COLOR VISION IN AND DISEASE HEALTH Craig Thomas, O.D. 3900 West Wheatland Road Dallas, Texas 75237 972-780-7199 thpckc@yahoo.com Financial Disclosure Craig Thomas, O.D. has received honorarium from the following companies: 1. KONAN MEDICAL U.S.A. 1
Clinical Indications The following conditions may have abnormal color vision as a component of their presentation Congenital color vision deficiency Lens and media opacities Retinopathies Compressive lesions of the optic nerve Demyelinating disease Glaucoma Diffuse central nervous system disease (e.g., stroke) Other acquired optic nerve diseases Principles of Visible Light Color vision is an illusion created by the interactions of neurons in our brain and then projected to the world we see Color vision is linked to the perception of form, where color facilitates detecting borders on objects Although all electromagnetic radiation is light, humans see only a small part of the electromagnetic spectrum that we call visible light Color is created by using two properties of light energy wavelength (e.g., frequency of vibration) 2
Normal Color Vision Color is perceived because objects selectively absorb certain wavelengths of light while transmitting the other wavelength The object will take on the color of the wavelength of light it transmits The perception of color is defined by 3 variables Hue - the dominant wavelength of the light the object transmits Saturation - the absence of white Brightness - the intensity of the color Normal Color Vision Color vision is a function of the retinal cones and each of the three types of retinal cones responds to different wavelengths of light in the visible spectrum A person with normal color vision requires all three primary colors to match all of the colors in the visible spectrum Red Green Blue Individuals with normal color vision are called trichromats 3
Neural Response of the Visual Pathway Receptors Photosensitive rods and cones in the retina are neurons specialized to detect light and they encode the initial neural response Circuitry for color coding begins with the parallel ganglion cell systems that are organized throughout the subcortical pathway Structures involved in the transmission of chromatic sensory information along the visual pathway Parallel Ganglion Cell Systems Transmitters Optic nerve, optic chiasm, optic tract, lateral geniculate nucleus, optic radiations Parvocellular division High-resolution achromatic vision Red-green color vison - (64% red cones / 34% green cones) 80% of fibers with high redundancy Magnocellular division Low-resolution achromatic vision Sensitive to motion 5-10% of fibers with low redundancy Koniocellular division Blue-yellow color vision - (2% cones) 5-10% of fibers with low redundancy Lui SJ, Bryan RN, Miki A, Woo JH, Lui GT, Elliott MA. Magnocellular and Parvocellular Visual Pathways Have Different Blood Oxygen Level-Dependent Signal Time Courses in Human Primary Visual Cortex. American Journal of Neuroradiology. 27:1628-1634, Sept 2006 4
Neural Response of the Visual Pathway Primary Visual Cortex Receives axonal projections from the lateral geniculate nucleus Uses neural circuits to process the following Color Form Movement Direction Stereopsis Lateral Geniculate Nucleus Reorganizes the parallel ganglion cell systems into separate layers where the axons project to specific layers in the visual cortex Genetic Color Vision Defects People with an inherited cone pigment abnormalities produce decreased sensitivity to perception of one of the three primary colors The people are termed anomalous trichromats Protan deficiency red cone pigment Deutan deficiency green cone pigment Tritan deficiency blue cone pigment Anomalous trichromats are not color blind, they have a color matching deficit 5
Prevalence of Genetic Defects Red-Green Defects Blue-Yellow Defects North European ancestry 8% of males Deutan-type defect 6% Protan-type defect 2% 0.5% of females African ancestry 3% - 4% of males Asian ancestry 3% of males Not X-linked Tritanomaly 0.01% Tritanopia >>0.01% Tritan deficiencies are typically acquired Ishihara does not test for tritan deficiencies! Pacheco-Cutilla M, Edgar DF. Acquired colour vision defects in glaucoma-their detection and clinical significance. Br J Ophthalmo/1999;83:1396-1402. Acquired Color Vision Defects Affects 15% of the general population Patient is often unaware of changes in their color vision Color defects are describable in unambiguous terms Color defects are widely spread over the color spectrum Asymmetric color defects are common Color defects can be unstable over time Normal age-related deterioration in chromatic discrimination ability Yellowing caused by cataract results in a loss of hue discrimination Diseases that result in a loss of foveal function Optic nerve disease Retinal dystrophies Neurologic disease Neurologic injury Visual field defects Common drugs and substances Ivan, D. J. (2013). Ophthalmology. In Rayman s Clinical Aviation Medicine 5 th Edition. (pp. 235-292). New York, NY: Castle Connoly Graduate Medical Publishing, LTD. 6
Pathogenesis of Acquired Defects Structural damage may occur at any of the following anatomical depths Prereceptor ocular media absorption properties Receptor cells red cones, blue cones, green cones and their ganglion cells Postreceptor retinocortical neural pathways in the brain to the visual cortex In contrast to genetic color vision defects, which are always bilateral, acquired color vision defects can be monocular or different in each eye 7
Dyschromatopsia of Aging Pupillary miosis Yellowing of the crystalline lens Change in density of the crystalline lens Age-related short-wavelength cone fallout Cones that are sensitive to blue light are lost at an elevated rate compared with cones that are sensitive to red and green light Suzuki S, Horiguchi M, Tanikawa A, Miyake Y, Kondo M. Effect of Age On Short-Wavelength Sensitive Cone Electroretinogram and Long- Middle-Wavelength Sensitive Cone Electroretinogram. Japanese Journal of Ophthalmology 42, 424-430. (1998) Dyschromatopsia of Aging Pupillary miosis Yellowing of the crystalline lens Change in density of the crystalline lens Age-related short-wavelength cone fallout Cones that are sensitive to blue light are lost at an elevated rate compared with cones that are sensitive to red and green light Suzuki S, Horiguchi M, Tanikawa A, Miyake Y, Kondo M. Effect of Age On Short-Wavelength Sensitive Cone Electroretinogram and Long- Middle-Wavelength Sensitive Cone Electroretinogram. Japanese Journal of Ophthalmology 42, 424-430. (1998) 8
Dyschromatopsia of Plaquenil The pathogenic effect of plaquenil is the induction of lysosomal dysfunction in the photoreceptors and the retinal pigment epithelium Lysosomal dysfunction creates abnormal retinal metabolism and leads to increased phagocytosis photoreceptor outer segments Early photoreceptor damage is revealed as perifoveal ganglion cell damage on an OCT scan Cone cell fallout results in dyschromaptopsia Kellner U, Renner AB, Tillack H. Fundus Autofluorescence and mferg for Early Detection of Retinal Alterations in Patients Using Cholorquine/Hydroxychloroquine. Investigative Ophthalmology and Visual Science. August 2006;47(8):3531-3538. of Natural History of Glaucoma Some studies suggest that glaucoma must not be considered as a disease exclusively involving ocular structures, but is a pathology in which brain structures are also damaged First indication involves the early impairment of the ganglion cells of the outer retina Second indication involves impairment of the brain s retinocortical neural pathways secondary to transynaptic degeneration Third indication involves impairment of brain function at the level of the lateral geniculate nucleus Parisi V, Coppola G, Centofanti M, Oddone F, Angrisani AM, Ziccardi L, Ricci, B, Quaranta, Manni G. Evidence of the neuroprotective role of citicoline in glaucoma patients. Progress in Brain Reasearch. Elsevier B.V. 2008. 9
Dyschromatopsia of Glaucoma Color vision defects may precede field loss in patients with glaucoma Generalized loss of chromatic discrimination affects 20% - 30% of patients with glaucoma Some patients only develop color loss in advanced disease Pacheo-Cutilla M, Edgar DF. Acquired colour vision defects in glaucoma. Br J Ophthalmo/1999;83:1396-1402. Dyschromatopsia of Diabetes Chromatic visual disturbance in association with presumed hypoxia precedes diabetic retinopathy in 55% of patients OCT scans may show retinal atrophy at the macula 55%-65% of patients with retinopathy have color defects Blue-yellow deficiency is found in almost 90% of patients with diabetic retinopathy Silverman SE, Hart WH, Gordon MO, Kilo C. The Dyschromatopsia of Optic Neuritis Is Determined in Part by the Foveal/Perifoveal Distribution of Visual Field Damage. Invest Ophthalmol Vis Sci 31:1895-1902, 1990. 10
Optic Neuritis Most common cause is demyelinating event on the optic nerve hallmark sign of multiple sclerosis Second most common cause is systemic inflammatory process or infection Unilateral vision loss in younger (under 50) mostly female patients Other clinical signs and symptoms include pain that increases with eye movement, relative afferent pupillary defect, decreased color vision in the involved eye, abnormal VEP waveforms and variable visual field defects McCann AL. Identify Acquired Optic Nerve Disease. Review of Optometry. 2006 June 15; 65-80. Dyschromatopsia of Optic Neuritis No single type of color vision defect is consistently associated with optic neuritis The majority of selective defects were blue-yellow at the time of the acute demyelination Red-green and non-selective color defects were also seen at the time of the acute event Defects can change over time or remain the same Red-green defects are more common in persistent dyschromatopsia (6 months or later) Katz B. The dyschromatopsia of optic neuritis: a descriptive analysis of data from the optic neuritis treatment trial. Trans Am Ophthalmol Soc 1995; 93:685-708. 11
Detecting Hidden Vision Loss In one study of multiple sclerosis patients without a history of optic neuritis and 20/20 visual acuity, color vision testing had the most value in detecting subclinical visual pathway involvement 70% had dyschromatopsia of optic neuritis 55% had delayed P100 peak times on VEP testing 30% had retrograde axonal degeneration that is revealed on a retinal scanning laser Gundogan FC, Tas A, Altun S, Oz O, Erdem U, Sobaci G. Color vision versus pattern visual evoked potentials in the assessment of subclinical optic pathway involvement in multiple sclerosis. Indian Journal of Ophthalmology. March 2013; 61(3): 100-103. Color Vision Testing A finding of abnormal color vision is non-specific and can occur in a wide variety of ocular, neurologic and genetic conditions Screening Tests Ishihara pseudoisochromatic plates Designed to detect congenital red-green defects No plates for blue-yellow testing Test is 100 years old* American Optical HRR plates Designed to detect congenital red-green defects Plates for blue-yellow testing are included 12
Extended Color Vision Testing Extended color vision testing is performed to assess the integrity of, and to diagnose disease of, the retina, optic nerve and visual pathways Farnsworth D-15 panel Designed as a vocational test to detect genetic redgreen color vision deficiencies Farnsworth-Munsell 100-hue testing Most sensitive arrangement-type test Designed for genetic and acquired color vision defects Very long test time (45 minutes to 1 hour) Anomaloscope testing Color matching test requires special instrument Historically referred to as The Gold Standard ColorDx Pediatric Testing No more negative instructions don t touch the caps don t touch the plates 13 plates with shapes Children as young as 2-years-old Perfect for any language Used by the US Special Olympics 13
KONAN MEDICAL -- ColorDx Computer-Assisted Color Vision Testing One of the characteristics of acquired color defects is a raised saturation threshold that gives colors a washed-out appearance These subjective changes in the saturation threshold are often brought out most clearly with luminous test targets like those in Konan s ColorDx applications ColorDx test strategies evaluate the full color spectrum Tests for genetic color vision defects Tests for acquired color vision defects ColorDx provides quantitative and qualitative test results Type of color deficiency, severity of deficiency, hue circle ColorDx Color Vision Diagnostics Validated by Naval Aerospace Medical Institute as comparable to anomaloscope Self-administering Self-scoring Self-reporting Adaptive 14
ColorDx Color Vision Diagnostics Software scores the examination and then plots the test results Extended Adult Adaptive Evaluation General - (26 plates) 10-20 minute test time Tritan - (12 plates) Protan* Deutan* D-15 arrangement test Extended Color Vision Testing CPT code 92283 Costs of Extended Color Vision Tests Farnsworth D-15 panel = $250 Farnsworth-Munsell D-100 hue test = $800 Anomaloscope = $11,000 Rabin Cone Test = $7,000 Konan ColorDx = $1,300 (tablet + app) $800 (Win ios OSX) Medicare fee in Texas is approximately $57 ROI = 25 16 patients 15
Treatment Options ChromaGen FDA marketing clearance for use in genetic red-green color deficiencies Specialized tinted lenses that filter specific wavelengths of light may minimally improve color discrimination The tint selection process requires that the patient select a preferred tint from a group of colors across the visible spectrum Adaptive Techniques Genetic Counseling Treatment Options Acquired Color Vision Deficiencies Differentiate if the defect is genetic or acquired Determine if the defect is unilateral, asymmetric or transient Identify the primary condition that is producing the color vision defect Prescribe a treatment program 16
We Are Done! 17