Uveal effusion syndrome

Key Points at a Glance

Uveal effusion syndrome (UES) is a rare disease that causes idiopathic exudative detachment of the choroid, ciliary body, and retina.
An epidemiological survey in the UK estimates the annual incidence at approximately 1.2 per 10 million people.
The main cause is thought to be impaired drainage of intraocular fluid due to scleral abnormalities.
It is classified into three types: type I (nanophthalmos), type II (normal eye with scleral thickening), and type III (normal eye with normal sclera).
Scleral window surgery is effective for types I and II, with anatomical improvement achieved in about 83% of cases after a single surgery.
In type III, steroid therapy has been reported to resolve exudation in 95% of cases.
The rate of bilateral involvement is 65% or higher, and attention to the fellow eye is necessary.

1. What is uveal effusion syndrome?

Uveal effusion syndrome (UES) is a rare syndrome characterized by idiopathic exudative detachment of the choroid, ciliary body, and retina. It was first reported by Schepens and Brockhurst in 1963¹⁾. It is also called idiopathic ciliochoroidal effusion.

It typically occurs in healthy middle-aged men. In the initial report of 17 cases, almost all patients were male¹⁾. A prospective epidemiological survey in the UK (BOSU; 2009–2011) estimated an annual incidence of approximately 1.2 per 10 million people¹⁾. The frequency of bilateral involvement is high, at 65% or more¹⁾.

Patients present with visual field defects, decreased visual acuity, and metamorphopsia as main complaints¹⁾. In the early stage, differentiation from other diseases is difficult, and one report found that only 16% were correctly diagnosed with UES at the initial visit¹⁾.

UES is classified into the following three types.

Type	Ocular features	Sclera
Type I	Microphthalmos (axial length around 16 mm)	Thickened and abnormal
Type II	Normal eye (axial length around 21 mm)	Thickened/abnormal
Type III	Normal eye	Normal

Type I is associated with true nanophthalmos and presents with high hyperopia (average +16 diopters). Type II involves normal eye size but thickened sclera. Type III is idiopathic, with both the eye and sclera being normal.

Q How rare is uveal effusion syndrome?

A national prospective surveillance study in the UK reported an annual incidence of approximately 1.2 per 10 million people ¹⁾. The exact prevalence is unknown, but it is among the rarest types of uveitis and retinal diseases.

2. Main Symptoms and Clinical Findings

Subjective Symptoms

Onset often occurs in the 30s to 40s. Early symptoms include the following.

Decreased visual acuity: Gradually worsens as macular edema progresses.
Visual field defect: When bullous retinal detachment occurs, the patient notices a visual field defect corresponding to the affected area.
Metamorphopsia: A symptom where objects appear distorted, reflecting macular damage.
Blurred vision: Perceived as overall haziness of the visual field.

Clinical Findings

A characteristic feature is the absence of inflammatory findings or floating pigment cells in the anterior segment and vitreous, which is useful for differentiation from other inflammatory diseases.

Anterior Segment Findings

Dilated episcleral vessels: May be observed in type I.

Blood in Schlemm’s canal: A characteristic finding in type I.

Anterior chamber inflammation: Usually mild or absent¹⁾.

Fundus Findings

Choroidal and ciliary body detachment: Begins peripherally and progresses circumferentially. Observed as an orange-brown solid elevation¹⁾.

Exudative retinal detachment: Non-rhegmatogenous detachment with highly mobile subretinal fluid. The fluid shifts with changes in body position.

Leopard spots: Leopard-like pigment changes due to hypertrophy and proliferation of the RPE. Characteristic of chronic cases and a cause of permanent vision loss¹⁾.

Optic disc edema: May be accompanied by mild disc swelling.

Fluorescein angiography shows widespread granular hyperfluorescence and leopard spot patterns, but no obvious leakage. Indocyanine green angiography reveals marked leakage from choroidal vessels in the early phase, suggesting increased vascular permeability.

3. Causes and Risk Factors

The etiology of UES is not fully understood, but a primary abnormality of the sclera is thought to play a central role.

Scleral abnormality: The sclera thickens due to disorganization of collagen fiber bundles and accumulation of glycosaminoglycan (GAG)-like deposits ¹⁾. This impairs the transscleral outflow of proteins and fluid.
Vortex vein compression: The thickened sclera constricts the vortex veins at their scleral exit points, impairing venous drainage from the choroid ¹⁾.
Nanophthalmos: In a registry study of nanophthalmos patients, 26.1% had uveal effusion and 17.4% had asymptomatic effusion ¹⁾.
Decreased scleral permeability: In nanophthalmic eyes, albumin concentration in the subretinal fluid is 2–3 times higher than normal, suggesting impaired transscleral protein outflow ¹⁾.
Venous overload: Recent studies suggest that UES and central serous chorioretinopathy (CSC) may be part of a spectrum of diseases caused by venous overload choroidopathy ⁵⁾.

Cataract surgery and glaucoma surgery can trigger UES in nanophthalmic eyes. Among 114 nanophthalmic eyes undergoing cataract surgery, 29 developed complications, half of which were uveal effusion ¹⁾.

UES has also been reported after COVID-19 vaccination ²⁾. Agarwal et al. reported a 71-year-old man who developed unilateral type III UES two weeks after receiving the inactivated whole-virus vaccine (Covaxin BBV152) ²⁾. It is speculated that the adjuvant (Alhydroxiquim-II) triggers an abnormal immune response ²⁾.

4. Diagnosis and Examination Methods

UES is a diagnosis of exclusion, and other causes of choroidal effusion must be carefully ruled out ¹⁾. The differential diagnoses are as follows.

Vogt-Koyanagi-Harada disease: Bilateral, with meningeal symptoms, hearing loss, and skin manifestations. Responds to steroids.
Posterior scleritis: Shows a “T-sign” on B-scan and is associated with eye pain.
Choroidal tumors (malignant melanoma, metastatic tumors): Solid lesions are seen on ultrasound.
Central serous chorioretinopathy (CSC): Differs by showing localized fluorescein leakage, but differentiation from bullous CSC can be difficult ⁵⁾.
Drug-induced: Sulfa drugs (e.g., topiramate, acetazolamide) may be causative ¹⁾.

Imaging Tests

Characteristic findings of each imaging test are shown below.

Test	Main Findings
B-scan ultrasound	Choroidal thickening/detachment, negative T-sign
UBM	Fluid accumulation in the supraciliary space, measurement of scleral thickness
OCT	Choroidal swelling, subretinal fluid, RPE changes

B-scan ultrasound: Choroidal detachment appears as a smooth, thick dome-shaped elevation. The T-sign of posterior scleritis is absent. It is distinguished from neoplastic lesions by the absence of internal echoes ¹⁾. It is also useful for measuring axial length and evaluating scleral thickening. While the normal scleral thickness is 0.95 mm (SD 0.18 mm), in UES cases with intraoperative scleral thickening, it was 2.3 mm (1.5–2.9 mm) ¹⁾.
Ultrasound biomicroscopy (UBM): Allows visualization of separation between the ciliary body and sclera, and detects early fluid accumulation in the supraciliary space. Scleral thickness is measured at a position 2–3 mm posterior to the scleral spur.
Optical coherence tomography (OCT): Visualizes choroidal swelling, subretinal fluid, and focal thickening of the RPE (leopard spots)³⁾. Swept-source OCT is useful for evaluating deep choroidal thickness and choroidal folds⁴⁾. In type III UES, features of pachychoroid (choroidal thickening) may be observed¹⁾.
Fluorescein fundus angiography (FA): Diffuse punctate hyperfluorescence is observed, but no clear leakage like in VKH or CSC is seen¹⁾. It is useful for excluding other causes of exudative retinal detachment.
Indocyanine green angiography (ICG): Diffuse choroidal hyperfluorescence is observed from the early phase and persists into the late phase¹⁾³⁾. This reflects dilation and increased permeability of choroidal vessels.
MRI: In types I and II, scleral thickening is clearly visualized on T1- and T2-weighted images ¹⁾. It is also useful for excluding tumors and posterior scleritis. CT can also confirm microphthalmos and scleral thickening.

Combining multimodal imaging improves the diagnostic accuracy of type III UES in particular³⁾⁵⁾.

Q How is type III UES diagnosed?

Type III is a diagnosis of exclusion because axial length and scleral thickness are normal. Multimodal imaging (OCT, ICG, ultrasound, FA) is used to confirm choroidal thickening, choroidal congestion, and peripheral choroidal detachment, while excluding other causes such as VKH, posterior scleritis, and tumors ³⁾.

5. Standard Treatment

Treatment for UES is selected based on the type classification. Surgery is the mainstay for types I and II, while pharmacotherapy is the first choice for type III.

Surgical Therapy (Standard Treatment for Types I and II)

For types I and II, scleral window surgery is performed to improve scleral outflow obstruction.

Sclerectomy: A partial-thickness (50–75%) scleral window is created near the equator, and a 0.75-mm full-thickness scleral incision is made in the center using a Kelly punch ¹⁾. This procedure was first reported by Gass in 1983, and the basic approach involves performing it in four quadrants.
Treatment outcomes: Anatomical improvement is achieved in approximately 83% of eyes after one surgery and about 96% after two surgeries¹⁾. Final visual acuity improves by 2 or more lines in 56% of eyes, remains stable in 35%, and worsens in 9%.
Treatment strategy: In the initial surgery, one sclerostomy is created in each of the two lower quadrants. If improvement is insufficient, the choroid is re-exposed at the same site, or new scleral windows are added in the upper quadrants.
Mitomycin C: Intraoperative application helps prevent re-occlusion of the transscleral outflow pathway due to fibrosis¹⁾.
Postoperative adjuvant therapy: If subretinal fluid absorption is poor, intravenous osmotic diuretics or oral carbonic anhydrase inhibitors may promote absorption.

Vitrectomy

Vitrectomy is considered when multiple scleral window surgeries fail to achieve improvement. An artificial posterior vitreous detachment is created, followed by drainage of subretinal fluid and gas tamponade. However, in microphthalmic eyes, the ora serrata is located anteriorly, so the scleral incision is placed 1–1.5 mm closer to the limbus than usual. Creating a posterior vitreous detachment and draining viscous subretinal fluid is challenging and requires surgical expertise.

Pharmacotherapy (especially for type III)

Shields et al. reported in a study of 104 eyes with UES that 95% of type III UES resolved with steroid therapy (oral, sub-Tenon, topical, or a combination) ¹⁾. Only 5% required surgery.

Agarwal et al. (2023) treated a 71-year-old man with type III UES after COVID-19 vaccination with oral prednisolone 60 mg/day (1 mg/kg) and mycophenolate mofetil 1 g twice daily, achieving complete resolution in one year ²⁾. No recurrence was observed at 18 months.

Kumarasamy et al. (2026) reported a 47-year-old man with CSC in one eye and type III UES in the other; tapering oral prednisolone from 60 mg led to complete resolution of lesions in both eyes ⁵⁾. No recurrence in the UES eye was noted during 2 years of follow-up.

Other pharmacotherapies reported include the following ¹⁾.

Carbonic anhydrase inhibitors: Acetazolamide promotes fluid drainage from the RPE. Improvement has been reported when used alone or in combination with sclerectomy.
Prostaglandin-related drugs: Latanoprost may improve transscleral macromolecular permeability by increasing scleral metalloprotease activity and reducing collagen ¹⁾.
NSAIDs: Oral indomethacin has been reported to suppress increased choroidal vascular permeability ¹⁾.
Anti-VEGF drugs: Intravitreal injections of ranibizumab or bevacizumab have been reported to improve refractory cases after sclerectomy ¹⁾.

Q Can it be cured with medication alone?

In type III UES, improvement with steroids has been reported in 95% of cases ¹⁾. However, in types I and II, scleral abnormality is the root cause, so medication alone is often insufficient, and scleral window surgery is the standard treatment. Treatment selection based on type classification is important.

6. Pathophysiology and Detailed Mechanism of Onset

The pathology of UES involves multiple factors centered on scleral abnormality.

Aqueous humor passes from the anterior chamber through the ciliary muscle into the uveoscleral outflow pathway, and exits the eye via the suprachoroidal space, choroidal vessels, and vortex veins ¹⁾. Disruption of this outflow pathway leads to UES.

Scleral Abnormalities and Transscleral Outflow Obstruction

In type I and II UES, the sclera histologically shows abnormal arrangement of collagen fiber bundles and proteoglycan deposition ¹⁾. These GAG-like deposits reduce scleral permeability, impairing transscleral drainage of intraocular proteins and fluid.

Accumulation of proteins in the suprachoroidal space increases tissue colloid osmotic pressure ¹⁾. This leads to fluid retention in the suprachoroidal space, forming choroidal detachment. Chronic exudation causes decompensation of the retinal pigment epithelium (RPE), impairing ion channel-mediated water transport, resulting in exudative retinal detachment.

Stimulated by high protein concentration and RPE phagocytosis, RPE cells migrate and proliferate into the subretinal space, forming a leopard spot pattern ¹⁾.

Vortex Vein Compression Hypothesis

There is a hypothesis that thickened sclera compresses the vortex veins, impairing venous return from the choroid. The human eye typically has 3 to 8 vortex veins, but in UES cases, 2 to 4 have been reported ¹⁾. Brockhurst reported improvement after vortex vein decompression in 10 eyes with nanophthalmic UES ¹⁾.

Relationship with the pachychoroid spectrum

In recent years, attention has been drawn to the possibility that UES (especially type III) and CSC are connected via the pachychoroid spectrum (a group of diseases based on choroidal thickening). Spaide et al. proposed venous overload choroidopathy as a common pathophysiological basis ⁵⁾. CSC and UES share short axial length, scleral thickening, choroidal circulatory disturbance, and fluid accumulation in the suprachoroidal space ⁷⁾. However, pigment epithelial detachment (PED), focal RPE leakage, gravitational tracts, and fibrin are rare in UES and are considered specific findings of CSC ⁷⁾.

Kumarasamy et al. (2026) reported a case with chronic CSC in one eye and type III UES in the fellow eye, demonstrating that both diseases lie on the spectrum of venous overload choroidopathy ⁵⁾.

7. Latest research and future perspectives (reports at research stage)

Ex-PRESS Shunt

Attempts to apply the Ex-PRESS shunt used in glaucoma surgery to UES treatment have been reported.

Yepez et al. reported that in three eyes with type II UES, an Ex-PRESS shunt was inserted through a conjunctival incision and oblique scleral incision, and choroidal effusion resolved within 48 hours ¹⁾. No recurrence was observed during 1–2 years of follow-up.

Although its low invasiveness is an advantage, data on long-term outcomes and adaptation to other types are still limited.

Association with vaccination

Since the COVID-19 pandemic, multiple cases of UES onset after vaccination have been reported ²⁾. It is speculated that adjuvants contained in vaccines may trigger Shoenfeld syndrome (autoimmune/inflammatory syndrome), leading to uveal effusion ²⁾. The causal relationship remains unconfirmed, and at present, it is limited to case reports showing a temporal association between vaccination and UES.

Concept of venous overload choroidopathy

Research is progressing to understand UES and CSC comprehensively under the common pathology of choroidal venous overload ⁵⁾⁷⁾. If this concept is established, it may lead to the identification of common therapeutic targets for both diseases.

8. References

Li HH, Hunter KC, Thomson AC, Hunter AA. Medical therapy and scleral windows for uveal effusion syndrome: a case series and literature review. Ophthalmol Ther. 2023;12:35-53.
Agarwal M, Patnaik G, Gupta A. Uveal effusion syndrome following COVID-19 vaccination. Am J Ophthalmol Case Rep. 2023;32:101884.
Markan A, Moharana B, Dogra M, Singh R. Multimodal imaging to aid in diagnosis of uveal effusion syndrome type 3. BMJ Case Rep. 2021;14:e239556.
Ouederni M, Nefaa F, Maamouri R, Cheour M. Swept source OCT in monitoring uveal effusion after trabeculectomy in a nanophthalmic eye. La Tunisie Medicale. 2021;99(10):961-963.
Kumarasamy C, Manayath GJ, Ninan R, Verghese S. Venous overload choroidopathy with coexisting chronic central serous chorioretinopathy and uveal effusion syndrome. J VitreoRetinal Dis. 2026;1-9.
Sharma K, et al. Vogt-Koyanagi-Harada disease: differential diagnosis considerations. Cureus. 2024;16:e58867.
Spaide RF, Gemmy Cheung CM, Matsumoto H, et al. Venous overload choroidopathy: a hypothetical framework for central serous chorioretinopathy and allied disorders. Prog Retin Eye Res. 2022;86:100973.
European Glaucoma Society. European Glaucoma Society Terminology and Guidelines for Glaucoma, 6th Edition. Br J Ophthalmol. 2025;109(Suppl 1):1-212. PMID:41026937. doi:10.1136/bjophthalmol-2025-egsguidelines.

Related keywords