Chorioretinal folds are far more than incidental findings; they represent a significant “biomarker” for mechanical alterations of the posterior globe. For the specialist, these undulations serve as a diagnostic gateway to a vast spectrum of pathology, ranging from benign refractive shifts to sight-threatening orbital and intracranial diseases. Mastering the multimodal interpretation and etiological classification of these folds is essential for the evidence-based management of vitreoretinal disease.
1. Introduction: Refining the Terminology
Chorioretinal folds are defined as wrinkles or undulations involving the contiguous tissues of the posterior pole, specifically the anterior choroid, Bruch membrane, and the retinal pigment epithelium (RPE). While these folds often involve the overlying neurosensory retina, the primary structural change resides deeper.
Historically, the condition was first described in 1884 by Nettleship, who observed “peculiar lines in the choroid” in a patient with papilledema secondary to an intracranial mass. Norton popularized the term “choroidal folds” in 1969, but J.D.M. Gass provided the seminal distinction in 1981, arguing that “chorioretinal folds” is the superior anatomical descriptor. Gass noted that these undulations invariably involve the RPE—a crucial component of the retina—regardless of whether the inner retinal layers are affected. In the modern era, high-resolution multimodal imaging has validated this distinction, allowing us to visualize the RPE/Bruch membrane complex with unprecedented granularity.
2. Pathophysiology and Biomechanics: The Stress of Undulation
The formation of chorioretinal folds is a mechanical response to stress applied to the globe. These mechanical origins generally fall into three categories: compressive stress, traction, and hypotony.
The Bullock and Egbert Experimental Framework
Current understanding is rooted in the 1974 experimental studies by Bullock and Egbert. Utilizing both human cadaver eyes and in vivo feline models, they demonstrated that chorioretinal folds could be induced by manual manipulation of the anterior choroid, Bruch membrane, and RPE. In their feline models, folds were successfully generated via traction on the optic nerve or through hypotony following paracentesis. These studies established that choroidal thickening—whether from hemorrhage, inflammation, or vascular engorgement—leads to wrinkling as the choroid adapts to the fixed volume of the globe.
The Emmetropization Effect
The most prevalent cause of folds is the “emmetropization effect,” typically occurring in the fifth and sixth decades of life. In a physiological effort to counteract the progressive myopic changes of the crystalline lens, the eyeball undergoes axial shortening. This acquired hyperopia results in a flattened posterior globe, which creates compressive stress on the posterior choroid, manifesting as benign, often bilateral, chorioretinal folds.
Crowded Disc Syndrome and ICP
The “crowded disc syndrome” illustrates the transmission of stress from the optic nerve to the posterior globe. Whether due to elevated intracranial pressure (ICP) or orbital masses, increased fluid pressure within the optic nerve sheaths acts as a space-occupying force. This pressure is transmitted to the back of the eye, forcing the choroid and RPE to wrinkle, often radiating from the optic nerve head.
3. Multimodal Imaging: The Diagnostic Gold Standard
The diagnosis of “true” chorioretinal folds relies on identifying alternating light and dark bands, though their signatures vary across imaging platforms.
Fluorescein Angiography (FA)
FA remains a traditional pillar for identifying fold orientation. It reveals a characteristic alternating pattern:
- Peaks (Crests): Appear hyperfluorescent. This is a transmission (window) defect caused by RPE thinning and stretching at the apex of the fold.
- Troughs (Valleys): Appear hypofluorescent. This is due to RPE redundancy (clumping) at the base of the fold, which blocks underlying choroidal fluorescence.
Fundus Autofluorescence (FAF): The Inverse Pattern
FAF provides a critical “inverse pattern” to FA, which is essential for the specialist to synthesize.
- Peaks: Appear hypoautofluorescent. Stretched RPE cells at the crest contain a lower density of lipofuscin.
- Troughs: Appear hyperautofluorescent. RPE cells are compacted in the valleys, resulting in a higher relative density of lipofuscin. Additionally, chronic mechanical damage to compressed RPE cells in the troughs can further increase autofluorescence signal.
Optical Coherence Tomography (OCT)
- En face OCT: This noninvasive tool leverages dense volumetric scans to localize undulations specifically to the RPE/Bruch complex, displaying them as alternating hyporeflective and hyperreflective bands.
- Cross-sectional B-scans: These reveal a characteristic “sawtooth” or “jagged” configuration of the RPE.
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- Vertical B-scans are often superior for capturing horizontal or oblique folds.
Indocyanine Green Angiography (ICGA)
For the specialist, ICGA is indispensable for assessing choroidal vascularity. Research by Haruyama (2001) identified choroidal vascular congestion and choroidal venous dilatation in idiopathic cases. In patients with posterior scleritis or orbital compression, ICGA may specifically reveal filling delays, highlighting the underlying vascular compromise driving the folds.
B-Scan and A-Scan Ultrasonography
B-scan assesses the external globe shape, identifying posterior wall flattening (hyperopia) or the “T-sign.” The T-sign, pathognomonic for posterior scleritis, is caused by retrobulbar edema squaring off the normally rounded optic nerve shadow. Crucially, A-scan should be used to assess for axial length asymmetry or bilateral shortening, which supports a diagnosis of acquired hyperopia.
Summary: FA vs. FAF Findings
| Feature | Fluorescein Angiography (FA) | Fundus Autofluorescence (FAF) |
| Peaks (Crests) | Hyperfluorescent (RPE thinning/Transmission) | Hypoautofluorescent (Lower lipofuscin density) |
| Troughs (Valleys) | Hypofluorescent (RPE redundancy/Blocking) | Hyperautofluorescent (Higher lipofuscin density) |
4. Differential Diagnosis: Folds vs. Mimickers
Distinguishing true chorioretinal folds from anatomical mimickers is vital for accurate triage.
- Retinal Folds: These involve only the neurosensory retina and are often narrower and radial (e.g., associated with epiretinal membranes). Crucially, they are “silent” on FA, lacking the alternating banding pattern.
- RPE Folds: Linked to Type 1 Macular Neovascularization (MNV) or pigment epithelial detachments (PEDs). These are tractional folds caused by fibrovascular contraction, often radiating like “bicycle spokes” around the lesion.
- Paton Folds (Paton Lines): Peripapillary lines associated with papilledema. The Idiopathic Intracranial Hypertension Treatment Trial identified three distinct types:
- Peripapillary wrinkles (inner retinal).
- Retinal folds.
- True choroidal folds (found in ~10% of papilledema cases).
5. Etiological Classification: A Step-Wise Approach
Primary Causes (Often Bilateral and Benign)
- Idiopathic (10–20%): Folds present without underlying pathology despite exhaustive imaging.
- Acquired Hyperopia (15–25%): Associated with the emmetropization shift. B-scan shows posterior flattening.
Secondary Causes (Unilateral or Symptomatic)
- Orbit: Thyroid Eye Disease (TED), orbital pseudotumor (idiopathic orbital inflammatory disease), and orbital tumors (e.g., cavernous hemangioma, lymphoma, meningioma).
- Optic Nerve: IIH, papilledema, and optic nerve drusen.
- SANS (Spaceflight-Associated Neuro-ocular Syndrome): A novel etiology in astronauts involving globe flattening and disc edema. Advanced theories suggest impairment of the glymphatic system (CSF/interstitial fluid exchange) and a “one-way valve” theory where pressurized CSF is compartmentalized around the optic nerve.
- Choroid/Sclera:
- Posterior Scleritis: Often associated with systemic conditions like Behcet disease or sarcoidosis.
- VKH Syndrome and Sympathetic Ophthalmia: Granulomatous uveitis causing massive choroidal thickening.
- Pachychoroid Spectrum: Central Serous Chorioretinopathy (CSCR) and Peripapillary Pachychoroid Syndrome (PPS).
- Choroidal Fibrosis: Seen in chronic CSCR or Behcet maculopathy, where sub-RPE scarring causes tractional folds.
- Miscellaneous:
- Hypotony (IOP < 5mmHg): Characteristic random, broad horizontal or vertical folds.
- Uveal Effusion Syndrome (UES): Can be idiopathic or follow triggers like COVID-19 vaccination.
- Medication-Induced: Topiramate-induced maculopathy is a well-documented cause of uveal effusion and chorioretinal folds.
6. Chorioretinal Folds-Related Maculopathy (CFRM)
CFRM is the sequela of chronic mechanical stress on the RPE/Bruch membrane complex. We utilize a 3-stage classification system:
- Stage 1: Folds with RPE disruption (clumping/thickening) or vitelliform lesions on OCT/FAF.
- Stage 2: Folds associated with definitive RPE atrophy on OCT/FAF.
- Stage 3: Folds with RPE disruption or atrophy complicated by subretinal fluid or CNV.
Management Insight: While Stage 3 CNV is treated with anti-VEGF, evidence from Corvi et al. indicates that Stage 3 fluid in the absence of frank CNV is often resistant to anti-VEGF therapy. In such cases, the fluid may be a result of chronic RPE pump failure rather than neovascular leakage.
7. Clinical Diagnostic Algorithm: Retina Clinic Checklist
- Laterality and IOP: Unilateral folds demand a search for secondary pathology. Ensure IOP is > 5 mmHg to exclude hypotony.
- Multimodal Confirmation: Use OCT and FAF to confirm the folds are “true” chorioretinal undulations.
- Refractive Shift: Assess for an acute or progressive hyperopic shift.
- Advanced Imaging: Perform B-scan to check for the T-sign or orbital masses. Supplement with A-scan to measure axial length and ICGA to assess choroidal filling.
- Neurological/Systemic Screen: If folds are peripapillary, consider IIH/SANS. Screen for systemic inflammatory symptoms (e.g., Behcet, TED).
8. Conclusion: The Specialist’s Takeaway
Chorioretinal folds are a high-yield clinical finding. While often benign and stable in the context of bilateral idiopathic hyperopia, they can be the initial harbinger of serious orbital or intracranial pathology. The role of the retina specialist is to utilize multimodal imaging—especially the inverse FAF pattern and ICGA vascular analysis—to differentiate these etiologies. We must “chase the etiology” in new-onset unilateral cases while providing conservative monitoring for stable, bilateral hyperopes, always remaining vigilant for the development of CFRM and its neovascular complications.
References:
Cheng, John Yu, et al. “Chorioretinal folds: A review and update of new and old etiologies.” Surv. Ophthalmol., vol. 71, no. 2, 1 Mar. 2026, pp. 405-22, doi:10.1016/j.survophthal.2025.07.004.
