
==== Front
Medicine (Baltimore)
Medicine (Baltimore)
MD
Medicine
0025-7974
1536-5964
Lippincott Williams & Wilkins Hagerstown, MD

39312352
MD-D-24-02725
00053
10.1097/MD.0000000000039675
3
5800
Research Article
Observational Study
Investigation of traditional Chinese medicine constitution in individuals afflicted by dry eye disease: A retrospective study
https://orcid.org/0000-0001-6910-0657
Yu Jing PhD yujing0806@21cn.com
a
Guo Yihan MD yihanguogyh@skiff.com
a
Tian Lei PhD leijgodnlrhzh10@21cn.com
ab
Qiu Lixin PhD linxinqiulx6@skiff.com
a
Chen Xiaoniao PhD xndongodr@21cn.com
c
Cao Kai MD cfodnltigno09@21cn.com
a
Zhu Lei BS leijgodnlrhzh10@21cn.com
a
https://orcid.org/0000-0003-2649-8241
Jie Ying PhD a*
a Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University; Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, China
b Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University and Capital Medical University, Beijing, China
c Department of Ophthalmology, The Third Medical Center of Chinese People’s Liberation Army General Hospital, Beijing, China.
* Correspondence: Ying Jie, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University; Beijing Ophthalmology & Visual Sciences Key Laboratory, Dongcheng District, Beijing 100730, China (e-mail: jie_yingcn@aliyun.com).
20 9 2024
20 9 2024
103 38 e3967521 3 2024
18 8 2024
23 8 2024
Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

The aim of this study is to explore the traditional Chinese medicine (TCM) constitution among individuals suffering from dry eye disease. Following the diagnostic criteria outlined in TFO DEWS II, a total of 114 patients with dry eye were included in this study. Based on the classification criteria for dry eye, the patients were categorized into 3 distinct dry eye subtypes. Each participant underwent a thorough clinical assessment for dry eye, and their TCM pattern manifestations were assessed using the “Traditional Chinese Medicine Questionnaire for Dry Eye.” The Nine Constitutions Assessment Method was utilized for TCM pattern differentiation and classification. Spearman’s correlation analysis was employed to investigate the associations between TCM constitution and dry eye subtypes, clinical indicators, and the relationships between TCM syndromes and dry eye subtypes. Among the 114 patients, the Qi-Stagnation constitution was the most common, with variations in constitution distribution among different dry eye subtypes. Significant correlations were observed between the Blood-Stasis, Yin-Deficiency, Qi-Deficiency, and Yang-Deficiency constitutions and 2, 4, 1, and 4 dry eye indicators, respectively. Spearman’s analysis revealed that 5 out of 50 TCM syndromes were associated with mixed dry eye, 5 with evaporative dry eye, and 3 with aqueous tear deficiency dry eye. Further analysis, using lasso regression and binary unconditional logistic regression identified dizziness, lumbago, and weakness as influencing factors for both mixed-type and evaporative-type dry eye. In this study, we extensively examined the TCM constitution in individuals with dry eye, offering valuable insights and guiding future TCM-related research in the context of dry eye. Additionally, we established correlations between TCM syndrome patterns and dry eye indicators.

dry eye
traditional Chinese medicine
traditional Chinese medicine constitution
“Beijing Municipal Administration of Hospitals Incubating Program”PZ2020002 Not ApplicableOPEN-ACCESSTRUE
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pmc 1. Introduction

Dry eye disease is a persistent ocular surface disorder influenced by numerous factors. It is typified by irregular tear quality, quantity, and dynamics, resulting in an unstable tear film or an imbalanced microenvironment of the ocular surface. This ailment may coincide with ocular inflammation, tissue deterioration, and neural irregularities, which can produce an array of distressing symptoms and, in severe cases, visual impairment.[1] Presently, dry eye disease has emerged as one of the most widespread ocular surface disorders across the globe, exerting a substantial influence on the quality of life for affected individuals. The documented prevalence of dry eye disease varies, encompassing a range from roughly 5.5 to 33.7%.[2] In the context of China, it is estimated to affect approximately 21% to 30% of the population.[3–5] Even mild instances of dry eye can induce ocular discomfort, manifesting as sensations of dryness, pain, itching, and foreign body perception, thereby impinging on routine tasks such as driving and reading. With prolonged disease progression, there is a potential for corneal damage and, in severe cases, visual impairment.

In the field of traditional Chinese medicine, dry eye disease is often associated with the concept of “deficiency of vital essence leading to exhaustion of the essential fluid. It is additionally categorized under designations such as “white astringency syndrome and “dryness, astringency, visual dimness, and blurred vision.”[6] According to historical records in traditional Chinese medicine (TCM), the primary symptomatic characteristics of this condition encompass ocular dryness, visual blurriness, and a bright white sclera without puffiness but with delicate red veins.[7] The Inner Classic of Huangdi elucidates, “The essence originating from the five zang organs and six fu organs ascends to nurture the eyes, thus becoming their essence.” The Zhubing Yuanhou Lun affirms, “The five zang organs and six fu organs house vital fluids, and tears act as a conduit to the eyes.” The proper operation of the visual system hinges on the sustenance supplied by the essence and qi emanating from the 5 zang organs and 6 fu organs.[8]

The TCM constitution theory, rooted in TCM principles, examines the physiological and pathological attributes of different constitutional traits and categories in individuals. It scrutinizes disease response patterns, the character of pathological alterations, and their progression tendencies, furnishing insights for the prevention and management of diseases.[9] The constitution concept clarifies an individual’s vulnerability to specific causative factors and their inclination toward particular diseases. It contributes to disease prevention, the recognition of high-risk groups for specific conditions, and proactive interventions. Moreover, drawing from the principles derived from constitution theory, it establishes parameters for distinguishing diagnoses and therapeutic approaches, serving as an integral element of TCM theory with real-world utility. The correlation between constitution and diseases establishes a theoretical underpinning for the prevention and treatment of disorders prominently associated with specific constitutional types.[7]

Prior research has highlighted the efficacy of TCM herbal remedies,[10] acupuncture,[11] fumigation therapy,[12] and various methods in ameliorating dry eye symptoms and indications. Nevertheless, contemporary clinical management of dry eye frequently relies on personal expertise, encompassing multifaceted and varied differentiation patterns. This poses difficulties in establishing standardized TCM diagnostic and therapeutic protocols for dry eye. Additionally, TCM diagnosis of dry eye predominantly hinges on macroscopic differentiation, with limited exploration into the microscopic distinctions unique to this condition. In this study, our primary focus was the distribution patterns of TCM constitutions among patients with dry eye and their corresponding associations with clinical symptoms and objective findings. We also examined the correlation between TCM constitutions, pattern differentiation, and specific dry eye indicators at a micro-level. By unifying the fundamental TCM principles of a “holistic perspective” and “prevention and treatment of disease,” our aim is to establish a theoretical groundwork for the TCM-oriented management of dry eye.

2. Materials and methods

2.1. General information

This cross-sectional study was conducted at the Dry Eye Diagnosis and Treatment Center of Beijing Tongren Hospital. We meticulously selected 114 patients who had been diagnosed with dry eye from January 2022 to November 2022, comprising 29 male and 85 female participants. Every individual was subjected to an accurate diagnosis adhering to the diagnostic criteria defined by TFOS DEWS II. To avoid any potential confounding factors arising from inter-eye correlation within the same patient, we opted for the eye that exhibited more pronounced symptoms for subsequent analysis. All patients underwent a comprehensive diagnostic assessment encompassing the completion of the “Traditional Chinese Medicine Questionnaire for Dry Eye” to assess their TCM pattern manifestations. The differentiation and classification of TCM patterns were executed using the Nine Constitutions Assessment Method. The schematic representation of this study is provided in Figure 1 for reference.

Figure 1. Flowchart of this study. CFS = corneal fluorescein staining, LLT = lipid layer thickness, NIKBUT = non-invasive tear breakup time, OSDI = Ocular Surface Disease Index, TCM = traditional Chinese medicine, TMH = tear meniscus height.

The patients were categorized into age groups, each spanning a decade, encompassing the following brackets: 20 to 30 years, 31 to 40 years, 41 to 50 years, 51 to 60 years, and over 60 years.

The inclusion criteria were as follows: meet the diagnostic criteria for dry eye, provide written informed consent, and have the capacity to complete the “Traditional Chinese Medicine Questionnaire for Dry Eye” based on their current health status.

Exclusion criteria were as follows: under 18 years or over 75 years of age, individuals with severe cardiovascular or cerebrovascular disorders, those with mental health conditions, non-compliant with medical assessments, individuals with a history of ocular surgery, chemical eye injuries, or prolonged use of ocular medications.

This study strictly followed the principles outlined in the Helsinki Declaration and was approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University.

2.2. Diagnosis criteria and diagnostic process of dry eye

In accordance with the clinical examination protocol for dry eye, all participants underwent a series of assessments in the following sequence: Firstly, participants completed the Ocular Surface Disease Index (OSDI) questionnaire before any other examinations. Subsequently, measurements of tear meniscus height and non-invasive tear break-up time, as well as evaluation of meibomian gland images, were conducted using an ocular surface analyzer (Oculus, Wetzlar, Germany). The LipiView interferometer (TearScience, Morrisville) was then utilized to measure tear film lipid layer thickness (LLT), incomplete blink rate, and total blink rate. Following this, 1% to 2% fluorescein sodium dye was instilled into the lower conjunctival sac, and the corneal fluorescein staining scores (CFS) were evaluated. After a 30-minute rest period, the Schirmer test (without anesthesia) was administered for 5 minutes.

Utilizing the measurements of dry eye indicators, the diagnosis adhered to the TFOS DEWS II criteria as follows: Symptoms: OSDI questionnaire score ≥ 13 or dry eye severity score (VAS) ≥ 6; Presence of at least 1 positive outcome from the following tests: fluorescein tear breakup time ≤ 10 seconds, inter-eye difference in tear osmolarity > 8 mOsm/L, ocular surface staining: corneal staining > 5 points, conjunctival staining > 9 points, or lid margin staining [≥2 mm length or ≥ 25% width]. Additionally, in accordance with the dry eye classification criteria, patients were categorized as having mixed dry eye, evaporative dry eye, or aqueous tear deficiency dry eye. All assessments were consistently conducted under uniform conditions by the same physician in a standardized examination room.

2.3. TCM assessment

The clinical data for each participant meeting the specified inclusion criteria were systematically collected and organized. The categorization and identification of constitutional types followed the guidelines outlined in the “Classification and Determination of Traditional Chinese Medicine Constitution” standards issued by the China Association of Traditional Chinese Medicine in 2009.[13] The constitution was classified into 9 fundamental types: balanced constitution, Qi-deficiency constitution, Yang-deficiency constitution, Yin-deficiency constitution, phlegm-dampness constitution, damp-heat constitution, blood stasis constitution, Qi-stagnation constitution, and special sensitivity constitution.

2.4. Statistical analysis

Statistical analyses were carried out using SPSS software (version 26.0). The sample size calculation was per the following formula: n = Z2α/2 ·P(1−P)/E2. The incidence rate of dry eye is: P = 33.7%, and the expected error is: E = 0.1.Consequently, a minimum enrollment of 86 participants is needed. Descriptive statistics are presented in the form of mean ± standard deviation for continuous variables. Spearman’s correlation analysis was used to investigate the correlation between constitution and dry eye subtypes, constitution and dry eye indicators, and the interplay between TCM syndromes and dry eye indicators within specific constitutions or dry eye subtypes. In the analysis of the relationship between 50 TCM syndromes and dry eye subtypes, an initial Spearman’s correlation analysis identified 9 constitutions with correlations to dry eye subtypes. Subsequently, binary unconditional logistic regression was conducted with the 9 TCM syndromes as independent variables and dry eye subtypes as dependent variables to pinpoint the factors influencing TCM syndromes on dry eye subtypes. The statistical tests employed were 2-sided, and a significance level of P < .05 was considered indicative of statistical significance.

3. Results

3.1. General information

3.1.1. Sample size and age

In this study, we enrolled a total of 114 individuals, corresponding to 114 eyes. The participants had an average age of 40.43 ± 13.12 years, with ages ranging from 20 to 73 years. Among the participants, 85 were female, constituting 74.56% of the cohort, and 29 were male, representing 25.44% of the cohort. The participants were categorized into age groups, each spanning a 10-year interval: 20 to 30 years, 31 to 40 years, 41 to 50 years, 51 to 60 years, and over 60 years (Table 1). Notably, the highest incidence of dry eye was observed in the age group of 31 to 40, with a total of 38 cases, constituting 33.33% of the overall participants.

Table 1 Patient Characteristics.

Age (yr)	Number, n (%)	Disease course (mo)	Mixed dry eye, n (%)	Evaporative dry eye, n (%)	Queous tear deficiency dry eye, n (%)	
20–30	28 (24.6%)	27.11 ± 28.14	18 (26.5%)	9 (22.0%)	1 (20%)	
31–40	38 (33.3%)	26.11 ± 21.95	20 (29.4%)	18 (43.9%)	0 (0%)	
41–50	16 (14.0%)	43.63 ± 36.30	8 (11.8%)	7 (17.1%)	1 (20%)	
51–60	24 (21.1%)	44.14 ± 32.99	16 (23.5%)	6 (14.6%)	2 (40%)	
>60	8 (7%)	61.00 ± 45.55	6 (8.8)	1 (2.4)	1 (20%)	
Total	114	34.89 ± 31.33	68 (59.65%)	41 (35.96%)	5 (4.39%)	

3.1.2. Duration of disease

The duration of disease ranged from 6 months to 30 years, with a mean duration of 34.89 ± 31.33 months. The specific disease durations for each of the age groups are described in Table 1.

3.1.3. Classification of dry eye

The distribution of dry eye subtypes within the study cohort is depicted in Table 1 in accordance with the classification defined in TFOS DEWS II.

3.2. TCM constitution

3.2.1. Frequency distribution of TCM constitutions

In order to facilitate clinical observation by researchers, the Nine Constitutional Types in Traditional Chinese Medicine were used as the framework of the survey questionnaire, proposing 60 questions related to traditional Chinese medicine symptoms. Based on the results of the answers for the 60 questions, values are assigned to determine the participants’ constitution. We categorized the constitutions of the 114 participants and conducted an analysis of the distribution of each TCM constitution across different dry eye subtypes. The relative prevalence of TCM constitutions, in descending order, was as follows: Qi-Stagnation Constitution > Blood-Stasis Constitution > Yin-Deficiency Constitution > Qi-Deficiency Constitution > Yang-Deficiency Constitution. Among the 68 participants with mixed-type dry eye, the most commonly observed TCM constitutions were as follows: Qi-Stagnation Constitution > Blood-Stasis Constitution = Yin-Deficiency Constitution > Qi-Deficiency Constitution > Yang-Deficiency Constitution.

Among the 41 participants with evaporative-type dry eye, the predominant TCM constitutions were as follows: Qi-Stagnation Constitution = Yin-Deficiency Constitution > Qi-Deficiency Constitution = Yang-Deficiency Constitution = Blood-Stasis Constitution. Among the 5 patients with aqueous-deficient dry eye, the predominant TCM constitutions were as follows: Blood-Stasis Constitution > Qi-Deficiency Constitution > Qi-Stagnation Constitution > Yin-Deficiency Constitution (Table 2). We carried out a correlation analysis to explore the associations between dry eye subtypes and TCM constitutions. The outcomes revealed a notable correlation between the Blood-Stasis Constitution and aqueous-deficient dry eye (r = 0.223, P = .017; Table 3).

Table 2 Distribution and relationship between TCM constitution types and dry eye subtypes.

Constitution type		Dry eye classification	Total, n (%)	
Mixed dry eye (N1 = 68)	Evaporative dry eye (N2 = 41)	(N3 = 5)	
Peaceful	n (%)	1 (1.47)	0 (0.00)	0 (0.0)	1 (0.88)	
r	0.077	−0.071	−0.020	
P	.413	−.021	.832	
Qi deficiency	n (%)	18 (26.47)	11 (26.83)	2 (40.00)	31 (27.19)	
r	−0.003	−0.021	0.057	
P	.971	.827	.548	
Yang deficiency	n (%)	14 (20.59)	11 (26.83)	0 (0.00)	25 (21.93)	
r	−0.039	0.089	−0.114	
P	.677	.348	.229	
Yin deficiency	n (%)	20 (29.41)	13 (31.71)	1 (20.00)	34 (29.82)	
r	0.005	0.016	−0.050	
P	.960	.863	.600	
Phlegm	n (%)	1 (1.47)	1 (2.44)	0 (0.00)	2 (1.75)	
r	−0.026	0.039	−0.029	
P	.781	.680	.762	
Moisture	n (%)	1 (1.47)	0 (0.00)	0 (0.00)	1 (0.88)	
r	0.077	−0.071	−0.020	
P	.413	.456	.832	
Blood stasis	n (%)	20 (29.41)	11 (26.83)	4 (80.00)	35 (30.70)	
r	−0.018	−0.077	0.223	
P	0.847	0.418	0.017	
Temperament	n (%)	23 (33.82)	13 (31.71)	2 (40.00)	38 (33.33)	
r	0.028	−0.040	0.026	
P	.769	.676	.783	
Special quality	n (%)	2 (2.94)	0 (0.00)	0 (0.00)	2 (1.75)	
r	0.110	−0.100	−0.029	
P	.244	.289	.762	
TCM = traditional Chinese medicine.

Table 3 Correlation analysis between TCM constitution types and dry eye indicators (n = 114).

	Temperament	Blood stasis	Yin deficiency	Qi deficiency	Yang deficiency	Other	
r	P	r	P	r	P	r	P	r	P	r	P	
Tear river height (TMH)	0.002	.986	−0.037	.695	−0.028	.771	−0.124	.190	0.079	.401	−0.016	.870	
 NIKBUT													
 Time to first rupture	0.097	.306	0.155	.099	−0.230	.014	−0.153	.103	0.050	.600	0.075	.430	
 Mean rupture time	0.103	.274	0.098	.298	−0.228	.015	−0.155	.099	0.164	.082	0.004	.965	
 Grading	−0.166	0.078	−0.115	.222	0.283	.002	0.189	.044	−0.163	.083	0.012	.896	
 Tear film lipid layer thickness (LLT)	−0.047	.624	0.036	.703	0.002	.980	0.028	.773	0.025	.797	−0.016	.867	
 Schirmer (no surface hemp)	−0.006	.954	−0.140	.142	0.132	.164	0.075	.431	0.028	.771	−0.092	.335	
 OSDI score													
 OSDI total score	0.090	.368	0.207	.036	0.152	.126	0.136	.171	−0.352	<.001*	−0.018	.856	
 Eye symptoms	0.007	.941	0.141	.159	0.098	.328	0.112	.262	−0.249	.012	−0.070	.487	
 Visual function	0.160	.109	0.145	.145	0.029	.776	0.022	.825	−0.217	.029	0.081	.416	
 Envirnmental factor	0.046	.647	0.214	.031	0.204	.040	0.162	.104	−0.368	<.001*	−0.131	.189	
Image analysis of meibomian glands													
 Upper eyelid	−0.138	.144	−0.088	.350	0.132	.162	0.029	.756	0.115	.222	−0.056	.555	
 Lower eyelid	−0.093	.323	−0.106	.264	0.074	.434	0.016	.862	0.115	.223	−0.154	.101	
 Corneal fluorescein staining total score (CFS)	0.045	.636	−0.004	.968	0.001	.990	−0.069	.468	−0.052	0.583	−0.059	.535	
CFS = corneal fluorescein staining, LLT = lipid layer thickness, NIKBUT = non-invasive tear breakup time, OSDI = Ocular Surface Disease Index, TCM = traditional Chinese medicine, TMH = tear meniscus height.

* P < .001.

3.2.2. Relationship between TCM constitution types and dry eye indicators

We examined the association between prevalent TCM constitution types among all dry eye patients and the indicators of dry eye. The findings revealed the subsequent correlations:

The Blood-Stasis constitution type exhibited positive correlations with elevated scores in OSDI total score (R = 0.207, P = .036) and OSDI environmental factor score (R = 0.214, P = .031).

The Yin-Deficiency constitution type displayed negative correlations with NIKBUT initial breakup time (r = −0.230, P = .014) and average breakup time (r = −0.228, P = .015); it also exhibited positive correlations with NIBUT grading (r = 0.283, P = .002) and OSDI environmental factor score (r = 0.204, P = .040).

The Qi-Deficiency constitution type displayed a positive correlation with increased NIBUT grading (r = 0.189, P = .044). On the other hand, Yang-Deficiency constitution type exhibited negative correlations with reduced scores in OSDI total score (r = −0.352, P < .001), OSDI ocular symptoms (r = −0.249, P = .012), OSDI visual function (r = −0.217, P = .029), and OSDI environmental trigger (r = −0.368, P < .001).

We further categorized participants with dry eye based on the etiology and examined the associations between TCM constitution types and dry eye indicators within each specific dry eye classification. The results were as follows:

Among the 68 participants diagnosed with mixed-type dry eye, it was observed that participants with Yin-Deficiency had a noteworthy increase in their OSDI Environmental Factor Score (r = 0.311, P = .014). Patients with Qi-Deficiency displayed a substantial reduction in tear meniscus height (r = −0.267, P = .028). In contrast, participants with Yang-Deficiency experienced significant declines in OSDI Total Score and OSDI Environmental Factor Score (r = −0.292, P = .020; r = −0.299, P = .018).

In the group of 41 participants diagnosed with evaporative dry eye, participants with a Qi-Stagnation constitution exhibited a noteworthy reduction in NIKBUT grading (r = −0.318, P = .043). Conversely, those with a Yin-Deficiency constitution displayed significant decreases in NIBUT initial breakup time and NIBUT average breakup time, along with noteworthy increases in NIBUT grading (r = −0.348, P = .026; r = −0.381, P = .014; r = 0.418, P = .007). Participants with a Qi-Deficiency constitution demonstrated notable decreases in NIBUT initial breakup time, NIBUT average breakup time, and significant increases in NIBUT grading (r = −0.347, P = .026; r = −0.372, P = .017; r = 0.320, P = .041). Participants with a Yang-Deficiency constitution exhibited significant increases in OSDI Total Score, OSDI Ocular Symptoms Score, OSDI Visual Function Score, and OSDI Environmental Factor Score (r = −0.427, P = .010; r = −0.406, P = .016; r = 0.363, P = .032; r = −0.463, P = .005; Table 4).

Table 4 Correlation analysis between TCM constitution and dry eye indicators under dry eye classification.

		Mixed dry eye	Other	Evaporative dry eye	Aqueous tear deficiency	
Temperament	Blood stasis	Yin deficiency	Qi deficiency	Yang deficiency	Temperament	Blood stasis	Yin deficiency	Qi deficiency	Yang deficiency	Other	Temperament	Blood stasis	Yin deficiency	Qi deficiency	
TMH	r	0.060	0.011	−0.078	−.267*	0.120	0.043	−0.069	−0.168	0.018	−0.023	0.084	−0.141	−0.577	−0.354	0.354	0.866	
P	.624	.927	.527	.028	.331	.727	.669	.294	.912	.885	.602	.380	.308	.559	.559	.058	
NIKBUT																		
 Time to first rupture	r	0.034	0.019	−0.157	−0.053	0.014	0.070	0.179	0.270	−.348*	−.347*	0.154	0.201	0.289	−0.354	0.354	0.289	
P	.785	.875	.202	.670	.910	.568	.262	.088	.026	.026	.338	.209	.638	.559	.559	.638	
 Mean rupture time	r	0.050	0.020	−0.159	−0.053	0.115	−0.050	0.195	0.116	−.381*	−.372*	0.307	0.227	<0.001	−0.354	0.354	<0.001	
	P	.685	.870	.195	.665	.351	.684	.222	.469	.014	.017	.051	.153	1.000	.559	.559	1.000	
 Grading	r	−0.083	−0.052	0.203	0.146	−0.161	0.048	−.318*	−0.121	.418**	.320*	−0.232	−0.147					
	P	.499	.677	.096	.236	.191	.697	.043	.450	.007	.041	.145	.359					
 LLT	r	−0.110	−0.048	−0.034	0.023	0.180	−0.052	0.087	0.175	0.104	0.046	−0.241	0.137	−0.866	<0.001***	<0.001***	0.289	
	P	.372	.698	.782	.849	.141	.675	.597	.286	.528	.782	.140	.404	.058	1.000	1.000	.638	
 Schirmer	r	0.067	−0.116	0.203	0.199	−0.084	−0.082	−0.057	−0.070	0.062	0.027	0.049	0.085	0.577	−0.354	0.354	−0.289	
	P	.594	.352	.103	.109	.500	.510	.725	.662	.701	.867	.763	.595	.308	.559	.559	.638	
OSDI score																		
 OSDI Total Score	r	0.119	0.146	0.186	0.056	−.292*	−0.044	0.018	0.299	0.103	0.227	−.427*	<0.001***	0.289	−0.354	0.354	0.289	
	P	.355	.254	.145	.663	.020	.734	.919	.081	.555	.191	.010	1.000	.638	.559	.559	.638	
 Eye symptoms	r	0.016	0.120	0.055	0.035	−0.169	−0.007	−0.024	0.318	0.085	0.191	−.406*	−0.264	<0.001***	−0.707	0.707	0.577	
	P	.899	.355	.671	.788	.190	.959	.892	.063	.628	.271	.016	.126	1.000	.182	.182	.308	
 Visual function	r	0.163	0.065	0.030	−0.069	−0.140	0.085	0.105	0.318	0.028	0.146	−.363*	0.119	0.444	−0.363	0.363	0.148	
	P	.205	.618	.815	.596	.277	.514	.550	.063	.872	.403	.032	.495	.454	.548	.548	.812	
 Envirnmental factor	r	0.049	0.119	0.311*	0.093	−.299*	−0.131	0.021	0.213	0.143	0.286	−.463**	−0.215	0.304	0.745	−0.745	−0.152	
	P	.703	.358	.014	.473	.018	.309	.904	.218	.413	.096	.005	.214	.619	.148	0.148	.807	
Image analysis of meibomian glands																		
 Upper eyelid	r	−0.115	−0.001	0.078	0.060	0.143	−0.172	−0.244	−0.205	0.195	−0.013	0.077	0.258	0.323	−0.395	0.395	<0.001***	
	P	.352	.994	.525	.629	.243	.161	.124	.198	.221	.937	.633	.104	.596	.510	.510	1.000	
 Lower eyelid	r	−0.098	−0.041	−0.061	0.021	0.185	−0.179	−0.199	−0.279	0.266	<0.001***	0.070	−0.100	0.456	−0.559	0.559	<0.001***	
	P	.427	.743	.623	.866	.131	.144	.211	.077	.093	1.000	.665	.533	.440	.327	.327	1.000	
 CFS	r	−0.046	−0.035	0.075	0.024	0.042	−0.232	0.164	−0.071	0.005	−0.142	−0.172	0.246	<0.001***	0.707	−0.707	−0.577	
	P	.710	.777	.548	.849	.735	.059	.313	.663	.977	.383	.289	.127	1.000	.182	.182	.308	
CFS = corneal fluorescein staining, LLT = lipid layer thickness, NIKBUT = non-invasive tear breakup time, OSDI = Ocular Surface Disease Index, TCM = traditional Chinese medicine, TMH = tear meniscus height.

* P < .05.

** P < .01.

*** P < .001.

3.3. TCM syndromes

3.3.1. Correlation between dry eye classifications and TCM syndromes

We employed Spearman’s correlation analysis to investigate the relationships between TCM syndromes and mixed-type dry eye, evaporative dry eye, and aqueous-deficient dry eye. Among the 50 TCM syndromes assessed, 5 TCM syndromes exhibited significant correlations with mixed-type dry eye, 5 with evaporative dry eye, and 3 with aqueous-deficient dry eye (P < .05; Table 5). To address potential collinearity, we applied Lasso regression to the TCM syndrome data, employing the minimum Cp value as the selection criterion. Based on the analysis, the following TCM syndromes were identified as significantly associated with mixed-type dry eye: “restlessness and irritability,” “sweating with aversion to heat or night sweats,” “dizziness,” and “soreness and weakness of the waist and knees.” For evaporative dry eye, the relevant TCM syndromes were “sweating with aversion to heat or night sweats,” “dizziness,” “dryness of the throat,” “dry mouth,” “bitter taste or stickiness in the mouth,” and “soreness and weakness of the waist and knees.” Notably, no TCM syndrome indicators were found to be associated with aqueous-deficient dry eye (Fig. 2).

Table 5 Correlation analysis of TCM syndromes and dry eye types.

	Mixed dry eye	Evaporative dry eye	Aqueous tear deficiency	
r	P	r	P	r	P	
Irritable	0.195	.038	−0.134	.154	−0.152	.107	
Afraid to sweat or have night sweats	0.206	.028	−0.215	.022	0.009	.927	
Squamous and dry skin	−0.144	.126	0.048	.615	0.234	.012	
Dark complexion	0.028	.770	−0.144	.127	0.270	.004	
Dizziness	0.248	.008	−0.240	.010	−0.031	.746	
Dry throat	0.174	.064	−0.185	.049	0.017	.860	
Bitter or sticky mouth	0.184	.049	−0.209	.026	0.048	.615	
Poor appetite	0.003	.977	−0.129	.170	0.297	.001	
Soreness of the waist and knees	0.205	.028	−0.208	.027	−0.006	.953	

Figure 2. Lasso regression models of dry eye subtypes and TCM constitution types: (a) Lasso regression between mixed-type dry eye and 5 TCM constitution types, (b) Lasso regression between excessive evaporation-type dry eye and 5 TCM constitution types, (c) Lasso regression between deficient aqueous-type dry eye and 3 TCM constitution types.

The TCM syndromes selected via Lasso regression were employed as independent variables, while the presence of mixed-type dry eye or evaporative dry eye in participants served as the dependent variable. We conducted binary unconditional logistic regression, and the results revealed that dizziness and soreness and weakness of the waist and knees were significant factors influencing both mixed-type dry eye and evaporative dry eye (P < .05; Table 6).

Table 6 Binary unconditional logistic regression to assess the impact of TCM syndromes on mixed-type and evaporative dry eye.

Dry eye type	Index	B	SE	Waldx2 value	P value	OR value	95% CI	
Mixed dry eye	Dizziness	1.411	0.517	7.455	0.006	4.101	(1.489, 11.293)	
Soreness of the waist and knees	1.308	0.560	5.461	0.019	3.698	(1.235, 11.076)	
Evaporative dry eye	Dizziness	−1.442	0.547	6.943	0.008	0.236	(0.081, 0.691)	
Soreness of the waist and knees	−1.396	0.601	5.404	0.020	0.247	(0.076, 0.803)	
TCM = traditional Chinese medicine.

4. Discussion

In previous years, numerous scholars have conducted research on the association between dry eye and TCM constitution.[14] Several studies unveiled a strong association between dry eye disease and specific TCM constitutions, notably yin deficiency, yang deficiency, and phlegm stasis constitutions. Among these, yin deficiency constitution was the most prominent, and it was predominantly observed in female patients.[15]

In a study examining the interplay between TCM constitution and anxiety and depression among individuals with dry eye, several noteworthy findings emerged. Specifically, individuals characterized by the yin deficiency dampness heat syndrome were more susceptible to experiencing anxiety and depression. Moreover, those engaged in mentally demanding occupations predominantly exhibited symptoms associated with both qi and yin deficiency. Furthermore, individuals manifesting the spleen stomach dampness heat syndrome were at an elevated risk of meibomian gland dysfunction. Notably, those with yin deficiency dampness heat syndrome tended to have a longer disease duration, while individuals with qi yin deficiency syndrome experienced a relatively shorter disease course.[16]

Another study analyzed the frequency patterns of TCM syndrome types within a cohort of 116 patients with dry eye. The analysis revealed a descending order in the frequency distribution of syndrome types, with kidney deficiency syndrome being the most prevalent, followed by qi yin deficiency syndrome, yin deficiency dampness heat syndrome, and lung yin deficiency syndrome.[17]

The findings from the aforementioned studies largely align with our study results. Nonetheless, it is important to note that the various studies have employed diverse methods for categorizing TCM constitutions, resulting in a lack of standardized classification across the research landscape. Furthermore, changes in lifestyles and physical attributes of patients over time may necessitate further investigations to keep the data up-to-date.

Li,[7] employed the Nine Constitutions Assessment Method of TCM to examine the constitutions of 120 individuals with dry eye in Guangzhou. The analysis led to the identification of the following frequency distribution of traditional Chinese medicine constitutions: Yin-Deficiency Constitution, Damp Heat Constitution, Qi-Deficiency Constitution, Qi-Stagnation Constitution, Yang-Deficiency Constitution, Balanced Constitution, Phlegm-Dampness Constitution, Special Sensitivity Constitution, and Blood Stasis Constitution. Among individuals with dry eye, Yin-Deficiency Constitution and Damp Heat Constitution emerged as the most prevalent constitution types. This constitution classification approach addresses the challenges associated with the diverse and often incompatible TCM constitution classification methods encountered in clinical practice, thereby alleviating statistical complexities. The findings suggest that the TCM constitution characteristics of dry eye in the Lingnan region of China offer valuable insights. However, given regional variations and the need for a more refined classification of dry eye types, further research is warranted.

In light of the aforementioned challenges, we have restructured our research approach and employed the Nine Constitutions Assessment Method[18] to investigate the TCM constitution profiles of individuals with dry eye.

The results of this study revealed that individuals exhibiting the Qi stagnation constitution, blood stasis constitution, and Yin deficiency constitution were at a higher risk of developing dry eye, primarily characterized by the mixed-type and evaporative dry eye subtypes. Notably, individuals with the blood stasis constitution were more susceptible to developing aqueous deficiency dry eye. Furthermore, the examination of the association between TCM constitution and dry eye parameters in individuals with dry eye revealed a positive correlation between OSDI total scores, as well as subscale scores, and the blood stasis constitution, along with the Yin deficiency constitution. This implies that individuals with these constitution types encounter more severe dry eye symptoms, exhibit heightened susceptibility to environmental influences, and experience more intense self-reported symptoms. In contrast, individuals with a Yang deficiency constitution displayed lower OSDI scores, signifying a relatively less pronounced perception of dry eye symptoms. Additionally, the Yin deficiency constitution was linked to a shorter NIKBUT initial breakup time and average breakup time, indicating a greater propensity for developing evaporative dry eye or mixed-type dry eye. The correlation analysis between TCM syndromes and different types of dry eye revealed that symptoms such as dizziness, soreness, and weakness of the waist and knees, irritability, and increased perspiration or night sweats were more prevalent among individuals with mixed-type dry eye and evaporative dry eye. Notably, dizziness and soreness and weakness of the waist and knees displayed a stronger association with Qi stagnation, blood stasis, and Yin deficiency constitutions, which are frequently encountered in individuals with dry eye. Furthermore, a bitter taste or stickiness in the mouth tended to manifest as a systemic symptom in individuals with evaporative dry eye. These findings offer a foundational reference for the clinical treatment of dry eye. In future endeavors, we will continue to accumulate cases and further validate these conclusions while exploring new patterns to consistently enhance and refine dry eye treatment guided by TCM constitution theory.

The Ocular Surface Disease Group’s specialists advocate the approach to addressing dry eye as a chronic ailment. This strategy involves applying TCM constitution theory to evaluate the constitutional attributes and syndrome profiles of individuals with dry eye. The pivotal step is the amalgamation of these insights with the clinical presentations of dry eye, as this integration is essential for crafting personalized preventive and therapeutic interventions. Such an approach is effective in diminishing the occurrence of dry eye and enhancing clinical results.[19] Recognizing the TCM constitution of a patient and the associated TCM interventions constitute integral facets of TCM clinical practice, epitomizing the core of TCM syndrome discrimination and individualized therapy. The Nine Constitution Types of TCM represents an extensively employed classification system for TCM constitutions in clinical investigations. Presently, extensive research efforts are dedicated to exploring TCM constitution within different branches of internal medicine.[20] Within the field of ophthalmology, investigations have examined the relevance of TCM constitution in the context of primary open-angle glaucoma.[21,22]Dry eye is characterized by a high prevalence, impacting a broad cross-section of the population, and significantly influencing patients’ work and quality of life. While modern medicine has made advancements in comprehending the underlying etiology of dry eye and provides a range of therapeutic choices, it remains insufficient in fully addressing the clinical requirements. Notably, TCM syndrome differentiation and treatment exhibit substantial advantages in effectively managing specific challenging cases of dry eye. However, it is crucial to recognize the limitations of this study, including a relatively small sample size, gender imbalance, and the lack of data on lifestyle and eye-related habits associated with dry eye. These limitations could potentially impact the robustness of the research findings, particularly concerning the relationships between syndrome, symptoms, and clinical signs. Therefore, we hope that this study will lay the groundwork and stimulate the formulation of a systematic, prospective research framework, incorporating large-scale, multicenter epidemiological inquiries, in the pursuit of establishing a standardized system for researching TCM constitution in the context of dry eye.

5. Conclusion

In this study, we explored the complex relationship between TCM constitution, different dry eye subtypes, and diagnostic markers associated with dry eye. This study provided an initial exploration into their distribution patterns and potential correlations. Additionally, our study has unveiled correlations between TCM syndrome patterns and dry eye indicators. Our initial analysis of the distribution of TCM constitutions among individuals with dry eye shows potential directions for future TCM research on dry eye and lays a foundation for the convergence of Chinese and Western medical approaches in addressing dry eye management.

Author contributions

Conceptualization: Ying Jie.

Data curation: Yihan Guo.

Investigation: Jing Yu, Lei Tian, Lixin Qiu, Xiaoniao Chen, Kai Cao, Lei Zhu.

Resources: Jing Yu, Yihan Guo, Lixin Qiu, Xiaoniao Chen, Kai Cao.

Software: Kai Cao.

Supervision: Ying Jie.

Validation: Lei Zhu.

Writing – original draft: Yihan Guo, Jing Yu.

Abbreviations:

TCM traditional Chinese medicine.

This study was supported by “Beijing Municipal Administration of Hospitals Incubating Program” (PZ2020002).

The authors have no conflicts of interest to disclose.

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

How to cite this article: Yu J, Guo Y, Tian L, Qiu L, Chen X, Cao K, Zhu L, Jie Y. Investigation of traditional Chinese medicine constitution in individuals afflicted by dry eye disease: A retrospective study. Medicine 2024;103:38(e39675).

JY and YG contributed equally to this study.
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