In recent years, the understanding of development and progression of glaucomatous optic nerve damage has changed. There is accumulating evidence for a multifactorial pathogenesis of glaucomatous optic neuropathy. Besides an elevated intraocular pressure, there is special emphasis on cardiovascular and haematological risk factors and also on genetic and immunological aspects ^1-3. Recently, Kremmer et al ⁴ found elevated levels of a subgroup of antiphospholipid antibodies in patients with normal tension glaucoma (NTG) compared to patients with primary open angle glaucoma (POAG) and age matched healthy controls. These findings may be interpreted as a sign for a generalised disease.

Although the pathogenesis of progressive sensorineural hearing loss (PSHL) often remains unclear some research activities have focused on the role of autoantibodies against antigens in the inner ear. This concept was introduced by Reinhardt ⁵ and is supported by the fact that hearing loss is associated with different autoimmune diseases such as Cogan syndrome, rheumatoid arthritis, Sjögren syndrome, and Behçet's disease ^6-8.

Hisashi et al ⁹ were the first to demonstrate an association between progressive sensorineural hearing loss in patients with lupus erythematosus and antiphospholipid antibodies. They proposed that in patients with lupus erythematosus these antibodies are causative for thrombosis of the labyrinth leading to progressive sensorineural hearing loss.

Phospholipids are constituents of all membranes and are divided in many subspecies such as phosphatidylserine (APSA). It has been theorised that APSA can be generated by any pathological conditions shifting phosphatidylserine from the inner membrane leaflets to the external membrane leaflets of cells ¹⁰. This shift is the beginning of the apoptotic mechanism and leads to cell destruction and ischemia in endothelial cells ¹¹. This permits a number of phospholipid binding proteins to be presented to the immune system in unique antigenic conformations, giving rise to antibody production.
The aim of this study was to investigate a possible coincidence between NTG, PSHL and the association to APSA.

This prospective study was conducted in South Shouna Hospital during the period between 2003 - 2005. 26 patients attending ophthalmology clinic and diagnosed as normal tension glaucoma (typical optic disc and visual field damage and intraocular pressure below 21 mmHg) were referred to the ENT clinic. Ophthalmologic examination included Snellen's visual acuity testing, anterior segment examination via slit lamp, and posterior segment examination after mydriasis via indirect ophthalmoscope, Goldmann's applanation tonometry to measure intraocular pressure, and visual field assessment via Goldmann's perimeter. In ENT clinic, audiograms, stapedial thresholds and otoacoustic emissions were obtained.

Hearing loss was compared to previously established hearing thresholds in patients with normal hearing and presbyacusis. Presbyacusis was defined as hearing loss of high frequencies in elderly people whereas PSHL was age independent. Serological testing of antiphospholipids antibodies were done for all patients. APSA level of >15 U/ml was considered elevated.

The mean age of patients with NTG was 64.8 years; 15 females and 9 males (Table 1). 18 normal tension glaucoma patients (75%) had sensorineural hearing loss: 10 (41.7%) were pathological and 8 (33.3%) had presbyacusis (Table 2). Elevated antiphospholipids antibodies concentrations were more frequent in patients with normal tension glaucoma and hearing loss compared with normal tension glaucoma patients with normacusis (Table 3) or other types of glaucoma. Among the other types of glaucoma, primary open angle glaucoma was seen in 10 patients and pseudoexfoliation glaucoma in 8 patients.

In the past few years it was shown that autoimmune phenomena are associated with hearing loss. Namedrop et al ¹² found a correlation between sudden hearing loss and systemic lupus erythematosus. Moreover, progressive hearing loss may be associated with increased autoantibody levels: Tomato et al ⁷ were able to demonstrate an increased concentration of IgG anticardiolipin antibodies in 30% of patients with Sjögren's syndrome and sensorineural hearing loss.

In principle, two different entities of autoantibodies were found to be associated with glaucoma: autoantibodies against specific proteins of the retina and the optic nerve ^13-14 or against more common antigens ^15-16 such as extractable nuclear antigens, small heat shock proteins and serum antibodies against neuron specific enolase.

Interestingly, Shokoohi et al ¹⁷ reported on elevated antiphospholipid antibodies in NTG and POAG patients. APSA are a subgroup of antiphospholipid antibodies which are one of the hallmarks of the antiphospholipid syndrome. APSA may be important because of their binding specificity to phosphatidylserine molecules which become accessible during apoptosis, which in turn may lead to local thrombosis.

Interestingly, a higher prevalence of antiphosphatidylserine antibodies was seen in NTG patients with hearing loss in comparison to NTG patients with normacusis. This finding suggests a similar pathological pathway as a sign for generalised disease. The increase of the same antibody entity in patients suffering from both, NTG and PSHL may indicate an association with similar systemic autoimmune processes.

Patients with presbyacusis or PSHL showed a small difference compared to patients with normacusis, suggesting that some patients with presbyacusis also have elevated antiphosphatidylserine antibodies. This is not surprising because antiphospholipid antibodies increase with age. The smaller occurrence of hearing loss compared to normal tension glaucoma might be explained by the fact that the terminal vessel pathway in the eye seems to be more vulnerable to blood supply disturbances or patients are more sensitive to the sense of vision than to hearing. It has been shown that apoptosis can be induced by antiphosphatidylserine antibodies, which results in occlusion of small vessels by thromboemboli and finally leads to disturbance of the microcirculation in the inner ear and eye.

Pseudoexfoliative glaucoma was associated with PSHL but with almost similar APSA level with normal people of same age group. This may be explained by the fact that Pseudoexfoliation is considered as a systemic disease affecting many organs in the body ¹⁸.

The association between hearing loss, normal tension glaucoma and antiphospholipid antibody indicates that they are part of autoimmune systemic process. Based on these findings all patients with NTG or significant hearing loss and elevated levels of antibodies against phosphatidylserine should have further ophthalmological or otological work up

Table 1. Patient distribution according to age and sex

Table 2. Progressive sensorineural hearing loss in different types of glaucoma

Table 3. Antiphospholipid antibodies in different types of glaucoma in patients with PHSL and in normacusis

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