Botulinum toxin type A is produced by Clostridium botulinum and is used commercially as Botox. It works by inhibiting the release of acetylcholine at neuromuscular junctions, causing localized muscle weakness. In ophthalmology, it is used to treat blepharospasm, hemifacial spasm, strabismus, dry eye, and for cosmetic purposes to reduce wrinkles. Complications are usually minor and transient.

1. Botox in
ophthalmology
Presenter: Dr Vikram S Nakhate
Moderator: Dr Preeti Joshi

2. Botulinum neurotoxin
 There are seven distinct strains of Clostridium
botulinum that have been identified.
 Each of these different strains is characterized by the
type of botulinum neurotoxin they are capable of
producing and have been classified as type A, B, C1, D,
E, F, and G.
 Botulinum toxin type A is felt to exert the most
powerful neuromuscular blockade and is also capable
of exerting its effect for the longest duration of time.

3.  Botulinum toxin type A and type B are composed of a
150-kDA polypeptide consisting of a light chain and
heavy chain joined by a disulfide bond ( Fig. 12-18-1 ).
 While the heavy chain is responsible for binding to
the nerve terminal receptors, the light chain exerts its
effect by preventing the release of acetylcholine from
the nerve terminal

4. Mechanism of action

7.  The light chain exerts paralytic effect of botulinum
toxin by inactivating group of proteins that are
responsible for fusion of vesicles containing Ach with
the nerve cell membrane
 This group of proteins are referred as
 SNARE complex(soluble N-ethylmalemide-sensitive
factor attachment protein receptor)
 Inhibition of Ach release results in localised muscle
weakness that gradually reverses over time

8.  Approximately 2 mths after administration of
botulinum toxin,new nerve terminal sprouts
emerge,and extend towards the muscle surface
 Once one of the new sprouts forms a physical
synaptic connection with the previous NM junc,the
motor nerve unit is re-established

9. Commercially available
 Botulinum toxin type A is commercially available as
two preparations:
 Botox (Allergan Inc, Irvine, CA) ( Worldwide)
 Dysport (Ipsen Pharmaceuticals, France). (European
Union )
 Botulinum toxin type B
 Myobloc (Élan Pharmaceuticals, South San Francisco,
CA). (United States)

10. Clinical applications
 Eyelid:
 Facial dystonia-blepharospasm
 Hemifacial spasm
 Reduce lid retraction- thyroid eye disease
 Apraxia of lid opening
 Induce ptosis in exposure keratopathy
 Lower lid spastic entropion

11.  Strabismus:
 Infantile esotropia/acquired esotropia
 Intermittent exotropia
 Nerve palsies
 Thyroid eye disease related strabismus
 Congenital nystagmus

12.  Cosmetic:
 Glabellar lines
 Crow’s feet

13.  Others:
 Chronic dry eye
 Lacrimal hypersecretion
 Pain relief in acute angle closure glaucoma

14. Eyelids
 Blepharospasm:
 Is a focal dystonia characterized by recurrent
involuntary contraction of the orbicularis oculi
muscles leading to frequent blinking or forceful eyelid
closure

16. Hemifacial spasm
 Hemifacial spasm (HFS) is characterized by unilateral
irregular clonic or tonic movements of muscles
innervated by cranial nerve VII.
 The condition is believed to result from vascular
compression of the facial nerve at its root exit zone,
leading to irritation of the nerve and causing the
innervated muscles to contract involuntarily.

17.  inject 2.5 units of BoNT-A (BOTOX) into the
orbicularis oculi in the medial and lateral upper
eyelids and 12.5 units in the lateral canthus. Lower
facial spasms are treated with 2.5 to 5 units in the
malar region.

18. Induce ptosis/Reduce lid
retraction
 Botox can be used to chemically denervate the eyelids
to induce ptosis
 Has a therapeutic indication in management of lid
retraction in thyroid eye disease, neurotropic
keratopathy or bell’s palsy to improve eyelid closure
in order to protect cornea

19. Apraxia of lid opening
 Inability to raise the upper eyelid in the absence of
levator muscle injury , paralysis or orbicularis oculi
muscle contraction
 Described in isolation or in association with other
extrapyramidal disorders like Parkinson syndrome &
progressive supranuclear gaze palsy

20.  Btx-A injection into the pretarsal orbicularis oculi
allows the levator action to resume and has some
beneficial effect on eyelid opening in this subset of
patients

21. Entropion
 Lower lid entropion may arise due to spastic
contraction of the pretarsal orbicularis oculi muscle
 This can propogate a vicious cycle of ocular irritation
and further lid spasticity
 Injection of 5-10 units of Btx-A into the pretarsal or
preseptal orbicularis muscle can eliminate the spastic
component of the entropion

22. Strabismus
 When an extremely small quantity of Botox is injected
into an eye muscle that is pulling the eye out of
position, the drug causes temporary weakness in this
muscle for some weeks.
 This usually causes a large overcorrection of the
strabismus.
 During this time the opposite muscle pulls the eye
across and tightens while the paralysed muscle is
stretched.
 This weakening, stretching and tightening process
may result in a more balanced position of the affected
eye when the paralysis wears off.

23.  < 2.5 u to 5 u injected
 Stabilize eye with forcep - slide needle along muscle
orbital surface - muscle on stretch initially - then
some contraction to give EMG signal. Inject when
signal heard

25. Retrobulbar botox
 The "ideal" patient for retrobulbar Botox has
restricted movement, oscillopsia, and is willing to use
only one eye.

26.  Botox can be injected in the retrobulbar space for
oscillopsia - rare indication - treat one eye only.
 In most cases, patient will have systemic problem
such as brain stem stroke.

27. Complications
 Ptosis - always transient
 Induced deviations - usually transient
 Diplopia - transient
 Lip droop - very bothersome; may be persistent
 Dilated pupil - rare
 Reduced accommodation - rare
 Scleral perforation - rare - potentially serious

28. Cosmetic use
 The cosmetic use of botulinum toxin is well-studied
for the treatment of glabellar frown lines, horizontal
forehead rhytids, and lateral canthal lines (crow’s
feet).
 Currently, physicians are beginning to explore other
uses in the face, such as contouring of the jawline, the
neck, and the nasolabial fold.

29. Glabellar frown lines
 Glabellar frown lines
are the most common
reason for cosmetic
injection of botulinum
toxin

30.  Facial rhytides and folds in this area result from
action of the depressor muscles.
 The corrugator superciliaris, medial orbital portion of
the orbicularis oculi, and more horizontally oriented
fibers of the depressor supercilii produce the vertical
lines of the glabella.

31.  The corrugator muscle is a
brow adductor moving the
eyebrow downward and
medially.
 It arises from the nasal
bone just above the rim of
the orbit medially and
extends laterally and
upward, inserting in the
skin above the middle of
the eyebrow.
 It lies deep to the frontalis,
procerus, and orbicularis
oculi muscles.

32.  The vertically oriented
procerus muscle, which
originates from the upper
nasal cartilage and the
lower nasal bone,
produces the horizontal
lines of the glabella and
nasal root.
 It inserts into the skin
between the brows and the
frontal belly of the
occipitofrontalis.
 Its fibers interdigitate with
those of the orbicularis,
frontalis, and corrugator
muscles.

33.  A glabellar "spread test" may be performed prior to
injection by spreading the glabellar wrinkles apart
with the thumb and index fingers.
 This may allow an estimate of the expected benefit
from botox injections.
 Patients with thick sebaceous skin and deep dermal
scarring that are not improved with manual spreading
usually respond poorly to botulinum toxin injections.

34.  One site on each side is used to inject the corrugator,
one site on each side is used to inject the orbicularis
oculi and depressor supercilii, and one site is used to
inject the procerus in the mid line.

35.  The patient is asked initially to frown and scowl, and the
target muscles are palpated.
 The first injection is placed into the belly of the corrugator
muscle.
 The needle is inserted at the origin of the corrugator fibers
just above the medial canthus and superciliary arch until
bone is felt, and then withdraw it slightly.
 The needle is then advanced within the belly of the muscle
upward and lateral as far as the medial third of the
eyebrow, 1 cm superior to the orbital rim. 4-6 units are
injected as the needle is withdrawn.

36.  The next site is approximately 1 cm above the upper
medial aspect of the supraorbital ridge. The needle is
advanced slightly in a vertical direction toward the
hairline. 4-6 units are injected into the orbicularis
oculi and depressor supercilii as the needle is
withdrawn.

37.  The last injection is central into the belly of the
procerus to eliminate the horizontal lines at the root
of the nose.
 4-6 units are injected at a point where 2 lines drawn
at 45° from the medial aspect of the eyebrows
converge in the center of the nasal root, just superior
to the horizontal plane of the medial canthi.

38.  To avoid resultant accentuation of eyebrow arching in
men, an additional 4-6 units are injected 1 cm above
the supraorbital prominence vertical to the mid point
of the eyebrow.

39. Complication
 The most common
complication in
treatment of the
glabellar complex is
ptosis of the upper
eyelid.
 This is caused by
diffusion of the toxin
through the orbital
septum, where it
affects the levator
palpebrae muscle.

40. Precautions
 To avoid ptosis, injections should not cross the
midpupillary line, and should be 1 cm above the
eyebrow.
 Digital pressure at the border of the supraorbital
ridge while injecting the corrugator also reduces
the potential for extravasation.
 Patients often are instructed to remain in an
upright position for 3-4 hours following injection
and to avoid manual manipulation of the area.
 Active contraction of the muscles under
treatment may increase the uptake of toxin and
decrease its diffusion.

41. Horizontal Forehead Lines
 Performing botulinum toxin injections to treat
horizontal forehead lines is relatively easy, and
the result usually is quite satisfying.
 Treatment can be combined with injections for
glabellar frown lines when appropriate.

42.  The frontalis muscle
elevates the eyebrows
and the skin of the
forehead.
 The fibers of the
frontalis are oriented
vertically, and wrinkles
of the forehead are
oriented horizontally.

43.  The medial fibers usually are more fibrous than the
lateral fibers, thus requiring less toxin for paralysis.
 Total paralysis of the frontalis should be avoided,
since this is likely to cause brow ptosis and loss of
expression.
 Injection too close to the lateral eyebrow can cause
lateral eyebrow ptosis.

44.  Multiple injections of small amounts of toxin
create weakness without total paralysis.
 3-5 sites on each side of the mid line are injected,
usually using 2 units (1-3 U) per site.
 Sites are separated by 1-2 cm.
 The initial injection site is approximately 1 cm
above the eyebrow directly above the medial
canthus.

45.  Additional sites diverge laterally and upward to
the hairline in a "V" configuration, often for a total
of 3 sites.
 Additional sites can be added in the mid line or
more laterally depending on individual and
clinical response.

46.  Injections of the upper face and periocular region
usually are performed with the patient seated, and the
patient is asked to remain upright for 2-3 hours to
prevent spread of toxin through the orbital septum.

47. Complication
 The most significant complication of treatment of the
frontalis is brow ptosis.
 Injections in the forehead should always be above the
lowest fold produced when the subject is asked to elevate
their forehead (frontalis).
 If the patient has a low eyebrow, treatment of the forehead
lines should be avoided, or limited to that portion of the
forehead 4.0 cm or more above the brow.

48.  An equally esthetically unfavorable outcome is the
brow that assumes a quizzical or “cockeyed”
appearance.
 This occurs when the lateral fibers of the frontalis
muscle have not been appropriately injected.
 The central brow then becomes lowered and the
lateral brow is still able to contract and is pulled
upward. sides of the brow.

49.  The treatment is to inject a small amount of botox into the
fibers of the lateral forehead that are pulling upward.
 However, only a small amount of Botox is required, as
overcompensation can cause hooded brow that partially
covers the eye.

50. Lateral Canthal Lines (crow’s
feet)
 Aging and photodamage cause much of the wrinkling
in this area.
 However, the component of hyperfunctional
contraction of the lateral aspect of the orbicularis
oculi is targeted for improvement with botulinum
toxin injections.

51.  The lateral fibers of
the orbicularis oculi
are arranged in a
circular pattern
around the eye.
Contraction of these
fibers produces
wrinkles that extend
radially from the
region of the lateral
canthus.

52.  3 or 4 subcutaneous injections are applied
approximately 1 cm lateral to the lateral orbital rim
using 2-3 units per injection site (for a total of 6-12 U
per side).
 Sites are spaced 0.5-1 cm apart in a vertical line or
slightly curving arch. Doses that are too high or
injections that are too medial can lead to eyelid ptosis
or diplopia.

53. Complication
 The most common reported complications in the
“crow’s feet” area are bruising, diplopia, ectropion
and an asymmetric smile due to injection of
zygomaticus major.
 If severe lower lid weakness occurs, an exposure
keratitis may result.

54. Precautions
 These complications are avoided by injecting at
least 1 cm outside the bony orbit or 1.5 cm lateral
to the lateral canthus, not injecting medial to a
vertical line through the lateral canthus and not
injecting close to the inferior margin of the
zygoma.
 Violating these boundaries has on occasion also
resulted in diplopia due to medial migration of
Botox and resultant paralysis of the lateral rectus
muscle.

55. Other uses
 Lacrimal hypersecretion:
 Aberrant regeneration of 7 th cranial nerve can
present with a condition called gustatory epiphora or
crocodile tears( excessive lacrimation with salivary
stimulation)
 Injection of 2.5-5 units of Btx-A into the palpebral
lobe of the lacrimal gland can result in a reduction of
tear production and symptomatic relief
 Effect lasts upto 3-4 mths

56.  Chronic dry eye:
 Dry eye is due to imbalance in the composition of the
aqueous,mucin and lipid layers of tear film
 The drainage system consists of the lacrimal pump
and its mech of action is regulated by the orbicularis
oculi during blinking

57.  In blepharospasm or hemifacial spasm a chronic dry
eye state may result due to excessive blinking
 Btx-A injection is administered into the medial
portion of the upper and lower eyelids to minimise
the lacrimal pump action ,thus allowing the tears to
pool in the fornix and provide symptomatic relief

58.  Novel application of Btx-A is its use to relieve
periorbital pain after an acute angle closure attack
 However, this application has to be viewed and
applied with caution as botulinum toxin inhibits
acetylcholine release which can result in pupil
mydriasis

59. Conclusion
 Botulinum injections have become widely popular for
combating the effects of aging.
 Aging patients will continue to seek out the
procedure.
 Knowledge of optimal treatment patterns and adverse
effects will allow physicians to safely and effectively
deliver this therapy.