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DIAGNOSTIC EDITIONThe Present andFuture of Diagnosticsin GlaucomaGlaucoma Today held a roundtable discussion at the 2007 Annual Meeting of the AmericanGlaucoma Society. Participants shared their views on current technologies, methods forevaluating patients, the challenges that clinicians face, and the possibilities of the near future.PARTICIPANTSRichard A. Lewis, MD, moderator, is ChiefMedical Editor of Glaucoma Today and is in private practice in Sacramento, California. He is aconsultant to and member of the speakers’bureaus for Alcon Laboratories, Inc.; Allergan, Inc.; IstaPharmaceuticals, Inc.; Pfizer Inc.; Santen, Inc.; TranscendMedical; and Carl Zeiss Meditec, Inc. Dr. Lewis may bereached at (916) 649-1515; [email protected] P. Mills, MD, MPH, was ClinicalProfessor of Ophthalmology at the University ofWashington and is in private glaucoma practicein Seattle. Dr. Mills is a consultant for Allergan,Inc., and Pfizer Inc., and he has received lecturing fees fromPfizer Inc.; Alcon Laboratories, Inc.; Merck & Co., Inc.; andHeidelberg Engineering, Inc. Dr. Mills may be reached at (206)682-3447; [email protected] D. Brandt, MD, is Professor of Ophthalmology and Director of the Glaucoma Serviceat the University of California, Davis. He is a consultant to and member of the speakers’ bureausfor Alcon Laboratories, Inc.; Allergan, Inc.; and Pfizer Inc.Dr. Brandt may be reached at (916) 734-6818;[email protected] S. Schuman, MD, is the Eye and EarFoundation Professor and Chairman of Ophthalmology at the Eye and Ear Institute of the University of Pittsburgh School of Medicine. He isalso Director of the University of Pittsburgh Medical CenterEye Center and Professor of Bioengineering at the Universityof Pittsburgh School of Engineering. During the past 3 years,Dr. Schuman has received research funding, research equipment, honoraria, and/or payment of faculty travel expensesfrom Alcon Laboratories, Inc.; Allergan, Inc.; Carl ZeissMeditec, Inc.; Heidelberg Engineering, Inc.; Merck & Co., Inc.;and Pfizer Inc. He receives royalties from intellectual propertylicensed by M.I.T. to Carl Zeiss Meditec, Inc. Dr. Schuman maybe reached at (412) 647-2205; [email protected] W. Herndon, MD, is Associate Professor ofOphthalmology at Duke University Eye Center inDurham, North Carolina. Dr. Herndon is a memberof the speakers’ bureaus for Alcon Laboratories, Inc.;Allergan, Inc.; Ista Pharmaceuticals, Inc.; Merck & Co., Inc.; andPfizer Inc. He sits on the advisory boards of Alcon Laboratories,Inc., and Ista Pharmaceuticals, Inc. Dr. Herndon may be reachedat (919) 684-6622; [email protected] A. Medeiros, MD, is Associate Professorof Ophthalmology at the Hamilton GlaucomaCenter, University of California, San Diego. He hasreceived research support and honoraria fromAlcon Laboratories, Inc.; Allergan, Inc.; Heidelberg EngineeringGmbH; Pfizer Inc.; and Carl Zeiss Meditec, Inc. Dr. Medeirosmay be reached at [email protected] N. Weinreb, MD, is Distinguished Professor of Ophthalmology and Director of theHamilton Glaucoma Center, University of California, San Diego. He is a consultant to AlconLaboratories, Inc.; Allergan, Inc.; Bausch & Lomb; Merck &Co.,Inc.; Novartis Pharmaceuticals; Pfizer Inc.; and Carl Zeiss Meditec, Inc. He has received research instruments from Carl ZeissMeditec, Inc., and Heidelberg Engineering GmbH. Dr. Weinrebmay be reached at [email protected]/DECEMBER 2007 I GLAUCOMA TODAY I 21

DIAGNOSTIC EDITION(Courtesy of Heidelberg Engineering GmbH.)Figure 1. The HRT Glaucoma Module Premium Edition: Topographical Change Analysis uses three images to identify areas ofchange and progression.IM AGING SYSTE MSLewis: Is there a clear advantage of one imaging systemover another, and what is the latest information abouttheir abilities to document progression?(Courtesy of Carl Zeiss Meditec, Inc.)Medeiros: I do not see any clear evidence of any oneinstrument’s superiority over another, but each has advantages and disadvantages. The Heidelberg Retina Tomograph (HRT; Heidelberg Engineering GmbH, Heidelberg,Germany) has been available the longest, so there aremany longitudinal studies demonstrating that the device isable to detect progression. For example, the ConfocalScanning Laser Ophthalmoscopy Ancillary Study to theOcular Hypertension Treatment Study has shown thatmeasurements with the HRT are able to predict the futuredevelopment of glaucoma in people with ocular hypertension1 (Figure 1). On the other hand, the Stratus OCT andGDx (both manufactured by Carl Zeiss Meditec, Inc.,Dublin, CA) can evaluate the retinal nerve fiber layer(RNFL) (Figure 2), which the HRT can only do indirectly.Although these two instruments have not been availableas long as the HRT, the technologies are promising, andlongitudinal studies evaluating these instruments shouldoccur soon.Lewis: In terms of diagnosing early glaucoma versusassessing more advanced disease, do you have a preference on technologies?Figure 2. Testing with the GDx reveals extensive loss of theRNFL superiorly in the patient’s left eye and wedge-shapeddefects in his left.Medeiros: The assessment of the RNFL is fundamental tothe early diagnosis of glaucoma, and I find the instrumentsthat evaluate the RNFL to be helpful in this situation, because they provide complementary information to what weobtain from evaluations of the optic nerve at the slit lampor with photographs. Because the RNFL is difficult to examine at the slit lamp or with photographs, these instrumentscan help us to decide whether or not a glaucoma suspecthas early damage. It is important to note, however, that wecurrently have little evidence to determine the utility ofthese instruments in early versus advanced disease.22 I GLAUCOMA TODAY I NOVEMBER/DECEMBER 2007Schuman: In the real world, doctors have to get paidfor services that they provide, and many payers are saying

DIAGNOSTIC EDITIONthat these instruments are not useful in late disease andwill not pay for their use. It is difficult for clinicians to getpaid fairly for the services they provide. I think Felipe’spoint is important in that we do not really know if thesetechnologies are less valuable in patients with advancedversus early disease.RNFL imaging devices allow us to quantitatively andobjectively measure something that we otherwise cannot.A clinical examination may reveal an area of RNFL dropout,but you do not know how much. These devices let you puta number on that. The HRT is the only instrument that hasvalidated progression software. Data from late-stage-development progression software have already been presentedat events sponsored by Carl Zeiss Meditec, Inc., during the2006 AAO Annual Meeting as well as other more recentconclaves for the GDx and the Stratus OCT. The information presented to date shows promise.Mills: As validation studies are laboriously conducted,we will accumulate the evidence that will allow us toanswer your original question, Rick. We are in a growthphase for this technology. In the meantime, what hasproven to be clinically useful is largely an anecdotal exercise, and we just have to accept that.Schuman: I am not sure that I agree. There are studiesshowing that the HRT, Stratus OCT, and GDx are at leastas good as an expert observer.2-8 Making these technologies available in communities where people rarely havetheir optic nerves examined could raise the standard tothat of an expert observer in a standardized quantitativeobjective way, which I think has great value.Brandt: Yet, how many of us have seen patients whowere terrified, because they have what we now call reddisease? Their test was “positive” and showed numbers inred. The clinicians who saw these patients handed themthis printout and said, “You have glaucoma.” They are notputting the imaging results into the context of the clinical examination.Schuman: Clinicians must ensure that the test theyhave performed is of adequate quality to be evaluated.There are parameters on each of the devices to helpdetermine if the quality of a particular test is good. If it isnot, you cannot trust the result.Weinreb: There are few published data on glaucomatous progression. These technologies are in great flux.The hardware generally has not been stable, and the software has changed even more. By the time a particularconfiguration of hardware and software is validated, anew instrument has often been introduced that is toutedas an improvement. Clinicians are often left with instruments that are out of date, or they have a new instrument with new software that has not been validated.Lewis: Artifacts are a problem with imaging technologies, not that Humphrey visual fields (Carl Zeiss Meditec,Inc.) do not have their own set of problems. It seems,however, as if these imaging systems are so prevalentamong ophthalmologists and optometrists that glaucoma specialists often receive inappropriate referrals.How often should patients with glaucoma undergoimaging? How soon can you document change?Weinreb: In an ideal world, the answer is as many timesas possible. The more information one obtains, the betterone is able to detect disease and progression. Many insurers, however, only reimburse once annually for an imagingsession. Moreover, many patients balk at frequent imagingsessions, even if they are possible. Because you might needseveral sets of images to assess progression, the reality isthat, often, you cannot make that evaluation appropriatelyexcept over several years.Schuman: Certainly, imaging patients once a year ishelpful, but it is not enough. As Bob implied, it is sometimes important to perform extra testing for which thedoctor waives the fee or the patient pays. It is critical toremember that insurers do not tell you what to do, onlywhat they are going to pay for.Lewis: What provokes you to get another imaging testin a 12-month period? Would it be a change in the visualfield, an elevated IOP, the presence of a disc hemorrhage?Brandt: All of the above.Mills: You also might obtain another test if youthought you found change in one image. As with visualfields, if you repeat the same test immediately, you mayget a different result. A second test can help you separateout a lot of noise.Medeiros: It is always important to confirm abnormality.Weinreb: An attractive aspect of visual field technologyis that the software has largely been stable. The HRT hashad a stable hardware platform, and many of the imagesobtained years ago can be utilized to determine whether ornot there is progression. There has not been the same opportunity with other instruments. One hopes that all manufacturers now consider the stability of their platforms toNOVEMBER/DECEMBER 2007 I GLAUCOMA TODAY I 23

DIAGNOSTIC EDITIONenable clinicians to use the information that they havealready acquired with future instruments.Brandt: I want to raise the issue of electronic medicalrecords (EMRs). None of the imaging devices talk to eachother or to the programs for EMRs. As physicians arepushed to become more efficient in the way they seepatients, manufacturers really must give us the tools toallow us to perform progression analyses and integrate allresults into the EMRs at the desktop computer in theexamination lane.Lewis: I had to move to a second office to accommodate the new diagnostic equipment I had accumulated. Itwould be so helpful if these devices could share printersand hard drives and if we could integrate diagnostic testsinto the medical record.Brandt: If I am concerned that a patient’s visual fieldhas progressed, I want to be able to perform a glaucomaprogression analysis at the desktop computer. I shouldnot have to ask a technician to access the Humphreyperimeters to pull and run all of the historical fields. Ishould be able to do that while I see the patient.PER IMETRYLewis: Although the platform for standard automaticperimetry has been stable for 15 to 20 years, we still haveproblems with the reproducibility of results.9 What is thebest initial test for diagnosing glaucoma? Is it the SwedishInteractive Threshold Algorithm (SITA), short wavelengthautomated perimetry (SWAP), or frequency doublingtechnology (FDT) (all from Carl Zeiss Meditec, Inc.)?Herndon: I think SITA-Standard is the gold standardfor assessing patients’ visual fields. SITA-Fast may havesome short-term fluctuation, whereas the results withSITA-Standard are more reproducible over time.Mills: I would point out that SITA-Fast performs fairlywell, except for the very earliest glaucomatous defect,where the program seems to assume normality to anunacceptable degree. Those patients are few and farbetween, but their disease is exactly what you would liketo be able to detect. Plus, as Leon mentioned, the noisefactors are greater with SITA-Fast. If you plan to use avisual field as a baseline against which to measure futurechange, SITA-Standard is a better choice. Of course, SITAFast has an advantage with an uncooperative or easilytired patient, but it really does not save that much time.There is a screening platform using FDT that has beenadopted by Prevent Blindness America, and there is the24 I GLAUCOMA TODAY I NOVEMBER/DECEMBER 2007Humphrey Matrix (Carl Zeiss Meditec, Inc.). The latter isthe threshold version of the FDT, and I think that has alot more merit for detecting early defects in ocularhypertensive patients. I find that FDT is more generallyapplicable to a wider patient population than SWAP,although it arguably may be a little less sensitive.Medeiros: My colleagues and I compared FDT on theHumphrey Matrix with SITA-Standard.10 In our analysis,the Humphrey Matrix performed well in people with earlydamage, and its results were substantially better than withSITA. It is important to point out that, to adequately compare these tests, one has to evaluate the influence of thedisease’s severity and control for that. It is possible that agiven test performs better in the early stages of disease,whereas another performs better in the late stages. If onedoes not stratify or adjust for the disease’s severity, thesedifferences will be missed when the entire sample is analyzed. When we stratified the results by the disease’s severity, we found that the FDT on the Humphrey Matrix outperformed SITA-Standard, especially in the early stages ofdisease. In advanced disease, as expected, the two modalities performed similarly. It is important to emphasize,however, that we still do not have well-defined criteria fordiagnosing abnormalities with the Humphrey Matrix.Schuman: My colleagues and I published a couple ofarticles on the Humphrey Matrix versus SITA, and wefound that the former is no better than the latter. TheHumphrey Matrix performed about as well, although itmissed a large number of defects. SITA-Standard foundmore defects than the Humphrey Matrix FDT did.11-12 I amnot convinced that the Humphrey Matrix is any better orworse than SITA-Standard. Because we do not have theanalytical software for the Humphrey Matrix that we dofor SITA, we pretty much stick with SITA-Standard.Brandt: In terms of SITA SWAP, I find it most useful forconfirming the normality of an eye with an optic nervethat is difficult to interpret such as with high myopia. If twotests with SITA SWAP are reliable and normal, I feel fairlyconfident about following the patient a little less frequently.Lewis: When would you repeat testing?Brandt: If I had two normal SITA SWAP tests but wassomewhat concerned about the optic nerve, I might seethe patient every 6 months and then decrease to onceper year if the tests continued to be normal.Lewis: In reality, how often should clinicians repeat thevisual field test?

DIAGNOSTIC EDITIONSchuman: Whenever there is a new defect.Lewis: Would you repeat the test at 6 months?Schuman: It depends on how bad the defect is andwhether there is a structural/functional correspondence.If there is a correspondence, it is much easier to acceptthe early defect on a single test. If not, the defect mightbe real, but you should repeat the test.Weinreb: Selective functional testing is often useful forsuspected glaucoma. I use it when a patient suspiciousfor glaucoma has a normal standard visual field, whetherhe is a myope with an unusual optic disc, has glaucomatous neuropathy (namely, a glaucomatous-appearing discwithout standard achromatic visual field loss), or an ocular hypertensive. Selective functional tests are best fordetecting damage early in glaucoma’s continuum. Later inthe course of the disease, one might be better served bySITA-Standard.Herndon: Many years ago, I was asked whether Iwould treat a patient if I found defects with selectivefunctional testing but with normal standard testingstrategies. Currently, I think we would consider treatingpatients with some selective functional abnormalities,whereas most doctors would have only followed thesepatients 5 or 6 years ago.Mills: Rick, regarding when to repeat visual fields, Ithink clinicians should do so a lot more often than theydo. The specific time I would recommend, however, iswhen a clinical decision depends on the result. In acase with a structural/functional correlation, the decision does not hinge simply on the visual field but alsoon the structural result. If only the visual field changed,you need only repeat the field to confirm the change.The most common error that I see is for practitionersto make clinical changes (as minor as an alteration inmedication or as major as performing a trabeculectomy) on the basis of a single, unconfirmed visual fieldchange.Weinreb: Perimetry is most useful if you have theopportunity to confirm the presence of a defect repeatedly. This often is not possible, due to logistics or a lackof resources. It would be useful to have an objectivefunctional test that does not need to be repeated andmight have even higher sensitivity and specificity thanthat of standard perimetry.Technologies come and go. There was an electrophysiological test a few years ago that was promoted withgreat enthusiasm, but its sensitivity and specificitycould not be confirmed. It is back in development andno longer commercially available. It is not clear whenstandard perimetry will be challenged as the norm byanother functional test.Mills: My background in neuro-ophthalmology makesme a bit cynical about the so-called objective tests, because they require just as much concentration on thepart of the subject as does a subjective one. It is true thatyou eliminate the variability of pushing the button. If thesubject is not paying attention to the stimulus, however,the cortical response changes dramatically. Objectivetesting still has a subjective element.Lewis: What are your feelings about progression software packages?Brandt: They are not perfect, but these tools are betterthan anything we have had before. That said, they are notparticularly user friendly or usable in a busy practice. Weneed these tools to be usable in real time as we are seeing patients.Schuman: I think the Glaucoma Progression Analysis(GPA) software on the Humphrey Field Analyzer II (bothfrom Carl Zeiss Meditec, Inc.) is a useful test for mypatients. It shows how many points have changed andwhether there was a statistically significant change over anumber of tests (Figure 3). You still need to take theresults with a grain of salt, because we are asking patientsto look into a bowl and press a button when they see alight. It is still a very variable test. We need to interpretthe results.Weinreb: One often needs to change the baselinedepending on whether there are alterations in therapyor in the patient’s condition. It would be best if thiscould be done at the desktop instead of requiring areturn to the machine or the technician. The GPA software is a huge improvement. It is considerably easier touse and is most likely a better test than anything wehave had before. It still can be improved, however, interms of its user friendliness and efficacy.Medeiros: The GPA software is helpful, but physiciansshould keep in mind that they need to correlate theresults with the other clinical findings. Also, they shouldconsider that glaucoma usually progresses slowly, so theyhave the time to make correct decisions and do not needto take actions without confirmation and a correlationwith other clinical findings.NOVEMBER/DECEMBER 2007 I GLAUCOMA TODAY I 25

(Courtesy of the Glaucoma Imaging Group, UPMC Eye Center, Eye and Ear Institute, Ophthalmology andVisual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine.)DIAGNOSTIC EDITIONIOPs that we know are based on some form of Goldmannapplanation tonometry, and I think it will be the goldstandard for the foreseeable future. It is going to take timebefore the new tonometers are mainstream.Brandt: Part of Hans Goldmann’s genius was devising arelatively inexpensive device that fit into the workflow ofthe slit-lamp examination. All of the new devices aregoing to have to jump that hurdle before they becomewidely accepted. A 3,000 to 4,000 device that sits onone slit lamp in an office with eight lanes is not going tobe widely used.Lewis: Some physicians routinely use pneumotonometry in their practices, but a long-standing argument hasbeen that it is less accurate than Goldmann applanationtonometry. Any comments?Figure 3. This series of Humphrey SITA 24-2 visual fields demonstrates glaucomatous progression over several years.The toptwo fields are considered the baseline,and the subsequent fieldsare compared with these baseline fields as well as to each other.The top two fields show the grayscale,followed by the absolutesensitivity at each point in decibels,followed by the total deviation and pattern deviation significance maps.The lower threesets of visual fields show the grayscale,followed by the patterndeviation significance map and pattern deviation in decibels,and finally the GPA.An open triangle denotes a statistically significant reduction of sensitivity at a given point in the visual fieldon one test,the half-shaded triangles show a statistically significant reduction in sensitivity at a given point on two consecutivetests,and a black triangle indicates a statistically significantreduction in sensitivity at a given point on three consecutivetests.Three half-shaded points qualify a visual field as possibleprogression,and three black points indicate likely progressionaccording to the GPA.TONOMETRYLewis: Tonometry is probably more confusing andprone to error than ever with the introduction of cornealpachymetry, correlations, and all the fudge factors. Doesanybody have any advice for the clinician?Herndon: I do not think that Goldmann applanationtonometry is going anywhere soon. This technology hasbeen here for more than 50 years, and all of the clinicaland multicenter trials are based on it. The true range of26 I GLAUCOMA TODAY I NOVEMBER/DECEMBER 2007Mills: We should also insist that tonometers havereproducibility under a variety of clinical circumstances.Once you have a reproducible tonometer, it really doesnot matter so much whether the number you are gettingis actually the pressure inside the eye. I am not talkingabout a large discrepancy, but the errors we are all awareof with Goldmann applanation tonometry. The mainissue is how that pressure changes over time with therapy. Certainly, I think it is important to understand thatmaybe you have an underestimate relating to cornealthickness or that other factors are in the equation, but,ultimately, therapeutic decisions are based on change.Medeiros: I think one of the reasons why new tonometers have not been widely used is because the information that currently guides our clinical practice still comesfrom clinical trials that have used Goldmann tonometry.We need prospective studies that demonstrate the clinical relevance of these new tonometers in managingpatients. We also need information on how to incorporate the values that we get from these tonometers intoclinical practice.Brandt: To some degree, it comes down to a push-pullrelationship between accuracy and precision. A precisetonometer is highly reproducible and, under the sameconditions, will give the same results every time. An accurate tonometer reflects the “true” IOP. The problem withtrying to correct IOP measurements with algorithmsbased on corneal thickness is that the underlying measurement is incredibly imprecise. You are fooling yourself ifyou think that you are getting a more accurate result. Arecent study in the United Kingdom showed that fewophthalmologists checked the calibration of their

DIAGNOSTIC EDITIONtonometers. In this study, 50% of the devices were out ofcalibration by more than 2.5 mm Hg.13 Consider thatmost of the nomograms that supposedly adjust IOP forcentral corneal thickness apply “corrections” in thatrange. You are therefore trying to apply a correctivealgorithm to a measurement that has noise of 2 or3 mm Hg. It is a fool’s errand.Schuman: I think we use tonometry to identify apatient’s baseline measurement and set a target IOP. Youconsider follow-up measurements in the context of everything else in the case. If you assume that the tonometeris going to measure IOPs within 1 to 2 mm Hg of reproducibility, you can use it as a guide. You must also look atthe optic nerve, the visual field, the family history, etc.You are not just treating the IOP.Brandt: I would suggest that people think of the analogy of glaucoma to diabetes. Technology in the latterfield has advanced so that practitioners have transitionedfrom measuring sugar in urine to analyzing blood andthen fasting blood sugars to analyzing hemoglobin A1Clevels to obtain a trailing average. Diabetic patients nowhave portable glucometers and adjust their therapy inreal time. In glaucoma, we are stuck with random, individual IOP measurements. A tonometer that measuredthe true IOP to within 0.1 mm Hg would not be a significant advance in the management of this disease. Weneed equivalents in glaucoma of both hemoglobin A1Cand the Holter monitor for IOP.Lewis: Bob, the sleep studies conducted at the Hamilton Glaucoma Center, University of California, San Diego,are important because they demonstrated that nocturnal IOP measured while subjects are supine is much higher than we thought when people are sleeping. How canclinicians incorporate that information into our understanding of glaucomatous progression?Weinreb: The answer is not clear, because we do notknow the implications of the increased pressure. Earlierstudies largely evaluated IOP while patients were seated for24 hours. My colleagues, including John Liu, PhD, and Ithought studying habitual pressures with patients supineduring the nocturnal period and seated during the diurnalperiod should be investigated. We found that at least twothirds of patients had peak IOPs during the nocturnal period and not during usual office hours. We wondered ifthere were a way to measure IOP throughout the day thatwould enable clinicians to estimate a patient’s peak pressure. The best that we have determined is that measuringIOP during the day while the patient is in a supine position28 I GLAUCOMA TODAY I NOVEMBER/DECEMBER 2007better reflects peak pressure than any other in-office IOPmeasurement. This approach is not effective in all patients,however, and there is no way to determine in advancewhen it will be successful. Moreover, we do not know thesignificance of increased IOP during the nocturnal period.Until we understand the full pattern of other concurrentphysiologic changes, including changes in perfusion pressure and blood flow, we are not going to make therapeuticrecommendations.14Brandt: Based on your group’s data, if a patient’s glaucoma is progressing despite good IOP control, should the clinician communicate with that individual’s internist to saymaybe he is overtreating the individual’s blood pressure orto suggest changing the dosing time of his hypertensivemedications?Weinreb: There is considerable evidence that low perfusion pressure and blood pressure (particularly diastolic) arerisk factors for glaucoma. Many patients’ blood pressures,particularly diastolic, were considerably lower during theevening than we expected. With high IOP, a low diastolicpressure might not be good for a patient with moderateglaucoma. Should we recommend that patients also havetheir blood pressure monitored? If so, and their blood pressures are low, how do you elevate them? There are manyquestions for which we have no answer.Lewis: Has anyone changed his manner of practicebased on the sleep study in terms of diagnosing normaltension glaucoma?Weinreb: My primary therapy continues to be aprostaglandin analog. In the past, I added a beta blockerto a prostaglandin when an additional medication wasneeded. Our work showed that timolol has virtually noeffect on nocturnal IOP,15 something predicted byBrubaker based on measurements of aqueous flow.16 Itherefore am no longer using beta blockers for secondline therapy but rather select agents that are more likelyto provide 24-hour pressure lowering.Mills: Regarding ocular perfusion pressure, StephenDrance, MD; Andrew Crichton, MD; and I found thatprostaglandins have an advantage over beta blockers interms of the calculated measurement of an optic nervecapillary’s perfusion.17Schuman: Beyond that, a beta blocker does not have alarge additive effect to a prostaglandin.Herndon: If we use beta blockers, obviously, aqueous

DIAGNOSTIC EDITIONproduction is down at night while patients are sleeping.The classic teaching is that you administer a beta blockerin the morning. Should the agent we add to a prostaglandin not affect aqueous production?Weinreb: I use beta blockers as primary therapy inpatients who cannot tolerate a prostaglandin or in thevery few patients who do not respond to a prostaglandin. These drugs are effective at lowering pressurewhen used as first-line therapy. The local ocular effectsare minimal, but they have some systemic effect. The

tages and disadvantages. The Heidelberg Retina Tomo-graph (HRT; Heidelberg Engineering GmbH, Heidelberg, Germany) has been available the longest, so there are many longitudinal studies demonstrating that the device is able to detect progression. For example, the Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the