Transcript Document

Gonin Medal
Alan Bird
Moorfields Eye Hospital
Institute of Ophthalmology
University College London
Teachers and Colleagues
R Ali
J Anderson
G Arden
N Ashton
R Black
D Bok
S Bhattacharya
A Brannon
C Bunce
I Chisholm
P Coffey
C Ernst
F Fitzke
J Flannery
M Friedlander
H Fuglsang
Z Gregor
C Gregory
J Greenwood
A Hardcastle
P Hamilton
G Hageman
C Hammond
E Hèon
G Holder
D Hunt
C Inglehearn
M Jay
B Jay
B Jones
C Kemp
E Kohner
I Lengyel
P Luthert
S Lightman
WI McDonald
J Marshall
A Milam
D Minassian
S Moss
A Moore
S Ono
T Peto
A Robson
G Ruben
K Sehmi
G Sheriadah
G Serjeant
E Stone
J Vingerling
R Weale
A Webster
A Wright
J Yates
R Ahuja
A Ambresin
I Audo
R Barnes
M Barondes
S Beatey
C Bellman
T Berninger
D Bessant
P Betancourt
J Bowbyes
S Boyd
C Blythe
J Bowbyes
R Brecher
M Brantley
R Braunstein
A Calcagni
M Capon
A Casswell
G Chaine
C Chee
J Chen
I Chisholm
V Chong
V Christopoulos
E Chuang
P Cleary
R Clemmet
R Coco
J Cosgrove
N Cox
J R Coco
Cosgrove
N Cox
R Coco
J Cosgrove
N Cox
L Da Cruz
S Dandekar
H Dollfus
S Downes
S Dubovy
C Egan
A Ekstein
K Evans
J Fan
D Farnworth
G Fish
C Flaxel
T Gillow
T Gin
B Godley
M Goldstein
M Gorin
Z Gregor
M Gross
R Grey
E Gurwin
R Guymer
Fellows
R Haimovici
P Hamilton
R Hampton
N Harper
E Hay
F Holz
J Hopkins
D Hornan
A Hoskin
H Jackson
S Kabanarou
S Kaushall
H Klassen
J Keis
R Kim
A Koh
D Kohen
F v Kuijk
M Kurz
C Lane
N Lansel
N Lois
B Leroy
A Luckie
L Lyness
M McGibbon
I Mantel
A Marinescu
J Marks
J McKibbin
M Michaelides
A Moore
P Ng
D Newman
R Ober
A Okubo
S Owen
S Pagliarini
I Palmvang
D Pauleikhoff
M Perks
L Pelosini
T Peto
P Polkinghorne
B Piguet
S Qureshi
S Ransome
P Rath
A Reck
D Rosen
A v Rückmann
P Rush
R Rosa
J Sandbach
D Sarraf
R Schlingerman
S Schwartz
G Schoepner
H Scholl
D Sharpe
G Silvestri
S Schmitz-Valckenberg
J van Soellen
A Smith
P Stanga
R Steinmetz
T Stout
J Sung
D Swanson
H Tabandeh
J Talbot
J Talks
V Tanner
V Teeters
T Tsang
G Turner
A Ullis
V Vaclavik
E Vankuijk
J Vingerling
M Vortruba
S Vujosevic
D Wagner
A Webster
J Wells
T Wolfensberger
B Wright
J Wroblewski
N Young
World blindness 1972
Trachoma
Onchocerciasis
Nutritional
Infective keratitis
Cataract
Onchocerciasis – world distribution
Onchocerciasis
Vector – black fly
Onchocerciasis
adult worms
Onchocerciasis
microfilariae
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 / Belgian
blindness largely corneal
other lesions:
retinal
optic nerve - peripheral loss
British
surface disease – skin and cornea
retinal lesions genetic
Savannah worse than rain forest
John Anderson
Harald Fuglsang
MRC fillaraisis
unit, Douala
Brian Duke
Clinic - Tcholire
Onchocerciasis
Age
5-9
Savannah
Rain Forest
4
1
10-19
48
11
20-29
43
20
30-39
29
25
40-49
13
31
3
16
140
104
50+
Total
Onchocerciasis
retinal 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 disease
peripheral VF loss
Onchocerciasis
Pattern of optic nerve disease
as percentage of population
Swelling
Atrophy
Total
Savannah
27
56
83
Rain Forest
12
67
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.
Treatment of
Onchocerciasis
WHO recommendations:
Head nodule
15 mfs/ snip near eye
Remove head nodule
Give:
Banacide (DEC)
Suramin
BUT
DEC treatment of Onchocerciasis
Bird 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
Day 0
Day 4
visual field loss
Day 8
Treatment of Onchocerciasis
DEC - makes them blind
Suramin - kills them
Ivermectin - infertility in female
adult worms
Vector control
Treatment of Onchocerciasis
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
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 factors
Gene therapy
Cell transplantation
CNV in age-related macular disease
Responsible 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
Neovascularisation
RAP
PEDF/VEGF
CNV
Secondary Endpoint:
Mean Change in Visual Acuity Over Time
* P < 0.0001
Ranibizumab 0.5 mg (n=240)
Ranibizumab 0.3 mg (n=238)
10
Sham (n=238)
8
+7.2
+6.5
6
4
17.7 letter
benefit *
ETDRS letters
2
0
1
-2
2
3
4
5
6
7
8
9
10
11
12
Visit (months)
17.0 letter
benefit *
-4
-6
-8
-10
-10.5
Institutions
Therapeutic 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, 1926
On 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 grows
That hardly anybody knows
If those are these and these are those.
A.A. Milne; Winnie-the-Pooh, 1926
On Wednesday, when the sky is blue,
And I have nothing else to do
I sometimes wonder if it’s true
That who is what and what is who?
On Thursday, when it starts to freeze
And hoar-frost twinkles on the trees,
How very readily one sees
That these are whose but whose are these?
A.A. Milne; Winnie-the-Pooh, 1926
On Wednesday, when the sky is blue,
And I have nothing else to do
I sometimes wonder if it’s true
That who is what and what is who?
On Thursday, when it starts to freeze
And hoar-frost twinkles on the trees,
How very readily one sees
That these are whose but whose are these?
On Friday.…………………….