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Botox and dry eye (TFOS DEWS II Iatrogenic report)

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  • Botox and dry eye (TFOS DEWS II Iatrogenic report)

    BOTOX, in addition to its cosmetic uses, is being used to treat a great many eye conditions (discussed in 22 referenced studies). These include:
    • blepharospasm
    • hemifacial spasm
    • persistent epithelial defects or ulcers in which protective ptosis is induced
    • lid retraction in thyroid eye disease
    • entropion
    • strabismus
    • abducens paralysis
    • nystagmus
    • gustatory tearing
    • superior limbic keratoconjunctivitis (SLK)
    • refractory filamentary keratitis
    • dry eye
    However, Botox may also be causing dry eye in some patients.

    Excerpt from the Iatrogenic report,

    4. Major causes of dry eye
    4.5. Procedures
    4.5.1 Botulinum toxin
    Botulinum toxin (BTX) is produced by Clostridium botulinum, an anaerobic, gram-positive bacterium, which blocks acetylcholine release at the cholinergic nerve terminals of the neuromuscular synapses [431] and autonomic cholinergic nerve fibers of the sweat [432], lacrimal [433] and salivary [434] glands. Various BTX serotypes (A-G) exist, of which types A and B are commercially available for clinical use [435]. Periocular BTX injection has become the first-line treatment for patients with blepharospasm and hemifacial spasm [435441]. Further ophthalmological indications include persistent epithelial defects or ulcers in which protective ptosis is induced [442,443], lid retraction in thyroid eye disease [444], entropion [445,446], strabismus, abducens paralysis [447], nystagmus, gustatory tearing [433,448], superior limbic keratoconjunctivitis [449], refractory filamentary keratitis [450] and dry eye [451455]. Periocular BTX injections are also currently widely used in facial rejuvenation to reduce lateral periocular wrinkles (crow's feet), medial nose-bunny lines and glabellar rhytids [456,457].

    A randomized, placebo-controlled, double-blind, single-dose trial in 109 blepharospasm patients reported dry eye symptoms in 18.9% of patients after injection of highly purified botulinum neurotoxin A [458]. In retrospective studies, symptomatic dry eye was found in 0.57.5% of blepharospasm patients after BTX injection [438,459]. Injection of BTX-A into the lateral canthal region for aesthetic correction of crow's feet can trigger dry eye of varying severity [460,461] as reported in 15% of recipients [104].

    The possible mechanisms responsible for the development of dry eye after BTX treatment are weakness of the orbicularis oculi muscle, causing reduced tone, blink strength and delayed tear clearance, and direct diffusion of toxin into the lacrimal and meibomian glands, decreasing secretory function [461]. Orbicularis muscle weakness [437,438,462] leading to poor blink function and incomplete eye closure (lagophthalmos) has been observed in up to 64% of toxin-treated blepharospasm patients [441,463]; impaired blinking led to corneal exposure and desiccation, often associated with superficial keratopathy, photophobia, and epiphora [435,437,438,441]. BTX-induced paralysis of the medial pretarsal fibers of the orbicularis muscle causes absence of contractive forces around the walls of the lacrimal drainage pathway and weakness of the punctal apposition during blinking, which leads to reduced tear outflow [437,451,460]; consequently, the delayed tear clearance after BTX injections with a stagnant tear meniscus [464] may provide an environment favorable to microorganism growth and allow inflammatory products to accumulate, leading to conjunctivitis and dry eye [302,465,466]. Alternatively, medial canthal injection may lessen the blink-induced removal of tears and extend lacrimal lubrication of the ocular surface [451,452]; this aids in the treatment of DED [103,104,451454,467], with observed improvements in Schirmer test scores or TBUT measurements [453,454,464,468] and improvement of dry eye symptoms [451,452,464,468]. BTX injection also impairs autonomic cholinergic transmission and inhibits lacrimal gland secretory function [448,469]; thus, it is still used to treat disorders related to pathologic tearing [433,468,470,471].

    BTX chemodenervation paralyzes the orbicularis oculi and Riolan muscles and decreases the driving force for delivery of meibomian secretion [461]. BTX may also diffuse to nearby meibomian glands. Since parasympathetic innervation of the meibomian glands was observed [472], it has become obvious that meibum secretion can be blocked, contributing to lipid deficiency and an unstable tear film after injection [461].

    The literature is inconclusive regarding tear volume measured by Schirmer test after BTX-A injections to periocular tissues; some studies report increased tear volume [453], whereas others report decreased tear volume [103,460,461] and still others report no change [455,468,473475]. Differential changes in tear function parameters may result from the diverse techniques used for BTX injection, such as the number and position of injection sites (pre-septal, pre-tarsal, medial, lateral, intra-subcutaneous, intramuscular) and differing dosages and dilutions of BTX [103,439,476,477].
    Patients scheduled to receive BTX treatment, especially for cosmetic reasons such as lateral canthal rhytids, should be informed of the possible complication of dry eye [461,475]. Since blepharospasm patients often have dry eyes [463,473], and symptomatic dry eye is one of the most common side effects [438], it may be prudent to use artificial tears as a supplement to BTX treatment. In a mouse model of dry eye secondary to BTX, treatment with topical immunomodulators, such as cyclosporine A and tacrolimus ophthalmic solutions, has demonstrated some effectiveness [478,479]. Snap-test and distraction tests are recommended before any periocular BTX injection to test for poor tone and contractility of the orbicularis oculi muscles and for lid laxity resulting from the stretching of canthal ligaments [104]. Keeping the toxin volume low helps to reduce uncontrolled diffusion from the injection site [435,480]. Persistent complications of dry eye unresponsive to 12 months of medical treatment may necessitate surgical management, such as lateral musculoplasty [104].
    Rebecca Petris
    The Dry Eye Zone
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