Transcript newer avenues in management of nystagmus

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
Financial Disclosure
• I hereby declare that I don’t have any financial interests in any of the
products or procedures mentioned in the forthcoming presentation
Nystagmus Work-up
• History 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/subcortical causes
• Genetic analysis -FRMD7 in CIN
EYE MOVEMENT RECORDINGS
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Electo-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
Various treatment modalities available
• PRISMS
• OPTICAL METHODS
• SOMATOSENSORY / AUDITORY FEEDBACK
• ELECTRONIC METHODS
Fields in which newer
• PHARMACOTHERAPY
avenues have developed
• SURGERY
• GENE THERAPY
Clinical division of treatment options
Older
Less
practiced
Widely
practiced
Rx
Widely
practiced
Somatosensory Auditory stimuli
Optical methods , Prisms
Old drugs, Botox Inj , Stereotactic
NeuroSx and Artf.diverg.Surg
Wide recessions , AHP Surgeries
Drugs- Gabapentin , Baclofen
Drugs- Memantine, 4-Aminopyridines
Newer
Surgery- Tenotomy , Aug. Tend. Suture
Futuristic
Electronic methods
Molecular genetics / Gene therapy
OLDER- LESSER PRACTICED
TREATMENT OPTIONS
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 Sci
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).
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LimitationsDisables 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 ;44750
AUDITORY/SOMATOSENSORY STIMULI &
BIOFEEDBACK METHOD
• Suppression 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
: 2371-82
ARTIFICIAL DIVERGENCE SURGERY
• Aim - induce exophoria by bi- medial rectus recessions or recessresect 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
.
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.
OLDER – WIDELY PRACTICED
TREATMENT OPTIONS
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-NoordenHelveston (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), 299-309
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), 433-7
RECESS- RESECT PROCEDURES
• 1953, 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
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), 341-346
HEAD POSTURE CORRECTION SURGERIES
Surgery
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 Head turn above 30 deg
/ Classic Plus
(Calhoun-Harley)
Necessary augmentaions of 40 % and 60
% required ( for 40 and 45 deg resp)
Vert Kestenbaum Chin elevation/depression Bilateral recess-resect of SR & IR
/Parks
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 recti
PHARMACOTHERAPY
Pharmacology in Nystagmus
Name 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
Sodium valproate
Na+ channel blocker & GABA Pendular nystagmus
agonists
Acetozolamide &
Brinzolamiode
Carbonic anhydrase inhibitor
Infantile Nystamus
Benztropine &
Trihexphenydyl
Anti-Cholinergic
Oculopalatal tremor
Propranolol
B- Blocker
Opsoclonus
Sup Oblique Myokimia
NEWER- WIDELY PRACTICED
TREATMENT OPTIONS
BACLOFEN
• Useful 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 :627-32
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.
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GABAPENTIN
• Useful 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 : 107-11
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.
•
Source- The effects of gabapentin and memantine in acquired and congenital nystagmus : a retrospective
study, T Shery, I Gottlob, Br J O, 2006 ; 90: 839-843
Before Gabapentin
RIGHT EYE
LEFT EYE
After Gabapentin
NEWER- FUTURE TRENDS
MEMANTINE
• Useful 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: 839-843
Memantine dosage schedule
(Source- Dept of Ophthalmology, Leicester Royal Infirmary
,England)
New cases
10 mg BD for 56 days
If responds
adequately
If response is poor /
inadequate
Shift to maintenance
dosage
Increase the dosage to 20
mg BD for 56 days
10 mg OD
If responds, shift to
maintenance dose
Maintain on
10 mg BD dose
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.
•
Source- The effects of gabapentin and memantine in acquired and congenital nystagmus : a retrospective
study, T Shery, I Gottlob, Br J O, 2006 ; 90: 839-843
BEFORE TREATMENT
AFTER TREATMENT
Gabapentin
RIGHT
EYE
LEFT
EYE
Memantine
4- AMINOPYRIDINES
• A latest study by Strupp et al established the role of 4Aminopyridines 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.
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), 1084-90
Prototype electronic device
Infrared device
Prism assembly
Acuity card
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;8:539-548
Source- Effects of tenotomy on patients with infantile nystagmus syndrome, Wang, Dell Osso et
al, JAAPOS,2006,10: 552-560
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;46:337-344
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;46:337-344
GENETICS IN NYSTAGMUS
GENE THERAPY
• Applicable in SENSORY DEFICIT NYSTAGMUS secondary to
retinal pathologies
• Applied 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), 2231–2239
GENETIC ANALYSIS & COUNSELLING
• Individual 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, 1259-1267
SOCIAL ISSUES
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Need extra help at school
Positioning : 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/
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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 awareness
Thank You