NEW AVENUES IN - PowerPoint Presentation

Slide1

NEW AVENUES IN MANAGEMENT OF NYSTAGMUS

From

Dr.Shashank

Ranade

DNB, DO, DOMS,FCPS,FICO(UK)

Fellow, Pediatric Ophthalmology, Strabismus & Ocular motility disorders

[International Guest Speaker, UK]

RANADE SUPER-SPECIALITY EYE CENTRE

Mumbai

Expert panelist talk given at ALL INDIA OPHTHALMOLOGICAL SOCIETY MEET

held at KOCHI, February 2012

Slide2

Financial DisclosureI hereby declare that I don’t have any financial interests in any of the products or procedures mentioned in the forthcoming presentationSlide3

Nystagmus Work-upHistory taking- Onset, consanguinity and family history

Vision assessment

- Dilated refraction

Slit lamp examination

- iris

transillumination

defects ?

Fundus

examination

- Optic nerve or retinal pathologies ?

Eye Movement recordings

/ EOG / ENG

ERG &

pVEP

-

CSNB, Cone

dyst

, Ocular albinism, ON disorders

MRI/ CT Scan

and Neurologist opinion -suspected central/sub-cortical causes

Genetic analysis

-FRMD7 in CIN Slide4

EYE MOVEMENT RECORDINGSElecto-oculography (EOG)

Infrared reflectance (IR)

Scleral

search coil

Video-

electronystagmography

( VENG)-

Latest & most preferred choice

amongst all. Good saccadic resolution and linearity for testing saccades and pursuit, less noisy Slide5

Various treatment modalities available PRISMSOPTICAL METHODS

SOMATOSENSORY / AUDITORY FEEDBACK

ELECTRONIC METHODS Fields in which newer

PHARMACOTHERAPY avenues have developed

SURGERY

GENE THERAPYSlide6

Clinical division of treatment optionsSlide7

OLDER- LESSER PRACTICED TREATMENT OPTIONSSlide8

PRISMS Used in 3 scenario’s-

Pre-surgical evaluation purpose

Congenital Nystagmus

which gets suppressed while viewing near targets- we use 7 D BO prisms

Nystagmus with altered head postures-

Amount of prism required ( > 30 pd ), hence it obscures functional vision , are

cumbersome and cause chromatic aberration.

Dell’Osso

LF .Developments of new treatments for congenital nystagmus, Ann N Y

Acad

SciSlide9

OPTICAL METHODS More useful in Acquired Nystagmus of Neurological type

.

It

Stabilises

the image on the retina through

high convex specs

coupled with

high negative power CL ( RGP, PMMA).

Limitations

-

Disables all eye movements, works

monocularly

and in stationary state only

Field of view -limited

Difficult to handle

Refinement of an optical device that stabilizes vision in patients with nystagmus,

Yaniglos

SS, Leigh RJ,

Optom

Vis

Sci

, 1992,June, 69 ;447-50Slide10

AUDITORY/SOMATOSENSORY STIMULI & BIOFEEDBACK METHODSuppression via trigeminal afferents by using a contact lens over cornea

or

auditory stimuli over forehead

or

acupuncture over neck muscles

and has been primarily found with some effects in CIN.

Biofeedback has not been reported to be useful.

Dell

Osso,Tracis,Abel,Erzurum

-Contact Lens in congenital

nystagmus,Clin

Vis

Sci

1988 ; 3: 229-32

Sheth,Dell

Osso,Leigh,Van

Doren

-The effects of afferent stimulation on congenital nystagmus

foveation

periods. Vision Res 1995 ; 35 : 2371-82Slide11

ARTIFICIAL DIVERGENCE SURGERYAim - induce

exophoria

by

bi- medial rectus recessions or recess-

resect

procedure

which in turn the patient overcomes by exerting

fusional

convergence

The former is useful in

Congenital nystagmus

which dampens on convergence while the later in

AHP

cases

Sedler

S,

Shallo

-Hoffman J,

Muhlendyck

H. Die

Artifizielle

-

Divergenz

-Operation

beim

kongenitalen

Nystagmus.

Fortschritte

Ophthalmol

1990; 87: 85-9

.

Zubcov

AA, Stark N, Weber A,

Wizov

SS,

Reinecke

RD. Improvement of visual acuity after surgery for nystagmus. Ophthalmology 1993;100: 1488-97

Kestenbaum

and artificial divergence surgery for abnormal head turn secondary to nystagmus. Specific and nonspecific effects of artificial divergence, Graf. M, Strabismus, 2002 ; June; 10(2): 69-74

.Slide12

BOTOX 25 U of

Botulinum

Toxin A Injection is injected

directly into the

retrobulbar

space.

Used in : Acquired Nystagmus

( Post CVA

)-

reduces

oscillopsia

and improve visual acuity

Effect is short lived (3 to 6 months approx),

diplopia

and

ptosis

Might need to cover the other eye to prevent ‘competition/

diplopia

’

Helveston

EM,

Pogrebiank

AE: Treatment of acquired nystagmus with

botulinum

A toxin. Am J

Ophthalmol

, 106:584, 1988.

Lennerstrand

G,

Nordbo

OA,

Tian

S, et al: Treatment of strabismus and nystagmus with

botulinum

toxin A.

Acta

Ophthalmol

Scand 76:27, 1998

Ruben ST, Lee JP, O’Neill D, et al: The use of

botulinum

toxin for treatment of acquired nystagmus and

oscillopsia.Ophthalmology

101:783, 1994.Slide13

OLDER – WIDELY PRACTICED TREATMENT OPTIONSSlide14

HORIZONTAL RECTUS MUSCLE RECESSIONS

Maximal recession

of all 4 horizontal muscles

i.e

, as high

BMRc

of 10 mm &

BLRc

of 12 mm

First suggested by

Briti-Bagolini

(1960) but revived by Von-

Noorden

-

Helveston

(1991)

Not only

decreases nystagmus intensity

and

improve visual acuity

but also

addresses strabismus and head posture issue effectively after thorough surgical planning.

The effect of horizontal rectus muscle surgery on clinical and eye movement recording indices in infantile nystagmus syndrome,

Bagheri

et al, Strabismus, 2010,June, 18(2) ; 58-64

Vertical rectus muscle surgery for nystagmus patients with vertical abnormal head posture,

Yang

MB,Archer

et al, J AAPOS, 2004,Aug ; 8 (4), 299-309Slide15

SOURCE-

The effect of bilateral horizontal rectus recession on visual acuity, ocular deviation or head posture in patients with nystagmus,

BagheriA

,

Farahi

A,

Yazdani

,

J AAPOS, 2005, Oct, 9(5), 433-7Slide16

RECESS- RESECT PROCEDURES1953, Anderson and

Kestenbaum

independantly

suggested them. Anderson had mentioned about recession of horizontal

rectii

,While

Gotto

had suggested resection,

Kestenbaum

came with idea of operating all the 4 muscles (5mm)

Parks modified it (5,6,7,8) & Calhoun-Harley -Nelson ‘Augmented’ it.

The surgery not only

shifts the eye to null position

to correct AHP but also improves

nystagmus

waveforms

and

broaden the null zone

Anderson JR. Causes and treatment of congenital eccentric nystagmus. Br J

Ophthalmol

1953;37: 267-80.

Kestenbaum

A. Nouvelle opération du nystagmus. Bull Soc

Ophthamol

Fr 1954

Parks MM. Congenital nystagmus surgery. Am

Orthopt

J 1973;23: 35-9

Slide17

FIG 1. Comparison of preoperative (A) and 3 months postoperative (B)

electronystagmogram

showing shift of null position from 30° right gaze

preoperatively to primary position after augmented Anderson procedure

FIG 1

-Prospective Clinical Evaluation of Augmented Anderson Procedure for Idiopathic Infantile Nystagmus ,

Pradeep

Sharma,

Vimala

Menon

,

JAAPOS,Aug

2006, 10 (4), 312-317

FIG 2

- Improvement in Visual Acuity Following Surgery for Correction of Head Posture in Infantile Nystagmus Syndrome

Vijayalaxmi

, A Kumar, J POS, Nov 2011,48 (6), 341-346Slide18

HEAD POSTURE CORRECTION SURGERIESSurgery

Indication

What is

done ?

Kestenbaum

Head

turn

Bilateral 5mm recess-

resect

of hor.

recti

Augmented Anderson’s

Head Turn

Yolk muscle

recess ( MR-9, LR-12 )

Classic

Parks

Head turn

upto

30 deg

5,6,7,8

Rule

Aug

Kestenbaum

/

Classic Plus

(Calhoun-Harley)

Head turn above 30 deg

Necessary

augmentaions

of 40 % and 60 % required ( for 40 and 45 deg

resp

)

Vert

Kestenbaum

/

Parks

Chin elevation/depression

Bilateral recess-

resect

of SR & IR

Torsional

Kesten

Nyst

with Head tilt

SO & IO surgeries

Decker’s

Same

as above

Vertical transposition of horizontal

recti

Spielmann’s

Same as above

Surgical slanting

of insertion of all 4

recti

Von

Noorden’s

Same

as above

Horizontal transposition of Vertical

rectiSlide19

PHARMACOTHERAPY Slide20

Pharmacology in NystagmusName of the drug

Mode of action

Preferred

drug of choice

Gabapentin

&

Baclofen

GABA

receptor

agonists

Acquired

pendular

nystagmus

Memantine

NMDA receptor

antagonist

Congenital

Idiopathic Nystagmus

4-Aminopyridines

K+ channel blocker

Vertical upbeat-

downbeat nystagmus

Clonazepam

Benzodiazapine

/ GABA a receptor agonist

Carbamazepine

Na+

channel blocker

Sup Oblique

Myokimia

Sodium

valproate

Na+ channel blocker & GABA

agonists

Pendular

nystagmus

Acetozolamide

&

Brinzolamiode

Carbonic

anhydrase

inhibitor

Infantile

Nystamus

Benztropine

&

Trihexphenydyl

Anti-Cholinergic

Oculopalatal

tremor

Propranolol

B-

Blocker

OpsoclonusSlide21

NEWER- WIDELY PRACTICED TREATMENT OPTIONSSlide22

BACLOFENUseful in- Acquired

Pendular

Nystagmus ( esp. post

fossa

tumors and Post MS)

Recommended dosage schedule

- 5 -10 mg TDS

Visible changes noted

- reduced amplitude of horizontal

pendular nystagmus ( 70 % times ), subjective improvement of

oscillopsia

( 45 % times ) and visual acuity improvement ( 35 % times )

Side effects

- Drowsiness(63%),dizziness (15%), Nausea (12%)

Effects of

baclofen

on upbeat and downbeat

nystagmus,M

Dietrich, A

Straube

et al, J of Neurology, neurosurgery and Psychiatry, 1991 ;54 :627-32Slide23

CASE REPORT

26 yr old, male with h/o horizontal

diplopia

and dizziness since 2 weeks

Confirmed to have right INO with upbeat nystagmus

MRI -

Hyperintense

area in right midbrain

tegmentum

and anterior

cerbellar

vermis

s/o of inflammatory plaque

EEG and evoked potentials were normal

Introduced on 5mg TDS dose of

baclofen

Decrease in nystagmus intensity in primary , right , left , up and down gaze

was noticed.Slide24

GABAPENTINUseful in- Acquired

Pendular

–Jerk

Nystagmus

(esp. Post MS, Post ocular pathology) and CIN

Recommended dosage schedule

- 300 – 800 mg TDS

Visible changes noted

- reduced amplitude of horizontal

pendular

nystagmus ( 95 % times ), subjective improvement of

oscillopsia

( 60 % times ) and visual acuity improvement ( 35 % times )

Side effects

- Fatigue, dizziness, emotional and behavioral problems in children

The effects of

gabapentin

and

memantine

in acquired and congenital nystagmus : a retrospective study, T

Shery

, I

Gottlob

, Br J O, 2006 ; 90: 839-843

Gabapentin

but not

vigabatrin

is effective in acquired nystagmus in multiple sclerosis, F

Bandini

, E

Castello

et al, Journal of Neurology Neurosurgery Psychiatry, 2001; 71 : 107-11Slide25

CASE REPORT

60 yr old, male , K/C/O Multiple sclerosis

Presented with elliptical

pendular

nystagmus

BCVA -OD 6/24, OS 6/60.

Patient put on oral

gabapentin

. Started on 300 mg TDS and since the patient

was able to tolerate with inadequate response the dosage was further

increased to 800 mg TDS.

BCVA improved in OD to 6/12 OS to 6/18.

Nystagmus amplitude also showed 50 % improvement.

Now almost 6 years he is still on

gabapentin

with good tolerance and

consistent response.

After

Gabapentin

Before

Gabapentin

RIGHT EYE

LEFT EYE

Source

- The effects of

gabapentin

and

memantine

in acquired and congenital nystagmus : a retrospective study, T

Shery

, I

Gottlob

, Br J O, 2006 ; 90: 839-843Slide26

NEWER- FUTURE TRENDSSlide27

MEMANTINEUseful in- Congenital idiopathic nystagmus, Acquired

pendular

Nystagmus ( even those refractory to

gabapentin

)

Recommended dosage schedule

- 10 -20 mg BD

Visible changes noted

- reduced amplitude of horizontal

pendular

nystagmus ( 70 % times ), subjective improvement of

oscillopsia

( 45 % times ) and visual acuity improvement ( 35 % times )

Side effects

- Dizziness(7%), headache (6%), confusion (6%), constipation(5%)

The effects of

gabapentin

and

memantine

in acquired and congenital nystagmus : a retrospective study, T

Shery

, I

Gottlob

, Br J O, 2006 ; 90: 839-843Slide28

Memantine dosage schedule (Source- Dept of Ophthalmology, Leicester Royal Infirmary ,England)Slide29

CASE REPORT

65 yr old, male with c/o

oscillopsia

, ataxia, hyper-

reflexia

of right

extremities

MRI showed plaques

CSF confirmed the same

Diagnosed with MS

Started on

gabapentin

300 and then 800 TDS with poor response

Patient was shifted to

memantine

10 mg TDS and showed a spontaneous

improvement in nystagmus intensity.

RIGHT EYE

LEFT EYE

Gabapentin

Memantine

AFTER TREATMENT

BEFORE TREATMENT

Source

- The effects of

gabapentin

and

memantine

in acquired and congenital nystagmus : a retrospective study, T

Shery

, I

Gottlob

, Br J O, 2006 ; 90: 839-843Slide30

4- AMINOPYRIDINESA latest study by Strupp

et al established the role of 4-Aminopyridines and 3,4-diaminopyridines in

Upbeat nystagmus

secondary to any lesion between pathway from vestibular to

oculomotor

nuclei

Reduction in

oscillopsia

and

improvement in upward smooth pursuit

movement during attempted fixation in daylight ( abolished in darkness !)

Dosage

used was- 10 mg OD with no documented side

efffects

Probable

mode of action

is via increased excitability of

cerebellar

purkinje

cells from K+ channel blockade

4-aminopyridine restores visual ocular motor function in upbeat nystagmus ,

S Glasauer, M Strupp et al, Jour.

Neurol

Neurosurg

Psychiatry 2005;76:451–453

.Slide31

Electronic methods Device uses infrared sensor guided measurement of eye movements and feeding the same to a phase locked loop

/

adaptive filters

which generates an electric signal which in turn

rotate the riley prisms synchronous

with the nystagmus and through which the person views the world.

In future we might have specs which uses this miniature principle to cancel out the visual effects of pathological nystagmus.

Application of adaptive filters to visual testing and treatment in acquired

pendular

nystagmus, Ryan M. Smith, John S. Stahl, Journal of Rehabilitation, Research &

Development,Vol

41,June 2004, 313-324

Prospects for Treating Acquired

Pendular

Nystagmus with Servo-Controlled Optics, John Stahl et al, Invest

Ophthal

Vis

Sci

, 2000, Apr, 41(5), 1084-90Slide32

Prototype electronic device

Infrared device

Prism assembly

Acuity cardSlide33

T & R (Tenotomy & Resuturing)

Principle

- Operating on the tendon where the

Proprioceptive

feedback loop

for ocular-motor control is located.

Method

- Surgically detach the muscles from the globe and suture them back to their original insertions without resection or recession

Holds lots of promise for CIN where AHP is not an issue

There are group of people who don’t believe in and find it contentious

Improves

NAFX (

eXpanded

Nystagmus

Acuity Function)

- an indicator of target

foveation

, fastens target acquisition time and also reduce

oscillopsia

.

.

Dell'Osso

LF,

Hertle

RW, Williams RW, Jacobs JB. A new surgery for congenital nystagmus: effects of

tenotomy

on an

achiasmatic

canine and the role of

extraocular

proprioception

. J AAPOS 1999;3: 166-82

Hertle

RW,

Dell’Osso

LF,

FitzGibbon

EJ, Yang D, Mellow SD. Horizontal rectus muscle

tenotomy

in patients with infantile nystagmus syndrome: a pilot study. J AAPOS. 2004;8:539-548Slide34

Source- Effects of tenotomy on patients with infantile nystagmus syndrome, Wang, Dell Osso et al, JAAPOS,2006,10: 552-560Slide35

Simple Augmented Tendon Suture ( ATS) No

tenotomy

is required.

3 cross sword sutures with 6-0

vicryl

are placed in the tendon towards the

myotendinous

junction,not

suturing the globe

Probable mode of action- ischemia, irritation and scarring which

would act through the

proprioceptive

loop. It causes relaxation of the

resting muscle /steady state

innervation

and puts it on lower portion of

length- tension curve.

Two hypothetical Nystagmus procedures : Augmented

Tenotomy

and Reattachment and Augmented tendon suture ( Sans

Tenotomy

), Dell’

Osso

, J

Pediatr

Ophthalmol

Strabismus, 2009;46:337-344Slide36

Split Tendon, ATS method

As the name suggests you need to do a tendon split along the length and then pass the sutures on either side taking care of the vascular arcades.

No concrete evidence has yet been established about this procedure

Its efficacy needs to be established and is just a hypothesis in current scenario

Two hypothetical Nystagmus procedures : Augmented

Tenotomy

and Reattachment and Augmented tendon suture ( Sans

Tenotomy

), Dell’

Osso

, J

Pediatr

Ophthalmol

Strabismus, 2009;46:337-344Slide37

GENETICS IN NYSTAGMUSSlide38

GENE THERAPYApplicable in SENSORY DEFICIT NYSTAGMUS secondary to retinal pathologiesApplied to the retina to correct genetic deficits that impair vision directly and may facilitate the development of nystagmus

E.g

- RPE65 gene deficiency in

Leber’s

Congenital

Amaurosis

Achromatopsia

Moorefields

hosp performed

recombinant adenovirus vector

guided delivery of missing gene

in 3 patients

Maguire, A. M.,

Simonelli

, F et al. (2008). Safety and efficacy of gene transfer for

Leber's

congenital

amaurosis

The New England journal of medicine, 358(21), 2240–2248.

Bainbridge, J. W. B., Smith et al. (2008). Effect of gene therapy on visual function in

Leber's

congenital

amaurosis

The New England journal of medicine, 358(21), 2231–2239Slide39

GENETIC ANALYSIS & COUNSELLINGIndividual cases- History taking and thorough documentation of family tree will help us know the

mode of transmission, associated conditions

and

penetrance

.

Helpful in CIN- FRMD7 gene mutation, if documented then its known to have better vision, lesser AHP issue and better prognosis

Genetic analysis provides

scope for research

, which might turn a milestone for gene therapy in future

Phenotypical

characteristics of idiopathic infantile nystagmus with and without mutations in FRMD7,

Gottlob

I,

Shery

et al, Brain (2008), 131, 1259-1267Slide40

SOCIAL ISSUESNeed extra help at schoolPositioning

:

Front benches

of classroom to match AHP which will improve visual acuity, teachers need to adopt

bold writing

, high

contrast boards

Extra-curricular activities-

Avoid sports requiring fine vision i.e., ball games. Instead swimming can be preferred

Carrier guidance

- Prefer visually less demanding professions

Personality development workshops

Helpline / Networking

-

In India we don’t have any helpline like NN (Nystagmus Network) in Europe

http://www.nystagmusnet.org

/

In US they have the ANN ( American Nystagmus Network)

http://nystagmus.org/

The main intent of these sites/ networks is to improve the quality of life for all persons and families affected by nystagmus, through organized community support, education and public awarenessSlide41

Thank You