A study recently published in the American Journal of Ophthalmology evaluated whether migraines are associated with an increased risk of developing central serous chorioretinopathy (CSCR).
Give me some background.
CSCR is a retinal disorder characterized by serous neurosensory detachment secondary to choroidal vascular hyperpermeability and retinal pigment epithelium (RPE) dysfunction.
- A migraine is a neurological disorder with well-documented vascular and autonomic dysregulation, involving cortical spread depression, endothelial dysfunction, and impaired cerebrovascular reactivity.
Previous studies have suggested that migraines and CSCR share overlapping mechanisms, including:
- Dysregulated vascular tone
- Increased susceptibility to stress-related hormonal fluctuations
- Common comorbidities, such as depression and anxiety
However: The study authors noted that the relationship between migraines and CSCR remains poorly explored.
Now talk about the study.
In this retrospective cohort study, investigators identified adults aged 18-40 with a diagnosis of migraine from the TriNetX platform and compared them to individuals without migraine or other headache syndromes who underwent routine medical examinations.
Patients with a history of CSCR or corticosteroid use within 1 month before or after the index migraine diagnosis were excluded.
- Plus: All included patients had at least 1 year of follow-up data after the index date.
The main outcome measure: Incident CSCR within 5 years of the index date.
Anything else?
Propensity score matching (PSM) was performed in a 1:1 ratio to balance baseline demographic and clinical characteristics.
Subgroup and sensitivity analyses assessed the robustness of the association across the following parameters:
- Sex
- Migraine subtypes (with and without aura)
- Follow-up duration
- Corticosteroid exposure
And the findings?
After PSM, 413,663 patients with balanced baseline characteristics remained per cohort.
During the 5-year follow-up, migraine patients demonstrated a higher risk of CSCR compared to controls (1.43 vs. 0.51 per 10,000), with a hazard ratio (HR) of 2.74 (95% confidence interval [CI]: 1.66-4.51).
Keep going …
The association remained consistent across all subgroups and sensitivity analyses, while positive and negative control outcomes further supported the specificity and internal validity of the associations.
Analysis of migraine-related medication exposure showed no significant differences in CSCR risk across the following drug types:
- Nonsteroidal anti-inflammatory drugs
- Beta-blockers
- Topiramate
- Valproate
- Antidepressants
Expert opinion?
CSCR and migraine demonstrated distinct yet potentially interrelated choroidal changes:
- CSCR (sustained venous outflow impairment)
- Pachyvessels
- Hyperpermeability
- Venous congestion
- Migraine (episodic vascular changes)
- Acute migraine attacks may induce transient choroidal expansion
- Choroidal changes may be secondary to systemic autonomic and neurovascular mechanisms rather than a localized pathology
And their hypothesis?
The study authors hypothesized that the balance between transient vasospasm and sustained venous overload may determine the phenotypic divergence between migraine and CSCR.
- As such: Migraineurs (patients diagnosed with migraines) who develop CSCR may potentially represent a subgroup with an exaggerated autonomic and vascular response—leading to a maladaptive shift from episodic to chronic choroidal dysfunction.
So what should clinicians keep in mind for these patients?
While corticosteroid exposure remains the most established trigger, a history of migraines may provide relevant context when assessing patients with CSCR, particularly those with vascular comorbidities.
Neurologists may also consider CSCR in migraine patients presenting with persistent or atypical visual symptoms, such as those listed below, as these may be otherwise misattributed to aura:
- Blurred vision
- Metamorphopsia
- Dyschromatopsia
- Central scotoma
- Hypermetropization
- Micropsia
Anything else?
The study authors further explained that although the relative hazard was elevated, the absolute incidence of CSCR was low, with an absolute risk difference of 0.92 per 10,000 persons over 5 years.
- Meaning: While migraine is statistically associated with CSCR, it does not represent a major public health driver of disease burden.
Were there any limitations with this study?
A few … including:
- CSCR diagnosis in electronic medical record (EMR) data is prone to misclassification, and differentiation between acute and chronic disease was unavailable, which limited phenotypic resolution
- Migraine classification relied on International Classification of Diseases (ICD) codes rather than standardized clinical criteria, which may have introduced heterogeneity
- Diagnostic timing is imperfect in EMR studies; consequently, migraines may have been under-recorded or first documented late and the course of CSCR raises the possibility of subclinical or pre-existing disease before documentation
- While corticosteroid exposure was excluded in the primary analysis (1 month before the index date) and further examined in a 6-month sensitivity analysis, CSCR has occasionally been reported after longer intervals
- The absence of imaging data precluded assessment of CSCR severity and complications
- The exploratory medication analysis lacked information on adherence, dose–response, and treatment duration
Take home.
These findings demonstrate that migraine was associated with a significantly increased risk of incident CSCR in a large, real-world cohort.
As such: The consistency of this association across multiple associations suggests a potential shared neurovascular pathophysiologic mechanism—warranting further investigation.
And the next steps?
A more definitive study would require a prospective design with standardized diagnostic criteria, systematic capture of migraine and CSCR onset, as well as longitudinal multimodal imaging to identify subclinical disease and clarify temporal sequencing.