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Important trials in Glaucoma

Important trials in Glaucoma

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Important trials in Glaucoma

  1. 1. IMPORTANT TRIALS IN GLAUCOMA Presenter-Dr Ravneet Moderator- Dr Hetal Shah Dr Rita Dhamankar Dr Vijay Shetty
  2. 2. Landmark studies in glaucoma  Ocular Hypertension Treatment study (OHTS)  Collaborative Initial Glaucoma treatment Study (CIGTS)  Advanced Glaucoma Intervention Study (AGIS)  Early Manifest Glaucoma trial (EMGT)  Collaborative Normal Tension Glaucoma (CNTGS)  Tube versus Trabeculectomy study (TVT)  European Glaucoma prevention study(EGPS)  Low Tension Glaucoma prevention Study(LoGTS)
  3. 3. Ocular Hypertension Treatment study (OHTS) 3 Arch Ophthalmol 120: 701-713, 2002.
  4. 4. Ocular Hypertension Treatment study (OHTS) Objective:  To evaluate the safety and efficacy of topical ocular hypotensive medications in preventing or delaying onset of visual field loss and or optic nerve damage in subjects with ocular hypertension.  Identify baseline demographic and clinical factors that predict which participants will develop POAG 4
  5. 5. Ocular Hypertension Treatment study (OHTS) Participants:  1637 patients with ocular hypertension recruited between 1994 and 1996 Study design:  Multicentre randomized controlled clinical trial comparing observation with medical therapy for ocular hypertension. 5
  6. 6. Methods:  1637 participants  no evidence of glaucomatous damage,  40 to 80 years  IOP 24 mmHg - 32 mmHg in one eye 21mmHg and 32 mmHg in other eye  The goal in the medication group was to reduce the IOP by 20% or more and to reach an IOP of 24 mmHg or less. Ocular Hypertension Treatment study (OHTS)
  7. 7. OHTS Phase 1 Begins February 28, 1994 Eligibility Criteria Medication Topical treatment to lower IOP 20% and IOP < 24 mm Hg Observation No topical treatment to lower IOP Randomization Reproducible Abnormality 3 consecutive visual fields and/or 2 consecutive sets of optic disc photographs Monitoring Humphrey 30-2 q6 months Stereoscopic disc photos annually POAG Visual field and/or optic disc changes attributed to POAG Adjust therapy if target not met
  8. 8. Ocular Hypertension Treatment study (OHTS) Results : At 5 years followup  Incidence of POAG 9.5% in controls 4.4% in treatment group  22.5% decrease in IOP in the treatment group 8
  9. 9. OHTS Summary of results CCT < 555 & IOP > 25 CCT < 555 & CD > 0.5 Risk 36% Risk 22% CCT > 588 &IOP > 25 CCT > 588 & CD >0.5 Risk 6% Risk 8%
  10. 10. Ocular Hypertension Treatment study (OHTS) Increased risk of the onset of POAG was associated with:  Increased age  Vertical and horizontal cup disc ratio  Pattern standard deviation  IOP at baseline  Central corneal thickness (CCT) was found to be a powerful predictor for the development of POAG.
  11. 11. Ocular Hypertension Treatment study (OHTS)  The corneas in OHTS subjects were thicker  lower corneal thickness in black subjects than whites.  The effect of CCT may influence the accuracy of applanation tonometry in the diagnosis, screening and management of patients with glaucoma and ocular hypertension. 1 2
  12. 12. Clinical useful points from OHTS  OHT – What to do * Treat all * Treat no one * Treat some -- Is treatment effective DOES OHTS HAVE ANSWERS FOR THIS
  13. 13. Clinical useful points from OHTS  Treat only patients at high risk.  Risk factors – risk calculator  Importance of CCT  ONH & VF monitoring at every FU  Study – Rx effective , of the 9.6% that converted half could be prevented by Rx  OHTS - ? Conversion after longer FU Age Vertical C/D IOP DM+ CCT PSD If not high risk waiting to treat OHT till conversion- better strategy ( vision related QOL)
  14. 14. OHTS PHASE2 March OHTS Phase 2 Medication Group N = 694 Medication is continued in the Medication group OHTS Phase 2 N = 672 Medication is Initiated in the Observation group
  15. 15. OHTS Phase 2: Rationale  OHTS Phase 1 provides proof of concept: medication reduces the incidence of POAG.  OHTS Phase 1 does not indicate when medication should begin.  OHTS Phase 1 does not indicate if all OHT patients should receive early medication.
  16. 16. OHTS Phase 2: Methods After 7.5 years of observation, participants originally randomized to observation group start medication. This creates: Delayed treatment group Observation group followed for 7.5 years then treated for 5.5 years Early treatment group Medication group treated for median of 13 years from the beginning Compare incidence of POAG at 13.0 years
  17. 17. OHTS PHASE 2 RESULTS  Median Time to develop POAG: Observation group-6 yrs Medication group-8.7 yrs  Increased cumulative incidence of POAG at 13 yrs (22% vs 16%)  More eyes with structural and functional damage(8% vs 5%)  More participants with bilateral disease (6% vs 4%)
  18. 18. Ocular Hypertension Treatment study (OHTS)  The primary purpose of the follow up study was to determine whether delaying treatment resulted in persistently increased risk of conversion to glaucoma, even after the initiation of therapy. 2 0
  19. 19. Ocular Hypertension Treatment study (OHTS) Implications:  Ocular hypertensives can be seperated into categories of high,medium & low risk.  People with high risk factors may benefit from close followup and early treatment  Low risk patients can have less frequent followup and may not need early treatment. 2 1
  20. 20. Ocular Hypertension Treatment study (OHTS  Subjects with corneal thickness of 555μm or less had three times the risk of developing primary open-angle glaucoma compared with those who had corneal thickness of 588μm or more.  Therefore, measure central corneal thickness of all new glaucoma suspects.
  21. 21. Early Manifest Glaucoma trial (EMGT) 2 4
  22. 22. Early Manifest Glaucoma trial (EMGT) Purpose:  To compare the effect of immediate therapy to lower the intraocular pressure versus late or no treatment on the progression of newly detected open-angle glaucoma,as measured by increasing visual field loss and or optic disc changes 2 5
  23. 23. Early Manifest Glaucoma trial (EMGT) Participants:  Newly diagnosed POAG patients (255)  50 to 80 years of age  255 patients were randomized between 1993 and 1997. 2 6
  24. 24. Early Manifest Glaucoma trial (EMGT) Study design:  Multicenter randomized controlled clinical trial comparing observation with betaxolol and argon laser trabeculoplasty for OAG. 2 7
  25. 25. EMGT • Randomised to -ALT and betaxolol -No treatment • If IOP >25mmHg in treated (>35 untreated) → Latanoprost added • If remains high → individualised treatment
  26. 26. Early Manifest Glaucoma trial (EMGT) Results:  At 6 years, 62% of untreated patients showed progression, whereas 45% of treated patients progressed. Treatment reduced IOP by 25%.  Median time to progression 66 months in treated versus 48 months in untreated . 2 9
  27. 27. EMGTS – results  Progression  62% - control  45% - treated group  25% IOP - risk of progression by 50%  Risk of progression less with larger initial IOP drop  Risk of progression by 10% / mm Hg IOP from baseline
  28. 28. Early Manifest Glaucoma trial (EMGT)  In the control group , the rate of visual field progression was fastest in the subgroup of patients with exfoliation and slowest in those with normal IOPs at baseline. 3 1
  29. 29. Early Manifest Glaucoma trial (EMGT) Baseline risk factors:  Higher IOP  Exfoliation  Older age  Lower systolic perfusion pressure  Lower CCT among patients with higher IOPs  follow up higher IOP,  disc hemorrhages. 3 2
  30. 30. Early Manifest Glaucoma trial (EMGT) Implications:  In eyes with glaucoma ,IOP that was lowered by an average of 25%, treatment was of benefit versus no treatment .  There is beneficial effect of immediate therapy to lower the intraocular pressure versus late or no treatment on the progression of newly detected OAG 3 3
  31. 31. Clinical Implications  Even small reductions in IOP can make a difference.  Every 1mm of IOP reduction was associated with a risk reduction of 10% to 13%, depending on the analysis,  But that doesn't necessarily mean all patients must be treated, because we can't know which patients will progress, in some cases, we can observe closely and tailor management to the individual patient  It's beneficial to lower pressure in patients progressing quickly, even if IOP levels have been in the range of 15 to 18mm Hg,
  32. 32. Clinical useful points from EMGTS  25% IOP - progression from 62 – 45%  Regular FU every 3 – 6 months with ONH & VF must – not commonly practiced.  Pts with low risk of progression left untreated – no effect on QOL till lifetime  Drawbacks – Rx options limited – better drugs now
  33. 33. Collaborative Initial Glaucoma treatment Study (CIGTS) Am J Ophthalmol 1998;126:498-505
  34. 34. Collaborative Initial Glaucoma treatment Study (CIGTS) Purpose:  To determine whether patients with newly diagnosed open angle glaucoma (OAG) are better treated by initial treatment with medications or by immediate filtering surgery.  In addition, a secondary measure—a health- related quality of life questionnaire—looked at how the treatment affected the patient's lifestyle.3 9
  35. 35. Collaborative Initial Glaucoma treatment Study (CIGTS) Participants:  607 patients with OAG ( primary, pigmentary, or pseudoexfoliative) recruited between 1993 and 1997. Study design:  Multicenter randomized controlled clinical trial comparing initial medical with initial surgical therapy for OAG. 4 0
  36. 36.  First time the concept of Target IOP was used. March CIGTS MEDICATION GROUP N = 307 SURGICAL GROUP N = 300
  37. 37. CIGTS  RESULTS  At 5 yrs both effective  Control of IOP lower by surgery (48%), medical (35%)  VF loss greater in surgery (cataract)  QOL initially better with medical group
  38. 38. CIGTS – Results at 5yrs Medical Treatment Surgical Treatment IOP reduction 28mmHg→17-18mmHg (38%) 27mmHg→14-15mmHg (46%) Progression at 5 years No progression No progression • Surgical group is at increased risk of visual loss initially but by 4yrs both groups are comparable •The rate of cataract removal was greater in the surgically treated group.
  39. 39. Collaborative Initial Glaucoma treatment Study (CIGTS) Results  Patients with diabetes were more likely to progress if treated with surgery first.  The quality of life (QOL) impact reported by the 2 treatment groups was very similar.  Increased impact of local eye symptoms reported by the surgery group 4 5
  40. 40. Collaborative Initial Glaucoma treatment Study (CIGTS) Results  The overall rate of progression of OAG in CIGTS was lower than in many clinical trials, potentially the result of more aggressive IOP goals and the stage of the disease.
  41. 41. CIGTS summary  Surgery resulted in  Lower IOP  More cataract  More ocular side effects  Initial ↓ vision  Initial ↓ visual field
  42. 42. Collaborative Initial Glaucoma treatment Study (CIGTS) Implications  In moderate to advanced disease initial surgical therapy may be preferred.  The results also revealed that either treatment had a remarkably similar effect on patients' quality of life.  Though not associated with a particular treatment group, the fear of blindness was common, affecting 34% at diagnosis.  Patients who reported a decrease in visual functioning were more likely to experience depression and mood changes 4 8
  43. 43. Clinical useful points from CIGTS  Early POAG – medical Rx effective  Our scenario – compliance/cost – deciding factor for either modality  Concept of target IOP – must in our management.  Drawback – study duration too short for Rx recommendation.
  44. 44. Advanced Glaucoma Intervention Study (AGIS) 5 1
  45. 45. Advanced Glaucoma Intervention Study (AGIS) Purpose: To compare the clinical outcomes of 2 treatment sequences in cases of advanced glaucoma 5 2
  46. 46. Advanced glaucoma intervention study (AGIS)  Objective – to determine if ALT or surgery is preferred Rx for advanced glaucoma on max tolerated medical Rx. 789 eyes ALT TRAB TRAB (ATT) TRAB ALT TRAB (TAT)
  47. 47. Advanced Glaucoma Intervention Study (AGIS) Participants:  789 eyes of 591 patients with medically uncontrolled OAG recruited from 1988 to 1992.  POAG uncontrolled on maximum accepted and tolerated medical therapy(IOP ≥ 18 mm Hg)  35 to 80 yr 5 4
  48. 48. Advanced Glaucoma Intervention Study (AGIS) Study design:  Multicenter randomized controlled clinical trial comparing 2 treatment sequences (TAT and ATT ) for patients with OAG uncontrolled by medical therapy.
  49. 49. Advanced Glaucoma Intervention Study (AGIS) Results:  Black patients had less combined visual acuity and visual field loss if treated with the ATT sequence.  White patients had less combined visual acuity and visual field loss at 7 years if treated with the TAT sequence.  Visual function scores improved after cataract surgery. 5 6
  50. 50. AGIS - Results  Relationship of IOP & VF progression.  Predictive analysis – IOP < 14 mm Hg did better  Associative analysis – low IOP & low IOP fluctuation - Decreased progression
  51. 51. Advanced Glaucoma Intervention Study (AGIS Results:  Lower IOP was associated with less visual field loss.  First 18 months after the first surgical intervention, or eyes with IOP of 18mmHg or less at all visits throughout the study had significantly less visual field loss  Approximately half of the study patients developed cataract in the first 5 years of follow up.  Trabeculectomy increases the relative risk of cataract formation by 78%. 5 8
  52. 52. Advanced Glaucoma Intervention Study (AGIS) Results  ALT failure is associated with -younger age -higher IOP.  Trabeculectomy failure associated with -younger age, -higher IOP, -diabetes, and postoperative complications such as particularly elevated IOP and marked inflammation. -IOP fluctuation was an independent predictor of progression of OAG in eye with lower baseline IOPs.
  53. 53. Results - AGIS  TAT  IOP  Better for whites  ATT  Failure  Better for blacks Risk of cataract after TRAB after 5 years – 78 %
  54. 54. AGIS  Effects of IOP on visual field progression were also specifically evaluated from AGIS data, and it was found that patients with an average IOP of greater than 17.5mm Hg had greater worsening of their visual fields than those with an average IOP of less than 14mm Hg.  AGIS was one of the first studies to show that lower mean IOP results in a decreased risk of visual field progression.
  55. 55. AGIS  Each patient requires individualized care.  AGIS demonstrated that race is an important consideration for surgical intervention in advanced glaucoma.  This is not to say, for instance, that a white patient with medically-uncontrolled glaucoma should only be offered the option of trabeculectomy.  Potential operative complications associated with the more invasive surgery may sway the patient toward laser intervention as a first option.
  56. 56. AGIS  Conversely, a black patient presented with the option of laser intervention should be warned of the likely future need for both additional medications and additional glaucoma surgery after the laser procedure is completed.
  57. 57. AGIS  There is no magic number for target IOP.  Patients in the AGIS group who consistently maintained IOP less than 18mm Hg at every visit over six years, with mean IOP of 12.3mm Hg as a group, had good preservation of visual field—yet a number of patients in this group still showed progressive visual field loss.
  58. 58. Advanced Glaucoma Intervention Study (AGIS) Implications:  Keep race in mind when choosing therapy.  Lower IOP was associated with less visual field loss  IOP fluctuation was an independent predictor of progression of OAG in eye with lower baseline IOPs. 6 5
  59. 59. Collaborative Normal Tension Glaucoma (CNTGS) 6 6
  60. 60.  Lowering IOP in patients with normal-tension glaucoma (NTG) can be challenging.  Is it even worth trying to lower an already-low IOP?
  61. 61. Collaborative Normal Tension Glaucoma (CNTGS) Purpose:  To determine if IOP plays a part in the pathogenic process of NTG by comparing a treatment group (with a 30% reduction in IOP) to a no treatment group. . 6 8
  62. 62. Collaborative Normal Tension Glaucoma (CNTGS) Participants :  230 patients  20-90 yrs  Patients had unilateral or bilateral NTG  Three reliable visual fields within 1 month  Average IOP ≤20 mmHg,no reading above 24 mmHg 6 9
  63. 63. NTGS - methods  Randomised immediately if  VF defect threatening fixation  Previously documented disease progression  Others randomised when evidence of progression
  64. 64. NTGS  145 (of 239) patients randomised  One eye randomised to  Treatment  Drops, ALT or surgery to achieve 30% reduction in IOP  No treatment until evidence of progression  Other eye could be treated in this group
  65. 65. Collaborative Normal Tension Glaucoma (CNTGS) Study design:  In both arms, neither eye could receive beta- adrenergic blockers or adrenergic agonists, because they might have systemic cardiovascular effects that could conceivably alter the course of the treated or untreated disease, confounding the analysis of data. 7 2
  66. 66. CNTGS RESULTS  30% drop achieved in half without surgery  Once 30% drop achieved rate of progressive field loss was lower than group that did not receive treatment (after allowing for cataract effect which was higher in treated group)
  67. 67. CNTGS RESULTS:  Rate of progression in untreated NTG highly variable  Half did not progress on VF in 5 years  Factors associated with progression  Female  Migraine  Disc haemorrhages on presentation
  68. 68. CNTG – results  Prog in 12% of Rxed eyes & 35% in untreated group.  30% reduction possible even by medicines.  Treated pts that progressed  Non IOP related  target IOP wrong
  69. 69. CNGTS  Overall, lowering IOP in NTG slows progression.  However, over half of patients did not progress without treatment at 5 years.
  70. 70. Collaborative Normal Tension Glaucoma (CNTGS) IMPLICATIONS:  The natural course of NTG is quite variable, some cases slow enough that they may never need treatment, but others progressing rapidly to potential blindness. 7 7
  71. 71.  Because of the variable natural course of NTG, it is important to distinguish between patients who have progressive vs. non-progressive disease.  In cases of mild NTG, consider monitoring until progression is confirmed.  However, factors that weigh more heavily for treatment are female gender, history of migraine and disc hemorrhage at diagnosis.
  72. 72.  When you suspect progression, be sure to confirm that it is actual progression and not testing variability.  This may require multiple visual fields to prevent over-diagnosing progression.  Once the decision is made to begin treatment, set a goal (at least 30% IOP reduction) and be diligent in attaining it.  The large arsenal of IOP-lowering medications available today makes this goal much more achievable without surgery
  74. 74. TVT  PURPOSE: To report 5 year treatment outcomes in the tube versus trabeculectomy study.  DESIGN: Multicenter randomized clinical trial
  75. 75. TVT  STUDY POPULATION: -Patients 18 to 85 years -Prior cataract or glaucoma filtering surgery - Uncontrolled glaucoma with IOP of 18mmHg to 40 mmHg on maximum tolerated medical therapy  OUTCOME MEASURES -IOP, Visual acuity, visual fields, surgical complications, glaucoma medications and treatment failure
  76. 76. TVT  RESULTS: -Trabeculectomy with MMC and tube-shunt surgery both produced sustained IOP reduction to the low teens during 5 years of followup -Tube-shunt surgery was associated with use of more glaucoma medications than trabeculectomy with MMC during the first 2 yrs of study,but medical therapy equalized with longer followup
  77. 77. TVT  RESULTS -Trabeculectomy with MMC had a higher failure rate (46.9%)compared with tube shunt surgery(29.8%) -Higher rate of reoperation for glaucoma(29%) compared to tube group(9%0 -vision loss occurred at similar rate in both groups -Early postoperative complications occurred more frequently after trabeculectomy with MMC relative to tube shunt surgery.similar rate for late complications
  78. 78. TVT  Implications -No procedure superior for treating glaucoma -Factors for selecting surgical procedure o Surgeons skill and experience o Patients willingness to undergo repeat glaucoma surgery o Surgeons planned surgical approach should failure occur
  79. 79.  The researchers maintain that the TVT study does not demonstrate clear superiority of one glaucoma operation over the other, but that both surgeries are viable options.  Potential pitfalls exist with the use of tube shunts. Subsequent surgical options after failure of tube- shunt devices become limited—surgeons are left with the choice of a second, inferiorly placed tube or cyclophotocoagulation.
  80. 80.  The TVT Study supports the expanding use of tube shunts beyond the surgical management of refractory glaucoma.  Tube shunt surgery was shown to be effective in a patient population at lower risk of surgical failure than has traditionally been designated for this procedure.
  81. 81.  Trabeculectomy is not without its travails. It requires the surgeon to tailor the procedure to each patient (i.e., number of scleral flap sutures and dosage of an antifibrotic agent) whereas tube-shunt surgery is a more standardized procedure  Also, trabeculectomies require more frequent and more vigilant postoperative care than tube shunts.
  83. 83. EUROPEAN GLAUCOMA PREVENTION STUDY  OBJECTIVE Efficacy of reduction of IOP by dorzolamide versus placebo in preventing or delaying POAG in patients affected by Ocular hypertension
  84. 84. EGPS  PARTICIPANTS: -1081 patients -Age ≥30 yrs -IOP 22 to 29 mmHg -2 normal and reliable visual fields -Normal optic discs  Outcome measures: Safety end point was IOP >35 mmHg on 2 consecutive examinations
  85. 85. EGPS  RESULTS -Dorzolamide reduced IOP by 15-22% in 5 yrs period -At 60 months ,cumulative probability of converting to an efficacy end point was 13.4%(dorzolamide group) 14.1%(placebo group) -No statistically significant difference between medical therapy and placebo group in reducing incidence of POAG
  86. 86. EGPS  Risk factors for progression 1.Older age 2.Thinner CCT 3.Higher vertical cup disc ratio 4.Higher Pattern standard deviation
  87. 87. EGPS  The role of systemic blood pressure appears important  Regression to the Mean  Minimised by multiple IOP measurements at different times of the day (diurnal variation) or on a different day.  For each mm Hg higher IOP per 12 months, the risk of converting to POAG in increased by 9% in the next 5 years.
  88. 88. LOW TENSION GLAUCOMA PREVENTION STUDY  OBJECTIVE To evaluate visual field stability in low-pressure glaucoma patients randomized to intraocular pressure reduction in both eyes with topical twice daily brimonidine tartrate 0.2% versus twice daily timolol maleate 0.5%
  89. 89. LOGTS  PARTICIPANTS -Low-pressure glaucoma patients - 30 years of age or older -untreated pressure of more than 21 mmHg and advanced visual field loss were excluded  Randomization of both eyes to double-masked monotherapy with brimonidine or timolol.
  90. 90. LOGTS  Follow-up visits included Humphrey 24-2 full- threshold perimetry, tonometry every 4 months, and annual optic disc photography.  MAIN OUTCOME MEASURE: - Progression of visual field loss.
  91. 91. LOGTS RESULTS  showed similar IOP reduction for each medication.  patients on brimonidine had less visual field loss (9.1%) compared with patients on timolol (39.2%) during an average of 30 months  28 of the 99 patients in the brimonidine arm of the study dropped out due to drug-related adverse events, compared with only 9 of the 79 timolol patients
  92. 92. LOGTS RESULTS  low-pressure glaucoma patients treated with brimonidine are less likely to have field progression than patients treated with timolol  Conclusion: Brimonidine better than Timolol??
  93. 93.  The study attempted to find correlations between many other baseline factors of the 2 study groups and the slower progression of glaucoma in the group that received brimonidine.  Age, sex, family history, diabetes mellitus, risk factors for low-tension glaucoma (such as migraine and the Raynaud phenomenon), and ocular perfusion pressure were investigated..
  94. 94. LOGTS  Drawbacks -Data may have been skewed due to the high number of patients dropping out of the brimonidine group. -No therapeutic goal for either medication -Baseline untreated IOP was just over 15mm Hg and the mean treated IOP was around 14mm Hg
  95. 95. LOGTS  For now,we should use the therapy that reduces IOP in normal-tension patients to significant levels (minimum 30%), and modify treatment if the optic nerve, retinal nerve fiber layer or visual field changes.  Prostaglandins have superb efficacy and less effect than other agents in lowering heart rate. These should be used as a first-line treatment whenever possible.
  96. 96.  Remember to check blood pressure and heart rate before initiating treatment with a beta-blocker such as timolol.  Also, check if the patient is already taking a systemic beta- blocker.  Be sure that patients use timolol earlier in the evening rather than before bedtime to avoid the hypotensive effect that might compromise ocular blood flow and induce systemic hypotension.
  97. 97. TAKE HOME MESSAGE In OHT cases:  Not all OHT need treatment – assess risk on individual basis and then decide  People with high risk factors may benefit from close followup and early treatment  Low risk patients can have less frequent followup and may not need early treatment.
  98. 98. TAKE HOME MESSAGE In NTG cases:  Rate of progression in NTG highly variable  Only proven treatment is reducing IOP  Treat if risk factors present
  99. 99. TAKE HOME MESSAGE POAG cases  Start early treatment in diagnosed cases of POAG  Choice of medical therapy first – change only if target IOP not achieved.  Surgical therapy safe  In moderate to advanced disease initial surgical therapy may be preferred
  100. 100. TAKE HOME MESSAGE  Efficient patient care – practice of evidence based Rx  IOP is the main risk factor for all glaucomas  Recognize threat – lower IOP – lower risk of progression  Set a target IOP after assessing risk factors for progression

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Important trials in Glaucoma


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