The Case Report
A 58-year old white male, presented with sudden, painless onset of blurred central vision in his right eye, two days prior to the visit, with no other associated symptoms. He described the vision in his right eye as ‘smudgy’, as if someone had used a khoki pen at the centre of his vision but the peripheral vision was good. The left eye was unaffected. The patient thought his vision would clear spontaneously, hence the delay in seeking assistance. His spectacles were less than a year old and he had not used them since collecting them, as he was “unable to see well through them”. The lack of follow up on spectacles was attributed to the fact that he had recently relocated from a different province for work purposes.
He had LASIK approximately 18 years ago. He was currently on Pharmapress for hypertension. At the time of presentation, his blood pressure was poorly managed, averaging 160/110 mmHg , and he was undergoing a stressful period. He had no other medical conditions.
Unaided Visual Acuity (VA):
RE: light perception centrally (with head turn and use of peripheral vision it was 6/24)
LE: 6/9
Distance Spectacle Prescription:
RE: no improvement in central VA with lenses
LE: Plano/-1.00×76 (6/6)
IOP (non-contact tonometry) RE and LE: 10mmHg
Fundus examination revealed retinal haemorrhages and exudate formation around the inferior macular region of the right eye. (Image 1).
The patient was referred for specialist care, and branch retinal vein occlusion with secondary macula oedema in the right eye was diagnosed (Image 2), Optical Coherence Tomography (OCT) results).
The OCT scan (image 2) reveals significant macular oedema. The patient is profoundly needle-phobic, and is of the belief that non-invasive techniques should be attempted before use of invasive procedures. He did not opt for intravitreal treatment, and decided to strictly manage his hypertension in the hope of resolving the BRVO.
He returned five months later, reporting that his blood pressure was well controlled, averaging at 120/80 mmHg. He was still on Pharmapress for his hypertension. Several investigations were completed by his family doctor, and no other health conditions were found. The central vision in his right eye had not improved and he wanted to update his pectacles as his left eye was feeling some strain.
The OCT image (image 3) shows slight resolution of macular oedema and some photoreceptor loss. Refraction revealed no improvement in central VA of the right eye. He chose to have single vision distance spectacles. Follow-up examination with the ophthalmologist was scheduled.
Branch Retinal Vein Occlusion
Retinal vein occlusion (RVO) is the second most common retinal vascular disorder after diabetic retinopathy. There are two main types of RVO:
- central retinal vein occlusion
- branch retinal vein occlusion
Branch Retinal Vein Occlusion (BRVO), the more common type of RVO, is a venous occlusion at any branch of the central retinal vein, and may be described as:
- Major BRVO when one of the major branch retinal veins is occluded
- Macular BRVO when a venule within the macula is occluded.
BRVO is further classified into perfused (non-ischemic) or non-perfused (ischemic), with the latter being greater than five disc diameters of non-perfusion on fluorescein angiography (FA). The Beaver Dam Eye Study revealed the fifteen-year cumulative incidences of CRVO and BRVO as 0.5% and 1.80%, respectively.
There is a sharing of the adventitial sheath by the arteriole and venule at an arteriovenous crossing point. Sclerosis of the arterioles at the arteriovenous crossing causes narrowing of the lumens of the adjacent venules. These narrowed venules have to change their course at the arteriovenous crossing, with subsequent turbulent blood flow causing chronic damage to the venous endothelial cells, leading to venule endothelial cell proliferation and thrombosis. Once venous occlusion has occurred, an increase in venous and capillary pressure with stagnation of blood flow ensues, resulting in retinal hypoxia. This in turn, results in damage to the capillary endothelial cells, retinal haemorrhages and release of mediators such as vasoactive endothelial growth factor (VEGF).
BRVO causes a unilateral, painless decrease in VA. Fundus examination may reveal clinical features of flame-shaped haemorrhages, dot and blot haemorrhages, cotton wool spots, hard exudates, retinal oedema, and dilated tortuous veins. Patients with Major BRVO can be asymptomatic or present with a peripheral visual field defect corresponding to the retinal quadrant that is affected, while those with Macular BRVO, present with a central visual field defect and normal peripheral vision. The field defects can become absolute scotomas in long-standing occlusions.
Macular oedema is the main cause of vision loss in BRVO. Reduced blood flow to the macula results in increased upregulation of endothelin-1, inflammatory cytokines, and VEGF, which increases endothelial permeability, leading to macular oedema and exudates. Macular oedema can also be further divided into perfused and non-perfused, with the latter having a better VA prognosis.
Possible factors for visual loss include macular oedema, haemorrhage, ischemia and foveal haemorrhage, vitreous haemorrhage, epi-retinal membrane and retinal detachment. It is possible that retinal oedema and haemorrhages may resolve spontaneously in time, with some recovery of vision. Development of collateral vessels in BRVO have a positive effect on visual prognosis. Current treatment options focus on treating the consequences of BRVO, that is, macular oedema, vitreous haemorrhage and traction retinal detachment from neovascularisation.
Systemic risk factors for BRVOs include hypertension, diabetes mellitus, atherosclerosis, hyperlipidaemia, haematological disorders and cardiovascular disease. Ocular risk factors include glaucoma, hyperopia and ocular hypertension. Other risk factors include advancing age, history of smoking, migraine headaches, and use of barbiturate sedatives or chloroquine.
Diagnosis can be confirmed with fundus examination, fluorescein angiography (FA) and OCT scans. A detailed patient history is essential, especially regarding known risk-factors.
In patients with BRVO, FA provides information on the extent of non-perfusion, macular ischemia, macular oedema and leakage. The presence of intra-retinal haemorrhages may affect the quality of FA image. Unlike FA, OCT images are minimally affected by intra-retinal haemorrhages and a further advantage of OCT is that it allows for quick, non-invasive analysis of the macula. Typical findings of BRVO on OCT are cystoid macular oedema, intra-retinal hyper-reflectivity from haemorrhages, shadowing from oedema and haemorrhages, and possibly sub-retinal fluid. A high reflectance band in the para-foveal area, called the ellipsoid zone, corresponds to the photoreceptor layer and is significant with respect to VA prognosis. An absence or interruption of this zone indicates photoreceptor cell death or disruption, resulting in poor visual outcome.
Management
Assessment of all systemic risk factors, including hypertension, diabetes mellitus, atherosclerosis, hyperlipidaemia, and haematological disorders, and appropriate treatment of these conditions, if present, is warranted.
Current management options concentrate on treating the consequences of BRVO, that is, macular oedema, vitreous haemorrhage or traction retinal detachment from neovascularisation, rather than the underlying aetiology of the BRVO.
Observation without invasive treatment may indicated if VA on presentation is 6/9 or better, or marginally worse than 6/9 but improving with time. Some studies have shown that with an initial VA of 6/15 or better, the visual prognosis may be good even without treatment, while some cases of BRVO with presenting VA of 6/60 or worse may have poorer visual prognosis. Final VA is dependent on the location and extent of occlusion, the integrity of arterial perfusion to the affected sector, and development of collateral circulation. Even though the macular oedema may resolve over a period of up to twenty-four months, the final VA may not improve due to irreversible retinal damage.
Options available for treatment of BRVO with poor VA on presentation include:
1. Laser treatment
Laser photocoagulation may improve VA in BRVO, provided that there is adequate macular perfusion and the presenting VA is approximately 6/12. Techniques that can be used include macula grid photocoagulation, peripheral scatter photocoagulation for treatment of retinal and/or disc neovascularisation, arterial crimping for treatment of macular oedema, and micro pulse laser.
a) Macular Grid Laser Photocoagulation
This is a recommended treatment to reduce macular oedema secondary to BRVO in the period of 3 – 6 months after onset. According to the Branch Vein Occlusion Study Group, only those patients with VA of 6/12 or less showed a significant visual benefit compared with the untreated control group, provided there is good central macular perfusion on FA. Collateral vessels should not be treated. This used to be the gold standard treatment until newer treatment modalities, such as intravitreal steroids and anti-VEGF agents, showed to be more effective than laser in this condition.
b) Scatter Photocoagulation>
A significant reduction in the development of retinal neovascularisation and vitreous haemorrhage has been reported by the Branch Vein Occlusion Study Group with use of this technique. Using sectoral scatter photocoagulation, treated eyes without neovascularisation developed significantly less neovascularisation during follow up, and treated eyes with neovascularisation, developed significantly less vitreous haemorrhage. Sectoral scatter photocoagulation should be performed as soon as neovascularisation is detected.
c) Arteriolar Constriction
Called the “crimping technique,” this involves placing coagulations using argon laser along the arteriole. This reduces the inflow into the occluded area and allows for better drainage of the macular oedema. It is suggested that arteriolar constriction along with grid pattern laser photocoagulation may be more effective for resolving macular oedema in patients with BRVO.
The use of conventional laser photocoagulation results in a visible whitening of the retina due to thermal damage of the retinal pigment epithelium and the inner retina. Besides the positive visual outcome, this treatment can lead to unwanted side effects such as visual field defects, epi-retinal fibrosis, and choroidal neovascularisation in the area of the laser scar.
d) Micro pulse laser
In conventional continuous-wave mode, a single laser pulse delivers the pre-set laser energy, whereas in the micro pulse mode, a series of repetitive short laser pulses is delivered. Subthreshold micro pulse laser has a slower onset of action, but may be as effective as conventional laser photocoagulation for macular oedema secondary to BRVO. A further advantage of micro pulse laser is that it does not cause thermal retinal damage as there is a decrease in diffusion of heat into surrounding tissues and therefore scarring can be prevented. This is essential if treatment close to the fovea is required.
2. Intravitreal application of steroids
a) Intravitreal triamcinolone
In a preservative-free preparation, this has been used in treatment of macular oedema secondary to BRVO, with results similar to that of laser photocoagulation. Treatment provides only moderate, temporary improvement in VA and there may be need for repeat injections.
b) Intravitreal dexamethasone implant
This may be used alone or in conjunction with laser, and may be an alternative when patients with chronic macular oedema are non-responsive to repeated anti-VEGF therapies. It has shown better VA improvement compared to VA results from observation alone. The treatment can be repeated after 4 – 6 months.
There are adverse effects associated with the use of intravitreal steroids, including an increase in intraocular pressure and a high rate of cataract formation.
3. Intravitreal anti-VEGF agents
This is currently the widely accepted treatment for macular oedema secondary to BRVO. It potentially improves VA more significantly than laser alone and the treatment can commence immediately. Intravitreal bevacizumab treatment has produced a reduction in retinal thickness and an increase in VA as soon as one day after commencement of treatment. However, it does not resolve macular oedema completely and repeated injections are necessary, with no defined endpoint for the repeat injections. Further indications for use of anti-VEGF treatment include: retinal neovascularisation, rubeosis iridis, and neovascular glaucoma.
Common adverse events associated with use of anti-VEGF treatment are conjunctival hyperaemia and subconjunctival haemorrhage at the site of injection.
Combining intravitreal injections with laser may allow a reduction in the frequency of injections, but the optimal regimen has yet to be defined.
Conclusion
The management of BRVO requires a practical approach involving a collaboration between the relevant health care practitioners, including the ophthalmologist, other physicians, and general practitioner. Assessment of risk-factors is essential, and appropriate treatment plans should be developed. Cases that do not require early intervention should be reviewed after three months and then at 3 – 6 monthly intervals for up to two years. This is primarily to detect neovascularisation.
Acknowledgements:
OCT images used with kind permission of Dr Matt Young.
Fundus photograph used with kind permission of Mr Jurgen Tolksdorf.
References
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