De acuerdo al Número Poblacional

4.4.1 Lichen Planus

Lichen planus (LP), an idiopathic autoimmune disease of the skin and oral or genital mucosa, may rarely aff ect con- junctiva [15, 28] and lead to severe canalicular obstruc- tion [10, 22]. Etiological mechanisms include autoreactive T cells to keratinocytes and activated tissue matrix metal- loproteinases and mast cells. Systemic lesions show sub- and intraepithelial lymphocytic infi ltration with degeneration of basal keratinocytes, and although con- junctival disease is less well characterized, case reports describe reticular subconjunctival scarring, forniceal shortening, and symblepharon formation. Th ese features resemble those seen in ocular cicatricial pemphigoid [21, 25], but immune complex deposition within the conjunc- tival basement membrane—pathognomonic for ocular cicatricial pemphigoid—is absent in LP.

Canalicular LP leads to extensive bilateral, bicanalic- ular occlusion in three quarters of patients with symp- tomatic disease [10]; these changes probably refl ect infl ammation within the subepithelial substantia propria of the canaliculus, with consequent deep fi brosis “throt- tling” the canaliculus (Fig. 4.3a). LP patients with proxi- mal or midcanalicular block are off ered DCR with retrograde canaliculostomy [36] but are warned of the high likelihood of requiring secondary placement of a Jones bypass tube.

4.4.2 Ocular Cicatricial Pemphigoid

Distal spillover of the severe conjunctival infl ammation of ocular cicatricial pemphigoid will oft en cause proximal canalicular blockage (Figs. 4.3c, d). Retention of infl am- matory debris will, in some cases, be associated with an exacerbation of ocular surface disease, and consideration will be given to the reestablishment of tear drainage; in

Table 4.3. Microbial isolates in canaliculitis

Actinomycetes spp.

Arcanobacterium haemolyticum Eikenella corrodens

Haemophilus aphrophilus Lactococcus lactis cremoris Molluscum contagiousuma Mycobacterium chelonae Nocardia asteroides

Propionobacterium propionicum Staphylocococcus spp.

a_{Primary involvement of the conjunctiva or cornea by mollus-} cum is rare and is oft en associated with HIV infection

a

d b

c

Fig. 4.3 (a) Infl ammatory sequelae of lichen planus, identifying complete destruction of the epithelium (chevrons), dense subepi- thelial fi brotic changes (short arrow), and lymphocytic infi ltrate (long arrow) (hematoxylin and eosin, original magnifi cation ×20); (b) Stevens–Johnson syndrome presenting with severe pseudomembranous conjunctivitis; (c) advanced bilateral ocular cicatricial pemphigoid demonstrating bilateral medial ankyloblepharon and punctal occlusion; (d) magnifi ed view of left eye showing severe synblepharon and medial ankyloblepharon completely obstructing punctum (arrow shows probable location)

most cases, these patients will require DCR and retro- grade canaliculostomy, with occasional later placement of a glass bypass tube.

4.4.3 Drug Eruptions (Stevens–Johnson Syndrome)

Stevens–Johnson syndrome (SJS), the bullous form of erythema multiforme, is an acute and self-limiting infl am- matory disorder of the skin and mucous membranes. Severe, and oft en hemorrhagic, conjunctivitis with pseudomembrane formation may occur in over half of patients (Fig. 4.3b), with the resultant subepithelial fi bro- sis leading to conjunctival symblepharon, cicatricial entropion, loss of limbal stem cells, and obliteration of the lacrimal gland ductules. Th ese changes reduce pro- duction of tear-fi lm mucin and aqueous tears, making any punctal or canalicular occlusion less troublesome; indeed, in one study, objective evidence for lacrimal out- fl ow disease was noted in most cases, although none required surgery, presumably due to the simultaneous reduction in the quantity of tear fi lm [37]. Other authors have reported signifi cant lacrimal outfl ow obstruction

requiring surgery, with this occurring at the level of the common canaliculus in one case and at both the canali- culi and nasolacrimal duct in another patient [2].

4.5 Iatrogenic Causes

Canalicular or pericanalicular infl ammation may arise from a number of iatrogenic causes, with these typically due to systemic medications or local radiotherapy.

4.5.1 Systemic Drugs

4.5.1.1 5-Fluorouracil (5-FU)

A potent inhibitor of DNA synthesis, 5-FU is widely used in the management of systemic malignancy, with rapidly proliferating tissues, including normal epithelial surfaces, most aff ected. Healthy canalicular epithelium may be aff ected in about 6% of patients, with this leading to punctal narrowing and focal or diff use canalicular steno- sis; over a quarter of these individuals require DCR with placement of a bypass tube [14].

4

Th ere are two putative mechanisms for canalicular damage: First, bathing of the puncta and canaliculi in 5-FU secreted into the tears may lead to chronic mucosal infl ammation per se. Second, 5-FU may damage rapidly proliferating canalicular epithelium, causing chronic infl ammation and fi brosis within the underlying substan- tia propria. Th ese theories are similar to those proposed for the canalicular stenosis associated with docetaxel (Taxotere , v.i.), discussed below.

4.5.1.2 Docetaxel (Taxotere)

Docetaxel is a semisynthetic taxane used in the treatment of advanced solid malignancies, especially those of breast, prostate, and non-small cell lung cancers. It is secreted into the tears [13] and may lead to canalicular stenosis or occlusion, with this troublesome side eff ect related to both the dosing frequency and total cumulative dose. Histological studies have shown fi brosis within the mucosal lining of the lacrimal drainage apparatus [11].

Clinical features of docetaxel toxicity include symp- tomatic punctal and canalicular stenosis or occlusion in up to a half of patients while on a weekly dosing schedule [12, 32]. Temporary canalicular intubation has been rec- ommended for patients on weekly therapy, but probing

and syringing (followed by a short course of topical ste- roids) appear adequate to prevent problems in most patients on a ie every 3 weeks dosing schedule. Docetaxel is, however, an increasingly used chemotherapy, and with a trend toward weekly dosing to reduce systemic compli- cations, lacrimal complications are set to increase. Treating physicians should counsel patients about the risk of lacrimal problems and seek appropriate early refer- ral if symptoms arise.

4.5.2 Radiotherapy

Due to their propensity to invade the medial orbit, tumors at the medial canthus carry a relatively worse prognosis, and Mohs surgery is now the preferred approach in managing such basal or squamous cell carcinomas. Historically, radiotherapy has oft en been used in this location, with almost universal canalicular occlusion (Fig. 4.4a). In 1981, Call and Welham described 13 patients with severe epiphora following radiotherapy for medial basal cell carcinomas, all of whom had complete obstruction of both upper and lower canaliculi; 12 were successfully managed by DCR and insertion of a Jones tube, and 1 settled with canaliculo-DCR for a common canalicular block [6].

a

d e

b c

Fig. 4.4 (a) Radiation treatment for medial canthal BCC causing canalicular occlusion and requiring subsequent DCR and second- ary bypass tube (note lash loss and depigmentation); (b) drop sensitivity to unpreserved chloramphenicol with secondary canalicu- litis and epiphora; (c) silicone stent-induced canalicular infl ammation with developing granuloma (arrow) and medial canthal staphylococcal infection; (d) medial canthal granuloma secondary to monocanalicular stent; (e) impacted intracanalicular plug at the entrance of the common canaliculus to the sac. Note the infl amed sac mucosa due to recurrent episodes of dacrocystitis

Systemic radioiodine (131_{I) is used for the manage-}

ment of thyroid carcinoma and has well-documented ocular side eff ects, including xerophthalmia and chronic conjunctivitis [31]. Symptomatic lacrimal outfl ow obstruction is less well recognized, occurring in at least 5% of patients, with the distal nasolacrimal duct more commonly aff ected than the canalicular systems [5]1_;

whether this eff ect is mediated by local toxicity from passive fl ow of 131_{I into the tears or is due to active}

uptake by the sodium–iodide symporter (known to exist in both lacrimal and thyroid gland) remains uncer- tain, although at least one report supported the latter mechanism [4].

4.5.3 Topical Ophthalmic Treatments

4.5.3.1 Preservative-Related Chronic Conjunctivitis

Lacrimal canalicular occlusion may occur aft er exposure to topical ocular medications, with one study reporting obstruction as little as a month aft er beginning treatment [21]. Outfl ow obstruction is most commonly observed 2–5 mm from the lacrimal punctum, with other associ- ated fi ndings including symblepharon, keratinization of the medial canthal tissues, and cicatricial medial entropion.

Canalicular occlusion may follow a chronic infl amma- tory response to drop preservatives and, if a patient has symptoms of dry eye, features suggestive of chronic allergy (e.g., skin changes, ocular redness or irritation, and a conjunctival papillary response) (Fig. 4.4b) should not be confused with those of aqueous insuffi ciency.

4.5.3.2 Mitomycin C (MMC) Therapy

Topical MMC is proven in the treatment of ocular sur- face malignancy, such as intraepithelial carcinoma, pri- mary acquired melanosis with atypia, superfi cial conjunctival malignant melanoma, and sebaceous carci- noma with pagetoid spread. Transient side eff ects of MMC include an allergic reaction in a third of patients in addition to kerato-conjunctivitis and punctate epithelial keratopathy.

Canalicular disease has been reported in 3/14 (21%) patients receiving topical MMC for 2 weeks [16], although another report found punctal stenosis in only 14/100 eyes of 91 patients who received the drop for 1 week (of which only 1 required lacrimal surgery), sug- gesting that symptomatic canalicular stenosis occurs only rarely and may be related to duration of topical therapy [17]. To reduce canalicular toxicity, some authors advocate temporary punctal occlusion with removable plugs while using MMC drops, which has the additional advantages of increasing drug bioavailability on the ocu- lar surface.

4.5.4 Lacrimal Stents and Plugs

All foreign bodies within the lacrimal outfl ow tract, including stones, stents, and plugs, incite a mucosal infl ammatory response. At about a month aft er lacrimal surgery, silicone stents typically cause medial canthal irri- tation and mucus production due to punctal and canalic- ular infl ammatory changes; when stent removal is delayed beyond 3 months, frank exophytic granulomas may occur (Fig. 4.4c, d). Th us, even the most inert of materials is capable of inciting mucosal infl ammation, with second- ary submucosal fi brosis and risk of canalicular stricture.

Although the vast majority of lacrimal plugs are not used appropriately, a variety of punctal and canalicular plugs are available to treat symptoms of true aqueous insuffi ciency. Self-degrading collagen plugs are eff ective for a few weeks, and silicone punctal plugs, which are rea- sonably well tolerated, are best used to identify those patients in whom permanent outfl ow occlusion would be appropriate. Other materials include a fl exible thermo- sensitive acrylic material (SmartPlug) that molds to the internal contour of the ampullae, but none is without complication, and all may cause canaliculitis [8, 9, 29, 30]. Intracanalicular plugs have been advocated for the treat- ment of dry eye for some years, but these tend to migrate into the nasolacrimal sac, be held up at the entrance to the sac (Fig. 4.4e), or become embedded through the com- mon canalicular wall. Th e presence of a chronic intrac- analicular foreign body can fuel a gross conjunctival infl ammatory response, and the retrograde discharge of purulent debris further compromises the ocular surface. Indeed, intracanalicular plugs were the cause of lacrimal outfl ow symptoms in 6% of eyes in one series, with the high prevalence possibly refl ecting practice within one particular catchment population [19]; over a quarter of eyes in this study had persistent epiphora aft er plug removal or reparative lacrimal surgery, presumably due to persistent canalicular stenosis.

1 _{A lower dose} 131_{I is used in controlling hyperthyroidism (ther-} apeutic activity 10–15 mCi 131_{I) compared to managing thyroid} carcinoma (30–200 mCi 131_{I), which in the context of metastatic} disease may require substantial cumulative activities (up to 300 mCi 131_I).

4

4.6 The Surgical Approach to Managing