what recent nei trials tell us about treatment and therapy 12pg 11-1-04.pdfjan 04, 2011 ·...

EyeWorld Supplement — October 2004

Glaucoma and Ocular Hypertension: New Thinking

S trict, around-the-clock control of IOP iscrucial in the treatment of susceptibleocular hypertensive and glaucoma

patients. IOP lowering not only can preventor retard the onset of glaucoma, but also canstop its progression, regardless of the type orstage of the disease.

The old standard of achieving an IOPless than 21 mm Hg is now extinct. Youmust go as low as you can safely. Just 1mmHg can mean a corresponding reduction of10% in visual field loss. Even early- to mod-erate-stage glaucoma has been shown tonegatively impact patients’ quality of life.

We should strive to treat these patientsin a way that will reduce the progression ofglaucoma, maintain the health related quali-ty of life, and prevent blindness.

With this in mind, it is important topick the right therapy the first time.Prostaglandin analogues have emerged asthe newest standard in the medical manage-ment of open-angle glaucoma. These agentstend to induce compliance in patients thathave minimal symptoms, and are an effec-tive first line therapy for individuals withthicker corneas and that may not respondwell to beta-blockers.

The studiesThe NEI-sponsored multicentered glaucomatrials — the Ocular Hypertension TreatmentStudy (OHTS), Collaborative InitialGlaucoma Treatment Study (CIGTS), EarlyManifest Glaucoma Treatment Study(EMGTS), and Advanced GlaucomaIntervention Study (AGIS) — were focusedon the preservation of visual function.

Their goals for IOP reduction were mod-est compared with the reductions thatprostaglandins can provide. OHTS andEMGTS, for example, called for only a 20%drop in pressure, while AGIS used an IOPendpoint of less than 18mm Hg. The CIGTSstudy was unique in that it was both visualfield loss- and IOP-dependent. (figure 1)

What recent NEI trials tell usabout treatment and therapyby Alan L. Robin, M.D.

Alan L. Robin, M.D., is clinicalprofessor of ophthalmology,University of Maryland, associateprofessor of ophthalmology,Johns Hopkins School ofMedicine, associate professor ofinternational health, BloombergSchool of Public Health, JohnsHopkins University, Baltimore.Dr. Robin has received a retainer,ad hoc fees, or other consultingincome from Alcon Laboratories,Inc., Merck Pharmaceuticals, andPfizer Pharmaceuticals.

“The old stan-dard of achieving anIOP under 21 mm Hgis now extinct. Youmust go as low as youcan safely.”— Alan L. Robin, M.D.

Figure 1

Figure 2

What happens if glaucoma is leftuntreated? A prevalence study involvingmore than 1,600 subjects in St. Lucia wasconducted in 1986-87.1 At the time, 364 sub-jects (8.8%) were diagnosed with glaucoma.Ten years later, the group was summonedand diagnosed again. Applying the AGISstandard of less than a three-step change, orthe CIGTS standard of less than two steps, amajority of the subjects had progressed,with between one-third and one-half reach-ing end stage disease. (figure 2)

These findings were reinforced by a1998 report from the Mayo Clinic thatcapped a 30-plus-year study of glaucomapatients in Olmstead County, Minn.2

A CME Supplement from an EyeWorld Educational Symposium held at ASCRS•ASOA 2004 in San Diego

CME EDUCATION

Supported by an unrestrictededucational grant from PfizerOphthalmics, Inc.

Citations:

1 Mason RP, Kosoko O, WilsonMR, Martone JF, Cowan CL Jr,Gear JC, Ross-Degnan D.National survey of the preva-lence and risk factors of glau-coma in St. Lucia, West Indies.Part I. Prevalence findings.Ophthalmology 1989;96:1363-1368.

2 Hattenhauer, MG, JohnsonDH, Ing HH, Herman DC,Hodge, DO, Yawn BP,Butterfield LC, Gray DT, TheProbability of Blindness fromOpen-angle Glaucoma,Ophthalmology1998;105:2099-2104.

3 Gutierrez P, Wilson MR,Johnson C, Gordon M, CioffiGA, Ritch R, Sherwood M,Meng K, Mangione CM,Influence of glaucomatousvisual field loss on health-related quality of life, ArchOphthalmol, Jun 1997; 115:777 - 784.

2

Twenty-two percent of the patients haddeveloped bilateral blindness after 20 yearsof under-treatment. (figure 3)

Glaucoma is not pregnancy. It’s noteither you go blind or you don’t. ElevatedIOP can cause varying degrees of damage tothe optic nerve.

In fact, there is almost a linear relation-ship between one’s ability to operate a motorvehicle and visual field function.3 Many indi-viduals report a measurable impact fromglaucoma on their quality of life, includingmental health, color and peripheral vision,dependency, and social function.

In the early stages of glaucoma, ophthal-mologists should perform visual fields inocular hypertensives as well as stereoscopi-cally evaluate patients’ optic nerves. In theOHTS study, up to 41% of subjects convertedto glaucoma through visual fields examina-tions before they converted through discs.(figure 4)

If we look at all the NEI multicenteredtrials, we find that lowering IOP statisticallydecreases the development of glaucoma.Specifically, from CIGTS, we know that tightIOP control minimizes the progression ofglaucoma. And from AGIS, we find that earlyand consistent IOP control prevents thedevelopment of progressive visual field loss.Optic nerve preservation was obtained witheven minor lowering of IOP.

Can the studies tell us which therapy to use?The OHTS study found that subjects withthicker corneas responded less well to beta-blockers. With these patients, you may wantto choose a prostaglandin as your first-linetherapy. Also, we see from AGIS that differ-ent racial groups respond differently to dif-ferent therapies. (figure 5)

With OHTS, the primary risk factors forthe development of glaucoma were old age,thinner corneas, advanced visual field loss,and larger cup to disc ratios. Also, those withgreater visual field loss to begin with tendedto go on to develop blindness.

Therefore, we should be more aggressivein preventing visual field loss in thesepatients. Pay particular attention to their fel-low eyes. If you have a patient who hassevere damage in one eye and moderatedamage in the other, be extremely aggressiveyour attempts to prevent blindness in thebetter eye.

The patient’s family history and the ageof the onset of glaucoma compared to theirlife expectancy should also be prime consid-erations. All of this means more yearly visitsand possibly more medication changes toreduce the threat of vision loss. Again, earlytreatment is key, and prostaglandin ana-

logues are more likely to succeed the firsttime.

Most importantly, weigh your risk fac-tors. Think about each patient individually.This is important because you want to pre-vent your patients from going blind.

Figure 5

Figure 3

Figure 4

Glaucoma and Ocular Hypertension: New Thinking

3Glaucoma and Ocular Hypertension: New Thinking

Comparative prostaglandin trialsby Quang H. Nguyen, M.D.

“The take-home message is tolook at the methodol-ogy of new studiescarefully and comparefindings with those ofpreviously publishedstudies.”— Quang H. Nguyen, M.D.

Quang H. Nguyen, M.D., isDirector of GlaucomaService, Division ofOphthalmology, ScrippsClinic, La Jolla, Calif. Dr.Nguyen has no financialinterest in the informationpresented.

T he introduction of IOP-loweringprostaglandins was a significant break-through in the field of glaucoma. In the early development, the parent

prostaglandin, F-2 Alpha, showed IOP-lower-ing effect but was not well tolerated. After10 years of development, an analogue mole-cule was developed in a way to preserve thedrug's efficacy, while at the same time mak-ing it more tolerable to the eye.

Latanoprost (Xalatan, Pfizer, New York,New York), which came out in 1996, fea-tured some significant improvements. First,an isopropyl group was attached to give it apro-drug structure. Once this molecule is onthe cornea after instillation, the cornealesterase converts it into an active molecule.The pro-drug allows a lower concentrationand minimizes side effects. The second strat-egy is to remove the double bond at the car-bon 13-14. This makes the drug more tolera-ble, while maintaining its stability and effi-cacy. (Figure 1)

Travaprost (Travatan, Alcon, Fort Worth,Texas) and bimatoprost (Lumigan, Allergan,Irvine, Calif.) were introduced into the mar-ket in 2001. Travatan's chemical structure issimilar to Xalatan's, with minor modifica-tions, but essentially it is a pro-drug as well.

Lumigan was initially launched as aprostamide, not a pro-drug.

However, mounting evidence demon-strates that bimatoprost does, in fact, workin a similar fashion as latanoprost andtravaprost, and does get broken down intofree-acid form and binds to the FP receptor.

Head-to-head studies reveal no statistically significant differencesbetween prostaglandinsIn a randomized, double-masked, 30-daystudy , the IOP-lowering effects of once-dailybimatoprost 0.03% (n=21), latanoprost(n=22), and vehicle control (n=21) were com-pared in patients with POAG or OHT.1 Theprimary end point was reduction of IOP frombaseline on days 14 and 29. Mean baselineIOP values measured at 8 a.m. were compara-ble among the groups, following appropriatewashout of previous IOP-lowering medica-tions.

Both Lumigan and Xalatan significantlydecreased IOP from baseline after 14 and 29days of treatment (P <.001). The differencebetween treatment groups was not statisti-cally significant at either follow-up interval.(Figure 2)

In a similar three-month, multicenter,investigator-masked, parallel-group study,

232 patients with OAG or OHT were ran-domized to receive bimatoprost 0.03% orlatanoprost once daily in the evening.2 IOPwas measured at baseline, week one, and atmonths one, two, and three.

IOP measured at 8 a.m. was significant-ly reduced from baseline at every interval.The study found no statistically significantdifferences in mean IOP measured at 8 a.m.between treatment groups at week one,month two, or month three. IOP was alsomeasured at noon, 4 p.m. and 8 p.m. atbaseline and month three.

Mean IOP values measured at noon and4 p.m. were statistically significantly lowerwith bimatoprost at month three. Gandolfitook the trial one step further in assessingconjunctival hyperemia. The moleculesappeared to cause more conjunctival hyper-emia, even though the scale was very small.

Peter Netland conducted a 12-monthhead-to-head study comparing latanoprostand travaprost.3 Pressure readings weretaken at 8 a.m., 10 a.m. and 4 p.m. Again,the results showed no statistically signifi-cant difference in efficacy between the twodrugs. (Figure 3)

Figure 1

Figure 2

4 Glaucoma and Ocular Hypertension: New Thinking

Different approach favors bimatoprostA rigorously designed head-to-head efficacystudy between Lumigan and Xalatan wasconducted to meet standards for evidence-based clinical medicine.4 Patients that hadbeen prescribed bimatoprost or latanoprostpreviously were washed out for eight weeks.

Other medications were washed out forperiods ranging from four days to fourweeks. After washout, patients were assignedto one of two treatment groups: bimatoprost0.03% or latanoprost 0.005% once daily inthe evening for six months. Visits werescheduled at prestudy, baseline, week one,and months one, three, and six.

The primary endpoints were a meanchange in baseline pressure at 8 a.m., noon,and 4 p.m. Secondary endpoints includedspecific target pressures and IOP reductionof 15% and 20%. In addition, the study alsoexamined other safety parameters.

In this particular study, Lumiganshowed better efficacy at every time point(P<.025) and better pressure reduction atmonth six at three time points (8 a.m.,noon, and 4 p.m.). Baseline mean IOPswere almost identical between the treat-ment groups at 8 a.m. and 4 p.m.

At noon, the baseline IOP for bimato-prost was statistically significantly higherthan for latanoprost (P=.028). At month six,the mean reduction from baseline IOP withbimatoprost at 8 a.m. was 1.53 mm Hgmore than with latanoprost (P<.001).

Mean reduction from baseline IOP withbimatoprost at noon was 2.15 mm Hg morethan with latanoprost (P<.001). Meanreduction from baseline IOP with bimato-prost at 4 p.m. was 1.18 mm Hg more thanwith latanoprost (P = .004).

Three-product study shows Xalatan isequally effective, produces less ocularirritation In 2003, the first head-to-head-to-headstudy involving Lumigan, Xalatan andTravatan was conducted in patients withelevated IOP over a 12-week period.5 Theprimary end point of the study was themean change in pressure from baseline atweek 12 measured at the time of peak drugeffect. Again, the 8 a.m. time point waschosen, as it approximates the time of max-imal IOP reduction by the three drugs.

The secondary objective included ocu-lar and systemic adverse events, as well asfindings of visual acuity, lid and slit lampexaminations, ophthalmoscopy, and a grad-ing scale to assess conjunctival hyperemia.The Parrish study shows equivalent efficacyamong the three prostaglandins.Furthermore, the mean change in IOP frombaseline for Xalatan is consistent withnumerous previously published studies,except for Noecker.

The Parrish study also went a step fur-ther to assess conjunctival hyperemia bythe investigator as well as the patients.Fewer latanoprost-treated patients reportedan ocular adverse event compared withthose receiving bimatoprost (P<.001).

The most frequently reported eventswere hyperemia and eye irritation. In all,68.6% of bimatoprost patients reported ocu-lar hyperemia as a side effect, versus 58% oftravoprost patients and only 47.1% oflatanoprost patients. This is significantbecause at the end of the day, the patientgives the most important response. (Figure 4)

Figure 3

Figure 4


The masked investigators' assessmentsof hyperemia were not statistically signifi-cantly different across treatments at baseline(P=.827). However, at weeks two and 12,average hyperemia scores were lower forlatanoprost-treated patients than for bimato-prost-treated patients (P=.001 for both vis-its). Hyperemia consistently was rated low-est in latanoprost-treated patients and high-est in bimatoprost-treated patients, withthose in the travoprost group receivingintermediate average ratings. Throughoutthe 12 weeks of treatment, the degree ofhyperemia associated with each medicationremained consistent.

The conclusion from this study was thatIOP reduction from baseline was not signifi-cantly different in patients treated withlatanoprost, bimatoprost or travoprost. Allthree agents were generally well toleratedsystemically. Significantly fewer patientsreported symptoms of ocular hyperemiawith latanoprost treatment. Investigatorsreported ocular hyperemia in significantlyfewer patients treated with latanoprost thanwith bimatoprost. (Figure 5)

A few caveats about the different studiesComparing the Noecker and Parrish studiesside-by-side reveals important differences indesign and methodology.

The Parrish study compared the IOP-lowering efficacy of latanoprost versus bimatoprost versus travoprost over 12 weeks. The study was single-masked andconducted at 45 clinics in the United States.The planned enrollment was 375 patients,and final enrollment was 411 patients —about a 10% increase. This 10% over-recruitment is standard in any multicentertrial study due to the fact that a patientmay be lost to or otherwise unavailable forfollow up. Mean baseline IOP levels at 8a.m., noon, 4 p.m., and 8 p.m. were not sig-nificantly different across therapies.

Noecker compared the IOP-loweringefficacy of latanoprost versus bimatoprostover a period of six months. The study wassingle-masked and conducted at 18 clinicsin the United States. The planned enroll-ment was 192 patients, and the final enroll-ment was 269 patients - about 40% over-recruitment. Mean baseline IOP levels at 8 a.m. and 4 p.m. were not differentbetween the two prostaglandins. However,mean baseline IOP levels at noon were sig-nificantly different between the two groups.

There are a few other notable differ-ences between the Parrish and Noeckerstudies. In the Parrish publication, theresults are given in absolute numbers in achart format, whereas the results of theNoecker study were presented as a bargraph. Also, the Parrish study lists standarddeviations and attempts to exclude bias aswell as present its weaknesses. The Noeckerstudy did not discuss their weaknesses.

The take-home message is to look atthe methodology of new studies carefullyand compare findings with those of previ-ously published studies.

Figure 5

Citations:

1 DuBiner H, Cooke D, DirkdsM, et al. Efficacy and safety ofbimatoprost in patients withelevated intraocular pressure: a30-day comparison withlatanoprost. Surg Ophthalmol.2001;45(suppl 4):S353-S360.

2 Gandolfi S, Simmons ST, SturmR, et al. Three-month compari-son of bimatoprost andlatanoprost in patients withglaucoma and ocular hyperten-sion. Adv Ther. 2001;18:110-121.

3 Netland PA, Landry T, SullivanER, et al. Travoprost comparedwith latanoprost and timololin patients with open-angleglaucoma or ocular hyperten-sion. Am J Ophthalmol.2001;132:472-484.

4 Noecker RS, Dirks MS, ChoplinNT, et al. A six-month random-ized clinical trial comparingthe intraocular pressure-lower-ing efficacy of bimatoprost andlatanoprost in patients withocular hypertension or glauco-ma. Am J Ophthalmol.2003:135:55-63.

5 Parrish RK, Palmberg P, Wang-Pui S, for the XLT study group.A comparison of latanoprost,bimatoprost, and travoprost inpatients with elevated intraoc-ular pressure: A 12-week, ran-domized, masked-evaluatormulticenter study. Am JOphthalmol. 2003;135:688-703.


L aser trabeculoplasty was introduced inthe early 1970s, initially thought of as amethod of puncturing holes through the

trabecular meshwork to lower IOP in glauco-ma patients.

With the evolution of argon laser tra-beculoplasty (ALT), the mechanisms are atonce mechanical (producing contraction ofthe individual burns in the meshwork), bio-logical (in effect replenishing the trabecularcells), and chemical (resulting in the releaseof cytokine). These mechanisms worktogether to improve the outflow of aqueousfrom the eye.

ALT was widely used in the late 1980sand early 1990s. However, over the lastdecade, the popularity of the procedure haswaned due to its limitations.

These include long-term attrition, a gen-eral lack of repeatability (it can really onlybe applied once, with a secondary enhance-ment), post-operative IOP spikes, and thepotential for coagulative damage to themeshwork. There are also some concernsabout the effect of ALT on the success offuture filtering surgery.

A 2003 study published in GraefesArchives of Clinical and Experimental

Ophthalmology1 found that there was anincrease in the production of transforminggrowth factor-beta 2 concentration and blebscarring in patients that had undergone ALT.

Enter selective laser trabeculoplasty(SLT).

SLT is a safer alternative to ALT becauseit provides a target within the meshwork.Pigmented melanin cells can be selectivelyburned without significant damage to adja-cent, non-pigmented cells. The result is thedesired biological and chemical effect of LTwith only minimal collateral damage.

SLT is applied using a Q-switched, fre-quency doubled YAG laser that producesvery short pulses of energy — about 3 ns,compared to ALT’s continuous wave laser.This is significant, allowing for selectivephotothermolysis, whereby the heat generat-ed by the short pulses is confined to the pig-mented melanin cells.

A comparison of the specifications ofthe ALT and SLT laser treatments revealssome important differences. Both are appliedover about 50 spots at 180 degrees, but SLT’slarger beam diameter reduces the need forfine focusing, angle appearance, and anglevisibility.

ALT vs. SLT: What’s new in laser therapyby Ike K. Ahmed, M.D.

Ike K. Ahmed, M.D., runs atertiary glaucoma clinic in thegreater Toronto area, and isassistant professor, Universityof Toronto and the University ofUtah, Salt Lake City. Dr. Ahmedhas no financial interest in theinformation presented.

“With SLT,there is increasedsafety and less tissuedamage, particularlywhen you consider thelikelihood that thesepatients may requirefuture surgery downthe road.”— Ike K. Ahmed, M.D.

Figure 1

Figure 2

ALT must be applied over a much small-er area and, therefore, is not easy to applyconsistently. Moreover, the energy levelswith SLT are less than 1% of those with ALT-induced burns. The fluence and exposuretime of SLT are also significantly less. All ofthis translates into minimum, if any, dam-age to the trabecular meshwork with SLT.(figures 1 and 2 )

The studiesAn in vitro study led by Mark Latina, M.D.,2

looked at thermal transfer, indicated in red,of ALT versus SLT lasers. ALT showed highthermal absorption across the entire surfacearea, while only the pigmented melanincells were affected with SLT. (figure 3)

Another head-to-head study 3 inducedcellular response in human cadaveric eyeswith SLT and ALT.

SLT was shown to cause a gentleresponse of the autoimmune system tobegin cleaning the trabecular meshwork,without the coagulative damage of ALT.


Further, if one compares the SLT-treatedeyes to control eyes, there is little visible dif-ference between the two. One can achievethe desired result, not necessarily by stretch-ing the contraction, but by creating more ofa biological or chemical cytokinetic pathway.(figure 4)

U.S. clinical trial results of SLT lasers,again headed up by Latina,4 looked at efficacyamong three groups: A maximum medicaltherapy group, a group that had previouslyfailed laser trabeculoplasty, and a combinedgroup. The results showed mean IOP reduc-tions of greater than 3 mm Hg at 26 weeksout among all three groups. These findingsmay open the door for SLT treatment ofthose that had previously failed LT. (figure 5)

A study out of Ottawa, Canada5 presentslonger-term data looking at SLT versus ALT foruncontrolled patients on medical therapy. Thestudy found no meaningful differences in IOPlowering from baseline to three years.Interestingly, it did find that those that hadprevious ALT treatments experienced a greaterdrop in pressure in the SLT-treated eyes thanin the ALT eyes. (figure 6)

The efficacy of SLT as a primary therapyis currently being studied. The GLT trial,6

published in 1995, compared ALT to topicalmedical therapy in a stepped regimen using271 untreated COAG patients.

Two years out, there was lower IOP con-trol with ALT. After seven years, again therewas lower IOP with ALT, with better visualfield and optic nerve endpoints. There weresome design problems with this study —patients were on medical therapy in their fel-low eye — but ALT was shown to be at leastas efficacious as topical medical therapy.Notably, the majority of patients did requiremedications in the ALT group in the post-operative period.

A prospective, non-comparative trial byan Israeli group7 involved 31 patients with 18-month follow-up. The researchers found amean IOP reduction of 30%. Eleven percentof patients had an IOP spike greater than 5mm Hg within one hour, and there were noserious complications with the SLT treat-ment.

A similar new study, to be conducted at15 centers in the United States and one inCanada, will look at SLT treatment versusstepped medical treatment as initial therapyin a large group of glaucoma patients(n=340). The initial recruitment has begunfor what is intended as an 18-month trial. Itwill also look at cost, compliance, and qual-ity-of-life considerations.

With repeatability, we're talking aboutthe ability to perform laser therapy on aspecific area of the eye. ALT produces gener-ally poor results in repeatability, in largepart because there is a higher risk of com-plication from the treatment.

Because of the less tissue trauma, SLT istheoretically an argument for repeatability.Although there are no clear-cut studies todemonstrate this, Latina and Damji haveshown that SLT appears to be effective inpatients who have previously failed ALT.

Do pre-treatment medications affectthe end outcome of SLT?

In a recent poster that was presented atAGS 2004, Latina showed that thosepatients that were on prostaglandin ana-logues had less of a response with SLT treat-ment. Perhaps this is related to matrix met-alloproteinase (MMP) enhancement. Bothprostaglandin analogues and SLT work bythis mechanism in the meshwork.

Figure 3 Figure 4

Figure 5


With regard to phacoemulsification,studies have shown that ALT treatment doesbetter in phakic than in pseudophakic eyes.8

Beyond that, there is only speculation amongsurgeons that those patients that may belooking at combined procedures considerlaser trabeculoplasty pre-operatively, andthen we can assess whether or not to go withphaco.

There have been other studies thathave looked at differences in the angle usedin SLT. A U.K. study by Nagar (IGS 2003)showed a slightly more effective responsewith 360-degree treatment as opposed tothe 180- or 90-degree treatment. However,the 360-degree treatment did result in morecomplications.

There are others that argue that theeffect between 90 and 180 degrees is fairlysimilar, that the mechanism is, indeed,some sort of cytokinetic or biochemicaleffect, and perhaps we only need to treat asmall part of the meshwork. (figure 7)

In Toronto, we looked at a series of 579patients and found that there was an effectof ALT treated eyes (publication in process).In fact, the response rate was 68.4% com-pared to only one-third of the patients thathad posterior chamber IOL.

So, again, there does appear to be a dif-ference with pseudophakic eyes.Specifically, we found that higher pre-opIOPs tended to respond better than the nor-mal-tension glaucoma patients.

As expected, those that had primarytherapy and those that were older respond-ed better. Negative predictors includedgreater pre-operative medications, posteriorchamber IOLs, and prior laser trabeculoplas-ty in younger patients. Angle, pigmenta-tion, race, and iris color were negligible interms of the effects. (figure 8)

We will likely see more of these typesof targeted lasers coming out - lasers thatare less costly and help with complianceissues. The efficacy of ALT and SLT seems tobe fairly similar over five years of data. Butwith SLT there is increased safety and lesstissue damage, particularly when you con-sider the likelihood that these patients mayrequire future surgery down the road.

Figure 7

Figure 8

Figure 6Citations:

1 Wimmer I, Welge-Lueseen U,Picht G, Grehn F. Influence ofargon laser trabeculoplasty ontransforming growth factor-beta 2 concentration and blebscarring following trabeculecto-my. Graefes Arch Clin ExpOphthalmol 2003; 241:631-636

2 Latina MA, Park C. Selectivetargeting of trabecular mesh-work cells: In vitro studies ofpulsed and CW laser interac-tions. Exp Eye Res 1995;60:359-371

3 Kramer TR, Noecker RJ.Comparison of the morpholog-ic changes after selective lasertrabeculoplasty and argon lasertrabeculoplasty in human eyebank eyes. Ophthalmology2001; 107:773-779

4 Latina MA, Sibayan SA, ShinDH, et al. Q-switched 532nmNd :YAG laser trabeculoplasty(Selective LaserTrabeculoplasty).Ophthalmology 1998;105:2082-2090

5 Damji KF, Shah KC, Rock WJ,et al. Selective laser trabeculo-plasty vs argon laser trabeculo-plasty: A prospective random-ized clinical trial. Br JOphthalmol 1999; 83:718-722

6 Glaucoma Laser Trial ResearchGroup: VII. The glaucoma lasertrial (GLT) and glaucoma laserfollow-up study results. Am JOphthalmol 1995;120: 718-731

7 Melamed S, Ben Simon GJ,Levkovitch-Verbin H. Selectivelaser trabeculoplasty as primarytreatment for open-angle glau-coma. Arch Ophthalmol 2003;121:957-960

8 Thomas JV, Simmons RJ,Belcher CD 3rd. Argon lasertrabeculoplasty in the presurgi-cal glaucoma patient.Ophthalmology 1982; 89:181-197


I s there a role for combined procedures inmodern cataract and glaucoma manage-ment? The short answer is yes. Evidence-

based data supports the use of these same-daytechniques. Specifically, I believe the safetyand increased ease of temporal cataractextraction outweigh any slight disadvantages.

The indications for performing combinedsurgery include the presence of glaucoma andcataract, cataract in an eye with a compro-mised optic nerve, and cataract in an eyewith a failed trabeculectomy.

Weighing the pros and consFiltration surgery followed by cataract at alater date has long been the gold standard.Many physicians feel that the success rate ishigher with separate procedures, althoughthe modern literature seems to dispute thatclaim. Perhaps the biggest advantage of usingthis particular method is that the pupil willoften enlarge, making the cataract procedureeasier to perform.

But following up filtration surgery withcataract surgery has inherent disadvantages aswell. The first is obvious: It is two procedures.From the patient's standpoint, that means anadditional expense and a significant delay invisual rehabilitation.

From a surgical standpoint, trabeculecto-my has been known to induce rapid advance-ment of the cataract, or at least the onset of acataract. And, of course, cataract surgery maycause bleb failure, particularly if you use con-junctival incisions.

Cataract surgery alone may reduce IOPby 3 mm Hg to 4 mm Hg, especially when asuccessful phaco with an IOL in the bag hasbeen implanted. However, it is important toremember that 30% of controlled glaucomapatients will experience a pressure spike ofgreater than 15 mm Hg on the day of surgery.

To minimize the risks, I try to schedulepatients early in the day so that I can meas-ure their pressures about six to eight hoursfollowing the cataract extraction.

The most commonly used procedure isphaco trabeculectomy, with or without anti-metabolites. You can do one side or you cando two sides, and multiple studies over timehave shown the results to be excellent.1

There is a little tissue disturbed so that ifyou have a need for future surgery there isstill plenty of space available.

Keep in mind, however, that this proce-dure is technically more difficult. Also, deal-

ing with pupil abnormalities, particularlypseudoexfoliation, can be challenging,though there are now at least eight or ninedifferent modalities available to handlethese sorts of aberrations. Phaco-trabeculec-tomy does not always yield equivalentresults to separate procedures.

Another potential way of managingcataract and glaucoma is a superior tra-beculectomy with a temporal clear corneacataract. With this approach, there is lessmanipulation of the trabeculectomy site,which may yield better results. Temporalcataract phacoemulsification has beenshown to decrease endothelial stress, whichis important in glaucoma eyes.

Many of us have already moved towardthe temporal approach because we find thecataract surgery is technically easier to per-form. (Figures 1 and 2)

Unless you do clear corneal incisions,you're likely to disturb too much conjuncti-va, reducing your chances of success. Studieshave shown that if you look at all the param-eters, such as giant cell with proliferation andposterior capsule opacification, all of thethird-generation silicones are actually betterthan PMMA in glaucoma eyes.2

Figure 1

Figure 2

Practical approach to combined proceduresby Alan S. Crandall, M.D.

“I believe the anatomy of thecornea favors a temporal incision,particularly a cataractincision.”— Alan S. Crandall, M.D.

Alan S. Crandall, M.D., isprofessor and senior vicechair of ophthalmology andvisual sciences, director ofglaucoma and cataract,Moran Eye Center, Universityof Utah, Salt Lake City. Dr.Crandall has no financialinterest in the informationpresented.Supported in part by a grantfrom Research to PreventBlindness, New York, to theDepartment of Ophthalmologyand Visual Sciences, theUniversity of Utah.

Glaucoma and Ocular Hypertension: New Thinking10

Figure 3

Figure 4

One additional modality that is becom-ing more common for same-day surgery iscataract extraction with endophotocoagula-tion of the ciliary processes. This procedureis billed as a simple cataract extraction witha simple laser procedure. But again, there arepotential pitfalls.

If the technique is cyclo-destructive, itcan lead to phthisis; conversely, if it is notcyclo-destructive, it may not be permanent.The data in this field is largely anecdotal.

Non-penetrating surgery combined withcataract surgery is a viable option. Theadvantage here is that there are likely to befewer complications when compared tostandard combines. Some European studiesseem to confirm this. Another advantage isthat there is more rapid visual recovery.Thirdly, you should experience a significantdecrease in late complications of filteringprocedures.

The downside of non-penetrating sur-gery combined with cataract surgery is thatit requires a very steep learning curve just todo the procedure. It is also more time con-suming. A regular combined procedure canbe done in 20-25 minutes, but this proce-dure may take up to 45-50 minutes.

And in the end, they may not yield aslow a pressure as you can get from mito-mycin C combined trabeculectomy. Thereare currently no long-term results of studiesavailable.

Recommended procedureMy present technique is a combined two-side procedure. I've done about 1,300 ofthese over the last eight years. I havedecreased the amount of mitomycin expo-sure to 0.2 mg/cc for 90 seconds instead ofthe 0.4 for estimated three to five minutesthat we used before. And, of course, I use allfoldable lenses. I no longer do any periph-eral iridectomies in combined procedures.(Figure 3)

I start superiorly and do the fornix-based peritomy, dissect the scleral flap, puton the mitomycin sponge, and rotate tem-porally. I insert a clear cornea/phaco/IOLand place a 10-0 suture but leave it untied.Later, I return superiorly to complete theglaucoma procedure.

Most evidence-based medicine nowshows that the two procedures are equiva-lent in their pressure-lowering effect.1,2

Some may point to the time involvedin rotating the machinery. I like to manipu-late my instruments while the mitomycin isbeing placed on the eye, and I rotate themicroscope and foot pedals during the 90seconds while the sponge is on the eye.

Critics also may claim that by beinglimited to clear corneal incisions there is anincreased incidence of endophthalmitis. Butthe data suggests that this is most oftenrelated to poor wounds.

With combined procedures, I alwayssuture the temporal incision because of therisk for hypotony, and having bacteria enterthe eye during a hypotonus state.

As for the use of foldable lenses, allrecent generations of these lenses havebeen shown to be as bio-compatible asPMMA. Both acrylic and silicone lenses areexcellent.

So, what's the point of moving tempo-rally when one site is technically much eas-ier? I believe the anatomy of the corneafavors a temporal incision, particularly acataract incision. Moreover, there's morespace temporally and less endothelial stress.(Figure 4)

There continues to be rapid evolutionof these combined surgical techniques,which are an important part of the surgicalarmamentarium. Long-term goals of visualfield stabilization and good acuity seemwithin our grasp.

Citations:

1 Wyse T, Meyer M, Ruderman,et al, Combined trabeculecto-my and phacoemulsification: Aone-site vs. a two-siteapproach. Am J Ophthalmol1998, 125:334--339.

2 Park HJ, Weitzman M, CaprioliJ, Temporal corneal pha-coemulsification combinedwith superior trabeculectomy.Arch Ophthalmol 1997.115:318--323.


CME EDUCATION

Educational ObjectivesOphthalmologists reviewing this material will:

• Review the results of multi-centered studies and devel-op a better understanding of the implications of theirresults;

• Review and evaluate current surgical treatment forglaucoma; and

• Determine and develop the appropriate treatment planfor each patient.

Notice about Off-Label Use PresentationsThese programs may include presentations on drugs ordevices, or uses of drugs or devices, that may not havebeen approved by the Food and Drug Administration (FDA)or have been approved by the FDA for specific uses only.The FDA has stated that it is the responsibility of the physi-cian to determine the FDA clearance status of each drug ordevice he or she wishes to use in clinical practice.

ASCRS is committed to the free exchange of medical edu-cation. Inclusion of any presentation in these programs,including presentations of off-label uses, does not imply anendorsement by ASCRS of the uses, products, or tech-niques presented.

Continuing Medical Education (CME)The American Society of Cataract and Refractive Surgeryis accredited by the Accreditation Council for ContinuingMedical Education (ACCME) to provide continuing med-ical education for physicians. ASCRS takes responsibilityfor the content, quality, and scientific integrity of theseCME activities.

CME CreditThe American Society of Cataract and Refractive Surgerydesignates this educational activity for a maximum of 1Category 1 credit toward the AMA Physician'sRecognition Award. Each physician should claim onlythose hours of credit he/she actually spent in the activity.

Continuing Medical Education

Claiming CME CreditQuestions have been developed for this written supple-ment of the material covered within the EyeWorldEducational Symposia, Glaucoma & Ocular Hypertension:New Thinking, presented on Saturday, May 1, 2004 at theManchester Grand Hyatt San Diego.

Participants must take the written test once they havecompleted their review of all presentations. To receive theCME credit, 80% (4) of the questions must be answeredcorrectly. The test must be completed individually andanswers based on personal knowledge gained fromreviewing the written material. Completed tests should bemailed to:

ASCRS4000 Legato Road, Suite 850

Fairfax, VA 22033Attn: EyeWorld Educational Supplement CME

CME certificates will be mailed to participants whoreceive a score of 80% or higher. ASCRS will keep theearned CME information on file for the required time.Participants who receive a score of less than 80% willhave the opportunity to review the material and take thetest again.

Expiration DateCME credit is valid through November 2005. CME creditwill not be awarded after that date.

CME Questions?Please contact Laura Johnson with the American Societyof Cataract and Refractive Surgery at (703) 591-2220 x162 or by email at [email protected] if you have anyquestions regarding CME credit for these programs.

See CME test on reverse side


How was the CIGTS study different than OHTS,EMGTS, and AGIS studies?

It focused on preservation of visual function.

It focused on IOP reduction.

It focused on both visual field loss and IOP reduction.

It was not different from the other multicentered studies.

According to Dr. Robin, ophthalmologists should con-sider the following factors when developing a treat-ment plan: (1) the patient's family history, and (2) theage at glaucoma onset compared to patient's lifeexpectancy.

True

False

Dr. Ahmed's series of 579 eyes noted no difference inthe response rate of pseudophakic eyes to SLT.

TrueFalse

A combined procedure would not be indicated in aneye with a cataract and a compromised optic nerve.

True

False

The available prostaglandins have been shown to beequally effective at reducing IOP.

True

False

Name: Degree:

Address:

City/State/Zip:

Phone: Fax:

Email:

I certify that I have completed this educational activity in accordance with the guidelines above.

Signature Date

CME EDUCATIONContinuing Medical Education Test

4000 Legato Road, Suite 850Fairfax, VA 22033

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what recent nei trials tell us about treatment and therapy 12pg 11-1-04.pdfjan 04, 2011 ·...

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