The etiological spectrum of epiphora: Functional epiphora as an overlooked cause

Abstract

Purpose:

To investigate the etiologies of patients presenting with epiphora at a tertiary hospital ophthalmology clinic and the frequency of functional epiphora among these etiologies and to examine the diagnostic value of the combined use of lacrimal syringe and dacryoscintigraphy (DSG).

Methods:

The patients who presented with symptomatic epiphora between January 2022 and December 2023 and who underwent ophthalmologic examination, lacrimal syringing, and DSG were retrospectively evaluated. The cause of epiphora was determined based on patient history, clinical examination, and test results.

Results:

This study included 247 eyes from 159 patients, consisting of 57 (36%) males and 102 (64%) females. The mean age of the patients was 54.9 ± 15.57 years (range, 19–88 years). The duration of symptoms was 47.1 ± 28.0 months (range, 3–120 months). The most common cause of epiphora was nasolacrimal duct (NLD) obstruction found in 76 (30.7%) cases. Functional epiphora, found in 56 eyes (22.6%), was the second most common cause of epiphora. Reflex tearing was the cause of epiphora in 45 eyes (18.2%). Other causes of epiphora included eyelid malposition (in 40 eyes, 16.1%), multifactorial epiphora (in 24 eyes, 9.7%), and pre-sac obstruction (in 6 eyes, 2.4%). Functional epiphora was more common in females and often unilateral.

Conclusion:

Although NLD obstruction is the most common cause of epiphora, functional epiphora is a more frequent cause than previously anticipated. Observing complete patency in the lacrimal syringing is insufficient to rule out NLD stenosis and functional problems.

In ophthalmology practice, epiphora is a common patient complaint that is critical for both differential diagnosis and management. Although epiphora does not threaten vision, it significantly reduces the quality of life by affecting daily activities.[1] The lacrimal process includes the steps of tear production in the lacrimal gland, spreading over the ocular surface through blinking, and the elimination of tears from the ocular surface both by evaporation and through the lacrimal drainage system, which includes the puncta, canaliculi, lacrimal sac, and nasolacrimal duct. An abnormality in any of these stages, categorized as either reflex excessive tearing or insufficient drainage, can cause epiphora.[2] While reflex tearing can be seen due to rare causes like abnormal regeneration after facial paralysis, it often arises due to ocular surface diseases such as dry eye disease or conjunctivochalasis.[3,4] Tear drainage impairment can result from eyelid malposition such as ectropion or punctal eversion, eyelid laxity causing lacrimal pump failure, or obstruction at the level of the punctum, canaliculus, lacrimal sac, or nasolacrimal duct.[5] The simultaneous combination of multiple causes leading to epiphora is termed “multifactorial epiphora”.[1] In cases where the lacrimal system is anatomically normal but functionally insufficient, it is referred to as “functional epiphora”.[6]

Various methods such as lacrimal syringing, Jones test, canalicular probing, dacryocystography (DCG), dacryoscintigraphy (DSG), and lacrimal endoscopy can be used to understand the cause of epiphora.[7] Among these, DSG is a simple and noninvasive test used to determine whether the pathology is due to an anatomical problem or a nonanatomical functional delay.[8,9,10] There are numerous studies examining and classifying the causes of epiphora. While some of these studies primarily cite dry eye disease as a leading cause of reflex tearing, others indicate various levels of nasolacrimal duct obstruction as the most common cause.[4,5] However, it is observed that the number of studies mentioning functional epiphora is quite limited.[6] The aim of this study is to investigate the etiologies of patients complaining of epiphora who applied to a tertiary hospital ophthalmology clinic and the frequency of functional epiphora among these etiologies and to examine the diagnostic value of the combined use of lacrimal syringe and DSG.

Methods

The medical records of patients who presented with symptomatic epiphora to the ophthalmology outpatient clinic of Konya City Hospital between January 2022 and December 2023 and who underwent ophthalmologic examination, lacrimal syringing, and DSG were retrospectively evaluated. The study protocol was approved by the local ethics committee (KTO Karatay University Faculty of Medicine Ethics Commitee, Konya, Türkiye, Date: 09/05/2024, and Number: 2024/05), and the study was conducted in accordance with the principles of the Helsinki Declaration. Patients with a history of lacrimal drainage system surgery or ocular surgery, a history of ocular trauma, facial nerve paralysis, or active ocular infection during the examination were excluded from the study.

The cause of epiphora was determined based on patient history, clinical examination, and test results. Demographic data such as age and gender, the duration of symptoms, and whether the condition was unilateral or bilateral were recorded. Symptoms related to the dry eye such as burning, foreign body sensation, itching, watery eyes, and blurred vision were noted. Complaints of constant tearing and discharge, independent of time and place, were recorded as symptoms related to obstruction. All cases underwent slit-lamp biomicroscopic examination, Schirmer test, tear break-up time, and fluorescein staining test. During slit-lamp examination, eyelid position and laxity; presence of entropion, ectropion, and trichiasis; and the location and patency of the puncta were noted. The presence of blepharitis and meibomian gland dysfunction in the eyelids, and the presence of ocular surface disorders such as pterygium, pinguecula, or conjunctivochalasis were evaluated.

Lacrimal syringing was performed using a 2 ml lacrimal cannula. The lacrimal cannula was advanced vertically 1–2 mm along the punctum and canaliculus. The presence of hard or soft stop was evaluated, and soft stop was accepted as pre-sac obstruction. Patients were asked whether they felt the saline in the nasal cavity, and, if present, the degree of reflux was recorded. Patency on syringing was defined as saline being felt in the nasal cavity or reflux of less than 20%. All patients with suspected possible nasolacrimal duct pathology had undergone DSG to rule out functional epiphora. For DSG, patients were seated upright in front of a gamma camera, and 1 cc of 0.5 microcurie technetium-99 m pertechnetate was instilled into the inferior fornix of each eye. Dynamic imaging was immediately initiated, with sequential images taken every minute for the first 10 minutes, followed by static images at 15, 20, 25, 30, and 45 minutes. During the procedure, the appearance of the tracer in the lacrimal sac, lacrimal duct, or nasal cavity and the times of entry into these locations were recorded by the same experienced observer. Results were classified as normal or delayed transit based on the time taken for the tracer to reach the nasal cavity. A cutoff time point of 5 minutes was used to determine the grading of each patient.[11,12] The concordance rate between lacrimal syringing and DSG was quantified as the proportion of cases with aligned results (either patent/normal or obstructed/delayed) among all evaluated cases.

Patients presenting with dry eye disease, meibomian gland dysfunction, conjunctivochalasis, or trichiasis initially received targeted treatment. In cases where hyperlacrimation persisted despite therapeutic intervention, DSG was performed to exclude underlying nasolacrimal duct pathology.

The primary researcher (N.Ö.A) classified the most significant cause of epiphora into subcategories based on predetermined criteria: (Ia) pre-sac obstruction (punctal stenosis and canalicular stenosis); (Ib) post-sac obstruction (nasolacrimal duct obstruction including mucocele and dacryocystitis); (II) eyelid malposition (entropion, ectropion, punctal eversion) or lacrimal pump failure (lower lid laxity without eyelid malposition); (III) reflex tearing (ocular surface diseases such as dry eye disease, pterygium, blepharitis, or meibomian gland dysfunction); (IV) functional epiphora (patency confirmed by syringing, exclusion of other causes by clinical examination, presence of functional delay in DSG[6,7,8,9]); and (V) multifactorial epiphora (the combination of two or more of these causes).

All descriptive statistical analyses were performed using SPSS software (SPSS Inc. version 22). Normal distribution was checked using skewness and kurtosis tests and histograms. Continuously variable data showing normal distribution were described as mean ± SD. Categorical variables between groups were compared using the Chi-square test, while continuous variables were compared using the independent t-test. A P value of less than 0.05 was considered statistically significant.

Results

This study included 247 eyes from 159 patients, consisting of 57 (36%) males and 102 (64%) females. The mean age of the patients was 54.9 ± 15.57 years (range, 19–88 years). The duration of symptoms was 47.1 ± 28.0 months (range, 3–120 months). Symptoms were unilateral in 71 (45%) cases and bilateral in 88 (55%) cases.

The demographic and clinical characteristics of the patients are shown in Tables 1 and 2. The most common cause of epiphora was nasolacrimal duct obstruction found in 76 (30.7%) cases. Among these, 36 (47.3%) had a nasolacrimal stenosis, while 40 (52.6%) had a nasolacrimal obstruction. Functional epiphora, found in 56 eyes (22.6%), was the second most common cause of epiphora. Among cases with functional epiphora, 5 (8.9%) had pre-sac delay, while 51 (91.0%) had post-sac delay. Reflex tearing was the cause of epiphora in 45 eyes (18.2%). Other causes of epiphora included eyelid malposition (in 40 eyes, 16.1%), multifactorial epiphora (in 24 eyes, 9.7%), and pre-sac obstruction (punctal stenosis and canalicular stenosis) (in 6 eyes, 2.4%).

Table 1.

Demographic and clinical characteristics of patients with epiphora

Etiology	Patients (n, %)	Gender (Male/female ratio)	P	Laterality (Unilateral/Bilateral)	P
Nasolacrimal duct obstruction	76 (30.7%)	28/48 (36.8%/63.1%)	<0.001*	55/21 (72.3%/27.6%)	<0.001*
Functional epiphora	56 (22.6%)	25/31 (44.6%/55.3%)	0.25	35/21 (62.5%/37.5%)	0.008*
Reflex tearing	45 (18.2%)	21/24 (46.6%/53.3%)	0.52	9/36 (20%/80%)	<0.001*
Eyelid malposition	40 (16.1%)	24/16 (60%/40%)	0.07	17/23 (42.5%/57.5%)	0.17
Multifactorial epiphora	24 (9.7%)	15/9 (62.5%/37.5%)	0.08	10/14 (41.6%/58.3%)	0.24
Pre-sac obstruction	6 (2.4%)	2/4 (33.3%/66.6%)	0.24	(4/2) (66.6%/33.3%)	0.24

n: number of eyes; *statistically significant

Table 2.

The mean age of patients with epiphora according to gender and etiology

Etiology	Gender
	Male (mean±SD, years)	Female (mean±SD, years)
Nasolacrimal duct obstruction	58.4±14.3	56.1±10.3
Functional epiphora	60.8±10.3	57.8±8.9
Reflex tearing	52.4±12.5	50.8±12.5
Eyelid malposition	61.2±11.3	57.3±7.8
Multifactorial epiphora	55.2±7.5	54.6±9.2
Pre-sac obstruction	51.7±14.8	52.8±9.1

Ocular surface diseases causing reflex tearing were dry eye disease (n = 24, 53.3%), conjunctivocalasis (n = 13, 28.8%), blepharitis (n = 7, 15.5%), allergic conjunctivitis (n = 3, 6.6%), and trichiasis (n = 1, 2%). When the etiologies of epiphora were compared in terms of laterality, nasolacrimal duct obstruction and functional epiphora were significantly more unilateral, while reflex tearing was significantly more bilateral (P < 0.05). Considering gender, nasolacrimal duct obstruction was significantly more common in females than in males (P < 0.001). Last, the concordance rate between lacrimal syringing and DSG was 70.0%.

Discussion

According to our results, the most common causes of epiphora were post-sac anatomical obstruction and stenosis, and functional epiphora, accounting for 30.7% and 22.6% of cases. This result is similar to the rates reported in previous studies for nasolacrimal duct obstruction (26% and 33.3%).[3,6] However, some studies report higher rates of nasolacrimal duct (NLD) obstruction but lower rates of functional epiphora.[6] This discrepancy may arise because both NLD obstruction and stenosis—alongside patent but dysfunctional lacrimal systems—are often grouped under the same diagnostic category. Consequently, many functional epiphora cases could be misclassified as post-sac drainage disorders. Therefore, failure to adequately evaluate functional delay might have led to confusion or combination with other causes of epiphora, leading to insufficient recognition in previous studies.

However, according to our findings, the second most common cause of epiphora was functional epiphora. In our study, we defined the diagnosis of functional epiphora as confirmed patency by irrigation, exclusion of other causes in clinical examination, and the presence of functional delay in DSG.[6,9] As previously described, in a patient presenting with epiphora, tests that can be performed to understand the etiology are lacrimal syringing, Schirmer’s test, Jones test, DCG, DSG, lacrimal endoscopy, computed tomography, and nasal endoscopy.[2,3,4] Although lacrimal irrigation is a simple and easy procedure, it is not a physiological test by nature as it is performed with a more pressurized fluid flow than normal conditions. Additionally, it does not have high sensitivity because it does not determine the exact location of the obstruction. While many studies report that lacrimal irrigation is the first test performed for epiphora, there is no consensus on the superiority of tests in evaluating epiphora. On the other hand, ophthalmologists seem to prefer conventional methods to radiological tests when evaluating epiphora in the clinic. However, in this way, the lacrimal system, which is found patent by syringing but actually nonfunctional, is incompletely evaluated.[7] In the study of Usmani et al.,[6] which is compatible with our results, the rate of functional epiphora was reported as 26%, and it was shown that using lacrimal syringing as the sole criterion for investigating the cause of epiphora would not be reliable in distinguishing between nasolacrimal duct stenosis and functional epiphora. Similarly, Shapira et al.[8] compared the combined findings of lacrimal syringing with DCG and DSG to explain the role of lacrimal syringing in evaluating nasolacrimal duct stenosis and nonanatomical functional delay. The authors reported that complete patency with irrigation is not reliable for distinguishing between NLD obstruction and functional delay, and a positive irrigation test could be related to functional delay.

On the other hand, although functional epiphora is mentioned as a separate category in the literature, there are studies suggesting that it is not sufficiently represented as a cause of epiphora. In these studies, patency is evaluated only by lacrimal syringing and/or Jones test.[9,13] In the study by Bukhari et al.,[14] which reported the rate of functional epiphora as 1.7%, it was mentioned that only lacrimal syringing was performed, and the diagnosis of functional epiphora was made by excluding all other causes. In the study by Williams et al.,[3] functional epiphora was defined as patients with normal probing and irrigation without an obvious cause for epiphora, and the rate of functional epiphora among the causes of epiphora was reported as 6.9%. These results indicate that lacrimal syringing alone is insufficient in determining the exact region of obstruction and in distinguishing between stenosis and nonanatomical functional obstruction.[8,9] However, when DSG is used in combination with lacrimal syringing in the evaluation of epiphora, a large proportion of functional epiphora cases can be diagnosed.

The diagnostic accuracy of the etiology of epiphora is a critical parameter that directly affects the surgical planning process and postoperative outcomes; therefore, it should be meticulously addressed in the pathophysiologic evaluation. Although some oculoplastic surgeons plan DCR surgery without further investigation if they suspect a lacrimal drainage disorder, the surgical outcomes of complete anatomical obstruction, partial obstruction, and functional delay may differ. Cheung et al.[15] compared preoperative and postoperative symptoms in patients undergoing DCR for functional delay and primary acquired nasolacrimal duct obstruction. Postoperatively, the percentage of patients suffering from each type of symptom decreased in the functional delay group, whereas the percentage of patients reporting each symptom in the obstruction group decreased only in some areas. Brewis et al.[16] performed endoscopic DCR in patients with functional obstruction and reported that 65% of the patients had complete recovery, 13% had partial recovery, and 22% had no recovery in the postoperative period. Shapira et al.[17] compared lacrimal intubation and endoscopic DCR in patients with functional obstruction and recovery after intubation was approximately 59%, while recovery after endoscopic DCR was 91%. In summary, these results suggest that the differentiation of complete anatomical obstruction, partial obstruction, and functional delay can help in the choice of surgical option and this may affect postoperative results.

The etiology of functional epiphora has not yet been fully elucidated, and there are many different hypotheses.[18] Rosenstock et al.[19] suggested that dysfunction of the peri-ductal vascular plexus with spirally arranged collagen fibrils that facilitate tear flow may be responsible for functional epiphora. Park et al.[20] reported that aquaporin expression in the lacrimal sac epithelium was higher in functional obstruction than in primary NLD obstruction; therefore, functional obstruction may be a precursor of anatomical NLD obstruction. Mishra et al.[21] reported intermittent functional epiphora associated with dacryolithiasis obstructing the junction of the lacrimal sac and nasolacrimal canal. Therefore, further clinical studies are needed to investigate the etiology of functional epiphora and to shed light on this issue.

In our study, the eyelids and ocular surface of the patients were examined in detail during the preoperative examination and the presence of concomitant pathologies such as entropion, ectropion, trichiasis, conjunctivochalasis or dry eye disease was specifically evaluated. In these patients, DSG testing was performed after appropriate treatment had been initiated and hyperlacrimation had not been partially or completely resolved. Therefore, it is critical to perform a detailed anamnesis, thorough clinical examination, and relevant procedures before performing DSG in cases where other causes of epiphora have been excluded. The reason for performing DSG in such suspicious cases was that we wanted to investigate whether there was an anatomical obstruction or functional delay accompanying these pathologies. Indeed, a recent cross-sectional, observational study showed that the prevalence of dry eye disease in patients with NLD obstruction was 29.1% and that this was particularly likely to occur in older patients, those with hypertension, and those with a positive regurgitation sign in the pressure over the lacrimal sac.[22] On the other hand, epiphora caused by primary NLD obstruction has also been shown to result in lower tear osmolarity.[23] Moreover, postmenopausal women with primary NLD obstruction have been reported to have significant meibomian gland loss.[24] However, it is important to note that the use of the DSG test should not be considered a universal solution for all patients with epiphora. Rather, its application should be a judicious decision, made after a comprehensive clinical evaluation and a thorough consideration of all available treatment options.

On the other hand, the reason for performing DSG in patients with NLD obstruction detected by lacrimal syringing was to determine the level of obstruction.[7,8] Indeed, it has been suggested that DSG may be useful in predicting postoperative success in patients with epiphora.[25] Although DSG and DCG have good agreement in detecting and localizing obstruction in primary acquired NLD obstruction, DCG examination is considered to be more painful.[26] Similarly, in the study by Chung et al.,[27] patients were classified according to DSG results as those with delayed distal NLD (class I), delayed proximal NLD (class II), and delayed secretion from the prelacrimal sac to the lacrimal sac (class III). The authors reported symptomatic improvement in the postoperative period in all 6 cases of distal NLD obstruction (100%), 14 of 18 cases of proximal obstruction (77.8%), and 8 of 12 cases of prelacrimal obstruction (66.7%). Therefore, it can be useful to determine the level of obstruction by DSG in patients with NLD obstruction detected by lacrimal syringing. Furthermore, it has been suggested in the literature that lacrimal syringing is inadequate to precisely localize the obstruction and has the potential to miss abnormalities in the lacrimal drainage pathway.[28] Since lacrimal syringing depends on the experience and subjective assessment of the practitioner, it has been reported to give false negative or false positive results.[29] These results suggest that when investigating the etiology of epiphora, it may be useful to use and interpret lacrimal syringing in combination with more sensitive and objective methods such as DSG for a more accurate and comprehensive evaluation in appropriate and necessary patients.[30] According to our results, the concordance rate between lacrimal syringing and DSG was 70.0%.

Another common cause of epiphora in our study was reflex tearing, accounting for 18.2% of cases. Our results were similar to those of Sibley et al.,[5] who reported that reflex tearing due to evaporative dry eye accounted for 29% of epiphora cases, and Williams et al.,[3] who reported 22%. Additionally, we detected eyelid malposition as the cause of epiphora in 16.1% of cases. In the study by Nemet et al.,[1] the rate of eyelid malposition as the etiology of epiphora was 33.3%. However, in many studies, the rate of epiphora associated with eyelid malposition is reported between 1.25% and 12.6%.[3,4,31,32,33] When multiple causes complexly lead to epiphora, it is referred to as multifactorial epiphora. In various studies, the rate of multifactorial epiphora is reported as 22–28.7%.[1,5] In our study, we detected multifactorial epiphora at a rate of 9.7%. We believe that the low rate in our study is due to the precise determination of the cause of epiphora with detailed clinical examination and imaging, whereas in other studies, cases, where the cause was not fully identified, might have been included in the multifactorial epiphora category. According to our findings, the rate of pre-sac obstruction among the causes of epiphora was 2.4%. Although the rates of pre-sac obstruction among all causes of epiphora are reported between 4.2% and 11% in the literature,[6] it is understood that in these studies, the diagnosis of canalicular obstruction was made only by the presence of a “soft stop” during lacrimal syringing in the examination and reflux from the same or opposite punctum.

When the demographic results of our study were analyzed, it was observed that functional epiphora, NLD obstruction, and reflex tearing were significantly more common in women than in men, in accordance with other studies.[34,35] Indeed, different studies have shown that the bone structure around the NLD is narrower and longer in women, and the angled structure of the bone canal-nasal junction makes them more susceptible to chronic inflammation and consequently NLD obstruction.[36,37] We believe that both anatomical and functional epiphora being more common in women are related to this. In our study, we also found that functional epiphora, NLD obstruction, and pre-sac obstruction were more frequently unilateral, whereas reflex tearing, multifactorial epiphora, and epiphora due to eyelid malposition were mostly bilateral, which is consistent with previous studies.[1,31,33]

The main limitations of our study were that it was a single-center study and its retrospective design. In addition, not performing DCG in the definition and evaluation of functional epiphora was another limitation. On the other hand, compared to DSG, lacrimal syringing has several limitations. While DSG evaluates the lacrimal drainage system with natural tear flow, syringing involves a mechanical intervention. Therefore, DSG reflects functional obstructions more realistically. Objective parameters such as drainage time and flow rate can be measured with DSG. Syringing, on the other hand, is subjective (limited to the sensation of “backflow” or “resistance”). Moreover, lacrimal syringing can show complete obstructions but may miss stenosis or pump failure. The strength of the study lies in the effective and appropriate use of comprehensive clinical assessment, lacrimal syringing testing, and DSG to identify cases of functional epiphora that might otherwise be overlooked.

Conclusion

According to our study, although NLD obstruction is the most common cause of epiphora, functional epiphora is a more frequent cause than previously anticipated. Observing complete patency in the lacrimal syringing is insufficient to rule out NLD stenosis and functional problems. We think that the effective and appropriate use of detailed clinical examination, lacrimal syringing test, and DSG will be very useful in the detection of functional epiphora. However, it is critical to perform a detailed anamnesis, comprehensive clinical examination, and related procedures before the tests to be performed. For more definitive results, further studies with multicenters and large patient participation will be useful.

Author contributions’ statement

All authors have critically reviewed the letter and have equally contributed to the manuscript.

Patients’ consent form

An informed consent form was obtained from all patients

Approval of the institutional review board

KTO Karatay University, Faculty of Medicine Ethics Committee, Konya, Turkey. Date: 09/05/2024, The project number: 2024/004.

Conflicts of interest:

There are no conflicts of interest.

Funding Statement

Nil.