DOCSLIB.ORG

Do Tinted Lenses Or Filters Improve Visual Performance in Low Vision?

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Do Tinted Lenses Or Filters Improve Visual Performance in Low Vision? Ophthal. Physiol. Opt. 2002 22 68±77 Do tinted lenses or ®lters improve visual performance in low vision? A review of the literature Frank Eperjesi1,2, Colin W. Fowler1 and Bruce J. W. Evans3 1Neurosciences Research Institute, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK, 2Low Vision Centre, Birmingham Focus on Blindness, 62 Woodville Road, Harborne, Birmingham B17 9AX, UK and 3The Institute of Optometry, 56-62 Newington Causeway, London SE1 6DS, UK Abstract This is a review of studies that have investigated the proposed rehabilitative bene®t of tinted lenses and ®lters for people with low vision. Currently, eye care practitioners have to rely on marketing literature and anecdotal reports from users when making recommendations for tinted lens or ®lter use in low vision. Our main aim was to locate a prescribing protocol that was scienti®cally based and could assist low vision specialists with tinted lens prescribing decisions. We also wanted to determine if previous work had found any tinted lens/task or tinted lens/ocular condition relationships, i.e. were certain tints or ®lters of use for speci®c tasks or for speci®c eye conditions. Another aim was to provide a review of previous research in order to stimulate new work using modern experimental designs. Past studies of tinted lenses and low vision have assessed effects on visual acuity (VA), grating acuity, contrast sensitivity (CS), visual ®eld, adaptation time, glare, photophobia and TV viewing. Objective and subjective outcome measures have been used. However, very little objective evidence has been provided to support anecdotal reports of improvements in visual performance. Many studies are ¯awed in that they lack controls for investigator bias, and placebo, learning and fatigue effects. Therefore, the use of tinted lenses in low vision remains controversial and eye care practitioners will have to continue to rely on anecdotal evidence to assist them in their prescribing decisions. Suggestions for future research, avoiding some of these experimental shortcomings, are made. Keywords: adaptation, age-related macular degeneration, colour vision, contrast sensitivity, ®lters, glare, low vision, photophobia, retinitis pigmentosa, rehabilitation, tinted lenses, visual acuity, visual ®eld albinism. This review will concentrate on studies that Introduction have investigated the use of tinted lenses in the Tinted lenses are currently used by eye care practition- rehabilitation of people with visual loss, and highlight ers to assist people with low vision in maximising use of areas where more research would be useful. Proposed residual vision, improve visual function, control glare eects of tinted lenses on progressive eye disease and improve orientation and mobility skills. Tinted (especially RP) are controversial and will not be lenses are often prescribed to people with various ocular discussed here. diseases, including age-related macular degeneration (ARMD), retinitis pigmentosa (RP), cataract, diabetic Terminology retinopathy, cone dystrophy and oculo-cutaneous Terminology in this ®eld can be confusing. The following de®nitions are after Millodot (1999). Glare-a Received: 17 February 1998 Revised form: 6 December 2000 visual condition in which the observer feels either Accepted: 4 July 2001 discomfort and/or exhibits a lower performance in Correspondence and reprint requests to: Frank Eperjesi. visual tests. Photophobia-abnormal fear or intolerance E-mail address: [email protected] to light. Dark adaptation-adjustment of the eye such 68 ã 2002 The College of Optometrists Tinted lenses and low vision: F. Eperjesi et al. 69 that after observation in the dark, sensitivity to light is A prescription can be ground on to the surface and the greatly increased. These meanings will be used in the lens glazed into a spectacle frame. discussion and conclusions sections of this paper, There are currently six CPFÒs, marketed under the however, it is not possible to determine how these terms Glare Control trademark (Corning SA, Division Op- were interpreted by the investigators of the various tique, 77167 Bagneaux-sur-Loing, France) each with a studies described. dierent wavelength cut-o level: CPFÒ450, CPFÒ511, CPFÒ527, CPFÒ550, CPFÒ527X (improved colour rendition and better cosmetic appearance than the Commercially available tinted lenses standard CPFÒ527) and the CPFÒ GlareCutterTM (improved colour rendition compared with the other Corning photochromic ®lters ®lters). The number corresponds to the wavelength in The optical division of Corning Glass developed the nanometers, above which light is transmitted. See Corning photochromic ®lters (CPFÒ) range, which is Table 1 for CPFÒ characteristics. considered by some practitioners to be the gold standard Corning recommend certain ®lters for certain tasks for use in low vision rehabilitation. These tints have and for certain eye conditions. For example, CPFÒ450 been designed, and are marketed speci®cally, to improve is recommended for indoor use, for reading, watching the comfort and visual performance of visually impaired TV, VDU and oce work, for `hobbyists' and as a people who suer from a range of ocular disorders. The shopping aid; CPFÒ511 and CPFÒ527 `have been found tints evolved from research in the late 1970s investi- to be of bene®t by many people who experience visual gating the possible detrimental eects of visible light on problems associated with cataract or macular degener- the ocular system. ation'. The CPFÒs can be glazed into a spectacle frame, According to Corning marketing literature, `short with or without side-shields and in a variety of lens wavelength light has been shown to cause visual forms and materials (see Table 2 for details). Corning discomfort, hazy vision, reduced contrast and prolonged advise that prospective users are given enough time to adaptation times'. It is implied that CPFÒs can alleviate test the ®lters and recommend the use of a plano, ®xed- some or all of these eects by ®ltering out blue light in tint, plastic clip-on to give the user experience with all the visible portion of the spectrum, `at the wavelengths the ®lters, both in and outdoors over a trial period. that create problems for the photophobic or ageing eye'. There are several CPFÒ facsimiles that are claimed to They are designed to ®lter short wavelength light of perform in a similar way to CPFÒs, but none have as yet solar and arti®cial origin. been scienti®cally appraised. A base borosilicate, photochromic glass is used in the manufacturing process. This goes through a ®ring UVShieldÒ and NoIRÒ ®lters treatment that changes the chemical structure of the silver halide crystals at the surface of the lens. The tint NoIR Medical Technologies (South Lyon, MI, USA) produced by this `chemtempering technique' is inde- market two types of ®lter for use in low vision; the pendent of thickness and is even across the lens surface. UVShieldÒ and the NoIRÒ ®lter. According to the Table 1. Transmission details for CPFÒ range (from Corning marketing material) CPFÒ450 CPFÒ511 CPFÒ527 CPFÒ550 CPFÒ527X GlareCutterTM Wavelength cut-off (nm) 450 511 527 550 ± ± % Light transmission (lightened state) 67 44 32 21 33 18 % Light transmission (darkened state) 19 14 11 5 15 6 Absorption % in darkened state Minimum UVB 100 100 100 100 100 100 Minimum UVA 97 98 98 99 98 98 Blue light 95 98 98 98 98 98 Table 2. CPF lens forms, power ranges and materials (from Corning marketing material) Lens form Refractive index Spherical power range (DS) Cylindrical power range (DC) Addition (DS) Single vision 1.50 glass +6.00 to )8.00 Up to 4.00 ± Single vision 1.80 glass +6.00 to )23.00 Up to 4.00 ± C28 bifocal 1.50 glass +6.00 to )8.00 Up to 4.00 0.75±4.00 Progressive 1.50 glass +6.00 to )8.00 Up to 4.00 0.75±3.50 Fixed tint clip-on 1.50 plastic Plano Plano ± ã 2002 The College of Optometrists 70 Ophthal. Physiol. Opt. 2002 22:No1 manufacturer's marketing literature, the UVShieldÒ studies have been divided into those that used mainly provides protection for 100% UV and visible light and objective outcome measures and those that used mainly the NoIRÒ ®lter eliminates near infrared, 100% UV and subjective outcome measures in the determination of `provides visible light protection, for maximum eye eects of tinted lenses on visual performance. Those comfort'. At the time of writing there are 22 UVShieldsÒ studies with an objective outcome measure have been and 12 NoIRÒ ®lters. Constructed from polycarbonate, further divided according to the measure used, for they retain their original shape and will not stretch or example, the eect of tinted lenses and ®lters on VA. deform with use. Supplied in large ®tover moulded form, with wide temples that double as side-shields, and Objective outcome measures made from the same material with the same colour as the front. The design helps to shield the eyes from light Visual acuity incident from above and that re¯ected from below and allows a wide ®eld of view. During the manufacturing The literature search located six papers that reported a process an ultraviolet and infrared absorbing chemical is positive eect of tinted lenses on VA. Lynch and Brilliant blended with polycarbonate before it is moulded into the (1984) compared the eects of CPFÒ550 and a 20% ®nal product. A hard-coated version is available. transmission neutral density (ND) ®lter on the VA of 16 From discussions with several low vision specialists, it RP subjects. CPFÒ550 improved VA in 24 eyes, one seems that the current mode of determining whether decreased, and in seven it remained unchanged. Eight tinted lenses will be of bene®t to a particular person is to eyes that had improved VA with the ND ®lter had even have a brief indoor clinic based trial, with a plano plastic greater improvement with the CPFÒ550.
Load more

Recommended publications
  • Albinism Terminology
    Albinism Terminology Oculocutaneous Albinism (OCA): Oculocutaneous (pronounced ock-you-low-kew- TAIN-ee-us) Albinism is an inherited genetic condition characterized by the lack of or diminished pigment in the hair, skin, and eyes. Implications of this condition include eye and skin sensitivities to light and visual impairment. Ocular Albinism (OA): Ocular Albinism is an inherited genetic condition, diagnosed predominantly in males, characterized by the lack of pigment in the eyes. Implications of this condition include eye sensitivities to light and visual impairment. Hermansky Pudlak Syndrome (HPS): Hermansky-Pudlak Syndrome is a type of albinism which includes a bleeding tendency and lung disease. HPS may also include inflammatory bowel disease or kidney disease. The severity of these problems varies much from person to person, and the condition can be difficult to diagnose with traditional blood tests Chediak Higashi Syndrome: Chediak Higashi Syndrome is a type of albinism in which the immune system is affected. Illnesses and infections are common from infancy and can be severe. Issues also arise with blood clotting and severe bleeding. Melanin: Melanin is pigment found in a group of cells called melanocytes in most organisms. In albinism, the production of melanin is impaired or completely lacking. Nystagmus: Nystagmus is an involuntary movement of the eyes in either a vertical, horizontal, pendular, or circular pattern caused by a problem with the visual pathway from the eye to the brain. As a result, both eyes are unable to hold steady on objects being viewed. Nystagmus may be accompanied by unusual head positions and head nodding in an attempt to compensate for the condition.
    [Show full text]
  • Partial Albinism (Heterochromia Irides) in Black Angus Cattle
    Partial Albinism (Heterochromia irides) in Black Angus Cattle C. A. Strasia, Ph.D.1 2 J. L. Johnson, D. V.M., Ph.D.3 D. Cole, D. V.M.4 H. W. Leipold, D.M.V., Ph.D.5 Introduction Various types of albinism have been reported in many Pathological changes in ocular anomalies of incomplete breeds of cattle throughout the world.4 We describe in this albino cattle showed iridal heterochromia grossly. paper a new coat and eye color defect (partial albinism, Histopathological findings of irides showed only the heterochromia irides) in purebred Black Angus cattle. In posterior layer fairly pigmented and usually no pigment in addition, the results of a breeding trial using a homozygous the stroma nor the anterior layer. The ciliary body showed affected bull on normal Hereford cows are reported. reduced amount of pigmentation and absence of corpora Albinism has been described in a number of breeds of nigra. Choroid lacked pigmentation. The Retina showed cattle.1,3-8,12,16,17 An albino herd from Holstein parentage disorganization. Fundus anomalies included colobomata of was described and no pigment was evident in the skin, eyes, varying sizes at the ventral aspect of the optic disc and the horns, and hooves; in addition, the cattle exhibited photo­ tapetum fibrosum was hypoplastic.12 In albino humans, the phobia. A heifer of black pied parentage exhibited a fundus is depigmented and the choroidal vessels stand out complete lack of pigment in the skin, iris and hair; however, strikingly. Nystagmus, head nodding and impaired vision at sexual maturity some pigment was present and referred to also may occur.
    [Show full text]
  • Wavelength of Light and Photophobia in Inherited Retinal Dystrophy
    www.nature.com/scientificreports OPEN Wavelength of light and photophobia in inherited retinal dystrophy Yuki Otsuka1, Akio Oishi1,2*, Manabu Miyata1, Maho Oishi1, Tomoko Hasegawa1, Shogo Numa1, Hanako Ohashi Ikeda1 & Akitaka Tsujikawa1 Inherited retinal dystrophy (IRD) patients often experience photophobia. However, its mechanism has not been elucidated. This study aimed to investigate the main wavelength of light causing photophobia in IRD and diference among patients with diferent phenotypes. Forty-seven retinitis pigmentosa (RP) and 22 cone-rod dystrophy (CRD) patients were prospectively recruited. We designed two tinted glasses: short wavelength fltering (SWF) glasses and middle wavelength fltering (MWF) glasses. We classifed photophobia into three types: (A) white out, (B) bright glare, and (C) ocular pain. Patients were asked to assign scores between one (not at all) and fve (totally applicable) for each symptom with and without glasses. In patients with RP, photophobia was better relieved with SWF glasses {“white out” (p < 0.01) and “ocular pain” (p = 0.013)}. In CRD patients, there was no signifcant diference in the improvement wearing two glasses (p = 0.247–1.0). All RP patients who preferred MWF glasses had Bull’s eye maculopathy. Meanwhile, only 15% of patients who preferred SWF glasses had the fnding (p < 0.001). Photophobia is primarily caused by short wavelength light in many patients with IRD. However, the wavelength responsible for photophobia vary depending on the disease and probably vary according to the pathological condition. Inherited retinal degenerations (IRDs) represent a diverse group of diseases characterized by progressive photo- receptor cell death that can lead to blindness 1.
    [Show full text]
  • What Is Hermansky-Pudlak Syndrome?
    American Thoracic Society PATIENT EDUCATION | INFORMATION SERIES What is Hermansky-Pudlak Syndrome? Hermansky-Pudlak Syndrome (HPS) is a rare inherited disease, named after two doctors in Czechoslovakia who, in 1959, recognized similar health conditions in two unrelated adults. Since the discovery of HPS, the condition has occurred all over the world but is most often seen in Puerto Rico. The most common health conditions with HPS are albinism, the tendency to Journal of Hematology bleed easily, and pulmonary fibrosis. A Figure 1. Normal platelet with dense bodies growing number of gene mutations have visualized by electron microscopy. been identified causing HPS (including numbers HPS1 to HPS10). What is albinism? Albinism is an inherited condition in which CLIP AND COPY AND CLIP reduced pigmentation (coloring) is present in the body. As a result, people with albinism are often fair-skinned with light hair. However, skin, hair, and eye color may vary, as some people with albinism may have dark brown hair and green or hazel/brown eyes. Journal of Hematology People with albinism all have low vision and Figure 2. Patient’s platelet with virtually absent dense bodies visualized by electron microscopy. varying degrees of nystagmus. All people who have HPS have albinism, but not all circulate in the blood stream and help the people with albinism have HPS. blood to clot. HPS patients have normal Skin problems—The reduction of numbers of platelets, but they are not pigmentation in the skin from albinism made correctly and do not function well, so results in an increased chance of developing the blood does not clot properly.
    [Show full text]
  • Common Eye Conditions
    COMMON EYE CONDITIONS AMBLYOPIA Reduced acuity because of non-use of eye or extreme difference in acuities. Eye may be patched or surgery to correct. NYSTAGMUS - Cause unknown Involuntary rhythmic side-to-side, up-and-down, or circular (oscillating), eye movement that may be faster in one direction than the other (may be more marked in one eye than the other), reduced acuity due to inability to fixate. STRABISMUS - Defects of eye muscle Eyes are not aligned correctly, images may not fuse, brain may suppress one image resulting in permanent acuity reduction in eye where image is suppressed. ALBINISM – Hereditary – congenital (may involve all or part of body – non-progressive) Lack of pigment in eye, decreased acuity, nystagmus, strabismus, photophobia, visual fields variable, retina and macular involvement. ANIRIDIA – Hereditary Underdeveloped or absent iris. Decreased acuity, photophobia, nystagmus, cataracts, under developed retina. Visual fields normal unless glaucoma develops. CATARACTS – Congenital, hereditary, traumatic, disease, or age related (normal part of aging process) Lens opacity (chemical change in lens protein), decreased visual acuity, nystagmus, photophobia (light sensitivity). DIABETIC RETINOPATHY – Pathologic Retinal changes, proliferative – growth of abnormal new blood vessels, hemorrhage, fluctuating visual acuity, loss of color vision, field loss, retinal detachment, total blindness. GLAUCOMA (Congenital or adult) – “SNEAK THIEF OF SIGHT” hereditary, traumatic, surgery High intraocular pressure (above 20-21 mm of mercury) – (in children often accompanied by hazy corneas and large eyes), often due to obstructions that prevent fluid drainage, resulting in damage to optic nerve. Excessive tearing, photophobia, uncontrolled blinking, decreased acuity, constricted fields. HEMIANOPSIA – (Half-vision) optic pathway malfunction pathologic or trauma (brain injury, stroke or tumor) Macular vision may or may not be affected.
    [Show full text]
  • Guidelines for Universal Eye Screening in Newborns Including RETINOPATHY of Prematurity
    GUIDELINES FOR UNIVERSAL EYE SCREENING IN NEWBORNS INCLUDING RETINOPATHY OF PREMATURITY RASHTRIYA BAL SWASthYA KARYAKRAM Ministry of Health & Family Welfare Government of India June 2017 MESSAGE The Ministry of Health & Family Welfare, Government of India, under the National Health Mission launched the Rashtriya Bal Swasthya Karyakram (RBSK), an innovative and ambitious initiative, which envisages Child Health Screening and Early Intervention Services. The main focus of the RBSK program is to improve the quality of life of our children from the time of birth till 18 years through timely screening and early management of 4 ‘D’s namely Defects at birth, Development delays including disability, childhood Deficiencies and Diseases. To provide a healthy start to our newborns, RBSK screening begins at birth at delivery points through comprehensive screening of all newborns for various defects including eye and vision related problems. Some of these problems are present at birth like congenital cataract and some may present later like Retinopathy of prematurity which is found especially in preterm children and if missed, can lead to complete blindness. Early Newborn Eye examination is an integral part of RBSK comprehensive screening which would prevent childhood blindness and reduce visual and scholastic disabilities among children. Universal newborn eye screening at delivery points and at SNCUs provides a unique opportunity to identify and manage significant eye diseases in babies who would otherwise appear healthy to their parents. I wish that State and UTs would benefit from the ‘Guidelines for Universal Eye Screening in Newborns including Retinopathy of Prematurity’ and in supporting our future generation by providing them with disease free eyes and good quality vision to help them in their overall growth including scholastic achievement.
    [Show full text]
  • Idiopathic Intracranial Hypertension
    IDIOPATHIC INTRACRANIAL HYPERTENSION William L Hills, MD Neuro-ophthalmology Oregon Neurology Associates Affiliated Assistant Professor Ophthalmology and Neurology Casey Eye Institute, OHSU No disclosures CASE - 19 YO WOMAN WITH HEADACHES X 3 MONTHS Headaches frontal PMHx: obesity Worse lying down Meds: takes ibuprofen for headaches Wake from sleep Pulsatile tinnitus x 1 month. Vision blacks out transiently when she bends over or sits down EXAMINATION Vision: 20/20 R eye, 20/25 L eye. Neuro: PERRL, no APD, EOMI, VF full to confrontation. Dilated fundoscopic exam: 360 degree blurring of disc margins in both eyes, absent SVP. Formal visual field testing: Enlargement of the blind spot, generalized constriction both eyes. MRI brain: Lumbar puncture: Posterior flattening of Opening pressure 39 the globes cm H20 Empty sella Normal CSF studies otherwise normal Headache improved after LP IDIOPATHIC INTRACRANIAL HYPERTENSION SYNDROME: Increased intracranial pressure without ventriculomegaly or mass lesion Normal CSF composition NOMENCLATURE Idiopathic intracranial hypertension (IIH) Benign intracranial hypertension Pseudotumor cerebri Intracranial hypertension secondary to… DIAGNOSTIC CRITERIA Original criteria have been updated to reflect new imaging modalities: 1492 Friedman and Jacobsen. Neurology 2002; 59: Symptoms and signs reflect only those of - increased ICP or papilledema 1495 Documented increased ICP during LP in lateral decubitus position Normal CSF composition No evidence of mass, hydrocephalus, structural
    [Show full text]
  • Management of Nystagmus in Children: a Review of the Literature and Current Practice in UK Specialist Services
    Eye https://doi.org/10.1038/s41433-019-0741-3 REVIEW ARTICLE Management of nystagmus in children: a review of the literature and current practice in UK specialist services 1,2 3 3 4 5 6 1,2 6 J. E. Self ● M. J. Dunn ● J. T. Erichsen ● I. Gottlob ● H. J. Griffiths ● C. Harris ● H. Lee ● J. Owen ● 7 1 8,9 10 J. Sanders ● F. Shawkat ● M. Theodorou ● J. P. Whittle ● Nystagmus UK Eye research group (NUKE) Received: 18 October 2019 / Accepted: 24 November 2019 © The Author(s) 2020. This article is published with open access Abstract Nystagmus is an eye movement disorder characterised by abnormal, involuntary rhythmic oscillations of one or both eyes, initiated by a slow phase. It is not uncommon in the UK and regularly seen in paediatric ophthalmology and adult general/ strabismus clinics. In some cases, it occurs in isolation, and in others, it occurs as part of a multisystem disorder, severe visual impairment or neurological disorder. Similarly, in some cases, visual acuity can be normal and in others can be severely degraded. Furthermore, the impact on vision goes well beyond static acuity alone, is rarely measured and may vary on a minute-to-minute, day-to-day or month-to-month basis. For these reasons, management of children with nystagmus in 1234567890();,: 1234567890();,: the UK is varied, and patients report hugely different experiences and investigations. In this review, we hope to shine a light on the current management of children with nystagmus across five specialist centres in the UK in order to present, for the first time, a consensus on investigation and clinical management.
    [Show full text]
  • Triple Ptosis
    TRIPLE PTOSIS ABSTRACT This is a case in which aberrant regeneration after a remote facial palsy confounds the diagnosis of an early ipsilateral third nerve palsy. CASE HISTORY A 54 year old Caucasian male presented to the emergency department for an acute increase in left ptosis x 1 day. The patient had a previously existing left ptosis residual from a left lower motor neuron facial palsy in 2004. Initial assessment by the ER physician revealed left eye ptosis with accompanying left retrobulbar pain. Pupils and extraocular motilities were recorded as normal. Other cranial nerve testing was remarkable for left facial weakness involving the upper and lower face. No other focal neurological deficits observed. CBC, electrolytes plus and head CT were obtained. (See Laboratory/Radiology Studies). CT of the head without contrast revealed no acute intracranial hemorrhage, infarct or mass. The patient was admitted to neurology service for workup of recurrent left facial lower motor neuron palsy vs acute facial nerve palsy of infectious etiology vs. ptosis of unclear etiology (unlikely myasthenia gravis). The patient was consulted to optometry for an evaluation of the ptosis. OPTOMETRY CASE HISTORY The patient presented to the optometry clinic complaining of an exacerbation of longstanding left ptosis upon wakening x 1 day with accompanying significant left retrobulbar pain which started 3 days prior. He denied double vision, blurry vision, photophobia, eyelid swelling, variability of ptosis size. He noted no additional facial weakness from baseline and reported the ability to fully close the left eye. His wife who accompanied him to the exam claimed that the change in his facial appearance was limited to the left lid.
    [Show full text]
  • ACHROMATOPSIA Clinical Overview and Updates on Clinical Trial
    ACHROMATOPSIA Clinical overview and updates on clinical trial Christine Nichols Kay, M.D. University of Florida Gainesville, Florida Achromatopsia • Autosomal Recessive • Prevalence of 1:30,000-50,000 • Mild congenital pendular nystagmus • Protan (red), deutan (green), and tritan (blue) color defects • Severe photophobia • Decreased VA around 20/100-20/200 • ERG shows normal rod function and no cone function • Can have normal fundus or classic foveal atrophy • OCT with characteristic foveal photoreceptor atrophy Anatomy overview Macula Between temporal arcades 6 mm or 4 DD in width 2 or more layers of ganglion cells Photoreceptors • Light sensitive cells found in the retina. • Rods (93% of cells) and Cones (7%) – Rods: night vision, visual field – Cones: visual acuity, color vision Achromatopsia foveal atrophy ERG CNGB3-Achromatopsia OCT Genetics of Achromatopsia • CNGA3 or CNGB3, Cyclic Nucleotide Gated Channel (Subtype A or Subtype B) – CNGA3 (25%) – CNGB3 (50%): • Most frequent mutation is Thr383fsx mutation (80%) – this frameshift mutation causes truncation of pore-forming loop and C-terminal cytoplasmic domain, and no intact CNGB3 is formed. • GNAT2 (1%) • PDE6C (1%) Retinal Physiology • Quick overview… Physiology of Photoreception: THE MAJOR PLAYERS • Photoreceptor outer segment: –Phototransduction • RPE cell: –Visual cycle The Outer Segment: the light sensitive part of a photoreceptor First step in phototransduction is activation of rhodopsin by light causes isomerization of 11-cis to all-trans Cyclic Nucleotide Gated Channels • CNG channels are localized to plasma membrane of outer segment • Belong to superfamily of voltage-gated ion channels • Play pivotal role in phototransduction: – CNGA1/B1: in rods – CNGA3/B3: in cones CNGA3 versus CNGB3 • Two channel subunits, alpha and beta • Alpha subunits are ion transporting structures • Beta subunits modulate the behavior of alphas but do not function as channels by themselves • CNGA3 and CNGB3 mutations involve inability to properly control or respond to altered levels of cGMP.
    [Show full text]
  • A Nonhuman Primate Model of Achromatopsia
    The Journal of Clinical Investigation COMMENTARY Blinded by the light: a nonhuman primate model of achromatopsia Katherine E. Uyhazi and Jean Bennett Center for Advanced Retinal and Ocular Therapeutics, F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA. sitely light-sensitive rod photoreceptors for both night- and daytime vision. How- Achromatopsia is an inherited retinal degeneration characterized by the ever, rods are specialized to function well loss of cone photoreceptor function. In this issue of the JCI, Moshiri et in dimly lit conditions, but are too sensitive al. characterize a naturally occurring model of the disease in the rhesus to work efficiently in bright light, resulting macaque caused by homozygous mutations in the phototransduction in glare. Rods also have low spatial resolu- enzyme PDE6C. Using retinal imaging, and electrophysiologic and tion, leading to decreased acuity. biochemical methods, the authors report a clinical phenotype nearly There are currently six known caus- identical to the human condition. These findings represent the first genetic ative genes of achromatopsia, almost all of nonhuman primate model of an inherited retinal disease, and provide an which are components of the phototrans- ideal testing ground for the development of novel gene replacement, gene duction cascade in cone photoreceptors editing, and cell replacement therapies for cone dystrophies. (3). Approximately 75% of affected individ- uals have mutations in cyclic nucleotide- gated channel beta 3 or alpha 3 (CNGB3 or CNGA3), while the remainder of cases are caused by mutations in the remaining four Color blindness vivors, one of whom was a heterozygous genes (GNAT2, PDE6C, PDE6H, or ATF6) On the remote South Pacific island of carrier of the disease (2).
    [Show full text]
  • Clinical and Molecular Genetic Aspects of Leber's Congenital
    Clinical and Molecular Genetic Aspects 10 of Leber’s Congenital Amaurosis Robert Henderson, Birgit Lorenz, Anthony T. Moore | Core Messages of about 2–3 per 100,000 live births [119, 50]. ∑ Leber’s congenital amaurosis (LCA) is a It occurs more frequently in communities severe generalized retinal dystrophy which where consanguineous marriages are common presents at birth or soon after with nystag- [128]. mus and poor vision and is accompanied by a nonrecordable or severely attenuated ERG 10.1.1 ∑ As some forms are associated with better Clinical Findings vision during childhood and nystagmus may be absent, a wider definition is early LCA is characterized clinically by severe visual onset severe retinal dystrophy (EOSRD) impairment and nystagmus from early infancy with LCA being the most severe form associated with a nonrecordable or substantial- ∑ It is nearly always a recessive condition but ly abnormal rod and cone electroretinogram there is considerable genetic heterogeneity (ERG) [32, 31, 118]. The pupils react sluggishly ∑ There are eight known causative genes and and, although the fundus appearance is often three further loci that have been implicated normal in the early stages,a variety of abnormal in LCA/EOSRD retinal changes may be seen. These include pe- ∑ The phenotype varies with the genes ripheral white dots at the level of the retinal pig- involved; not all are progressive. At present, ment epithelium, and the typical bone-spicule a distinct phenotype has been elaborated pigmentation seen in retinitis pigmentosa. for patients with mutations in RPE65 Other associated findings include the ocu- ∑ Although LCA is currently not amenable to lodigital sign, microphthalmos, enophthalmos, treatment, gene therapy appears to be a ptosis, strabismus, keratoconus [28], high re- promising therapeutic option, especially fractive error [143],cataract,macular coloboma, for those children with mutations in RPE65 optic disc swelling, and attenuated retinal vas- culature.
    [Show full text]