Ординатура / Офтальмология / Учебные материалы / Retinal Vascular Disease Joussen Springer

ity varies from 20/25 to 20/40. It cannot be determined whether the telangiectasis precedes, accompanies or follows the occlusive phenomena.

In addition to telangiectasis of Group 3A, in Group 3B IJRT an association with central nervous system disease has been evidenced (Table 22.1.2).

22 III 22.1.3 Electron Microscopic and Light

Microscopic Changes

In microscopic studies of Group 1A IJRT, changes in the superficial and deep juxtafoveolar retinal capillary plexus were observed. Deformed capillaries with endothelial decompensation lead to a serous exudation and retinal swelling primarily of the outer plexiform layer (Fig. 22.1.1B). The biomicroscopic picture of cystoid macula edema is caused by an extension of exudation into the foveal area. The often seen yellow exudates are accumulated large lipoproteins escaped from the insufficient vessels.

In electron microscopic and light microscopic studies of Group 2A IJRT [8], some narrowing of the capillary lumina has been observed. This is associated with thickening of the capillary wall by multilaminated basement membrane, focal endothelial defects and perithelial degeneration. A slight thickening of the retina by intraand extracellular edema confined to the inner half of the retina has been noted. This suggests that the juxtafoveolar retinal capillaries are the primary tissue involved, and the late fluorescein staining is occurring within the sensory retina. Early fluorescein staining of the thickened capillary walls is responsible for the early angiographic appearance of telangiectatic vessels. The altered structure of the capillary wall is associated with decreased endothelial permeability, inciting chronic nutritional damages of retinal cells, particularly those at the level of the inner nuclear layer. The late staining in fluorescein angiography is probably caused by staining of extracellular matrix and intracellular diffusion into these damaged cells. Further changes and the nutritional deprivation of retinal cells in the median retinal layers lead to degeneration and atrophy of these cells and the connecting photoreceptor cells. This is responsible for the loss of visual acuity and a picture that may simulate a lamellar macular hole.

The yellow deposits are found in the inner surface of the retina, often anterior to the retinal blood vessels. The cause is unknown. It is suggested that they are composed of lipid. Their location in the region of the internal limiting membrane suggests that they might be a product of degenerating Müller cells whose nuclei are located in the inner nuclear layer at the site of the altered deep retinal capillary plexus.

Other groups of IJRT have not been investigated ultrastructurally in the literature.

22.1.4 Natural Course of IJRT

Essentials

The natural course of most groups of IJRT demonstrates a very slow progression

The natural course of Group 2A IJRT is unknown, but slow progression from one stage to the next is suggested. Gass observed a progression from Stage 4 to Stage 5 in 24 % of patients after a 6-year-follow up. The risk of disease progression in the early stages and future visual loss is unknown. Only a very slow rate of progression and the hope of possible stabilization at a specific stage of the disease can be postulated at the present time.

In order to obtain more insight into the pathogenesis, clinical presentations, genetic background and prognosis of Group 2A IJRT, an international prospective multicenter study (the Mac-Tel Study) has been initiated.

22.1.5Association with Systemic Diseases and Differential Diagnosis

Idiopathic juxtafoveolar retinal telangiectasis must be differentiated from other systemic and ocular diseases associated with telangiectasis like diabetic retinopathy, retinal vascular occlusions, Eales disease, retinopathy of prematurity or sickle cell retinopathy.

Group 1A telangiectasis may be assigned to the great spectrum of congenital telangiectasis [3] and may be grouped with Leber’s miliary aneurysms or central Coats’ syndrome [12].

An association with systemic diseases seems to be typically in Group 3 IJRT. In his study of IJRT, Gass assigned only seven patients to Group 3A IJRT. Gass described in all seven patients other medical complications that may have contributed to the retinal changes: polycythemia, gouty arthritis, hypoglycemia and cardiovascular disease [5].

The evidence of atrophy of the juxtafoveolar retina and minimal exudation associated with capillary occlusion are similar to that found in patients with sickle cell retinopathy [14].

Group 3B IJRT are suspected to be an autosomally dominantly inherited cerebroretinal vasculopathy [5, 7]. This familial disorder is associated with central nervous system pseudotumor characterized by an unusual vasculopathy with fibrinoid necrosis and necrosis of white matter.

22.1.6 Therapy

Essentials

In Group 1A a focal photocoagulation of the telangiectatic vessels is recommended, if lipid exudates progress toward the fovea

In Group 1B a focal photocoagulation of the telangiectatic vessels is only very rarely recommended in case of progressive visual loss

In Group 2A a focal photocoagulation can be suggested in Stage 1 – 3 in case of progressive visual loss. In case of subretinal neovascularization a photodynamic therapy or photocoagulation may be therapeutic options

In Group 2B, 3A and 3B no therapy is recommend in the literature

Due to the different pathogenesis the therapy of IJRT is group and stage dependent.

In Group 1A IJRT photocoagulation of the telangiectatic vessels is effective by reducing the foveolar exudation and improves or preserves the visual function. Early treatment is recommended when visual loss combined with progression of lipid exudates toward the fovea is detected [1, 3, 4, 5, 6].

Focal photocoagulation of the telangiectatic capillaries is recommended only in a minority of Group 1B patients, because often no progression and visual loss will develop [5].

Different studies have shown that there are no proven therapeutic options available to treat Group 2A IJRT [5]. Many studies investigated photocoagulation as a possible treatment in Stage 1 – 3, but there were no significant differences between treated and untreated eyes with telangiectasis in Stage 1 – 3 [11] (Table 22.1.3). Photocoagulation leads to a stable visual acuity, but there has been no evidence that untreated eyes develop a decrease in visual acuity more rapidly. Probably intravitreal triamcinolone acetonide may reduce the intraretinal edema for a decent period [9]. Photodynamic therapy in bilateral parafoveal telangiectasis without subretinal neovascularization is not beneficial because there is no

improvement of either the visual acuity or the macula edema [2]. In Stage 4 no therapy is recommended in the literature. In Stage 5 photocoagulation, photodynamic therapy or anecortave acetate could be therapeutic options, but only case reports or small series of treated patients with photocoagulation and consecutive stability of visual acuity have been reported

(Table 22.1.3). Photodynamic therapy in combina- III 22 tion with intravitreal triamcinolone acetonide has

also demonstrated a regression of subfoveal neovascular membrane and improvement in visual acuity [13].

In the literature no therapy is recommended for treatment of the occlusive telangiectasis of Group 3A and 3B IJRT.

References

1.Chopdar A (1978) Retinal telangiectasis in adults: fluorescein angiographic findings and treatment by argon laser. Br J Ophthalmol 62:243 – 250

2.De Lahitte GD, Cohen SY, Gaudric A (2004) Lack of apparent short-term benefit of photodynamic therapy in bilateral, acquired, parafoveal telangiectasis without subretinal neovascularization. Am J Ophthalmol 138:892 – 894

3.Gass JD (1968) A fluorescein angiographic study of macular dysfunction secondary to retinal vascular disease. V. Retinal telangiectasis. Arch Ophthalmol 80:592 – 605

4.Gass JD (1987) Stereoscopic atlas of macular diseases: diagnosis and treatment, 3rd edn. Mosby, St. Louis, pp 390 – 396

5.Gass JD, Blodi BA (1993) Idiopathic juxtafoveolar retinal telangiectasis. Update of classification and follow-up study. Ophthalmology 100:1536 – 1546

6.Gass JD, Oyakawa RT (1982) Idiopathic juxtafoveolar retinal telangiectasis. Arch Ophthalmol 100:769 – 780

7.Grand MG, Kaine J, Fulling K, Atkinson J, Dowton SB, Farber M, Craver J, Rice K (1988) Cerebroretinal vasculopathy. A new hereditary syndrome. Ophthalmology 95:649 – 659

8.Green WR, Quigley HA, de la CZ, Cohen B (1980) Parafoveal retinal telangiectasis. Light and electron microscopy studies. Trans Ophthalmol Soc U K 100:162 – 170

9.Martinez JA (2003) Intravitreal triamcinolone acetonide for bilateral acquired parafoveal telangiectasis. Arch Ophthalmol 121:1658 – 1659

10.Moisseiev J, Lewis H, Bartov E, Fine SL, Murphy RP (1990) Superficial retinal refractile deposits in juxtafoveal telangiectasis. Am J Ophthalmol 109:604 – 605

11.Park DW, Schatz H, McDonald HR, Johnson RN (1997) Grid laser photocoagulation for macular edema in bilateral juxtafoveal telangiectasis. Ophthalmology 104:1838 – 1846

Core Messages

Wyburn-Mason syndrome is a rare congenital oculocerebral syndrome consisting of retinal arteriovenous anastomoses and ipsilateral cerebral arteriovenous vascular abnormalities. It may, but does not always, also involve nevi and vascular malformations in the skin and mucosa in the area of the trigeminal nerve. WyburnMason syndrome is one of the phacomatoses There is a wide range of arteriovenous anastomoses in the retina, from small uncomplicated short-circuits to hugely dilated ones. The arteries and veins fuse with each other directly, without a capillary plexus

Small anastomoses are usually monosymptomatic; large ones are associated with cerebral anomalies in up to 90 % of cases. Loss of vision is often the initial symptom, usually caused by central nervous damage

Treatment for retinal arteriovenous anastomoses is not required, or not possible. Spontaneous remissions occur

An interdisciplinary examination including neurological and neurosurgical consultation, with computed tomography (CT) or magnetic resonance imaging (MRI), is absolutely imperative, at least for patients with larger anastomoses

22.2.1 History

The first description of arteriovenous anastomoses dates back to the end of the 19th century [26, 33, 39, 52, 54]. In 1915, in Graefe-Saemisch’s Handbuch der gesamten Augenkrankheiten, Leber presented the first comprehensive presentation of the condition [35]. The article includes highly instructive sketches of the cases reported by Schleich and Seydel. Further review articles were published by Weve in 1923 [67], Rentz in 1925 [48], and Junius in 1933 [29].

A 1903 report by Kreutz [33] is of particular interest, as it describes for the first time the combination of retinal arteriovenous anastomoses with arteriovenous vascular anomalies in the orbit. One of the earliest descriptions of cerebral arteriovenous vascular anomalies (cirsoid aneurysm) was provided by Heitmüller in 1904 [27]. From the mid-1920s onward, there were increasing numbers of reports on the simultaneous occurrence of retinal and cerebral arteriovenous anastomoses [10, 18, 34, 42, 43]. The first comprehensive presentation of the syndrome was published by P. Bonnet, J. Dechaume, and E. Blanc in 1937 with the title “L’an´evrysme cirsoide de la r´etine (an´evrysme rac´emeux), ses r´elations avec l´an´evrysme cirsoide de la face et avec l´an´evrysme cirsoide du cerveau” [8]. In 1943 followed an article by

R. Wyburn-Mason: “Arteriovenous aneurysm of mid-brain and retina, facial naevi and mental changes” [69]. This finally defined the disease as a clinical entity consisting of retinal and intracerebral vascular abnormalities. The complex of symptoms was later assigned to the phacomatoses [20, 21, 36].

It is perhaps of general biogenetic interest that arteriovenous anastomoses also occur in other primates. In rhesus monkeys, the typical vascular anomalies were observed ophthalmoscopically, imaged angiographically, and analyzed histologically by Bellhorn et al. in 1972 [5] and Horiuchi et al. in 1976 [28].

The nomenclature has changed over the course of time. Early authors speak of “aneurysma arteriovenosum” [39, 52] or “varix aneurysmaticus [54]. On the basis of Virchow’s nomenclature, Leber in 1915 [35] recommended the term “aneurysma racemosum” or “aneurysma racemosum arteriovenosum”

(Latin: racemus = bunch or cluster of grapes). Bonnet et al. [8] chose the term “aneurysma cirsoides” (Greek: kirsoeides = varicose). From the 1930s onwards, as familiarity with cerebral pathology increased, the condition was more and more frequently classified among hemangiomas and thus tumors [47]. Archer et al. use the term “arteriovenous communications” [1]. The terms “arteriove-

nous anastomoses” and “arteriovenous shunts” are used synonymously.

„Neuroretino-angiomatosis Syndrom,” “angiome enc´ephalo-r´etino-faciale,” “syndrome an´evrismatique r´etino-optico-mesenc´ephalic,” “arteriovenous cerebroretinal aneurysm,” “retino-cephalic vascular malformation” and other localizing and descriptive

22 III terms represent the pattern of symptoms of retinal and cerebral vascular changes. However, it is more frequent for the condition to be named after the authors of the first comprehensive descriptions of it, as “Syndrome de Bonnet, Dechaume et Blanc” or “Wyburn-Mason syndrome” – the term most frequently used in the international literature.

22.2.2 Classification

Arteriovenous anastomoses are congenital vascular malformations (Fig. 22.2.1a). They arise due to disturbances in the maturation process of the retinal vascular system. Individual or multiple short-circu- its of widely varying caliber develop between the arteries and veins in the retina. The surface extension of the malformation is also extremely variable, ranging from the involvement of small sectors to involvement of the entire retina [16, 19, 34, 24, 56, 57, 66].

Archer, Deutman, Ernest and Krill [1] distinguished two forms of arteriovenous anastomoses: firstly, arteriovenous anastomoses in which normal capillaries, or at least one more or less normal capillary plexus, are present between the arteries and veins; and, secondly, arteriovenous anastomoses with a direct transition from arteries to veins, without intermediate capillary or arteriolar links.

The arteriovenous anastomoses that occur in Wyburn-Mason syndrome, either monosymptomatic or as a retinocerebral symptom complex, belong

exclusively to the second category. The artery and vein communicate directly, without any intervening capillary elements. Archer et al. [1] distinguish two more subgroups:

Small and circumscribed arteriovenous anastomoses, completely without retinal complications, or with comparatively few. Vision is usually good. It is exceptional to find this combined with cerebral vascular anomalies (group 2 in Archer et al. [1]). The anastomoses are extremely extensive, immensely complex, and produce severe retinal complications. Cerebral involvement is usually found (group 3 in Archer et al. [1]).

The classification is based on the extreme variability of arteriovenous anastomoses and attempts to take into account the wide differences in the morphological appearance, the occurrence of retinal complications, and the association with cerebral, orbital, and facial vascular malformations.

Other classifications, such as that of Mansour et al. [40], are more detailed. But in view of the small numbers of cases they can only be used with difficulty.

22.2.3 Clinical Features

Arteriovenous anastomoses occur with equal frequency in both sexes. They are usually identified in adolescence, but can already be present in neonates as well. They occur in a strictly unilateral pattern. The few exceptions reported in the literature prove the rule [12, 40]. Smaller and medium-sized anastomoses (group 2 in the Archer classification) may be single or multiple, consisting of solitary channels or with a branching pattern (Fig. 22.2.2a). The location of preference is the central or temporal retina, and they are limited to individual sectors and quadrants.

Individual vascular loops can reach as far as the perifoveal arcades, and sometimes even into the fovea itself (Fig. 22.2.3a). A cilioretinal artery is sometimes incorporated into the arteriovenous vascular loop. The anastomotic vessels can be 60 – 150 μm in diameter.

In severe cases (group 3 in the Archer classification), the anastomoses can develop huge, contorted shapes. The vessels are intertwined and convoluted. They can reach a diameter up to 10 – 12 times that of normal retinal vessels. They usually spread over the entire fundus. The dilated anastomotic vessels may hide the optic disk completely. Occasionally the anastomosis is limited to the disk area [64]. Even extremely dilated vessels do not show any pulsations.

Large vascular diameter creates a high flow rate, so that the venous side of the anastomosis also carries oxygenated blood. The arterial and venous vascular limbs are often only distinguishable angiographically. The intravascular pressure is increased [41, 51], and damage to the vascular walls consequently develops over time. The anastomoses devel-

op white-yellowish sheathings and are accompanied by serous exudates, lipid deposits, and reactive pigmentary hyperplasia (Fig. 22.2.4a, b). Bleeding can also occur [22, 41]. Large anastomoses cause extensive alterations in the surrounding capillary bed. The hyperoxia in the anastomoses is probably the reason why practically no reactive vascular proliferations develop or secondary glaucoma arises. There have only been two or three cases reported in the literature in which the patients with extremely massive retinal damage developed rubeosis iridis with glaucoma [7, 17]. Some of the complications appear to be due to central or branch vein occlusion or spontaneous thrombosis of the anastomosis (see p. 539). The observation reported by Tilanus et al. [60] is exceptional. They noted several bleeding macroaneurysms developing in the course of an arteriovenous vascular loop.

Loss of vision is rare in cases of simple anastomoses, and only arises when the macula or optic nerve is involved. In the severe forms, by contrast, visual field defects and loss of vision of varying degree, ranging

up to complete blindness, usually develop. The functional deficits are usually due to the cerebral or orbital vascular changes. Overall, two-thirds of patients with anastomoses have functional defects (Meyer, cited in [57]).

22.2.4 Fluorescein Angiography

Fluorescein imaging (Figs. 22.2.1b, 22.2.2b, 22.2.3b) reveals that the anastomoses have a substantial influence on neighboring vascular areas and in some cases can also affect the entire vascular system of the retina. A particularly impressive finding on the fluorescein angiogram, however, is the extremely high blood flow velocity in the arteriovenous anastomoses. The larger the vascular diameter, the higher the flow rate.

The increase in blood flow is evidently the cause of severe damage to the surrounding capillary bed. Initially, broad avascular zones are observed along the anastomoses. Later, the capillaries are occluded even in distant areas of the retina. Large avascular zones can arise. The capillaries are obliterated either due to the hyperoxia or as a result of a steal effect. In con-

trast to other retinal vascular diseases, the avascular areas do not stimulate neovascularization. If damage to the vascular walls develops over time, the angiogram shows dye leakage from the dilated vessels, which can even extend to complete collapse of the blood-retina barrier.

22.2.5 Differential Diagnosis

Arteriovenous anastomoses do not give rise to any substantial differential-diagnostic difficulties and are relatively easy to distinguish from other vascular diseases in the retina.

The anastomoses most resemble the dilated nutritive vessels of retinal capillary hemangiomas in von Hippel-Lindau’s disease. In the latter conditions, however, arterial and venous elements are separated by the capillaries of the hemangioma. Fluorescein angiography is helpful to detect small or hidden angiomas.

Congenital retinal macrovessels are obviously dilated vessels that lie between the optic disk and

the central retina, with end branches that extend beyond the horizontal raphe. The arteriovenous transition takes place via the capillary plexus.

Primary congenital tortuosity of the retinal vessels is usually bilateral. Here again, the arteriovenous connection is via the capillary plexus.

Acquired anastomoses, as in Coats’ disease. Eales disease, after venous occlusion, in Takayasu’s syndrome [59] and other forms of retinal angiopathy, are not difficult to identify on the basis of the underlying disease.

22.2.6 Natural Course

Arteriovenous anastomoses are regarded as being static and unchanging [9, 48, 49]. However, spontaneous remissions have been noted during long-term observations [6, 8, 9, 15, 25, 41, 45, 51, 66, 68]. The anastomotic vessels are transformed into ischemic, whitish bands or regress to such an extent that they are no longer distinguishable from their surroundings. Arteriovenous anastomoses represent a highpressure system, with the corresponding hemodynamic stress on the vascular structures [51]. Sclerosis and thickening of the vascular walls develop. Increasing turbulence in the blood flow arises. The hemodynamic disturbances are intensified by mechanical compression of the vascular lumen within the optic nerve, at the optic disk, or at vascular crossings. Ultimately, the process leads to thrombosis and vascular obliteration.

There is evidence that the anastomosis formation itself is a dynamic process. Effron et al. [17] reported increasing size and increasing dilatation. In other cases, it has been observed that new arteriovenous connections develop after spontaneous occlusion of an anastomosis [45, 65, 66] (Fig. 22.2.4a–d). These develop from branches of the primary anastomosis, or at other points in the retina, including even previously uninvolved vessels. Augsburger et al. [2] reported obliteration of an anastomosis after ligation of the internal carotid artery and observed a new anastomosis arising subsequently.

22.2.7 Histopathology

The histological appearance of arteriovenous anastomoses is that of hypertrophic, normally matured blood vessels [70]. The vessels extend into all layers of the retina. Larger anastomoses bulge into the vitreous cavity and may also come into contact externally with Bruch’s membrane. Segments of the vascular walls may be either thinned or thickened. Gigantically dilated arteries and veins are histopathologically barely distinguishable from one another. The vascular walls are fibrotic and interspersed with

hyaline and lipid infiltrations. The surrounding retina shows cystoid changes and loss of ganglia cells and axons [14, 22, 34].

22.2.8 Systemic Involvement

Retinal arteriovenous anastomoses may be associat-

ed with analogous vascular malformations in the III 22 orbit and central nervous system, and more rarely

with mucous and cutaneous vascular changes in the face [8, 69]. Cerebral malformations and retinal anastomoses are strictly ipsilateral in location and mainly appear to involve the complete optic tract as far as the optic cortex [16]. They only occur bilaterally very rarely [44]. In the cerebral region as well, the spectrum of arteriovenous aneurysms and angiomas ranges from small and medium-sized to extensive and voluminous malformations. Neurological symptoms due to compression and bleeding include corticospinal tract signs, cranial nerve pareses, epileptic fits, strabismus, visual field defects and visual loss ranging up to complete blindness ([8, 10, 13, 32, 38, 50, 53, 63, 69], etc.). Some 30 % of Wyburn-Mason patients have homonymous hemianopia [19]. The more severe the changes in the retina are, the more likely it is that there will be cerebral involvement. Central aneurysms and angiomas are found in 90 % of patients with huge, contorted anastomoses (group 3 in the Archer classification). According to Bech and Jensen [4], 17 % of patients with retinal arteriovenous anastomoses have cerebral changes; this figure, however, dates from the period before computed tomography (CT) and magnetic resonance imaging (MRI). Wyburn-Mason originally reported an incidence of 81 %. Conversely, he found retinal changes in 70 % of patients with mesencephalic aneurysms.

Aneurysmal and angiomatous vascular malformations in the orbit can occur either in isolation or in various combinations with ocular and cerebral aneurysms and angiomas [30, 31, 33, 46, 50, 63, 69]. These are usually also located unilaterally, ipsilateral to the changes in the eye or brain. Bilateral findings are rare here as well [44]. Vascular anomalies in the orbit may lead to exophthalmos, with or without pulsation, vascular murmur, papilledema, optic atrophy, and loss of vision.

There are vascular malformations in the area of the maxilla, mandible, and pterygoid fossa, with epistaxis and hemorrhage [11, 32]. In the area of the face, telangiectasias and soft subcutaneous vascular tumors or nevi are found [8, 10]. These changes appear to be limited to the innervation area of the first trigeminal branch. In 1990, Patel and Gupta [44] reported a neonate with cerebral arteriovenous malformations combined with vascular malformations

in both orbits and bilateral extensive cutaneous nevi in the innervation area of the trigeminal nerve.

22.2.9 Genetics

Congenital arteriovenous anastomoses are vascular malformations that are due to developmental distur- 22 III bances in the early gestational period [46, 61, 62]. The embryological causes of the disturbances are unknown. A familial incidence has occasionally been discussed. However, MacDonald et al. clearly demonstrated in 1997 that Wyburn-Mason syndrome

does not have genetic causes [37].

22.2.10 Therapy

Arteriovenous anastomoses do not initially have any therapeutic implications for the ophthalmologist. Basically, laser coagulation of smaller arteriovenous anastomoses is unnecessary, while coagulation of larger vessels is unpromising and hazardous. A few reports describing coagulation attempts do not alter this statement. To reduce the blood flow, Stucci and Höpping [58] attempted to narrow the lumen of dilated anastomoses by xenon arc photocoagulation burns. Baurmann et al. [3] attempted to arrest bleeding from damaged vessels, and Tilanus et al. [60] were able to stop hemorrhages from secondary aneurysms by laser photocoagulation. Shah et al. [55] recommended regular check-up examinations for eyes with secondary venous occlusion to allow timely coagulation in case of reactive neovascularizations. In general, however, laser coagulation is limited to individual selected cases with a specific pattern of symptoms.

It should be noted once again that the majority of patients with Wyburn-Mason syndrome are initially seen by ophthalmologists. One of the ophthalmologist’s fundamental duties is therefore to refer the patient for neurological and neurosurgical work-up. This includes CT and MRI, as well as cerebral angiography when appropriate.

Patients with smaller anastomoses (group 2 in the Archer classification) and with no serious suspicion of cerebral involvement need not necessarily undergo invasive diagnostic measures [19].

In patients with extensive arteriovenous anastomoses (group 3 in the Archer classification), which are practically always associated with cerebral processes, comprehensive neurological and radiological diagnosis is absolutely imperative.

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