Birdshot Chorioretinopathy: Symptoms, Types, Causes and Treatment

Birdshot chorioretinopathy (BCR) is a rare, chronic autoimmune eye disease that affects the back of the eye (the choroid and retina). Despite its rarity, BCR is a significant cause of visual impairment in middle-aged adults. Its unique clinical appearance, characterized by multiple cream-colored lesions on the retina, gives the disease its distinctive “birdshot” name. Understanding its symptoms, subtypes, underlying causes, and treatment options is crucial for timely diagnosis and management to preserve vision and quality of life.

Symptoms of Birdshot Chorioretinopathy

Birdshot chorioretinopathy often sneaks up on patients, with symptoms that can be subtle or nonspecific at first. Because the disease affects the retina and choroid, patients may experience a range of vision-related complaints. Many notice problems even when their visual acuity tests as “normal,” which can make early recognition challenging.

Symptom	Description	Frequency/Details	Source(s)
Blurred Vision	Difficulty seeing clearly	Most common initial complaint	1 4
Floaters	Small moving spots or threads in vision	Very frequent at presentation	1 4
Nyctalopia	Difficulty seeing in low light/night	Common, often with pigmented lesions	4 5
Poor Contrast	Trouble distinguishing shades	Associated with visual field deficits	5
Vibrating Vision	Perception of oscillating or unstable view	Linked to increased lesion pigmentation	4
Visual Field Loss	Peripheral or patchy blind spots	Arcuate defects, multiple foci	5
Macular Edema	Swelling in the central retina	Leading cause of reduced acuity	1 2 4

Table 1: Key Symptoms

Common Initial Complaints

• Blurred vision and floaters are the most prevalent symptoms and often prompt patients to seek care. These can occur even when standard vision tests (Snellen acuity) appear normal, highlighting the disease’s insidious onset 1 4.

Night Vision and Contrast Sensitivity

• Nyctalopia (night blindness) is another frequent issue, making it hard to navigate in dim lighting. Patients may also struggle with poor contrast sensitivity, noticing that shades of gray or similar colors become harder to distinguish, particularly as the disease progresses 4 5. These functional deficits are often linked to pigment changes in the retinal lesions.

Unique Visual Disturbances

• Some patients report vibrating vision, describing their view as shaky or unstable. This is notably linked to lesions with increased pigmentation, suggesting a relationship between lesion appearance and visual symptoms 4.

Visual Field Changes

• Visual field loss can occur even when central vision remains relatively good. Automated testing often reveals multiple foci or arcuate defects—patterns of patchy vision loss that may not be obvious to the patient at first 5.

Macular Edema and Visual Acuity

• Macular edema (swelling in the retina’s center) is the most common cause of reduced sharpness in vision among BCR patients. Even with treatment, some degree of visual decline can occur, and about 20% of eyes may lose two or more lines on vision charts over several years 1 2 4.

Types of Birdshot Chorioretinopathy

While birdshot chorioretinopathy is often described as a single clinical entity, it presents with a spectrum of manifestations. The disease can be classified based on activity, lesion characteristics, and disease course.

Type	Defining Features	Course/Prognosis	Source(s)
Active	Vitreous haze, retinal vasculitis, edema	Progressive, needs therapy	1 4 8
Inactive	Stable lesions, minimal inflammation	May still progress slowly	8
Early-stage	Few lesions, subtle symptoms	May progress to active	1 4
Advanced-stage	Extensive lesions, retinal atrophy	More visual impairment	3 8

Table 2: Types of Birdshot Chorioretinopathy

Disease Activity: Active vs. Inactive

• Active BCR is marked by ongoing inflammation—vitreous haze, retinal vasculitis, and swelling of the macula (macular edema). This stage is when most vision-threatening damage can occur, and prompt anti-inflammatory treatment is needed 1 4 8.
• Inactive BCR is when inflammation subsides, but the disease can still cause progressive choroidal thinning and degeneration. Even eyes that seem quiet clinically may continue to lose choroidal tissue over time 8.

Early vs. Advanced Disease

• In the early stage, patients may have only a few hypopigmented lesions and minimal complaints. Vision may remain near-normal, but subtle field loss or night vision disturbances can occur 1 4.
• Advanced-stage disease shows extensive lesions, often with pigment changes and retinal or choroidal atrophy. Patients are more likely to have marked visual field loss, poor contrast, and even central vision deficits 3 8.

Lesion Characteristics

• Lesions vary in quantity, distribution, morphology, and pigmentation. Increased pigmentation is associated with more severe symptoms, particularly blurred and vibrating vision, and nyctalopia 4.

Causes of Birdshot Chorioretinopathy

The precise causes of BCR are still under investigation, but recent research has uncovered critical genetic and immunological factors. It is now recognized as an autoimmune condition, with a striking genetic predisposition.

Factor	Role in Disease	Evidence/Details	Source(s)
HLA-A29	Strong genetic association	Present in >95% of patients	1 6 7 9 11
ERAP1/2 Genes	Modulate peptide processing	Affect antigen presentation	9 11
Autoimmunity	Immune attack on retina/choroid	Elevated intraocular cytokines	7 10
Inflammation	Drives retinal and choroidal damage	IL-17, TNF-α, IL-6 elevated	10

Table 3: Causes and Risk Factors

Genetic Predisposition: The Role of HLA-A29

• The HLA-A29 gene is the single most significant risk factor for birdshot chorioretinopathy. Over 95% of patients carry this allele, making it one of the strongest HLA-disease associations known in medicine 1 6 7 9 11.
• Specifically, the HLA-A*29:02 subtype confers the highest risk, with odds ratios exceeding 150 in some studies 9.

ERAP1 and ERAP2: The Peptide Editors

• Genes encoding endoplasmic reticulum aminopeptidases (ERAP1 and ERAP2) are also implicated. These enzymes help process peptides for presentation by HLA molecules. Certain genetic variants increase the likelihood of BCR, likely by altering which peptides are presented to the immune system and triggering autoimmunity 9 11.

Autoimmune Mechanisms

• BCR is considered a T cell-mediated autoimmune disease. The immune system mistakenly attacks retinal and choroidal tissues, resulting in inflammation and tissue damage 7 10.
• Elevated levels of proinflammatory cytokines—including IL-17, IL-2, IL-1β, IL-6, and TNF-α—are found in the eyes of BCR patients, supporting the idea of a localized autoimmune process 10.

Inflammatory Cascade

• The local production of cytokines in the eye drives the cycle of inflammation and tissue injury. The inflammation can continue even when systemic symptoms are minimal, underscoring the need for local and targeted treatment approaches 10.

Treatment of Birdshot Chorioretinopathy

Managing birdshot chorioretinopathy is a balancing act: the goal is to control inflammation, preserve vision, and minimize side effects from therapy. Treatment regimens have evolved over time as we better understand the disease’s immune mechanisms.

Treatment	Mechanism/Approach	Outcomes/Considerations	Source(s)
Corticosteroids	Systemic or local anti-inflammation	Widely used, but systemic side effects	1 12
Cyclosporine	Immunosuppression (calcineurin inhibitor)	Better outcomes than steroids alone	1
Methotrexate	Immunomodulatory (antimetabolite)	Improved visual prognosis, safe long-term	14
Intravitreal Implants	Sustained corticosteroid delivery	Reduces systemic therapy, risk of glaucoma/cataract	12
Daclizumab	Biologic (anti-IL-2 receptor)	Stabilizes vision in refractory cases	13
Other Immunosuppressants	Various mechanisms	Used when first-line fails	7 13

Table 4: Treatment Options

Corticosteroids: The Traditional Mainstay

• Oral corticosteroids are often the first line of defense, quickly reducing inflammation. However, long-term use carries risks like osteoporosis, hypertension, and diabetes 1.
• Local corticosteroid implants (e.g., fluocinolone acetonide) have been shown to improve vision and control intraocular inflammation, often reducing or eliminating the need for systemic therapy. However, they come with a high risk of cataract and increased eye pressure, sometimes necessitating surgery 12.

Immunosuppressive Agents

• Cyclosporine has been shown to preserve vision better than corticosteroids alone. It suppresses the immune response specifically, making it a key part of many treatment regimens 1.
• Methotrexate is another immunomodulator, shown to improve long-term visual outcomes in BCR and to be safer for chronic use compared to high-dose steroids 14.

Biologic Therapies

• Daclizumab, an anti-interleukin-2 receptor antibody, has been used in refractory cases (where traditional therapies fail or are not tolerated). Most patients see stabilized or improved vision and reduced inflammation, though careful monitoring for adverse effects is essential 13.

Monitoring and Supportive Care

• Regular imaging (OCT and fluorescein angiography) and visual field testing are crucial for tracking disease activity and guiding therapy 2 3 5.
• Treatment is highly individualized, and some patients may require combination therapy or alternative immunosuppressants if standard options are ineffective or not tolerated 7 13.

Conclusion

Birdshot chorioretinopathy is a rare but sight-threatening autoimmune eye disease with distinct clinical and genetic features. Early recognition, close monitoring, and tailored immunosuppressive therapy are vital to preserving vision and quality of life.

Key takeaways:

• Symptoms: Blurred vision, floaters, night vision loss, poor contrast, and visual field changes are hallmarks; symptoms often precede measurable vision loss.
• Types: BCR varies by disease activity (active/inactive), lesion characteristics, and stage (early/advanced).
• Causes: Strongly linked to HLA-A29 (especially A*29:02), with additional roles for ERAP1/2 genes and autoimmune inflammation driven by local cytokine production.
• Treatment: Combines corticosteroids, immunosuppressants (like cyclosporine and methotrexate), biologics for refractory cases, and local steroid implants—each with unique risks and benefits. Regular monitoring is essential for optimal outcomes.

Understanding and addressing birdshot chorioretinopathy requires a multidisciplinary, patient-centric approach—one that incorporates evolving insights from genetics, immunology, and advanced eye imaging.