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Primary and Secondary Lacrimal Canaliculitis: A Review of Literature
SURVEY OF OPHTHALMOLOGY
VOLUME 56 NUMBER 4 JULY–AUGUST 2011
MAJOR REVIEW
Primary and Secondary Lacrimal Canaliculitis: A Review of Literature Joshua R. Freedman, MS,1 Matthew S. Markert, MS,2 and Adam J. Cohen, MD, FACS3 1 3
Rush University Medical Center, Chicago, Illinois; 2University of Miami, Miller School of Medicine, Miami, Florida; and Private Practice, The Art of Eyes— Eyelid and Facial Plastic and Reconstructive Surgery, Skokie, Illinois, USA
Abstract. Canaliculitis is an uncommon inflammation of the proximal lacrimal drainage system that is frequently misdiagnosed. It classically presents with symptoms of unilateral conjunctivitis, mucopurulent discharge, medial canthal inflammation, epiphora, and a red, pouting punctum. We summarize the literature on canaliculitis published from antiquity to the modern era and explore therapeutic options. (Surv Ophthalmol 56:336--347, 2011. Ó 2011 Elsevier Inc. All rights reserved.) Key words. actinomyces actinomycosis canaliculitis canaliculostomy canaliculotomy chronic conjunctivitis pouting punctum streptothricosis
I. Introduction
streptothrix
The clinical distinctions and treatment approach separating primary canaliculitis and canaliculitis secondary to plug insertion have not yet been identified.32,39,58 We reviewed the case literature on presentation, diagnosis, and treatment outcome, and generate a differential diagnostic strategy for the identification of primary canaliculitis, as well as treatment recommendations for both primary and secondary canaliculitis.
Canaliculitis is an uncommon inflammation of the lacrimal canaliculi usually caused by infection5,6,9,28,73 or as a complication of punctal or intracanalicular plug insertion35,58 or intubation.29,47 Canaliculitis is often misdiagnosed as conjunctivitis.2,70 Described in Harrison’s Principles of Internal Medicine as ‘‘the most misdiagnosed disease’’ and that ‘‘no disease is so often missed by experienced clinicians,’’ primary canaliculitis is the result of an infection of the canaliculus and proximal lacrimal duct associated with eyelid thickening and/or erythema, and/or the presence of a classic pouting punctum.74 Recognition of canaliculitis as an infectious condition is attributed to Von Graefe (1854).21 Actinomyces isrealli, then classified as a fungus, was initially found to be the most common causative organism. For this reason, canaliculitis was originally known by the names of streptothrix canaliculitis1,18,22 or streptothricosis.17,50
A. ANATOMY AND HISTOLOGY
The lacrimal canaliculi, also known as canals or ducts, run vertically within the eyelids and converge to form the common canaliculus. They begin as branches of the lacrimal punctae and traverse the eyelids for approximately 8 mm. The upper eyelid canaliculi are shorter and narrower compared to the lower canals. The upper canal travels at a sharp angle before coalescing with lower canaliculus to form the common canal. The lower canaliculi run 336
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almost completely horizontal before joining the upper canaliculus, where the vertical components become enshrouded by fibrous tissue to form the punctum. Canalicular obstructions may be anatomically divided into proximal, mid-, or distal. Proximal canalicular obstructions typically occur within the first 2--3 mm of the canaliculi. Causes include punctal stenosis, punctal occlusion, and swelling. Mid-canalicular obstructions often follow injury or are secondary to infection, canaliculiths, or medications. These obstructions occur 6--8 mm from the punctal os. Distal obstructions are often congenital malformations of the membrane (valve of Rosenmuller) where the common canaliculus opens into the lacrimal sac. Lacrimal sac infections may also result in distal canalicular obstruction. Distal obstructions occur more than 6--8 mm distal to the eyelid punctum. Case studies were analyzed for clinical presentation reported, microbiological cause of infection, demographic data, and whether patients had previous lacrimal plug insertion or canalicular intubation.
II. Epidemiology In the last 20 years a number of case series of canaliculitis have been reported, the majority of which cited the prevalence of signs and symptoms. The infrequency of canaliculitis limits statistical analysis of reported cases. What an analysis of reported cases does provide is a more qualitative portrait of presenting clinical features, demonstrating a relatively consistent pattern when viewed across the decades. Demographic information from reviewed papers is included in Table 1. Analysis of data obtained
from the literature indicates the most common causative organisms of lacrimal canaliculitis are the Actinomyces species (see Table 2). Other microorganisms known to be associated with canaliculitis are listed in Table 3. Recent studies demonstrate greater rates of infection with streptococcal, and staphyloccal species than Actinomyces.35,74 Lacrimal canaliculitis occurs at a mean age of 59 years, but has been reported in patients from 5--90 years of age. There is a 5:1 female:male ratio, consistent with earlier studies.4 No racial or ethnic association was found. Accurate measures of the prevalence of primary canaliculitis in the general population are unavailable, owing to the frequency of misdiagnosis, relative rarity, and general underreporting of the disease. Historical incidence of canaliculitis in ophthalmic records screened for relevant symptoms ranged between 2% and 4%.16,74 Secondary canaliculitis is most commonly related to punctal or intracanalicular plug placement. Punctal occlusion to prevent tear drainage is the most common non-pharmalogical treatment for dry eye.12 Women represent 92% of secondary canaliculitis cases in the literature, likely because of the preponderance of women treated with placement of a plug for dry eye syndrome. A summary of case reports in canaliculitis secondary to punctal and intracanalicular plugs is included in Table 4. The generalizability of these cases is difficult to measure, and the first studies conducted especially to determine iatrogenic rates of lacrimal disease were only recently published.25 Among 235 patients with a total of 403 placed plugs from a single ophthalmology practice, the prevalence rate of canaliculitis per patient was 7.23%, and per plug inserted was 4.73%. The study was limited to SmartPlug (Medennium, Inc., Irvine, CA) placement by a single physician.
TABLE 1
Demographic Information from Literature Reviews and Case Reports Sullivan, 1993 Anand, 2004 Pavilack and Freuh 1992 Zaldivar and Bradley 2009 Repp, 2009 Vecsei, Huber-Spitzy et al. 1994 Briscoe, Edelstein 2004 Berlin, 1980 Lee, 2009 Hill, 2009 Hussain, 1993 Lin, 2010 Information from Case Reports (see Table 4) Means
Mean Age
Range
Female
Total
(%Fm)
52.0 69.6 51.0 60.0 70.6 52.3 71.7 60.3 61.5 64.0 49.9 64.0 45.7 59.4
14--86 45--87 10--84 22--86 50--87 26--82 43--90 n/a 29--77 41--88 n/a 30--89 5--80 14--90
13 13 8 15 9 25 4 6 23 15 5 24 24 184
18 15 11 23 11 40 7 9 30 17 7 34 29 251
72.2 86.7 72.7 65.2 81.8 62.5 57.1 66.0 76.7 88.2 71.4 70.6 82.8 73.31
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FREEDMAN ET AL
TABLE 2
Microorganism Prevalence Organism
# Cases (188 Total)
%
67 52 26 22 11 15 2 32
30.3 21.8 11.8 9.9 4.9 6.7 0.9 14.4
Actinomyces None Found Strep Staph Fungus Nonspecific gram() Nonspecific gram(þ) Other
III. Clinical Presentation The most commonly seen clinical presentation among 29 case reports and 12 reviews (total 5 280 patients) of primary canaliculitis are described. The typical patient is a post-menopausal woman who presents with epiphora, lower eyelid erythema, and a red, pouting punctum with yellowish, mucopurulent discharge. Massage or curretage of the canalicula frequently produces removable concretions histologically positive for Actinomyces.
A. CLINICAL SYMPTOMS AND SIGNS
The classic presenting symptoms associated with primary canaliculitis include epiphora, medial canthal swelling, non-resolving or recurrent conjunctivitis, and a swollen, pouting punctum, with or without yellowish or mucopurulent discharge.10,16,20,49,74 Also found is mattering on the eyelids49,74 and sulfur granules, stones, or concretions expressed from the punctum by massage or recovered during surgery.4,16,32,49,70 TABLE 3
All Known Organisms Associated with Canaliculitis Actinomyces Actinomyces israeli Mycobacterium Mycobacterium abcessus Mycobacterium chelonae Nocardia asteroides Staphylococcus aureus Streptococcus faecalis Arcanaebacterium hemolytica Streptothrix Propionibacterium acnes Cornyebacterium Haemophilus influenza Pseudomonas aeruoginosa Fusobacterium Citrobacter Chryseobacterium Proteus mirabellus Bacteriodes fragillus
Cases of secondary canaliculitis have been associated with epiphora, conjunctivitis, eyelid induration and erythema, pain, swelling, canalicular inflammation, inflammatory mass projecting from the punctum, granuloma formation, intermittent blood-stained tears, blood-tinged or mucopurulent discharge, and the presence of canaliculiths and dacryoliths.14,19,31,39,48,55,58 Vecsei et al reported that his group’s in-office diagnostic procedures included slit lamp examination of upper and lower eyelids, medial canthus, conjunctival fornices, upper and lower lacrimal puncta, and lacrimal syringing.69,70 They believe lacrimal syringing allows for the assessment of functional or mechanical stenosis and serves a therapeutic purpose when astringent or antibiotic drops are administered.69 B. HISTORICAL USE OF EXAMINATION
Although no consensus exists, there is precedent for making the presumptive diagnosis of canaliculitis based on the clinical symptoms alone.4,16,32,36,49,70 Ellis et al reported the finding of concretions as diagnostic.18 Demant et al stated the presence of chronic unilateral conjunctivitis, canalicular swelling, a pouting punctum, plical congestion, and expression of discharge or stone from the punctum were all suggestive of canaliculitis.16 Pavilack et al established the diagnosis of chronic canaliculitis in 11 cases by the presence of expressible canalicular concretions and signs of pericanalicular inflammation, distinguishing it from dacryocystitis by the absence of lacrimal sac involvement.49 Lee et al diagnosed 41 cases by swelling and erythema of the affected punctum and canaliculus accompanied by purlulent discharge or concretions extruding from the punctum.32 Hill et al defined canaliculitis in patients with epiphora or mucopurulent conjunctivitis and swelling at the medial ends of the upper or lower eyelids or reflux of mucopurulent material with gentle compression of the affected canaliculus.25 Zaldivar et al defined primary canaliculitis as mucopurulent punctal regurgitation on palpation, no eyelid thickening or erythema, or the presence of a classic pouting punctum.74 Anand et al suggest that more elaborate diagnostic methods such as dacryocystography are not only unnecessary, but may predispose an already inflamed canaliculus to scarring from the associated iatrogenic trauma.4 Case series detailing the most prevalent presenting signs and symptoms differ. When these studies are compared, there is no evidence to suggest change over time in the presentation of canaliculitis. Their differences most likely reflect normal
Case Report Information
a. Primary Canaliculitis Leung et al 200634 Charles et al 200613 Fulmer et al 199920 Hatton and Durand 200824 Tost et al 200067 Serin et al 200760 Moscato and Sires 200845 Varma and Chang 200569 Varma and Chang 200569 Park et al 200448 Romano et al 197853 Sullivan et al 199365 Shauly et al 199361 McKellar and Aburn 199742 Liyanage and Wearne 200936 Abdul and Sathiavakesan 19841 b. Secondary Canaliculitis Fowler et al 200819 Fowler et al 200819 Fowler et al 200819 Scheepers et al 200758 Chen and Lee 200714 Chen and Lee 200714 Chen and Lee 200714 Ahn et al 20093 Lee and Flanagan 200131 Lee and Flanagan 200131 Gerding, Kuppers 200320a Rumelt et al 199755
Age
Female
80 66 24 60 36 51 34 78 65 5 61 42 62 10
+ + + + + + +
Plugs
Months before presentation
Punctal Discharge
Upper Eyelid
+
+ +
+ +
+ +
23
+
+ + +
Reported Concretions
Lasik
Sjogrens
Surgical Treatment
+ +
+ + + + + +
+ +
+ + + +
+ + +
+
+ + + + +
+ + +
+ + + + + + + +
Reported Dry Eye
+ +
+ +
48
41 42 38 60 68 28 26 44 41 72 55 42
Lower Eyelid
+ + + + + + + + + + + +
24 4 72 14 10 5 6 36 1 14 12 3
+
+ + +
+
+
+ + +
+ + +
+
+
+
+
+
+ + + + + + + +
+
+
+ +
+
+ + + + + + + + +
+
+
+ + +
+
+
+
PRIMARY AND SECONDARY LACRIMAL CANALICULITIS
TABLE 4
+ + + +
+ +
+ + +
+ + 339
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variability accentuated by a small number of patients. Zaldivar et al found the most common presenting symptoms to be epiphora and mattering, and punctal regurgitation was the most common clinical finding.74 Repp et al report a 73% prevalence of concretions.51 Mohan et al44 reported epiphora, discharge, irritation, and recurrent conjunctivitis as the most common symptoms. Sixty percent (60%) had punctal regurgitation, and all 12 cases had a pouting punctum, erythema, and thickening of the medial aspect of the eyelid.44 The Smart Plug study group found that many of their 17 cases presented with eyelid edema and erythema, conjunctivitis, or an inflammatory mass projecting from the punctum.39 Briscoe et al reported all of their patients had epiphora, chronic conjunctivitis, thickened canaliculus, and yellow discharge.10 The common findings in Anand et al’s patients were mucopurulent discharge (93.3%) and medial canthal inflammation (66.6%), whereas epiphora was present in only 46.6%.4 Earlier cases corroborate high prevalence of punctal regurgitation, concretions, medial eyelid thickening and erythema, pouting punctum, and expressible yellowish or bloody mucopurulent discharge among study populations.49,57,70 Regarding patients with punctal or intracanalicular plugs, silicone intubation, or any foreign body in the eye, the literature consistently supports a high index of suspicion for canaliculitis in any patient with irritation, epiphora, and purulent discharge.7,14,19,25,29,31,39,40,47,54,55,58
FREEDMAN ET AL
streptococcal and staphylococcal infection.4,35,70,74 Actinomyces was first cited by Harz in 1879 to describe organisms found in the cattle. Their lesions appeared radially arranged like fungal mycelia, leading to the name Actinomyces (ray fungus). Actinomyces species are now considered Gram positive bacilli which occur singly, in pairs, or in chains and are non-motile obligate or facultative anaerobes. They are normal constituents of human and cattle oral flora and are capable of causing chronic granulomatous infections, typically spreading by direct extension. Actinomyces has been reported to cause multiple forms of ocular infections, including canaliculitis, conjunctivitis, dacryocystitis, keratitis, and endophthalmitis.28 Actinomyces characteristically appears as branching filaments on Gram stain. There is substantial evidence that follow-up cultures will support an alternative diagnosis, even when histopathological analysis reveals actinomycotic concretions.10,16,52,74 The low success rate in isolation of organisms is frequently attributed to the fastidious nature of Actinomyces,18,28,42 the difficulty of culturing this anaerobic organism, and high tendency for polymicrobial infection.24,28,44,48,59,63 Successful culture of these organisms from concretions ranges from 11.1% to 71.4%.4,8,10,16,28,35,49,51,70 In spite of these known problems, it is still common for clinicians reporting cannaliculitis to base the diagnosis on histopathology alone. One must keep in mind that a lacrimal system neoplasm may present with unilateral tearing and discharge. A. MICROBIOLOGICAL CULTURE
IV. Diagnosis Despite decades of literature detailing the constellation of clinical signs and symptoms, lacrimal canaliculitis continues to be undiagnosed, misdiagnosed, and improperly treated.4,10,28,49,68,70 Because of the variability of symptoms, coincidence of symptomatology with other disorders of the eye, and the possibility of canaliculitis presenting without classic symptoms,45,60,61 more objective measures should be used. The majority of published studies and case reports on canaliculitis detail an attempt to determine the causative organism, either by culture or histopathological examination. Samples are taken from tears, punctal discharge, concretions, or particulate matter recovered via massage or curettage. Actinomyces israelli is often cited as the most common pathogen of lacrimal canaliculitis,20,23,28,46,49,63,65 although studies published within the last decade demonstrate higher rates of
Methods of obtaining culture include conjunctival swabbing,28,30,42 sampling of punctal discharge44,58,59 and conjunctival sac materials, abscess culture,s and culture of particulate matter and concretions.4,19,31,32,35 Some physicians choose to send for only aerobic and anaerobic cultures,16 whereas others report culturing for bacteria, fungus, and mycobacteria.19 Innoculums placed on blood agar, chocolate agar, and Sabouraud dextrose agar and incubated anaerobically have been successful in identifying Actinomyces israelli from canalicular concretions.42 Urgent collection and transport methods have been reported to improve yields, and delayed processing may negatively affect results.28 Improved detection rates have also been reported using a PD Plus/F blood culture bottle (Beckton, Dickinson & Co., Franklin Lakes, NJ).10 Less common organisms have been cultured by a variety of means. Eikenella corrodens was identified by the Vitek 1 system using the Neisseria/Haemophius identification card (BioMerieux, Marcy
341
PRIMARY AND SECONDARY LACRIMAL CANALICULITIS
l’Etoile, France).34 Lactoccocus lactis cremoris has been identified by the Rapid ID 32 Strep kit (BioMerieux).34 Some fungi like Pitysporum pacydermatitis have required not just culture for identification, but also analysis of sugar, ammonium, potassium, and nitrogen assimilations.53 Because of the wide breath of possible microbial pathogens when canaliculitis is suspected, the microbiology lab should be informed of the possible need for special testing. B. HISTOPATHOLOGY
Histopathological examination is the most commonly reported diagnostic test performed on canalicular concretions.10,16,32,51,57,70 The concretions found consistently in case series typically portray the histopathological characteristics of Actinomyces,10,70,74 although the success rate of culturing these organisms is low.4,10,74 Sulfur granules, which have been described as yellow, cheese-like granules with a gritty consistency, are considered the pathologic hallmark of Actinomyces canaliculitis.20 On hematoxylin-eosin (H&E) stain these are basophilic masses originating from aggregated filamentous bacteria with peripheral club-like eosinophilic structures.10 These actinomyotic granules typically show numerous, radially oriented, Gram-positive, filamentous bacteria with peripheral clubs that stain positively with Periodic Acid-Schiff (PAS). Although highly suggestive of Actinomycosis, they are also seen with Staphylococci, Fusobacterium, Nocardiosis, Chromomycosis, and Botryomycosis,11,32,72 so culture should always be attempted. Filamentous bacteria demonstrating a Gram-positive, acid-fast negative pattern are also characteristic of propionibacterium.48 The typical findings associated with secondary cases of canaliculitis can be centered about the foreign body. Histopathologic examination of extracted foreign bodies shows inflammatory cells infiltrated along the margins, as well as mass excisions consistent with papillomas.3 Findings consistent with pyogenic granuloma have also been reported.39 Histological methods that may aid in diagnosis include H&E staining, Gomori’s methenamine silver stain, Brown and Brenn Gram-stain, and PAS. H&E stain may be helpful in revealing the general appearance and type of material present, whereas Gram and PAS stains are more useful in making a specific diagnosis.10 Gomori methenamine silver stain can help to differentiate Actinomyces from other microorganisms.11,32 Repp et al made a presumptive diagnosis from the presence of numerous filamentous organisms on Gomoroi’s methanamine silver stain, if the organisms were also Gram positive and clearly visible on PAS stain.51
Histopathological diagnosis may be misleading. Weinberg et al reports three cases where Gram stains show weakly Gram-positive branching filamentous organisms, thought to be Actinomyces.72 Aerobic cultures grew either a collection of Diphtheroids, Staphylococci, and Haemophilus, or nothing at all. Anaerobic cultures grew Fusobacterium, Nucleatum, or Fusobacterium Necrophorum, but no Actinomyces. The authors call attention to the fact that the classic ‘‘sulfur granules’’ composed of aggregates of filamentous branching microorganisms, typically associated with Actinomyces, are not always present in Actinomyces infection and in fact can be formed by other bacteria such as Staphyloccoccus aureus. They point out that both Actinomyces and Fusobacterium are anaerobic, non-sporeforming bacilli. Although Actinomyces should stain Gram positive and Fusobacterium should stain Gram negative, both are subject to irregularities in this pattern, and the two can be confused histopathologically. C. GENETIC TESTING
Very limited reports of using polymerase chain reaction to search for Actinomyces DNA exist. One report details cases diagnosed by histopathology as Actinomyces canaliculitis, having all yielded negative results for Actinomycotic DNA.4 An isolated report demonstrates DNA in the ‘‘concretion’’ of a suspected case of canaliculitis found positive for human papillomavirus types 16, 18. In the event it was evident on histopathology that this was in fact carcinoma of the lacrimal sac.13 At present, there is little evidence to support genetic testing in the diagnostic work-up of suspected canaliculitis. D. IMAGING
Imaging techniques can be used to confirm the diagnosis of canaliculitis and provide information that may facilitate surgical planning. Early imaging was carried out with intubation macrodacryocystography (roentgenography), and more recently the utility of ultrasound images has been explored. In a case series identifying post-herpetic canaliculitis, electron microscopy was used to image viral particles in tissue samples, although the clinical use of such techniques is uncommon.43 X-rays26 and, in rare cases, radioisotope lacrimal scanning,27 have been used to aid in the diagnosis of canaliculitis.4,16,33,57,65 Demant et al used x-rays to depict non-filling of the involved canaliculus, or marked dilatation and raggedness of the canaliculus is associated with canaliculitis.16 They noted that stones are not demonstrated by dacryocystography because they are usually amorphous. Santhananthan
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et al designated filling defects of the lacrimal canaliculi as diagnostic of canaliculitis.57 Additional findings associated with canaliculitis included dilatation of the canaliculus, beading, and small diverticuli. More recently, ultrasound imaging has been used in the diagnosis of canaliculitis.64,67 Ultrasonic images of chronic canaliculitis showed ectasia of the canaliculus and sulfur grains. High-resolution ultrasonic examination of the lacrimal drainage system demonstrated that a 20-MHz scanner is able to show reflective structures such as sulfur granules measuring 12 mm in diameter, which are pathognomic for canaliculitis. Scarce data are available to support the practical utility of ultrasound as a diagnostic measure at this time. E. CANALICULAR PATENCY
Patency of the lacrimal drainage system to syringing is typical in canaliculitis.18,28,44,52,57 Passage of a syringe into the canaliculus and fluid expression ascertains patency of the nasolacrimal drainage system and generally excludes dacryocystitis from the differential. Patency of the lacrimal excretory passages to syringing does not suggest the absence of stones, as stones in the canaliculi may still allow saline flow.16 Similarly, co-morbidities may exist that obstruct the system but do not exclude canaliculitis, such as swelling and coexisting obstructions of the tear sac.16 Anand et al4 conducted extensive lacrimal workups on patients, including complete adnexal and anterior segment examination. They identified lid position, punctal position, and any cause of reflex epiphora including blepharitis or corneal surface abnormalities, and reported tear film break-up time and Schirmer’s test results. Lacrimal pump function was assessed using the Jones dye disappearance test. Lacrimal syringing and probing were used to establish patency of the lacrimal system and the site of any obstruction. These authors proposed that detailed assessments would preclude the necessity of invasive diagnostic imaging techniques. Other reports in the literature reflect similar drainage assessment.43 F. MISDIAGNOSIS
Misdiagnosis and delayed diagnosis are frequent. Physicians should suspect canaliculitis in patients with chronic unilateral epiphora, chronic conjunctivitis, mucopurulent discharge, pouting punctum, or concretions.4,10,16,42,49,70 If the literature accurately reflects clinical practice, it would appear that it is more common to misdiagnose patients with canaliculitis than to identify this condition. Case
FREEDMAN ET AL
studies of canaliculitis report percentages of patients previously misdiagnosed as 45%,49 60%,4,70 and 100%,10 and one study noted that 33% of patients had been previously misdiagnosed multiple times.4 Some patients have received empirical treatment without any specific diagnosis.4 Speculations on why canaliculitis is so frequently misdiagnosed include its low prevalence, once cited as 2% of lacrimal disease,16 or the atypical presentations which can mimic conjunctivitis70 or dacryocystitis.60 Reported misdiagnoses include chronic conjunctivitis, chronic dacryocystitis, chalazion, mucoceles, and blepharitis.4,49,68,70 The delay of diagnosis, or amount of time from becoming symptomatic to the eventual correct diagnosis, manifests a spectacular spectrum. Individual case reports of patients have delays over 10, 15, and 20 years.10,52 Misdiagnosis results in inappropriate treatment, often with broad spectrum topical antibiotics, which may transiently alleviate the symptoms, but usually do not result in a lasting cure.28 In other cases, misdiagnosis results in unnecessary procedures, often irrigation of lacrimal system, which can force concretions into more distal portions of the canaliculus.4,10,60 One report described a patient previously diagnosed with acute dacryocystitis who had undergone multiple irrigations, and finally a one-snip punctoplasty, without complete resolution of symptoms. Several weeks after the surgery the patient expressed a dozen dacryolyths.60 Analysis of the stones demonstrated their composition to be of previously formed canalicular concretions. The authors suggest that misdiagnosis as dacryocystitis led to unnecessary irrigations that may have pushed previously formed concretions and granules into more distal canalicular regions, explaining why concretions were not evident during initial compression or canaliculotomy. Distinguishing canaliculitis from look-alike pathologies can be challenging. Differentiation of canaliculitis from dacryocystitis is important to prevent inappropriate treatment with irrigation that can exacerbate symptoms. On exam, canaliculitis can be distinguished from dacryocystitis by the lack of lacrimal sac distention, nasolacrimal duct obstruction, and signs of lacrimal sac inflammation. In contrast with the blennorrhea of dacryocystitis, debris in canaliculitis is usually expressed with direct massage of the involved canaliculus and not with lacrimal sac compression.49
V. Treatment of Canaliculitis Althought relatively little has changed in the presentation or microbiological etiologies of
343
PRIMARY AND SECONDARY LACRIMAL CANALICULITIS
canaliculitis over the years,74 the treatment of canaliculitis may in fact be evolving. Where it was once believed that conservative treatment is ineffective in long-term treatment of canaliculitis,4,10,16,28,49,68,70 there are newer reports which suggest increasing cure rates with non-surgical approaches.44,74 A. MEDICAL MANAGEMENT
Conservative therapy includes warm compresses, digital massage, topical and systemic antibiotics, antifungals, corticosteroids, as well as some nonsurgical procedures such as irrigation and syringing. It is widely reported that medical therapy is rarely effective in clearing canalicular infections. The concretions present may prevent antibiotics from eradicating the bacterial source by virtue of obstruction to flow and protection of bacteria within the stones.4,28,49,69,70 Others have postulated the thick mucopurulent and particulate discharge and abscess-like accumulation of infected debris are responsible for resisting the penetration of topical and systemic antibiotics.16,49 The thick granular debris formation may cause a self-perpetuating cycle of canalicular stasis and infection persisting for many years. Antibiotics may improve symptoms, even when failing to achieve long term resolution.4,10,16,19,25,28 A recent study cites a 33% rate of recurrence in conservatively treated patients.35 In many cases conservative measures fail to provide any improvement,4,14,19 although case reports of resolution with medical management exist.14,34,39,44,74 Rare cases of secondary canaliculitis that resolve with medical management are also described,39 but plug removal should be a part of any treatment regimen. Complete resolution with medical management is typically limited to those patients who present early in the course of the disease.16,34,69,70,74 A recent series showed complete resolution without recurrence at an average of 150 days follow-up for those treated within the first 30 days of symptoms.74 Symptomatic improvement has been noted with systemic penicillin and topical neomycin, polymyxin, or bacitracin regardless of whether Actinomyces was cultured.16 A recent study demonstrated success in all patients with combined topical antibiotic and canalicular irrigation using fortified cefazolin solution, prepared at 50 mg/ml.44 Patients were again irrigated at 48 hours if clinical improvement was not evident. The number of irrigations necessary per patient averaged 4.5 (range, 1--8); all patients had excellent resolution of canaliculitis without the need for surgical treatment.
Medical regimens not proven to give lasting resolution include combinations of oral penicillins, sulfamethoxazole-trimethoprim, tetracyclines, metronidazole, and indomethacin. Reported topical combinations include penicillins; cephalosporins; tetracyclines; chloramphenicol; macrolides; flouroquinolones; the antifungals fucithalmic, zinc and adrenaline; neomycin; polymyxin; and bacitracin.4,10,16,28,44,69 Topical dexamethasone10 alone was not successful but was efficacious when combined with tobramycin.14 Many studies use culture sensitivities to guide their treatment regimen;however, this does not appear to improve response rates to conservative therapy. Lacrimal irrigation is sometimes effective in resolving cases of canaliculitis secondary to intracanalicular plug placement. A notable risk of this procedure, however, is the possibility of the plug dislodging from its canalicular position and moving distally into the lacrimal system, resulting in permanent obstruction.39 Hyperbaric oxygen therapy was used by Shauly et al61 treating an A. israelli canaliculitis that had proven refractory to curettage and topical penicillin for four weeks in a patient who refused further surgery. The regimen included antibiotics and daily 90-minute sessions at 100% O2 at 2--2.5 atmospheres 6 days a week for 4 weeks. The patient noted gradual improvement over this period, and complete resolution by 2 months, with no recurrence at 1 year follow-up. B. SURGICAL MANAGEMENT
Most studies support surgical management as the definitive treatment for canaliculitis.10,16,35,49,70 Surgery removes concretions that serve as a reservoir for bacteria. The least invasive methods involve dilation of the punctum to facilitate curettage of the stones.66 When dilatation is insufficient to allow passage of the probe into the punctum or withdrawal of the concretions, various punctoplasty techniques are shown to sufficiently widen the os. Canaliculotomy allows greater access to the canaliculus, after which the incision can be left open or closed with or without stent placement. Syringing and probing can be used to determine the presence and location of strictures in the canalicular system. Length and patency of the canaliculus can be determined in this fashion. Dilation of the punctum followed by curettage of the canaliculus has proven effective in primary canaliculitis.49,51 This carries a low risk of scarring the canaliculus, and the pump function is preserved by avoiding canaliculotomy. Pavilack et al49 reported high success rates treating patients with curettage,
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followed by a 10-day course of 10% sulfacetamide sodium drops four times per day. If resolution of symptoms had not occurred by two weeks, the curettage and antibiosis regimen was repeated. In this series all patients were successfully treated with one (45%), two (45%), or three (10%) sessions of curettage. Punctoplasty was first performed in the study group to allow passage of the curette, but the authors later found that dilation alone was sufficient to allow curetting. A more recent retrospective analysis of curettage outcomes with the use of one snip punctoplasty in thirty patients with primary canaliculitis demonstrated the successful resolution of symptoms in 83% of patients at their 3-week follow-up.32 Patients with mild, persistent symptoms were treated with continued antibiotics for one month, and their infection resolved. Two patients required a second curettage. Complications included formation of canalicular strictures. Two-snip42 and three-snip43 punctoplasty procedures have been reported. Risks of canaliculotomy include canalicular luminal narrowing or scarring, lacrimal pump dysfunction, canalicular fistula formation,4,39 failure to diagnose and treat stones lodged deeper in the canaliculus, and need for subsequent surgery,74 as well as the standard risks associated with any surgical procedure. Complications of the canaliculotomy include the need to reconstruct the canaliculus,10 intubation,25 stent placement, canalicular fistula formation,39 and orbital cellulitis and abscess formation.24 Although continued epiphora in patients after canaliculotomy was considered a possible sequela,70 Anand et al reported that long-term follow-up did not reveal a direct relationship between persistent epiphora and canaliculotomy.4 Canaliculotomy allows for greater access and easier curettage of canalicular contents. It is widely regarded at the procedure of choice for both primary and secondary canaliculitis.4,10,14,16,25,36, 45,58,60,68,70,71,74 A canaliculotomy is performed by passing a probe into the canaliculus and making a horizontal incision through the eyelid margin to open the canaliculus and expose the probe. The incision should begin about 2 mm medial to the ampula and is usually about 8 mm in length.66 Once the canaliculus is opened, the probe is removed, and the stones are extracted with a small curette. The canaliculus may then be irrigated with antibiotic solution. At the surgeon’s discretion a canaliculostomy may be performed in which silicone tubing stent such as a Mini-Monoka (FCI Ophthalmics, Pembroke, MA) is passed into the canaliculus, and the wound is closed with small caliper absorbable sutures. The tube is usually removed in a few weeks.
FREEDMAN ET AL
Some authors recommend irrigation of aqueous penicillin or povidine iodine and meticulous repair of the canaliculus.18,28 Others have found that, in most cases, the canaliculus will return to its preinflammatory state when just left to heal.10,16 Silver nitrate cauterization following removal of canalicular stones has been reported.16 This theoretically could cause injury to the epithelium, although no evidence of this was noted. Multiple case reports also detail patients where no reconstruction of the canaliculus is undertaken, and full recovery with patent syringing is seen on follow-up.20,52 Systemic Actinomyces involving other organs is treated with high dose antimicrobial agents for extended durations as a result of the tendency of this pathogen to recur.56 Briscoe et al10 report no recurrence in any of their patients with a regimen that included an initial high-dose IV penicillin therapy of 20 million units daily for at least 3 weeks, followed by oral administration of 2 g per day for at least 3 months. Favorable treatment outcomes following canaliculotomy are reported among all case series on canaliculitis, with complete resolution in the majority of primary canaliculitis patients.4,10,35,70 Resolution of canaliculitis occurs in between 80%69 and 100% of cases after canaliculotomy.4,10,16 Continued symptoms of epiphora and recurrent canaliculitis are reported.35,70 Intubation or stent placement is employed in circumstances where patency of the canaliculus is in question.14,19,25,51 In treatment of secondary canaliculitis following SmartPlug insertion, an initial trial of topical and broad-spectrum antibiotics followed by retrograde massage is suggested should plug removal be indicated.39 Irrigation of the nasolacrimal duct is recommended by the manufacturer, and this has been demonstrated to resolve a number of SmartPlug related cases.39 Irrigation is also thought to risk dislodgement of the plug from its canalicular position, causing permanent obstruction of the lacrimal drainage system.41 Canaliculotomy with removal of foreign body is frequently performed if conservative therapy with medical management and/ or lacrimal irrigation fails to improve epiphora or canaliculitis.25,39 If canaliculotomy fails to improve the condition, dacryocystorhinostomy with intubation20 or placement of a Jones tube may be necessary.
VI. Prognosis The long-term resolution of primary canaliculitis treatment may be affected by the duration of the disease prior to diagnosis, the management employed, patient co-morbidities, and lesser
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understood factors such as patient age, sex, the presence of concretions, and microbiology.4,35,74 Acutely, treatment often progresses from conservative to surgical management until satisfactory resolution is achieved. In primary canaliculitis the presence of continued symptoms varies with treatment modality. Successful initial resolution with conservative treatments have been reported in 0%,4 20%,70 ,26%,35 and 34.7%74—with recurrence rates as high as 33%.35 Several authors have noted patients with acute canaliculitis achieve higher success rates with conservative treatment, whereas those with longer disease courses typical fair better with surgical or combination treatment.15,16,74 In the single case series describing combination therapy with intracanalicular antibiotic irrigation and topical antibiotics, resolution was reported in all patients after a mean of 4.5 treatments.44 Continued symptoms after canaliculotomy—such as epiphora4,70 and mattering74—occur in as many as 27% of patients. Recurrence of canaliculitis after canaliculotomy may develop in up to 21% of patients undergoing canaliculotomy, with a mean time of recurrence of 24 months.35 Some patients have had recurrent canaliculitis in a previously unaffected canaliculus.74 Pre-existing nasolacrimal duct pathology or a history of inappropriate lacrimal sac washout procedures may predispose to the development of new, or the exacerbation of old, nasolacrimal duct obstruction after canaliculotomy.4 Curettage success rates have been reported in as many as 83.3% of patients at a mean follow-up of 10.76 weeks.32 With SmartPlug-related canaliculitis, topical and systemic antibiotics are infrequently associated with resolution. Lacrimal irrigation may resolve symptoms but is associated with the risk of lacrimal system obstruction. Canaliculotomy is the definitive therapy. Complete resolution of symptoms may not always be achieved, however, and persistent epiphora following surgery has been reported.41
VII. Summary In patients who present with epiphora, chronic or recurrent unilateral conjunctivitis, a thickened canaliculus, pouting punctum, or expressible yellow discharge, a diagnosis of canaliculitis should be considered and evaluation and treatment instituted. Manual expression of discharge or concretions should be attempted. Microbiological investigation of the expressed material should include histopathological examination and culture. Imaging may be considered in situations where the diagnosis is not
clinically evident or where further information is required for surgical planning. Ultrasound offers a noninvasive means of identifying concretions; intubation macrodacryocystography, however, remains the more well studied method for the identification of filling defects in the lacrimal drainage system. Conservative medical therapy has a higher rate of success with new onset canaliculitis and should be considered as a first line treatment. Topical and/or systemic antibiotic therapy may begin with broad spectrum and then be tailored to the culture sensitivity. Repeated intracanalicular antibiotic irrigation is suggested as an alternative to surgery and demonstrates promising initial results, but has not been widely reproduced or adopted at present. Curettage of the punctum via dilation or punctoplasty may be successful in removal of concretions and resolution of canaliculitis. Canaliculotomy remains the definitive therapy. Continued symptoms of epiphora and mattering are common. Recurrent canaliculitis occurs in approximately one-fifth of patients 2 years after surgery. Patients should be apprised of this possibility and advised to seek treatment early if symptoms recur. Canaliculostomy may be performed at the discretion of the surgeon.
VIII. Conclusion There is a clear need for greater awareness among clinicians, especially those in training, to recognize canaliculitis. A higher index of suspicion would prevent delays in diagnosis and unnecessary manipulation of the lacrimal system.4
IX. Method of Literature Search A systematic review was conducted to survey all published case reports of lacrimal canaliculitis, all reviews of ophthalmic disease and surgical intervention where canaliculitis was recorded as an outcome or described as a complication, and all previous scientific studies on lacrimal canaliculitis. Search was not limited to Medline or English-language papers. A full-text search of the term canaliculitis in the Cochran Collection yielded 2 of 608,405 records.37,38 A Medline search for ophthalmic streptothricosis yielded 409,770 results with no filters for language or journal type. Adding the keyword punctum reduced this number to 228, which were each reviewed for relevance to canalicular disease and additional references contained therein. An independent Medline search for canaliculitis yielded 105 results, which were surveyed in a similar manner. Identical search via Embase, OldMedline
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or ISI did not return additional citations. The reference lists for relevant papers was reviewed, and papers not electronically databased were individually acquired through library loan or a handreview of the historical journals collection of the Rush University Medical Library, and the University of Miami Norton Library, Bascom Palmer Eye Center. Every effort was made to cite only original sources, and to avoid secondary citations among studies making more recent claims; for example, the Norton library contains a rare print collection that was useful for some of the less distributed examples.17,18,22,50,62
X. Disclosure The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article.
References 1. Abdul Kareem S, Sathiavakesan S. Streptothrix canaliculitis. Indian J Ophthalmol. 1984;32:179--80 2. Adenis JP, Saint-Blancat P. [Conjunctivitis and lacrimal apparatus infections]. Rev Prat. 1992;42:947--51 3. Ahn HB, Seo JW, Roh MS, et al. Canaliculitis with a papilloma-like mass caused by a temporary punctal plug. Ophthal Plast Reconstr Surg. 2009;25:413--4 4. Anand S, Hollingworth K, Kumar V, et al. Canaliculitis: the incidence of long-term epiphora following canaliculotomy. Orbit. 2004;23:19--26 5. Asghar S, Mahmood A, Khan MA. Nocardia canaliculitis presenting as pouted punctum. J Coll Physicians Surg Pak. 2008;18:55--7 6. Baldursdottir E, Sigurdsson H, Jonasson L, et al. Actinomycotic canaliculitis: resolution following surgery and short topical antibiotic treatment. Acta Ophthalmol. 2010;88(3): 367--70 7. Becker BB. Retained veirs rod and canaliculitis. Am J Ophthalmol. 1991;111:251--2 8. Berlin AJ, Rath R, Rich L. Lacrimal system dacryoliths. Ophthalmic Surg. 1980;11:435--6 9. Brazier JS, Hall V. Propionibacterium propionicum and infections of the lacrimal apparatus. Clin Infect Dis. 1993;17: 892--3 10. Briscoe D, Edelstein E, Zacharopoulos I, et al. Actinomyces canaliculitis: diagnosis of a masquerading disease. Graefes Arch Clin Exp Ophthalmol. 2004;242:682--6 11. Brown JR. Human actinomycosis. A study of 181 subjects. Hum Pathol. 1973;4:319--30 12. Calonge M. The treatment of dry eye. Surv Ophthalmol. 2001;45(Suppl 2):S227--39 13. Charles NC, Lisman RD, Mittal KR. Carcinoma of the lacrimal canaliculus masquerading as canaliculitis. Arch Ophthalmol. 2006;124:414--6 14. Chen SX, Lee GA. SmartPlug in the management of severe dry eye syndrome. Cornea. 2007;26:534--8 15. Chumbley LC. Canaliculitis caused by Enterobacter cloacae: report of a case. Br J Ophthalmol. 1984;68:364--6 16. Demant E, Hurwitz JJ. Canaliculitis: review of 12 cases. Can J Ophthalmol. 1980;15:73--5 17. Elliot A. Streptothricosis in the lacrimal canaliculi. Am J Ophthalmol. 1941;24:682--6
FREEDMAN ET AL 18. Ellis PP, Bausor SC, Fulmer JM. Streptothrix canaliculitis. Am J Ophthalmol. 1961;52:36--43 19. Fowler AM, Dutton JJ, Fowler WC, et al. Mycobacterium chelonae canaliculitis associated with SmartPlug use. Ophthal Plast Reconstr Surg. 2008;24:241--3 20. Fulmer NL, Neal JG, Bussard GM, et al. Lacrimal canaliculitis. Am J Emerg Med. 1999;17:385--6 20a. Gerding H, Ku¨ppers J, Busse H. Symptomatic cicatrizial occlusion of canaliculi after insertion of Herrick lacrimal plugs. Am J Ophthalmol. 2003;136(5):926--8 21. Graefe AV. Koncretionen im unteren Thraenenroerchen durch Pilzbildung. Arch fur Ophthalmol. 1854;1:284--8 22. Greeves RA. Streptothrix conjunctivitis. Br J Ophthalmol. 1952;36:653 23. Hass C, Pittasch K, Handrick W, et al. [Actinomycetes canaliculitis----case reports]. Immun Infekt. 1995;23:222--3 24. Hatton MP, Durand ML. Orbital cellulitis with abscess formation following surgical treatment of canaliculitis. Ophthal Plast Reconstr Surg. 2008;24:314--6 25. Hill RH 3rd, Norton SW, Bersani TA. Prevalence of canaliculitis requiring removal of SmartPlugs. Ophthal Plast Reconstr Surg. 2009;25:437--9 26. Hurwitz JJ, Welham RA, Lloyd GA. The role of intubation macro-dacryocystography in management of problems of the lacrimal system. Can J Ophthalmol. 1975;10:361--6 27. Hurwitz JJ, Welham RA, Maisey MN. Intubation macrodacryocystography and quantitative scintillography: the ‘‘complete’’ lacrimal assessment. Trans Sect Ophthalmol Am Acad Ophthalmol Otolaryngol. 1976;81:OP575--82 28. Hussain I, Bonshek RE, Loudon K, et al. Canalicular infection caused by Actinomyces. Eye (Lond). 1993; 7(Pt 4):542--4 29. Hwang SW, Khwarg SI, Kim JH, et al. Bicanalicular double silicone intubation in external dacryocystorhinostomy and canaliculoplasty for distal canalicular obstruction. Acta Ophthalmol. 2009;87:438--42 30. Jordan DR, Agapitos PJ, McCunn PD. Eikenella corrodens canaliculitis. Am J Ophthalmol. 1993;115:823--4 31. Lee J, Flanagan JC. Complications associated with silicone intracanalicular plugs. Ophthal Plast Reconstr Surg. 2001; 17:465--9 32. Lee MJ, Choung HK, Kim NJ, et al. One-snip punctoplasty and canalicular curettage through the punctum: a minimally invasive surgical procedure for primary canaliculitis. Ophthalmology. 2009;116: 2027--30, e2022 33. Lee V, Bentley CR, Olver JM. Sclerosing canaliculitis after 5fluorouracil breast cancer chemotherapy. Eye (Lond). 1998; 12(Pt 3a):343--9 34. Leung DY, Kwong YY, Ma CH, et al. Canaliculitis associated with a combined infection of Lactococcus lactis cremoris and Eikenella corrodens. Jpn J Ophthalmol. 2006;50:284--5 35. Lin SC, Kao SC, Tsai CC, et al. Clinical characteristics and factors associated the outcome of lacrimal canaliculitis. Acta Ophthalmol. 2010 (EPub ahead of print. doi: 10.1111/j. 1755-3768.2009.01827.x) 36. Liyanage SE, Wearne M. Lacrimal canaliculitis as a cause of recurrent conjunctivitis. Optometry. 2009;80:479--80 37. Maichuk Iu F, Diadina UV. [Itraconazole in the treatment of ophthalmomycoses]. Antibiot Khimioter. 1994; 39:54--6 38. Malet T, David N, Maalouf T, et al. Scintigraphic evaluation of the degree of lacrimal duct occlusion after implantation of an intracanalicular plug. Orbit. 1997;16:241--6 39. Management of complications after insertion of the SmartPlug punctal plug: a study of 28 patients. Ophthalmology. 2006;113(10):1859 40. Mauriello JA Jr, Abdelsalam A. Use of a modified monocanalicular silicone stent in 33 eyelids. Ophthalmic Surg Lasers. 1996;27:929--34 41. Mazow ML, McCall T, Prager TC. Lodged intracanalicular plugs as a cause of lacrimal obstruction. Ophthal Plast Reconstr Surg. 2007;23:138--42
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PRIMARY AND SECONDARY LACRIMAL CANALICULITIS 42. McKellar MJ, Aburn NS. Cast-forming Actinomyces israelii canaliculitis. Aust NZ J Ophthalmol. 1997;25:301--3 43. McLean CJ, Rose GE. Postherpetic lacrimal obstruction. Ophthalmology. 2000;107:496--9 44. Mohan ER, Kabra S, Udhay P, et al. Intracanalicular antibiotics may obviate the need for surgical management of chronic suppurative canaliculitis. Indian J Ophthalmol. 2008;56:338--40 45. Moscato EE, Sires BS. Atypical canaliculitis. Ophthal Plast Reconstr Surg. 2008;24:54--5 46. Munk PL, Lin DT, Morris DC. Epiphora: treatment by means of dacryocystoplasty with balloon dilation of the nasolacrimal drainage apparatus. Radiology. 1990;177: 687--690 47. Pan XJ, Mao A, Zhao GQ, et al. Clinical effects of three types of silicone intubations in repairing lacerations of canaliculus. Chin J Traumatol. 2009;12:173--6 48. Park A, Morgenstern KE, Kahwash SB, et al. Pediatric canaliculitis and stone formation. Ophthal Plast Reconstr Surg. 2004;20:243--6 49. Pavilack MA, Frueh BR. Through curettage in the treatment of chronic canaliculitis. Arch Ophthalmol. 1992;110: 200--2 50. Raynaut F. Streptothricosis in lacrimal canaliculi. Arch d’Opht. 1920;38:311 51. Repp DJ, Burkat CN, Lucarelli MJ. Lacrimal excretory system concretions: canalicular and lacrimal sac. Ophthalmology. 2009;116:2230--5 52. Richards WW. Actinomycotic lacrimal canaliculitis. Am J Ophthalmol. 1973;75:155--7 53. Romano A, Segal E, Blumenthal M. Canaliculitis with isolation of Pityrosporum pachydermatis. Br J Ophthalmol. 1978;62:732--4 54. Rootman DS, Insler MS, Wolfley DE. Canaliculitis caused by Mycobacterium chelonae after lacrimal intubation with silicone tubes. Can J Ophthalmol. 1989;24:221--2 55. Rumelt S, Remulla H, Rubin PA. Silicone punctal plug migration resulting in dacryocystitis and canaliculitis. Cornea. 1997;16:377--9 56. Russo T. Harrison’s Principles of Internal Medicine. Burr Ridge, Illinois, McGraw--Hill, 1998 57. Sathananthan N, Sullivan TJ, Rose GE, et al. Intubation dacryocystography in patients with a clinical diagnosis of chronic canaliculitis (‘‘streptothrix’’). Br J Radiol. 1993;66: 389--93 58. Scheepers M, Pearson A, Michaelides M. Bilateral canaliculitis following SmartPLUG insertion for dry eye syndrome post LASIK surgery. Graefes Arch Clin Exp Ophthalmol. 2007;245:895--7
59. Seal DV, McGill J, Flanagan D, et al. Lacrimal canaliculitis due to Arachnia (Actinomyces) propionica. Br J Ophthalmol. 1981;65:10--3 60. Serin D, Karabay O, Alagoz G, et al. Misdiagnosis in chronic canaliculitis. Ophthal Plast Reconstr Surg. 2007;23:255--6 61. Shauly Y, Nachum Z, Gdal-On M, et al. Adjunctive hyperbaric oxygen therapy for actinomycotic lacrimal canaliculitis. Graefes Arch Clin Exp Ophthalmol. 1993;231: 429--31 62. Soares AD. [Septic canaliculitis due to an enterococcus Streptococcus faecalis; treatment with massive doses of penicillin]. Med Contemp. 1951;69:405--12 63. Struck HG, Hohne C, Tost M. [Diagnosis and therapy of chronic canaliculitis]. Ophthalmologe. 1992;89:233--6 64. Stupp T, Pavlidis M, Busse H, et al. Presurgical and postsurgical ultrasound assessment of lacrimal drainage dysfunction. Am J Ophthalmol. 2004;138:764--71 65. Sullivan TJ, Hakin KN, Sathananthan N, et al. Chronic canaliculitis. Aust NZ J Ophthalmol. 1993;21:273--4 66. Cohen AJ, Mercandetti M, Brazzo BG. The Lacrimal System: Diagnosis, Management, and Surgery. New York, Springer, 2006 67. Tost F, Bruder R, Clemens S. Clinical diagnosis of chronic canaliculitis by 20-MHz ultrasound. Ophthalmologica. 2000; 214:433--6 68. Varma D, Chang B, Musaad S. A case series on chronic canaliculitis. Orbit. 2005;24:11--4 69. Vecsei V. Canaliculitis—conservative versus operative therapy. Wiener Klinische Wochenschrift. 1993;105:116--8 70. Vecsei VP, Huber--Spitzy V, Arocker--Mettinger E, Steinkogler FJ. Canaliculitis: difficulties in diagnosis, differential diagnosis and comparison between conservative and surgical treatment. Ophthalmologica. 1994;208:314--7 71. Wearne MJ, Beigi B, Davis G, et al. Retrograde intubation dacryocystorhinostomy for proximal and midcanalicular obstruction. Ophthalmology. 1999;106:2325--8, discussion 2328--9. 72. Weinberg RJ, Sartoris MJ, Buerger GF Jr, et al. Fusobacterium in presumed Actinomyces canaliculitis. Am J Ophthalmol. 1977;84:371--4 73. Zaldivar RA, Bartley GB, Bradley EA. Microbiologic and pathologic features of primary canaliculitis. Investigative Ophthalmol Vis Sci. 2005;46 74. Zaldivar RA, Bradley EA. Primary canaliculitis. Ophthal Plast Reconstr Surg. 2009;25:481--4 Reprint address: Adam J. Cohen, MD, FACS, The Art of Eyes, Concourse Office Plaza Tower IL, 12th Floor, 4709 Golf Road, Skokie, IL 60076. e-mail: [email protected].
Outline I. Introduction
D. Imaging E. Canalicular patency F. Misdiagnosis
A. Anatomy and histology II. Epidemiology III. Clinical presentation
V. Treatment of canaliculitis A. Medical management B. Surgical management
A. Clinical symptoms and signs B. Historical use of examination IV. Diagnosis A. Microbiological culture B. Histopathology C. Genetic testing
VI. VII. VIII. IX. X.
Prognosis Summary Conclusion Method of literature search Disclosure
VOLUME 56 NUMBER 4 JULY–AUGUST 2011
MAJOR REVIEW
Primary and Secondary Lacrimal Canaliculitis: A Review of Literature Joshua R. Freedman, MS,1 Matthew S. Markert, MS,2 and Adam J. Cohen, MD, FACS3 1 3
Rush University Medical Center, Chicago, Illinois; 2University of Miami, Miller School of Medicine, Miami, Florida; and Private Practice, The Art of Eyes— Eyelid and Facial Plastic and Reconstructive Surgery, Skokie, Illinois, USA
Abstract. Canaliculitis is an uncommon inflammation of the proximal lacrimal drainage system that is frequently misdiagnosed. It classically presents with symptoms of unilateral conjunctivitis, mucopurulent discharge, medial canthal inflammation, epiphora, and a red, pouting punctum. We summarize the literature on canaliculitis published from antiquity to the modern era and explore therapeutic options. (Surv Ophthalmol 56:336--347, 2011. Ó 2011 Elsevier Inc. All rights reserved.) Key words. actinomyces actinomycosis canaliculitis canaliculostomy canaliculotomy chronic conjunctivitis pouting punctum streptothricosis
I. Introduction
streptothrix
The clinical distinctions and treatment approach separating primary canaliculitis and canaliculitis secondary to plug insertion have not yet been identified.32,39,58 We reviewed the case literature on presentation, diagnosis, and treatment outcome, and generate a differential diagnostic strategy for the identification of primary canaliculitis, as well as treatment recommendations for both primary and secondary canaliculitis.
Canaliculitis is an uncommon inflammation of the lacrimal canaliculi usually caused by infection5,6,9,28,73 or as a complication of punctal or intracanalicular plug insertion35,58 or intubation.29,47 Canaliculitis is often misdiagnosed as conjunctivitis.2,70 Described in Harrison’s Principles of Internal Medicine as ‘‘the most misdiagnosed disease’’ and that ‘‘no disease is so often missed by experienced clinicians,’’ primary canaliculitis is the result of an infection of the canaliculus and proximal lacrimal duct associated with eyelid thickening and/or erythema, and/or the presence of a classic pouting punctum.74 Recognition of canaliculitis as an infectious condition is attributed to Von Graefe (1854).21 Actinomyces isrealli, then classified as a fungus, was initially found to be the most common causative organism. For this reason, canaliculitis was originally known by the names of streptothrix canaliculitis1,18,22 or streptothricosis.17,50
A. ANATOMY AND HISTOLOGY
The lacrimal canaliculi, also known as canals or ducts, run vertically within the eyelids and converge to form the common canaliculus. They begin as branches of the lacrimal punctae and traverse the eyelids for approximately 8 mm. The upper eyelid canaliculi are shorter and narrower compared to the lower canals. The upper canal travels at a sharp angle before coalescing with lower canaliculus to form the common canal. The lower canaliculi run 336
Ó 2011 by Elsevier Inc. All rights reserved.
0039-6257/$ - see front matter doi:10.1016/j.survophthal.2010.12.001
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almost completely horizontal before joining the upper canaliculus, where the vertical components become enshrouded by fibrous tissue to form the punctum. Canalicular obstructions may be anatomically divided into proximal, mid-, or distal. Proximal canalicular obstructions typically occur within the first 2--3 mm of the canaliculi. Causes include punctal stenosis, punctal occlusion, and swelling. Mid-canalicular obstructions often follow injury or are secondary to infection, canaliculiths, or medications. These obstructions occur 6--8 mm from the punctal os. Distal obstructions are often congenital malformations of the membrane (valve of Rosenmuller) where the common canaliculus opens into the lacrimal sac. Lacrimal sac infections may also result in distal canalicular obstruction. Distal obstructions occur more than 6--8 mm distal to the eyelid punctum. Case studies were analyzed for clinical presentation reported, microbiological cause of infection, demographic data, and whether patients had previous lacrimal plug insertion or canalicular intubation.
II. Epidemiology In the last 20 years a number of case series of canaliculitis have been reported, the majority of which cited the prevalence of signs and symptoms. The infrequency of canaliculitis limits statistical analysis of reported cases. What an analysis of reported cases does provide is a more qualitative portrait of presenting clinical features, demonstrating a relatively consistent pattern when viewed across the decades. Demographic information from reviewed papers is included in Table 1. Analysis of data obtained
from the literature indicates the most common causative organisms of lacrimal canaliculitis are the Actinomyces species (see Table 2). Other microorganisms known to be associated with canaliculitis are listed in Table 3. Recent studies demonstrate greater rates of infection with streptococcal, and staphyloccal species than Actinomyces.35,74 Lacrimal canaliculitis occurs at a mean age of 59 years, but has been reported in patients from 5--90 years of age. There is a 5:1 female:male ratio, consistent with earlier studies.4 No racial or ethnic association was found. Accurate measures of the prevalence of primary canaliculitis in the general population are unavailable, owing to the frequency of misdiagnosis, relative rarity, and general underreporting of the disease. Historical incidence of canaliculitis in ophthalmic records screened for relevant symptoms ranged between 2% and 4%.16,74 Secondary canaliculitis is most commonly related to punctal or intracanalicular plug placement. Punctal occlusion to prevent tear drainage is the most common non-pharmalogical treatment for dry eye.12 Women represent 92% of secondary canaliculitis cases in the literature, likely because of the preponderance of women treated with placement of a plug for dry eye syndrome. A summary of case reports in canaliculitis secondary to punctal and intracanalicular plugs is included in Table 4. The generalizability of these cases is difficult to measure, and the first studies conducted especially to determine iatrogenic rates of lacrimal disease were only recently published.25 Among 235 patients with a total of 403 placed plugs from a single ophthalmology practice, the prevalence rate of canaliculitis per patient was 7.23%, and per plug inserted was 4.73%. The study was limited to SmartPlug (Medennium, Inc., Irvine, CA) placement by a single physician.
TABLE 1
Demographic Information from Literature Reviews and Case Reports Sullivan, 1993 Anand, 2004 Pavilack and Freuh 1992 Zaldivar and Bradley 2009 Repp, 2009 Vecsei, Huber-Spitzy et al. 1994 Briscoe, Edelstein 2004 Berlin, 1980 Lee, 2009 Hill, 2009 Hussain, 1993 Lin, 2010 Information from Case Reports (see Table 4) Means
Mean Age
Range
Female
Total
(%Fm)
52.0 69.6 51.0 60.0 70.6 52.3 71.7 60.3 61.5 64.0 49.9 64.0 45.7 59.4
14--86 45--87 10--84 22--86 50--87 26--82 43--90 n/a 29--77 41--88 n/a 30--89 5--80 14--90
13 13 8 15 9 25 4 6 23 15 5 24 24 184
18 15 11 23 11 40 7 9 30 17 7 34 29 251
72.2 86.7 72.7 65.2 81.8 62.5 57.1 66.0 76.7 88.2 71.4 70.6 82.8 73.31
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FREEDMAN ET AL
TABLE 2
Microorganism Prevalence Organism
# Cases (188 Total)
%
67 52 26 22 11 15 2 32
30.3 21.8 11.8 9.9 4.9 6.7 0.9 14.4
Actinomyces None Found Strep Staph Fungus Nonspecific gram() Nonspecific gram(þ) Other
III. Clinical Presentation The most commonly seen clinical presentation among 29 case reports and 12 reviews (total 5 280 patients) of primary canaliculitis are described. The typical patient is a post-menopausal woman who presents with epiphora, lower eyelid erythema, and a red, pouting punctum with yellowish, mucopurulent discharge. Massage or curretage of the canalicula frequently produces removable concretions histologically positive for Actinomyces.
A. CLINICAL SYMPTOMS AND SIGNS
The classic presenting symptoms associated with primary canaliculitis include epiphora, medial canthal swelling, non-resolving or recurrent conjunctivitis, and a swollen, pouting punctum, with or without yellowish or mucopurulent discharge.10,16,20,49,74 Also found is mattering on the eyelids49,74 and sulfur granules, stones, or concretions expressed from the punctum by massage or recovered during surgery.4,16,32,49,70 TABLE 3
All Known Organisms Associated with Canaliculitis Actinomyces Actinomyces israeli Mycobacterium Mycobacterium abcessus Mycobacterium chelonae Nocardia asteroides Staphylococcus aureus Streptococcus faecalis Arcanaebacterium hemolytica Streptothrix Propionibacterium acnes Cornyebacterium Haemophilus influenza Pseudomonas aeruoginosa Fusobacterium Citrobacter Chryseobacterium Proteus mirabellus Bacteriodes fragillus
Cases of secondary canaliculitis have been associated with epiphora, conjunctivitis, eyelid induration and erythema, pain, swelling, canalicular inflammation, inflammatory mass projecting from the punctum, granuloma formation, intermittent blood-stained tears, blood-tinged or mucopurulent discharge, and the presence of canaliculiths and dacryoliths.14,19,31,39,48,55,58 Vecsei et al reported that his group’s in-office diagnostic procedures included slit lamp examination of upper and lower eyelids, medial canthus, conjunctival fornices, upper and lower lacrimal puncta, and lacrimal syringing.69,70 They believe lacrimal syringing allows for the assessment of functional or mechanical stenosis and serves a therapeutic purpose when astringent or antibiotic drops are administered.69 B. HISTORICAL USE OF EXAMINATION
Although no consensus exists, there is precedent for making the presumptive diagnosis of canaliculitis based on the clinical symptoms alone.4,16,32,36,49,70 Ellis et al reported the finding of concretions as diagnostic.18 Demant et al stated the presence of chronic unilateral conjunctivitis, canalicular swelling, a pouting punctum, plical congestion, and expression of discharge or stone from the punctum were all suggestive of canaliculitis.16 Pavilack et al established the diagnosis of chronic canaliculitis in 11 cases by the presence of expressible canalicular concretions and signs of pericanalicular inflammation, distinguishing it from dacryocystitis by the absence of lacrimal sac involvement.49 Lee et al diagnosed 41 cases by swelling and erythema of the affected punctum and canaliculus accompanied by purlulent discharge or concretions extruding from the punctum.32 Hill et al defined canaliculitis in patients with epiphora or mucopurulent conjunctivitis and swelling at the medial ends of the upper or lower eyelids or reflux of mucopurulent material with gentle compression of the affected canaliculus.25 Zaldivar et al defined primary canaliculitis as mucopurulent punctal regurgitation on palpation, no eyelid thickening or erythema, or the presence of a classic pouting punctum.74 Anand et al suggest that more elaborate diagnostic methods such as dacryocystography are not only unnecessary, but may predispose an already inflamed canaliculus to scarring from the associated iatrogenic trauma.4 Case series detailing the most prevalent presenting signs and symptoms differ. When these studies are compared, there is no evidence to suggest change over time in the presentation of canaliculitis. Their differences most likely reflect normal
Case Report Information
a. Primary Canaliculitis Leung et al 200634 Charles et al 200613 Fulmer et al 199920 Hatton and Durand 200824 Tost et al 200067 Serin et al 200760 Moscato and Sires 200845 Varma and Chang 200569 Varma and Chang 200569 Park et al 200448 Romano et al 197853 Sullivan et al 199365 Shauly et al 199361 McKellar and Aburn 199742 Liyanage and Wearne 200936 Abdul and Sathiavakesan 19841 b. Secondary Canaliculitis Fowler et al 200819 Fowler et al 200819 Fowler et al 200819 Scheepers et al 200758 Chen and Lee 200714 Chen and Lee 200714 Chen and Lee 200714 Ahn et al 20093 Lee and Flanagan 200131 Lee and Flanagan 200131 Gerding, Kuppers 200320a Rumelt et al 199755
Age
Female
80 66 24 60 36 51 34 78 65 5 61 42 62 10
+ + + + + + +
Plugs
Months before presentation
Punctal Discharge
Upper Eyelid
+
+ +
+ +
+ +
23
+
+ + +
Reported Concretions
Lasik
Sjogrens
Surgical Treatment
+ +
+ + + + + +
+ +
+ + + +
+ + +
+
+ + + + +
+ + +
+ + + + + + + +
Reported Dry Eye
+ +
+ +
48
41 42 38 60 68 28 26 44 41 72 55 42
Lower Eyelid
+ + + + + + + + + + + +
24 4 72 14 10 5 6 36 1 14 12 3
+
+ + +
+
+
+ + +
+ + +
+
+
+
+
+
+ + + + + + + +
+
+
+ +
+
+ + + + + + + + +
+
+
+ + +
+
+
+
PRIMARY AND SECONDARY LACRIMAL CANALICULITIS
TABLE 4
+ + + +
+ +
+ + +
+ + 339
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Surv Ophthalmol 56 (4) July--August 2011
variability accentuated by a small number of patients. Zaldivar et al found the most common presenting symptoms to be epiphora and mattering, and punctal regurgitation was the most common clinical finding.74 Repp et al report a 73% prevalence of concretions.51 Mohan et al44 reported epiphora, discharge, irritation, and recurrent conjunctivitis as the most common symptoms. Sixty percent (60%) had punctal regurgitation, and all 12 cases had a pouting punctum, erythema, and thickening of the medial aspect of the eyelid.44 The Smart Plug study group found that many of their 17 cases presented with eyelid edema and erythema, conjunctivitis, or an inflammatory mass projecting from the punctum.39 Briscoe et al reported all of their patients had epiphora, chronic conjunctivitis, thickened canaliculus, and yellow discharge.10 The common findings in Anand et al’s patients were mucopurulent discharge (93.3%) and medial canthal inflammation (66.6%), whereas epiphora was present in only 46.6%.4 Earlier cases corroborate high prevalence of punctal regurgitation, concretions, medial eyelid thickening and erythema, pouting punctum, and expressible yellowish or bloody mucopurulent discharge among study populations.49,57,70 Regarding patients with punctal or intracanalicular plugs, silicone intubation, or any foreign body in the eye, the literature consistently supports a high index of suspicion for canaliculitis in any patient with irritation, epiphora, and purulent discharge.7,14,19,25,29,31,39,40,47,54,55,58
FREEDMAN ET AL
streptococcal and staphylococcal infection.4,35,70,74 Actinomyces was first cited by Harz in 1879 to describe organisms found in the cattle. Their lesions appeared radially arranged like fungal mycelia, leading to the name Actinomyces (ray fungus). Actinomyces species are now considered Gram positive bacilli which occur singly, in pairs, or in chains and are non-motile obligate or facultative anaerobes. They are normal constituents of human and cattle oral flora and are capable of causing chronic granulomatous infections, typically spreading by direct extension. Actinomyces has been reported to cause multiple forms of ocular infections, including canaliculitis, conjunctivitis, dacryocystitis, keratitis, and endophthalmitis.28 Actinomyces characteristically appears as branching filaments on Gram stain. There is substantial evidence that follow-up cultures will support an alternative diagnosis, even when histopathological analysis reveals actinomycotic concretions.10,16,52,74 The low success rate in isolation of organisms is frequently attributed to the fastidious nature of Actinomyces,18,28,42 the difficulty of culturing this anaerobic organism, and high tendency for polymicrobial infection.24,28,44,48,59,63 Successful culture of these organisms from concretions ranges from 11.1% to 71.4%.4,8,10,16,28,35,49,51,70 In spite of these known problems, it is still common for clinicians reporting cannaliculitis to base the diagnosis on histopathology alone. One must keep in mind that a lacrimal system neoplasm may present with unilateral tearing and discharge. A. MICROBIOLOGICAL CULTURE
IV. Diagnosis Despite decades of literature detailing the constellation of clinical signs and symptoms, lacrimal canaliculitis continues to be undiagnosed, misdiagnosed, and improperly treated.4,10,28,49,68,70 Because of the variability of symptoms, coincidence of symptomatology with other disorders of the eye, and the possibility of canaliculitis presenting without classic symptoms,45,60,61 more objective measures should be used. The majority of published studies and case reports on canaliculitis detail an attempt to determine the causative organism, either by culture or histopathological examination. Samples are taken from tears, punctal discharge, concretions, or particulate matter recovered via massage or curettage. Actinomyces israelli is often cited as the most common pathogen of lacrimal canaliculitis,20,23,28,46,49,63,65 although studies published within the last decade demonstrate higher rates of
Methods of obtaining culture include conjunctival swabbing,28,30,42 sampling of punctal discharge44,58,59 and conjunctival sac materials, abscess culture,s and culture of particulate matter and concretions.4,19,31,32,35 Some physicians choose to send for only aerobic and anaerobic cultures,16 whereas others report culturing for bacteria, fungus, and mycobacteria.19 Innoculums placed on blood agar, chocolate agar, and Sabouraud dextrose agar and incubated anaerobically have been successful in identifying Actinomyces israelli from canalicular concretions.42 Urgent collection and transport methods have been reported to improve yields, and delayed processing may negatively affect results.28 Improved detection rates have also been reported using a PD Plus/F blood culture bottle (Beckton, Dickinson & Co., Franklin Lakes, NJ).10 Less common organisms have been cultured by a variety of means. Eikenella corrodens was identified by the Vitek 1 system using the Neisseria/Haemophius identification card (BioMerieux, Marcy
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PRIMARY AND SECONDARY LACRIMAL CANALICULITIS
l’Etoile, France).34 Lactoccocus lactis cremoris has been identified by the Rapid ID 32 Strep kit (BioMerieux).34 Some fungi like Pitysporum pacydermatitis have required not just culture for identification, but also analysis of sugar, ammonium, potassium, and nitrogen assimilations.53 Because of the wide breath of possible microbial pathogens when canaliculitis is suspected, the microbiology lab should be informed of the possible need for special testing. B. HISTOPATHOLOGY
Histopathological examination is the most commonly reported diagnostic test performed on canalicular concretions.10,16,32,51,57,70 The concretions found consistently in case series typically portray the histopathological characteristics of Actinomyces,10,70,74 although the success rate of culturing these organisms is low.4,10,74 Sulfur granules, which have been described as yellow, cheese-like granules with a gritty consistency, are considered the pathologic hallmark of Actinomyces canaliculitis.20 On hematoxylin-eosin (H&E) stain these are basophilic masses originating from aggregated filamentous bacteria with peripheral club-like eosinophilic structures.10 These actinomyotic granules typically show numerous, radially oriented, Gram-positive, filamentous bacteria with peripheral clubs that stain positively with Periodic Acid-Schiff (PAS). Although highly suggestive of Actinomycosis, they are also seen with Staphylococci, Fusobacterium, Nocardiosis, Chromomycosis, and Botryomycosis,11,32,72 so culture should always be attempted. Filamentous bacteria demonstrating a Gram-positive, acid-fast negative pattern are also characteristic of propionibacterium.48 The typical findings associated with secondary cases of canaliculitis can be centered about the foreign body. Histopathologic examination of extracted foreign bodies shows inflammatory cells infiltrated along the margins, as well as mass excisions consistent with papillomas.3 Findings consistent with pyogenic granuloma have also been reported.39 Histological methods that may aid in diagnosis include H&E staining, Gomori’s methenamine silver stain, Brown and Brenn Gram-stain, and PAS. H&E stain may be helpful in revealing the general appearance and type of material present, whereas Gram and PAS stains are more useful in making a specific diagnosis.10 Gomori methenamine silver stain can help to differentiate Actinomyces from other microorganisms.11,32 Repp et al made a presumptive diagnosis from the presence of numerous filamentous organisms on Gomoroi’s methanamine silver stain, if the organisms were also Gram positive and clearly visible on PAS stain.51
Histopathological diagnosis may be misleading. Weinberg et al reports three cases where Gram stains show weakly Gram-positive branching filamentous organisms, thought to be Actinomyces.72 Aerobic cultures grew either a collection of Diphtheroids, Staphylococci, and Haemophilus, or nothing at all. Anaerobic cultures grew Fusobacterium, Nucleatum, or Fusobacterium Necrophorum, but no Actinomyces. The authors call attention to the fact that the classic ‘‘sulfur granules’’ composed of aggregates of filamentous branching microorganisms, typically associated with Actinomyces, are not always present in Actinomyces infection and in fact can be formed by other bacteria such as Staphyloccoccus aureus. They point out that both Actinomyces and Fusobacterium are anaerobic, non-sporeforming bacilli. Although Actinomyces should stain Gram positive and Fusobacterium should stain Gram negative, both are subject to irregularities in this pattern, and the two can be confused histopathologically. C. GENETIC TESTING
Very limited reports of using polymerase chain reaction to search for Actinomyces DNA exist. One report details cases diagnosed by histopathology as Actinomyces canaliculitis, having all yielded negative results for Actinomycotic DNA.4 An isolated report demonstrates DNA in the ‘‘concretion’’ of a suspected case of canaliculitis found positive for human papillomavirus types 16, 18. In the event it was evident on histopathology that this was in fact carcinoma of the lacrimal sac.13 At present, there is little evidence to support genetic testing in the diagnostic work-up of suspected canaliculitis. D. IMAGING
Imaging techniques can be used to confirm the diagnosis of canaliculitis and provide information that may facilitate surgical planning. Early imaging was carried out with intubation macrodacryocystography (roentgenography), and more recently the utility of ultrasound images has been explored. In a case series identifying post-herpetic canaliculitis, electron microscopy was used to image viral particles in tissue samples, although the clinical use of such techniques is uncommon.43 X-rays26 and, in rare cases, radioisotope lacrimal scanning,27 have been used to aid in the diagnosis of canaliculitis.4,16,33,57,65 Demant et al used x-rays to depict non-filling of the involved canaliculus, or marked dilatation and raggedness of the canaliculus is associated with canaliculitis.16 They noted that stones are not demonstrated by dacryocystography because they are usually amorphous. Santhananthan
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Surv Ophthalmol 56 (4) July--August 2011
et al designated filling defects of the lacrimal canaliculi as diagnostic of canaliculitis.57 Additional findings associated with canaliculitis included dilatation of the canaliculus, beading, and small diverticuli. More recently, ultrasound imaging has been used in the diagnosis of canaliculitis.64,67 Ultrasonic images of chronic canaliculitis showed ectasia of the canaliculus and sulfur grains. High-resolution ultrasonic examination of the lacrimal drainage system demonstrated that a 20-MHz scanner is able to show reflective structures such as sulfur granules measuring 12 mm in diameter, which are pathognomic for canaliculitis. Scarce data are available to support the practical utility of ultrasound as a diagnostic measure at this time. E. CANALICULAR PATENCY
Patency of the lacrimal drainage system to syringing is typical in canaliculitis.18,28,44,52,57 Passage of a syringe into the canaliculus and fluid expression ascertains patency of the nasolacrimal drainage system and generally excludes dacryocystitis from the differential. Patency of the lacrimal excretory passages to syringing does not suggest the absence of stones, as stones in the canaliculi may still allow saline flow.16 Similarly, co-morbidities may exist that obstruct the system but do not exclude canaliculitis, such as swelling and coexisting obstructions of the tear sac.16 Anand et al4 conducted extensive lacrimal workups on patients, including complete adnexal and anterior segment examination. They identified lid position, punctal position, and any cause of reflex epiphora including blepharitis or corneal surface abnormalities, and reported tear film break-up time and Schirmer’s test results. Lacrimal pump function was assessed using the Jones dye disappearance test. Lacrimal syringing and probing were used to establish patency of the lacrimal system and the site of any obstruction. These authors proposed that detailed assessments would preclude the necessity of invasive diagnostic imaging techniques. Other reports in the literature reflect similar drainage assessment.43 F. MISDIAGNOSIS
Misdiagnosis and delayed diagnosis are frequent. Physicians should suspect canaliculitis in patients with chronic unilateral epiphora, chronic conjunctivitis, mucopurulent discharge, pouting punctum, or concretions.4,10,16,42,49,70 If the literature accurately reflects clinical practice, it would appear that it is more common to misdiagnose patients with canaliculitis than to identify this condition. Case
FREEDMAN ET AL
studies of canaliculitis report percentages of patients previously misdiagnosed as 45%,49 60%,4,70 and 100%,10 and one study noted that 33% of patients had been previously misdiagnosed multiple times.4 Some patients have received empirical treatment without any specific diagnosis.4 Speculations on why canaliculitis is so frequently misdiagnosed include its low prevalence, once cited as 2% of lacrimal disease,16 or the atypical presentations which can mimic conjunctivitis70 or dacryocystitis.60 Reported misdiagnoses include chronic conjunctivitis, chronic dacryocystitis, chalazion, mucoceles, and blepharitis.4,49,68,70 The delay of diagnosis, or amount of time from becoming symptomatic to the eventual correct diagnosis, manifests a spectacular spectrum. Individual case reports of patients have delays over 10, 15, and 20 years.10,52 Misdiagnosis results in inappropriate treatment, often with broad spectrum topical antibiotics, which may transiently alleviate the symptoms, but usually do not result in a lasting cure.28 In other cases, misdiagnosis results in unnecessary procedures, often irrigation of lacrimal system, which can force concretions into more distal portions of the canaliculus.4,10,60 One report described a patient previously diagnosed with acute dacryocystitis who had undergone multiple irrigations, and finally a one-snip punctoplasty, without complete resolution of symptoms. Several weeks after the surgery the patient expressed a dozen dacryolyths.60 Analysis of the stones demonstrated their composition to be of previously formed canalicular concretions. The authors suggest that misdiagnosis as dacryocystitis led to unnecessary irrigations that may have pushed previously formed concretions and granules into more distal canalicular regions, explaining why concretions were not evident during initial compression or canaliculotomy. Distinguishing canaliculitis from look-alike pathologies can be challenging. Differentiation of canaliculitis from dacryocystitis is important to prevent inappropriate treatment with irrigation that can exacerbate symptoms. On exam, canaliculitis can be distinguished from dacryocystitis by the lack of lacrimal sac distention, nasolacrimal duct obstruction, and signs of lacrimal sac inflammation. In contrast with the blennorrhea of dacryocystitis, debris in canaliculitis is usually expressed with direct massage of the involved canaliculus and not with lacrimal sac compression.49
V. Treatment of Canaliculitis Althought relatively little has changed in the presentation or microbiological etiologies of
343
PRIMARY AND SECONDARY LACRIMAL CANALICULITIS
canaliculitis over the years,74 the treatment of canaliculitis may in fact be evolving. Where it was once believed that conservative treatment is ineffective in long-term treatment of canaliculitis,4,10,16,28,49,68,70 there are newer reports which suggest increasing cure rates with non-surgical approaches.44,74 A. MEDICAL MANAGEMENT
Conservative therapy includes warm compresses, digital massage, topical and systemic antibiotics, antifungals, corticosteroids, as well as some nonsurgical procedures such as irrigation and syringing. It is widely reported that medical therapy is rarely effective in clearing canalicular infections. The concretions present may prevent antibiotics from eradicating the bacterial source by virtue of obstruction to flow and protection of bacteria within the stones.4,28,49,69,70 Others have postulated the thick mucopurulent and particulate discharge and abscess-like accumulation of infected debris are responsible for resisting the penetration of topical and systemic antibiotics.16,49 The thick granular debris formation may cause a self-perpetuating cycle of canalicular stasis and infection persisting for many years. Antibiotics may improve symptoms, even when failing to achieve long term resolution.4,10,16,19,25,28 A recent study cites a 33% rate of recurrence in conservatively treated patients.35 In many cases conservative measures fail to provide any improvement,4,14,19 although case reports of resolution with medical management exist.14,34,39,44,74 Rare cases of secondary canaliculitis that resolve with medical management are also described,39 but plug removal should be a part of any treatment regimen. Complete resolution with medical management is typically limited to those patients who present early in the course of the disease.16,34,69,70,74 A recent series showed complete resolution without recurrence at an average of 150 days follow-up for those treated within the first 30 days of symptoms.74 Symptomatic improvement has been noted with systemic penicillin and topical neomycin, polymyxin, or bacitracin regardless of whether Actinomyces was cultured.16 A recent study demonstrated success in all patients with combined topical antibiotic and canalicular irrigation using fortified cefazolin solution, prepared at 50 mg/ml.44 Patients were again irrigated at 48 hours if clinical improvement was not evident. The number of irrigations necessary per patient averaged 4.5 (range, 1--8); all patients had excellent resolution of canaliculitis without the need for surgical treatment.
Medical regimens not proven to give lasting resolution include combinations of oral penicillins, sulfamethoxazole-trimethoprim, tetracyclines, metronidazole, and indomethacin. Reported topical combinations include penicillins; cephalosporins; tetracyclines; chloramphenicol; macrolides; flouroquinolones; the antifungals fucithalmic, zinc and adrenaline; neomycin; polymyxin; and bacitracin.4,10,16,28,44,69 Topical dexamethasone10 alone was not successful but was efficacious when combined with tobramycin.14 Many studies use culture sensitivities to guide their treatment regimen;however, this does not appear to improve response rates to conservative therapy. Lacrimal irrigation is sometimes effective in resolving cases of canaliculitis secondary to intracanalicular plug placement. A notable risk of this procedure, however, is the possibility of the plug dislodging from its canalicular position and moving distally into the lacrimal system, resulting in permanent obstruction.39 Hyperbaric oxygen therapy was used by Shauly et al61 treating an A. israelli canaliculitis that had proven refractory to curettage and topical penicillin for four weeks in a patient who refused further surgery. The regimen included antibiotics and daily 90-minute sessions at 100% O2 at 2--2.5 atmospheres 6 days a week for 4 weeks. The patient noted gradual improvement over this period, and complete resolution by 2 months, with no recurrence at 1 year follow-up. B. SURGICAL MANAGEMENT
Most studies support surgical management as the definitive treatment for canaliculitis.10,16,35,49,70 Surgery removes concretions that serve as a reservoir for bacteria. The least invasive methods involve dilation of the punctum to facilitate curettage of the stones.66 When dilatation is insufficient to allow passage of the probe into the punctum or withdrawal of the concretions, various punctoplasty techniques are shown to sufficiently widen the os. Canaliculotomy allows greater access to the canaliculus, after which the incision can be left open or closed with or without stent placement. Syringing and probing can be used to determine the presence and location of strictures in the canalicular system. Length and patency of the canaliculus can be determined in this fashion. Dilation of the punctum followed by curettage of the canaliculus has proven effective in primary canaliculitis.49,51 This carries a low risk of scarring the canaliculus, and the pump function is preserved by avoiding canaliculotomy. Pavilack et al49 reported high success rates treating patients with curettage,
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Surv Ophthalmol 56 (4) July--August 2011
followed by a 10-day course of 10% sulfacetamide sodium drops four times per day. If resolution of symptoms had not occurred by two weeks, the curettage and antibiosis regimen was repeated. In this series all patients were successfully treated with one (45%), two (45%), or three (10%) sessions of curettage. Punctoplasty was first performed in the study group to allow passage of the curette, but the authors later found that dilation alone was sufficient to allow curetting. A more recent retrospective analysis of curettage outcomes with the use of one snip punctoplasty in thirty patients with primary canaliculitis demonstrated the successful resolution of symptoms in 83% of patients at their 3-week follow-up.32 Patients with mild, persistent symptoms were treated with continued antibiotics for one month, and their infection resolved. Two patients required a second curettage. Complications included formation of canalicular strictures. Two-snip42 and three-snip43 punctoplasty procedures have been reported. Risks of canaliculotomy include canalicular luminal narrowing or scarring, lacrimal pump dysfunction, canalicular fistula formation,4,39 failure to diagnose and treat stones lodged deeper in the canaliculus, and need for subsequent surgery,74 as well as the standard risks associated with any surgical procedure. Complications of the canaliculotomy include the need to reconstruct the canaliculus,10 intubation,25 stent placement, canalicular fistula formation,39 and orbital cellulitis and abscess formation.24 Although continued epiphora in patients after canaliculotomy was considered a possible sequela,70 Anand et al reported that long-term follow-up did not reveal a direct relationship between persistent epiphora and canaliculotomy.4 Canaliculotomy allows for greater access and easier curettage of canalicular contents. It is widely regarded at the procedure of choice for both primary and secondary canaliculitis.4,10,14,16,25,36, 45,58,60,68,70,71,74 A canaliculotomy is performed by passing a probe into the canaliculus and making a horizontal incision through the eyelid margin to open the canaliculus and expose the probe. The incision should begin about 2 mm medial to the ampula and is usually about 8 mm in length.66 Once the canaliculus is opened, the probe is removed, and the stones are extracted with a small curette. The canaliculus may then be irrigated with antibiotic solution. At the surgeon’s discretion a canaliculostomy may be performed in which silicone tubing stent such as a Mini-Monoka (FCI Ophthalmics, Pembroke, MA) is passed into the canaliculus, and the wound is closed with small caliper absorbable sutures. The tube is usually removed in a few weeks.
FREEDMAN ET AL
Some authors recommend irrigation of aqueous penicillin or povidine iodine and meticulous repair of the canaliculus.18,28 Others have found that, in most cases, the canaliculus will return to its preinflammatory state when just left to heal.10,16 Silver nitrate cauterization following removal of canalicular stones has been reported.16 This theoretically could cause injury to the epithelium, although no evidence of this was noted. Multiple case reports also detail patients where no reconstruction of the canaliculus is undertaken, and full recovery with patent syringing is seen on follow-up.20,52 Systemic Actinomyces involving other organs is treated with high dose antimicrobial agents for extended durations as a result of the tendency of this pathogen to recur.56 Briscoe et al10 report no recurrence in any of their patients with a regimen that included an initial high-dose IV penicillin therapy of 20 million units daily for at least 3 weeks, followed by oral administration of 2 g per day for at least 3 months. Favorable treatment outcomes following canaliculotomy are reported among all case series on canaliculitis, with complete resolution in the majority of primary canaliculitis patients.4,10,35,70 Resolution of canaliculitis occurs in between 80%69 and 100% of cases after canaliculotomy.4,10,16 Continued symptoms of epiphora and recurrent canaliculitis are reported.35,70 Intubation or stent placement is employed in circumstances where patency of the canaliculus is in question.14,19,25,51 In treatment of secondary canaliculitis following SmartPlug insertion, an initial trial of topical and broad-spectrum antibiotics followed by retrograde massage is suggested should plug removal be indicated.39 Irrigation of the nasolacrimal duct is recommended by the manufacturer, and this has been demonstrated to resolve a number of SmartPlug related cases.39 Irrigation is also thought to risk dislodgement of the plug from its canalicular position, causing permanent obstruction of the lacrimal drainage system.41 Canaliculotomy with removal of foreign body is frequently performed if conservative therapy with medical management and/ or lacrimal irrigation fails to improve epiphora or canaliculitis.25,39 If canaliculotomy fails to improve the condition, dacryocystorhinostomy with intubation20 or placement of a Jones tube may be necessary.
VI. Prognosis The long-term resolution of primary canaliculitis treatment may be affected by the duration of the disease prior to diagnosis, the management employed, patient co-morbidities, and lesser
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PRIMARY AND SECONDARY LACRIMAL CANALICULITIS
understood factors such as patient age, sex, the presence of concretions, and microbiology.4,35,74 Acutely, treatment often progresses from conservative to surgical management until satisfactory resolution is achieved. In primary canaliculitis the presence of continued symptoms varies with treatment modality. Successful initial resolution with conservative treatments have been reported in 0%,4 20%,70 ,26%,35 and 34.7%74—with recurrence rates as high as 33%.35 Several authors have noted patients with acute canaliculitis achieve higher success rates with conservative treatment, whereas those with longer disease courses typical fair better with surgical or combination treatment.15,16,74 In the single case series describing combination therapy with intracanalicular antibiotic irrigation and topical antibiotics, resolution was reported in all patients after a mean of 4.5 treatments.44 Continued symptoms after canaliculotomy—such as epiphora4,70 and mattering74—occur in as many as 27% of patients. Recurrence of canaliculitis after canaliculotomy may develop in up to 21% of patients undergoing canaliculotomy, with a mean time of recurrence of 24 months.35 Some patients have had recurrent canaliculitis in a previously unaffected canaliculus.74 Pre-existing nasolacrimal duct pathology or a history of inappropriate lacrimal sac washout procedures may predispose to the development of new, or the exacerbation of old, nasolacrimal duct obstruction after canaliculotomy.4 Curettage success rates have been reported in as many as 83.3% of patients at a mean follow-up of 10.76 weeks.32 With SmartPlug-related canaliculitis, topical and systemic antibiotics are infrequently associated with resolution. Lacrimal irrigation may resolve symptoms but is associated with the risk of lacrimal system obstruction. Canaliculotomy is the definitive therapy. Complete resolution of symptoms may not always be achieved, however, and persistent epiphora following surgery has been reported.41
VII. Summary In patients who present with epiphora, chronic or recurrent unilateral conjunctivitis, a thickened canaliculus, pouting punctum, or expressible yellow discharge, a diagnosis of canaliculitis should be considered and evaluation and treatment instituted. Manual expression of discharge or concretions should be attempted. Microbiological investigation of the expressed material should include histopathological examination and culture. Imaging may be considered in situations where the diagnosis is not
clinically evident or where further information is required for surgical planning. Ultrasound offers a noninvasive means of identifying concretions; intubation macrodacryocystography, however, remains the more well studied method for the identification of filling defects in the lacrimal drainage system. Conservative medical therapy has a higher rate of success with new onset canaliculitis and should be considered as a first line treatment. Topical and/or systemic antibiotic therapy may begin with broad spectrum and then be tailored to the culture sensitivity. Repeated intracanalicular antibiotic irrigation is suggested as an alternative to surgery and demonstrates promising initial results, but has not been widely reproduced or adopted at present. Curettage of the punctum via dilation or punctoplasty may be successful in removal of concretions and resolution of canaliculitis. Canaliculotomy remains the definitive therapy. Continued symptoms of epiphora and mattering are common. Recurrent canaliculitis occurs in approximately one-fifth of patients 2 years after surgery. Patients should be apprised of this possibility and advised to seek treatment early if symptoms recur. Canaliculostomy may be performed at the discretion of the surgeon.
VIII. Conclusion There is a clear need for greater awareness among clinicians, especially those in training, to recognize canaliculitis. A higher index of suspicion would prevent delays in diagnosis and unnecessary manipulation of the lacrimal system.4
IX. Method of Literature Search A systematic review was conducted to survey all published case reports of lacrimal canaliculitis, all reviews of ophthalmic disease and surgical intervention where canaliculitis was recorded as an outcome or described as a complication, and all previous scientific studies on lacrimal canaliculitis. Search was not limited to Medline or English-language papers. A full-text search of the term canaliculitis in the Cochran Collection yielded 2 of 608,405 records.37,38 A Medline search for ophthalmic streptothricosis yielded 409,770 results with no filters for language or journal type. Adding the keyword punctum reduced this number to 228, which were each reviewed for relevance to canalicular disease and additional references contained therein. An independent Medline search for canaliculitis yielded 105 results, which were surveyed in a similar manner. Identical search via Embase, OldMedline
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or ISI did not return additional citations. The reference lists for relevant papers was reviewed, and papers not electronically databased were individually acquired through library loan or a handreview of the historical journals collection of the Rush University Medical Library, and the University of Miami Norton Library, Bascom Palmer Eye Center. Every effort was made to cite only original sources, and to avoid secondary citations among studies making more recent claims; for example, the Norton library contains a rare print collection that was useful for some of the less distributed examples.17,18,22,50,62
X. Disclosure The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article.
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Outline I. Introduction
D. Imaging E. Canalicular patency F. Misdiagnosis
A. Anatomy and histology II. Epidemiology III. Clinical presentation
V. Treatment of canaliculitis A. Medical management B. Surgical management
A. Clinical symptoms and signs B. Historical use of examination IV. Diagnosis A. Microbiological culture B. Histopathology C. Genetic testing
VI. VII. VIII. IX. X.
Prognosis Summary Conclusion Method of literature search Disclosure