurnal curves) |
- The role of a diurnal tension curves is to assess IOP in relationship to either a risk factor for the development or progression of glaucoma or achievement of a target pressure which may direct a therapeutic change.
- Candidates for a diurnal curve are usually limited to glaucoma suspects (based on optic disc changes or less commonly visual field changes) to assess the risk for development of glaucoma or in patients with progressive glaucoma despite normal single
- office IOP measurements.
- Clinically diurnal tension curves are used to determine the peak IOP and range.
- A tonometry measurement takes about 15 minutes to perform per patient, and a diurnal tension curve should run for a minimum of 12 hours (personal communication, expert consultant).
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The usual course of treatment for a patient who experiences progression of their glaucoma despite normal single office IOPs (without the use of a diurnal tension curve) is:
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If the IOP was in mid teens or higher:
- set a lower target pressure and step up the therapy (additional medication or intervention)
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If IOP ≤ 12 mmHg:
- Add another medication or surgery
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Single IOP Measurements
Water Drinking Test
Evidence-Based Analysis
Objective of Analysis
- To determine whether the use of a diurnal tension curve (multiple IOP measurements over a minimum 8 hour duration) is more effective than not using a diurnal tension curve (single IOP measurements) to assess IOP fluctuation as a risk factor for the development or progression of glaucoma.
- To determine whether the use of a diurnal tension curve is beneficial for glaucoma suspects or patients with progressive glaucoma (based on optic disc changes or less commonly visual field changes) despite normal single office IOP measurements and leads to a more effective disease management strategy.
Research Methods
Literature Search
Search Strategy
Inclusion Criteria
- Open angle glaucoma (established or OHT high risk) in an adult population
- IOP measurement by Goldmann applanation tonometry (the gold standard)
- Number and timing of IOP measurements explicitly reported (e.g., 5 measurements a day for 5 visits to generate a diurnal curve or 1 measurement a day [no diurnal curve] every 3 months for 2 years)
- IOP parameters include fluctuation (range [peak minus trough] or standard deviation) and mean
- Outcome measure = progression or development of glaucoma
- Study reports results for ≥ 20 eyes
- Most recent publication if there are multiple publications based on the same study.
Exclusion Criteria
- Angle closure glaucoma or pediatric glaucoma
- Case reports
- IOP measured by a technique other than GAT (the gold standard)
- Number and timing of IOP measurements not explicitly reported
Outcomes of Interest
- Progression or development of glaucoma
Quality of Evidence
- Quality refers to the criteria such as the adequacy of allocation concealment, blinding and follow-up.
- Consistency refers to the similarity of estimates of effect across studies. If there are important and unexplained inconsistencies in the results, our confidence in the estimate of effect for that outcome decreases. Differences in the direction of effect, the magnitude of the difference in effect, and the significance of the differences guide the decision about whether important inconsistency exists.
- Directness refers to the extent to which the interventions and outcome measures are similar to those of interest.
High | Further research is very unlikely to change confidence in the estimate of effect. |
Moderate | Further research is likely to have an important impact on confidence in the estimate of effect and may change the estimate. |
Low | Further research is very likely to have an important impact on confidence in the estimate of effect and is likely to change the estimate. |
Very Low | Any estimate of effect is very uncertain |
Results of Evidence-Based Analysis
- Studies Using 8-Hour (“Office-Hours”) Diurnal Curve for IOP Measurement
- Studies Using >8-Hour Diurnal Curve for IOP Measurements
- Studies Using Serial Single IOP Measurements
Studies Comparing a Diurnal or 24-Hour Curve to Single IOP Measurements
- Which measurement method (diurnal or 24-hour vs. single measurement) is more effective for assessing the risk of development or progression of glaucoma.
NonComparative Studies Examining IOP Parameters as a Risk Factor for Glaucoma Progression
Studies Using an 8-Hour (“Office-hours) Diurnal Curve for IOP Measurement
Malmo Ocular Hypertension Study
- Mean of all IOP measurements
- Mean of the maximum IOP
- Mean of a randomly chosen IOP out of the 3 values that made up a diurnal curve
- Mean of the range of each diurnal tension curve
- Maximum range in all curves
- Difference between the lowest and highest IOP values measured during the study
- Retrospective design
- The drug study was not powered or designed to examine IOP parameters as risk factors for development of glaucoma
- IOP was measured over 3 time points during office hours. More measurements (during and/or outside office hours) may improve estimates of fluctuation.
Bergea et al. 1999
- IOP at start defined as the mean of a daytime IOP curve recorded before any therapy was given
- Mean IOP defined as the mean value of all daytime IOP curves taken during followup
- IOP range defined as the mean of all daytime IOP ranges taken during followup
- IOP % change defined as the IOP change during followup in percent of the IOP at start
- Peak IOP defined as the highest IOP recorded during followup
- The effects of followup mean IOP and followup IOP range were not simultaneously tested in the same model. Therefore it is not possible to determine if IOP range is a risk factor for glaucoma progression independent of mean IOP.
- The study, which included a subset of patients from a RCT who were treated with primary laser trabeculoplasty or medication to lower their IOP, was not powered or designed to examine IOP parameters as risk factors for progression of glaucoma.
Studies Using a >8-Hour Diurnal Curve for IOP Measurements
Choi et al. 2007
- Fluctuation defined as the difference between the highest and lowest IOPs recorded during the 24 hour period.
- Mean IOP
- Peak IOP
- Restrospective chart review design
Jonas et al. 2007
- Fluctuation
- Mean
- Peak
- Trough
- Study design (patients were part of a registry study).
- The patients were being treated by one or a various combination of different topical IOP lowering drugs.
Studies Using Serial Single IOP Measurements
Advanced Glaucoma Intervention Study (AGIS)
- Mean
- Fluctuation (reported as SD)
- Retrospective subset analysis of a RCT
- All patients received either laser trabeculoplasty or trabeculectomy (interventions used to lower IOP)
- Limited generalizability due to the patient population being restricted to moderate/advanced glaucoma that was uncontrolled despite maximal drug therapy.
Diagnostic Innovations in Glaucoma Study (DIGS)
- Mean
- Fluctuation (reported as SD)
- IOP was measured annually. Optimal frequency of risk factor measurements is unknown.
- Retrospective study design.
Early Manifest Glaucoma Trial (EMGT)
- Mean
- Fluctuation (reported as SD)
- Retrospective study design
- The results are applicable to patients who are newly diagnosed and have mostly mild to moderate VF loss
Studies on Diurnal Tension Curves for Glaucoma Suspects or Patients with Progressive Glaucoma Despite Normal Single Office IOP Measurements
- Retrospective case series design
- No information was reported about a change in therapeutic management.
Summary of Results
- The populations studied, i.e., OHT but no VF or optic disc defects, or patients with newly diagnosed or advanced glaucoma
- Type of OAG, i.e., POAG, NTG, or exfoliative glaucoma
- Variability of the results, i.e., significance of mean IOP or IOP fluctuation as an independent risk factor for development or progression of glaucoma
GRADE Quality of the Evidence
Conclusion
Status in Ontario
Schedule of Benefits
- IOP measurement is currently billed under G435A-Tonometry ($5.10). This is limited to a single IOP measurement per day.
- There is a code (G-426) for glaucoma provocative tests, including water drinking tests ($9.70). According to an expert consultant, the water drinking test is not an accepted practice in North America or Europe to predict the IOP peak during an IOP measurement curve.
- A new fee code proposal was submitted to Provider Services for multiple IOP measurements per day (starting no later than 8am and running for a minimum of 12 hours) (Proposed fee $75).
- A fee code for a diurnal curve measurement exists in Quebec (0819 – $75), Saskatchewan (332S -$64.80) and British Columbia (22023 – $33.91 or 2018/2019 – $46.38).
- The ophthalmology section of the Alberta Medical Association are preparing a submission for a diurnal curve fee code.
Target Population
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According to a glaucoma specialist in Ontario:
- Diurnal tension curves would be limited to a glaucoma suspect to assess the risk for the development of glaucoma and in a progressive glaucoma patient despite normal single office IOP measurements.
- The estimated number of patients who would be candidates for a minimum 12-hour diurnal curve at a glaucoma specialty centre would be at most ~ 16 per month.
- A general ophthalmologist may perform ~ 5 diurnal tension curves per year.
- The estimated number of candidates at other glaucoma specialty centres in the province is unknown.
- The feasibility or acceptability of a minimum 12-hour diurnal curve to patients with glaucoma is not reported or discussed in the literature.
- According to an expert consultant, the usual course of treatment for a patient who experiences progression of their glaucoma despite normal single office IOPs (without the use of a diurnal tension curve) is to treat presumptively with another treatment or surgery. Furthermore, if the IOP is in mid-teens or higher, set a lower target therapy
Prevalence of Glaucoma in the Literature
Guidelines
Canadian Ophthalmological Society Evidence-Based Clinical Practice Guidelines for the Management of Glaucoma in the Adult Eye
- Studies of Prognosis
- Level 1
- (i) Inception cohort of patients with the condition of interest, but free of the outcome of interest
- (ii) Reproducible inclusion/exclusion criteria
- (iii) Follow-up of at least 80% of subjects
- (iv) Statistical adjustment for extraneous prognostic factors (confounders)
- (v) Reproducible description of outcome measures
- Level 2
- Meets criterion (i) above, plus 3 of the other 4 criteria
- Level 3
- Meets criterion (i) above, plus 2 of the other criteria
- Level 4
- Meets criterion (i) above, plus 1 of the other criteria
Progression
Economic Analysis
Study Question
Economic Literature Review
Ontario-Based Cost Impact Analysis
Appendices
Appendix 1: Literature Search Strategies
- exp Ocular Hypertension/ (15857)
- (glaucoma* or (eye adj2 hypertension) or ocular hypertension or intraocular hypertension or intra-ocular hypertension).ti,ab. (17140)
- 1 or 2 (19976)
- exp Tonometry, Ocular/ (1987)
- (tonometer or tonometry or oculoplethysmography).ti,ab. (2945)
- (Tono-Pen or Pneumatonometer or GAT).ti,ab. (1085)
- exp circadian rhythm/ (24448)
- (diurnal adj2 curve).ti,ab. (92)
- (intravisit or intervisit or intra-visit or inter-visit).ti,ab. (51)
- ((intra-ocular pressure or intraocular pressure or ocular pressure or IOP) adj2 (nocturnal or diurnal or measurement*or fluctuat* or varia* or mean or peak or range or sd or standard deviation or parameter*)).ti,ab. (2264)
- or/4-10 (30544)
- 3 and 11 (3066)
- limit 12 to (english language and humans and yr=”2005 -Current”) (1256)
- limit 13 to (case reports or comment or editorial or letter) (105)
- 13 not 14 (1151)
- exp glaucoma/ (33236)
- (glaucoma* or (eye adj2 hypertension) or ocular hypertension or intraocular hypertension or intra-ocular hypertension).ti,ab. (26154)
- 1 or 2 (36647)
- exp oculoplethysmography/ (688)
- exp tonometer/ or exp pressure measurement/ (54057)
- (Tono-Pen or Pneumatonometer).ti,ab. (230)
- exp circadian rhythm/ (35110)
- (diurnal adj2 curve).ti,ab. (117)
- (intravisit or intervisit or intra-visit or inter-visit).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name] (54)
- ((intra-ocular pressure or intraocular pressure or ocular pressure or IOP) adj2 (nocturnal or diurnal or measurement*or fluctuat* or varia* or mean or peak or range or sd or standard deviation or parameter*)).ti,ab. (2770)
- or/4-10 (89762)
- 3 and 11 (3703)
- limit 12 to (human and english language and yr=“2005 -Current”) (1227)
- limit 13 to (editorial or letter or note) (91)
- case report/ (1113858)
- 13 not (14 or 15) (1088)
Appendix 2: Design of Studies Included in the Evidence-Based Analysis
Table 10:
Design | Comparators in Parent RCT if Subset Analysis |
---|---|
Retrospective subset analysis of RCT (Malmo Ocular Hypertension Study [MOHS]) (22)
2005 Sweden |
Timolol vs. placebo |
Retrospective analysis of RCT (Bergea et al.) (23) 1999 Sweden |
Surgery vs. pilocarpine |
Observational (unclear if prospective or retrospective) (Jonas et al.) (25) 2007 Germany |
NA |
Retrospective chart review (Choi et al.) (24) 2007 Korea |
NA |
Retrospective subset analysis of an RCT (Advanced Glaucoma Intervention Study [AGIS]) (15)
2008 US |
2 sequences of glaucoma surgery |
Retrospective subset analysis of an observational study (Diagnostic Innovations in Glaucoma Study [DIGS]) (16)
2008 US |
Diagnostic and monitoring techniques |
Retrospective subset analysis of an RCT (Early Manifest Glaucoma Trial [EMGT]) (26)
2007 Sweden/US |
Surgery plus betaxolol vs. no surgery/betaxolol |
Appendix 3: Results of Studies Included in the Evidence-Based Analysis
Table 11:
Study, Year | Design | Population | Objective | IOP Parameters | Statistical Method | Timing of IOP Measurement | Results | Comment |
Malmo OHTS, 2005 (22) | Retrospective analysis of RCT N=90 eyes | Ocular hypertension Participated in RCT for topical timolol vs. placebo |
To study the effect of IOP fluctuations on the incidence of glaucomatous VF loss in patients with ocular hypertension. | Mean Range Peak | Cox multivariable analysis | Diurnal curve 8am, 11:30am and 3:30 pm obtained every 3 months. | Mean followup 8.5 years Cox Multivariable Analysis: Mean IOP of all measurements Risk 1.21 (1.09 to 1.38), P=0.005 Mean of daily range Risk 1.13 (0.80 to 1.60), P=0.49 Cox Univariate Analysis (Different parameters for IOP level) Cox Univariate Analyses (Different parameters for IOP variability) |
IOP measured during office hours.
No published studies establish the optimum number of IOP measurements during office hours. |
Bergea et al. 1999 (23) | Prospective? Secondary objective of a RCT. N=76 eyes 55 Exfoliative 21 Simple |
Newly detected high pressure OAG.
Participated in RCT comparing argon laser trabeculoplasty compared with pilocarpine. |
To investigate the correlation of different parameters of IOP visual field decay in open angle glaucoma. | Mean Range Peak | Hierarchical linear regression analysis and principal component analysis | Daytime diurnal curve (8am, 12pm and 3pm) obtained every second month | Followup period=24 months.
2 models were used. Hierarchical Linear Regression Model (VF progression linear over time) Hierarchical Regression with Partition into Quintiles (nonlinear VF progressions over time) |
55% of patients had exfoliative glaucoma.
Prior to risk analysis, the authors carried out principal-component analysis to avoid multicollinearity (avoid highly intercorrelated explanatory variables in the same model). This produced a number of multivariate regression models including different IOP parameters. Two of them included IOP range similar to the Malmo OHTS study. In 1 of the 2 regression models IOP range was combined with untreated baseline IOP and in the other with IOP % change (i.e., treatment effect calculated as the difference between untreated baseline IOP and mean of treated followup IOP divided by IOP at start). Therefore, the effects of followup IOP level and followup IOP fluctuation were not simultaneously tested in the same model. No published studies establish the optimum number of IOP measurements |
Table 12:
Study, Year | Design | Population | Objective | IOP Parameters | Statistical Method | Timing of IOP Measurement | Results | Comment |
Jonas et al. 2007 (25) | Unclear if retrospective or prospective observational analysis.
855 eyes |
Chronic OAG
NTG=174 eyes High pressure OAG=681 eyes |
To evaluate whether the amplitude of day and night IOP profiles influence the rate of progression of chronic OAG. | Mean Fluctuation Peak | Multiple Cox proportional hazard regression | At least 2 IOP curves with measurements 5pm, 9pm, midnight, 7am and noon. | Median followup=51.5 months; range 5.4 to 124.9 months
163/855 eyes showed progression. High Pressure OAG NTG |
All patients were on routine ophthalmic care including topical application of antiglaucoma drugs. |
Choi et al. 2007 (24) | Retrospective chart review
113 eyes |
NTG
No previous or current use of antiglaucoma drugs |
To investigate systemic and ocular hemodynamic risk factors for glaucomatous damage in eyes with NTG. | Mean Fluctuation Peak | Multivariate regression | Every 2 hours between 12pm and 10am, except for the period between 12am and 6am when measurements were every 3 hours. | Mean IOP, peak IOP and fluctuation were not significantly associated with VF or optic disc worsening (p<0.05). | Patients on hypertension or other hemodynamically active drugs not excluded. |
Table 13:
Study, Year | Design | Population | Objective | IOP Parameters | Statistical Method | Timing of IOP Measurement | Results | Comment |
AGIS, 2008 (15) | Retrospective subset analysis N=301 eyes (only eyes that underwent 1 surgical intervention included in analysis) |
Advanced glaucoma
Uncontrolled IOP at maximum therapy Participated in RCT and underwent argon laser trabeculoplasty or trabeculectomy. |
Clarify relationship between IOP parameters and VF progression. | Fluctuation(SD) Mean | Multivariate logistic regression | 3 months after intervention and every 6 months thereafter | Mean(SD) followup 7.2(2.2) years
IOP fluctuation OR (95%CI) 1.39 (1.09-1.79); P=0.009 Because of a weak correlation between mean IOP and SD, (0.03, p=0.006), mean IOP divided into terciles to evaluate presence of interaction between mean and SD Fluctuation significantly associated with VF progression in the low mean IOP group (P=0.002) but not the high mean IOP group (P=0.2) |
SD used as surrogate for fluctuation since no diurnal tension curves were obtained.
Only IOPs after surgery and up to time of first evidence of VF worsening (if any) used in calculation of mean/SDof IOP. |
DIGS, 2008 (16) | Retrospective subset analysis N=252 eyes
(selected cohort from DIGS) |
Untreated ocular hypertension
Untreated patients who participated in a longitudinal study designed to evaluate optic nerve structure and visual function in early or suspected glaucoma. |
Investigate whether long term IOP fluctuation is a risk factor for conversion from ocular hypertension to glaucoma. | Fluctuation(SD) Mean | Multivariable Cox proportional hazards model | Annual followup visit. | Mean followup until conversion to glaucoma 82.8 months (nonconverters 86.3 months).
Mean IOP predictive of conversion (adjusted HR 1.20 per 1 mmHg higher; 95%CI 1.06-1.36; P=0.005). IOP fluctuation not significantly associated with conversion |
None of the patients received ocular hypotensive drugs at baseline and were left untreated during followup. |
EMGT, 2007 (26) | Retrospective analysis N=255 eyes
(all patients in trial whether treated or not) |
Untreated newly detected glaucoma
Participated in RCT comparing trabeculoplasty compared to no treatment. |
Examine role of IOP fluctuation as an independent risk factor for glaucoma progression. | Fluctuation (SD) Mean | Cox regression with time dependent variables | 3 months after assignment to treatment to time of progression or last followup visit. | Median followup 8 years (range 0.1-11.1 years)
Treatment and Control Groups Combined (mmHg) Hazard ratio (95%CI) |
– |
Notes
Suggested Citation
Permission Requests
How to Obtain Issues in the Ontario Health Technology Assessment Series
Conflict of Interest Statement
About the Medical Advisory Secretariat
About the Ontario Health Technology Assessment Series
Disclaimer
List of Abbreviations
- CI
- Confidence interval(s)
- GAT
- Goldmann applanation tonometer
- IOP
- Intraocular pressure
- MAS
- Medical Advisory Secretariat
- NTG
- Normal tension glaucoma
- OAG
- Open angle glaucoma
- OHT
- Ocular hypertension
- OR
- Odds ratio
- OHTAC
- Ontario Health Technology Advisory Committee
- POAG
- Primary open angle glaucoma
- RCT
- Randomized controlled trial
- RR
- Relative risk
- SD
- Standard deviation
- VF
- Visual field
References
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