|Year : 2020 | Volume
| Issue : 1 | Page : 64-68
Evaluation of efficacy and safety of Botulinum toxin injection in treatment of epiphora
Nashwa A Elshaieb1, Sameh S Mandour2, Fahad R Almarshed3, Hatem M Marey2, Hassan G Farahat2
1 Department of Ophthalmology, Ophthalmology Hospital, Egypt
2 Department of Ophthalmology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
3 Department of Oculoplastic and Orbital, Saudi Arabia Kingdom
|Date of Submission||29-Aug-2019|
|Date of Decision||21-Nov-2019|
|Date of Acceptance||05-Dec-2019|
|Date of Web Publication||28-Feb-2020|
Nashwa A Elshaieb
El-Batanon, Shebeen El-Kom, Menoufia, 32511
Source of Support: None, Conflict of Interest: None
Purpose The aim of this study was to evaluate the efficacy and safety of Botulinum toxin injection in the palpebral lobe of the lacrimal gland for treatment of epiphora.
Patients and methods A total of 20 patients with epiphora (crocodile tears syndrome, lower lid laxity, malposition of the lower lid, and obstruction of lacrimal drainage system in which lacrimal surgery was impossible) received intralacrimal gland injection of Botulinum toxin (2.5 IU/0.1 ml). Follow-up was performed on the first day, first week, first month, third month, and sixth month after injection to evaluate the efficacy, safety, and occurrence of any complications and to record the rate of recurrence.
Results Cure was successfully achieved in 60% of the patients after the first injection and in 90% of patients after the second injection. There were 15% of recurrent cases after the first injection, and there were no recurrent cases after the second injection. Temporary ptosis occurred in 10% of this study group after the first injection and in 5% after the second injection. There was a highly significant decrease in Schirmer’s test and tear meniscus height among the study group regarding the pre-injection and follow-up values (P<0.01). In addition, there was a highly significant decrease in Munk scale and time of dye disappearance test among the study group regarding the pre-injection and follow-up values (P<0.01).
Conclusion The injection of Botulinum toxin in the palpebral lobe of the lacrimal gland was effective and safe as a temporary measure to reduce excessive tearing until a more permanent measure can be taken.
Keywords: Botulinum toxin, epiphora, lacrimal gland, Munk scale
|How to cite this article:|
Elshaieb NA, Mandour SS, Almarshed FR, Marey HM, Farahat HG. Evaluation of efficacy and safety of Botulinum toxin injection in treatment of epiphora. Delta J Ophthalmol 2020;21:64-8
|How to cite this URL:|
Elshaieb NA, Mandour SS, Almarshed FR, Marey HM, Farahat HG. Evaluation of efficacy and safety of Botulinum toxin injection in treatment of epiphora. Delta J Ophthalmol [serial online] 2020 [cited 2020 Apr 6];21:64-8. Available from: http://www.djo.eg.net/text.asp?2020/21/1/64/279723
| Introduction|| |
Normal drainage of tears from the conjunctival sac into the nose is dependent on the patency of the nasolacrimal passages, including the lacrimal puncta, the lacrimal canaliculi, the common canaliculus, the lacrimal sac, and the nasolacrimal duct, which opens into the inferior meatus of the nose. Epiphora results from blockage of any portion of this passage by inflammation, scarring, trauma, stone, or neoplasm .
Surgery as a treatment of epiphora may not be the best option for all patients, especially in the elderly population and in those who have undergone excision of the lacrimal drainage system for treatment of malignant lesions affecting the neighboring anatomical structures. Botulinum toxin injection in the lacrimal gland blocks the presynaptic release of acetylcholine, which is required for tear secretion .
Botox (Botulinum) has been successfully used to treat excessive tear production in the setting of crocodile tears syndrome owing to aberrant regeneration in proximal facial nerve injuries ,. There are two publications reporting its use in the treatment of either functional epiphora or lacrimal obstruction. Botulinum toxin has been suggested as a promising treatment for those with resistant cases of excessive tearing or irreparable damage to the lacrimal drainage system ,.
In the current study, the efficacy and safety of Botulinum toxin injection in the palpebral lobe of the lacrimal gland for treatment of some cases of epiphora were evaluated.
| Patients and methods|| |
This was a prospective clinical trial on twenty patients during the period from January 2017 to July 2017. The approval for the study was obtained from the Department of Ophthalmology in Shebin El-Kom University Hospital. Ethics approval from the Institutional Review Board was obtained. All patients signed a written informed consent to participate in the study and for publication of data before enrollment in the study.
All patients underwent detailed history taking including age, sex, occupation, any other ocular disease, operations, trauma, allergy, and family history of epiphora as well as full clinical examination to detect the original disease responsible for epiphora. Best-corrected visual acuity was measured using the Landolt’s broken ring chart at 20 feet distance. Intraocular pressure was measured using Goldman applanation tonometry (Topcon Corp., Tokyo, Japan). Anterior segment examination was performed by the slit-lamp to examine the lid position, punctal position, inflammatory changes, tear film, cornea, and conjunctiva.
Diagnostic probing and syringing was done . Dye disappearance test was performed with a drop of 2% fluorescein sodium dye in the inferior fornix with assessment after 5 min of the remaining dye in the tear meniscus height . Munk score was evaluated according to the times of dabbing per day ,. Tear meniscus height was also measured . Schirmer’s test was measured by placing a small strip of filter paper inside the inferior fornix; the eyes were closed for 5 min, the paper was then removed, and the amount of moisture was measured. Checkup of the nasal vestibule was done by an otolaryngologist.
Inclusion criteria were epiphora grade III–V according to Munk score, malposition of lower lid, crocodile tears, obstruction of the lacrimal drainage system in which lacrimal surgery was impossible, or lower lid laxity.
Exclusion criteria were previous hypersensitivity to Botulinum toxin or human albumin, neuromuscular junction disorders, ocular motility defects, motor neuropathies, active ocular infection, dry eye, and women during pregnancy or lactation.
Injection of Botulinum toxin
The injection of Botulinum toxin [Clostridium botulinum type; A neurotoxin complex (900 kD); Allergan, Westport Co., Mayo, Ireland) was performed in the operating room. Eyes were anesthetized with Benoxinate hydrochloride 0.4 eye drops (Egyptian Int. Pharmaceutical Industries Co., E.I.P.I.CO., 10th of Ramadan City, Egypt). The lateral upper eyelid was everted over a retractor, and the patient was asked to look inferomedially as far as he/she can to expose the palpebral lobe of the lacrimal gland. Then, 0.1 ml (2.5 IU/0.1 ml) of diluted Botulinum toxin (the vial contains 100 IU of freeze-dried Botulinum toxin, 0.5 mg human albumin, and 0.9 mg sodium chloride − the vial was diluted with 4 ml of normal saline, resulting in a concentration of 25 IU/ml) was injected into the palpebral lobe of the lacrimal gland using a 30-G needle ([Figure 1]). Transconjunctival approach is better than transcutaneous approach to allow for direct visualization of the gland.
|Figure 1 Injection of diluted Botulinum toxin into the palpebral lobe of the lacrimal gland using a 30-G needle.|
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A combination of tobramycin and dexamethasone eye drops was given four times daily for 1 week. Postoperative follow-up visits were carried out on the first day, first week, first month, third month, and sixth month after the initial injection. The changes in Munk score, dye disappearance test, Schirmer’s test, and tear meniscus height were reported.
Data were collected, revised, coded, and entered into the statistical package for social science (IBM SPSS; SPSS Inc., Chicago, Illinois, USA), version 20 software (IBM Corporation, Somers, New York, USA). Paired t test was used to detect the difference between preoperative and postoperative data in the study group. Significance was considered if P value was less than 0.05.
| Results|| |
This study included 13 (65%) female patients and seven (35%) male patients, with a mean age of 46.85±14.22 years (range, 28–77 years). We included patients with epiphora grade III–V according to Munk score. The main cause of epiphora among the study group was nasolacrimal duct obstruction in which lacrimal surgery was impossible (55%), whereas crocodile tears syndrome was 15%, lower lid laxity was 10%, hypersecretion of the lacrimal gland was 10%, and punctal ectropion was 10%.
The mean pre-injection tear meniscus height was 2.13±0.39 mm. It decreased to 1.7±0.51 mm at 6 months after injection, with a statistically significant difference (P=0.002). However, there was no statistically significant difference between post-injection measures all through ([Table 1]).
|Table 1 Comparison between the tear meniscus height among study group regarding pre-injection and follow-up assessments|
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The mean pre-injection Schirmer’s test result was 30.1±2.8 mm. It decreased to 19.5±8.5 mm at 6 months after injection, with a statistically significant difference (P=0.001). There was no statistically significant difference between post-injection measures all through ([Table 2]).
|Table 2 Comparison between Schirmer’s test among study group regarding pre-injection and follow-up assessments|
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Concerning the Munk scale, there were 12 patients in grade V, seven patients in grade IV, and one patient in grade III before injection. Three months after injection, the number decreased to two patients in grade V, five patients in grade IV, one patient in grade III, seven patients in grade II, and five patients in grade I. There was a highly significant difference in the Munk scale when comparing the pre-injection and post-injection measures (P<0.001, [Table 3]).
|Table 3 Comparison between Munk score test among study group regarding pre-injection and follow-up assessments|
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Regarding the dye disappearance test, all 20 patients were in grade III before injection. Three months after injection, the number decreased to eight patients in grade III, six patients in grade II, and six patients in grade I. There was a highly significant difference between the results of the dye disappearance test before injection when compared with post-injection measures (P<0.001, [Table 4]).
|Table 4 Comparison between dye disappearance test among study group regarding pre-injection and follow up assessments|
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After the first injection, 60% of patients were successfully cured, whereas 90% of patients were successfully cured after the second injection. The tear meniscus height, Schirmer’s test, Munk score, and dye disappearance test were significantly decreased in 60% of the group after the first injection of Botulinum toxin, and they were decreased in 90% of the group after the second injection.
The recurrence rate was 15% after the first injection, and there were no recurrent cases after the second injection.
The only complication in this study group was temporary ptosis, which occurred in 10% of the group after the first injection and in 5% after the second injection. Ptosis was relieved within 6 months.
| Discussion|| |
The first study to explore the effects of Botulinum toxin in a series of patients with epiphora was the study of Keegan et al. , which demonstrated that there was one patient with epiphora who showed some subjective improvement in his/her condition, but it was not demonstrable with clinical tests. The study of Whittaker et al.  investigated the usefulness of Botox in patients with functional epiphora. It achieved symptomatic relief with transconjunctival injections of 2.5–5 U of Botox in the palpebral lobe of the lacrimal gland.
In the current study, Botulinum toxin was injected into the palpebral lobe of the lacrimal gland to reduce tear production. This is a new approach to the management of epiphora. It is easy to perform, relatively inexpensive and noninvasive, and is well tolerated with few adverse effects. A disadvantage of Botox injection is that it provides only temporary symptomatic relief for most patients. However, it is repeatable, and the patients who are only troubled significantly during the colder months of the year may only require very infrequent injections. However, the safety and acceptability of repeated injections need to be investigated .
Ziahosseini et al.  evaluated the effect of Botox injection for epiphora by the reduction of the mean Munk score after injection from 3.4 to 1.6 in a series of 22 eyes. Kaynak et al.  reported both quantitative and qualitative evaluations of epiphora in a comparative study including 20 eyes treated with Botox injection. The mean Munk and Schirmer’s scores were 3.95 and 12 mm before injection, respectively. They decreased to 1.05 and 5.4 mm, respectively, at 1 month after injection and to 1.36 and 5.8 mm, respectively, at 3 months after injection. These results of previous studies ,,,,, were in agreement with the findings of the present study, which revealed significant improvement of epiphora at 1 and 3 months after Botulinum toxin injection.
In the present study, the mean Schirmer’s and Munk score were significantly decreased in 60% of the group after the first injection and in 90% of the group after the second injection, whereas in the study of Ziahosseini et al. , they were decreased in 63% after the first injection and 71% after the second injection. Similarly, in the study of Montoya et al. , they were decreased in 75% of the patients after the first injection.
In the present study, two patients had ptosis after the first injection and one patient had ptosis after the second injection, whereas in the study of Ziahosseini et al. , temporary bruising and diplopia occurred in two patients. In the study of Montoya et al. , one patient had ptosis and two patients had mild stinging and dryness of the treated eye after the first injection, whereas in the study of Whittaker et al. , two patients had transient ptosis and diplopia.
In conclusion, the intraglandular injection of Botulinum toxin in the palpebral lobe of the lacrimal gland was a safe, effective, reliable, reversible, and less invasive procedure than surgical alternatives. It is a well-tolerated treatment for epiphora and should be considered for patients who do not have a response to topical treatment and in the elderly patients or those for whom surgery may be contraindicated such as patients with previous malignancy involving the lacrimal apparatus. The use of Botulinum toxin may be valuable as a temporary measure to decrease excessive tearing until a more permanent measure can be taken.
Financial disclosure and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]