10 years

By Nick Lane PhD Pioneers Past and Present – But where are the boundaries of the justifiable?

heir names justly echo down the halls Elder, his colleagues walked out of early example was the supplanting of horse- “I don’t think for a moment that we’re Tof fame of – Sir presentations; the very concept of IOL drawn carriages by cars; there were many going to see the end of LASIK or corneal Harold Ridley, Peter Choyce, Cornelius implantations was openly repudiated, and people at the time who could see no refractive in general, but as the Binkhorst, Edward Epstein, Svyatoslav dismissed by the AAO as “not sufficiently advantages of cars over horses,” Dr Fine new generations of accommodating IOLs Fyodorov, Charles Kelman, Benedetto proven for use in the US”. Ridley spent told EuroTimes. come into their own, we’re likely to see Strampelli, José Barraquer, Luis Ruiz,Theo years terrified that his early failures would Of course pioneers need more than just more and more people in their fifties and Seiler, Ioannis Pallikaris, to take just a few. come back to haunt him through the vision to succeed; they also need the sixties opting for exchange, maybe Their techniques transformed the world courts. In Barcelona, in 1970, Joachim ability to see a technical way through the even before they’ve developed the first and restored sight for millions. But had it Barraquer was forced to explant half of problem, to convert their vision into signs of a cataract.This is not really a not been for their failures, the successes the anterior IOLs that he had implanted in action.And they need to be able to get it technical leap, at least not surgically – it is of today might never have been possible. 500 patients, as a result of corneal across to their colleagues in an intelligible in terms of lens technology – but it is Failure is an occupational hazard in decompensation.And despite his way, so that other people can test their certainly a major sea-change in attitudes,” surgery, but how much failure is too successful anterior IOL designs, the name ideas properly, and refine the technology. said Dr McDonald.“ much? of Peter Choyce is muddied by the Horses didn’t give way to cars before unlicensed manufacture of shoddily there’d been a lot of engineering Innovation versus clinical data produced copies (inadequately sized and improvements. Even so, refractive lens exchange is only finished, and prone to warpage).After In cataract and refractive surgery, one way through the quagmire, and herein “In society in general 100,000 defective implants in the 1970s, Ridley’s concept of implanting an IOL was lies the problem.What of phakic IOLs? many of which caused the so-called UGH the first such leap. Implanting anything into What of the use of advancing wavefront there have been many syndrome (uveitis, glaucoma and the eye went against the ethos of the technology in laser ablations, reducing the hyphaema) they were finally withdrawn times, when ophthalmologists were taught risk of glare and haloes in more highly such leaps. Mechanical from the market. only to remove things from the eye. myopic patients? These and other Charles Kelman, too, was subject to was a similar leap, techniques are advancing rapidly, and it is typewriters were scathing criticism for his pioneering of making modern microincision cataract phacoemulsification, not altogether surgery possible; improved to the surprisingly given the secretive failure of and the use of his first case.After 4? hours in a room the excimer laser electric version, but marked ‘contaminated’, with an hour and was another 19 minutes of ultrasound using his bulky lateral leap, then were prototype phacoemulsifier, the patient which solved developed endophthalmitis, lost vitreous many of the unexpectedly fluid, and finally had his eye enucleated the problems following day. Of course, the cumulative associated with supplanted altogether technical improvements of radial phacoemulsification ultimately enabled the keratotomy, by computers.” successful development of modern notably the lack microincision , with of predictive Howard Fine MD implantation of foldable intracapsular power and the “You can tell the pioneers from the lenses. Ironically – even pioneers get set in (small but arrows in their backs” joked Marguerite their ways – Ridley and Choyce never serious) risk of McDonald, MD, clinical professor of accepted intracapsular IOL implantation. traumatic globe ophthalmology at Tulane University, to rupture. EuroTimes. The conceptual leap of innovation How much comfort Certainly the greatest advances in So is there a common theme to these The refractive do you want ? cataract and refractive surgery have met pioneers? According to Howard Fine, MD, lens exchange with vituperative criticism from peers. Dr clinical professor of ophthalmology at revolution McDonald herself, after performing the Casey Eye Institute, Oregon Health & So which of the It‘s your decision ! first photorefractive keratectomy (PRK) Science University, true innovation comes numerous on a normally-sighted myopic patient in from a conceptual leap, when the current techniques and LDWIDE 1987 (following years of research on eye- techniques have run up against an ideas being SOLE WOR bank eyes and animals), was accused by a image inversion immovable barrier.The breakthrough is tested today will • electrically switched s senior colleague, in the letters pages of a often an inspired lateral leap from an be seen as a • microscope independent motorized focu journal, of either being irresponsible or unexpected quarter, which might seem pioneering leap, • ergonomics well-proved for 20 years lying.And that was the barbed reward for obvious with the benefit of hindsight.The with the benefit immediate success; initial failure is far first attempts may be technically of hindsight? Oculus BIOM 3c /SDI 3c – more commonly the fate of successful rudimentary, but the conceptual leap Interestingly, The fully motorized and most versatile version. innovation. forwards is the beginning of a completely both Dr Fine and Fits to the common microscopes used for vitreo- History furnishes many examples of new path leading to refinements, until the Dr McDonald retinal surgery. Not depending on microscope’s brand. Also available for cost-effective retrofi tting. how far the disavowal of peers can go, 110 years next barrier blocks the way again. agreed that the 110 years even when an innovative technique proves “In society in general there have been most important Trust in 20 years experience of the world leader in non contact wide angle observation. enormously beneficial in the end (or not many such leaps. Mechanical typewriters current as the case may be – see the side bar). were improved to the electric version, but conceptual leap Ridley’s own troubles are the stuff of then were unexpectedly supplanted is refractive lens Oculus Optikgeraete GmbH • D-35549 Wetzlar legend. Castigated by Sir Stewart Duke altogether by computers.Another exchange. Tel. +49-641-20 05-0 • Fax +49-641-20 05-295 • www.oculus.de

EuroTimes January 2006 7 10 years

hard to say which will provide the best successful but ultimately limiting treatment “This is the closest we’ve got so far to our profession, and is a violation of the long-term solution. Unless we pursue is drawn too soon, then the negative the crystalline lens. It can be custom made, implied pact between physician and them all, we’ll never know; but equally, comparisons may stifle successful using MRI measurements of the exact size patient.” some rapidly advancing innovations are innovation.What if Kelman’s early of the capsular bag, and implanted through Wise words.Yet patient choice is also likely to do as much harm as good. attempts at phacoemulsification had been an incision as small as 1.0 mm.” ultimately the answer, so long as patients According to Roger Steinert, MD, data on dismissed as disastrous, as well they Personalising to individual are well informed. phakic IOLs (published in AJO, November could? His lasting testament, like Ridley’s, patients in this way is achievable in 2004) “shine a bright yellow caution light” was the proof of a concept, not its surgery, but goes against the grain of on angle-fixated anterior-chamber IOLs perfection. It is his vision that stood the evidence-based medicine, which insists on pigeonholing patients into comparable “Given that refractive groups with high statistical power. No doubt cataract and refractive surgeons will surgery affects quality- “As the new generations of accommodating IOLs continue to earn the opprobrium of colleagues in other disciplines. But while of-life, it’s reasonable come into their own, we’re likely to see more monolithic medicine served 20th century science well, it may be that its days are that patients should and more people in their fifties and sixties numbered, as the impact of genomics makes itself felt. choose, and pay. But opting for lens exchange, maybe even before The human genome project is set to revolutionise the practice of clinical trials we have a they’ve developed the first signs of a cataract. through the application of pharmac- Marguerite McDonald MD ogenomics – the tailoring of drug therapies responsibility to to the genetic makeup of individual and posterior-chamber IOLs. But perhaps test of time; and the early data were best patients. By searching for individual single educate the patients this rap across the knuckles is just the ignored. nucleotide polymorphisms (known as stimulus for better innovative design. Some modern examples are more ‘snips’) that influence the pharmacology as honestly as we can.” On the other hand, cataract and subtle, but still hinge on the playoff and pharmacokinetics of drugs, and by Howard Fine MD refractive surgeons sometimes seem between data, on the one hand, and long- tailoring therapies to the specific genotype almost incorrigibly innovative.There are term potential on the other. of individual patients, pharmac-ogenomics nearly as many different models of IOL as A recent prospective, comparative trial is set to break the stranglehold of both “Given that refractive surgery affects there are surgeons – at least 1,500 by Charles Claoue MD, at Hartswood blockbuster drugs and the mega-trials that quality-of-life, it’s reasonable that patients different designs registered to 33 Hospital, Brentwood, is case in point. He support them. should choose, and pay. But we have a companies worldwide. Most of these have compared a multifocal IOL (Array Patient-driven innovation responsibility to educate the patients as never been compared formally; the multifocal IOL,Advanced Medical Optics) So it is fair in surgical sciences, and in honestly as we can – we need to be clear unsuccessful models simply disappear from with an accommodating IOL (1CU ophthalmology in particular (where about the potential complications of the market, or are superseded by new accommodating IOL, Human Optics AG). In refractive endpoints are as objective as different techniques, and whether they are ‘improved’ marks. Several commentators most respects the multifocal lens proved any), to tailor novel treatments to still experimental.We need to spend a lot have complained that negative results are superior, despite the small size of the trial. patients, rather than insisting on of time with patients, talking it through. seldom published. In this sense, innovation Yet as a vision, it is plain that the ultimate comparators, placebos or, god-forbid, But if we do that, then innovations will be stands against the ponderous goal is an accommodating lens with similar sham surgery. Dr Fine hails the new era as driven by market forces, and measurement, recording, and the properties to the crystalline lens. Only by the transition from “high volume, low ophthalmologists who over-promise, or comparison of outcomes. trying and failing to produce an effective cost, efficient care, to high-quality, mislead, or over-charge for poor But while cataract and refractive accommodating lens, and by learning from personalised care.” outcomes, will be sued or drummed out. surgeons have been criticised for their the mistakes to refine and refine again, can However, there is a balance between It’s the market economy at its best,” Dr attitude to evidence-based medicine the vision be realised. the need to innovate, to aspire to a grand Fine told EuroTimes. (including by me, in an earlier column), it This process has recently culminated in vision, and the need to ‘first do no harm’. is also true that too tight an embrace of the remarkable Smart lens (Medennium), Only the patient can choose between the the ‘gold standard’ of the double-blind able to change its shape at body possibility of perfection, as offered by a clinical trial may hamper surgical research. temperature from a solid rod to an perfected accommodating IOL, and the There are two big problems with clinical optically imprinted gelatinous acceptance of a reliable second-best, with trials in cataract and refractive surgery. accommodating lens that fills the capsular a well-established risk profile.And to One is that the slow, measured tempo of bag. Dr Fine extolled its virtues to establish the risks, it is necessary to clinical trials simply can’t keep pace with EuroTimes: collect clinical data, ideally on a the speed of technical refinements. By the standardised multicentre basis, and to time the National Eye Institute’s PERK innovate only on those patients who wish trial was completed, for example, radial “This is the closest to be ‘innovated upon’. keratotomy had already been effectively First and foremost, patients are entitled replaced by excimer laser treatments. But we’ve got so far to the to a clear exposition of the outcomes of in the worst case scenario, radial new interventions.As Douglas Koch, MD, keratotomy was worth the effort because crystalline lens. It can editor of the JCRS, and others have it showed that successful corneal pointed out, the inevitable uncertainty refractive surgery was possible; and in the be custom made, using over outcomes in innovative surgery best case, surgical refinements over the means that it is critical for the integrity of last decade, coupled with its speed and MRI measurements of the profession to maintain honest ease, still make RK effective in many standards in advertising. situations, especially if laser surgery is not the exact size of the Cataract and refractive surgery is available. leading the way in direct-to-consumer The second drawback is perhaps more capsular bag, and marketing. For LASIK alone, some $140 is profound: conceptual leaps forward almost spent on advertising per treated eye.All inevitably begin in a rudimentary fashion, implanted through an too often claims are simplistic and like the earliest cars, and it is the many misleading (“20/20 for $2995” or “20/20 small obstacles themselves that lead incision as small as 1.0 promise”), and not supported by data. ultimately to the refined and Says Koch:“False advertising deceives technologically superior product. If the mm.” Howard Fine MD patients, fosters poor patient decisions comparison with an existing, moderately regarding having a procedure, demeans

EuroTimes January 2006 10 years

The Fruits of Innovation And a few that didn’t…yet The kind of derision that greeted Sir Harold Ridley’s invention of the intraocular IOL Frontal Lobotomy has by no means been restricted to ophthalmology. It’s always been difficult to judge the The first attempt at human psychosurgery was a series of prefrontal lobotomies lasting value of innovative treatments. Here are a few examples from outside performed by Egas Moniz, who received the Nobel Prize in 1949.The idea was ophthalmology that incurred similar wrath from peers, and went on to greater things – popularised by Walter Freeman, who invented the ‘ice-pick lobotomy’, hailed as a great or not, as the case may be. advance in ‘minimally invasive surgery.’ Freeman travelled the US in his ‘lobotomobile’ during the ‘40s and ‘50s, and his treatment was carried out on some 50,000 patients, Crazy innovations that worked… even misbehaving children.The era is now regarded as a barbaric episode in psychiatric history. In vitro fertilisation The first successful in vitro fertilisation was performed in 1978 by Robert Edwards (an Hysterectomy for hysteria embryologist) and Patrick Steptoe (a gynaecologist) in England. Since then more than The ancient Greeks considered hysteria to be ‘womb fury’ and advocated manipulation 20,000 test-tube babies have been born worldwide.The possibility of a continuing of the genitals to orgasm as the cure. By the 1800s, the uterus was considered the pregnancy being achieved by IVF has improved from practically zero to around 20% at origin of women’s psychological neuroses, said to be the most common of all diseases top IVF centres. except fever.The obvious cure for distress was hysterectomy, which was perfected in the 1870s. Even today, one in three women have a hysterectomy by the age of 60, a procedure found to be unnecessary in at least 50% of cases by the AMA. The first corneal allograft was performed in 1837 in a gazelle model, and the first successful human transplant by Eduard Zirm in Austria in 1905.The first successful Blood-letting kidney transplant was carried out by and David Hume at Brigham The history of phlebotomy goes back to ancient Egypt at least 3000 years ago, and was Hospital, in 1954, and the first heart transplant by in South based on the four humours, blood, phlegm, black bile and yellow bile. Health was Africa in 1967.The advent of cyclosporine, approved by the FDA in 1983, made restored by purging, starving, vomiting or bloodletting. Phlebotomy was used specifically transplantation the successful treatment it is today. to cure spiritual or physical weaknesses (as blood carried the vital force) from tumours to tonsillitis. Modern phlebotomy is still used to treat erythraemia and congestion Blood transfusion following acute heart failure. Blood transfusions have been attempted since ancient times, with Pope Innocent VIII apparently receiving the blood of three boys on his deathbed (all of whom died).After Transplantation of goat for virility centuries of failure, the discovery of blood groups early in the nineteenth century led In 1889, French physiologist Charles Brown-Sequard reported he had rejuvenated mind to the first successful transfusion by James Blundell in 1818, to treat a patient for and body by injecting himself with an extract from the testicles of dogs. By the 1920s, postpartum haemorrhage, and later, in 1840, to treat haemophilia. Leo Stanley, surgeon at San Quentin, was implanting boar testes into willing prisoners, and in Paris Serge Voronoff transplanted monkey glands to extend the lives of wealthy Irradiation of tumours clients. John Brinkley eventually transplanted hundreds of sliced goat testicles into Roentgen discovered X-rays in 1895, when experimenting with a vacuum tube; he noticed elderly patients in Kansas, before fleeing to Mexico and succumbing to poor health and a fluorescent screen glowing on the other side of the lab. He tried to block the unknown endless lawsuits. rays by holding out cardboard and was shocked to see an image of the bones in his own hand.Weeks later, medical student Emil Grubbé became the first person to use radiation to treat cancer. Early radiotherapy consisted of a single, massive one-hour dose of radiation, and side effects were severe. In 1922, Claudius Regaud proved that fractionated therapy was as effective as a single-dose, but caused fewer side effects.

EuroTimes January 2006