Consecutive Microscopic Anatomical Characteristics of the Lacrimal Sac and Nasolacrimal Duct: Cases With or Without Inflammation

Abstract

Purpose.: We examined the consecutive microscopic anatomy of the lacrimal sac and nasolacrimal duct with or without conspicuous inflammation.

Methods.: We used 18 postmortem lacrimal sacs and nasolacrimal ducts of 12 Japanese subjects (5 males, 7 females, aged 75–98 years at death). The removed mucosal wall was transversely sectioned. The first slice was cut around the internal canalicular punctum, the second slice was at the superior opening of the bony nasolacrimal canal, and the other four were harvested from the nasolacrimal duct. All specimens were dehydrated and embedded in paraffin, cut into 7-μm thick sections, and stained with Masson's trichrome.

Results.: The lumen was larger in the lacrimal sac than in the nasolacrimal duct. The lacrimal sac wall was less developed than the nasolacrimal duct wall. All specimens but two showed a narrowed area in the nasolacrimal duct. Specimens without conspicuous inflammation showed some subepithelial inflammatory cell infiltration. Goblet cells were smaller in number in the lacrimal sac with an increasing tendency in the inferior direction. Specimens with conspicuous inflammation showed narrowed portions in the nasolacrimal duct, in which severe inflammation and exudate in the lumen was observed. The epithelium was denuded and goblet cells were lost. A specimen with focal inflammation illustrated similar findings in the inflammatory part, but the other parts were similar to the specimens without inflammation.

Conclusions.: Consecutive microscopic anatomical characteristics of the lacrimal sac and nasolacrimal duct were different from each other. A narrowed part of the nasolacrimal duct lumen is speculated to be a risk for obstruction.

Introduction

The microscopic anatomy of the lacrimal sac and nasolacrimal duct has received little attention in the field of ocular adnexa. To our knowledge, only two studies have illustrated the normal microscopic anatomy of this entity, ^1,2 although structural variations and the anatomical transition from superior to inferior edges were not sufficiently presented. Knowledge of the microscopic anatomy of these areas still is limited to the pathogenic concept of a primary acquired nasolacrimal duct obstruction, a syndrome of unknown origin. ^1,2 We, therefore, examined the consecutive microscopic anatomical characteristics of the lacrimal sac and nasolacrimal duct with or without conspicuous inflammation to analyze the modified characteristics of these regions. 

Methods

We analyzed 18 postmortem lacrimal systems (9 right, 9 left) of 12 Japanese subjects (5 were male, 7 were female, aged 75–98 years at death, mean age 84.4 years) that were fixed in 10% buffered formalin. None of the cadavers had any history or clinical evidence of a previous eyelid, orbital, lacrimal, maxillofacial, or nasal trauma, surgery, tumor, or any other periocular pathology. Consent and approval to use the cadavers for educational purposes and studies were obtained, and all cadavers were registered with the cadaveric service of Aichi Medical University. All methods for securing human tissue were humane and complied with the tenets of the Declaration of Helsinki. 

The mucosal wall of the lacrimal sac and nasolacrimal duct was harvested with part of the periosteum. The tissues in front and on the lateral side of the lacrimal sac were removed to expose the lacrimal sac. The periosteum on the lacrimal fossa subsequently was elevated. The inferior orbital rim, orbital floor, anterior maxillary wall, and the lateral half of the bony nasolacrimal canal were removed to expose the lateral half of the nasolacrimal duct. The periosteum of the bony nasolacrimal canal was elevated and the mucoperiosteal wall was cut around the opening to the inferior nasal meatus. The mucosal walls were marked at the superior and inferior openings of the bony nasolacrimal canal. 

The harvested lacrimal sac and nasolacrimal duct were sectioned transversely against the longitudinal axis. The first slice was cut around the internal canalicular punctum, the second slice was at the superior mark, and the bottom slice was at the inferior mark. From the superior to the inferior marks, the mucosal wall was divided into four equal parts. The superior aspects were used in the first and second slices, and from the third to sixth, the inferior aspects were used. These were subjected to microscopic examination. All sliced specimens were dehydrated and embedded in paraffin, cut into 7-μm thick sections and stained with Masson's trichrome. Micrographs were taken with a digital camera system attached to a microscope (Moticam 2000; Shimadzu Rika Kikai, Tokyo, Japan) and merged with Adobe Photoshop CS5 Extended (Adobe Systems, Inc., San Jose, CA, USA). 

Results

Comprehensive Findings

The lumen of the lacrimal sac was larger than that of the nasolacrimal duct (Figs. 1 1552 1552 1552–5). A large lumen of the nasolacrimal duct was only shown in six specimens (Fig. 1), but the others demonstrated a narrowed nasolacrimal duct cavity (Figs. 2 1552 1552–5). The wall of the lacrimal sac was less developed than that of the nasolacrimal duct. The stroma illustrated a developed venous plexus. These anatomies illustrated variation in the specimens. All specimens but two had a narrowed area in the nasolacrimal duct. Scattered serous grounds were demonstrated in the lacrimal sac and nasolacrimal duct, although they typically were shown in the lower part of the nasolacrimal duct (Figs. 1 1552 1552 1552–5). 

Figure 1

 

A specimen without conspicuous inflammation with a large cavity throughout the length. From ([B] superior) to ([F] inferior) slices are shown with the same interval. This rule also is applied to Figures 2 to 5. The centers of the circles are magnified in Figure 6. The arrowhead in (B) represents serous glands, magnified in Figure 6G. (A, B) Lacrimal sac. (C–F) Nasolacrimal duct. Scale bar: 1 mm.

Figure 2

 

A specimen without conspicuous inflammation with a narrow nasolacrimal duct cavity with congestion of the stromal vessels. The arrowhead in (A) represents serous glands, and the asterisk in (C) shows intraepithelial serous glands. (A, B) Lacrimal sac. (C–F) Nasolacrimal duct. Scale bar: 1 mm.

Figure 3

 

A specimen without conspicuous inflammation with a partition and an epithelial ingrowth. The centers of the circles in (C–E) are magnified in Figure 7A, 7C, 7D. (C) shows a partition constituted simply by the stratified columnar epithelium. The circle in (D) represents an epithelial ingrowth in the nasolacrimal duct stroma. (A, B) Lacrimal sac. (C–F) Nasolacrimal duct. Scale bar: 1 mm.

Figure 4

 

A specimen with focal conspicuous inflammation with a narrow nasolacrimal duct cavity. The arrowhead in (B) represents the focal inflammatory area of the nasolacrimal duct, magnified in (G). (G) Shows a denuded epithelium and lost goblet cells. (A, B) Lacrimal sac. (C–F) nasolacrimal duct. (A–F) Scale bars: 1 mm. (G) Scale bars: 0.1 mm.

Figure 5

 

A specimen with conspicuous inflammation. The centers of the circles are magnified in Figure 8. The lumens in (C–F) are filled with exudate. (A, B) Lacrimal sac. (C–F) Nasolacrimal duct. Scale bar: 1 mm.

Figure 6

 

Magnified photos around the centers of the circles of Figure 1 (A–F). (A) Corresponds to the circle of Figure 1A, for example. This rule is applied to Figure 8 as well. (G) serous glands in the lacrimal sac shown in Figure 1B (arrowhead). Scale bar: 0.1 mm.

Specific Findings of Specimens Without Conspicuous Inflammation

All specimens but two did not demonstrate conspicuous inflammation (Figs. 1 1552–3), although they had some subepithelial inflammatory cell infiltration (Figs. 6, 7). The distribution of this infiltration was variable without a specific tendency. Goblet cells were smaller in number in the lacrimal sac with an increasing tendency toward the inferior edge (Fig. 6). Three specimens (two from the same case) showed an intraepithelial serous gland (Fig. 2C). Three specimens (two from the same case above) illustrated severe stromal venous congestion and edema with a normal epithelium and goblet cells. Bilateral sides in one case (Figs. 3C, 7A) and the right side in another (Fig. 7B) demonstrated a separated lacrimal sac. The partitions in the former were made simply of a stratified columnar epithelium (Fig. 7A), but that in the latter was similar to the lacrimal sac wall lined with the same epithelium (Fig. 7B). The former case also showed an ingrowth of the epithelium to the nasolacrimal duct stroma (Figs. 3D, 7C). Focal mild epithelial hyperplasia was present in nine specimens (Fig. 7D). 

Figure 7

 

Magnified photos around the centers of the circles of Figure 3C to 3E, and a specimen with a lacrimal sac partition (B). (A) Magnified Figure 3C, shows a partition constituted simply by the stratified columnar epithelium (yellow arrowhead), although the tissue is a little broken. (B) A specimen with a lacrimal sac partition (white arrowhead) similar to the lacrimal sac wall. (C) Magnified Figure 3D, represents an epithelial ingrowth in the nasolacrimal duct stroma. (D) Magnified Figure 3E, illustrates a hyperplasia of the epithelium (asterisk). Scale bar: 0.1 mm (A, C, D). Scale bar: 2 mm (B).

Specific Findings of Specimens With Conspicuous Inflammation

One specimen (Figs. 5, 8) showed inflammation from the lacrimal sac to the nasolacrimal duct, but the density of inflammation was variable in each portion. Narrowed parts of the nasolacrimal duct were observed and severe inflammation was shown with exudate filling in the lumen (Figs. 5D, 5E). The epithelium was denuded and the goblet cells were lost in this region (Figs. 8A, 8C–E). The area without inflammation, however, had epithelium and goblet cells (Fig. 8B). Figure 8F shows an area close to the nasal cavity. Although inflammation and exudate were observed, the epithelium was not denuded and still had goblet cells. Although severe subepithelial infiltration of inflammatory cells also was shown in the lacrimal sac, the sac cavity demonstrated a larger space without obstruction (Figs. 5A, 8A). The lacrimal sac and nasolacrimal duct–illustrated conspicuous congestion. Squamous metaplasia or fibrosis was not illustrated in this specimen. 

Figure 8

 

Magnified photos around the centers of the circles of Figure 5. The epithelium is denuded and the goblet cells are lost in the severe inflammation area (A, C–E). However in the noninflammation area, the epithelium and goblet cells are intact (B). (F) Shows an area close to the nasal cavity. Although inflammation and exudate are observed, the epithelium is not denuded and goblet cells remain. Scale bar: 0.1 mm.

The other specimen (Fig. 4) with a small cavity in the nasolacrimal duct showed focal inflammation and the epithelium was denuded with loss of goblet cells (Fig. 4), but without exudate in the lumen. A moderate degree of congestion was shown in the stromal vessels. The other parts without conspicuous inflammation were similar to the specimens without conspicuous inflammation. 

Discussion

The lacrimal sac and nasolacrimal duct appears to have a different role in reabsorption of the tear fluid as the venous plexus is more developed in the nasolacrimal duct. A narrower nasolacrimal duct cavity may enhance this ability. 

Although the diameter of the bony canal had been thought to be stable at 4 mm, ³ a recent study illustrated variation in the diameter. ⁴ This variation may be related to a narrowed portion in the nasolacrimal duct, although we, unfortunately, did not examine the relationship between the narrowed portions of the lumen and the bony nasolacrimal canal. Most specimens with a narrowed lumen did not show nasolacrimal duct obstruction, but the specimen with conspicuous inflammation demonstrated severe inflammation at the narrowed portion with exudate filling in the lumen. Although the lacrimal sac in the same specimen showed subepithelial inflammatory cell infiltration, it demonstrated a larger cavity without obstruction. The other specimen with conspicuous inflammation was a small nasolacrimal duct type and demonstrated focal inflammation without exudate in the lumen. A narrowed portion of the nasolacrimal duct lumen may be a risk area for nasolacrimal duct obstruction, although it does not always occur. 

The subepithelial inflammatory cell infiltration in specimens without conspicuous inflammation indicates a defense system of the lacrimal excretory system. ^5,6 Using aged cadavers in the present study may be related to this phenomenon, which is similar to an increase in lacrimal gland inflammation with age. ⁷ Distribution of this infiltration was variable without a specific tendency. This result is similar to that of Ali et al., ⁶ who showed that 81% of the lymphoid infiltrate pattern was diffuse, but is different from the report of Paulsen et al. ² in that it was more prevalent in the lacrimal sac. ² Although our study did not show a germinal center, and the lacrimal sac and nasolacrimal duct have been believed not to have a germinal center in general, ^2,3,5 Ali et al. ⁶ reported approximately one-fourth demonstrated a germinal center. The reason that our study did not show a germinal center was attributed to the old age of the tissue donors, since germinal centers are known to reduce with age. ^5,6  

An emergence of the epithelial hyperplasia, shown in half of the specimens without conspicuous inflammation, has been speculated as a secondary phenomenon of chronic inflammation. ¹ Ali et al. ⁶ reported epithelial hyperplasia as well, although they used specimens with dacryocystitis. As our specimens did not have an obstruction, restoration after inflammation may prevent an obstruction. Inflammation over this restoration mechanism possibly results in the initiation of a nasolacrimal duct obstruction. 

Goblet cell distribution with increasing tendency toward the inferior edge means that a more inferior area can secrete more mucus. A nasolacrimal duct obstruction is seen less often in the distal part of the nasolacrimal duct, ¹ which may be caused by the distribution of the goblet cells that secrete mucins with an antiadhesion effect. ⁸ The mucus prevents pathogens from adhering to the epithelium as well. ⁹ This adhesion block consists of a simple covering on the epithelium and surrounding adhesive agents constituted by glycoproteins and/or glicolipids expressed on the surface of the pathogens or toxins. ⁹ Excess production of mucus may make an anaerobic environment, resulting in the persistence of chronic inflammation. ⁶ However, as some pathogens have enzymes that can dissolve mucus, a mucus defense is insufficient for pathogens. ^5,9 Lactoferrin, lysozomes, and immunogloburin in the mucus contribute to a defense against pathogens. ⁹  

Typical sporadic serous glands distribution in the lower part of the nasolacrimal duct is caused by the similar histology with the nasal passage. ³ Serous glands also were shown intraepithelially in three specimens of the same case (Fig. 2C). Secretion from the glands contributes to form a one-way flow from superior to inferior edges to prevent a retrograde infection from the nasal cavity. Collagen fascicules, and elastic and reticular fibers helically arranged from a superior to inferior direction in the stroma ¹⁰ also contribute to drain the lacrimal fluid inferiorly, producing a defense against pathogens. ⁹ This function also was supported by cilia ² and gravity. ¹¹ The nasolacrimal duct running beneath the nasal mucosa after leaving the osseous channel ^12,13 is a structure mechanically blocking a retrograde infection from the nasal cavity. 

Two specimens from the same case showed a lacrimal sac partition only with a stratified columnar epithelium, and a partition from one specimen was similar to the lacrimal sac wall with the same epithelium. Although only the latter type has been described, ¹⁴ the former membranous septum is first reported in the present study to our knowledge. This type may be a congenital anomaly of the lacrimal sac, such as known entities of the diverticula, fistula, and supernumerary sacs, ^15,16 as the anomaly was similarly shown on both sides. The partitions do not appear to make a closed space, which is similar to the previous study, ¹⁴ because no mucinous pooling is seen in the specimens. 

A large sac cavity may have prevented the sac from obstruction irrespective of the subepithelial severe inflammation although fewer goblet cells were shown in this area. Although the number of goblet cells increases in the nasolacrimal duct, as the diameter of the nasolacrimal duct lumen is narrower than that of the lacrimal sac and most specimens showed a narrow area in their course, obstruction may occur more frequently in the nasolacrimal duct. Two specimens from the same case illustrated an epithelial ingrowth to the nasolacrimal duct stroma. This is not a postinflammatory reaction because the epithelium is denuded in the inflammatory process. ^1,2  

Simple congestion of blood does not result in nasolacrimal duct obstruction. ³ Although transient nasolacrimal duct obstruction during acute allergic reactions has been demonstrated radiographically, it is not known whether this is secondary to engorgement of the venous plexus or to other reactions. ³ Congestion and secondary infection have been suggested to lead to complete obstruction and several microbiologic studies have documented colonization of the lacrimal pathways by an increased number of pathologic organisms. ³ This cycle of congestion influenced by inflammation remains a likely scenario in the pathogenesis of chronic nasolacrimal duct obstruction. However, excisional biopsy specimens, including those with acute inflammation and ulceration, do not show significant numbers of organisms or invasive infections. ³  

The specimens all coming from elderly individuals are a limitation of this study and it is possible that the anatomical findings might be different in younger individuals. The other disadvantage is that the study was performed on a small number of specimens because of the low availability of cadavers. A larger number of specimens may demonstrate alternative findings. 

In conclusion, consecutive microscopic anatomical characteristics of the lacrimal sac and nasolacrimal duct showed different characteristics from each other, and a narrowed area of the nasolacrimal duct lumen is speculated as a risk for obstruction. We believe that this study will aid in the understanding of the modified microscopic anatomy of the lacrimal sac and nasolacrimal duct, and will shed light to uncover a pathogenic concept of primary acquired nasolacrimal duct obstruction. 

Acknowledgments

The authors alone are responsible for the content and writing of the paper. 

Disclosure: H. Mito, None; Y. Takahashi, None; T. Nakano, None; K. Asamoto, None; H. Ikeda, None; H. Kakizaki, None