OCULAR FEATURES IN BLOOD DISORDERS

BLOOD DISORDERS IN OPHTHALMOLOGY

Anaemia

Definition

• The anaemias are a common group of disorders affecting the red blood cells,

• characterized by either a decrease in the number of circulating red blood cells or a decrease in the amount of haemoglobin in each cell, or both, that occurs when the equilibrium between blood loss and production are disturbed.( > RBC or > in Hb)

• Retinal changes in anaemia are usually innocuous and rarely of diagnostic importance.

Systemic features

• The symptoms common to all anaemias are fatigue and weakness.

• Patients with iron deficiency anaemia may have pallor, brittle nails, koilonychias, an atrophic tongue and angular stomatitis.

Ocular features

Retinopathy

• Although retinal changes in anaemia are common, they are usually innocuous and rarely of diagnostic importance. 

• The three main findings are haemorrhages, cotton-wool spots and venous tortuosity. 

• Retinal venous tortuosity is related to severity of anaemia. It may occur in isolation or may seen in patients particularly with beta-thalassaemia major. It seems to be related to the reduction in haematocrit and severity of anaemia. 

• Dot/blot and Flamed-shaped hemorrhages and cotton-wool spots may occur in the absence of other haematological abnormalities. but they are more common when anaemia coexists with thrombocytopenia in aplastic anemia. The duration and type of anaemia do not influence the occurrence of these changes..

• Roth's spots - In anaemia the retinal haemorrhages may have white centres (Roth's spots) which are thought to represent a fibrin thrombus occluding a ruptured blood vessel with surrounding haemorrhage. Roth's spots are also seen in infective endocarditis and the leukaemias.

Optic neuropathy

• Patients with severe pernicious anaemia may develop bilateral centrocaecal scotomata due to optic neuropathy.

• Unless treated with vit B12, permanent visual impairment due to optic atrophy may ensue.

• Pernicious anaemia may also cause dementia, peripheral neuropathy and subacute combined degeneration of the spinal cord characterized by posterior and lateral column disease.

Leukaemias  

Definition  

The leukaemias are a group of neoplastic disorders characterized by abnormal proliferation of
white blood cells.  (The leukaemias are malignancies of the haematopoietic stem cells characterized by abnormal proliferation of white blood cells.) 

Acute leukaemias are characterized by replacement of bone marrow with very immature
(blast) cells.  
Chronic leukaemias are associated, at least initially, with well-differentiated (mature)
leucocytes and occur almost exclusively in adults.

Systemic features 

Acute leukaemias  

• The acute leukaemias typically present with anaemia, haemorrhage and infection, as well as with infiltration of the lymph nodes, spleen and liver.  
• Acute lymphocytic leukaemia typically affects children. 90% of cases respond to treatment  and with appropriate chemotherapy the cure rate is about 70%.  
• Acute myelocytic leukaemia occurs more frequently in adults and has a much worse prognosis. It is curable in 30% of those under the age of 60 years 

Chronic leukaemias  

• Chronic leukaemias typically affect the elderly and the presentation is usually more vague and gradual (e.g. fatigue, weight loss, infection). 
• In some cases the diagnosis is made by chance. 
• Chemotherapy often does not prolong survival although it may improve the quality of life.
• Chronic lymphocytic Leukaemia has a very chronic course and many patients die from an unrelated cause.
• Chronic myelocytic Leukaemia has a progressive clinical course and a less favourable prognosis.

Ocular features  

• Ocular involvement is more common in the acute than in chronic leukaemias. 
• Virtually any or all of the ocular structures may be involved.  
• It is,however, important to distinguish primary leukaemic infiltration, which is  rare, from the more common
• secondary changes such as those due to associated anaemia, thrombocytopenia, hyperviscosity, opportunistic infections and the side effects of treatment (e.g. steroid-induced cataracts). 
• It is due to   
  -primary leukemic infiltration, which is  rare, or
  -the more common secondary changes such as those due to associated anaemia, thrombocytopenia, hyperviscosity, opportunistic infections and the side effects of treatment (e.g. steroid-induced cataracts). 

Anterior segment 

Anterior segment disease is seen most frequently in patients with acute lymphocytic leukaemia. It is rare in patients with acute myeloid leukaemia an very rare in the chronic leukaemias.
The main features are:  

• Iritis and pseudohypopyon - the most common.
• Iris thickening, either diffuse or nodular.
• Spontaneous subconjunctival haemorrhage and 
• hyphema (Spontaneous bleeding into  anterior chamber)   

Orbit  

• Orbital involvement, particularly in children.
  Orbital involvement is more common in acute than in chronic leukaemias, and it occurs more frequently in the lymphocytic then in the myeloid type.  

• Orbital infiltration usually presents with painful proptosis, lid oedema and Chemosis. 

Retinopathy 

Retinal involvement is common and is characterized by the following: 

• Venous tortuosity and dilatation are early changes.

•  Retinal haemorrhages, cotton wool spots and retinal haemorrhages with white centres (Roth spots) occur in acute leukaemias. 

• Flame-shaped haemorrhages are usually located at the posterior pole and Roth's spots may also be present.  

• Cotton-wool spots may be due to leukemic infiltration or associated with anaemia or hyperviscosity.  

• Peripheral retinal neovascularization is an occasional feature of chronic myeloid leukaemia. 

• Choroidal deposits in chronic leukaemia may give rise to a ‘leopard skin’ appearance

Optic neuropathy  

• Optic nerve infiltration may cause swelling and visual loss. 

• Infiltration of the optic nerve typically occurs in children with myeloid leukaemia and, unless promptly treated by radiotherapy, the risk of blindness is very high. 

• Disc involvement is characterized by a fluffy infiltrate associated with variable disc oedema and haemorrhage.  

• It is important to differentiate leukemic optic neuropathy from papilloedema due to raised intracranial pressure secondary to meningeal infiltration.  

Fundus changes in haematological disorders. (A) Retinal haemorrhages, cotton wool spots and Roth spots in acute leukaemia and anaemia associated with thrombocytopenia; (B) peripheral retinal neovascularization in chronic myeloid leukaemia; (C) ‘leopard-skin’ appearance due to choroidal infiltration in chronic leukaemia; (D) retinal haemorrhages, and gross venous dilatation and segmentation in hyperviscosity

Hyperviscosity syndrome  

Definition  

Hyperviscosity syndromes are a diverse group of rare disorders characterized by
increased blood viscosity due to one of the following:  

• Increased number of  RBC in polycythaemia rubra vera and secondary polycythaemia.
• Increased number of white cells WBC in the chronic leukaemias. 
• Abnormal plasma proteins in Waldenstrom's macroglobulinaemia and rarely in multiple myeloma.
• Polycythaemia is caused by neoplastic proliferation of erythrocytes leading to hyperviscosity and increased bone marrow activity; plethora, splenomegaly, pruritus, hypertension, angina, gout, thrombosis and haemorrhage. 
• Waldenström macroglobulinaemia is a malignant lymphoproliferative disorder with monoclonal IgM production that most frequently affects elderly men. It is characterized by fatigue, easy bruising, lymphadenopathy, hepatosplenomegaly, Raynaud phenomenon and peripheral vascular disease 

Ocular features  

Fundus features include retinal haemorrhages and venous dilatation, occasionally retinal vein occlusion...
Retinopathy findings include 

 venous dilatation, segmentation and tortuosity, as well as
 superficial and deep retinal haemorrhages,
 cotton-wool spots, retinal oedema and disc oedema
 retinal vein occlusion
 and conjunctival telangiectasia.

Sickle-cell disease 

Pathogenesis  

Sickling haemoglobinopathies are due to the presence of one, or a combination of, abnormal
haemoglobins which cause the red blood cells to adopt an anomalous shape under conditions
of hypoxia and acidosis.

Because these deformed red blood cells are more rigid than normal cells, they may become
impacted in, and obstruct, small blood vessels and cause tissue ischaemia with a marked
local increase in acidosis and hypoxia, and even more sickling,

Abnormal haemoglobins  

The sickling disorders in which the mutant haemoglobins S and C are inherited as alleles of normal haemoglobin A are of particular importance because of their ocular manifestations. 

These abnormal haemoglobins may occur in combination with normal haemoglobin A or in association with each other as follows:  

 AS (sickle-cell trait) is present in 8% of American Blacks. It is the mildest form and usually requires severe hypoxia or other abnormal conditions to produce sickling. 

 SS or sickle-cell disease or sickle-cell anaemia which is present in 1% of American Blacks. and is caused by a point mutation on the beta-globulin gene. The disease is characterized by severe chronic haemolytic anaemia and periodic potentially fatal, crises due to vaso occlusive disease involving most organs, resulting in liver necrosis, painful crises (largely bone marrow infarcts), abdominal pain, acute chest syndrome and CNS symptoms. Despite the severity of systemic manifestations ocular complications are usually mild 

 SC or sickle-cell C disease which is present in 0.2% of American Blacks. It is characterized by haemolytic anaemia and infarctive crises that are less severe than in SS disease but may be associated with severe retinopathy. 

  SThal or sickle-cell thalassaemia. is characterized by mild anaemia but may be associated with severe retinopathy. 

Systemic features  

 Sickle-cell trait (AS) is the mildest form and usually requires severe hypoxia or other abnormal conditions to produce sickling.  

  SC and SThal are associated with mild anaemia but severe ocular complications. 

 Sickle-cell disease (SS) causes severe systemic complications such as painful crises and severe haemolytic anaemia. 

 Ocular complications, however, are usually mild and asymptomatic. 

Ocular features 
Proliferative sickle retinopathy 

The most severe form of retinopathy occurs in SC and SThal. It can be divided into the  following five stages:

 Stage 1 This is characterized by peripheral arteriolar occlusion. 

 Stage 2 This shows peripheral arteriovenous anastomoses of dilated pre-existing capillary channels.

 Stage 3 Sprouting of new vessels from the anastomoses; these have a ‘sea-fan’ configuration and are usually fed by a single arteriole and drained by a single vein.
About 30–40% of sea-fans involute spontaneously as a result of auto-infarction and appear as greyish fibrovascular lesions. Involution most frequently occurs about 2 years after the development of retinopathy. 

 Stage 4 This is characterized by haemorrhage from the new vessels. The neovascular tufts may continue to proliferate and bleed into the vitreous.

 Stage 5 This is characterized by tractional retinal detachment and extensive fibrovascular proliferation. 

FFA in stage 3 shows filling of sea-fans and peripheral capillary non-perfusion followed byextensive hyperfluorescence due to leakage from new vessels. 

Stage 1 This is characterized by peripheralarteriolar occlusion. 

Stage 2 This shows peripheral arteriovenousanastomoses. 

Stage 3 This is characterized by 'sea-fan'neovascularization from the anastomoses. 

Stage 4 This is characterized by haemorrhagefrom the new vessels. 

Stage 5 This is characterized by tractional retinaldetachment

Treatment 

• Treatment is not required in most cases because new vessels tend to auto-infarct and involute spontaneously without treatment. 
• PRP probably does not alter the natural history 
• Occasionally vitreoretinal surgery may be required for tractional retinal detachment and/or persistent vitreous haemorrhage. 

Non-proliferative retinopathy  

 Asymptomatic lesions are venous tortuosity, areas of peripheral chorioretinal atrophy (black

sunbursts), peripheral pink superficial ('salmon patch') retinal haemorrhages, peripheral

refractive spots consisting of haemosiderin deposits, 'silver-wiring' of peripheral arterioles

and, rarely, angioid streaks.  

  Symptomatic lesions are caused by vascular occlusions. 

Asymptomatic lesions

1. Venous tortuosity is one of the first ocular signs of sickling and is due to peripheral arteriovenous shunts.
2. ‘Silver-wiring’ of arterioles in the peripheral retina which represents previously occluded vessels. 
3. ‘Salmon patches’ are pink, preretinal or superficial intraretinal haemorrhages at the equator, which lie adjacent to arterioles and usually resolve without sequelae.
4. ‘Black sunbursts’ are patches of peripheral RPE hyperplasia
5. Macular depression sign is an oval depression of the bright central macular reflex due to atrophy and thinning of the sensory retina.
6. Peripheral retinal holes and areas of whitening similar to ‘white-without-pressure’ are occasionally seen.

Symptomatic lesions

1. Macular arteriolar occlusion occurs in about 30% of patients
2. Acute CRAO is rare.
3. Retinal vein occlusion is uncommon.
4. Choroidal vascular occlusion may occasionally be seen, particularly in children. 
5. Angioid streaks occur in a minority of patients

Non-retinal manifestations 

 Conjunctival isolated comma or corkscrew shaped vascular segments.

  Ischaemic iris atrophy and occasionally rubeosis.