Exudative Retinitis (Coats Disease)

Article Author:
Abhishek Gupta
Article Author:
Vivek Paulbuddhe
Article Editor:
Koushik Tripathy
Updated:
8/15/2020 12:05:09 AM
PubMed Link:
Exudative Retinitis (Coats Disease)

Introduction

Coats disease is an idiopathic ocular condition characterized by retinal telangiectasia, aneurysms, and exudation.[1][2][3] George Coats first described it in 1908 as a unilateral condition with retinal exudation and telangiectasia in male children. Later, Theodor von Leber described a similar case with telangiectatic and aneurysmal vessels but without the subretinal exudation.[2] This condition was later known as Leber multiple miliary aneurysms.[2] It was identified as an earlier disease process of Coats. Subsequently, Shields et al. defined Coats disease as idiopathic retinal telangiectasia associated with exudation and frequent exudative retinal detachment with no signs of retinal or vitreal traction.’[4]

Etiology

Coats disease is usually sporadic. Considering the unilateral and sporadic nature of the disease, a somatic mutation is more likely.[5] Coats disease is characterized by peripheral retinal avascularity similar to other diseases like Norrie disease, familial exudative vitreoretinopathy (FEVR), facioscapulohumeral muscular dystrophy (FSHD), and the osteoporosis pseudoglioma syndrome.[6][7][8][9][10][11][12] All of these conditions are related to abnormalities in the Wnt signaling pathway during retinal angiogenesis.[6][7] 

Cremers found a mutation in the CRB1 gene in 55% of eyes with retinitis pigmentosa and Coats-like secondary exudative vasculopathy.[13] He suggested that CRB1 could be involved in primary Coats disease as well as other retinal conditions. Several reports have suggested a missense mutation within the Norrie disease pseudoglioma gene, NDP, on chromosome Xp11.2. in the pathogenesis of Coats.[14][15][16][17][18] Mutation in the PANK2 gene has also been implicated in Coats disease.[5]

Epidemiology

Morris et al. conducted a population bases study of Coats disease.[19] The incidence was 0.09 per 100,000 population. All cases were unilateral, and 85% were male.[19] The mean age at presentation was 146 months (median 96 months). Some authors have reported that the disease could be present at birth.[20] In a large series, only 5% of cases were bilateral.[2] The fellow eye was usually without symptoms and had subtle peripheral telangiectatic changes.[2]

Pathophysiology

In Coats disease, there is a breakdown of the blood-retinal barrier, which causes plasma leakage into the vessel wall. As a result, the blood vessels become thickened and necrosed.[21] This leads to a ‘sausage-like’ shape of the vessel. The abnormal pericytes and endothelial cells in retinal blood vessels subsequently degenerate. These blood vessels form aneurysms and later occlude, leading to ischemia and rarely neovascularization.[22]

Histopathology

Coats studied the histologic features of enucleated eyes. He described the subretinal fibrous tissue masses as tightly adherent to the outer retina. Most of the eyes had associated retinal thickening, degeneration, detachment, hemorrhages, cholesterol crystals, and vascular abnormalities. One eye had evidence of bone formation. Other authors have also described the histopathologic features such as bullous retinal detachment and the presence of subretinal fluid. The outer retina is thickened due to exudation, and the inner retina contains telangiectatic vessels. The retinal vessels have perivascular sheathing and are degenerated. There is capillary dropout with areas of neovascularization.[23][24][25][26][27] 

Kase et al. have reported increased vascular endothelial growth factor (VEGF) levels in eyes with vascular abnormalities. They noted VEGF immunoreactivity in retinal macrophages and endothelium of blood vessels.[28]

History and Physical

The presenting symptoms are varied. The patients can present with decreased visual acuity (43%), strabismus (23%), leukocoria/xanthocoria (20%), pain (3%), heterochromia (1%), and nystagmus (1%).[2] 8% of patients may be asymptomatic and are detected coincidentally on routine examination.[2] 

Visual acuity can range from 20/20 to 20/50 in 12% of cases, 20/60 to 20/100 in 11%, 20/200 to counting fingers in 18%, and hand motions to no light perception in 58%.[2] The main causes of poor vision include subfoveal fluid or lipids, subfoveal fibrosis, macular edema, epiretinal membrane, and optic atrophy.[4] The anterior-segment is normal in 90% of cases. Those with findings include cataract, iris neovascularization, shallow anterior chamber, corneal edema, cholesterol in the anterior chamber, and megalocornea.[29][30] 

Retinal findings include telangiectasia, fusiform aneurysms, and intraretinal exudation. There may be sheathing of the vasculature.[4] These findings are generally noted in the inferotemporal quadrant in the peripheral zones between the equator to ora serrata.[4] As the disease progresses, exudation of fluid leads to exudative retinal detachment, retinal hemorrhage, vasoproliferative tumor, macular fibrosis, and optic disc neovascularization.[31] Advanced complications such as iridocyclitis, cataract, and secondary neovascular glaucoma can lead to phthisis bulbi.[32][33][34]

Evaluation

The diagnosis of Coats disease is clinical. Ancillary investigations are done when the diagnosis is in doubt, particularly with bullous retinal detachment with exudation and dilated vessels.

Fundus fluorescein angiography (FFA)

The typical fluorescein angiographic features are telangiectasia, aneurysms, beading of vessel walls, and peripheral retinal nonperfusion. The anomalous vessels show early leakage, which continues until the late phase.[35] On the larger blood vessels, the aneurysms are clearly visible as ‘light bulb’ dilations. In the periphery, areas of capillary drop out and rarely neovascularization can be seen. FFA helps in treatment by identifying the telangiectatic leaking vessels, which can be selectively lasered. It also highlights the areas of nonperfusion which can be treated with photocoagulation in cases of neovascularization.[4][36][37] With the development of wide-field angiography machines such as Retcam and Optos, the peripheral vascular anomalies can be detected and selectively laser targeted.[38]

Computed tomography (CT) 

CT is useful to rule out retinoblastoma. The presence of a solid mass with calcification is present in retinoblastoma. This is better delineated in the CT scan. In Coats disease, the scan would be clear of these lesions.[39][40] CT also highlights the intraocular morphology and the subretinal exudation.

Magnetic resonance imaging (MRI)

MRI may be useful in the diagnosis of advanced Coats disease and ruling out retinoblastoma. The exudate in Coats disease is hyperintense on both T1-weighted and T2-weighted MRI images, whereas in retinoblastoma, the T1-weighted image will show a hyperintense mass, but the T2-weighted image shows a hypointense mass.[39][41] Retinoblastoma shows enhancement with gadolinium contrast, a feature not seen in Coats disease.[1]

Optical coherence tomography (OCT)

OCT is helpful in monitoring for macular involvement. It helps in the documentation of cystoid macular edema, epiretinal membrane, subretinal/intraretinal fluid, subfoveal lipids, central macular thickness, and subfoveal choroidal thickness.[42]

Ultrasonography (USG)

It depicts the extent of retinal detachment. It characterizes the subretinal space, which is usually acoustically clear, but sometimes hyperechogenicity can be seen due to the presence of cholesterol deposits. Calcification can occur in advanced Coats disease along the retinal pigmentary epithelium. It is seen as a curvilinear pattern in contrast to retinoblastoma, where it is randomly distributed.

The analysis of subretinal fluid sometimes helps in diagnosis by demonstrating lipid-laden macrophages and cholesterol crystals.[2]

Treatment / Management

The treatment for Coats disease depends on the stage of the disease. Mild cases with only retinal telangiectasia and no exudation can be observed and followed up at regular intervals. Treatment is done when exudation develops. In less severe cases of exudation, laser photocoagulation to telangiectatic vessels is done.[43][44][45] 

FFA helps in detecting the leaking vessels.[38] They are directly treated with moderate intensity burns. Laser therapy causes inflammation and leads to a transient increase in exudation. So, multiple sessions of laser are needed at intervals of 2 to 3 months. But the laser is ineffective in cases of extensive subretinal exudation and retinal detachment. Cryotherapy is useful in such cases. It is done by a double freeze-thaw technique over the affected retina. Cryotherapy is associated with more inflammation and pain, so two quadrants are treated per session.

Advanced cases with bullous exudative detachment abutting the lens might benefit from surgery. The subretinal fluid is drained either transsclerally or internally. The detached retina gets approximated. Pan retinal photocoagulation or cryo is then done. In cases with the rhegmatogenous or tractional component, pars plana vitrectomy is done with or without tamponade. Surgery aims to prevent painful blind eye and avoid enucleation rather than vision restoration.

Enucleation is done in endstage disease with neovascularization or angle-closure glaucoma.[4][46] Alternatively, transscleral diode laser cyclophotocoagulation can be tried in eyes with neovascular glaucoma.[47] 

Pharmacologic therapy: Intravitreal corticosteroids and anti-VEGF agents are effective in reducing macular edema and subretinal fluid.[48][49][50][51][52][53][54][55][56] They are employed as adjunctive agents. They can also be given before laser and cryotherapy to reduce the reactive exudation associated with them.[57]

Differential Diagnosis

Diseases that produce leukocoria and strabismus can simulate Coats disease. The differential diagnosis includes retinoblastoma, FEVR, retinal detachment, Noorie disease, persistent hyperplastic primary vitreous (PHPV), retinopathy of prematurity (ROP), congenital cataract, retinal hemorrhage, hemangioblastoma, toxocariasis, choroidal hemangioma, coloboma, endophthalmitis, cytomegalovirus retinitis, and toxoplasmosis. The most important differential is retinoblastoma. Retinoblastoma is the most common intraocular malignancy in children and is fatal if left untreated. Coats disease is the most common cause of erroneous enucleation reported.[2] 

Retinoblastoma can present in a younger child below one year, Coats is not as common in this age group and generally presents after 2-3 years. The large vessels in retinoblastoma go subretinally within the tumor, whereas in Coats disease, the telangiectatic vessels are always noted in the retinal surface. Bilaterality is common in retinoblastoma but very rare in Coats disease. Retinoblastoma often has a family history, but family history is not present in Coats disease. Retinoblastoma presents with leukocoria, and Coats disease has xanthocoria. On USG, retinoblastoma presents as a solid mass and calcification with shadowing. This feature is absent in Coats. The calcification in retinoblastoma is randomly distributed. Calcification in Coats is rare, but if present is curvilinearly distributed along the retinal pigment epithelium.

On MRI in retinoblastoma, the T1-weighted image is hyperintense, and the T2-weighted image is hypointense.[39][41] The exudate in Coats disease is hyperintense on both T1-weighted and T2-weighted MRI images, whereas retinoblastoma shows enhancement with gadolinium contrast, a feature not seen in Coats disease.[1]

FEVR and Noorie disease can be differentiated based on bilaterality, a positive family history, and the presence of retinal dragging, all of which are rare in Coats disease. Retinopathy of prematurity (ROP) is seen in preterm low birth-weight babies. Proliferative retinopathy due to chronic rhegmatogenous retinal detachment and pars planitis is another differential.

The classical finding in Coats is dilated telangiectatic vessels, aneurysms, hard exudates, peripheral avascularity, and exudative retinal detachment.

Sometimes a mass forms which might simulate

  • Melanoma
  • Papillary hemangioblastoma
  • Vasoproliferative tumor

Other differential diagnoses of diseases with extensive hard exudates include

  • Branch retinal venous occlusion
  • Vasoproliferative tumor
  • Capillary hemangioma
  • Chronic retinal detachment
  • Trauma 
  • Inflammation

A Coats-like response (retinal telangiectasia, aneurysm, and hard exudates) may also be noted in

  • Retinitis pigmentosa
  • Facioscapulohumeral muscular dystrophy and deafness
  • Progressive facial hemiatrophy
  • Isolated hemihyperplasia
  • Tuberous sclerosis
  • Alport's syndrome
  • Epidermal nevus syndrome

Staging

Shields et al. introduced the staging of Coats disease in 2000 which is most widely used:[4][58]

  • Stage 1 is characterized by retinal telangiectasia
  • Stage 2 has telangiectasia and intraretinal exudation 
    • Stage 2A denoting extrafoveal exudation 
    • Stage 2B defining foveal involvement
  • Stage 3 denotes exudative retinal detachment
    • 3A is a subtotal detachment
      • 3A1 and 3A2 denoting extrafoveal and foveal involvement, respectively
    • 3B is a total retinal detachment
  • Stage 4 has a total retinal detachment plus increased intraocular pressure
  • Stage 5 is an endstage disease, occasionally with phthisis bulbi

Prognosis

Shields et al. reported the visual outcome of 160 patients with Coats disease.[59] In this study, they found that the advanced stage of the disease was associated with poor visual acuity after treatment. The advanced disease showed less frequent resolution of disease, subretinal fluid, and exudation. The enucleation rate was higher in Stages 4 and 5. Poor visual acuity in advanced stages was mainly due to persistent retinal detachment and macular fibrosis. For stages 1 and 2, telangiectatic vessels resolved completely (47%) or partially (53%) over a mean interval of 15 months following treatment.[4] 

Overall most cases (76%) stabilized or improved anatomically following treatment, with the minority (8%) progressively worsening.[4] Approximately 20% required enucleation for neovascular glaucoma or painful phthisis bulbi. The risk of recurrence persists even after the resolution of the disease. Patients should be followed lifelong for recurrence.[3][60][61]

Complications

The clinical course of Coats disease is progressive. Acute exacerbations of the disease infrequently occur, followed by a quiescent state. Spontaneous remissions are rare. In untreated eyes, secondary complications can develop, including:

  • Orbital cellulitis (which may simulate retinoblastoma)
  • Neovascularization
  • Vitreous hemorrhage 
  • Cataract, rubeosis iridis
  • Neovascular glaucoma
  • Phthisis bulbi

Deterrence and Patient Education

As Coats disease is idiopathic and sporadic, there are no preventative measures that can be taken by the patients' families. The patients' family members should be counseled properly regarding the prognosis of Coats disease and the importance of long term followup.

Enhancing Healthcare Team Outcomes

Any patient presenting with Coats disease should not only receive treatment by an ophthalmologist as it requires an interprofessional team evaluation by pediatricians and oncologists. Interprofessional communication can lead to better patient management. The patient will most often present to the primary clinician, and these professionals should be aware of the condition as it is treatable.

Prompt referral to an ophthalmologist is necessary. These patients can then be followed by their primary clinicians and should ensure compliance with treatment. Nursing staff will be the first to the department to come in contact with patients on followup and can assess treatment progress as well as evaluate compliance with both medication and lifestyle measures, and report any issues to the primary care clinician. This collaborative, interprofessional approach to care can ensure optimal patient outcomes.


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