Each installment of “The Literature” column will examinethe most important recent studies of relevance to the physicianswho treat patients with glaucoma. The authors areselected by Section Editor James C. Tsai, MD.
THE UTILITY OF THE MONOCULAR TRIAL:DATA FROM THE OCULAR HYPERTENSIONTREATMENT STUDY1
Bhorade AM, Wilson BS, Gordon MO,Palmberg P, Weinreb RN, Miller E, Chang RT, Kass MA;Ocular Hypertension Treatment Study Group.*Ophthalmology, November 2010
Is the Monocular Trial Useful?
A traditional monocular trial is performed by placing atopical ocular hypotensive agent in one eye and thenchecking the subsequent IOP after an interval of 4 to8 weeks. The difference in IOP in the fellow eye betweenvisits is then subtracted from the change in the treatedeye. If the medication appears effective, therapy is startedin both eyes. Multiple studies have drawn various andcontradictory conclusions with regard to the usefulnessof the monocular trial. The general consensus, however, isthat multiple pre- and posttreatment IOP measurementson different days are the best estimate of the effectivenessof an ocular hypotensive agent.2-14
The Ocular Hypertension Treatment Study (OHTS)was a multicenter, clinical study in which 206 participantswere randomized to either treatment with topical ocularhypotensive medication or observation.15 In June 2002,participants in the observation group were offered topicalmedication based on results from the OHTS.15 Thisstudy only examined participants who were in the observationgroup and began taking a prostaglandin analogue(PGA). IOP measurements of the trial and fellow eyeswere taken at three pretreatment and three posttreatmentvisits. IOP was also measured at a baseline visit,which was also when the medication was started and at1 month. IOP change was measured using both anadjusted and an unadjusted method. The latter methodwas the difference in IOP of the trial eye at the baselineversus the 1-month visit. For the adjusted method, investigatorssubtracted the difference in IOP of the fellow eyeat these same visits from the difference in IOP of the trialeye. The “gold standard” for IOP response was defined asthe difference in mean IOP from three pretreatment and three posttreatment visits. The baseline and 1-month visitswere not part of the gold standard calculation.
The OHTS sought to answer two questions. First, is itbetter to use a monocular trial to determine medicationresponse? Second, is the response to a medication in oneeye similar to the fellow eye's response to the same medicationamong participants receiving a topical PGA trial?
Are Monocular Trials Good Estimates ofMedication Response?
The results of the OHTS suggested that both theadjusted (monocular trial) and unadjusted methods forIOP change were equivalent to the gold standard andthat neither was a good predictor of a patient's responseto a topical PGA. Additionally, the IOP response of oneeye to a medication was similar to the response of thefellow eye to the same medication. The study's authorsconcluded that monocular trials and bilateral simultaneoustrials are equivalent for estimating medication response, butboth methods are inaccurate compared with using multiplepre- and posttreatment IOP measurements.
*Financial disclosures: the authors stated that they heldno proprietary interest in the materials discussed herein.
DIAGNOSTIC PERFORMANCE OF ANTERIORCHAMBER ANGLE MEASUREMENTS FORDETECTING EYES WITH NARROW ANGLES16
Quigley HA, Broman AT.*Archives of Ophthalmology, October 2010
Can Anterior Segment Optical Coherence TomographyBe Used as a Screening Tool?
It is estimated that 60.5 million people worldwide will beblind because of glaucoma by 2010 and that the cause of halfof these cases will be due to angle closure. In a communitybased,cross-sectional study of 883 individuals 50 years of ageor older who were phakic, researchers set out to determinethe diagnostic performance of Anterior Segment OpticalCoherence Tomography (AS-OCT) for identifying eyes withnarrow angles.17
In the dark, participants underwent AS-OCT by a singleoperator. This test was followed by gonioscopy, whichwas performed in the dark by an ophthalmologist whowas masked as to the AS-OCT results. An eye was designatedas having a narrow angle if the posterior pigmented trabecular meshwork was not visible for at least 180° onnonindentation gonioscopy. AS-OCT images were obtainedusing the Visante OCT (Carl Zeiss Meditec, Inc., Dublin, CA).An algorithm was then used to calculate angle-opening distance,angle recess area, and trabecular-iris space area. Due tosoftware limitations, only the horizontal angles were quantified.
Narrow angles were diagnosed in 315 participants withgonioscopy. AS-OCT images were analyzed using various cutoffvalues. The area under the receiver-operating characteristiccurve was highest in the nasal (0.90 [95% corneal indentation,0.89-0.92]) and temporal quadrants (0.91 [95% corneal indentation,0.90-0.93]) of the angle-opening distance, the distancebetween the iris and the trabecular meshwork, which measured750 µm from the scleral spur. The specificity was notgreater than 90% at any cutoff value. It was noted that 25.2%of the community-based study participants had to be excludedbecause of difficulty locating the scleral spur, a critical landmarkfor angle measurements. The investigators felt the limitedresolution of the AS-OCT was the main factor contributingto difficulty identifying the scleral spur. Another limitationwas that only the temporal and nasal quadrants were analyzedbecause of software parameters, but previous studieshave found that the superior and inferior angles are narrower.18-20 Correcting this limitation would likely decrease thespecificity of the test further. The researchers concluded thatAS-OCT image analysis is a promising approach for detectingangles at risk for closure. They also suggested that futureimprovements would likely overcome the major drawback ofthe inability to identify the scleral spur, which currently limitsthe technology's use for population screening.
*Financial disclosures: the authors stated that they heldno proprietary interest in the materials discussed herein.
OCULAR BIOMETRY ANDOPEN-ANGLE GLAUCOMA:THE LOS ANGELES LATINO EYE STUDY21
Kuzin AA, Varma R, Reddy HS, Torres M, Azen SP;Los Angeles Latino Eye Study Group.*Ophthalmology, September 2010
Is There an Association Between Axial Lengthand Glaucoma?
The goal of the Los Angeles Latino Eye Study (LALES)was to examine the relationship between myopic refractiveerror, axial length, corneal power, and the prevalenceof primary open-angle glaucoma (POAG). LALES was apopulation-based survey of adult Latinos living in LosAngeles County. This study did not consider IOP in thedefinition of POAG and defined ocular hypertension asan IOP greater than 21 mm Hg in either eye.
Because myopic refractive error can be explained by nuclear opacification, axial length was used to evaluate therelationship of myopic refractive error to POAG. Myopicrefractive error was quantified as low (-1.00 to > -3.00 D)or moderate to high (≤ -3.00 D). Corneal power was anaverage of three measurements. Axial length was an averageof three measurements using the A-Scan Pachymeter(Ultrasonic, Exton, PA). Nuclear opacification was gradedusing the Lens Opacities Classification System, gradingopacities into five nuclear grades of increasing density.Nuclear opacification was defined as having a LensOpacities Classification System score of NII or greater.
Myopes were significantly more likely to have POAGthan nonmyopes (unadjusted prevalence of 8.1% and3.7%, respectively), and this was true across all agegroups. After adjustments for age, diabetes, gender, IOP,and family history, myopes were still twice as likely tohave POAG compared with nonmyopes. When axiallength was taken as a continuous variable, each millimeterincrease in axial length was associated with a 26% risein the prevalence of POAG independent of myopicrefractive error. The prevalence of POAG increased exponentiallyin eyes with an axial length greater than 25 mm.It rose by 15% with each diopter decrease in cornealpower, and this increase remained significant after adjustmentsfor age, gender, IOP, diabetes, family history, nuclearopacification, and myopic refractive error or axial length.
Axial Length May Be an Important Factor in theRisk for POAG
*Financial disclosures: the authors stated that they heldno proprietary interest in the materials discussed herein.
Section Editor James C. Tsai, MD, is the chairman andRobert R. Young professor of ophthalmology and visual scienceat Yale University School of Medicine in New Haven,Connecticut. He acknowledged no financial interest in theproducts or companies mentioned herein. Dr. Tsai may bereached at (203) 785-7233; james.tsai@yale.edu.
Charles A. Cole, MD, is a clinical assistantprofessor at Weill Cornell Medical College inNew York. He is a paid speaker for Allergan,Inc. Dr. Cole may be reached at (212) 753-6464;eyesurgeonpc@gmail.com.
