Introduction

Haemodialysis is an important and by far the commonest treatment for end stage renal failure (ESRF). In the 14th Report of the Malaysian Dialysis and Transplant Registry 2006, approximately 13 600 out of 15 000 patients (91%) with ESRF were undergoing haemodialysis1 (the number being more than 200 000 patients in the United States in 1995)2.

Despite technical advances, haemodialysis is still far from ideal. Patients are exposed to potential complications, such as hypotension, muscle cramps, arrhythmias, bleeding disorders, hypoxia, and anaphylactic reactions.3 Ocular complications include reduced corneal endothelium cell density,4 ischaemic optic neuropathy,5 occipital lobe blindness,6 and endogenous endophthalmitis.7 Changes in intraocular pressure (IOP) during or after haemodialysis have also been widely reported in the literature. However, various studies have shown different and conflicting findings; many indicate that it may increase,8, 9, 10, 11, 12 some indicate that it does not change,13, 14 and some indicate that it even decreases.15, 16

Levy et al17 performed a systematic review in 2005, and concluded that the influence of haemodialysis on IOP was still unclear. They suggested that further studies need to be performed. An extensive literature search has shown that until now, there have not been any published studies of this kind on the Malaysian population.

Materials and methods

Study design

This is a prospective, single centre study on patients undergoing haemodialysis at the University Malaya Medical Centre, Kuala Lumpur. Data collection was performed in December 2007.

Procedure

All patients registered for outpatient haemodialysis at the centre were invited to participate. Informed consent was taken from all participants. After taking a clinical history, ocular examination, including Snellen visual acuity, slit-lamp fundoscopy, applanation tonometry, and gonioscopy, was performed on both eyes. IOP measurements were taken within 30 min before and after haemodialysis. The volume of fluid removed was recorded. Pre- and post-haemodialysis blood samples were collected for osmolarity analysis by freezing-point depression.

IOP was measured (average of two readings) with the patient sitting upright at the slit-lamp microscope, using the same calibrated Goldmann applanation tonometer (Haag-Streit, Switzerland) for the whole period of study. To eliminate the intraobserver bias, one investigator (AS) performed all the measurements. Intradialysis IOP measurements were not recorded. Many studies have shown that IOP changes follow a linear trend with maximal changes occurring at the end of haemodialysis.9, 10, 15

Non-indentation gonioscopy with a Sussman gonioscope (Ocular Instruments, USA) was performed after taking the initial IOP measurement. To eliminate the intraobserver bias, the same investigator (AS) performed all the observations. For this study, the term ‘occludable angle’ was used when the posterior pigmented trabecular meshwork was not visible for 270° of the angle circumference. This arbitrary definition has been used in earlier epidemiological studies to divide subjects into categories of primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG).18

Patients had uniform 4 h, high-flux haemodialysis with total body heparinisation. These sessions started between 0600-0800 hours in the morning. Hollow-fibre cellulose acetate dialysers (Asaki Kasei, Japan) were used. Blood pump speed was between 180–200 ml/min. Dialysate flow rate was 500 ml/min. The dialysate contents were as follows: Na+ 140 mEq/l, K+ 2 mEq/l, Ca2+ 2.5 mEq/l, Mg2+ 1 mEq/l, Cl- 106.5 mEq/l, and glucose 1 g/l.

Exclusions

Patients on antiglaucoma treatment or who have had earlier laser or surgical procedures for it (n=1), or physically unable to be examined at the slit-lamp microscope (n=2) were excluded. Glaucoma patients were those with at least two of these changes—typical glaucomatous visual field defects/typical glaucomatous optic disc features/raised IOP.

Sample size calculation

Before the study, an estimate of the sample size needed was derived using Win Episcope 2.0 (http://www.clive.ed.ac.uk/winepiscope) software. On the basis of the data derived from the study by Tokuyama et al15 (means: 11.9 and 13.6, SD: 2.7, level of confidence: 95%, power: 80%), the minimum sample size needed was 84 eyes.

Statistical analysis

The mean±SD of each parameter for the whole group was calculated. These values were also separately determined in different groups. The significance of the change in IOP after haemodialysis was determined by the Student's t-test (paired samples). The Pearson coefficient test was used to determine the correlation between changes in IOP and that of plasma osmolarity, and the volume of fluid removed. A level of <0.05 was accepted as statistically significant.

Ethical approval

Ethical approval was obtained from the Medical Ethics Committee of the University Malaya Medical Centre before the start of the study. We certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during this research.

Results

This study included 98 eyes from 49 patients (25 men and 24 women, mean age: 54.4±12.5 years, range: 20–84 years) with ESRF. All patients had been undergoing regular maintenance haemodialysis for 4 h three times weekly for 1–192 months (mean duration: 40.7±41.1 months).

Of the ocular disorders found, 16 eyes had proliferative diabetic retinopathy (PDR), 14 eyes had non-PDR (NPDR), 3 eyes had earlier pars plana vitrectomies (PPVs), 16 eyes were pseudophakic, and 13 eyes had cataracts. One eye had a central retinal vein occlusion (CRVO) previously. There were no eyes with angle neovascularisation or pseudoexfoliation.

During haemodialysis, none of the patients had symptoms or signs of acute raised IOP, such as blurring of vision, eye pain, headache, or corneal oedema.

Plasma osmolarity was decreased by −11.6±10.0mOsm/l (P<0.001). The volume of fluid removed was 3.0±0.8 l (P<0.001).

There were 90 eyes in the non-occludable angle group and 8 eyes in the occludable angle group. IOP changes were not significant in the non-occludable angle group, but significant in the occludable angle group (Table 1).

Table 1 IOP change after haemodialysis in the non-occludable and occludable angle groups
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From the non-occludable angle group, we subanalysed the eyes by dividing them into non-operated (n=72) and operated (n=18), as well as diabetic (n=46) and non-diabetic (n=44) groups. Although the results were all non-significant, operated eyes averaged a small increase in IOP, whereas the non-operated, diabetic and non-diabetic eyes had small reductions in IOP (Tables 2 and 3). We could not differentiate between the effects of different procedures, for example, cataract surgery or vitrectomy on the eyes as the vitrectomised eyes also had earlier cataract surgery.

Table 2 IOP change after haemodialysis in the non-operated and operated eyes
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Table 3 IOP change after haemodialysis in the diabetic and non-diabetic groups
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Discussion

In this study, in which 92% of patients did not have occludable angles, there was no increase in IOP following haemodialysis, despite the reduction in plasma osmolarity and fluid volume. It implies that acute reductions in plasma osmolarity or fluid shifts between body compartments are not enough to explain the changes as first reported by Sitprija et al12 in 1964. In that study, they suggested that the fall in plasma osmolarity (as solutes are removed during haemodialysis) results in the formation of a gradient between plasma and ocular tissue. This gradient encourages the movement of water from plasma into the tissue, namely the ciliary bodies, leading to the increased aqueous production and raised IOP.

We postulate that the use of newer and better haemodialysis techniques may be influential on our findings. Firstly, slower haemodialysis may have helped to prevent significant changes in IOP by reducing the rate of change in plasma osmolarity. The findings of significantly raised IOP by Sitprija et al12 were obtained when the rates were −11 mOsm/l/h, but Austin et al11 found no significant changes when the rate was −7.7 mOsm/l/h. In this study, the rate was −2.9 mOsm/l/h. Additionally, although not strictly investigated in this study, all patients underwent high-flux haemodialysis. With this system, haemodialysis membranes allow larger molecules to pass, but not albumin.3 The resulting relative increase in plasma albumin concentration leads to higher colloid osmotic pressures, which draw water out of ocular tissue and into the plasma. As a result, a balance is formed, minimising the tendency for reduced plasma osmolarity to increase IOP.

There was a significant decrease in IOP in patients with occludable angles. This is in contrast to the findings of Tawara et al14 who reported that eyes with obstructed aqueous outflow pathways (including primary angle closure, peripheral anterior synechiae, angle neovascularisation, and ghost cell glaucoma) may develop IOP elevation due to a defective compensatory mechanism of aqueous humour drainage. We believe that our occludable angle eyes did not have any of the other features mentioned above. Additionally, the sample size for this particular group was small, and the decrease in IOP could be the result of a normal diurnal variation.

The state of the eye, whether operated or not, did not produce any significant changes. However, we are suspicious of the average increase in IOP in previously operated eyes, especially considering its small sample size. Yoon et al19 reported that eyes which previously underwent vitrectomies were at risk of IOP elevation due to postoperative aqueous outflow compromise. In their sample of 36 vitrectomised eyes, 55.6% of them had an increase of >4 mmHg during haemodialysis. They suggested monitoring IOP during haemodialysis in these cases.

There were no significant changes in IOP during haemodialysis in both diabetic and non-diabetic eyes. It has been previously reported that high glucose levels in aqueous humour can increase fibronectin and extracellular matrix synthesis in the trabecular meshwork, again leading to aqueous outflow compromise.20 From our findings, we are unable to support that the effect is large enough to have a significant effect on IOP changes during haemodialysis.

This study did not take into account the duration after surgery or the control of diabetes. More accurate angle determination by ultrasound or optical coherence tomography (OCT) was also not performed. These could have assisted in the interpretation of changes.

Conclusion

Haemodialysis does not cause significant changes in IOP in non-glaucomatous and non-occludable angle eyes.