eye diseases

what does the eye detect

different wavelength and patterns of light

what does light entering the eye trigger

photochemical reaction in rods and cones at back of retina

what determines the pattern of vision loss

the faulty region/ cell type in the retina

different causes of blindness

diabetic retinopathy, residual causes of vision loss, glaucoma, age-related macular degeneration, cataract, undercorrected refractive error, degeneration macular and posterior pole

What is age related macular degeneration

multifactorial disease with demographic environmental, and genetic risk factors contributing to disease development

what does age-related macular degeneration vision look like

what does retinitis pigmentosa vision look like

what does acquire trauma vision look like

risk factors of AMD

age, smoking, diet and exercise

what does early AMD imaging include

yellow spots- lipids, hypopigmented-scarring, peripheral degeneration

what is drusen

focal deposits of extra-cellular debris (lipids), yellow-white mound-like elevations under the RPE

The size of drusens at intermediate AMD

(>125um) migrating retinal pigment epithelium cells and subretinal drusenoid deposits (reticular pseudodrusen)

Treatment for early/intermediate AMD

Current trials- AREDS…

•No direct evidence that patients with early AMD should take lutein / multivitamin supplementation

•Dietary advice: Plenty of fruit, leafy green vegetables

•For those with the following in at least one eye, consider supplementation with a preparation based on AREDS 2 study: •Extensive, intermediate-sized /large drusen

•Geographic atrophy

•Advanced AMD in either eye

Consideration of treatment

• Is there definitely macular neovascularization present? (new vessels)

• NICE:  Vision has to be worse than 6/12- but not as bad as 6/96 (governing body who determines who gets which treatment because of money)

• Discussion with patient about risks/benefits and overall quality of life impact

The types of antiVEGF treatments available

ranibizumab, aflibercept, bevacizumab, farucimab and brolucizumab

How does Kd value affect receptor binding

The smaller the Kd value, the lower the concentration of drug required to achieve 50% receptor binding; therefore, the greater the binding affinity of the drug for its receptor

symptoms of wet AMD

distortion or sudden deterioration of vision

treatment of wet AMD

anti-VEGF

What is dry AMD (geographic atrophy)

no fluid at the end of the end, fibrosis, persistent scarring and atrophy of the retina. Nothing to perceive light. NO treatments. Loss of photoreceptors, retinal pigment, epithelium and choriocapilaris

What is unifocal

one spot of atrophy

Current complement therapies

• Pegcetacoplan:  blocks complement C3.  Has FDA approval in  USA since Feb 2023, awaiting EMA/NICE approval

• Avacincaptad Pegol:  blocks complement C5, USA FDA approval granted August 2023, awaiting EMA/NICE approval

Requirements for anti-complement therapies to reduce the rate of progression of GA

People needed to already have geographic atrophy at the start of the trials.  They were not permitted to have had previous wet AMD in the treated eye.

What is the complement system

innate immunological network and helps with the detection and removal of pathogens

What part of the chromosome is responsible for AMD

1q31 which carries the gene for complement factor F (CFJ) and 10q26 which includes the ARMS2/HTRA1 genes

Which antiVEGF drug targets all VEGFR-1 ligands

afibercept

What does afilbercept target

VEGF and PIGF

what does VEGF and PIGF play a role in

in pathological vascular permeability, macular oedema, inflammation, and neovascularisation in retinal diseases