Epiphora often indicates an obstruction in the lacrimal duct system arising from diverse etiological factors (1). The drainage system is anatomically divided into proximal and distal segments. These obstructions, whether of congenital or acquired origin, may lead to chronic epiphora and mucopurulent discharge (2). Acquired lacrimal duct obstruction (LDO) can result from multiple causes, including severe viral conjunctivitis, chemical burns, chemotherapy, blepharitis, and prior trauma (3). Clinical observations have revealed that patients with a history of anterior uveitis (AU) frequently present significant adhesive obstructions in their lacrimal ducts, indicating a potential association between AU and these obstructions. Chronic inflammation in AU may lead to cytokine-driven fibrosis—mediated by factors such as IL-6 and TNF-α, potentially causing lacrimal duct epithelial damage and adhesion. This hypothesis is supported by elevated tear cytokine levels in uveitis patients (4). The management of such cases remains a significant therapeutic challenge, and surgical interventions often yield suboptimal outcomes. To investigate this relationship more thoroughly, a retrospective analysis was conducted on 40 patients who were diagnosed with and treated for LDO. This study aimed to examine and evaluate the clinical characteristics of patients with LDO and a history of AU, specifically focusing on those treated at the Third Medical Center of the Chinese People’s Liberation Army General Hospital.

General demographic data, including sex, age, and other relevant characteristics, were collected. Clinical data collected included several parameters: the timing of the onset of epiphora and initial AU, ocular laterality of epiphora, systemic conditions associated with AU, anatomical location and extent of LDO, severity of obstruction, surgical intervention methodology, and therapeutic outcomes. A comparative analysis was performed between patients with a history of AU and a control cohort comprising individuals with LDO, but no history of uveitis during the same period. Demographic factors (age and sex), ocular involvement, anatomical characteristics of the LDO (location and extent), obstruction severity, and treatment efficacy were compared between the two groups.

The lacrimal drainage system consists of the lacrimal puncta, upper and lower canaliculi, common lacrimal duct, lacrimal sac, and nasolacrimal duct (2). Stenosis or obstruction of any segment of the system can result in varying degrees of epiphora. Lacrimal punctal and canalicular obstruction, alternatively termed proximal LDO (5), is characterized by a membranous obstruction anterior to the lacrimal sac and includes various obstructive conditions, such as lacrimal puncta stenosis, canalicular obstruction, and common canalicular obstruction (6). Lacrimal canalicular obstruction was further classified as proximal lacrimal canalicular obstruction (<4 mm from the lacrimal punctum), middle lacrimal canalicular obstruction (≥4 mm and ≤8 mm from the lacrimal punctum), or distal lacrimal canalicular obstruction (>8 mm from the lacrimal punctum) (1). The etiology of lacrimal punctal and canalicular obstruction is complex and involves multiple factors, including bacterial and viral infections, ocular surface diseases, medication use, chemical burns, and cicatricial conditions (6).

Lacrimal punctal obstruction, a common cause of epiphora with reported incidence rates between 8 and 54.3% (1), manifests in either congenital or acquired forms. Congenital absence of the lacrimal puncta typically results from a developmental failure of the lacrimal canaliculus to bud from the superior portion of the solid lacrimal cord during the embryonic stage of 18–24 mm (7). The pathogenesis of acquired lacrimal puncta obstruction involves multiple factors, including age-related degenerative changes, such as eyelid relaxation, displacement, and ectropion (8). Contributing factors encompass chronic blepharitis; viral and bacterial infections, including chlamydia, herpes simplex virus, actinomycetes, and human papillomavirus (9, 10); and systemic and topical medications, including 5-fluorouracil, docetaxel, and paclitaxel (11). Furthermore, various systemic conditions, including enteropathic acrodermatitis, porphyria tarda, Stevens–Johnson syndrome, ocular cicatricial pemphigoid, and graft-versus-host disease, may lead to lacrimal puncta obstruction (11).

Canalicular obstruction constitutes 16–25% of epiphora cases (7) and manifests as either a congenital or acquired condition. Unilateral or bilateral canalicular hypoplasia occurs in 4% of patients and may present in isolation or alongside other developmental abnormalities (12). Various conditions can result in canalicular obstruction, including conjunctivitis, chronic blepharitis, cicatricial pemphigoid, Stevens–Johnson syndrome, and lichen planus. In addition, chemical and thermal burns, traumatic lacerations, skin cancer, papilloma, and radiotherapy can affect the canalicular system, leading to obstruction (11). Furthermore, several medical interventions can lead to canalicular stenosis or obstruction, including verteporfin photodynamic therapy for choroidal neovascularization (13), local anti-glaucoma medications (14), and chemotherapeutic agents, such as 5-fluorouracil, docetaxel, mitomycin C, and pemetrexed (15, 16). Additional contributing factors to LDO include dislodgment of lacrimal plugs (11) and iatrogenic trauma.

This study demonstrated that patients with a history of AU predominantly displayed proximal obstruction, including lacrimal punctal atresia and/or proximal LDO. By contrast, the control group, without a history of AU, primarily presented with distal LDO, with this difference between the groups showing statistical significance. LDO in patients with AU occurs in the segment anterior to the lacrimal sac. However, the relationship between AU and LDO has not been reported in existing literature and is worthy of further investigation.

Uveitis, characterized by inflammation of one or more components of the uveal tract (17), is a significant cause of vision loss worldwide (18). This condition accounts for 10% of blind cases in industrialized nations (19) and approximately 25% of irreversible blindness cases in developing countries (20). With an estimated annual incidence of 17 cases per 100,000 people (19, 21), uveitis predominantly affects individuals aged 20–50 years (22). The condition is classified into infectious and non-infectious uveitis based on etiology, with non-infectious cases occurring more frequently.

AU represents the most common manifestation of uveitis (23). This condition encompasses three subtypes: iritis, iridocyclitis, and anterior ciliary body inflammation. Research data demonstrate that AU accounts for 30–73% of all uveitis cases, with associated blindness rates ranging from 0.6 to 11% (16, 19). Common clinical presentations include ocular redness, photophobia, lacrimation, and impaired vision. Visual deterioration may result from inflammatory processes and subsequent complications, such as macular edema, glaucoma, and cataract formation. This condition primarily affects individuals aged 20–40 years (64%) and is less prevalent in those aged >60 years (10%) (21).

The current study found that patients with a history of LDO and AU had a mean age of 49.88 years (range: 24–66 years), which is consistent with existing literature. In Western nations, the predominant forms of AU are HLA-B27 (+) uveitis, Fuchs’ heterochromic iridocyclitis, and herpes zoster uveitis (24). HLA-B27-related AU and syphilitic uveitis occur more frequently in men, whereas women more frequently experience chronic AU associated with juvenile idiopathic arthritis, multiple sclerosis, granulomatous disease, and Vogt–Koyanagi–Harada disease. Evidence suggests that non-infectious AU occurs more frequently in women (23). Moreover, the incidence of LDO is higher in women. Female predominance was notable in uveitis-associated lacrimal obstruction (75% women vs. 25% men), consistent with the higher prevalence of chronic AU in women.

This study investigated the initial onset of AU in 40 patients with a history of LDO and AU. The mean onset interval was 10.02 years, with patients experiencing tearing for an average of 5.20 years before uveitis diagnosis. All patients with a history of AU were HLA-B27 positive, and 11 were diagnosed with ankylosing spondylitis (four men and seven women). Intraoperative examination revealed extensive adhesive obstruction of the lacrimal duct in 32 cases, whereas eight cases exhibited no extensive adhesive obstruction. Statistical analyses demonstrated significant differences between the experimental and control groups, indicating that patients with a history of AU predominantly present with extensive adhesions within their lacrimal ducts. Furthermore, AU may cause tearing symptoms that mimic inflammatory recurrence, potentially leading to misinterpretation of these symptoms and a consequent delay in lacrimal duct examination. As epiphora becomes apparent, LDO frequently progresses to a severe and extensive stage.

The literature presents a comprehensive treatment framework for proximal LDO. For patients with LDO, established procedures include three-snip punctoplasty or punctal dilation in conjunction with either single or double lacrimal duct stents, such as the Mini-Monoka, O’Donoghue, Crawford tube, or Ritleng tubes (11). Recent studies have introduced canaliculotomy as a viable treatment option for lacrimal punctal and canalicular atresia (25). Patients with severe lacrimal canalicular obstruction can be classified into three categories: (1) patients with proximal lacrimal canalicular obstruction, who require dacryocystorhinostomy with retrograde catheterization (26); (2) patients with middle lacrimal canalicular obstruction, for whom treatment options include retrograde catheterization via dacryocystorhinostomy, insertion of an LJT/StopLossTM tube combined with conjunctival dacryocystorhinostomy, or utilization of a LacriJetTM tube with a trephine; and (3) patients with distal lacrimal canalicular obstruction, for whom the standard approach is conjunctival dacryocystorhinostomy with an LJT/StopLoss tube or trephine surgery combined with artificial lacrimal duct insertion.

Among patients with a history of AU, the treatment outcomes were as follows: 8 achieved complete cure, 21 demonstrated improvement, and 11 showed no improvement. Multivariate logistic regression analysis examining the correlation between treatment outcomes and AU revealed that the surgical group had significantly poorer results than those of the control group.

Research work indicates that uveitis is strongly associated with inflammatory and immune cytokines, including tumor necrosis factor, interleukin 1 (IL-1), IL-2, IL-6, IL-8, and interferon gamma (IFN-γ) (27). Patients with uveitis have elevated levels of cytokines and chemokines in the serum and aqueous humor (28, 29). Additionally, tear samples from these patients show significantly higher concentrations of IL-1RA, IL-8/CXCL8, fractalkine/CX3CL1, IP-10/CXCL10, vascular endothelial growth factor (VEGF), and TGF-β2 compared to those of healthy individuals (4). A total of 10 proinflammatory cytokines, including matrix metalloproteinase 9, serine protease E1, IL-6, hepatocyte growth factor, VEGFA, VEGFR2, platelet endothelial cell adhesion molecule 1, C-reactive protein, chemokine ligand 2, and platelet-derived growth factor-AA (PDGF-AA), are significantly upregulated in patients with nasolacrimal duct obstruction (nasoLDO) (30). Wang et al.’s preliminary investigation of cytokines in the tears of patients with LDO indicated that inflammatory factors play a fundamental role in disease onset and progression (31). Elevated concentrations of IFN-α2a, IFN-β, IFN-γ, IL-17A, IL-6, IL-8, tumor necrosis factor-α, and VEGF-A may serve as predictive markers for lacrimal duct obstructive disorders. Considering the critical role of cytokines in the pathogenesis of duct obstruction, evidence suggests an association between AU and this condition.

Inspired by those studies and considering the significant role of cytokines in the pathogenesis of LDO, we believe that there is a tight association between AU and LDO. Elevated levels of IL-6 and TNF-α in uveitis patients may promote fibroblast activation and collagen deposition, leading to lacrimal duct fibrosis. This finding aligns with our finding of extensive adhesions in 80% of surgical cases, suggesting chronic inflammation as a key driver of obstruction. This condition primarily affects women, with the obstruction most commonly occurring anterior to the lacrimal sac, specifically involving lacrimal punctal atresia and proximal lacrimal canalicular blockage. These conditions frequently result in substantial adhesion. Clinicians should maintain a high index of suspicion for proximal lacrimal obstruction in uveitis patients, particularly among women presenting with refractory epiphora.

To establish a definitive correlation between AU and duct obstruction, extensive data collection and multicenter follow-up studies are required. This research necessitates large-scale sample analysis, histopathological examination, and investigation of cytokine concentration variations in affected patients. Such a systematic investigation is critical for studying the pathogenic mechanisms underlying these conditions and for establishing a foundation to examine the relationship between AU and duct obstruction, ultimately facilitating the development of effective preventive measures.

In this study, we summarize clinical characteristics of LDO patients with prior AU, revealing distinctive features such as lacrimal punctal atresia, proximal canalicular obstruction, and extensive adhesive obstructions that present significant therapeutic challenges. We explored the relationship between AU and LDO from multiple perspectives, including statistical analysis and the study of inflammatory and immune cytokines. Our findings indicate that clinicians should maintain a high index of suspicion for proximal lacrimal obstruction in uveitis patients, particularly in women presenting with refractory epiphora. Future research will focus on establishing a definitive correlation using a large sample size from multiple centers.