Is There an Association of Topical Ocular Hypotensive Medication with Lens Opacification and Decreased Visual Function?

Transcription

1 Is There an Association of Topical Ocular Hypotensive Medication with Lens Opacification and Decreased Visual Function? Supported by the National Eye Institute (EY 09307, EY 09341) National Center on Minority Health and Health Disparities Research to Prevent Blindness Merck Research Laboratories

2 Evidence from The Ocular Hypertension Treatment Study (OHTS) David Herman Julia Beiser Anjali Bhorade Leo Chylack Mae O. Gordon Michael A. Kass Kathleen Lamping Oliver Schein Joern Soltau and The Ocular Hypertension Treatment Study Group

3 OHTS History Feb, 1994: Randomization to observation or to medication, n = 1,636 Jun, 2002: Publication of paper on treatment efficacy Jun, 2002: Medication offered to previous observation group

4 Indicators of Decreased Visual Function and Lens Opacification in OHTS Feb, 1994 Jun, 2002: Compare observation and medication groups Foveal Sensitivity Mean Deviation ETDRS Visual Acuity Refraction Cataract Surgery or Combined Procedure Mar, 2003 Oct, 2004: One time masked LOCS III grading, n= 1,017

5 Change Analysis of Visual Function and Refraction Baseline to 6/02, median f/up 84 months Both eyes of 1,620 participants Data censored after these events... Reasons for Censoring n F/up Available (Yr) Mean + S.D. Not Censored Developed POAG Cataract sx or glaucoma sx VF not evaluable Obs pt. starts meds Med pt. stops meds

6 Foveal Sensitivity (db) by Randomization Group (Mean of R & L eyes + S.D.) Baseline Last Visit before 6/02 Change Coefficient db/year Obs n = * Meds n = * *p = 0.53 Change coefficient for each eye adjusting for age, race, topical medication use prior to OHTS, diabetes, corticosteroid use. Models with these covariates and smoking yielded similar results.

7 Mean Deviation (db) by Randomization Group (Mean of R & L eyes + S.D.) Baseline Last Visit before 6/02 Change Coefficient db/year Obs n = * Meds n = * *p = 0.32 Change coefficient for each eye adjusting for race, topical medication use prior to OHTS, diabetes, corticosteroid use. Models with these covariates and smoking yielded similar results.

8 ETDRS Visual Acuity by Randomization Group (Mean letters correct for R & L eyes + S.D.) Baseline Last Visit before 6/02 Change Coefficient Letters/Year Obs n = * Meds n = * *p = 0.89 Change coefficient for each eye adjusting for age, race, topical medication use prior to OHTS, diabetes, corticosteroid use. Models with these covariates and smoking yielded similar results.

9 Spherical Equivalent (Diopters) by Randomization Group (Mean of R & L eyes + S.D.) Baseline Last Visit before 6/02 Change Coefficient Diopters/Year Obs n = * Meds n = * *p = 0.82 Change coefficient for each eye adjusting for age, race, topical medication use prior to OHTS, diabetes, corticosteroid use. Models with these covariates and smoking yielded similar results.

10 Proportion MD abnormal Participants with 1 st Abnormal Humphrey VF Test (Mean Deviation p <0.05) P-value=0.96, Multivariate Hazard Ratio 0.99; 95% CI, Medication Observation Months * through June 2002

11 Proportion ETDRS < 35 Letters Correct Participants with 1 st ETDRS < 39 letters correct (< 20/40 equivalent) P-value=.68, Multivariate Hazard Ratio 0.95; 95% CI, Medication Observation Months * through June 2002

12 Cataract Surgery or Combined Procedures to 6/02 by Randomization Group Cataract n % Combined n % Total n % Obs n = % 2 0.2% 45* 5.6% Meds n = % 5 0.6% 62* 7.6% *Multivariate hazards ratio for medication 1.56; 95% C.I., ; p-value Covariates include age, race, baseline IOP, baseline vision, topical medication use prior to OHTS, diabetes, corticosteroid use, mean deviation, baseline calcium channel blocker use. Models with these covariates and smoking yielded similar results.

13 Proportion cataract surgery or combined procedure Participants having Cataract Surgery or Combined Procedure P-value=0.03, Multivariate Hazard Ratio 1.56; 95% CI, Medication Observation Months * through June 2002

14 During f/up no differences were found between the MED participants who had undergone cataract/combined surgery and OBS participants who had undergone cataract/combined surgery in: ETDRS Visual Acuity, *p = 0.89 Refraction, *p = 0.27 Mean Deviation, *p = 0.56 Foveal Sensitivity, *p = 0.35 *P-value for change coefficient for eye undergoing surgery adjusting for age, race, topical medication use prior to OHTS, diabetes and corticosteroid use.

15 Masked LOCS III Grading Graders trained by Dr. Leo Chylack Masked LOCS III performed 3/03-10/04 Duration of medication at LOCS III grading 1.2 yrs in Observation group 8.5 yrs in Medication group LOCS III Completed in 78% of participants Medication n=511 Observation n=506

16 LOCS III One-Time Grading after 6/02 (Mean + S.D. of R & L Eyes on One Grading) Duration of Medication at LOCS III Grading OBS N=506 Median 1.2 Years MEDS N=511 P* Median 8.5 Years N/A Nuclear Opalescence Scale Nuclear Color Scale Cortical Scale Posterior Subcapsular Scale *Multivariate model utilized data from right and left eyes and adjusted for age, race, topical medication use prior to OHTS, corticosteroid use, diabetes. Models with these covariates and smoking yielded similar results.

17 LOCS III One-Time Grading after 6/02 (Mean + S.D. of Worst Eye on One Grading) OBS N=506 MEDS N=511 P* Duration of Medication at LOCS III Grading Median 1.2 Years Median 8.5 Years N/A Nuclear Opalescence Scale Nuclear Color Scale Cortical Scale Posterior Subcapsular Scale *Multivariate model adjusted for age, race, topical medication use prior to OHTS, corticosteroid use, diabetes. Models with these covariates and smoking yielded similar results.

18 Percent LOCS III Posterior Subcapsular Cataract Grades for Worst Eye of Each Participant 100 Medication Observation

19 Conclusion Increased rate of cataract surgery in medication group Borderline increased risk of LOCS III posterior subcapsular opacity 1 point increase in a 60 point standard scale No evidence of general decrease in visual function or an overall large effect Possible effect of medication in a subset of susceptible patients