CHROMATIC-CONTRAST THRESHOLD IMP AIRMENT IN DIABETES

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1 CHROMATCCONTRAST THRESHOLD MP ARMENT N DABETES S. J. TREGEAR 1, P. J. KNOWLES 2, L. G. RPLEy 3 and A. G. CASSWELL 2 Glasow and Brihton SUMMARY A prospetive study was arried out to investiate aquired olourvision defiits in diabetis usin an automated, ompnterontroued, athoderaytube based test of hromati ontrast. Chromationtrast thresholds estimates were measured alon both a red/ reen (onstant Sone) onfusion axis and a tritan (onstant MLone) onfusion axis for 305 eyes of 305 diabetis. The diabeti data were partitioned into roups based on a linial ateorisation of retinopathy. The diabeti data were ompared with both aemathed and 'lensequated' ontrol data obtained from a bank of 347 normal subjets. Further analysis of differenes between diabetistatus roups was performed. Assoiations between hromati ontrast threshold estimates and ae, duration of disease, and severity of both maular oedema and ishaemia were investiated. The diabeti roup was found to have sinifiantly redued hromationtrast threshold estimates when ompared with normal ontrols, even in the absene of retinopathy. This redution in hromati ontrast was predominantly tritanopi in nature. nterestinly, no redution in red/reen hromationtrast threshold estimate was found in diabetis without retinopathy. The tritan defiit seen in diabetis without retinopathy was stronly orrelated with duration of disease, but when adjustments were made to aount for the effets of durationdependent lens yellowin, the tritan defiit was no loner apparent. A orrelation between both the severity of maular oedema and severity of ishaemia with hromationtrast loss was established. Aquired redutions in both red/reen and tritan hromationtrast threshold estimates seen in diabetis are stronly orrelated with the severity of retinopathy. The results provide evidene that the speifi tritan defiits seen in diabetis an be explained by the effets of lens yellowin rather than by seletive l From: Glasow Caledonian University, Cowaddens Road, Glasow; 2 Sussex Eye Hospital, Eastern Road, Brihton, East Sussex; 3 University of Sussex, Brihton, East Sussex, UK. Correspondene to: S. 1. Treear, Department of Vision Siene, Glasow Caledonian University, Cowaddens Road, Glasow G4 OBA, UK. damae of the blue one system as has been hypothesised by other roups. The results provide support for the potential use of automated CRT based tests of olour vision in diabeti retinopathy sreenin protools. An assoiation between diabetes and aquired olourvision defiieny has been known to exist for more than 40 years. The earliest studies, however, were of small sale and did not examine the assoiations between fundus hanes and olourvision defiits.1 6 The first published studies to demonstrate a relationship between diabeti retinopathy and olourvision defiits were by Kinnear, Lakowski and Aspina1l7,8 who surveyed a population of 500 diabetis both with and without retinopathy usin the FarnsworthMunsell (FM) 100hue test and the PikfordNiholson anomalosope. They found that FM 100hue sores were sinifiantly poorer for diabetis than for normals and that the sores of those diabetis with retinopathy were sinifiantly poorer than the sores of those diabetis without retinopathy. The losses seen within the diabeti roup did not show any axis of olourvision deterioration. Similar results were obtained with the PikfordNiholson anomalosope exept that the olourvision defiits appeared to be of an aquired tritanopi type. Sine then, other studies have onvininly demonstrated a orrelation between olourvision loss, espeially tritantype loss, and diabeti retinopathy Reffin 16 and de Alwis 17 reently investiated the relationship between fundus features and olourvision defiits in 137 diabeti subjets usin an automated CRTbased test of olour vision performed with the Sussex Gratins Mahine (SGM). The SGM test, like other CRTbased olourvision tests, has many advantaes over more traditional methods of olourvision testin used in linial researh, suh as the FarnsworthMunsell 100hue test. t allows preise measurement of olourvision performane alon speifi hromati onfusion axes, Eye (1997) 11, Royal Collee of Ophthalmoloists

2 538 is quik and easy to perform and to sore, and does not suffer from problems of unsuitable illumination or piment deeneration. ;fhe SGM produes an equiluminant, sinusoidal, hromati ratin on a hihresolution olour monitor. The hromatiity of the sinusoid an be haned alon a red/reen (onstant Sone) onfusion axis or alon a tritan (onstant M/Lone) onfusion axis about a white point. The maximum amplitude of the hromati exursion about the white point is haned under prorammed ontrol and the value at whih a subjet just pereives oloured stripes is found usin an interleaved doublestairase reversal method. This value is taken to be the hromationtrast threshold estimate for that partiular opponentproess system and it is with these two fiures, one for red/reen ontrast threshold and one for tritan ontrast threshold, that we have ateorised olour vision in the subjets disussed in this paper. Usin the SGM system, Reffin and de Alwis found that ae, duration of disease, the deree of maular oedema and the deree of ishaemia all had a sinifiant orrelation with olour vision. nterestinly, their study also showed that some of the fundus features that are used linially to determine whether laser photooaulation is indiated, suh as the presene of hard exudates or miro aneurysms within 500 flm of the maula, or the presene of new vessels, had no sinifiant orrelation with olour vision. n this paper we report on further work, also arried out usin the SGM system, on the investiation of aquired olourvision defiienies found in diabeti subjets. The work was arried out at the Sussex Eye Hospital, Brihton, over a 3 year period and this paper summarises the results and onlusions drawn from the hromationtrast data obtained from 305 diabeti subjets. Three main areas of interest onernin the relationship between aquired olourvision loss and diabetes are examined in this paper. Firstly, the relationship between linial lassifiation of diabeti retinopathy and olour vision is investiated. Seondly, the effets of ae and of duration of disease on olour vision are examined. Finally, the effets of maular oedema and ishaemia on olour vision are onsidered. SUBJECTS AND METHODS Subjets ChromationtrasHhreshold data obtained from 305 randomly hosen eyes of 305 diabeti subjets were inluded in this study (mean ae = 56 years (rane 1788 years), mean duration of disease = 14 years (rane years)). The subjets onsisted of 92 type diabetis and 213 type diabetis. All the subjets were onsentin volunteers reruited at the Sussex Eye Hospital, Brihton, or via the diabeti S. 1. TREGEAR ET AL. photoraphi lini at the Royal Sussex County Hospital, Brihton. Exlusion riteria inluded previous laser treatment, sins of sinifiant lens opaifiation as determined by slitlamp examination throuh dilated pupils, or a orreted visual auity of worse than 6/18. Sine one of the ultimate aims of this work was to develop a test with whih to aid in sreenin the diabeti population for sihtthreatenin diabeti retinopathy we have deliberately not exluded those diabetis who are takin any form of mediation other than those used to ontrol luose levels. t is well known that some mediations will affet olour vision but we deided that a sreener should be tested on diabetis who are as representative as possible of the diabeti population. Many diabetis, espeially in later life, will be on some form of mediation. Classifiation of Diabeti Retinopathy Followin assessment of Snellen visual auity and hromati ontrast, eah diabeti eye was dilated with % tropiamide. Fundal examination was then arried out by an ophthalmoloist experiened in diabetiretinopathy lassifiation usin a slitlamp biomirosope and a 78dioptre lens. Eah eye was ateorised dependin on its stae of retinopathy based on the followin linially orientated system: No retinopathy: No evidene of retinopathy an be seen linially. Bakround: Charaterised by the development of miroaneurysms; superfiial and deep retinal haemorrhaes; the formation of hard exudates. Preproliferative: Charaterised by five or more ottonwool spots on the fundus; the presene of white vessels, venous bleedin and venous loops; features assoiated with severe bakround retinopathy suh as widespread blothy dark haemorrhaes. Proliferative: Charaterised by the presene of new blood vessels: at the opti dis; elsewhere on the retina if more than half a dis diameter in size; less than half a dis diameter if assoiated with vitreous haemorrhae; or by vitreous haemorrhae anywhere. Maulopathy: Clinially sinifiant maular oedema as haraterised by the ETDRS roupyl.19 Charaterised by the presene of a thikenin of the retina within 500 flm of the entre of the maula; presene of hard exudates assoiated with retinal thikenin within 500 flm of the entre of the maula; a zone of retinal thikenin one dis area or larer in size within a dis diameter of the entre of the maula. The ophthalmoloist makin the ateorisation had no knowlede of the results obtained from the hromationtrast test, whih had been arried out prior to the linial assessment.

3 CHROMATCCONTRAST THRESHOLD MPARMENT N DABETES 539 Table. Summary of the data obtained from the 305 eyes of 305 diabeti patients inluded in this study. The data have been partitioned into diabeti retinopathy ateory (see text) No retinopathy Bakround retinopathy Maulopathy Preproliferative retinopathy Proliferative retinopathy (n = 87) (n = 116) (n = 63) (n = 26) (n = 13) TCT (0.17) (9) (0.31) (6) (0.31) RGCT (0.17) (4) (9) (0.19) (0.34) Ae (16.89) (14.95) (11.94) (14.39) (18.72) Test Proedure The SGM has been desribed in detail elsewhere and is essentially a olourvision testin system desined to sreen for, and quantify, aquired olourvision defiienies in a linial situation The SGM was set up to produe vertial, lowspatialfrequeny, equiluminant, sinusoidal ratins on a hihresolution olour monitor (mean luminane 20 d m 2 ) whih were randomly tritan or red/reen. The hromatiity of the ratins was haned alon either a tritan or red/reen onfusion axis about the equal enery, neutral white point (CE 1976 u', v', oordinates: 1, 0.47). The maximum exursion of the hromati ratin about the white point was haned under omputerproram ontrol usin a doublestairase reversal method 21 and the value at whih the subjet just pereived oloured stripes was found for eah stimulus. These values were taken to be the tritanontrast threshold (TCT) estimate and the red/reenontrast threshold (RGCT) estimate respetively, and it was with these measures that we ateorised olourvision defiits. Sine TCT and RGCT estimates are thresholds, it should be noted that an inrease in either will denote a derease in the respetive opponentproess hannel interity. Eah subjet was positioned 2 m from the CRT display so that the stimuli subtended a visual anle of 4. At this distane the ratins produed on the CRT had a spatial frequeny of 0.66 yles/de. Havin been randomly hosen by the throw of a oin, one of the subjet's eyes was oluded and the subjet was instruted to look at the CRT sreen. f, followin an auditory warnin tone, the subjet saw oloured stripes, a handheld button was to be pressed. f the subjet did not see any stripes, or was unsure, the button was not to be pressed. As this test is a psyhophysial test, it was very important that idential instrutions were iven to eah subjet to ensure that they employed the same riteria when deidin whether or not to press the button. To ensure that the subjet understood the proedure orretly, one manually ontrolled test trial was arried out. The test proper was then ommened under automated omputer ontrol and ended after five doublestairase reversals had been ompleted for both the tritan and red/reen stimuli. Chromationtrast threshold estimates were determined based on the mean of only the last four reversals. The TCT and RGCT data for eah eye were stored in the omputer database, alon with all the subjets' details, for reall and analysis at a later date. RESULTS The diabeti data set was partitioned into roups aordin to the ophthalmi ateorisation of retinopathy. Both TCT and RGCT data distributions for eah of the five retinopathy ateories were tested for normality usin the KS (Lilliefors) normality test. All the data sets were found to be normally distributed. The mean and standard deviation of eah data set are summarised in Table. Paired ttests onfirmed that TCT estimates were sinifiantly poorer than RGCT estimates in all retinopathy roups (Table ). A oneway ANOV A established that statistially sinifiant differenes existed between some of the retinopathy ateories for both the TCT and RGCT data (TCT: F ratio = 53.16; p<o.oool; RGCT: F ratio = 28.25, p<o.oool). nterroup omparisons were made usin the Sheffe proedure with the sinifiane level set at p::s:5; the results are shown in Table. Table. The results of ttests used to determine whether a statistially sinifiant differene existed between the RGCT and TCT data within eah diabeti retinopathy ateorisation roup No retinopathy Bakround retinopathy Maulopathy Preproliferative retinopathy Proliferative retinopathy RGCT Mean Variane TCT Mean Variane t P <001 <001 <001 <001 <005 t an be seen that in all retinopathy roups the TCT data are sinifiantly elevated when ompared with the RGCT data. This indiates that tritan olour vision is more severely impaired by diabeti retinopathy than red/reen olour vision.

4 540 S. J. TREGEAR ET AL. Table. Results of the Sheffe interroup omparison test for both RGCT data and TCT data Bakround Preproliferative Proliferative No retinopathy retinopathy Maulopathy retinopathy retinopathy RGCTdata No retinopathy * * * * Bakround retinopathy * * * * Maulopathy * * * Preproliferative retinopathy * * * Proliferative retinopathy * * TCT data No retinopathy * * * * Bakround retinopathy * * * * Maulopathy * * Preproliferative retinopathy * * Proliferative retinopathy * * This test was only performed if the oneway ANOV A showed that a sinifiant interroup differene existed. The asterisk indiates that a sinifiant interroup differene exists at the p<o.05 level. Fi. 1 shows a satterplot of both TCT data and RGCT data versus ae for those diabeti eyes lassified as havin no retinopathy. The ontinuous urves represent the standard deviation limit of normality derived from data obtained from 347 normal eyes. A twosample ttest found that no sinifiant differene in RGCT existed between diabeti eyes with no retinopathy (n = 87) and an aemathed ontrol roup (t = 0.95, p = 0.345). However, TCT estimates were found to be sinifiantly elevated in the noretinopathy roup ompared with the same ontrol roup (t = 2.72, p<o.ool). A reression analysis of the relationship between ae and RGCT in both the noretinopathy roup and the orrespondin aemathed ontrol roup A 1.6 showed that no sinifiant inrease in RGCT was assoiated with inreasin ae in either roup (noretinopathy roup: t = 2.01, p = 529; ontrols: t = 0.645; p = 0.523). However, this was not the ase when a reression analysis of TCT versus ae was performed for both roups. t turned out that the TCT data from the ontrol roup showed no sinifiant inrease with ae (t = 00, p = 40), whereas the TCT data from the noretinopathy roup did (t = 3.463, p<05). The effets of ae were analysed more losely for the noretinopathy roup by partitionin the ae variable into its onstituents: ae at onset of diabetes; duration of diabetes. Sine duration annot be estimated aurately for type diabetis, only type diabetis were onsidered in this analysis. Multiple B 1.6 Zl." :: S 0.8 e a e a 0.6 e s a a ra a C t. e e a a a e a e a e ED a a dl a e 0.4 a EB aa e ae a e e ae e e a a ee a as S a a a a Ae (years) a. " :: 0.8 e & '" ". "'" : _ '" Ae (years) Fi. 1. Satterplots for both RCGT (A) and TCT (B) estimates obtained from 87 diabeti eyes lassified as havin no diabeti retinopathy plotted aainst ae. The ontinuous urve represents the respetive 2 standard deviation limit of normality. Estimates whih fall below the urve should be onsidered as normal.

5 CHROMATCCONTRAST THRESHOLD MPARMENT N DABETES 541 reression analysis found that no sinifiant relationship existed between ae at onset, or duration, and RGCT in diabetis with no retinopathy (ANOY A: F ratio = 2.53, p = 0.10). However, a sinifiant relationship was found to exist between ae at onset or duration and TCT (ANOY A: F ratio = 8.81,p<0l). Further analysis showed that duration was sinifiantly assoiated with an inrease in TCT (t = 4.188, p<005) but ae at onset was not (t = 0.461, p = ). These results indiate that the inrease in TCT seen in type diabetis with no retinopathy an be attributed to durationdependent effets and miht be aused by the development of mirosopi diabetesindued hanes in the retina whih seletively affet the tritan olourvision system. Alternatively, it is possible that the inrease in TCT is in part, if not ompletely, due to preretinal absorption of shortwavelenth liht resultin from lens yellowin.22 n order to investiate this possibility, a omparison was arried out between type diabetis with no retinopathy and a roup of 'lensequated' ontrols. The rate of lens yellowin in diabetis has been shown to be linearly related to diabeti duration.22 Moreland23 has derived two simple equations (Equations 1 and 2) whih relate Lutze and Bresnik's2 2 linear lens yellowin model with Pokorny et al.'s24 linear model of normal lens 'aein': A 1.6 E A T 3.8 (1) E = 0.30A T (2) where E is the ae of a normal subjet havin the same lensabsorption harateristis as a diabeti, A is the ae of the diabeti and T is the duration of the diabetes, whih must be reater than 1.5 years. Equation (1) is used when E is reater than 20 but less than 60. Equation (2) is used when E, derived from Equation (1), is reater than 60. As an example of the use of these equations, onsider two diabetis both aed 35 years. Diabeti A has suffered from diabetes for 3 years whereas diabeti B has suffered for 22 years. For diabeti A, apply Equation (1) with A = 35 and T = 3: E = A T 3.8 = = 38.8 For diabeti B apply Equation (1) with A = 35 and T= 22: E = A T2 3.8 = = 87.1 Sine E is reater than 60 then apply Equation (2) with A = 35 and T = 22: E = 0.30A T = = 68.1 Thus diabeti A would be ompared with a normal subjet of ae 39 years, whereas diabeti B would be ompared with a normal subjet of ae 68 years. The lensequated ae of eah diabeti was determined usin the Moreland tehnique desribed above and the appropriate 'lensequated' ontrol data were then seleted from the normal ontrol database. Fi. 2 shows both TCT and RGCT B 1.6 s " Q<; " A.A "' 6.. ::,.\... ; Lensequated ae (years) Lensequated ae (years) Fi. 2. Satterplots for both RGCT (A) and TCT (B) estimates obtained from 87 diabeti eyes lassified as havin no diabeti retinopathy plotted aainst 'lensequated' ae. The ontinuous urve represents the respetive 2 standard deviation limit of normality. Estimates whih fall below the urve should be onsidered as normal.

6 542 estimates plotted aainst 'lensequated' ae. When omparisons were made of both the TCT and RGCT data between the noretinopathy roup and the 'lensequated' ontrols usin a twosample ttest, it turned out that no sinifiant differenes ould be found for either TCT or RGCT (TCT: t = 0.182, p = 0.856; RGCT: t = 0.547, p = 0.586). A twosample omparison between diabeti eyes lassified as havin bakround retinopathy (n = 116) and aemathed ontrol eyes showed that both TCT and RGCT estimates are sinifiantly hiher in the bakround roup (TCT: t = 9.16, p<o.oool; RGCT: t = 5.26, p<o.oool). A similar twosample omparison between diabeti eyes ateorised as havin bakround retinopathy and a orrespondin roup of 'lensequated' ontrol eyes also showed that both TCT and RGCT estimates were sinifiantly hiher in the bakround roup (TCT: t = 7.02, p<o.oool; RGCT: t = 3.30, p<o.ool). The fat that bakround retinopathy, in the absene of maular oedema or ishaemia, had a deleterious effet on entral olour vision, even after aountin for the effet of the lens, is interestin. t is possible that damae may have ourred at the maula in some of the bakround retinopathy eyes due to sins of maular oedema or ishaemia bein unreonised. f this was the ase, one miht expet that those diabeti eyes oriinally lassified as havin A 1.6 S. J. TREGEAR ET AL. bakround retinopathy with abnormal olour vision (after ompensation for lens absorption) would develop linially sinifiant maular oedema or ishaemia in the near future. To test this hypothesis, all diabetis whose eyes were oriinally lassified as havin bakround diabeti retinopathy were realled for fundus reassessment 18 months after their oriinal assessment Of the 116 eyes oriinally ateorised as havin bakround diabeti retinopathy, we reassessed 87. The remainin 29 eyes were not reassessed due to death (7 ases), movin out of the distrit (8 ases) and repeated nonreattendane (14 ases). A normal/abnormal riterion was established so that a TCT or RGCT estimate was said to be abnormal if it was 2 or more standard deviations above the 'lensequated' roupmathed mean. Based on this riterion, 19 of the 87 bakround retinopathy eyes had abnormal TCT estimates on initial assessment and 11 of the 87 bakround retinopathy eyes had abnormal RGCT estimates on initial assessment. Of the 19 eyes whih oriinally had an abnormal TCT estimate, 12 (63 %) developed either linially sinifiant maular oedema or ishaemia whereas, of the remainin 68 eyes, whih oriinally had a normal TCT estimate, only 6 (9% ) developed linially sinifiant maular oedema or ishaemia. Of the 11 B 1.6 :::s 0.8 Eo< E C B 0.6 B C D 2 :::s B Maulopathy Grade Maulopathy Grade Fi. 3. Satterplots showin RGCT (A) and TCT (B) versus rade of maulopathy. Spearman's rank orrelation analysis found that a deterioration in both RGCT and TCT is assoiated with severity of maulopathy. Note that the TCT data are effetively apped due to the severity of the losses seen in eyes with maulopathy whih resulted in some patients bein unable to see any of the tritan stimuli presented by the SGM.

7 CHROMATCCONTRAST THRESHOLD MPARMENT N DABETES 543 eyes whih oriinally had an abnormal RGCT estimate, 6 (55%) developed sinifiant maular oedema or ishaemia whereas 12 (18%) of the remainin 76 eyes oriinally havin normal RGCT estimates developed linially sinifiant maular oedema or ishaemia. A hisquared analysis of the data found that those diabetis with bakround diabeti retinopathy and an abnormal TCT estimate or RGCT estimate are sinifiantly more at risk of developin sihtthreatenin diabeti retinopathy within 18 months of the test (hisquared, p<o.oool for both TCT and RGCT estimates). A twosample omparison between diabeti eyes lassified as havin maulopathy (n == 63) and aemathed normal eyes (n == 63) found that both TCT and RGCT estimates were sinifiantly hiher in the maulopathy roup (TCT: t == 14.89, p<o.oool; RGCT: t == 8.85, p<o.oool). A similar omparison between diabeti eyes ateorised as havin maulopathy and a orrespondin roup of 'lensequated' eyes also found that both TCT and RGCT estimates were sinifiantly hiher in the maulopathy roup (TCT: t == 13.00, p<o.oool; RGCT: t == , p<o.ooo). A multiplereression analysis of the maulopathy data found a sinifiant relationship between TCT estimate and ae at onset of diabetes (t == 2.57, p<5). No suh assoiation was found between TCT estimate and duration of disease, presene of hard exudates within 500 flm of the fovea, or presene of miroaneurysms within 500 flm of the fovea. An idential multiplereression analysis usin RGCT as the dependent variable found no sinifiant assoiation between RGCT and ae at onset, duration of disease, presene of hard exudates within 500 flm of the fovea, or presene of miro aneurysms within 500 flm of the fovea. Data obtained from eyes with maulopathy were further subdivided into one of five roups whih were ateorised aordin to their deree of maular oedema. A subjet with minimal maular oedema was raded as rade 1 and a subjet with ystoid maular oedema was raded as rade 5. Any diabeti eyes showin evidene of ishaemia were exluded from this analysis. Fi. 3 shows the distribution of both TCT and RGCT estimates with inrease in maular oedema severity. A Spearman's rank orrelation test of the data shows that both TCT and RGCT inrease with inreasin maular oedema rade (TCT: TS p == 0.37, p<05; RGCT: TS p == 0.36, p<o.o). A twosample omparison between diabeti eyes lassified as havin ishaemia (n == 33) and aemathed ontrol eyes (n == 33) found that both TCT and RGCT estimates were sinifiantly hiher in the ishaemi eyes (TCT: t == 9.41, p<o.oool; RGCT: t == 7.23, p<o.ooo). A similar omparison between diabeti eyes ateorised as havin ishaemia and a orrespondin roup of 'lensequated' ontrol eyes also found that both TCT and RGCT estimates were sinifiantly hiher in the ishaemi roup (TCT: t == 6.42, p<o.ooo; RGCT: t == 5.21, p<o.ooo). A 1.6 B 1.6 J " Ol e ' 8 '2 " Ol ; shaemia rade shaemia rade Fi. 4. Satterplots showin RGCT (A) and TCT (B) versus the rade of ishaemia. t an be seen that both RGCTand TCT tend to inrease with inreased severity of ishaemia. Spearman's rank orrelation analysis found that there was a tentative assoiation between RGCT and severity of ishaemia. However, no sinifiant assoiation between TCT and ishaemi severity ould be found (see text).

8 544 A multiplereression analysis of the data obtained from the ishaemi eyes found that neither ae nor ae at onset showed an assoiation with either TCT or RGCT inrease. The same multiplereression analysis of the ishaemi data showed that neither TCT nor RGCT were affeted by the presene of new vessels. Data obtained from the ishaemi eyes were further subdivided into mild (rade ) ishaemia, moderate (rade 2) ishaemia and severe (rade 3) ishaemia. This further lassifiation of ishaemi eyes was based on the number of ishaemi features present on the fundus. For example, an eye with only a few ottonwool spots was lassified as rade 1. An eye with many ottonwool spots, deep retinal haemorrhaes, intraretinal mirovasular abnormalities and sins of venous hanes was lassified as rade 2. An eye whih had peripheral or dis new vessels was lassified as rade 3. t should be noted that in this study the deree of ishaemia was not juded on the results of fluoresein anioraphy. Fi. 4 shows that inreases in both TCT and RGCT estimates seem to be assoiated with the deree of ishaemia. However, Spearman's rank orrelation test found only a tentative assoiation between an inrease in RGCT and inreased severity of ishaemia, and no suh assoiation was found for TCT and severity of ishaemia (TCT: rs p = 0.19, p = 5; RGCT: rs p = 0.32, p = 5). DSCUSSON The results reported here onfirm that olour vision as determined by hromationtrast threshold estimates, espeially TCT estimates, is affeted by diabetes. This study has shown that the prinipal fators whih affet olour vision in the diabeti eye are ae at onset, duration of disease, the presene and deree of maular oedema and, finally, the presene of retinal ishaemia. These findins are in areement with the earlier work of Reffin16 and de Alwis 17 who also found these same fators to have a sinifiant effet on olour vision as determined by the SGM. Whilst sinifiant losses in olour vision were seen in the reat majority of diabeti eyes with retinopathy lassified as bein sihtthreatenin, it is interestin to note that olour vision was also redued in some diabeti eyes whih either showed no evidene of retinopathy or were lassified as havin mild, nonsihtthreatenin retinopathy. The results reported in this paper show that patients with no linial evidene of retinopathy tend to have redued TCT estimates and normal RGCT estimates, indiatin a seletive tritan olourvision loss. Several other studies into olourvision hanes in diabetis with no retinopathy have also identified a seletive tritan loss. For example, Kinnear et al? 8 found, usin the PikfordNiholson s. J. TREGEAR ET AL. anomalosope, that a tritan loss was the most ommon form of olourvision loss in their noretinopathy diabeti population. Zisman and Adams26 used an eletroretinoraphi tehnique to demonstrate a redued Sone pathway sensitivity in type diabetis without linially observed retinopathy. On further analysis of the data obtained from type diabetis with no retinopathy we found that the tritan loss was duration dependent, and when the data were orreted for the effets of durationdependent lens yellowin the speifi tritan loss disappeared. This findin lends support to the hypothesis that the relative redution in tritan olour vision seen in diabetis with no retinopathy is due to lens yellowin, and not to seletive damae to the tritan olourvision system aused by mirosopi retinal hanes. These results are ontrary to those reported in a reent paper by Hardy et al.27 who ompared the FM 100hue error sores obtained from 25 type diabetis with no retinopathy as determined by fluoresein anioraphy with those of 25 'lensequated' ontrols. They onluded that some, but not all the losses seen in diabetis with no retinopathy ould be explained by lens hanes. f one aepts that durationdependent effets are responsible for some of the tritan olourvision losses seen in diabetis, then it is reasonable to arue that the relatively reater inrease in all the diabeti roups of TCT ompared with RGCT is, in fat, due to the seletive filterin out of shortwavelenth liht by the yellowed lens rather than to an inreased suseptibility of the Sone olourvision hannel to retinal damae. ndeed, de Alwis 17 found that when one adjusted for the effets of duration as determined by multiplereression analysis on olour vision, the relative diferenes between RGCT and TCT aross all retinopathy roups disappeared. A similar analysis of the data obtained from our type diabetis of all retinopathy rades produed idential results This would indiate that the diabeti retinopathy itself affets both red/reen and tritanontrast threshold equally and that the relative inrease in tritanontrast threshold, when ompared with red/reenontrast threshold, is, in fat, due to the superimposition of the effets on tritanontrast threshold due to lens yellowin. t should be noted that one annot, on the basis of these results alone, disreard the possibility that mirosopi hanes in the retina are indeed seletively damain the Sone system and hene reduin the sensitivity of the tritan olourvision system. However, one should onsider, a little more septially than miht otherwise be the ase, reports whih laim that tritan olourvision is more suseptible than red/reen olour vision to the effets of retinal damae due to diabetes.

9 CHROMATCCONTRAST THRESHOLD MPARMENT N DABETES 545 Another important point demonstrated by the results presented in this paper is that those subjets with bakround retinopathy who have abnormal hromationtrast thresholds (after ompensation for lens yellowin) are at a hiher risk of developin linially sinifiant sihtthreatenin retinopathy than those who have hromationtrast thresholds whih fall within the normal rane. t is possible that had fluoresein anioraphy been arried out on those subjets who had abnormal olour vision, many of them would have turned out to have sihtthreatenin diabeti retinopathy whih was undetetable with a slit lamp. Unfortunately, it was not possible for us to arry out suh a study for ethial reasons, sine fluoresein anioraphy is an invasive tehnique whih arries a small, but sinifiant, risk to the subjet. Despite this, it is obvious that measurement of hromationtrast thresholds, partiularly alon a tritan onfusion axis, usin a sensitive linial testin system suh as the SGM, is useful in preditin whih diabetis with nonsihtthreatenin retinopathy are likely to suffer a sihtthreatenin form of retinopathy within a relatively short period of time. This findin is of profound linial importane sine it shows that measurement of hromationtrast thresholds an provide a powerful noninvasive approah by whih one an monitor those diabetis with nonsihtthreatenin retinopathy and fla those who are most at risk of deterioratin to a sihtthreatenin stae, thus allowin early treatment as soon as treatable lesions develop. Previous reports by other authors support our findin that olour vision deteriorates in the presene of maulopathy. 1 O, 13, 1 4, 16, 17,2 8 Bresnik et al. 1 4 found that the manitude of error sore as determined by the FM 100hue test was assoiated with deree of maular oedema. Green et al. io reported that, in their study, 95% of the diabeti eyes with maulopathy had abnormal vision. Both Bresnik et al.14 and Greenstein et al. 2 8 also showed that the FM 100hue error sore inreased with the severity of maular oedema. Reffin 1 6 and de Alwis 17 found that no assoiation existed between the presene of hard exudates or miroaneurysms within 500 flm of the fovea and olourvision loss. However, our results differ from those of Reffin and de Alwis in that the duration of disease showed no measurable effet on either TCT or RGCT in those diabetis with linially sinifiant maulopathy. t is possible that the effets of maulopathy on olour vision are so severe that any relationship between duration and olourvision deterioration is masked. However, the fat that ae at onset was sinifiantly assoiated with an inrease in TCT indiates that the duration estimates in this roup of diabetis, who are predominantly type, are poor and that muh of the effet of duration on tritan olour vision is hidden within the aeatonset variable. Unfortunately, many of the subjets in this study with maular oedema had olourvision losses whih were so severe that they ould not see the stimuli at all. This problem, whih is ommon to all CRTbased olourvision testin systems, only ourred with the TCT data and one must aept that the reression analysis ives us little more information than that there is indeed an inrease in TCT with inrease in maular oedema severity. The manitude of the inrease annot be determined sine the data have effetively been apped. t is possible that had fluoresein anioraphy been used to better lassify the ishaemi eyes in this study, the lassifiation of the deree of ishaemia would have been more aurate and perhaps an assoiation between inrease in hromationtrast threshold and the deree of retinal ishaemia miht have been found. Reffin and de Alwis have reported that a sinifiant relationship does exist between the ishaemi rade, as determined by ophthalmosopy, and an inrease in both TCT and RGCT estimates as determined with the SGM. 1 6, 1 7 As a result it is advisable that the reader treat with aution the results reported here reardin the effets of ishaemi severity on olour vision. Further studies usin a more strinent protool need to be arried out to larify the situation. The findin that the presene of new vessels seemed to have no effet on hromati ontrast is in areement with those of Reffin and de Alwis who also found that the presene of new vessels had no effet on olour vision. 1 6, 17 This is not a surprise sine newvessel rowth is a response to severe ishaemia of the retina. t would seem loial to doubt that new vessels on their own would have any effet on visual funtion exept when they haemorrhae or are responsible for a trational retinal detahment. Finally, the fat that olour vision seems to be so intimately assoiated with diabetes lays opens the possibility that hromationtrast testin miht provide the liniian with a noninvasive tehnique for sreenin for sihtthreatenin diabeti retinopathy. We are at present arryin out a 2 year prospetive study at the Sussex Eye Hospital, in onjuntion with the Royal Sussex County Hospital diabeti and medial photoraphy departments, aimed at determinin whether a role does exist for hromationtrast testin in sreenin the diabeti population for sihtthreatenin diabeti retinopathy. We envisae that automated hromationtrast threshold testin systems suh as the SGM will supplement other sreenin proedures suh as fundus photoraphy and that the two modalities will provide an overall sreenin system that will not only effetively detet those with sihtthreatenin

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