1. History
a. Biggest drugs in the last 5 years
i. Macugen
1. Mechanism of action
2. Indication for use
3. Efficacy
ii. Triamcinalone
1. Mechanism of action
2. Combo treatment and PDT
3. Combo Efficacy
iii. Visudyne
1. Mechanism of Action
2. Indications for use
3. Efficacy
4. Radical study
iv. Lucentis
1. Mechanism of Action
2. Indications for use
3. Efficacy
v. Avastin
1. Difference from Lucentis
2. Treatment outcomes
b. Prevalence of disease leading to drug development
i. AMD
1. Wet vs Dry
ii. Macular edema
iii. Diabetic Retinopathy
2. New Understandings in Pathology
a. Angiogenesis
i. Pathways to attack
ii. Upstream regulators
b. Evolving VEGF theories
c. Compliment Activation
- Compliment inhibitors
- Potentia
d. Differentiating subtypes of macular disease
e. Genotype vs Phenotype
f. Fenretinide
i. A synthetic retinoid derivative
1. Stargardt’s
3. Drugs close to market
a. Bringing a drug to market
i. Process
ii. Timeframe
iii. Phase trials
iv. Clinical end points
b. Combination therapy drugs
i. Mechanism
ii. Benefit
iii. Limitations
c. Dry AMD drug?/CTNF (ciliary tropic neuro factor)
i. Mechanism
1. Encapsulated cell technology
ii. Benefit
iii. Limitations
d. Dry and Wet AMD drug complement inhibitors
i. Mechanism
ii. Benefit
iii. Limitations
e. TKI’s(tyrosinase kinase inhibitors) VEGF receptor blockers
i. Mechanism
ii. Benefit
iii. Limitations
iv. VEGF-Trap
f. Copaxone ( glatiramer acetate)
i. Mechanism
1.
an immunomodulator that affects different levels of the
immune response, as an MHC blocker, T cell receptor
antagonist, and as a potent inducer of regulatory T cells
ii. Limitations
g. Rapamycin
i.
Mechanism
1.
inhibits the response to interleukin - 2 (IL-2) and thereby
blocks activation of T and B-cells
ii. Limitations
h.
Synthetic derivatives
i.
Fenretinide
1.
Early promise
2.
Current struggles
4. Drug delivery models
a. Systemic
i. Avastin
ii. Squalamine
iii. Tnp-470 (endothelial cell cycle arrest)
iv. Thalidomide/ Thalidomide and prednisone
v. Arxxant for diabetic retinopathy
b. Topical
i. TKI’s
ii. Nsaids
c. Intravitreal
i. Injections – Anti-VEGF’s, Microplasmin
1. Risks
ii. Sustained release - posturdex, flucinalone, ganciclovir, osurdex
iii. Trans-scleral – triamcinalone, anecortane
5. Conclusions
a. The evolution of retinal treatments
i. Stem cell research
1. Type of cells available
2. Target tissues
3. Major stem cell problems
4. Somatic cell nuclear transfer