Lacrimal drainage pathway disease-associated keratopathy effectively diagnosed with dacryoendoscopy: a report of two cases

Abstract

Background

We described two cases of lacrimal drainage pathway disease-associated keratopathy (LDAK) wherein lacrimal irrigation tests revealed no abnormalities, and there were few signs and symptoms suggestive of lacrimal drainage pathway disease.

Case presentation

Case 1 involved a 66-year-old woman with Sjögren’s syndrome who presented with corneal perforation in her left eye. Slit-lamp examination revealed a non-infiltrative corneal ulcer and perforation in the inferior peripheral cornea. LDAK was suspected; however, there were minimal signs of lacrimal drainage pathway disease. Despite treatment with contact lenses and topical steroids, there was no improvement. Dacryoendoscopy was performed, revealing multiple concretions within the canaliculus. LDAK caused by lacrimal canaliculitis was confirmed, and the corneal ulcer rapidly re-epithelialized after removing the concretions. Case 2 involved a 78-year-old woman with Sjögren’s syndrome who presented with epiphora in her right eye. Slit-lamp examination revealed two non-infiltrative ulcers in the inferior cornea, one of which had perforated. LDAK was suspected, but there were minimal signs of lacrimal drainage pathway disease. Dacryoendoscopy was performed, revealing concretions within the lacrimal sac and confirming chronic dacryocystitis. After removing the concretions, the corneal ulcer rapidly re-epithelialized.

Conclusions

We encountered two cases of LDAK that presented with minimal signs of lacrimal drainage pathway disease. When LDAK is suspected, dacryoendoscopy is a valuable tool for diagnosing lacrimal drainage pathway disease and removing concretions.

Background

Lacrimal drainage pathway diseases are predisposing factors for corneal ulceration. Most reports involve infectious keratitis resulting from pathogen of infectious lacrimal drainage pathway diseases infecting the cornea [1]. The incidence of non-infectious corneal ulcers associated with infectious diseases of the lacrimal drainage pathways has been increasing [2–7]. In 2022, we reported on lacrimal drainage pathway disease-associated keratopathy (LDAK) [2]. Lacrimal drainage pathway diseases that cause LDAK include chronic dacryocystitis and lacrimal canaliculitis. Chronic dacryocystitis, which is due to the narrowing or obstruction of the nasolacrimal duct, results in accumulation of tears and lacrimal secretions in the lacrimal sac that causes purulent eye discharge and epiphora. Lacrimal canaliculitis is caused by the disruption of the canaliculus mucosa, leading to infection and formation of concretions within the canaliculus along with purulent eye discharge and redness as well as swelling of the puncta. In LDAK, these diseases lead to the formation of non-infectious ulcers on the cornea. An important feature of LDAK is the minimal cellular infiltration at the site of corneal ulcer, which is different from that in infectious keratitis [2]. The ulcers are primarily located around the nasal or inferior periphery of the cornea and occasionally at the paracentral cornea, and they may lead to corneal perforation [2]. Treatment of LDAK involves addressing the infectious lacrimal drainage pathway disease, which results in rapid improvement of the corneal ulcer [2].

Herein, we describe two cases of LDAK wherein dacryoendoscopy was instrumental in its diagnosis in the absence of overt clinical characteristics of lacrimal drainage pathway diseases.

Case presentation

Case 1

A 65-year-old woman with Sjögren’s syndrome-associated dry eyes presented with left eye pain she had been experiencing for several days. She had been using topical fluorometholone 0.1%, rebamipide 2.0%, and hyaluronic acid 0.1% for treatment of dry eye. Upon examination, her best-corrected visual acuity and intraocular pressures were 20/25 and 20/32, and 10 mmHg and 3 mmHg in the right and left eyes, respectively. The right eye had a Schirmer’s test value of 4 mm in 5 min. Slit-lamp examination revealed conjunctival hyperemia and mild purulent discharge in the left eye without redness or swelling of the lacrimal puncta. A corneal ulcer with few cellular infiltrations was noted at the inferonasal periphery of the left cornea along with perforation and iris prolapse (Fig. 1A, B, C). Mild superficial punctate keratopathy (SPK), which was located predominantly in the inferior cornea, was observed in both eyes using fluorescein staining. In addition, the anterior chamber was nearly collapsed. Rheumatoid factors, which are commonly associated with peripheral ulcerative keratitis (PUK), were negative, and the corneal ulcer exhibited minimal cellular infiltration with a clear stromal band, making the possibility of other causes of PUK unlikely. Given the purulent discharge and the nature of the corneal ulcer, LDAK was suspected as this is not a characteristic finding associated with dry eye keratitis. However, lacrimal irrigation did not induce pain or purulent reflux, and obstruction was not observed. Due to the corneal perforation, treatment was initiated with a soft contact lens, topical fluoroquinolone four times daily, and fluorometholone 0.1% twice daily. After 7 days of treatment, the purulent discharge persisted, corneal perforation had not improved, and aqueous leakage continued. Culture of the initial ocular discharge identified Actinomyces odontolyticus. Accordingly, lacrimal canaliculitis was suspected, and dacryoendoscopy was performed, revealing multiple concretions and a misplaced punctal plug within the upper and lower canaliculi of the left eye (Fig. 1D). Thus, lacrimal canaliculitis of the left eye was confirmed. The concretions and plug were removed, and nasolacrimal duct intubation was performed. Treatment with topical cefmenoxime 0.5% four times daily and fluorometholone 0.1% twice daily was maintained along with the use of a soft contact lens. Six days after initiating treatment for lacrimal canaliculitis, the corneal ulcer epithelialized and healed (Fig. 1E, F). Furthermore, the best-corrected visual acuity improved to 20/16, and the corneal ulcer did not recur.

Fig. 1.

Slit-lamp photographs and dacryoendoscopy findings in Case 1. (a), (b), and (c) Slit-lamp photograph of the left eye shows corneal ulceration with perforation in the inferior peripheral cornea. There is mild purulent discharge but no redness or swelling of the upper and lower puncta. (d) Dacryoendoscopy shows multiple concretions and a dislocated punctal plug within the canaliculus. (e) (f) The site of corneal perforation has re-epithelialized after treatment of lacrimal canaliculitis

Case 2

A 78-year-old woman with a history of Sjögren’s syndrome-related dry eyes had been receiving topical treatment with fluorometholone 0.1%, rebamipide 2.0%, and diquafosol sodium 3.0%. She presented with a few days of decreased vision and epiphora in her right eye. Upon examination, her best-corrected visual acuity and intraocular pressures were 20/125 and 20/300, and 4 mmHg and 10 mmHg in the right and left eyes, respectively. Fluorescein staining with slit-lamp examination　confirmed diffuse SPK and reduced tear meniscus height in both eyes. Additionally, the right eye exhibited multiple peripheral corneal ulcers with minimal cellular infiltration, with the inferotemporal ulcer being perforated and resulting in iris prolapse (Fig. 2A, B). No redness or swelling of the lacrimal puncta was noted. Considering the lack of significant cellular infiltration in the ulcer, LDAK was highly suspected, and the possibility of other causes of PUK was considered unlikely. A lacrimal irrigation test was performed, revealing no purulent reflux and no evidence of passage obstruction. Due to the corneal findings suggestive of LDAK, dacryoendoscopy was performed, revealing multiple concretions within the right lacrimal sac, signs of inflammation in the lacrimal sac mucosa, and narrowing of the nasolacrimal duct, confirming chronic dacryocystitis (Fig. 2C). The concretions suggested the possibility of bacterial concretions; however, they could not be retrieved, and microbiological testing was not conducted. The concretions were instead removed, and nasolacrimal duct intubation was performed (Fig. 2D). Considering the corneal perforation, treatment was initiated with a soft contact lens and topical fluoroquinolone, fluorometholone 0.1%, and rebamipide 2.0% four times daily. Eighteen days after chronic dacryocystitis treatment initiation, tear meniscus remained mildly reduced, diffuse SPK did not worsen, corneal ulcer had epithelialized, and the perforated site had healed (Fig. 2E, F). Rapid epithelialization of the corneal ulcer following treatment for lacrimal drainage pathway disease suggests that the possibility of dry eye keratitis or PUK as the primary cause of the corneal ulcer was unlikely. Post-healing, the best-corrected visual acuity improved to 20/32, and corneal ulcer did not recur.

Fig. 2.

Slit-lamp photographs and dacryoendoscopy findings in Case 2. (a) and (b) Slit-lamp photograph of the right eye reveals two ulcerations in the inferior peripheral cornea, with the temporal ulcer showing perforation. No purulent discharge is observed. (c) and (d) Dacryoendoscopy shows multiple concretions in the lacrimal sac. After removing concretions, nasolacrimal duct intubation was performed. (e) and (f) Corneal ulcerations re-epithelialized after chronic dacryocystitis treatment

Discussion and conclusions

Recently, LDAK has been reported, particularly in Japan. Diagnosing LDAK requires confirmation of the presence of chronic dacryocystitis or lacrimal canaliculitis. Slit-lamp examination findings and lacrimal irrigation, which are minimally invasive and simple procedures, are useful for identifying lacrimal drainage pathway diseases. Previous reports, have highlighted the usefulness of lacrimal irrigation in diagnosing lacrimal drainage pathway diseases that cause LDAK [2, 5]. Lacrimal irrigation detects abnormalities in cases of severe stenosis or obstruction of the lacrimal pathways. In our cases, stenosis of the canaliculi and nasolacrimal duct was mild, and no obstruction was detected, leading to normal lacrimal irrigation findings. Symptoms of canaliculitis, such as epiphora (40.5%) and pain (21.4%), were reportedly present in less than half of the cases, and 51.1% of cases exhibited no obstruction on lacrimal irrigation, indicating that canaliculitis can be challenging to diagnose based solely on clinical findings or lacrimal irrigation [8]. Dacryoendoscopy is useful for the diagnosis and treatment of lacrimal drainage pathway diseases such as chronic dacryocystitis and lacrimal canaliculitis [9, 10]. In both of our cases, dacryoendoscopy confirmed the presence of concretions and inflammation in the lacrimal mucosa, allowing us to diagnosis LDAK.

LDAK frequently develops in patients with autoimmune diseases, such as rheumatoid arthritis and Sjögren’s syndrome, which is why a differential diagnosis from corneal ulcers caused by these conditions is important [2, 4, 5]. A characteristic feature of LDAK is the absence of cellular infiltration, which is different from that of corneal ulcers associated with rheumatoid arthritis. Additionally, LDAK differs from rheumatoid arthritis-associated corneal ulcers in that the corneal ulcer does not improve with local steroid treatment. Sjögren’s syndrome is the most common underlying condition in patients with LDAK, similar to our cases. Sjögren’s syndrome typically results in the formation of corneal ulcers with minimal cellular infiltration that often affects the peripheral or paracentral cornea [11]. These characteristics make them similar in appearance to LDAK. Both LDAK and Sjögren’s syndrome-related corneal ulcers predominantly develop in middle-aged and elderly women. However, LDAK can often be differentiated from Sjögren’s syndrome-related corneal ulcers by the presence of purulent discharge from the lacrimal infection and, in cases of lacrimal canaliculitis, by redness and swelling of the puncta. The diagnostic challenge in our cases arose from the absence of definitive slit-lamp findings and normal results on lacrimal irrigation tests despite lacrimal drainage pathway diseases.

In both our cases, the lacrimal disease itself was mild with few significant symptoms and clinical findings; however, it still resulted in LDAK. The lack of symptoms, such as tearing, may be attributed to the reduction of tear flow caused by Sjögren’s syndrome. Sjögren’s syndrome may increase levels of inflammatory cytokines in tears, reduce the density of corneal epithelial cells, and thin the corneal stroma [12]. These pathophysiological changes associated with Sjögren’s syndrome may have played a role in the development of LDAK in our cases. Meanwhile, the improvement in corneal ulcers in our cases was due to the removal of the concretions. Removing concretions is crucial for the definitive treatment of both the lacrimal disease and the associated corneal ulcers [13, 14]. Dacryoendoscopy allowed for the precise removal of concretions, which contributed to the successful treatment of LDAK.

This report has several limitations. First, the small sample size limits the ability to generalize the usefulness of dacryoendoscopy in diagnosing LDAK. Although the number of reports of LDAK are increasing, its pathophysiology remains poorly understood. Furthermore, in this study, pathological examination of the concretions could not be performed, and it remains unclear whether the concretions observed using dacryoendoscopy were caused by bacteria or rebamipide. Thus, in future cases wherein LDAK is suspected, collecting concretions whenever possible and performing pathological examinations could contribute to further elucidation of the disease mechanism. Hence, the detailed mechanisms underlying the relationship between LDAK and Sjögren’s syndrome necessitate further investigation. Future research should focus on elucidating the detailed pathophysiology of LDAK to clarify its relationship with Sjögren’s syndrome.

Herein, we described two cases wherein lacrimal drainage pathway disease was confirmed through dacryoendoscopy, leading to the diagnosis of LDAK. When LDAK is suspected based on clinical findings, dacryoendoscopy should be considered even in the absence of clinical signs and symptoms suggestive of lacrimal drainage pathway disease. Additionally, in patients with Sjögren’s syndrome, even mild lacrimal drainage pathway disease may lead to the development of LDAK, which clinicians should consider.

Abbreviations

LDAK

Lacrimal drainage pathway disease-associated keratopathy

SPK

Superficial punctate keratopathy

PUK

Peripheral ulcerative keratitis

Author contributions

All authors (HI, KT, AM, YT, YS, TK, and AS) were responsible for study design. HI, KT, AM, YT, YS, and TK were contributed to collect the date. HI made major contributions to writing the manuscript. HI and AS were involved in drafting the manuscript and revising it. All authors read and approved the final manuscript.

Funding

No funding was received for this study.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

This single-center, retrospective study was approved by the Ehime University Review Board (1503007), and the procedures conformed to the tenets of the Declaration of Helsinki. Written informed consent was obtained from all patients.

Consent for publication

The authors declare that the written informed consent was obtained from the patients for publication of this case report and any accompanying images.

Competing interests

The authors declare no competing interests.