The relationship between colour vision defects and visual field tests in glaucoma

The relationship between colour vision defects and visual field tests in glaucoma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article The relationship between colour vision defects and visual field tests in glaucoma Jesse Gale, Zung Mai, Anthony Wells, Robin Willink This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6458135/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose The relationship between colour vision defects (CVD) and visual field test results in glaucoma can be counterintuitive. We sought to examine the relationship between three tests of colour vision and three types of perimetry in glaucoma. Materials and methods In this cross-sectional study, we included both eyes of 53 patients with glaucoma. We conducted white-on-white Standard Automated Perimetry (SAP), blue-on-yellow Short Wave Automatic Perimetry (SWAP) and sine-grating Frequency Doubling Technology (FDT) perimetry, as well as Ishihara, Hardy-Rand-Rittler (HRR) and desaturated Lanthony D-15 tests of central colour vision. Our primary analysis used Kendall’s tau to measure the probability that an increase in one variable, the average of SAP or SWAP of FDT central point sensitivities, is accompanied by concordant increase in colour vision. Results There are weak concordances between D15 and SAP (-0.01 ≤ τ ≤ 0.21), D15 and SWAP (-0.03 ≤ τ ≤ 0.22), and D15 and FPT (0.03 ≤ τ ≤ 0.30). There was insufficient evidence in the sample to conclude that these concordances differ (p = 0.08). There appear to be stronger concordances between HRR and the results of visual field tests (0.09 ≤ τ), the strongest being with FDT (0.13 ≤ τ). Conclusions The effect of glaucoma on colour vision appears to be diffuse, not closely concordant with overall or central visual field function. Health sciences/Diseases/Eye diseases/Optic nerve diseases Health sciences/Signs and symptoms/Eye manifestations Glaucoma optic neuropathy color vision defects automated perimetry Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction In glaucoma the central vision, represented by both visual acuity and colour vision, is usually preserved until late, when visual field loss has become advanced and encroaching on central vision. This pattern is clinically familiar, and colour vision tests are useful to help to detect non-glaucomatous optic neuropathy 1 . However, contrary to clinical experience subtle colour-vision defects (CVD) are commonly detected in glaucoma in a research setting, generally non-specific or in the blue-yellow axis. 2 – 7 In studies of ocular hypertensive patients and early glaucoma, CVD occurred in 40% (as compared to 15% of controls) 8 , 9 and were associated with high intraocular pressure (IOP) and indicative of future visual field loss. 3 , 9 – 13 The correlation between these CVD and the visual field is not strong, so there are patients with normal visual fields in early glaucoma who have CVD, and there are patients with advanced visual field loss from glaucoma who have normal colour vision. Visual fields in glaucoma are typically measured with white-on-white standard automated perimetry (SAP, size III stimulus, 0.43° diameter). Alternative visual field testing stimuli include: 1) short-wave automated perimetry (SWAP) where blue stimuli (size V, approximately 1.7° diameter) are presented on a yellow background; 14 , 15 or 2) frequency doubling technology (FDT) where larger square stimuli of sine-wave gratings (0.5 cycles per degree, approximately 5° grating) are presented with 18 Hz counterphase flickering against an isoluminant background. 16 – 19 These alternative visual field tests have some limitations, for example SWAP can be sensitive but suffers from longer test times, greater variation between tests, more susceptibility to age and cataract, and is no longer in common clinical usage. 20 – 28 The purpose of this study was to investigate whether the clinically recognised relationship between visual fields and CVD is stronger with alternative visual field stimuli or alternative colour vision tests. Colour vision tests vary in their sensitivity and their ability to reveal mild blue-yellow CVD. While subtle CVD may occur with normal central SAP results in mild glaucoma, we hypothesised that SWAP or FDT stimuli might have higher concordance with CVD. This would be of clinical interest because it would indicate either a regional or a diffuse effect of glaucoma on the colour vision function. The sensitivity values provided by SAP, SWAP and FDT cannot be compared on the same scale (there is non-linearity between variables), and when continuous variables are rounded to discrete values it results in ties that affect measurement of correlation: for these reasons our analysis required a new approach to estimating concordance between tests, using Kendall’s tau. In our secondary analysis we also sought to identify whether features of the eye are associated with more discrepancy between colour vision tests and central visual field sensitivity. Materials and methods Approvals The University of Otago Human Ethics Committee (Health) approved this study (reference H20/093). The Ngāi Tahu Research Consultation Committee (Te Komiti Rakahau ki Kāi Tahu) acknowledged the goals of the project. The study was conducted in accordance with the Declaration of Helsinki and all participants gave written informed consent. Design This was a cross-sectional observational study recruiting participants with a diagnosis of glaucoma, confirmed by fellowship-trained glaucoma specialists (JG and APW). The inclusion criteria were: participants aged 18–80 years with a confirmed diagnosis of glaucoma, who were willing and able to give informed consent, with corrected acuity of at least 6/12 in included eyes. Exclusion criteria were congenital CVD, inability to attend for testing, other diseases affecting the retina, optic nerve, or visual field, and previous intraocular surgery (other than surgery for cataract or glaucoma more than 3 months previously). Participants were invited from clinics to attend one additional session of visual field and colour vision testing. Procedures All tests were performed separately in each eye, with the other eye patched. Participants all performed three visual field tests: 1) SAP was Humphrey perimetry using the Swedish Interactive Testing Algorithm (SITA) Standard 24 − 2 protocol (HFA3, Zeiss, Dublin, CA, USA); 2) SWAP was Humphrey SITA-SWAP 24 − 2 protocol (HFA2, Zeiss, Dublin, CA, USA); 3) FDT was Matrix perimeter FDT 24 − 2 Threshold protocol (Matrix, Zeiss, Dublin, CA, USA). The order of perimetry testing was not pre-determined, but not randomised; participants completed the tests in a flexible sequence based on availability of equipment. When not performed at the same visit, all visual field tests were completed within 3 months of each other. Autorefraction or focimetry was performed, for suitable refractive correction. Participants also performed three tests of central colour vision separately with each eye: 1) Ishihara plates, scored as an integer of 0–12 test plates correct; 2) Hardy Rand Rittler (HRR) plates (4th edition), scored as 0–2 blue-yellow (B-Y) screening plates correct and 0–4 red-green (R-G) screening plates correct; and 3) the desaturated Lanthony D-15 panel test. 29 The D15 colour test results were processed using the website www.torok.info which generates a range of error scores: we used the “total error score” as our primary measure. Only the screening plates of HRR were used, because the other HRR plates have greater colour contrast and are only useful to characterise the nature and extent of more-severe CVD. The colour tests were all performed under standard illumination with a lamp 0.5 m above the testing surface (Philips LED 2300 lumen 19 W bulb, 6500 K colour temperature, with colour rendering index 80) and illuminance on the testing table was measured between 1850–1950 lux with Mastech MS6612 lux meter). Data and description All completed tests were included, we did not exclude or adjust results based on reliability measures. The results of each field test were summarised as (i) a mean deviation, MD, which is the average difference between the sensitivity value at each point and the age-specific sensitivity, averaged over the 24 − 2 field, (a discrete variable with a large number of possible values), (ii) the average (i.e. arithmetic mean) of the sensitivity values at the four central points (a discrete variable in 0.25 dB intervals), and (iii) the maxima and minima of the sensitivity values at the four central points (a discrete variable with integer values of dB). Individual sensitivity values expressed as < 0 dB were imputed to be 0 dB. Each colour test resulted in an integer value. For the purpose of description, the severities of glaucoma and CVD were assigned to predefined categories. The severity of glaucoma was categorized using the mean deviation MD recorded with SAP: mild when ‘MD > -6 dB (including 7 eyes with no definite glaucoma), moderate when ‘-12 dB < MD ≤ -6 dB’, and severe if ‘MD ≤ -12 dB’. With D15 data, colour-vision status was categorized as normal when ‘error score = 0’, borderline when ‘1 ≤ error score ≤ 25’, and abnormal when ‘error score ≥ 26’. With the Ishihara test, the status was categorized as normal when the results were correct for all 12 plates, borderline when the results were correct for 11 plates, and abnormal otherwise. With HRR R-G, the status was categorized as normal when the results were correct for all four plates, borderline when the results were correct for three plates, and abnormal otherwise. With HRR B-Y, the status was categorized as normal when the results were correct for both plates, borderline when the results were correct for one plate, and abnormal if the results were incorrect for both plates. Statistical analysis In analysing the visual-field sensitivities and colour-vision test results, the data from each test were considered to be outcomes of random variables with non-normal distributions and with conditional means related by non-linear relationships. This is appropriate because of the logarithmic nature of the sensitivity data and the unknown scales of colour vision test scores. Consequently, the familiar Pearson measure of linear correlation, r, lacks meaning. Sometimes, the analysis of such data is carried out using Spearman’s rank-correlation coefficient, r S , but the analogous population parameter, ρ S , does not have a useful interpretation. Therefore, we studied this problem using Kendall’s statistic of concordance, t, which is an estimate of an unknown population parameter τ (tau). This parameter is defined to be τ = 2 π c -1, where π c is the probability that two variables are ‘concordant’, i.e. the probability that when two members, A and B, of the population are chosen randomly the differences in the two variables are in the same direction. In the present problem, this would be the probability that, given A has a better visual-field result than B, A also has a better colour-vision result than B. So, Kendall’s τ can take any value from − 1 to 1, and it has a clear and meaningful interpretation. Figure 1 gives an illustrative example of the type of scatter plot presented later in Figs. 3 and 4. It imagines colour-vision results plotted against visual-field results in a sample from a population occupying the ellipse uniformly. The orientation of the ellipse is such that most, but not all, of the line-segments joining random points in the ellipse have positive slope. So there is a concordant relationship between the two results, but not perfect concordance, so τ lies between 0 and 1. Figure 1a shows the results for a fictitious sample of nine eyes, connected by line-segments each indicating either a concordant pair (solid line segment) or a discordant pair (dotted line segment). The proportion of pairs that are concordant is p a = 30/36 = 5/6, resulting in the point estimate of τ being t a = 2/3. A confidence interval for τ can then be found by bootstrapping, in which repeated samples of the same size are taken with replacement, to approximate the unknown distribution of error in the population. From numerous re-samplings, an approximate 95% confidence interval for τ is found using the 2.5th and 97.5th percentiles of the set of t a values. This description applies to continuous variables. However, in clinical testing, the continuously variable levels of colour vision or visual field are rounded into discrete scales, as illustrated in Fig. 1b. Such rounding means that some subjects incorrectly appear to have the same level of vision, with the associated line segments being horizontal or vertical. The corresponding pairs appear ‘tied’, rather than concordant or discordant. The existence of these artificial ties means that t a tends to underestimate the magnitude of τ. A natural adjustment for this is to estimate the proportion of concordant pairs amongst only the concordant or discordant pairs (not tied). This leads to an estimate p d that is greater than p a because of the smaller denominator, which results in an estimate of t d further from zero than t a . However, as seen when comparing Fig. 1b with Fig. 1a, rounding leads to the removal of disproportionately more discordant pairs than concordant pairs, so t d tends to overestimate the magnitude of τ . For our primary analysis, we assessed the hypothesis that, in the population of eyes, the D15 results are equally concordant with the results when averaging the central points on each of the three perimeters. The analysis involved carrying out a test of the hypothesis that the three individual values of τ are equal ( α = 0.05). Bootstrapping was used to estimate the null error distribution: if x is the estimate of the vector of parameter-differences, X* is an estimator from a bootstrap-sample and v is the covariance matrix of the bootstrap-estimates then the p-value of the test that the parameters are equal, i.e., that the vector of parameter differences is 0 , is the probability that ( X* - x ) T v − 1 ( X* - x ) equals or exceeds the quantity ( x - 0 ) T v − 1 ( x - 0 ). Post-hoc analyses included the comparison of concordances between each of the four colour-vision tests and MD or the maxima and minima of the four central points, for all three types of perimetry. Results Participants A total of 54 participants were recruited, and one was excluded due to a congenital protanomaly. The mean age was 65.3 years (standard deviation 10.5 years, range 31–79 years) and 23 (43%) were female. Their clinical characteristics are shown in Table 1 . Of the 106 eyes, 63 had mild glaucoma, 27 were moderate in severity, and nine were severe. There were seven normal fellow eyes, included in analyses. Due to equipment availability, only 93 of the 106 eyes had results for all three of SAP, SWAP and FDT, so three-way hypothesis testing was based on this slightly reduced data set. Table 1 Clinical characteristics Number (%) Glaucoma type Primary open angle 53 (50%) Normal tension 31 (29%) Primary angle closure 6 (6%) Secondary 9 (8%) Unaffected fellow eye 7 (7%) Cataract surgery 24 (23%) Glaucoma drainage surgery 20 (19%) Mean ± SD Glaucoma severity SAP mean deviation (dB) -5.28 ± 4.99 SWAP mean deviation (dB) -7.27 ± 5.15 FDT mean deviation (dB) -6.04 ± 5.93 Most recent IOP (mmHg) 13.8 ± 3.4 (8–22) Colour vision Figure 2 shows the proportion of 106 eyes in the study, with normal, borderline or abnormal colour vision test results, for each severity of glaucoma (based on SAP definitions above, normal eyes included with ‘mild’). This shows that D15 was more sensitive than other colour-vision tests (more often abnormal, especially in mild glaucoma or fellow eyes, see Table 2 ), but the proportion that were abnormal with D15 did not correlate as well as other tests with the severity of glaucoma. Table 2 Number (and percentage) with abnormal colour vision by sub-group Number of eyes Lanthony D15 Ishihara HRR B-Y HRR R-G Male 60 29 (48%) 13 (22%) 5 (8%) 15 (25%) Female 46 18 (39%) 8 (17%) 8 (17%) 12 (26%) Age 65 68 31 (46%) 18 (26%) 12 (18%) 23 (34%) Glaucoma Type POAG 53 23 (43%) 10 (19%) 10 (19%) 13 (25%) NTG 31 12 (39%) 3 (10%) 2 (6%) 6 (19%) PACG 6 4 (67%) 6 (100%) 0 (0%) 5 (83%) Secondary 9 5 (56%) 1 (11%) 1 (11%) 2 (22%) Unaffected 7 3 (43%) 1 (14%) 0 (0%) 1 (14%) Glaucoma surgery 20 11 (55%) 7 (35%) 7 (35%) 11 (55%) No glaucoma surgery 86 36 (42%) 14 (16%) 6 (7%) 16 (19%) Cataract surgery 24 11 (46%) 11 (46%) 8 (33%) 13 (54%) No cataract surgery 82 36 (44%) 10 (12%) 5 (6%) 14 (17%) IOP 14 40 18 (45%) 7 (18%) 4 (10%) 9 (23%) As suggested in Table 2 , demographic and clinical characteristics did not affect the extent of colour-vision abnormality in a clinically significant way. There was a trend towards more abnormality in those with a history of raised IOP (primary angle closure or secondary glaucoma) compared to those with normal tension glaucoma. Cataract surgery seemed to be associated with more CVD using Ishihara and HRR tests, which could reflect older participants with more advanced glaucoma (phakic eyes average age 62 years, average SAP MD -5.2 dB; pseudophakic eyes average age 73 years, average SAP MD -6.4 dB). Concordance between colour and fields The relationships between colour-vision test results and each of the visual-field test results are shown in Fig. 3 (average of the four central points, a measure of central visual field sensitivity) and Fig. 4 (mean deviation, an overall measure of field sensitivity). Each of the 12 scatter plots in each figure also displays both t a and t d (estimates of Kendall’s τ ) with 95% confidence intervals for τ . As seen in Fig. 3, the estimates of τ for D15 and the average of central points from the three visual field tests range from 0.06 to 0.23, which we interpret as being small. The 95% confidence intervals for the individual concordances overlap. (These intervals were obtained with bootstrap samples of size 9999.) In relation to the primary research question, there is insufficient evidence in the data to reject the hypothesis that the D15-SAP, D15-SWAP and D15-FDT concordances are equal: the p-value for the three-way test of equality was 0.08 using t a and 0.09 using t d . (This test was carried out with a bootstrap sample of size 999999.) To summarise Figs. 3 and 4, there was relatively weak concordance between most field test results and D15 or Ishihara results, but some patterns were observed: 1) FDT perimetry tended to have higher concordance with colour-vision tests, as compared to SAP and SWAP; 2) HRR screening plates (both B-Y and R-G) had higher concordance despite the large numbers of ties due to the highly discretized values (that is, both t a and t d were higher for HRR than other colour-vision tests); 3) there was no meaningful difference between the concordance of colour vision with overall field sensitivity (MD, Fig. 4) as compared with the concordance of colour vision with central field sensitivity (average of central points, Fig. 3). The average, maxima, or minima of the four central points all showed similar levels of concordance with colour vision tests. Intraocular pressures in the eyes with colour/field discrepancy The similar concordance measures for MD and the central field sensitivities indicated that there was no localised central field defect to explain CVD using any of the visual field test stimuli. This concurs with reported findings in early glaucoma and ocular hypertension (with normal visual fields), where it was suggested that CVD were more common with raised IOP and predicted glaucomatous progression. 6 , 30 We pursued this hypothesis by considering the eyes with the most clear discrepancy between visual fields and colour vision, and the most recent IOP. In our study there were 70 eyes with SAP MD > -6 dB of which 28 had abnormal D15 results, eight had abnormal Ishihara results, eight abnormal HRR R-G and four abnormal HRR B-Y results. In all of these groups of eyes, the last recorded IOP value ranged from 8 to 20 mmHg with no pattern or trend observed, so these eyes were not hypertensive, contrary to previous suggestions. There were nine eyes with SAP MD ≤ -12 dB, and we considered the most recent IOP in those with normal colour-vision results. Three of these eyes with severe glaucoma had normal D15 results (IOP 13, 18, 20 mmHg), four had normal Ishihara results (IOP 9, 11, 18, 20 mmHg), and the same three eyes had normal HRR R-G and B-Y results (IOP 11, 18, 20 mmHg). At least two of these eyes in each group had IOP that was probably greater than ideal target IOP of 12 mmHg for eyes with advanced glaucoma, so the discrepancy could not be explained by a very low IOP. 31 Discussion The concordance between the central visual field sensitivity and tests of colour vision remains fairly low in glaucoma, regardless of the visual field stimulus. The FDT, with a larger 5 degree stimulus coming closer to the foveal centre, appeared to have greater concordance with CVD than SAP or SWAP, but this did not reach significance in our primary hypothesis with a sample of 53 people. Various measures of central visual field function (average, maxima or minima of central points) appeared no more closely associated with CVD than overall MD. Together these data suggest no regional or localised central visual field defect can explain the high prevalence of CVD in glaucoma, and infers a generalised diffuse effect of glaucoma on the colour function. In comparing colour tests, the Lanthony D15 was most often abnormal, but it was less closely associated with glaucoma severity than Ishihara and HRR screening tests (see Fig. 2). This finding suggests the more sensitive D15 test is not superior in clinical use, indeed it was abnormal in 3 of 7 unaffected fellow eyes (43%). This study was not designed to consider which colour vision test was best able to indicate a non-glaucomatous optic neuropathy. 1 The weak relationships between CVD and visual fields suggest that when colour is reduced in glaucoma it is a diffuse effect, or related to extraneous factors (age, cataract, acuity). We did not find a trend towards higher IOP in those with CVD and mild glaucoma, but those with secondary or angle closure glaucoma were more likely to have CVD. Angle closure patients were also older (average age 75 years, compared to 64 years in other participants), and had mildly worse glaucoma (average MD -6.9 dB ,compared to -5.4 dB in other eyes). This remains an intriguing area for future study and raises new hypotheses for investigation. Clinical tests that might correlate with this diffuse loss of CVD in glaucoma include macular optical coherence tomography (OCT) of ganglion cell layer thickness, microperimetry, or provocative IOP challenges. It remains possible that a small and very central defect in vision from glaucoma affected the colour vision in some subjects while paracentral visual field test points were normal. This seems unlikely as there were very similar levels of concordance between overall and central visual field sensitivity, and glaucoma does not generally cause central foveal pathology. The central visual field can be scrutinized more closely with a 10 − 2 protocol, but only a 24 − 2 protocol was available for SWAP perimetry. The clinical implications of this study are that colour vision is often diffusely abnormal in glaucoma, so neuroimaging is not required for everyone with an abnormal result. The FDT (with larger stimuli) appeared more concordant with CVD but this does not imply improved clinical utility. Quick colour testing books (Ishihara and HRR) were more concordant with visual function than D15, only indicating that the more time consuming D15 test is not a superior screening test. Understanding the pathophysiology underlying CVD in glaucoma remains an interesting area for investigation, with improved imaging and electrophysiological techniques. 312 Declarations Conflict of interest No conflicting relationship exists for any author. No funding was received for this work. Acknowledgments The authors gratefully acknowledge Dr Andrew Logan and Mariana Eaton of Wellington Eye Centre, Wellington, for the generous facilitation of this study through use of their Humphrey short-wave automated perimetry device. Meeting presentation This work was presented at the Australia and New Zealand Glaucoma Society annual meeting held virtually in February 2021 and the Royal Australian and New Zealand College of Ophthalmologist, New Zealand Branch Annual Scientific Meeting 2023. References Waisberg E, Micieli JA. Neuro-Ophthalmological Optic Nerve Cupping: An Overview. Eye Brain 2021; 13: 255-268. Flammer J, Drance SM. 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Journal francais d'ophtalmologie 1986; 9 (12) : 843-847. Yu TC, Falcao-Reis F, Spileers W, Arden GB. Peripheral color contrast. A new screening test for preglaucomatous visual loss. Invest Ophthalmol Vis Sci 1991; 32 (10) : 2779-2789. Fortune B. Pulling and Tugging on the Retina: Mechanical Impact of Glaucoma Beyond the Optic Nerve Head. Invest Ophthalmol Vis Sci 2019; 60 (1) : 26-35. Additional Declarations There is no conflict of interest Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6458135","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":449503238,"identity":"70fe9c94-3d35-4dfd-ba68-ba8e985ef396","order_by":0,"name":"Jesse Gale","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6klEQVRIiWNgGAWjYBACxgYog4+B+QCQkpAhXgsbA1sCSAsP8daxMfAYgGjCWpjb2x9/+MBQK8/G3vP51Y0aCx4G9sNHN+B1WM8ZM8kZDMcN23jObrPOOQZ0GE9a2g28WmbksDHzMBxjbJPI3WacwwbUIsFjhl/L/OePP/9hOGbfJv/mmXHOP2K0zGAwkGZgqElsk+BhfpzbRoyWnhwzyR6DA8ltPGlmzLl9EjxshPxi2H788YcfFXW2/eyHH3/O+VYnx89++Bh+LQ0g0uAwiGSTAJP4lIOAPISqAxHMHwipHgWjYBSMgpEJAAQ1Q9YB6lqcAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-6616-445X","institution":"University of Otago Wellington","correspondingAuthor":true,"prefix":"","firstName":"Jesse","middleName":"","lastName":"Gale","suffix":""},{"id":449503239,"identity":"7c9f8a1b-f04a-4a28-8d52-500d4f24cb27","order_by":1,"name":"Zung Mai","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Zung","middleName":"","lastName":"Mai","suffix":""},{"id":449503240,"identity":"141d430a-34a0-4434-a536-9410cb3209e9","order_by":2,"name":"Anthony Wells","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Anthony","middleName":"","lastName":"Wells","suffix":""},{"id":449503241,"identity":"e796dbc8-4d8e-4d3f-90fa-d53448d1104d","order_by":3,"name":"Robin Willink","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Robin","middleName":"","lastName":"Willink","suffix":""}],"badges":[],"createdAt":"2025-04-15 22:40:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6458135/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6458135/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82162397,"identity":"18564a2e-5f03-4ce1-9ee9-d5008ba0d1ca","added_by":"auto","created_at":"2025-05-07 08:44:53","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":322804,"visible":true,"origin":"","legend":"\u003cp\u003eHypothetical scatter plots similar to Figures 3 and 4, with nine samples from an elliptical population.\u0026nbsp; Figure 1a shows continuous variables with precise measurement, and estimates of \u003cem\u003eτ\u003c/em\u003e, \u003cem\u003et\u003c/em\u003e\u003csub\u003ea\u003c/sub\u003e and \u003cem\u003et\u003c/em\u003e\u003csub\u003ed\u003c/sub\u003e are equal.\u0026nbsp; Figure 1b shows the same continuous variables discretised by rounding into a low number of possible measurements, illustrating how \u003cem\u003et\u003c/em\u003e\u003csub\u003ea\u003c/sub\u003e will underestimate \u003cem\u003eτ\u003c/em\u003e and \u003cem\u003et\u003c/em\u003e\u003csub\u003ed\u003c/sub\u003e will overestimate \u003cem\u003eτ\u003c/em\u003e.\u003c/p\u003e","description":"","filename":"fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6458135/v1/cc5bc6a0cde7fbab208cab4c.jpg"},{"id":82162399,"identity":"1386e083-ab77-4b59-ad52-2b483adfd921","added_by":"auto","created_at":"2025-05-07 08:44:53","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":390556,"visible":true,"origin":"","legend":"\u003cp\u003eThe proportion of eyes with normal (white), borderline (grey) or abnormal (black) results on four colour-vision tests, by severity of glaucoma on SAP perimetry.\u003c/p\u003e","description":"","filename":"fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6458135/v1/15ae8368719999b530b8c468.jpg"},{"id":82162401,"identity":"665ead23-68d7-4e1f-9da5-4b3645a36c20","added_by":"auto","created_at":"2025-05-07 08:44:53","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":540628,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plots showing the relationship between colour vision (y axes) and the average sensitivity of the four central points (x axes) of each perimeter. The D15 error score is shown on an inverted scale so that all plots show better colour vision toward the top of the plot.\u003c/p\u003e","description":"","filename":"fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6458135/v1/b105e578b6a59a53bf41afca.jpg"},{"id":82163992,"identity":"766adf1e-cbeb-4a0b-9afe-f1f62cf6b56a","added_by":"auto","created_at":"2025-05-07 09:00:53","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":522396,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plots showing the relationship between colour vision (y axes) and the mean deviation (x axes) of each perimeter. The D15 error score is shown on an inverted scale so that all plots show better colour vision toward the top of the plot.\u003c/p\u003e","description":"","filename":"fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6458135/v1/126f639378559091383d3462.jpg"},{"id":86644449,"identity":"002799d9-d6eb-43d3-a86e-3eac63305cb4","added_by":"auto","created_at":"2025-07-14 08:39:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2513035,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6458135/v1/3c5bc476-271e-435a-b7e4-a9e2087fb455.pdf"}],"financialInterests":"There is no conflict of interest","formattedTitle":"The relationship between colour vision defects and visual field tests in glaucoma","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn glaucoma the central vision, represented by both visual acuity and colour vision, is usually preserved until late, when visual field loss has become advanced and encroaching on central vision. This pattern is clinically familiar, and colour vision tests are useful to help to detect non-glaucomatous optic neuropathy \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. However, contrary to clinical experience subtle colour-vision defects (CVD) are commonly detected in glaucoma in a research setting, generally non-specific or in the blue-yellow axis.\u003csup\u003e\u003cspan additionalcitationids=\"CR3 CR4 CR5 CR6\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e In studies of ocular hypertensive patients and early glaucoma, CVD occurred in 40% (as compared to 15% of controls)\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e and were associated with high intraocular pressure (IOP) and indicative of future visual field loss.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e The correlation between these CVD and the visual field is not strong, so there are patients with normal visual fields in early glaucoma who have CVD, and there are patients with advanced visual field loss from glaucoma who have normal colour vision.\u003c/p\u003e \u003cp\u003eVisual fields in glaucoma are typically measured with white-on-white standard automated perimetry (SAP, size III stimulus, 0.43\u0026deg; diameter). Alternative visual field testing stimuli include: 1) short-wave automated perimetry (SWAP) where blue stimuli (size V, approximately 1.7\u0026deg; diameter) are presented on a yellow background;\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e or 2) frequency doubling technology (FDT) where larger square stimuli of sine-wave gratings (0.5 cycles per degree, approximately 5\u0026deg; grating) are presented with 18 Hz counterphase flickering against an isoluminant background.\u003csup\u003e\u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e These alternative visual field tests have some limitations, for example SWAP can be sensitive but suffers from longer test times, greater variation between tests, more susceptibility to age and cataract, and is no longer in common clinical usage.\u003csup\u003e\u003cspan additionalcitationids=\"CR21 CR22 CR23 CR24 CR25 CR26 CR27\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe purpose of this study was to investigate whether the clinically recognised relationship between visual fields and CVD is stronger with alternative visual field stimuli or alternative colour vision tests. Colour vision tests vary in their sensitivity and their ability to reveal mild blue-yellow CVD. While subtle CVD may occur with normal central SAP results in mild glaucoma, we hypothesised that SWAP or FDT stimuli might have higher concordance with CVD. This would be of clinical interest because it would indicate either a regional or a diffuse effect of glaucoma on the colour vision function.\u003c/p\u003e \u003cp\u003eThe sensitivity values provided by SAP, SWAP and FDT cannot be compared on the same scale (there is non-linearity between variables), and when continuous variables are rounded to discrete values it results in ties that affect measurement of correlation: for these reasons our analysis required a new approach to estimating concordance between tests, using Kendall\u0026rsquo;s tau. In our secondary analysis we also sought to identify whether features of the eye are associated with more discrepancy between colour vision tests and central visual field sensitivity.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eApprovals\u003c/h2\u003e \u003cp\u003e The University of Otago Human Ethics Committee (Health) approved this study (reference\u003c/p\u003e \u003cp\u003eH20/093). The Ngāi Tahu Research Consultation Committee (Te Komiti Rakahau ki Kāi Tahu) acknowledged the goals of the project. The study was conducted in accordance with the Declaration of Helsinki and all participants gave written informed consent.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDesign\u003c/h3\u003e\n\u003cp\u003eThis was a cross-sectional observational study recruiting participants with a diagnosis of glaucoma, confirmed by fellowship-trained glaucoma specialists (JG and APW). The inclusion criteria were: participants aged 18\u0026ndash;80 years with a confirmed diagnosis of glaucoma, who were willing and able to give informed consent, with corrected acuity of at least 6/12 in included eyes. Exclusion criteria were congenital CVD, inability to attend for testing, other diseases affecting the retina, optic nerve, or visual field, and previous intraocular surgery (other than surgery for cataract or glaucoma more than 3 months previously). Participants were invited from clinics to attend one additional session of visual field and colour vision testing.\u003c/p\u003e\n\u003ch3\u003eProcedures\u003c/h3\u003e\n\u003cp\u003eAll tests were performed separately in each eye, with the other eye patched. Participants all performed three visual field tests: 1) SAP was Humphrey perimetry using the Swedish Interactive Testing Algorithm (SITA) Standard 24\u0026thinsp;\u0026minus;\u0026thinsp;2 protocol (HFA3, Zeiss, Dublin, CA, USA); 2) SWAP was Humphrey SITA-SWAP 24\u0026thinsp;\u0026minus;\u0026thinsp;2 protocol (HFA2, Zeiss, Dublin, CA, USA); 3) FDT was Matrix perimeter FDT 24\u0026thinsp;\u0026minus;\u0026thinsp;2 Threshold protocol (Matrix, Zeiss, Dublin, CA, USA). The order of perimetry testing was not pre-determined, but not randomised; participants completed the tests in a flexible sequence based on availability of equipment. When not performed at the same visit, all visual field tests were completed within 3 months of each other. Autorefraction or focimetry was performed, for suitable refractive correction.\u003c/p\u003e \u003cp\u003eParticipants also performed three tests of central colour vision separately with each eye: 1) Ishihara plates, scored as an integer of 0\u0026ndash;12 test plates correct; 2) Hardy Rand Rittler (HRR) plates (4th edition), scored as 0\u0026ndash;2 blue-yellow (B-Y) screening plates correct and 0\u0026ndash;4 red-green (R-G) screening plates correct; and 3) the desaturated Lanthony D-15 panel test.\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e The D15 colour test results were processed using the website \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ewww.torok.info\u003c/span\u003e\u003cspan address=\"http://www.torok.info\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e which generates a range of error scores: we used the \u0026ldquo;total error score\u0026rdquo; as our primary measure. Only the screening plates of HRR were used, because the other HRR plates have greater colour contrast and are only useful to characterise the nature and extent of more-severe CVD. The colour tests were all performed under standard illumination with a lamp 0.5 m above the testing surface (Philips LED 2300 lumen 19 W bulb, 6500 K colour temperature, with colour rendering index 80) and illuminance on the testing table was measured between 1850\u0026ndash;1950 lux with Mastech MS6612 lux meter).\u003c/p\u003e\n\u003ch3\u003eData and description\u003c/h3\u003e\n\u003cp\u003eAll completed tests were included, we did not exclude or adjust results based on reliability measures. The results of each field test were summarised as (i) a mean deviation, MD, which is the average difference between the sensitivity value at each point and the age-specific sensitivity, averaged over the 24\u0026thinsp;\u0026minus;\u0026thinsp;2 field, (a discrete variable with a large number of possible values), (ii) the average (i.e. arithmetic mean) of the sensitivity values at the four central points (a discrete variable in 0.25 dB intervals), and (iii) the maxima and minima of the sensitivity values at the four central points (a discrete variable with integer values of dB). Individual sensitivity values expressed as \u0026lt;\u0026thinsp;0 dB were imputed to be 0 dB. Each colour test resulted in an integer value.\u003c/p\u003e \u003cp\u003eFor the purpose of description, the severities of glaucoma and CVD were assigned to predefined categories. The severity of glaucoma was categorized using the mean deviation MD recorded with SAP: mild when \u0026lsquo;MD \u0026gt; -6 dB (including 7 eyes with no definite glaucoma), moderate when \u0026lsquo;-12 dB\u0026thinsp;\u0026lt;\u0026thinsp;MD \u0026le; -6 dB\u0026rsquo;, and severe if \u0026lsquo;MD \u0026le; -12 dB\u0026rsquo;. With D15 data, colour-vision status was categorized as normal when \u0026lsquo;error score\u0026thinsp;=\u0026thinsp;0\u0026rsquo;, borderline when \u0026lsquo;1\u0026thinsp;\u0026le;\u0026thinsp;error score\u0026thinsp;\u0026le;\u0026thinsp;25\u0026rsquo;, and abnormal when \u0026lsquo;error score\u0026thinsp;\u0026ge;\u0026thinsp;26\u0026rsquo;. With the Ishihara test, the status was categorized as normal when the results were correct for all 12 plates, borderline when the results were correct for 11 plates, and abnormal otherwise. With HRR R-G, the status was categorized as normal when the results were correct for all four plates, borderline when the results were correct for three plates, and abnormal otherwise. With HRR B-Y, the status was categorized as normal when the results were correct for both plates, borderline when the results were correct for one plate, and abnormal if the results were incorrect for both plates.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eIn analysing the visual-field sensitivities and colour-vision test results, the data from each test were considered to be outcomes of random variables with non-normal distributions and with conditional means related by non-linear relationships. This is appropriate because of the logarithmic nature of the sensitivity data and the unknown scales of colour vision test scores.\u003c/p\u003e \u003cp\u003eConsequently, the familiar Pearson measure of linear correlation, r, lacks meaning.\u003c/p\u003e \u003cp\u003eSometimes, the analysis of such data is carried out using Spearman\u0026rsquo;s rank-correlation coefficient, r\u003csub\u003eS\u003c/sub\u003e, but the analogous population parameter, \u003cem\u003eρ\u003c/em\u003e\u003csub\u003eS\u003c/sub\u003e, does not have a useful interpretation. Therefore, we studied this problem using Kendall\u0026rsquo;s statistic of concordance, t, which is an estimate of an unknown population parameter \u003cem\u003eτ\u003c/em\u003e (tau). This parameter is defined to be \u003cem\u003eτ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2\u003cem\u003eπ\u003c/em\u003e\u003csub\u003ec\u003c/sub\u003e-1, where \u003cem\u003eπ\u003c/em\u003e\u003csub\u003ec\u003c/sub\u003e is the probability that two variables are \u0026lsquo;concordant\u0026rsquo;, i.e. the probability that when two members, A and B, of the population are chosen randomly the differences in the two variables are in the same direction. In the present problem, this would be the probability that, given A has a better visual-field result than B, A also has a better colour-vision result than B. So, Kendall\u0026rsquo;s \u003cem\u003eτ\u003c/em\u003e can take any value from \u0026minus;\u0026thinsp;1 to 1, and it has a clear and meaningful interpretation.\u003c/p\u003e \u003cp\u003eFigure 1 gives an illustrative example of the type of scatter plot presented later in Figs.\u0026nbsp;3 and 4. It imagines colour-vision results plotted against visual-field results in a sample from a population occupying the ellipse uniformly. The orientation of the ellipse is such that most, but not all, of the line-segments joining random points in the ellipse have positive slope. So there is a concordant relationship between the two results, but not perfect concordance, so \u003cem\u003eτ\u003c/em\u003e lies between 0 and 1.\u003c/p\u003e \u003cp\u003eFigure 1a shows the results for a fictitious sample of nine eyes, connected by line-segments each indicating either a concordant pair (solid line segment) or a discordant pair (dotted line segment). The proportion of pairs that are concordant is \u003cem\u003ep\u003c/em\u003e\u003csub\u003e\u003cem\u003ea\u003c/em\u003e\u003c/sub\u003e = 30/36\u0026thinsp;=\u0026thinsp;5/6, resulting in the point estimate of \u003cem\u003eτ\u003c/em\u003e being \u003cem\u003et\u003c/em\u003e\u003csub\u003e\u003cem\u003ea\u003c/em\u003e\u003c/sub\u003e = 2/3. A confidence interval for \u003cem\u003eτ\u003c/em\u003e can then be found by bootstrapping, in which repeated samples of the same size are taken \u003cem\u003ewith\u003c/em\u003e replacement, to approximate the unknown distribution of error in the population. From numerous re-samplings, an approximate 95% confidence interval for \u003cem\u003eτ\u003c/em\u003e is found using the 2.5th and 97.5th percentiles of the set of \u003cem\u003et\u003c/em\u003e\u003csub\u003ea\u003c/sub\u003e values.\u003c/p\u003e \u003cp\u003eThis description applies to continuous variables. However, in clinical testing, the continuously variable levels of colour vision or visual field are rounded into discrete scales, as illustrated in Fig.\u0026nbsp;1b. Such rounding means that some subjects incorrectly appear to have the same level of vision, with the associated line segments being horizontal or vertical. The corresponding pairs appear \u0026lsquo;tied\u0026rsquo;, rather than concordant or discordant. The existence of these artificial ties means that \u003cem\u003et\u003c/em\u003e\u003csub\u003e\u003cem\u003ea\u003c/em\u003e\u003c/sub\u003e tends to \u003cem\u003eunderestimate\u003c/em\u003e the magnitude of \u003cem\u003eτ.\u003c/em\u003e A natural adjustment for this is to estimate the proportion of concordant pairs amongst only the concordant or discordant pairs (not tied). This leads to an estimate \u003cem\u003ep\u003c/em\u003e\u003csub\u003ed\u003c/sub\u003e that is greater than \u003cem\u003ep\u003c/em\u003e\u003csub\u003ea\u003c/sub\u003e because of the smaller denominator, which results in an estimate of \u003cem\u003et\u003c/em\u003e\u003csub\u003ed\u003c/sub\u003e further from zero than \u003cem\u003et\u003c/em\u003e\u003csub\u003ea\u003c/sub\u003e. However, as seen when comparing Fig.\u0026nbsp;1b with Fig.\u0026nbsp;1a, rounding leads to the removal of disproportionately more discordant pairs than concordant pairs, so \u003cem\u003et\u003c/em\u003e\u003csub\u003e\u003cem\u003ed\u003c/em\u003e\u003c/sub\u003e tends to \u003cem\u003eoverestimate\u003c/em\u003e the magnitude of \u003cem\u003eτ\u003c/em\u003e.\u003c/p\u003e \u003cp\u003eFor our primary analysis, we assessed the hypothesis that, in the population of eyes, the D15 results are equally concordant with the results when averaging the central points on each of the three perimeters. The analysis involved carrying out a test of the hypothesis that the three individual values of \u003cem\u003eτ\u003c/em\u003e are equal (\u003cem\u003eα\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.05). Bootstrapping was used to estimate the null error distribution: if \u003cb\u003ex\u003c/b\u003e is the estimate of the vector of parameter-differences, \u003cb\u003eX*\u003c/b\u003e is an estimator from a bootstrap-sample and \u003cb\u003ev\u003c/b\u003e is the covariance matrix of the bootstrap-estimates then the p-value of the test that the parameters are equal, i.e., that the vector of parameter differences is \u003cb\u003e0\u003c/b\u003e, is the probability that (\u003cb\u003eX*\u003c/b\u003e-\u003cb\u003ex\u003c/b\u003e)\u003csup\u003eT\u003c/sup\u003e \u003cb\u003ev\u003c/b\u003e\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (\u003cb\u003eX*\u003c/b\u003e-\u003cb\u003ex\u003c/b\u003e) equals or exceeds the quantity (\u003cb\u003ex\u003c/b\u003e-\u003cb\u003e0\u003c/b\u003e)\u003csup\u003eT\u003c/sup\u003e \u003cb\u003ev\u003c/b\u003e\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (\u003cb\u003ex\u003c/b\u003e-\u003cb\u003e0\u003c/b\u003e).\u003c/p\u003e \u003cp\u003ePost-hoc analyses included the comparison of concordances between each of the four colour-vision tests and MD or the maxima and minima of the four central points, for all three types of perimetry.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003eA total of 54 participants were recruited, and one was excluded due to a congenital protanomaly. The mean age was 65.3 years (standard deviation 10.5 years, range 31\u0026ndash;79 years) and 23 (43%) were female. Their clinical characteristics are shown in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Of the 106 eyes, 63 had mild glaucoma, 27 were moderate in severity, and nine were severe. There were seven normal fellow eyes, included in analyses. Due to equipment availability, only 93 of the 106 eyes had results for all three of SAP, SWAP and FDT, so three-way hypothesis testing was based on this slightly reduced data set.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlaucoma type\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary open angle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (50%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal tension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (29%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary angle closure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnaffected fellow eye\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCataract surgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (23%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGlaucoma drainage surgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (19%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGlaucoma severity\u003c/b\u003e\u003c/p\u003e \u003cp\u003eSAP mean deviation (dB)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-5.28\u0026thinsp;\u0026plusmn;\u0026thinsp;4.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSWAP mean deviation (dB)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-7.27\u0026thinsp;\u0026plusmn;\u0026thinsp;5.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFDT mean deviation (dB)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-6.04\u0026thinsp;\u0026plusmn;\u0026thinsp;5.93\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMost recent IOP (mmHg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4 (8\u0026ndash;22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eColour vision\u003c/h3\u003e\n\u003cp\u003eFigure 2 shows the proportion of 106 eyes in the study, with normal, borderline or abnormal colour vision test results, for each severity of glaucoma (based on SAP definitions above, normal eyes included with \u0026lsquo;mild\u0026rsquo;). This shows that D15 was more sensitive than other colour-vision tests (more often abnormal, especially in mild glaucoma or fellow eyes, see Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), but the proportion that were abnormal with D15 did not correlate as well as other tests with the severity of glaucoma.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eNumber (and percentage) with abnormal colour vision by sub-group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of eyes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLanthony\u003c/p\u003e \u003cp\u003eD15\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIshihara\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHRR B-Y\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHRR R-G\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (48%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (22%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15 (25%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (17%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (17%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12 (26%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u0026thinsp;\u0026lt;\u0026thinsp;65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (11%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u0026thinsp;\u0026gt;\u0026thinsp;65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (46%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (26%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12 (18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23 (34%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGlaucoma Type\u003c/b\u003e\u003c/p\u003e \u003cp\u003ePOAG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (43%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13 (25%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNTG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6 (19%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePACG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5 (83%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (56%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (11%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (11%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (22%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnaffected\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (43%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (14%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlaucoma surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11 (55%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo glaucoma surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (16%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16 (19%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCataract surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (46%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (46%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13 (54%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo cataract surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14 (17%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIOP\u0026thinsp;\u0026lt;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (21%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18 (27%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIOP\u0026thinsp;\u0026gt;\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (45%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9 (23%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAs suggested in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, demographic and clinical characteristics did not affect the extent of colour-vision abnormality in a clinically significant way. There was a trend towards more abnormality in those with a history of raised IOP (primary angle closure or secondary glaucoma) compared to those with normal tension glaucoma. Cataract surgery seemed to be associated with more CVD using Ishihara and HRR tests, which could reflect older participants with more advanced glaucoma (phakic eyes average age 62 years, average SAP MD -5.2 dB; pseudophakic eyes average age 73 years, average SAP MD -6.4 dB).\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eConcordance between colour and fields\u003c/h2\u003e \u003cp\u003eThe relationships between colour-vision test results and each of the visual-field test results are shown in Fig.\u0026nbsp;3 (average of the four central points, a measure of central visual field sensitivity) and Fig.\u0026nbsp;4 (mean deviation, an overall measure of field sensitivity).\u003c/p\u003e \u003cp\u003eEach of the 12 scatter plots in each figure also displays both \u003cem\u003et\u003c/em\u003e\u003csub\u003ea\u003c/sub\u003e and \u003cem\u003et\u003c/em\u003e\u003csub\u003ed\u003c/sub\u003e (estimates of Kendall\u0026rsquo;s \u003cem\u003eτ\u003c/em\u003e) with 95% confidence intervals for \u003cem\u003eτ\u003c/em\u003e. As seen in Fig.\u0026nbsp;3, the estimates of \u003cem\u003eτ\u003c/em\u003e for D15 and the average of central points from the three visual field tests range from 0.06 to 0.23, which we interpret as being small. The 95% confidence intervals for the individual concordances overlap. (These intervals were obtained with bootstrap samples of size 9999.)\u003c/p\u003e \u003cp\u003eIn relation to the primary research question, there is insufficient evidence in the data to reject the hypothesis that the D15-SAP, D15-SWAP and D15-FDT concordances are equal: the p-value for the three-way test of equality was 0.08 using t\u003csub\u003ea\u003c/sub\u003e and 0.09 using t\u003csub\u003ed\u003c/sub\u003e. (This test was carried out with a bootstrap sample of size 999999.)\u003c/p\u003e \u003cp\u003eTo summarise Figs.\u0026nbsp;3 and 4, there was relatively weak concordance between most field test results and D15 or Ishihara results, but some patterns were observed: 1) FDT perimetry tended to have higher concordance with colour-vision tests, as compared to SAP and SWAP; 2) HRR screening plates (both B-Y and R-G) had higher concordance despite the large numbers of ties due to the highly discretized values (that is, both \u003cem\u003et\u003c/em\u003e\u003csub\u003ea\u003c/sub\u003e and \u003cem\u003et\u003c/em\u003e\u003csub\u003ed\u003c/sub\u003e were higher for HRR than other colour-vision tests); 3) there was no meaningful difference between the concordance of colour vision with overall field sensitivity (MD, Fig.\u0026nbsp;4) as compared with the concordance of colour vision with central field sensitivity (average of central points, Fig.\u0026nbsp;3).\u003c/p\u003e \u003cp\u003eThe average, maxima, or minima of the four central points all showed similar levels of concordance with colour vision tests.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eIntraocular pressures in the eyes with colour/field discrepancy\u003c/h2\u003e \u003cp\u003eThe similar concordance measures for MD and the central field sensitivities indicated that there was no localised central field defect to explain CVD using any of the visual field test stimuli. This concurs with reported findings in early glaucoma and ocular hypertension (with normal visual fields), where it was suggested that CVD were more common with raised IOP and predicted glaucomatous progression.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e We pursued this hypothesis by considering the eyes with the most clear discrepancy between visual fields and colour vision, and the most recent IOP.\u003c/p\u003e \u003cp\u003eIn our study there were 70 eyes with SAP MD \u0026gt; -6 dB of which 28 had abnormal D15 results, eight had abnormal Ishihara results, eight abnormal HRR R-G and four abnormal HRR B-Y results. In all of these groups of eyes, the last recorded IOP value ranged from 8 to 20 mmHg with no pattern or trend observed, so these eyes were not hypertensive, contrary to previous suggestions.\u003c/p\u003e \u003cp\u003eThere were nine eyes with SAP MD \u0026le; -12 dB, and we considered the most recent IOP in those with normal colour-vision results. Three of these eyes with severe glaucoma had normal D15 results (IOP 13, 18, 20 mmHg), four had normal Ishihara results (IOP 9, 11, 18, 20 mmHg), and the same three eyes had normal HRR R-G and B-Y results (IOP 11, 18, 20 mmHg). At least two of these eyes in each group had IOP that was probably greater than ideal target IOP of 12 mmHg for eyes with advanced glaucoma, so the discrepancy could not be explained by a very low IOP.\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe concordance between the central visual field sensitivity and tests of colour vision remains fairly low in glaucoma, regardless of the visual field stimulus. The FDT, with a larger 5 degree stimulus coming closer to the foveal centre, appeared to have greater concordance with CVD than SAP or SWAP, but this did not reach significance in our primary hypothesis with a sample of 53 people. Various measures of central visual field function (average, maxima or minima of central points) appeared no more closely associated with CVD than overall MD. Together these data suggest no regional or localised central visual field defect can explain the high prevalence of CVD in glaucoma, and infers a generalised diffuse effect of glaucoma on the colour function.\u003c/p\u003e \u003cp\u003eIn comparing colour tests, the Lanthony D15 was most often abnormal, but it was less closely associated with glaucoma severity than Ishihara and HRR screening tests (see Fig.\u0026nbsp;2). This finding suggests the more sensitive D15 test is not superior in clinical use, indeed it was abnormal in 3 of 7 unaffected fellow eyes (43%). This study was not designed to consider which colour vision test was best able to indicate a non-glaucomatous optic neuropathy.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe weak relationships between CVD and visual fields suggest that when colour is reduced in glaucoma it is a diffuse effect, or related to extraneous factors (age, cataract, acuity). We did not find a trend towards higher IOP in those with CVD and mild glaucoma, but those with secondary or angle closure glaucoma were more likely to have CVD. Angle closure patients were also older (average age 75 years, compared to 64 years in other participants), and had mildly worse glaucoma (average MD -6.9 dB ,compared to -5.4 dB in other eyes). This remains an intriguing area for future study and raises new hypotheses for investigation. Clinical tests that might correlate with this diffuse loss of CVD in glaucoma include macular optical coherence tomography (OCT) of ganglion cell layer thickness, microperimetry, or provocative IOP challenges.\u003c/p\u003e \u003cp\u003eIt remains possible that a small and very central defect in vision from glaucoma affected the colour vision in some subjects while paracentral visual field test points were normal. This seems unlikely as there were very similar levels of concordance between overall and central visual field sensitivity, and glaucoma does not generally cause central foveal pathology. The central visual field can be scrutinized more closely with a 10\u0026thinsp;\u0026minus;\u0026thinsp;2 protocol, but only a 24\u0026thinsp;\u0026minus;\u0026thinsp;2 protocol was available for SWAP perimetry.\u003c/p\u003e \u003cp\u003eThe clinical implications of this study are that colour vision is often diffusely abnormal in glaucoma, so neuroimaging is not required for everyone with an abnormal result. The FDT (with larger stimuli) appeared more concordant with CVD but this does not imply improved clinical utility. Quick colour testing books (Ishihara and HRR) were more concordant with visual function than D15, only indicating that the more time consuming D15 test is not a superior screening test. Understanding the pathophysiology underlying CVD in glaucoma remains an interesting area for investigation, with improved imaging and electrophysiological techniques.\u003csup\u003e312\u003c/sup\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of interest\u003c/h2\u003e \u003cp\u003eNo conflicting relationship exists for any author. No funding was received for this work.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eThe authors gratefully acknowledge Dr Andrew Logan and Mariana Eaton of Wellington Eye Centre, Wellington, for the generous facilitation of this study through use of their Humphrey short-wave automated perimetry device.\u003c/p\u003e\u003ch2\u003eMeeting presentation\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThis work was presented at the Australia and New Zealand Glaucoma Society annual meeting held virtually in February 2021 and the Royal Australian and New Zealand College of Ophthalmologist, New Zealand Branch Annual Scientific Meeting 2023.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWaisberg E, Micieli JA. Neuro-Ophthalmological Optic Nerve Cupping: An Overview. \u003cem\u003eEye Brain \u003c/em\u003e2021; \u003cstrong\u003e13: \u003c/strong\u003e255-268.\u003c/li\u003e\n\u003cli\u003eFlammer J, Drance SM. 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Method of quantification and normal scores]. \u003cem\u003eJournal francais d\u0026apos;ophtalmologie \u003c/em\u003e1986; \u003cstrong\u003e9\u003c/strong\u003e(12)\u003cstrong\u003e: \u003c/strong\u003e843-847.\u003c/li\u003e\n\u003cli\u003eYu TC, Falcao-Reis F, Spileers W, Arden GB. Peripheral color contrast. A new screening test for preglaucomatous visual loss. \u003cem\u003eInvest Ophthalmol Vis Sci \u003c/em\u003e1991; \u003cstrong\u003e32\u003c/strong\u003e(10)\u003cstrong\u003e: \u003c/strong\u003e2779-2789.\u003c/li\u003e\n\u003cli\u003eFortune B. Pulling and Tugging on the Retina: Mechanical Impact of Glaucoma Beyond the Optic Nerve Head. \u003cem\u003eInvest Ophthalmol Vis Sci \u003c/em\u003e2019; \u003cstrong\u003e60\u003c/strong\u003e(1)\u003cstrong\u003e: \u003c/strong\u003e26-35.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Glaucoma, optic neuropathy, color vision defects, automated perimetry ","lastPublishedDoi":"10.21203/rs.3.rs-6458135/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6458135/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003ePurpose\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe relationship between colour vision defects (CVD) and visual field test results in glaucoma can be counterintuitive. We sought to examine the relationship between three tests of colour vision and three types of perimetry in glaucoma.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMaterials and methods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eIn this cross-sectional study, we included both eyes of 53 patients with glaucoma. We conducted white-on-white Standard Automated Perimetry (SAP), blue-on-yellow Short Wave Automatic Perimetry (SWAP) and sine-grating Frequency Doubling Technology (FDT) perimetry, as well as Ishihara, Hardy-Rand-Rittler (HRR) and desaturated Lanthony D-15 tests of central colour vision. Our primary analysis used Kendall\u0026rsquo;s tau to measure the probability that an increase in one variable, the average of SAP or SWAP of FDT central point sensitivities, is accompanied by concordant increase in colour vision.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThere are weak concordances between D15 and SAP (-0.01\u0026thinsp;\u0026le;\u0026thinsp;τ\u0026thinsp;\u0026le;\u0026thinsp;0.21), D15 and SWAP (-0.03\u0026thinsp;\u0026le;\u0026thinsp;τ\u0026thinsp;\u0026le;\u0026thinsp;0.22), and D15 and FPT (0.03\u0026thinsp;\u0026le;\u0026thinsp;τ\u0026thinsp;\u0026le;\u0026thinsp;0.30). There was insufficient evidence in the sample to conclude that these concordances differ (p\u0026thinsp;=\u0026thinsp;0.08). There appear to be stronger concordances between HRR and the results of visual field tests (0.09\u0026thinsp;\u0026le;\u0026thinsp;τ), the strongest being with FDT (0.13\u0026thinsp;\u0026le;\u0026thinsp;τ).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe effect of glaucoma on colour vision appears to be diffuse, not closely concordant with overall or central visual field function.\u003c/p\u003e","manuscriptTitle":"The relationship between colour vision defects and visual field tests in glaucoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-07 08:44:48","doi":"10.21203/rs.3.rs-6458135/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2dfe131b-9aff-4dc7-a314-a7fa8be2a064","owner":[],"postedDate":"May 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":47831725,"name":"Health sciences/Diseases/Eye diseases/Optic nerve diseases"},{"id":47831726,"name":"Health sciences/Signs and symptoms/Eye manifestations"}],"tags":[],"updatedAt":"2025-07-14T08:31:16+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-07 08:44:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6458135","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6458135","identity":"rs-6458135","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}