Pseudoxanthoma elasticum (PXE) is a rare autosomal recessive genetic disorder primarily affecting connective tissues, characterized by abnormal mineralization and fragmentation of elastic fibers. While PXE affects multiple organs, including the skin and cardiovascular system, its impact on the eyes can be particularly severe. This article provides an in-depth exploration of PXE’s ocular manifestations, covering its causes, symptoms, diagnosis, management, and prognosis.

PXE is primarily caused by mutations in the ABCC6 gene, located on chromosome 16. This gene encodes a transmembrane transporter protein primarily expressed in the liver and kidneys. The exact mechanism by which ABCC6 mutations lead to elastic fiber calcification remains under investigation, but it is thought to involve impaired transport of substrates involved in inhibiting mineralization.

The mineralization and fragmentation of elastic fibers affect various tissues, including the skin, blood vessels, and eyes. In the eyes, elastic fiber changes occur in Bruch’s membrane, a layer between the retinal pigment epithelium and the choroid. This disruption leads to the formation of angioid streaks, which are characteristic of ocular PXE.

1. Angioid Streaks:

• Angioid streaks appear as irregular, dark lines radiating from the optic nerve head into the peripheral retina. These streaks result from breaks in Bruch’s membrane due to calcification and fragmentation of elastic fibers. Angioid streaks are typically asymptomatic initially but can lead to severe complications such as choroidal neovascularization (CNV).

2. Choroidal Neovascularization (CNV):

• CNV is a significant complication of PXE where abnormal blood vessels grow beneath the retina. These vessels can leak fluid or blood, causing sudden central vision loss. CNV is often preceded by angioid streaks and is a major cause of visual impairment in PXE patients.

3. Retinal Manifestations:

• PXE-related changes in the retina include a “peau d’orange” appearance, characterized by yellowish subretinal deposits resembling an orange peel. This occurs due to fibrosis and calcification beneath the retina, leading to progressive loss of central vision. Geographic atrophy may also develop, further contributing to visual impairment.

4. Maculopathy:

• Macular involvement in PXE can lead to macular atrophy, pigmentary changes, and progressive deterioration of central vision. Macular complications significantly impact visual function and quality of life in affected individuals.

PXE-related ocular symptoms often manifest gradually and may include:

• Visual Disturbances: Patients may experience blurred vision, metamorphopsia (distorted vision), and central scotomas (dark spots in central vision).
• Floaters and Flashes: Vitreous changes and retinal pathology can cause floaters (spots or cobweb-like shapes) and flashes of light.
• Color Vision Defects: PXE can affect color discrimination, leading to difficulty distinguishing certain colors, particularly in advanced stages of the disease.

Diagnosing ocular PXE involves a combination of clinical examination, imaging studies, and genetic testing:

• Clinical Examination: Ophthalmologists conduct a comprehensive eye examination, including dilated funduscopy, to detect angioid streaks, retinal changes, and signs of CNV.
• Imaging Modalities: Fluorescein angiography (FA) and optical coherence tomography (OCT) are crucial for visualizing angioid streaks, CNV lesions, and assessing retinal structure.
• Genetic Testing: Molecular genetic testing identifies mutations in the ABCC6 gene, confirming the diagnosis and aiding in genetic counseling and family screening.

Management of ocular PXE focuses on monitoring disease progression and addressing complications:

• Ocular Monitoring: Regular eye examinations are essential to monitor disease progression and detect complications such as CNV early.
• Anti-VEGF Therapy: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents, such as ranibizumab or aflibercept, are used to treat CNV-associated vision loss by reducing abnormal blood vessel growth and leakage.
• Low Vision Aids: Visual rehabilitation may include the use of low vision aids and devices to optimize remaining vision and improve quality of life.
• Genetic Counseling: Patients and families benefit from genetic counseling to understand inheritance patterns, risks, and family planning options.

The prognosis of ocular PXE varies depending on the severity of ocular manifestations and the presence of complications:

• Variable Course: The disease course can be unpredictable, with some patients experiencing gradual vision loss over time, while others may remain stable for extended periods.
• Vision Loss: Central vision loss from CNV and macular involvement significantly impacts daily activities and quality of life.
• Research and Advances: Ongoing research aims to elucidate the pathogenesis of PXE and develop novel therapeutic approaches targeting elastic fiber calcification and CNV management.

Ocular pseudoxanthoma elasticum (PXE) is a complex genetic disorder affecting elastic fiber integrity in various tissues, notably the eyes. Understanding its pathophysiology, recognizing early ocular manifestations, and implementing timely management strategies are critical in preserving vision and improving outcomes for affected individuals. Multidisciplinary collaboration involving ophthalmologists, geneticists, and supportive care providers plays a pivotal role in managing PXE-related ocular complications and optimizing patient care.

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