Retinal nerve fiber layer thickness and retinal vascular caliber alterations in coal miners in northern China: a community-based observational study

INTRODUCTION

Nowadays, coal is still one of the most important energy sources providing energy and electricity worldwide.Work-place exposure to coal mine dust during coal mining remains a significant hazard worldwide. The occupational exposure to crystalline silica may cause progressive lung inflammation culminating in forming of pneumoconiosis.Coal mine dust may lead to systemic silica-associated inflammatory response triggered by cytokines released from macrophages, lymphocytes and epithelial cells. Such cytotoxic effect of inhaled silica dusts may cause alterations of various organs throughout the body, including inner structures of the eye such as choroid and retinal tissue. Previous investigations revealed that active inflammation led to a significantly thickened retinal nerve fiber layer (RNFL), which can be clearly detected by optical coherence tomography(OCT), a high-resolution imaging technique suitable for evaluating the RNFL at and around the optic nerve head(ONH).

The metabolism in the outer retina and retinal blood flow had been demonstrated to be increased in darkness, such alterations may affect the progression of retinal disease during coal mining. However, studies on the retinal thickness changes in long-term effects of working underground by means of OCT have been scarce so far. Besides, our group also would like to explore the retinal vessel caliber alterations in the dark working environment, since the retinal hemodynamics and oxygen saturation can be different in the dark.

We applied a non-mydriatic approach in a dimly lit room by using a digital fundus camera (Type CR6‐45NM; Canon, ōta,Tokyo, Japan) to obtain retinal photographs. Two 45° color fundus photographs of each participant were obtained, centered on optic disc and fovea. The retinal vessel diameters were measured using a semiautomated algorithm interactive vessel analysis software (IVAN; Vasculomatic ala Nicola, University of Wisconsin-Madison, WI, USA), as described in our previous studies. Central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) diameters were measured through an area of 0.5 to 1 disc diameter surrounding the optic disc margin, estimated by means of the Big-6 formula on the infrared fundus photographs. The arteriovenous ratio (AVR)was calculated as CRAE divided by CRVE.

SUBJECTS AND METHODS

This research conducted in accordance with the ethical standards of the Helsinki Declaration and the study protocol was approved by the Institutional Ethics Committee of the Beijing Tongren Hospital. All participants in our study gave their written informed consent before enrolment.

The community-based observational study was a subgroup of the longitudinal Kailuan Study which included 101 510 employees and retirees of a coal mining company (Kailuan Group Company), as described in our previous studies. From 2012 to 2013, randomly selected participants completed baseline data collection, out of whom 4004 individuals eventually met the inclusion criteria and underwent fundus photography and OCT from 2013 to 2014.Exclusion criteria were history of any ocular diseases and ocular surgeries, or any use of medications that affect the eyes.Cataract and pseudophakia not affecting the quality of OCT and fundus photography images were not exclusion criteria.Among them, individuals that worked underground were included as study group, and participants working above the ground were defined as control group.

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（98）齒萼羽苔 Plagiochila hakkodensis Steph.熊源新等（2006）；楊志平（2006）

The aim of this study was to explore the potential alterations of retinal thickness and retinal vessel calibers in coal mine workers. In attempt to reduce the risk of a referral bias, we chose the design of a relatively community-based study population.

目前我國公共圖書館系統未成年人服務很大程度上落后于成人服務，少兒圖書館事業發展很不平衡，農村地區無此項服務[33](P18)，而學校圖書館面臨著專業化、規范化的建設任務，其發展同樣有較嚴重的區域、年級和管理部門等的差距[34]（P254-285）。沒有有效、強有力的圖書館未成年人服務的理論與實踐支撐，可以說語文教育的概念就會成為絕大多數師生的空中樓閣與極少數人的游樂園。另外這兩類主要的未成年人服務機構分屬我國文化和教育系統，容易出現力量分散、資源浪費、各行其是等問題，兩者間的合作與協調也有賴于行政部門的積極作為。

All the study participants underwent a spectral-domain OCT(iVue SD-OCT; Optovue Inc, Fremont, California, USA)examination obtaining images of the ONH, macula and adjacent retina. A 6×6 mmraster scan was centered on the optic disc and macula. The mean temporal, nasal, inferior,superior quadrant peripapillary RNFL thicknesses and central macular thickness (CMT) were assessed from high resolution images. RNFL segmentation was checked for every OCT image. Images not centered, or a signal strength index less than 40, any algorithm failures, motion artifacts, poor focusing were excluded from the assessment. As described in our previous study, two experienced ophthalmologists scanned all subjects.

Estimates of cumulative silica dust exposure (CDE), presented in milligrams/cubic meter-years, was calculated as follow:the duration of exposure in years multiplied by the dust concentration during the same time of employment period for each coal worker. Given by the department of dust detection and monitoring of the Kailuan Colliery Company,dust concentration and free silica content were measured using national standard methods in order to calculate the geometric means yearly. These numerical data were collected by gravimetric method, and then used to calculate the CDE for each subject.

This community based study found that the retinal vessels diameters was significantly thicker in coal workers than in the control group. In addition, the RNFL thickness was significantly higher in the study group while the CMT was lower in the underground coal workers as compared to the controls. As a corollary, thicker RNFL was significantly associated with higher CDE, and wider retinal veins were also significantly correlated to higher CDE after adjustment for age. A higher CDE was significantly associated with a thicker RNFL in multivariable analysis.

Structured interviews with standardized questions included information on the working areas, history of occupational exposure, level of education, history of systemic medical disorders such as diabetes and hyperlipidemia,alcohol consumption and smoking, were performed by trained investigators, as described in our previous study. The working areas in the Kailuan Colliery Group were defined as above the ground and underground. We also measured height and weight and calculated body mass index (BMI). Systolic blood pressure and diastolic blood pressure were measured twice with the participant sitting for at least 5min using a mercury sphygmomanometer. For all study participants,we collected blood samples under fasting conditions and transfused into vacuum tubes containing ethylene diamine tetraacetic acid (EDTA). All blood samples were analyzed using an auto-analyzer and underwent a biochemical analysis of the serum concentration of glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride,total cholesterol and uric acid.

RESULTS

A total of 4004 participants [1720 women (43.0%)] with a mean age of 59.7±11.0y were included into the present investigation. After matched with age (±1y), spherical equivalent and gender, we included 659 coal workers (working underground) as study group, and 477 participants (working above the ground) as control group. There is no significant difference between study and control group in gender(=0.41), age (51.0±7.8y51.8±7.5y;=0.077), diabetes status (=0.105), alcohol consumption (=0.242) or smoking history (=0.714; Table 1).

As compared to the control group, the study group showed a significantly thicker retinal artery (154.52±19151.56±19.8 μm;=0.012) and vein diameters (236.27±27.3230.35±27.75 μm;<0.001), while the AVR did not differ significantly (0.66±0.120.67±0.11;=0.687) between both groups (Table 2). Additionally, the RNFL thickness was significantly higher in the study group than the control in superior and temporal quadrants (124.15±14.93121.66±16.76 μm,=0.012; 81.59±14.1479.02±12.21 μm,=0.002, respectively), while the CMT was lower in the downhole workers as compared to the control (246.17±22.1249.06±19.61 μm;=0.032; Table 2).

The retinal vein diameter was correlated with the CDE in both univariate and multivariable analysis. Nemmarmeasured the distribution of radioactivity after the inhalation of pollutant particles and found that inhaled pollutant particles can cross the pulmonary epithelium into the cardiovascular system and thus exert direct effects on the cardiovascular system or the indirect effects mediated by the inflammatory response on the heart and vessels. With the central retinal artery as branch of the ophthalmic artery and internal carotid artery, the microvascular system of the retina can be assumed as part of the cardiovascular system. In addition, Nagaoka and Yoshidadetected that the stage of chronic kidney disease was a significant variable for the serum concentration of low‐density lipoprotein and retinal blood flow. Both retina and kidney are low-resistance end organs that are supplied by small blood vessels, which are vulnerable to fluctuations in blood flow. The anatomical similarities in the vascularization of the retina and kidney may lead to similar aspects in the pathogenesis of cellular apoptosis and upregulation of pro-inflammatory markers in both organs. Therefore, it is reasonable to assume that long-term silica dust exposure can initiate the inflammation response on vascular endothelial cells which may influence ocular structures.

引理1.3[8] 設τ1,τ2為集合X上的兩個拓撲且τ1?τ2,則CIrrτ2(X)?CIrrτ1(X)。

DISCUSSION

The statistical analysis of this study was applied using a commercially available statistical package(SPSS for Mac, version 25.0; IBM/SPSS, Chicago, Illinois,USA). For the first analysis, we described the mean values(presented as mean standard deviation) of the participants’characteristics. Then the Studenttest for un-paired sampleswas to evaluate the statistical significance of differences between the coal workers and the controls. Multiple linear regression analysis was applied to evaluate the potential associations between ocular and systematic risk factors. The 95% confidence intervals of each risk factor were presented.Two-tailed-values were considered to be statistically significant if lower than 0.05.

一個潔凈的外部環境，能夠讓患者更好的配合治療。現代醫院中生殖醫學中心的外部環境要保持干凈、整潔，室內安裝空氣調節過濾器，保證診室內部的空氣質量較好，溫度適宜，為患者提供一個溫馨、舒適的就醫環境。在選址的過程當中，盡量避免化學放射源，減小化學放射源對胚胎的影響。……