A Review of Achromatopsia

Congenital achromatopsia is a hereditary form of day blindness caused by cone photoreceptor dysfunction, with an incidence of approximately 1 in 30,000. This inherited disorder is characterized by a lack of color discrimination, nystagmus, photophobia, and low visual acuity (< 0.2). The most typical genetic mutations are autosomal recessive changes in CNGA3, CNGB3, GNAT2, PDE6H, PDE6C, or ATF6. It should not be confused with cerebral achromatopsia, which is an acquired form of total color blindness that can result from illness, trauma, or some other cause. Color plays an essential role in our lives. It can change actions, influence thinking, and cause reactions. As a powerful type of communication, color is irreplaceable. Green means “go” and red means “stop”. Traffic lights send this global meaning. Color vision deficiency, creates challenges in the daily lives of those who have an insufficient visual sense. Purpose: The aim of this review is to examine the literature published on achromatopsia and summarize the diagnosis, management, genetic characteristics, and the recent advances in gene therapy. Conclusions: Congenital achromatopsia is a complex inherited disease. Management of achromatopsia is multifaceted. There is currently no cure for achromatopsia, although gene therapy is a therapeutic option already being studied in clinical trials. The most recent study in human adults can be classified as safe and positive in terms of efficacy.

mistaken for congenital achromatopsia but physiological deficits of both disorders are completely different. It is a consequence of cortical damage that arises through ischemia or infarction of a specific area in the ventral occipitotemporal cortex of humans [7].
This damage is almost always the result of injury or illness [8].
Medical history and age at presentation will help to differentiate this condition from congenital achromatopsia. Additionally, these patients nearly always have additional neurologic symptoms beyond the loss of color vision [8].

Epidemiology
Achromatopsia is a relatively uncommon disorder that affects an estimated 1 in 30,000 people worldwide [9]. Complete achromatopsia is more common than incomplete achromatopsia.
Its incidence varies in different parts of the world. Because there is a genetic link, it is more common in regions where there is a high rate of consanguineous marriages (marriages between relatives) and in the eastern Pacific islands of Pingelap [10], approximately five percent of the atoll's 3,000 inhabitants are afflicted [11,12].
The people of this region have termed achromatopsia "maskun", which literally means "not see" in Pingelapese [13]. The condition can be traced back to 1775, when Typhoon Lengkieki decimated the population in the island, leaving only a handful of survivors to repopulate the islands. One of the few survivors was a carrier of the rare genetic mutation and passing it on to his descendants, he became the genetic founder for the vision disorder four generations later [14]. Oliver Sacks wrote his book, The Island of the Colorblind  Rod and cone photoreceptors are specialized neurons that function in the initial step of vision [15]. These light-sensitive cells lie at the back of the retina adjacent to the retinal pigment epithelium (RPE), a cell layer that is vital for the survival of photoreceptors [15]. Cones are mostly in the center of the retina. When retinitis pigmentosa affects them, there is a slowly loss of central vision and of the ability to see colors [15]. Rods work at very low levels of light. Only a few bits of light (photons) can activate a rod, that's why we use these for night vision. Rods don't help with color vision, which is why at night, we see everything in a gray scale [16]. Rods are more numerous, about 120 million, and more sensitive than cones. However, they are not sensitive to color. Rods are much more concentrated in the macula (central yellow spot) and they provide the eye's color sensitivity. In the center of the macula is the "fovea centralis", a 0.3 mm diameter rod-free area with densely packed and very thin cones. Rod and cone photoreceptors have similar structures ( Figure 1). Photoreceptors have diameters ranging from 1 to 4 µm, being smaller at the fovea, enhancing visual acuity there.

Photoreceptors: rods and cones
The inner segment contains the nucleus and has an axon-like process connected to a synaptic terminal. The outer segment in the cone cell has its plasma membrane invaginated into numerous closely packed parallel folds [17], forming discs. In rod cells the discs are pinched off the plasma membrane to become completely intracellular [17].
The disc membrane is densely packed with visual pigment. In rod cells, this is rhodopsin. Each type of cone cells has its characteristic cone opsin. The outer segment is continually regenerated from the base, whilst its apical tip is phagocytosed by pigment epithelial cells at the rate of 3-4 discs per hour. Photoreceptors are incapable of mitotic division [17].
In 1965 came experimental confirmation of a long-expected result -there are three types of color-sensitive cones in the retina of the human eye, red or L cones (long wavelength-64%), green or M cones (medium wavelength-32%), and blue or S cones (short wavelength-2%). They are each sensitive to different portions of the spectrum of light. Visible colors correspond to light wavelengths ranging from 400 to 700 nm [16]. Even though each cone is most sensitive to a specific color of light (where the line peaks), they also can detect other colors ( Figure 2) [16].

Figure 2:
The three types of cones, capable of recognizing light wavelengths that peak at green, red and blue. Retrieved from Rods and Cones, C J Kazilek, Kim Cooper 2010.
The "blue" cones are sensitive to the peak of the light response curve at about 445nm. They are found outside the fovea centralis where the green and red cones are concentrated and they constitute only about 2% of the total number of cones. Their disadvantage in number is clear but, on the contrary, they are much more light sensitive than green and red cones [18]. However, the blue sensitivity of the final visual perception is equivalent to that of red and green, proposing that there is a somewhat selective "blue amplifier" somewhere in the visual processing in the brain [18]. Morphological studies have allowed us to differentiate the short wavelength specific (blue) cone from the medium and long wavelength specific cones in the human retina even without special antibody staining techniques [19]. S-cones have longer inner segments that project further into subretinal space than longer wavelength cones ( Figure 3).
The S-cones also have smaller and morphologically different pedicles than the other two wavelength cones. Throughout the retina, the S-cones have a different distribution and do not fit into the regular hexagonal mosaic of cones typical of the other two types [20].

Different kinds of color blindness
Most of us have the ability to perceive a million different colors [21]. This is due to the presence of the three types of cones in our eyes that send color messages to our brain. Some people who have a faulty cone or only two cones can suffer a greatly decreased color perception. This condition is known as color blindness [21].

That color vision is trichromatic was first recognized by Thomas
Young at the beginning of the nineteenth century (thus, people with normal color vision are called trichromats). Trichromats have normal cones and light sensitive pigment and they can see all the different colors and delicate mixtures of them by using cones sensitive to one of three light wavelengths (red, green, and blue).
Monochromacy and Achromatopsia, also known as "total color blindness" [22], is the lack of ability to distinguish colors; caused by cone defect or absence [23]. Monochromacy occurs when two or all three of the cone pigments are missing and color and lightness vision is reduced to one dimension [22].
Cases of achromatopsia are classified as complete when the patient has a total loss of color discrimination or incomplete when this loss of color discrimination is partial. The variability across this spectrum is believed to be due, in part, to the degree of residual cone photoreceptor function. Patients with complete achromatopsia have a total absence of color discrimination, and they are only able to perceive white, black, and shades of gray.  Patients with incomplete achromatopsia have better color discrimination and visual acuity, in comparison to patients with complete achromatopsia. Some patients with incomplete achromatopsia have particular types of color vision impairment, such as a loss of photoreceptor function in medium-wavelength cones but residual function in short-wavelength and long-wavelength cones [24,25]. This example of incomplete achromatopsia is associated with deuteranopia-like green color blindness, but it is distinct from true X-linked deuteranopia's, which are caused by mutations in the gene that encodes medium-wavelength-sensitive opsin [26]. Achromatopsia and Monochromacy describes a range of conditions that include Achromatopsia, rod-Monochromacy and S-cone Monochromacy. Sometimes, these are collectively referred to as types of achromatopsia, as the word "achromat" meaning "no color" [27]. However, not all cases of achromatopsia have "no color" vision. Trichromats, Dichromats and Monochromats are terms used in the vision science community to refer to different possible configurations of the human visual system having three (tri-), di (two) or one (mono) channel of color information [27]. People with dichromatic color vision have only two types of cones which are able to perceive color, that is, they have a total absence of function of one cone type [28]. Lack of ability to see color is the simplest way to explain this condition but in actual fact it is a specific section of the light spectrum which can't be perceived. For convenience we call these areas of the light spectrum 'blue', 'green' or 'red'. The sections of the light spectrum which the 'green' and 'red' cones perceive overlap and this is why green and red color vision deficiencies are often known as red/green color blindness and why people with red and green deficiencies see the world in a similar way [28].   People with 'defective' trichromatic vision will be color blind to some degree and are known as anomalous trichromats. In people with this disorder all of their three cone types are used to perceive light colors but one type of cone perceives light slightly out of alignment, so that there are three different types of effect produced depending upon which cone type is 'defective' [28].
The different anomalous conditions are protanomaly, which is a diminished sensitivity to red light, deuteranomaly which is a diminished sensitivity to green light and is the most usual form of color blindness and tritanomaly which is a diminished sensitivity to blue light and is extremely rare [28]. About half of people with anomalous trichromacy will see the world in a similar way to those with dichromacy but their capacity to perceive colors will worsen in poor light and improve in good light. Often their color perception can be as poor as it is for those with dichromacy [28] (Figure 7).

Figure 7:
Color vision deficiencies can be either due to a mutation that shifts one of the color cones or a lack of one of them. The affected color cone can be red (protan), green (deutan) or blue (tritan). Figured adapted from Okatobe and Ito 2008.
Tetrachromatic color vision allows an individual to discriminate colors along a perceptual dimension that is unavailable to the normal person. Most people's color perception is "trichromatic" [29]. Organisms with tetrachromacy are called tetrachromats. For these organisms, the perceptual effect of any arbitrarily chosen light from its visible spectrum can be matched by a mixture of no fewer than four different pure spectral lights [30]. The normal explanation of tetrachromacy is that the organism's retina contains four types of cone cells with different absorption spectra [30]. This means the animal may see wavelengths beyond those of a typical human being's eyesight, and may be able to differentiate colors that to a human are identical. However, the relationship between the existence of a fourth class of retinal cone and the dimensionality of color vision is more complex than previously thought [29]. The zebrafish (Danio rerio) is an example of a tetrachromat, containing cone cells sensitive for red, green, blue, and ultraviolet light [31].
Tetrachromacy is expected to occur in several species of birds, fish, amphibians, reptiles, arachnids, and insects.

Phototransduction
Phototransduction is a process by which light is converted into electrical signals in the rod cells, cone cells and photosensitive ganglion cells of the retina of the eye. The visual cycle is the biological transformation of photons into an electrical signal in the retina. This process occurs through G-protein coupled receptors called opsins which contain the chromophore 11-cis retinal. 11cis retinal is the chromophore present in all photoreceptors; it is a derivative of vitamin A [32]. Phototransduction in rods is initiated when light isomerizes the 11-cis-retinal chromophore of rhodopsin to its all-trans isomer that induces a conformational change [33][34][35][36]. 11-cis retinal is covalently linked to the opsin receptor via Schiff base forming retinylidene protein. Opsin therefore undergoes a conformational change to metarhodopsin II, which activates the regulatory G protein transducin (Gt). The alpha subunit of Gt activates phosphodiesterase, also known as PDE6, which hydrolyses cGMP to 5'-GMP. As high level of cGMP keeps cGMP-gated sodium channels open, the lowering of cGMP levels closes these channels [37] which causes hyperpolarization of the cell due to the ongoing   The visual phototransduction cycle yields 11-cis-retinal from 11-cis-retinol using 11-cis-retinol dehydrogenase. Retrieved from the 11-cis-retinol dehydrogenase activity of RDH10 and its interaction with visual cycle proteins, Thompson [42,43].

Causes
Achromatopsia can be acquired or congenital. Brain damage can produce acquired deficiencies of color perception, or cerebral achromatopsia. Cerebral achromatopsia is a type of acquired color blindness that is caused by damage to the cerebral cortex of the brain, rather than defectiveness in the cells of the eye's retina. In patients with cerebral achromatopsia, lesions tend to overlap on a restricted region in the ventral occipitotemporal cortex, close to the reported locations of the putative V4 complex and to foci of increased blood-oxygen-level-dependent (BOLD) activity related to color perception in normal participants [44]. As an only sequel to a stroke, cerebral achromatopsia is rare [45]. The common causes of the congenital forms of achromatopsia are all caused by malfunction of the retinal phototransduction pathway. Specially, this form of achromatopsia seems to result from the inability of cone cells to properly respond to light input by hyperpolarizing. Achromatopsia is an autosomal recessive disease that is caused by mutations in any of six associated genes that have been identified to date: CNGA3, CNGB3, GNAT2, PDE6H, and ATF6 [46,47]. Five of the genes that have been associated to achromatopsia encode proteins that impact phototransduction in cone photoreceptors. Approximately half of achromatopsia cases are caused by mutations in the CNGB3 gene [48], and about a quarter are caused by mutations in the CNGA3 gene [49]. Mutations in the genes CNGA3 and CNGB3 encoding the α and β subunits of cone photoreceptor CNG channels have been described in subjects with achromatopsia [49][50][51][52]. CNG channels in the cone photoreceptor are composed of three α subunits and one β subunit, and are located in the plasma membrane of the outer segment [53,54]. When open, CNG channels allow the nonselective flow of cations across the photoreceptor membrane. These proteins are functionally important in all three classes of human cones.
GNAT2, mapped to locus ACHM4 on chromosome 1p13, encode the catalytic α-subunit of the G-protein transducing [55,56] and PDE6C (ACHM5) and PDE6H encode the catalytic α-and the inhibitory γ-subunits, respectively, of the cone photoreceptor-specific phosphodiesterase [55,[57][58]. Recently, ATF6 was identified as a new ACHM gene, suggesting an essential and unpredicted role of ATF6A in human foveal development and cone function. This was surprising as ATF6 encodes the ubiquitously expressed ATF6, a key regulator of the UPR, and cellular endoplasmic reticulum (ER) homeostasis. This adds to the list of genes that, despite a ubiquitous expression, when mutated can result in an isolated retinal photoreceptor phenotype [47]. Mutations in GNAT2 and PDE6C are rare and are found in fewer than 2% of all achromats [59]. ACHM is transmitted in an autosomal recessive manner, which means that for the disease to develop, the two copies or alleles of the gene should be mutated. Normally, each gene in the body has two copies or alleles, one allele comes from the mother and the other allele comes from the father. A carrier is a person who only has one copy or allele of the mutated gene and does not have achromatopsia. For achromatopsia to develop, an individual must inherit one allele of the mutated gene from each parent. This means that both parents must be either carriers or have the disorder involving mutations in the same achromatopsia gene.
If both parents are carriers, each sibling of an affected individual with achromatopsia has a 25% chance of having the disease, a 50% chance of being an asymptomatic carrier, and a 25% chance of not having the disease and not being a carrier [10].

Symptoms
The clinical signs and symptoms of achromatopsia vary.
Achromatopsia is characterized by a pendular nystagmus, reduced visual acuity, a small central scotoma, eccentric fixation, an increased sensitivity to light (photophobia) and reduced or complete loss of color discrimination. All achromats have impaired color discrimination along all three color vision axes, each one corresponding to the three cone classes. These symptoms usually start at birth or early infancy and their severity varies depending on genetic and phenotypic variability. Visual acuity is usually less than 20/200 for those with complete achromatopsia but may be as good as 20/80 for those with incomplete achromatopsia. Visual acuity is usually stable [60], in contrast to other cone dystrophies in which visual acuity progressively worsens.
Clinically, the first signs of achromatopsia in infants are the presence of nystagmus, a pendular quivering of the eyes, and photophobia as evidenced by squinting in bright light [60]. In usual complete achromatopsia, patients present typically by 6 months old with nystagmus and photophobia. As one example, many achromats have been given the diagnosis of "congenital nystagmus." Nystagmus (involuntary movement of the eyes) is a symptom of achromatopsia, one that is especially obvious during infancy and childhood, but having this symptom is not the same as having the medical eye condition which is known as "congenital nystagmus" [61]. Nystagmus and sensitivity to bright light may improve faintly.

Diagnosis
The diagnosis of ACHM is established in a proband through clinical and family history, examination for visual acuity testing, nystagmus, fundoscopic examination, and color vision assessment.
If ACHM is suspected, supplementary tests will be recommended, such as optical coherence tomography, fundus autofluorescence, visual fields, and electroretinogram. Identification of biallelic pathogenic variants in , CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, or ATF6 verify the clinical diagnosis. The family history is useful to orientate the diagnosis by the inheritance mode. Family trees are useful in these cases [64]. Visual field examination usually demonstrates small central scotomas by careful testing, but this test can be difficult to perform due to a lack of steady fixation [63]. The color perception of individuals with achromatopsia (achromats) is unreliable; many achromats learn to associate certain colors with objects and to recognize some colors by discerning differences in brightness [65]. Patients with achromatopsia demonstrate defectiveness in all three axes of color vision. The most important and diagnostic tests include the Rayleigh anomaloscope (which is the most reliable test), Farnsworth Munsell 100-Hue, and Panel D-15 tests [66]. The most common electrophysiology tests used in the diagnosis of achromatopsia are electroretinogram and visual-evoked potentials [67,68]. This technique sometimes fails to show pathologic changes in cases of achromatopsia due to a limited number of photoreceptors within the fovea compared to the entire retina [64]. A full-field ERG evaluates the whole retina.
The photopic response (including the 30-Hz flicker response) is absent or notably diminished; the scotopic response is normal or slightly abnormal. Genead [69] found that 75% of patients with achromatopsia showed normal responses in this test.
Optical coherence tomography (OCT) is a great instrument for the imaging and study of different structures in the eye.
No differences in the age, visual acuity, contrast sensitivity, or retinal sensitivity were found between patients in these five groups [62]. A variable degree of foveal hypoplasia as well as disruption and/or loss of inner-/outer-segment junction of the photoreceptors and an attenuation of the RPE layer within the macular region can be observed at an early age [62,69,72,78,79]. Fundus autofluorescence is a relatively new imaging technique that takes advantage of the autofluorescent properties of lipofuscin to document its accumulation. Fahim described fundus autofluorescence in patients with achromatopsia [80]. Fundus autofluorescence imaging shows missing or variable formation of foveal hypofluorescence or a larger lesion with a surrounding hyperautofluorescent ring and a central region of absent autofluorescence corresponding to the lesion area seen on OCT [47,73]. Genetic testing can be useful for securing the diagnosis, risk assessment in relatives, prenatal diagnosis, and prognosis, and identifying carriers and new affected genes [66].
Molecular genetic testing approaches can include serial singlegene testing, use of a multi-gene panel, and more comprehensive genomic testing [66]. Targeted analysis for the most common

Treatment
There is usually no treatment to cure achromatopsia. In certain circumstances, patients can be worn red-tinted contact lenses or dark or special filter glasses to help reduce photophobia, increase brightness, improve visual acuity, and make it easier to identify colors, but many patients find them disorientating and difficult to wear. Tinted contact lenses supplemented with sunglasses or wrap-around glasses or use of opaque side-shields may also be used [82]. Tinted central contact lenses typically transmitting light at wavelengths between 400-480nm [83] are an improvement over simple cutoff filters in alleviating photophobia [82]. Additionally, these contacts have reduced the stigma of wearing dark wraparound sunglasses indoors. However, such red central contacts only decrease the amount of light entering the retina and do nothing to enhance high-resolution vision or color sensitive tasks. A partial solution is to use tinted contact lenses with magnification to boost what central vision is still present from functional photoreceptors [84]. If jurisdictional laws and visual acuity permit, patients with achromatopsia can drive a car with the use of bio-optics.

Management targets symptoms and associated findings, striving
to improve quality of life. Achromats frequently improve their own strategy that best works for them. Refractive errors should be checked (need for glasses). Prescribing glasses to correct refractive conditions such as far-sightedness (hyperopia), near-sightedness (myopia) and astigmatism can improve the vision somewhat but will not restore the normal levels of vision [10]. Children with achromatopsia should have preferential seating in the classroom (i.e., in the front to benefit maximally from magnifying devices and away from windows to reduce the effects of glare on vision) [6].

Consultation with low vision services would be valuable and often
recommended to find appropriate low vision aids for school, work, or activities of daily living [10]. Psychosocial issues need to be also addressed with the patient and family. Low vision aids include high-powered magnifiers for reading as well as digital/electronic devices. There are small, handheld color detecting tools such as Colorino that allow detection of color for particular activities. These

Volume 3 -Issue 1
Copyrights @ Sandra Abeijón Martínez. Tr Ophtha Open Acc J Neil Harbisson who suffered from achromatopsia was one of the first to use this device in early 2004 [10]. The color sensor in the Eyeborg detects colors, and then convert them to sounds, based on how high or low the pitch of the sound can provide a way to determine the color. Enormous efforts have been made in research in recent years to develop a possible cure for ACHM, and the new gene replacement therapeutic approaches are promising [85]. A specific vector is always required to deliver the target gene into the cell because DNA alone is not able to complete the task. Vector choice depends on the size of the cDNA of the type of targeted cells, the relevant gene, stability of expression, and immunogenicity [86]. Ongoing studies in mice, primates, and canines using adeno- administered in childhood, as the brain is still highly plastic and the visual cortex has yet to fully develop. It is suggested in the study the ideal age may be before a patient reaches approximately seven years old as, after that point, the visual cortex has mostly developed and the primary structural loss of cone photoreceptors has taken place [88].

Objectives
The purpose of the thesis is to conduct a narrative review of achromatopsia and to examine the literature published to summarize the clinical disease, the genetic characteristics, and the recent advances in gene therapy. Specifically, this review will describe the management strategies with particular interest for the latest advances in gene therapy in humans.

Study design
A literature review has been carried out to contribute to the scientific literature on achromatopsia and provide a comprehensive

Exclusion criteria
Articles that did not meet the inclusion criteria mentioned above were rejected.

Selection of articles
The selection of the articles was done analyzing the title, followed by reading the abstract to identify those that would be fully read. The exclusion and inclusion criteria expressed above were applied to the search results.

Genes identified as responsible for ACHM
To date, mutations in six different genes have been identified as responsible for ACHM: CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6 (Table 1&2)

ATF6
Autosomal recessive ATF6 mutations group into three distinct molecular pathomechanisms Kohl [47] Encodes the ubiquitously expressed ATF6, a key regulator of the UPR, and cellular endoplasmic reticulum (ER) homeostasis

Changes in retinal morphology
Optical coherence tomography (OCT) provides visualization of retinal lamination, enabling measurements of retinal layer thickness and intensity. Of particular interest are the hyperreflective (ellipsoid zone, EZ, and interdigitation, IZ) and hyporeflective (outer nuclear layer, ONL) bands associated with the photoreceptors [89][90]. Another imaging tool, adaptive optics scanning light ophthalmoscopy (AOSLO), enables noninvasive, cellular resolution imaging of the rod and cone photoreceptors mosaic. A confocal detector enables visualization of cones based on their waveguiding ability [91,92]. The waveguiding ability is thought to require intact outer segments [93] (Table 3). Table 3: EZ, ONL and AOSLO in the different genes identified as responsible for ACHM.
Remnant cone function in some patients (Stockman 2007).
Thiadens [71] examined 40 ACHM patients using spectral-domain optical coherence tomography (SD-OCT), and reported that increased cone cell "decay" and retinal thinning was correlated with age, and began in early childhood [71]. Thomas [70], also showed progressive longitudinal changes in retinal morphology in children and described an interesting OCT sign, i.e. a hyperreflective zone which appears to be the precursor of the hyporeflective zone seen in later ages [70]. In contrast to these studies, Genead [69], provided evidence that cone loss is not age dependent [69].
Although the retinal structure seems to show great variety and a slow progressive cone loss has been suggested [62,71,76,104,105], no clear association between retinal structure and function could be described [62]. Therefore, ACHM can be best described as a functional stationary disorder with slow degeneration of cone photoreceptors. Marked variability in the cone mosaic has been observed across patients; among the two most common genotypes, CNGA3 and CNGB3 [62,69,102]. Carroll [75], observed a severely disrupted cone mosaic in the fovea and parafoveal area of a single patient with mutations in CNGB3 [75]. Genead [69], reported residual cone structures in all 9 patients carrying mutations in either CNGA3 or CNGB3, though the majority of cones had a reduced reflectance [69]. In contrast, in ATF6-ACHM and PDE6C-ACHM, few if any residual foveal cones were identified [102][103][104][105][106].
The GNAT2-ACHM genotype is associated with the relatively least disrupted photoreceptor mosaic .

Conclusion
Achromatopsia is a complex inherited disease. There is currently no approved treatment for ACHM. Management of achromatopsia is multifaceted, including making the appropriate diagnosis, reducing photophobia, correcting refractive error, and utilizing low vision devices, such as high-powered magnifying glasses. To reduce photophobia and potentially improving visual acuity can be helpful the use of dark or special filter glasses or red-tinted contact lenses.
However, even with the best aid techniques, daily tasks such as going to school and driving present significant obstacles. New diagnostic and therapeutic tools are being studied. Fundus autofluorescence and OCT are important imaging techniques that supply significant information about the progression of the disease. Gene therapy is an ongoing therapeutic option already being studied in clinical trials. The new gene therapy being trialed centers on correcting a defect in the CNGA3 gene. The results of a first human trial testing for achromatopsia suggest that the experimental gene therapy is safe, and potentially efficacious, opening the door to larger human trials in the future. The evidence to date suggests that gene therapy will need to be applied early in childhood in order to achieve the best possible effect. The remarkable advances in genetics have opened an exciting world to ophthalmologists to offer patients new treatments for achromatopsia. In the future, gene therapy will be a routine treatment offered to patients.