Progress made in longwar on river blindnessLatin America gainsground as Africa battlesonPage 4

FT Health EyecareFT SPECIAL REPORT

www.ft.com/reports | @ftreportsThursday October 13 2016

Inside

Big pharma looks to ablockbusting futureHealthy revenuesanticipated as peoplelive longerPage 2

Biotech start-upsEntrepreneurs spypromise of profit infading powers of sightPage 2

Digital technologyImplant breakthroughmeans images can beseen with eyes closedPage 3

Minds focus on dangerof modern screen useMany of us spend moretime looking at devicesthan we do asleepPage 4

O f the five senses, none maybe more precious thansight. Yet even as otherareas of medicine haveadvanced rapidly in recent

decades, the area of eyecare has beencomparatively static, especially when itcomestodevelopingnewdrugs.

“Eyecare between the 1980s and early2000s was essentially the domain ofsurgeons, who were eventually helpedby lasers,” says Dr Bernard Gilly, thechief executive of GenSight Biologics, aParis-based company developing genetherapies foreyediseases.

In recent years, eyecare research hashad something of a renaissance, how-ever, thanks to the combination of esca-lating need for treatments and someimportantscientificdiscoveries.

By 2050, the number of people withvisual impairment or blindness is set todouble to more than 8m in the US alone,

according to official figures. “Novelapproaches are being tested across allthe major ophthalmology conditions,”notes Dominic Trewartha, an analyst athealthcare investment specialist GBIResearch. He estimates that pharma-ceutical companies are developingalmost 160 first-of-a-kind drugs to treateverything from diseases associatedwith ageing, such as macular degenera-tion and glaucoma, to rare genetic con-ditions that cause blindness in youngerpeople.

The runaway success of two drugsthat treat a form of age-related maculardegeneration, known as wet AMD, haslifteddrugmakers’ spirits.Lucentis, soldin a partnership between Swiss pharmagroups Novartis and Roche, generatesbillions of dollars in annual sales, asdoes Eylea, which was discovered byNewYork-basedbiotechRegeneron.

“The very big success of these two

Drugmakersrespond togrowing needfor treatmentsThe fast rise in numbers of people going blind hasprompted a revival in research, reportsDavid Crow

Testing times: eyecare has emerged from a relatively static period —Getty Images

drugs has clearly pulled the domain ofeyecaretotheforefront,”saysDrGilly.

Several conditions still have no treat-ment, such as dry AMD. Roche is testingone potential treatment, Lampalizu-mab, in late-stage clinical trials. None-theless, Umer Raffat, analyst at invest-ment banking services adviser EvercoreISI, says: “We’re hearing a lot moreabouteyecarerecently,muchmorethanwedid, say, twoorthreeyearsago.”

He points to the approval of a newdrug fordryeyes,Xiidra,madebyShire,the Anglo-Irish drugmaker, which isexpected to become a blockbuster med-icine, defined as one with sales of a bil-liondollarsayearandmore.

The rise in activity has led to moredealmaking in eyecare. The past decadehas brought $20.9bn of licensing deals,where larger pharma groups buy therights to drugs developed by smallercompanies. There have been a further$12.9bn of development agreements,where drugmakers pursue a new medi-cine inpartnership, saysGBIResearch.

Among the most active companieshas been Allergan, the maker of wrinklesmoothener Botox, which has one of theworld’s biggest eyecare franchises. InAugust, the company bought ForSight,which makes a so-called periocular ring— a device that rests on the eye underthe lids. The hope is to use it to adminis-ter Lumigan, a glaucoma treatment atpresentavailableasaneyedrop.

Such a device could help combat pooradherence — patients not taking theirmedication regularly enough — which isa big obstacle to tackling glaucoma. Themajority of patients are elderly andmanyforget tousetheireyedrops.Glau-coma is expected to affect more than80m people worldwide by 2020 and hasthe potential to become one of the lead-ing causes of blindness. It might alsohelp Allergan protect its revenuesearned from Lumigan, which is antici-pated to lose patent protection in thenextdecade.

Continuedonpage3

2 ★ FINANCIAL TIMES Thursday 13 October 2016

FT Health Eyecare

M ost blockbuster medi-cines, that is to say drugswith sales of $1bn andmore a year, fall intothree categories: anti-in-

flammatory wonder drugs that treateverything from arthritis to psoriasis,cancer therapiesandtreatments fordia-betes. A fourth is becoming increasinglyimportant to “big pharma” — ophthal-mologyor,moresimply,eyecare.

Few illnesses correlate more closelywith an ageing population than eye dis-eases. By 2022, the world’s fifth best-selling drug with $7.7bn in annual reve-nues is expected to be Eylea, made byRegeneron, the large New York biotechgroup, says a recent report fromresearch group Evaluatepharma. Eyleais used to treat one of the most commoneye conditions, known as wet AMD that,with age, causes a breakdown of themacula, a small area of light-sensitivetissueat thebackof theretina.

Left untreated, wet AMD can lead to apermanent loss of central vision. Itaffects about 4 per cent of white adultsover 75, rising to 14 per cent for those of80 and over. It is less common in black,HispanicandAsianpeople.

The number of patients with AMD isset to rise steeply over the next few

decades as people live longer, says theUS National Eye Institute. It forecaststhat by 2050, the number of Americanswith the condition will have risen fromabout2min2010toalmost5.5m.

As with many new drugs, Eylea isadministered by injection. Regeneronhas been able to steal market share withthe product because it needs to beinjected only every eight weeks. Thiscompares with four for Lucentis, whichis sold in a partnership between SwisspharmagroupsNovartisandRoche.

Allergan, one of the biggest players ineyecare, is developing Abicipar, now inthe final stages of clinical testing and

with blockbuster sales potential, ana-lysts say. It might be administered asinfrequently as every three months. “Ifyou’re going to be poked in the eye, it’squite an advantage,” says David Nichol-son,Allergan’sheadofR&D.

When late-stage trials of Abiciparbegan in 2014, Allergan looked to theglobal AMD market being about $10bnby 2019. That was predicated on highprices: Eylea costs about $1,800 perinjection and Lucentis $2,000. It isunclear whether cash-strapped health-care systems will pay for such costlydrugs, especially when other, lessexpensive alternatives are at hand.

Avastin, a cancer chemotherapy madeby Roche, can be used to treat wet AMD.Since it is priced to be used in largetumour-killing quantities — and onlytiny amounts need to be injected intothe eye — it costs just $50 per averagetreatment every four weeks, says theAmericanAcademyofOphthalmology.

The UK is debating whether doctorsshould routinely use Avastin “off label”,that is to say deploying the drug to treatwet AMD even though it has never beentested or approved for the condition.The UK’s Royal College of Ophthalmolo-gists says switching from Lucentis orEylea to off-label Avastin would save the

NationalHealthService£100mayear.Allergan is best-known for its wrinkle

smoothing treatment Botox but its nexttop seller is Restasis for dry eyes. Resta-sisgenerated$1bninsales lastyear.

It too faces competition from Shire,the Anglo-Irish drugmaker which inJuly won regulatory approval for Xiidra.Unlike Restasis, Xiidra is intended notjust forpatientswhoaresufferingsymp-toms of dry eye, such as difficulty pro-ducing tears, but also for those withsigns of the condition — meaning theydo not realise they have it but are diag-nosedafterbeingexaminedbyadoctor.

Shire reckons some 16m Americansdisplay either symptoms or signs of dryeye and analysts expect Xiidra tobecome a blockbuster, in part by steal-ing share from Allergan. Andrew Baum,an analyst at Citi, forecasts peak annualsalesof$2.5bnby2030.

The biggest threat to established oph-thalmology companies may come fromsmaller companies (see article downpage). New York biotech group Ophtho-tech is developing the drug Fovista forAMD, which has been shown to providea significant improvement in visionwhen added to Lucentis. Analysts atinvestment bank Leerink say the drughas huge potential to become a “founda-tion therapy” for AMD sufferers. Recog-nising the threat, Novartis and Rochehave jointly secured rights to sales out-sidetheUSinadealworthupto$1bn.

New companies such as Spark Thera-peutics are investigating gene therapiesto stave off blindness. Such smallergroups could win a big slice of the eye-care market, which is set to grow by 10per cent a year from $13.7bn today to$26bnby2022,saysGBIResearch.

Ophthalmology closes in on the blockbustersPharmaceuticalsAs people live longer,big companies arelooking to increasinglylucrative returns,writesDavid Crow

Light sensitive:goggles cansimulate theeffect of AMD, acondition that isbecoming farmorewidespreadJohn Birdsall/Alamy

Diseases ofthe eyecorrelatecloselywith anageingpopulation

Eyecare is attracting growing interestfrom early-stage biotech entrepreneursand venture capital investors. Lastmonth, French biotech specialist Eye-vensys closed a $10m first round fund-ing, bringing total venture capital raisedby ophthalmology start-ups in the yearto date to $143m, notes online newsserviceBioWorldToday.

US funding for ophthalmology com-panies was $1.9bn in the decade from2006 to 2015, trade body BiotechnologyInnovation Organisation reports. Thatwas5percentof totalUSventure invest-ment inbiotech.

The figures do not paint a full picture,however, because companies develop-ing technologies for a number of diseaseareas have ophthalmology products intheir portfolios. Apellis, a US companyspecialising in complement inhibition, aformof immunotherapy, raised$47minFebruary. Among the uses the funds willbe put to is developing a treatment fordryage-relatedmaculardegeneration,aprecursor to wet AMD, a leading causeofvision lossamongelderlypeople.

Venture capital investors cite severalattractions of ophthalmology. Not least,eye disease is as much a part of growingold as memory loss and osteoarthritis.Biotech has developed very commer-cially successful treatments, notablyantibody drugs for controlling wetAMD, which have also been approved totreatdiabetes-relatedeyeconditions.

“The success with treating wet AMDand diabetes complications underlinedthe value of the ophthalmology

market,” says Robert Tansley at Cam-bridge Innovation Capital, Cambridgeuniversity’s venture capital fund. “Peo-plehavemademoney.”

M&A involving eyecare companieshas delivered good returns for venturecapital backers. Examples includeFovea Pharmaceuticals’ $538m sale toSanofi and ESBATech’s acquisition byAlconfor$589m.

Silicon Valley Bank cites eight merg-ers and acquisitions of ophthalmologystart-ups between 2013 and June 2016,while 11 companies completed initialpublicofferings.

Biotechs with the ambition to do sohave a reasonable chance of commer-cialising their products, argues OmarAmirana, seniorvice-presidentatAlliedMinds in Boston, Massachusetts, andchief executive of SciFluor, which isdevelopingatreatment forAMD.“Smallcompanies with good products will getsupport toget tomarket,”hesays.

In gene therapy, companies are work-ing to correct inherited eye disorders byadministering a correct copy of a faultygene, thus promoting the production ofa beneficial protein. The cells in the ret-ina are long-lasting and relatively few innumber, making the eye a good provinggroundforgenetherapy.

ViewPoint Therapeutics, headquar-tered in San Francisco, aims to providean alternative to surgery for treatingcataracts, the leading cause of visionloss and blindness. Cataracts form ascrystallins, the main structural proteinsin the lens of the eye, become unstableand aggregate, causing the lens tolose its transparency. ViewPoint is

developing eye drops that stabilise crys-tallin,preventingaggregation.

Conversely, in glaucoma the market isshifting from drugs to devices, as eyedrops are replaced with surgicallyimplanted micro stents to drain awaythe fluid that is the root cause of the dis-ease. One of the pioneers is Glaukos inCalifornia, whose iStent is designed tobe inserted during cataract surgery inglaucomasufferers.

Glaucoma, the second leading causeof vision impairment, is a progressivecondition in which a build-up of fluidincreases pressure in the eye, damagingthe optic nerve. The intention is that asingle procedure could replace decadesofdailyuseofeyedrops.

Other companies are developingextended release versions of existingglaucoma drugs. ENV515, produced byNorth Carolina-based Envisia Thera-peutics, is a nanoparticle slow releaseversion of travoprost, the active ingredi-

ent in glaucoma eye drops. The aim is tocontrol pressure within the eye for sixmonthsatatimewithasingle injection.

“In other conditions, there is anemerging interplay of therapeutics anddevices,” says Genghis Lloyd-Harris,partner at London venture capital firmAbingworth. He points to Avedro, basedin Waltham, Massachusetts, which hasdeveloped a combination treatment forkeratoconus, a progressive thinning ofthecorneathatcausesblurredvision.

The treatment involves administer-ing eye drops which, activated by expos-ing the eye to ultraviolet light, promotecross-linkingofcollagenmolecules.

The process restores the cornea’sstructural integrity and strength. Ave-dro’s combination of drug and deviceprovides very fine control over collagencross-linking. It is developing the tech-nique as a non-invasive alternative tolaser surgery in treating myopia, orshortsightedness.

Market visionaries spot promise in fading powers of sightBiotech

Attractions grow for early-stage entrepreneurs andventure capital investors,writes Nuala Moran

Although our understanding of thenature of sight is advancing, some bigmysteries still need to be unravelled.Recognising everyday objects such aschairs and tables is child's play forhumans. Computer vision experts,meanwhile, struggle to build machineswiththesameabilities.

While the function of the eye —among the body’s most complex organs— is to supply data on the visual envi-ronment to the brain, the capture oflight and its conversion into electricalsignals is just the first step in a longsequence of computations that resultsinourseeingcolourorrecognising faces.

The interpretation of the eye’s “datastream” occurs in the intricate circuitryof the brain. At a broad level, this cir-cuitry is quite well understood. Thebrain is subdivided into distinct lobes.The occipital lobe (one of four in the pri-mate brain) and a substantial part of thetemporal lobe serve vision. These aretiled with more than 30 smaller brainareas, each of which is thought to con-tribute a distinct set of computationsthat transform information for the nextstageofprocessing.

A recent study based on datafrom the Human Connectome Projecthas provided a map of these areas in

exquisite detail that goes beyond justthebrain’svisualareas.

At a smaller scale, though, much lessis known about the computations in thenetworks of neurons that ultimatelycauseoursensations.

This is partly because the problem thebrain needs to solve is ill-defined. Thedata coming to it from the eyes are lim-ited by the biological process that con-verts light into electrical signals.Humans can only, for instance, makeuse of light in a relatively limited part ofthespectrum.

Eyes-to-brain data are also ambigu-ous, since many different states of theworld can give rise to the same sensoryinformation. For example, the eyes cancapture only two-dimensional repre-sentationsof the3Dworld.

Large numbers of scientists and agreat diversity of approaches areengaged in solving the puzzle of how thebrain converts the deluge of data arriv-ing from our eyes into a sense of sight.The annual meeting of the US Societyfor Neuroscience, for example, attractssome30,000attendees.

The toolkit available to neuroscien-tists — to address questions from themolecular level up to the behaviour ofcircuits of brain cells, and even thewholeorganism—israpidlyexpanding.

At the microscopic scale, the recentdevelopment of optogenetics hasenabled scientists to control the activityof individual neurons by shininglight directly on to them, in effect pro-viding an experimental on-off switch.This allows researchers to silence spe-cific neuron populations in order to

understand their role in shaping sensa-tionandperception.

The potential of the technique totransform neuroscience has been recog-nised by — among others — the award ofthe prestigious Brain Prize for outstand-ing research by neuroscientists by theDanish industrial foundation, Lund-beckfonden.

These tools are both useful for under-standing the functioning of healthy vis-ual systems and in detecting what is dis-rupted after trauma or stroke, cases ofneurodegenerativedisease,orbyabnor-maldevelopment.

A hugely versatile set of techniquesbased on magnetic resonance imaging(MRI) allows scientists to measure theanatomy and function and even local-ised chemical changes in brain tissue.This has enabled them to tackle ques-tions at the macroscopic scale, namelywhere objects are visible with the nakedeye. To track tiny electromagneticchanges outside the skull caused by theactivity of neurons with millisecondaccuracy, scientists can now use magne-toencephalography,orMEG.

Such techniques permit a “lookinside” the human brain while partici-pants perform various cognitive tasks.By picking the right set of experimentalquestions, neuroscientists hope to puttogetherthepuzzleonepieceatatime.

With glaucoma, theaim is to treat thebuild-up of fluidand pressure in theeye with farsimpler procedures

Doors of perceptionremain concealed inbrain of beholderScience

Neurologists scratch theirheads on how we convertthe data deluge from oureyes, writes Denis Schluppeck

Eyes may well be windows to the soul,though it turns out that they tell usplentyaboutourbodies, too.

The eye affords early indications ofthe onset of conditions such as diabetesand cardiovascular disease. Someexperts argue for more regular eyeexaminations as a tool in preventivehealthcare.

The advantage of the eye in diagnos-ing disease is, simply, that it is open toview. Assessing blood vessels or nervefibres elsewhere in the body wouldrequireaninvasiveprocedure.

“There are very few places where youcan directly observe blood vesselsbecause we’re covered in a skin,” saysChristopher Owen, professor of epide-miology at the Population HealthResearch Institute at St George’s, Uni-versity of London. “You can do it in thefingernails but it’s not as easy as taking apictureof thebackof theeye.”

The technology is rapidly improving.For example, digital retinal camerasdeveloped by Japanese company Canon,that eliminate the need for bright lightsanddilatingeyedrops,haveincreasedinsensor resolution from 3 megapixels in2003 to 20 megapixels today. “Thatallows the doctor to zoom up on thatimage,” says Tom Russo, regional salesmanager in Canon’s US healthcare divi-sion.

Canon has developed software filters

that clean up the retinal images of cata-ract sufferers and elderly people whoseeye lenses commonly become yelloweras they age. “The technology hasevolvedfordecadesandit’sonlygoingtogetbetter,”saysMrRusso.

Being able to obtain clear and detailedimages of blood vessels or nerve fibrescreates the potential for faster, moreconvenient non-invasive health teststhat yield insights into the developmentofawiderangeofdiseases.

Prof Owen and his University of Lon-don team are looking at how the shapeand size of retinal vessels may relate toheart disease and diabetes. Using soft-ware that the institute developed, theteam is analysing thousands of imagesfrom participants in UK Biobank, aresearch charity that has recruited500,000 volunteers for a project thataims to improve the prevention, diagno-sisandtreatmentofserious illnesses.

With UK Biobank data, the university

is exploring whether changes observedin retinal vessels are occurring beforethe onset of disease, allowing earlydetection and chances for prevention.“Those retinal eye vessels are part of thevesselsof thebody,”ProfOwennotes. “Ifwe can look at those directly, it mightgive us clues as to what’s happening tovessels elsewhere in the body — that’swhy it’s considered a potential markerofsystemicdisease.”

Eye scans might be used to detectearly stages of Alzheimer’s. Researchers

at Moorfields Eye Hospital and the UCLInstitute of Ophthalmology in Londonhave found a link between thinning ofthe retinal nerve and poor cognitiveability, a sign of early stages of this formofdementia.

Beyond the retina, other eye abnor-malities can indicate the start of life-threatening illness, says Kausik Ray,professor of public health at ImperialCollege School of Public Health in Lon-don. Drooping eyelids could indicate aneuromuscular disorder in someonewhose only symptom is fatigue. “Itmightbeasubtle sign,but theonly thingyousee,”hesays.

An eyeball turned in slightly towardsthe nose might, he adds, indicate a braintumour, which stretches the nerve con-necting to it. Double vision possiblyindicates a brain tumour, which causesincreasedintracranialpressure.

Optometrists could play a key role.“You could go to a high street optome-trist, getan imageofyoureyesentoff foranalysis or preferably analysed thereand then,” says Prof Owen. In combina-tion with data such as body mass index,blood pressure and age “we could betterdiscernthose likelytodevelopdisease.”

The barrier to going to an optometristfor broader advice is not cost or absenceof technology but lack of knowledge ofwhat is available. “Most people go tothese places because their glasses arebroken or they’re having difficulty see-ing,” Prof Owen adds. “We need to raiseawarenessamongthegeneralpublic.”

Eye tests as a routine preventivescreen might not just save lives, but alsohuge sums of money for health servicesby catching diseases before they haveprogressed. “That’s what we should bethinking about,” says Prof Ray. “Other-wise it’samissedopportunity.”

Windows to the soul shed lighton our broader state of healthDiagnostics

Regular screening has animportant part to play as atool in preventive care,reports Sarah Murray

The eye: a most complex organ

‘A high street optometristcould get an image of youreye sent off for analysis’

Thursday 13 October 2016 ★ FINANCIAL TIMES 3

FT Health Eyecare

Large companies are not alone inleading the charge. As with other areasof the industry, it is often smaller bio-tech groups that are developing themost exciting treatments. Shares inAerie Pharmaceuticals, which is testinga glaucoma treatment, have jumped bymore than 200 per cent in the past sixmonths, after success in clinical trialspavedthewayforAerie toseekapprovalfor Roclatan. When added to anotherdrug, Latanoprost, Roclatan reducesthe pressure caused by glaucoma, whichcanleadtoblindness if leftunchecked.

Perhaps the most exciting area of eye-care is the emerging field of gene ther-apy, whereby genetic material isinserted directly into a person’s cells inorder to treat or prevent a disease. Theeye is “an almost perfect target for genetherapy”, Dr Gilly says. “We are bornwith a pool of retina cells that are notrenewed in our lifetimes. So when youtransfer genes into those cells they willprobably last for the rest of our lives —and it is quite easy to inject geneticmaterialdirectly intotheeye.”

GenSight Biologics has just started alate-stage clinical trial of a drug forLeber’s hereditary optic neuropathy,which affects people aged between 15and 25. It is a brutal, sudden diseasecausing vision loss in both eyes, with a98 per cent probability that suffererswill experience complete loss of visionwithin a year. It affects more than 1,400people a year in Europe and the US. In asmaller study, GenSight proved the drugcould restore vision to the extent thatpatients were able to read three lines of

previously illegible letters on a chartsimilar tothatusedbymostopticians.

Such an improvement in letter read-ing is the gold standard for companiesaiming to secure approval for drugs forvision loss but some believe it is notideal for people with severe forms ofblindness. For many of these patients,the ability to make out objects and col-ours, and to avoid bumping into things,would be a life-altering improvement.The US Food and Drug Administrationhas therefore recently approved somemorecreativeclinical trialdesigns.

Spark Therapeutics, a US companydeveloping gene therapies, is testing atreatment for a rare retinal disorder in alate-stage clinical trial. Rather than let-tersonachart, itusesa functionalvisiontest where people are asked to maketheir way around a maze without walk-ing intovariousobjects.

Big questions remain about the long-termsuccessofgenetherapiesandthereare signs that their effectiveness mayfade after several months. Yet somelarge pharma groups appear ready todip their toes in the water. Allerganrecentlypaid$60mtobuyRetroSense,asmall gene therapy group that aims torestore light sensitivity to people with thediseaseretinitispigmentosa.

Continued frompage1

ContributorsDavid CrowFT senior US business correspondent

Denis SchluppeckUniversity of Nottingham associateprofessor (neuroscience and vision)

Sarah MurrayFreelance journalist

Nuala MoranFreelance science journalist

Madhumita MurgiaFT European technology correspondent

Clive CooksonFT science editor

Andrew JackFT head of curated content

Brian GroomFreelance journalist and former FT UKbusiness and employment editor

Steven BirdDesigner

Alan KnoxPicture editor

Peter ChapmanCommissioning editor

Advertising details care of Ian Edwards,+44 020 7873 3272, ian.edwards@ft.comor your usual FT representative.

Drugmakersrespond tohuge need fortreatments

8mBy 2050, numberof people in USexpected to suffervisual impairment

80mBy 2020, numberof people in theworld expected tohave glaucoma

The eye is a tempting target forresearchers developing innovativestem cell and gene therapies. It is small,easily accessible, biologically wellunderstood and transparent, so theeffect of treatment can be evaluatednon-invasively.

It isalso“immuneprivileged”tosomeextent, meaning genetically differentcells are less likely to be rejected than inmost other tissues. Since we have twoeyes, furthermore, the ophthalmologistcan carry out a procedure on one whileleaving the other untreated as a basis forcomparison.

A growing need exists for better treat-ments. Millions of people worldwidehave lost some or all of their sightthrough diseases ranging from the com-mon age-related macular degeneration(AMD) and diabetic retinopathy to ahostofraregeneticconditions.

The Cell and Gene Therapy Catapult,set up by the UK government to pro-mote the technology, says ophthalmol-ogy is the most popular field for pre-clinical cell and gene therapy research,accounting for14outof60UKstudies inall areas. These experimental therapiesare judged to be three years or less fromstartingclinical trials inpatients.

Six cell and gene therapies for the eyeare already in the clinic in the UK out ofa total of 57 trials, making ophthalmol-ogy the third most popular area for clin-

ical studybehindcancerandneurology.Cell therapy involves the injection of

newcells torepopulatearetinadepletedby disease. Gene therapy aims to restorethe function of existing cells by correct-inggeneticdefects.

No ophthalmic gene or stem cell ther-apy has yet received full marketingapproval anywhere in the world. Mostadvanced, says a recent review byresearchers at the University of Massa-chusetts, is Spark Therapeutics based inPhiladelphia. Spark’s lead producttreats Leber’s congenital amaurosis 2(LCA2), a form of retinal degenerationcaused by a defect in a gene calledRPE65. It uses adeno-associated virus(AAV), which infects humans withoutcausing disease, to carry a functioningcopyof theRPE65gene intoretinalcells.

If the final phase of clinical trials con-firms the improvements shown in ear-lier patients, the RPE65 product couldbe approved and launched in 2017. It “is

expected to become the first approvedgene therapy product [of any sort] inthe US, marking a pivotal step for theentire gene therapy field”, notes theUniversityofMassachusettsreview.

While Spark is developing gene ther-apy for the liver and central nervoussystem as well as the eye, NightstaRx, aUKbiotechcompanyspunoutofOxforduniversity in2014,concentratesonoph-

thalmology. It, too, uses AAV, the mostpopular vector for gene therapy, tocarry a correct copy of a defective geneintoretinalcells.

London-based NightstaRx’s leadproduct delivers a type of the REP1 geneto treat choroideremia, an inheritedform of progressive blindness. A studyof six patients, published this year in theNew England Journal of Medicine,found that the therapy maintained orimproved vision in the treated eye whilethe untreated eye continued to deterio-rate.

Thecommercialappealofophthalmicgene therapy was shown last monthwhen Allergan, the Dublin-based phar-maceutical group, bought RetroSenseTherapeutics, a private Michigan com-pany, for $60m cash and the promise offuturemilestonepayments.

RetroSense is pioneering the clinicalapplication of optogenetics — makingcells in the eye sensitive to light. Its RST-001 experimental therapy delivers theChR2genetomakeretinalganglioncellsrespond to light, compensating for theloss of natural photoreceptor cells indegenerative eye disease. The approachis being tested on patients with retinitispigmentosa, which affects some100,000people intheUS.

Cell therapy has attracted more pub-lic attention than gene therapy for theeye, because stem cells — and embry-onic stem cells in particular — are morenewsworthy than genetic vectors, eventhough far fewer patients have receivedtheminclinical trials.

An early stem cell pioneer wasAdvanced Cell Technology of the US. Itchanged its name in 2014 to Ocata andwas acquired in February 2016 by Astel-las, the Japanese pharmaceuticals

group, which is continuing its ophthal-micprogrammeonafairlysmall scale.

In the UK, the London Project to CureBlindness launched a clinical trial inSeptember 2015 of a stem cell treatmentfor wet AMD at Moorfields Hospital in apartnership with the UCL Institute ofOphthalmology and Pfizer, the US drugcompany. Patches of new retinal pig-ment epithelial (RPE) cells, derivedfrom embryonic stem cells, have beentransplanted into the eyes of twopatients toreplacethose lost inAMD.

Professor Pete Coffey of UniversityCollege London, co-leader of theproject, says clinical results from thefirst two patients will be published soonand he hopes the trial will be extendedto ten people, as originally planned.

Pfizer says more cautiously that thereare “no current plans to enrol additionalpatients inthis trial”.

The next UK clinical trial of ophthal-mic cell therapy may come from Profes-sor Alan Stitt at Queen’s University Bel-fast, working with the Cell and GeneTherapy Catapult and Scottish BloodTransfusion Service. His team is gener-ating “endothelial progenitor cells”from umbilical cord blood. These wouldrestore the vasculature (network ofblood vessels) within the retina, whichgoeswrong in ischemiceyedisease.

“In ophthalmology we need to moveon from trying to treat end-stage dis-ease,” says Prof Stitt. “We want to usethese new therapies to treat earlier andbetter, topreventblindness.”

Pioneering techniques leaddrive to prevent blindnessCell and gene research

Clinical trials ofexperimental therapies arealready under way inpatients, writes Clive Cookson

Optogenetics: tests offer hope to thousands of people —Getty Images/Science Photo Library RM

‘In ophthalmologywe needtomove on from trying totreat end-stage diseaseand treat earlier and better’

A t 81 years of age, Britishpensioner Ray Flynn cansee with his eyes closed.Last year, the former fac-tory supervisor from Man-

chesterwasalmostcompletelyblindbutthis summer he became the first personto receive a bionic eye implant to restorehis lost vision — without the need for hisowneyes.

Mr Flynn was diagnosed eight yearsago with age-related macular degenera-tion. AMD results in the total loss of cen-tral vision and affects half a million peo-ple in Britain. He could only see out ofthe corner of his eyes and was unable toget on with activities like weeding hisgardenorwatchingfootball.

He recently had a £150,000 artificialretina implanted, which receivesimages from a miniature cameramounted on special glasses. The pic-tures are transformed into electricalpulses that are sent wirelessly to a chipattachedtothebackof theretina.

This stimulates his working retinalcells, which send a message to the brain.Because the camera and implant act ashis eyes, this means he can see outlinesof images even with his own eyes closed.With time, he can train his brain tointerpret the imagesmoreclearly.

The implant, known as Argus II andmanufactured by US company SecondSight, is one of a range of innovationsthat are helping doctors restore vision.Argus II has been implanted in morethan 150 patients across the US andEuropewhohavetherare inheritedcon-ditionofretinitispigmentosa.

A system developed by Monash Uni-versityscientists inAustraliacanbypassthe eye completely. An external camerafeeds image information directly to thebrain via a neural chip, using a technol-ogy potentially able to help more than80 per cent of clinically blind people tosee visual outlines or patterns. A firsthumanimplant isexpectedthisyear.

Digital developments to treat blind-ness are not just happening in well-funded laboratories in wealthier regionsof the world. Hubs of innovation exist indevelopingcountriessuchas India.

At the LV Prasad Eye Institute in

Hyderabad nearly 15m people havebeen treated for serious eye conditions,halfof themfreeofcharge. It is responsi-ble for research on pioneering ways toimprove vision, including 3D printedeyes, grow-your-own cornea techniquesand bionic implants. The institute runsthe largest eye bank in Asia, implantingmore than 40,000 corneas a year fromorgandonors.

“What is unique about our network ofhospitals is we try to treat all patientsthat need us, irrespective of whetherthey can pay or not,” says VirenderSangwan, director of LV Prasad’s stemcell centre and innovation labs. “Wedevelop technologies so our treatmentscan be scaled up to provide access inruralpartsof India.”

Dr Sangwan’s team focuses on cornealblindness, a cluster of conditions thataffectabout12mpeopleglobally,aquar-ter of them in India. Although trans-planting donor corneas is the moststraightforwardmethod, it isdependenton having a steady supply of healthyhuman corneas, donated by people whohaverecentlydied.

“Bio-synthetic cornea will eliminatethe supply-side problem,” Dr Sangwanadds. “If we can create artificial corneas,that will significantly improve the livesof millions.” He is collaborating withresearchers at Sweden’s Linköping uni-versity to design a new material, similarto human collagen, that is cheap andeasy to synthesise in a lab. The materialwill be used to create artificial corneasand has been tested in animals. It startshumantrials inearly2017.

The corneas could ultimately beassembled by 3D printers. Dr Sangwansays his institute is in talks with printingpioneers such as Pandorum, a Banga-lore-based start-up specialising in 3Dprintingofhumantissuessuchas livers.

Beyond implants, companies such asGoogle, Samsung and Intel are workingon designs for smart, connected contactlenses. Google’s life sciences arm Verily,in partnership with Swiss multinationalNovartis, plans to test a prototype onhumans this year. This lens is supposedto correct vision in people with presbyo-pia, or age-related farsightedness, help-

ing them focus between long- and short-rangevision.

This year, Columbia University scien-tists found that smart contact lenses,from Swiss company Sensimed, werethe best clinical tool to measure pro-gression of glaucoma. Sensors in thelenses can detect changes in the eye’sinternal pressure over an extendedtime, rather than just by way of a snap-shot measurement when a patientcomes in for a visit, as users wear themcontinuously. This gives clinicians cluesas to how fast the glaucoma is develop-

ing. “With this device we can see thechanges that occur over 24 hours, whichis the best clinical predictor of progres-sion,” saysGustavoDeMoraes, associateophthalmologyprofessoratColumbia.

Eventually we may even be able toexploit digital implants in eyes thatnever tire and connect to smartphones.Google filed a patent this year for aninjectable artificial lens with sensorsthat enhance sight and stream data.Conceivably, it would enable us to readelectronic bar codes and sense irritatingallergens,allowingtimelytreatment.

Implants pointway to livinglife with youreyes closedTechnologyA range of innovations is helpingdoctors restore vision, reportsMadhumitaMurgia

‘If we can create artificialcorneas, it will improve thelives ofmillions’

The surgery is fiddly. Making tiny, precise incisions in theinside of the eye requires extreme skill. Surgeons need toslow down their pulse and time movements between heartbeats to avoid the smallest of hand tremors. Today, lasers arethe most frequently used technology in surgeries rangingfrom cataract operations to corrective vision procedures.

Among the most sophisticated is the ultrafast femtosecondlaser. It is used as an alternative to other manual techniquesin the tearing of the eye’s lens capsule in cataract surgery, orcutting a corneal flap during so-called Lasik eye surgery.Surgical methods that involve lasers are also being improvedto provide better control. A 3D visualisation system, designedby Novartis subsidiary Alcon, helps guide surgeons throughthe procedures of retinal operations.

Florida-based Lensar’s laser is used for corneal incisionsand cataract operations. Lensar says it uses augmented

reality, similar to the Pokémon Go game that overlayscharacters on to the real world, to reconstruct a detailed 3Dmodel of the anatomy of each patient’s eye to help inpreparation for operations.

The first robotic operation inside the eye took placerecently at the University of Oxford’s John Radcliffe Hospital.Once robotic surgery was not feasible at the microscopic levelrequired but, in September, Oxford surgeons used a remotelycontrolled robot to lift a membrane 100th of a millimetre thickfrom the retina at the back of a patient’s right eye.

To counter the surgeon’s tremors, the operation took placethrough a hole less than 1mm in diameter. Dutch companyPreceyes built the robot, the like of which may in the futurehelp speed up cataract surgery and perform tasks thathuman hands cannot do, such as injecting drugs or stem cellsinto retinal veins, which are thinner than human hair. MM

Surgical equipment Lasers are with us, robots on their way

Bionic man: Ray Flynn of Manchester was the first person to undergo this type of surgery—Peter Byrne/PA Images

4 ★ FINANCIAL TIMES Thursday 13 October 2016

The amount of time people spend look-ing at screens has grown dramatically,from using computers at work to watch-ing television at home and being gluedto a smartphone or tablet most of theday. It is a wonder how little trouble thisappears tobecausingoureyes.

The number of people complaining oftired, dry or sore eyes — some optome-trists call this “digital eye strain” or“computer vision syndrome” — hasrisen but experts note that little reliableevidenceexistsof longer-termdamage.

While smartphone and tablet use hasgreatly increased the average person’sexposure, says Chris Hammond, oph-thalmology professor at King’s CollegeLondon, “we are not seeing any epidem-icsofeyeproblemsrelatedtothat”.

Hedoes, though, recommendlimitingchildren’s screen use because the phe-nomenon of pre-school children spend-ing hours on phones and tablets isrecentandeffectsareunknown.

Globally, a 16-45-year old typicallyspends 418 minutes — two minutesshort of seven hours — a day looking atscreens, say researchers MillwardBrown (see graphic). This compriseswatching television, using the interneton a laptop or personal computer andviewingsmartphonesandtablets.

Smartphones have become theworld’s largest screen medium. Com-bining smartphone minutes with tabletuse, mobile devices account for nearlyhalfofall screentime.

In many cases, people may spendlonger on screens than they do sleeping.Figures range from 317 minutes in Italyto 540 in Indonesia. The average USuser clocks up 444 minutes (480 inChina,411 intheUK).

One concern has been the effect ofhigh-energy visible light — “blue light”— emitted by devices. Laboratory stud-ies suggest that high levels of exposurecandamageretinatissue.ButProfHam-mond, who sits on the scientific com-mittee of the Royal College of Ophthal-mologists, says there is no evidence thatlow levels of blue light are harmful:

“The energy level emitted by phonesand iPads is extremely small. Even on agrey day outside, your blue light expo-sure issomething like30-foldmorethanlookingatatabletorascreen.”

Some evidence does show that usingscreens before going to bed disrupts thecircadian cycle, or sleep-wake cycle,since blue light inhibits release of mela-tonin, the hormone that makes us sleep.Daniel Hardiman-McCartney, clinicaladviser at the UK’s College of Optome-trists, advises people not to use devicesforanhourbeforetheygotobed.

Another concern is myopia amongchildren. A big increase in short-sight-edness has emerged particularly inurban east Asia where children spend alot of time reading and little time out-doors. Research results this year fromthe UK College of Optometrists and Uni-versity of Ulster say 16.4 per cent ofUK children are myopic, compared with7.2percent inthe1960s.

Studies in Australia and the US

indicate that spending time outdoorsprotects children against myopia.Some people suggest there may be alink between the condition and close-upwork, though that could apply tobooksaswellasscreens.ProfHammondsays close-up work seems not to be

the problem because indoor activity insports halls does not protect childreneither,whereasoutdooractivitydoes.

That leaves eye strain as the mostcommon problem. Some 50-90 per centofpeoplewhoworkatcomputerscreenshave symptoms of “digital eye strain”,say studies. This can include dry, soreeyes,headachesorblurredvision.

“We are now spending the vast major-ity of our day looking at things less thana metre away,” says Mr Hardiman-McCartney. “Our eyes are not designedtofocusthatclose.”

Even a small defect in vision can leadto strain as the eyes seek to compensate.If your eyes do not work well together,looking at a screen all day can causeheadaches. People also tend to blinkincompletely when they stare at ascreen,whichcanleadtodryness.

Productivity may be affected if eyestrain causes workers to read moreslowly or make errors. Research by theUniversity of Alabama at Birmingham’sSchool of Optometry has suggested thatuncorrected vision problems couldreduceworkratebyupto29percent.

Optometrists recommend frequentbreaks or the 20-20-20 rule: every20 minutes, look 20ft away (6m) for20 seconds to give your eye musclesa break. Also, they say, make sure totakefullblinks.

Mr Hardiman-McCartney sayspeople need to sit upright at screenswith eyes looking down at about45 degrees, adjust brightness to the low-est level at which they can see a screenclearly and use a text size large enoughto read. They should also have regulareyetests.

Think how you blink andother tips for the digital ageVision syndrome

Many people spend moretime staring at devices suchas smartphones, laptops andtablets than they dosleeping, writes Brian Groom

FT Health Eyecare

R oy Vagelos remembers thethrill in the 1980s when hesaw test results of his com-pany’s prototype drugagainst river blindness and

the parasitic worm, Onchocerca volvu-lus, that causes pain, scarring and blind-ness in hundreds of thousands of peopleacross Africa and Central and SouthAmerica.

Scientists at Merck led by WilliamCampbell — who last year shared theNobel Prize for medicine for the work —showed that a variant of avermectin, adrug originally developed to combatparasites in dogs, could prove effectivein tackling onchocerciasis in humans.Under Mr Vagelos, who from the posi-tion of head of research had beenappointed Merck’s chief executive, thecompany would launch a programme todonate as much of the drug as wasrequiredforas longasnecessary.

“It was one of the most excitingresults we had ever seen,” Mr Vagelosrecalls, looking back on his time atMerck. “I was a physician who switchedto basic research, then drug discovery,as a way to close the loop to get impor-tant new drugs to treat people beyondthe normal small groups a doctor canhelp.”

Yet more than three decades afterMerck began its programme, the bur-den of the disease remains heavy, rais-ing questions about whether interna-tional goals for its elimination by 2025arerealistic.

Little doubt exists about the contin-ued need for the drug, called ivermectinor Mectizan, or some improved versionof it. Onchocerciasis affects an esti-mated37mpeople,nearlyall inAfrica.

It occurs close to fast-flowing rivers,breeding grounds for blackflies whose

bites transmit the worms. These growinto adults (macrofilariae) in humansand cluster in nodules, where they pro-duce large quantities of young worms(microfilariae) some of which are trans-mittedbackintoflies.

Themicrofilariaecauseinflammationleading to severe itching, loss of visionand sometimes epilepsy and prematuredeath. The stigma of the disease forcesinfected people to emigrate from fertilelandandcutsproductivity.

Large-scale programmes to sprayinsecticides to kill the flies in the 1970shad some success but lost momentum.In the absence of government funding,Merck has donated treatments since1987 — 176m last year — and has pro-vided an average additional $5m annu-ally tohelpwithdelivery.

In South and Central America, effortsto eliminate the disease have provedsuccessful everywhere except a stretchof the Amazon between Brazil and Ven-

ezuela. In Africa, progress has been farslower and concentrated instead oncontrol of the disease. Sharp reductionsin the disease’s burden have beenrecordedinNigerandMalawi.

One measure required is to raise thefrequency of Mectizan use across Africafrom once to twice or even four times ayear. “The time is now,” says FrankRichardsof theCarterCentre—thenon-profit founded by former US PresidentJimmy Carter and his wife Rosalynn —and a veteran of the treatment pro-grammes.

AlthoughMectizan isgenerallysafe, itis dangerous to patients in some parts ofAfrica who are infected with the diseaseloa loa, commonly known as “eyeworm”. Given that some evidence existsof emerging resistance to the treatment,scientistsareseekingnewdrugs.

“Mectizan has been phenomenallysuccessful, hugely reducing the burdenand saving the sight of millions,” saysRobert Don from the Drugs forNeglected Diseases Initiative, a charityinvolved in several research pro-grammes. But, he adds, “we need a tool-boxof improveddrugs,diagnostics, san-itationandvectorcontrol.”

Supplies of Mectizan are vulnerableto such as “distributor fatigue” amongthe largely unpaid community volun-teers who administer drugs to local peo-ple. Capacity and expertise to kill theinsects is limited. Civil wars and otherpolitical unrest reduce opportunities tofight thedisease inseveralcountries.

The extent of the World HealthOrganisation’s support prompts somescepticism. Last year, its programme foronchocerciasis control was abolished.The Expanded Special Project for Elimi-nation of Neglected Tropical Diseasesthat replaced it has a remit far beyondriverblindnessandless funding.

“When demand is there, supply hasalways been, too,” says Ken Gustavsen,who runs Merck’s Mectizan donationprogramme for both onchocerciasis andlymphatic filariasis, which also uses thedrug incombinationwithothers. “We’restill aiming for onchocerciasis elimina-tionbyabout2025.”

“We need more flexible approaches,”Mr Richards cautions. “These parasiteswant to play the long game. They waitforustotire.”

River blindness parasites ‘play long game’AidA campaign toeliminate the diseasehas scored significantsuccess in LatinAmerica, while Africacontinues to carry aheavy burden,reportsAndrew Jack

Treatment:organisers lookto conquer riverblindness inAfrica and LatinAmerica over thenext decade—KayHinton/Tom Saater/PeterDiCampo

‘Mectizan has beenphenomenally successful,saving the sight ofmillions’

Daily screen use

Source: MillwardBrown

In minutes

˜°˛ ˜˜˝ ˜˙ˆ ˇ˙

Smartphone TV Laptop Tablet

Total: °˜ˆ(two minutes short of seven hours)

‘We now spend the vastmajority of our day lookingat things less than onemetre away’