Causes of Tearing in Patients With Chemotherapy: Meibomian Gland Dysfunction Versus Lacrimal Drainage Obstruction.

Numerous ocular toxicities that have been associated with the use of chemotherapeutic agents present as problems with the ocular surface, ocular adnexa, and lacrimal system, and many chemotherapeutic agents have tearing as a side effect. In this study, 34 eyes from 17 patients with a mean age of 62.4±14.8 years were analyzed. Chemotherapy was administered for a mean of 13.8±7.6 months. Chemotherapeutic agents of the following types were included: titanium silicate-1 (58.8%), Docetaxel (23.5%), Paclitaxel (11.8%), and 5-fluorouracil (5.9%). Tearing began 9.1 to 10.9 months after chemotherapy treatment. Within 3 months of beginning chemotherapy, tearing occurred in 9 patients (52.9%), and within 6 months, it occurred in 11 patients (64.7%). Mean tear break-up time was 5.4±2.6 sec. Ten eyes (29.4%) had normal fluorescein dye disappearance test findings (within grade 1), and the mean fluorescein dye disappearance test was 1.91±0.87. Among the 34 eyes, 24 (70.6%) had normal puncta and 9 (26.5%) and 1 (2.9%) had stenosis and blockage, respectively. Ten eyes (29.4%) showed total regurgitation, 19 eyes (55.9%) showed partial regurgitation, and 5 eyes (14.7%) showed no regurgitation upon syringing. Four eyes (11.8%) and 30 eyes (88.2%), respectively, showed soft and hard stops upon probing. Dacryoscintigraphy confirmed that 6 eyes (17.6%) were normal, 8 eyes (23.5%) showed post-sac delay or obstruction, and 20 eyes (58.8%) showed pre-sac delay or obstruction. The mean meiboscores for the upper and lower eyelids on LipiView were 2.15±0.86 and 2.53±0.79, respectively. The difference in meiboscores between the upper and lower eyelids was significant ( P=0.004 ). Obstruction of the lacrimal drainage system is a significant contributing factor to tearing in chemotherapy patients. However, reflex tearing because of meibomian gland dysfunction should also be fully considered to effectively manage the tearing because of the high incidence of accompanying meibomian glands loss when the lacrimal drainage system is obstructed.

A rare case of pemetrexed-induced diffuse punctal and canalicular stenosis: management by coronary balloon puncto-canaliculoplasty.

Several chemotherapeutic agents are known to induce lacrimal drainage stenosis and obstruction, resulting in epiphora. Pemetrexed is one such drug and is used in the management of mesotheliomas and non-small cell lung carcinomas. Pemetrexed inhibits folate metabolism at multiple levels. The present case is the second report of pemetrexed induced punctal and canalicular stenosis, but the first to document dacryoendoscopy findings and report balloon puncto-canaliculoplasty as a minimally-invasive treatment option.

Obstrução lacrimal pós-tratamento oncológico: revisão de literatura / Lacrimal drainage system obstruction after cancer treatment: a literature review

RESUMO A obstrução de via lacrimal é uma possível complicação decorrente de tratamentos oncológicos sistêmicos e locais. A epífora crônica gera grande impacto na qualidade de vida desses pacientes, e, como a fibrose terminal da via lacrimal pode necessitar de procedimentos complexos para sua resolução, é importante estarmos atentos a esse efeito adverso, com o objetivo de reconhecê-lo e tratá-lo precocemente, ou mesmo preveni-lo. Nesta revisão da literatura, os autores analisam todos os agentes quimioterápicos e radioterápicos associados à obstrução lacrimal e descrevem os mecanismos, a frequência, os tratamentos e a profilaxia. Os tratamentos oncológicos associados à obstrução lacrimal foram: radioterapia em cabeça e pescoço (dosagem acima de 45 a 75Gy), radioiodoterapia (dosagem acima de 150mCi) e quimioterapia com 5-FU, S-1, capecitabine e docetaxel. A obstrução lacrimal pode ser irreversível, e a intubação profilática das vias lacrimais é uma possibilidade descrita de tratamento profilático em casos de radioterapia e uso do 5-FU, S-1 e docetaxel. O tratamento cirúrgico de todos os casos é a dacriocistorrinostomia.

ABSTRACT Lacrimal duct obstruction can be a side effect of systemic and/or local cancer treatments. Chronic epiphora has a great impact on the quality of life of oncological patients. Since terminal fibrosis of the lacrimal system may require complex procedures, it is important to be aware of this adverse effect in order to recognize and treat it, or even prevent it. A literature review was performed to identify all types of systemic cancer treatment associated with lacrimal obstruction and to describe the mechanisms, frequency, treatment, and prophylaxis. The oncological treatments associated with lacrimal obstruction were head and neck radiotherapy (dosage above 45-75 Gy), radioiodine therapy (dosage above 150 mCi), and chemotherapy with 5-FU, S-1, Capecitabine and Docetaxel. Depending on the dose, this complication may be irreversible. Prophylactic intubation of the lacrimal system is an option for prophylaxis in cases of radiotherapy, use of 5-FU, S-1, and Docetaxel. Final surgical treatment is dacryocystorhinostomy.

Mascara-induced nasolacrimal duct obstruction.

A 35-year-old woman underwent left external dacryocystorhinostomy (DCR) following a recent bout of left acute dacryocystitis. She had a right DCR 14 years earlier. Her relatively young age of presentation prompted suspicion of secondary nasolacrimal duct obstruction and, although the left lacrimal sac appeared macroscopically normal peroperatively, a lacrimal sac biopsy was taken. Histopathology revealed florid chronic inflammation, with abundant granular brown pigment and polarisable crystals suggestive of an exogenous material in the lacrimal sac mucosa compatible with mascara. After initial improvement, her epiphora has recurred 1-year postoperatively, but her ocular discharge has resolved. Mascara-induced conjunctival pigmentation is well established. However, there are very few published reports of nasolacrimal duct obstruction due to mascara. Since cosmetic application of mascara and kohl eyeliner is widespread, patients and practitioners should be aware of their potential to migrate into the lacrimal apparatus and cause chronic inflammation with secondary nasolacrimal duct obstruction.

Nasolacrimal Duct Obstruction Following Hyaluronic Acid Rejuvenation of the Tear Trough.

Although generally safe, hyaluronic acid rejuvenation of periorbital tissue has been reported to cause minor and major adverse events. The authors document a case of nasolacrimal duct obstruction due to hyaluronic acid rejuvenation of the tear trough. Nasolacrimal duct obstruction immediately resolved following irrigation of hyaluronidase into the affected lacrimal system. To the authors' knowledge, this is the first reported case of nasolacrimal duct obstruction due to filler injection.

Clinical features and treatment outcomes of patients with tearing after chemotherapy.

PURPOSE: To evaluate the clinical features and treatment outcomes of patients complaining of tearing after receiving chemotherapy. METHODS: The clinical records of patients who complained of tearing between August 2014 and February 2016, and underwent or were undergoing chemotherapy were retrospectively reviewed. Clinical measurements were as follows: LipiView® interferometer (lipid layer thickness and meibography), lacrimal drainage examinations (syringing), and outcomes at 6 months after treatment. RESULTS: This study included 34 eyes of 17 patients with a mean age of 62.4 ± 14.82 years. The mean follow-up period was 9.6 months. On syringing, 10 eyes (29.4%) showed total regurgitation, 19 eyes (55.9%) showed partial regurgitation, and 5 eyes (14.7%) showed no regurgitation. On LipiView®, mean lipid layer thickness was 34.5 nm (range, 20-89 nm). Mean meiboscore was 2.15 ± 0.86 in upper eyelid and 2.53 ± 0.79 in lower eyelid. Patients were treated with silicon tube intubation (STI) (10 eyes, 29.4%), dacryocystorhinostomy (DCR) (4 eyes, 17.6%), conjunctivodacryocystorhinostomy (CDCR) (8 eyes, 11.8%), DCR combined with CDCR (1 eyes, 8.8%), and conservative care (11 eyes, 32.4%). Mean time interval from onset of tearing to first clinic visit was 1.4 months in the conservative care group, 2.9 months in the STI and DCR groups, and 6.0 months in the CDCR group. CONCLUSION: Because of the high incidence of accompanying meibomian gland loss in cases of lacrimal drainage system (LDS) obstruction, reflex tearing by mebibomian gland dysfunction should also be considered for proper management of tearing. Early recognition and management of LDS stenosis could result in patients undergoing surgery with a lower burden.

Meibomian Gland Dysfunction in Patients With Chemotherapy-Induced Lacrimal Drainage Obstruction.

PURPOSE: To investigate the relationship between chemotherapy-induced lacrimal drainage (LD) obstruction and obstructive meibomian gland dysfunction. METHODS: Twenty patients who had received chemotherapy were divided into 2 groups, according to the presence of LD obstruction: the LD obstruction group (n = 10) and control group (n = 10). Upper and lower meibomian gland loss was evaluated using noncontact meibography, and tear film lipid layer thickness was measured using an interferometer. The mean values of the right and left eyes of each patient were used to compare parameters between both groups. RESULTS: The LD obstruction group had higher levels of meibomian gland loss in both upper (42.9% ± 16.4%) and lower meibomian glands (80.1% ± 16.7%) than did the control group (17.3% ± 6.7% and 22.8% ± 13.0%, respectively) (P < 0.001 and P < 0.001, respectively). In the LD obstruction group, meibomian gland loss in the lower eyelid was significantly higher than that in the upper eyelid (P < 0.001). The lipid layer was significantly thinner in the LD obstruction group (28.4 ± 9.7 nm) than it was in the control group (72.9 ± 22.5 nm) (P < 0.001). CONCLUSIONS: Patients with chemotherapy-induced LD obstruction had greater meibomian gland loss and thinner lipid layers than did patients without LD obstruction. Chemotherapeutic agents that induce LD obstruction can also block the meibomian gland orifice, resulting in obstructive meibomian gland dysfunction through the same mechanism.

Evaluation and Management of Chemotherapy-Induced Epiphora, Punctal and Canalicular Stenosis, and Nasolacrimal Duct Obstruction.

PURPOSE: To describe the frequency, mechanisms, and treatment of epiphora caused by chemotherapeutic agents. METHODS: Review of relevant articles published in PubMed. RESULTS: The chemotherapeutic drugs best documented to cause epiphora are 5-fluorouracil and docetaxel; with both of these drugs, the main mechanism underlying epiphora is canalicular stenosis. Drugs less commonly reported to cause epiphora include S-1, capecitabine, imatinib, topical mitomycin C, and radioactive iodine for treatment of papillary thyroid carcinoma. While all the above-mentioned drugs can be associated with epiphora, some drugs and administration schedules cause only punctal and canalicular inflammation, whereas others cause significant canalicular stenosis. For example, weekly administration of docetaxel is far more likely to cause canalicular stenosis than every-3-weeks administration. The literature suggests that, in patients who receive weekly docetaxel, silicone stenting at the first sign of recurrent or progressive canalicular stenosis can prevent severe irreversible canalicular stenosis and avoid the need for a conjunctivodacryocystorhinostomy. S-1 and radioactive iodine have been reported to cause nasolacrimal duct obstruction. Early recognition of punctal and canalicular stenosis or nasolacrimal duct blockage and early intervention with topical steroids and canalicular stenting in patients at risk for permanent canalicular scarring are important to avoid the need for more invasive and complicated procedures. CONCLUSION: A variety of chemotherapeutic agents have been reported to cause epiphora, and some of these drugs have also been documented to cause obstructions of the lacrimal drainage system. Early recognition and management of epiphora is important and leads to better outcomes.

Predictive factors for ocular complications caused by anticancer drug S-1.

PURPOSE: To identify predictive factors for ocular complications caused by the anticancer drug S-1. METHODS: A questionnaire was administered to 39 patients who underwent S-1 chemotherapy at Kobe City Medical Center General Hospital, with the aim to determine whether these patients were aware of the ocular complications caused by S-1. Cognition rate was determined. The 26 patients who requested opthalmological examination for further evaluation studied further and classified into two groups-those who had developed corneal epithelial complications, conjunctival injection or chemosis, or lacrimal duct blockages (referred to as the positive group) and those without these findings (referred to as the negative group). Predictive factors, such as age, sex, total administration days, total dose, presence or absence of anticancer drug pretreatment, and single-drug or combination-drug therapy, were investigated and compared between groups. RESULTS: Of the 39 patients who completed the questionnaire, ten were aware of the potential for ocular complications due to S-1 chemotherapy (cognition rate 25.6 %). Of the 26 patients who had requested opthalmological examination and entered into the study, 13 (26 eyes) were classified into the positive group, with corneal complications observed in 15 eyes (57.7 %), conjunctivitis in 26 eyes (100 %), and lacrimal duct blockage in 14 eyes (53.8 %). Cognition rate in the 13 patients in the positive group and the 13 patients in the negative group was 38.5 % (5 patients) and 7.7 % (1 patient), respectively. Patient age was significantly different between the two groups, with the patients in the positive group being significantly older than those in the negative group (mean age ± standard deviation: 71.6 ± 6.8 vs. 63.5 ± 7.3 years, respectively; P = 0.0077, Student's t test). No other significant predictive factors were detected. CONCLUSION: Older patients were at greater risk of S-1-related ocular complications, but these complications were not associated with total administration days or total dose.

[A case of lacrimal duct obstruction caused by capecitabine].

In recent years, the incidence of adverse ocular reactions, including corneal problems and lacrimal duct obstruction, due to antineoplastic agents such as S-1 has increased. Very few reports of adverse ocular reactions caused by capecitabine, a fluorinated pyrimidine antineoplastic agent like S-1, exist, and consequently, the mechanism underlying these reactions is not well understood. This report describes our recent experience with a case of lacrimal duct obstruction caused by capecitabine. The patient was a 71-year-old woman who was being administered trastuzumab plus capecitabine combination chemotherapy for breast cancer-related bone metastasis. She complained of epiphora 7 days after capecitabine was initiated. Thereafter, her capecitabine dose was reduced owing to exacerbation of hand-foot syndrome, but the epiphora persisted. Capecitabine was discontinued 287 days after initiation owing to exacerbation of the hand-foot syndrome. However, because the epiphora persisted, the patient visited the ophthalmology department. The ophthalmologist diagnosed the patient with binocular nasolacrimal duct obstruction and cataract, and prescribed a 0.3% gatifloxacin ophthalmic solution and 0.1% fluorometholone ophthalmic suspension. Thereafter, the epiphora reduced. When the patient returned to the ophthalmology department, symptom improvement was confirmed. In this case, lacrimal duct obstruction likely developed due to capecitabine. The symptoms were reversible with discontinuation of capecitabine and ophthalmic treatment. We believe that reporting this case could be valuable in discussing capecitabine-induced lacrimal duct obstruction.

Dacryocystitis secondary to intranasal cocaine abuse: a case report and literature review.

PURPOSE: To report a case of dacryocystitis secondary to intranasal cocaine abuse and to review the literature on the effects of cocaine on sinus, nasal and lacrimal structures. METHODS: Case report and literature review. RESULTS: A 33-year-old male presented with unilateral epiphora and discharge, and clinical examination was consistent with dacryocystitis. He had a 2-year history of intranasal cocaine use. Computed tomography revealed extensive bilateral intranasal and sinus destruction, consistent with cocaine abuse. He was treated with antibiotics followed by dacryocystorhinostomy with silicone intubation. He had 2 recurrences of dacryocystitis and underwent one additional lacrimal surgery. CONCLUSIONS: Cocaine abuse and its accompanying intranasal and sinus destruction should be considered when determining the etiology of nasolacrimal obstruction and dacryocystitis. A medical and social history with specific questions about drug abuse may be useful. Computed tomography is helpful in delineating damage to the sinuses, nose and lacrimal system. Management with antibiotics and dacryocystorhinostomy surgery may result in resolution of symptoms.

Prevalence of excessive tearing in women with early breast cancer receiving adjuvant docetaxel-based chemotherapy.

PURPOSE: To define the incidence and impact of tearing in patients receiving adjuvant docetaxel-based chemotherapy and assess for lacrimal duct obstruction (LDO) as a causative factor. PATIENTS AND METHODS: Consecutive patients with early breast cancer recommended for docetaxel-based chemotherapy with no prior ocular symptoms were included. Before and after completion of chemotherapy, patients underwent lacrimal drainage evaluation by computed tomographic dacrocystography (CT-DCG) and ophthalmic assessment. Eye symptoms were assessed at baseline, during, and after completion of chemotherapy. RESULTS: Over a 22-month period, 100 patients were recruited. Asymptomatic LDO was present at baseline in 17% and 18% of patients, as assessed by ophthalmic review and CT-DCG, respectively. Overall, 86% of patients developed tearing, with no significant difference between those who did and did not have LDO (94% v 84%; P = .45). Blepharitis occurred in 37% and minor corneal epitheliopathy in 22% of patients, with neither condition predicting for the development of tearing. Impairment of visual activities was greatest after cycle one (70% of patients) but had decreased to < 5% by 4 months after treatment. CONCLUSION: Tearing occurs in the majority of patients receiving adjuvant docetaxel-based chemotherapy regimens and occurred similarly in patients with and without LDO. There was poor concordance between CT-DCG and ophthalmic examination in the detection of LDO. Tearing and other eye symptoms impaired visual activities, but in nearly all patients, both symptoms and functional impairment were mild and had resolved by 4 months after chemotherapy. Our study demonstrates docetaxel-related tearing is not caused by LDO, and as such, evaluation or stenting of the duct is not considered necessary.

Nasolacrimal system obstruction, ptosis and esotropia due to chemotherapy in acute lymphoblastic leukemia.

Eight-year-old girl was admitted to our clinic with the complaint of constant epiphora in the right eye. It was reported that this complaint began after the start of chemotherapy with a diagnosis of Acute Lymphoblastic Leukemia (ALL) about 5 years ago. In addition, eyelid ptosis associated with esotropia also occurred during that period. We found that nasolacrimal duct obstruction did not improve with medical treatment but ptosis and esotropia improved with pyridoxine and pyridostigmine treatment during that period. Examination of the eye on admission revealed nasolacrimal duct obstruction on the right side. Other ocular findings were normal. Nasolacrimal system obstruction, ptosis and esotropia combination has not been reported previously in patients using systemic drugs or receiving chemotherapy due to ALL.

Lacrimal drainage obstruction in gastric cancer patients receiving S-1 chemotherapy.

BACKGROUND: This study was conducted to determine the incidence and clinical characteristics of lacrimal drainage obstruction (LDO) in patients receiving S-1 chemotherapy. PATIENTS AND METHODS: Consecutive 170 patients with gastric cancer who underwent curative surgery and received adjuvant S-1 chemotherapy were enrolled. S-1 was administered orally (40 mg/m2 b.i.d. on days 1-28 every 6 weeks) for 1 year. Ophthalmologic examinations were carried out on patients complaining of epiphora. RESULTS: Thirty-one patients (18%) developed epiphora. Among 31 patients, 25 underwent ophthalmologic examinations and 22 (88%) were diagnosed with LDO. The median time to the onset of LDO was 2.9 months. The most common site of obstruction was the nasolacrimal duct [86% (19/22)]; punctal [23% (5/22)] and canalicular obstruction [14% (3/22)] were also noted. In multivariate analysis, total gastrectomy [versus partial gastrectomy: hazard ratio (HR), 2.9; P=0.014] and creatinine clearance<50 ml/min (versus ≥50 ml/min: HR, 2.9; P=0.038) were independent risk factors for the development of LDO. CONCLUSION: Considering the high incidence of LDO in patients receiving S-1 chemotherapy, oncologists should be alert to epiphora and cooperate with ophthalmologists in the early stages to improve the quality of life of patients and avoid more complicated ophthalmologic procedures.

Dacryoendoscopic observation and incidence of canalicular obstruction/stenosis associated with S-1, an oral anticancer drug.

PURPOSE: To report dacryoendoscopic observations and the incidence of lacrimal obstruction/stenosis associated with S-1, an oral anticancer drug. DESIGN: Retrospective, nonrandomized clinical trial. METHODS: A total of 52 patients (41 men, 11 women; age 42-93 years) who were prescribed the anticancer drug S-1 were studied. Patients who suffered eye complaints following S-1 treatment underwent ophthalmic examination, probing and lacrimal irrigation. Patients whose tear meniscus was high or had abnormal lacrimal irrigation were evaluated by dacryoendoscopy. RESULTS: Overall, 5 of 52 S-1-treated patients (9.6%) experienced lacrimal passage stenosis/obstruction. One patient had punctal stenosis, and four patients had canalicular obstruction/stenosis. The onset of epiphora ranged from 2 to 8 months (4.4 ± 2.2 months, mean ± SD) after the initiation of chemotherapy. CONCLUSIONS: Patients receiving S-1 treatment should be evaluated for potential lacrimal disorders, particularly canalicular obstruction/stenosis. Dacryoendoscopic observation is effective for the diagnosis of this side effect.

Ocular manifestations of long-term mascara use.

Mascara, a widely used cosmetic, is associated with eye pathology. The authors report 3 cases of eye problems secondary to long-term mascara use. Two patients had multiple pigmented conjunctival lesions; one of these had a history of melanoma of the hand. Conjunctival biopsy revealed nonmelanocytic pigment granules within conjunctival stroma cells in both cases. The other patient had a history of dry eye, and also showed pigment clumping around a punctal plug. The third patient had canalicular obstruction from a mascara-laden dacryolith ("dacryomascaralith"), the first such case reported. A literature review revealed cases of eyelid dermatitis, infectious keratitis, a conjunctival mass ("mascaroma"), and others. Ophthalmologists should be aware of mascara's associated eye problems. The physical findings combined with a high index of suspicion, especially in cases of heavy mascara use, may allow for an accurate diagnosis and spare the patient an otherwise unnecessary invasive procedure.