TREATMENT TRIALS FOR AGE RELATED MACULAR DEGENERATIONS

TRIALS FOR PHOTODYNAMIC THERAPY (PDT)

TAP STUDY ( P for PDT & Predominantly classic CNVM) : 

• PDT vs Sham group in Predominantly classic CNVM.
• Showed statistically significant benefit in predominantly classic CNVM.

VIP STUDY ( P for PDT; VIPs are Occult)

• PDT vs placebo
• Included patients with Occult CNVM without classic component.
• No significant benefit in visual acuity.

Conclusion :  PDT is effective only in Predominantly Classic CNVM. 

TRIALS FOR PEGAPTANIB (MACUGEN)

• Pegaptanib is VEGF-165 inhibitor.
• First FDA approved drug for treatment of AMD in 2004.
• Got approval on the basis of VISION( VEGF inhibitor study in ocular neovascularisation) trial. 
• KEY : VISION = MACULA (macugen).

VISION TRIAL:

• Intravitreal Macugen (0.3 mg, 1mg & 3mg)  vs sham injection at 6 weekly interval.
• 0.3 mg dose proved to be more effective than 1mg and 3mg injections and sham injections with statistically significant reduction in moderate to severe visual acuity loss over 2 years of follow up.

TRIALS FOR RANIBIZUMAB (LUCENTIS)

• FDA approved in 2006 on the basis of the results of MARINA & ANCHOR TRIALS.
• First FDA approved anti VEGF agent that has shown improvement in visual acuity in all isoforms of CNVM and prevented leakage and further growth of the lesion.

MARINA TRIAL ( Minimally classic/Occult CNVM anti VEGF Ranibizumab in Neovascular AMD).

• Intravitreal Ranibizumab (0.3 & 0.5 mg) monthly injection in minimally classic or occult CNVM vs sham group.
• Statistically significant reduction in visual acuity loss along with improvement in visual acuity over 1 year of follow up.
• Clinical improvement was associated with improved angiographic and OCT picture.

ANCHOR STUDY ( Anti VEGF Ranibizumab for the treatment of predominantly Classic CNVM in neovascular AMD ).

• PDT controlled trial
• 0.3 & 0.5 mg intravitreal Ranibizumab monthly injection vs 3 monthly PDT in Classical CNVM.
• Statistically significant reduction in visual acuity loss along with improvement in visual acuity with 0.5 mg Ranibizumab over 2 year of follow up as compared to PDT.

PIER STUDY ( R for Ranibizumab)

• 3 consecutive monthly injections of Ranibizumab followed by 3 monthly injection.
• Improvement in visual acuity observed during first 3 months which was not sustained after discontinuance of monthly injections over 1 year of follow up.

PRONTO TRIAL ( Prospective OCT imaging of patient with Neovascular AMD treated with intraocular Ranibizumab )

• 3 consecutive monthly injections of Ranibizumab followed by monthly OCT evaluation.
• Injections repeated only when OCT showed progression.
• Comparable visual acuity outcomes with ANCHOR & MARINA trials.

TRIALS FOR BEVACIZUMAB (AVASTIN)

• FDA approved in 2004 for systemic use in colorectal cancer.
• 5mg/kg intravenous also tried in AMD cases, 3 injections @ 2 weekly interval, later injections were OCT guided.                                                                                                                         

SANA TRIAL ( Systemic Avastin for Neovascular AMD) 

• 5mg/kg I.V dose.
• Advantage of systemic  Avastin - bilateral disease can be treated.
• Increased B.P controllable with medication was the only reported adverse effect.
• First intravitreal Avastin was given in May 2005, has shown comparable results with systemic Avastin and intravitreal Ranibizumab.

CATT TRIAL ( Comparison of ARMD treatment trial ) 

• Comparison between intravitreal Avastin and Lucentis in all isoforms of neovascular AMD.
• Both came out to be equally effective in the treatment of all isoforms of neovascular AMD.