Your time starts now — translation time lines for major ophthalmic discoveries

Treatment of AMD with anti-VEGF agents is one of the greatest advances in ophthalmology. In 1971, Judah Folkman proposed a blocking drug8 against a vascular factor that had first been identified in 1945.9 In 2002, a rare eye cancer was treated with an anti-VEGF antibody with dramatic success10 and, in 2006, the ANCHOR (Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-related Macular Degeneration) and MARINA (Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD) studies showed the efficacy of anti-VEGF antibodies in the treatment of AMD.11,12 This treatment was so successful that an editorial published in The New England Journal of Medicine described it as miraculous!13 A search of the Web of Knowledge indexing service showed that more than half the top 20 most frequently cited articles in ophthalmology journals from 2005 to 2010 relate to anti-VEGF treatments. Folkman died just after the fruition of 35 years of work.

Gerhard Meyer-Schwickerath first used sunlight coagulation to treat a retinal detachment in 1949.14 He went on to develop the Xenon arc light coagulator in the 1950s.15 The first functioning laser was developed in 196016 and laser’s utility as a surgical tool was recognised in 1965.17 The first major translation of laser in ophthalmology came in 1976, when laser treatment was shown to be effective for diabetic retinopathy in the Diabetic Retinopathy Study.18 Other lasers, such as the Nd:YAG and excimer lasers, expanded the scope of treatment. The translation time line from 1949 to 1976 is 27 years, and from 1960 to 1976 it is 16 years.

IOL development began with the serendipitous observation of an injured World War II fighter pilot who had part of the perspex (polymethyl methacrylate) from his aircraft cockpit canopy lodged in his eyeball. The eye tolerated the perspex quite well. This led Harold Ridley to develop a perspex IOL, first implanted in 1949, but the initial work was unpromising.19 Phakoemulsification, developed in the 1960s, provided a suitable method of cataract extraction to maximise the benefit of IOLs. Ridley met enormous opposition from the ophthalmic establishment. Because of high complication rates for inexperienced surgeons, Ralph Nader’s consumer organisation, Public Citizen, campaigned against IOLs, wanting them banned by the United States Food and Drug Administration.20 It was not until the early 1980s that IOLs became the standard of care — over 30 years after the first one was implanted.21 Before IOLs, the standard was to operate on people when the better eye deteriorated to a visual acuity of worse than 6/60. With many refinements to IOLs, ophthalmologists now operate on people with mild visual loss, such as a visual acuity better than 6/12 (the cut-off for driving in many countries). Ridley was belatedly recognised for his work and perseverance with a knighthood at the age of 93 years.

Norman Gregg’s 1941 paper reporting the association of maternal rubella infection and congenital cataract6 is the most cited paper in an ophthalmic journal in over 160 years.22 The impact of rubella embryopathy is enormous; major epidemics in countries such as the US in the 1960s affected tens of thousands of pregnancies.23 Gregg was knighted in 1953 but died in 1966, before the final step in translating his discovery. The virus was isolated in 1962 and the rubella vaccine released in 1969, virtually eliminating this major health problem.23 The translation time line from 1941 to 1969 is 28 years.

In the case of penicillin, bread with a blue mould to treat suppurating wounds was a staple of folk medicine since the Middle Ages in Europe.24 Alexander Fleming’s famous observation in 192825 was rapidly followed when Cecil Paine used penicillin to (unsuccessfully) treat sycosis barbae in 1930. Paine then went on to treat ophthalmia neonatorum, a gonococcal infection in infants. He achieved the first recorded cure with penicillin on 25 November 1930. He then cured four additional patients (one adult and three infants) of eye infections, but failed to cure a fifth.7 In the United Kingdom, 28.5% of children in schools for the blind in 1922 had been blinded by ophthalmia neonatorum; estimates from 1884 were 30%–41%.26 The decline in cases of blindness due to ophthalmia neonatorum occurred before the widespread use of penicillin because of improved notification, Crede’s prophylaxis (early treatment with asepsis and silver, such as Argyrol) and, in the 1930s, the use of sulphonamides.26 Howard Florey read Fleming’s work in 193828 and by 1941, with Ernst Chain and Norman Heatley, they had treated their first patient, Albert Alexander, who had been scratched with a rose thorn. His face and scalp were swollen, and his eye had been removed to relieve some of the pain from the periorbital cellulitis. Within 24 hours of being given penicillin, he began to recover. Unfortunately, when they ran out of penicillin he relapsed and died. By 1945, penicillin production was an industrial process for the allies of World War II. So 1928–1945 represents a relatively rapid 17-year translation time line. The even more rapid recognition of this translation came with the Nobel Prize in Physiology or Medicine being awarded to Florey, Chain and Fleming in 1945. The development of new antimicrobials and the race against microbial resistance continues today.