Albert & Jakobiec's Principles & Practice of Ophthalmology, 3rd Edition

CHAPTER 139 - Coats' Disease and Retinal Telangiectasia

Grant M. Comer,
Mark W. Johnson

PRIMARY OR CONGENITAL RETINAL TELANGIECTASIA (COATS' DISEASE)

INTRODUCTION

Coats'; disease (idiopathic retinal telangiectasia, Leber';s miliary aneurysms) is an idiopathic, progressive exudative retinopathy consisting of incompetent retinal telangiectasia that results in a variable clinical spectrum ranging from isolated vascular abnormalities with no exudation to extensive sub- and intraretinal exudation and detachment. Initially described as separate entities, the milder (Leber's miliary aneurysms)[1] and more severe (Coats' disease)[2,3] forms of this retinal vascular anomaly are now considered by most authorities to be variable expressions of the same disease and are, therefore, currently grouped under the common name of Coats' disease.[4,5]

 

 

CLASSIFICATION

Coats initially divided this entity into three varieties: type I included cases of abnormal exudation without apparent vascular changes; type II included both exudation and abnormal vessels; and type III exhibited exudation surrounding a large retinal angioma.[2,3] With the advent of fluorescein angiography, it became apparent that abnormal retinal vessels were present in both types I and II. Type III was subsequently determined synonymous with von Hippel's angiomatosis retina.[6] Other authors[6,7] have attempted to stage Coats' disease based on specific clinical findings at presentation.

More recently, reports have attempted to classify Coats' disease by associating the degree of retinal involvement with prognosis. Cahill and associates classified Coats' disease as severe, focal, juxtafoveal, or associated with other diseases. While severe Coats' disease had a dismal prognosis, the other groups were generally amenable to treatment with 67% achieving a visual acuity at or better than presentation.[8] Similarly, Shields and co-authors classified Coats' disease as: stage 1, telangiectasia only; stage 2, telangiectasia and exudation (2A, extrafoveal; 2B foveal); stage 3, exudative retinal detachment (3A, subtotal; 3B total); stage 4, total detachment with secondary glaucoma; and stage 5, advanced end-stage disease. Despite attempts at treatment, visual prognosis decreased as the extent of retinal involvement increased, especially once the fovea was involved.[9]

 

 

DEMOGRAPHICS

No strong evidence supports a specific racial or ethnic predisposition or inheritance pattern.[10] Coats' disease has reportedly occurred in patients ranging from 3 months of age[11] to those in the eighth decade of life;[12] however, the majority of cases occur by 20 years of age, with a median age at diagnosis of 5 years.[10] Roughly 75% of cases occur in males, and 95% of cases are limited to one eye with asymmetric involvement when bilateral. Most cases are diagnosed after parents note decreased vision, leukocoria or strabismus (Fig. 139.1).[10] Milder cases may be detected at the time of routine ophthalmic examination.

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FIGURE 139.1  Leukocoria secondary to total exudative retinal detachment in a child with Coats' disease.

 

 

 

 

ETIOLOGY

Although numerous authors have described Coats'-like conditions associated with a number of ocular and systemic diseases, Coats' disease, by definition, is isolated and idiopathic with no known inheritance pattern.[10] One report suggested involvement of the Norrie disease pseudoglioma (NDP) gene (Xp11.3), which produces norrin protein.[13] Norrin affects retinal angiogenesis by modification of endothelial cell development. Known phenotypic manifestations of NDP gene mutations include Norrie disease, X-linked primary retinal dysplasia, and X-linked exudative vitreoretinopathy, which all exhibit variable degrees of congenital vascular abnormalities within the retina.[14,15] Black and colleagues reported an NDP mutation in a mother with Coats' disease who gave birth to a son with Norrie disease and suggested that a somatic NDP gene mutation may be responsible for Coats' disease. They also found a mixture of both normal and mutant NDP alleles within retinal tissue, but not nonretinal tissue, of an enucleated eye from a patient with Coats' disease.[13]

 

 

CLINICAL PRESENTATION

Although the extent and rate of development of clinical findings are variable, the disease is usually progressive.[16] Primary abnormalities in Coats' disease are confined to retinal vessels, with a spectrum of secondary findings depending on the degree and chronicity of vascular incompetence. Abnormalities can occur in all levels of the vasculature and include: micro- and macroaneurysms, capillary dilation (telangiectasis) and nonperfusion, and saccular outpouchings of retinal venules.[12,17] In mild cases, one or more localized foci of retinal telangiectasia are noted within the retinal capillary bed, typically in the temporal quadrants between the equator and ora serrata; however, all quadrants, including the macula, can be affected (Fig. 139.2).[18,19]

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FIGURE 139.2  Asymptomatic focus of retinal telangiectasia in a patient with mild Coats' disease.

 

 

In more advanced Coats' disease, areas of lipoproteinaceous exudation develop adjacent to telangiectatic vessels, which have permeable endothelial cells, and slowly progress to involve the entire retina (Fig. 139.3a-c).[19] With accumulation of exudate, a yellow or greenish-yellow subretinal deposit may develop in association with localized exudative retinal detachment. This subretinal lipid may coalesce into crystalline bodies and multiple subretinal deposits. Intraretinal macular exudation often occurs in a stellate pattern without connection to the peripheral telangiectasis.[19] With further progression, total exudative retinal detachment may develop.[10] Although often asymptomatic in the periphery, vision usually becomes affected with the onset of hard exudates beneath the fovea, cystoid macular edema, or exudative macular detachment (Fig. 139.4).

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FIGURE 139.3  (a) Retinal telangiectasia and exudation in the superotemporal quadrant.(b) Focal vascular incompetence and nonperfusion on composite fluorescein angiogram.(c) Subfoveal exudation extending from distant nidus of leakage as seen on optical coherence tomography.

 

 

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FIGURE 139.4  Massive lipid exudation in macula associated with inferior exudative retinal detachment.

 

 

Massive exudation contributes to numerous secondary abnormalities throughout the eye. While often normal, the anterior segment can demonstrate corneal edema, megalocornea, cholesterolosis in the anterior chamber, neovascularization of the iris, cataract, peripheral anterior synechiae, angle closure, and neovascular or secondary open-angle glaucoma.[10,18,20,21] Secondary posterior segment abnormalities may include: retinal hemorrhages, macrocysts, vasoproliferative tumors, neovascularization, vitreous hemorrhage, lamellar macular holes, and preretinal membranes.[10,12,18,22,23]

The clinical presentation differs in adult patients in that the -vascular abnormalities are often present in both the peripheral as well as juxtamacular areas. In addition, adults more commonly demonstrate localized lipid deposition, hemorrhage around macroaneurysms, and slower disease progression.[12] Long-term surveillance is important, even after treatment, as multiple recurrences are seen to occur in up to 33% patients with Coats' disease.[24]

 

 

ANCILLARY TESTS

Fluorescein angiography and optical coherence tomography provide an objective measure of disease extent. Fluorescein angiography demonstrates areas of capillary nonperfusion, saccular and beadlike 'light bulb' dilatations of larger retinal vessels, and general dilatation (telangiectasia) of the capillary bed (Fig. 139.5a,b).[19,25] Abnormal retinal vessels typically fill in the late arterial or early venous phase and slowly leak fluorescein, which may pool within the intraretinal spaces of associated cystoid edema or within the subretinal space.[19,25,26] Children as young as 11 months, under general anesthesia,[27] and 4 years, unsedated,[28] have tolerated optical coherence tomography (OCT) to document and quantify subretinal fluid and macular edema to a resolution of 10 ?m.[29]

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FIGURE 139.5  (a) Typical 'light bulb' dilations and (b) capillary nonperfusion with focal leakage in late-phase angiogram.

 

 

Additional tests help differentiate Coats' disease from ocular tumors such as retinoblastoma, since a definitive diagnosis cannot be established from clinical examination alone in 20% of cases.[19,30] In A- and B-scan echography, advanced Coats' disease often demonstrates a narrow or closed funnel retinal detachment, poor retinal mobility, retinal thickening, low to medium reflective subretinal opacities with a slow convection movement, and absence of a solid mass lesion or calcium.[31] Computed tomography demonstrates subtle homogeneous subretinal densities without contrast enhancement. This is differentiated from retinoblastoma which demonstrates foci of calcium and diffuse contrast enhancement of the mass.[32] Subretinal fluid demonstrates homogeneous hyperintensity on T2-more than T1-weighted magnetic resonance images without further enhancement on -contrast-enhanced sequences.[30,33,34] In contrast, solid intraocular tumors greater than 2.0 mm in thickness, such as retinoblastoma, demonstrate variable intensity on T1-weighted images and are hypointense on T2-weighted images.[30,34] Calcification is accentuated on T2-weighted images.[30] Finally, subretinal fluid aspiration can establish a cytopathologic diagnosis characterized by lipid-laden macrophages and cholesterol crystals.[35,36]

 

 

DIFFERENTIAL DIAGNOSIS

-Since Coats' disease spans a large spectrum of clinical presentations and ages, the differential is vast. Coats' disease often presents in children as leukocoria and strabismus, as such, the differential diagnosis includes retinoblastoma, toxocariasis, persistent hyperplastic primary vitreous, advanced retinopathy of prematurity, congenital cataract, incontinentia pigmenti, -endophthalmitis, Norrie disease, and inflammatory uveitis.[14,18,19] In both children and adults, other retinal telangiectatic and vascular diseases may also mimic Coats' disease, including branch retinal vein occlusion,[37] diabetic retinopathy,[38] radiation retinopathy,[39] familial exudative vitreoretinopathy,[18] juxtafoveal telangiectasia,[40] Eales' disease,[41] retinal capillary hemangioma,[19] retinal cavernous hemangioma,[19] and various causes of vasculitis (Table 139.1).[42]


TABLE 139.1   -- Differential Diagnosis of Coats' Disease

Retinoblastoma

Familial exudative vitreoretinopathy

Retinopathy of prematurity

Retinal toxocariasis

Persistent hyperplastic primary vitreous

Retinal angiomatosis

Incontinentia pigmenti

Pars planitis

Congenital cataract

Malignant melanoma

Choroidal metastasis

Choroidal hemangioma

Eccentric disciform age-related macular degeneration

Exophytic retinal capillary hemangioma

Branch retinal vein occlusion

Idiopathic acquired juxtafoveal telangiectasia

Other causes of acquired juxtafoveal telangiectasia (see Table 139.2)

 

Retinoblastoma, which is potentially lethal if untreated, is the most significant condition that must be differentiated from Coats' disease. Coats' disease generally presents as a unilateral disorder in older boys with no family history, whereas retinoblastoma is more often bilateral with no sex predilection and a positive family history.[19] The presence of sub- and intraretinal calcification strongly suggests retinoblastoma; however, limited reports have confirmed the presence of subretinal[43] and intraretinal calcium[44] in enucleated eyes found to have Coats' disease.

True Coats' disease is defined as an idiopathic, progressive exudative retinopathy with associated retinal telangiectasia. How-ever, numerous reports have described predominantly nonocular disorders, in which Coats'-like changes can comprise an element of the condition, including pericentric inversion on chromosome 3,[45] chromosome 13 deletion,[46] fasciocapsulohumeral muscular dystrophy,[47] Turner's syndrome,[48] Senior-Loken syndrome (familial renal-retinal dystrophy),[49] epidermal nevus syndrome,[50] VATER association (vertebral defects, imperforate anus, tracheo-esophageal fistula, and radial and renal dysplasia),[51] congenital plasminogen deficiency type I,[52] Hallermann-Streiff syndrome,[53] Coats' plus syndrome,[54] Cornelia de Lange syndrome,[55] Alport's syndrome,[56] renal transplantation,[57]aplastic anemia,[58] multiple glomus tumors,[59] and telangiectasia of the nasal mucosa.[60]

Similarly, other reports have described ocular conditions associated with separate Coats'-like changes, including: idiopathic retinal gliosis,[61] branch retinal vein occlusion,[37] retinitis pigmentosa,[62,63]morning glory optic disk,[64] uveitis,[65] ocular toxoplasmosis,[66] and retinal dysplasia.[67]

 

 

PATHOLOGY

Pathologic specimens usually come from globes enucleated because of advanced disease causing a blind and painful eye or when retinoblastoma could not be excluded in the diagnosis.[18] These specimens allow extensive investigation into the primary and secondary abnormalities in Coats' disease.

The primary mechanism underlying Coats' disease is abnormal permeability of the vascular endothelial cells from hyalinization and endothelial cell separation. This vascular incompetence results in subsequent leakage of blood components into the retinal tissue and subretinal space.[68] Light microscopy reveals variability among the retinal vessels including: dilation, hyaline thickening, intraluminal and perivascular gliosis, intraluminal narrowing, and aneurysms devoid of endothelium. In addition, spindle cells, eosinophils, polymorphonuclear leukocytes, and mononuclear cells are found both around and within vessels.[69] Electron microscopy demonstrates intramural thickening with a basement membrane-like material, patchy absence of endothelium and pericytes, and plasmoid and fibrinous infiltration of aneurysmal and telangiectatic vessel walls.[69]

With breakdown of the blood-retinal barrier, massive outpouring of lipid-rich exudate occurs into the retina and subretinal space. Light microscopy reveals irregular thickening of the inner retina from cystic cavities with periodic acid-Schiff (PAS) positive eosinophilic fluid and infiltration of foam and 'ghost' cells. In addition, subretinal fibrin, cholesterol crystals, and cholesterol- and pigment-laden macrophages are observed (Fig. 139.6).[18,69,70] Electron microscopy reveals inner retina infiltration by foam and 'ghost' cells, along with macrophages, hypertrophic Muller cells, and perivascular proliferation of glial cells. The outer retina demonstrates patchy degeneration and atrophy of the photoreceptors. The subretinal space is generally electron-optically empty.[69] The external globe, cornea, trabecular meshwork, iris, ciliary body, Bruch's membrane, and choroid are usually normal.[10,69]

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FIGURE 139.6  Cholesterol crystals of subretinal fluid aspirate in a patient with Coats' disease as visualized with H & E staining (a) and polarized microscopy (b).

 

 

 

 

TREATMENT

The primary goal of treatment is obliteration of the abnormal leaking retinal vessels to allow subsequent absorption of the lipid exudates. In mild cases, ablation of these vessels may be accomplished with laser photocoagulation or transscleral cryopexy. In more advanced cases, excessive exudate may require drainage through a sclerotomy or retinotomy to allow for adequate treatment of the telangiectasis. As it is important to treat the entire area of abnormal vessels, fluorescein angiography may aid in visualizing the full extent of vascular disease.[71]

Shields and associates recommend management based on their staging scheme. Stage 1 disease, telangiectasia only, receives either periodic observation or laser photocoagulation. Stage 2, telangiectasia and exudation, is treated with cryopexy or laser photocoagulation. Stage 3A, subtotal detachment, requires cryopexy or laser photocoagulation; however, 3B, total detachment, receives cryopexy for shallow detachments and either scleral buckling or pars plana vitrectomy for more extensive involvement. Stage 4, total retinal detachment and glaucoma, usually requires enucleation to relieve severe pain. However, stage 5, advanced end-stage disease, requires no treatment because the eye is usually blind but comfortable.[9]

Reports have described resolution of exudation using xenon arc,[72] argon,[73] yellow-dye,[74] and large spot diode[75] lasers; however, resolution often takes months and the final visual acuity is often poor. Areas of thick exudation may prevent adequate absorption of laser energy; in such areas, the triple freeze-thaw method of transscleral retinal cryopexy may be more effective.[76] Multiple treatment sessions are often necessary to accomplish complete vascular closure, and careful follow-up is required to document regression of the abnormal vessels and to detect new areas of telangiectasia, which have been reported to occur as late as 5 years after the initial treatment (Fig. 139.7).[77]

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FIGURE 139.7  Nearly complete resolution of exudation observed in Figure 139.3 after laser photocoagulation.

 

 

In advanced cases associated with exudative retinal detachment, surgical drainage of subretinal fluid and exudate may be necessary to allow treatment of abnormal retinal vessels with either photocoagulation or cryopexy.[72,76,77] Although scleral buckling with external drainage remains a viable treatment option (Fig. 139.8),[6,16] accumulations of cholesterol deposits can hinder subretinal fluid outflow at the draining sclerotomy site, insulate retinal telangiectasia from the cryoablation, and prevent anatomical retinal reattachment.[78] Pars plana vitrectomy with[78,79] or without[80] scleral buckling achieves anatomic success and allows controlled subretinal fluid and cholesterol drainage through an internal retinotomy, direct ablation of telangiectasia with diathermy or laser, and the ability to peel associated preretinal membranes. Although visual function may be severely limited, particularly in cases of total retinal detachment, these surgical maneuvers may stabilize the eye and prevent the subsequent development of phthisis, painful neovascular glaucoma, and the need for enucleation.[16]

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FIGURE 139.8  (a) B-scan ultrasound depicts total exudative retinal detachment in a patient with Coats' disease.(b) This patient's retina was successfully reattached via pars plana vitrectomy with internal drainage of subretinal fluid and endolaser photocoagulation.

 

 

With the recent advent of anti-vascular endothelial growth factor (anti-VEGF) therapy, Smithen and associates[12] speculate that anti-VEGF medications may limit vascular leakage found in Coats' disease since VEGF injections into nonhuman primates caused vascular changes similar to those found in Coats' disease.[81,82] However, no published reports have evaluated intravitreal VEGF levels or the use of anti-VEGF therapy in Coats' patients.

 

 

IDIOPATHIC MACULAR TELANGIECTASIA

Retinal telangiectasia localized to the foveal region alone in one or both eyes is termed macular (juxtafoveal) telangiectasia. Such changes may be congenital, and thus a mild variant of Coats' disease, or may be acquired and seen as an isolated finding in middle-aged or older patients.[40] These idiopathic forms of telangiectasia must be distinguished from secondary telangiectasia caused by other retinal vascular diseases (Table 139.2).


TABLE 139.2   -- Differential Diagnosis of Idiopathic Telangiectasia

Diabetic retinopathy

Branch retinal vein occlusion/central retinal vein occlusion

Radiation retinopathy

Tapetoretinal dystrophy

Inflammatory retinopathy/Irvine-Gass syndrome

Coats' disease

Eales' disease

Adult-onset pseudovitelliform foveal macular dystrophy

Best's disease

Age-related macular degeneration

Choroiditis

Sickle-cell retinopathy

Polycythemia vera retinopathy

Canthaxanthine crystalline retinopathy

Other crystalline retinopathies

Localized retinal capillary hemangioma

Hypertensive retinopathy

Ocular ischemic syndrome/carotid artery obstruction

 

Gass and Blodi classified these patients into three groups with multiple subgroups based on historical, biomicroscopic, and fluorescein angiographic findings.[83] Recently, Yannuzzi and associates simplified the classification scheme into two types of idiopathic macular telangiectasia by eliminating rare forms of the disease.[84]

TYPE 1 (ANEURYSMAL TELANGIECTASIS)

Also known as group 1, visible and exudative idiopathic juxtafoveal retinal telangiectasia under the Gass and Blodi classification, middle-aged male patients typically present with a unilateral mild blurring of central vision.[83] This form of macular telangiectasia is considered a form of Coats' disease that is limited to the macula.[83,84] Biomicroscopy reveals arteriolar, capillary, and venular aneurysms and telangiectasia which are found in both the superficial and deep retinal capillary circulations.[84] Vascular abnormalities are noted within 2 disk diameters of the center of the fovea, primarily along the temporal parafoveal region, and often associated with localized capillary leakage and lipid -exudate (Fig. 139.9a,b). Visual loss in this group of patients tends to occur with the accumulation of foveolar exudate and associated cystoid macular edema.[83,84] Despite maintenance of excellent visual acuity for years without treatment and spontaneous reso-lution in occasional patients, Gass and Blodi recommended early photocoagulation when visual loss is associated with central accumulation of yellow exudate.[83]

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FIGURE 139.9  (a) Unilateral type 1 aneurysmal telangiectasis. Note the aneurysms and telangiectatic capillaries in the parafoveolar region associated with lipid exudates. (b) Fluorescein angiogram demonstrating capillary telangiectasia, microaneurysms, and leakage.

 

 

 

 

TYPE II (PERIFOVEAL TELANGIECTASIA)

Also known as group II, occult and nonexudative idiopathic juxtafoveal retinal telangiectasia under the Gass and Blodi classification, this is the most common form of macular telangiectasia and occurs equally in both sexes. Patients typically present in the fifth and sixth decades of life with mild blurring of vision in one or both eyes that can progress, primarily from foveolar atrophy or subretinal neovascularization.[83] Biomicroscopy reveals symmetric blunting of the foveal reflex with a mild grayish appearance of the parafoveal retina, minimal serous exudation, and no lipid deposition.[83,84] In addition, glistening white or yellowish-white crystalline deposits may be noted in the superficial parafoveal retina in ?40% of patients.[85] In some patients, a small, yellow lesion, 1/3 disk diameter in size, develops within the foveal avascular zone and appears to represent an inner retinal cavitation on OCT evaluation.[83,84]

Initially, telangiectasis is not visible on biomicroscopy, and fluorescein angiography shows only mild staining within one disk diameter of the foveola, especially temporally Fig. 139.10 a-f). With progression, these eyes may develop dilated right-angled retinal venules and arterioles and stellate plaques of retinal pigment epithelial hyperplasia, as well as intra- and subretinal anastomosis and subretinal neovascularization.[26,40,84] Optical coherence tomography can demonstrate hyporeflective intraretinal cavitation without foveolar thickening (Fig. 139.11) and middle or inner layer hyperreflectivity corresponding to areas of retinal pigment epithelial migration.[86] When subretinal neovascularization occurs, central visual acuity loss may be rapid, and 81% of untreated eyes have a final acuity of 20/200 or worse (Fig. 139.12a-c).[87]

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FIGURE 139.10  (a and b) Right and left color fundus photographs of type II idiopathic macular telangiectasia demonstrating a mild parafoveal grayish appearance. (c and d) Classic fluoroscein staining temporal to fovea on late-phase angiogram of right and left eyes. (e and f) Horizontal 5 mm optical coherence tomography scans through fovea of right and left eyes demonstrating a nearly normal appearance without fluid in areas of staining on angiogram. There are tiny hyporeflective spaces in the foveola of each eye.

 

 

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FIGURE 139.11  Hyporeflective inner layer cavitation without retinal thickening on optical coherence tomography scan.

 

 

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FIGURE 139.12  (a) Color photograph of subretinal neovascularization secondary to type II idiopathic macular telangiectasia. (b) Early phase fluorescein angiogram demonstrating subretinal neovascularization with probable retinal feeding and draining vessels. (c) Horizontal 5 mm optical coherence tomography image demonstrating a hyperreflective subretinal focus corresponding to the area of neovascularization on clinical exam.

 

 

Grid laser is not indicated for treatment of type II perifoveal telangiectasia because it does not improve or stabilize long-term visual acuity.[88] In addition, laser has led to the development of subretinal hemorrhage[89] and choroidal neovascularization.[88] A variety of therapeutic modalities have been employed to treat subretinal neovascularization complicating this disorder. Photodynamic therapy[90,91] and transpupillary thermotheraphy[92,93] have demonstrated efficacy; however, the subretinal neovascularization in idiopathic juxtafoveal retinal telangiectasis arises from the retina, as opposed to the choroid, and activation of photosensitizing dye in the retinal layers may cause iatrogenic damage.[90,93] Laser photocoagulation may help stabilize central visual acuity but induces an iatrogenic scotoma,[94] and submacular surgery has demonstrated poor outcomes.[95] Anti-VEGF drugs hold promise for treating neovascularization associated with this disease.

 

 

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