This lecture is based on postgraduate ophthalmic students (DO. DCO. MS. FCPS Neuro-ophthalmology (Myotonic dystrophy. CPOE. Neurofibromatosis

3. Myotonic dystrophy
Myotonic dystrophy is characterized by delayed muscular relaxation after
cessation of voluntary effort (myotonia).
There are two forms: the classic form, dystrophia myotonica 1 (DM1), proximal
muscle myopathy (DM2)
DM2 has fewer systemic features (although cataract is frequent), and a better
long-term prognosis, but is less common.
Inheritance in both forms is AD; sporadic cases are rare.

4. Systemic features
Symptoms typically first occur in the third–sixth decades with weakness of the
hands and difficulty in walking.
Peripheral: Difficulty in releasing grip, muscle wasting and weakness.
Central. Mournful facial expression caused by bilateral facial wasting with hollow
cheeks (myotonic facies),
slurred speech from involvement of the tongue and pharyngeal muscles.

5. Systemic features
frontal baldness in males,
somnolence,
hypogonadism,
endocrine abnormalities,
cardiomyopathy,
pulmonary disease,
intellectual deterioration and bone changes.

6. Characteristic cataracts may develop with myotonic
dystrophy and may be an early and prominent feature in
90% of patients. In a sharply limited zone of the cortex
underneath the capsule both anteriorly and posteriorly,
fine dust-like opacities appear interspersed with tiny
iridescent spots. The polychromatic dots and flakes in the
superficial cortex resemble a ‘Christmas tree’ in
appearance. The cataract may remain stationary or
progress. As the opacities mature a characteristic stellate
opacity appears at the posterior pole. The operative
prognosis is good. (Parsons’ 259)
Stellate posterior subcapsular
cataract in myotonic dystrophy

7. Ophthalmic features
Ptosis and hypermetropia are also extremely common.
Uncommon. Motility dysfunction (strabismus, nystagmus, abnormal saccades and
smooth pursuit),
light–near dissociation, iris vascular tufts, mild pigmentary retinopathy, optic
atrophy and hypotony.

8. Investigation
Genetic testing will confirm the defect, and can be performed
prenatally.

9. Treatment
Genetic counselling,
cardiac monitoring and
symptomatic treatment such as cataract surgery, eyelid crutches and frontalis
suspension.
Patients should be warned of a substantially increased risk of anaesthetic
complications.

11. • Chronic progressive external ophthalmoplegia (CPEO), also known as progressive
external ophthalmoplegia (PEO), is a disorder characterized by slowly progressive
paralysis of the extraocular muscles. Patients usually experience bilateral,
symmetrical, progressive ptosis, followed by ophthalmoparesis months to years
later. Ciliary and iris muscles are not
• The ocular features may occur in isolation
• or in association with Kearns–Sayre syndrome or oculopharyngeal dystrophy.

12. Ptosis , usually the first sign, is bilateral and may be asymmetrical. Surgical
correction may improve a compensatory head posture but does not restore normal
lid movement and risks corneal exposure.
Pupils are usually not involved.

13. Severe bilateral ptosis with
defective up gaze;
defective downgaze;
defective left gaze; defective right gaze

14. External ophthalmoplegia begins in young adulthood and is typically
symmetrical.
It is characterized by a progressive course without remission or
exacerbation. Initially up gaze is involved; subsequently lateral gaze is
affected so that the eyes may become virtually fixed.
Because of this symmetrical loss of eye movement, diplopia is rare
although reading may be a problem due to inadequate convergence.

15. Investigations. Electromyography shows myotonic and myopathic potentials;
serum creatine kinase is elevated.
Treatment involves exercise and prevention of contractures. A minority of patients
with diplopia may benefit from surgery.

16. Kearns–Sayre is a mitochondrial myopathy associated with mitochondrial DNA
deletions.
Presentation is in the first and second decades with an insidious progressive
external ophthalmoplegia.
It is usually sporadic, though inheritance can occur. No proven treatment is
currently available

17. The classic triad is
 CPEO,
 cardiac conduction abnormalities and
 pigmentary retinopathy,
 the latter typically in a ‘salt and pepper’ appearance that
is most striking at the macula (Fig. left);
 mild visual impairment and
 nyctalopia may occur.
 Less common is typical retinitis pigmentosa, or
 choroidal atrophy similar to choroideremia
Fundus changes in Kearns–Sayre
syndrome. ‘Salt and pepper’
pigmentary retinopathy;

18. Genetic testing.
Lumbar puncture: elevation of CSF protein.
Electrocardiography demonstrates cardiac conduction defects and should be
performed periodically; pacemaker implantation may be required.
Histology of extraocular muscles shows ‘ragged red fibers' due to intramuscular
accumulation of abnormal mitochondria.
Endocrine screening is important

19. • Phakomatoses (also referred to as neurocutaneous syndromes) are a group of
genetic and acquired disorders that derive their collective name from the Greek
noun phakos ("lentil, spot") and the Greek word terminations -oma (signifying a
tumor or neoplasm) and -osis (signifying a process, especially a disease or
abnormal process).
• Phakomatoses are characterized by variable multisystem involvement. Typically,
they affect the central nervous system (CNS), the eyes, and the skin, all of which
derive from the same ectodermal origin

20. Following diseases are the group of Phakomatoses:
a) Neurofibromatosis (NF)
b) tuberous sclerosis,
c) von Hippel–Lindau disease, and
d) Sturge–Weber syndrome.
This heterogeneous group of diseases has been alternatively defined as
Phakomatoses

21. Neurofibromatosis is a disorder that primarily affects cell growth in neural tissues.
The two main forms are neurofibromatosis
type I (NF1) and
type II (NF2).
• Both may show segmental involvement in which the features are confined to one
or more body segments.

22. NF1 (von Recklinghausen disease) is the most common phacomatosis, affecting
1 : 4000 individuals.
Inheritance is AD with irregular penetrance and variable expressivity, though
about 50% have new mutations;
the gene is NF1 on chromosome 17, the normal function of which is tumour
suppression.

23. The presence of
optic nerve glioma and
Lisch nodules (iris hamartomas) are important ophthalmic diagnostic signs;
genetic testing has around 95% specificity
a few positive individuals will not develop NF1

24. Lisch nodules are melanocytic hamartomas of the iris, often associated with
neurofibromatosis (NF) I. They are usually elevated and tan in appearance. Their
incidence in NF1 increases with age and their prevalence raises by about 10% per
year of life, up to age 9

25. Neurofibromas may develop anywhere along the course of peripheral or autonomic
nerves or on internal organs but do not occur on purely motor nerves. They appear
as either solitary nodules (Fig. next slide) or more diffuse plexiform lesions,
sometimes with associated soft tissue overgrowth (elephantiasis nervosa – Fig. next
slide) and may also involve internal organs.

26. Systemic features of neurofibromatosis type I. (Left) Discrete cutaneous neurofibromas;
(Middle) elephantiasis nervosa; (Right) cafe-au-lait macule

27. Skin. Café-au-lait macules are light-brown patches most commonly found on the
trunk. They appear during the first year of life and increase in size and number
throughout childhood.
Axillary or inguinal freckles usually become obvious around the age of 10 years and
are pathognomonic.
Skeletal abnormalities may include short stature and facial hemiatrophy.
Intracranial tumours, primarily meningiomas and gliomas.

28. Associations include
Malignancy (especially malignant peripheral nerve sheath tumours),
gastrointestinal stromal tumours,
hypertension and
learning difficulties.
Recent research suggests that autism spectrum disorder affects nearly half of all
NF1 patients.

29. Regular eye examinations are critical from the time of diagnosis to detect lesions
such as optic nerve glioma.
Eyelid plexiform neurofibroma gives a characteristic S-shaped deformity of the
upper lid and classically is texturally reminiscent of a ‘bag of worms’.

30. Eyelid plexiform neurofibroma
gives a characteristic S-shaped
deformity of the upper lid and
classically is texturally
reminiscent of a ‘bag of worms’.
Nodular plexiform
neurofibroma of the eyelid;

31. Optic nerve glioma (15–40%), a pilocytic astrocytoma, typically occurs in
young children. It gives a fusiform enlargement of the nerve (Fig: Left) and
may present with slowly increasing painless proptosis (Fig. Right),

32. visual impairment (often marked),
optic atrophy and
strabismus.
It can be bilateral and may extend posteriorly to involve the chiasm, optic tract and
hypothalamus, sometimes with obstructive hydrocephalus. Slow growth is typical.

33.  Other orbital neural tumours, e.g.
 neurilemmoma (schwannoma),
 plexiform neurofibroma and meningioma.
 Spheno-orbital encephalocele is caused by
absence of the greater wing of the sphenoid
bone (Fig: Left), characteristically causing a
pulsating proptosis.
coronal CT image shows absence
of the greater wing of the left
sphenoid bone;

34. Bilateral Lisch nodules (at least 95%) are hamartomas that develop during the
second–third decades, seen as tiny nodular pigmented lesions protruding above the
iris surface

35. Congenital ectropion uveae
(Fig. left) is uncommon; it
Congenital ectropion uveae (Fig:
Left) is uncommon; it may be
associated with glaucoma.
Congenital ectropion uveae

36. Prominent or enlarged corneal nerves may be asymptomatic and detected
accidentally or may be associated with other local disease conditions such as
keratoconus. The corneal nerves are known to be enlarged in the:

37. Multiple endocrine neoplasia (MEN) syndrome Type IIb (combination of
medullary carcinoma of the thyroid, phaeochromocytoma, mucosal neuromas and
possibly marfanoid habitus).
Other systemic diseases associated with prominent corneal nerves include
neurofibromatosis and
Refsum syndrome.

38. Local ocular disorders with this clinical sign include
keratoconus,
keratitis (most characteristically seen in acanthamoebic keratitis),
Fuchs endothelial dystrophy,
trauma and
congenital glaucoma.

39. • Choroidal naevi may occur, NF1 patients with naevi are at increased risk of
developing choroidal melanoma
• Retinal “corkscrew” vessels are found in about a third of patients and do not leak
• Choroidal hyper-reflective nodules are multiple small flat pigmented lesions,
which are commonly seen on OCT analysis. These are found in over 80% of
patients and are highly sensitive and specific for NF1

40. Other lesions that may be more common than in unaffected individuals include
congenital hypertrophy of the RPE,
myelinated nerve fibres,
combined hamartoma of the retina and RPE (possibly increased only in NF2) and
retinal capillary haemangioma.

41. Neurofibromatosis type II (NF2) is less common than NF1;
mutations in the NF2 gene on chromosome 22 are causative.
Inheritance is autosomal dominant, but 50% are sporadic.
Various diagnostic criteria have been described,
but often include bilateral acoustic neuroma (90%)

42. Other characteristic lesions such as
juvenile cataract,
neurofibroma,
meningioma,
glioma, and
schwannoma. Ocular lesions are often the first manifestations of the disease

43. Cataract affects about two-thirds of patients. The opacities develop prior to the age
of 30 years and may be posterior subcapsular or capsular, cortical or mixed.
Fundus. Epiretinal membrane is frequent, and combined hamartoma of the retina
and retinal pigment epithelium is relatively common.
Ocular motor defects (10%).
Less common. Optic nerve sheath meningioma, optic nerve glioma, unilateral
Lisch nodules, abnormal electroretinogram.

44. SUPRANUCLEAR AND INFRANUCLEAR
PATHWAYS
Anatomical pathways, which extend from the
cortical centers of the brain to the cranial nerve
nuclei, are called the supranuclear pathways.
From the cranial nerve nuclei to the ocular muscle
exist the intranuclear pathways