Ocular changes during hemodialysis in patients with end-stage renal disease

CKD stage 5 patients undergoing hemodialysis treatment for at least 3 months at the Blood Purification Center of Ruijin Hospital affiliated with Shanghai Jiao Tong University from February 2014 to October 2014 were enrolled in this study. Hemodialysis was performed 3 times a week, each lasting 3–5 h.

The inclusion criteria were visual acuity over 20/200 as well as Oculus Pentacam® anterior segment analyzer (Oculus Inc., Wetzlar, Germany) results and OCT reports of acceptable quality. The exclusion criteria were a history of surgical or laser-based operations to the eye, other ocular diseases such as corneal scarring, uveitis, macular holes, and other conditions, or a history of renal replacement therapy, including peritoneal dialysis and kidney transplantation.

The hemodialysis group was divided into primary kidney disease (KD), hypertensive KD and diabetic KD (DM-KD) subgroups strictly according to the initial etiology of renal insufficiency. When patients failed to provide reliable supporting materials or when two or more etiologies were suspected, the patients were included in the etiology unknown subgroup. Nineteen healthy people without HD history were set as normal control.

This study adhered to the Declaration of Helsinki and was approved by the institutional review board of Shanghai Ruijin Hospital. Informed consent was obtained from the subjects after verbal and written explanations of the nature and possible consequences of the study were provided.

Blood reports, including urea, creatinine, uric acid, serum electrolytes (Na, K, Ca, P, Mg), parathyroid hormone (PTH), and fasting blood glucose levels, were collected before hemodialysis.

Blood pressure and detailed ophthalmological examinations, including spherical and cylinder powers, BCVA, IOP, dry eye analysis, corneal endothelial measurements, central corneal thickness (CT), anterior chamber depth (ACD), lens measurements, retinal thickness (RT) around the fovea, RNFL thickness, and choroidal thickness (CHT), were performed. BCVA was examined using a standard vision chart, and the logarithmic minimum angle of resolution (logMAR) was recorded. Refractive parameters were measured by a full auto ref-keratometer (Canon, Japan). IOP was measured by non-contact tonometer (NCT) (Canon, Japan). Dry eye syndrome was estimated by the tear break-up time (TBUT) and Schirmer’s I test. Endothelial cell density (ECD), the average endothelial cell size (ECS), and the endothelial cell size variation coefficient (ECSCV) were obtained using a Tomey EM-3000 non-contact specular microscope corneal endothelial cell counter. The CT, ACD and lens thickness (LT) were automatically calculated using a Pentacam® anterior segment analyzer (Oculus Inc., Wetzlar, Germany). The RT and RNFL thickness was measured using Cirrus HD-OCT (Carl Zeiss Meditec, Inc., Dublin CA, United States) under the Macular Cube 512 × 128 mode. The RT was defined as the average thickness of the 6 mm × 6 mm scan. The nine subfields of the RT map were measured separately. The inner, intermediate, and outer rings had radii of 1 mm, 3 mm, and 6 mm, respectively. The average thickness within the inner ring was defined as the central foveal subfield (CSF) thickness [14]. The average CHT was measured in the EDI mode of OCT. The subfoveal, nasal and temporal choroidal thicknesses were each measured 1 mm and 2 mm away from the center of the macula, averaged, and recorded as the average thickness of the choroid.

All examinations were measured within an hour before and after a single session of hemodialysis.

Paired t-tests were used for indexes measured before and after HD if homogeneity of variance was verified. If homogeneity of variance was not verified, then a non-parametric test was used. Multiple linear regression analyses were conducted to identify correlations between parameters. Then, single factor analysis of variance (one-way ANOVA) and least-significant difference (LSD) tests were performed to determine parameters with significant changes during HD among subgroups according to their etiological classification. Lastly, one-way ANOVA was used to compare parameters with significant changes. A box plot was drawn, and Tukey’s test was used to isolate data with large deviations. The P-values, Estimated Marginal Means and their standard errors (SEs) were calculated by General Estimating Equations (which automatically take into account paired eye data from the same subject) after adjusting for age, sex, eyes, measurement times, HD duration, and primary diseases.

A total of 90 eyes from both sides of 45 HD patients were included in the study, including 27 pairs of male eyes (60.00%) and 18 pairs of female eyes (40.00%). The average age was 57.48 ± 13.57 years. The mean dialysis time was 70.09 ± 58.03 months. The patients were divided into 3 subgroups: the primary KD subgroup, the hypertensive KD subgroup and the DM-KD subgroup. No differences were found in age (P = 0.639) or dialysis time (P = 0.270) among the 3 subgroups.

Thirty-eight eyes from 19 healthy people were set as normal control. The blood pressure (both systolic and diastolic), urea, creatinine, uric acid, Na, K, P, Mg, PTH, fasting plasma glucose were found statistically different from the pre-HD ESRD patients. However, most of the ocular parameters, except for Spherical power and a few part of the retinal thickness showed no statistical difference (Table 1).

The average systolic pressure (SP) before HD was 147.14 ± 22.43 mmHg, which increased to 136.09 ± 24.37 mmHg after HD (P = 0.001). The mean diastolic blood pressure (DP) decreased from 83.75 ± 16.03 mmHg to 76.48 ± 13.47 mmHg (P = 0.006).

Visible calcium deposits were spotted on the cornea or conjunctiva in 22 (48.89%) of the 45 hemodialysis patients. These deposits were located in the nasal and/or temporal side of the cornea, conjunctiva and limbus. They were either white or gray and were point-, line- or block-shaped (Fig. 1).

After HD, the TBUT decreased from 6.957 ± 0.861 s to 5.205 ± 0.670 s (P = 0.020), and the Schirmer’s I test results decreased from 12.014 ± 2.020 mm to 9.964 ± 1.912 mm (P = 0.030). However, no significant change was observed in the BCVA (P = 0.880), spherical power (P = 0.442) or cylinder power (P = 0.937) measurements during HD (Table 2).

A significant positive correlation was found between the TBUT change within each HD session and the duration of all HD treatments (B = 0.040, T = 3.670, P = 0.001). Meanwhile, the change in the Schirmer’s I test results (B = − 0.566, T = − 5.121, P < 0.001) and blood urea levels (B = − 0.271, T = − 2.179, P = 0.036) were negatively correlated.

The ACD decreased from 2.642 ± 0.073 mm to 2.613 ± 0.077 mm after HD (P = 0.006). The mean LT dropped from 4.153 ± 0.413 mm to 4.056 ± 0.389 mm (P < 0.001). No significant differences were observed in IOP (P = 0.113), CT (P = 0.643), ECD (P = 0.807), ECS (P = 0.164), or ECSCV (P = 0.348) during HD (Table 3).

We found a negative correlation between changes in IOP during HD and diastolic pressure (B = − 0.068, T = − 3.606, P = 0.001).

The average retinal thickness increased from 273.40 ± 3.302 μm to 275.60 ± 3.180 μm (P = 0.071), especially in the nasal inner macula (NIM) subfield (P < 0.001), the inferior inner macula (IIM) subfield (P = 0.004) and the superior outer macula (SOM) subfield (P = 0.012). The remaining subfields had no significant differences. The RNFL thickness increased from 90.65 ± 1.829 μm to 93.18 ± 1.974 μm (P = 0.001). The CHT decreased from 289.55 ± 11.385 μm to 254.134 ± 11.46 μm (P < 0.001) (Table 4).

A positive correlation was found between the average RT change and the central corneal thickness (B = 0.130, T = 5.127, P < 0.001) and the potassium level (B = 3.950, T = 2.650, P = 0.012) before HD. The choroidal thickness change was positively related to TBUT (B = 3.120, T = 3.637, P = 0.001) and was negatively correlated with sodium level (B = − 4.163, T = − 2.241, P = 0.031) and ACD (B = − 30.190, T = − 2.356, P = 0.024) before HD.

Both eyes of all HD patients were divided into 4 subgroups according to the etiology of ESRD: the primary kidney disease (KD) subgroup (n = 27), the hypertensive KD subgroup (n = 9), the diabetic mellitus KD (DM-KD) subgroup (n = 6) and the etiology unknown subgroup (n = 3). The 3 etiology unknown patients were not included in the following analysis (Table 5).

There were no differences in the sex, age and HD duration among the 3 subgroups. However, four parameters, logMAR of BCVA, CT, RNFL thickness and CHT, were significantly different among subgroups (Fig. 2).

In summary, primary KD, hypertension and diabetes mellitus are three conditions that affect eye examination results during HD to a certain degree. However, the different causes of CRF requiring hemodialysis tend to have the same overall trend in most parameter changes except the logMAR of the BCVA, CT, RNFL thickness and CHT. Lower BCVA, increased central corneal thickness, and decreased RNFL thickness and CHT were observed in the DM-KD patients.