Functional Visual Loss in Amblyopia and the Effect of Occlusion Therapy · 2008. 9. 8. · the...

Functional Visual Loss in Amblyopia and the Effect ofOcclusion Therapy

Anita J. Simmers,1 Lyle S. Gray,2 Paul V. McGraw,3 and Barry Winn3

PURPOSE. The aim of this study was to define the nature of functional visual loss in amblyopia andto identify those subjects whose amblyopia is chiefly due to one or more of the following deficits:abnormal contour interaction, abnormal eye movements, abnormal contrast perception, or posi-tional uncertainty.

METHODS. Fifty amblyopic children with a mean age of 5.6 6 1.3 years were referred from diversesources. In addition to routine orthoptic and optometric evaluation the principal visual deficits inthe amblyopic eye of each subject were identified using the following measures of visual acuity:high contrast linear, single optotype, repeat letter and low contrast linear, plus Vernier anddisplacement thresholds. These measures were repeated as the children underwent a prescribedocclusion therapy regime, after parental consent.

RESULTS. All amblyopic subjects demonstrated a functional loss in each of the tests used, andocclusion therapy appeared to improve all aspects of the amblyopia. High contrast visual acuity wasnot always the primary deficit in visual function, and when amblyopic subjects were dividedaccording to their primary visual loss, this visual function was found to show the greatestimprovement with treatment.

CONCLUSIONS. These results suggest that to successfully identify the primary visual deficit andmonitor the success of occlusion therapy it is necessary to assess other aspects of visual functionin amblyopia. (Invest Ophthalmol Vis Sci. 1999;40:2859–2871)

Previous investigations into amblyopia treatment oftencontain methodological difficulties, such as small sub-ject numbers or inadequate measurement of sensory

function and motor function,1–5 which prevents accurate con-clusions being drawn. Although there have been extensivepsychophysical and electrophysical investigations (see Ciuf-freda et al. 1991)6 into both human and animal models ofamblyopia, there is still no conclusive evidence as to why someamblyopic subjects respond to treatment and others do not.1–5

The associated conditions thought to be responsible forthe amblyopia (anisometropia, strabismus, refractive error, ordeprivation) are normally used to classify the condition. Theuse of the apparent causal agent in classifying amblyopia isconvenient and leads to immediate corrective action but maynot be of value in assessing the multifaceted loss in visualfunction. The current underlying hypothesis in the treatmentof amblyopia is that therapy treats the whole condition, assum-ing all aspects of visual function are equally reduced, and that

the success of amblyopia therapy is most often defined in termsof improvement in high contrast visual acuity, which onlymeasures one aspect of visual function.7,8 Active therapies foramblyopia treatment, have been used over the years by clini-cians and are designed to stimulate a specific visual function,either accommodation, eye movements and fixation pattern, orform recognition in an attempt to eliminate what is thought tobe the underlying cause of reduced vision.9 A full review ofthese training procedures is not in the scope of this article; formore detailed treatment of this area other sources should beconsulted.6,10

If the success of amblyopia therapy is to be evaluated it isessential to quantify and monitor the loss in visual functionwith a range of sensory tests and not by the use of high contrastvisual acuity alone. The purpose of this study was to try anddefine the nature of functional visual loss in amblyopia and toidentify those children whose amblyopia is chiefly due to oneor more of the following deficits: abnormal contour interac-tion,11–13 which can be assessed using the difference betweenlinear and single optotype acuity14–16; abnormal contrast per-ception,12,17 which can be assessed using the difference be-tween a high and low contrast linear acuity measure14–16;abnormal eye movements,18,19 which can be assessed usingthe difference between a high contrast and repeat letter formatacuity measure14–16; and positional uncertainty,20,21 which isassessed by hyperacuity measurements.

Amblyopic subjects can be assigned to these groups usinga battery of simple clinical and psychophysical tests of visualfunction,14–16 the following tests were included in the study:LogMAR Crowded Acuity Test (CAT), Single Letter AcuityCards (SLA), Low Contrast Glasgow Acuity Cards (LC), Regan

From the 1Visual Perception Unit, Department of Psychology,University of Essex, Wivenhoe Park, Colchester, CO4 3SQ; the 2De-partment of Vision Sciences, Glasgow Caledonian University, Cowcad-dens Road, Glasgow, G4 0BA; and the 3Department of Optometry,University of Bradford, Richmond Road, Bradford, West Yorkshire,BD7 1DP.

Supported by a Vision Research Training Fellowship from theWellcome Trust (PVM).

Submitted for publication January 22, 1999; revised June 17, 1999;accepted July 12, 1999.

Commercial relationships policy: N.Corresponding author: Anita J. Simmers, Visual Perception Unit,

Department of Psychology, University of Essex, Wivenhoe Park,Colchester, UK.E-mail: [email protected]

Investigative Ophthalmology & Visual Science, November 1999, Vol. 40, No. 12Copyright © Association for Research in Vision and Ophthalmology 2859

TABLE 1. Clinical Details of All Subjects

Subject Age, ySpectacle

PrescriptionOcular

AlignmentPrevious

Occlusion

JL 9.2 RE plano/13.50 3 90 R SOT ✘LE plano/13.00 3 80 10D

SW 9.1 RE 13.50 DS Straight ✘LE 10.75/10.50 3 90

SA 10 Nil R SOT ✘12D

ST 6.4 Nil L SOT ✘12D

GA 8 RE 12.50/11.50 3 175 Straight ✔LE plano

ND 8 RE plano Straight ✘LE 22.00/15.00 3 65

JC 8 RE 12.00/11.00 3 30 Straight ✘LE 13.00/11.00 3 145

GS 5.3 Nil R SOT ✘10D

AK 6.7 RE 12.00 DS Straight ✔LE 13.00 DS

NB 4.6 Nil R SOT ✘14D

FD 6.0 RE 10.50 DS L SOT ✘LE 13.00 DS 10D

AH 6.0 RE 12.00/22.00 3 180 R SOT ✘LE 10.50 DS 16D

WD 6.1 Nil R SOT ✘12D

SWt 6.0 Nil L SOT ✘16D

ST 5.8 Nil L XOT ✔12D

KA 6.0 RE 12.00/11.00 3 30 L SOT ✘LE 14.00/11.00 3 145 12D

DC 5.8 Nil R SOT ✘18D

LK 5.3 RE 12.00 DS Straight ✘LE 14.00 DS

LC 6.8 RE 12.00 DS L SOT ✔LE 15.00/11.00 3 145 20D

MC 5.2 RE 12.00/11.00 3 30 Straight ✘LE 10.50 DS

LC 5.2 RE 14.00 DS Straight ✘LE 13.00 DS

CW 6.2 RE 12.50/10.50 3 90 Straight ✔LE 11.25/10.50 3 90

PD 6.0 RE 14.00 DS Straight ✔LE 13.00 DS

TA 4.7 RE 12.25 DS Straight ✘LE 10.50 DS

DM 4.2 RE 11.50/11.00 3 180 Straight ✘LE 13.00 DS

HG 4.2 RE 10.50 DS LE SOT ✘LE 14.00 DS 20D

BN 4.6 RE 17.50/20.50 3 10 LE SOT ✘LE 19.00/20.50 3 170 12D

HM 6.0 RE 12.75/11.00 3 40 Straight ✘LE 14.00/10.50 3 135

AJ 5.9 RE 15.75/10.50 3 80 Straight ✘LE 14.25 DS

CS 5.9 RE 12.00/11.00 3 30 LE SOT ✘LE 13.00/11.00 3 145 20D

LMc 6.5 Nil LE SOT ✘25D

(continues)

2860 Simmers et al. IOVS, November 1999, Vol. 40, No. 12

Repeat Letter Acuity Cards (RRL), and Alignment and Displace-ment Thresholds (AT, OMDT).

These tests will divide the amblyopic subjects into thefour functionally based categories outlined above and quantifythe different aspects of functional visual loss in the majoramblyopic groupings.

The aims of these investigations were as follows: to deter-mine the functional characteristics of amblyopia, to ascertainthe pattern of recovery of each characteristic during therapy,and to relate each characteristic and its recovery pattern to theclassic diagnostic categories.

METHODS

Subjects

Referral of children suitable to participate in the study wasinvited from various sources (school screening, General Prac-

titioners, optometrists, and health visitors) in and around thegreater Glasgow area. All experimental procedures conformedto the recommendations of the Declaration of Helsinki. Thestudy was conducted jointly in the Eye Clinic at GlasgowCaledonian University and the pediatric clinic at Glasgow EyeInfirmary. Subsequently, 50 amblyopic children were referredfrom diverse sources to provide a prescreened subject base.Amblyopia for the purpose of this study was defined as acorrected acuity of 6/9 or poorer in the amblyopic eye. Themean age of the sample was 5.6 6 1.3 years. Many of thesesubjects had not received treatment previously and providedan opportunity to investigate the condition before and duringtherapy.

Clinical diagnosis revealed an amblyopic population thatconsisted of 16 strabismic children, 20 anisometropic children,and 14 children with a combination of both anisometropic andstrabismic amblyopia. Anisometropia was defined as an intero-cular difference of greater than 1.00 diopter sphere or 1.0

TABLE 1 (continued). Clinical Details of All Subjects

Subject Age, ySpectacle

PrescriptionOcular

AlignmentPrevious

Occlusion

WL 5.2 RE 10.25 DS Straight ✘LE 10.75/10.75 3 90

BA 4.2 Nil RE SOT ✘30D

CM 4.1 RE 12.00 DS Straight ✘LE 10.25/11.00 3 90

GL 5.0 RE 10.25/10.75 3 90 RE SOT ✘LE 20.75/10.75 3 80 10D

MJ 4.0 RE 12.00 DS LE SOT ✘LE 13.00 DS 12D

NN 4.0 RE 11.75/10.75 3 180 RE SOT ✘LE 10.50/10.25 3 180 8D

SD 4.9 RE 12.00/11.00 3 30 LE XOT ✘LE 12.50/13.00 3 145 8D

JMc 4.5 Nil LE SOT ✘25D

TC 5.5 Nil LE SOT ✔10D

WG 6.0 RE plano Straight ✔LE 22.00/15.00 3 65

WR 4.4 RE 12.25/11.50 3 175 Straight ✘LE plano

CJ 4.3 RE 11.25/10.75 3 115 RE SOT ✘LE 10.75 DS 10D

TS 5.2 Nil LE SOT ✘10D

PI 6.2 RE 13.5 DS Straight ✔LE 10.75/10.50 3 90

BS 4.3 Nil RE SOT ✘18D

FJ 4.0 RE 11.00/11.00 3 30 LE SOT ✘LE 13.00/12.00 3 145 20D

LD 4.1 RE 15.00/11.00 3 30 Straight ✘LE 16.00/11.00 3 145

GR 4.2 Nil RE SOT ✘25D

MK 4.2 RE 12.50/20.75 3 25 RE SOT ✘LE plano 12D

RE, right eye; LE, left eye; DS, diopters sphere; D, prism dioptres; ✘, no previous occlusion; ✔,previous occlusion; SOT, esotropia; XOT, exotropia.

IOVS, November 1999, Vol. 40, No. 12 Visual Deficits in Amblyopia 2861

diopters of cylinder. Clinical details of all subjects can be foundin Table 1.

Procedure

In addition to routine orthoptic and optometric evaluation, thetests outlined above were performed to identify the principalvisual deficit/s in the amblyopic eye of each subject. For a fulldescription of these tests, see Simmers and Gray 1999.16

All letter charts were based on a six-alternative forcedchoice procedure. The logarithmic scale used in all chartsprovides a constant change in resolution between each acuitylevel of 0.1 log units. In addition the use of a logarithmic scaleallows the facility to extend the scale in either direction, byincreasing or reducing the distance. A modified logMAR scor-ing system22 was used, with four letters presented at eachacuity level. The system designates 6/6 a score of 1 and 6/60 ascore of 0 with visual acuities of less than 6/60 carrying anegative sign (1 2 logMAR). Because the angular size of theletters changed by a factor of 0.1 log unit, and because all theletters were equally legible, each letter was scored individually(0.025 log units). The end point was defined when no letterscould be identified at a particular acuity level, with the subjectbeing encouraged to guess until this point was reached. Thisequated the scoring systems between all acuity cards.

The order of presentation of the test charts and hypera-cuity measures was assigned randomly, and all acuity testswere externally illuminated to 300 lux. The same test roomwas used for each visit. Younger children performed the acuitytests as letter matching tests using an appropriate key card, inolder children verbal responses were pursued. Test sessionduration was approximately 40 minutes.

From the results of these investigations and after a fullrefraction, each subject was prescribed occlusion therapybased on the management plan outlined below.

Type of Amblyopia Present. Ametropic and meridionalamblyopias are usually bilateral, therefore early and accuratecorrection of refractive error is very important. Alternate oc-clusion was prescribed if residual amblyopia was present.

Strabismic or anisometropic amblyopia, correction of anyrefractive error, and then occlusion prescribed according todegree of amblyopia and state of binocular single vision (BSV).

Degree of Amblyopia. High contrast linear acuity 6/18or worse was defined as full-time (6 hours per day), highcontrast linear acuity 6/12 or better as part-time (3–4 hours perday).

Presence of BSV. If BSV was constant or intermittentthen occlusion was always part-time. If microtropia waspresent then part-time occlusion was also deemed necessary.

Baseline data collection were taken with the subjectswearing their full correction but before any occlusion therapywas prescribed. Each subject then received a full orthoptic

FIGURE 1. Comparison of mean alignment threshold (A) and meanoscillatory displacement threshold (B) plotted against mean high con-trast visual acuity (CAT) pretherapy.

TABLE 2. Mean Pretherapy Visual Acuity Thresholds

Acuity Card

AnisometropicAmblyopes

(n 5 20)

StrabismicAmblyopes

(n 5 16)

Anisometropic,and Strabismic

Amblyopes(n 5 14)

All Amblyopes(n 5 50)

CAT 0.485 6 0.2 0.511 6 0.2 0.487 6 0.2 0.499 6 0.2SLA 0.708 6 0.3 0.679 6 0.3 0.692 6 0.1 0.663 6 0.2LC 0.428 6 0.2 0.386 6 0.2 0.350 6 0.2 0.322 6 0.2RRL 0.603 6 0.3 0.557 6 0.2 0.575 6 0.3 0.567 6 0.3

Values are mean 6 SD, modified logMAR.


examination, including all five acuity tests, once a month dur-ing the course of treatment prescribed.

Measurement of compliance with the occlusion regimeprescribed was undertaken using a diary system, in which theparents logged the number of hours’ occlusion achieved eachday and the visual tasks undertaken.

RESULTS

For ease of interpretation the results of this study have beendivided into pre- and posttherapy.

Pretherapy

The mean values for initial visual acuity scores with the differ-ent acuity cards are summarized below in Table 2. A two-factor

ANOVA was carried out for the factors of the amblyopic sub-ject group (anisometrope versus strabismic versus ani-sometrope 1 strabismic) and acuity card (CAT versus SLAversus LC versus RRL). The mean visual acuities obtained usingthe various acuity cards were found to be significantly different(P 5 0.003). No significant difference was found in the visualacuity scores between the amblyopic subject groups (P 50.99), and no significant interaction was revealed betweensubject group and acuity card (P 5 0.1).

Ten children failed to complete either hyperacuity mea-sure due to a lack of comprehension or a short attentionspan. No significant difference was obtained between thevertical and horizontal alignment thresholds (P 5 0.82),therefore the mean of these two measurements was taken asthe threshold value. The remaining children obtained an

FIGURE 2. Comparison of improve-ments in visual function for all ambly-opic subjects during occlusion ther-apy. The absolute change in score(log units 6 SD) is relative to theinitial pretherapy value and was cal-culated for each visit. The number ofsubjects may vary between visits.

TABLE 3. Identification of the Amblyopes with Primary Functional Visual Deficit asDetermined by the Tests Outlined

Primary VisualDeficit Determined by

Number of AmblyopicSubjects

Group A CAT 12Reduced High

Contrast VisualAcuity (4 A, 5 S, 3 S 1 A)

Group B LC 10Reduced Low Contrast

Visual Acuity (4 A, 2 S, 4 S 1 A)Group C OMDT 13Reduced Hyperacuity

Thresholds AT (6 A, 4 S, 3 S 1 A)Group D RRL . CAT 8Increased Fixation

Instability (3 A, 3 S, 2 S 1 A)Group E SLA–CAT 7Increased Contour

Interaction (3 A, 2 S, 2 S 1 A)

A, anisometropia; S, strabismus; and A 1 S, anisometropia and strabismus.


alignment threshold (AT) of 234.37 6 83.92 seconds of arcand a mean oscillatory motion displacement threshold(OMDT) of 100.62 6 26.44 seconds of arc. Statistical anal-ysis revealed a significant difference between AT and OMDTmeasures (P 5 0.0001).

Regression analysis revealed a significant correlation be-tween high contrast visual (CAT) acuity and both hyperacuitymeasurements (AT: Fig. 1; r2 5 0.368; P 5 , 0.01; and OMDT:Fig. 2; r2 5 0.296; P , 0.05). Measurements of AT (P 5 0.0013)and OMDT (P 5 0.003) thresholds in amblyopic subjects withstrabismus (strabismic only and strabismus associated withanisometropia) yielded significantly higher values than thosewithout (i.e., anisometropic amblyopes).

As previously stated, classification of amblyopia with re-gard to the associated amblyogenic factor revealed 20 ani-sometropes, 16 strabismic amblyopes, and 14 anisometropic 1strabismic amblyopes. These children may alternatively be clas-sified with regard to any functional visual loss as determined bythe clinical and psychophysical tests outlined above. The pri-mary functional visual deficit was established by dividing thepretherapy score with the normal mean value for the test. Theprimary functional deficit was then identified as the test withthe lowest score. Using this criteria the amblyopic subjectscould be subdivided into the following groups illustrated inTable 3 (each individual amblyopic subject was assigned to onegroup).

The mean visual acuity and hyperacuity scores when iden-tifying the amblyopic subjects with respect to the primaryvisual deficit are summarized in Table 4. This provides extrainformation with regard to the specific visual deficits present.For instance, group B demonstrated the greatest differencebetween CAT and LC, therefore indicating a low contrastacuity visual deficit (the difference between CAT and LC isindicative of the difference between points being sampled onthe contrast sensitivity function). The mean difference inscores of 0.394 log units (nearly 4 lines better with CAT), amean difference outside previously set 95% confidence limits(60.175 log units) for normality.14,15

Group D demonstrated the greatest difference betweenCAT and RRL, therefore indicating increased fixation instability(revealed by a higher score with RRL in comparison with CAT).The mean difference in scores was 0.212 log units (more than2 lines better with RRL), a mean difference outside previouslyset 95% confidence limits (60.175 log units) for normality.14,15

Group E demonstrated the most significant difference be-tween CAT and SLA indicative of increased levels of contourinteraction (revealed by a higher score with SLA than withCAT). The mean difference in scores was 0.3 log units (3 linesbetter with SLA), a mean difference outside previously set 95%confidence limits (60.150 log units) for normality. The magni-tude of this crowding effect can also be measured by means ofthe crowding ratio.13,14 Group E had a mean ratio of 2.3, againthis value is outside previously set 95% confidence limits fornormality.14,15

Posttherapy

So that the relative improvements in visual acuity thresholdsand hyperacuities could be compared, the absolute change inscore (in log units) relative to the initial pretherapy value wascalculated for each visit.

Due to cancellations and non-attendance, not every childwas seen at identical intervals, therefore visits were catego-rized with visit 1 representing baseline measurements; visit 2,4 to 8 weeks after initial visit; visit 3, 10 to 12 weeks; and so on.

The mean posttherapy visual acuity and hyperacuityscores for the amblyopic subjects with respect to the primaryvisual deficit are summarized in Table 4.

When the amblyopic subjects are grouped according toprimary visual loss, it is this visual function that shows thegreatest improvement in response to treatment. It is interestingthen to compare the mean changes posttherapy in thosegroups with a specific visual deficit. For instance, group Ddemonstrated increased fixation instability. The mean differ-ence in scores posttherapy reduced to 0.060 log units (2 or 3letters better with RRL) due to an increase in high contrastlinear acuity (CAT), a mean difference now within the previ-

TABLE 4. Mean Visual Function Thresholds Pretherapy and Posttherapy (Final Visit) 1 Standard Deviation(Modified LogMAR) and Hyperacuity Thresholds 1 Standard Deviation (Seconds of Arc), for All AmblyopicSubjects Grouped with Respect to the Primary Visual Deficit (see Table 3)

Test of VisualFunction

Primary Visual Deficit

A (n 5 12) B (n 5 10) C(n 5 13) D(n 5 8) E(n 5 7)

CAT 0.522 6 0.193 0.490 6 0.096 0.648 6 0.138 0.447 6 0.119 0.232 6 0.0790.89 6 0.07 0.782 6 0.169 0.783 6 0.137 0.835 6 0.113 0.731 6 0.116 0.675 6 0.102SLA 0.710 6 0.201 0.518 6 0.093 0.777 6 0.162 0.703 6 0.099 0.532 6 0.1681.02 6 0.08 0.873 6 0.137 0.830 6 0.122 0.873 6 0.125 0.891 6 1.120 0.811 6 0.117LC 0.408 6 0.175 0.096 6 0.158 0.369 6 0.139 0.412 6 0.171 0.153 6 0.1230.62 6 0.09 0.562 6 0.134 0.397 6 0.098 0.625 6 0.091 0.575 6 0.127 0.479 6 0.094RRL 0.619 6 0.216 0.400 6 0.234 0.719 6 0.150 0.659 6 0.180 0.329 6 0.0740.96 6 0.07 0.829 6 0.173 0.792 6 0.147 0.814 6 0.117 0.791 6 0.125 0.714 6 0.117OMDT 100.63 6 21.60 102.12 6 44.01 124.14 6 25.33 97.32 6 21.19 86.29 6 22.1959.69 6 8.59 64.72 6 21.31 72.01 6 48.42 67.59 6 25.33 61.78 6 18.15 74.25 6 25.59AT 211.85 6 78.44 241.26 6 70.84 268.92 6 95.73 226.68 6 45.08 236.09 6 94.7769.18 6 19.38 137.08 6 73.15 176.09 6 68.48 183.55 6 46.73 116.12 6 51.75 180.14 6 95.61

Values in italics represent the mean visual thresholds in a group of visually normal children of comparable age,14,15 that is, the primary visualdeficit is established by dividing the pretherapy score with the normal mean value for that test (i.e., in group A the greatest deficit is identified byCAT0.522/0.89).


FIGURE 3. Comparison of improve-ments in visual function for anisome-tropic amblyopes (A); strabismic am-blyopes (B), and anisometropic andstrabismic amblyopes (C) during oc-clusion therapy. The absolute changein score (log units 6 SD) is relative tothe initial pretherapy value and wascalculated for each visit. The numberof subjects may vary between visits.


ously set 95% confidence limits (60.175 log units) for normal-ity.14,15

Group E demonstrated increased levels of contour inter-action. The mean difference in scores posttherapy reduced to0.136 log units (1.5 lines better with SLA), a mean differencenow within the previously set 95% confidence limits (60.150log units) for normality.14 The mean crowding ratio also re-duced to 1.2, a value now within previously set 95% confi-dence limits for normality.14,15

Group B demonstrated significantly reduced low contrastacuity pretherapy; although this visual function improved, thechanges were concurrent with high contrast acuity. Therefore,the mean difference in scores posttherapy remained un-

changed (0.385 log units), a value still outside previously set95% confidence limits (60.175 log units) for normality.14,15

Figure 2 shows the cumulative improvement for allsubjects (absolute change in log units) during the course oftherapy. Occlusion therapy appeared to improve all aspectsof visual function, with these results demonstrating concur-rent changes in both the acuity card measurements andhyperacuities. High and low contrast linear acuity appearedto have the greatest overall relative improvement in perfor-mance. The greatest improvement in visual function ap-peared to occur with the first 4 to 6 visits, although in thecumulative data high contrast acuity appeared to suddenlysurge after visit 6.

FIGURE 4. Comparison of improvements in visual function inrelation to the primary functional visual deficit in the amblyopicsubjects Reduced High Contrast Visual Acuity (A); Reduced LowContrast Visual Acuity (B); Reduced Hyperacuity Thresholds (C);Increased Fixation Instability and Reduced Hyperacuity Thresh-olds (D); and Increased Contour Interaction (E) during occlusiontherapy. The absolute change in score (log units 6 SD) is relativeto the initial pretherapy value and was calculated for each visit.The number of subjects may vary between visits.


Figure 3 illustrates the relative improvement in perfor-mance in all measurements during the course of occlusiontherapy individually in anisometropic (Fig. 3A), strabismic (Fig.3B), and anisometropic 1 strabismic amblyopes (Fig. 3C).Again all measurements show improvement.

In the anisometropic subject group, high and low contrastlinear acuity showed a significant improvement (0.300–0.350log units). In this subject group both high and low contrastacuity showed improvements as late as visits 7 and 9. Hypera-cuity thresholds demonstrated the smallest degree of improve-ment.

In the strabismic subject group all visual functions show asteady and significant improvement, with low contrast linearacuity showing the greatest degree of improvement (just under0.300 log units). Again, the majority of visual function improve-ment levels off after visit 4 to 6. Compared with the ani-sometropes, AT and OMDT improved to a greater extent instrabismic amblyopes.

In the anisometropic 1 strabismic subject group all visualfunctions showed a steady and significant improvement, with

high contrast linear acuity showing the greatest degree ofimprovement (around 0.250 log units). The majority of visualfunction improvement levels off after visit 4 to 6. Again, inter-estingly, compared with the pure anisometropes, AT andOMDT improved to a greater extent in this group.

Figure 4 indicates the rate of improvement with occlusiontherapy in relation to the primary functional visual deficit inthe amblyopic subjects, as described in Table 4. In all cases theprimary visual deficit demonstrated the most prominent rate ofimprovement in performance.

Figure 4A shows that the primary visual deficit in thisgroup was revealed by a significantly reduced CAT score; withocclusion therapy it was this deficit (high contrast linear acu-ity) that showed the greatest degree of improvement (nearly0.300 log units).

The primary visual deficit in the group illustrated in Figure4B was revealed by a significantly reduced LC score; withocclusion therapy it was this deficit (low contrast linear acuity)that showed the greatest degree of improvement (0.300 logunits). However because of the concurrent changes in high

FIGURE 5. Regression analysis illus-trating the relationship between theinitial pretherapy value and the abso-lute change in visual function withacuity card measures (A; in log units)and hyperacuity measures (B; in sec-onds of arc).


contrast acuity, to a similar extent this group maintained a lowcontrast deficit (mean difference 0.387 log units), a value stilloutside previously set 95% confidence limits (60.175 log units)for normality.14

The primary visual deficit shown in Figure 4C was re-vealed by significantly reduced hyperacuity thresholds; andwith occlusion therapy, it was this deficit that showed thegreatest degree of improvement (0.150–0.300 log units). RRLand SLA failed to demonstrate a substantial improvement(,0.100 log units). Again, the majority of visual function im-provement levels off after visit 4 to 6, with the exception of thehyperacuity measures in a single amblyopic subject (whichcontinue to show improvement up to visit 9).

The group shown in Figure 4D demonstrated an increasedfixation instability (revealed by a higher score with RRL than inCAT). The mean difference in scores reduced from 0.212 logunits pretherapy to 0.060 log units posttherapy, with a signif-icant increase in CAT score demonstrated (0.275 log units).

Interestingly, this group of amblyopic subjects also demon-strated a deficit with hyperacuity measures which also im-proved significantly posttherapy. Again, it was the primaryvisual deficit in this group which showed the greatest degree ofimprovement.

Group E shown in Figure 4E demonstrated increased lev-els of contour interaction (revealed by a higher score with SLAthan with CAT). The mean difference in scores reduced from0.300 log units pretherapy to 0.136 log units posttherapy, witha significant increase in CAT score demonstrated (0.443 logunits). The mean crowding ratio also reduced from 2.3 to 1.2.However, CAT and SLA visual thresholds are still below previ-ously set 95% confidence limits for normality.14 Visual functionimprovement is very slow for most visual functions; however,in this subject group high contrast acuity surges ahead at aboutvisit 7 to 9, which is very similar to the plot for anisometropicamblyopes in Figure 3 (anisometropia was present in 72% ofthe amblyopic subjects in group E).

FIGURE 6. Regression analysis illus-trating the relationship between theabsolute change in visual functionand the age of the amblyopic patientwith acuity card measures (A; in logunits) and hyperacuity measures (B;in seconds of arc).


Linear regression analysis revealed a significant correlationbetween the initial pretherapy score and the absolute changein visual function with acuity card measures, the lower theinitial value the greater the improvement (Fig. 5A; P , 0.01);however, no correlation was evident with either hyperacuitymeasure (Fig. 5B; P . 0.05).

Linear regression analysis revealed no significant correla-tion between the absolute change in visual function during thecourse of occlusion therapy and the age of the amblyopicsubject at the beginning of treatment with either acuity cardmeasures (Fig. 6A; P . 0.05) or hyperacuity measures (Fig. 6B;P . 0.05).

Demonstrable binocular vision was evident in 34 children,with 28 of these children achieving stereopsis. The meanstereoacuity values were 654.6 6 853.4 seconds of arc with theTNO stereotest and 338.7 6 351.02 seconds of arc with theFrisby stereotest; these values improved to 501.8 6 740.4seconds of arc (TNO) and 195.5 6 158.8 seconds of arc

(Frisby) during occlusion therapy. A significant difference be-tween thresholds obtained using TNO and Frisby was evidentpretherapy (P 5 0.001) and posttherapy (P 5 0.03); the highervalues with the TNO test may be due to its more dissociativedesign. No amblyopic subjects regained binocularity throughthe course of occlusion therapy.

Treatment diaries were completed and returned in 35cases. Part-time occlusion hours appeared easily administrated,although those children who required full-time occlusion oftendivided the prescribed time during the course of the day. Asmay be expected, there was a significant difference (P 50.001) between part-time hours (mean, 3.8 6 0.5 hours) ad-ministered and full-time hours (mean, 7.9 6 1.3 hours) ofocclusion administered. The most common activities whilewearing the patch were school, computer games, and televi-sion. In children who wore the patch at school (part-time orfull-time) the vision tended to improve quicker, consequentlyproducing a shorter duration of therapy.

FIGURE 7. Regression analysis illus-trating the relationship between theabsolute change in visual functionand the duration of daily occlusionwith acuity card measures (A; in logunits) and hyperacuity measures (B;in seconds of arc).


No significant relationship could be found between the ab-solute improvement in visual function and the amount of occlu-sion therapy administered in either visual acuity thresholds (Fig.7A; P . 0.05) or hyperacuity measures (Fig. 7B P . 0.05).

DISCUSSION

In this study we have examined periodically various parame-ters of visual function in a group of young amblyopic subjectsthroughout the course of occlusion therapy.

The results of this study suggest strongly that other as-pects of visual function should be monitored during occlusiontherapy. We provide evidence that many aspects of visualfunction are adversely affected by the presence of amblyopia;all the subjects in this study demonstrated a functional loss ineach of the tests used. Initial pretherapy values can be used toidentify the visual deficit that is most impaired. Interestingly,when the amblyopic subjects were divided according to thisprimary visual loss, it was this visual function that was found tohave the greatest improvement during occlusion therapy (Fig.4). Thus, an amblyopic patient could show little or no improve-ment on a traditional Snellen visual acuity test, althoughchanges are occurring in other aspects of visual function (e.g.,low contrast perception, fixation steadiness, motion detec-tion). Often these visual functions are not affected equally, thatis, a reduction in low contrast may be greater than the deficitwith traditional high contrast letter charts. Our results alsoreveal a significant correlation between the initial pretherapyscores and the absolute improvement in visual function, withthe greater deficit leading to the more substantial degree ofimprovement (Fig. 6).

There is no consensus in the literature as to the correcttreatment or the factors influencing the treatment of amblyo-pia.6,23–25 We could find no relationship between the hours ofocclusion prescribed (part-time or full-time) and the absoluteimprovement in visual function (Fig. 7), in those children whocompleted the treatment diaries. Our results show that it is thetime course of treatment and not necessarily the duration(hours per day) of occlusion that is a key factor.

The greatest improvement in visual function(s) occurredwithin the first 4 to 5 visits (16–24 weeks), although certainsubjects did show changes over a longer time interval. In clinicalpractice, occlusion therapy is often prescribed over many monthsand sometimes years; the results of our study question the need tocontinue occlusion beyond this time scale.

In practice, many clinicians feel that treatment after 6 to 8years of age is ineffective, and in many cases treatment wouldremain uninitiated. Nevertheless, several reports in the litera-ture now exist that detail the successful treatment of amblyo-pia in older children and adults.5,16,26–28 In the present studywe could find no relationship between age and degree of visualfunction improvement (Fig. 6), compliance with treatmentrather than the patient’s age appears to be a key factor. Theclinical pertinence of the treatment of older subjects has beenquestioned, however,29 with amblyopic subjects reportedlystill maintaining fixation with the dominant eye and eventuallydemonstrating a regression of visual function. The risk of insu-perable diplopia in strabismic amblyopia is also a factor thatdeters treatment in an older age-group. If suppression is over-come, subjects may find it impossible to resuppress or learn toignore the diplopia at this age, and if fusion is absent it will beimpossible to re-join the diplopia

The results of this study provide further evidence for themultifarious reduction in visual performance that occurs inamblyopia. Success must be assessed not simply by a change inhigh contrast visual acuity but by examining a number ofparameters that relate to an individual’s visual capacity.

Occlusion therapy appeared to improve all aspects of theamblyopia, with a significant difference between pre- and post-therapy results (Table 5). However, to establish the most ef-fective form of treatment in amblyopia, it would be interestingto compare in isolation and in combination the effects ofocclusion therapy and specific active therapies targeted at anindividual’s primary functional visual deficit. If individual ther-apies for the different functional subcategories could be found,then these individuals could be identified and subsequentlytargeted with a specific therapy.

It is, therefore, important to appreciate this diverse reduc-tion in visual performance that occurs in amblyopic eyes andthe need to monitor other aspects of visual function duringocclusion therapy to allow for the optimum management ofthe patient.

References

1. Wick B. Amblyopia: a case report. Am J Optom. 1973;50:727–730.2. Kageyama CJ, Loomis SA. Central fixation amblyopia: a case report.

Optom Monthly. 1980;2:333–336.3. Jenkins TCA, Pickwell D. Success rate in the treatment of ambly-

opia by conventional methods. Ophthalmic Physiol Opt. 1982;2:213–219.

4. Watson PG, Sanac AS, Pickering MS. A comparison of variousmethods of treatment of amblyopia: a block study. Trans Ophthal-mol Soc. 1985;104:319–328.

5. Selenow A, Ciuffreda KJ. Visual function recovery during orthoptictherapy in an exotropic amblyope with high unilateral myopia.Am J Optom Physiol Opt. 1983;60:659–666.

6. Ciuffreda KJ, Levi DM, Selenow A. Amblyopia: Basic and ClinicalAspects. Boston: Butterworth–Heinemann; 1991.

7. Pickwell DL. The management of amblyopia without occlusion.Br J Ophthalmol. 1976;31:115–118.

8. Wick B, Schor CM. A comparison of the Snellen chart and theS-chart for visual acuity assessment in amblyopia. J Am OptomAssoc. 1984;55:359–361.

9. Campbell FW, Hess R, Watson PG, Banks RV. Preliminary results ofa physiologically based treatment of amblyopia. Br J Ophthalmol.1978;62:747–755.

10. Von Noorden GK. Burian and Von Noorden’s Binocular Visionand Ocular Motility. St. Louis: Mosby; 1996.

11. Flom MC, Weymouth FW, Kahneman D. Visual resolution andcontour interaction. J Opt Soc Am A. 1963;53:1026–1032.

12. Giaschi ED, Regan D, Kraft SP, Kothe AC. Crowding and contrastin amblyopia. Optom Vision Sci. 1993;70:192–197.

TABLE 5. Comparison of Pre- and Posttherapy findings

Test Pretherapy Posttherapy P

CAT 0.499 6 0.193 0.736 6 0.140 0.0001SLA 0.663 6 0.182 0.873 6 0.124 0.0001LC 0.322 6 0.206 0.564 6 0.120 0.0001RRL 0.567 6 0.231 0.795 6 0.140 0.0001OMDT 100.62 6 26.44 69.79 6 14.72 0.0001AT 234.37 6 83.92 166.54 6 28.69 0.0001

Visual acuity measurements are mean 6 SD (modified logMAR),and hyperacuity thresholds are given as mean 6 SD (in seconds of arc).Probability represents the outcome of a t-test between pre- and post-therapy results.


13. Simmers AJ, Gray LS, McGraw PV, Winn B. Contour interaction forhigh and low contrast optotypes in normal and amblyopic observ-ers. Ophthalmic Physiol Opt. 1999;19:253–260.

14. Simmers AJ. Clinical Evaluation of Visual Dysfunction in Hu-man Amblyopia and the Effect of Occlusion Therapy. PhD thesis.Glasgow, Scotland: Glasgow Caledonian University; 1997.

15. Gray LS, Simmers AJ, Winn B. Functional classification of the visualdeficit in childhood amblyopia using clinical tests-normal values[ARVO Abstract]. Invest Ophthalmol Vis Sci. 1998;39(4):S553.Abstract nr 2545.

16. Simmers AJ, Gray LS. Improvement of visual function in an adultamblyope. Optom Vision Sci. 1999;76:82–87.

17. Solo S, Moskowitz A, Reese D, Brown B. Low contrast letter acuityin childhood amblyopia. Clin Vision Sci. 1990;5:243–247.

18. Regan D, Giaschi DE, Kraft SP, Kothe AC. Method for identifyingamblyopes whose reduced line acuity is caused by defective se-lection and/or control of gaze. Ophthalmic Physiol Opt. 1992;12:425–432.

19. Simmers AJ, Gray LS, Winn B. The effect of abnormal fixational eyemovements upon visual acuity in congenital nystagmus. Curr EyeRes. 1999;18:194–202.

20. Levi DM, Klein SA, Yap YL. Positional uncertainty in peripheraland amblyopic vision. Vision Res. 1987;27:581–597.

21. McGraw PV, Winn B, Whitaker D, McFadzean R. Positional acuityin amblyopia: does a perceptual consequence of neural recruit-ment exist? Ophthalmic Physiol Opt. 1998;18:423–429.

22. McGraw PV, Winn B. Glasgow acuity cards: a new test for themeasurement of letter acuity in children. Ophthalmic Physiol Opt.1993;13:400–404.

23. Garzia RP. Efficacy of vision therapy in amblyopia: a literaturereview. Am J Optom Physiol Opt. 1987;64:393–404.

24. Rutstein RP, Fuhr PS. Efficacy and stability of amblyopia therapy.Optom Vision Sci. 1992;69:747–754.

25. Woodruff G, Hiscox F, Thompson JR, Smith LK. Factors affecting theoutcome of children treated for amblyopia. Eye. 1994;8:627–631.

26. Ciuffreda KJ, Kenyon RV, Stark L. Different rates of functionalrecovery of eye movements during orthoptic treatment in an adultamblyope. Invest Ophthalmol Vis Sci. 1979;18:213–219.

27. Hokoda SC, Ciuffreda KJ. Different rates and amounts of visionfunction recovery during orthoptic therapy in an older strabismicamblyope. Ophthalmic Physiol Opt. 1986;6:213–220.

28. Wick B, Wingard M, Cotter S, Scheiman M. Anisometropicamblyopia: is the patient ever too old to treat? Optom Vision Sci.1992;69:866–878.

29. Campos E. Amblyopia. Surv Ophthalmol. 1995;40:23–39.


Functional Visual Loss in Amblyopia and the Effect of Occlusion Therapy · 2008. 9. 8. · the...

Documents

Transcript of Functional Visual Loss in Amblyopia and the Effect of Occlusion Therapy · 2008. 9. 8. · the...