British Journal of Ophthalmology 1995; 79: 585-589

Compliance in amblyopia therapy: objectivemonitoring of occlusion

Alistair R Fielder, Mary Irwin, Rosemary Auld, Kenneth D Cocker, Helen S Jones,Merrick J Moseley

AbstractAimn/Background-This study aimed todetermine the feasibility ofobjective com-pliance monitoring of amblyopia therapyin clinical research. Occlusion has beenthe mainstay of amblyopia therapy forover 250 years, yet it has never been sub-jected to rigorous evaluation. Treatmentregimens range arbitrarily from a fewminutes to most ofthe waking hours oftheday. Compliance is problematic and as,hitherto, accurate objective monitoringhas been impossible it is not known howmuch occlusion is required to effect animprovement in vision.Methods-An occlusion dose monitor(ODM) has been developed. The ODMconsists ofa modified occlusion patch anda miniature battery driven dataloggerwhich periodically monitors patch skincontact. The patch is a standard dispos-able item with two miniature electro-cardiogram electrodes attached to itsundersurface. The datalogger comprises ahigh speed static RAM and a clock drivenaddress counter. Data are retrieved usingan IBM PC/AT computer. Fifteen childamblyopes were randomly allocated uni-lateral occlusion of 1, 4, or 8 hours per dayfor 4 weeks. Owing to data loss, presumedbecause of accumulation and discharge ofstatic electricity, an additional child wasincluded in the 8 hour group. Outcomemeasures were objective (ODM) and sub-jective (diary) compliance with treatment,logMAR visual acuity, and contrast sensi-tivity.Results-Objective monitoring of occlu-sion is technically feasible and clinicallyinformative.Conclusion-Objective monitoring ofocclusion has opened up new researchopportunities which, it is hoped, willenable the dose-effect relation of occlu-sion therapy in the various types ofambly-opia to be investigated objectively, andfacilitate the design of effective therapeu-tic regimens.(BrJ Ophthalmol 1995; 79: 585-589)

Amblyopia is the commonest vision defect ofchildhood, with a prevalence of about 1% to51.l Over the past few decades it has attractedtremendous interest with neuroscientific inves-tigations, exemplified by the work of the Nobelprize winners Hubel and Weisel who demon-strated that the developing visual system isexquisitely sensitive to deprivation. This led to

the concept of a sensitive period for amblyopia,its genesis and treatment, and the recognitionthat this defect must be identified in earlychildhood if treatment is to be successful. Theimpact of this fundamental research on healthservice delivery has been dramatic with theestablishment of vision screening programmes,both preschool in at least 160 of 203 UKhealth authorities,2 and again on school entry.Thus, by 5 or 6 years of age the vast majority ofthe 500 000 or so annual UK school entrantshave been screened for amblyopia two, three,or more times.2With such a massive investment of research

and clinical resources it behoves us to ensurethat amblyopia therapy is effective. Introducedover 250 years ago, occlusion remains eventoday the mainstay of treatment with reportedsuccess rates ranging from 30%3 to 93°/0.4 5Even 'success' needs defining as a recentpopulation based study6 found that only 60%of children achieved acuities of 6/12 or better,and of those with very poor acuity (-6/60)only 13% reached 6/18.

In 1973 Duke-Elder7 pronounced that'occlusion should be total and continuous ...the use of an intermittent form ... is an illusoryand valueless procedure' a sentiment echoed17 years later by von Noorden who recom-mended that occlusion should be worn 'com-pletely and constantly during all wakinghours'.' Contrary to this advice, lesseramounts of occlusion are in everyday use, evenfor as little as a few minutes a day.8 Thesediverse regimens serve only to highlight thatthe amount of occlusion necessary to producean improvement of vision is quite unknownand at a clinical level this has resulted in theproduction of the simple pragmatically derivedocclusion protocols found in paediatric oph-thalmic texts.9 10

For many medical treatment regimenscompliance is a critical issue and reviews of thisliterature quote an overall non-compliance rateof around 50%."1 Amblyopia therapy is notexempt from the problem of poor compliance;indeed, occlusion as a mode of treatment itselfhas been identified as one of the major deter-minants ofpoor outcome.12-14 This is not at allsurprising because occlusion has many featuresfavouring non-compliance such as patientunacceptability (for example, forced to use theworse eye, occlusor on face, cosmetic issues),parental inconvenience, and lengthy treatmentduration. Thus in two crude qualitative com-pliance studies,'2 14 low initial acuity has beenreported to be associated with poorcompliance which reduced the chance of afavourable outcome. To increase the amount

Academic Unit ofOphthalmology,University ofBirmingham MedicalSchool, BirminghamA R FielderM IrwinK D CockerH S JonesM J Moseley

Department ofOrthoptics,Birmingham andMidland Eye Hospital,BirminghamR Auld

Correspondence to:Professor Alistair R Fielder,Academic Unit ofOphthalmology, Birminghamand Midland Eye Hospital,Church Street, BirminghamB3 2NS.Accepted for publication2 February 1995

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Fielder, Irwin, Auld, Cocker, J7ones, Moseley

1...cFilgure I Child wearinlg the occlucsionl dose monzitor.

of time the occlusor is worn by a child a

range of methods is employed includingencouraging, ordering, pleading, threateningor bribery,5 9 and sometimes hospital admis-sion.15 The extreme methods of arm restraintby a plaster cast5 and eyelid suturing'6 mustbe confined to the past. While the above mightall improve compliance as defined by theOxford English Dictionary - 'action in accor-

dance with request or command' they are notembodied in a more user friendly definition -

'patient acceptance of recommended healthbehaviours'. 1As we have not so far been able objectively

to monitor compliance we are a long way frombeing able 'to assess completely the impact ofvarious occlusion regimens oh long-term gainsin visual performance'.'7 In other words wehave no understanding of the dose-effectrelation of occlusion in amblyopia therapy. Todetermine treatment effectiveness, we requireaccurate dosage information: the daily regimen(dose rate) and accumulated dose (dose),which are dependent upon accurate compli-ance data being available. In general, there are

three methods to evaluate compliance: listen-ing to the patient, counting 'pills', and assess-

ing a drug metabolite or other marker. I Whenapplied to amblyopia therapy, the first of theseis clearly not applicable in childhood, and theclosest one can approach the second is thekeeping of an occlusion diary by the parent.'4However, not every 'pill' prescribed enters thebody, and similarly not every occlusion patch isworn for the specified period, and while onecan count patches, that may be no indicationof the time worn. While a diary is an attempt tomonitor occlusion it has a few fundamentalweaknesses: it is not free of bias, its completion

is likely to be influenced by the monitoringprocess,'8 and it requires observation of theentire treatment period which is impossible inalmost every case. In amblyopia therapy theanalogue of measuring a metabolite for drugcompliance is the monitoring of visual func-tions. However, as such outcome measurespresuppose precise knowledge of the doseadministered they are not appropriate. Thusfor a number of reasons, none of thesemethods is suitable to monitor occlusiontherapy accurately and objectively.

Smith refers to the 'poverty of medicalevidence'"9 in describing treatments which areaccepted as clinical dogma but have never beensubjected to rigorous evaluation. Occlusiontherapy for amblyopia falls into this categoryowing to our paucity of knowledge on thedose-effect relation - a situation one finds hardto imagine for any comparably establishedtherapy outside ophthalmology.

In this paper we describe pilot work using arecently developed occlusion dose monitor(ODM) which enables, for the first time,objective monitoring of occlusion therapy.20Our aim was to determine the feasibility ofobjective monitoring of occlusion therapyusing the ODM in clinical research. Visual per-formance data are included solely to demon-strate how clinical outcomes can bemisinterpreted in the absence of knowledge ofcompliance. The dose-effect relation, whichmay be affected by age, amblyopia type, initialacuity, etc, will be the subject of futureresearch.

Patients and methodsThe occlusion dose monitor (ODM) consistsof a modified occlusion patch and a miniaturebattery driven datalogger (Fig 1). The patch isa standard, commercially available, disposableitem, with two miniature electrocardiogramelectrodes attached to its undersurface.Occlusor-skin contact is inferred from reducedresistance across the patch electrodes, sampledevery 64 seconds. Leads, easily concealedunder clothing, connect the patch to thedatalogger (weight 150 g and dimensions1 15X70X30 mm) 'Walkman-style' which iscarried in a shoulder bag. The datalogger com-prises a high speed static RAM and a clockdriven address counter. There are no patientoperated controls. On return to the clinic, theODM is interrogated by an IBM PC/AT com-puter (a process taking less than 10 minutes)and the occlusion time-history stored for sub-sequent analysis.

Parents were given the modified patchesand instructed how to connect the leads to thedatalogger which could be plugged in eitherway ignoring polarity. After each occlusionperiod the patch was peeled off and the leadsdisconnected. A new patch was used for eachocclusion period.The pilot study was directed entirely

towards the evaluation of the ODM within aclinical research setting and was based on thesingle case research design.2' Permission wasobtained from the ethics committee of the

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Compliance in amblyopia therapy: objective monitoring ofocclusion

Table 1 Details ofdata loss by accumulation ofstaticelecticity within the ODM. The child who withdrew fromthe study, and the additional illustrative case 3 are notincluded

Prescribed Treatment Days ProportionSubject (hours duration containing ofdatanumber per day) (days) data loss loss (%/0)

1 1 29 3 102 1 28 0 03* 1 29 0 04** 1 28 2 75 4 32 27 846 4 29 13 457 4 29 7 248 4 43 14 339 4 28 0 010 8 29 7 2411 8 38 3 812 8 30 17 5713 8 31 13 4214 8 32 25 78

*and **indicate illustrative cases 1 and 2 in the text.

West Birmingham Health Authority, andparents gave informed consent before theirchildren entered the study. Subjects wererecruited using the following inclusion criteria:children presenting with untreated amblyopia,an ability to perform a (logMAR) linear visualacuity test22 and the Pelli-Robson contrastsensitivity test, and a willingness to attend forreview on a weekly basis for the trial period.The study consisted of three phases: assess-ment, baseline, and treatment. In the assess-ment phase, children underwent a fullophthalmic (including cycloplegic -refraction)and orthoptic examination. Spectacles wereprescribed if necessary. After a minimum of 14days of adaptive spectacle wear, or immedi-ately if spectacles were not prescribed, subjectsentered the baseline phase in which visualperformance was measured on two occasions,1 week apart. This provided a quantitativeindication of the combined effects of testreliability, practice (perceptual learning), andadaptation to spectacle wear. Treatment beganconcurrently with the end of the baseline phaseand children were randomly prescribedminimal (1 hour per day), part time (4 hoursper day), or full time (8 hours per day) occlu-sion.

Parents were instructed in the use of theODM and were also provided with a diary torecord the start and finish of all periods ofocclusion. Treatment duration was 4 weekswith subjects returning at weekly intervals forvisual performance assessment, and subjective(diary) and objective (ODM) occlusion dataretrieval. Standard clinical care was resumed atthe end of treatment.One additional patient was recruited from a

later study of children with complex ophthalmicproblems ofwhich amblyopia was but one com-ponent (but who otherwise met the inclusioncriteria of the pilot study). For reasons to beexplained later, the ODM had by this time beenmodified and utilised a commercially availabledatalogger (Tinytalk', Orion ComponentsChichester Ltd, UK) with a revised sampleinterval of 3-2 minutes. Outcome measureswere: distance visual acuity, contrast sensitivity,compliance, and patient and parental impres-sions ofODM use. To quantify compliance weformulated three indices:

(1) Monitor cQmpliance ratio (MCR)=occlusion recorded by the ODM/prescribedocclusion.

(2) Diary compliance ratio (DCR) =occlu-sion recorded in the diary/prescribed occlu-sion.

(3) Precision index (PI)=MCR/DCR - thatis, agreement between objective and subjectiverecords.

ResultsFourteen children have so far completed ourprotocol for ODM evaluation. Withoutexception the device has proved acceptable toall children and their parents. There were nocomplaints specific to the use of the ODM asopposed to occlusion itself (t and Table 1).Three children developed skin allergiescaused by the adhesive occlusor, which wererelieved by changing to a non-allergenic mod-ified patch. One child fell off his bike whileundergoing occlusion and dislodged the com-ponents within the ODM. Generally, parentscompleted the occlusion diary satisfactorily,with only a few gaps, although in some entrieshandwriting was difficult to decipher. WhereODM and diary data were available theygenerally correlated well, as shown in theillustrative case studies below. There weresome exceptions, and in these cases, diarydata were often better matched to the pre-scribed regimen than to the ODM data, withinstances of both under and overrecording ofocclusion in the diary. In addition, there werea few occasions when a continuous occlusionperiod in the diary corresponded to a periodof ODM data containing several shortbreaks where intermittent occlusor-skin con-tact may have occurred.

ILLUSTRATIVE CASE STUDIESUnlike more familiar methods, the single caseresearch design is essentially the application ofrigorous quantitative methods (in terms oftreatment and outcome variables) to the tradi-tional case history. Having demonstrated thefeasibility ofODM use, we present three casesto emphasise the benefits that this new tech-nique may bring to clinical practice.

Subject 1 (pilot study)A 4-year-old girl with anisometropic ambly-opia of the right eye was prescribed 1 hour ofocclusion per day. Full clinic attendance wasattained and only on 2 out of 28 days' occlu-sion was there no attempt made to patch thechild's eye. The total prescribed dose was 1680minutes, with objective (ODM) and subjective(diary) recordings of 1605 and 1563 minutes

tWe did, however, initially encounter technical difficulties ofdata loss resulting from previously stored ODM data beingoverwritten. This was presumed to be due to the accumulationand discharge of static electricity within the ODM and espe-cially prone to occur with long periods of occlusion. To over-come this problem ODM construction was modified asdescribed earlier to include a commercially available dataloggerwhich has subsequently achieved a degree of reliability accept-able for routine use.

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Trial duration (weeks)Figure 2 Given the excellent objectively determined compliance we can rule outnon-compliance as an explanation for poor outcome (subject 1). Two upper line graphshow visual acuity and contrast sensitivity as a function of trial duration; (0) ambl3eye; (X) fellow eye. Broken lines indicate visualfunction during baseline phase. Lowgraph shows daily occlusion recorded objectively (ODM, U) and subjectively (diary,Horizontal line indicates the prescribed occlusion dose ....

respectively yielding the following compliindices: MCR=0-96, DCR=0-93,PI= 1 03. Compliance, as a function of tment duration and the corresponding chin visual performance, is shown in Figu:Despite a small unpredicted improveme:acuity in the fellow eye (0 11 log uicompared with the mean baseline,improvement in either acuity (005 log uor contrast sensitivity in the amblyopic(0-08 log units) was not clinically siicant.

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Trial duration (weeks)Figure 3 Compliance is generally only questioned in the case of outcome failure andsuccess in this case would have been incorrectly attributed to strict adherence to theprescribed regimen (subject 2). Hatched area on lower bar graph indicates days loss ojdata. Key as for Figure 1.

Subject 2 (pilot study)-x This 4-year-old boy had anisometropic

amblyopia of his left eye, was prescribed* spectacles and, after adaptation, allocated 1

hour of occlusion per day. The total pre-scribed dose was 1560 minutes, with ODMrecord of 624 minutes and diary record of

o 675 minutes respectively: MCR=040,DCR=0-43, PI=0-93. In this case, compli-ance was poor, but although occlusion wasworn only 40% of the prescribed time, acuityimproved from mean baseline 034 logMARto 0 1 logMAR in the amblyopic eye (Fig 3).~A concomitant improvement in contrast sen-sitivity (0-23 log units) was also recorded.

Subject 3 (modified ODM)This male child, born at 26 weeks' gestation,developed early stage 3 retinopathy of prema-turity in each eye, which resolved, and thenat 3 years presented with a left convergentstrabismus.There was no posterior pole retinal abnor-

ks mality (major vessel angle 1100 right and leftvoPic eyes). Refraction revealed +0 75 DS in the2b right and emmetropia in the left eye. He was

prescribed 8 hours of occlusion per day,13440 minutes in total, and achieved ODMand diary recordings of 8976 and 9429

iance minutes. Compliance indices: MCR=0-67,and DCR=0-70, and PI=0-95 (Fig 4). Acuity

treat- in the amblyopic eye improved by about 6ange lines during the baseline phase (0-9 to 0-34re 2. log units) and three additional letters withnt in occlusion; note also the improvement in con-nits), trast sensitivity (0 43 log units from meanthe baseline). This subject demonstrates that even

inits) lengthy periods of occlusion can be monitoredeye objectively.

gnifi-DiscussionOcclusion therapy can now be monitoredusing an occlusion dose monitor (ODM). Atthis early stage we are not concerned with theeffectiveness ofmonitored occlusion on ambly-opia, but simply with validating objective com-pliance monitoring in the 'field' - that is, itsfeasibility for future clinical research. We areaware of potential pitfalls, such as failure toconnect the leads to the ODM, or placing theocclusor on an arm, for instance, rather thanover the eye. While the latter remains a pos-sibility, for a child to repeatedly wear a falselylocated occlusor for up to 8 hours per day for4 weeks requires a vivid imagination and adevious tenacity of unlikely proportions.Notwithstanding these concerns, we haveshown that the amount of occlusion that achild receives between visits can now be moni-tored objectively using an ODM, even for long

1occlusion periods (subject 3). It has proved5 acceptable to patients and their parents, and

-! no patient related issues have been encoun-tered which might pose major problems for itsfuture clinical use, at this age and in youngerchildren.

f In our study we would expect the parentaldiary to correlate well with ODM data as

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Figure 4 Example of compliance monitoring of an 8 hours per day regimen (subject 3).Key as for Figure 1.

parents were aware that occlusion was beinginvestigated. Legibility sometimes introducedinterpretative difficulties. The primary pur-

pose of the diary was as an equipment checkand to highlight possible misunderstandingsresulting from ODM use, rather than as a

compliance monitor. One might concludethat since records were almost as accurate as

the ODM, the latter was superfluous, butobviously diary accuracy could be influencedby ODM usage.18 Furthermore, the ODMprovides us with accurate information on theintegrity of occlusor-skin contact duringocclusion periods, revealing episodes of'peeping' - something we could not expect togain from a diary. We also recognise that theparents involved in this research might not befully representative of routine clinical prac-

tice, being keen to participate.Even these preliminary studies have pro-

vided clinical insight into occlusion therapyhitherto unavailable. For subject 1, compliancewould certainly have been doubted, but giventhe excellent objectively determined results wecan rule out non-compliance as an explanationfor poor outcome. Compliance is generally

only questioned in outcome failure, and suc-

cess in subject 2 might therefore have beenincorrectly attributed to strict adherence to theprescribed regimen. This raises the issue thatperhaps some patching regimens prescribedare excessive.

Compliance can now be evaluated accuratelythus permitting precise titration of occlusion

against visual function. This is not before time,as around 48% and 28% of amblyopic childrenare prescribed respectively 200-499 hours andmore than 500 hours of this unpleasant treat-ment.7 Objective monitoring has opened upnew research avenues and hopefully this willenable the dose-effect relation of occlusiontherapy in the various types of amblyopia to beinvestigated objectively, and with a precisionnot previously possible. The design of effectivetherapeutic regimens should follow which willensure that children receive enough occlusion,but no more.We thank the mother of illustrative case 3 for permission to pre-sent Figure 1. We acknowledge Roger Bunce, Wolfson AppliedTechnology Laboratories, University of Birmingham, for helpwith development of the ODM and Graham Hollins,Birmingham Maternity Hospital for help with ODM modifica-tions.

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7 Duke-Elder S, Wybar K. Abnormal ocular motility.In: Duke-Elder S, Wybar K, eds. Ocular motility andstrabismus. System of ophthalmology. Vol VI. London:Kimpton, 1973: 425.

8 Watson PG, Sanac AS, Pickering MS. A comparison ofvarious methods of treatment of amblyopia: a block study.Trans Ophthalmol Soc UK 1985; 104: 319-28.

9 Eggers HM. Amblyopia. In: Diamond GH, Eggers HM,eds. Strabismus and pediatric ophthalmology. In: Podos SM,ed. Textbook of Ophthalmology. St Louis: Mosby, 1993:13.2-13.14.

10 Day S. Normal and abnormal visual development. In:Taylor D, ed. Pediatric ophthalmology. Oxford: BlackwellScientific Publications, 1990: 7-20.

11 Wright EC. Non-compliance - or how many aunts hasMatilda? Lancet 1993; 342: 909-13.

12 Oliver M, Neumann R, Chaimovitch Y, Gotesman N.Shimshoni M. Compliance and results of treatment foramblyopia in children more than 8 years old. Am JOphthalmol 1986; 102: 340-5.

13 Lithander J, Sjostrand J. Anisometropic and strabismicamblyopia in the age group 2 years and above: a prospec-tive study of the results of treatment. Br J Ophthalmol1991; 75: 111-6.

14 Nucci P, Alfarano R, Piantanida A, Brancato R.Compliance in antiamblyopia occlusion therapy.Acta Ophthalmol 1992; 70: 128-31.

15 Fells P. Amblyopia - an historical perspective. Eye 1990; 4:775-86.

16 Weckert H. Neue Wege zur Bekampfung derSchiefamblyopie. Zentralblatt fiar die gesamte Ophthal-mologie und ihre grenzgebiete 1932; 27: 239.

17 Fulton AB, Mayer DL. Esotropic children with amblyopia:effects of patching on acuity. Graefes Arch Clin ExpOphthalmol 1988; 226: 309-12.

18 Claydon BE, Efron N. Non-compliance in general healthcare. Ophthalm Physiol Optom 1944; 14: 257-64.

19 Smith R. Where is the wisdom...? BMJ 1991; 303: 798-9.20 Fielder AR, Auld R, Irwin M, Cocker KD, Jones HS,

Moseley MJ. Compliance monitoring in amblyopiatherapy. Lancet 1994; 343: 547.

21 Aldridge D. Single-case research designs for the clinician.J Roy Soc Med 1991; 84: 249-5 1.

22 Moseley MJ, Jones HS. Visual acuity: calculating appro-priate averages. Acta Ophthalmol 1993; 71: 296-300.

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