6 RESEARCH

A novel discovery maylead to treatments forwet AMD and diabeticretinopathy.

OphthalmologyUpdate

2 7 16REFRACTIVESURGERY

Current and comingadvances in technologyare improving resultsfor first-time patientsand reoperations.

PUZZLER

Patient with recentonset of binocular horizontal diplopia unable to abduct herleft eye across the midline.

PEARL

Clinical trial biases raise questions aboutcomparisons of glaucoma medications.

Fall 2003

Shack-Hartmann centroid image showingspherical aberrations in a 26-year-old patient previously treated with LASIK and complaining of visual symptoms. Forpost-CustomCornea image, see Page 3.

Page

CLEVELAND CLINIC COLE EYE INSTITUTE

REFRACTIVE SURGEONS AND RESEARCHERS

ARE INVOLVED IN A NUMBER OF PROJECTS

AIMED AT IMPROVING OUTCOMES FOR PA-

TIENTS UNDERGOING REFRACTIVE SURGERY

PROCEDURES.

Ronald R. Krueger, M.D., has beenusing the recently FDA approved Custom-Cornea application for the LADARVision®System to treat patients undergoing pri-mary keratorefractive surgery. He hasdocumented a statistically significantreduction in several types of aberra-tions, and no increase in other aberra-tions, with wavefront-guided surgery.He has also discovered how to obtainexcellent results without overcorrectionin patients requesting upgrades afterconventional LASIK, an off-label use.

David Huang, M.D., Ph.D. has de-veloped a mathematical model to pre-dict corneal surface smoothing afterexcimer laser ablation. By using the in-formation to adjust the ablation pattern,he hopes it will be possible to optimizecorrection and minimize surgically in-duced aberrations. Dr. Huang is also in-volved in the development of dedicated

corneal and anterior segment(CAS) optical coherence to-mography (OCT) with the goalof producing an instrumentthat provides high-resolutionimages together with accuratemeasurements (see pages 4and 5).

asl;dkjnpojnogniporjknkjn

‘pasedkl;sdklgjg

Commercial Application of Wavefront-Guided Customized Ablation

EXPERIENCE WITH WAVEFRONT-GUIDED CUS-

TOMIZED ABLATION AT THE COLE EYE INSTI-

TUTE HAS SHOWN THE SYSTEM TO BE

SUPERIOR TO CONVENTIONAL LASIK IN MINI-

MIZING THE INDUCTION OF ABERRATIONS. THIS

IS LIKELY THE REASON FOR IMPROVED VISION

RESULTS, SAYS DR. KRUEGER, MEDICAL DIREC-

TOR OF THE DEPARTMENT OF REFRACTIVE

SURGERY.

“LASIK corrects myopia and astigma-tism, but in the process, generates moreaberrations, leading to symptoms such ashalo, glare, starburst and double vision.We have recently observed a statisticallysignificant association of these symptomswith certain aberrations – for example,double vision with coma under photopicconditions (p=0.008), and glare and star-burst with spherical aberration under sco-topic conditions (p≤0.014). This helps usunderstand the impact of induced aberra-tions on visual quality,” he explains.

“Our hope was that CustomCornea®would induce fewer aberrations than con-ventional refractive surgery, and maybeeven reduce some preoperative values.This, indeed, has been our experience.”

The Cole Eye Institute was the thirdcenter in the United States to begin com-mercial treatment of patients with Cus-

tomCornea following itsapproval by the FDA inOctober 2002. From De-cember 27, 2002, to June1, 2003, Cole refractivesurgeons performed cus-tom ablation on 363eyes. Included in this co-hort were patients withinone diopter of the fullrange of correction indi-cated: up to 7.0 D of

Improving Outcomes in Refractive Surgery

2

Above Low- and high-order aberrations 1-week post-

CustomCornea (n=75).

Right Low- and high-order aberrations 3-weeks post-

CustomCornea (n=22).

0

1

2

3

4

5

6

3 Months

Preop

OtherSAComaAstigDefHO AbTotal Ab

CustomCornea Results – 3 Months

RM

S

5.86

0.450.450.680.68

0.14 0.360.36 0.330.33 0.410.41 0.340.340.60

0.82

0.320.260.26

0.34

5.64

0

1

2

3

4

5

6

7

1 Week

Preop

OtherSAComaAstigDefHO AbTotal Ab

CustomCornea Results – 1 Week

RM

S

6.79

1.051.050.680.68 0.18

0.380.38 0.340.34 0.400.40 0.360.360.54 0.60 0.300.30 0.200.20 0.300.30

6.71

CM

E

CME Objective for

Commercial Application

of Wavefront-Guided

Customized Ablation:

To assess the value of

wavefront-guided tech-

nology in reducing the

induction of aberrations

during keratorefractive

surgery.

▲

3

myopia and 0.5 D of astigmatism. Thismeans their wavefront refraction had tobe >8.00 D of myopia and 1.50 D ofastigmatism.

Baseline measurements were takenand aberrations were assessed in a subsetof patients at postoperative week 1 (n=75)and at 3 months (n=22). Overall, thesepatients showed a statistically significantreduction in total aberrations, defocusand astigmatism at both time points, saysDr. Krueger.

“At week 1, however, a significant in-crease in total higher-order aberrations,spherical aberration and other terms wasseen (Figure 1). At 3 months, we found nostatistical increase in higher-order aberra-tions, including coma and other terms(Figure 2). This means that about half theeyes we treated had higher-order aberra-tion values that were lower than preoper-ative levels, and half had values that werehigher. That’s good, because higher-orderaberration values normally double ortriple,” he says.

Dr. Krueger has been exploring fur-ther indications for CustomCornea usingpatients dissatisfied with symptoms orresidual correction resulting from LASIK.

He discovered that some upgrades re-sult in overcorrection, which he attributesto the large number of pulses required totreat peripheral aberrations and whichtend to dry the central corneal tissue,causing excessive tissue to be removedwith each pulse.

Dr. Krueger found that using an off-set feature in the CustomCornea platformallows him to treat up to 0.5 D less. “Wenow use it in all our custom upgrades. Ialso hydrate the surface of the corneaduring treatment, which keeps it moistand prevents greater tissue removal witheach pulse. With these modifications, I getexcellent results with little chance forovercorrection,” he says. ■

Case study: Use of CustomCornea for reoperation

In May 2003, a 54-year-old malepresented at the Cole Eye Institutefor re-evaluation. He had under-gone H-LASIK in 2001 in botheyes, and although he had goodacuity, still noted mild starburstand vertical double vision in theright eye. Despite his low manifestreaction, +0.50 –0.50 x 101°(20/25), Dr. Krueger elected tocorrect his symptoms due to hisnotable vertical coma value of0.37 mm (6.5mm pupil), whichwas related to his double vision.The offset feature was used toavoid overcorrection, and thecornea was irrigated with BSSafter lifting the flap and prior totreatment.

After surgery, the patient’ssymptoms were markedly im-proved, with a manifest refrac-tion of –0.25 –0.25 x 5° (20/25)and a reduction of his comavalue to 0.14 µm. “Selective cor-rection of his coma resulted inimproved vision,” says Dr.Krueger.

Shack-Hartmann

centroid image of

the cover patient

following Custom-

Cornea LASIK up-

grade showing

marked reduction

of spherical aber-

ration with im-

provement in

visual symptoms.

CME Credit

To receive a maximum of

0.5 AMA-PRA Category 1

credits:

• Read the articles on

pages 2, 4 and 6

• Go online at www.cleve-

landclinicmeded.com/

ophthupdatef3.htm

• Take the multiple-choice

quiz

• Complete the evaluation

and registration form

You will then be able to

print your CME credit

certificate immediately on

your own printer. CME

credit for this activity will

only be available up to

January 31, 2004.

The corneal smoothing model waspublished in Am J Ophthal.2003;135:267–278.

Corneal smoothing effects change theintended laser correction for weeks aftersurgery, often leaving patients with less-than-optimal vision. Visual side effectscan be particularly pronounced at nightand in dim light when the pupil enlargesto accept more light into the eye, leadingto problems such as ghosting, glare andhalo. Healing-induced aberration is pro-portional to the amount of laser ablation.Therefore, problems can be particularlyprofound in patients who undergo higherlevels of correction.

“By anticipating this healing processin the preoperative ablation calculations,surgeons can compensate for it and avoidinducing higher-order aberrations,” ex-plains Dr. Huang.

He believes that combining his for-mula, which he calls Advance HealingAdjusted Ablation (AHAA), with state-of-the-art flying spot lasers with trackingand adequately sized treatment zones willgreatly improve overall refractive surgeryoutcomes.

“The ability to avoid aberrations maybe even more clinically significant thanthe use of wavefront imaging to detectand try to correct aberrations once theyhave been induced,” he says. “Without atime machine, wavefront-guided lasertreatment can only correct pre-existingaberrations. Even with state-of-the artwavefront treatment, post-surgical aberra-tion still exceeds pre-existing aberrationin most patients. Only a predictive algo-rithm such as AHAA can pre-compensatefor induced aberration.”

Dr. Huang believes the AHAA algo-rithm is complementary to current ad-vances in wavefront sensing. “Bycombining wavefront sensing and AHAA,both pre-existing and induced aberrationscan be treated, leading to better resultsthan with either method alone.”

The Cleveland Clinic has filed apatent application based on the AdvanceHealing Adjusted Ablation invention. Dr.Huang maintains a proprietary interest inthe technology. ■

4

Advance Healing Adjusted Ablation(AHAA)

ANTICIPATING HOW THE EPITHELIUM

WILL HEAL AFTER REFRACTIVE

SURGERY AND MODIFYING TREATMENT

ALGORITHMS ACCORDINGLY MAY BE

THE KEY TO ELIMINATING THE ABER-

RATIONS THAT CAN BE INDUCED BY

THE SURGERY, SAYS DR. HUANG.

“Most refractive surgery pa-tients experience some surgicallyinduced aberrations that affecttheir vision after the healingprocess is complete,” he explains.“If we can anticipate that healingand compensate for it upfront, thiswill produce a better outcome.”

Dr. Huang developed a mathe-matical model based on a set ofpartial differential equations to an-ticipate the effect of epithelial mi-gration, regeneration, sloughing,and corneal surface smoothingafter LASIK and PRK.

“Our intuitive understandingof corneal surface smoothing isthat the epithelium thins overbumps and islands and thickensover divots and relative depres-sions. “Our mathematical modelclarifies this intuitive understand-ing,” he says.

The model uses a single con-stant to characterize corneal sur-face smoothing effects. Once thesmoothing constant is known, themodel can design ablation patternsthat more accurately achieve theintended correction and minimizethe induction of additional aberra-tion, he explains.

The smoothing constant wasestimated by matching the predict-ed effects with clinical results.Clinical data analysis was based ona computer database of LASIK per-formed by Dr. Huang at the ColeEye Institute over an 18-month pe-riod, in addition to other publisheddata.

TOP A myopic astigmatism ablation profile

change predicted by the model.

BOTTOM Post-ablation epithelial thickness.

CME Objective of

Advance Healing Adjusted

Ablation: To understand

how advance prediction

of corneal healing can be

used to avoid the induc-

tion of aberrations during

keratorefractive surgery.

▲

CM

E

New High-Speed OCT Prototype Enters Clinical Evaluation

DR. HUANG IS ALSO A PIONEER IN THE DEVEL-

OPMENT OF NON-CONTACT, HIGH-SPEED CAS

OCT IMAGING. WORKING WITH A TEAM OF

OTHER ACADEMIC-BASED RESEARCHERS, HE

INITIALLY DESIGNED A PROTOTYPE SLIT LAMP-

MOUNTED WIDE-FIELD CAS OCT SCANNER,

SHOWN IN PILOT TESTING TO BE QUITE VERSA-

TILE WITH UTILITY IN MEASURING CORNEAL

THICKNESS, PROFILING THE ENTIRE LASIK FLAP

(FIGURE 1), AND PERFORMING ANTERIOR

CHAMBER BIOMETRY (FIGURE 2).

With interest in the commercializa-tion of CAS OCT to allow its widespreadclinical application, Dr. Huang has beencollaborating with scientists and engi-neers at Carl Zeiss Meditec in instrumentdesign, and they have introduced a proto-type that entered clinical trials in July.

The investigational system features a1.3-micron wavelength able to penetratethrough highly scattering tissues, such asthe limbus and sclera, while allowingvideo-rate imaging. It obtains 2000 axialscans per second and incorporates an in-ternal fixation target to optimize centra-tion on the cornea.

In one initial study, the OCT devicewas used in pre- and postoperative evalu-ation of patients undergoing LASIK toprofile the thickness of the cornea and theLASIK flap. In their ongoing research, thedevelopment team is working to expandthe capabilities of the system so that itcan capture three-dimensional cornealanatomy and produce maps of cornealtopography, thickness and internal layers.

“So far we have concentrated on get-ting measurements and other informationfrom single, cross-section images, but athree-dimensional depiction will have thegreatest value for the refractive surgeonperforming excimer laser ablative visioncorrection procedures,” Dr. Huang says.

Unlike existing Placido ring-basedcorneal topography systems that produceonly anterior cornea elevation maps, theCAS OCT scanner has the potential to

5

characterize both the anteriorand posterior surfaces of thecornea. In that regard, the CASOCT device is similar to the Orb-scan slit-scanner. However, withits higher axial resolution, theCAS OCT device may offergreater reliability in evaluatingthe posterior surface. CAS OCTalso has the unique capability ofnoncontact mapping of the flapand posterior stromal bed thick-ness after LASIK.

Anterior chamber biometryis another potential use of theCAS OCT scanner, and studiesare also being planned to evalu-ate the performance of the newprototype system in that applica-tion. Dr. Huang points out thatthe ability of this technology todirectly measure the recess-to-recess anterior chamber widthalong with such other parame-ters as anterior chamber depthand crystalline lens vault couldhave important implications forimproving the safety of refrac-tive surgery using angle-sup-ported phakic IOLs, a type ofanterior-chamber IOL (AC-PIOL).

“Safety has been a promi-nent concern relating to the

phakic IOLs. By allowing thesedirect measurements, CAS OCTmay at least permit more accu-rate sizing of AC-PIOLs andthereby reduce complications aspupil ovalization, which occurswhen the implant is too large, orPIOL dislocation, which can de-velop if the device is too small,”he explains.

Looking to the future, Dr.Huang notes that as AC-PIOLsmove into the next generation ofeasy-to-implant foldable devices,the ability to select an appropri-ately sized implant can be a keyfactor in determining the suit-ability of the technology forwidespread use in the treatmentof high ametropias.

“Thus, the new CAS OCTsystem may be an important en-abling technology for the adap-tation of phakic AC-PIOLs intoclinical practice,” Dr. Huangsays.

Top OCT of the cornea

after LASIK. The wide

field (12 mm) image

shows the flap interface.

Flap and posterior stro-

mal bed thickness can

be measured.

Bottom Horizontal OCT

section of the anterior

segment of the eye. The

wide field (16 mm)

image allows measure-

ment of anterior cham-

ber depth and width as

well as angle depth.

6

within the retina,” saysHilel Lewis, M.D., direc-tor of the Cole Eye Insti-tute. “It could also havedramatic implications be-yond ophthalmology,such as in cancer.”

Results of the studyappeared in Nat Med.2003;9(4):407–415.

The next step on theroad to what may ulti-mately be synthetic drugsand gene therapies tocontrol angiogenesis isfor Dr. Anand-Apte’steam to try to learnwhich part of TIMP-3binds to the VEGF-2 re-ceptor and which domainof the receptor is in-volved.

Cleveland Clinic researchers who haveworked on this projectinclude Jian Hua Qi, Ph.D., QutebaEbrahem, M.D. and Nina Moore, Ph.D.(former CCF staff). External collabora-tors include Gillian Murphy of Cam-bridge University in the UnitedKingdom, Lena Classson-Welsh of Upp-sala University, Sweden, Mark Bond ofthe University of Bristol, U.K., and An-drew Baker of the University of Glas-gow, U.K.

This research is funded by the Na-tional Institutes of Health, the Founda-tion Fighting Blindness and TheCleveland Clinic Cole Eye Institute. ■

Natural Protein Found to Inhibit Angiogenesis

A NOVEL DISCOVERY BY RESEARCHERS AT

THE CLEVELAND CLINIC COLE EYE INSTITUTE

INTO HOW THE BODY PREVENTS ANGIOGEN-

ESIS MAY LEAD TO NEW TREATMENTS FOR

OCULAR DISEASES SUCH AS THE EXUDATIVE

FORM OF AGE-RELATED MACULAR DEGEN-

ERATION AND DIABETIC RETINOPATHY.

TIMP-3, or tissue inhibitor of met-alloproteinases-3, is one of a family offour proteins naturally produced by thebody that are able to prevent the break-down of specific cellular barriers. TheCole researchers, led by Bela Anand-Apte, M.B.B.S., Ph.D., have learned thatTIMP-3 also works to prevent abnormalblood vessel growth.

“For angiogenesis to occur, a mole-cular lock must be opened,” says Dr.Anand-Apte. “Scientists have knownfor some time that the body seeks toprevent this from occurring by produc-ing a number of proteins, one of whichis TIMP-3. What wasn’t known, andwhat we have found, is how TIMP-3actually works.”

Her team discovered that TIMP-3blocks the binding of vascular endothe-lial growth factor (VEGF) to its receptor.In other words, the VEGF “key” nolonger is able to open its VEGF-2 re-ceptor “lock,” which initiates eventsleading to abnormal blood vesselgrowth. This inhibits downstream sig-naling and angiogenesis.

“This may be our body’s naturaldefense to stop tumor growth,” says Dr.Anand-Apte, who has been with TheCleveland Clinic since 1996. “This in-sight will help us to better explore itspotential in medical treatments.”

“This important discovery at theCole Eye Institute could lead to the pre-vention of the two most common caus-es of severe visual loss and blindness inthe western world, the exudative formof AMD and proliferative diabeticretinopathy, by preventing the growthof abnormal blood vessels around and

A life image using intravital fluorescent microscopy of a

mouse cornea expressing a green fluorescent protein

(GFP). Using an intrastromal injection technique, the

cornea was transfected in vivo 24 hours earlier with an

adenoviral vector containing a DNA gene encoding for

the green protein.

CM

E

CME Objective of

Natural Protein Found

to Inhibit Angiogenesis:

To study how a natural

protein may someday

be used to block the ab-

normal growth of blood

vessels in the eyes.

▲

7

RETINAL CLINICIANS AND RESEARCHERS FROM ACROSS THE UNITED STATES AND AS FAR AWAY

AS JAPAN, CENTRAL AMERICA AND AUSTRALIA ATTENDED THE IVTH RETINA SUMMIT AT THE

COLE EYE INSTITUTE ON MAY 2 AND 3, 2003. IN ADDITION TO OFFERING EXCITING, THOUGHT-

PROVOKING CLINICAL AND RESEARCH PRESENTATIONS, THIS YEAR’S CONFERENCE TOOK AN IN-

NOVATIVE TURN BY BROADCASTING SURGERY LIVE ON THE INTERNET.

On Friday, Hilel Lewis, M.D., performed proliferative vitreoretinopathy surgery,which was narrated for the live and electronic audience by Peter K. Kaiser, M.D. Dur-ing the procedure, Dr. Lewis answered questions emailed from ophthalmologists as faraway as Japan and Israel. More than 3,000 physicians, health professionals and con-sumers viewed the surgery over the Internet.

On Saturday, conference attendees watched Jonathan Sears, M.D., remove a largeciliary body tumor. This procedure was teleconferenced to physicians in Bogota,Colombia at their request. Three overflow seating areas enabled Cole Eye Institutestaff, fellows, residents, nurses and technicians to watch the procedure on large-screentelevisions and monitors outside the James P. Storer Conference Center.

The popularity of the Retina Summit will require the meeting to move from state-of-the-art meeting facilities at the Cole Eye Institute to larger high-tech accommoda-tions. The next Retina Summit will be held across the street in the newInterContinental Hotel and Conference Center, where a larger number of participantscan take advantage of what the meeting offers.

IVth Retina Summit a Worldwide Success

Ophthalmic Puzzler

By Linda A. Lam, M.D. and Careen Y. Lowder, M.D., Ph.D.

A 29-year-old female presented with intermittent binocular horizontal diplopia of two days’ duration. On the day of hervisit she was unable to abduct her left eye across the midline. She denied changes in vision, pain, flashes, photophobia,or history of trauma. She had a 2-week history of painless left-sided facial numbness, particularly over her left lip. Herocular history was significant only for hyperopia of her right eye since childhood, without patching. Her medical histo-ry was significant for relapsing polychondritis and hypertension. She had a history of recurrent sinusitis and underwenta nasal biopsy. Current medications included prednisone, methotrexate, Nexium, Norvasc, Flonase, folate, calcium, andmultivitamins. No eye medications. For 9 months she had been drinking frequently and urinating up to 6 liters daily.She was born in China, and had come to the United States one year earlier to attend college.

The patient’s best-corrected visual acuity was 20/25 in the right eye and 20/20 in the left eye. Intraocular pressurewas 20 mm Hg in each eye. Pupillary reflexes, visual fields, and color plates were normal. Her right eye demonstratedfull range of extraocular movements. Slit lamp examination of the anterior segment and the dilated fundus exam werenormal in both eyes.

What is the diagnosis? Turn to Page 8

2003 ARVO Abstracts from Cole Eye Institute Staff

Cleveland Clinic Cole Eye Institute re-searchers and clinicians submitted morethan 75 papers and posters to the 2003Association for Research in Vision andOphthalmology (ARVO) meeting. Whilethe largest number of submissions dealtwith retinal disease, abstracts oncataract, glaucoma, refractive surgery, pe-diatric ophthalmology and uveitis werealso published.

All abstracts are available onwww.ccf.org/eye/research. Click on retinaresearch, refractive research or other re-search on the left-hand menu. The re-searchers may be contacted directly bycalling the Cole Eye Institute at 216/444-2020, or 800/223-2273, ext. 42020.

structures, and meninges. However, theleft mandibular branch of the trigeminalnerve in its course from the cavernoussinus to the foramen ovale was thick-ened (Figure). Mucosal thickening wasalso found in the maxillary, sphenoid,and ethmoid sinuses, indicating exten-sive sinus inflammation. Head MRA andvenogram were normal. A thyroid ultra-sound showed an enlarged homogenousthyroid gland. Water deprivation testconfirmed diabetes insipidus.

Diagnosis

The cranial neuropathies in this patientwere most likely due to Wegener’sgranulomatosis, which had been diag-nosed one year earlier with a nasalbiopsy. Hyperthyroidism is present in3% of patients with Wegener’s, and dia-betes insipidus occurs due to enlarge-ment of the pituitary gland byinflammatory infiltrates.

Classic Wegener’s granulomatosiswas first described as a triad featuringdisease in the upper and lower respira-tory tracts and kidneys. Biopsy speci-mens show necrotizing vasculitis,granuloma formation, eosinophilia, andtissue necrosis. Pulmonary involvement

Ophthalmic PuzzlerSolution to Part 1 (from page 7)

8

Differential diagnosis

Vasculopathies are a common cause ofisolated sixth nerve palsy, particularlyin patients with diabetes or hyperten-sion. When multiple cranial nerves areinvolved, Wegener’s, Churg-Strauss,temporal arteritis, and Kawasaki diseaseshould be considered. Arteriovenousmalformations, cavernous sinus throm-bosis, carotid aneurysm, and stroke mayalso be factors.

Infectious etiologies in immuno-suppressed patients must be ruled out.Herpes, syphilis, tuberculosis of thecavernous sinus, Lyme, mumps-measles-rubella vaccinations, meningi-tis, Gradenigo syndrome, and sinusitishave all been implicated. Sarcoid,myesthenia gravis, and Guillian-Barré,as well as intracranial tumors maycause abducens palsy. Nasopharyngealcarcinoma, lymphoma and leukemiahave been implicated in multiple cra-nial neuropathies.

Evaluation

The patient was admitted and evaluatedby the neurology, rheumatology, andendocrinology services. On physical ex-amination, she had bilateral nasal mu-cosal crusting and congestion. She hadsevere tenderness over her maxillaryand frontal sinuses bilaterally, especial-ly over the left side. No lymphadenopa-thy was found. Neurologic exam wasnormal, except for left lower facial hy-pesthesia and inability to abduct theleft eye. Complete blood count, meta-bolic profile, sedimentation rate, C-re-active protein, thyroid function tests,anti-neutrophilic cytoplasmic antibodies(ANCA), and urinalysis were obtained.All serologic and urine laboratory re-sults were normal except for an elevat-ed C-ANCA, T4, and thyroidmicrosomal antibody.

Neuroimaging demonstrated normalbrain parenchyma, cavernous sinus

occurs in more than 90% of patients.Renal involvement has been reported in77% of patients, and is the major causeof mortality. Neurologic complicationshave been reported in up to 50% of pa-tients. The most common neurologicmanifestation of Wegener’s is peripheralneuropathy. Cranial neuropathies, oph-thalmolplegia, Horner’s syndrome, pa-pilledema, hearing loss, headaches,meningitis, and strokes have also beendescribed. Cardiac involvement in theform of pericarditis and vasculitis oc-curs in about 8% of patients. Cranialnerve palsies have been described asthe initial manifestation in the limitedform of Wegener’s granulomatosis,which involves the upper and/or lowerrespiratory tract without renal disease.These patients have a better prognosisthan those with the classic diffuse formof disease.

Serological testing is of value inthe diagnosis of Wegener’s; however,pathologic confirmation is key. Cyto-plasmic or cANCA is a highly specificmarker for Wegener’s, being positive in90% of patients with classic Wegener’s,65% in patients with limited form, and30% of patients in remission.

Involvement of the orbit or eye isseen in 25%-58% of patients with We-gener’s. They may have limited extraoc-ular movements, proptosis, diffuse ornecrotizing scleritis, and peripheral ul-cerative keratitis. Retinal findings occurin about 10%-18% of patients in theform of retinal hemorrhages, edema, orcotton-wool spots. Branch and centralretinal artery occlusions and branchretinal vein occlusion have been report-ed as complications. Uveitis, often inthe form of vasculitis, occurs in 10% ofpatients.

Untreated, Wegener’s is a rapidlyprogressive, fatal disease. For severe sys-temic disease or patients with glomeru-lonephritis, the most effective treatmentregimen is a combination of cyclophos-phamide and prednisone. The prognosiswith this regimen is good, with 90% ofpatients achieving improvement and75% achieving remission.

Coronal section of head MRI showing

thickening of the left mandibular branch of

the trigeminal nerve

9

Bennie H. Jeng, M.D., joined the staffof The Cole Eye Institute in July aftercompleting a fellowship in cornea andexternal diseases at the Francis I. Proc-tor Foundation at the University of California San Francisco. Dr. Jeng com-pleted his internship and residency atThe Cole Eye Institute in 2002, servingas chief resident in his final year. Hereceived his medical degree from theUniversity of Pennsylvania School ofMedicine in Philadelphia.

Dr. Jeng’s primary interests are incorneal transplantation, ocular surfacedisease, limbal stem cell transplanta-tion, and artificial corneas. He plans to spend about 75 percent of his timein patient care, with the remainder de-voted to research. He is particularly interested in finding ways to improveeyebanking techniques that will in-crease the health and viability of donortissue, leading to improved transplan-tation success rates.

He says the dynamic environmenthe experienced during his residency atCCF is what motivated him to returnafter his fellowship. “The Eye Institutehas always impressed me with its con-tinuous upward movement in a timewhen other institutions are strugglingto expand,” he comments.

Dr. Jeng is a member of the Amer-ican Academy of Ophthalmology, theAssociation for Research in Vision andOphthalmology, the American Societyof Cataract and Refractive Surgery, andthe Contact Lens Association of Oph-thalmologists.

After five years as professor and chairof ophthalmology and the holder of theGrace E. Hill Chair in Vision Researchat the University of Washington inSeattle, Steven E. Wilson, M.D., has returned to the Cole Eye Institute as director of corneal research.

Dr. Wilson received his M.S. inmolecular biology and biochemistryfrom the University of California,Irvine, and M.D. from the University of California, San Diego. He served hisresidency at the Mayo Clinic, and hisfellowship in cornea, external disease,and refractive surgery at the LouisianaState University Eye Center in New Orleans. He then joined the Department of Ophthalmology at the University of Texas Southwestern Medical Center in Dallas.

Dr. Wilson is recognized as one ofthe world’s leading cornea and refrac-tive surgery specialists. An NIH-fundedinvestigator, he leads a research labora-tory that explores cellular and molecu-lar interactions in the cornea involvedin development, homeostasis, woundhealing, and disease. He is the author of more than 130 peer-reviewed clinicaland research papers.

Dr. Wilson is currently a trustee of the Association for Research in Vi-sion and Ophthalmology. He serves onthe executive board of ISRS-RSIG, theprogram committee for the AmericanAcademy of Ophthalmology, and theeditorial boards for Experimental EyeResearch, The Journal of RefractiveSurgery, and Cornea. He is the chiefmedical editor of Review of RefractiveSurgery.

Announcing the 2003Cleveland Clinic Medical InnovationSummit

October 7 – 9, 2003

Physicians interested in technologytransfer and commercialization ofmedical advances are invited to agathering of CEOs from the world’slargest medical technology com-panies, venture capitalists, patentattorneys and the commissioner of the FDA at The Cleveland ClinicInterContinental Hotel and MBNAConference Center on October 7-9, 2003. With the theme, “FromBoardroom to Patient Bedside: TheNeed for Speed,” the event willfocus on the responsible transla-tion of new technologies intosafe, effective patient care. Talkswill center on how to secure ac-cess to capital, protect intellectualproperty, and find a way throughthe regulatory tangle separatingnew discoveries from global mar-kets and the patient care arena.

For additional information,please contact Christopher Coburn,executive director of CCF Innova-tions, at 216/445-4008. To regis-ter online for the Summit, go to

www.clevelandclinic.org/innovations

New StaffBennie H. Jeng, M.D. (left)Steven E. Wilson, M.D. (right)

CURRENTLY RECRUITING

GENETICS

STUDIES OF THE MOLECULAR GENETICS OF EYE DISEASES

Objective To map the genes for inheritedeye diseases. To screen candidate genesfor mutations in a variety of genetic ocular disorders, including ocular malfor-mations, congenital cataracts and retinaldystrophies. Contact E. Traboulsi, M.D., 216/444-4363or S. Crowe, C.O.T., 216/445-3840

GENETICS AND MOLECULAR ANALYSIS OF RETINAL DISEASES

Objective The Cole Eye Institute is recruiting patients with a family history of macular degeneration to participate in a genetic study. Our goal is to find thegene that causes macular degeneration. Eligibility Criteria Participants musthave at least two family members whohave been diagnosed with macular degen-eration and who are willing to participatein our study. There is no age limit, and itdoes not matter if you have the wet ordry type of AMD. Contact H. Lewis, M.D., 216/444-0420, orE. Simpson, R.N., 216/445-9886

THE GENETICS OF STRABISMUS

Objective To discover the genes thatcause some strabismus syndromes, includ-ing those for accommodative esotropia,congenital esotropia, congenital ocular fibrosis syndrome, intermittent exotropia,Brown syndrome and Duane syndrome. Contact E. Traboulsi, M.D., 216/444-4363or S. Crowe, C.O.T., 216/445-3840

GLAUCOMA

GLAUCOMA DIAGNOSIS BY OPTICAL COHERENCE TOMOGRAPHY ANALYSIS OFRETINA AND OPTIC NERVE

Objective The purpose of this study is to evaluate the ability of the Optical Coherence Tomography Unit Model 2010 to accurately measure and reproducemeasurements of the optic nerve head excavation, retinal fiber thickness layer

and the perifoveal retinal thickness in patients suspected of having glaucoma or patients with glaucoma.Contact S. Smith, M.D., M.P.H., 216/444-1995, or R. Scott, 216/444-0680

PEDIATRICS AND STRABISMUS

COMPARISON OF LEA GRATING PADDLESWITH TELLER ACUITY CARDS FOR EVALUATIONOF VISUAL ACUITY IN PREVERBAL PATIENTS

Objective Pediatric ophthalmologists areinvestigating a new method of checkingvisual acuity in preverbal children. Thismethod uses the principle of preferentiallooking. Infants' acuity is tested usingTeller acuity cards and Lea Grating Pad-dles during the same clinical visit. The investigators are trying to determine ifLea Grating Paddles are accurate and if they offer any advantage over the widelyaccepted Teller Acuity Cards.Contact E. Traboulsi, M.D., 216/444-4363or D. Peralta, M.D., 216/444-4363

COLOR SORT TEST

Objective This project compares an individual's performance on four tests of color vision.Contact E. Traboulsi, M.D., 216/444-4363

REFRACTIVE SURGERY

THE EFFECT OF CREATING A LASIK FLAP ASDETERMINED BY WAVEFRONT ANALYSIS

Objective To determine the effect of creating a LASIK flap.Eligibility Criteria Subjects more than18 years of age and eligible for LASIK.Contact R. Krueger, M.D., 216/444-8158,or R. Scott, 216/444-0680

USE OF WAVEFRONT DEVICE FOR DIAGNOSTIC MEASUREMENTS

Objective The CustomCornea WavefrontDevice from Alcon/Summit Autonomouswill be evaluated for repeatability and accuracy of measurements as comparedwith manifest refraction and topography.Eligibility Criteria Must be 18 years ofage or older. Participants will have eyesdilated. Must be eligible for LASIK, PRKor AK.

Contact R. Krueger, M.D., 216/444-0848,or R. Scott, 216/444-0680

CUSTOMCORNEA LASIK SURGERY

Objective To evaluate the ability of theCustomCornea Device in its ability to im-prove keratorefractive surgery. Custom-Cornea is a new method of measuring thevisual system of the eye. These measure-ments are used in conjunction with theexcimer laser system to customize the ap-plication of the laser beam to the individ-ual’s needs. This allows the excimer laserto reshape the cornea so that light enter-ing the eye is properly focused. If thistechnology proves reliable, it stands toimprove keratorefractive surgery by mini-mizing or eliminating common postopera-tive side effects such as glare, halos,double vision, night vision difficulties,and residual refractive error.Contact R. Krueger, M.D., 216/444-8158,or R. Scott, 216/444-0680

VISION THERAPY: A PROGRESSIVE CONTROLLED STUDY ON THE EFFECT-IVENESS OF VISION THERAPY IN ELIMINATING ASTHENOPIA IN A SYMPTOMATIC POPULATION

Eligibility Criteria Patients who are 18to 35 years old and have any of the fol-lowing symptoms: eye strain, occasionalblurred vision when using a computer orperforming other near work, occasionalheadaches, have words run together orfall asleep when doing prolonged comput-er work or near work. If eligible, partici-pation will involve approximately threevisual assessments at the Cleveland ClinicDivision of Ophthalmology at Beachwoodand required equipment for therapy. Com-pensation of $100 will be allotted fortravel expenses.Contact D. Tucker, O.D., 216/831-0120, orK. Danko, C.O.T., 216/831-0120

RETINAL DISEASES

DIABETIC MACULAR EDEMA IMPLANT STUDY(CDS FL-007)

Objective This 4-year multi-center con-trolled study is designed to evaluate thesafety and efficacy of an intravitreal fluo-cinolone acetonide implant, Retisert, inpatients with diabetic macular edema. Pa-tients will be randomly assigned to one of three study groups: 1. Vitrectomy with Retisert implant;

Cole Eye Institute

Clinical Trials All studies have been approved by the Institutional Review Board.

10

THE CLEVELAND CLINIC COLE EYE INSTITUTE IS PROUD TO PRESENT THE 2003 DISTIN-

GUISHED LECTURE SERIES, WHICH PROVIDES A FORUM FOR RENOWNED RESEARCHERS

IN THE VISUAL SCIENCES TO PRESENT THEIR LATEST RESEARCH FINDINGS. THIS SERIES

OF LECTURES WILL FEATURE ADVANCES IN MANY AREAS OF OPHTHALMIC RESEARCH

PRESENTED BY NOTED BASIC AND CLINICAL SCIENTISTS FROM THROUGHOUT THE WORLD.

AMPLE OPPORTUNITY FOR QUESTIONS AND DISCUSSION WILL BE PROVIDED.

PLEASE JOIN US FOR THESE INSIGHTS INTO OPHTHALMIC RESEARCH AND THE

PROMISES THEY HOLD FOR PATIENT CARE. NO REGISTRATION IS REQUIRED. CALL 216/444-5832

WITH QUESTIONS.

ALL PROGRAMS ARE HELD AT THE CLEVELAND CLINIC COLE EYE INSTITUTE’S JAMES

P. STORER CONFERENCE CENTER FROM 7 TO 8 A.M. ATTENDEES SHOULD PARK IN THE

EAST 102ND STREET PARKING LOT (FACING THE FRONT OF THE COLE EYE INSTITUTE) OR

THE VISITORS’ PARKING GARAGE AT EAST 100TH STREET AND CARNEGIE AVENUE. WE

WILL VALIDATE YOUR PARKING TICKET.

September 25, 2003UPDATE ON THERAPIES FOR AGE-RELATED MACULAR DEGENERATION

Joan W. Miller, M.D.Professor of OphthalmologyHarvard Medical School, Boston, Mass.

October 16, 2003STRATEGIES FOR RPE REPLACEMENT IN PATIENTS WITH AGE-RELATED MACULAR DEGENERATION

Marco A. Zarbin, M.D., Ph.D.Professor and ChairInstitute of Ophthalmology and Visual ScienceNew Jersey Medical SchoolUniversity of Medicine and Dentistry of New Jersey, Newark, N.J.

November 20, 2003ENERGY METABOLISM IN RETINAL NEURONS AND GLIA: IMPLICATIONS FOR PHYSIOLOGY AND PATHOLOGY

Barry S. Winkler, Ph.D.Professor of Biomedical SciencesEye Research InstituteOakland University, Rochester, Mich.

Thursday, December 11, 2003FISHING FOR NOVEL GENES

John E. Dowling, Ph.D.Llura and Gordon Gund Professor of NeurosciencesDepartment of Molecular and Cellular BiologyHarvard University, Cambridge, Mass.

5 11

2. Vitrectomy without Retisert implant; 3. Retisert implant alone Contact P. Kaiser, M.D., 216/444-6702, orK. Schach, 216/444-2566

TRANSPUPILLARY THERMOTHERAPY (TTT) OFOCCULT SUBFOVEAL CHOROIDAL NEOVAS-CULAR MEMBRANES IN PATIENTS WITH AMD

Objective To determine if a diode laserwith lower power will close abnormalvessels, yet preserve normal retina.Eligibility Criteria Patients must havethe wet (exudative) form of AMD, havevisual acuity of 20/50 to 20/400 and beage 50 or older.Contact P. Kaiser, M.D., 216/444-6702, orL. Schaaf, R.N., 216/445-4086

VIO: VISUDYNE IN OCCULT MACULAR DEGENERATION

Objective To determine if Visudyne ther-apy will slow vision loss in patients withoccult, “wet” macular degeneration. Thisstudy will measure vision loss in patientstreated with Visudyne therapy comparedwith those receiving placebo.Contact P. Kaiser, M.D., 216/444-6702, orL. Holody, C.O.A., 216/445-3762

ANECORTAVE ACETATE VS. VISUDYNE

Objective To evaluate the safety and effectiveness of an investigational med-ication called anecortave acetate in pre-venting growth of blood vessels under the retina in patients with macular degen-eration as compared to treatment with Visudyne.Contact P. Kaiser, M.D., 216/444-6702 orK. Schach, 216/444-2566

UVEITIS

NONINFECTIOUS PANUVEITIS, INTERMEDIATEUVEITIS AND POSTERIOR UVEITIS

Objective Overproduction of TNF-α, akey mediator of inflammation, may leadto disease processes associated with in-flammation. Neutralizing TNF-α by bind-ing an antagonist to it may preventinflammation. The objective of this study is to evaluate the safety of multiple sub-cutaneous administrations of the humanmonoclonal antibody to human TNF-α(CNTO 148) in patients with intermediateuveitis, posterior uveitis or panuveitis at3-dose levels compared with placebo.Contact C. Lowder, M.D., 216/444-3642,or C. Rosal, R.N., 216/445-1256

Distinguished Lecture Series

12

Hilel Lewis, M.D.Chairman, Division of OphthalmologyDirector, Cole Eye InstituteSpecialty/Research Interests Vitreoretinalsurgery for complicated retinal detach-ment and trauma, age-related maculardegeneration, diabetic retinopathy, retinalphotocoagulation, instrument development

Bela Anand-Apte, M.B.B.S., Ph.D.Ophthalmic Research DepartmentResearch Interest Angiogenesis

John W. Crabb, Ph.D.Ophthalmic Research DepartmentResearch Interests Age-related macular degeneration, inherited retinal diseases

Marc A. Feldman, M.D.Ophthalmic AnesthesiaSpecialty/Research Interests Ophthalmicsurgery anesthesia, preoperative assess-ment, resident education

Philip N. Goldberg, M.D.Comprehensive Ophthalmology DepartmentSpecialty/Research Interests Cataract,glaucoma

Froncie A. Gutman, M.D.Vitreoretinal DepartmentSpecialty Interests Retinal vascular dis-eases, laser therapy, diabetic retinopathy

Stephanie A. Hagstrom, Ph.D.Ophthalmic Research DepartmentResearch Interests Inherited forms ofretinal degeneration, including maculardegeneration and retinitis pigmentosa

Joe G. Hollyfield, Ph.D.Ophthalmic Research DepartmentResearch Interests Retinal degeneration,retinal diseases

David Huang, M.D., Ph.D.Cornea and External Disease and Refractive Surgery DepartmentsSpecialty/Research Interests Kerato-refractive surgery, instrumentation and equipment development, corneal disease,cataract/anterior segment surgery

Bennie H. Jeng, M.D.Cornea and External Disease DepartmentSpecialty/Research Interests Cornealtransplantation, ocular surface disease,limbal stem cell transplantation, artificialcorneas, eyebanking

Peter K. Kaiser, M.D.Vitreoretinal DepartmentSpecialty/Research Interests Vitreo-retinal diseases, age-related macular de-generation, retinal detachment, diabeticretinopathy, endophthalmitis, posterior

Cole Eye Institute

StaffEdward J. Rockwood, M.D.Glaucoma DepartmentSpecialty Interests Glaucoma, glaucomalaser surgery, combined cataract and glau-coma surgery, glaucoma filtering surgerywith antimetabolite therapy, glaucomatousoptic nerve damage

Allen S. Roth, M.D.Comprehensive Ophthalmology DepartmentSpecialty Interests Corneal transplanta-tion, refractive surgery, cataract and implant surgery

Jonathan E. Sears, M.D.Vitreoretinal DepartmentSpecialty/Research Interests Pediatricand adult vitreoretinal diseases, pediatricretinal detachment, inherited vitreoretinaldisorders, retinopathy of prematurity,other acquired proliferative diseases

David B. Sholiton, M.D.Comprehensive Ophthalmology DepartmentSpecialty Interests Cataract and implantsurgery, glaucoma, oculoplastics

Scott D. Smith, M.D., M.P.H.Glaucoma DepartmentSpecialty/Research Interests Glaucoma,cataract, prevention of eye disease, inter-national ophthalmology

O. David Solomon, M.D.Comprehensive Ophthalmology DepartmentSpecialty Interests Contact lens research,general ophthalmology

Elias I. Traboulsi, M.D.Pediatric Ophthalmology and Strabismus Department, Center for Genetic Eye DiseasesSpecialty/Research Interests Ocular diseases of children, genetic eye diseases,strabismus, retinoblastoma, congenital cataracts, childhood glaucoma

Steven E. Wilson, M.D.Cornea and External Disease and Refrac-tive Surgery DepartmentsSpecialty/Research Interests Corneal andexternal disease, corneal transplantation,refractive surgery, corneal healing

216/444-2020The Cleveland ClinicCole Eye Institute

Visit The Cleveland Clinic onlineat www.clevelandclinic.org and the Cole Eye Institute atwww.clevelandclinic.org/eye

segment complications of anterior seg-ment surgery

Gregory S. Kosmorsky, D.O.Neuro-Ophthalmology DepartmentSpecialty Interests Neuro-ophthalmology,cataract, refractive surgery

Ronald R. Krueger, M.D.Refractive Surgery DepartmentSpecialty/Research Interests Refractivesurgery, lasers, refractive corneal pathology,lamellar corneal transplants, investigationalclinical trials

Roger H.S. Langston, M.D.Cornea and External Disease DepartmentSpecialty Interests Cornea and externaldisease, corneal transplantation

Michael S. Lee, M.D.Neuro-Ophthalmology DepartmentSpecialty/Research Interests Neuro-ophthalmology, optic neuropathies, doublevision

Careen Y. Lowder, M.D., Ph.D.Uveitis DepartmentSpecialty/Research Interests Uveitis, in-traocular inflammatory diseases, pathology

Andreas Marcotty, M.D.Pediatric Ophthalmology and StrabismusDepartmentSpecialty Interests Pediatric ophthalmol-ogy, adult strabismus

David M. Meisler, M.D.Cornea and External Disease DepartmentSpecialty/Research Interests Corneal and external disease, inflammatory andinfectious diseases of the cornea, cornealtransplantation, refractive surgery

Michael Millstein, M.D.Comprehensive Ophthalmology DepartmentSpecialty Interests Cataract, glaucoma,refractive surgery

Neal S. Peachey, Ph.D.Ophthalmic Research DepartmentResearch Interest Visual loss associatedwith hereditary retinal degeneration

Victor L. Perez, M.D.Cornea and External Disease DepartmentSpecialty/Research Interests Medical and surgical treatments of autoimmuneinflammatory conditions of the corneaand ocular surface, uveitis, corneal trans-plantation, cataract surgery

Julian D. Perry, M.D.Oculoplastic and Orbital Surgery DepartmentSpecialty/Research Interests Aestheticfacial surgery/fat transplantation andrepositioning, acellular human dermalgraft matrix, new bovine hydroxyapatiteorbital implant, thyroid eye disease/rate of strabismus after decompression surgeryfor dysthyroid orbitopathy

13

Programs in Ophthalmic EducationSeptember 2003-March 2004

PHYSICIANS ARE CORDIALLY INVITED TO

ATTEND THE FOLLOWING OPHTHALMIC CON-

TINUING MEDICAL EDUCATION COURSES AT

THE CLEVELAND CLINIC COLE EYE INSTITUTE.

ALL COURSES WILL BE HELD IN THE JAMES

P. STORER CONFERENCE CENTER ON THE

FIRST FLOOR OF THE COLE EYE INSTITUTE,

UNLESS OTHERWISE NOTED.

For more details, contact Jane Sardelle,program coordinator, at 216/444-2010or sardelj@ccf.org. View the entirecourse catalog online at http://www.clevelandclinic.org/eye/physician_info.

Saturday, September 6, 2003CONJUNCTIVAL INFLAMMATION: A STEPLADDER APPROACH IN DIAGNOSIS,TREATMENT AND OCULAR SURFACE SURGICAL RECONSTRUCTION

Course Co-DirectorsVictor L. Perez, M.D.David M. Meisler, M.D.Cole Eye Institute

Guest FacultyClaes H. Dohlman, M.D., Ph.D.Professor of OphthalmologyCornea and External DiseaseMassachusetts Eye & Ear InfirmaryHarvard Medical SchoolBoston, Mass.

Bennie Jeng, M.D.Anterior Segment/Cornea DepartmentCole Eye InstituteCleveland Clinic FoundationCleveland, Ohio

Ophthalmic

Continuing Medical Education

Francis S. Mah, M.D.Assistant ProfessorDepartment of OphthalmologyCornea and External Disease and Refractive SurgeryUniversity of Pittsburgh Medical CenterPittsburgh, Pa.

Julian D. Perry, M.D.Ophthalmic Plastic & Orbital SurgeryDepartmentCole Eye InstituteCleveland Clinic FoundationCleveland, Ohio

E. Lee Stock, M.D.Professor of OphthalmologyCornea-External Disease Service Eye InstituteMedical College of WisconsinMilwaukee, Wis.

Scheffer C. G. Tseng, M.D., Ph.D. Associate ProfessorUniversity of Miami/Bascom PalmerEye InstituteOcular Surface Center and Ocular SurfaceResearch & Education FoundationMiami, Fla.

Conjunctival inflammation is one of themost common diseases evaluated andtreated by ophthalmologists. The differ-ential diagnosis is broad, complex andincludes local or systemic diseases thatcan lead to significant ocular morbidityand blindness. Moreover, the etiologyof the inflammation will determine theappropriate course of action and treat-ment that will prevent progression andcomplications. The goal of this course is to present ophthalmologists with acomprehensive review of the differentcauses that should be considered whenevaluating a patient with conjunctivalinflammation. These include infections,immune-mediated inflammation, trau-ma, malignancies and other disorderspresenting as a masquerade syndrome.

The course will provide updated infor-mation with regard to the medical andsurgical management of conjunctivalinflammatory disorders. Experts in thefield will review the new informationavailable for the role and use of thenew family of anti-microbials and im-munomodulation therapy available forspecific conjunctivitis. In addition tothese, our guest faculty will present the most recent surgical techniquesavailable for the vision rehabilitationand treatment of these diseases, includ-ing the latest concepts in conjunctivalresection, amniotic membrane grafts,limbal stem-cell grafting and kerato-prosthesis.

At the conclusion of this course,participants should be able to:• Describe the different clinical man-

ifestations of conjunctival diseases.

• Identify the newest anti-microbialtreatment of infectious conjunctivalinflammation.

• Recognize other non-infectious causes of conjunctival inflammationand approaches to treatment.

• Summarize the newest development in amniotic membrane and limbalstem-cell grafting and keratoprosthesis.

Saturday, October 11, 2003UPDATE ON DIABETIC RETINOPATHY: CURRENT KNOWLEDGE, NEW DEVELOPMENTSAND CASE PRESENTATIONS

Course DirectorHilel Lewis, M.D.Chairman, Division of OphthalmologyDirector, Cole Eye Institute

Guest FacultyThomas R. Friberg, M.D.University of PittsburghEye and Ear InstitutePittsburgh, Pa.

Thomas W. Gardner, M.D.Professor of Ophthalmology andCellular and Molecular PhysiologyPennsylvania State College of MedicineHershey, Pa.

14

nosis and management that will allowthe participant to identify distinct fea-tures of diabetic retinopathy, interpretthe clinical angiographic and OCT find-ings and manage and treat commonand difficult cases.

At the conclusion of this course,participants should be able to:• Recognize biochemical mechanisms

and implication for pharmacologictherapies.

• Summarize evidence on the role ofdiabetic control and medical therapyin the prevention and treatment ofdiabetic retinopathy.

• Recognize the role of serum lipids as a predictor of macular edema.

• Determine the role of OCT in the diagnosis and treatment of diabeticmacular edema.

• Describe the indications, approachesand techniques for laser photocoagu-lation for both diabetic macularedema and proliferative diabetic retinopathy.

• Describe new and experimental treat-ment options, such as the use of intravitreal steroids.

• Identify indications for surgery.

Saturday, November 1, 2003UPDATE ON NEURO-OPHTHALMOLOGY: VISION LOSS WITH A “NORMAL” EYE EXAMINATION

Course Co-DirectorsMichael S. Lee, M.D.Gregory S. Kosmorsky, D.O.Cole Eye Institute

Guest FacultyRandy H. Kardon, M.D., Ph.D.Associate ProfessorDepartment of OphthalmologyUniversity of Iowa HospitalsIowa City, Iowa

Simmons Lessell, M.D.Professor of OphthalmologyDirector, Neuro-Ophthalmology UnitMassachusetts Eye and Ear InfirmaryHarvard Medical SchoolBoston, Mass.

Nancy Newman, M.D.Leo Delle Joley, Professor of OphthalmologyProfessor of Ophthalmology and NeurologyInstructor, NeurosurgeryEmory University School of MedicineAtlanta, Ga.

Some patients complain of vision losswithout apparent ocular abnormalities.Functional vision loss, however, is a diagnosis of exclusion. This course willpresent clinical approaches to the pa-tient with a “normal” eye examinationand reduced visual acuity.

At the conclusion of this course,participants should be able to:• Incorporate strategies to test patients

with functional vision loss.• Localize sources and causes of visual

decline in the setting of a normal-appearing eye.

Friday to Monday, February 13-16, 2004INTERNATIONAL COURSE: NEW INSIGHTS, ADVANCES AND PRACTICALAPPROACHES IN OPHTHALMOLOGY

Cabo San LucasBaja California, Mexico(Hotel: Presidente InterContinental)

Course Co-DirectorsHilel Lewis, M.D.Chairman, Division of OphthalmologyDirector, Cole Eye InstituteThe Cleveland Clinic FoundationCleveland, Ohio, USA

Hugo Quiroz-Mercado, M.D.Director, Vitreoretinal DepartmentAsociacion Para Evitar La Ceguera En Mexico, IAPMexico City, Mexico

Peter K. Kaiser, M.D.Vitreoretinal Department Cole Eye InstituteCleveland Clinic FoundationCleveland, Ohio

Leonid Lerner, M.D., Ph.D.Vitreoretinal Department Cole Eye InstituteCleveland Clinic FoundationCleveland, Ohio

S. Sethu Reddy, M.D.ChairmanDepartment of EndocrinologyCleveland Clinic FoundationCleveland, Ohio

Jonathan E. Sears, M.D.Vitreoretinal Department Cole Eye InstituteCleveland Clinic FoundationCleveland, Ohio

This program is designed to providecomprehensive ophthalmologists andretina specialists with a comprehensivereview of prevention and treatment of diabetic retinopathy and its comp-lications. New information on the bio-chemical mechanisms and the implica-tions for pharmacotherapy will bepresented. In addition, new informationfrom prevention, such as the role of diabetic control and the role of lipids,will be discussed and interpreted. Spe-cial topics will include the role that optical coherence tomography plays inthe diagnosis and management of com-plications from diabetic retinopathy;new laser strategies for diabetic macu-lar edema; and the role of intravitrealsteroids and vitreoretinal surgery in thetreatment of diabetic macular edema.Current clinical trials will be discussedand interpreted.

A special practical and clinicallyoriented approach utilizing case presen-tations will emphasize details of diag-

Continuing MedicalEducation continued

15

Guest Facultyfrom the Asociacion Para Evitar La Ceguera En Mexico, Hospital Dr. Luis Sanchez Bulnes

Lourdes Arellanes-Garcia, M.D.Uveitis/Inflammatory Diseases Department

Mateo de Regil, M.D.Anterior Segment Department

Felix Gil-Carrasco, M.D.Glaucoma Department

Eduardo Moragrega-Adame, M.D.Ultrasound Department

Virgilio Morales-Canton, M.D.Retina Department

Ramon Naranjo-Tackman, M.D.Cornea Department

Abelardo Rodriguez, M.D.Pathology Department

Guillermo Salcedo-Casillas, M.D.Chairman, Oculoplastic Department

Jorge Villar-Kuri, M.D.Head, Medical Personnel

Jaime Villaschor-Solares, M.D.Chairman, Asociacion Para Evitar La Ceguera En MexicoHospital Dr. Luis Sanchez Bulnes

Guest Facultyfrom the Cole Eye Institute,The Cleveland Clinic

David Huang, M.D., Ph.D.Refractive Surgery Department

Michael S. Lee, M.D.Neuro-Ophthalmology Department

Victor L. Perez, M.D.Cornea and External Disease Department

Scott D. Smith, M.D., M.P.H.Glaucoma Department

Elias I. Traboulsi, M.D.Pediatric Ophthalmology and Adult Strabismus Department

This international course will provide a comprehensive review of new devel-opments in clinical practice and willemphasize state-of-the-art management,problem-solving, case presentations andevaluation of new interventions andtechnology. There will be ample timefor questions and answers and the fac-ulty will be available throughout thecourse for informal consultation anddiscussion.

At the conclusion of this course,participants should be able to:• Describe the pathogenesis of

different ocular disorders.• Evaluate and utilize new diagnostic

and surgical techniques.• Develop effective management

strategies.

AccreditationThe Cleveland Clinic Center forContinuing Education is accredit-ed by the Accreditation Councilfor Continuing Medical Educationto provide continuing medical education for physicians.

The Cleveland Clinic Centerfor Continuing Education desig-nates this educational activity fora maximum of 0.5 Category 1credit toward the AMA Physician’sRecognition Award. Each physi-cian should claim only those cred-its that he/she actually spent inthe activity.

This activity may be submit-ted for American Osteopathic As-sociation Continuing MedicalEducation Credits in Category 2.

Faculty DisclosureCurrent guidelines state that participants in CME activities should be made aware ofany affiliation or financial interest that may affect the faculty’s presentation(s) and/orwho will be discussing off-label therapies.

The following faculty have indicated thatthey have a relationship which, in the contextof their presentations, could be perceived asa potential conflict of interest:

David Huang, M.D., Ph.D.: The Cleveland Clinic has filed a patent application based on the Advance HealingAdjusted Ablation invention. Dr. Huang has a proprietary interest in the technology.

Ronald R. Krueger, M.D.: Grant/Research Support and Speaker’s Bureau – Alcon.

The following faculty will be discussingtherapies that are not yet labeled (FDA approved) for the use under discussion, orthe products are still investigational:

David Huang, M.D., Ph.D., Ronald R. Krueger, M.D.

The following faculty have indicated theyhave no relationship which, in the contextof their articles, could be perceived as a potential conflict of interest:

Bela Anand-Apte, Ph.D.

Ophthalmology Update, a publication of The ClevelandClinic Cole Eye Institute, provides information forophthalmologists about state-of-the-art diagnosticand management techniques and current research.Please direct any correspondence to:

Scott D. Smith, M.D., M.P.H.Cole Eye Institute / i32The Cleveland Clinic Foundation9500 Euclid AvenueCleveland, Ohio 44195Phone 216/444-4821Fax 216/445-8475

Director and Division ChairmanHilel Lewis, M.D.

Editor-in-ChiefScott D. Smith, M.D., M.P.H.

Editorial BoardDavid Huang, M.D., Ph.D.Julian D. Perry, M.D.Jonathan E. Sears, M.D.

Managing EditorsBeth Thomas HertzHolly Strawbridge

Graphic DesignerBarbara Ludwig Coleman

PhotographersDon Gerda and Tom Merce

The Cleveland Clinic Foundation is an independent,not-for-profit, multispecialty academic medical center.It is dedicated to providing quality specialized careand includes an outpatient Clinic, a hospital with approximately 927 staffed beds, an Education Divisionand a Research Institute.

Ophthalmology Update is written for physicians andshould be relied upon for medical education purposesonly. It does not provide a complete overview of thetopics covered and should not replace the independentjudgment of a physician about the appropriateness orrisks of a procedure for a given patient.

Physicians who wish to share this information withpatients need to make them aware of any risks orpotential complications associated with any procedures.

Release date September 1, 2003Expiration date February 29, 2004

© The Cleveland Clinic Foundation, 2003

Non-Profit Org.U.S. Postage

PAIDCleveland, OH

Permit No. 41849500 Euclid Avenue / W14Cleveland, OH 44195

Ophthalmic Pearl

ADVANCES IN THE MEDICAL THERAPY OF GLAUCOMA HAVE PRODUCED A VARIETY

OF OPTIONS FOR THE TREATMENT OF GLAUCOMA. IS ONE AGENT BETTER THAN

ANOTHER? POORLY DESIGNED STUDIES MAKE IT DIFFICULT TO ACCEPT DATA FROM

PHARMARCEUTICAL COMPANIES AT FACE VALUE.

When selecting an effective treatment regimen for patients, we areoften faced with choosing from among medications without having seen a direct comparison of the relative efficacy and safety of each agent. Phar-maceutical representatives frequently present us with data from clinicalstudies comparing their medication to others. However, these data alwayshighlight the benefits of their particular product. Such studies should beviewed with extreme skepticism. Here is one example why:

Recently, I was shown the results of a “study” that purported to showthat drug A was better than drug B in lowering intraocular pressure (IOP).The study involved switching patients from drug B to drug A, and comparedIOP before and after this switch. A “statistically significant” reduction inIOP after switching to drug A had been found.

While this seems simple enough, I asked the pharmaceutical represen-tative why patients were switched from drug B to drug A. I wondered ifthis was a clinical trial in which patients were switched as part of a studyprotocol or switched because their doctor felt the IOP was too high. As itturns out, patients were switched because their IOP was felt to be too high.

This fact alone makes the “study” results impossible to interpret. Weare all aware that patients experience periodic fluctuations in IOP. Selectingonly those patients with high IOP virtually guaranteed that the average IOPon the following visit would be lower, regardless of whether the medicationwas switched or not. The competitor could have done the same study,switching from drug A to drug B, and would have found their drug to be“better.” This well-known phenomenon, called regression to the mean, is a form of selection bias that frequently affects clinical studies. Such formsof bias are abundant in clinical studies that are not properly designed.

Until you see a randomized, blinded clinical trial specifically designedto eliminate bias, you should maintain a healthy skepticism about compar-ative studies of glaucoma medications.

– Scott D. Smith, M.D., M.P.H.