Gonin Medal Alan Bird Moorfields Eye Hospital Institute

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 Jones C Kemp E Kohner I Lengyel P Luthert S Lightman WI Mc. Donald 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 Mc. Gibbon I Mantel A Marinescu J Marks J Mc. Kibbin 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 -2 1 2 3 4 5 6 7 8 9 10 11 12 Visit (months) 17. 0 letter benefit * -4 -6 -8 -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. ………….