Central Areolar Choroidal Dystrophy

Dr. Samantha A. Vergano, MD - Clinical Genetics, Genomics, Cytogenetics, Biochemical Genetics Specialist. Dr. Samantha A. Vergano, MD - Clinical Genetics, Genomics, Cytogenetics, Biochemical Genetics Specialist.
December 16, 2025
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Central areolar choroidal dystrophy (often shortened to CACD) is a rare inherited (genetic) eye disease that mainly damages the macula, the small center area of the retina that you use for reading and seeing fine details. Over time, a clear “bald spot” (an atrophy area) forms in the macula where important layers are missing or very thin. AAO Journal+3EyeWiki+3Orpha.net+3

Central areolar choroidal dystrophy (CACD) is a rare inherited (genetic) macular disease where the center of the retina (macula) slowly loses important cells (retinal pigment epithelium, photoreceptors, and nearby support tissue), creating a round “central atrophy” area that mainly damages central vision (reading, recognizing faces, fine work) while side vision may stay better for a long time. It often starts with mild blur and trouble in dim light, then progresses over years as the central “seeing spot” becomes weaker. There is no proven cure yet, so care focuses on protecting remaining vision, low-vision help, and treating complications (like choroidal neovascularization/CNV) if they happen. PubMed+2EyeWiki+2

In CACD, the retinal pigment epithelium (RPE) (a support layer), the photoreceptors (light-sensing cells), and the choriocapillaris (tiny blood vessels under the retina) gradually break down in the same central area. Because these layers work together, losing them causes slow but progressive loss of central vision. AAO Journal+3Orpha.net+3Genetic Diseases Info Center+3

Most CACD cases are autosomal dominant, meaning one changed gene copy can cause disease and it can run in families, but other patterns (rare recessive or sporadic cases) have also been described. The most common gene linked with “classic” CACD is PRPH2 (peripherin-2), but CACD is genetically heterogeneous (more than one gene can be involved). Frontiers+3EyeWiki+3NCBI+3

Symptoms often start in early to mid-adulthood, and many people notice bigger problems between about 30–60 years, though timing can vary by family and gene change. The condition usually affects both eyes in a fairly similar way. AAO Journal+3Orpha.net+3Genetic Diseases Info Center+3

CACD can look like dry age-related macular degeneration (AMD) or some other macular diseases, so doctors often use multimodal imaging (several retina scans) and sometimes genetic testing to confirm the diagnosis. AAO Journal+3EyeWiki+3Fighting Blindness+3

Clinically, doctors often describe CACD in stages from early pigment/RPE changes to a well-defined central atrophy that finally involves the fovea (the very center of the macula) and causes marked loss of sharp vision. EyeWiki+1

Another names

  • Central areolar choroidal atrophy (older name for the same idea: central “areolar” loss in the choroid/retina area). EyeWiki

  • Familial central areolar choroidal atrophy (used when it clearly runs in families). EyeWiki

  • Central areolar choroidal sclerosis / choroidal angiosclerosis (older historical terms used before modern imaging and genetics). EyeWiki

  • Central senile areolar choroidal dystrophy (an older term that can be confusing because CACD is genetic, not simply “senile”). EyeWiki

  • Choroidal dystrophy, central areolar (a formal registry-style name). NCBI

  • Central areolar choroidal dystrophy-2 (CACD2) (used in some genetic resources, often linked with PRPH2). NCBI+1

Types

  • Clinical Stage 1 (early): very small parafoveal pigment/RPE changes that may be subtle on routine exam. EyeWiki

  • Clinical Stage 2: a round/oval pale (hypopigmented) area that is still poorly defined. EyeWiki

  • Clinical Stage 3: one or more well-demarcated patches of RPE atrophy near (but not yet fully involving) the fovea. EyeWiki

  • Clinical Stage 4 (advanced): a well-defined central atrophy that involves the fovea, usually causing major central vision loss. EyeWiki

  • Genetic subtype often labeled CACD2 (PRPH2-related): the most common classic cause in many families, with variable severity. EyeWiki+2PMC+2

  • Genetic subtype often labeled CACD1 (17p13 / GUCY2D-related in some reports): described in specific families and resources, showing genetic heterogeneity. Eye Disorders Database+2PMC+2

  • Other gene-associated “CACD-like” forms: variants in genes such as GUCA1A and others have been reported to produce a CACD pattern in the macula in some people. Nature+2Orpha.net+2

Causes

  1. PRPH2 (peripherin-2) gene mutation: This is one of the best-known causes; PRPH2 helps keep photoreceptor outer segments stable, and harmful variants can lead to gradual macular layer loss that fits CACD. EyeWiki+2PMC+2

  2. GUCY2D gene mutation (reported in some CACD families): Some families have CACD linked to 17p13 and described with GUCY2D involvement in at least certain reports/resources, supporting genetic heterogeneity. Eye Disorders Database+2PMC+2

  3. GUCA1A gene mutation: GUCA1A variants can cause different macular problems, and CACD has been reported as one severe pattern in that spectrum in some families. Nature+2Orpha.net+2

  4. CDHR1 gene involvement (reported in reviews of CACD genetics): Some genetics reviews include CDHR1 among genes implicated in CACD-like inherited macular atrophy patterns. Frontiers

  5. ABCA4 gene involvement (reported in reviews of CACD genetics): ABCA4 is more famous for Stargardt disease, but some reviews list it among genes reported in CACD-like presentations, showing overlap in macular disease genetics. Frontiers

  6. TTLL5 gene involvement (reported in reviews of CACD genetics): Some reviews list TTLL5 as another gene reported in CACD genetics, again highlighting heterogeneity. Frontiers

  7. Autosomal dominant inheritance (family transmission): In many families, CACD is passed from an affected parent to a child, and a strong family history is a key “cause clue.” EyeWiki+2NCBI+2

  8. De novo (new) gene change: Sometimes a person can have the disease-causing variant even when parents seem unaffected, because a new mutation can occur (this is a general genetic mechanism in inherited retinal diseases). NCBI+1

  9. Variable penetrance (a carrier may look unaffected early on): In autosomal dominant retinal disorders, some people with a variant may have mild or later findings, which can hide the family pattern for years. PMC+2AAO Journal+2

  10. Variable expressivity (same gene, different severity): Even within PRPH2-associated disease, people can show different retinal patterns and levels of severity, so the same “cause gene” can look different across patients. IOVS+3PMC+3ScienceDirect+3

  11. Primary tissue target: RPE dysfunction: CACD involves loss of RPE support in the macula; when RPE fails, photoreceptors lose key support and gradually die. EyeWiki+1

  12. Primary tissue target: choriocapillaris atrophy: The tiny blood vessel layer under the macula (choriocapillaris) is also lost in CACD, reducing local support for the retina. Genetic Diseases Info Center+2EyeWiki+2

  13. Age-related stress on the macula (timing trigger): CACD is genetic, but symptoms often appear as the macula ages, commonly in adult decades, suggesting time-related stress interacts with the gene defect. Orpha.net+2Genetic Diseases Info Center+2

  14. Oxidative stress vulnerability of RPE and photoreceptors: RPE and photoreceptors are naturally exposed to high oxygen use and light, making them vulnerable to oxidative damage; this does not “create” CACD, but may help explain why stressed cells fail faster once the genetic problem exists. Physiology Journals+1

  15. Light exposure as a potential stressor (general retinal disease evidence): Research in retinal disease biology suggests high-energy light can add stress to the retina; this is not proven as a direct cause of CACD, but it is a plausible stress factor in retinal degeneration in general. PMC+1

  16. Smoking as a retina stressor (general macular degeneration evidence): Smoking increases oxidative stress and inflammation in retinal tissues and is a strong risk factor for macular degeneration; it likely cannot cause CACD by itself, but it may worsen overall retinal health in someone with CACD. PMC+2PMC+2

  17. Choroidal blood-flow and metabolic stress (general concept): The retina depends on healthy blood supply and cell energy; stress to these systems is discussed in macular disease biology and may influence progression speed in atrophy conditions. Physiology Journals+1

  18. Co-existing “drusen-like” changes in some PRPH2 families: Some PRPH2-related cases show drusen-like lesions; this does not change the genetic cause, but it can complicate the picture and may relate to how the disease expresses. EyeWiki+1

  19. Genetic heterogeneity (different families, different genes/loci): CACD can be linked to PRPH2 and also to a 17p13 locus in some families, showing that “CACD” is a clinical pattern with more than one possible genetic cause. EyeWiki+2PMC+2

  20. Misdiagnosis with AMD or Stargardt (a “cause of confusion”): Many people first get labeled as AMD or Stargardt because the macula looks similar; careful imaging and genetics can uncover the true inherited cause. EyeWiki+2Fighting Blindness+2

Symptoms

  1. Slow loss of sharp central vision: You may notice the center of what you see is not as clear, especially for reading small print, while side vision stays better at first. Genetic Diseases Info Center+2EyeWiki+2

  2. Blurred reading vision: Words may look washed out or blurred because the macula is the main reading area and it is the area being damaged. Orpha.net+1

  3. Central scotoma (a spot in the center): Some people describe a dark, gray, or missing spot in the middle of vision, matching the central atrophy zone. EyeWiki+1

  4. Metamorphopsia (lines look wavy): Straight lines may look bent or wavy if the macular layers become irregular near the atrophy border. EyeWiki+1

  5. Trouble recognizing faces: Face recognition depends heavily on central sharp vision, so it often becomes difficult as the fovea becomes involved. Genetic Diseases Info Center+1

  6. Color vision becomes weaker: Colors may look dull or less distinct because cone cells (color-sensing cells) in the macula are affected. EyeWiki+1

  7. Needing brighter light for reading: You may need more light to see clearly because the damaged macula processes fine detail less efficiently. Orpha.net+1

  8. Glare sensitivity: Bright sunlight or headlights can feel more uncomfortable, especially when central retina health is reduced. AAO Journal+1

  9. Reduced contrast sensitivity: Things may look “flat,” and it can be hard to see light gray on white or dark gray on black, even if you can still see the object shape. IOVS+1

  10. Difficulty driving, especially in complex visual scenes: Reading signs, judging lanes, and noticing details can get harder because these tasks need strong central vision. Genetic Diseases Info Center+1

  11. Trouble with fine work: Tasks like sewing, reading medicine labels, or using a phone can become difficult because they rely on fine detail vision. Orpha.net+1

  12. Vision is often similar in both eyes: Many people notice both eyes change in a comparable way because CACD is usually bilateral and fairly symmetric. EyeWiki+1

  13. Slow progression over years: The disease usually worsens gradually, not overnight, as the atrophy area enlarges in the macula. EyeWiki+1

  14. Peripheral (side) vision usually stays better early: The outer retina is often less affected at the start, so side vision can remain useful for a long time. EyeWiki+1

  15. Symptoms may be mild at first and found on routine exam: Some people do not notice problems early, and the doctor first sees macular changes during an eye check. EyeWiki+1

Diagnostic tests

Physical exam

  1. History + family history: The doctor asks about when symptoms started and whether others in the family have similar vision problems, which is very important because CACD is often inherited. EyeWiki+1

  2. Best-corrected visual acuity test: This is the standard “eye chart” test with the best glasses, used to measure how much central sharp vision has dropped over time. Genetic Diseases Info Center+1

  3. Dilated fundus exam (ophthalmoscopy): After dilating drops, the doctor looks at the macula and may see a well-defined atrophy area that can expose larger choroidal vessels in advanced stages. EyeWiki+1

  4. Slit-lamp exam of the front of the eye: This checks the cornea, lens, and other front structures to rule out other causes of blurred vision (like cataract) that can occur at the same time. EyeWiki+1

  5. General retina and optic nerve check: The doctor checks retinal vessels, the optic nerve, and the peripheral retina because CACD mainly targets the macula and those other parts are often less affected. EyeWiki

Manual tests

  1. Amsler grid test: You look at a grid of lines; wavy, missing, or distorted lines can suggest macular damage and help monitor changes at home or in clinic. EyeWiki+1

  2. Color vision testing (example: Ishihara plates): This checks if color perception is reduced, which can happen when macular cone function is weaker. EyeWiki

  3. Contrast sensitivity testing: This checks how well you see low-contrast letters or patterns, a common functional problem in macular atrophy conditions. IOVS+1

  4. Central visual field testing (perimetry, often 10-2): This maps the central field and can show a central scotoma that matches the atrophy area as the disease progresses. EyeWiki+1

Lab and pathological (genetic) tests

  1. Targeted genetic test for PRPH2: A blood or saliva sample can be used to look for PRPH2 variants, which are a common genetic cause in autosomal dominant CACD. EyeWiki+2NCBI+2

  2. Inherited retinal disease (IRD) multi-gene panel: Because CACD can be genetically heterogeneous, a broader panel can check many retina genes at once (including CACD-related genes reported in studies). Frontiers+1

  3. Family segregation testing (testing relatives): If a likely disease-causing variant is found, testing affected and unaffected relatives can help confirm whether the variant tracks with the disease in that family. NCBI+1

Electrodiagnostic tests

  1. Full-field ERG (electroretinogram): This measures whole-retina electrical responses; it can be normal when only the macula is involved, but it helps check whether disease extends beyond the center. EyeWiki

  2. Multifocal ERG (mfERG): This focuses on many small central retina areas and is useful for detecting macular dysfunction and mapping how function changes beyond the obvious atrophy border. EyeWiki

  3. EOG (electro-oculogram): This test looks at RPE-related electrical function and may be used when doctors want more information about the health of the RPE system. Physiology Journals+1

  4. VEP (visual evoked potential): This measures signals from the eye to the brain and can help when doctors need to separate macular disease from other nerve/brain vision problems. AAO Journal+1

Imaging tests

  1. Optical coherence tomography (OCT): OCT is a “retina ultrasound with light” that shows cross-sections; in CACD it can show loss of outer retina/RPE and characteristic border changes as stages advance. EyeWiki+1

  2. Fundus autofluorescence (FAF): FAF highlights RPE stress and loss; CACD often shows stage-related autofluorescence patterns, with absent signal in areas of established atrophy. EyeWiki+1

  3. Fluorescein angiography (FA): This dye test can outline areas where RPE is missing (window defects) and can help separate CACD from other macular diseases in some cases. EyeWiki+1

  4. Indocyanine green angiography (ICGA): This dye test looks more at choroidal circulation and can show patterns related to choriocapillaris changes described in CACD imaging workups. EyeWiki+1

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: December 16, 2025.

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