Forty years ago, Research to Prevent Blindness (RPB)

published a comprehensivestudy of the state of visionresearch in the United States,“Ophthalmic Research: U.S.A.”

We had already committed, asan organization, to stimulate anintensive research assault on eyedisease. The findings containedin that survey clarified the frontson which we were to wage thatbattle. In the following years, RPBshaped Congressional testimonythat led to the creation of theNational Eye Institute.We assistedin raising capital for new labora-tory space in institutions acrossthe country and, perhaps mostimportant, stimulated the creation of many departmentsof ophthalmology.Today, RPB plays a pivotal role in the partnership of vision

Advances in the Preservation of Vision and the Restoration of Sight

researchers, doctors, serviceproviders and educators whosegoal is to treat and eliminatevision loss and eye disease.We support bench-to-bedsidediscoveries, providing unrestrict-ed funds to departments ofophthalmology and to visionresearchers at every stage oftheir careers. This approach,true to the intention of ourfounder, Jules Stein, encouragesthe pursuit of potentially revolutionary treatments anddiagnostic tools for eye disease.

In 2004, RPB vigorously contin-ued to fulfill its mission. Wefunded 50 departments of oph-thalmology, and 185 individualophthalmic scientists receivedRPB grant support. But our visionfor the science of ophthalmologydoes not end in the lab.

“It is the purpose of the Trusteesto create in RPB an organizationthat will act as a catalyst betweenthe ophthalmologic researcherand all available sources of finan-cial support.”

– From “Ophthalmic Research: U.S.A.”

“Support of eye research is not charity—it is an investmentthat will pay dividends manytimes over.”

Jules Stein, M.D.,Founder, Research to Prevent Blindness

We will continue to catalyze eyeresearch wherever we can beeffective: by attracting the bestand brightest individuals tocareers in the field; by hostinginterdisciplinary research semi-nars; and by translating researchinto lay terms, making it accessi-ble to doctors and patients for amore informed dialogue onhealth care.Jules Stein once said,“The role ofthe catalyst […] must reach deepinto the private sector of our soci-ety, seeking out individuals, corpo-rations and foundations that havenot only the capacity for financialsupport, but also the interest tomake that support effective.”In the following pages you willlearn about recent, promisingdiscoveries we have been proudto support. We invite you to readon… and to become interested.

Research to Prevent Blindness645 Madison Avenue, New York, NY 10022-1010

Jules Stein, M.D., Founder (1896-1981)

OfficersDavid F. Weeks, ChairmanDiane S. Swift, President

Jean Stein, Vice President & SecretaryRichard E. Baker, Treasurer

Board of Trustees* Robert H. Ahmanson

* Richard E. BakerGavin S. Herbert, Sr.

Richard G. HewittJohn Kusmiersky

Sidney J. SheinbergHerbert J. Siegel

* Jean SteinDiane S. Swift

Katrina vanden HeuvelCasey Wasserman * David F. Weeks

* Members of the Executive Committee

James V. Romano, Chief Operating Officer

Matthew Levine, Director of Communications and Marketing

Condon O’Meara McGinty & Donnelly LLP, Auditors

Mary Elizabeth Hartnett, M.D.,an RPB Physician-Scientist (see p. 31),provides fresh media to culturedhuman choroidal endothelial cells.

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Advances In Vision Research

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An estimated 1.75 million Americans over age40 have decreased vision from AMD. Thatnumber is expected to go up to 3 million by2020. AMD is the leading cause of functionalblindness in Americans over 65.

The rising tide of blinding eyedisorders can be measured

across many dimensions. Forinstance, in 1963, providing care for people blind from eye diseasecost the nation $1 billion. In 2003,visual disorders and disabilitiescost the U.S. $68 billion. Or, today,20.5 million Americans over 40have cataract in either eye; basedon current trends, by 2020, thatnumber will jump to 30.1 million.

The following section containsresearch highlights from the reportsof hundreds of RPB-supportedvision scientists throughout the U.S. who are pursuing areas of basicand clinical research in an all-outattempt to reverse this rise. In 2004,more than one thousand publishedscientific studies cited RPB support.A complete bibliography of these studies can be found atwww.rpbusa.org/library.php.

Age-Related MacularDegeneration (AMD)The macula is a tiny area of theretina that allows clear centralvision. The dry form of AMD ischaracterized by a slow breakdownof photoreceptor cells (rods andcones). The less common wet formcauses about 90 percent of thecases of severe visual impairmentand is characterized by the growthof abnormal blood vessels thatleak and sometimes cause suddenvision loss.

Studies indicate that, after aging,smoking is the most significantrisk factor for AMD. A diet low in

fruits and vegetables increasesAMD risk, but nutritional supple-ments with high levels of antioxi-dants, such as lutein, zeanthaninand zinc reduce the risk ofadvanced AMD by about 25 per-cent. They cannot, however, reversethe disease or restore lost vision.

AMD research highlightsDoes cataract surgery lead to AMD?An RPB-supported study indicatesthat cataract patients who have hadtheir natural lens replaced with aconventional intraocular lens (IOL)will increase the amount of poten-tially harmful blue light that is trans-mitted to the retina. Other studieshave already shown a significantincrease in patients who develop thewet form of AMD within a year ofcataract surgery. The researcherssuggest that those at risk for AMDwear glasses that block blue light. Y

Statins (cholesterol-lowering drugs)and aspirin may protect older peo-ple from developing wet AMD,according to a study by RPB-fundedresearchers. Patients already taking

Macugen and Other Hopeful Treatments for AMDMacugen, a treatment for wet AMD that wasapproved by the Food and Drug Administration inDecember 2004, is bringing new hope to thosealready suffering from the disease and the almost onemillion people over the age of 55 years in the U.S. whoare expected to develop AMD across the next fiveyears. Studies have shown that Macugen reduces therisk of progression to legal blindness and promotesstability of vision.

Macugen, which is injected into the vitreous of theeye, inhibits the activity of the substance in the bodycalled Vascular Endothelial Growth Factor 165. VEGF165 is responsible for the growth of only the leaky newblood vessels in the wet (or neovascular) form of AMD.Macugen does not affect the other forms of VEGF necessary for normal capillary growth.

Scientists supported by grants from RPB were amongthe first to study the role of VEGF and VEGF-blockingdrugs. Their inquiries formed the basis for the develop-ment and clinical trials of anti-VEGF therapies. OtherRPB researchers are studying approaches using RNAinhibitors (RNAi). Instead of blocking the action of VEGF,RNA inhibitors prevent VEGF from being formed at all.

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statins were half as likely as thosewithout statins to develop wetAMD; patients already on aspirinwere about 40 percent less likely to develop leaky, new blood vesselgrowth, the complicating symptomof the disease. Other RPB-fundedresearch has found that statins mayalso reduce the risk of developingopen-angle glaucoma. Y

Early data from RPB-funded studiesshow most fats may contribute toAMD, but that fish oils and certainnut oils may reduce risk.Y

One of the most effective AMDtreatments, photodynamic therapy(PDT), seals leaky blood vessels butcan also damage areas of the nearby retina and cause somevision loss. A recent, RPB-supportedstudy shows that adding a neuro-protective, brain-derived agent canprotect photoreceptor cells andimprove PDT outcomes. Y

An RPB Career Developmentawardee has isolated a gene connected to AMD and is the lead

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Dr. Tongalp H. Tezel, M.D., an RPB Career Development Awardrecipient (see p. 29), has introducedthe concept of “maculoplasty,” aninnovative potential therapy formacular degeneration that involvesreconstruction of the damaged subretinal architecture.

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author on a breakthrough, multi-center study that could open thedoor to profound changes in theidentification of those at risk fordeveloping the disease as well asnew ways to treat it. n

GlaucomaGlaucoma, the second leadingcause of blindness in all Americans,is a general term for a family of eyediseases which, in most cases, leadto increased pressure within the eyeand, as a result, possible damage tothe optic nerve. The most commonform, primary open-angle glauco-ma, initially causes painless loss ofperipheral vision and may lead toblindness if untreated over manyyears. A less common form, acuteangle-closure glaucoma, may devel-op suddenly, accompanied byintense pain, and blindness mayoccur within a day or two if leftuntreated. In some cases of glauco-ma, optic nerve damage occurs eventhough eye pressure is normal.

Lihua Marmorstein, Ph.D.,right, a 2003 RPB CareerDevelopment awardeefrom the University ofArizona, identified the firstlink between two genesassociated with forms ofmacular degenerations,implying a common pathogenic mechanism.

Dr. Karen Holopigian, Ph.D., Associate Professor ofOphthalmology at NYU School of Medicine, prepares to generate multifocal electroretinography to map theretina of a patient with early onset glaucoma.

Because more than half of thosewith glaucoma are unaware theyhave the disease, better detectiontools, public education programsand greater access to eye care willbe critical to an aging U.S. popula-tion in reducing the progression ofirreversible vision loss.

Glaucoma research highlightsAn RPB-funded pilot study suggeststhat lowering fluid pressure in the eye(IOP, or intraocular pressure) inpatients with early glaucoma andearly vision impairment may at leastpartially restore the activity of dys-functional retinal nerve cells, and is yetanother indication that people witha high risk for developing glaucomashould regularly see an eye doctor.The study contradicts the currentlyheld opinion that nerve cell deathcannot be reversed once it begins. Y

Maintaining the softness of certaintissues within the eye (the trabecu-lar meshwork, which regulates theoutflow of eye fluids) is critical tomaintaining optimum eye pressure.RPB-funded scientists have discov-

ered that increased pressure withinthe eye alters a set of genes normal-ly involved in preventing hardeningof tissue. The goal for theseresearchers is now to determine ifdelivering therapeutic genes andproteins to the trabecular meshworkcan modify intraocular pressure. Y

While glaucoma involves damageto the optic nerve, usually in associ-ation with increased intraocularpressure, how this occurs and whatpressures are dangerous may varyfrom person to person. Somepatients with high IOP never sufferoptic nerve damage, and some withnormal IOP lose vision. RPBresearchers are trying to develop away to predict who will suffer glau-comatous damage by identifyingthe factors that contribute to thesusceptibility of an individual’s opticnerve to IOP-related damage, withthe long-term goal of developingindividualized glaucoma therapytailored to each patient’s particularrisk factors and condition. n

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A recent study suggests that a history of hypothyroidism should be recognized as a potential risk factor for developingglaucoma. Both conditions are treatable,and early intervention usually slows theprogression of glaucoma.

According to the RPB-supported EyeDiseases Prevalence Research Group:1 in 300 Americans 18 and older has DR;1 in 600 has vision-threatening DR.

Diabetic Retinopathy (DR)The American Diabetes Associationestimates that there are at least 18million people diagnosed with dia-betes in the United States. After 10years with the disease, 75 percent ofdiabetics have developed someform of diabetic retinopathy, whichoccurs when the blood vessels thatnourish the retina leak and causescar tissue to form or when abnor-mal new blood vessels grow on thesurface of the retina. While lasersurgery, developed in part with sup-

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Paul Sternberg, Jr., M.D. andChairman of the Departmentof Ophthalmology and VisualSciences at the VanderbiltUniversity School of Medicine,examines the fundus photo-graphs of a patient withadvanced AMD, along with resident Jaclyn Leske, M.D.

port from RPB, is effective in haltingloss of vision, diabetic retinopathycontinues to be the leading cause ofblindness among working-ageAmericans and is now the leadingcause of blindness in the industrial-ized world in people between theages of 25 and 74.

DR research highlightsResults from the Los Angeles LatinoEye Study, partially funded by RPB,show high rates of eye diseases suchas diabetic retinopathy and open-angle glaucoma among Latinos overage 40. The older Latino populationhas the highest rate of visual impair-ment among all other racial or eth-nic groups in the country, accordingto lead author, RPB Special Scholarrecipient Rohit Varma, M.D., Ph.D. Y

Studies have shown that highblood sugar initiates a series of bio-chemical responses in the bodythat lead to the death of cells(apoptosis) that form the inner lin-ing of blood vessels, includingthose in the eye. RPB researchershave determined that a protein,

manufactured by the body to inter-rupt the apoptosis process, mayeventually be used as a treatmentto save vascular cells (in the eyesand beyond) from high-blood-sugar-induced cell death. Y

In a related RPB investigation,scientists have established themolecular mechanism by whichhigh blood sugar can also nega-tively affect cells responsible forproviding nutrients to the retina,called Mueller cells. The death ordecreasing function of these criti-cal cells can affect the survival ofsurrounding tissues, which mayexplain the association betweendiabetic retinopathy and retinalcell death. n

Roughly 400,000Americans have retinitispigmentosa and otherrelated retinal disorders.

David W. Parke II, M.D., Chairman of theDepartment of Ophthalmology at theUniversity of Oklahoma and a memberof RPB’s Ad Hoc Committee (see p. 22),conducts clinical research in diabeticretinopathy. Here he utilizes digitalimaging technology to explain eye disease to a patient.

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Roughly 400,000 Americanshave retinitis pigmentosa andother related retinal disorders.

Retinitis Pigmentosa (RP)A family of inherited diseases that usually begins in childhood,retinitis pigmentosa causes pro-gressive deterioration of the retinaresulting in night blindness, tunnelvision, and loss of sight. An estimat-ed one out of 80 people carry therecessive gene for RP.

RP research highlightsResearchers have determined thata clinically safe drug, minocycline,which has been shown to protectnerve cells in degenerative diseasesof the brain, is also highly protectiveof the eye’s photoreceptor cells. Y

Scientists have uncovered a way to encourage transplanted retinalcells to connect to the retinalnerve, overcoming a significantobstacle in restoring vision lostto degeneration of the retina. Y

RPB investigators now have confirming evidence that exposureto light (a previously suspectedfactor) leads to loss of vision in adominant form of retinitis pigmen-tosa. The investigators stronglyrecommend limiting excess lightexposure in RP patients. n

CataractA clouding of the normally trans-parent lens of the eye, cataractaccounts for nearly half of all blind-ness in the world, is the leadingcause of low vision in the U.S., andis estimated to consume 60 percentof the Medicare budget for vision.Several of the risk factors for cataractare tied to behavior, includingsmoking, alcohol use and prolongedexposure to ultraviolet B radiation.

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In addition to increasing age,scientists have also linked cataractto: gender (women are more likelyto develop cataract than men);diabetes; nearsightedness; and theuse of certain medications (corticos-teroids and gout drugs, for example).Surgical removal of the clouded lensand implantation of a replacement—a development supported by fundsfrom RPB—restores or improves thesight of more than a million peopleeach year.

Cataract research highlightsRecent RPB-supported research isthe first to suggest that reducingcaloric intake can delay the age-related degeneration of the lens—and that it should probably bestarted as early as age 30 (the currently-suggested age is 55).Studies have shown that lack ofsufficient antioxidants in a person’sdiet increases the risk of cataract,but taking an oversupply of antioxi-dants does not reduce that risk. Y

RPB researchers are getting closerto establishing a non-surgical

treatment for cataracts. A study hassupported earlier findings that thestress-factor-scavenging propertiesof alpha-ketoglutarate, a stablemolecule, significantly reducecataract development. Furtherstudies with this and similar compounds are underway. Y

Cataracts frequently develop in the eyes of patients who haveundergone vitrectomy, a surgicalprocedure usually performed toclear vitreous gel that has becomeclouded with debris, scar tissue orblood from leaking capillaries asso-ciated with various retinopathies.RPB scientists have confirmed thatan overexposure to oxygen causescataract growth in these patients.Next: Preserving a low-oxygenenvironment before and aftervitrectomy may prevent cataractdevelopment. n

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At the University of Louisville Kentucky Lions Eye Center,Grace Li Huang, M.D., is changing culture mediums forhuman lens epithelial cells as part of a long-term study ofthe pathogenesis of cataracts. RPB funds the investigationthrough an unrestricted grant.

Uyen Tran, M.D., of VanderbiltUniversity, determines the effectof amniotic membrane transplan-tation on corneal would healing.

Corneal DiseaseThe cornea is the clear front surfaceof the eye, which can become cloud-ed, distorted, or scarred by injury,disease, or hereditary defects.About 120 million people in theUnited States wear eyeglasses orcontact lenses to correct nearsight-edness, farsightedness, or astigma-tism. These vision disorders, calledrefractive errors, affect the corneaand are the most common of allvision problems in this country.

Corneal disease research highlightsAn RPB Senior Scientific Investigatoris mapping the genes for kerato-conus, a progressive thinning of the cornea that can lead to severeastigmatism or nearsightedness.

It is the most common corneal dystrophy in the U.S. and the mostcommon cause for corneal trans-plantation in North America. Y

With funding from RPB, scientistshave discovered a previouslyunknown immune response thatcauses the body to reject cornealtransplants. They have also shownthat when this growth factor isblocked, corneal transplants survive.The ability to block this response canhave major implications for thenearly 40,000 Americans whoreceive corneal transplants everyyear and must take rejection-sup-pressing medicines that can causeglaucoma and cataracts. Y

Investigators have discovered that,in some refractive surgery (LASIK),more corneal tissue is removed thanpredicted from the laser settings, andthere may be some loss of cornealnerves that do not completely regen-erate. These findings are importantfor understanding the potentiallong-term effects of this widespreadsurgery on the cornea and vision. n

Findings by an RPBCareer DevelopmentAward recipient indicatethat 20% of pre-schoolchildren may be pre-scribed unnecessaryglasses at a potentialannual, national costof $200 million.

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Eye Movement DisordersStrabismus, a disorder where theeyes point in different directions, is amajor cause of amblyopia, some-times called lazy eye, which occurswhen the brain ignores signals fromthe affected eye and shuts down thevisual pathway. The condition canlead to permanent blindness, usuallyin just one eye, if not detected andtreated by the time a child is five orsix years old. The exact cause of eyemisalignment that leads to strabis-mus is not fully understood. Currentapproaches to the treatment ofamblyopia, which are not alwayssuccessful, involve forcing thepatient to use the affected eye,strengthening its potential for visionas well as its muscles so that botheyes can align properly.

Strabismus and Amblyopiaresearch highlightsRPB funds were used to determinethe best way to stimulate paralyzedmuscles in the eye. The goal is to usesignal output from another eyemuscle to stimulate the paralyzed

Jean Bennett, M.D., Ph.D., Professorof Ophthalmology, University ofPennsylvania and Lew R.WassermanMerit Awardee (see p. 27), is developinggene transfer techniques (shown here using microinjection) in order to create models of retinal disease.

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muscle via an implantable electrode.If successful, this has clinical impli-cations for paralyzed muscles inother parts of the body as well. Y

One of last year’s RPB DisneyAwardees has completed majorhardware development for a newtechnique that could lead to morerapid and accurate diagnosis ofamblyopia. n

Ocular Cancer andRetinoblastoma Retinoblastoma is a malignant (can-cerous) tumor of the retina, the thinnerve tissue that lines the back ofthe eye that senses light and formsimages. It most often occurs inyounger children, usually before theage of five years.The tumor may bein one eye only or in both eyes.Retinoblastoma is usually confinedto the eye but, if left untreated, willspread to nearby tissues and otherparts of the body. Retinoblastomamay be hereditary or nonhereditary.Because of the hereditary factor,brothers and sisters of children with

John S. Penn, Ph.D., RPBSenior Scientific Investigator(see p.28), discusses themolecular basis of ocularangiogenesis (growth ofsmall blood vessels) as well as preventive and therapeutic strategies.

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retinoblastoma warrant examinationto find out if they may develop thedisease. A child with retinoblastoma,particularly the hereditary type, hasan increased chance of developing asecond cancer in later years.

Ocular Cancer research highlightsDoctors treating patients withintraocular retinoblastoma maysoon have a new tool to add to thecurrent treatments (radiation andchemotherapy) for this disease.Scientists operating with an RPBgrant have determined that a drug,originally derived from a SouthAfrican shrub, can be effective inreducing the growth of blood ves-sels necessary for the growth ofretinoblastoma tumors—withoutthreat of toxicity to the surroundingeye tissue or to the body system. Y

Ocular melanoma is the leadingform of cancer in the eye.Scientists supported by RPB identi-fied a novel molecular classificationfor uveal melanoma that stronglypredicts which patients will devel-op metastatic disease. n

Retinoblastoma affectsone in every 18,000 birthsin the United States eachyear and represents 12%of infant cancers.

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Uveitis and InfectiousDiseases of the Eye Research highlights

HerpesHerpes of the eye, caused by theHerpes simplex virus type 1, is themost common infectious cause ofcorneal blindness in the U.S.

In a surprise discovery, 98 percentof those tested in an RPB-support-ed study carried and shed herpessimplex virus type I (HSV-1) DNA intheir tears and saliva, even thoughthey showed no symptoms ofinfection. Approximately 500,000people develop corneal herpesevery year in the United States, andshedding in infected individualswhen they are asymptomatic is amajor factor in the transmission ofthe virus. The researchers conclud-ed that controlling excretion ofHSV-1 through the use of antiviraldrugs could limit transmission, andthat hand washing and not shar-ing towels may also help. Y

ToxoplasmosisToxoplasmosis is a disease causedby an infectious parasite transmit-ted to humans by cats or under-cooked meat. A-symptomatic preg-nant women may acquire the par-asite and transmit it to the fetus.Toxoplasmosis also can cause serious problems in adults withweakened immune systems, suchas HIV/AIDS patients.

An RPB scientist has uncovered evidence of a special ability of theparasite that causes toxoplasmosisto bind to the cells lining bloodvessels within the eye and is alsoinvestigating how blood vesselcells react to toxoplasmosis infection in order to developpotential treatments. Y

RPB researchers studying an epidemic of toxoplasmosis in Brazil used a newly developedblood test to identify the strain ofparasite with which a patient isinfected to determine if differentstrains may have different poten-tial for causing disease. Y

TrachomaTrachoma, caused by a strain ofchlamydia, is the world’s leadingcause of preventable blindness.

The World Health Organization has a major initiative to eliminatethe disease through mass antibiot-ic treatments. By monitoring morethan 60 villages in Nepal andEthiopia, RPB investigators demon-strated that trachoma infectionreturns to communities after a single mass antibiotic treatment,but slowly enough that repeattreatments should be sufficient toeventually eliminate infection. Y

Currently there is no cure for toxoplasmosis.About 3,000 infants are born in the U.S. eachyear with manifestations of toxoplasmosis,which may include retinal damage, deafness,mental retardation and even early death.

Ivan R. Schwab, M.D., of the University of California, Davis,School of Medicine, received a 2004 RPB Sabbatical Grant(see p.32) to continue his development of the scaffoldingfor a bioengineered ocular surface.

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Hundreds of RPB-supported vision scientists throughout the U.S. are investigating theareas of basic and clinical research graphed above. Basic research refers to fundamentallaboratory research such as molecular biology, genetics, biochemistry, immunology andpharmacology. Clinical investigation refers to research applied to the human condition.

UveitisUveitis is an inflammation of theuvea, the middle layer of tissuebehind the white of the eye.The con-dition can be sight-threatening andresults in about 10 percent of theblindness that occurs in the U.S.

Investigators seeking better diagnostic tools for determiningthe various causes and types ofinflammatory eye conditions thatfall under the general term uveitishave, for the first time, used a non-invasive imaging technique to study the structure of uveitisindicators called keratic precipitates.This tool may become importantin accurately diagnosing the causeof inflammation—infection asopposed to another, non-infectiousfactor—in order to apply appropri-ate treatments. n

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The RPB Grant Program comesunder critical review every year

to insure that RPB remains focusedon its role as catalyst within thevision research community andthat promising careers within eyeresearch are nourished. Conversely,RPB regularly evaluates granteeinstitution programs in order toconcentrate its investments on richand promising environments.

Every application receives the highest level of scientific scrutiny,first by a rotating committee ofchairmen of departments of oph-thalmology, then by a panel of the nation’s most distinguished scientists representing a broadrange of scientific interests andexpertise who bring multi-discipli-nary perspectives to the final cut.Both the committee and the panelmeet twice annually to review grant proposals.

Throughout every grant cycle, one element remains constant. RPB offers a wide range of competitiveawards that help individuals conductresearch at every stage of a career,from medical school to mid-career tothe most senior investigator positions.

Says RPB Ad Hoc Committee memberCarmen A. Puliafito, M.D., M.B.A.,University of Miami Miller Schoolof Medicine:“You can see that RPB’sgoals are being accomplished bythe quality of the grant applicants.We have some solid people in thepipeline, and that bodes well forthe health of vision research.”

J. Crawford Downs, Ph.D.,Claude Burgoyne, M.D.,and Juan Reynaud, B.S.,(clockwise from top)view a section of an opticnerve head (ONH) of aglaucomatous eye (right).

3-D reconstruction of theONH connective tissue(left), which is based ondata from the ONH sec-tions, allows researchersat the Louisiana StateUniversity HealthSciences Center in NewOrleans to visualize andtest hypotheses regard-ing intraocular pressure-related damage to ONH.

The RPB Grant Program

“The unrestricted grant from RPB has been invaluable,” states Robert D. Yee, chairman of theIndiana University Department of Opthalmology.“We use the funds to create new research labora-tories and begin new programs, which later cansuccessfully compete for funding from othersources. Almost every program in the departmenthas directly benefited from RPB grants.”

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RPB Ad Hoc Committees convene each spring and fall to conduct initial reviews of all RPB grant applications.The Committees are comprised of selected ophthalmologydepartment heads whose recommendations are forward-ed to the Scientific AdvisoryPanel for further evaluation.Membership on the Committeechanges from meeting tomeeting. This year’s partici-pants were:

Stanley Chang, M.D.Columbia University Collegeof Physicians & Surgeons

Steven E. Feldon, M.D., M.B.A.University of Rochester Schoolof Medicine & Dentistry

Michael A. Kass, M.D.Washington University in St. LouisSchool of Medicine

Hilel Lewis, M.D.Case Western Reserve UniversitySchool of Medicine

The RPB Grant Review ProcessA Record of Economy and EfficiencyHow RPB Funds Were Expended 1960-2004RPB’s fund-raising cost has been less than 2% for overfour decades of service. Its staff of nine is among thesmallest of all major organizations in the voluntaryhealth field.

81% RESEARCH

2%Fund-raising

71%Eye research grants

3%Scientificsymposia,seminarsand surveys

2%Laboratory construction support projects

5%Researchprogram development

9%Public andprofessionalinformation

8%Administration

Mark J. Mannis, M.D.University of California, Davis,School of Medicine

James P. McCulley, M.D., F.A.C.S.The University of Texas SouthwesternMedical Center at Dallas

Peter J. McDonnell, M.D.The Johns Hopkins University School of Medicine

David W. Parke II, M.D.University of Oklahoma HealthSciences Center

Steven M. Podos, M.D.Mount Sinai School of Medicine

Carmen A. Puliafito, M.D., M.B.A.University of Miami Miller School of Medicine

Joel S. Schuman, M.D., F.A.C.S.University of Pittsburgh School ofMedicine

Ronald E. Smith, M.D.Keck School of Medicine of theUniversity of Southern California

Thomas A. Weingeist, Ph.D., M.D.The University of Iowa Carver College of Medicine

RPB Ad Hoc Committees

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The RPB Scientific AdvisoryPanel, comprised of distin-guished scientists representinga broad range of scientificinterests, meets twice annuallyto review grant proposals.

Harold F. Spalter, M.D.Chairman, RPB ScientificAdvisory Panel, 1966-present

Professor of Clinical Ophthalmology,Columbia University College ofPhysicians & Surgeons

Alan C. Bird, M.D.Professor of Clinical Ophthalmology,Institute of Ophthalmology,University College London

John E. Dowling, Ph.D.Professor of Neurosciences,The Biological Laboratories,Harvard University

Scientific Advisory Panel

Public AwarenessComplements Vision ResearchFounded on the principle that informationempowers, RPB’s Public Education Programis an important component in its strategicassault on the eye diseases that affectmore than 80 million Americans.

In 2004, RPB made online bibliographies ofpublished findings by our grantees more accessible, we upgraded our public informa-tion kits and launched a new publication,available on our web site. The Eye ResearchNews brings useful research findings topatients to help them with lifestyle decisionsand to equip them to ask more informedquestions of care providers. All of theseefforts are supported by a national aware-ness campaign in print and, soon, online.

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The new, patient-orientednewsletter, Eye ResearchNews, is available atwww.rpbusa.org. Go therefor brochures and researchinformation on eye diseases,to locate an eye doctor whoactively supports research,for information on RPB’sgrant program, direct linksto its grantee institutions,for ways to support eyeresearch and more.

Frederick T. Fraunfelder, M.D.Professor of Ophthalmology, OregonHealth & Science University, Casey EyeInstitute

Morton F. Goldberg, M.D., F.A.C.S.Professor of Ophthalmology, TheWilmer Institute, The Johns HopkinsUniversity School of Medicine

Anita E. Hendrickson, Ph.D.Professor, Departments of BiologicalStructure & Ophthalmology, TheUniversity of Washington

Joe G. Hollyfield, Ph.D.Director of Ophthalmic Research,The Cleveland Clinic Foundation

Haig H. Kazazian, Jr., M.D.Professor & Chair, Department ofGenetics, University of PennsylvaniaSchool of Medicine

Gordon K. Klintworth, M.D., Ph.D.Professor, Departments of Pathology and Ophthalmology, Duke UniversityMedical Center

Robert B. Nussenblatt, M.D.Chief, Laboratory of Immunology,National Eye Institute

RPBhas now channeledmore than $230 million

into eye research, second only tothe U.S. government… and price-less in terms of the flexibility RPBallows scientists in the use of itsfunds. RPB investigators are tack-ling the entire spectrum of eyedisease—cataracts, glaucoma,and diabetic retinopathy to mac-ular degeneration, retinitis pig-mentosa, eye movement disor-ders, eye cancer and others. Wehave made sure, in the structur-ing of our grants program, thatwe offer grant opportunities totalented, qualified scientists atevery stage of their careers sothey can see their innovationsthrough to conclusion.

Here are the grants approved by RPB in 2004.

The RPB Grant Awards

M. Elizabeth Fini, Ph.D., an RPB SeniorScientific Investigator, prepares a reagentas part of her project to investigate the roleof ganglion cell attachment to matrix inneuroprotection at the University of MiamiMiller School of Medicine.

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James L. Funderburgh, Ph.D., examines the function ofcorneal stem cells in culture.

The Stein Professorship (SP) is RPB’spremier award, providing up to$525,000 over seven years, with apossible additional $100,000 inmatching funds to equip lab space.Only outstanding basic scientists,conducting clinically relevantresearch within a department of oph-thalmology, are considered for a SteinProfessorship. In 2004, RPB grantedone SP and extended four others.

Paulo A. Ferreira, Ph.D.Duke University School of Medicine Dr. Ferreira’s research will focus onidentifying the genetic and proteinnetworks underlying retinal diseaseprocesses, with the goal of devisingnew pharmacological approaches todelay or avert retinal disorders, such asmacular degeneration and glaucoma.

Jules and Doris Stein RPBProfessorship Extensions:

Daniel J. J. Carr, Ph.D.University of Oklahoma Health Sciences Center Dr. Carr continues his work towarddelivery of an anti-viral gene to the

cornea to stop the reactivation ofHerpes simplex virus type 1.

James L. Funderburgh, Ph.D.University of Pittsburgh School of Medicine Dr. Funderburgh’s work has demon-strated the feasibility of cell-basedtherapy for the cornea, and may leadto treatment for corneal scarringbased on injection of replacementcells instead of the current cornealtransplantation therapy.

Edward N. Pugh, Jr., Ph.D.University of Pennsylvania School of Medicine Dr. Pugh has been investigating themechanisms involved in rod andcone function, quantifying proteinexpression and movement in liveretinal tissue with the use of a high-resolution, photon-counting confo-cal microscope built with RPB funds.

John S. Werner, Ph.D.University of California, Davis,School of MedicineAt present, it is not possible to studyretinal disease at a cellular level in

Jules and Doris Stein RPB Professorship

the living eye. Dr.Werner’s lab isdeveloping methods that have thepotential to provide a new tool fordirect visualization of cellularchanges associated with retinal dis-eases before they are apparent withconventional diagnostic measures.

25

Joseph L. Demer, M.D., Ph.D., uses toys and puppets tostudy amblyopia and other visual disorders in young children at the David Geffen School of Medicine at UCLA.

RPB Walt and Lilly Disney Awards for Amblyopia Research

The RPB-Walt and Lilly Disney Awardfor Amblyopia Research, createdthrough a $500,000 pledge fromThe Walt and Lilly DisneyFoundation, provides funds torespected ophthalmic scientists forresearch into improved detection,treatment or cures for amblyopia,which develops in two to three per-cent of all children—usually beforethey can speak, making it particular-ly difficult to detect.

In 2004, RPB provided a total of$100,000 to two scientists:

Joseph L. Demer, M.D., Ph.D.David Geffen School of Medicine at UCLA Dr. Demer pioneered the use ofpositron emission tomography tostudy brain processing in amblyopiaand, with his research team, hasdeveloped magnetic resonanceimaging (MRI) techniques capable ofnearly microscopic resolution forstudy of the eyeball and nerves ofthe eye socket in living people. Hewill study possible relationships of

optic nerve size, and eyeball shapeand focus error, to the developmentof amblyopia.

Joseph M. Miller, M.D., M.P.H.University of Arizona College of MedicineDr. Miller’s professional career is ded-icated to the care of children withvision problems and to the develop-ment of health care tools and sys-tems to detect and prevent ambly-opia. His work has been supportedand facilitated by a Native Americantribe, the Tohono O’Odham Nation.He will investigate and furtherdevelop infant- and child-friendlyvision testing methods as well asthe economic impact of variousvision screening strategies.

26

Dr. Wallace Alward, studying a family with congenital optic nerve abnormalities.

As part of RPB’s approach to support top investigators and tohelp make it feasible for them tomaintain a career in research, theLew R. Wasserman Merit Award pro-vides a $55,000 grant to mid-careerscientists who are actively engagedin vision research, creating a contin-uum of financial resources for aresearcher building on earlier work.

RPB selected three investigators toreceive the Lew R. Wasserman MeritAward in 2004:

GlaucomaWallace L.M. Alward, M.D., TheUniversity of Iowa Carver Collegeof Medicine, is applying moleculargenetic techniques to the possibleprevention of childhood glaucoma.

Retinal DegenerationJean Bennett, M.D., Ph.D., Universityof Pennsylvania School of Medicine,is expanding the uses of viral vectortechniques (delivering transgenes tospecific cells in the retina) to test

RPB Lew R. Wasserman Merit Awards

experimental treatments of retinaldegenerative diseases.

Corneal diseaseW. Matthew Petroll, Ph.D.,University of Texas SouthwesternMedical Center at Dallas, will bedeveloping new insights into thecomplex cellular, biochemical andbiomechanical events duringcorneal wound healing and embry-onic development of the cornea.

27

28

The Sybil B. Harrington Endowment generatesfunds for several RPB grant awards every year andhas enabled RPB to create an additional SeniorScientific Investigator Award, selecting gifted scien-tists and providing them the means to focus theirenergies on finding cures and preventives for age-related macular degeneration. This year’s recipient,Michael B. Gorin, M.D., Ph.D., University of PittsburghSchool of Medicine, pioneered the use of complexgenetic methods to expand current knowledge ofage-related maculopathy (ARM).Previous Harrington RPB Senior Scientific Investigators1994 Dean Bok, Ph.D., UCLA1995 John R. Heckenlively, M.D., UCLA1996 Peter Gouras, M.D., Columbia University1997 Paul A. Sieving, M.D., Ph.D.,

University of Michigan1998 Matthew M. LaVail, Ph.D.,

University of California, San Francisco1999 Mark O.M. Tso, M.D., D.Sc.,

The Johns Hopkins University2000 Samuel G. Jacobson, M.D., Ph.D.,

University of Pennsylvania2001 Donald G. Puro, M.D., Ph.D.,

University of Michigan2002 Donald J. Zack, M.D., Ph.D.,

The Johns Hopkins University2003 Anand Swaroop, Ph.D.,

University of Michigan School of Medicine

RPB’s Senior Scientific InvestigatorAwards category was conceived toextend the productivity of seasonedvision scientists whose wisdom andexpertise will contribute to cures ortreatments for eye diseases and whocan play a crucial role in training thenext generation of vision scientists.The $65,000 grant supportsresearchers whose accomplish-ments in vision science are widelyrecognized by their peers for havingdeveloped preventives, treatmentsand cures for blinding diseases. Inthe past year, RPB conveyed fiveSenior Scientific Investigator awards.

M. Elizabeth Fini, Ph.D., Universityof Miami Miller School of Medicine,is identifying molecules that medi-ate a neuroprotective effect on theretina and optic nerve.

Michael B. Gorin, M.D., Ph.D.,University of Pittsburgh School ofMedicine, is exploring gene splicingto reduce damage caused by age-related maculopathy.

Todd P. Margolis, M.D., Ph.D.,University of California, SanFrancisco, School of Medicine, isdeveloping strategies to eliminatelatent infection or prevent viral reac-tivation in (and thus cure) recurrentHerpes simplex virus eye disease.

John S. Penn, Ph.D., VanderbiltUniversity School of Medicine, will beimproving our understanding of ocu-lar angiogenesis (the hallmark of dia-betic retinopathy, age-related macu-lar degeneration, retinopathy of pre-maturity, sickle cell retinopathy andocclusion retinopathies, among oth-ers), so that new, less invasive, thera-peutic strategies can be developed.

Steven L. Wechsler, Ph.D.,University of California, Irvine,College of Medicine, is elucidatingthe molecular mechanisms behindthe recurrent ocular herpes (HSV-1)latency-reactivation cycle and, even-tually, developing therapeutic drugsto decrease recurrent ocular diseaseand corneal blindness.

RPB Senior Scientific Investigator Awards

29

RPB Career Development Awards

A special $10 million board-designat-ed fund enabled RPB to createCareer Development Awards whichprovide $200,000 across four yearsto outstanding young clinical andbasic scientists conducting researchin departments of ophthalmology.In 2004, nine researchers wereselected to receive the award.

Rajendra S. Apte, M.D., Ph.D.,Washington University in St. LouisSchool of Medicine: possible contri-butions of the immune system inthe development of choroidal neo-vascularization in wet age-relatedmacular degeneration.

Sanjay G. Asrani, M.D., DukeUniversity School of Medicine: non-invasive visualization of the collectoroutflow channels and Schlemm’scanal in glaucoma; development oftelemetry-based intraocular pres-sure measuring devices.

Tiffany A. Cook, Ph.D., University of Cincinnati College of Medicine:methods of differentiating implant-

Michael A. Dyer, Ph.D., selects samples for analysis in his studies of strategies for improvingthe current treatment for retinoblastoma.

ed or injected pluripotent cells intomature retinal pigment epitheliumcells and photoreceptors.

Michael A. Dyer, Ph.D., University of Tennessee Health Science Center:disturbances in cell division duringdevelopment of the retina; tumorprogression; new therapies for thetreatment of retinoblastoma.

Abigail S. Hackam, Ph.D., Universityof Miami Miller School of Medicine:biology of the dying retina; identifi-cation of genes that reduce disease-related photoreceptor death in reti-nal degenerative diseases.

Albert S. Jun, M.D., Ph.D., The Johns Hopkins University School of Medicine: gene therapy to treatFuch’s dystrophy.

Todd E. Scheetz, Ph.D.,The Universityof Iowa Carver College of Medicine:identification and prioritization of can-didate genes involved in the causes ofglaucoma, macular degeneration andretinitis pigmentosa.

Tongalp H. Tezel, M.D., University ofLouisville School of Medicine: patho-genesis of macular degenerationand novel treatment modalities,including proteomic analysis.

Xiangun Wei, Ph.D., University ofPittsburgh School of Medicine:mechanisms of cellular pattern for-mation in the retina toward a foun-dation for future retinal engineering.

30

RPB Special Scholar Awards

RPB Special Scholar Awards are giveneach year in honor of former Trusteesand others who have made generouscontributions of time, energy andfinancial resources in support of eyeresearch.The Awards, which rangefrom $40,000 to $70,000 each, rec-ognize and reward promising youngscientists of exceptional merit.

Esen K. Akpek, M.D.,WILLIAM &MARY GREVE SCHOLAR at The Johns Hopkins University School ofMedicine, elucidates the pathogenicmechanisms of ocular surface dis-eases and dry eye conditions.

Rando L. Allikmets, Ph.D., DOLLYGREEN SCHOLAR at ColumbiaUniversity College of Physicians &Surgeons, determines genetic causesof complex inherited retinal diseases.

Philip J. Gage, Ph.D., JAMES S.ADAMS SCHOLAR at the Universityof Michigan School of Medicine,utilizes gene microarray and gene

technologies to understand theregulation of normal eye develop-ment and function.

Chia-Yang Liu, Ph.D., OLGA KEITHWIESS SCHOLAR at the University ofMiami Miller School of Medicine,characterizes corneal disease genestoward prevention and treatment ofinjury and blinding disorders.

Eric A. Pierce, M.D., Ph.D., SYBIL B.HARRINGTON SCHOLAR at theUniversity of Pennsylvania School ofMedicine, uses gene targeting tech-niques to investigate inherited reti-nal degenerative diseases.

Gülgün Tezel, M.D., SYBIL B. HAR-RINGTON SCHOLAR at the Universityof Louisville School of Medicine,identifies the precise mechanisms ofcell death in glaucoma toward newtreatment possibilities.

Esen Akpek, M.D., an RPB William & Mary GreveScholar at The Johns Hopkins University School ofMedicine (see p. 30), examines a patient diagnosedwith atopic keratoconjunctivitis.

31

RPB Physician-Scientist Awards

RPB Physician-Scientist Awards provide $55,000 each to supportnationally recognized M.D.’sengaged in clinical eye research atmedical institutions in the UnitedStates. The award is meant to pro-vide greater funding opportunitiesfor specialized study with directapplication to the human condition.It recognizes that physician-scien-tists today face greater challengesas vision research grows more specialized, costly and complex.

The physician-scientists who canoperate effectively in both theresearch laboratory and in the clinicalpractice of medicine do so becausethey bring to the laboratory a practi-cal understanding of patients’needs.In turn, their research efforts yieldnew knowledge that doctors canapply in treating patients.

Reza Dana, M.D., M.P.H., HarvardMedical School, will be identifyingand modulating mechanismsresponsible for generation of the

immune response against cornealproteins in diseases of the cornea.

Christopher A. Girkin, M.D.,University of Alabama at BirminghamSchool of Medicine, is quantifyingglaucomatous damage based on opticdisc structural characteristics andmeasurements of nerve fiber layerintegrity,with a particular interest indetermining racial susceptibility tointraocular presssure-related injury.

James T. Handa, M.D., The JohnsHopkins University School ofMedicine, will be determining howcholesterol gets into Bruch’s mem-brane and how advanced glycationend-products accelerate age-relatedmacular degeneration (AMD).

Mary Elizabeth Hartnett, M.D.,University of North Carolina atChapel Hill School of Medicine, isinvestigating signaling pathways for vascular endothelial growth fac-tor (VEGF) expression in retinopathyof prematurity.

Reza Dana, M.D., M.P.H., shown here drawing for his labgroup, illustrates the affect of pro- and anti-inflammatorycytokines in regulating immunogenic inflammation in the eye over time.

32

RPB Sabbatical Grants RPB InternationalResearch Scholar Awards

In 1993, RPB established the RPBMedical Student Eye ResearchFellowship program to enable students to take a year off from theirusual course of studies to pursue alaboratory research project within adepartment of ophthalmology. RPBselected four medical students toreceive fellowships of $25,000 eachin 2004.They are: Elma Kim of theWashington University in St. LouisSchool of Medicine, seeking the caus-es of culture-negative corneal ulcers;Michael Mulhern of the University of Nebraska School of Medicine,studying the relationship betweenlens epithelium-derived growth factor and HIV; David J. Ramsey ofthe University of Illinois at ChicagoCollege of Medicine, elucidating the mechanism by which diabetesinduces early retinal dysfunction;and Radha ‘Krishna’ Sanka of theDuke University School of Medicine,investigating the role of matrix met-alloproteinases in regulating outflowfacility in glaucoma.

The RPB Research Sabbatical Grantsupports mid-career researchersinvolved in educational and scientif-ic programs that either enhancetheir scientific expertise or allowthem to pursue a new ophthalmicresearch career path. In 2004, RPBselected Ivan R. Schwab, M.D.,F.A.C.S., University of California,Davis, School of Medicine to receivethe award to continue the develop-ment of a bio-engineered ocular sur-face using corneal epithelial stemcells and different carrier platforms.

In 2004, RPB’s International ResearchScholar program provided a grantthat enabled David Hicks, Ph.D., ofFrance, to collaborate with 2003 RPB Senior Scientific InvestigatorAnand Swaroop, Ph.D., University of Michigan School of Medicine,to identify genes involved in coneand rod development, cellular signaling and eye disease. AnotherInternational Scholar award allowedTakeshi Iwata, Ph.D., NationalTokyo Medical Center, to conductcollaborative studies of the geneticsand biochemical mechanisms ofmacular degeneration with RadhaAyyagari, Ph.D., University ofMichigan School of Medicine.

RPB Medical StudentEye Research Fellowships

Elma Kim extracting DNAfrom bacteria.

33

RPB’s National Network of Eye ResearchLeading medical institutions throughout the United States received RPBgrant support for vision research in 2004. The flexible nature of that

support allows directors of ophthalmic research considerable, andmuch appreciated latitude in developing their scientific investigations.

STATE/UNIVERSITY 2004 SUPPORT TOTAL SUPPORT

ALABAMAUniversity of Alabama at Birmingham School of Medicine $ 165,000 $ 2,570,000

ARIZONAUniversity of Arizona College of Medicine 135,000 955,000

ARKANSASUniversity of Arkansas for Medical Sciences 110,000 1,412,500

CALIFORNIAUniversity of California, Davis, School of Medicine 310,000 2,458,900David Geffen School of Medicine at UCLA 185,000 6,245,750University of California, San Diego, School of Medicine 110,000 2,100,000University of California, San Francisco, School of Medicine 175,000 3,814,256University of Southern California Keck School of Medicine 110,000 3,331,500University of California, Irvine, College of Medicine 285,000 285,000

CONNECTICUTYale University School of Medicine 110,000 2,667,224

FLORIDAUniversity of Miami Miller School of Medicine 425,000 * 2,930,200

GEORGIAEmory University School of Medicine 110,000 2,597,100

ILLINOISNorthwestern University Feinberg School of Medicine 110,000 1,655,000The University of Chicago Pritzker School of Medicine 110,000 3,006,550 University of Illinois at Chicago College of Medicine 135,000 2,921,712

INDIANAIndiana University School of Medicine 110,000 1,999,000

IOWAThe University of Iowa Carver College of Medicine 365,000 * 2,787,425

KENTUCKYUniversity of Louisville School of Medicine 350,000 * 2,554,800University of Kentucky College of Medicine 220,000 440,000

LOUISIANALouisiana State University Health Sciences Center in New Orleans 220,000 1,972,100

MARYLANDThe Johns Hopkins University School of Medicine 425,000 * 5,503,140University of Maryland School of Medicine 110,000 1,269,700

MASSACHUSETTSHarvard Medical School 165,000 5,135,215

MICHIGANUniversity of Michigan School of Medicine 162,450 3,591,450Wayne State University School of Medicine 110,000 2,833,000

MINNESOTAMayo Medical School 110,000 1,924,600University of Minnesota, Academic Health Center, MedicalSchool 110,000 2,103,701

STATE/UNIVERSITY 2004 SUPPORT TOTAL SUPPORT

MISSOURIUniversity of Missouri-Columbia School of Medicine 110,000 1,272,300Washington University in St. Louis School of Medicine 341,000 * 4,852,900

NEBRASKAUniversity of Nebraska Medical Center 25,000 765,000

NEW JERSEYUniversity of Medicine & Dentistry of New Jersey Medical School 110,000 1,397,000

NEW YORKColumbia University College of Physicians & Surgeons 180,000 3,448,167Weill Medical College of Cornell University 110,000 3,448,700Mount Sinai School of Medicine 110,000 3,125,700SUNY Upstate Medical University 110,000 1,270,000SUNY at Buffalo School of Medicine & Biomedical Sciences 220,000 220,000

NORTH CAROLINADuke University School of Medicine 810,000 * # 4,633,350University of North Carolina at Chapel Hill School of Medicine 55,000 750,500

OHIOUniversity of Cincinnati College of Medicine 200,000 * 485,000Case Western Reserve University School of Medicine 110,000 1,222,500

OKLAHOMAUniversity of Oklahoma Health Sciences Center 260,000 3,525,000

OREGONOregon Health & Science University School of Medicine 110,000 2,847,150

PENNSYLVANIAUniversity of Pennsylvania School of Medicine 375,000 4,133,500University of Pittsburgh School of Medicine 525,000 * 2,654,175

SOUTH CAROLINAMedical University of South Carolina 110,000 1,327,500

TENNESSEEUniversity of Tennessee Health Science Center 310,000 * 1,200,000Vanderbilt University School of Medicine 285,000 1,350,500

TEXASBaylor College of Medicine 110,000 3,164,060The University of Texas Health Science Center at Houston 110,000 2,415,000The University of Texas Health Science Center at San Antonio 110,000 1,712,900The University of Texas Southwestern Medical Center at Dallas 165,000 2,631,000

UTAHUniversity of Utah Health Sciences Center 110,000 3,265,300

WISCONSINMedical College of Wisconsin 110,000 2,824,215

* Includes a four-year $200,000 Research to Prevent Blindness Career Development Award, payable atthe rate of $50,000 per year.

# Includes a five-year $375,000 Jules and Doris Stein Research to Prevent Blindness Professorship, payable at $75,000 per year and a $100,000 Stein Professorship laboratory renovation grant.

34

To date, RPB has awarded $1.15million to the University of

Tennessee Department ofOphthalmology. RPB sat downwith Dr. Barrett Haik (BH), Chair,and Research Director Dr.Dianna Johnson (DJ) to discussthe effect its grant support hashad on their operations.BH: Research to Prevent Blindnessapplies a seemingly simple princi-ple to a complex and unfortunateset of circumstances: the preven-tion of blindness. Coming from afamily of ophthalmologists, thatappealed to me, and it is exactlywhat we are trying to do here atthe University of Tennessee. Ourclinicians are as committed toresearch as the basic scientists. Wemake sure that every one of ourdoctors and scientists knows whatevery one else is doing—and thatnone of this is for personal gain or

“Our goal is what everybody’s goal is in thiskind of work: to put ourselves out of business.We are working hard, but we have a long wayto go before we get to that point,” says Haik,shown consulting with a patient.

self-aggrandizement, but purely tofight blindness.

DJ: RPB gives us two layers of sup-port—one for the Department as awhole, which has been so criticalfor Dr. Haik in establishing a strongresearch presence within thedepartment of ophthalmology andmaintaining it at such a highlevel… and the other level of sup-port for the individual scientist.RPB has allowed us to take theoutstanding researchers we haveidentified—in whom we want toinvest—and has given us themeans to do so.

BH: In a very real sense, RPB is partof our infrastructure. When Iarrived here, 10 years ago, ours hadbeen a very good clinical depart-ment but it never had a strongresearch program, so it neverreceived RPB support. In fact, it hadbeen turned down three times. I

Profit on Investment:The RPB Grants Program Nurtures A Department

35

was very fortu-nate to meet Dr.Dianna Johnson,who had justcompleted anRPB Jules & Doris SteinProfessorship atUniversity ofTexas-Houston.We hired her as our Director ofResearch, and that earned usgreater confidence from RPB.

I didn’t have sufficient startupfunds to explore pilot projects. Theinitial Development Grant fromRPB—$200,000 across four years—was the single most criticalendorsement we could havereceived because other donors,who knew RPB to be the pinnacleof objectivity and of quality, cameforward with another four milliondollars in local commitments. It’staken us 10 years, but we haveraised over 40 million dollars. We’llfinish an eye institute this summer.

Without RPB, it neverwould have happened.

DJ: RPB funds allow youto react quickly tochanges in opportunity,to focus your effort onone project if you want,or on multiple projects.The support from RPB is not like an NIH grant,

for which we have to detail a cer-tain set of experiments. Rather,RPB wants to know the direction ofthe research, the quality of theresearcher and the richness of theresearch environment—and thendecides where it will get the bestscience return from its money. Oursuccess at producing material ofsignificance, that other physiciansand scientists can use and believein, has been greatly amplified byRPB’s commitment.

BH: Before Jules Stein insisted thatvision research be done in ophthal-mology departments, there was lit-tle research conducted in U.S. insti-

tutions in ophthalmology depart-ments themselves. Almost all ofthe science would flow back to abasic department and you’d losethat translational edge that is soessential to going from bench tobedside. A healthy, collegial envi-ronment is critical because clini-cians need to know that newstrategies are being developed.You have to hope for somethingbetter and you have to be work-ing towards it.

RPB is a sophisticated investor,going after truth and knowledgeabout eye diseases and their treat-ment, purely based on scientificopportunity and on priorities thatits Scientific Advisory Panel sees asbeing primary for the nation. Someof the things going on in the labsin our Hamilton Eye Institute andelsewhere across this country aregoing to make a tangible differ-ence for people and change theway that we deliver medical careor detect abnormalities. n

The new Hamilton EyeInstitute houses state-of-the-art research laboratories andclinical facilities.

RPB RPBEFAssets

Cash and cash equivalents ..........................................................................$ 1,654,875 $ 2,522,618

Investments, at market value ..................................................................... 7,530,387 226,930,148

*Amounts due from RPBEF.............................................................................. 4,336,872 0

Interest receivable.............................................................................................. 34,311 682,858

Contributions receivable ................................................................................ 145,940 0

Due from investment managers—net .................................................... 0 0

Prepaid expenses and refundable deposits ..................................... 2,280 0

Net fixed assets ................................................................................................... 249,899 0

Leasehold improvements.............................................................................. 15,322 0

Other assets ........................................................................................................... 6,000 0

Total assets........................................................................................................ 13,975,886 230,135,624

LiabilitiesAccounts payable and accrued expenses ............................................ 94,264 65,851

Due to investment managers—net............................................................ 0 129,036

Grants payable ...................................................................................................... 57,881 6,023,057

*Amounts due to RPB......................................................................................... 0 4,336,872

Total current liabilities .............................................................................. 152,145 10,554,816

Net AssetsUnrestricted net assets

Unrestricted—general operating ............................................................ 9,040,919 136,233,558

Unrestricted—designated........................................................................... 0 26,690,176

Total unrestricted net assets................................................................. 9,040,919 162,923,734

Temporarily restricted net assets ............................................................. 864,808 10,675,263

Permanently restricted net assets ........................................................... 3,918,014 45,981,811

Total net assets .............................................................................................. 13,823,741 219,580,808

Total liabilities and net assets.............................................................$ 13,975,886 $ 230,135,624

R E S EA R C H TO P R EVE NT B L I N D N E S S, I N C . ( R P B ) R E S EA R C H TO P R EVE NT B L I N D N E S S E N D OWM E NT F U N D ( R P B E F )C O M B I N E D S TAT E M E N T O F F I N A N C I A L P O S I T I O ND E C E M B E R 3 1 , 2 0 0 4

RPB—RPBEF COMBINED BUDGET—2005

Research Grants and Other Program Allocations:Unrestricted, Developmentand Challenge Grants to MedicalSchools and Other Institutions...................$ 6,930,000

Research Professorships, Senior Scientific Investigators, Research Manpower and Visiting Professors Awards ............................ 4,165,000

Special Scientific Scholarsand International Research Scholars Grants..................................................... 490,000

Special, Emergency & LRW Grants ........... 1,035,000

Direct Research Support.................................. 430,000

Research Program Development and Research Facility Construction Grants.... 335,000

Scientific Seminars, Surveysand Symposia......................................................... 270,000

Public and Professional Information....... 700,000

Total Program Services.....................$ 14,355,000

Management and General Allocations:Salaries, Employee Benefitsand Payroll Tax....................................................... 210,000

Professional/Consultant Fees...................... 1,180,000

Office Equipment/Supplies........................... 6,500

Rent and Occupancy.......................................... 26,500

Depreciation, Amortization and Insurance ........................................................ 39,000

Travel & Meetings ................................................ 1,500

Telephone ................................................................. 1,500

Printing, Stationery, Postage and Shipping....................................... 1,000

Miscellaneous(Dues, Subscriptions, Other, etc.) ............ 25,000

Total Management and General .... 1,491,000

Fund-Raising Allocations: ............................. 125,000

Total ................................................................. 1,616,000

Grand Total ..............................................................$ 15,971,000

36

* Amounts due to RPB and from RPBEF are eliminated upon combination.

UNRESTRICTEDGENERAL TEMPORARILY PERMANENTLY

OPERATING DESIGNATED TOTAL RESTRICTED RESTRICTED TOTALPublic support and revenue

Public supportContributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . $ 1,413,528 $ — $ 1,413,528 $ 93,616 $ — $ 1,507,144Combined Federal Campaign . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52,628 — 52,628 — — 52,628Ophthalmological associate memberships. . . . . . . . . . . . . . . . . . 125,400 — 125,400 — — 125,400Donated investments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 879 — 879 — — 879

Total public support. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1,592,435 — 1,592,435 93,616 — 1,686,051Revenue

Interest and dividends. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6,309,775 — 6,309,775 483,696 5,647 6,799,118Other revenue. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1,884 — 1,884 — — 1,884

Total revenue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6,311,659 — 6,311,659 483,696 5,647 6,801,002Net assets released from restrictions or designation

Satisfaction of program restrictions or designations . . . . . . . . . 3,281,766 (2,766,641) 515,125 (515,125) — —Satisfaction of Matching Fund restrictions . . . . . . . . . . . . . . . . . . . . . 1,000,000 — 1,000,000 (1,000,000) — —

Total net assets released from restrictions or designation 4,281,766 (2,766,641) 1,515,125 (1,515,125) — —Total public support and revenue . . . . . . . . . . . . . . . . . . . . . . . . . . 12,185,860 (2,766,641) 9,419,219 (937,813) 5,647 8,487,053

ExpensesProgram services

Research grants, net of canceled grantsof $179,778 in 2004 and $493,426 in 2003 . . . . . . . . . . . . 10,191,424 — 10,191,424 — — 10,191,424

Direct research support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 428,357 — 428,357 — — 428,357Program development to stimulate laboratory

expansion and eye research activities . . . . . . . . . . . . . . . . . . . . 314,912 — 314,912 — — 314,912Scientific symposia, seminars and surveys . . . . . . . . . . . . . . . . . 267,521 — 267,521 — — 267,521Laboratory construction support projects . . . . . . . . . . . . . . . . . . . 15,617 — 15,617 — — 15,617Public and professional information. . . . . . . . . . . . . . . . . . . . . . . . . . 662,817 — 662,817 — — 662,817

Total program services . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11,880,648 — 11,880,648 — — 11,880,648Supporting services

Management and general . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1,261,320 — 1,261,320 — — 1,261,320Fund raising . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122,580 — 122,580 — — 122,580

Total supporting services . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1,383,900 — 1,383,900 — — 1,383,900Total expenses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13,264,548 — 13,264,548 — — 13,264,548Excess (deficiency) of revenue over expenses before

realized and unrealized gain (loss) on investments . (1,078,688) (2,766,641) (3,845,329) (937,813) 5,647 (4,777,495)Realized and unrealized gain (loss) on investments

Realized gain (loss) on sale of investments . . . . . . . . . . . . . . . . . 4,910,201 — 4,910,201 256,366 — 5,166,567Unrealized gain (loss) on investments . . . . . . . . . . . . . . . . . . . . . . . 12,002,082 — 12,002,082 — — 12,002,082

Total net realized and unrealized gain (loss) on investments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16,912,283 — 16,912,283 256,366 — 17,168,649

Increase (decrease) in net assets . . . . . . . . . . . . . . . . . . . . . . . . . . 15,833,595 (2,766,641) 13,066,954 (681,447) 5,647 12,391,154

Net assets, beginning of year . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129,440,882 29,456,817 158,897,699 12,221,518 49,894,178 221,013,395Net assets, end of year . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . $145,274,477 $26,690,176 $171,964,653 $11,540,071 $49,899,825 $233,404,549

R P B - R P B E FCO M B I N E D S T A T E M E N T O F A C T I V I T I E S

YEAR ENDED DECEMBER 31, 2004

A complete set of RPB’s combined financial statements has been reproduced,along with the report of independent accountants, as a separate document.A copy may be obtained by contacting RPB at 1-800-621-0026.

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Investing with RPB to save sight

The U.S. government estimatesthat by the year 2020:

• Almost 3 million people will haveage-related macular degeneration;

• Even more will suffer glaucoma;• The number of people with

diabetic retinopathy will almostdouble to more than 7 million;

• 30 million people will havecataracts, a 50% jump from today;

• 1.6 million Americans will belegally blind, up 70%.

At the same time, the financial costsof health care continue to rise.

RPB’s legacy… and yoursIn addition to our collaboration withscientists, research centers and doc-tors, RPB pursues another partner-ship in fulfilling its mission—withdonors.We seek new sources of sup-port from selected foundations, cor-porations and individuals, ratherthan soliciting funds from the gener-al public through mass appeals.Have you considered your legacyand how you might help pass thegift of sight to others? You mightcreate a will with this goal in

The Jules and Doris Stein Matching Fund matches dollar-for-dollar all gifts that RPB receives from others,up to a total of a million dollars,doubling the valueof contributions in support of eye research.

mind—or rewrite your currentwill. Another option is among themost important gifts that can beoffered in support of science: abequest that assures the continu-ity of research. To make a bequest,this simple form may be followed:

I give and bequeath to Researchto Prevent Blindness, Inc., thesum of $ or % of myresiduary estate or the followingdescribed property, i.e., securitiesand other assets to be used infurtherance of its general pur-poses or for research related to aspecific eye disease, i.e., maculardegeneration, glaucoma.

To learn more about bequests orother options for giving, consult withyour attorney or financial advisor.Please be sure to consult your attor-ney regarding the final form of anylifetime or testamentary transfer.ALL GIFTS AND BEQUESTS ARE TAX-DEDUCTIBLE. Research to Prevent Blindness, Inc.(RPB) is recognized by the U.S. Internal RevenueService as a publicly supported tax-exemptorganization under section 501(c)(3) of theInternal Revenue Code.

THE ESTABLISHMENT OF ENDOWMENT FUNDS by gener-ous contributors has helped assure an unusual degree ofstability and continuity in the development of RPB’s far-reaching programs. Existing funds include the following:Jules and Doris Stein Endowment Fund $ 45,087,782Jules and Doris Stein Matching Fund 9,771,424Lew R. and Edie Wasserman Endowment Fund 1,407,412William and Mary Greve Memorial Fund 519,943Dolly Green Endowment Fund 500,000Sybil B. Harrington Endowment Funds 2,613, 369Desiree L. Franklin Endowment Fund 138,700Eugene G. Blackford Memorial Fund 28,000John D. and Patricia Sakona Endowment Fund 50,362David B. Sykes Family Endowment Fund 167,626

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own reports. Dialing a phone was difficult. In the laboratory,reagents were the wrong color.In Orlando, I was examined by awonderful and skillful profession-al and he gave me the news with-out pulling any punches. I hadcataracts in both eyes. I neededsurgery to replace my lenses. Theprocedures were done while I wasawake. There was no pain, and Ifound myself with 20-20 sight. Icould see my wife and kids incolor. I started going to the super-market with my wife, and gazingendlessly at fruits and vegetables.In 1991, I developed a detachedretina. Another great professionalrepaired my eye, in his officewhile I was awake and feeling nopain, with a gas bubble insertedinto my eyeball. I have maintained20-20 vision to this day.In addition to my physical rehabil-itation, I had a spiritual rebirth. Iam grateful to civilization and anaffluent society that can fund andafford the training of such superi-or doctors and develop these won-

derful technologies. I asked mydoctor how I could participate in aprogram of preventive care. Herecommended that I contact RPB.I now have two programs, for myretirement years, to help preventblindness. As a part-time highschool teacher, I urge my studentsto care for their eyes as well as theirminds and bodies. I also raise toma-toes and flowers in my backyard.From time to time, I run a yard sale.All the proceeds go to RPB and everydonor gets one of RPB’s brochures.So, that is my story. I hope that itwill encourage sufferers to seekmedical help when their eyesightis in question. I also hope itencourages those who can to opentheir purses and be rewarded byhelping the blind to see again. n

A Donor’s Story: Bill Miller

Iwas born in 1935 in the BathBeach section of Brooklyn, a short

trolley car ride to Coney Island. Mymaternal grandmother, who hadcome to America late in the 19thcentury, taught me to read usingher night-school primer. I enteredP.S. 200 as a reader.When I was in the first grade, Ifell ill. A local doctor said I hadpneumonia and prescribed mus-tard plasters. I developed a bodyrash and another doctor said Ihad the measles. When I returnedto school I could no longer read,until someone realized that Ineeded glasses.My eyes continued to deteriorate.Selective Service rated me as 3-A.Still, I managed two Bachelors degreesand a Masters in Geochemistry.In 1986, I was employed by achemical manufacturer, travelingconstantly: on an airliner everyMonday morning and driving athousand miles a week.Something was very wrong. I wasseeing multiple images. I neededa magnifying glass to read my

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RPB extends its sincerestgratitude to BillMiller, to thosewho support usthrough him,and to all of ourvaluable donors.

Research to Prevent Blindness645 MADISON AVENUE, NEW YORK, NY 10022-1010

212-752-4333 or 1-800-621-0026 • FAX: 212-688-6231 • website: www.rpbusa.org • E-mail: inforequest@rpbusa.org

Research to Prevent Blindness (RPB) mobilizes financial resources in

support of eye research, making available essential laboratory space,

sustaining scientific personnel and providing advanced technological

equipment in its mission to preserve vision and restore sight.