Produção Nacional
Revisado por pares
Red-Green Color Vision Impairment in Duchenne Muscular Dystrophy
2007; Elsevier BV; Volume: 80; Issue: 6 Linguagem: Inglês
10.1086/518127
ISSN1537-6605
AutoresMarcelo Fernandes Costa, A. G. F. Oliveira, Cláudia Feitosa-Santana, Mayana Zatz, Dora Fix Ventura,
Tópico(s)Muscle Physiology and Disorders
ResumoThe present study evaluated the color vision of 44 patients with Duchenne muscular dystrophy (DMD) (mean age 14.8 years; SD 4.9) who were submitted to a battery of four different color tests: Cambridge Colour Test (CCT), Neitz Anomaloscope, Ishihara, and American Optical Hardy-Rand-Rittler (AO H-R-R). Patients were divided into two groups according to the region of deletion in the dystrophin gene: upstream of exon 30 (n=12) and downstream of exon 30 (n=32). The control group was composed of 70 age-matched healthy male subjects with no ophthalmological complaints. Of the patients with DMD, 47% (21/44) had a red-green color vision defect in the CCT, confirmed by the Neitz Anomaloscope with statistical agreement (P<.001). The Ishihara and the AO H-R-R had a lower capacity to detect color defects—5% and 7%, respectively, with no statistical similarity between the results of these two tests nor between CCT and Anomaloscope results (P>.05). Of the patients with deletion downstream of exon 30, 66% had a red-green color defect. No color defect was found in the patients with deletion upstream of exon 30. A negative correlation between the color thresholds and age was found for the controls and patients with DMD, suggesting a nonprogressive color defect. The percentage (66%) of patients with a red-green defect was significantly higher than the expected <10% for the normal male population (P<.001). In contrast, patients with DMD with deletion upstream of exon 30 had normal color vision. This color defect might be partially explained by a retina impairment related to dystrophin isoform Dp260. The present study evaluated the color vision of 44 patients with Duchenne muscular dystrophy (DMD) (mean age 14.8 years; SD 4.9) who were submitted to a battery of four different color tests: Cambridge Colour Test (CCT), Neitz Anomaloscope, Ishihara, and American Optical Hardy-Rand-Rittler (AO H-R-R). Patients were divided into two groups according to the region of deletion in the dystrophin gene: upstream of exon 30 (n=12) and downstream of exon 30 (n=32). The control group was composed of 70 age-matched healthy male subjects with no ophthalmological complaints. Of the patients with DMD, 47% (21/44) had a red-green color vision defect in the CCT, confirmed by the Neitz Anomaloscope with statistical agreement (P<.001). The Ishihara and the AO H-R-R had a lower capacity to detect color defects—5% and 7%, respectively, with no statistical similarity between the results of these two tests nor between CCT and Anomaloscope results (P>.05). Of the patients with deletion downstream of exon 30, 66% had a red-green color defect. No color defect was found in the patients with deletion upstream of exon 30. A negative correlation between the color thresholds and age was found for the controls and patients with DMD, suggesting a nonprogressive color defect. The percentage (66%) of patients with a red-green defect was significantly higher than the expected <10% for the normal male population (P<.001). In contrast, patients with DMD with deletion upstream of exon 30 had normal color vision. This color defect might be partially explained by a retina impairment related to dystrophin isoform Dp260. Duchenne muscular dystrophy (DMD [MIM 310200]), which affects 1:3,500 newborn males,1Matsuo M Duchenne/Becker muscular dystrophy: from molecular diagnosis to gene therapy.Brain Dev. 1996; 18: 167-172Abstract Full Text PDF PubMed Scopus (47) Google Scholar, 2Nobile C Marchi J Nigro V Roberts RG Danieli GA Exon-intron organization of the human dystrophin gene.Genomics. 1997; 45: 421-424Crossref PubMed Scopus (31) Google Scholar, 3O'Brien KF Kunkel LM Dystrophin and muscular dystrophy: past, present, and future.Mol Genet Metab. 2001; 74: 75-88Crossref PubMed Scopus (85) Google Scholar is the most common form of progressive muscular dystrophy disease. It is caused by a deficiency in the protein called "dystrophin."4Hoffman EP Brown Jr, RH Kunkel LM Dystrophin: the protein product of the Duchenne muscular dystrophy locus.Cell. 1987; 51: 919-928Abstract Full Text PDF PubMed Scopus (3383) Google Scholar The dystrophin gene, at Xp21, has 79 exons.2Nobile C Marchi J Nigro V Roberts RG Danieli GA Exon-intron organization of the human dystrophin gene.Genomics. 1997; 45: 421-424Crossref PubMed Scopus (31) Google Scholar DMD is caused by deletions in the dystrophin gene in 60%–65% of patients, by duplications in 5%–10%, and by point mutations or small rearrangements in the remaining 20%–30%. The main pathological effects caused by mutations in the dystrophin gene are in the skeletal and cardiac muscles, although dystrophin is present in several other tissues of the body, including a widespread distribution in the nervous system.5Koenig M Monaco AP Kunkel LM The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein.Cell. 1988; 53: 219-226Abstract Full Text PDF PubMed Scopus (1210) Google Scholar In addition to full-length dystrophin, four other shorter proteins are transcribed from the DMD gene: Dp260 (transcripts spliced to exon 30), Dp140 (transcripts spliced to exon 44), Dp116 (transcripts spliced to exon 56), and Dp71 (transcripts spliced to exon 63).6Pillers DA Fitzgerald KM Duncan NM Rash SM White RA Dwinnell SJ Powell BR Schnur RE Ray PN Cibis GW et al.Duchenne/Becker muscular dystrophy: correlation of phenotype by electroretinography with sites of dystrophin mutations.Hum Genet. 1999; 105: 2-9Crossref PubMed Scopus (48) Google Scholar, 7Schmitz F Drenckhahn D Localization of dystrophin and beta-dystroglycan in bovine retinal photoreceptor processes extending into the postsynaptic dendritic complex.Histochem Cell Biol. 1997; 108: 249-255Crossref PubMed Scopus (49) Google Scholar In the retina, dystrophin is expressed at the level of the outer plexiform layer (Dp260) in the inner limiting membrane (Dp71).7Schmitz F Drenckhahn D Localization of dystrophin and beta-dystroglycan in bovine retinal photoreceptor processes extending into the postsynaptic dendritic complex.Histochem Cell Biol. 1997; 108: 249-255Crossref PubMed Scopus (49) Google Scholar, 8Claudepierre T Dalloz C Mornet D Matsumura K Sahel J Rendon A Characterization of the intermolecular associations of the dystrophin-associated glycoprotein complex in retinal Muller glial cells.J Cell Sci. 2000; 113: 3409-3417PubMed Google Scholar, 9Claudepierre T Mornet D Pannicke T Forster V Dalloz C Bolanos F Sahel J Reichenbach A Rendon A Expression of Dp71 in muller glial cells: a comparison with utrophin- and dystrophin-associated proteins.Invest Ophthalmol Vis Sci. 2000; 41: 294-304PubMed Google Scholar, 10Connors NC Kofuji P Dystrophin Dp71 is critical for the clustered localization of potassium channels in retinal glial cells.J Neurosci. 2002; 22: 4321-4327Crossref PubMed Google Scholar, 11Schmitz F Drenckhahn D Dystrophin in the retina.Prog Neurobiol. 1997; 53: 547-560Crossref PubMed Scopus (41) Google Scholar, 12Ueda H Baba T Terada N Kato Y Tsukahara S Ohno S Dystrophin in rod spherules; submembranous dense regions facing bipolar cell processes.Histochem Cell Biol. 1997; 108: 243-248Crossref PubMed Scopus (30) Google Scholar Dp260 is also found at the cone pedicle, in the region of the ribbon synapse.13Ueda H Tsukahara S Kobayashi T Ohno S Immunocytochemical study of dystrophin-related protein in the rat retina.Ophthalmic Res. 1995; 27: 219-226Crossref PubMed Scopus (11) Google Scholar Electrophysiological studies showed that Dp260 is essential for the physiology of the retina, since patients with DMD and deletions downstream of exon 30 had serious impairment in both scotopic and photopic responses obtained by full-field electroretinogram (ERG).6Pillers DA Fitzgerald KM Duncan NM Rash SM White RA Dwinnell SJ Powell BR Schnur RE Ray PN Cibis GW et al.Duchenne/Becker muscular dystrophy: correlation of phenotype by electroretinography with sites of dystrophin mutations.Hum Genet. 1999; 105: 2-9Crossref PubMed Scopus (48) Google Scholar, 14Pillers DA Bulman DE Weleber RG Sigesmund DA Musarella MA Powell BR Murphey WH Westall C Panton C Becker LE et al.Dystrophin expression in the human retina is required for normal function as defined by electroretinography.Nat Genet. 1993; 4: 82-86Crossref PubMed Scopus (140) Google Scholar, 15Pillers DM Sigesmund DA Ray PN Musarella MA Tremblay F Seltzer WK Powell B Mccabe ERB Schnur RE Panton C et al.Genotype-phenotype correlations identified by electrophysiology of the retina in Duchenne and Becker muscular-dystrophy patients.Am J Hum Genet Suppl. 1993; 53: A146Google Scholar, 16Fitzgerald KM Cibis GW Harris DJ Rothberg PG On-responses and off-responses of the photopic ERG in Duchenne muscular-dystrophy and congenital stationary night blindness.Invest Ophthalmol Vis Sci. 1993; 34: 1076Google Scholar, 17Fitzgerald KM Cibis GW Gettel AH Rinaldi R Harris DJ White RA ERG phenotype of a dystrophin mutation in heterozygous female carriers of Duchenne muscular dystrophy.J Med Genet. 1999; 36: 316-322PubMed Google Scholar, 18Tremblay F De Becker I Riddell DC Dooley JM Duchenne muscular dystrophy: negative scotopic bright-flash electroretinogram and normal dark adaptation.Can J Ophthalmol. 1994; 29: 280-283PubMed Google Scholar, 19De Becker I Riddell DC Dooley JM Tremblay F Correlation between electroretinogram findings and molecular analysis in the Duchenne muscular-dystrophy phenotype.Br J Ophthalmol. 1994; 78: 719-722Crossref PubMed Scopus (31) Google Scholar, 20D'Souza VN Nguyen TM Morris GE Karges W Pillers DA Ray PN A novel dystrophin isoform is required for normal retinal electrophysiology.Hum Mol Genet. 1995; 4: 837-842Crossref PubMed Scopus (213) Google Scholar, 21Drenckhahn D Holbach M Ness W Schmitz F Anderson LV Dystrophin and the dystrophin-associated glycoprotein, beta-dystroglycan, co-localize in photoreceptor synaptic complexes of the human retina.Neuroscience. 1996; 73: 605-612Crossref PubMed Scopus (42) Google Scholar, 22Pascual Pascual SI Molano J Pascual-Castroviejo I Electroretinogram in Duchenne/Becker muscular dystrophy.Pediatr Neurol. 1998; 18: 315-320Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 23Yang Y Zhang C Sheng W Pan S Wu D Jiang F Correlation between electroretinographic findings, clinical phenotypic and genotypic analysis in Duchenne and Becker muscular dystrophy.Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2001; 18: 32-34PubMed Google Scholar, 24Green DG Guo H Pillers DA Normal photoresponses and altered b-wave responses to APB in the mdxCv3 mouse isolated retina ERG supports role for dystrophin in synaptic transmission.Vis Neurosci. 2004; 21: 739-747Crossref PubMed Scopus (18) Google Scholar The role of Dp71 in the retinal electrophysiology is still unknown. In the work of Claudepierre et al.,8Claudepierre T Dalloz C Mornet D Matsumura K Sahel J Rendon A Characterization of the intermolecular associations of the dystrophin-associated glycoprotein complex in retinal Muller glial cells.J Cell Sci. 2000; 113: 3409-3417PubMed Google Scholar it was associated with the b-wave Muller cells' contribution to the ERG. Dp427 and Dp140 are also present in mouse retina but do not appear to make an important contribution to the ERG.25Pillers DAM Weleber RG Green DG Rash SM Dally GY Howard PL Powers MR Hood DC Chapman VM Ray PN et al.Effects of dystrophin isoforms on signal transduction through neural retina: genotype-phenotype analysis of Duchenne muscular dystrophy mouse mutants.Mol Genet Metab. 1999; 66: 100-110Crossref PubMed Scopus (50) Google Scholar Previous studies of color vision in patients with DMD or Becker muscular dystrophy (BMD), based on Ishihara and American Optical Hardy-Rand-Rittler (AO H-R-R) tests, found that the proportion of red-green defect in this group26Zatz M Itskan SB Sanger R Frota-Pessoa O Saldanha PH New linkage data for the X-linked types of muscular dystrophy and G6PD variants, colour blindness, and Xg blood groups.J Med Genet. 1974; 11: 321-327Crossref PubMed Scopus (26) Google Scholar, 27Sigesmund DA Weleber RG Pillers DA Westall CA Panton CM Powell BR Heon E Murphey WH Musarella MA Ray PN Characterization of the ocular phenotype of Duchenne and Becker muscular dystrophy.Ophthalmology. 1994; 101: 856-865Abstract Full Text PDF PubMed Scopus (75) Google Scholar was in accordance with the proportion observed for the normal population. However, the Ishihara and AO H-R-R tests are screening tests used to detect severe red-green deficiency,28Birch EE O'Connor AR Preterm birth and visual development.Semin Neonatol. 2001; 6: 487-497Abstract Full Text PDF PubMed Scopus (60) Google Scholar, 29Birch J Diagnosis of defective colour vision. Buttenworth-Heinemann, Oxford, United Kingdom2001Google Scholar but they are not sufficiently sensitive to detect moderate or light impairment. Recent studies have demonstrated an advantage of computerized color vision tests over the semiquantitative tests classically used in the evaluation of color vision, such as the Farnsworth-Munsell 100-Hue Test. The advantage is due to several aspects inherent to the programmed presentation of testing trials and to the advances in computerized color reproduction, since (1) rigorous psychophysical methodology is used, (2) changes in the chromatic steps can be varied according to the subject being tested, (3) the resolution of the chromatic steps is sufficiently fine to allow threshold measurement, and (4) online computation of the results is available. A shortcoming of the computerized tests is that they are new and experimental, and most are not commercially available. An exception to this limitation is a test designed by Mollon and Reffin,30Mollon JD Reffin JP A computer-controlled colour vision test that combines the principles of Chibret and of Stilling.J Physiol Lond. 1989; 414: 5Google Scholar which is available commercially as the Cambridge Colour Test (CCT). In the present study, we therefore reexamined color vision in patients with DMD, using this new color vision test, which is much more detailed and has been rated as more sensitive than the traditional tests.31Ventura DF Costa MF Gualtieri M Nishi M Bernick M Bonci DM de Souza J Early vision loss in diabetic patients assessed by the Cambridge Colour Test.in: Mollon JD Pokorny J Knoblauch K Normal and defective colour vision. 1st ed. Oxford University Press, New York2003: 395-403Crossref Scopus (1) Google Scholar, 32Ventura DF Silveira LC Rodrigues AR de Souza J Gualtieri M Bonci DM Costa MF Preliminary norms for the Cambridge Colour Test.in: Mollon JD Pokorny J Knoblauch K Colour and defective colour vision. 1st ed. Oxford University Press, New York2003: 331-339Crossref Scopus (4) Google Scholar, 33Ventura DF Costa MTV Costa MF Berezovsky A Salomao SR Simoes AL Lago M Pereira LHMC Faria MAM de Souza JM et al.Multifocal and full-field electroretinogram changes associated with color-vision loss in mercury vapor exposure.Vis Neurosci. 2004; 21: 421-429Crossref PubMed Scopus (52) Google Scholar, 34Ventura DF Simoes AL Tomaz S Costa MF Lago M Costa MTV Canto-Pereira LHM de Souza JM Faria MAM Silveira LCL Colour vision and contrast sensitivity losses of mercury intoxicated industry workers in Brazil.Environ Toxicol Pharmacol. 2005; 19: 523-529Crossref PubMed Scopus (56) Google Scholar, 35Castelo-Branco M Faria P Forjaz V Kozak LR Azevedo H Simultaneous comparison of relative damage to chromatic pathways in ocular hypertension and glaucoma: correlation with clinical measures.Invest Ophthalmol Vis Sci. 2004; 45: 499-505Crossref PubMed Scopus (45) Google Scholar Because it is programmed to simultaneously test the three cone-isolation axes, the CCT allows a more refined analysis of the visual pathways involved in chromatic processing—the parvocellular pathway, which mediates red-green color vision, and the koniocellular pathway, which mediates yellow-blue color vision.31Ventura DF Costa MF Gualtieri M Nishi M Bernick M Bonci DM de Souza J Early vision loss in diabetic patients assessed by the Cambridge Colour Test.in: Mollon JD Pokorny J Knoblauch K Normal and defective colour vision. 1st ed. Oxford University Press, New York2003: 395-403Crossref Scopus (1) Google Scholar, 32Ventura DF Silveira LC Rodrigues AR de Souza J Gualtieri M Bonci DM Costa MF Preliminary norms for the Cambridge Colour Test.in: Mollon JD Pokorny J Knoblauch K Colour and defective colour vision. 1st ed. Oxford University Press, New York2003: 331-339Crossref Scopus (4) Google Scholar, 34Ventura DF Simoes AL Tomaz S Costa MF Lago M Costa MTV Canto-Pereira LHM de Souza JM Faria MAM Silveira LCL Colour vision and contrast sensitivity losses of mercury intoxicated industry workers in Brazil.Environ Toxicol Pharmacol. 2005; 19: 523-529Crossref PubMed Scopus (56) Google Scholar, 35Castelo-Branco M Faria P Forjaz V Kozak LR Azevedo H Simultaneous comparison of relative damage to chromatic pathways in ocular hypertension and glaucoma: correlation with clinical measures.Invest Ophthalmol Vis Sci. 2004; 45: 499-505Crossref PubMed Scopus (45) Google Scholar We also used the Anomaloscope test—a gold standard for the detection of red-green defect—and, in addition, the Ishihara and AO H-R-R tests, which had been used in the early studies of patients with DMD. We evaluated 50 patients with DMD ranging in age from 9 to 21 years (mean 14.9 years; SD 4.3) who were referred by the Associação Brasileira de Distrofia Muscular (ABDIM) and had been given diagnoses and been followed up by the Human Genome Research Center of the Institute of Biosciences of the University of São Paulo. This study followed the tenets of the Declaration of Helsinki. Informed consent was obtained from the subjects after the nature of the study was explained. The diagnosis of DMD was established by clinical and neurological examination, family history, grossly elevated serum creatinine levels, and DNA analysis. It is known that ∼60%–65% of patients with DMD have deletions in the dystrophin gene. Deletion screening used a set of 18 primers that allowed detection of 98% of the deleted exons and that were developed by Chamberlain36Chamberlain JS Gibbs RA Ranier JE Nguyen PN Caskey CT Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification.Nucleic Acids Res. 1988; 16: 11141-11156Crossref PubMed Scopus (979) Google Scholar and Beggs.37Beggs AH Koenig M Boyce FM Kunkel LM Detection of 98% of DMD/BMD gene deletions by polymerase chain reaction.Hum Genet. 1990; 86: 45-48Crossref PubMed Scopus (635) Google Scholar Motor performance of the patients with DMD was assessed and classified according the Vignos Scale, a scale of motor-function evaluation specific to neuromuscular diseases.38Vignos Jr, PJ Diagnosis of progressive muscular dystrophy.J Bone Joint Surg Am. 1967; 49: 1212-1220PubMed Google Scholar The assessment was made by physiotherapists from the ABDIM staff. A total of 50 patients with known deletions in the dystrophin gene were selected for this study. They were classified into two groups according to the deleted region: patients with deletions upstream of exon 30 (n=12) and patients with deletions downstream of exon 30 (n=38). This distinction was made because retinal dystrophin, Dp260, is known to splice in at exon 30. The demographic data of the 50 patients with DMD are shown in table 1.Table 1Demographic Data and Color Test Results for the Patients with DMDCCT TrivectorCCT EllipsesPatientAgeDeletion in ExonProtanDeutanTritanAreaAngleT/PT/DNeitzIshiharaH-R-RVignos12185669109437.275.01.91.6NNN…2207496288608.460.31.81.4NNN93105–139798130793.7178.71.31.3NNN84178–27393558169.867.61.51.7………85178–9464675569.772.61.61.6…NN96233–71764706410,000.0159.6.4.1DDD771011–15695497587.170.11.41.8NNN68158–12586259509.868.31.02.95NNN691819485692336.250.21.921.64NNN71098–131371441411,279.461.41.03.98NNN411118–13119102113765.841.3.951.11NNN612108–138656127626.953.01.52.3NNN713947–52991052094,441.123.02.12.0PNN714948–521411341181,251.546.8.8.9…NRG71515508889110881.252.11.31.2NNN…161547–486979117708.857.71.71.5…NN9171250816481478.5105.51.01.3NNN9182040–42…………………………71912501561741491,498.9145.71.0.9…NN9201347–501171202053,365.981.61.81.7…NN721850119107821,264.767.3.7.8NNN72294510274122955.162.91.21.6PNN7231649–50728980528.028.61.1.9PNN9241138–42…………………………7259432811951442,827.0164.2.5.7DRGRG726947–5213946103747.259.6.72.2PNN8271846–55363553257.550.61.51.5…NN72813518791136627.552.11.61.5NNN…292149–521461882491,563.378.41.71.3PNN7302045–47424026502.795.0.6.7…NN…311550…………………………9322051–52466969578.589.61.51.0NNN9331848–518484129739.085.51.51.5…NN9349…………………………3351950516381711.065.71.61.3NNN7361348–52265282647.5119.13.21.6NNN8371443–458170132629.246.01.61.9NNN9381451393367384.175.71.72.0NNN6391347646089405.888.31.41.5NNN9401348–50827984711.069.71.01.1NNN7411047–521641251671,708.066.91.01.3PNN742123–60111811707,795.169.11.52.1PNN8431636…………………………8441643122731541,432.853.51.32.1…NN74510457985107830.384.81.41.3NNN146846–55…………………………3472450–52838179683.437.71.01.0PNN9481045–521632471303,315.9158.7.8.5DND1491645–52434261650.380.91.41.5NNN950945–5212798142957.294.11.11.4NNN6Note.—N = normal; D = deutan defect; P = protan defect; RG = red-green defect. Open table in a new tab Note.— N = normal; D = deutan defect; P = protan defect; RG = red-green defect. An ophthalmological examination was performed for all subjects, to eliminate confounding pathologies, such as cataracts, retinopathy, or neuropathy. Fundoscopy was performed with indirect ophthalmoscopy. Visual acuity was measured at 3 m with use of an ETDRS chart (tumbling E). All patients had normal eye fundus and 20/20 or better best-corrected visual acuity. To constitute the control group, 75 healthy male subjects ranging in age from 9 to 22 years (mean 13.9 years; SD 4.3) were tested. Inclusion criteria for this group were normal eye fundus, 20/20 or better best-corrected visual acuity, and absence of color vision defects. Five (7%) male subjects did not meet the criteria, since they had congenital color vision defect, and were excluded from the analysis. With these exclusions, the control group was composed of 70 subjects ranging in age from 9 to 22 years (mean 14.6 years; SD 4.9). The evaluation of the color discrimination was performed using the commercial version of CCT (v2.0 [Cambridge Research Instruments]) installed in a personal computer (Dell Dimension XTC-600) with a graphic board VSG 2/5 (Cambridge Research Instruments). The stimuli were generated in a high-resolution color monitor, Sony FD Trinitron model GDM-F500T9 (Sony). Testing was conducted in a dark room with the patients positioned 3 m away from the monitor. The stimulus provided by the CCT was similar to those used in the pseudoisochromatic plate tests, such as the Ishihara test (Kanehara & Co.) or the AO H-R-R (Richmond Products). The target consisted of a Landolt "C" that differed in chromaticity from the single neutral background (coordinates 0.1977, 0.4689 of u′v′ of the International Commission on Illumination [CIE] 1976 color space) (fig. 1). The Landolt C gap size corresponded to 1.25° of visual angle, with the outer diameter 5.4° and the inner diameter 2.75° at the test distance of 3 m. Both target and background were composed of small patches of varying sizes (0.5–2 cm in diameter) and six luminance levels (8, 10, 12, 14, 16, and 18 candela [cd]×m−2) randomly distributed in the display. This design used spatial and luminance noise to avoid the influence of cues derived from luminance differences or from target contours in the intended hue discrimination. The target was randomly presented with its opening in one of four positions: up, bottom, right, and left (4-Alternative Forced Choice strategy). The patient's task was to press one of the four buttons of the response box (CT3 [Cambridge Research Instruments]), to indicate the position of the "C" opening. The patients had up to 15 s to give the response. Patients with motor impairment verbally indicated the gap position, and the examiner pressed the buttons. A psychophysical staircase procedure was used for threshold determination. Each staircase began with a saturated chromaticity, which was changed along the vector connecting it to the background chromaticity. The change depended on the patient's response: the target chromaticity approached the background chromaticity every time there was a correct response and moved away from it every time there was an incorrect response or no response. The chromaticity excursion along the vectors ranged from 0.1100 to 0.0020 units of CIE 1976 u′v′. After six staircase reversals, the program automatically calculated the threshold for that vector as the average of the chromaticities corresponding to the reversals. The step size used in the staircase followed a dynamic rule (for more details on the CCT methodology, see the work of Regan et al.,39Regan BC Reffin JP Mollon JD Luminance noise and the rapid determination of discrimination ellipses in colour deficiency.Vision Res. 1994; 34: 1279-1299Crossref PubMed Scopus (243) Google Scholar and, for CCT norms, see the work of Ventura et al.32Ventura DF Silveira LC Rodrigues AR de Souza J Gualtieri M Bonci DM Costa MF Preliminary norms for the Cambridge Colour Test.in: Mollon JD Pokorny J Knoblauch K Colour and defective colour vision. 1st ed. Oxford University Press, New York2003: 331-339Crossref Scopus (4) Google Scholar). The CCT has two testing procedures. The Trivector test is used to determine thresholds along the protan, deutan, and tritan confusion lines (fig. 1). In this procedure, the three corresponding staircases are conducted simultaneously, in an interleaved way, changing randomly from one to the other. Periodically, a control target at maximum saturation is presented, as a catch trial. The other CCT procedure is used for the construction of a discrimination ellipse (MacAdam ellipse). In this study, we used eight vectors spaced 45° apart to determine the discrimination ellipse around the same background chromaticity that had been used for the Trivector test. The staircases corresponding to these vectors were run in interleaved pairs, randomly chosen by the software. After the detection of the threshold in each vector, the ellipse was traced by interpolation, with use of the minimum squares method. Inside the boundaries of the MacAdam ellipses, color discrimination is lost. This means that, the smaller the ellipse, the better the patient's discrimination ability. The quantitative parameters that are used to describe this ability are the ellipse length, the axis ratio, and the ellipse angle in color space. Ellipse length and angle are indicative of magnitude and type of color defect. We used ellipse area to quantify these changes, as an indicator of the patient's performance in color discrimination. To confirm the type of red-green defect, the patients were also tested with the type I Neitz Anomaloscope (model OT-II [Neitz Instruments]), a standard test for the detection of red-green color defects.40Pokorny J Procedures for testing colour vision—report of working group 41.Committee on Vision, Assembly of Behavioral and Social Sciences, National Research Council. National Academy Press, Washington D.C1981Google Scholar The Neitz Anomaloscope determines the Rayleigh equation for the patient: the mixture of red (670 nm) and green (545 nm) light that matches a reference yellow (589 nm) light.41Siegel IM The X-Chrom lens: on seeing red.Surv Ophthalmol. 1981; 25: 312-324PubMed Google Scholar All three lights are produced by filters of equal luminance. The experimental procedure consisted of the observation of a circular horizontally bipartite field with 2° of visual angle. The yellow stimulus is in the lower hemifield, which can vary in luminance from dark to bright yellow. The task of the patient is to adjust the color of the upper hemifield to match the color and luminance of that presented at the lower hemifield. This is done by adjusting the proportion of the mixture of the green (545 nm) and red (670 nm) lights, whose combination is projected in the upper field. When both fields are matched in chromaticity, the luminance of the field is about 5 cd×m−2. The proportion used by trichromatic subjects with normal color vision is known from normative studies and was determined here for the control group. The exam was performed in a dark room, in accordance with the procedure recommended by the 1981 National Research Council Committee on Vision.40Pokorny J Procedures for testing colour vision—report of working group 41.Committee on Vision, Assembly of Behavioral and Social Sciences, National Research Council. National Academy Press, Washington D.C1981Google Scholar The two pseudoisochromatic color plate tests, used in the genetic studies reported elsewhere,26Zatz M Itskan SB Sanger R Frota-Pessoa O Saldanha PH New linkage data for the X-linked types of muscular dystrophy and G6PD variants, colour blindness, and Xg blood groups.J Med Genet. 1974; 11: 321-327Crossref PubMed Scopus (26) Google Scholar, 27Sigesmund DA Weleber RG Pillers DA Westall CA Panton CM Powell BR Heon E Murphey WH Musarella MA Ray PN Characterization of the ocular phenotype of Duchenne and Becker muscular dystrophy.Ophthalmology. 1994; 101: 856-865Abstract Full Text PDF PubMed Scopus (75) Google Scholar were also used for the evaluation of color vision defects: Ishihara Test for Color Blindness (24 plates edition [Kanehara & Co.]) and AO H-R-R Pseudoisochromatic Plates (AO H-R-R [Richmond Products]). These tests consist of a series of printed plates with spatial and luminance noise forming a multicolored figure, which is also observed against a multicolored background. The only systematic difference between the figure and the background is the color. Patients with normal vi
Referência(s)