Gyrate Peripapillary Chorioretinal Degeneration

Key Points at a Glance

Key Points of This Disease

• Helicoid peripapillary chorioretinal degeneration (HPCD) is a rare hereditary disease characterized by spiral chorioretinal atrophy originating from around the optic disc.
• The cause is a Y421H mutation in the TEAD1 gene on chromosome 11 (11p15), with an autosomal dominant inheritance pattern.
• Also called Sveinsson chorioretinal atrophy, first and most frequently reported in an Icelandic family.
• Onset occurs in early childhood, and atrophy progresses slowly throughout life.
• Visual prognosis depends on the extent of macular atrophy.
• There is no established treatment; anti-VEGF therapy is an option when choroidal neovascularization (CNV) is present.

1. What is Helicoid Peripapillary Chorioretinal Degeneration?

Helicoid Peripapillary Chorioretinal Degeneration (HPCD) is a rare hereditary degenerative disease of the choroid, retinal pigment epithelium (RPE), and retina. It is characterized by spiral (helical) or “tongue-shaped” atrophy centered on the optic disc. The atrophy does not follow the retinal vascular pattern and is not accompanied by inflammatory signs.

First reported in 1939 by the Icelandic ophthalmologist Sveinsson in four patients (including a mother and child), it is also called Sveinsson chorioretinal atrophy. Since then, cases have been continuously identified in Icelandic families, and reports from other regions, such as a Serbian family (TEAD1 p.Tyr421Asn), have also been published¹. The incidence is not quantified, and it is a very rare disease.

The inheritance pattern is autosomal dominant. The causative gene is TEAD1 (chromosome 11p15), and the Y421H mutation (tyrosine to histidine substitution) has been identified². Homozygotes have not been confirmed, and no systemic complications have been reported.

Q Is this disease inherited?

A

Since it follows an autosomal dominant inheritance pattern, an affected parent has a 50% chance of passing it to a child. It affects both males and females, and no homozygotes (inheriting the mutation from both parents) have been reported.

2. Main Symptoms and Clinical Findings

Subjective Symptoms

Subjective symptoms vary greatly among patients.

• Asymptomatic: In early stages when atrophy does not involve the fovea, patients are often asymptomatic.
• Visual field defects and scotomas: Visual field loss occurs corresponding to the area of atrophy.
• Blurred vision and decreased visual acuity: When atrophy extends to the macula, visual acuity decreases. Visual acuity can range from 20/20 (normal) to counting fingers.

Clinical Findings

Fundus examination characteristically reveals helicoid peripapillary chorioretinal atrophy. The atrophy may extend toward the fovea in a “tongue-like” pattern and is distributed independently of retinal blood vessels ³. The optic disc may appear slightly smaller ⁴.

FAF

Fundus autofluorescence (FAF): Shows hypoautofluorescence corresponding to the atrophic areas. It is useful for visualizing the extent of RPE damage.

FA

Fluorescein angiography (FA): Due to the loss of RPE and choriocapillaris in atrophic areas, window defects with hyperfluorescence are observed.

Full-field Electroretinogram

Full-field electroretinogram: Both scotopic (rod) and photopic (cone) responses are reduced. The degree of reduction varies from normal to severe among patients.

Visual field testing confirms visual field defects corresponding to the atrophic areas.

3. Causes and Risk Factors

The cause of HPCD is the Y421H mutation in the TEAD1 gene (chromosome 11p15) ². TEAD1 encodes a transcriptional enhancer factor (TEA domain family member 1) involved in cell proliferation and differentiation. The Y421H mutation affects the binding region with YAP65 (Yes-associated protein 65), impairing this binding and leading to abnormal transcription of retinal structural genes.

Onset begins in early childhood, and atrophy slowly progresses throughout life. No known environmental risk factors have been reported.

Daily Life and Precautions

Currently, no preventable environmental factors for HPCD are known. Regular eye examinations are important to monitor the progression of atrophy and to detect complications such as choroidal neovascularization early.

Q If a parent has this disease, does it always develop in the child?

A

Because it is an autosomal dominant inheritance, the theoretical risk of developing the disease is 100% if the mutated gene is inherited from an affected parent. However, the severity of symptoms (expressivity) varies among individuals, and some may have mild or no symptoms for a long time.

4. Diagnosis and Testing Methods

The diagnosis of HPCD is confirmed by a combination of characteristic fundus findings and genetic testing.

Diagnostic Procedure

1. Fundus examination: Confirms the spiral chorioretinal atrophy around the optic disc. The absence of inflammatory signs and the distribution that does not match the vascular pattern are important findings.
2. Auxiliary tests: FAF, FA, full-field electroretinogram, and visual field tests evaluate the extent of RPE and photoreceptor damage.
3. Genetic testing: Confirmation of the Y421H mutation in TEAD1 provides a definitive diagnosis.

Summary of Tests

The main tests and their findings are shown below.

Test	Finding	Significance
Fundus examination	Spiral atrophy	Basis for clinical diagnosis
FAF	Low autofluorescence	Confirmation of RPE damage
Genetic testing	TEAD1 mutation	Definitive diagnosis

Differential diagnosis

It is important to differentiate from diseases with similar fundus findings.

Disease name	Distribution of atrophy	Inheritance pattern
HPCD	Peripapillary helical	Autosomal dominant
Central areolar choroidal dystrophy	Macular center	Autosomal dominant/recessive
Peripapillary choroidal dystrophy	Peripapillary diffuse	Autosomal recessive

• Central areolar choroidal dystrophy: Atrophy centered on the macula, not extending to the peripapillary area.
• Peripapillary choroidal dystrophy: Autosomal recessive inheritance, with a different pattern of atrophy from HPCD.
• Serpiginous choroiditis: Inflammatory, with active phase findings of choroiditis (white lesions).

Q How is it differentiated from other choroidal dystrophies?

A

HPCD is characterized by spiral atrophy around the optic disc and a non-progressive course without inflammatory findings. When suspected, TEAD1 genetic testing is useful for definitive diagnosis. Central areolar choroidal dystrophy can be differentiated by atrophy centered on the macula, not involving the peripapillary area.

5. Standard Treatment

Currently, there is no established treatment for HPCD. The mainstay of management is regular follow-up and management of complications.

Follow-up

Regularly assess the rate of progression of atrophy and involvement of the macula. Periodic monitoring with visual field testing, FAF, and optical coherence tomography (OCT) is recommended.

Management of Complications

• When choroidal neovascularization occurs: Treatment with anti-VEGF agents (ranibizumab) is an option. There is a report of a case with bilateral CNV where the lesions subsided after 1-2 injections of ranibizumab per eye ⁵.

Visual Prognosis

Visual prognosis depends on the extent of macular atrophy. If atrophy does not involve the fovea, good visual acuity may be maintained for a long time; however, if it extends to the macula, significant vision loss may occur.

Treatment considerations

Currently, there is no established treatment to halt the progression of HPCD. Regular ophthalmologic examinations are important for early detection and treatment of complications such as choroidal neovascularization.

Q How much vision can be preserved?

A

If atrophy does not involve the macula (fovea), good visual acuity may be maintained. However, if atrophy extends to the fovea, vision may decrease to the level of counting fingers. There is significant individual variation, and regular follow-up is necessary.

Q Are there effective treatments?

A

Currently, there is no established treatment to suppress the progression of HPCD itself. When choroidal neovascularization occurs, anti-VEGF drugs are an option, and reports of quiescence exist. Regular ophthalmologic follow-up is the mainstay.

6. Pathophysiology and detailed pathogenesis

Histopathological changes in HPCD differ between atrophic areas and the transition zone.

Atrophic area

Extent of tissue loss: Full-thickness loss of sensory retina, RPE, choriocapillaris, and choroid occurs ⁴.

Absence of inflammation: No inflammatory cell infiltration is observed; changes are predominantly degenerative and atrophic.

Transition zone

Selective damage: Only the RPE and photoreceptor outer segments are affected ⁴.

Primary site of disease: Findings in the transition zone indicate the stage of disease progression and are considered the area of active degeneration.

Molecular Mechanism

TEAD1-YAP65 binding defect: The Y421H mutation impairs the binding between TEAD1 and YAP65.

Transcriptional abnormality: Transcription of genes necessary for the development and maintenance of RPE and photoreceptor cells is not properly carried out, leading to progressive degeneration.

TEAD1 interacts with YAP65, a downstream effector of the Hippo signaling pathway, and functions as a transcription factor that regulates cell proliferation, survival, and differentiation. The Y421H mutation directly affects the binding site with YAP65, impairing the gene programs essential for the normal development and maintenance of RPE and photoreceptor cells². This molecular mechanism is consistent with the clinical picture of onset in early childhood and slow progression throughout life.

References

Footnotes

1. Grubisa I, Jankovic M, Nikolic N, et al. Novel TEAD1 gene variant in a Serbian family with Sveinsson’s chorioretinal atrophy. Exp Eye Res. 2021;207:108580. PMID: 33864784 ↩

2. Fossdal R, Jonasson F, Kristjansdottir GT, et al. A novel TEAD1 mutation is the causative allele in Sveinsson’s chorioretinal atrophy (helicoid peripapillary chorioretinal degeneration). Hum Mol Genet. 2004;13(9):975-981. PMID: 15016762 ↩ ↩² ↩³

3. Kumar V, Trehan H, Goel N. Sveinsson Chorioretinal Atrophy: Helicoid Peripapillary Chorioretinal Degeneration. JAMA Ophthalmol. 2017;135(12):e173656. PMID: 29049677 ↩

4. Jonasson F, Hardarson S, Olafsson BM, Klintworth GK. Sveinsson chorioretinal atrophy/helicoid peripapillary chorioretinal degeneration: first histopathology report. Ophthalmology. 2007;114(8):1541-1546. PMID: 17339054 ↩ ↩² ↩³

5. Triantafylla M, Panos GD, Dardabounis D, Nanos P, Konstantinidis A. Helicoid peripapillary chorioretinal degeneration complicated by choroidal neovascularization. Eur J Ophthalmol. 2016;26(3):e63-e66. PMID: 26541114 ↩