13.1.1 Clinical Features

Retinal vascular changes secondary to hypertension most commonly do not cause visual loss or other ocular symptoms. In typical primary, chronic hypertension, the most common fundus sign is focal narrowing of the major retinal arterial branches. ¹ There can also be generalized retinal arteriolar narrowing, with the vessels taking on a “copper wire” or “silver wire” appearance, reflecting moderate and severe arteriolosclerosis, respectively. ² These color changes of the vessels are the result of diffusion of the normal light reflex secondary to the diminution of the size of the vascular lumen. Finally, arteriovenous “nicking” is sometimes seen in chronic hypertension. It refers to the focal narrowing of a retinal vein at an arteriovenous crossing. Because there is a common adventitial sheath at the crossings, enlargement of the retinal arteriolar wall by arteriolosclerosis will cause some degree of venous compression or narrowing at that point. ³

When the hypertension is severe or acute, a variety of other fundus changes can be seen. In the retina, there can be pronounced focal arteriolar narrowing or closure, intraretinal hemorrhages, cotton-wool spots, or lipid exudates (Fig. 13-1). Complications include hemorrhagic detachment of the internal limiting membrane as well as epiretinal membrane formation in the perimacular area. ¹ Hemorrhages, cotton-wool spots, and lipid exudate eventually disappear once the blood pressure is brought under reasonable control (see “Management and Course”). However, subtle microvascular abnormalities or focal areas of retinal depression corresponding to previous cotton-wool spots may persist. ⁴

With very high blood pressure, optic nerve head swelling may occur. This is, by definition, malignant hypertension (or grade 4 hypertensive retinopathy according to the modified Scheie’s classification). ⁵ Optic nerve head swelling in this setting could represent papilledema from intracranial hypertension, especially if bilateral, or it could be a result of optic nerve head ischemia from local vascular compromise (see later). A macular star pattern of lipid exudate associated with optic nerve head swelling is a classic but not specific finding of severe systemic hypertension.

In summary, the modified Scheie’s classification allows the clinician to stratify hypertensive retinopathy as such: it can be absent (grade 0), minor with mild focal narrowing of arterioles (grade 1), moderate with widespread arteriolar narrowing (grade 2), maked as when retinal hemorrhage is present in concert with widespread arteriolar narrowing (grade 3), or severe when optic disc edema is present (grade 4). ⁵

Hypertensive choroidopathy may accompany the retinal vascular disease. Clinically evident choroidal involvement is indicative of acute hypertensive disease, which leads to focal choroidal hypoperfusion. Ophthalmoscopically, hypertensive choroidopathy may manifest as Elschnig’s spots with or without exudative retinal detachment (Fig. 13-2). ⁶ The spots represent foci of retinal pigment epithelial (RPE) infarction from underlying choriocapillaris fibrinoid necrosis. ^{6 ,​ 7} In the acute phase, these RPE changes appear as deep, gray-yellow spots; with time, they become hyperpigmented. The overlying exudative retinal detachment resolves as the blood pressure comes under better control. Similar foci of ischemia and resultant fibrinoid necrosis along choroidal arterioles leads to the clinical development of linear, pigmented lesions known as Siegrist’s streaks. ^{6 ,​ 7}

Women whose pregnancies are complicated by preeclampsia are at risk for the acute manifestations of hypertensive retinopathy and choroidopathy. Rapid vision loss may be due to macula-involving, serous retinal detachment overlying areas of choroidal hypoperfusion. ⁸ More insidious evidence of choroidal hypoperfusion has been demonstrated in such patients with the recent advent of enhanced depth imaging of spectral-domain optical coherence tomography (EDI-SDOCT). While pregnancy is associated with an increase in subfoveal choroidal thickness, it is significantly decreased in preeclamptic women compared with healthy pregnant controls, matching that of a third group of age-matched nongravid healthy women. ^{9 ,​ 10 ,​ 11} In a study of retinal macular volume and choroidal thickness in postpartum preeclamptic women, healthy postpartum women, and age-matched nongravid controls, increased choroidal thickness and retinal macular volume were noted in preeclamptic postpartum women compared with both normal postpartum and nonpregnant controls, who were similar with respect to choroidal thickness and retinal macular volume. ¹² Taken together, these studies suggest dysfunction in choroidal vascular autoregulation in women with preeclampsia both during and after delivery, with increased susceptibility to hypertensive choroidopathy.

Visual loss resulting directly from hypertensive retinopathy can be caused by exudation of lipid or serous material into the foveal area from incompetent paramacular capillaries. In the setting of grade 4 disease, ischemic damage to the optic nerve head may be the source of vision loss. Finally, significant choroidal involvement can also contribute to vision loss, particularly if there is an exudative retinal detachment that involves the macula.

Fluorescein angiographic findings in hypertensive retinopathy include microaneurysmal dilation of capillaries, telangiectasis, capillary nonperfusion, and leakage from retinal vessels or the optic nerve head (Fig. 13-1). Following hypertensive control, these small-vessel alterations may persist to some degree, being mainly evident in the peripapillary area and the posterior pole. Angiographic findings in hypertensive choroidopathy include focal hyperfluorescence and leakage at the level of the RPE corresponding to the location of the “acute” Elschnig’s spots (Fig. 13-2) ¹³ (see also ¦Chapter 30¦).

Common ophthalmic diseases associated with systemic hypertension include retinal vein occlusions, arterial macroaneurysm, and ischemic optic neuropathy. Eyes with these conditions may or may not have fundus findings of hypertensive retinopathy.

13.1.2 Differential Diagnosis

The differential diagnosis of hypertensive retinopathy is extensive because of the wide spectrum of acute and chronic manifestations. Patients with evidence of capillary abnormalities, such as capillary nonperfusion or microaneurysms, may have diabetic retinopathy, radiation retinopathy, venous occlusive disease, perifoveal telangiectasis, or systemic illness, such as a collagen vascular disease. Not uncommonly, two disease entities may be at play (e.g., systemic lupus erythematosus [SLE] and secondary hypertension). Patients with optic nerve head swelling and macular star (lipid) must have blood pressure checked immediately. With this clinical presentation, the differential diagnosis includes neuroretinitis (cat-scratch disease, toxoplasmosis), diabetic papillopathy, and optic neuritis of infectious (sarcoidosis, syphilis, Lyme disease) or inflammatory etiology. Often, headache is present in patients with malignant hypertension; nevertheless, papilledema secondary to intracranial disease also presents with headache and must be ruled out.

13.1.3 Pathogenesis

Arteriolosclerosis refers to the alteration of the arteriolar wall secondary to long-standing hypertension. Early changes result from an increase in the elastic tissue in the intima. Gradually, the intima is replaced by hyaline and the muscular wall becomes fibrotic. ^{2 ,​ 14} In acute cases, damage to blood vessel walls can also result from leakage of blood components into the arteriolar wall. This results in narrowing or closure of the vascular lumen. In addition, focal areas of capillary nonperfusion to the nerve fiber layer result in ischemic zones, which appear as cotton-wool spots. Cotton-wool spots appear white because of axoplasmic stasis in the area of retinal ischemia. ^{4 ,​ 13} Remodeling of the retinal microcirculation results in microaneurysmal formation and telangiectasis, and it can also result in intraretinal exudation secondary to increased vascular permeability. ¹ Macular star formation results from damage to optic nerve head capillaries and parafoveal capillaries, with passage of lipid-rich material along a plane in the outer plexiform layer into the macula to form a starlike pattern. ¹ Experimental evidence in an animal model suggests that optic nerve head swelling may result from the accumulation of axoplasmic components secondary to axoplasmic stasis, as shown by Tso and Jampol. ⁷

13.1.4 Management and Course

Fundus changes from chronic hypertensive retinopathy, such as retinal arterial narrowing and arteriovenous nicking, tell little about recent blood pressure control. Because these features represent permanent changes in the vessel walls, they persist long after blood pressure has normalized.

In contrast, the acute manifestations indicate poor blood pressure control at the time of the ocular examination. Retinal hemorrhages and cotton-wool spots would be expected when the autoregulatory mechanisms of the retinal arterioles are overwhelmed. In normal individuals, this occurs when the mean arterial blood pressure rises suddenly above 115 mm Hg. ¹⁴ In individuals with preexisting hypertension, still higher levels of blood pressure are probably needed to produce the acute retinal changes.

Management consists of controlling the blood pressure; appropriate systemic therapy leads to resolution of the acute, potentially sight-threatening manifestations. Some degree of permanent visual loss may be encountered if there is significant macular or optic nerve involvement. When there are signs of severe hypertensive retinopathy, choroidopathy, or any optic nerve head swelling, the blood pressure must be checked in the office immediately. Very high systemic blood pressure is a medical emergency and necessitates prompt referral to a comprehensive health care facility.

13.2.1 Clinical Features

Congenital retinal telangiectasis, or Coats’ disease, is predominantly a disease of childhood; however, a less severe form of the disease may develop in adults. ^{18 ,​ 19 ,​ 20 ,​ 21 ,​ 22 ,​ 23 ,​ 24} The majority of cases are diagnosed by 20 years of age, with a peak incidence at the end of the first decade. ^{18 ,​ 19} Male patients are affected up to four times as frequently as female patients and there is no racial or ethnic predisposition. ¹³ It is classically thought of as an exclusively unilateral process. ^{21 ,​ 23 ,​ 25 ,​ 26} Recent reports, however, have shown a high incidence of subtle retinal vascular abnormalities in the fellow eyes of patients with Coats’ disease; these abnormalities include peripheral nonperfusion, telangiectasias, and microaneurysms observed with fluorescein angiography. ²⁷

Traditionally, the term Coats’ disease is used to describe the most severe end of the disease spectrum, characterized by massive yellow subretinal lipid exudation and secondary retinal detachment in children. ²⁶ Infants and young children can present with leukocoria secondary to subretinal lipid deposition and exudative retinal detachment or strabismus from the poor vision that results. Because of the common presentation of leukocoria and strabismus in other childhood diseases, other diagnoses must be investigated (Table 13-1). ^{27 ,​ 28}

The diagnosis is typically made by ophthalmoscopy alone. The term retinal telangiectasis is appropriate, as this is a disease principally of the retinal capillaries. Telangiectasis, increased tortuosity, and exudation from incompetence of small-caliber vessels are typical features (Fig. 13-3). However, larger vessels, including large arteries and veins, can be affected with sheathing, aneurysmal dilations, and exudation. Interestingly, retinal neovascularization is rare despite the presence of capillary nonperfusion and adjacent, relatively normal blood vessels. Vitreous hemorrhage and neovascularization are seen only when larger zones of capillary nonperfusion or retinal detachment are present. Despite the low incidence of neovascularization, it has been demonstrated that in vivo vascular endothelial growth factor (VEGF) levels rise in accordance with the stage of Coats’ disease compared to controls. ²⁸ In addition, elevated levels of VEGF and VEGF-receptor 2 were demonstrated in enucleated eyes of patients with Coats’ disease. ²⁹ This has led researchers to investigate new treatment modalities, namely, the adjunctive use of antiangiogenic agents such as bevacizumab and ranibizumab.

In contrast to the often aggressive childhood presentation and course, adult-onset disease—known as idiopathic macular telangiectasia (IMT) type 1, discussed later—is typically less severe, with telangiectasis and intraretinal exudation often simulating other diseases. Visual loss is secondary to leakage from perifoveal telangiectases, causing cystoid macular edema and often a circinate ring of lipid deposition around the macula (Fig. 13-4). Often, the ophthalmoscopic and angiographic picture in the adult form of disease is difficult to differentiate from that of other perifoveal microvascular abnormalities (Table 13-1). Exudative retinal detachment typical of the childhood form is rarely seen in adults.

The aggressive form of the disease is typically seen in children and infants. Initially, severe retinal vascular leakage causes subretinal deposition of protein and lipid-rich exudate. Massive accumulation of yellow subretinal exudation causes the bullous retinal detachment characteristic of Coats’ disease. In time, nonresolving subretinal lipid deposition can lead to fibrovascular tissue formation and even choroidal neovascularization (CNV). Disciform scars can then develop from CNV and these scars are, unfortunately, most common in the macula, where lipid from peripheral exudative lesions tend to track. In fact, disciform scars are most common in children and infants with broader zones of peripheral involvement. ²²

Other than disciform scars, the complications of long-standing exudative retinal detachments are numerous. Cataract, iridocyclitis, neovascular glaucoma, and eventually phthisis bulbi can occur. Rarely, organization of subretinal fluid in long-standing detachments can lead to a clinical picture simulating that of other diseases. Coalescence of intraretinal cystic spaces in unresolved detachments have reportedly led to hemorrhagic retinal macrocysts. ³⁰ There is also a report of orbital cellulitis developing from transscleral leakage of subretinal toxins in a child with advanced Coats’ disease. ³¹

Although no conclusive evidence of a genetic transmission of Coats’ disease has been demonstrated, multiple associations with systemic and ocular diseases have been reported. Alport’s disease, tuberous sclerosis, Turner’s syndrome, Senior–Løken syndrome, and the ichthyosis hystrix variant of epidermal nevus syndrome have all anecdotally been reported to be associated with a Coats’-like response. Multiple reports of an association with muscular dystrophy, and more recently with facioscapulohumeral dystrophy, exist. In 1956, Zamorani ³² was the first to report an association of retinitis pigmentosa with Coats’ disease. Morgan and Crawford ³³ have since described multiple cases of Coats’-like findings in patients with retinitis pigmentosa. In a literature review, Khan et al ³⁴ reported 46 cases of retinitis pigmentosa associated with Coats’-like findings, or 1.2 to 3.6% of retinitis pigmentosa patients affected among the sites reporting data. Pruett differentiated Coats’-like findings in patients with retinitis pigmentosa from traditional Coats’ disease, noting that the aneurysmal telangiectasias and exudative detachments in patients with retinitis pigmentosa are more often bilateral, without gender predilection, and found in the inferior fundus. ³⁵ The adult form of Coats’ disease has also been associated with hypercholesterolemia.

Fluorescein angiography demonstrates the vascular origin of Coats’ disease and helps confirm the diagnosis. Both children and adults present with the same angiographic findings. Large-vessel involvement is seen as saccular (“light bulb”) aneurysmal dilations, anomalous vascular communications, and telangiectasia (Fig. 13-3). Occasionally, beading of vessel walls is seen. ¹⁶ Capillary involvement is demonstrated by telangiectasia as well as capillary nonperfusion. Large areas of capillary nonperfusion are typically associated with neighboring abnormal large vessels with aneurysmal dilations. ²¹ These areas of vascular pathology have a tendency to occur in the temporal and superotemporal portions of the retina. ²⁰ Fluorescein dye does leak into the subretinal space but stains only minimally. Large zones of exudative retinal detachment distal to the telangiectasias do not stain. However, fluorescein dye does fill intraretinal cystic spaces, often showing a pattern characteristic of cystoid macular edema. ²¹ Interestingly, many cases with exudation originally reported as not having a frankly visible vascular origin have since been shown to have associated vascular anomalies by fluorescein angiography. Most recently, ultrawide-field color fundus and fluorescein imaging has contributed to a greater understanding of this spectrum of peripheral retinal vascular disease, particularly in the realm of pediatric retina. Single-shot images of the posterior pole and retinal periphery are obtained quickly without the need for examination under anesthesia. Fluorescein angiograms may be obtained with oral intake of sodium fluorescein. While precise choroidal fills are difficult to time with this modality, useful angiographic images are nonetheless obtainable with a modicum of cooperation (see Fig. 13-3e–f). This is helpful both to document novel findings in known conditions—such as the previously mentioned subtle fellow-eye vasculopathy in patients with Coats’ disease—as well as for diagnostic purposes in new or challenging cases. ³⁶

There may be some benefit to fluorescein angiography in differentiating Coats’ disease from retinoblastoma. Endophytic retinoblastomas may have a feeder vessel leading to the subretinal mass. The treatment of Coats’ disease also may be enhanced by fluorescein angiography. Unsuspected areas of vascular leakage can be readily identified, and treatment in the form of photocoagulation or cryotherapy then directed to those areas (see Management and Course). ¹⁵

13.2.2 Differential Diagnosis

The differential diagnosis in the childhood form of Coats’ disease presenting with leukocoria or exudative retinal detachment is extensive (see text box Differential Diagnosis of Coats’ Disease). ³⁷ Most importantly, retinoblastoma must be ruled out, as it is life threatening. In a large series by Howard and Ellsworth, ³⁸ 3.9% of children initially thought to have retinoblastoma were found to have Coats’ disease. A thorough history and clinical examination are most important for an accurate diagnosis; unlike retinoblastoma, Coats’ disease occurs primarily in males and has no genetic predisposition. ³⁷ Furthermore, Coats’ disease presents with more lipid exudation than retinoblastoma, and the characteristic vascular anomalies are usually recognizable in patients with Coats’ disease.

Angiomatosis retinae (retinal capillary hemangioma, or von Hippel’s lesion) and the peripheral, acquired retinal angioma can present with significant lipid exudation. In angiomatosis retinae, the rate of bilaterality is high, and the lesions are often associated with dilated feeder and draining vessels, unlike the lesions of Coats’ disease. ³⁷ The acquired peripheral capillary angioma, however, can be more difficult to differentiate from Coats’ disease, as it also does not have very prominent feeder and drainer vessels and can present with heavy lipid exudation, serous detachment, epiretinal membrane, and telangiectatic vascular change. Despite these associated similarities, a discrete, peripheral retinal vascular mass is usually identifiable (see ¦Chapter 27¦).

Ancillary tests may be pivotal in the differentiation of Coats’ disease from retinoblastoma. Ultrasound and computed tomographic (CT) imaging help detect intraocular calcification, which would support the diagnosis of retinoblastoma. ³⁹ Also, thin sections with contrast CT imaging can detect vascularization of the subretinal space, sometimes found in retinoblastoma lesions. Fluorescein angiography may also be useful in evaluating the vasculature of an endophytic mass, as described earlier. ¹⁶ Retinoblastomas can present with a feeder vascular stalk seen by angiography. Aqueous lactate dehydrogenase and isoenzyme levels have not assisted in the diagnosis. However, the presence of cholesterol-laden macrophages in the subretinal fluid is unique to Coats’ disease but is of little help clinically when one is trying to establish the diagnosis noninvasively. ^{38 ,​ 40}

Localized telangiectasis and leakage are seen in the adult form of Coats’ disease. Gass ²¹ referred to these cases as unilateral congenital parafoveolar retinal telangiectasis (group 1A of his classification of idiopathic perifoveal retinal telangiectasis, see later) and is termed IMT type 1 in the updated Yannuzzi’s classification (Table 13.1). The differential diagnosis includes all perifoveal retinal microvascular abnormalities that can present with or without leakage (see text box). Certainly, diabetic retinopathy and venous occlusive disease present more commonly in this manner than does Coats’ disease. Idiopathic, acquired perifoveal retinal telangiectasis (group 2 by Gass’ classification) can have minimal intraretinal serous exudation but, by definition, does not have lipid exudation. ⁴¹ It is also typically a bilateral disease and has no gender predilection. (Other features unique to this form of perifoveal telangiectasis are discussed in the next section.) Capillary nonperfusion and perifoveal microvascular disease seen in the adult form of Coats’ disease are also seen in radiation retinopathy and sickle-cell retinopathy. Cavernous hemangioma is a relatively discrete retinal vascular anomaly that can be likened to a cluster of grapes. There is no clinical or angiographic evidence for vascular incompetence, as there is in Coats’ disease. Acquired arterial macroaneurysms have a zone of leakage typically surrounding a single lesion by angiography. Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) presents with a constellation of findings not typical of Coats’ disease.

13.2.3 Pathogenesis and Histopathology

Historically, infectious and inflammatory processes were implicated in Coats’ disease. A vascular etiology has also been described; this is supported by the presence of material that stains with periodic acid–Schiff (PAS) and thickening of endothelial basement membrane. ⁴² However, these histopathologic changes may be nonspecific and seen with other etiologies. For example, an endocrine disturbance for Coats’ disease has been suggested based on the similarity in basement membrane disease to diabetes and pregnancy-related vascular diseases. Other systemic abnormalities have been investigated. A defect in cholesterol transport has been proposed. ⁴³ The known association between hypercholesterolemia and the adult form of Coats’ disease may be further evidence of a serum lipid abnormality. ⁴⁴

Because of improvements in diagnostic testing, enucleation of eyes with Coats’ disease is now very rare. Most histopathologic reports of Coats’ disease are from earlier studies. By light microscopy, all reports describe abnormal telangiectatic vessels that leak plasma and exudate into retinal tissues as well as subretinally. ^{42 ,​ 45 ,​ 46} Lipid-engorged macrophages are found in the subretinal space. Green ⁴⁶ reported that it is uncertain whether these macrophages originate from retinal vessels and migrate subretinally or travel from the choroidal circulation to phagocytose lipid in the subretinal space.

Electron microscopy confirms abnormalities at the level of the retinal vascular endothelium in eyes with Coats’ disease. ⁴⁷ In addition, Egbert et al ⁴² demonstrated retinal vascular aneurysms and deposition of PAS-positive material in retinal vascular walls after trypsin digestion in 10 eyes. Trypsin digestion studies demonstrate diffuse capillary involvement, even in the peripheral retina. ⁴⁵

Chronic lipid deposition leads to the growth of fibrovascular tissue and, eventually, a disciform scar clinically. Histopathologically, RPE hyperplasia is often seen overlying this organized subretinal fibrovascular tissue. ⁴⁶ Fibrous metaplasia of the RPE has been reported, with the occasional presence of calcium and even bone in these organized fibrous nodules. ⁴⁵

13.2.4 Management and Course

An understanding of the spectrum of disease severity and the remitting and exacerbating nature of the disease is crucial. Although rare, complete remissions have been reported. ^{48 ,​ 49} The rare patient with bilateral disease typically presents with only mild involvement of the second eye, often to a clinically insignificant level. ²⁰

Multiple treatment strategies have been proposed for the management of Coats’ disease. Early treatments for the disease with corticotropin (adrenocorticotropic hormone), steroids, and antibiotics were unsuccessful. Although some authors reported an occasional benefit to transscleral diathermy and radiotherapy, it was not until Meyer-Schwickerath ⁵⁰ applied his new laser techniques to eyes with Coats’ disease that significant cure rates were established.

In the 1970s, treatments of vascular lesions in Coats’ disease by xenon arc, argon laser photocoagulation, or cryotherapy were minimally successful. The major prognostic factor despite the most aggressive treatment was the area of involvement of disease. ^{20 ,​ 22 ,​ 51} Egerer and colleagues ²⁰ reported visual improvement only in eyes with two or fewer quadrants of pathology. The previous report of Harris ²² echoed this finding. Harris also concluded that lipid deposition in the macula was irreversible. Later, Spitznas ⁵² reported several cases of Coats’ disease with resolution of lipid deposition in the macula after treatment. However, he surmised that early treatment was preferred, as more severe lipid deposition did not resolve and often led to permanent visual loss. Most investigators deduced that early treatment of vascular lesions, before lipid accumulation in the macula, was beneficial. ^{20 ,​ 22 ,​ 51 ,​ 52}

Stay updated, free articles. Join our Telegram channel

Join