gonin medal alan bird moorfields eye hospital institute of ophthalmology university college london
TRANSCRIPT
Gonin Medal
Alan Bird
Moorfields Eye Hospital
Institute of Ophthalmology
University College London
R AliJ AndersonG ArdenN AshtonR BlackD BokS BhattacharyaA BrannonC BunceI ChisholmP CoffeyC ErnstF FitzkeJ FlanneryM FriedlanderH FuglsangZ GregorC Gregory
J GreenwoodA HardcastleP Hamilton G Hageman C HammondE HèonG HolderD HuntC InglehearnM Jay B JayB JonesC KempE KohnerI LengyelP Luthert S LightmanWI McDonald
J MarshallA MilamD MinassianS MossA MooreS OnoT PetoA RobsonG RubenK SehmiG SheriadahG SerjeantE StoneJ VingerlingR WealeA WebsterA WrightJ Yates
Teachers and Colleagues
R AhujaA AmbresinI AudoR Barnes M BarondesS BeateyC BellmanT BerningerD BessantP BetancourtJ BowbyesS BoydC BlytheJ BowbyesR BrecherM BrantleyR BraunsteinA CalcagniM CaponA CasswellG ChaineC CheeJ ChenI ChisholmV ChongV ChristopoulosE ChuangP ClearyR ClemmetR Coco
J CosgroveN CoxJ R CocoCosgroveN CoxR CocoJ Cosgrove N CoxL Da CruzS DandekarH DollfusS DownesS DubovyC EganA EksteinK EvansJ FanD FarnworthG FishC FlaxelT GillowT GinB GodleyM GoldsteinM GorinZ GregorM GrossR GreyE GurwinR Guymer
R HaimoviciP HamiltonR HamptonN HarperE HayF HolzJ HopkinsD HornanA HoskinH JacksonS Kabanarou S Kaushall H KlassenJ KeisR KimA KohD KohenF v KuijkM KurzC LaneN LanselN LoisB LeroyA LuckieL LynessM McGibbonI MantelA MarinescuJ Marks
J McKibbinM MichaelidesA MooreP NgD NewmanR OberA OkuboS OwenS PagliariniI PalmvangD PauleikhoffM PerksL PelosiniT PetoP PolkinghorneB PiguetS QureshiS RansomeP RathA ReckD RosenA v RückmannP RushR RosaJ SandbachD SarrafR SchlingermanS SchwartzG Schoepner
H SchollD SharpeG SilvestriS Schmitz-Valckenberg J van SoellenA SmithP StangaR SteinmetzT StoutJ SungD SwansonH TabandehJ TalbotJ TalksV TannerV TeetersT TsangG TurnerA UllisV VaclavikE VankuijkJ VingerlingM VortrubaS VujosevicD WagnerA WebsterJ WellsT WolfensbergerB WrightJ WroblewskiN Young
Fellows
World blindness 1972
Trachoma
Onchocerciasis
Nutritional
Infective keratitis
Cataract
Onchocerciasis – world distribution
Onchocerciasis
Vector – black fly
Onchocerciasis
adult worms
Onchocerciasismicrofilariae
Onchocerciasis
Adult worms live for 20 years
Produce 1,000 mfs. each day
Microfilariae live for 2 years
Infected early in life - anergy
Disease due to reaction of dead mfs.
Onchocerciasis
French / Belgianblindness largely cornealother lesions:
retinal optic nerve - peripheral loss
Britishsurface disease – skin and cornearetinal lesions genetic
Savannah worse than rain forest
John Anderson
Harald Fuglsang
MRC fillaraisis unit, Douala
Brian Duke
Clinic - Tcholire
OnchocerciasisAge Savannah Rain Forest
5-9 4 1
10-19 48 11
20-29 43 20
30-39 29 25
40-49 13 31
50+ 3 16
Total 140 104
Onchocerciasisretinal disease:temporal lesions over insertion of long cilliary
arteries into choroid
Anderson J, et al Trans R Soc Trop Med 1976; 70: 378-95.
Onchocerciasis
optic nerve diseaseperipheral VF loss
OnchocerciasisPattern of optic nerve disease
as percentage of population
Savannah Rain Forest
Swelling 27 12
Atrophy 56 67
Total 83 79
Onchocerciasis
Of those blind from posterior segment
involvement: 80% due to optic nerve disease
Bird AC, et al Br J Ophthalmol 1976; 60: 2-20.
WHO recommendations:
Head nodule
15 mfs/ snip near eye
Remove head nodule
Give: Banacide (DEC)
Suramin
BUT
Treatment of Onchocerciasis
DEC treatment of OnchocerciasisBird AC et al, Lancet 1979; 46-7.
18 moderately to heavily infected
(mf counts – buttock > 100 / snip
outer canthus > 15 / snip)
9 with and 9 without visual field loss
All had itching
14 had vertigo
12 had headaches
10 had arthalgia
DEC treatment of Onchocerciasis
10 day: observation
Visual field loss 5 of 18, 1 bilateral
OD swelling: new in 9
worse in 3
New RP lesions in 7
Compression of 2 years disease into 10 days
DEC treatment of Onchocerciasis
DEC treatment of Onchocerciasis
visual field loss
Day 0
Day 4
Day 8
Treatment of OnchocerciasisDEC - makes them blindSuramin - kills them
Ivermectin - infertility in female adult worms
Vector control
Ivermectin causes diminution of microfilaria without inflammation
Aziz et al . Lancet 1982; 2: 171-3.
Dadzie et al. Trop Med Parasitol 1989; 40: 355-60
Ivermectin treatment does not cause optic neuritis
Murdoch I et al. Eye 1994; 8: 456-61.
Ivermectin causes diminution of the weight of infection
Taylor H et al. Science 1990; 250: 116-8.
Treatment has had a major effect on ocular morbidity although elimination of the disease has yet to be achieved
Treatment of Onchocerciasis
Retinal dystrophies
1969: Known to be genetic – dominant and recessive
More that one disease
Variable phenotype: sine pigmento, sector, unilateral
Can be associated with multi-system disease
Involvement of rods
Cause unknown: vitamin A deficiency simulates RP
No Treatment
Nettleship: On retinitis pigmentosa and allied diseases.
The Royal London Ophthalmic Hospital. Reports.
I 1907;7:1-56.
II 1908;7:152-166.
III 1908; 7:333-439.
Retinal dystrophies
Identify prevalence of different genetic forms
Identify sequence of photoreceptor loss
Identify genes involved
Relate phenotype to mutation
Identify disease mechanisms
Initiate treatment
Potential biological therapy for retinal dystrophies
Growth factorsGene therapyCell transplantation
CNV in age-related macular diseaseResponsible for over 50% of blindness in Western Society
Physical treatments disappointing:
Laser photocoagulation
Photodynamic therapy
Transpupillary thermo-therapy
Ionising radiation
Biological treatment CNV
Based on an understanding:
of the physical changes
of the biological processes
initiating of biological treatment
RAP
PEDF/VEGF
CNV
Neovascularisation
Secondary Endpoint:Mean Change in Visual Acuity Over Time
17.7 letter benefit *
17.0 letter benefit *
* P < 0.0001
1 2 3 4 5 6 7 8 9 10 11 12
Visit (months)
-10
-8
-6
-4
-2
0
2
4
6
8
10
ET
DR
S le
tter
s
Sham (n=238)
Ranibizumab 0.3 mg (n=238)
Ranibizumab 0.5 mg (n=240)
-10.5
+6.5+7.2
InstitutionsTherapeutic advances resulted from importation of
knowledge from the laboratory to clinical management
Institute of ophthalmology Moorfields Eye Hospital
A.A. Milne; Winnie-the-Pooh, 1926
A.A. Milne; Winnie-the-Pooh, 1926On Monday, when the sun is hot I wonder to myself a lot:“Now is it true or is it not, That what is which, and which is what?”
On Tuesday, when it hails and snows, The feeling on me grows and growsThat hardly anybody knowsIf those are these and these are those.
A.A. Milne; Winnie-the-Pooh, 1926On Wednesday, when the sky is blue,And I have nothing else to doI sometimes wonder if it’s trueThat who is what and what is who?
On Thursday, when it starts to freezeAnd hoar-frost twinkles on the trees,How very readily one seesThat these are whose but whose are these?
A.A. Milne; Winnie-the-Pooh, 1926On Wednesday, when the sky is blue,And I have nothing else to doI sometimes wonder if it’s trueThat who is what and what is who?
On Thursday, when it starts to freezeAnd hoar-frost twinkles on the trees,How very readily one seesThat these are whose but whose are these?
On Friday.…………………….