Risk stratification and calculators Dr Parul Ichhpujani MS, MBA(HA) Associate Professor Glaucoma and Neuroophthalmology Service Government Medical College and Hospital Chandigarh, India Predicting the development of glaucoma from ocular hypertension is a cornerstone to deciding on whether or not to treat. Risk calculators may be an innovative approach to simplify the management of ocular hypertension and glaucoma patients and provide evidence-based treatment. No Financial Disclosures

Glaucoma Continuum

Risk factors: Strength of evidence Risk stratification: Roots in Cardiovascular medicine; Framingham Study Similarities between CHD and Glaucoma: Chronic disease; modifiable risk factors Globally, the prevalence is thought to be higher in African and Japanese populations (Kyari et al ., 2013), in males and in those living in urban areas. Worley A. Australian Journal of Primary Health, 2011; 17: 233–9

Risk Factors: Major RCTs

Ocular risk factors: Consensus Guidelines Parameter Independent Predictive factor Independent Risk Factor IOP + CCT Insufficient evidence IOP Fluctuation + Provocative tests Low OPP Low CH Myopia Disc hemorrhage

To treat or not to treat? Ocular hypertension and Suspects What to do with these patients? How often should they be examined? Is preventative treatment effective? Who should be treated? Large range of predictions, sometimes differing from the actual risk by 40% Ophthalmologists’ estimate of risk (%) and whether or not they would treat. Dashed represents the risk calculator estimate. Mansberger SL.J Glaucoma 15:426--31, 2006

Risk of Progression Unilateral vision loss: Relevant conservative end point. Risk of Progression to functional impairment is linear. 15 yr period is relevant for the disease Olmsted Co. results (treated patients) can conservatively be used to estimate progression in untreated patients. Treatment may reduce the risk of progressing from untreated OHTN to blindness between 1.2% and 8.1% over 15 years.

Basis of Risk calculators: Cut down the math OHTN to POAG in 5years OHTS and EGPS Multivariate Regression Analysis: Increasing age, thin CCT, increase C:D ratio, and higher PSD index in VF. Even if one simplifies the continuous variables of age, CCT, IOP, and PSD into thirds and uses 9 different combinations for C/D (0.0--0.8), 729(3X 3x 3X 3 X9)different results exist for OHTN patients; creating large number of different combinations. Provided the basis for the development and validation of the prediction models available today. Arch Ophthalmol. 2004;122:813–820 Ophthalmology. 2007;114(1):3–9

Educated Guesswork to Risk calculators Variables Risk Score STAR (2002) Age, IOP, CCT, VCDR, VF PSD, DM 5yr risk of glaucoma, if left treated STAR II (2005) Age, IOP, CCT, VCDR, VF PSD Dever’s (2002) 5yr risk of glaucoma; with Rx Vs. No Rx Glaucoma 5 year (2006) Age, Mean IOP, CCT, VCDR, VF PSD Estimated 5yr risk of developing POAG Medisoft IOP, HRT, VF PSD Factors Overlooked: Family history, race, myopia, PEX, pigment dispersion, DM and cardiovascular disease.

STAR: Scoring Tool for Assessing Risk STAR II Based on OHTS 6 variables Kass, 2002 126 patients with OHT were followed as part of DIGS; to calculate the c-index. c-index: 0.7 5 variables: DM excluded Mederios, 2005 Risk stratification: Low: <5% Moderate: 5-15% High: > 15% Arch Ophthalmol. 2005;123:1351–60.

Devers Eye Institute Risk calculator Data only from OHTS https://www.deverseye.org/grc/index.cfm

Glaucoma 5 yr risk estimator http://ohts.wustl.edu/risk/formula.html. Calculator truncates predictor values at the bounds of the values recorded for each predictor in the OHTS-EGPS cohort Medisoft Pointwise linear regression available in the Progressor (Medisoft Ltd, Leeds, UK) Arch Opthalmol. 2002;12(6):701–830.

Two Methods for Glaucoma 5 yr risk estimator Continuous method: Actual Values Point method: Range of age and average value of measurements

Calculators on Smartphones/Tablets Glaucoma Calc S.T.A.R II

Impact of Risk Calculation Using simulated case scenarios consistent with the population of the OHTS, average treatment threshold for 56 glaucoma specialists was seen: 23% chance of developing glaucoma over a 5-year period when they did not have the results of a risk calculator 17% when they were provided with the risk calculator J Glaucoma. 2008;17:631-8.

Threshold to treat Calculator http://oil.wilmer.jhu.edu/threshold At what IOP should the Rx be started? Caveat: Static measurements of IOP, even if repeated, do not capture short- term fluctuation or peak IOP J Glaucoma. 2014;23(8):485-6.

Which Calculator is better? C-index: Measure of the discriminating ability of a model. Closer the c-index gets to 1, better the discriminating ability of model. STAR II: 0.7 Glaucoma 5 year Risk Estimator: 0.74 No head to head study to compare the different risk calculators available. STAR II : Most widely used, available on smart phone

Caveats in OHTS based calculators Can only be used for patients with similar demographics to the participants of OHTS and EGPS Cannot predict rate of progression of glaucoma. Not useful for patients with established disease.

Risk calculator for patients with treated glaucoma?? Prediction model Moderate accuracy in estimating future VF outcomes in an independent glaucoma population Generated Two equations : Provides the risk of glaucoma progression (%) based on pre-defined PLR criteria in a given number of years, Estimates future rates of VF change based on clinical characteristics. C-Index: 0.78 Good agreement; Invest Ophthalmol Vis Sci. 2012 ; 53(6): 2702-7.

So, All We Need Is a Good Risk Calculator, Right? Wrong!

Benefit to patients Treatment patient-centered rather than population- based. Patients are more likely to adhere to therapy if they have a more definitive expectation of risk

Future… Intelligent programming; Cloud based EMR An EMR system programmed to consider all of the factors that are known to be associated with a higher risk of glaucoma? What if your EMR system had instant access to all of the data from millions of patient encounters over many years? “Our imagination is the only limit to what we can hope to have in the future.” ….Charles Kettering

Take Home Message Just as cholesterol levels are changing in regards to the CHD risk model, so is IOP and other factors in regard to the OHTN risk calculator. One size doesn’t fit all Don’t use as a cookbook but as adjunct information.

Thank You!! itsdrparul@gmail.com