Coats disease

Key points at a glance

Highlights of this disease

• Coats disease is an idiopathic retinal telangiectasia that is sporadic and non-hereditary.
• Approximately 75% of patients are male, and 95% have unilateral disease. The average age of onset is around 5 years.
• Initial symptoms in infants are often noticed as strabismus or leukocoria.
• Among diseases presenting with leukocoria, differentiation from retinoblastoma is the most important issue.
• The mainstay of treatment is occlusion of abnormal vessels using laser photocoagulation and cryotherapy.
• Anti-VEGF drugs are expected as an adjunctive therapy, but consensus as standard treatment has not been established.
• Adult-onset cases are rare but milder and slower in progression than the childhood type, and treatment response is also favorable.

1. What is Coats disease?

Coats disease is an idiopathic retinal vascular disease reported by George Coats in 1908. Its essence is abnormal dilation of retinal capillaries (telangiectasia) and accumulation of exudates within and beneath the retina from the vessel walls.

The disease is sporadic and non-hereditary, with no association with systemic diseases or family history ¹⁾. The incidence is rare at 0.09 per 100,000 people ²⁾. Approximately 75% of patients are male, 95% have unilateral disease, and it commonly occurs in individuals under 20 years (average around 5 years).

Adult onset is very rare but presents a different clinical picture from the childhood type. Adult-onset cases are milder and slower in progression than the childhood type, and treatment response is also favorable ³⁾. In one report, only 21% of 48 adult-onset eyes developed exudative retinal detachment, significantly lower than 81% in childhood-onset cases ³⁾.

The mild form is also called Leber’s miliary aneurysms and forms part of the spectrum of Coats disease. Type 1 idiopathic macular telangiectasia is also considered to be within the same disease spectrum.

Q Can adults develop Coats disease?

A

Cases of onset at age 35 or older have been reported and are recognized as adult-onset Coats disease ³⁾. Compared to the childhood type, the progression of lesions is slower, the frequency of exudative retinal detachment is lower, and treatment response is often favorable. However, onset itself is rare, and when similar findings are observed in adults, differentiation from other diseases is important.

2. Main symptoms and clinical findings

Fundus photograph and OCT of Coats disease. Massive yellowish-white exudation and elevation in the macula.

Wang CT, et al. Optical Coherence Tomography and Optical Coherence Tomography Angiography in Pediatric Retinal Diseases. Diagnostics (Basel). 2023. Figure 3. PMCID: PMC10138206. License: CC BY.

Fundus photograph shows extensive yellowish-white exudation centered on the macula, confirming the spread of exudation to the macula as a fundus finding of Coats disease. OCT reveals macular elevation and subretinal fluid.

Subjective Symptoms

When onset occurs in infancy, the affected child rarely complains of symptoms.

• Leukocoria (white pupil): Often noticed by family members during photography. Differential diagnosis from retinoblastoma is an urgent issue.
• Strabismus: Arises from fixation abnormalities due to decreased vision in one eye. Reported as the chief complaint at initial visit in 23% of cases.
• Decreased vision: About 34% complain of decreased vision at initial visit, and in 76% of cases, vision has already dropped to 20/200 or worse.

In adult-onset cases, vision is relatively preserved, and it may be discovered incidentally during health checkups ³⁾.

Clinical Findings

Characteristic fundus findings include abnormally dilated retinal vessels concentrated in the periphery and accumulation of yellowish-white subretinal and intraretinal exudates. Fluorescein angiography reveals peripheral retinal vascular occlusion, telangiectasia, microaneurysms, and neovascularization as characteristic findings. As the disease progresses, exudative retinal detachment occurs, eventually leading to total detachment. On ultrasound, CT, and MRI, subretinal fluid appears uniformly throughout, which is an important imaging differential point from retinoblastoma, which presents with a heterogeneous appearance with calcification.

In later stages, anterior segment complications such as rubeosis iridis and neovascular glaucoma occur. Macular hole is a rare complication, with only about 7 cases reported in the literature ⁴⁾. Fibrous nodules are a factor for poor visual prognosis, and OCTA has confirmed type 3 neovascularization (SVC→DVC→avascular complex) within the nodules ⁵⁾.

Shields Classification

The Shields classification divides the stages of Coats disease into the following 5 stages. It is used for selecting treatment strategies and estimating prognosis.

Stage 1–2

Stage 1: Only retinal telangiectasia is present, without exudation.

Stage 2A: In addition to telangiectasia, exudates are present outside the fovea.

Stage 2B: Exudates extend to the fovea. Visual acuity decline becomes apparent.

Stage 3

Stage 3A1: Associated with subtotal retinal detachment outside the fovea.

Stage 3A2: Associated with subtotal retinal detachment involving the fovea. Visual prognosis is poor.

Stage 3B: Total retinal detachment has occurred. Urgent intervention is required.

Stages 4–5

Stage 4: Total retinal detachment complicated by secondary glaucoma, a pre-end-stage condition. May be painful.

Stage 5: End stage. Phthisis bulbi (atrophy) has occurred. Enucleation may be considered.

Q Is every white pupil Coats disease?

A

Several diseases present with a white pupil, and Coats disease is only one of them. The most important differential diagnosis is retinoblastoma (Rb), which requires urgent evaluation as it directly affects life prognosis. Other differentials include retinopathy of prematurity, persistent hyperplastic primary vitreous (PHPV), and endophthalmitis. For details, see the “Diagnosis and Testing Methods” section.

3. Causes and Risk Factors

The cause of Coats disease is unknown, and no association with systemic diseases or family history has been identified. Reports suggesting a genetic background have indicated instability of chromosomes 3 and 13, and associations with the NDP gene (Norrie disease-related) and CRB1 gene, but these are not established.

As the starting point of the pathology, disruption of the inner blood-retinal barrier (iBRB) is thought to play a central role¹⁾. Decreased pericytes (cells that support vascular endothelium) weaken the vessel walls, leading to the formation of abnormally dilated capillaries and aneurysms¹⁾. Plasma components leak and accumulate within the vessel wall and retinal layers, causing thickening of the vessel wall and further exudation, creating a vicious cycle²⁾.

A high VEGF environment is also suggested to promote dilation of peripheral capillaries²⁾, and this mechanism provides the theoretical basis for anti-VEGF therapy.

Coats disease and genetics

Coats disease is not a hereditary disease, so the risk of family members developing the same condition is the same as for the general population. However, if symptoms are noticed, it is important to see an ophthalmologist early. Strabismus or leukocoria in children can sometimes be noticed during home observation.

4. Diagnosis and examination methods

Diagnosis involves a combination of multiple tests, and the most important task is to reliably differentiate it from retinoblastoma (Rb).

Ophthalmoscopy and slit-lamp examination

Fundus examination under mydriasis reveals tortuous abnormal vascular networks and yellowish-white subretinal exudates in the peripheral retina. When exudates extend to the macula, they may appear as hard white plaques.

Fluorescein angiography (FA)

This is one of the most important tests for diagnosing Coats disease. Characteristic findings include marked dilation of capillaries, capillary aneurysms, arteriovenous anastomoses, and “light bulbs” (bulbous fluorescein leakage). It is essential for determining the extent of abnormal vessels and planning laser photocoagulation.

Optical coherence tomography (OCT/OCTA)

• OCT: Useful for quantitative assessment of subretinal fluid and for identifying septal structures in the outer retina (partition-like changes in the outer nuclear layer)⁶⁾.
• OCTA: Can noninvasively detect type 3 neovascularization within fibrous nodules in the macula⁵⁾. It is used for monitoring treatment effects and early detection of nodule formation.

Ocular ultrasound (B-scan)

Confirms the absence of a solid mass. Rb often shows hyperechoic foci (calcification) within a solid mass on B-scan, whereas Coats disease does not form a solid mass.

CT and MRI

Evaluate the presence of calcification. Rb is frequently associated with calcification, while Coats disease does not cause calcification. This finding is an important basis for differentiation.

Main differences between Coats disease and retinoblastoma

The main differences between Coats disease and retinoblastoma are shown below.

Feature	Coats disease	Retinoblastoma
Typical age of onset	Around 5 years old	1 to 2 years old
Sex predilection	75% male	None
Bilaterality	About 5%	About 40%
Calcification	Absent	Present (high rate)
Solid mass	None	Present
Ultrasound	Subretinal fluid accumulation	Solid mass, internal calcification, posterior shadowing
MRI	Subretinal fluid is homogeneous	Heterogeneous (mass signal)

Other differential diagnoses include retinal hemangioma, von Hippel-Lindau disease, persistent hyperplastic primary vitreous (PHPV), familial exudative vitreoretinopathy (FEVR), toxocariasis, vasoproliferative tumor, and Eales disease.

Specialist Supplement

Bilateral retinal vein occlusion may present with an appearance similar to Coats disease ⁷⁾. If similar findings are observed in adults, primary retinal vein occlusion, diabetic retinopathy, and familial exudative vitreoretinopathy (FEVR) should also be included in the differential diagnosis.

5. Standard Treatment

The goal of treatment is to occlude abnormal blood vessels and stop the production of exudates. A stepwise approach is taken depending on the disease stage.

Laser Photocoagulation (Basic Treatment)

This is the first-line treatment. Abnormal dilated vessels and microaneurysms identified by FA are directly coagulated, and photocoagulation is also applied to the surrounding non-perfusion areas. In children, it is performed under general anesthesia. Multiple sessions are often required, and regular FA re-evaluation and additional coagulation are repeated after treatment.

Cryocoagulation (Transscleral Cryotherapy)

This is the next option for lesions in the anterior periphery or areas difficult to treat with photocoagulation. It may be used in combination with photocoagulation.

Laser Coagulation

Indications: Abnormal vessels and exudative lesions in Stages 1 to 3A.

Method: Direct coagulation of telangiectatic areas and non-perfusion regions under FA guidance. Performed under general anesthesia in children.

Features: Can be performed repeatedly. Regular FA re-evaluation and additional coagulation after treatment are standard management.

Cryocoagulation

Indications: Anterior peripheral lesions difficult to treat with photocoagulation, and as an adjunct in severe cases up to Stage 3B.

Method: A cryoprobe is applied transsclerally to coagulate and occlude abnormal vessels.

Features: It has the advantage of being feasible even under opaque media or in the far periphery.

Vitreoretinal Surgery

Indications: Stage 3B (total retinal detachment) or higher, and cases where cryocoagulation is ineffective.

Method: Drainage of subretinal fluid via external drainage or vitrectomy, and internal retinal reattachment ⁸⁾. In severe cases, subretinal fluid drainage combined with scleral buckling may be performed.

Features: In cases with macular hole, the inverted internal limiting membrane (ILM) flap technique has been reported to be effective ⁴⁾.

Photocoagulation in children

In pediatric cases of Coats disease, lesions tend to progress rapidly, so it is important not to hesitate to perform photocoagulation under general anesthesia. Active treatment at the appropriate time improves visual prognosis.

Anti-VEGF therapy (adjuvant therapy)

The use of anti-VEGF agents for Coats disease has not yet reached a consensus; it is not a standard treatment but is positioned as an adjuvant therapy in combination with photocoagulation.

A report describes a case of adult-onset Coats disease treated with a combination of intravitreal injection of ranibizumab 0.5 mg and laser photocoagulation, with final best-corrected visual acuity improving from counting fingers to 20/60³⁾.

In a pediatric case, combination therapy with intravitreal bevacizumab 1.25 mg, sub-Tenon triamcinolone, and laser was performed every 6 weeks under EUA (examination under anesthesia). It has been noted that paradoxical exudative retinopathy may occur after treatment²⁾.

There is also a report that brolucizumab was effective in a case resistant to bevacizumab²⁾. Anti-VEGF therapy may contribute to preventing the formation of fibrous nodules⁵⁾.

Enucleation

Enucleation is chosen for painful blind eyes (Stage 4–5) when it is difficult to rule out retinoblastoma.

Treatment considerations

• New abnormal vessels may form after treatment, so regular follow-up with FA (fluorescein angiography) is necessary even after treatment completion.
• Paradoxical exudative retinopathy may occur after anti-VEGF administration, requiring careful observation after treatment initiation²⁾.
• If fibrous nodules form in the macula, visual prognosis is poor. Early appropriate treatment is important to prevent nodule formation⁵⁾.

Q Can recurrence occur after laser treatment?

A

In Coats disease, some cases experience recurrence or re-detachment over several years, and some cases are bilateral with different onset times. Even after treatment completion, regular re-evaluation with fluorescein angiography is necessary, and if new lesions are found, additional photocoagulation or cryotherapy should be performed.

Q Is anti-VEGF drug a standard treatment for Coats disease?

A

At present, there is no established consensus on the use of anti-VEGF drugs for Coats disease, and they are not considered standard treatment. Although reports are accumulating on their use as adjunctive therapy combined with laser photocoagulation, evaluation of efficacy and safety requires further research.

6. Pathophysiology and detailed pathogenesis

The central mechanism of Coats disease is the breakdown of the inner blood-retinal barrier (iBRB)¹⁾.

The iBRB is composed of retinal capillary endothelial cells and supporting pericytes. In Coats disease, the number of pericytes is markedly reduced, leading to decreased vascular endothelial support function¹⁾. Immunostaining and electron microscopy have confirmed that the number of endothelial cells themselves is also reduced¹⁾.

Breakdown of the endothelial BRB causes plasma components (mainly lipoproteins and cholesterol) to leak and accumulate within the vessel wall, retina, and subretinal space¹⁾. The accumulated lipids trigger infiltration of lipid-laden macrophages (foam cells) and a granulomatous immune response, exacerbating tissue damage¹⁾.

A high VEGF environment promotes further dilation of peripheral capillaries and contributes to disease progression²⁾. OCTA observations have confirmed type 3 neovascularization (formed in the order SVC → DVC → avascular complex) within macular fibrous nodules in advanced lesions⁵⁾, advancing the understanding of the neovascularization process.

The mechanism of macular hole formation is thought to involve retinal shortening due to peripheral laser photocoagulation, which creates tangential traction and leads to a macular perforation⁴⁾.

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

For patients: Please read this

The following content is currently at the research stage or under clinical trial and is not standard treatment available at general hospitals. It is reference information for professionals regarding future medical developments.

OCTA evaluation of microvasculature within nodules

OCTA has enabled non-invasive evaluation of microvascular structures within fibrous nodules.

Ong et al. (2021) used OCTA to analyze the vascular structure within macular nodules in detail, revealing the presence of type 3 neovascularization formed in the order SVC → DVC → avascular complex⁵⁾. This finding is important for elucidating the mechanism of nodule formation and as a target for anti-VEGF therapy.

Paradoxical exudative retinopathy

A phenomenon of paradoxical worsening of exudation after initiation of anti-VEGF therapy has been reported, and elucidation of the mechanism and establishment of management methods are needed.

Kalavar et al. (2022) reported a case of pediatric Coats disease with transient worsening of exudation and macular star formation after treatment initiation ²⁾. Brolucizumab was effective in a bevacizumab-resistant case, attracting attention as a new treatment option ²⁾.

Inverted Internal Limiting Membrane (ILM) Flap Technique for Cases with Macular Hole

Nawrocka et al. (2023) reported a case of vitrectomy using the inverted internal limiting membrane flap technique for a macular hole associated with Coats disease ⁴⁾. Macular hole closure was confirmed at 18 months postoperatively, and final best-corrected visual acuity was 20/40. Coats disease-related macular hole is a rare complication with only about 7 cases reported on PubMed ⁴⁾.

Accumulation of Outcome Data from Large-Scale Case Analysis

Shields et al. (2019) analyzed 351 eyes with Coats disease over 45 years, showing improvement in treatment outcomes over time ⁹⁾. Dalvin et al. (2019) analyzed the same cohort by age category, showing that pediatric-onset cases tend to have more severe lesions and worse visual prognosis compared to adult-onset cases ¹⁰⁾.

Increased Recognition of Adult-Onset Coats Disease

Adult-onset Coats disease is a disease concept that has been underrecognized, and the number of reports is increasing ³⁾. Clinical differences from the pediatric type (milder, slowly progressive, good treatment response) are being clarified, and establishing appropriate treatment protocols for adults remains a challenge.

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8. References

1. O’Leary F, Campbell M. The blood-retina barrier in health and disease. FEBS J. 2023;290(4):878-891.
2. Kalavar M, Ashkenazy N, Acon Ramirez D, Berrocal A. Paradoxical exudative retinopathy and macular star formation after treatment initiation in Coats disease. J Vitreoretin Dis. 2022;6(6):452-456.
3. Mandura RA, Alqahtani AS. Coats’ disease diagnosed during adulthood. Cureus. 2021;13(7):e16303.
4. Nawrocka ZA, Partyka I, Nawrocka Z, Nawrocki J. Full-thickness macular hole in Coats disease treated using the inverted internal limiting flap technique. J Vitreoretin Dis. 2023;7(3):262-264.
5. Ong SS, Hsu ST, Ponugoti A, Toth CA, Vajzovic L. An evaluation of the microvasculature of macular nodules in Coats disease using optical coherence tomography angiography. J Vitreoretin Dis. 2021;5(5):431-437.
6. Tayal S, et al. OCT findings in Coats disease. Cureus. 2024;16(4):e58867.
7. Hua R, Zhang M. Bilateral retinal vein occlusion-simulated Coats’ disease. Diagnostics. 2021;11(5):909.
8. Kelkar A, Bolisetty M. Lifting the White Walker’s curse - Management of Coats’ disease. Indian J Ophthalmol. 2023;71(8):3060.
9. Shields CL, Udyaver S, Dalvin LA, et al. Coats disease in 351 eyes: analysis of features and outcomes over 45 years (by decade) at a single center. Indian J Ophthalmol. 2019;67:772-83.
10. Dalvin LA, Udyaver S, Lim LS, et al. Coats disease: clinical features and outcomes by age category in 351 cases. J Pediatr Ophthalmol Strabismus. 2019;56:288-96.