Choroideremia Disease: A Comprehensive Overview

Introduction

Choroideremia is a rare, inherited retinal degenerative disorder that primarily affects males and leads to progressive vision loss. The disease is characterised by the gradual degeneration of the choroid, retinal pigment epithelium (RPE), and photoreceptors, eventually culminating in blindness for many affected individuals. Despite being relatively uncommon, with an estimated prevalence of 1 in 50,000 to 1 in 100,000, choroideremia has profound implications for patients, families, and healthcare systems.

Etiology and Genetics

Genetic Basis

Choroideremia is caused by mutations in the CHM gene, located on the X chromosome (Xq21.2). The CHM gene encodes the Rab escort protein-1 (REP-1), which plays a vital role in intracellular trafficking and vesicle transport, particularly in the retinal cells. Loss or malfunction of REP-1 disrupts normal cellular processes in the retina, leading to progressive cell death and degeneration.

Inheritance Patterns

The disease follows an X-linked recessive inheritance pattern. Males, having only one X chromosome, are most commonly affected. Females, with two X chromosomes, are typically carriers and may experience mild symptoms or remain asymptomatic due to random X-chromosome inactivation (lyonisation). Affected males inherit the mutated gene from their carrier mothers, while female carriers have a 50% chance of passing the mutation to their sons (who would be affected) and a 50% chance of passing carrier status to their daughters.

Molecular Mechanisms

REP-1 is essential for prenylation of Rab proteins, which facilitate vesicular transport within cells. Mutations in CHM lead to a deficiency or absence of REP-1, resulting in impaired intracellular trafficking in retinal cells. Over time, this dysfunction causes degeneration of the choroid, RPE, and photoreceptors, which are critical for healthy vision. The molecular cascade triggered by the loss of REP-1 is a subject of ongoing research, with efforts focused on understanding the precise pathways involved in retinal degeneration.

Clinical Presentation

Early Symptoms

Choroideremia typically manifests in childhood or early adolescence. The earliest symptom is usually nyctalopia, or night blindness, reflecting the loss of rod photoreceptors responsible for vision in low-light conditions. Affected children may have difficulty seeing in dim environments, which can be mistaken for simple clumsiness or reluctance to participate in evening activities.

Progression of Symptoms

As the disease advances, patients experience progressive constriction of peripheral vision—commonly referred to as “tunnel vision.” This is a result of continued degeneration of the retinal periphery. Central vision is usually preserved until later stages, allowing patients to maintain activities such as reading or recognising faces for many years. However, with time, central vision is also lost, leading to legal or complete blindness.

Age of Onset and Impact on Vision

The age of onset varies, but most males are diagnosed before the age of 20. Vision loss is gradual, and the rate of progression can differ significantly between individuals. Some may retain useful vision into their 40s or 50s, while others experience more rapid decline. Female carriers may have subtle retinal changes detectable on specialised imaging but rarely experience significant vision loss.

Associated Features

Choroideremia is primarily an ocular disease. Systemic manifestations are rare, and patients generally do not exhibit complications outside the eye. The absence of extraocular symptoms helps distinguish choroideremia from other inherited retinal disorders, such as retinitis pigmentosa syndromes with systemic involvement.

Diagnosis

Diagnostic Criteria

Diagnosis is based on a combination of clinical history, ophthalmic examination, specialised retinal imaging, and genetic testing. Key diagnostic features include:

• Early-onset night blindness, followed by progressive peripheral vision loss.
• Characteristic fundus appearance: diffuse chorioretinal atrophy, with exposure of the underlying sclera.
• Family history consistent with X-linked inheritance.

Ophthalmic Examination

A comprehensive eye examination can reveal classic signs of choroideremia, such as patches of chorioretinal atrophy and pigment clumping. Visual field testing documents the extent of peripheral vision loss, while visual acuity tests assess central vision.

Imaging Techniques

• Fundus Photography: Visualises the extent of chorioretinal atrophy and helps monitor disease progression.
• Optical Coherence Tomography (OCT): Provides cross-sectional images of the retina, revealing thinning and loss of retinal layers.
• Fundus Autofluorescence: Highlights areas of RPE loss and can detect subtle changes in carriers.
• Electroretinography (ERG): Measures retinal function and demonstrates reduced or absent scotopic (rod-mediated) responses.

Genetic Testing

Molecular genetic testing is the gold standard for confirming a diagnosis of choroideremia. Identification of pathogenic mutations in the CHM gene not only confirms the diagnosis but also facilitates carrier detection, genetic counselling, and eligibility for clinical trials.

Differential Diagnosis

Choroideremia shares features with other inherited retinal diseases, notably retinitis pigmentosa, gyrate atrophy, and certain forms of cone-rod dystrophy. The absence of systemic features, characteristic fundus findings, and confirmatory genetic testing are essential for accurate differentiation.

Disease Progression

Stages of the Disease

1. Early Stage: Onset of night blindness, mild peripheral vision loss, subtle retinal changes.
2. Intermediate Stage: Marked peripheral vision constriction, more extensive chorioretinal atrophy visible on imaging.
3. Late Stage: Near-total loss of peripheral vision, preservation of a small central island, eventual central vision decline.

Rate of Progression

The progression of choroideremia is variable. Most patients experience a slow decline in vision over decades, with central vision typically preserved until the fourth or fifth decade of life. However, some may experience more rapid deterioration. Factors influencing progression include the specific mutation in the CHM gene, environmental factors, and possibly modifier genes.

Factors Influencing Severity

• Genetic Variability: Different mutations in CHM can influence age of onset and rate of progression.
• Carrier Status in Females: Severity in female carriers depends on the pattern of X-chromosome inactivation.
• Other Factors: Environmental factors, coexisting ocular conditions, and general health may modulate disease severity.

Treatment and Management

Current Therapies

At present, there is no cure for choroideremia. Management is largely supportive, aiming to maximise remaining vision and enhance quality of life. Interventions include:

• Low Vision Aids: Magnifiers, electronic devices, and adaptive technologies help patients utilise residual vision.
• Orientation and Mobility Training: Specialised training assists patients in navigating their environment safely.
• Educational and Vocational Support: Early intervention and accommodations in educational settings are vital for young patients.

Emerging Treatments

• Gene Therapy: The most promising avenue for choroideremia treatment is gene therapy, which aims to deliver a functional copy of the CHM gene to retinal cells using viral vectors (commonly adeno-associated virus, AAV). Early-phase clinical trials have shown encouraging results, with some patients experiencing stabilisation or improvement in vision.
• Pharmacological Approaches: Research is ongoing into drugs that may slow retinal degeneration or protect photoreceptors from cell death, though none have yet reached clinical application for choroideremia.
• Retinal Prostheses and Implants: For advanced disease, devices such as retinal implants are under investigation, but their role in choroideremia remains experimental.

Supportive Care

Comprehensive care involves a multidisciplinary approach, including ophthalmologists, genetic counsellors, low vision specialists, occupational therapists, and psychologists. Regular follow-up is essential to monitor disease progression, address emerging needs, and provide timely interventions.

Living with Choroideremia

Patient Experiences

Living with choroideremia poses unique challenges, from adapting to progressive vision loss to navigating social, educational, and occupational environments. Patients often report frustration, anxiety, and uncertainty about the future. Peer support, counselling, and access to information can significantly improve psychological well-being.

Coping Strategies

• Early Diagnosis and Planning: Early identification allows patients and families to plan for educational and vocational needs, adopt adaptive strategies, and access resources.
• Utilising Assistive Technology: Screen readers, voice-activated devices, and navigation aids enhance independence.
• Engaging with Support Networks: Connecting with others facing similar challenges provides emotional support and practical advice.
• Maintaining Physical and Mental Health: Regular exercise, a healthy diet, and psychological counselling contribute to overall well-being.

Quality of Life Considerations

Quality of life in choroideremia is influenced by the degree of vision loss, access to support services, and individual coping mechanisms. Proactive management, open communication with healthcare providers, and engagement with support groups can help patients maintain independence and a positive outlook.

Nursing Care of Patients with Choroideremia

Nursing Assessment

A thorough assessment is foundational to effective nursing care for patients with choroideremia. Key components include:

• Visual Function Assessment: Evaluate the patient’s current level of vision using standardized visual acuity and field tests. Document changes over time to guide interventions.
• Functional Abilities: Assess the impact of visual impairment on daily activities, mobility, self-care, and social participation.
• Psychosocial Evaluation: Explore the patient’s emotional response to vision loss, support systems, coping mechanisms, and potential mental health concerns such as anxiety or depression.
• Environmental Safety: Identify potential hazards in the home and community environments that may affect independence and safety.
• Medical History: Review associated health issues or comorbidities that may influence care needs.

Planning and Implementing Care

A patient-centered approach is critical, tailored to the individual’s needs, preferences, and progression of choroideremia.

Promoting Visual Function and Independence

• Low Vision Rehabilitation: Collaborate with low vision specialists and occupational therapists to optimize remaining vision. Introduce magnification devices, appropriate lighting, and high-contrast materials.
• Orientation and Mobility Training: Facilitate referral to certified trainers who can teach safe navigation techniques, use of white canes, and environmental cues.
• Adaptive Technology: Support access to electronic devices with speech output, screen readers, and apps designed for visually impaired users.
• Environmental Modifications: Advise on adaptations such as removing trip hazards, installing tactile markers, color-contrasting steps, and labeling household items.

Ensuring Safety

• Conduct regular safety audits in living spaces and workplaces.
• Educate patients and families about fall prevention and emergency response plans.
• Encourage use of non-slip mats, adequate lighting, and clear walkways.
• Monitor for potential risks arising from progressive vision loss, such as difficulties with medication management or food preparation.

Psychosocial Support

• Emotional Counseling: Provide empathetic listening and facilitate access to counseling or support groups.
• Family Education: Teach family members about the nature and progression of choroideremia, and strategies to foster independence without overprotection.
• Peer Support: Connect patients with local or online communities of individuals with visual impairments to reduce isolation.
• Vocational Counseling: Assist in exploring suitable educational and career opportunities, including adaptive work environments.

Education for Self-Management

• Teach patients about choroideremia, expected progression, and ways to monitor changes in vision.
• Train in use and maintenance of assistive devices and technologies.
• Review medication regimens and support health literacy.
• Promote healthy lifestyle habits, such as balanced nutrition and physical activity, to maintain overall well-being.

Coordinating Multidisciplinary Care

Nurses play an integral role in coordinating care among various healthcare providers:

• Ophthalmology: Arrange regular follow-up for monitoring disease progression, managing complications, and reviewing potential emerging therapies.
• Genetic Counseling: Facilitate referral for family members, as choroideremia is inherited and may impact future generations.
• Rehabilitation Services: Link patients to physical, occupational, and speech therapists as needed.
• Community Resources: Guide access to government or nonprofit services providing financial, transportation, or technological assistance.

Supporting Transitions and Life Stages

The nurse’s role adapts as the patient navigates various transitions:

• Children and Adolescents: Support educational accommodations, social inclusion, and emotional resilience. Advocate for individualized education plans (IEPs) and assistive technology in schools.
• Young Adults: Address vocational aspirations, independent living, and relationship issues. Empower autonomy in self-care and decision-making.
• Older Adults: Focus on maintaining independence, managing comorbidities, and addressing increased risks of falls or social isolation.

Ethical and Cultural Considerations

Nursing care must be sensitive to cultural background, beliefs, and values. This includes:

• Respecting diverse perspectives on disability and independence.
• Ensuring communication is accessible and adapted to the needs of visually impaired individuals.
• Advocating for equitable access to services and challenging societal stigma.

Patient and Family Advocacy

Nurses advocate for patients by:

• Promoting patient rights and informed choice in care and treatment.
• Supporting access to experimental therapies and clinical trials, when appropriate.
• Engaging with policy initiatives to improve resources and recognition for rare disorders like choroideremia.

Monitoring and Evaluation

Ongoing evaluation of nursing interventions is necessary to ensure effectiveness and responsiveness to changing needs. This involves:

• Regular review of functional abilities and independence.
• Adjustment of care plans based on disease progression and patient goals.
• Continuous feedback from patients and families regarding care experiences and outcomes.

REFERENCES

1. American Academy of Ophthalmology. Multiple pages were reviewed. Choroideremia. https://eyewiki.aao.org/Choroideremia.
2. Choroideremia Research Foundation. About CHM . https://www.curechm.org/.
3. Elnahry AG, Tripathy K. Gyrate Atrophy of the Choroid and Retina.. https://www.ncbi.nlm.nih.gov/books/NBK557759/ [Updated 2022 Apr 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.
4. MacDonald IM, Hume S, Zhai Y, et al. Choroideremia. https://www.ncbi.nlm.nih.gov/sites/books/NBK1337. 2003 Feb 21 [Updated 2021 Mar 4]. In: Adam MP, Mirzaa GM, Pagon RA, et al., eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022.
5. National Organization for Rare Disorders. Choroideremia. https://rarediseases.org/rare-diseases/choroideremia/.
6. Skorczyk-Werner A, Wawrocka A, Kochalska N, et al. Novel CHM mutations in Polish patients with choroideremia – an orphan disease with close perspective of treatment. https://doi.org/10.1186/s13023-018-0965-5). Orphanet J Rare Dis. 2018;13,221.