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Analysis of peripapillary choroidal thickness in non-arteritic anterior ischaemic optic neuropathy
  1. Ignacio García-Basterra1,
  2. Iliass Lahrach1,
  3. María Josefa Morillo Sánchez1,
  4. Radua Kamal-Salah2,
  5. Francisca Ríus-Díaz3,
  6. Marc Stefan Dawid Milner4,
  7. José Manuel García-Campos1,5
  1. 1Department of Ophthalmology, University Hospital Virgen de la Victoria, Málaga, Spain
  2. 2Department of Ophthalmology, Eye Clinic, Torbay Hospital, South Devon Healthcare NHS Foundation Trust, Torquay, UK
  3. 3Department of Preventive Medicine and Public Health, University of Málaga, Málaga, Spain
  4. 4Department of Human Physiology and Physical Sports Education, Centro de Investigaciones Médico-Sanitarias, University of Málaga, Málaga, Spain
  5. 5Department of Ophthalmology, Centro de Investigaciones Médico-Sanitarias, University of Málaga, Málaga, Spain
  1. Correspondence to Dr Ignacio García-Basterra, Department of Ophthalmology, Hospital Virgen de la Victoria, Campus Teatinos, S/N, Málaga 29010, Spain; ignaciobas{at}hotmail.com

Abstract

Purpose To analyse peripapillary choroidal thickness (PCT) in non-arteritic ischaemic optic neuropathy (NAION).

Methods 28 patients diagnosed with NAION (37 affected and 19 unaffected eyes) and 38 disease-free control individuals (38 eyes) were analysed using enhanced-depth imaging of spectral-domain optical coherence tomography. A vertical and a horizontal raster scan centred on the optic nerve were obtained per eye. PCT was measured at the superior, inferior, nasal and temporal quadrants from the posterior edge of the retinal pigment epithelium to the choroid–sclera junction at 500 μm intervals up to 2000 μm away from the optic nerve. Statistical analysis was used to compare average PCT and to correlate PCT with other ocular and systemic parameters.

Results Mean PCT in NAION eyes and control group was 148.18±42.68 μm and 182.90±59.81 μm, respectively (p=0.005). Except for inferior PCT (p=0.158), superior, nasal and temporal PCT were significantly thinner in the NAION eyes than in the control group (p=0.006, 0.002 and 0.046). Thinner PCT, adjusted for refractive error, was associated with the diagnosis of NAION (p=0.048). Similarly, unaffected contralateral eyes showed a significant thinner PCT compared with the control group (p=0.024). Diagnosis of NAION was negatively associated with PCT in NAION eyes (p=0.008; OR 0.98; 95% CI 0.97 to 0.99) and in their contralateral unaffected eyes (p=0.043; OR 0.98; 95% CI 0.97 to 0.99).

Conclusions Eyes affected by NAION and contralateral unaffected eyes showed significantly thinner PCT compared with disease-free control eyes after adjusting for refractive error.

  • Choroid
  • Optic Nerve
  • Imaging

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Introduction

Although non-arteritic anterior ischaemic optic neuropathy (NAION) is the most common cause of acute optic neuropathy in people over the age of 50, its pathogenesis is not completely known. It is assumed to be caused by a vascular insufficiency in the optic disc head, supplied by the posterior ciliary arteries (PCA) circulation via the peripapillary choroid and the short PCAs or the circle of Zinn and Haller.1 Currently, there is no satisfactory method of assessment of blood flow in optic nerve head,2 thus its study is only possible with indirect methods.

The development of enhanced depth imaging (EDI) has made choroidal examination with spectral-domain optical coherence tomography (SD-OCT) possible. Since it was reported by Spaide and colleagues,3 numerous studies have measured peripapillary choroidal thickness (PCT) in normal subjects and in patients with different pathologies.4–8 Despite the fact that choroidal thickness may not be a direct reflection of choroidal blood flow, quantitative and qualitative analyses of PCT may aid in elucidating the pathophysiology of NAION and other optic nerve diseases.2 ,9

The purpose of this investigation is to examine the PCT measurements in four different quadrants in patients with NAION and to compare with the PCT in normal subjects. As a second objective, PCT is correlated with age, gender, refractive error, axial length and other ocular and systemic factors.

Methods

A retrospective observational study analysed a study group of 28 patients with NAION (37 affected and 19 unaffected eyes) attended by our ophthalmology service from January 2014 to May 2015, and a contemporaneous control group formed by 38 patients (38 eyes).

NAION was defined as a sudden and painless visual loss, optic disc swelling and sectoral visual field defect often noted in the morning. The absence of systemic symptoms of giant cell arteritis, an unremarkable digital examination of the superficial temporal artery and the absence of a high erythrocyte sedimentation rate or a high C reactive protein ruled out arteritic anterior ischaemic optic neuropathy. All patients recruited had a complete resolution of the disc oedema without any treatment within 2 months and followed a clinical course consistent with NAION. The OCT was performed when the optic disc swelling had completely been resolved (3.1±0.7 months; range 2.9). Although two scans in the study group were excluded because of poor choroidal segmentation, no subjects were excluded from the analysis. Control subjects were randomly recruited from patients who attended our clinic for other reasons than vitreous, retina or optic nerve diseases. Exclusion criteria included media opacities (that could preclude OCT scanning), coexistence of neurological disease, previous ocular surgery (except uneventful cataract surgery) or refractive error >−6 dioptres.

All individuals underwent a detailed ophthalmological examination, slit-lamp-based examination, tonometry and ophthalmoscopy. The best-corrected visual acuity (BCVA) was measured using a Snellen chart at 6 m and converted into the logarithm of the minimum angle of resolution for statistical analysis. Refractometry was performed using an automated refractometer (RM-8900; Topcon, Tokyo, Japan) and axial length was measured using IOL Master (Carl Zeiss Meditec, Dublin, California, USA). PCT was measured using SD-OCT (wavelength 840 nm; Cirrus HD-OCT V.6; Carl Zeiss Meditec) with enhanced-depth imaging modality after pupil dilation with tropicamide 1% (Alcon Cusi, El Masnou, Barcelona, Spain). Two trained and masked technicians performed the scans after ophthalmoscopy examination. An optic disc OCT scan was obtained using the high-definition scan protocol, composed of a single 6 mm raster scan (20 B-scans averaged) centred on the papilla. A horizontal and a vertical scan were taken through the optic nerve, each one bisecting the optic nerve into approximately equal halves. Using the calliper provided by the software, PCT was measured at the superior, inferior, nasal and temporal quadrants at 500 μm intervals along the line of the retinal pigmentary epithelium (RPE) up to 2000 μm away from the optic nerve, following the protocol reported by Ho and colleagues.9 The measurements were made perpendicular to the RPE, from the posterior RPE edge to the choroid–scleral junction (figure 1). Average of each quadrant and the mean of the whole PCT were calculated. Only good quality scans (signal strength ≥6 in intensity and uniform brightness) were included in the study. The reproducibility of the technique and measurements had previously been examined in 20 individuals randomly selected from the control and study group. The results showed a statistically high repeatability (intraclass correlation coefficient 0.99, p<0.01 and Pearson's correlation coefficient 0.98, p<0.01).

Figure 1

Enhanced depth imaging optical coherence tomography images showing peripapillary choroidal measurements in non-arteritic ischaemic optic neuropathy.

All statistical analyses were performed via Microsoft Excel (V.14; Microsoft, Redmond, Washington, USA) and SPSS statistics (V.20, IBM-SPSS, Chicago, Illinois, USA). In the study group, both eyes were included in the study; meanwhile, for the individuals in the control group, only the right eyes were included. The left eye in the control group was only studied when an image worse than 6 out of 10 in intensity was obtained. Sample size was previously calculated using SD from previous studies in PCT,4 ,5 ,9 a precision of 40 μm, 10% expected loss and a two-sided significance of 0.05 with a power of 0.9. PCT measurements in the affected eyes were compared with the data obtained in the control group and with the data obtained in their contralateral unaffected eyes. Univariate analyses were performed to study associations between mean PCT and other ocular and systemic parameters. Then, multivariate analyses were conducted using mean PCT as a dependent variable and those parameters that were significantly associated as independent variables. Binary regression analyses were also performed with the diagnosis of NAION as the dependent variable and the other parameters, including PCT measurements, as independent variables. χ2 and Student's t contrast for independent and paired samples, considering homoscedasticity, were used to detect significant differences between groups, linear regression to quantify the relation among the parameters and logistic regression to estimate the ORs with significant variables and to perform a multivariate model. ORs and 95% CIs were presented. All p values were based on two-sided tests and were considered statistically significant when the values were <0.05.

Results

In total, 37 eyes with NAION, 19 contralateral unaffected eyes and 38 disease-free control eyes were examined. Table 1 provides a distribution of demographic and clinical characteristics of both groups. All individuals included were Caucasians. No statistically significant differences were observed between groups in terms of age (p=0.704), gender (p=0.223), axial length (p=0.285), intraocular pressure (p=0.178) and other systemic and vascular risk factors such as hypertension (p=0.465), diabetes (p=0.130), dyslipidemia (p=0.319), smoking (p=0.748) and obstructive sleep apnoea syndrome (p=0.680). Significant differences were found in refractive error (p=0.034) and in BCVA (p=0.000).

Table 1

Demographic and clinical characteristics of NAION group and disease-free control group

The mean PCT in eyes with NAION was 148.18±42.68 μm, and the mean PCT in the control group was 182.90±59.81 μm (p=0.005). In the univariate analyses, the superior, temporal and nasal PCT were thinner in NAION eyes than in the control group (all p values <0.05) while the inferior PCT did not show significant differences (p=0.158). The mean PCT in unaffected eyes contralateral to NAION eyes was 148.49±47.05 μm. No significant differences in the PCT values were found between the affected eyes and the contralateral unaffected eyes within the group of patients with unilateral NAION (all p values >0.2). Similarly, except for inferior PCT measurements (p=0.104), all sectoral PCT values and mean PCT were significantly thinner in unaffected eyes contralateral to NAION eyes than in the control group (all p values <0.05) (table 2).

Table 2

PCT measurements (μm) by optical coherence tomography (enhanced depth imaging) in NAION eyes, contralateral unaffected eyes and disease-free control eyes

Additionally, we investigated differences in the measurements within each quadrant between the study and control group. The distributions of measurements at 500 μm intervals within each quadrant are shown in figure 2. We observed that, comparing NAION eyes with the control group, the differences were significant for every measurement except for the superior PCT at 500 μm (p=0.060), temporal at 500 μm (p=0.300), 1000 μm (p=0.117) and 1500 μm (p=0.082) and all measurements in the inferior PCT (all p values >0.1). When contralateral unaffected eyes were compared with control eyes, significant differences were found in superior PCT at 2000 μm (p=0.021), nasal PCT at 500 μm (p=0.003), temporal PCT at 500 μm (p=0.030) and at 1000 μm (p=0.026), whereas no differences were observed in the rest of the PCT values (all p values >0.05).

Figure 2

Graphs showing distribution of peripapillary choroidal thicknesses at 500 μm intervals away from the optic nerve in eyes affected with non-arteritic ischaemic optic neuropathy (NAION), contralateral unaffected eyes and disease-free control group. (Top left: superior quadrant; top right: inferior quadrant; bottom left: nasal quadrant; bottom right: temporal quadrant). *p Value <0.05 (Student's t).

Possible associations between mean PCT and other ocular and systemic parameters in NAION and control eyes were studied. Mean PCT was found to be significantly associated with younger age (p=0.001; standardised coefficient β, −0.38) and hyperopic refractive error (p=0.035; standardised coefficient β, 0.24); meanwhile, gender (p=0.301), axial length (p=0.240) and other epidemiological factors were not significantly associated with PCT. To eliminate refractive error as a possible confounding factor, univariate analysis was performed with mean PCT as a dependent variable, diagnosis of NAION as independent variable and refractive error as covariate. Our results showed that thinner PCT was significantly associated with the diagnosis of NAION (p=0.048) after adjusting for refractive error. If only the unaffected eyes contralateral to the eyes with NAION and the control group were included in the same statistical analysis, mean PCT was only significantly associated with the variable diagnosis of NAION in their contralateral eyes (p=0.037).

Binary logistic regression analysis was performed to study associations between diagnosis of NAION and other factors such as age, gender, refractive error and mean PCT (table 3). In the univariate analysis, the diagnosis of NAION was negatively associated with mean PCT (p=0.008; OR 0.98; 95% CI 0.97 to 0.99) and refractive error (p=0.036; OR 0.71; 95% CI 0.51 to 0.97), while there were no significant associations with age (p=0.994) and gender (p=0.299). In multivariable binary regression, the diagnosis of NAION was not significantly associated with any of these factors (mean PCT: p=0.059; refractive error: p=0.080). If the unaffected eyes contralateral to the eyes with NAION and the control group were included in the same analysis, the diagnosis of NAION was only significantly associated with mean PCT (p=0.043; OR 0.98; 95% CI 0.97 to 0.99).

Table 3

Associations (univariate and multivariate analyses) between the diagnosis of non-arteritic anterior ischaemic optic neuropathy and age, gender, refractive error and PCT

Discussion

The current study showed significantly thinner PCT in NAION and contralateral unaffected eyes than in a disease-free control group after adjusting for refractive error. These differences were statistically significant in superior, nasal and temporal quadrants, whereas there were no significant differences in inferior quadrant thicknesses. It is interesting to note that the PCT was thinner in both affected and unaffected eyes, which suggests that a thin PCT is present preceding the ischaemic event rather than being its consequence. Correspondingly, PCT values did not differ significantly between eyes with NAION and their contralateral unaffected eyes. Mean PCT was found to be positively associated with younger age and hyperopic refractive error; meanwhile, gender, axial length and other epidemiological factors were not significantly associated with PCT.

The blood flow in the optic nerve head and intraocular vessels depends on the perfusion pressure and the resistance to flow.2 Fluorescein, indocyanine green angiography, colour Doppler ultrasound and histopathological studies in NAION have shown optic disc blood flow impairment in a pattern, suggesting transient hypoperfusion of the optic nerve head or posterior ciliary artery occlusion.10–13 Nocturnal arterial hypotension is also considered to play an important role in the pathogenesis by decreasing perfusion pressure in the optic nerve.14 Despite the fact that choroidal blood flow may not affect its thickness and that PCT measurements may not be a reliable indicator of peripapillary blood circulation, a thinner PCT may mean smaller vessel diameters, and consequently, an increase in the vascular resistance. Therefore, a thin PCT added to other predisposing factors for vascular insufficiency may reflect an optic nerve more vulnerable to choroidal circulation flow changes and more susceptible to hypoxia. Furthermore, a thin inferior PCT is consistently found in previous PCT studies, possibly explained by the development pattern of the eye.4 ,9 This concept may support the observation that the superior hemifield is affected more often and more severely than the inferior hemifield in glaucomatous eyes due to a thinner choroid in inferior sectors.15 ,16 In our investigation, although we did not find any statistically significant differences, both NAION and their contralateral unaffected eyes showed thinner inferior PCT compared with the control group.

Previous studies have reported that PCT decreases with age and varies with race,17 axial length, triglyceride levels and the presence of diabetes.8 In our study, no statistically significant differences were found between the study and control group in these parameters. Our results only showed statistically differences in refractive error between NAION and control eyes. This finding seems to be a consequence of the exclusion criteria in the control group, which excluded refractive error inferior to −6 dioptres and retina disorders such as high myopia. Even so, the association between PCT and NAION achieved statistical significance after adjusting for refractive error. In a reverse manner, NAION was associated with a thinner PCT in NAION eyes and in their contralateral unaffected eyes. In addition to a thinner PCT, we found that diagnosis of NAION was associated in NAION eyes with myopic refractive error in the univariate analysis. Even though previous papers have reported a relation between hyperopia and NAION,18–21 one later and larger study demonstrated no differences in refractive error between 608 NAION eyes and general population.22 Thus, our small sample size might have biased the results. Both associations did not show significant association in multivariate binary regression.

To date, two earlier publications about macular choroidal thickness in NAION have shown contradictory results. Schuster et al23 reported a thicker macular thickness in acute NAION eyes and their contralateral unaffected eyes compared with healthy controls. Dias-Santos and Ferreira24 found a thinner macular thickness in chronic NAION eyes compared with controls and a progressive thickening since the time of onset. Although Schuster et al also reported no differences between acute NAION eyes and their contralateral affected eyes within the subgroup with bilateral NAION, the time of performing the OCT appears to be the main difference between these studies. On the other hand, a recent study by Fard and colleagues investigated PCT in NAION using EDI SD-OCT and a 360° peripapillary circle scan around the optic nerve with a diameter of 3.4 mm.25 Contrarily to our results, this study showed significantly thicker PCT in NAION eyes and contralateral unaffected eyes in comparison with a control group. The disparities may arise from difference in ethnicity, in patient profiles, difference in the measuring software, the OCT light source or the time when the OCT was performed. As reported in macular choroidal thickness, there may be changes in PCT along the time, possibly showing an alteration in the autoregulatory capacity of the choroid. On the other hand, Ho and colleagues reported that choroidal thickness differs by a large magnitude depending on the location in the eye due to its cuneiform shape, which means that the PCT gradually increases further away from the optic nerve.9 Our data showed a gradual thickening of the peripapillary choroid in each quadrant in the study and control group. So, the place of measurement could cause large differences in comparison with an average of four measurements at 500 μm intervals in each quadrant. Furthermore, our PCT values in the control group were very similar to the ones already published in recent papers, which reflects a good compliance with our measurements.4–9 ,15 ,17 ,26

Several limitations of our study should be mentioned. First, as choroidal thickness was measured manually bisecting the optic nerve, the scan registration was inevitably subject to some variability and could be affected by local irregularities of the choroid–scleral boundary. Second, despite the fact that we underwent OCT randomly at various times of the day, there is still the possibility of a bias due to the circadian rhythm of choroidal thickness.27 Third, our control group was composed of disease-free individuals that attended our hospital, so the risk of referral bias is not excluded.

In conclusion, PCT is thinner in patients with NAION than in a disease-free control group. A thin PCT may be added to the NAION features and may be a predisposing factor for NAION. Further prospective studies are needed to fully understand the pathophysiology of these findings.

References

Footnotes

  • Contributors Drafting the work: IG-B, IL, MJMS, RK-S, FR-D, MSDM and JMG-C. Design and conduct of the study: IG-B, IL, MJMS and JMG-C. Collection, management, analysis and interpretation of the data: IG-B, RK-S, FR-D, MSDM and JMG-C. Preparation, review or approval of the manuscript: IG-B, IL, RK-S, MJMS, MSDM and JMG-C. All authors contributed to refinement of the study protocol and approved the final manuscript.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The provincial ethics committee of Málaga approved the study according to the Declaration of Helsinki and all federal laws in Spain.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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