A-Al~i 874 ARhOPINE AND HUMAN CONTRAST SENSITIVITY FUNCTION(U) 1"A1LETTERMAN ARMY INST OF RESEARCH PRESIDIO OF SANFRANCISCO CA D M PENETAR ET AL APR 87 LAIR-236

UNCLASSIFIED F/G 6/5 UL

1111111201.8.

11111 2 1.40 1.612

'pp

, C FILE COP'i

b INSTITUTE REPORT NO. 236

ATPOPINE AND HUMAN CONTRAST SENSITIVITY FUNCTION

N0___ David M. Penetar, PhD, WIAJ, 'S

W John J. Kearney, COL, WCYin-

pTIM

UDivision of Ocular HazardsLetterman Army Institute of Research

£

--.- I

April 1987

LETTERMAN ARMY INSTITUTE OF RESEARCHPRESIDIO OF SAN FRANCISCO, CALIFORNIA 94129

Atropine and human contrast sensitivity function--Penetar and Kearney

Reproduction of this document in whole or in part is prohibited except with the permission of theCommander, Letterman Army Institute of Research, Presidio of San Francisco, California 94129.However, the Defense Technical Information Center is authorized to reproduce the document forUnited States Government purposes.

MDestroy this report when it is no longer needed. Do not return it to the originator.

Citation of trade names in this report does not constitute an official endorsement or approval of the4, use of such items.

Human Subjects participated in these studies after giving their free and informed voluntary consent.Investigators adhered to AR 70-25 and USAMRDC Reg 50-25 on the use of volunteers in research.

This material has been reviewed by Letterman Army Instituteof Research and there is no objection to its presentation and/or publication. The opinions or assertions contained hereinare the private views of the author(s) and are not to be con-strued as official or as reflecting the views of the Departmentof the Army or the Department of Defense. (AR 360-5)

-4... 4 s-?i AT r- '

(Signature and date)

T

,,/ This document has been approved for public release and sale; its distribution is unlimited.

a...,.

UNCLASSIFIEDSECURITY CLASSIFICATION OF THIS PAGE ~A 1910 7 #i

Form ApprovedREPORT DOCUMENTATION PAGE OMBINo 0704-0188

__I Exp Date Jun30, 1986la REPORT SECURITY CLASSIFICATION lb. RESTRICTIVE MARKINGS

UNCLASSIFIED

2a. SECURITY CLASSIFICATION AUTHORITY 3. DISTRIBUTION /AVAILABILITY OF REPORT-___Approved for public release; distribution is

- 2b. DECLASSIFICATION /DOWNGRADING SCHEDULE unlimited.

4. PERFORMING ORGANIZATION REPORT NUMBER(S) 5. MONITORING ORGANIZATION REPORT NUMBER(S)

6a NAME OF PERFORMING ORGANIZATION 6b. OFFICE SYMBOL 7a- NAME OF MONITORING ORGANIZATIONDivisin ofOCular tazardSf s (if applicable) Letterman Army Institute of ResearchLetterman Acmt Institute of IescfircRhesearch

II

6c. ADDRESS (City, State, and ZIP Code) 7b- ADDRESS (City, State, and ZIP Code)Letterman Army Institute of Research Presidio of San Francisco, CA 94129-6800Presidio of San Francisco, CA 94129-6800

8a. NAME OF FUNDING/SPONSORING 8b. OFFICE SYMBOL 9. PROCUREMENT INSTRUMENT IDENTIFICATION NUMBER

ORGANIZATION (If applicable)

USAM DC SGRD8c. ADDRESS (City, State, and ZIP Code) 10. SOURCE OF FUNDING NUMBERSFort Detrick PROGRAM PROJECT TASK WORK UNITFrederick, ID 21701-5012 ELEMENT NO. NO E1677 NO ACCESSION NO

62777A 7A878V BA 860H005

11. TITLE (Include Security Classification)

Atropine and Human Contrast Sensitivity Function

12. PERSONAL AUTHOR(S)DM Penetar and JJ Kearney

13a. TYPE OF REPORT 13b TIME COVERED 14 DATE OF REPORT (Year, Month, Day) 115. PAGE COUNTInstitute Report FROM Jul 86 ToOct 87 1987 April 716. SUPPLEMENTARY NOTATION

Institute Report No. 236

17. COSATI CODES 18. SUBJECT TERMS (Continue on reverse if necessary and identify by block number)

FIELD GROUP SUB-GROUP

Atropine, Humans, Contrast Sensitivity, Visual Function

19 ABSTRACT (Continue on reverse if necessary and identify by block number)

A The effects of one and two autoinjector equivalents of atropine sulfate (2 and 4 mg/70kg im) on contrast sensitiviLy were mea'sured in Pight male volunteers, ages 22 to 39 yr.Using an automated contrast sensitivity machine, volunteers were required to detectsinusoidal gratings of 0.5, 1.0, 3.0, 6.0, 11.4, and 22.8 cycles per degree. At two hrafter injection, no atropine effect was observed for any frequency.._- -

20 DISTRIBUTION/AVA;LABILITY OF ABSTRACT 21 ABSTRACT SECURITY CLASSIFICATIONEl UNCLASSIF EDUNLIMITED (- SAME AS PPT [ DTIC USERS Unclassified

22a NAME OF RESPONSIBLE NDIVDUAL 22b TELEPHONE (Include Area Code) 22c OFFICE SYMBOLMAJ David Penetar (415) 561-3479 SGRD-UL-OH

DO FORM 1473, 84 MAR 83 APR edition may be used un!I exhausted SF(-i'RiTY CLASSIFICATION OF THIS PAGEAI! other editions are obsolete UNCLASSIFIED

PRE .ACE

We express appreciation to physicians CTI' PeterR'aningas, %!AJ Donald Warks, and MAJ William Pickell, whoseassistance was crucial to the completion of this experimentand to the health and safety of the volunteers. We thankSGT Sally Ruiz and SGI Helen Ford for their skillfultechnical assistance, and Dr. Virginia Gildengorin and Mr.Jerome %.olchany for their assistance with the statisticalanalysis of the data. Nlost of all, we express appreciationto the volunteers who willingly bore the atropine effects.

a

-. 0

ABSTRACT

fhe eftects of one and two autoinjecto' equivalents ofatropine sulfate (2 and 4 mg/70 kg ira) on contrastsensitivity were measured in eight male volunteers, ages 22to 39 yr. Using an automated contrast sensitivity machine,volunteers were required to detect sinusoidal gratings of0.5, 1.0, 3.0, 6.0, 11.4, and 22.8 cycles per degree. At twohr after injection, no atropine effect was observed for anyfrequency.

~DTICX

IcopyJ

A /b

Penetar and Eearney - 1

INTRODUCION

Atropine is a potent and long-lasting anticholinergicagent. Its mydriatic and cycloplegic effects on visualacuity anrid accommodation have been studied. Recently baker(1) and Jampolsky (2) and colleagues reported that followinginjections of 2 and 4 mg of atropine per 70 kg of bodyweight there was no effect on either high or low contrastvisual acuity at a distance of 20 feet. On the other hand,low-contrast visual acuity at 40 cm is affected by 4 mgatropine per 70 kg. These visual effects had a relativelyslow onset and were long-lasting, beginning about 4 hoursafter injection and persisting for at least 7 hours afterinjection. Recovery was observed the following day.

Visual acuity may be closely correlated with the abilityto resolve targets cf high spatial frequency. Measurementsof visual acuity do not provide information on the abilityto resolve low and mid-range spatial frequency details. P'anymilitary tasks, such as detection and tracking of vehicles,require resolution in these spatial frequency ranges.

ihe contrast sensitivity function measures at a fixedluminance the minimum amount of contrast between target andbackground required for discrimination of targets across thespatial frequency spectrum. It is the reciprocal of thethreshold contrast. k'easurement of the contrast sensitivityfunction makes it possible to characterize a broad range ofvisual Junctions rather than define only the upper boundaryof spatial resolution.

Veasurement of the contrast sensitivity function hasbeen employed in studies on the effects of 2 and 4 mg/70 kgdoses of atropine in humans. [our hours after a 2 mg/70 kgdose of atropine, a small but consistent loss in sensitivitywas found at all spatial frequencies, when tested at adistance of 40 cm. Significant decrements were found onlyfor spatial frequencies of 5 and 20 cycles per degree (1).In another study frequencies between 3 and 7 cycles perdegree were not affected by a dose of 4 mg/70 kg (3).

Although these studies show that atropine affectscontrast sensitivity when tested at reading distances (40

M(), they (ht not address the quest ion ,f t atropi ne ef fects ondi ,tane ( i v 20 It and beyond) contrast sezisi tivity. 'Ihenature of the contrast sensitivity function after atropinefor distances beyond 40 cm has important militaryconsequences as soldiers are required to resolve targets atdistances *ell beyond this distance.

%'4

4.. ¥ "W , : :. r -. "? '"' ' .

Penetar and Kearnev - 2

It has been observed that atropine's maximum effect onnursuit trackinq performance occurs in parallel to itsmaximum ef'ect on pupil size and accommodation and dues notcorrespond to this drua's maximum cardiovascular effects(3). The trackinn task is done at optical infinity and thereasons for the observed trackinq decrements are unlikely tobe due to pupil and accommodative chanqes alone. Changes indistance contrast sensitivity may be a factor. Therefore,durinq a recent field evaluation of atropine's effects ontrackinq (4), we also measured distance c-ontrast sensitivityon a hr,)ai-r r-i nq of sr-t ia I freciun -i s hian prey tV j l sYr 1),)r t vl

METHODS

Participants: Eioht male volunteers between the aqes of22 and 39 were selected for this study. All were inexcellent health. They all had either uncorrected visualacuity of 20/20, or were correctable to 20/20 with spectaclelenses. Most were emmetronic or had an error of refractionwithin 1 diopter of emmetropia. One volunteer had arefractive error of 3 diopters myopia. Ophthalmoscopy,tonometry and slit lamp examination were normal. Corrective..-o-ctacles were worn by those volunteers whose listance'Pvisual acuity wis less than 20/20.

Procedures: The contrast sensitivity function wasmeasured usinq a Nicolet CS-2000 test system. Thresholddeterminations were made for six frequencies: 0.5, 1.0,3.0, 6.0, 11.4, and 22.8 cycles per deqree. The test wasconducted in a briqht interior environment, with no directsunlight. Volunteers viewed a 13 inch black and white TV

C- monitor from a distance of 10 feet. The display contrastbeqan at 0 and increased under computer control. Volunteerswere required to press a button when they detected theappearance of a sinusoidal qratinq. Each frequency was

I. nresented five times and the mean Iori threshold contrast wasrecorded. This method is similar to an ascendinq method ofl imits nr, ychonhysical procedure.

' nt r-st 'n;(in t j i ty functions w-'re qornerateli for eachinflividut1 for fo-ir driiq conditions: 1) bhseline (no druq),2) saline pliacpho, 3) 2 mq/70 kq, and 4) 4 mq/70 kq atroninesulfate. Injections were aiven intramuscularly 2 hoursbefore tst in7 in a double masked fashion. Order wascounterblan'ed across volunteers. Data were analyzed byme-ans of , -wav ren,'atpd m;istires analysis o)f variance(f11P-2V) (5). Separaf,' ANOVAs were nerforme'1 on thf data

r-~ v~~ -. r, n *

Penetar and h'earney - 3

RESULTS

('oir~ s., :unsi L. I vi ty I unc t ioni lr each inljectioncondition across the frequencies tested is shown (Figure).The shape of the function observed under baseline conditionis typical of normal human functioning. Differences acrossfrequencies are highly significant (f-10.27, df=5,35,p<0.0000), confirming t he f R c t t h at humans aredifferentially sensitive to frequencies within the rangetested. Peak sensitivity occurs within the 5 to 8cycles/degree range with considerable less sensitivity atfrequencies higher or lower.

Sli... -------2 .s/70 K9 0----04 ./70Kg -----

ml 1000 3- -

O 2 S

0

0

0

05 10 30 60 114 221

SPATIAL FREOUENCY

rlgure. Contrast sensitivity functions for four drugconditions 2 hr after injection.

V Penetar and Kearney - 4

Inspnection of the f igure suciests dif ferences amono theinjection conditions, esnpially at frecinencies 3 cycles nerdegiree and above. The larQest differences wore observe3 ;it22 cycles ner dearee. All ohserved difference s were smalland nonsiginific-ant, however (F=0.77, dif=1,21, n<0.525P).

DISCUSSTON

Previouis reports have shown antichol i rierq ic ef fect-,~ onlcontrast sleni t iv ity us ina other tests (1,3,6). Otherresearchers kisina the same apparatus found a signif icanteffect with 4 mg.170 kg atropine. Behar ren~orted a reductiono)f up to 501% in sensitivity at freciuencies of 3, 9), and 16cycles/de.qree (7). These findinqs are not in conformitywith our results, and additional research is indicated toexplain this dIiscrepancy.

The ef fects of atronine on vision may be due to adecrease in the amlitude( of accommodation or to the reducedoptical qJUali'-v of the imacie seen through an ornlarged pupil.The loss in vi sual functio:n due to reduced accommodatio:n isino.t arprir ont for ne~i r vi S ion)r andI in the ca so of uincorrec'te~d

hvnr'r~j. hrofu hours -iftr-r a doseqq of 4 mq/7n0 kri oI

itropine, one wo)uld expect an accommnodat ive los OS f .-1 most3.5 diopters (2 . Recovery of accommodaition is incomplete at24 hours. F'ull recovery is not seen u~ntil 48 hours fol lowinriinjection.

One should not expect a reduction in distance visualfunction in subjects who either are emmetropic or arerendered emmetropic by the use of spectacles, or who are

A uncorrected myopes. The amount of accommodation required at$ our test distance is approximately 0.33 diopters, a verysmall amount, and one not expected to produce a siqni ficantvisual loss.

40 Atroninm-inducedo( visual l'5at our experin(ental

di stances i.; ;ocondiry to otiaIaertIfS1'Eml~nInmvriaisis. These includeli the veiling glare effect of theincreased linht transmitted to the retin, increased scatteras more lioht nasses!7 through the crystalline le ns, .inddecrease in the point spread function. These aberra-tions aresecondary to the imnerfections of the crystalline lens as anoptical mediuim. Other mechanisms inclule effects on theneural pathways of vision and the ovorall mnalaiseoxperi pnod by nperons who receive? modlertt( t.o hi ~1 i)1fP-fanchlnri'rmr.

Penetar and Kearney - 5

Our results indicate that under these conditions thevisual system remains essentially intact. Perhaps asignificant loss would be encountered under differentconditions, such as performance of the test outdoors inbright sunlight or in an environment where glare fromadditional sources is present.

The contrast sensitivity function measures overallvisual function. It is useful in assessing drug and otherphysiological and environmental effects. Altered thresholdsmay affect a soldier's ability to perform adequately in thefield when required to detect and identify landmarks orcamouflaged tarcets. If the growing threat of chemicalweapons is to be countered with druas such as atropine, anin-depth analysis of this and other anticholinerqic drugs'effects on vision must proceed in both the laboratory andthe field.

.d.

V.

*1o

I .

pb

Penptar and Kearnev -6

REFERENCES

I. Baker F, Brown B, Adams A, Haeqerstrom-Portnoy G,

Jampolsky A, Jones R. Effects of atropine on visualperformance. Milit Med 1983:148:530-535.

2. Jampolsky A, Haeqerstrom-Portnoy G, Adams A, Jones R.

Effects of atropine and 2-PAM Cl on vision and performance.

Fort Detrick, MD: UJSAMRDC Contract # DAMD17-83-C-3198 1986Ilin- , Report.

' 3. Haeqerstrom-Portnoy G, Jones R, Adams A, Jampolsky A.SEffects of atropine and 2-PAM chloride on vision and

performance in humans. Aviat Space Environ Med 1987;58:47-53.

4. Penetar DM, qtamper DA, Molchany JW. Atropine effects on

TOW missile launcher operation. Presidio of San Francisco,('A: Letterman Army Institute of Research, 1987 in press.

5. Dixon NJ (ed). BMDP statistical software. Los Anqeles,CA: UIniversity of California Press, 1985.

6. Brown B, Haeqerstrom-Portnoy G, Adams A, Jones R,Jampolsky A. Effects of an anticholinerqic druQ,benactyzine hydrochloride, on vision and vision performance.Aviat , Sace Environ Med, 1982;53:759-765.

7. Behar I. Visual contrast sensitivity. In: Aviatorperformance: Effects of CW antidotes (atropine). Ft. Rucker,AL: USA Aeromedical Research Laboratory Report, 1987 inpress•

__4--.

.

-(FF

OFFICIAL DISTRIBUTION I1151

5 ~ ~U rmy Mtdical Research US A! i Mcdica ii Bwnvinrerring

.Atd DeVelopinent Comman131d Research & Dcveioprnien Laborator yATTN: SCRD -RMS,'Mrs. M1vadigan ATTN: S(;RD k B(; -.\Fort Detrick. MD 21"10 1 -5012 For, IDetrik Bide Sos,

Frederick, Ml) 21701-5010D~efense Techinical Iniformration ('enter

ATTN DTCJ)DB ( copes)Co i ma riderN? AIN:DTIC'I))AI (2 olies)US Arni\ Medical Bioengineering

Cameron StationAlexandria. VA 22304-6145 Research & Dexeloprnent Laboratory

ATTN: Library

Office of Unider Secretary of Defense Fort Detrick, Bildg, 568Research and Engineering Frederick, MD 21701-5010

ATTN: R&AT(E&LS), Room 3D129The Pentagon Comm anmderWashington, DC 20301-3080 US Army Research Institute

of Environmental Medicine

The Surgeon General ATTN: SGRD--UE-RSAATTN: DASG-TLO Kansas StreetWashington. DC 20310 Natick. MA 01 760-5007

H Q D A (I)AS(G ZXA) Comndi~er-> WASH D IC 20310-2300 U'S Arniv lint i time of"SUrgical Research

Fort Saml HI Nsiomi TX 78234-0200

CommandantAcademyv of Health Sciences Comm1anderUS Army US Army Research InstituteATTN: IISHA-CDM of Chemical DefenseFort Saml Houston. T X 783-60 ATTN: SGRD-UV-AJ

Aberdeen Proving Ground. MD 21010-5425Uniformied Services Universityof I Healthi Sciences Co mmantder

Office of Grants Mana-enient US Army Aeroniedical Research Laboratory4301 Jones Bridge Road Fort Rucker, AL 36362-5000Bethesda, MD 20814-4799

AIR FORCE Office of Scientific

US Army Research Office Research (NL)A [ TN: Chemnical mrd IBiolmutcaI Building 410. Room .\2I 17

Sciences Division Boilingz Air Force Base. DC 20332-6448

5.~ ~ ~ ~ ~~~~~~( I~-ciII Ii m.Ii I~.kN'_7or _ ~iiiii~LISAI-SAM I S/

lDrrecimr Broroks Air Force Base, TX 7S235-5000.A\TT N: S(; R 1)iW Z -LWalter Reed Artrm Iristitute Head. Biological Sciences Division

if Research OFFICE OF NAVAL RESEARCHWaslimnron. DC 20307.5 100 800 North Quiincy Street

AtlingtonA A 22217-5000

I S Armr Medical Research Iisimiteot lirtect ins1 lDISCacSe

ArT N : SGRI) (T/ - AFort D~etrick. M1D 2 1701 -5011I

I

S.

.4,

444

5%

4~

.4.,

-4-4

,JS

4p

.45,

4~4~

I.

-. J4'-4

-. 45..,

~5'

~ W W U S V ~w V ~ -,

V ~ 4.4 '~.4 .,>~ ~ %'~ .4~ 4,4 %.4