**2.5 Clinical presentations**

#### **2.5.1 Branch retinal artery occlusion**

In BRVO, only a branch of the retinal venous system is affected. Risk factors for BRVO are listed above. The occlusion in BRVO occurs most commonly at an arteriovenous junction, where the artery and vein share a common adventitial sheath. Venous thrombosis results from arterial wall thickening, which compresses the adjacent vein.

Vision loss is the most common presentation in patients with BRVO. The vision loss is usually sudden, unilateral and painless. This loss can be variable and is dependent upon the amount of macular and retinal involvement. If there is macular involvement, vision is usually affected. Alternatively, if the BRVO is small or located in the peripheral retina, the patient may still have 6/6 vision. Metamorphopsia or distorted vision and a visual field defect may also occur.

Ocular fundus examination often reveals a wedge shaped area of retinal abnormality. The superior temporal retinal arcade is affected in 60% of all cases of BRVO due to the higher number of arteriovenous crossings in this area. The veins distal to the occlusion may demonstrate dilatation and tortuosity, while there may be some venous attenuation proximal to the occlusion. Retinal haemorrhages are a notable feature of BRVO. Superficial retinal haemorrhages appear flame shaped, while deep haemorrhages are characteristically referred to as dot-blot haemorrhages (Figure 5). Very rarely, there may be subhyaloid or vitreous haemorrhages. Other ocular fundus features of BRVO include retinal oedema and cotton-wool spots, which is also a sign of retinal ischaemia.

Fig. 4. Optical coherence tomography scan of the macular in an eye with retinal vein occlusion. Nasal to temporal (N→T) cross-sectional image of the macula demonstrates the presence of significant macula oedema and associated intra-retinal cysts (white arrow).

from arterial wall thickening, which compresses the adjacent vein.

cotton-wool spots, which is also a sign of retinal ischaemia.

In BRVO, only a branch of the retinal venous system is affected. Risk factors for BRVO are listed above. The occlusion in BRVO occurs most commonly at an arteriovenous junction, where the artery and vein share a common adventitial sheath. Venous thrombosis results

Vision loss is the most common presentation in patients with BRVO. The vision loss is usually sudden, unilateral and painless. This loss can be variable and is dependent upon the amount of macular and retinal involvement. If there is macular involvement, vision is usually affected. Alternatively, if the BRVO is small or located in the peripheral retina, the patient may still have 6/6 vision. Metamorphopsia or distorted vision and a visual field

Ocular fundus examination often reveals a wedge shaped area of retinal abnormality. The superior temporal retinal arcade is affected in 60% of all cases of BRVO due to the higher number of arteriovenous crossings in this area. The veins distal to the occlusion may demonstrate dilatation and tortuosity, while there may be some venous attenuation proximal to the occlusion. Retinal haemorrhages are a notable feature of BRVO. Superficial retinal haemorrhages appear flame shaped, while deep haemorrhages are characteristically referred to as dot-blot haemorrhages (Figure 5). Very rarely, there may be subhyaloid or vitreous haemorrhages. Other ocular fundus features of BRVO include retinal oedema and

**2.5 Clinical presentations** 

defect may also occur.

**2.5.1 Branch retinal artery occlusion** 

Fig. 5. Fundus photograph of an inferior branch retinal vein occlusion in the left eye showing different types of retinal haemorrhages. Superficial retinal haemorrhages (S) are flame shaped; deep retinal haemorrhages (D) are dot-blot.

#### **2.5.2 Central retinal vein occlusion**

Similar to BRVO, the most common presentation in patients with CRVO is vision loss. The vision loss is sudden, unilateral, painless and usually profound, in the range of counting fingers.

Examination reveals a relative afferent Pupillary defect. While fundus examination demonstrates tortuosity and dilatation of all the branches of the central retinal vein as well as superficial (flame-shaped) and deep (dot-blot) intraretinal haemorrhages. Cotton wool spots and oedema of the optic disc or macular may be present.

Fluorescein angiography is the ocular investigation of choice in patients with suspected CRVO. The general features of CRVO using fluorescein angiography include delayed arteriovenous transit time and blockage by retinal haemorrhages. Fluorescein angiography is vital in distinguishing between non-ischaemic and ischaemic CRVO (Figure 3). There is effective capillary perfusion in non-ischaemic CRVO and capillary non-perfusion in ischaemic CRVO.

#### **2.6 Treatment**

Treatment involves management of the systemic risk factors and local treatment for complications of RVO, such as macular oedema and neovascularisation.

With regard to systemic treatment of RVO, there is no strong evidence in current literature for the use of anticoagulant, fibrinolytic agents or antiplatelet agents. Best practice management involves treating the atherosclerotic risk factors, such as hypertension and hyperlipidaemia.

Local treatment for BRVO differs from the treatment of CRVO. For BRVO, the Branch Vein Occlusion Study (BVOS) suggested that retinal haemorrhages and any macular oedema should be observed for 3 months to allow for spontaneous resolution. After 3 months, if the macular oedema is still present, treatment may be warranted. The BVOS recommends grid laser photocoagulation for the treatment of macular oedema (1984). Use of intravitreal anti-VEGF agents, such as ranibizumab, has been shown to be beneficial (Campochiaro, Heier et

Venous Thrombosis and the Eye 167

CRVO and is characterised by a sudden increase in pain due to a rise in intraocular pressure. The risk factors for its development include poor visual acuity, extensive retinal haemorrhage and significant retinal non-perfusion on fluorescein angiography (1997). In patients with less than 10 optic disc areas of retinal non-perfusion, less than 10% of eyes will develop rubeosis iridis. However, if there are more than 30 optic disc areas of retinal nonperfusion, the risk of rubeosis iridis increases significantly. The prognosis of ischaemic CRVO is usually poor due to the development of macular ischaemia or neovascularization. RVO in one eye increases the risk for the development of a RVO in the contralateral eye. This occurs in 9-15% of patients within 5 years of the initial diagnosis of RVO (Hayreh, Zimmerman et al. 1994). Unfortunately, at present there is no treatment available to prevent the development of RVO in the contralateral eye or a recurrence of RVO in the same eye. RVO is also associated with an increased likelihood of death from cerebral vascular and

cardiovascular causes (Tsaloumas, Kirwan et al. 2000; Cugati, Wang et al. 2007).

conditions that predispose to a venous thrombosis, such as thrombophilias.

**3.1 Ophthalmic manifestations of cerebral venous sinus thrombosis** 

fossa vein and the deep cerebral venous system (straight sinus).

Systemic venous thrombosis can cause significant ocular symptoms and signs. Evidence suggests that ocular manifestation in systemic thrombosis increases the risk of cerebral events (Asherson, Khamashta et al. 1989) and ultimately, this impacts the prognosis of the patient. It is, therefore, important to consider ocular features of systemic venous thrombosis, but, it is also equally important that clinicians are aware of the ophthalmic features of systemic

It is clearly impossible to consider all systemic conditions that cause a predisposition to venous thrombosis in this chapter. Therefore, here we will consider two systemic conditions that have important ocular manifestations. Firstly, we will discuss cerebral venous sinus thrombosis and to highlight the ocular features of systemic thrombosis. Then we will examine anti-phospholipid syndrome to review the ocular features of a condition that is a

Cerebral venous sinus thrombosis (CVT) is a condition that results from thrombosis and occlusion of the cerebral veins or dural sinus. This thrombosis causes increased venous pressure and subsequently results in impairment of cerebrospinal fluid (CSF) absorption and increased intracranial pressure (ICP). Regardless of the site, all CVT can cause raised ICP. The common sites for CVT include the cavernous sinus, sigmoid sinus, transverse sinus and sagittal sinus. Rarer sites of thrombosis include the lateral sinus, jugular vein, posterior

Impaired CSF absorption is associated with increased intracranial pressure, while increased capillary pressure disrupts the blood-brain barrier, decreases capillary perfusion and results in capillary damage. This increased capillary pressure ultimately causes vasogenic and cytotoxic oedema as well as cerebral parenchyma lesions (Gotoh, Ohmoto et al. 1993;

CVT is a rare thrombotic occurrence with an incidence of 3-4 per million (Stam 2005). It is more common in females compared to males with a ratio of 3:1 (Ferro, Canhao et al. 2004),

and is also more common in children compared to adults (Agnelli and Verso 2008).

**3. Ophthalmic manifestations of systemic thrombosis** 

risk factor for venous thrombosis.

Yoshikawa, Abe et al. 2002).

**3.1.1 Prevalence** 

al. 2010). There has been some conflicting evidence regarding the use of triamcinolone acetonide in the treatment of macular oedema in BRVO. Jonas et al. found it to beneficial in the treatment of macular oedema (Jonas, Akkoyun et al. 2005), however Scott et al found intravitreal triamcinolone to be no more effective than grid laser photocoagulation and was even associated with a higher risk of adverse events (Scott, Ip et al. 2009). Dexamethasone has been shown to be beneficial, but there is also a risk that dexamethasone can increase intraocular pressure (Haller, Bandello et al. 2010). Optic disc or retinal neovascularisation requires treatment with pan-retinal (scatter) laser photocoagulation in the distribution of occluded vein (1986; Hayreh, Rubenstein et al. 1993). Prophylactic PRP is not indicated to prevent neovascularisation, as the harmful effects of PRP outweigh the benefits in prophylaxis (1984).

Treatment of CRVO should initially involve determining the type of CRVO present. In patients with non-ischaemic CRVO, the macular oedema can be treated with intravitreal steroids such as triamcinolone acetonide (Ip, Scott et al. 2009) or dexamethasone (Haller, Bandello et al. 2010). Treatment with intravitreal anti-VEGF agents, such as Ranibizumab has been shown to be useful in a double-blinded randomized controlled trial (Brown, Campochiaro et al. 2010). Laser photocoagulation for the treatment of macular oedema in CRVO has not been found to be beneficial (1995). In ischaemic CRVO, the presence of anterior chamber angle neovascularisation or rubeosis iridis should immediately be treated with laser pan-retinal photocoagulation (1995). Prophylactic PRP is not warranted and PRP is only indicated once anterior segment neovascularisation becomes apparent. Unproven treatments include the use of Ticlopidine, Troxerutin and Epoprostenol.

#### **2.7 Prognosis**

#### Prognosis is dependent upon the type of RVO.

BRVO tends to have a better prognosis, but it may take 6 to 12 months to resolve. The affected area is commonly replaced by hard exudates and venous sheathing. Collateral vessels can form between the affected and unaffected retina. If there are improvements in visual acuity and the development of efficient collaterals, the prognosis is often good. The prognosis is poor if there are complications associated with the BRVO such as the development of chronic macular oedema, which occurs in 57% of temporal branch occlusions. Another serious complication is neovascularisation, which can lead to recurrent vitreous and pre-retinal haemorrhages as well as retinal detachments and ultimately adversely affects the visual outcome.

Similarly, the acute stage of CRVO takes approximately 6 to 12 months to resolve. Disc collaterals between the retinal and choroidal vascular network usually form during this time. The final visual acuity is dependent upon the initial visual acuity following RVO (1997), with better visual outcomes in those with good initial visual acuity. The complications and prognoses are different for the different types of CRVO. The complications of non-ischaemic CRVO include chronic macular oedema and conversion to ischaemic CRVO. The prognosis of non-ischaemic CRVO is often good, unless a conversion to ischaemic CRVO occurs. One-third of non-ischaemic CRVO convert to become ischemic by 3 years, with half of these conversions occurring within the first 4 months following the CRVO (1997). Ischaemic CRVO may be complicated by neovascularization, which occurs in 5% of eyes. When rubeosis iridis develops, it results in neovascular glaucoma, due to the neovascular membrane occluding the trabecular meshwork where the aqueous fluid drains out of the eye. Neovascular glaucoma commonly occurs within 3 months of the onset of the

al. 2010). There has been some conflicting evidence regarding the use of triamcinolone acetonide in the treatment of macular oedema in BRVO. Jonas et al. found it to beneficial in the treatment of macular oedema (Jonas, Akkoyun et al. 2005), however Scott et al found intravitreal triamcinolone to be no more effective than grid laser photocoagulation and was even associated with a higher risk of adverse events (Scott, Ip et al. 2009). Dexamethasone has been shown to be beneficial, but there is also a risk that dexamethasone can increase intraocular pressure (Haller, Bandello et al. 2010). Optic disc or retinal neovascularisation requires treatment with pan-retinal (scatter) laser photocoagulation in the distribution of occluded vein (1986; Hayreh, Rubenstein et al. 1993). Prophylactic PRP is not indicated to prevent neovascularisation, as the harmful effects of PRP outweigh the benefits in

Treatment of CRVO should initially involve determining the type of CRVO present. In patients with non-ischaemic CRVO, the macular oedema can be treated with intravitreal steroids such as triamcinolone acetonide (Ip, Scott et al. 2009) or dexamethasone (Haller, Bandello et al. 2010). Treatment with intravitreal anti-VEGF agents, such as Ranibizumab has been shown to be useful in a double-blinded randomized controlled trial (Brown, Campochiaro et al. 2010). Laser photocoagulation for the treatment of macular oedema in CRVO has not been found to be beneficial (1995). In ischaemic CRVO, the presence of anterior chamber angle neovascularisation or rubeosis iridis should immediately be treated with laser pan-retinal photocoagulation (1995). Prophylactic PRP is not warranted and PRP is only indicated once anterior segment neovascularisation becomes apparent. Unproven

BRVO tends to have a better prognosis, but it may take 6 to 12 months to resolve. The affected area is commonly replaced by hard exudates and venous sheathing. Collateral vessels can form between the affected and unaffected retina. If there are improvements in visual acuity and the development of efficient collaterals, the prognosis is often good. The prognosis is poor if there are complications associated with the BRVO such as the development of chronic macular oedema, which occurs in 57% of temporal branch occlusions. Another serious complication is neovascularisation, which can lead to recurrent vitreous and pre-retinal haemorrhages as well as retinal detachments and ultimately

Similarly, the acute stage of CRVO takes approximately 6 to 12 months to resolve. Disc collaterals between the retinal and choroidal vascular network usually form during this time. The final visual acuity is dependent upon the initial visual acuity following RVO (1997), with better visual outcomes in those with good initial visual acuity. The complications and prognoses are different for the different types of CRVO. The complications of non-ischaemic CRVO include chronic macular oedema and conversion to ischaemic CRVO. The prognosis of non-ischaemic CRVO is often good, unless a conversion to ischaemic CRVO occurs. One-third of non-ischaemic CRVO convert to become ischemic by 3 years, with half of these conversions occurring within the first 4 months following the CRVO (1997). Ischaemic CRVO may be complicated by neovascularization, which occurs in 5% of eyes. When rubeosis iridis develops, it results in neovascular glaucoma, due to the neovascular membrane occluding the trabecular meshwork where the aqueous fluid drains out of the eye. Neovascular glaucoma commonly occurs within 3 months of the onset of the

treatments include the use of Ticlopidine, Troxerutin and Epoprostenol.

Prognosis is dependent upon the type of RVO.

adversely affects the visual outcome.

prophylaxis (1984).

**2.7 Prognosis** 

CRVO and is characterised by a sudden increase in pain due to a rise in intraocular pressure. The risk factors for its development include poor visual acuity, extensive retinal haemorrhage and significant retinal non-perfusion on fluorescein angiography (1997). In patients with less than 10 optic disc areas of retinal non-perfusion, less than 10% of eyes will develop rubeosis iridis. However, if there are more than 30 optic disc areas of retinal nonperfusion, the risk of rubeosis iridis increases significantly. The prognosis of ischaemic CRVO is usually poor due to the development of macular ischaemia or neovascularization. RVO in one eye increases the risk for the development of a RVO in the contralateral eye. This occurs in 9-15% of patients within 5 years of the initial diagnosis of RVO (Hayreh, Zimmerman et al. 1994). Unfortunately, at present there is no treatment available to prevent the development of RVO in the contralateral eye or a recurrence of RVO in the same eye. RVO is also associated with an increased likelihood of death from cerebral vascular and

cardiovascular causes (Tsaloumas, Kirwan et al. 2000; Cugati, Wang et al. 2007).
