Ocular Biologics

Question 1

Define biologics

Answer 1

large, complex molecules produced with biotechnology (bacteria/cultured cells expressed introducing encoding gene for drug) to address unmet medical needs for chronic/severe eye conditions

Question 2

Describe how SMEs are different to biologics

Answer 2

Biologics: made from live cells/organisms with many critical process steps (less easily characterised)
Undefined structure of heterogenous mixture (immunogenic)

SMEs: chemically synsthesised with fewer steps, well characterised/stuctured, homogenous mix (non-immunogenic)

Question 3

Explain the MoA, modes of delivery and targeted pathways of biologics

Answer 3

as a block it binds to mediators/receptors in physiological responses (BV growth, immune response)

targets VEGF, Tumor Necrosis Factor-alpha (TNF-a), interleukins (ILs) via IV injections, topicals, implants

Question 4

Describe 5 types of biologics

Answer 4

Monoclonal anti-bodies bind to targets involving disease/damage

Modified (water soluble) receptors/fusion proteins bind to endogenous agonists in disease/damage

Aptamers: modified synthetic nucleic acids (3D structure provides high affinity/selectivity)

Gene therapies
Cell-based therapies

Question 5

Describe 6 properties of biologics

Answer 5

relatively unstable in solution
very viscous, less soluble at high conc.
environment sensitive
prone to enzyme degradation (proteolysis)
susceptible to absorption, unfolding, aggregation, inactivation
Hard, expensive to manufacture

Question 6

Describe the immunogenicity of biologics

Answer 6

px immune system recognises/destroys biologic or provokes a dangerous reaction

related to degree of humanisation, administration route (SC/IM>IV) due to immune cells under skin, therapy duration (more likely over time)

Question 7

State 5 scenarios when biologics should not be used

Answer 7

TB px (can reactivate late TB or other active infections)
Pregnant/Breast-feeding
Demyelinating disease (make it worse)
Rule out malignancy (some cause cancer)
Monitor blood cell count (avoid adverse reactions)

Question 9

Describe the 3 stages of AMD

Answer 9

Early (mid-sized drusen no vision loss)
Intermediate (large drusen/retinal pigment change, damaged RPE, asymptomatic vission loss)
Late (large drusen, progressive visual loss due to macula damage)

Question 10

Describe 2 AMD types

Answer 10

Dry - drusen accumulates, RPE/phreceptor atrophy (gradual breakdown of macula light sensitive cells/supporting tissue 90% cases)

Wet - abnormal neovascularisation under retina, fragile vessels leak causing macul swelling/damage 10% cases)

Question 11

Describe the roles of VEGF-A

Answer 11

normal ocular develepment/homeostasis
maintains choriocapillaris
stimulates angiogenesis

secreted by RPE, endothelium, pericytes, muller cells, astrocytes

Question 12

Describe some problems with ocular use of Bevacizumab

Answer 12

initially for IV cancer use so dilated fo ocular use
stability issues, contamination, protein aggregation risk/raised IOPs

Question 13

Describe the use of Aflibercept (Eylea) as an anti-VEGF

Answer 13

recombinant fusion protein fusing VEGF binding sites to Fc domain of human IgG
binds VEGF-A/B/placental GFs
fewer injections/adverse side effects but needs IOP monitoring

Question 14

Describe 4 ocular biologics used in uveitis

Answer 14

abtacept (targets Tcell activation)
Rituximab/Alemtuzumab target B cells
Canakinumab (binds/sequesters IL-1)

Question 15

Describe TNFs

Answer 15

family of cytokine proteins produced by immune cells to modulate other immune cell
high levels in Crohn’s, rheumatoid arthiritis can cause uveitis)