Implementing what we have learnt from the Landmark Studies in Glaucoma

Dr Major Avinash Mishra (Military Hospital Jabalpur)

(Cross-references:

1. Introduction and Target Intra-ocular pressure - Dr. Ravin Das
2. The role of intra-ocular pressure in glaucoma (Landmark studies in Glaucoma) - Dr. Shabbir Hussain (Slide 1-28)
3. Implementing what we have learnt - Dr. Major Avinash Mishra (Slide 29-50)
4. Achieving the targets set by the studies & reaching difficult target pressures - Dr. Rahul Shukla (Slide 51-85)
5. Lumigan™ the Indian experience (L.E.E.D) - Dr. Shabbir Hussain. (Slide 86-100)

Choosing Glaucoma Therapy

Efficacy = IOP lowering

• Amount
  
• Consistency
  

Safety

• Systemic side effects
  

Tolerability

• Local ocular effects

In the Real World-

What Therapy Should I Start First?

Choosing Medical Therapy:

Monotherapy (Single Drug) Preferred
If a single medication can get you at or below target without side effects, what is the advantage of getting to the same place with multiple medications?
Are there disadvantages of multiple drug therapy?

Monotherapy (Single Drop) Preferred Patient Considerations

• Convenience
  
• Fewer drops to instill
  
• No need to wait between instillation of multiple drops
  
• Less chance for mistakes
  
• Simple regimen enhances compliance
  
• Possible cost savings

Monotherapy (Single Drug) Preferred

• Physician Considerations
  
• Fixed combinations and 2-drug regimens have combined side effects of 2 medications 1 + 1 may even be > 2
  
• If a problem-which agent responsible?
  
• Fewer drug interactions
  
• Less preservative corneal toxicity
• >30% reductions in IOP are possible
• Fewer medications means fewer potential side effects
• If on multiple agents and efficacy is inadequate, it is much more difficult to determine the contribution of each individual medication to the total.

Considerations in Choosing Monotherapy

• Efficacy
  
  • Mean IOP drop
    
  • Ability to get patient to target pressure
    
  • Responder rate
    
• Safety
  
• Tolerability
  
• Convenience
  
• Compliance
  
• Cost
  

Once-Daily Hypotensive Lipids Lower IOP Most Effectively

Hypotensive Lipids Are Superior to Timolol in Lowering IOP (Bimatoprost, Latanoprost, Travoplast in following diagram)

More Patients Reach Target Pressures With Bimatoprost Monotherapy (Bimatoprost - blue; following graph)

Treatment-Related Adverse Events*

Bimatoprost Monotherapy Is as Effective as Timolol / Latanoprost

• Crossover study design
  
• Patients received each regimen for 60 days
  
• No Change in Mean IOP at 8 AM After
  

Switching to Bimatoprost Monotherapy

Equivalent Clinical Success With Bimatoprost Monotherapy and Timolol / Latanoprost

Summary

• Bimatoprost monotherapy controlled IOP in most patients previously treated with timolol gel / latanoprost
  
• Most patients were clinically successful after switching to bimatoprost monotherapy
  
• Both treatments were well-tolerated
  
• Bimatoprost monotherapy is an effective alternative to dual therapy with timolol gel and latanoprost
  Safety of Hypotensive Lipids
  

Adverse event defined as:

• Any untoward medical occurrence - whether or not related to the use of an investigational agent
  
• Product label includes adverse events based predominantly on frequency of occurrence
  
  • Includes treatment-related and non treatment-related adverse events based on clinician's assessment
    
• If FDA has potential concern, information placed under "Warnings and Precautions"
  

Systemic Adverse Events

Once-Daily Hypotensive Lipids Are Systemically Safe

• No effects on cardiorespiratory function
  
• Pregnancy category "C"
  
• Travoprost should not be used in women who are or might become pregnant
  

Once-Daily Hypotensive Lipids Are Well-tolerated

• Low rates of discontinuations from clinical trials due to adverse events
  
• Most side effects are ocular
  

Common side effects:

• Conjunctival hyperemia (trace to mild)
  
• Changes in iris pigmentation
  
• Eyelash changes
  
• Incidence of allergy is low
  

Conclusions

• " Good Enough" IOP control may not always be "Low Enough" to prevent disease progression
  
• Patients should be treated with monotherapy whenever possible
  
• Monotherapy with once-daily hypotensive lipids provides the best IOP lowering
  
• Lowers IOP more effectively than timolol
  
• Lowers IOP as effectively as combined timolol / dorzolamide
  
• Allows more patients to reach low target pressures
  
• Patients on timolol / latanoprost can be switched to bimatoprost monotherapy with no loss in IOP-lowering efficacy
  

Benefits of hypotensive lipids

• Efficacy
  
• Systemic safety
  
• Once-daily convenient dosing