Achromatopsia

 

Achromatopsia is an inherited retinal disease that affects the cone cell function. It is a genetic dysfunction of all types of cones1 and is usually an autosomal-recessive disease that affects 1:30,000 to 1:50,000 births. It is characterized by presentation at birth or early infancy with pendular nystagmus, poor visual acuity, lack of color vision, and marked photophobia.

The clinical signs and symptoms of achromatopsia vary. Typical clinical presentation includes photophobia, pendular nystagmus, poor visual acuity, and color vision deficiency, among others. These symptoms usually start at birth or early infancy and their severity varies depending on genetic and phenotypic variability. Other symptoms such as central scotomas or eccentric fixation can also be features of achromatopsia, which can be clinically classified as complete or incomplete depending on the intensity and presence of the different clinical symptoms. 

Complete achromatopsia, also known as typical achromatopsia or rod monochromatism, presents during early infancy with photophobia, pendular nystagmus, and poor visual acuity (usually worse than 20/200). The nystagmus and photophobia may become less noticeable over time, but visual acuity remains stable. 

In incomplete achromatopsia, also known as atypical achromatopsia, this triad of symptoms may be less intense; in particular, visual acuity can reach up to 20/80.

 In these cases, one or more cone types may be partially functioning along with the rods. Fundus examination is usually unremarkable. Evidence of the disease is uncommon and may appear as the narrowing of blood vessels, retinal pigment epithelium disturbances (separated into three categories: presence of retinal pigment epithelium disturbance [50%], no retinal pigment epithelium  disturbance [27.5%], and atrophy [22.5%]),5 or alteration of the foveal reflex2 (Figure 1). 

The clinical signs and symptoms of achromatopsia vary. Typical clinical presentation includes photophobia, pendular nystagmus, poor visual acuity, and color vision deficiency, among others. These symptoms usually start at birth or early infancy and their severity varies depending on genetic and phenotypic variability. Other symptoms such as central scotomas or eccentric fixation can also be features of achromatopsia, which can be clinically classified as complete or incomplete depending on the intensity and presence of the different clinical symptoms. 

Complete achromatopsia, also known as typical achromatopsia or rod monochromatism, presents during early infancy with photophobia, pendular nystagmus, and poor visual acuity (usually worse than 20/200). The nystagmus and photophobia may become less noticeable over time, but visual acuity remains stable. 

In incomplete achromatopsia, also known as atypical achromatopsia, this triad of symptoms may be less intense; in particular, visual acuity can reach up to 20/80.

 In these cases, one or more cone types may be partially functioning along with the rods. Fundus examination is usually unremarkable. Evidence of the disease is uncommon and may appear as the narrowing of blood vessels, retinal pigment epithelium disturbances (separated into three categories: presence of retinal pigment epithelium disturbance [50%], no retinal pigment epithelium  disturbance [27.5%], and atrophy [22.5%]),5 or alteration of the foveal reflex2 (Figure 1). 

In both forms of congenital achromatopsia, the signs of achromatopsia may not present until age three to six months of age. The first signs are usually nystagmus, a shaky pendular movement of the eyes and squinting or other signs of aversion to bright light.  

The diagnosis of rod monochromatism and blue cone monochromatism is based on medical history, color vision testing, electroretinogram testing, and a lack of significant retinal signs in young patients. Mild pigmentary retinal changes or “bulls eye” pigmentation may occur in older patients.

In the past, early diagnosis was complicated since infants could not perform the color vision testing to confirm the diagnosis. Today, genetic testing may aid in diagnosis of some of the most common forms of rod monochromatism.

 

Medical History

A history of aversion to light, squinting, nystagmus, decreased vision and profound color vision loss together may suggest a diagnosis of a cone dysfunction syndrome, which could include achromatopsia. 


Age of Onset


An onset from near birth helps supports a diagnosis of achromatopsia versus progressive cone dystrophies, which may have a later onset. In infants, the squinting may not be present until three to six months of age.
 

Family History 

Rod monochromatism is an autosomal recessive condition. Thus it requires both parents to be carriers of the mutation. This means that there is usually no history of rod monochromatism in parents or grandparents. There may be cases in fellow siblings (brothers and/or sisters) as each child of a set of carrier parents has a 25% chance of having the condition.

Blue cone monochromatism is an X-linked recessive. It is also known a X-linked recessive monochromatism. It is inherited from the mother primarily to males. It is possible to occur in females, but may be as rare as 1 in 10 billion births. A pattern of occurrence of the problem in a grandfather or male cousins on the mother’s side could help support the diagnosis. 


Visual Acuity


Vision loss in rod monochromatism is usually in a range of 20/120 to 20/200. Incomplete cases may be slightly better. Blue cone monochromatism frequently presents with visual acuities of 20/60 to 20/120. Visual acuity can fluctuate greatly dependent on lighting levels in testing and the effects of increases in nystagmus that may occur when one eye is covered.

Refractive Error

There is a significant incidence of hyperopia or farsightedness in rod monochromats. This can make eyewear slightly thicker.However, there is a wide range of refractive error including myopia and astigmatism. Many blue cone monochromats show significant amounts of myopia.

Progression of Vision Loss

Generally achromatopsia does not show major progression of vision loss. It is usually stable with rare exceptions. If the vision loss shows significant progression over time, the patient may have a progressive cone dystrophy.

The Flynn Phenomenon

After exposure to bright light for several minutes, if the patient is placed in the dark, a paradoxical pupilliary constriction may occur in many rod monochromats. The pupil may constrict rather than dilate as expected. This also occurs in a number of other pediatric conditions thus it is of limited help in diagnosing achromatopsia.  It has been reported more commonly in rod monochromats, but studies now show it can also occur in blue cone monochromats.

Nystagmus

The nystagmus is usually pendular in the horizontal plane. However, other forms and directions of the nystagmus have been reported. Nystagmus may vary on stress and direction of gaze. It may increase when one eye is covered as in visual acuity testing.Nystagmus often decreases in the first decade of life. 



Molecular Genetic Testing

Rod monochromatism genetic mutations which are now referred to as “variants” have been identified in genes, CNGA3, CNGB3, and GNAT2 that account for about 77% cases of rod monochromatism. Blue cone monochromatism has been linked to two mutations in on the X-chromosome at OPN1W and OPN1MW. 

In the United States, the John and Marcia Carver Laboratory at the University of Iowa provides molecular genetic testing for a range of eye conditions. It is a not-for-profit laboratory and thus costs of genetic testing is not expensive. 

The John and Marcia Carver Laboratory currently provide testing for the two most common mutations associated with rod monochromatism CNGA3 and CNGB3. These two variants account for 75% of the cases of rod monochromatism. Counseling by the doctor or other designated health care provider is required. They will issue a report to the doctor that will indicate the likelihood of the gene causing the condition. 

They use a scoring system called the Estimate of Pathogenic Probability or EPP. An EPP of 0 would indicate the  variant is a non disease causing polymorphism while a score of 3 would indicate that the variant is highly likely to be a high penetrance disease causing variant.







Optical Coherence Tomography:
 The Photoreceptor Integrity Line

Optical Coherence Tomography or OCT, is a new method of scanning the fine structures of the central retina, whichcan help confirm dysfunction of cones in the center of the retina.  The signal from the outer and inner segments of the cones and rods in the retina can be imaged by OCT.  Only cones are normally present in the fovea, the very center of the retina. Thus, we can look at this region to see if there is a loss of signal helping to help confirm a cone dysfunction.

This line is created by the junction of inner/outer segment of the rods and cones and is now being designated the photoreceptor integrity line. It is very helpful in diagnosing cone dysfunction syndromes. 

Unfortunately, this test cannot be done on very young children and infants owing to the need to fixate in the target in the scanner. 

Below, a technician demonstrates the results of a Cirrus Optical Coherence Tomography scan on a patient with achromatopsia. The examples below show the impairment in the photoreceptor integrity line as it passes through the fovea where only cones would be present. In some cases, a serous detachment of the photoreceptor layer may be defined.

 Affected individuals are thought to have no cone function (though see Nishiguchi, et al. 2005).
Foveal Hypoplasia<br />Albinism<br />ACHM<br />
 Significant work remains:
BCM = Blue Cone Monochromatism
ACHM: Imaging Summary<br /><ul><li> OCT reveals foveal hypoplasia in a number of patients.  Unclear what the link is to th...
 OCT reveals significant variation in the disruption of the IS/OS, and variable thinning of the ONL – suggesting variable ...


Electroretinogram

The ERG (electroretinogram) tests the photopic bright light response that would have been produced by the cones, which are missing or profoundly reduced, but the scotopic low light response dependent on the rods is normal or only minimally reduced or delayed.

Image result for achromatopsia ERG

The ERG also has value in differentiating rod monochromatism, which demonstrate delayed scotopic ERG and loss of 30 Hz cone ERG from progressive cone dystrophies, which show normal scotopic ERG, and a partially maintained cone ERG.

This is a difficult test for infants and small children to perform. Hopefully, in the future, genetic testing will lesson the need for this test.


Color Vision Testing

The D-15 and Munsell 100 Hue tests require a patient to align the colored disks into a continuous progression. They can be used to demonstrate the severe impairment and can sometimes provide diagnostic help in differentiating rod monochromats from blue cone monochromats. 

Rod monochromats may demonstratean achromatic axis on on both the saturated and desaturated versions of the D-15. This is an axis in which the color disks are arranged to match the way rods would perceive their brightness rather than by color. 

The D-15 test result to the left shows an achromat axis common to Rod Monochromats.

There is no specific axis of color confusion on tests like the Munsell 100-Hue test. 

It may be possible to differentiate some blue cone monochromats from rod monochromats by the protan-like arrangement of the color disks on the D-15 or FM 100 Hue Test. However, not all blue cone monochromats behave in this manner. Some may appear more like the rod monochromat do on these tests.

The D-15 test results to the right demonstrates the typical protan-like results demonstrated in many blue cone monochromats.

Two tests useful in achromatopsia testing, the Sloan Achromatopsia test and the Berson test, are now very difficult to obtain. The Berson Test can help differentiate blue cone monochromatism from rod monochromatism, but cannot differentiate progressive cone dystrophies from the blue cone monochromat.

Many other color vision tests, as demonstrated below, may be used to initially screen color vision and demonstrate the severity of the color vision loss, but may not provide help in differentiating between each condition. The HRR test below can be helpful in some incomplete forms of achromatopsia.




Retinal Examination

Most achromats have normal retinal findings on ophthalmoscopy. Some may show a reduced or absent foveal reflex, slight attenuation of retinal vessels and pigmentary changes in the macula. The “normal” retinal picture and the rod monochromat retinal picture below look identical. We cannot diagnose achromatopsia from the retinal appearance alone but a lack of visible abnormalities can support the diagnosis in the presence of the symptoms of light aversion, decreased vision, profound color vision loss and nystagmus.
 

Older patients may sometimes demonstrate  “bull eye” pigmentary changes around the macula.

 
Visual Fields Testing

Visual fields testing may demonstrate small central scotomas, areas of vision loss corresponding to the central retina area. See the small black squares in the center of the cross. These are the only areas that the achromat missed. 

It has been reported that yellow-blue perimetry (Sita-swap) may be helpful in differentiating blue cone monochromats versus rod monochromats.


Dark Adaptation Testing


There is an absence of the Kohlrausch Kink, which represents the cone-rod break in dark adaptation. 


Measurements of Spectral Sensitivity

In rod monochromats, there may be a shift of the peak spectral sensitivity from the expected 555 nm, which is the peak wavelength sensitivity of cones to 507 nm, the peak wavelength of rods. 

read more @ http://www.achromatopsia.info

46 replies
  1. www.aniene.net says:

    I know this if off topic but I’m looking into starting my own weblog and was curious what all is
    required to get set up? I’m assuming having a blog like
    yours would cost a pretty penny? I’m not very web savvy so I’m not 100% sure.

    Any suggestions or advice would be greatly
    appreciated. Thank you

    My webpage – http://www.aniene.net

  2. this asmr says:

    hello!,I love your writing very so much! share we be in contact more about
    your article on AOL? I need an expert in this area to solve my
    problem. May be that’s you! Taking a look ahead to look you.

  3. where scoliosis surgery says:

    Fantastic beat ! I wish to apprentice while you amend your web site, how could i subscribe for a blog web site?

    The account aided me a acceptable deal. I had been tiny bit acquainted of this
    your broadcast provided bright clear idea

  4. meteoritegarden.com says:

    Greetings! Quick question that’s completely off topic.
    Do you know how to make your site mobile friendly?

    My website looks weird when viewing from my iphone 4.
    I’m trying to find a theme or plugin that might be able to resolve this problem.
    If you have any suggestions, please share.
    Thanks!

    Have a look at my website meteoritegarden.com

  5. www.iherb.com says:

    Awesome blog! Do you have any tips for aspiring writers?

    I’m hoping to start my own site soon but I’m a little lost on everything.

    Would you propose starting with a free platform like WordPress or go for a paid option? There
    are so many choices out there that I’m totally confused ..

    Any recommendations? Thanks! quest bars https://www.iherb.com/search?kw=quest%20bars quest bars

  6. bitly.com says:

    My brother suggested I might like this website. He was totally right.
    This post truly made my day. You cann’t imagine simply how much time I had spent for this information! Thanks!
    scoliosis surgery https://0401mm.tumblr.com/ scoliosis surgery

  7. Webkatalog says:

    What exactly is occurring within all these towards the world is absolutely terrible. I hope the issues prefer that around Egypt usually are resolved quickly. They need to get for just a pacific strategy to the condition and get initiative that this military services doesn´t require a violent activity contrary to the protests. It´s distinct the folks would like the particular chief executive released, nevertheless its possible the problems usually are deeper compared to just committing to any president in a state.

  8. Wilburn says:

    This is really fascinating, You’re a very skilled blogger.
    I’ve joined your feed and stay up for in search of extra of your magnificent post.
    Also, I’ve shared your website in my social networks!

    Here is my webpage :: Wilburn

  9. try weed doctor says:

    Hi! I just wanted to ask if you ever have any issues with hackers?
    My last blog (wordpress) was hacked and I ended up losing
    many months of hard work due to no back up. Do you have any solutions to prevent hackers?

    my web-site; try weed doctor

  10. lose weight says:

    Excellent blog here! Also your website loads up fast!
    What web host are you using? Can I get your affiliate link to your host?
    I wish my website loaded up as quickly as yours lol

    Look into my homepage: lose weight

  11. purchase hemp says:

    Its like you read my mind! You seem to understand so much approximately this, such as you wrote the book
    in it or something. I feel that you simply could do with a few percent to force the
    message house a bit, but other than that, that is wonderful blog.
    An excellent read. I’ll definitely be back.

    my web page :: purchase hemp

  12. mashed potato diet says:

    You really make it seem so easy with your presentation but I
    find this topic to be actually something which
    I think I would never understand. It seems too complicated and very broad for me.
    I am looking forward for your next post, I will try
    to get the hang of it!

    Here is my homepage; mashed potato diet

  13. NAFTA.XMC.pl says:

    Following my own exploration, thousands of people all over the world receive the home loans from different banks. Hence, there is great possibilities to get a credit loan in all countries.

  14. heal eczema says:

    Hey there! I realize this is kind of off-topic however I had to ask.
    Does managing a well-established blog like yours require a large amount of work?
    I am brand new to writing a blog however I do write in my journal daily.
    I’d like to start a blog so I will be able to share my experience and feelings online.
    Please let me know if you have any kind of ideas or tips for new aspiring bloggers.
    Thankyou!

    Review my blog: heal eczema

  15. flaxseed oil says:

    I simply could not go away your site before suggesting that I extremely loved the usual info an individual supply on your
    guests? Is gonna be back ceaselessly to check out new posts

    my web site – flaxseed oil

  16. great skin says:

    I do agree with all of the ideas you have introduced to your post.
    They’re really convincing and will definitely work. Still, the posts are
    too short for novices. May you please extend them a little
    from next time? Thank you for the post.

    Have a look at my webpage – great skin

  17. drug crime attorney says:

    Wonderful beat ! I wish to apprentice whilst you amend your website, how could i
    subscribe for a weblog web site? The account aided me a
    applicable deal. I were tiny bit familiar of this your broadcast provided brilliant clear idea.

    Also visit my web blog; drug crime attorney

  18. heal eczema says:

    Hey, I think your blog might be having browser compatibility
    issues. When I look at your blog site in Firefox, it looks fine but when opening in Internet Explorer, it has some overlapping.
    I just wanted to give you a quick heads up! Other then that, great blog!

    Feel free to surf to my blog post :: heal eczema

  19. eating plan says:

    I must thank you for the efforts you’ve put in writing this website.

    I am hoping to check out the same high-grade content
    from you in the future as well. In fact, your creative writing
    abilities has encouraged me to get my own website
    now 😉

    Look into my blog post; eating plan

  20. cannabis license maybe says:

    I must voice my appreciation for your generosity giving support to those people who need help on this one issue.

    Your special dedication to passing the message all around appeared to be quite beneficial and has frequently encouraged many people much like me to realize their targets.
    Your amazing useful advice entails this much to me and
    even further to my peers. Many thanks; from everyone
    of us.

    Have a look at my page … cannabis license maybe

  21. induce lucid says:

    I really wanted to send a comment so as to express gratitude to you for those magnificent facts
    you are showing at this site. My particularly long internet investigation has
    at the end of the day been compensated with extremely good facts and strategies to go over with
    my co-workers. I would claim that we readers are really blessed to live in a perfect community
    with many awesome professionals with helpful tactics. I feel very fortunate to have come across the web page
    and look forward to tons of more pleasurable moments reading here.
    Thanks a lot once more for a lot of things.

    My web-site … induce lucid

  22. http://www.meteoritegarden.com says:

    Excellent blog! Do you have any helpful hints for aspiring writers?
    I’m planning to start my own site soon but I’m a little lost
    on everything. Would you recommend starting with a free platform like
    Wordpress or go for a paid option? There are so many choices out there
    that I’m completely confused .. Any ideas?
    Cheers!

    Here is my website http://www.meteoritegarden.com

  23. omega 3 rich foods says:

    Wow that was odd. I just wrote an incredibly long comment but after I clicked submit my comment didn’t appear.
    Grrrr… well I’m not writing all that over again. Regardless, just wanted to say great blog!

    my web site … omega 3 rich foods

Trackbacks & Pingbacks

Leave a Reply

Want to join the discussion?
Feel free to contribute!

Leave a Reply

Your email address will not be published.