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`ORIGINAL ARTICLES
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`THE IDVANCED GLAUCOMA INTERVENTION STUDY (A015): 11. RISK FACTORS FOR FAILURE
`OF TRABECU LECTOMY AND ARGON LASTER TRABECULOPLASTY
`
`The A615 Investigators
`FEE ADVANCED GLAUCOMA INTERVENTION STUDY (A015): 12. BASELINE RISK FACTORS FOR
`gust-AIME!) LOSS OF VISUAL FIELD AND VISUAL ACUITY IN PATIENTS WITH ADVANCED GLAUCOMA
`The ACIS Investigamrs
`~ LOMPARISON 0F SURGICAL OUTCOMES OF COMBINED VISCOCANALOSTOMY AND
`ISATARACT SURGERY WITH COMBINED TRABECULOTOMY AND CATARACT SURGERY
`Tanito, Park, Nishékawa, Obira; Chihara
`
`A x ROSPECTWE RANDOMIZED TRIAL COMPARING INTRAOPERATWE 5~FLUOROURACIL VS
`MITOMYCIN C IN PRIMARY TRABECULECTOMY
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`EDITORIALS
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`A; «szRICAN JOURNAL OF OPHTHALMOLOGY: STATUS Ra’ORT FROM THE NEW EDITORJN-CHIEF
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`M’PLYING EVIDENCE-BASED MEDICINE IN OPflTHALMIC PRACTICE
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`lMERICAN JOURNAL
`OPHTHALMOLOGY®
`OF
`
`O CTOBER 2002 • VOLUME 134
`ORIGINAL ARTICLES
`THE ,\ DVANCED GLAUCOMA INTERVENTION STUDY (ACIS): 11. RISK FACTORS FOR FAILURE
`OF TRABECULECTOMY AND ARGON LASTER TRABECULOPLASTY
`Th e AG IS Investigators
`Tl'-\E ADVANCED GLAUCOMA INTERVENTION STUDY (ACIS): 12. BASELINE RISK FACTORS FOR
`SUSVINED LOSS OF VISUAL FIELD AND VISUAL ACUITY IN PATIENTS WITH ADVANCED GLAUCOMA
`The AG IS Investigators
`, ~OMPARISON OF SURGICAL OUTCOMES OF COMBINED VISCOCANALOSTOMY AND
`CATARACT SURGERY WITH COMBINED TRABECULOTOMY AND CATARACT SURGERY
`Tanito, Park, Ni shi kawa, O hira, Chihara
`A . ROSPECTIVE RANDOMIZED TRIAL COMPARING INTRAOPERATIVE 5-FLUOROURACIL VS
`MITOMYCIN C IN PRIMARY TRABECULECTOMY
`W uDunn, Cantor, Pa lanca-Capistrano, and Co-Authors
`MP·.:: ULAR TRANSLOCATION WITH 360 DECREE RETINOTOMY FOR MANAGEMENT OF ACE(cid:173)
`REL TED MACULAR DEGENERATION WITH SUBFOVEAL CHOROIDAL NEOVASCULARIZATION
`Perti le, Claes
`EDITORIALS
`A: ,i,ERICAN JOURNAL OF OPHTHALMOLOGY: STATUS REPORT FROM THE NEW EDITOR-IN-CHIEF
`Liesegang
`
`APPL YING EVIDENCE-BASED MEDICINE IN OPHTHALMIC PRACTICE
`Coleman
`BRIEF REPORTS
`, ~.)VERSE SYSTEMIC EFFECTS FROM PLEDCETS OF TOPICAL OCULAR PHENYLEPHRINE 10%
`Fraunfelder, Fraunfelder, Jensvo ld
`
`TREATMENT OF CENTRAL RETINAL VEIN OCCLUSION BY VITRECTOMY WITH LYSIS OF
`VITREOPAPILLARY AND EPIPAPILLARY ADHESIONS, SUBRETINAL PERIPAPILLARY TISSUE
`PLASMINOCEN ACTIVATOR INJECTION, AND PHOTOCOACULATION
`Lam, Blumenkranz
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`

`AMERICAN JOURNAL
`OF OPHTHALMOLOGY®
`
`ISSN 0002-9394 • VOL. 134, NO. 4 OCTOBER 2002
`
`EDITOR-IN-CHIEF
`THOMAS J. LIESEGANG, M.D.
`SENIOR ASSOCIATE EDITORS
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`EDITORIAL BOARD
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`
`Al~N on the corneal
`1~lc -d11\t' cnmaincrs or
`in n~,., ..:asc~. had m
`Par1l·n1.~ rn:1y slow! '
`'~ ~·~·c WARNI NGS{
`i.:~n. h~t thc cmire iril
`1 "J\';ulablc, C'(amine
`'bucs. During dinical
`~t·,ultan! color ch:mgr
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`_-•. ha~ Ileen repon.ru
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`H1<•n 111 1hc:,c paticms.
`om.1. XALATAN hat
`:-hould not adm inister
`
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`ctl . . ir_is pigmcmarion
`I\(> m(urm patients or
`C)..:~ rn ll'ngth. rhick(cid:173)
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`:~n.1111 \\'Omcn. Use
`
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`rr l·dcm;1, including
`
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`U \1:r,.:;1 p .
`
`8 -7 -S
`
`

`

`Comparative Effects of Latanoprost (Xalatan)
`and U noprostone (Rescu la) 1 n Patients With
`Open-angle Glaucoma and Suspected
`Glaucoma
`
`WILLIAM E. SPONSEL, MD, GIANMARCO PARIS, MD, YOLANDA TRIGO, COT,
`AND MELANIE PENA
`
`• PURPOSE: To compare, in paired eyes of open-angle
`glaucoma patients and glaucoma suspects, hydrodynamic
`and visual changes after 1 month of topical latanoprost in
`one eye and unoprostone in the other.
`• DESIGN: Single-center, institutional randomized clini(cid:173)
`cal trial.
`• METHODS: After completing a washout period off all
`topical medication, 25 adults (mean age 54 ± SEM 2
`years) with bilateral open-angle glaucoma or glaucoma
`suspect status underwent morning (8 to 10 AM) and
`afternoon ( 1 to 3 PM) measurements of intraocular pressure
`(IOP), pulsatile ocular blood flow (POBF), contrast, sensi(cid:173)
`tivity, frequency doubling technology, and Humphrey 10-2
`perimetry (HVF A II) in both eyes. Each then started
`unoprostone 0.15% (Rescula) in one randomly assigned
`eye and latanoprost 0.005% (Xalatan) in the other. Uno(cid:173)
`prostone was administered at 8 AM and 8 PM and latanoprost
`at 8 PM with placebo at 8 AM, both from masked bottles.
`After 28 days, differences were determined for each mea(cid:173)
`sured variable by two-tailed paired t test.
`• RESULTS: Starting from similar baseline IOP levels,
`after 1 month of treatment, the mean morning IOP
`values differed according to the topical agent received
`(16.2 ± SEM 0.6 mm Hg for latanoprost vs 17.9 ± 0.7
`mm Hg for unoprostone; P = .001). These morning
`pressures were 2.6 mm Hg lower than baseline in the
`
`Accepted for publication May 29, 2002.
`From the Department of Ophthalmology, University of Texas Health
`Science Center, San Antonio, T exas.
`T h is study was supported in part by grants fro m Pharmacia Corpora(cid:173)
`t ion, Kalamazoo, Michigan, and Research ro Prevent Blindness, New
`York, New York. Academic honoraria or research grants have been
`rece ived by W.E.S. from the manufacturers of both drugs used in th is
`study and from the manufacturer of anoth er competing prostaglandin
`analogue.
`Inquiries to W illiam Eric Sponsel, MD, South Texas Ocular Imaging
`Center, University of T exas Health Science Center Department of
`O phthalmology, 7703 Floyd Curl Dri ve; San A n ronio, T X 78229-3900;
`fax: (2 10) 567-84 13; e-mail: sponse l@uthscsa.edu
`
`eyes receiving latanoprost (P < .0001), and 1.6 mm Hg
`lower in unoprostone-treated eyes (P = .02). Afternoon
`values were 3.1 ± SEM 0.6 lower than corresponding
`baseline in eyes receiving latanoprost, and 2.4 ± SEM
`0.6 mm Hg in unoprostone-treated eyes (P < .0001 from
`baseline for both medications; interdrug mean IOP dif(cid:173)
`ference; P = .04). Eyes receiving unoprostone showed a
`1. 7-db improvement in frequency doubling mean devia(cid:173)
`tion (P = . . 03 ), the only significant visual function
`change observed. Pulsatile ocular blood flow increased
`30% relative to baseline in eyes receiving latanoprost,
`(P < .0001) and 16% in eyes receiving unoprostone
`(P = .05) by the morning of day 28. That afternoon,
`mean POBF had increased 30% (P < .0001) relative to
`afternoon baseline values among eyes receiving latano•
`prost and 18% (P = .03) among those receiving uno(cid:173)
`(interdrug change difference, P = .05).
`prostone
`Humphrey perimetry and contrast sensitivity remained
`stable with both prostanoids.
`• CONCLUSIONS: Both latanoprost and unoprostone
`produced significant reductions in IOP and increases in
`POBF, with stable central and perimacular visual func•
`tion. Latanoprost once daily produced IOP reduction and
`POBF increases nearly twofold greater than those ob(cid:173)
`tained with unoprostone twice daily. These differences in
`IOP and POBF change between unoprostone and latano•
`(Am J Ophthalmol
`prost were statistically significant.
`2002;134:552-559. © 2002 by Elsevier Science Inc. All
`rights reserved.)
`
`P ROST ANO IDS H A VE BECOME A MAINSTAY OF ANTI(cid:173)
`
`glaucoma therapy.1.2 Latanoprost and unoprostone
`are the two most extensively studied drugs in thts
`class. Both drugs have proven to be safe. Benign alterations
`in iris color and elongation of eyelash es have been ob(cid:173)
`served in a small proportion of patients.3 ,4 Latanoprost,
`(Xalatan; Pharmacia Corporation, Peapack, New Jersey,
`
`552
`
`© 2002 BY ELSEVIER SCIENCE INC. ALL RIGHTS RESERVED.
`
`0002-9394/02/$22.00
`Pl! 50002-9394(02)01643-4
`
`USA) which rr
`was initially int
`widely used as
`glaucoma. It ha
`hypotensive agt
`Unoprostone
`Georgia, USA )
`docosanoid) us,
`approved by tht
`use in the Unit
`sive efficacy da
`thalmic literan
`there was no
`Library of Med
`the 0.15% con
`keted in the U
`parative anim,
`unoprostone c,
`concentration ,
`several reports
`two drugs whe
`study commen,
`prostone was g
`The strong
`perfusion in Ii
`repeatedly in
`decade, 18 provi
`of pulsatile ocu
`population. n
`plied principle:
`
`THE PRIMARY C
`a masked evali
`the intraocula1
`prost 0.005% (
`daily). A seco
`function and c
`
`THIS STU DY ~
`clinical trial p1
`dations guidin
`ing human sul:
`discussion of ,
`subject under
`Board approvt
`
`• SETTING Al
`lected from l
`Eye Clinics a
`diagnosed gla1
`
`VOL. 134, No.
`
`

`

`ln)
`th
`
`T,
`
`6mmHg
`~fternoon
`!Sponding
`~ ± SEM
`1001 from
`IOP dif,
`showed a
`,an devia-
`function
`increased
`:anoprost,
`:>prostone
`.fternoon,
`·elative to
`1g latano,
`ving uno-
`=
`.05).
`remained
`
`:>pros tone
`:reases in
`,ual func-
`1ction and
`those ob(cid:173)
`!rences in
`1d latano(cid:173)
`,hthalmol
`e Inc. All
`
`OF ANTI(cid:173)
`oprostone
`gs in this
`1lterations
`been ob(cid:173)
`tanoprost,
`!W Jersey,
`
`4/02/$22 .00
`(02 )01643-4
`
`USA ) which mimics the action of prostaglandin F2cx,5,6
`was initially introduced as a second-line agent but is now
`widely used as primary therapy for various etiologies of
`glaucoma. It has become one of the most effective ocular
`hypotensive agents available for treating glaucoma.7,8
`Unoprostone (Rescula; Novartis Ophthalmics, Duluth,
`Georgia, USA) is a topical prostaglandin analog (a C-22
`docosanoid) used in Japan for many years and recently
`approved by the Food and Drug Administration (FDA) for
`use in the United States. Although good ocular hypoten(cid:173)
`sive efficacy data from Japan were available in the oph(cid:173)
`thalmic literature, 1.2 at the time this study commenced,
`there was no published report listed on the National
`Library of Medicine (PubMed) website on the efficacy of
`the 0.15% concentration of unoprostone currently mar(cid:173)
`keted in the United States. A number of excellent com(cid:173)
`parative animal and human studies using the 0.12%
`unoprostone concentration vs the latanoprost 0.005%
`concentration appeared recently.9- 13 There have also been
`several reports indicating some degree of additivity of the
`two drugs when used in combination. 14-17 The present
`study commenced shortly before FDA approval for uno(cid:173)
`prostone was granted.
`The strong association of visual function and ocular
`perfusion in glaucomatous eyes has been documented
`repeatedly in the ophthalmic literature over the past
`decade, is providing the impetus for our present assessment
`of pulsatile ocular blood flow (POBF) change in this study
`population. This concomitant bilateral study design ap(cid:173)
`plied principles discussed previously.18,19
`
`DESIGN
`
`THE PRIMARY OBJECTIVE OF THIS STUDY WAS TO CONDUCT
`a masked evaluator, randomized clinical trial to compare
`the intraocular pressure lowering effects of topical latano(cid:173)
`prost 0.005% (once daily) and unoprostone 0.15% (twice
`daily). A secondary objective was to compare the visual
`function and ocular perfusion effects of the two drugs.
`
`METHODS
`
`THIS STUDY WAS A MASKED EVALUATOR, RANDOMIZED
`clinical trial performed in accordance with the recommen(cid:173)
`dations guiding physicians in biomedical research involv(cid:173)
`ing human subjects. Informed consent was obtained after a
`discussion of any risks and benefits with each prospective
`subject under a University of Texas Institutional Review
`Board approved protocol.
`
`• SETTING AND STUDY POPULATION: Subjects were se(cid:173)
`lected from University of Texas Health Science Center
`Eye Clinics and included qualifying existing and newly
`diagnosed glaucoma patients and glaucoma suspects. De-
`
`mographic data, medical and ocular history, concomitant
`medication, and visual field measurements were recorded,
`and an ocular examination and tonometry were performed
`to ensure that the inclusion crite~ia were fully met and to
`verify patient identity and status relative to the source
`data.
`
`• INTERVENTION AND OBSERVATIONAL PROCEDURES: All
`the test evaluations were performed at the initial prestudy
`visit at the South Texas Ocular Imaging Center to ascer(cid:173)
`tain the patient's capabilities to complete the study. To
`avoid any learning effect on the data subsequently col(cid:173)
`lected for the treatment comparison, repetitive test train(cid:173)
`ing was carried out for any of the visual function tests
`unfamiliar to each subject. Inclusion criteria were as
`follows: (1) minimum of 18 years of age; (2) bilateral
`open-angle glaucoma or ocular hypertension (intraocular
`pressure [IOP] > 21) currently using no more than two
`ocular hypotensive agents, with glaucomatous visual field
`defect as defined by Hodapp, Parrish, Anderson criteria or
`Humphrey hemifield defect in either eye or disk cupping
`of 2=: 0.6 in either eye or cup/disk asymmetry between eyes
`of> 0.1; (3) current (at the screening visit) or previous
`monotherapy or dual therapy for paired open-angle glau(cid:173)
`coma or ocular hypertension; ( 4) best-corrected visual
`acuity no worse than 20/100 in each eye; (5) intraocular
`pressure ::5 27 mm Hg in each eye; (6) signed informed
`consent at the prestudy visit; (7) and able to adhere to
`treatment and visit plan. Exclusion criteria included the
`following: ( 1) any history of acute angle-closure glaucoma;
`(2) any history of ocular surgery (on the globe of the eye
`only); (3) hypersensitivity to unoprostone or latanoprost
`eyedrop solutions; ( 4) history of progressive ocular pathol(cid:173)
`ogy; (5) intraocular pressure asymmetry (right eye vs left
`eye) at prestudy visit of> 2 mm Hg; (6) any compromising
`systemic disease (AIDS, leukemia, cancer); (7) use of any
`systemic medication that is likely to affect IOP or ocular
`circulation (for example, adrenergic agents, calcium chan(cid:173)
`nel blockers, carbonic anhydrase inhibitors, acetylcho(cid:173)
`inhibitors and/or angiotensin II
`linesterase
`receptor
`blockers); (8) pregnancy (all consenting women of child(cid:173)
`bearing age received a pregnancy test at the prestudy visit);
`and (9) nursing mothers.
`The schedule of events is shown in T able 1. The study
`consisted of three visits (plus a follow-up visit during week
`5), as outlined below. Patient demographics such as age,
`sex, systemic medications not excluded by protocol edict,
`and visual acuity were recorded. A washout (discontinua(cid:173)
`tion) of as long as 4 weeks of antiglaucoma medication
`preceded study enrollment among consenting glaucoma
`patients and suspects qualifying for the study ( 4 weeks for
`prostaglandins and [3-blockers, 2 weeks for adrenergic
`receptor agonists, and 5 days for carbonic anhydrase
`inhibitors and cholinergic agonists). Monotherapy (8 PM)
`was started in one randomly selected eye of each subject
`with latanoprost and artificial tears (8 AM), and in the
`
`VOL. 134, No. 4
`
`COMPARATIVE EFFECTS OF LATANOPROST AND LJNOPROSTONE
`
`553
`
`

`

`TABLE 1. Scheduled Visits and lnvestigational Events
`
`Scheduled Visits
`
`Examination Hours
`
`Prestudy
`
`8-10 AM
`
`Baseline
`
`Day 28
`
`8-10 AM
`
`1-4 PM
`
`8-10 AM
`
`1-4 PM
`
`Week 5
`
`8 AM-4 PM
`
`Medical and ocular history
`Inclusion/exclusion
`Informed consent
`lntraocular pressure
`External/slit-lamp examination
`Ophthalmoscopy
`Visual acuity
`Blood pressure and heart rate
`Contrast sensitivity
`Frequency doubling
`technology p~rimetry
`Humphrey 10-2 technology
`perimetry
`Pulsatile ocular blood flow
`
`X
`X
`X
`xx
`X
`X
`X
`
`xx
`xx
`
`X
`
`xx
`
`X
`
`xx
`
`X
`
`X
`
`X
`X
`
`X
`
`xx
`
`X
`
`X
`
`xx
`
`X
`
`X
`
`X
`
`X
`X
`
`X
`
`X
`
`X
`
`X
`
`X
`
`X
`
`X
`X
`X
`X
`X
`
`other eye with unoprostone twice daily (8 AM and 8 PM)
`using appropriately-masked bottles. To-determine whether
`the once-daily latanoprost vs the twice-daily unoprostone
`dosing regimen might be associated with any observed
`differences in measured variables (as peak and trough
`differences have been observed clinically for both drugs8 ),
`intraocular pressures, visual function tests, and POBF were
`measured in both eyes, right eye first, beginning at 8 AM
`and again at 1 PM on day zero, before initiating topical drug
`administration. The four bottles were clearly labeled to
`indicate their time of intended application, subjects were
`coached on their use, called at home, and questioned at
`follow -up to ensure maximal compliance. Studies were
`repeated at the same times on the morning and afternoon
`of day 28, during latanoprost/unoprostone bilateral mono(cid:173)
`therapy. The study sessions were strategically timed to
`provide comparative measurements at the unoprostone
`intraocular hypotensive peak and latanoprost trough ( 1 to
`3 PM) and at the latanoprost peak and unoprostone trough
`(8 to 10 AM). Intraocular pressures and pulsatile ocular
`blood flow on the morning of day 28 were measured before
`administration of the morning eyedrops.
`Intraocular pressures were measured by pneumotonom(cid:173)
`etry (OBF Laboratories Malmesbury, United Kingdom)
`and Goldmann applanation tonometry (Haag-Streit, Ma(cid:173)
`son, Ohio, USA) . We measured pulsatile ocular blood flow
`by analyzing five consecutive tonometric ocular pulse
`waves (OBF Laboratories, Malmesbury, United Kingdom;
`marketed in United States by Paradigm, Denver, Colo(cid:173)
`rado, USA). Brachia! systolic and diastolic blood pressures
`were measured by sphygmomanometry. Central retinal
`contrast sensitivity (7-degree pattern, 1 and 4 cycles per
`degree, 15 reversals per second) was performed using a
`two-step positive forced choice algorithm (NeuroScientific
`8010, New York, New York, · USA). Central 10-degree
`
`visual fields were performed at the outset and conclusion of
`the study. (HVFA II, Hu~phrey/Zeiss, San Leandro, Cal(cid:173)
`ifornia, USA). Full-thresholding frequency doubling peri(cid:173)
`metric analysis was conducted at the same time intervals
`using the frequency doubling technology device (FDT;
`Humphrey/Zeiss).
`
`• MAIN OUTCOME MEASURES AND DATA ANALYSIS:
`Size of the treatment group (n = 25) was selected so as to
`have at least a 90% power to detect a 1.5-mm Hg
`difference of IOP between the two eyes at P < .005 . Dara
`are presented descriptively for all variables as the treat(cid:173)
`ment group mean± standard error of the mean (SEM) and
`evaluated by paired t test to determine the significance of
`any observed differences between treatment conditions for
`each of the visual function and ocular perfusion studies, as
`well as for IOP.
`
`RESU LTS
`
`TWENTY-FIVE SUBJECTS (4 MEN, 21 WOMEN) AGED 40 TO 75
`years (mean 54 ± SEM 2; median, 53) completed the
`study. Their ethnic composition was 11 Caucasian, 11
`Hispanic, and 3 African American. Their mean heart rate
`at baseline was 71 ± 2 beats per minute, with mean
`systolic blood pressure of 129 ± 3 and diastolic pressure of
`71 ± 3 mm Hg. These cardiovascular variables remained
`stable throughout the study. Qualifying subjects included
`both ocular hypertensive and normal-tension open-angle
`glaucoma patients and ocular hypertensive glaucoma sus(cid:173)
`pects. All had corrected DRS chart distance acuities of 2:
`20/40 in both eyes; 18 had cup/disk ratios > 0.5; 16 had
`Humphrey 30-2 mean deviation values more negative than
`- 2.50, and 13 had intraocular pressures 2: 20 mm Hg at
`
`554
`
`AMERICAN JOURNAL OF OPHTH ALMOLOGY
`
`O CTOBER 2002
`
`the prestudy visit
`tions throughout 1
`in both eyes. Tht
`any adverse evel1'
`
`• VISUAL FUNC
`(Swedish interac1
`old visual fields,
`completion of t:
`differences (initia
`deviation (MD) c
`· values among th<
`created and latar
`for the 25 subject
`for the right eye
`Average pattern
`mately 1.7 and 2
`tively, at both in
`Frequency dm
`duced one signifi,
`showed a statisti
`deviation betwee
`SEM 1.1
`to -(
`improvement wai
`and posttreatmer
`and left eyes in t
`tially equivalent,
`visits.
`Borderline inc
`with both drugs i•
`degree. There w,
`degree contrast st
`the latanoprost-t
`(2.1 ± 0.8; p = ,I
`The difference i
`sensitivity increa
`icant (P = .3 ).
`apparent trend i1
`patterned, tempc
`wave contrast pa
`
`• INTRAOCULA
`planation tonom
`and ocular hypt
`mean of 18.8 :!
`(baseline) amon1
`prost, and 19 .5 :±
`unoprostone. Af
`decreased 14%,
`among eyes tre,
`decreased 8%, l:
`unoprostone, to
`Figure 1). This
`therapy between
`(P < .001 ). Pne
`ilar to those obt
`
`V OL. 134, No. 4
`
`

`

`the prestudy visit. All 25 subjects tolerated both medica(cid:173)
`tions throughout the study period, with stable visual acuity
`in both eyes. There was no patient withdrawal, nor were
`any adverse events reported.
`
`, VI SUAL FUNCTION TESTS: Humphrey 10-2 SITA
`(Swed ish interactive thresholding algorithm) full-thresh(cid:173)
`old visual fields, performed at the initiation and upon
`completion of the study, demonstrated no significant
`differences ( initial vs .final, intradrug or interdrug) in mean
`deviation (MD) or pattern standard deviation. Mean MD
`values among the four sets of visual fields (unoprostone(cid:173)
`created and latanoprost-treated, prestudy and poststudy)
`for the 25 subjects remained approximately - 2.1 ± 0.5 db
`for the right eyes and - 3.6 ± 0.6 db for the left eyes.
`Average pattern standard deviation values were approxi(cid:173)
`mately 1.7 and 2.9 db for the right and left eyes, respec(cid:173)
`tively, at both intervals.
`Frequency doubling technology (FDT) findings pro(cid:173)
`duced one significant finding. Eyes receiving unoprostone
`showed a statistically significant increase in FDT mean
`deviation between baseline and day 28, from mean - 2.4 ±
`to -0.7 ±0.8 decibels. This 1.7 db mean
`SEM 1.1
`improvement was significant, at P = .03 . The pretreatment
`and posttreatment FDT mean deviation values for right
`and left eyes in the latanoprost treated group were essen(cid:173)
`tially equivalent, averaging around -1.5 ± 1 db at both
`visits.
`Borderline increases in visual function were observed
`with both drugs in contrast sensitivity testing at 1 cycle per
`degree. There was a fivefold increase in mean 1 cycle per
`degree contrast sensitivity (5.4 ± SEM 2.8; P = .1) among
`the latanoprost-treated eyes and a twofold mean increase
`( 2. 1 ± 0.8; P = .07) among eyes treat_ed with unoprostone.
`The difference in the mean 1-cycle per degree contrast
`sensitivity increases between the two drugs was not signif(cid:173)
`icant (P = .3 ). Neither drug was associated with any
`apparent trend in visual function change using the finer(cid:173)
`patterned, temporally modulated 4-cycles per degree sine(cid:173)
`wave contrast pattern.
`
`• INTRAOCULAR PRESSURE: lntraocular pressure by ap(cid:173)
`planation tonometry in this mixed group of normal tension
`and ocular hypertensive glaucoma patients measured a
`mean of 18.8 ± SEM 0.6 mm Hg at 8 AM on day 1
`(baseline) among eyes destined for treatment with latano(cid:173)
`prost, and 19.5 ±0.8 mm Hg among eyes to be treated with
`unoprostone. After 1 month of therapy, 8 A M IOP had
`decreased 14%, by 2.6 mm Hg (to 16.2 ± 0.6 mm Hg)
`among eyes treated with latanoprost (P < .0001 ), and
`decreased 8%, by 1.6 mm Hg, among eyes treated with
`unoprostone, to a level of 17.9 ±0.7 mm Hg (P < .02; see
`Figure 1 ). This difference in mean IOP after 1 week of
`therapy between the two drugs was statistically significant
`(P < .001) . Pneumotonometry data provided results sim(cid:173)
`ilar to those obtained by Goldmann applanation tonome-
`
`-C>
`E -Cl)
`
`:I:
`E
`
`'-::,
`Ill
`Ill
`Cl)
`'-a.
`'-
`C'CI
`::,
`(.)
`0
`
`e! -C
`
`20
`
`17.5
`
`15
`
`12.5
`
`P < 0.0001
`
`P < 0.02
`
`P = 0.001
`I
`I
`T
`
`T
`
`/l//~!///111
`:•:•:•:•:•:-:-:-:.:
`~~}~~~}~~{}
`
`,•,•,•,•,•,•,•,•.•.
`
`Baseline
`Day 28
`a.m.
`a.m.
`FIGURE 1. Histogram showing mean intraocular pressures at
`8 AM on the day of the pretreatment baseline visit and at 8 AM
`before the morning dose of topical ophthalmic on the 28th day
`of once-daily morning administration of latanoprost or twice(cid:173)
`daily unoprostone. Vertical bars (dotted bar = latanoprost;
`shaded bar = unoprostone) designate standard error of the
`mean, and horizontal bars represent the statistical significance
`of change from baseline or interdrug difference, on the basis of
`a paired Student t test.
`
`try. Both tonometry methods used had a > 90% power to
`detect a 4-mm Hg difference, and > 40% power to detect
`a 2-mm Hg difference from baseline at alpha 0.05.
`Afternoon pressures followed a similar pattern. The
`difference between latanoprost- and unoprostone-treated
`eyes remained significant (