Consecutive Microscopic Anatomical Characteristics of the Lacrimal Sac and Nasolacrimal Duct: Cases with Or Without Inﬂammation

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

Hidenori Mito,1,2 Yasuhiro Takahashi,1 Takashi Nakano,3 Ken Asamoto,3 Hiroshi Ikeda,4 and Hirohiko Kakizaki1

1Department of Ophthalmology, Aichi Medical University, Nagakute, Aichi, Japan 2Ide Eye Hospital, Kasumicho, Yamagata, Japan 3Department of Anatomy, Aichi Medical University, Nagakute, Aichi, Japan 4Department of Pathology, Aichi Medical University, Nagakute, Aichi, Japan

Correspondence: Hirohiko Kakizaki, PURPOSE. We examined the consecutive microscopic anatomy of the lacrimal sac and Department of Ophthalmology, Aichi nasolacrimal duct with or without conspicuous inflammation. Medical University, Nagakute, Aichi 480-1195, Japan; METHODS. We used 18 postmortem lacrimal sacs and nasolacrimal ducts of 12 Japanese [email protected]. 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 Submitted: March 26, 2014 Accepted: July 15, 2014 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 Citation: Mito H, Takahashi Y, Nakano paraffin, cut into 7-lm thick sections, and stained with Masson’s trichrome. T, Asamoto K, Ikeda H, Kakizaki H. Consecutive microscopic anatomical RESULTS. The lumen was larger in the lacrimal sac than in the nasolacrimal duct. The lacrimal characteristics of the lacrimal sac and sac wall was less developed than the nasolacrimal duct wall. All specimens but two showed a nasolacrimal duct: cases with or narrowed area in the nasolacrimal duct. Specimens without conspicuous inflammation without inflammation. Invest Oph- showed some subepithelial inflammatory cell infiltration. Goblet cells were smaller in number thalmol Vis Sci. 2014;55:5233–5237. in the lacrimal sac with an increasing tendency in the inferior direction. Specimens with DOI:10.1167/iovs.14-14449 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. Keywords: microscopic anatomy, lacrimal sac, nasolacrimal duct, inﬂammation

he microscopic anatomy of the lacrimal sac and nasolacri- buffered formalin. None of the cadavers had any history or T mal duct has received little attention in the field of ocular clinical evidence of a previous eyelid, orbital, lacrimal, adnexa. To our knowledge, only two studies have illustrated the maxillofacial, or nasal trauma, surgery, tumor, or any other normal microscopic anatomy of this entity,1,2 although struc- periocular pathology. Consent and approval to use the cadavers tural variations and the anatomical transition from superior to for educational purposes and studies were obtained, and all inferior edges were not sufficiently presented. Knowledge of cadavers were registered with the cadaveric service of Aichi the microscopic anatomy of these areas still is limited to the Medical University. All methods for securing human tissue were pathogenic concept of a primary acquired nasolacrimal duct humane and complied with the tenets of the Declaration of obstruction, a syndrome of unknown origin.1,2 We, therefore, Helsinki. examined the consecutive microscopic anatomical characteris- The mucosal wall of the lacrimal sac and nasolacrimal duct tics of the lacrimal sac and nasolacrimal duct with or without was harvested with part of the periosteum. The tissues in front conspicuous inflammation to analyze the modified characteris- and on the lateral side of the lacrimal sac were removed to tics of these regions. 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 METHODS nasolacrimal canal were removed to expose the lateral half of We analyzed 18 postmortem lacrimal systems (9 right, 9 left) of the nasolacrimal duct. The periosteum of the bony nasolacrimal 12 Japanese subjects (5 were male, 7 were female, aged 75–98 canal was elevated and the mucoperiosteal wall was cut around years at death, mean age 84.4 years) that were fixed in 10% the opening to the inferior nasal meatus. The mucosal walls

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FIGURE 1. A specimen without conspicuous inflammation with a large FIGURE 3. A specimen without conspicuous inflammation with a cavity throughout the length. From ([B] superior) to ([F] inferior) slices partition and an epithelial ingrowth. The centers of the circles in (C–E) are shown with the same interval. This rule also is applied to Figures 2 are magnified in Figure 7A, 7C, 7D. (C) shows a partition constituted to 5. The centers of the circles are magnified in Figure 6. The simply by the stratified columnar epithelium. The circle in (D) arrowhead in (B) represents serous glands, magnified in Figure 6G. (A, represents an epithelial ingrowth in the nasolacrimal duct stroma. B) Lacrimal sac. (C–F) Nasolacrimal duct. Scale bar: 1 mm. (A, B) Lacrimal sac. (C–F) Nasolacrimal duct. Scale bar: 1 mm.

were marked at the superior and inferior openings of the bony Japan) and merged with Adobe Photoshop CS5 Extended nasolacrimal canal. (Adobe Systems, Inc., San Jose, CA, USA). 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 RESULTS second slice was at the superior mark, and the bottom slice Comprehensive Findings was at the inferior mark. From the superior to the inferior marks, the mucosal wall was divided into four equal parts. The The lumen of the lacrimal sac was larger than that of the superior aspects were used in the first and second slices, and nasolacrimal duct (Figs. 1–5). A large lumen of the nasolacrimal from the third to sixth, the inferior aspects were used. These duct was only shown in six specimens (Fig. 1), but the others weresubjectedtomicroscopic examination. All sliced demonstrated a narrowed nasolacrimal duct cavity (Figs. 2–5). specimens were dehydrated and embedded in paraffin, cut The wall of the lacrimal sac was less developed than that of the nasolacrimal duct. The stroma illustrated a developed venous into 7-lm thick sections and stained with Masson’s trichrome. plexus. These anatomies illustrated variation in the specimens. Micrographs were taken with a digital camera system attached All specimens but two had a narrowed area in the nasolacrimal to a microscope (Moticam 2000; Shimadzu Rika Kikai, Tokyo, duct. Scattered serous grounds were demonstrated in the

FIGURE 4. A specimen with focal conspicuous inflammation with a FIGURE 2. A specimen without conspicuous inflammation with a narrow nasolacrimal duct cavity. The arrowhead in (B) represents the narrow nasolacrimal duct cavity with congestion of the stromal vessels. focal inflammatory area of the nasolacrimal duct, magnified in (G). (G) The arrowhead in (A) represents serous glands, and the asterisk in (C) Shows a denuded epithelium and lost goblet cells. (A, B) Lacrimal sac. shows intraepithelial serous glands. (A, B) Lacrimal sac. (C–F) (C–F) nasolacrimal duct. (A–F) Scale bars: 1 mm. (G) Scale bars: 0.1 Nasolacrimal duct. Scale bar: 1 mm. mm.

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FIGURE 7. Magnified photos around the centers of the circles of Figure FIGURE 5. A specimen with conspicuous inflammation. The centers of 3C to 3E, and a specimen with a lacrimal sac partition (B). (A) the circles are magnified in Figure 8. The lumens in (C–F) are filled Magnified Figure 3C, shows a partition constituted simply by the with exudate. (A, B) Lacrimal sac. (C–F) Nasolacrimal duct. Scale bar: stratified columnar epithelium (yellow arrowhead), although the tissue 1 mm. 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) lacrimal sac and nasolacrimal duct, although they typically Magnified Figure 3E, illustrates a hyperplasia of the epithelium were shown in the lower part of the nasolacrimal duct (Figs. 1– (asterisk). Scale bar: 0.1 mm (A, C, D). Scale bar: 2 mm (B). 5). (Fig. 7B) demonstrated a separated lacrimal sac. The partitions Specific Findings of Specimens Without in the former were made simply of a stratified columnar Conspicuous Inflammation epithelium (Fig. 7A), but that in the latter was similar to the lacrimal sac wall lined with the same epithelium (Fig. 7B). The All specimens but two did not demonstrate conspicuous former case also showed an ingrowth of the epithelium to the inflammation (Figs. 1–3), although they had some subepithelial nasolacrimal duct stroma (Figs. 3D, 7C). Focal mild epithelial inflammatory cell infiltration (Figs. 6, 7). The distribution of hyperplasia was present in nine specimens (Fig. 7D). this infiltration was variable without a specific tendency. Goblet cells were smaller in number in the lacrimal sac with an Specific Findings of Specimens With Conspicuous increasing tendency toward the inferior edge (Fig. 6). Three specimens (two from the same case) showed an intraepithelial Inflammation serous gland (Fig. 2C). Three specimens (two from the same One specimen (Figs. 5, 8) showed inflammation from the case above) illustrated severe stromal venous congestion and lacrimal sac to the nasolacrimal duct, but the density of edema with a normal epithelium and goblet cells. Bilateral inflammation was variable in each portion. Narrowed parts of sides in one case (Figs. 3C, 7A) and the right side in another 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

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 FIGURE 6. Magnified photos around the centers of the circles of Figure inflammation area (A, C–E). However in the noninflammation area, the 1(A–F). (A) Corresponds to the circle of Figure 1A, for example. This epithelium and goblet cells are intact (B). (F) Shows an area close to rule is applied to Figure 8 as well. (G) serous glands in the lacrimal sac the nasal cavity. Although inflammation and exudate are observed, the shown in Figure 1B (arrowhead). Scale bar: 0.1 mm. epithelium is not denuded and goblet cells remain. Scale bar: 0.1 mm.

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shows an area close to the nasal cavity. Although inflammation Goblet cell distribution with increasing tendency toward and exudate were observed, the epithelium was not denuded the inferior edge means that a more inferior area can secrete and still had goblet cells. Although severe subepithelial more mucus. A nasolacrimal duct obstruction is seen less often infiltration of inflammatory cells also was shown in the in the distal part of the nasolacrimal duct,1 which may be lacrimal sac, the sac cavity demonstrated a larger space caused by the distribution of the goblet cells that secrete without obstruction (Figs. 5A, 8A). The lacrimal sac and mucins with an antiadhesion effect.8 The mucus prevents nasolacrimal duct–illustrated conspicuous congestion. Squa- pathogens from adhering to the epithelium as well.9 This mous metaplasia or fibrosis was not illustrated in this adhesion block consists of a simple covering on the epithelium specimen. and surrounding adhesive agents constituted by glycoproteins The other specimen (Fig. 4) with a small cavity in the and/or glicolipids expressed on the surface of the pathogens or nasolacrimal duct showed focal inflammation and the epithe- toxins.9 Excess production of mucus may make an anaerobic lium was denuded with loss of goblet cells (Fig. 4), but without environment, resulting in the persistence of chronic inflam- exudate in the lumen. A moderate degree of congestion was mation.6 However, as some pathogens have enzymes that can shown in the stromal vessels. The other parts without dissolve mucus, a mucus defense is insufficient for patho- conspicuous inflammation were similar to the specimens gens.5,9 Lactoferrin, lysozomes, and immunogloburin in the without conspicuous inflammation. 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 DISCUSSION the nasal passage.3 Serous glands also were shown intra- epithelially in three specimens of the same case (Fig. 2C). The lacrimal sac and nasolacrimal duct appears to have a Secretion from the glands contributes to form a one-way flow different role in reabsorption of the tear fluid as the venous from superior to inferior edges to prevent a retrograde plexus is more developed in the nasolacrimal duct. A narrower infection from the nasal cavity. Collagen fascicules, and elastic nasolacrimal duct cavity may enhance this ability. and reticular fibers helically arranged from a superior to Although the diameter of the bony canal had been thought inferior direction in the stroma10 also contribute to drain the 3 to be stable at 4 mm, a recent study illustrated variation in the lacrimal fluid inferiorly, producing a defense against patho- 4 diameter. This variation may be related to a narrowed portion gens.9 This function also was supported by cilia2 and gravity.11 in the nasolacrimal duct, although we, unfortunately, did not The nasolacrimal duct running beneath the nasal mucosa after examine the relationship between the narrowed portions of leaving the osseous channel12,13 is a structure mechanically the lumen and the bony nasolacrimal canal. Most specimens blocking a retrograde infection from the nasal cavity. with a narrowed lumen did not show nasolacrimal duct Two specimens from the same case showed a lacrimal sac obstruction, but the specimen with conspicuous inflammation partition only with a stratified columnar epithelium, and a demonstrated severe inflammation at the narrowed portion partition from one specimen was similar to the lacrimal sac with exudate filling in the lumen. Although the lacrimal sac in wall with the same epithelium. Although only the latter type the same specimen showed subepithelial inflammatory cell has been described,14 the former membranous septum is first infiltration, it demonstrated a larger cavity without obstruction. reported in the present study to our knowledge. This type may The other specimen with conspicuous inflammation was a be a congenital anomaly of the lacrimal sac, such as known small nasolacrimal duct type and demonstrated focal inflam- entities of the diverticula, fistula, and supernumerary sacs,15,16 mation without exudate in the lumen. A narrowed portion of as the anomaly was similarly shown on both sides. The the nasolacrimal duct lumen may be a risk area for nasolacrimal partitions do not appear to make a closed space, which is duct obstruction, although it does not always occur. similar to the previous study,14 because no mucinous pooling is The subepithelial inflammatory cell infiltration in speci- seen in the specimens. mens without conspicuous inflammation indicates a defense A large sac cavity may have prevented the sac from system of the lacrimal excretory system.5,6 Using aged cadavers obstruction irrespective of the subepithelial severe inflamma- in the present study may be related to this phenomenon, tion although fewer goblet cells were shown in this area. which is similar to an increase in lacrimal gland inflammation Although the number of goblet cells increases in the with age.7 Distribution of this infiltration was variable without nasolacrimal duct, as the diameter of the nasolacrimal duct a specific tendency. This result is similar to that of Ali et al.,6 lumen is narrower than that of the lacrimal sac and most who showed that 81% of the lymphoid infiltrate pattern was specimens showed a narrow area in their course, obstruction diffuse, but is different from the report of Paulsen et al.2 in that may occur more frequently in the nasolacrimal duct. Two it was more prevalent in the lacrimal sac.2 Although our study specimens from the same case illustrated an epithelial did not show a germinal center, and the lacrimal sac and ingrowth to the nasolacrimal duct stroma. This is not a nasolacrimal duct have been believed not to have a germinal postinflammatory reaction because the epithelium is denuded center in general,2,3,5 Ali et al.6 reported approximately one- in the inflammatory process.1,2 fourth demonstrated a germinal center. The reason that our Simple congestion of blood does not result in nasolacrimal study did not show a germinal center was attributed to the old duct obstruction.3 Although transient nasolacrimal duct age of the tissue donors, since germinal centers are known to obstruction during acute allergic reactions has been demon- reduce with age.5,6 strated radiographically, it is not known whether this is An emergence of the epithelial hyperplasia, shown in half of secondary to engorgement of the venous plexus or to other the specimens without conspicuous inflammation, has been reactions.3 Congestion and secondary infection have been speculated as a secondary phenomenon of chronic inflamma- suggestedtoleadtocompleteobstructionandseveral tion.1 Ali et al.6 reported epithelial hyperplasia as well, microbiologic studies have documented colonization of the although they used specimens with dacryocystitis. As our lacrimal pathways by an increased number of pathologic specimens did not have an obstruction, restoration after organisms.3 This cycle of congestion influenced by inflamma- inflammation may prevent an obstruction. Inflammation over tion remains a likely scenario in the pathogenesis of chronic this restoration mechanism possibly results in the initiation of a nasolacrimal duct obstruction. However, excisional biopsy nasolacrimal duct obstruction. specimens, including those with acute inflammation and

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ulceration, do not show significant numbers of organisms or 4. Takahashi Y, Nakamura Y, Nakano T, et al. The narrowest part invasive infections.3 of the bony nasolacrimal canal: an anatomical study. Ophthal The specimens all coming from elderly individuals are a Plast Reconstr Surg. 2013;29:318–322. limitation of this study and it is possible that the anatomical 5. Knop E, Knop N. Lacrimal drainage-associated lymphoid tissue findings might be different in younger individuals. The other (LDALT): a part of the human mucosal immune system. Invest disadvantage is that the study was performed on a small Ophthalmol Vis Sci. 2001;42;566–574. number of specimens because of the low availability of 6. Ali MJ, Mulay K, Pujari A, Naik MN. Derangements of lacrimal cadavers. A larger number of specimens may demonstrate drainage-associated lymphoid tissue (LDALT) in human chron- alternative findings. ic dacryocystitis. Ocul Immunol Inflamm. 2013;21:417–423. In conclusion, consecutive microscopic anatomical charac- 7. McClellan AJ, Volpe EA, Zhang X, et al. Ocular surface disease teristics of the lacrimal sac and nasolacrimal duct showed and dacryoadenitis in aging C57BL/6 mice. Am J Pathol. 2014; different characteristics from each other, and a narrowed area 184:631–643. of the nasolacrimal duct lumen is speculated as a risk for 8. Takahashi Y, Watanabe A, Matsuda H, et al. Anatomy of obstruction. We believe that this study will aid in the secretory glands in the eyelid and conjunctiva: a photographic understanding of the modified microscopic anatomy of the review. Ophthal Plast Reconstr Surg. 2013;29:215–219. lacrimal sac and nasolacrimal duct, and will shed light to 9. Perra MT, Serra A, Sirigu P, Turno F. A histochemical and uncover a pathogenic concept of primary acquired nasolacri- immunohistochemical study of certain defense mechanisms in mal duct obstruction. the human lacrimal sac epithelium. Arch Histol Cytol. 1995; 58:517–522. Acknowledgments 10. Thale A, Paulsen F, Rochels R, Tillmann B. Functional anatomy of the human efferent tear ducts: a new theory of tear out flow The authors alone are responsible for the content and writing of mechanism. Graefes Arch Clin Exp Ophthalmol. 1998;236: the paper. 674–678. Disclosure: H. Mito, None; Y. Takahashi, None; T. Nakano, 11. Sahlin S, Chen E. Gravity, blink rate, and lacrimal drainage None; K. Asamoto, None; H. Ikeda, None; H. Kakizaki, None capacity. Am J Ophthalmol. 1997;124:758–764. 12. Bailey JH. Surgical anatomy of the lacrimal sac. Am J References Ophthalmol. 1923;6:665–671. 13. Onogi J. Nasal endoscopic findings of functional obstruction 1. Linberg JV, McCormick SA. Primary acquired nasolacrimal duct of nasolacrimal duct. Rinsho Ganka. 2001;55:650–654. obstruction: a clinicopathologic report and biopsy technique. Japanese. Ophthalmology. 1986;93:1055–1063. 14. Takahashi Y, Nakano T, Asamoto K, et al. Lacrimal sac septum. 2. Paulsen FP, Thale AB, Maune S, Tillmann BN. New insights into Orbit. 2012;31:416–417. the pathophysiology of primary acquired dacryostenosis. 15. Kavanagh MC, Cahill KV. Congenital lacrimal system anomalies Ophthalmology. 2001;108:2329–2336. mimicking recurrent acute dacryocystitis. Ophthal Plast 3. McCormick SA, Linberg JV. Pathology of nasolacrimal duct Reconstr Surg. 2008;24:53–54. obstruction: clinicopathologic correlates of lacrimal excretory 16. Mansour K, Versteegh M, Janssen A, Blanksma L. Epiphora due system disease. In: Linberg JV, ed. Lacrimal Surgery. New to compression of the lacrimal sac by a supernumerary blind York, NY: Churchill-Livingstone; 1988:169–202. sac. Orbit. 2002;21:43–47.

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