Ординатура / Офтальмология / Английские материалы / Retinal Vascular Disease_Joussen, Gardner, Kirchhof_2007

always at AV crossings [86] where there is either pressure on the vein or a thickened wall due to arterial disease or endothelial proliferation, or both. A triggering mechanism at the site of occlusion might set off a rheological vicious circle, the decrease in flow causing an increase in blood viscosity [200] fol-

21 III lowed by a further decrease in flow.

It was demonstrated that more eyes with BRVO develop partial vitreous separation than control eyes [212]. Thus, the vitreous may also play a role in compressing susceptible AV crossings as evidenced by studies demonstrating that eyes with decreased axial length and hyperopia are at increased risk for BRVO because of the higher likelihood of vitreomacular attachment at AV crossings [14, 165]. Interestingly, BRVO has not been reported in the literature in any eye following vitrectomy.

Dilated capillaries and microaneurysms are found in the area of BRVO

Cotton wool spots may be present indicating ischemia

The nearer the occlusion occurs to the optic disk, the greater the extent of the affected retina and the more serious the complications

Depending on the site of occlusion cystoid macular edema may be present

Macular BRVO may show only subtle features, such as microaneurysms in a limited sector

Due to their typical ophthalmoscopic features retinal vein occlusions are easily diagnosed (Fig. 21.3.6a–d). The first ophthalmoscopic signs are fine retinal hemorrhages at the AV crossing site. Distal from the crossing site the vein appears dilated, congested and tortuous. Retinal edema in the involved area is usually present. The involved retina demonstrates variable degrees of scattered superficial and deep retinal hemorrhages which respect the horizontal midline. Superficial hemorrhages are located in the nerve

b

a

c

Fig. 21.3.7. Macular BRVO with a an intense cotton wool spot formation (arrow). b Early and c late phase FLA highlights the blockage at the site of cotton wool spots (arrowheads) and cystoid macular edema (arrow). d OCT (scan, see a) illustrates the cystoid changes (asterisk)

*

d

Retinal vein thrombosis causes increased venous pressure and may lead to retinal capillary decompensation with macular edema, which is the most frequent cause of loss of vision in BRVO. At the macula, edema is clinically recognized by a thickening of the macular retina that is often accompanied by cystoid spaces (Fig. 21.3.8a–d). Microvascular abnormalities of BRVO include dilated capillaries and microaneurysms that develop within the area of

the vein occlusion. Chronic leakage from these abnormal vessels can contribute to macular edema and cause the deposition of lipid exudates in the retina (Fig. 21.3.9a–c). Large capillary or venous macroaneurysms may develop within the territory of the BRVO as well [250]. Serous retinal detachment with massive macular hard exudates has been described as a rare complication of BRVO (Fig. 21.3.10a, b) [229].

21.3.4.2 Late Findings and Complications

Essentials

Occluded, sheathed retinal venules in the affected area

Chronic leakage leading to chronic cystoid 21 III macular edema and lipid exudate deposi-

tion

Collateral vessel formation at the edge of the affected area mostly located temporal to the fovea draining into the uninvolved quadrant

Retinal neovascularizations (NVEs) develop in one-third of patients with major BRVO

NVEs occur mostly at the border of perfused and nonperfused retina; neovascularization at the disk (NVD) is rare

A significant risk for neovascularization exists when the area of capillary nonperfusion exceeds 5 disk diameters

Neovascularization of the iris is extremely rare

Complications of neovascularization include vitreous hemorrhage and fibrovascular membranes with consecutive tractional retinal detachment

Visually relevant late complications are epiretinal membranes, hard exudates, chronic cystoid macular edema, retinal pigmentary dispersion, subretinal fibrosis and macular hole formation

a

Older BRVOs are characterized by occluded and sheathed retinal venules in the affected sector (Fig. 21.3.11). Weeks to months after the onset of BRVO, collateral vessel formation can be observed characteristically located at the edge of the involved area. Typical collaterals are usually small tortuous venous channels that cross the horizontal raphe mostly temporal to the fovea and drain into the venous circulation of the uninvolved quadrant (Fig. 21.3.12a, b). They may be difficult to distinguish

Fig. 21.3.11. Occluded and sheathed retinal venules in a longstanding BRVO affecting the superotemporal quadrant of the left eye. Neovascularization is present (arrow)

b

from retinal neovascularizations. These collaterals may pass from the territory of the occlusion to a point proximal to the site of occlusion or to an uninvolved vein. They may take the form of a vein to vein anastomosis, bypassing the occluded segment and then exiting through the central retinal vein. Reversal of blood flow toward the arterial system can also occur in response to the elevated venous pressure [192], although systemic hypertension can prevent this release mechanism from occurring [20]. Alternatively, arteriovenous shunts that bypass the capillary bed may occur at the AV crossing site [232], whereas in some instances unrelieved venous pressure can result in rupture of the vein wall [214].

The risk of complications can be attributed to the location of the BRVO, the extent and severity of the damage, and the adequacy of compensatory mechanisms. Retinal neovascularization may occur at the border of perfused and nonperfused retina (Fig. 21.3.13a–c) but can rarely occur away from the territory of the BRVO [76]. Neovascularization of the disk is much less common, and when it occurs, it tends to be concurrent with retinal neovascularization. A significant risk for the development of retinal neovascularization exists when the area of capillary nonperfusion exceeds 5 disk diameters (see Fig. 21.3.16) [29]. In the ischemic type of BRVO the risk for neovascularization is 36 %, whereas it is 22 % overall. Hayreh et al. reported a 28.8 % incidence of retinal neovascularization following major BRVO.

c

Studies demonstrated that the majority of untreated eyes with retinal neovascularization will develop vitreous hemorrhage [27, 29, 98, 218]. In contrast to CRVO neovascularization of the iris is extremely rare. In a study on ocular neovascularization including 264 eyes with BRVO, no neovascular glaucoma was observed [109].

In advanced stages, preretinal hemorrhage (Fig. 21.3.14a–c) and vitreous hemorrhage, and more rarely fibrovascular membranes with consecutive tractional retinal detachment (Fig. 21.3.15), may develop. Rhegmatogenous retinal detachment is a rare complication of BRVO, but when breaks occur they tend to be located posterior to the equator and result from traction exerted by fibrovascular prolif-

21 III

a

*

b

*

*

*

c*

Fig. 21.3.14. a BRVO with secondary neovascularization, consecutive preretinal hemorrhage involving the macula, retinal edema, lipid exudates and sheathed venules. b Central and c peripheral FLA show extensive capillary nonperfusion (asterisks) and neovascularization (arrows)

*

Fig. 21.3.15. A fibrovascular epiretinal membrane along the inferior vessel arcade (arrow) appearing inactive after scatter LC (asterisk) but still exerting retinal traction

eration or secondary to ischemic retinal degeneration with hole formation [210, 211]. Vitreous hemorrhages occur in approximately 7 – 20 % of patients with BRVO [151]. Furthermore, less severe but still visually relevant complications in later stages include macular pucker, chronic cystoid macular edema, retinal pigmentary dispersion, subretinal scarring, macular hole and atrophy of inner retinal layers. Permanent and vision-limiting RPE changes can develop from long-standing edema. Rarely, exudative retinal detachment can develop within the affected area and is usually associated with ischemia [99].

21.3.5Clinical Evaluation

and Diagnostic Methods

21.3.5.1 Visual Function and Perimetry

Essentials

Visual acuity (VA) may be unaffected to severely impaired depending on the localization of the BRVO, the severity of macular edema and the extent of capillary bed nonperfusion

Tiny occlusions can be visually significant if the fovea is affected

Although vision may be acutely reduced, 50 – 60 % of patients may achieve 20/40 VA at the end of 1 year

VA alone may be misleading in evaluating the visual function and visual field testing may be more valuable

The visual impact of a BRVO is related to the site and size of the occlusion, but even very tiny occlusions can be visually significant if the fovea is affected [123]. Visual field defects or visual loss are reasons to consult the ophthalmologist. VA is reduced in BRVO; it is because the macula has been affected by intraretinal hemorrhages, edema or ischemia. Later, other complications such as vitreous hemorrhage or retinal detachment may also impair vision. However, VA alone may be misleading in evaluating the visual function in patients with BRVO. VA increase on fol- low-up does not necessarily reflect a genuine visual improvement, since the patient learns by experience to fixate eccentrically [109]. Therefore, Hayreh estimates the information provided by the visual fields, plotted with the Goldman perimeter, an indispensable tool that is found to be most valuable in evaluation and management of retinal vein occlusions [109].

21.3.5.2 Angiographic Features

Essentials

Angiographic findings in BRVO reflect changes in the permeability, caliber, and patency of retinal vessels

Fluorescein angiography (FLA) helps to distinguish leakage without capillary nonperfusion from leakage with capillary nonperfusion

Macular edema associated with ischemia may or may not be associated with fluorescein leakage

An intact perifoveal capillary perfusion is the prerequisite for macular grid laser photocoagulation

FLA maps out the extent of ischemia assisting in the detection of patients at higher risk of neovascularization and those requiring closer follow-up examinations

A peripheral FLA may be helpful to detect the whole extent of the avascular area

FLA helps to distinguish collateral vessel formation (which do not leak) from retinal neovascularization

At later stages, the correct diagnosis of BRVO can often only be established with the help of FLA

Angiographic findings in BRVO reflect changes in the permeability, caliber, and patency of retinal vessels. Venous filling in the area of the occlusion is delayed relative to the unaffected retina and often the fluorescein column is narrowed at the site of occlusion [47]. A small area of early hyperfluorescence may be observed just proximal to the occlusion site.

FLA helps to distinguish leakage without capillary III 21 nonperfusion (Fig. 21.3.9a–c) from leakage with cap-

illary nonperfusion (Fig. 21.3.16a–c). Macular edema associated with good capillary perfusion is always associated with fluorescein leakage on the fluorescein angiogram since the edema is of the vasogenic type, with leakage of the fluorescein molecule occurring through a break in the blood-retinal barrier. Macular edema associated with macular ischemia may or may not be associated with fluorescein leakage. This has therapeutic consequences: an intact perifoveal capillary perfusion is the prerequisite for macular grid laser coagulation. Retinal hemorrhages block fluorescence and sometimes make a distinct evaluation of the capillary bed impossible (Fig. 21.3.17). For the management of acute BRVO in patients with a vision of 20/40 or worse, the BRVO Study group recommends FLA evaluation for macular edema versus macular nonperfusion, and if necessary to wait for sufficient clearing of retinal hemorrhages to allow a high quality FLA for an adequate treatment decision [28, 235]. Furthermore, FLA maps out the extent of ischemia assisting in the detection of patients at higher risk of neovascularization and those requiring closer follow-up exami-

Objective documentation of macular edema is most readily obtained by fluorescein angiography (FLA) since most (but not all) occurrences of macular edema are associated with a disruption in the blood-ret- inal barrier at the level of the retinal capillaries.

a

Fig. 21.3.16. a A patient with a long-standing HCRVO affecting the superior quadrants.

Fig. 21.3.17. Intense retinal hemorrhages (arrow) in acute macular BRVO prevent an angiographic evaluation of the capillary bed

Particularly, at later stages, after reabsorption of the hemorrhages, the correct diagnosis of BRVO can often only be established with the help of FLA. nations. As such, a peripheral angiography may be helpful to detect the whole extent of the avascular area. Moreover, FLA helps to distinguish collateral vessel formation from retinal neovascularization at the edge of the affected area. In contrast to neovascularizations, shunt vessels do not leak (see Figs. 21.3.12, 21.3.13). Additional typical angiographic

findings of BRVO are vascular abnormalities including capillary dilatation, microaneurysms and retinal edema.

21.3.5.3 Optical Coherence Tomography

Essentials

OCT is helpful in determining the presence of macular edema, the foveal thickness and cystoid changes, but delivers only twodimensional morphologic information

OCT is able to demonstrate vitreofoveal adhesions

OCT is fast, noninvasive and has become an indispensable tool for follow-up examinations

Optical coherence tomography (OCT) has become an extremely important and sensitive tool with which to assess the extent of macular edema in patients with BRVO and their response to treatment. A typical cross-sectional OCT image of macular edema associated with BRVO shows intraretinal cystic spaces delineating exactly the uninvolved and the affected area (see Fig. 21.3.7d). Serous detachment can be distinguished from intraretinal and subretinal fluid accumulation and is thereby influencing therapeutic strategies markedly. Moreover, OCT is advantageous in the exact evaluation of the vitreoretinal interface visualizing vitreofoveal adhesions, macular thinning, incomplete or full thickness rup-

tured cysts. It was demonstrated recently that foveal retinal thickness measured by OCT in patients with BRVO correlated with visual acuity and multifocal electroretinograms from the central retinal area [118]. Since OCT is less invasive and faster than FLA, it has become an indispensable tool for follow-up examinations. Often OCT demonstrates striking resolution of macular edema after treatment (see Fig. 21.3.23).

21.3.5.4General Medical Examination and Laboratory Parameters

Essentials

Clinical evaluation should include a detailed medical history with special emphasis on the presence of vascular risk factors

A general medical examination should determine whether hypertension, diabetes, and hyperlipidemia might be present and should include a cardiovascular assessment

Laboratory tests should include standard hematologic blood cell count, erythrocyte sedimentation rate, standard coagulation tests, plasma viscosity, erythrocyte aggregation, fibrinogen level, immunoglobulins including serum protein electrophoresis, TSH, serum cholesterol – and triglyceride levels, blood glucose, and creatinine

Older patients with concurrent significant vascular diseases should not be screened for hemostatic defects

If myeloma is suspected, Bence Jones urine proteins should be determined

Only younger patients (50 years) or patients with recurrent CRVO/BRVO should undergo a large scale screening for the presence of thrombophilic disorders (see Sect. 3.7.3)

An expensive complete workup in each and every BRVO patient is unwarranted

Clinical evaluation should include a detailed history with special emphasis on the presence of vascular risk factors and laboratory test results. It is important to obtain a detailed medical history covering any current drug therapy. Current opinions indicate that patients with a BRVO should be offered a laboratory risk assessment. But with our present knowledge there is no justifiable reason for a complete hemostasiological investigation like that offered to patients with spontaneous major venous thromboembolism.

The general medical examination should include a complete cardiovascular assessment. Appropriate investigations should be carried out to determine

whether hypertension, diabetes, and hyperlipidemia might be present. Laboratory tests should include standard hematologic blood cell count and erythrocyte sedimentation rate, standard coagulation tests, plasma viscosity, erythrocyte aggregation, fibrinogen level, serum protein electrophoresis, serum cholesterol and triglyceride levels, blood glucose, and

creatinine. Autoimmunity as a cause of thrombosis III 21 deserves particular attention especially in patients

with recurrent BRVO. In this case, a test for the APC resistance phenomenon may be also considered, but this seems most relevant in patients younger than 50 years of age. Many patients with inherited heterozygous thrombophilic disorders do not develop thromboembolic events until the 2nd, 3rd or 4th decade. Scat et al. recommended the test for APC resistance only in younger patients and patients with recurrent thrombosis [209]. A further programme in these patients might include screening for hyperhomocysteinemia and such autoimmune phenomena that are known to play an important role in thrombosis, like an anticardiolipin antibody test and investigation for lupus anticoagulant. Older patients with concurrent significant vascular diseases such as diabetes, hypertension, or diffuse atherosclerosis should not be screened for hemostatic defects. Previous studies [37, 91, 171, 222] have clearly shown that evaluating elderly patients with retinal vein occlusions for the presence of antiphospholipid antibodies, and deficiencies of natural anticoagulants was not of much benefit. Therefore, it is advisable that only young patients should undergo a large scale screening for the presence of thrombophilic disorders. All tests should be standardized or samples processed centrally to avoid confusion brought about by interlaboratory variances.

An expensive complete workup in each BRVO patient is unwarranted. A routine, inexpensive hematologic evaluation is usually sufficient [109].

21.3.6 Natural Course

Essentials

The natural history of BRVO depends on the type of occlusion, the size and location of the affected area and on whether there is associated cystoid macular edema (CME), macular nonperfusion, retinal neovascularization and vitreous hemorrhage

Reduced baseline VA, older age and the extent of initial retinal ischemia were correlated strongly with poor visual outcome and with the development of retinal ischemia