The Association Between Taxane Use and Lacrimal Disorders.

PURPOSE: The current study seeks to investigate the association between lacrimal disorders and the use of docetaxel and paclitaxel. METHODS: A disproportionality analysis was conducted using the United States FDA Adverse Event Reporting System (FAERS). All adverse event reports containing the term docetaxel or paclitaxel were selected. Lacrimal adverse events were identified using the lacrimal disorders Standardized MedDRA Query (SMQ), which includes disorders that affect lacrimal gland and drainage system including blockage of nasolacrimal duct, occlusion/stenosis of punctum, lacrimal gland neoplasms, and inflammations and infections. RESULTS: The proportionate reporting ratio (PRR) comparing lacrimal events among docetaxel to paclitaxel users was 2.47 (95% CI, 2.03-3.02). With respect to specific lacrimal events, dacryostenosis (PRR 19.54 [95% CI, 7.19-53.13]), increased lacrimation (PRR 3.2 [95% CI, 2.42-4.23]), lacrimation disorder (p = 0.02), and xeropthalmia reports (p > 0.001) were significantly more common. CONCLUSIONS: The growing body of epidemiologic, clinical, and pathophysiologic research supports the case that docetaxel leads to adverse lacrimal events in certain patients and should be taken into consideration when oncologists consider docetaxel vs. paclitaxel.

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.

Current practice trends for lacrimal gland neurotoxin in the management of epiphora-a BOPSS survey.

PURPOSE: Injection of botulinum neurotoxin A (BoNTA) to the lacrimal gland (LG) offers a simple and effective treatment in the management of epiphora. However, there is little data on current practice trends or uptake as an alternative to surgery. This study assesses current practice trends of such treatment amongst BOPSS (British Oculoplastic Surgery Society) members. METHODS: All consultant BOPSS members were invited to participate in a web-based survey which consisted of 5 questions, with a reminder invitation to participate. The role, dose, potential side effects, use as an alternative to surgical intervention, and impact on service delivery were assessed. RESULTS: Fifty-one BOPSS consultants (43% uptake) completed the survey. Ninety percent of respondents were regularly using LG BoNTA in their management of epiphora. The main indicators for considering BoNTA use were medical comorbidities and elderly patients. The mean first treatment dose of Botox® was 3.6 units (SD 1.5). Diplopia and ptosis complications were always discussed in the consent for treatment in addition to dry eye. Twenty-five percent of surgeons reported doing less conjunctivo-dacryocystorhinostomies (cDCR) due to the availability of LG BoNTA. No respondents felt that the requirement for repeated BoNTA treatments was impacting on their service delivery. CONCLUSION: Uptake of LG BoNTA in the management of epiphora is at a similar rate to all other available treatments. As a result, respondents are performing less surgical procedures, particularly cDCR in patients at higher surgical morbidity.

Toxic Keratitis After Application of Custard Apple Seed for Head Lice Infestation.

PURPOSE: To report the clinical features and outcomes of toxic keratitis after application of powdered custard apple seeds for hair washing for head lice infestation. METHODS: Retrospective review of all patients with toxic keratitis after application of powdered custard apple seed for head lice infestation during the time period from January 2015 to December 2017. Demographic details, clinical features, and visual outcomes were documented. RESULTS: Thirty-one eyes of 19 patients with toxic keratitis after application of crushed custard apple seeds for head lice infestation were included in the study. Eighteen females and 1 male with a median age of 14 years [interquartile range (IQR) 12-34 years] presented with severe epiphora, congestion, photophobia, and defective vision (median logMar visual acuity 0.4, IQR 0.2-0.8) after application of custard apple seed powder for hair washing. Ten eyes (32.2%) had an epithelial defect (median size 9 mm, IQR 5-12 mm), and 21 (67.7%) eyes had punctate epithelial erosions. All the patients were treated with topical antibiotics, and at 3 days follow-up, all of them had resolution of symptoms and signs with a median logarithm of the minimum angle of resolution (logMAR) visual acuity of 0 (IQR 0-0.2). CONCLUSIONS: Health education about the harmful effect of this traditional practice for head lice infestation will prevent further similar events.

[A Retrospective Investigation of Lacrimation in Patients Treated with S-1].

Lacrimation is among the typical adverse drug reactions associated with S-1 treatment. However, lacrimation frequencies differ between reports, and a clear consensus regarding reaction times, risk factors, and symptomatic treatment for lacrimation is lacking. We retrospectively investigated the reaction times, risk factors, and outcomes of symptomatic treatment for lacrimation in 202 patients treated with S-1. The median estimated creatinine clearance noted upon initiation of cancer treatment was 75.8mL/min. The median of the relative treatment intensity was 87.1%, while the incidence of lacrimation was 26.7%. The median cumulative dose of S-1 before the onset of lacrimation was 23,520 mg in all patients, and 5,050 mg in those who developed lacrimation. Of the patients who developed lacrimation, 40.7% developed this symptom within 2 months after starting S-1 treatment. There were no apparent risk factors. The most frequently employed symptomatic treatment was a physiological saline ophthalmic solution provided as a hospital preparation. After treatment with this ophthalmic solution, 29.4% of the affected patients showed improvement and 70.6% showed no change; none however, experienced worsening of symptoms. These results suggest that clinicians should assess the presence of lacrimation after starting treatment with S-1. Symptomatic treatment with an ophthalmic solution that does not have a tear retention capacity may be useful in patients who have developed lacrimation.

Cyclophosphamide and/or Anthracyclines Induced Epiphora in Breast Cancer Patients: A Rare Side-effect.

BACKGROUND: Two female breast cancer patients developed epiphora after administration of cyclophosphamide and/or anthracyclines based 2-day chemotherapy regimen. An ophthalmologist was consulted and no apparent cause was found. CASE DESCRIPTION: Patients were managed by ciprofloxacin eye drops. Chemotherapy induced ocular complications are not uncommon, but under reported. Although epiphora is a mild reaction, if severe however, it can interfere with daily activities. Patients having chemotherapy induced ocular toxicity should go for ophthalmic examination to pick up ocular adverse effects of anticancer drugs and treat them at an early stage.

Bilateral subacute lacrimal gland enlargement mimicking dacryoadenitis in a 7-year-old boy: a rare adverse effect of valproic acid (sodium valproate).

A healthy 7-year-old boy presented with bilateral symmetrical lacrimal gland enlargement; a week later salivary gland enlargement was also noted. Clinical investigations suggested no diagnosis, and surgical biopsy was considered. Valproic acid (sodium valproate), which he was taking for absence seizures, has been reported to cause salivary gland swelling in adults. Suspecting that a similar mechanism could be causal, the drug was discontinued. Complete resolution of the lacrimal and salivary gland enlargement rapidly ensued. This is the first report of lacrimal gland enlargement caused by valproic acid.

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.

[A Retrospective Analysis of Epiphora Due to Docetaxel].

Docetaxel is an antineoplastic agent used to treat breast cancer and several other types of cancer. Typical adverse drug reactions with docetaxel include myelosuppression and edema, but there have also been numerous reports of eye disorders, such as epiphora and lacrimal duct obstruction. Reports from Japan on such reactions, however, are limited; the duration and frequency of their appearance and other factors have not been elucidated. Since this information would be useful in routine medical practice, we conducted a retrospective analysis of epiphora due to docetaxel. Of the 48 breast cancer patients who commenced new 3-weekly docetaxel dosage regimens during the study period, 6 (12.5%) presented with epiphora. The patients with epiphora were receiving docetaxel at a significantly greater dose intensity (mg/m 2/3 weeks) than those in whom epiphora did not present (72.7 vs 67.1, p=0.0427). The timing of the reaction had no fixed pattern, and the symptoms were reversible in all cases, recorded as Grade 1 or 2. Thus, epiphora due to docetaxel during a 3-weekly dosage regimen presented rather frequently in Japanese patients, and the symptoms were reversible and mild. We found that greater dose intensity might be a risk factor for epiphora. More detailed studies that include data from a large number of facilities should be conducted in the future.

Ocular toxicity assessment of chronic sildenafil therapy for pulmonary arterial hypertension.

PURPOSE: The aim of this study was to investigate possible functional and structural ocular changes caused by chronic sildenafil therapy to treat pulmonary arterial hypertension (PAH). METHODS: Case-control study included patients with pulmonary arterial hypertension: chronically using sildenafil and without sildenafil treatment. A comprehensive ophthalmologic exam including ectoscopy, extrinsic ocular motility, logMAR visual acuity measurement, contrast sensitivity test, color test, anterior segment biomicroscopy, Schirmer test 1, intraocular pressure, fundus exam under pupil dilation, fundus pictures, time domain and spectral domain optical coherence tomography, ocular Doppler ultrasound were performed. Full-field electroretinography (ERG) was tested for each eye in a subgroup of sildenafil-treated patients. RESULTS: Twenty patients from each group were tested. Bilateral severe keratitis was found in seven (35 %) patients under sildenafil therapy. Lacrimal film break-up time (BUT) was significantly reduced (p = 0.006 respectively) and Doppler ultrasound showed a reduced resistance index of the central retinal artery in the group of sildenafil users (p = 0.019). No diffuse retinal functional abnormalities were found in ERG in treated patients. Visual acuity, contrast sensitivity and color discrimination were normal in both groups. No abnormalities were found in both time-domain and spectral-domain OCT for retinal parameters. CONCLUSIONS: One-third of the treated PAH group showed severe bilateral keratitis. This finding could be related to connective tissue abnormalities usually present in patients with this condition that might be exacerbated with the sildenafil usage. The resistance index of the central retinal artery was diminished in the chronic users group and it could be associated to the vasodilation caused by the medication in the choroidal vessels. An ophthalmic assessment for these patients is recommended to diagnose and treat possible ocular surface and choroidal blood flow abnormalities caused by sildenafil.

Excessive watering eyes in gastric cancer patients receiving S-1 chemotherapy.

BACKGROUND: Watering eyes is a common late adverse event associated with S-1 chemotherapy; however, the frequency and predictive factors are not known. METHODS: This study included 304 consecutive gastric cancer patients treated with adjuvant S-1 monotherapy for 1 year at Shizuoka Cancer Center. We retrospectively evaluated the frequency of watering eyes, and explored other nonhematological adverse events during the first course of S-1 monotherapy which could become predictive factors for watering eyes. RESULTS: The severest grade of watering eyes during S-1 monotherapy was grade 2 in 41 patients (13.5 %) and grade 3 in 36 patients (11.8 %). The median time to onset of grade 2 and grade 3 watering eyes was 82 days (range 6-344 days) and 249 days (range 84-653 days), respectively, and the median cumulative S-1 dose at the onset of grade 2 and grade 3 watering eyes was 4174 mg/m(2) (range 491-16,095 mg/m(2)) and 10,243 mg/m(2) (range 4943-16,341 mg/m(2)), respectively. Multivariate analysis showed that anorexia (odds ratio 2.37, P = 0.008), oral mucositis (odds ratio 3.86, P = 0.0003), skin hyperpigmentation (odds ratio 3.84, P = 0.0001), and rash (odds ratio 3.76, P = 0.01) observed during the first course were significantly associated with watering eyes. CONCLUSION: The risk of watering eyes was higher in patients who also had anorexia, oral mucositis, skin hyperpigmentation, or rash during first course of S-1 monotherapy than in those without them.

Epiphora in lung cancer patients receiving docetaxel: a case series.

BACKGROUND: Docetaxel is a key antineoplastic drug for treatment of non-small cell lung cancer. Ocular adverse events of docetaxel include epiphora (excess tearing) and conjunctivitis. Epiphora has been reported to be associated with canalicular and nasolacrimal duct stenosis, but it is not necessarily caused by lacrimal duct obstruction. CASE PRESENTATION: We encountered three Japanese non-small cell lung cancer patients who developed epiphora after the administration of docetaxel-based chemotherapy. One patient with lacrimal puncta stenosis showed improvement with probing and irrigation. The other two patients resolved following cessation of docetaxel or administration of artificial tears. CONCLUSION: As epiphora can interfere with activities of daily life and negatively affect quality of life, it is important for thoracic oncologists to be aware of this adverse event.

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.

Bilateral lacrimal gland enlargement associated with isotretinoin treatment.

This report aims to raise awareness of the potential link between isotretinoin use and the development of lacrimal gland enlargement. A 23-year-old woman who was using isotretinoin 40 mg daily for acne vulgaris for 6 months presented with periocular pain and bilateral swelling of upper eyelids. She did not have any signs of inflammation. Her systemic workup including serological tests for autoimmune disorders were within normal limits. MRI of the orbits revealed bilateral enlargement of the lacrimal glands. Discontinuation of isotretinoin resulted in disappearance of her signs and symptoms and the size of the lacrimal glands reverted to normal after 2 months. Isotretinoin use may be associated with lacrimal gland enlargement, and this adverse effect seems to be transient and reversible on cessation of the drug.

Lacrimal duct cyst (dacryops) following ocular chemical injury.

A 37-year-old man presented with swelling under the lateral aspect of the right upper eyelid. He had sustained an alkali ocular chemical injury 10 years before resulting in persistent lateral canthal webbing. Diagnosis was made of lacrimal duct cyst (dacryops) and webbing of the lateral canthus and the findings were confirmed on computed tomography. He underwent lacrimal duct cyst marsupialisation and lateral canthoplasty with good cosmetic result, and there was no recurrence of symptoms at 2 months post-operatively. Lacrimal duct cyst is a rare clinical entity and has been postulated to result from localized inflammation or trauma to conjunctiva. To the best of our knowledge, this is the first report of dacryops following a chemical injury.

[Investigation of epiphora following S-1 therapy].

We report the frequency of lacrimal passage disorder and the outcomes of treatment. This retrospective study was performed on 55 cases that were treated with S-1 for at least 1 month. We asked patients about ocular symptoms. An ophthalmic surgeon examined all patients and diagnosed lacrimal passage disorder in 6 of 55 patients (12. 5%). The mean dose of S- 1 was 10, 300 mg, and the average period to onset of lacrimal passage disorder was 5. 7 months. The causes of epiphora included occlusion/stenosis of lacrimal canaliculus, occlusion of lacrimal puncta and stenosis of nasolacrimal duct. Lacrimal surgery was performed in all 6 patients and epiphora improved. Lacrimal passage disorder may result from systemic treatment of patients with S-1. Symptoms of lacrimal passage disorder improved with early detection and treatment by insertion of a silicone tube.