Landmark Glaucoma Studies

Transcription

1 Landmark Glaucoma Studies: How They Affect Our Management Strategies Today Disclosures None By: Alex Kabiri, O.D. & Devin Singh, O.D. Course Goals 1. Review series of glaucoma studies that: Evaluate when to treat OHTN. Determine efficacy of IOP lowering in glaucoma. Compare topical therapy vs surgery. 2. Understand risk factors in glaucoma/ohtn. 3. Discuss shortcomings or limitations of the studies. 4. Review series of glaucoma cases to apply these study lessons. Prevalence of Glaucoma 3 million Americans have glaucoma; half are diagnosed 1 Second leading cause of world blindness In the US, >120,000 are blind from glaucoma, accounting for 9% -12% of all cases of blindness 2 Blindness from glaucoma is 6-8timesmore common in African Americans than Caucasians 3 Glaucoma accounts for >10 million office visits per year 4 According to NEI, 1.5 million Americans with OHTN and no GLC damage are treated with topical hypotensives 5 (1)The Eye Diseases Prevalence Research Group, Arch Ophthalmol. 2004; Prevent Blindness America; (2) National Institutes of Health; Quigley and Vitale, Invest Ophthalmol Vis Sci. 1997; (3) Javitt et al, Undertreatment of Glaucoma Among Black Americans. N Eng J Med 1991; (4)Center for Disease Control and Prevention/National Center for Health Statistics, 2010&1995;(8)NEI,Report of the Glaucoma Panel, Fall 1998 (5)NEI NIH GOV/glaucomaeyedrops/OHTS backg Landmark Glaucoma Studies STUDY STUDY EARLY MANIFEST TRIAL RELATIONSHIP OF IOP AND ONSET OF NORMAL TENSION STUDY ADVANCE D GLAUCOM A STUDY TUBE VS. TRABECULECTOMY STUDY To treat ot not to treat, that is the question... 1

2 To determine the safety and efficacy of topical ocular hypotensive medication in delaying or preventing theonset ofpoag. n =1800 subjects with IOP 24-32mmHg with no glaucoma (enrollment ) RELATIONSHIP OF IOP AND ONSET OF Aimed to address these questions: When does one treat OHTN? RELATIONSHIP OF IOP AND ONSET OF To treat ot not to treat, that is the question... Is delaying treatment harmful? Does lowering IOP decrease risk of glaucoma or control glaucoma? To treat ot not to treat, that is the question... How do we determine level of risk of developing glaucoma? RELATIONSHIP OF IOP AND ONSET OF Determine patients with newly diagnosed POAG (primary, pigmentary, pseudoexfoliative) are better treated with medications or immediate trabeculectomy effects of medical and surgical tx on quality of life n =607 subjects attempted to compare medical vs. filtration surgery When do we suggest surgery in our newly diagnosed GLC patients? Does the study support earlier surgery for certain situations? Pros Surgery group had larger decrease in IOP Cons In general,with moreadvancedvf loss at baseline, lessvfprogression if theyunderwent trabeculectomy vs.on medications Diabetic patients more VF progression if surgery first African Americans also did less well with surgery first aftereither treatment CIGTS appears to support early surgicalintervention for patients whopresent with moreadvanced disease with the possible exception of diabetic and African Americans 2

3 CIGTS short comings... Although the study randomized assignment between treatment groups for most demographic and clinical measures... Moremalesvs.femalesenrolled (55%) Substantial percentage (38.1%) were blacks Majority (90.6%) diagnosed with POAG Smallpercentage had either pseudoexfoliative (4.8%) or pigmentary (4.6%) forms of open angle Certain socioeconomic factors can play a role in IOP control? consistently hadlower IOPs higher baseline IOP,worse baselinevf,and lower level education Smokers Comparing surgery vs. Drug Therapy with your patients In the study, an aggressive target IOP was established. Patients will ask which road is more effective at preventing permanent visionloss (ie.preserving VF & VA)? How does each road impact quality of life? Patient perspective on risk of vision loss? Have advents in surgery or topical treatment today altered the scale? SLT? Tube shunts/valves? Prostaglandins? Mitomycin-C? Discuss study findings with your patients: Aggressive IOP yields results Quality of life matters, when considering surgery, anticipate cataract surgery as well EARLY MANIFEST TRIAL (EMGT) To determine effectiveness of reducing intraocular pressure (IOP) inearly, previously untreated open-angle glaucoma. Study natural history of the disease Explore factors related to glaucoma progression When to initiate treatment: Now vs. Later? Compare treatment vs. observation in early untreated glaucoma Why is understanding natural history of glaucoma important? The natural history of glaucoma was not well defined before the EMGT ( ). We did not know how rapidly early stage glaucoma would progress ifitwere not treated initially. EMGT addressed: Clinical management of glaucoma Understanding the role of IOP and the natural history of glaucoma Evaluating the rationale for glaucoma testing Without this, it is unclear as to how effective treatment was for early stage glaucoma, because they did not know how rapidly the disease would progress without treatment. 3

4 What price, in terms of side effects, inconvenience, and cost, can be considered acceptable when treatment effects are uncertain? The EMGT control group participants were followed without treatmentaslong asprogression didnot occur, thus not exposing study participants to unacceptable risks. After 6 years,it took control group 4yearsto detect advancing glaucoma. In treatment group,it took 5.5 yearsto detect advancing disease, with anaverage IOP 25% less. EMGT short comings... Small study group, 255 people. 129 immediately treated with drops/laser, 126 untreated and followed. Majority (66%) were women Limitedagegroup 50-80y/owith early glaucomatous VF defects Population-based screening in Malmo and Hel-singborg, Sweden Exclusion criteria: advanced VFloss, mean IOP >30mmHg or any IOP >35mmHg; VA <0.5; inability to follow-up Thestudy doesnotindicatewhetherglaucoma naturalhistorychangesasdiseaseadvances. EARLY MANIFEST TRIAL (EMGT) Key Findings: EARLY MANIFEST TRIAL (EMGT) Treatment appears to postpone progression NORMAL TENSION STUDY E ON DY COLLABORATIV NORMAL TENSI STU At the time of the study, the role of IOP in NTG was debatable. Study showed it is worthwhile to lower pressure, but you must be moreaggressive! Slower rate of VF loss in cases with 30% IOPreduction or more. Rate of progression highly variable without treatment. Half of non-treatment group did not progress for 5 years without treatment! Does lowering IOP effectively work in slowing normal tension glaucoma? Does lowering IOP effectively work in slowing normal tension glaucoma? Highest risk factors for NTG progression: disc hemorrhages cardiovascular disease? 4

5 NORMAL TENSIO STUD N Y Inclusion criteria: n =260 subjects with NTG-NTG was either progressive or VF defect affecting central vision Treatment group received topical pilocarpine, systemic CAIs, laser, trabeculectomy or combination to attain 30% IOPreduction Bothgroupsfollowedupto5years N Y NORMAL TENSIO STUD Inclusion criteria: n =260 subjects with NTG-NTG was either progressive or VF defect affecting central vision Treatment group received topical pilocarpine, systemic CAIs, laser, trabeculectomy or combination to attain 30% IOPreduction Bothgroupsfollowedupto5years The Good News ADVANCED STUDY (AGIS) ADVANCED STUDY (AGIS) Does sequence of surgery matter in advanced glaucoma? Study Objective: Determine long-term effectiveness of surgical treatment in medically uncontrolled GLC: based on VF/ VA loss, IOP complications, time to treatment failure, and need to additional medication. Design: ( ) 591 patients onmaximum medicaltherapy years of age phakic eyes Study Groups (1) Initial trabeculectomy then ALT (TAT) vs. (2) Initial ALT then trabeculectomy (ATT) Both groups receivedsecondtrab if needed Advanced Glaucoma: visual field loss at enrollment despite topicaltherapy Why did race matter in study? ADVANCED STUDY (AGIS) Conclusion: Race affected outcomes: Caucasians did better with ALT first African Americans did better with Trab first For both races: IOP was lower in the TAT group IntermsofVF/VA,blacksubjects didbetterintheatt group Although disc hemorrhages were more prevalent in whites, blacks showed more severe glaucoma. Why? Subjects self-reported race. 57% self-reported as black This group overall was younger and more systemic disease (HTN/DM) Black subjects had worse VF VA and IOP were comparable to whites Average age of whites were higher - possible contribution to more disc hemorrhages Does sequence of surgery matter in advanced glaucoma? Consideration: 5-Fluorouracil and mitomycin C were introducedfor trab sx in 1990 (trab patients from did not have this benefit) DM subjects had higher average IOP and greater risk of cataracts, and trab failure (3X) but not with ALT 5

6 Why did black subjects experience higher failure rate with TAT sequence? AGIS short comings... One subsequent study suggests lack of antifibrotic agents in the primary trabeculectomy surgery 1 (1) Broadway et al. Racial differences in glaucoma filtration surgery. Br J Ophthalmol 1994:78 (6) : Antifibrotics (mitomycin-c) not available in first half of study Newer meds may affect surgical success SLT? DM patients need special consideration whendetermining surgical therapy Which glaucoma surgery is better? TUBE VS. TRABECULECTOMY (TVT) STUDY At time of study, tube shunts were reserved for high risk progression of glaucoma This study challenged this idea and questioned whether lower risk patients would benefit TVT supported expanding use of tube shunts Rate of vision loss or post-op complications similar in both group Subtledifference:tubeshuntshadhigher longterm success rate Failure rate trab was 10% per year; tube 5%per year TUBE VS. TRABECULECTOMY (TVT) STUDY Additional short comings from each study? OHTS racial disparity - Recruited 25% African American; rest EMGT: lack of racial disparity were caucasian Participants from only two Swedish Study did not assess other races cities; Participants were only >40YO Betaxolol was only medication used How do we manage younger OHTN patients due to PDS? CIGTS - Initial study went to 5 years What about role of cataract progression s/p trab after5 years? AGIS Cataract surgery was done more often in group after trab first How does this impact interpreting study results? Its effect on establishing VF progression? TVT? How has new therapies and surgeries changed management style? SLT? PGAs? Combo Role in Previous drops? managing CVD/DM? Previous cataract surgery? retinal laser therapy? use of OCT? 6

7 What studies are needed? 1. Large-scale comparative study of modern topical medications Case Study 1 2. Repeat OHTS with hispanic, asian, and indian ethnicities 3. Effect of cardiovascular disease/dm on GLC progression 4. Value of OCT in detecting progression vs. VF alone 5. Studies on pigmentary/pseudoexfoliation glaucoma 6. Studies to examine natural progression of narrow angles, how narrowing angles impact management in the OPEN angle glaucomas? Studies on pigmentary/pseudoexfoliation glaucoma 7. Others? 20 YO African American Male IOP 25/26 mmhg BVA 20/20 OD/OS pachymetry 545 OD/OS Healthy cupping (0.25 OD/OS) (+) Pigment dispersion Father is blind in one eye, sees poorly in other No systemic disease What additional information do you need? How do you manage this patient? Case Study 2 Sources 45 YO White Female Asymmetric IOP 18/26 mmhg BVA 20/20 OD/OS Glaucomatous cupping greater in right eye 0.60 OD vs OS Med Hx: (+)controlled DM (+)Pseudoexfoliation on the lens capsule OU What additional information do you need? Decision in made to treat; How do you treat? on-study what-we-have-learned-so-far/