Misdiagnosis of Achromatopsia and Genetic Testing for Diagnosing Inherited Retinal Diseases

Barriers to seeing a rainbow.


Gene therapies for inherited retinal diseases (IRDs) are finally becoming a reality, offering hope to patients with a variety of conditions, many of which have no available treatments. With numerous clinical trials rapidly advancing, gene therapies are changing the way that doctors and patients manage rare IRDs. Keeping up with new research and therapeutic advances is critical for ophthalmologists and other eye professionals to provide optimum patient care. Today, ophthalmologists can be more optimistic in offering their patients hope, with advancing research and ongoing or upcoming clinical trials for many of these IRDs. Also, it is important to refer patients for genetic testing, to receive a more targeted diagnosis, to educate them about clinical trials, and provide them with an opportunity to access IRD gene therapies. Achromatopsia (ACHM), a rare inherited retinal dystrophy, exemplifies the changing landscape in the care of patients with IRDs. People with ACHM tend to be affected by total or almost total color blindness, light sensitivity, and poor visual acuity, among other symptoms. The condition results from mutations in one of several genes, the more common of which are the CNGA3 and CNGB3 genes, which account for approximately 70% of patients with ACHM. It is a congenital, autosomal recessive condition that affects approximately 1 in 30,000 individuals in the United States and is associated with severe loss of cone function. There are no approved treatments for ACHM yet, although the use of red-tinted glasses or contact lenses can reduce symptoms of light sensitivity and daytime blindness.

Many patients with ACHM are often initially misdiagnosed as having retinal or cone dystrophy, and sometimes they are even diagnosed with neuro-ophthalmologic disorders. Many eyecare professionals are not trained in IRDs and electrophysiology — this is one of the major challenges in treating and managing ACHM. A recent survey conducted by the advocacy group, Achroma Corp., in partnership with Applied Genetic Technologies Corporation (AGTC), a biotechnology company developing gene therapies for IRDs, including ACHM, proves this point regarding the diagnosis of ACHM. Specifically, the survey found the following:

  • Adults living with ACHM saw an average of 7 health care providers over a period of more than 5 years before receiving a correct diagnosis of ACHM.
  • Similarly, children diagnosed with ACHM saw an average of 4 healthcare providers over 3 years before receiving an initial diagnosis, with only 32% receiving a diagnosis within a year of onset of symptoms.
  • Twenty-three percent of children received an incorrect diagnosis of retinal or cone dystrophy before being correctly diagnosed with ACHM.
  • The journey to diagnosis typically starts with the patient’s general practitioner, with the correct diagnosis finally made by an ophthalmologist or other eye care provider.

It is likely that rates of misdiagnosis may be even higher than shown by this survey, which was completed by patients and parents of patients who have already received a correct diagnosis.1 Referral to ophthalmology professionals who specialize in the field of IRD/genetic testing in a timely fashion would reduce the number of incorrect diagnoses.

Another aspect of rare IRDs management that deserves more attention from the medical community is genetic testing. Despite the genetic basis for this condition, the survey found that only 58% of adults and 65% of children with ACHM received genetic testing and were informed about the genetic cause of ACHM. The survey also found that one of the most common reasons patients and parents of patients did not pursue genetic testing was the perceived high cost (34%) and lack of knowledge about availability and how or where to access testing (60% for adults and 41% for children). Even though commercial genetic testing may be expensive, many eye care professionals are not aware of relatively inexpensive resources. Apart from the NIH, there are IRD-targeting organizations, such as the Foundation Fighting Blindness (FFB), that offer genetic testing to qualifying patients residing in the United States and have a clinical diagnosis of a rare IRD. The FFB offers this service, for a finite time, through their IRB-approved genetic testing and ocular genetic counseling research study, which is accessible through the organization’s registry ( ). Additionally, with several clinical studies underway for IRDs, including ACHM, patients also may receive genetic testing as part of a clinical trial eligibility assessment process.

A distinct advantage of a genetic diagnosis is to attempt to identify many more patients with ACHM, who are clinically diagnosed (but not genetically diagnosed yet) or those who may have been misdiagnosed. Increasing the pool of patients genetically diagnosed with ACHM may incentivize the researchers and biopharmaceutical industry to look at novel treatment options for these conditions more favorably.

At present, given the lack of treatment options, it is perhaps not surprising that patients with ACHM who participated in the survey perceived that having a genetic diagnosis will not change their treatment options. Instead, they resorted to managing the symptoms of the disease. Based on the survey results, management strategies for patients with ACHM included the following:

  • Using eyewear with a darker tint or extreme gradient (58%),
  • Expanding use of eyewear (53%), and
  • Avoiding the outdoors due to photosensitivity (44%).

It is interesting that most of these strategies are geared toward reducing the impact of photosensitivity, which the survey found to have the most profound impact of daily life and activities. While most parents prioritized their child’s photosensitivity over improved visual acuity, the majority of adult survey responders put greater emphasis on improved visual acuity.

Another key finding of the survey was that patients with ACHM are interested in clinical studies, especially regarding gene therapy. The majority of survey participants were aware of gene therapy (87% of adults, 91% of parents), and 74% of adults and 84% of parents were extremely or very interested in learning more about gene therapy clinical trials. These results underscore the fact that we, as health professionals, need to be educated about the resources for genetic testing and the clinical trials so that we can offer our patients with ACHM and other IRDs the choice to participate in clinical trials.

AGTC is presently recruiting for 2 phase 1/2 trials for individuals with ACHM caused by mutations in either the CNGB3 or the CNGA3 gene. Information about these clinical trials can be found at under the trial identifier numbers NCT02935517 and NCT02599922 for ACHM caused by the CNGA3 gene or by the CNGB3 gene, respectively.

As researchers and the biopharmaceutical industry are gearing up to new horizons in gene therapy for various IRDs, the role of clinicians is to identify these patients by offering them genetic testing, leading to a more accurate diagnosis. It is also imperative that eye professionals be more aware of clinical trials so that patients can be better educated about the potential treatment options in the future for these yet untreatable conditions. RP


  1. Achroma Corp. Achroma Corp. announces global survey results of 226 people with achromatopsia. . Accessed November 12, 2018.