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139-508: Clinically, there is an acute onset of visual loss, first in one eye , and then a few weeks to months later in the other. Onset is usually young adulthood, but age range at onset from 7-75 is reported. The age of onset is slightly higher in females (range 19–55 years: mean 31.3 years) than males (range 15–53 years: mean 24.3). The male-to-female ratio varies between mutations: 3:1 for 3460 G>A, 6:1 for 11778 G>A and 8:1 for 14484 T>C. This typically evolves to very severe optic atrophy and

278-465: A decimal number. Using the metre as a unit of measurement, (fractional) visual acuity is expressed relative to 6/6. Otherwise, using the foot, visual acuity is expressed relative to 20/20. For all practical purposes, 20/20 vision is equivalent to 6/6. In the decimal system, acuity is defined as the reciprocal value of the size of the gap (measured in arc minutes) of the smallest Landolt C , the orientation of which can be reliably identified. A value of 1.0

417-471: A hyperbola ). The decline is according to E 2 /( E 2 + E ), where E is eccentricity in degrees visual angle , and E 2 is a constant of approximately 2 degrees. At 2 degrees eccentricity, for example, acuity is half the foveal value. Visual acuity is a measure of how well small details are resolved in the very center of the visual field; it therefore does not indicate how larger patterns are recognized. Visual acuity alone thus cannot determine

556-451: A vitamin E metabolite, has had some success in small open-label trials in reversing early onset vision loss. Various treatment approaches have had early trials or been proposed, but so far none with convincing evidence of usefulness or safety for treatment or prevention, including brimonidine , minocycline , curcumin , glutathione , near infrared light treatment , and viral vector techniques. "Three person in vitro fertilization"

695-612: A "Tumbling E Chart" for illiterates, later used to study the visual acuity of Australian Aboriginals . Rick Ferris et al. of the National Eye Institute chooses the LogMAR chart layout, implemented with Sloan letters, to establish a standardized method of visual acuity measurement for the Early Treatment of Diabetic Retinopathy Study (ETDRS). These charts are used in all subsequent clinical studies, and did much to familiarize

834-720: A LHON mutation, preclinical markers may be used to monitor progress. For example, fundus photography can monitor nerve fiber layer swelling. Optical coherence tomography can be used for more detailed study of retinal nerve fiber layer thickness. Red green color vision testing may detect losses. Contrast sensitivity may be diminished. There could be an abnormal electroretinogram or visual evoked potentials . Neuron-specific enolase and axonal heavy chain neurofilament blood markers may predict conversion to affected status. Cyanocobalamin (a form of B12) should be avoided as it may lead to blindness in LHON patients. Avoiding optic nerve toxins

973-400: A combination of Rayleigh scattering and a moderate amount of melanin in the iris' anterior border layer. Hazel eyes often appear to shift in color from a brown to a green. Although hazel mostly consists of brown and green, the dominant color in the eye can either be brown/gold or green. This is why hazel eyes can be mistaken as amber and vice versa. The combination can sometimes produce

1112-414: A diffraction-limited acuity of 0.4 minutes of arc (minarc) or 6/2.6 acuity. The smallest cone cells in the fovea have sizes corresponding to 0.4 minarc of the visual field, which also places a lower limit on acuity. The optimal acuity of 0.4 minarc or 6/2.6 can be demonstrated using a laser interferometer that bypasses any defects in the eye's optics and projects a pattern of dark and light bands directly on

1251-402: A first lens (the cornea—the clear part of the eye ) that accounts for most of the optical power of the eye and accomplishes most of the focusing of light from the outside world; then an aperture (the pupil ) in a diaphragm (the iris—the coloured part of the eye ) that controls the amount of light entering the interior of the eye; then another lens (the crystalline lens ) that accomplishes

1390-474: A good illumination, the acuity is only equal to 1, the eye presents defects sufficiently pronounced to be easily established." Most observers may have a binocular acuity superior to 6/6; the limit of acuity in the unaided human eye is around 6/3–6/2.4 (20/10–20/8), although 6/3 was the highest score recorded in a study of some US professional athletes. Some birds of prey , such as hawks , are believed to have an acuity of around 20/2; in this respect, their vision

1529-458: A highly conserved arginine to histidine at codon 340 in the NADH dehydrogenase subunit 4 of complex I of the mitochondrial respiratory chain. The other two mutations known to cause this condition were identified in 1991 (G to A point mutation at nucleotide position 3460) and 1992 ( thymidine (T) to cytosine (C) mutation at nucleotide 14484). These three mutations account for over 95% of cases:

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1668-459: A homoplasmic primary LHON mutation has a ~40% risk of having an affected son and a ~10% risk of having an affected daughter. Additional factors may determine whether a person develops the signs and symptoms of this disorder. Environmental factors such as smoking and alcohol use may be involved, though studies of these factors have produced conflicting results. Researchers are also investigating whether changes in additional genes, particularly genes on

1807-500: A known family history of LHON the diagnosis usually requires a neuro-ophthalmological evaluation and blood testing for mitochondrial DNA assessment. It is important to exclude other possible causes of vision loss and associated syndromes such as heart electrical conduction system abnormalities. The prognosis for those left untreated is almost always continued significant visual loss in both eyes. Regular corrected visual acuity and perimetry checks are advised for affected people. There

1946-423: A measure of neural functioning. Visual acuity is typically measured while fixating, i.e. as a measure of central (or foveal ) vision, for the reason that it is highest in the very center. However, acuity in peripheral vision can be of equal importance in everyday life. Acuity declines towards the periphery first steeply and then more gradually, in an inverse-linear fashion (i.e. the decline follows approximately

2085-558: A multicolored iris, i.e., an eye that is light brown/amber near the pupil and charcoal or dark green on the outer part of the iris (or vice versa) when observed in sunlight. Definitions of the eye color hazel vary: it is sometimes considered to be synonymous with light brown or gold, as in the color of a hazelnut shell. Around 18% of the US population and 5% of the world population have hazel eyes. Hazel eyes are found in Europe , most commonly in

2224-489: A novel eye testing chart using letters that become invisible with decreasing acuity, rather than blurred as in standard charts. They demonstrate the arbitrary nature of the Snellen fraction and warn about the accuracy of visual acuity determined by using charts of different letter types, calibrated by Snellen's system. Daylight vision (i.e. photopic vision ) is subserved by cone receptor cells which have high spatial density (in

2363-414: A number of young men had abrupt loss of vision in both eyes either simultaneously or sequentially. This disease was initially thought to be X-linked but was subsequently shown to be mitochondrial. The nature of the causative mutation was first identified in 1988 by Wallace et al. who discovered the guanine (G) to adenosine (A) mutation at nucleotide position 11778 in nine families. This mutation converts

2502-500: A patient with LHON or toxic/nutritional optic neuropathy has a hypertensive crisis as a possible complication of the disease process, nitroprusside (trade name: Nipride ) should not be used, due to increased risk of optic nerve ischemia in response to this anti-hypertensive . Idebenone has been shown in a small placebo-controlled trial to have modest benefit in about half of patients. People most likely to respond best were those treated early in onset. α- Tocotrienol -quinone,

2641-526: A permanent decrease of visual acuity . Both eyes become affected either simultaneously (25% of cases) or sequentially (75% of cases) with a median inter-eye delay of 8 weeks. Rarely, only one eye is affected. In the acute stage, lasting a few weeks, the affected eye demonstrates an oedematous appearance of the nerve fiber layer, especially in the arcuate bundles and enlarged or telangiectatic and tortuous peripapillary vessels (microangiopathy). The main features are seen on fundus examination , just before or after

2780-427: A person has a visual acuity of 6/12, they are said to see detail from 6 metres (20 ft) away the same as a person with "normal" eyesight would see it from 12 metres (39 ft) away. The definition of 6/6 is somewhat arbitrary, since human eyes typically have higher acuity, as Tscherning writes, "We have found also that the best eyes have a visual acuity which approaches 2, and we can be almost certain that if, with

2919-419: A pixel pair (one white and one black pixel) this gives a pixel density of 128 pixels per degree (PPD). 6/6 vision is defined as the ability to resolve two points of light separated by a visual angle of one minute of arc, corresponding to 60 PPD, or about 290–350 pixels per inch for a display on a device held 250 to 300 mm from the eye. Thus, visual acuity, or resolving power (in daylight, central vision),

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3058-506: A saccade and larger than a microsaccade, subtend up to one tenth of a degree. Researchers vary in their definition of microsaccades by amplitude. Martin Rolfs states that 'the majority of microsaccades observed in a variety of tasks have amplitudes smaller than 30 min-arc'. However, others state that the "current consensus has largely consolidated around a definition of microsaccades that includes magnitudes up to 1°." The vestibulo-ocular reflex

3197-530: A solid gold hue. Even though amber is similar to gold, some people have russet or copper colored amber eyes that are mistaken for hazel, though hazel tends to be duller and contains green with red/gold flecks, as mentioned above. Amber eyes may also contain amounts of very light gold-ish gray. People with that eye color are common in northern Europe , and in fewer numbers in southern Europe, the Middle East , North Africa , and South America . Hazel eyes are due to

3336-434: A static contrast ratio of around 100:1 (about 6.5 f-stops ). As soon as the eye moves rapidly to acquire a target ( saccades ), it re-adjusts its exposure by adjusting the iris, which adjusts the size of the pupil. Initial dark adaptation takes place in approximately four seconds of profound, uninterrupted darkness; full adaptation through adjustments in retinal rod photoreceptors is 80% complete in thirty minutes. The process

3475-480: A surgical area, such as cornea , cataracts , laser , retina , or oculoplastics . Eye care professionals include: Almost all mammals have brown or darkly-pigmented irises. In humans, brown is by far the most common eye color, with approximately 79% of people in the world having it. Brown eyes result from a relatively high concentration of melanin in the stroma of the iris, which causes light of both shorter and longer wavelengths to be absorbed. In many parts of

3614-423: A virus expressing the functional version of ND4—the gene mutated in this variant of LHON—injected into one eye. A sham injection will be administered to the other eye for comparison. It is hypothesized that introduction of the viral vector may be able to rescue the function of the mutant gene. Preliminary results have demonstrated tolerability of the injections in a small number of subjects. Stealth BioTherapeutics

3753-403: A volume of 6 cubic centimetres (0.37 cu in). The eyeball grows rapidly, increasing from about 16–17 mm (0.63–0.67 in) diameter at birth to 22.5–23 mm (0.89–0.91 in) by three years of age. By age 12, the eye attains its full size. The eye is made up of three coats, or layers, enclosing various anatomical structures. The outermost layer, known as the fibrous tunic ,

3892-522: Is distance acuity or far acuity (e.g., "20/20 vision"), which describes someone's ability to recognize small details at a far distance. This ability is compromised in people with myopia , also known as short-sightedness or near-sightedness. Another visual acuity is near acuity , which describes someone's ability to recognize small details at a near distance. This ability is compromised in people with hyperopia , also known as long-sightedness or far-sightedness. A common optical cause of low visual acuity

4031-399: Is refractive error (ametropia): errors in how the light is refracted in the eye. Causes of refractive errors include aberrations in the shape of the eye or the cornea , and reduced ability of the lens to focus light. When the combined refractive power of the cornea and lens is too high for the length of the eye, the retinal image will be in focus in front of the retina and out of focus on

4170-441: Is a reflex eye movement that stabilizes images on the retina during head movement by producing an eye movement in the direction opposite to head movement in response to neural input from the vestibular system of the inner ear, thus maintaining the image in the centre of the visual field. For example, when the head moves to the right, the eyes move to the left. This applies for head movements up and down, left and right, and tilt to

4309-416: Is a measure of visual performance and does not relate to the eyeglass prescription required to correct vision. Instead, an eye exam seeks to find the prescription that will provide the best corrected visual performance achievable. The resulting acuity may be greater or less than 6/6 = 1.0. Indeed, a subject diagnosed as having 6/6 vision will often actually have higher visual acuity because, once this standard

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4448-426: Is a proof-of-concept research technique for preventing mitochondrial disease in developing human fetuses. So far, viable macaque monkeys have been produced. But ethical and knowledge hurdles remain before use of the technique in humans is established. Idebenone is a short-chain benzoquinone that interacts with the mitochondrial electron transport chain to enhance cellular respiration. When used in people with LHON, it

4587-417: Is an area of 4.17 steradians or 13700 square degrees for binocular vision. When viewed at large angles from the side, the iris and pupil may still be visible by the viewer, indicating the person has peripheral vision possible at that angle. About 15° temporal and 1.5° below the horizontal is the blind spot created by the optic nerve nasally, which is roughly 7.5° high and 5.5° wide. The retina has

4726-416: Is attained, the subject is considered to have normal (in the sense of undisturbed) vision and smaller optotypes are not tested. Subjects with 6/6 vision or "better" (20/15, 20/10, etc.) may still benefit from an eyeglass correction for other problems related to the visual system, such as hyperopia , ocular injuries, or presbyopia . Visual acuity is measured by a psychophysical procedure and as such relates

4865-419: Is believed to allow electrons to bypass the dysfunctional complex I. Successful treatment with idebenone was initially reported in a small number of patients. Two large-scale studies have demonstrated the benefits of idebenone. The Rescue of Hereditary Optic Disease Outpatient Study (RHODOS) evaluated the effects of idebenone in 85 patients with LHON who had lost vision within the prior five years. In this study,

5004-425: Is beneficial treatment for some cases of LHON, especially for early-onset disease, and experimental treatment protocols are in progress. Genetic counseling should be offered. Health and lifestyle choices should be reassessed, particularly in light of toxic and nutritional theories of gene expression. Vision aids assistance and work rehabilitation should be used to assist in maintaining employment. For those who carry

5143-477: Is caused by the combination of: 1) an amber or light brown pigmentation in the stroma of the iris (which has a low or moderate concentration of melanin) with: 2) a blue shade created by the Rayleigh scattering of reflected light. Green eyes contain the yellowish pigment lipochrome . The inheritance pattern followed by blue eyes was previously assumed to be a mendelian recessive trait, however, eye color inheritance

5282-485: Is changed for near focus (accommodation) and is controlled by the ciliary muscle. Between the two lenses (the cornea and the crystalline lens), there are four optical surfaces which each refract light as it travels along the optical path. One basic model describing the geometry of the optical system is the Arizona Eye Model. This model describes the accommodation of the eye geometrically. Photons of light falling on

5421-432: Is commonly used clinically and in research because the lines are of equal length and so it forms a continuous scale with equally spaced intervals between points, unlike Snellen charts, which have different numbers of letters on each line. A visual acuity of 6/6 is frequently described as meaning that a person can see detail from 6 metres (20 ft) away the same as a person with "normal" eyesight would see from 6 metres. If

5560-411: Is composed of the cornea and sclera , which provide shape to the eye and support the deeper structures. The middle layer, known as the vascular tunic or uvea , consists of the choroid , ciliary body , pigmented epithelium and iris . The innermost is the retina , which gets its oxygenation from the blood vessels of the choroid (posteriorly) as well as the retinal vessels (anteriorly). The spaces of

5699-451: Is considered normal is called 6/6 vision, the USC equivalent of which is 20/20 vision: At 6 metres or 20 feet, a human eye with that performance is able to separate contours that are approximately 1.75 mm apart. Vision of 6/12 corresponds to lower performance, while vision of 6/3 to better performance. Normal individuals have an acuity of 6/4 or better (depending on age and other factors). In

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5838-406: Is emerging as an effective therapeutic target for female mutation carriers. In one recent case study where the affected female converted following cessation of HRT, idebenone , and HRT were given together. Visual acuity improved much faster than is typically expected. The patient's vision returned to 20/40 and 20/60 from 20/60 and 20/200 in the right and left eyes respectively after only one month and

5977-421: Is equal to 6/6. LogMAR is another commonly used scale, expressed as the ( decadic ) logarithm of the minimum angle of resolution (MAR), which is the reciprocal of the acuity number. The LogMAR scale converts the geometric sequence of a traditional chart to a linear scale. It measures visual acuity loss: positive values indicate vision loss, while negative values denote normal or better visual acuity. This scale

6116-440: Is exerted on the globe that causes it to turn, in almost pure rotation, with only about one millimeter of translation. Thus, the eye can be considered as undergoing rotations about a single point in the centre of the eye. The approximate field of view of an individual human eye (measured from the fixation point, i.e., the point at which one's gaze is directed) varies by facial anatomy, but is typically 30° superior (up, limited by

6255-436: Is generally advised, especially tobacco and alcohol. Certain prescription drugs are potential risks, so all drugs should be treated with suspicion and checked before use by those at risk. Ethambutol, in particular, has been implicated as triggering visual loss in carriers of LHON. In fact, toxic and nutritional optic neuropathies may have overlaps with LHON in symptoms, mitochondrial mechanisms of disease and management. And when

6394-455: Is investigating the use of elamipretide (MTP-131), a mitochondrial protective agent, as a therapy for LHON. Elamipretide helps stabilize cardiolipin—an important component of mitochondrial inner membranes—and has been shown to reduce damaging reactive oxygen species in animal models. Human eye The human eye is a sensory organ in the visual system that reacts to visible light allowing eyesight . Other functions include maintaining

6533-481: Is largest (about 8 mm), which occurs in low-light conditions. When the pupil is small (1–2 mm), image sharpness may be limited by diffraction of light by the pupil (see diffraction limit ). Between these extremes is the pupil diameter that is generally best for visual acuity in normal, healthy eyes; this tends to be around 3 or 4 mm. If the optics of the eye were otherwise perfect, theoretically, acuity would be limited by pupil diffraction, which would be

6672-415: Is linked to the larger posterior segment, composed of the vitreous, retina, choroid and the outer white shell called the sclera. The cornea is typically about 11.5 mm (0.45 in) in diameter, and 0.5 mm (500 μm) in thickness near its centre. The posterior chamber constitutes the remaining five-sixths; its diameter is typically about 24 mm (0.94 in). An area termed the limbus connects

6811-411: Is most active in this state. Estrogens have been shown to have a protective role in the pathogenesis of LHON. Experiments using LHON cybrids have demonstrated that the estrogen receptor localizes to the mitochondria where it directly mediates mitochondrial biogenesis. Estrogens upregulate the antioxidant enzyme superoxide dismutase 2 and mitochondrial DNA synthesis. These experiments helped to explain

6950-401: Is much better than human eyesight. When visual acuity is below the largest optotype on the chart, the reading distance is reduced until the patient can read it. Once the patient is able to read the chart, the letter size and test distance are noted. If the patient is unable to read the chart at any distance, they are tested as follows: For example, the recording CF 5' would mean the patient

7089-459: Is nonlinear and multifaceted, so an interruption by light exposure requires restarting the dark adaptation process over again. The human eye can detect a luminance from 10 cd/m , or one millionth (0.000001) of a candela per square meter to 10 cd/m or one hundred million (100,000,000) candelas per square meter. (that is it has a range of 10 , or one hundred trillion 100,000,000,000,000, about 46.5 f-stops). This range does not include looking at

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7228-461: Is now recognized as a polygenic trait , meaning that it is controlled by the interactions of several genes. Blue eyes are predominant in northern and eastern Europe, particularly around the Baltic Sea . Blue eyes are also found in southern Europe, Central Asia , South Asia , North Africa and West Asia . Approximately 8% to 10% of the global population have blue eyes. A 2002 study found that

7367-592: Is performed at a testing distance of 1 foot or less.) Various countries have defined statutory limits for poor visual acuity that qualifies as a disability. For example, in Australia, the Social Security Act defines blindness as: A person meets the criteria for permanent blindness under section 95 of the Social Security Act if the corrected visual acuity is less than 6/60 on the Snellen Scale in both eyes or there

7506-425: Is responsible for, among many other things, absorbing light that crosses the retina so it cannot bounce to other parts of the retina. In many vertebrates, such as cats, where high visual acuity is not a priority, there is a reflecting tapetum layer that gives the photoreceptors a "second chance" to absorb the light, thus improving the ability to see in the dark. This is what causes an animal's eyes to seemingly glow in

7645-512: Is the preferred treatment protocol for people with LHON. Idebenone doses are prescribed to be taken spaced out throughout the day, rather than all at once. For example, to achieve a dose of 900 mg per day, patients take 300 mg three times daily with meals. Idebenone is fat-soluble, and may be taken with a moderate amount of dietary fat in each meal to promote absorption. It is recommended that patients on idebenone also take vitamin C 500 mg daily to keep idebenone in its reduced form, as it

7784-404: Is the property of cones. To resolve detail, the eye's optical system has to project a focused image on the fovea , a region inside the macula having the highest density of cone photoreceptor cells (the only kind of photoreceptors existing in the fovea's very center of 300 μm diameter), thus having the highest resolution and best color vision. Acuity and color vision, despite being mediated by

7923-577: The European norm (EN ISO 8596, previously DIN 58220). In later editions of his book, Snellen called the letters of his charts optotypes and advocated for standardized vision tests. Snellen's optotypes are not identical to the test letters used today. They were printed in an " Egyptian Paragon" font (i.e. using serifs ). Theodor Wertheim in Berlin presents detailed measurements of acuity in peripheral vision . Hugh Taylor uses these design principles for

8062-533: The Golovin–Sivtsev table , or other patterns – on a printed chart (or some other means) from a set viewing distance. Optotypes are represented as black symbols against a white background (i.e. at maximum contrast ). The distance between the person's eyes and the testing chart is set so as to approximate " optical infinity " in the way the lens attempts to focus (far acuity), or at a defined reading distance (near acuity). A reference value above which visual acuity

8201-471: The NADH dehydrogenase protein involved in the normal mitochondrial function of oxidative phosphorylation . Oxidative phosphorylation uses a series of four large multienzyme complexes, all embedded in the inner mitochondrial membrane, to convert oxygen and simple sugars to energy. Mutations in any of the genes disrupt this process to cause a variety of syndromes depending on the type of mutation and other factors. It remains unclear how these genetic changes cause

8340-761: The Netherlands and the United Kingdom , and have also been observed to be very common among the Low Saxon speaking populations of northern Germany. Green eyes are most common in Northern , Western and Central Europe . Around 8–10% of men and 18–21% of women in Iceland and 6% of men and 17% of women in the Netherlands have green eyes. Among European Americans , green eyes are most common among those of recent Celtic and Germanic ancestry, with about 16%. The green color

8479-444: The central fovea ) and allow high acuity of 6/6 or better. In low light (i.e., scotopic vision ), cones do not have sufficient sensitivity and vision is subserved by rods . Spatial resolution is then much lower. This is due to spatial summation of rods , i.e. a number of rods merge into a bipolar cell , in turn connecting to a ganglion cell , and the resulting unit for resolution is large, and acuity small. There are no rods in

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8618-425: The ciliary muscles surrounding the lens; this process is known as "accommodation". Accommodation narrows the inner diameter of the ciliary body, which actually relaxes the fibers of the suspensory ligament attached to the periphery of the lens, and also allows the lens to relax into a more convex, or globular, shape. A more convex lens refracts light more strongly and focuses divergent light rays from near objects onto

8757-423: The circadian rhythm , and keeping balance . The eye can be considered as a living optical device . It is approximately spherical in shape, with its outer layers, such as the outermost, white part of the eye (the sclera ) and one of its inner layers (the pigmented choroid ) keeping the eye essentially light tight except on the eye's optic axis . In order, along the optic axis, the optical components consist of

8896-404: The eye movements , the seventh controls the movement of the upper eyelid . The six muscles are four recti muscles – the lateral rectus , the medial rectus , the inferior rectus , and the superior rectus , and two oblique muscles the inferior oblique , and the superior oblique . The seventh muscle is the levator palpebrae superioris muscle . When the muscles exert different tensions, a torque

9035-489: The macula ) is represented by at least 60% of the visual cortex. Many of these neurons are believed to be involved directly in visual acuity processing. Proper development of normal visual acuity depends on a human or an animal having normal visual input when it is very young. Any visual deprivation, that is, anything interfering with such input over a prolonged period of time, such as a cataract , severe eye turn or strabismus , anisometropia (unequal refractive error between

9174-400: The midbrain called the lateral geniculate nucleus , part of the thalamus , and then to the visual cortex along a collection of nerve fibers called the optic radiation . Any pathological process in the visual system, even in older humans beyond the critical period, will often cause decreases in visual acuity. Thus measuring visual acuity is a simple test in accessing the health of the eyes,

9313-399: The nervous system : rods respond to low intensity light and contribute to perception of low-resolution, black-and-white images; cones respond to high intensity light and contribute to perception of high-resolution, coloured images; and the recently discovered photosensitive ganglion cells respond to a full range of light intensities and contribute to adjusting the amount of light reaching

9452-404: The pupil . A thin layer called the conjunctiva sits on top of this. The front part is also called the anterior segment of the eye. The eye is not shaped like a perfect sphere; rather it is a fused two-piece unit, composed of an anterior (front) segment and the posterior (back) segment. The anterior segment is made up of the cornea, iris and lens. The cornea is transparent and more curved and

9591-528: The 11778 mutation accounts for 50-70% of cases, the 14484 mutation for 10-15% and the 3460 mutation for 8-25%. Human clinical trials are underway at GenSight Biologics (ClinicalTrials.gov # NCT02064569) and the University of Miami (ClinicalTrials.gov # NCT02161380) to examine the safety and efficacy of mitochondrial gene therapy in LHON. In these trials, participants affected by LHON with the G11778A mutation will have

9730-517: The LHON ND6 T14484C mutation accounts for 86% of LHON cases in Quebec , Canada. More than 50% of males with a mutation and more than 85% of females with a mutation never experience vision loss or related medical problems. The particular mutation type may predict the likelihood of penetrance , severity of illness and probability of vision recovery in the affected. As a rule of thumb, a woman who harbors

9869-465: The X chromosome, contribute to the development of signs and symptoms. The degree of heteroplasmy , the percentage of mitochondria that have mutant alleles , may play a role. Patterns of mitochondrial alleles called haplogroup may also affect expression of mutations. LHON was first described by the German ophthalmologist Theodor Leber (1840–1917) in 1871. In a paper, Leber described four families in which

10008-410: The affected eye as well as cells connected to both eyes in cortical area V1 , resulting in a loss of stereopsis , i.e. depth perception by binocular vision (colloquially: "3D vision"). The period of time over which an animal is highly sensitive to such visual deprivation is referred to as the critical period . The eye is connected to the visual cortex by the optic nerve coming out of the back of

10147-408: The better-focused centre. In the eye, the pupil serves this purpose by constricting while the eye is focused on nearby objects. Small apertures also give an increase in depth of field , allowing a broader range of "in focus" vision. In this way the pupil has a dual purpose for near vision: to reduce spherical aberration and increase depth of field. Changing the curvature of the lens is carried out by

10286-476: The brain to determine the depth and distance of an object, called stereovision, and gives the sense of three-dimensionality to the vision. Both eyes must point accurately enough that the object of regard falls on corresponding points of the two retinas to stimulate stereovision; otherwise, double vision might occur. Some persons with congenitally crossed eyes tend to ignore one eye's vision, thus do not suffer double vision, and do not have stereovision. The movements of

10425-401: The brow), 45° nasal (limited by the nose), 70° inferior (down), and 100° temporal (towards the temple). For both eyes, combined ( binocular vision ) visual field is approximately 100° vertical and a maximum 190° horizontal, approximately 120° of which makes up the binocular field of view (seen by both eyes) flanked by two uniocular fields (seen by only one eye) of approximately 40 degrees. It

10564-591: The case of myopia, the correction is to reduce the power of the eye's refraction by a so-called minus lens. Neural factors that limit acuity are located in the retina, in the pathways to the brain, or in the brain. Examples of conditions affecting the retina include detached retina and macular degeneration . Examples of conditions affecting the brain include amblyopia (caused by the visual brain not having developed properly in early childhood) and by brain damage, such as from traumatic brain injury or stroke. When optical factors are corrected for, acuity can be considered

10703-423: The ciliary body by the suspensory ligament ( zonule of Zinn ), made up of hundreds of fine transparent fibers which transmit muscular forces to change the shape of the lens for accommodation (focusing). The vitreous body is a clear substance composed of water and proteins, which give it a jelly-like and sticky composition. Each eye has seven extraocular muscles located in its orbit . Six of these muscles control

10842-443: The clarity of vision , but technically rates an animal 's ability to recognize small details with precision. Visual acuity depends on optical and neural factors. Optical factors of the eye influence the sharpness of an image on its retina . Neural factors include the health and functioning of the retina, of the neural pathways to the brain, and of the interpretative faculty of the brain. The most commonly referred-to visual acuity

10981-401: The cornea and sclera. The iris is the pigmented circular structure concentrically surrounding the centre of the eye, the pupil, which appears to be black. The size of the pupil, which controls the amount of light entering the eye, is adjusted by the iris' dilator and sphincter muscles . Light energy enters the eye through the cornea, through the pupil and then through the lens. The lens shape

11120-446: The dark when a light is shone on them. The RPE also has a vital function of recycling the chemicals used by the rods and cones in photon detection. If the RPE is damaged and does not clean up this "shed" blindness can result. As in a photographic lens , visual acuity is affected by the size of the pupil. Optical aberrations of the eye that decrease visual acuity are at a maximum when the pupil

11259-406: The dark. The latter value decreases slowly with age; older people's eyes sometimes dilate to not more than 5–6mm in the dark, and may be as small as 1mm in the light. The visual system in the human brain is too slow to process information if images are slipping across the retina at more than a few degrees per second. Thus, to be able to see while moving, the brain must compensate for the motion of

11398-592: The death of cells in the optic nerve and lead to the specific features of Leber hereditary optic neuropathy. The eye pathology is limited to the retinal ganglion cell layer, especially the maculopapillary bundle. Degeneration is evident from the retinal ganglion cell bodies to the axonal pathways leading to the lateral geniculate nuclei . Experimental evidence reveals impaired glutamate transport and increased reactive oxygen species (ROS) causing apoptosis of retinal ganglion cells. Also, experiments suggest that normal, non-LHON-affected retinal ganglion cells produce less of

11537-416: The effects of idebenone 30 months after discontinuing therapy. A retrospective analysis of 103 LHON patients by Carelli et al. builds upon these results. This study highlighted that 44 subjects who were treated with idebenone within one year of onset of vision loss had better outcomes, and that these improvements persisted for years. Idebenone, combined with avoidance of smoke and limitation of alcohol intake,

11676-523: The examiner's hand from a maximum distance of 2 feet directly in front of the examiner. (The results of the Hand Motion test are often recorded without the testing distance. This is due to the fact that this test is performed after the patient cannot "pass" the Counting Fingers test. At this point, the examiner is usually directly in front of the patient, and it is assumed that the Hand Motion test

11815-419: The expression 6/x vision, the numerator (6) is the distance in metres between the subject and the chart and the denominator (x) the distance at which a person with 6/6 acuity would discern the same optotype. Thus, 6/12 means that a person with 6/6 vision would discern the same optotype from 12 metres away (i.e. at twice the distance). This is equivalent to saying that with 6/12 vision, the person possesses half

11954-462: The eye are controlled by six muscles attached to each eye, and allow the eye to elevate, depress, converge, diverge and roll. These muscles are both controlled voluntarily and involuntarily to track objects and correct for simultaneous head movements. Rapid eye movement, REM, typically refers to the sleep stage during which the most vivid dreams occur. During this stage, the eyes move rapidly. Saccades are quick, simultaneous movements of both eyes in

12093-404: The eye are filled with the aqueous humour anteriorly, between the cornea and lens, and the vitreous body , a jelly-like substance, behind the lens, filling the entire posterior cavity. The aqueous humour is a clear watery fluid that is contained in two areas: the anterior chamber between the cornea and the iris, and the posterior chamber between the iris and the lens. The lens is suspended to

12232-404: The eye at up to 100°/s in adult humans. It is more difficult to visually estimate speed in low light conditions or while moving, unless there is another point of reference for determining speed. The optokinetic reflex (or optokinetic nystagmus) stabilizes the image on the retina through visual feedback. It is induced when the entire visual scene drifts across the retina, eliciting eye rotation in

12371-417: The eye. The two optic nerves come together behind the eyes at the optic chiasm , where about half of the fibers from each eye cross over to the opposite side and join fibers from the other eye representing the corresponding visual field, the combined nerve fibers from both eyes forming the optic tract . This ultimately forms the physiological basis of binocular vision . The tracts project to a relay station in

12510-400: The fixation object to the fovea through an imaginary path called the visual axis. The eye's tissues and structures that are in the visual axis (and also the tissues adjacent to it) affect the quality of the image. These structures are: tear film, cornea, anterior chamber, pupil, lens, vitreous, and finally the retina. The posterior part of the retina, called the retinal pigment epithelium (RPE)

12649-450: The foveal cone diameter or the angle subtended at the nodal point of the eye. To get reception from each cone, as it would be if vision was on a mosaic basis, the "local sign" must be obtained from a single cone via a chain of one bipolar, ganglion, and lateral geniculate cell each. A key factor of obtaining detailed vision, however, is inhibition. This is mediated by neurons such as the amacrine and horizontal cells, which functionally render

12788-422: The group taking idebenone 900 mg per day for 24 weeks showed a slight improvement in visual acuity compared to the placebo group, though the difference was not statistically significant. But patients taking idebenone were protected from further vision loss, whereas the placebo group had a steady decline in visual acuity. Further, people taking idebenone demonstrated preservation of color vision and persistence of

12927-422: The head by turning the eyes. Frontal-eyed animals have a small area of the retina with very high visual acuity, the fovea centralis . It covers about 2 degrees of visual angle in people. To get a clear view of the world, the brain must turn the eyes so that the image of the object of regard falls on the fovea. Any failure to make eye movements correctly can lead to serious visual degradation. Having two eyes allows

13066-517: The ideal eye, the image of a diffraction grating can subtend 0.5 micrometre on the retina. This is certainly not the case, however, and furthermore the pupil can cause diffraction of the light. Thus, black lines on a grating will be mixed with the intervening white lines to make a gray appearance. Defective optical issues (such as uncorrected myopia) can render it worse, but suitable lenses can help. Images (such as gratings) can be sharpened by lateral inhibition, i.e., more highly excited cells inhibiting

13205-599: The iris. Eye irritation has been defined as "the magnitude of any stinging, scratching, burning, or other irritating sensation from the eye". It is a common problem experienced by people of all ages. Related eye symptoms and signs of irritation are discomfort, dryness, excess tearing, itchiness, grating, foreign body sensation, ocular fatigue, pain, soreness, redness, swollen eyelids, and tiredness, etc. These eye symptoms are reported with intensities from mild to severe. It has been suggested that these eye symptoms are related to different causal mechanisms, and symptoms are related to

13344-606: The lack of muscular control and the presence of demyelinating lesions in the CNS. It is therefore a subtype of MS, according to McDonald's definition. Leber hereditary optic neuropathy is a condition related to changes in mitochondrial DNA . Although most DNA is packaged in chromosomes within the nucleus, mitochondria have a distinct mitochondrial genome composed of mtDNA. Mutations in the MT-ND1 , MT-ND4 , MT-ND4L , and MT-ND6 genes cause Leber hereditary optic neuropathy. These genes code for

13483-411: The less excited cells. A similar reaction is in the case of chromatic aberrations, in which the color fringes around black-and-white objects are inhibited similarly. Visual acuity is often measured according to the size of letters viewed on a Snellen chart or the size of other symbols, such as Landolt Cs or the E Chart . In some countries, acuity is expressed as a vulgar fraction , and in some as

13622-444: The light that is reflected from the epithelium undergoes Mie scattering (which is not strongly frequency-dependent) rather than Rayleigh scattering (in which shorter wavelengths of light are scattered more). This would be analogous to the change in the color of the sky, from the blue given by the Rayleigh scattering of sunlight by small gas molecules when the sky is clear, to the gray caused by Mie scattering of large water droplets when

13761-423: The light-sensitive cells of the retina ( photoreceptor cones and rods ) are converted into electrical signals that are transmitted to the brain by the optic nerve and interpreted as sight and vision. The size of the eye differs among adults by only one or 2 millimetres. The eyeball is generally less tall than it is wide. The sagittal vertical (height) of a human adult eye is approximately 23.7 mm (0.93 in),

13900-420: The mechanism behind the lower penetrance of disease among female carriers. While additional factors have been theorized, the protective role of estrogens appears to be a significant contributor. In addition to the experimental evidence, clinical data also points towards the protective role of estrogens. Penetrance among female carriers is substantially lower (between 3 and 8 to 1 male to female ratios depending on

14039-471: The midday sun (10 cd/m ) or lightning discharge. At the low end of the range is the absolute threshold of vision for a steady light across a wide field of view, about 10 cd/m (0.000001 candela per square meter). The upper end of the range is given in terms of normal visual performance as 10 cd/m (100,000,000 or one hundred million candelas per square meter). The eye includes a lens similar to lenses found in optical instruments such as cameras and

14178-450: The mutation) while average age at onset is significantly higher. Multiple case series of various LHON pedigrees have described female carriers converting after menopause or cessation of hormone replacement therapies. Together, these form a shifting paradigm towards considering reduced estrogen states, such as menopause, as potential triggers of visual loss similar to smoking or excessive alcohol consumption. Hormone replacement therapy (HRT)

14317-510: The onset of visual loss. A pupillary defect may be visible in the acute stage as well. Examination reveals decreased visual acuity, loss of color vision , and a cecocentral scotoma on visual field examination . LHON Plus is a rare variant of the disorder with eye disease together with other conditions. Its symptoms include loss of the brain's ability to control the movement of muscles, tremors, and cardiac arrhythmia . Many cases of LHON plus have been compared to multiple sclerosis because of

14456-405: The overall quality of visual function. Visual acuity is a measure of the spatial resolution of the visual processing system. VA, as it is sometimes referred to by optical professionals, is tested by requiring the person whose vision is being tested to identify so-called optotypes – stylized letters, Landolt rings , pediatric symbols , symbols for the illiterate , standardized Cyrillic letters in

14595-417: The particular ocular anatomy involved. Several suspected causal factors in our environment have been studied so far. One hypothesis is that indoor air pollution may cause eye and airway irritation. Eye irritation depends somewhat on destabilization of the outer-eye tear film, i.e. the formation of dry spots on the cornea, resulting in ocular discomfort. Occupational factors are also likely to influence

14734-957: The perception of eye irritation. Some of these are lighting (glare and poor contrast), gaze position, reduced blink rate, limited number of breaks from visual tasking, and a constant combination of accommodation, musculoskeletal burden, and impairment of the visual nervous system. Another factor that may be related is work stress. In addition, psychological factors have been found in multivariate analyses to be associated with an increase in eye irritation among VDU users. Other risk factors, such as chemical toxins/irritants (e.g. amines , formaldehyde , acetaldehyde , acrolein , N-Decane , VOCs , ozone , pesticides and preservatives , allergens , etc.) might cause eye irritation as well. Certain volatile organic compounds that are both chemically reactive and airway irritants may cause eye irritation. Personal factors (e.g. use of contact lenses, eye make-up, and certain medications) may also affect destabilization of

14873-574: The physical characteristics of a stimulus to a subject's percept and their resulting responses. Measurement can be taken by using an eye chart invented by Ferdinand Monoyer , by optical instruments, or by computerized tests like the FrACT. Care must be taken that viewing conditions correspond to the standard, such as correct illumination of the room and the eye chart, correct viewing distance, enough time for responding, error allowance, and so forth. In European countries, these conditions are standardized by

15012-517: The potent superoxide radical than other normal central nervous system neurons. Viral vector experiments that augment superoxide dismutase 2 in LHON cybrids or LHON animal models or use of exogenous glutathione in LHON cybrids have been shown to rescue LHON-affected retinal ganglion cells from apoptotic death. These experiments may in part explain the death of LHON-affected retinal ganglion cells in preference to other central nervous system neurons that also carry LHON-affected mitochondria. Without

15151-468: The prevalence of blue eye color among the white population in the United States to be 33.8% for those born from 1936 through 1951. Like blue eyes, gray eyes have a dark epithelium at the back of the iris and a relatively clear stroma at the front. One possible explanation for the difference in the appearance of gray and blue eyes is that gray eyes have larger deposits of collagen in the stroma, so that

15290-542: The profession with the new layout and progression. Data from the ETDRS were used to select letter combinations that give each line the same average difficulty, without using all letters on each line. The International Council of Ophthalmology approves a new "Visual Acuity Measurement Standard", also incorporating the above features. Antonio Medina and Bradford Howland of the Massachusetts Institute of Technology develop

15429-481: The region. Amber eyes are a solid color with a strong yellowish/golden and russet/coppery tint, which may be due to the yellow pigment called lipochrome (also found in green eyes). Amber eyes should not be confused with hazel eyes. Although hazel eyes may contain specks of amber or gold, they usually tend to have many other colors, including green, brown and orange. Also, hazel eyes may appear to shift in color and consist of flecks and ripples, while amber eyes are of

15568-414: The remaining focusing of light into images ; and finally a light-sensitive part of the eye (the retina ), where the images fall and are processed. The retina makes a connection to the brain via the optic nerve . The remaining components of the eye keep it in its required shape, nourish and maintain it, and protect it. Three types of cells in the retina convert light energy into electrical energy used by

15707-455: The retina in both eyes. To look at a nearby object, the eyes rotate 'towards each other' ( convergence ), while for an object farther away they rotate 'away from each other' ( divergence ). Lenses cannot refract light rays at their edges as well as closer to the centre. The image produced by any lens is therefore somewhat blurry around the edges ( spherical aberration ). It can be minimized by screening out peripheral light rays and looking only at

15846-655: The retina, allowing closer objects to be brought into better focus. The human eye contains enough complexity to warrant specialized attention and care beyond the duties of a general practitioner . These specialists, or eye care professionals , serve different functions in different countries. Eye care professionals can have overlap in their patient care privileges. For example, both an ophthalmologist (M.D.) and optometrist (O.D.) are professionals who diagnose eye disease and can prescribe lenses to correct vision. Typically, only ophthalmologists are licensed to perform surgical procedures. Ophthalmologists may also specialize within

15985-405: The retina, to regulating and suppressing the hormone melatonin , and to entraining circadian rhythm . Humans have two eyes, situated on the left and the right of the face . The eyes sit in bony cavities called the orbits , in the skull . There are six extraocular muscles that control eye movements. The front visible part of the eye is made up of the whitish sclera , a coloured iris , and

16124-608: The retina, yielding myopia. A similar poorly focused retinal image happens when the combined refractive power of the cornea and lens is too low for the length of the eye except that the focused image is behind the retina, yielding hyperopia. Normal refractive power is referred to as emmetropia . Other optical causes of low visual acuity include astigmatism , in which contours of a particular orientation are blurred, and more complex corneal irregularities. Refractive errors can mostly be corrected by optical means (such as eyeglasses , contact lenses , and refractive surgery ). For example, in

16263-405: The retina. Laser interferometers are now used routinely in patients with optical problems, such as cataracts , to assess the health of the retina before subjecting them to surgery. The visual cortex is the part of the cerebral cortex in the posterior part of the brain responsible for processing visual stimuli, called the occipital lobe . The central 10° of field (approximately the extension of

16402-449: The right and left, all of which give input to the ocular muscles to maintain visual stability. Eyes can also follow a moving object around. This tracking is less accurate than the vestibulo-ocular reflex, as it requires the brain to process incoming visual information and supply feedback . Following an object moving at constant speed is relatively easy, though the eyes will often make saccades to keep up. The smooth pursuit movement can move

16541-403: The same cells, are different physiologic functions that do not interrelate except by position. Acuity and color vision can be affected independently. The grain of a photographic mosaic has just as limited resolving power as the "grain" of the retinal mosaic . To see detail, two sets of receptors must be intervened by a middle set. The maximum resolution is that 30 seconds of arc, corresponding to

16680-407: The same direction and at a velocity that minimizes the motion of the image on the retina. When the gaze direction deviates too far from the forward heading, a compensatory saccade is induced to reset the gaze to the centre of the visual field. For example, when looking out of the window at a moving train, the eyes can focus on a moving train for a short moment (by stabilizing it on the retina), until

16819-421: The same direction controlled by the frontal lobe of the brain. Even when looking intently at a single spot, the eyes drift around. This ensures that individual photosensitive cells are continually stimulated in different degrees. Without changing input, these cells would otherwise stop generating output. Eye movements include drift, ocular tremor , and microsaccades. Some irregular drifts, movements smaller than

16958-447: The same physics principles can be applied. The pupil of the human eye is its aperture ; the iris is the diaphragm that serves as the aperture stop. Refraction in the cornea causes the effective aperture (the entrance pupil ) to differ slightly from the physical pupil diameter. The entrance pupil is typically about 4 mm in diameter, although it can range from 2 mm ( f /8.3 ) in a brightly lit place to 8 mm ( f /2.1 ) in

17097-539: The size of a letter on the Snellen chart or Landolt C chart is a visual angle of 5 arc minutes (1 arc min = 1/60 of a degree), which is a 43 point font at 20 feet. By the design of a typical optotype (like a Snellen E or a Landolt C), the critical gap that needs to be resolved is 1/5 this value, i.e., 1 arc min. The latter is the value used in the international definition of visual acuity:       acuity = ⁠ 1 / gap size [arc min] ⁠ . Acuity

17236-439: The size of a patch of cortical tissue in visual area V1 that processes a given location in the visual field (a concept known as cortical magnification ) is equally important in determining visual acuity. In particular, that size is largest in the fovea's center, and decreases with increasing distance from there. Besides the neural connections of the receptors, the optical system is an equally key player in retinal resolution. In

17375-592: The sky is cloudy. Alternatively, it has been suggested that gray and blue eyes might differ in the concentration of melanin at the front of the stroma. Gray eyes can also be found among the Algerian Shawia people of the Aurès Mountains in Northwest Africa, in the Middle East / West Asia , Central Asia , and South Asia . Under magnification, gray eyes exhibit small amounts of yellow and brown color in

17514-401: The spatial resolution and needs twice the size to discern the optotype. A simple and efficient way to state acuity is by converting the fraction to a decimal: 6/6 then corresponds to an acuity (or a Visus) of 1.0 (see Expression below), while 6/3 corresponds to 2.0, which is often attained by well-corrected healthy young subjects with binocular vision . Stating acuity as a decimal number is

17653-422: The spread or convergence of signals inactive. This tendency to one-to-one shuttle of signals is powered by brightening of the center and its surroundings, which triggers the inhibition leading to a one-to-one wiring. This scenario, however, is rare, as cones may connect to both midget and flat (diffuse) bipolars, and amacrine and horizontal cells can merge messages just as easily as inhibit them. Light travels from

17792-455: The standard in European countries, as required by the European norm (EN ISO 8596, previously DIN 58220). The precise distance at which acuity is measured is not important as long as it is sufficiently far away and the size of the optotype on the retina is the same. That size is specified as a visual angle , which is the angle, at the eye, under which the optotype appears. For 6/6 = 1.0 acuity,

17931-453: The substantial risk of vision loss associated with menopause. In Northern European populations about one in 9,000 people carries one of the three primary LHON mutations. There is a prevalence of between 1:30,000 to 1:50,000 in Europe. The LHON ND4 G11778A mutation is the primary mutation in most of the world, with 70% of Northern European cases and 90% of Asian cases. Due to a Founder effect ,

18070-551: The tear film and possibly result in more eye symptoms. Nevertheless, if airborne particles alone should destabilize the tear film and cause eye irritation, their content of surface-active compounds must be high. An integrated physiological risk model with blink frequency, destabilization, and break-up of the eye tear film as inseparable phenomena may explain eye irritation among office workers in terms of occupational, climate, and eye-related physiological risk factors. Visual acuity Visual acuity ( VA ) commonly refers to

18209-400: The train moves out of the field of vision. At this point, the eye is moved back to the point where it first saw the train (through a saccade). The adjustment to close-range vision involves three processes to focus an image on the retina. When a creature with binocular vision looks at an object, the eyes must rotate around a vertical axis so that the projection of the image is in the centre of

18348-425: The transverse horizontal diameter (width) is 24.2 mm (0.95 in) and the axial anteroposterior size (depth) averages 22.0–24.8 mm (0.87–0.98 in) with no significant difference between sexes and age groups. Strong correlation has been found between the transverse diameter and the width of the orbit (r = 0.88). The typical adult eye has an anterior to posterior diameter of 24 mm (0.94 in), and

18487-428: The two eyes), or covering or patching the eye during medical treatment, will usually result in a severe and permanent decrease in visual acuity and pattern recognition in the affected eye if not treated early in life, a condition known as amblyopia . The decreased acuity is reflected in various abnormalities in cell properties in the visual cortex. These changes include a marked decrease in the number of cells connected to

18626-437: The very center of the visual field (the foveola ), and highest performance in low light is achieved in near peripheral vision . The maximum angular resolution of the human eye is 28 arc seconds or 0.47 arc minutes; this gives an angular resolution of 0.008 degrees, and at a distance of 1 km corresponds to 136 mm. This is equal to 0.94 arc minutes per line pair (one white and one black line), or 0.016 degrees. For

18765-431: The visual brain, or pathway to the brain. Any relatively sudden decrease in visual acuity is always a cause for concern. Common causes of decreases in visual acuity are cataracts and scarred corneas , which affect the optical path, diseases that affect the retina, such as macular degeneration and diabetes , diseases affecting the optic pathway to the brain such as tumors and multiple sclerosis , and diseases affecting

18904-460: The visual cortex such as tumors and strokes. Though the resolving power depends on the size and packing density of the photoreceptors, the neural system must interpret the receptors' information. As determined from single-cell experiments on the cat and primate, different ganglion cells in the retina are tuned to different spatial frequencies , so some ganglion cells at each location have better acuity than others. Ultimately, however, it appears that

19043-620: The world, it is nearly the only iris color present. Brown eyes are common in Europe , East Asia , Southeast Asia , Central Asia , South Asia , West Asia , Oceania , Africa and the Americas . Light or medium-pigmented brown eyes can also be commonly found in Europe , among the Americas , and parts of Central Asia , West Asia and South Asia . Light brown eyes bordering amber and hazel coloration are common in Europe, but can also be observed in East Asia and Southeast Asia, though are uncommon in

19182-413: Was able to count the examiner's fingers from a maximum distance of 5 feet directly in front of the examiner. (The results of this test, on the same patient, may vary from examiner to examiner. This is due more to the size differences of the various examiners' hands and fingers, than to fluctuating vision.) For example, the recording HM 2' would mean that the patient was able to distinguish movement of

19321-420: Was back normal by 8 months compared to the months to years timeframe seen in most cases. While the balance between risks and benefits of HRT remains controversial, the decision to start HRT requires an individualized approach based on the patient's context. While not applicable for all post-menopausal women, prophylactic (and therapeutic) HRT should be considered in all female carriers of a known LHON mutation given

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