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Familial thrombophilia and normal tension glaucoma
  2. M J MENAGE,
  3. B A McVERRY
  1. Leeds Teaching Hospitals NHS Trust, Leeds, UK
  1. obackhouse{at}

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Editor,—The aetiology of normal tension glaucoma (NTG) is still debatable. Abnormal blood flow, systemic hypotension, abnormal blood coagulability, and other factors associated with cerebrovascular disease may have a causative role in NTG.A study was designed to look at the prevalence of familial thrombophilia in cases of NTG.


Seventy two patients were identified from ophthalmological database records with the diagnosis of NTG (defined as intraocular pressure <21 mm Hg, open drainage angle on gonioscopy, absence of any secondary cause for a glaucomatous optic neuropathy, and typical optic disc cupping which correlates with the visual field loss). Strict criteria were used for entry into the study. Patients with NTG had to be under the age of 70 years with normal computerised tomography and normal day time intraocular pressure phasing. Forty five patients did not fulfil these criteria and so were excluded. Twenty seven patients formed the study group. None of these patients were on any medication which would be expected to have altered the values of the prothrombotic factors measured. The control group comprised 90 blood donors used by the regional thrombophilia laboratory as their control values of thrombophilic markers. The control group had an equal male:female ratio, an age range of 18–60 years, and no donor was on any medication or suffering from a medical illness. This gave a good control prevalence of the prothrombotic factors tested for in the study which are not altered by age variation. If any abnormality was found a repeat screen was performed to confirm the thrombophilic state. Blood for rheological factors (full blood count, plasma viscosity, lipid levels, glucose and liver function tests) and thrombophilic markers (protein S, protein C, factor V Leiden mutation, prothrombin G20210A allele, antiphospholipid antibodies, and hyperhomocysteinaemia) was taken for investigation. Informed consent was obtained and ethical approval had been given.

The study group was made up of 16 females and 11 males (ratio 1.5:1). The mean age of diagnosis was 60 years (range 43–69). Table 1 shows the patient details. Twenty three patients had a normal thrombophilia screen. Two patients had moderate hyperhomocysteinaemia (7% , controls 8% p>0.5), one was heterozygous for the factor V Leiden mutation (4% , controls 4.5% p>0.5) and another had a low titre of antiphospholipid antibodies (4%, controls 3% p>0.5). No patient had the prothrombin G20210A variant.

Table 1

Patient details


In trying to discover the aetiology of NTG, some studies have suggested that these patients may have altered rheology producing a greater tendency to thrombosis. There is also evidence of activation of the coagulation cascade and fibrinolytic pathway but there is no conclusive evidence of a general vascular aetiology in the causation of NTG.

The factor V Leiden mutation is a common hereditary abnormality with a 1–8% prevalence of heterozygous carriers depending on geographic location and accounts for the majority of activated protein C resistance. It is known that familial thrombophilia greatly increases the risk of venous thrombosis but it must be stressed that the most people with the Leiden mutation will not experience a thrombotic event. The prothrombin G20210A variant is another common abnormality with a carrier prevalence of 1–4% being more common in southern Europe and, like the Leiden mutation, rare in people from Asian or African descent. An association of the prothrombin variant and the factor V Leiden mutation with arterial disease has not been demonstrated convincingly and this therefore questions the role of these prothrombotic factors in the causation of ocular conditions suggested, in part, to be due to poor arterial supply. With this in mind, and the non-significant prevalence of factor V Leiden between the patient and control groups, it led us to conclude that the heterozygous state of factor V Leiden seen in patient 23 did not have a causative role in her glaucoma though may have contributed to her deep vein thrombosis.

Retinal artery and vein occlusions have been documented with hyperhomocysteinaemia. A raised homocysteine level has many causes and the haematological and vascular abnormalities associated with hyperhomocysteinaemia lead to a proatherogenic and prothrombotic metabolic environment. Levels can be easily reduced with dietary folic acid supplementation, with or without vitamin B12, but it is unknown if this reduces the risk of vascular disease. It is also unknown if the strong link of hyperhomocysteinaemia and cardiovascular events is actually causal. Both patients in the study with hyperhomocysteinaemia were commenced on folic acid and subsequent levels of homocysteine were in the normal range.

Other hereditary thrombophilic conditions, such as protein C and protein S deficiency, and antiphospholipid antibodies have been reported in association with ocular vascular pathology and a combination of these factors may further increase the risk of hypercoagulability. The low levels of antiphospholipid antibodies, as seen in patient 20, are thought not to be prothrombotic.

It is unlikely that familial thrombophilia plays a significant aetiological part in NTG. A larger study is needed to confirm our findings. On the available evidence, thrombophilia screening in patients with NTG is not indicated.


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