Ophthalmology – Nasolacrimal Developmental Anomalies

Basics

Description

Nasolacrimal developmental anomalies are congenital abnormalities arising during formation of the lacrimal drainage system.

They may involve the:

• Lacrimal puncta
• Canaliculi
• Lacrimal sac
• Nasolacrimal duct

Examples include:

• Supernumerary lacrimal puncta
• Accessory canaliculi
• Congenital lacrimal fistula
• Canalicular or lacrimal sac diverticulum
• Agenesis of puncta
• Punctal atresia
• Canalicular agenesis or atresia
• Abnormal communications within the lacrimal drainage system

Some anomalies are asymptomatic, whereas others cause:

• Epiphora
• Mucous or purulent discharge
• Recurrent dacryocystitis
• Periocular cellulitis

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Epidemiology

These abnormalities are rare.

The true incidence and prevalence are not well defined because minor anomalies may remain undiagnosed.

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Risk Factors and Associations

Congenital lacrimal drainage abnormalities may occur as isolated defects or as part of a systemic syndrome.

Reported associations include:

• Treacher Collins syndrome
• Other branchial arch syndromes
• Down syndrome
• Craniofacial clefts
• Amniotic band sequence
• Eyelid developmental abnormalities
• Other craniofacial dysmorphic syndromes

Congenital lacrimal fistula has been particularly described in association with Down syndrome.

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Genetics

The inheritance pattern usually reflects the underlying syndrome.

Isolated congenital lacrimal fistula may occasionally show:

Autosomal dominant inheritance

with variable expression.

Genetic counseling should be considered when:

• Other congenital abnormalities are present
• There is a positive family history
• A recognizable syndrome is suspected

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Embryology and Pathophysiology

The lacrimal drainage system develops from a cord of surface ectoderm located between the:

• Maxillary process
• Frontonasal process

This epithelial cord normally becomes buried and later canalizes to form the:

• Canaliculi
• Lacrimal sac
• Nasolacrimal duct

Developmental abnormalities may result from:

• Failure of normal ectodermal invagination
• Incomplete separation of the epithelial cord from the surface
• Abnormal outbudding of the epithelial cord
• Abnormal branching
• Incomplete canalization
• Failure of canalization at one or more levels

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Etiology

When isolated, the cause is often unknown.

Possible etiologies include:

• Sporadic developmental error
• Genetic syndrome
• Craniofacial dysmorphism
• Abnormal facial cleft development

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Types of Nasolacrimal Developmental Anomalies

Supernumerary Puncta

One or more additional lacrimal puncta may be present.

They may:

• Drain into the normal canalicular system
• Communicate with an accessory canaliculus
• Be completely nonfunctional

Most are asymptomatic.

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Accessory Canaliculus

An accessory canalicular channel may accompany a supernumerary punctum.

Symptoms depend on whether the channel:

• Communicates with the lacrimal sac
• Ends blindly
• Contributes to abnormal tear drainage

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Congenital Lacrimal Fistula

A lacrimal fistula is an abnormal epithelial-lined tract connecting the lacrimal drainage system to the skin.

It usually appears as a small opening:

• Inferonasal to the medial canthus
• Near the lacrimal sac region

It may communicate with the:

• Canaliculus
• Lacrimal sac
• Nasolacrimal duct

Possible symptoms include:

• Tear drainage through the skin opening
• Mucous discharge
• Recurrent infection
• Skin irritation

Some fistulae are completely asymptomatic.

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Lacrimal Diverticulum

A diverticulum is an abnormal outpouching from the:

• Canaliculus
• Lacrimal sac
• Nasolacrimal duct

It may cause:

• Local swelling
• Mucous retention
• Recurrent infection
• Intermittent discharge

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Punctal Agenesis or Atresia

One or more puncta may be:

• Completely absent
• Covered by epithelium
• Severely stenotic

This can produce:

• Chronic epiphora
• Tear overflow
• Recurrent irritation

The underlying canalicular system may also be absent or malformed.

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Canalicular Agenesis or Atresia

The canaliculus may be:

• Completely absent
• Partially developed
• Blind-ending
• Obstructed

The severity of symptoms depends on whether another patent drainage pathway exists.

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Diagnosis

Diagnosis is primarily clinical.

A complete assessment should determine:

• Whether puncta are present
• Whether the canaliculi are patent
• Whether an accessory opening or fistula exists
• Whether the lacrimal sac is enlarged or infected
• Whether the nasolacrimal system is obstructed

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History

Important history includes:

• Tearing since infancy
• Chronic or intermittent discharge
• Recurrent conjunctivitis
• Recurrent dacryocystitis
• Swelling near the medial canthus
• Discharge from an abnormal skin opening
• Previous probing or lacrimal surgery
• Associated congenital anomalies
• Family history of lacrimal abnormalities
• Known genetic syndrome

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Physical Examination

A full ophthalmic examination should include careful inspection of the:

• Upper punctum
• Lower punctum
• Lacrimal papillae
• Medial canthus
• Lacrimal sac area

Look for:

• Absent punctum
• Accessory punctum
• Fistulous opening
• Swelling
• Erythema
• Mucopurulent discharge

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Lacrimal Sac Compression

Gentle pressure over the lacrimal sac may produce:

• Mucous reflux
• Purulent reflux
• Discharge through a punctum
• Discharge through a congenital fistula

This suggests retained material within the lacrimal drainage system.

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Systemic Examination

Assess for:

• Facial asymmetry
• Craniofacial clefts
• Eyelid abnormalities
• Ear abnormalities
• Mandibular hypoplasia
• Other dysmorphic features

These findings may suggest an underlying syndrome.

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Diagnostic Testing

Laboratory Testing

Routine laboratory investigations are not required in uncomplicated developmental anomalies.

If infection is suspected, consider:

• Conjunctival or lacrimal discharge culture
• CBC in a systemically unwell patient
• Blood cultures if severe systemic infection is suspected

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Fluorescein Dye Disappearance Test

This is a simple test of lacrimal drainage.

A drop of fluorescein is placed into the lower conjunctival fornix.

The amount remaining after approximately 5 minutes is assessed.

Delayed clearance suggests:

• Impaired lacrimal drainage
• Partial or complete obstruction

The test is particularly useful in children.

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Probing and Irrigation

Probing and irrigation can serve both:

• Diagnostic
• Therapeutic

purposes.

It is particularly useful when at least one punctum is patent.

It may help determine:

• Level of obstruction
• Presence of canalicular continuity
• Communication with a fistula
• Patency of the nasolacrimal duct

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Imaging

Imaging is usually unnecessary.

Rarely, investigations may include:

• Dacryocystography
• CT
• MRI

when there is:

• Complex craniofacial anatomy
• Uncertain fistulous tract
• Recurrent infection
• Prior surgery
• Suspected mass or unusual structural abnormality

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Differential Diagnosis

Important differential diagnoses include:

• Congenital nasolacrimal duct obstruction
• Dacryocele
• Lacrimal sac mucocele
• Acquired punctal stenosis
• Canalicular obstruction
• Acute dacryocystitis
• Congenital glaucoma

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Important Differential: Congenital Glaucoma

A tearing infant should not automatically be assumed to have nasolacrimal obstruction.

Congenital glaucoma may also cause:

• Epiphora
• Photophobia
• Blepharospasm
• Corneal enlargement
• Corneal haze

These features require urgent ophthalmic evaluation.

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Treatment

Treatment depends on:

• Type of anomaly
• Degree of obstruction
• Presence of infection
• Severity of symptoms
• Associated syndromic abnormalities

Asymptomatic patients may require no treatment.

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Medical Treatment

There is no medication that corrects the developmental abnormality itself.

If infection is present, treatment may include:

• Systemic antibiotics
• Topical antibiotics as an adjunct in selected cases

Antibiotic choice should reflect:

• Severity
• Age
• Local microbiology
• Culture results when available

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Probing and Irrigation

When a patent punctum is present, probing and irrigation are often the first interventional steps.

They may:

• Establish anatomy
• Relieve obstruction
• Confirm communication with a fistulous tract

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Punctoplasty

Punctoplasty may be considered when:

• A punctum is present but stenotic
• There is a membranous covering
• Tear drainage is impaired

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Excision of Fistula or Diverticulum

Symptomatic congenital fistulae or diverticula may be treated surgically.

Options include:

• Complete excision
• Excision with tract closure
• Cauterization in selected cases

Complete tract identification is important to reduce recurrence.

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Dacryocystorhinostomy

Dacryocystorhinostomy (DCR) may be required when there is significant distal drainage obstruction involving the lacrimal sac or nasolacrimal duct.

It may be performed:

• With intubation
• Without intubation

depending on anatomy and age.

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When Observation Is Appropriate

If the anomaly causes:

• Minimal tearing
• No infection
• No significant discharge
• No functional or cosmetic concern

treatment may be entirely elective.

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Referral

Consider referral to:

• Oculoplastic/lacrimal specialist for complex anatomy or surgery
• Pediatric ophthalmologist in children
• Medical genetics for syndromic features
• Craniofacial team if facial clefting or major dysmorphism is present

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In-Patient Considerations

Hospital admission is generally unnecessary.

Admission may be required if the patient develops:

• Severe dacryocystitis
• Preseptal cellulitis
• Orbital cellulitis
• Systemic illness
• Sepsis

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Dacryocystitis

An obstructed but proximally patent lacrimal drainage system can predispose to infection.

Symptoms include:

• Painful swelling over the lacrimal sac
• Erythema
• Tenderness
• Purulent discharge
• Fever in severe cases

This requires prompt treatment.

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Cellulitis

Infection may spread into surrounding tissues and cause:

• Preseptal cellulitis
• Rarely orbital involvement

Young children require especially careful observation because infection may progress rapidly.

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Ongoing Care

Follow-Up

Follow-up depends on:

• Symptoms
• Type of anomaly
• Previous surgery
• Infection history

Patients who are asymptomatic may only require periodic observation.

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Patient Monitoring

Monitor for:

• Increasing epiphora
• New discharge
• Medial canthal swelling
• Recurrent conjunctivitis
• Dacryocystitis
• Cellulitis

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Patient and Family Education

Families should be advised to seek medical attention if there is:

• Increasing redness near the medial canthus
• Painful swelling
• Purulent discharge
• Fever
• Rapid progression of eyelid swelling

They should also understand that many congenital lacrimal anomalies are benign and have an excellent outcome when treatment is required.

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Prognosis

The prognosis is generally excellent.

Most patients either:

• Remain asymptomatic
• Respond well to surgical correction
• Have good long-term lacrimal drainage after appropriate management

Outcome depends on the degree of associated canalicular and nasolacrimal malformation.

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Complications

The main complications are:

• Dacryocystitis
• Preseptal cellulitis
• Chronic epiphora
• Recurrent mucopurulent discharge
• Recurrent conjunctivitis
• Cosmetic concerns
• Rare recurrence after fistula surgery

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Ophthalmology Pearls

• Nasolacrimal developmental anomalies include absent or accessory puncta, canalicular abnormalities, fistulae, and diverticula.
• Congenital lacrimal fistula may occur as an isolated defect or as part of a craniofacial syndrome.
• Always inspect both upper and lower puncta carefully in a child with unexplained epiphora.
• A small skin opening near the medial canthus may represent a congenital lacrimal fistula.
• Fluorescein dye disappearance testing is a simple way to assess lacrimal drainage, especially in children.
• Probing and irrigation can be both diagnostic and therapeutic when a patent punctum is present.
• If symptoms are minimal and there is no infection, treatment may be elective or unnecessary.
• A blocked but partially patent lacrimal system can predispose to dacryocystitis and cellulitis.
• In any infant with tearing, remember to exclude congenital glaucoma, particularly if photophobia, blepharospasm, corneal haze, or an enlarged cornea is present.

Ophthalmology – Nanophthalmos

Basics

Description

Nanophthalmos is a rare congenital developmental disorder in which the eye is globally small but otherwise relatively well formed.

Typical features include:

• Short axial length, often approximately 14.5–20 mm
• Marked hyperopia
• Shallow anterior chamber
• Crowded anterior segment
• Thick sclera
• Normal-sized or relatively large lens
• Increased lens-to-eye volume ratio
• Crowded optic disc with apparent disc elevation or pseudopapilledema
• Increased risk of angle-closure glaucoma
• Increased risk of uveal effusion and exudative retinal detachment

Unlike many forms of microphthalmia, nanophthalmos generally lacks major congenital structural malformations such as coloboma.

Epidemiology

Nanophthalmos is uncommon.

Men and women are affected approximately equally.

Risk Factors

Nanophthalmos is congenital, so there is no acquired environmental risk factor.

The major clinical risk relates to the anatomy of the small eye, particularly:

• Short axial length
• Shallow anterior chamber
• Crowded angle
• Thick sclera

These predispose to glaucoma and uveal effusion.

Genetics

Most cases are sporadic.

Familial disease can occur with:

• Autosomal dominant inheritance
• Autosomal recessive inheritance

Reported genes and loci include:

• MFRP – associated particularly with autosomal recessive nanophthalmos
• Autosomal dominant loci historically described on chromosome 11

Genetic heterogeneity is substantial.

Pathophysiology

Nanophthalmos is thought to result from abnormal or arrested ocular growth after closure of the embryonic fissure.

The eye remains disproportionately small.

Important anatomic consequences include:

• Reduced axial length
• Thickened sclera
• High lens-to-globe volume ratio
• Shallow anterior chamber
• Narrow or occludable drainage angle

Thick Sclera

The sclera is characteristically:

• Thick
• Abnormally rigid
• Histologically disorganized

This may impair normal transscleral fluid movement and vortex vein drainage.

As a result, nanophthalmic eyes are predisposed to:

• Choroidal congestion
• Choroidal detachment
• Uveal effusion
• Serous retinal detachment

Lens–Eye Disproportion

Although the globe is small, the lens is usually normal in size or relatively thick.

Therefore, the lens occupies a disproportionately large portion of the eye.

This pushes the:

• Iris
• Lens
• Iris-lens diaphragm

forward, producing a shallow anterior chamber and increasing the risk of:

Angle-closure glaucoma

Commonly Associated Ocular Conditions

Nanophthalmos may be associated with:

• High hyperopia
• Angle-closure glaucoma
• Optic disc crowding
• Optic nerve head drusen
• Retinal folds
• Macular folds
• Yellow macular pigmentation
• Macular hypoplasia
• Pigmentary retinal changes
• Retinal dystrophy
• Retinitis pigmentosa-like changes
• Acquired retinoschisis
• Uveal effusion
• Exudative retinal detachment

Systemic Associations

Most patients have isolated ocular disease.

Rare reported associations include:

• Cryptorchidism
• Hallermann–Streiff syndrome

Systemic findings should prompt consideration of a syndromic form rather than isolated nanophthalmos.

Diagnosis

Diagnosis is based on the combination of:

• Short axial length
• High hyperopia
• Shallow anterior chamber
• Thick sclera
• Crowded anterior and posterior segments

History

Typical history may include:

• Thick hyperopic spectacle lenses since childhood
• Longstanding high hyperopia
• Reduced vision from amblyopia
• Family history of glaucoma
• Intermittent headaches or ocular discomfort from angle closure
• Sudden blurred vision from acute angle closure or uveal effusion

Refractive Error

Marked hyperopia is typical.

Historical ranges include approximately:

+7 to +20 D

although severity varies.

Rare patients may be:

• Emmetropic
• Mildly myopic

because increased corneal or lenticular refractive power can partially offset the short axial length.

Amblyopia

Children with severe uncorrected hyperopia are at risk of:

• Bilateral ametropic amblyopia
• Anisometropic amblyopia
• Strabismic amblyopia

Early optical correction is therefore essential.

Slit-Lamp Examination

Typical findings include:

• Shallow anterior chamber
• Forward-positioned iris-lens diaphragm
• Crowded anterior segment
• Usually normal corneal diameter

The cornea is often near normal in size, which helps distinguish nanophthalmos from some other microphthalmic conditions.

Gonioscopy

Gonioscopy commonly demonstrates:

• Narrow angles
• Occludable angles
• Peripheral anterior synechiae in more advanced disease

Angle configuration should be reassessed periodically.

Intraocular Pressure

IOP may be:

• Normal
• Intermittently elevated
• Chronically elevated

Patients are at substantial lifetime risk of angle-closure glaucoma.

Fundus Examination

Typical posterior segment findings include:

• Crowded optic nerve head
• Apparent disc swelling or pseudopapilledema
• Optic disc drusen in some patients
• Macular folds
• Pigmentary retinal abnormalities
• Choroidal thickening
• Uveal effusion in complicated cases

Pseudopapilledema

A crowded optic disc in a very short eye can appear elevated.

This should be distinguished from true papilledema.

Helpful clues include:

• Small crowded disc
• Absence of other signs of true optic nerve edema
• Possible optic disc drusen
• Stable appearance over time

Diagnostic Testing

A-Scan Ultrasonography

A-scan is useful for measuring:

• Axial length

A short axial length strongly supports the diagnosis.

B-Scan Ultrasonography

B-scan can evaluate:

• Thickened sclerochoroidal wall
• Choroidal detachment
• Uveal effusion
• Serous retinal detachment
• Optic nerve head drusen in some cases

Ultrasound Biomicroscopy

UBM may help assess:

• Anterior chamber depth
• Ciliary body configuration
• Iris-lens relationship
• Angle crowding

This is particularly useful when mechanism of angle closure is uncertain.

OCT

Optical coherence tomography can demonstrate:

• Macular folds
• Retinoschisis
• Subretinal fluid
• Retinal architecture
• Optic nerve head crowding

Orbital MRI

MRI is usually unnecessary for straightforward nanophthalmos.

It may occasionally be useful in complex cases to evaluate:

• Globe size
• Choroidal thickening
• Choroidal detachment
• Associated orbital abnormalities

Pathology

Histologic abnormalities may include:

• Markedly thick sclera
• Abnormal collagen arrangement
• Altered extracellular matrix
• Reduced glycosaminoglycan content
• Increased fibronectin

These abnormalities contribute to poor scleral permeability.

Differential Diagnosis

Important differential diagnoses include:

• Microphthalmia
• Anterior segment microphthalmos
• Posterior microphthalmos
• High hyperopia without nanophthalmos
• Phthisis bulbi

Nanophthalmos vs Microphthalmia

Nanophthalmos

Usually:

• Globally small eye
• No major developmental structural defect
• Short axial length
• High hyperopia
• Thick sclera
• Shallow anterior chamber
• High angle-closure risk

Microphthalmia

May have:

• Small globe
• Coloboma
• Cataract
• Persistent fetal vasculature
• Retinal dysplasia
• Other congenital malformations

Nanophthalmos vs Posterior Microphthalmos

Posterior microphthalmos primarily affects the posterior segment.

Typical features include:

• Short axial length
• Relatively normal anterior chamber depth
• Less anterior segment crowding
• Papillomacular retinal fold
• High hyperopia

Nanophthalmos involves both anterior and posterior segments and has a much greater tendency toward:

• Angle closure
• Uveal effusion

Treatment

There is no treatment that increases the congenital axial length.

Management focuses on:

• Correcting refractive error
• Preventing amblyopia
• Detecting angle closure early
• Treating glaucoma
• Managing uveal effusion
• Minimizing surgical complications

Refractive Correction

Children should receive early correction of:

• Hyperopia
• Astigmatism
• Anisometropia

Options include:

• Spectacles
• Contact lenses

Early optical correction is essential to prevent amblyopia.

Amblyopia Treatment

If amblyopia develops, treatment may include:

• Full refractive correction
• Patching
• Penalization

depending on age and visual asymmetry.

Narrow Angles

Patients with narrow or occludable angles require close monitoring.

Management may include:

• Gonioscopy
• IOP monitoring
• Optic nerve assessment
• Consideration of laser peripheral iridotomy when pupillary block is an important component

Because nanophthalmic eyes are anatomically unusual, treatment should be individualized by an experienced glaucoma specialist.

Laser Peripheral Iridotomy

Laser peripheral iridotomy may help relieve a component of:

Pupillary-block angle closure

However, angle crowding may persist because of:

• Large lens relative to globe size
• Anterior ciliary body configuration
• Plateau-like anatomy

Therefore, iridotomy does not always fully open the angle.

Iridoplasty

If significant angle closure persists after a patent iridotomy and there is no major choroidal effusion, laser peripheral iridoplasty may occasionally be considered.

Glaucoma Medical Therapy

If IOP remains elevated, treatment may include standard pressure-lowering medications.

Miotics such as pilocarpine are generally used cautiously or avoided because they may:

• Relax zonules
• Allow further forward movement of the lens
• Worsen anterior chamber crowding

Lens Extraction

Lens extraction may deepen the anterior chamber and reduce angle crowding in selected patients.

However, surgery in nanophthalmos is technically difficult and carries increased risk of:

• Uveal effusion
• Choroidal detachment
• Suprachoroidal hemorrhage
• Malignant glaucoma
• Exudative retinal detachment

Therefore, intraocular surgery should be undertaken only when clearly indicated and with careful perioperative planning.

Cataract Surgery

Cataract surgery is particularly challenging because of:

• Very short axial length
• Shallow anterior chamber
• High-power IOL requirement
• Crowded anterior segment
• Increased postoperative complication risk

Accurate biometry is essential.

Modern IOL calculations should use formulas optimized for very short eyes when available.

Glaucoma Surgery

If glaucoma remains uncontrolled despite:

• Laser treatment
• Maximum tolerated medical therapy

surgery may be required.

Options include:

• Trabeculectomy
• Glaucoma drainage procedures
• Lens extraction in selected cases

Because postoperative hypotony can trigger major posterior segment complications, surgery should be performed cautiously.

Uveal Effusion

Uveal effusion may occur:

• Spontaneously
• After laser procedures
• After intraocular surgery

Possible manifestations include:

• Choroidal detachment
• Serous retinal detachment
• Vision loss

Treatment of Uveal Effusion

Management depends on severity.

Options may include:

• Observation in mild cases
• Systemic or local corticosteroids in selected inflammatory or postoperative settings
• Surgical scleral windows/sclerotomies
• Vortex vein decompression in selected severe cases

The goal of surgery is to improve transscleral drainage and reduce choroidal congestion.

Scleral Surgery

Surgical approaches may include:

• Partial-thickness sclerectomy
• Full-thickness sclerotomy
• Posterior scleral windows

These procedures are particularly useful in severe recurrent uveal effusion related to thickened sclera.

Surgical Risk

Nanophthalmic eyes are among the highest-risk eyes for intraocular surgery.

Potential perioperative complications include:

• Uveal effusion
• Choroidal detachment
• Suprachoroidal hemorrhage
• Exudative retinal detachment
• Malignant glaucoma
• Severe postoperative shallowing of the anterior chamber

Preoperative recognition of nanophthalmos is therefore critical.

Malignant Glaucoma

Nanophthalmos predisposes to aqueous misdirection, historically called malignant glaucoma.

Features include:

• Very shallow or flat anterior chamber
• Elevated IOP
• Forward displacement of the lens-iris diaphragm
• Patent peripheral iridotomy

This is an ophthalmic emergency requiring specialist management.

Issues for Referral

Referral may be required to:

• Glaucoma specialist for narrow angles or glaucoma
• Retina specialist for uveal effusion or retinal detachment
• Cataract/anterior segment surgeon for complex lens surgery
• Pediatric ophthalmologist for childhood hyperopia and amblyopia
• Medical genetics when familial disease is suspected

Ongoing Care

Follow-Up

All patients require regular ophthalmic monitoring.

Follow-up should assess:

• Visual acuity
• Refraction
• Anterior chamber depth
• Gonioscopy
• IOP
• Optic nerve
• Macula
• Signs of choroidal or retinal effusion

Patients with narrow angles or glaucoma risk may require review approximately every 3–6 months, depending on anatomy and clinical findings.

Childhood Monitoring

In children, priorities include:

• Early refractive correction
• Amblyopia prevention
• Strabismus monitoring
• Visual development

Adult Monitoring

With increasing age, patients require particular surveillance for:

• Progressive angle narrowing
• Peripheral anterior synechiae
• Glaucoma
• Cataract
• Uveal effusion

Risk becomes particularly important in middle and later adulthood.

Patient Education

Patients should understand that:

• Their eyes are anatomically smaller than normal
• High hyperopia is expected
• Angle-closure glaucoma can develop
• Intraocular surgery carries increased risk
• Sudden visual symptoms require urgent evaluation

Warning symptoms include:

• Severe ocular pain
• Headache
• Halos
• Sudden blurred vision
• Red eye
• Nausea or vomiting
• Sudden loss of vision

Prognosis

Visual prognosis can be good when:

• Refractive error is corrected early
• Amblyopia is prevented
• Glaucoma does not develop
• Uveal effusion does not occur

Prognosis becomes more guarded in patients with:

• Uncontrolled glaucoma
• Recurrent uveal effusion
• Exudative retinal detachment
• Major intraoperative or postoperative complications

Complications

Major complications include:

• Angle-closure glaucoma
• Chronic peripheral anterior synechiae
• Optic neuropathy
• Amblyopia
• Uveal effusion
• Choroidal detachment
• Exudative retinal detachment
• Malignant glaucoma
• Cataract
• Surgical complications

Ophthalmology Pearls

• Nanophthalmos = small but structurally formed eye + short axial length + high hyperopia + thick sclera + shallow anterior chamber.
• A major clue is the disproportionately large lens relative to globe size.
• The two major vision-threatening problems are angle-closure glaucoma and uveal effusion.
• Crowded optic discs may mimic papilledema, producing pseudopapilledema.
• Thick sclera interferes with normal transscleral fluid drainage and predisposes to choroidal and uveal effusion.
• Laser peripheral iridotomy may relieve pupillary block but may not completely resolve angle crowding.
• Miotics can worsen anterior segment crowding and should be used cautiously.
• Intraocular surgery carries unusually high risk of uveal effusion, malignant glaucoma, and exudative retinal detachment.
• Children need early hyperopic correction to prevent amblyopia.
• Always distinguish nanophthalmos from microphthalmia and posterior microphthalmos, because their anatomy and complications differ.

Ophthalmology – Myotonic Dystrophy

Basics

Description

Myotonic dystrophy is an inherited multisystem disorder characterized by:

• Myotonia
• Progressive muscle weakness
• Cataract formation
• Cardiac conduction disease
• Respiratory dysfunction
• Endocrine abnormalities
• Gastrointestinal dysmotility
• Variable cognitive and behavioral manifestations

It is the most common muscular dystrophy of adulthood.

Two major forms are recognized:

Type 1 – DM1

Also called Steinert disease.

Features include:

• Approximately 98% of classic cases
• Onset from childhood to adulthood
• Distal and facial weakness are common
• Can occur in a severe congenital form
• More prominent multisystem involvement

Type 2 – DM2

Also called proximal myotonic myopathy.

Features include:

• Usually milder than DM1
• Typically adult onset
• More proximal muscle weakness
• Muscle pain is relatively common
• Congenital form is not typical

Epidemiology

Myotonic dystrophy affects men and women equally.

Typical age ranges include:

• DM1: childhood to approximately 40 years
• DM2: approximately 20–60 years

Prevalence varies considerably by population and geographic region.

A commonly cited overall prevalence is approximately:

1 in 8,000

although modern estimates vary.

Genetics

Myotonic dystrophy is inherited in an:

Autosomal dominant pattern

Both forms are caused by unstable nucleotide-repeat expansions.

DM1 Genetics

DM1 results from expansion of a:

CTG trinucleotide repeat

in the:

DMPK gene on chromosome 19

The number of repeats often increases between generations.

DM2 Genetics

DM2 results from expansion of a:

CCTG tetranucleotide repeat

in the:

CNBP gene on chromosome 3

This gene was historically called ZNF9.

Anticipation

Myotonic dystrophy demonstrates anticipation, particularly DM1.

This means:

• Symptoms may appear earlier in successive generations
• Disease severity may increase
• Repeat expansion tends to enlarge during transmission

Severe congenital DM1 is particularly associated with maternal transmission.

General Prevention

The disease itself cannot currently be prevented, but reproductive counseling may include:

• Genetic counseling
• Prenatal diagnosis
• Preimplantation genetic testing

Pathophysiology

The expanded nucleotide repeats are transcribed into abnormal RNA.

These abnormal RNA molecules:

• Accumulate within the nucleus
• Bind RNA-splicing proteins
• Disrupt normal messenger RNA processing
• Cause widespread abnormalities in multiple tissues

Important affected pathways include:

• Skeletal muscle chloride channels
• Insulin receptors
• Cardiac conduction proteins
• Troponin pathways

This explains the multisystem nature of the disorder.

Mechanism of Myotonia

Abnormal splicing of skeletal muscle chloride-channel RNA reduces normal chloride conductance.

This produces:

Delayed muscle relaxation after contraction

which is the hallmark of myotonia.

Ophthalmic Features

The most important ocular abnormalities include:

• Cataract
• Ptosis
• Orbicularis weakness
• Delayed eyelid opening after forceful closure
• Slow saccades
• Progressive external ophthalmoplegia
• Low intraocular pressure
• Pigmentary retinal abnormalities

Cataract

Cataract is the most common ocular manifestation.

The classic early finding is the:

Christmas tree cataract

characterized by:

• Multicolored
• Iridescent
• Crystalline
• Polychromatic lens opacities

They may appear:

• Red
• Green
• Blue
• Gold

under slit-lamp illumination.

Later Cataract Changes

As disease progresses, patients may develop:

• Stellate posterior cortical cataract
• Posterior subcapsular opacity
• More generalized visually significant cataract

Cataract may eventually become a major cause of visual impairment.

Eyelid Findings

Ptosis

Ptosis occurs because of weakness of:

• Levator palpebrae
• Facial musculature

Ptosis may be bilateral and progressive.

Orbicularis Weakness

Orbicularis oculi weakness may cause:

• Incomplete forceful eyelid closure
• Exposure symptoms
• Reduced blink strength

Eyelid Myotonia

After forceful eyelid closure, patients may have:

Delayed reopening of the eyes

because of myotonia of the orbicularis muscle.

Ocular Motility

Patients may develop:

• Slow saccades
• Mild external ophthalmoplegia
• Reduced ductions

Despite motility abnormalities:

Diplopia is often surprisingly uncommon

because weakness progresses slowly and is frequently symmetric.

Intraocular Pressure

Low intraocular pressure has been reported.

This generally does not cause symptoms but may reflect reduced ciliary body or ocular muscle function.

Retinal Findings

A pigmentary retinopathy may occur.

Possible findings include:

• RPE mottling
• Peripheral pigmentary change
• Retinal degeneration resembling mitochondrial retinopathy in some cases

The retinal findings are usually less clinically important than cataract and systemic disease.

History

Important symptoms include:

• Delayed relaxation after gripping
• Difficulty releasing a handshake
• Muscle stiffness
• Progressive muscle weakness
• Dysphagia
• Dysarthria
• Muscle pain, particularly in DM2
• Daytime somnolence
• Disturbed sleep
• Hypoventilation
• Constipation
• Abdominal discomfort
• Urinary or fecal incontinence
• Infertility
• Palpitations
• Syncope
• Blackouts
• Cognitive or behavioral changes

Women may also have:

• Pregnancy complications
• Difficult labor
• Increased obstetric risk

Physical Examination

Characteristic findings include:

• Myotonia
• Facial muscle weakness
• Temporal wasting
• Masseter wasting
• Frontal balding
• Long, thin facial appearance
• Slack mouth
• Neck flexor weakness
• Limb-muscle wasting

The characteristic facial appearance has historically been described as a:

“Hatchet face.”

Handshake Myotonia

When the patient grips the examiner’s hand firmly, they may have difficulty releasing it promptly.

This is a classic demonstration of:

Grip myotonia

Percussion Myotonia

Tapping certain muscles may cause:

• Sustained contraction
• Delayed relaxation

This can be demonstrated over muscles such as:

• Thenar eminence
• Tongue

Bulbar and Speech Findings

Patients may develop:

• Nasal speech
• Monotonous voice
• Dysarthria
• Dysphagia

Bulbar dysfunction increases aspiration risk.

Respiratory Findings

Respiratory involvement may include:

• Hypoventilation
• Sleep-disordered breathing
• Respiratory muscle weakness
• Excessive daytime sleepiness

Respiratory complications are an important cause of morbidity.

Cardiac Findings

Cardiac manifestations are particularly important because they can cause sudden death.

Possible abnormalities include:

• Sinus bradycardia
• AV block
• Bundle branch block
• Atrial arrhythmias
• Ventricular arrhythmias
• Cardiomyopathy

Patients may report:

• Palpitations
• Syncope
• Presyncope

Endocrine Findings

Possible endocrine abnormalities include:

• Insulin resistance
• Diabetes mellitus
• Testicular atrophy
• Infertility
• Thyroid dysfunction

Gastrointestinal Findings

Patients may experience:

• Dysphagia
• Constipation
• Abdominal pain
• Gastrointestinal dysmotility

Diagnostic Testing

Molecular Genetic Testing

The gold standard is molecular confirmation of the repeat expansion.

Testing includes:

• DMPK CTG expansion testing for DM1
• CNBP CCTG expansion testing for DM2

This usually confirms the diagnosis without the need for muscle biopsy.

Electromyography

EMG may demonstrate:

Myotonic discharges

often described acoustically as a waxing-and-waning “dive-bomber” pattern.

EMG can support the diagnosis when the phenotype is uncertain.

Laboratory Testing

Possible abnormalities include:

• Mildly elevated creatine kinase
• Insulin resistance
• Glucose intolerance

Immunoglobulin studies may occasionally show:

• Reduced IgG
• Reduced IgM

These findings are not diagnostic.

Brain MRI

MRI may demonstrate:

• Bilateral white-matter hyperintensities
• Frontal predominance
• Temporal or insular predominance

These abnormalities are more relevant in patients with cognitive or neurologic symptoms.

Slit-Lamp Examination

Slit-lamp examination is important because the characteristic:

Christmas tree cataract

may be highly suggestive of myotonic dystrophy, particularly in a young adult.

Electrocardiography

ECG may show:

• Prolonged PR interval
• Widened QRS complex
• AV conduction delay
• Intraventricular conduction abnormalities

Because conduction disease may be asymptomatic, regular cardiac surveillance is essential.

Additional Cardiac Testing

Depending on symptoms and disease severity, monitoring may include:

• Holter monitoring
• Event monitor
• Echocardiography
• Electrophysiologic studies

Pulmonary Testing

Assessment may include:

• Forced vital capacity
• Sleep study
• Overnight oximetry
• Blood gas testing in selected patients

These help detect respiratory muscle weakness and nocturnal hypoventilation.

Swallowing Assessment

Formal swallowing evaluation may be needed in patients with:

• Choking
• Aspiration
• Recurrent chest infections
• Dysphagia

Muscle Biopsy

Muscle biopsy is rarely needed now because genetic testing is definitive.

Histologic findings may include:

• Central nuclei
• Fiber-size variability
• Disruption of myofibrils
• Sarcoplasmic abnormalities
• Mitochondrial changes

Differential Diagnosis

Important differential diagnoses include:

• Other muscular dystrophies
• Other myotonic disorders
• Myotonia congenita
• Paramyotonia congenita
• Mitochondrial disease
• Chronic progressive external ophthalmoplegia
• Polymyositis
• Stiff-person syndrome
• Mild tetanus

Treatment

There is currently no curative treatment that reverses the genetic defect.

Management is:

• Multidisciplinary
• Preventive
• Supportive
• Directed at organ-specific complications

Muscle Weakness

Management may include:

• Regular low-to-moderate intensity exercise
• Physical therapy
• Occupational therapy
• Ankle-foot orthoses for foot drop

Excessive fatigue should be avoided.

Myotonia

Myotonia does not always require treatment.

When clinically troublesome, selected medications may be used by neurology.

Treatment depends on:

• Functional limitation
• Cardiac status
• Drug tolerance

Daytime Sleepiness

Management may include:

• Evaluation for sleep-disordered breathing
• Noninvasive ventilation
• CPAP or BiPAP when indicated
• Wake-promoting medications in selected patients

Modafinil may be considered in selected individuals.

Respiratory Support

Patients with nocturnal hypoventilation may benefit from:

• Noninvasive positive-pressure ventilation
• BiPAP

Respiratory status should be monitored longitudinally.

Cardiac Treatment

Conduction disease may require:

• Pacemaker
• Implantable cardioverter-defibrillator in selected patients

Cardiology follow-up is essential.

Cataract Surgery

Visually significant cataracts can be treated with:

Cataract extraction and intraocular lens implantation

Visual prognosis is generally good if there is no significant retinal or optic nerve disease.

Ptosis Surgery

Ptosis repair may be considered when ptosis:

• Obstructs the visual axis
• Causes significant functional impairment

However, surgery should be performed cautiously because:

• Orbicularis weakness may impair eyelid closure
• Overcorrection can cause lagophthalmos
• Exposure keratopathy may result

Ophthalmic Follow-Up

Regular ophthalmic examinations should monitor for:

• Cataract progression
• Visual acuity changes
• Ptosis
• Exposure keratopathy
• Ocular motility abnormalities
• Retinal changes

Multidisciplinary Follow-Up

Patients may require ongoing care from:

• Ophthalmology
• Neurology
• Cardiology
• Pulmonology
• Physical therapy
• Endocrinology
• Gastroenterology
• Genetics
• Sleep medicine

Genetic Counseling

Genetic counseling is important because inheritance is:

Autosomal dominant

Each affected individual generally has a 50% chance of transmitting the mutation to each child.

Anticipation should be discussed, particularly in DM1.

Anesthesia Considerations

Patients with myotonic dystrophy have an increased risk of complications during general anesthesia.

Potential problems include:

• Respiratory depression
• Aspiration
• Cardiac arrhythmias
• Prolonged ventilatory failure
• Abnormal sensitivity to sedatives and neuromuscular medications

The anesthesia team should always be informed of the diagnosis before surgery.

Prognosis

DM1

DM1 may significantly reduce life expectancy, particularly when there is:

• Severe cardiac disease
• Respiratory failure
• Congenital disease

DM2

DM2 is generally milder, and life expectancy is often near normal.

Complications

Major complications include:

• Cataract
• Ptosis
• Exposure keratopathy
• Progressive muscle weakness
• Respiratory insufficiency
• Aspiration
• Sleep-disordered breathing
• Cardiac conduction block
• Arrhythmia
• Sudden cardiac death
• Diabetes and insulin resistance
• Infertility
• Gastrointestinal dysmotility
• Increased perioperative and anesthesia risk

Ophthalmology Pearls

• Christmas tree cataract is the classic ocular finding of myotonic dystrophy.
• It consists of multicolored, iridescent crystalline lens opacities.
• Bilateral early cataract in a young adult should prompt consideration of a systemic neuromuscular disorder.
• Delayed eyelid opening after forceful closure is due to orbicularis myotonia.
• Ptosis results from progressive levator weakness.
• Ocular motility may be reduced, but diplopia is often uncommon because the ophthalmoplegia is slow and relatively symmetric.
• Ptosis surgery requires caution because orbicularis weakness can lead to exposure keratopathy.
• The most dangerous systemic manifestations are cardiac conduction abnormalities and respiratory failure.
• Genetic testing for DMPK in DM1 or CNBP in DM2 confirms the diagnosis.
• Any patient undergoing ocular surgery requires careful preoperative assessment because myotonic dystrophy carries a significant anesthetic and cardiopulmonary risk.

Ophthalmology – Myopic Degeneration

Basics

Description

Myopic degeneration, also called pathologic myopia or degenerative myopia, refers to progressive structural changes of the posterior segment associated with excessive axial elongation.

It can cause mild to profound central visual loss through:

• Macular atrophy
• Chorioretinal degeneration
• Lacquer cracks
• Macular hemorrhage
• Myopic choroidal neovascularization (CNV)
• Posterior staphyloma
• Myopic traction maculopathy
• Retinal detachment

Unlike ordinary refractive myopia, pathologic myopia involves progressive degenerative changes of the sclera, choroid, RPE, Bruch membrane, and retina.

Classification of Myopia

Myopia has historically been divided into:

• Simple myopia
• Congenital myopia
• Degenerative/pathologic myopia

Simple and congenital myopia do not necessarily develop the characteristic posterior degenerative changes of pathologic myopia.

Epidemiology

Myopia commonly begins during:

• Childhood
• School years
• Adolescence

In patients who develop pathologic myopia, refractive error and axial length may continue increasing well beyond adolescence.

Degenerative macular changes can begin in:

• Young adulthood
• Middle age

and may progress throughout life.

Prevalence

The prevalence of myopia varies greatly according to:

• Age
• Ethnicity
• Geographic region
• Educational exposure
• Environmental factors

Pathologic myopia is considerably less common than simple myopia but represents an important cause of irreversible visual impairment worldwide.

Risk Factors

Major risk factors include:

• High axial myopia
• Long axial length
• Progressive myopia
• Posterior staphyloma
• Increasing age
• Existing lacquer cracks
• Patchy chorioretinal atrophy
• Previous myopic CNV in the fellow eye

Genetics

Myopia is genetically complex and generally multifactorial.

Both genetic and environmental factors contribute.

Pathologic myopia does not usually follow a simple single-gene inheritance pattern, although familial clustering is common and rare monogenic forms exist.

Pathophysiology

The fundamental process is progressive axial elongation of the globe, particularly at the posterior pole.

This produces mechanical stretching and thinning of multiple ocular layers.

Scleral Changes

The posterior sclera may become:

• Thin
• Ectatic
• Structurally weakened

Progressive posterior bulging can produce:

Posterior staphyloma

which is a hallmark of pathologic myopia.

Choroidal Changes

The choroid becomes markedly thinned.

Changes include:

• Attenuation of the choriocapillaris
• Reduction of choroidal melanocytes
• Increased visibility of large choroidal vessels
• Progressive choroidal atrophy

RPE Changes

The retinal pigment epithelium becomes:

• Stretched
• Thinned
• Irregular
• Atrophic

Loss of RPE and choroidal pigmentation contributes to the classic tessellated or tigroid fundus.

Bruch Membrane Changes

Bruch membrane may undergo:

• Thinning
• Splitting
• Mechanical rupture

Linear ruptures are known as:

Lacquer cracks

These are important because they indicate severe biomechanical stress and are associated with an increased risk of myopic CNV.

Etiology

The exact cause of the degenerative process is multifactorial.

A major mechanism is thought to be:

Progressive biomechanical stretching from excessive axial elongation

leading to thinning and disruption of:

• Sclera
• Choroid
• RPE
• Bruch membrane
• Retina

Commonly Associated Conditions

High myopia may also occur in association with:

• Prematurity
• Retinopathy of prematurity
• Connective-tissue disorders
• Certain inherited retinal disorders

Premature infants may develop substantial myopia even without retinopathy of prematurity.

Diagnosis

Diagnosis is based on:

• Refractive status
• Axial length
• Characteristic fundus changes
• Multimodal imaging

History

Patients may have:

• Longstanding high myopia
• Progressive refractive change
• Gradual reduction in central vision

A patient with high myopia who develops:

• Sudden visual loss
• New metamorphopsia
• New central scotoma

should be evaluated urgently for myopic CNV or macular hemorrhage.

Ophthalmic Features

Posterior Staphyloma

A posterior staphyloma is a localized outpouching of the posterior ocular wall.

It can contribute to:

• Progressive macular distortion
• Chorioretinal atrophy
• Myopic traction maculopathy
• Macular hole
• Retinal detachment

Optic Disc Changes

Typical findings include:

• Tilted optic disc
• Oval configuration
• Peripapillary atrophy
• Temporal myopic crescent
• Disc torsion

Glaucoma evaluation can be difficult in highly myopic eyes because of altered optic-disc anatomy.

Tessellated Fundus

Thinning of the RPE and choroid makes the underlying large choroidal vessels more visible.

This produces the classic:

Tessellated or tigroid fundus

appearance.

Chorioretinal Atrophy

Progressive atrophy can appear as sharply demarcated pale areas.

It may begin as:

• Diffuse chorioretinal atrophy
• Patchy atrophy

Over time, lesions may:

• Enlarge
• Coalesce
• Involve the fovea

Foveal atrophy can cause severe irreversible central visual loss.

Lacquer Cracks

Lacquer cracks are:

Linear breaks in Bruch membrane caused by mechanical stretching.

They appear as:

• Fine yellow-white lines
• Irregular linear lesions
• Occasionally stellate lesions

They are important markers of advanced pathologic myopia.

Macular Hemorrhage

Hemorrhage may occur when a lacquer crack develops.

A hemorrhage can occur:

• Without CNV
• After relatively minor trauma
• Spontaneously

Therefore, not every macular hemorrhage in a highly myopic eye represents CNV.

Choroidal Neovascularization

Myopic CNV is one of the most important vision-threatening complications.

Clinical findings may include:

• Subretinal hemorrhage
• Gray or dark subretinal lesion
• Subretinal fluid
• Intraretinal fluid
• RPE elevation
• Sudden metamorphopsia
• Central scotoma

Fuchs Spot

After myopic CNV regresses, it may leave a pigmented fibrotic macular scar known historically as a:

Fuchs spot

This can produce permanent central visual impairment.

Myopic Maculopathy

Modern descriptions of pathologic myopia often classify macular disease according to increasing severity of:

• Tessellation
• Diffuse chorioretinal atrophy
• Patchy atrophy
• Macular atrophy

Additional “plus” lesions include:

• Lacquer cracks
• Myopic CNV
• Fuchs spot

Myopic Traction Maculopathy

Highly myopic eyes are also prone to tractional complications, including:

• Epiretinal membrane
• Vitreomacular traction
• Foveoschisis
• Retinoschisis
• Foveal detachment
• Lamellar macular hole
• Full-thickness macular hole
• Macular hole retinal detachment

These complications are particularly common in eyes with posterior staphyloma.

Peripheral Retinal Changes

High myopia is associated with increased risk of:

• Lattice degeneration
• Retinal tears
• Peripheral retinal thinning
• Rhegmatogenous retinal detachment

A careful peripheral retinal examination is therefore important.

Diagnostic Testing

Optical Coherence Tomography

OCT is essential in evaluating pathologic myopia.

It can detect:

• Myopic CNV
• Subretinal fluid
• Intraretinal fluid
• Foveoschisis
• Retinoschisis
• Macular hole
• Tractional changes
• Atrophy
• Epiretinal membranes

Serial OCT is extremely useful for treatment monitoring.

Fluorescein Angiography

Fluorescein angiography can help distinguish:

• Myopic CNV
• Simple macular hemorrhage from lacquer crack
• Areas of chorioretinal atrophy

Active CNV typically demonstrates leakage.

OCT Angiography

OCT angiography can noninvasively demonstrate abnormal neovascular networks and may be useful for:

• Detecting CNV
• Monitoring vascular activity
• Follow-up after treatment

It should be interpreted alongside structural OCT and the clinical examination.

Fundus Photography

Useful for documenting:

• Atrophy
• Lacquer cracks
• Hemorrhage
• Pigmentation
• Progressive macular changes

Axial Length Measurement

Biometry may help document:

• Excessive axial length
• Progression of axial elongation

Differential Diagnosis

Conditions that may mimic or coexist with myopic macular changes include:

• Age-related macular degeneration
• Central serous chorioretinopathy
• Inflammatory CNV
• Ocular histoplasmosis-related CNV
• Angioid streaks
• Macular dystrophy
• Traumatic choroidal rupture

Treatment

There is no treatment that reverses the underlying structural elongation once pathologic changes are established.

Management is directed toward:

• Refractive correction
• Treatment of CNV
• Management of tractional complications
• Retinal detachment treatment
• Low-vision rehabilitation

Refractive Correction

Options include:

• Spectacles
• Contact lenses

Contact lenses can provide improved optical quality in very high myopia because they reduce:

• Image minification
• Peripheral distortion

Myopic CNV Treatment

Anti-VEGF Therapy

Intravitreal anti-VEGF therapy is the current first-line treatment for myopic CNV.

Agents may include:

• Ranibizumab
• Aflibercept
• Bevacizumab

Treatment often requires fewer injections than neovascular age-related macular degeneration, although follow-up remains essential.

Historical Treatments for CNV

Older approaches included:

• Thermal laser photocoagulation
• Photodynamic therapy

These are now much less commonly used because anti-VEGF therapy generally provides better outcomes with less collateral retinal damage.

Laser treatment is particularly problematic near the fovea because scars may enlarge over time in highly myopic eyes.

Myopic Traction Maculopathy Treatment

Surgery may be considered for progressive or visually significant:

• Foveoschisis
• Macular hole
• Foveal detachment
• Vitreomacular traction
• Macular hole retinal detachment

Options may include:

• Pars plana vitrectomy
• Internal limiting membrane techniques
• Gas tamponade
• Macular buckle in selected complex cases

Management should be individualized by a vitreoretinal specialist.

Retinal Detachment

Retinal detachment may require:

• Pars plana vitrectomy
• Scleral buckle
• Pneumatic retinopexy in selected cases
• Combined procedures

Highly myopic eyes may present additional surgical challenges because of:

• Thin sclera
• Posterior staphyloma
• Long axial length
• Macular hole-associated detachment

Low-Vision Support

Patients with irreversible macular damage may benefit from:

• Magnification devices
• Electronic visual aids
• High-contrast reading material
• Lighting optimization
• Low-vision rehabilitation

Follow-Up

Patients with pathologic myopia require regular ophthalmic surveillance.

Follow-up should assess:

• Visual acuity
• Refraction
• Macula
• Optic disc
• Peripheral retina
• CNV activity
• Progressive atrophy
• Tractional macular changes

Patient Education

Patients at risk of CNV should monitor each eye separately.

They should seek prompt review for:

• New metamorphopsia
• New central blur
• New central scotoma
• Sudden reduction in vision

An Amsler grid can be used for home monitoring.

Retinal Detachment Education

Patients should also be educated about symptoms of retinal tear or detachment:

• Sudden increase in floaters
• Flashing lights
• Curtain or shadow in the visual field
• Sudden peripheral field loss

These symptoms require urgent ophthalmic assessment.

Prognosis

Visual prognosis depends on:

• Degree of posterior staphyloma
• Extent of macular atrophy
• Development of CNV
• Tractional macular disease
• Retinal detachment

Patients with progressive staphyloma and increasing macular atrophy have a guarded long-term prognosis.

The risk of vision loss generally increases with age.

Complications

Major complications include:

• Myopic CNV
• Macular hemorrhage
• Fuchs spot
• Chorioretinal atrophy
• Macular atrophy
• Myopic foveoschisis
• Macular hole
• Macular hole retinal detachment
• Rhegmatogenous retinal detachment
• Epiretinal membrane
• Glaucoma
• Progressive irreversible central visual loss

Ophthalmology Pearls

• Pathologic myopia is more than refractive error—it is a structural degenerative disease of the posterior eye.
• Progressive axial elongation causes thinning of the sclera, choroid, RPE, Bruch membrane, and retina.
• Posterior staphyloma is a hallmark of advanced disease.
• Lacquer cracks are breaks in Bruch membrane and increase the risk of myopic CNV.
• Sudden metamorphopsia or central vision loss in a highly myopic patient should raise immediate concern for CNV.
• A macular hemorrhage in high myopia can occur from a lacquer crack without CNV.
• Anti-VEGF therapy is first-line treatment for myopic CNV.
• OCT is essential for detecting both neovascular and tractional complications.
• High myopia increases the risk of retinal tears and retinal detachment, so the peripheral retina must also be examined carefully.
• Long-term surveillance is important because macular atrophy and other degenerative changes may continue to progress throughout life.

Ophthalmology – Myelinated Nerve Fibers

Basics

Description

Myelinated retinal nerve fibers, also called medullated nerve fibers, are congenital areas of abnormal myelination of the retinal nerve fiber layer.

They appear ophthalmoscopically as:

• White, opaque, striated patches
• Usually adjacent to the superior or inferior margins of the optic disc
• Lesions with feathery or frayed borders that follow the orientation of normal retinal nerve fibers
• Partial obscuration of retinal vessels passing beneath the myelinated layer

Occasionally:

• Islands or slits of normal retina are visible within the lesion
• The myelination is discontinuous from the optic disc
• Rare acquired cases have been described after infancy or in adulthood, with trauma reported in some of these cases

Epidemiology

Myelinated nerve fibers occur in approximately:

1% of the general population

They are usually discovered incidentally during routine fundus examination.

Genetics

Most cases are sporadic.

Rare familial cases with an autosomal dominant inheritance pattern have been reported.

Myelinated nerve fibers have also been described in association with certain syndromes, including:

• Gorlin syndrome
• Rare inherited vitreoretinal dystrophy syndromes with extensive bilateral retinal nerve fiber myelination

One reported autosomal dominant vitreoretinopathy includes:

• Extensive bilateral retinal nerve fiber myelination
• Severe myopia
• Congenitally reduced vision
• Vitreous degeneration
• Retinal dystrophy
• Night blindness
• Reduced electroretinographic responses
• Limb abnormalities

Pathophysiology

Normally, retinal ganglion cell axons become myelinated posterior to the lamina cribrosa.

Myelination is produced by oligodendrocytes.

During normal fetal development:

• Myelination progresses anteriorly from the lateral geniculate region
• It normally stops at the lamina cribrosa
• Oligodendrocytes usually do not enter the retina

In myelinated nerve fibers, oligodendrocytes extend beyond the lamina cribrosa into the retinal nerve fiber layer.

Proposed Mechanisms

Possible developmental explanations include:

• Abnormality or defect in the lamina cribrosa
• Delayed formation of the lamina cribrosa
• Relatively large scleral canal with fewer axons, permitting oligodendrocytes to migrate anteriorly
• Abnormal persistence of access for oligodendrocytes into the retina

Etiology

The condition is usually congenital.

It represents retinal ganglion cell axons that have abnormally acquired a myelin sheath anterior to the lamina cribrosa.

Rare acquired cases have been described, particularly after:

• Ocular trauma
• Other optic nerve or retinal abnormalities

Commonly Associated Conditions

Myelinated nerve fibers may be associated with:

• High myopia
• Amblyopia
• Strabismus
• Tilted disc syndrome
• Anterior segment dysgenesis
• Rare craniofacial abnormalities

A classic association is the triad of:

• Extensive unilateral myelinated retinal nerve fibers
• High myopia
• Amblyopia

Gorlin Syndrome Association

Rarely, myelinated nerve fibers have been described with Gorlin syndrome, which may include:

• Multiple basal cell carcinomas or nevi
• Jaw cysts
• Skeletal abnormalities
• Increased risk of medulloblastoma in childhood

This association is uncommon.

Neurofibromatosis Type 2

A possible association with neurofibromatosis type 2 has been reported, although this remains debated.

Diagnosis

Diagnosis is usually made clinically on fundus examination.

History

Most patients are asymptomatic.

Possible historical findings include:

• Reduced vision in one eye
• Strabismus
• High myopia
• Amblyopia
• Rare history of trauma in acquired cases

Physical Examination

A complete ophthalmic examination should include:

• Visual acuity
• Cycloplegic refraction when appropriate
• Pupillary examination
• Ocular alignment
• Dilated fundus examination

Special attention should be paid to:

• Degree of myopia
• Presence of anisometropia
• Amblyopia
• Strabismus
• Extent of myelination

Fundus Appearance

Typical findings include:

• Bright white or gray-white patches
• Striated appearance
• Feathery borders
• Distribution along the retinal nerve fiber layer
• Frequently extending from the optic disc
• Retinal vessels partially hidden by the superficial myelinated fibers

Approximately a minority of cases may show lesions that are not directly contiguous with the optic disc.

Optical Coherence Tomography

OCT can be helpful.

It may demonstrate:

• Thickened retinal nerve fiber layer
• Increased reflectivity in the region of myelination
• Shadowing of deeper retinal structures

OCT can also help evaluate associated optic nerve or macular abnormalities.

Neuroimaging

Routine neuroimaging is generally not required for isolated myelinated retinal nerve fibers.

Imaging may be considered if:

• A systemic syndrome is suspected
• Neurologic abnormalities are present
• Gorlin syndrome is suspected
• The appearance is atypical

Differential Diagnosis

Important differential diagnoses include:

• Cotton-wool spots
• Hard exudates
• Retinal gliosis
• Chorioretinal scars
• Tilted disc syndrome
• Other congenital white retinal lesions

Myelinated Nerve Fibers vs Cotton-Wool Spots

Myelinated fibers:

• Follow the nerve fiber layer
• Have feathery, striated margins
• Are usually stable over time
• Commonly arise adjacent to the optic disc

Cotton-wool spots:

• Represent retinal ischemia
• Are acquired
• Usually resolve over weeks
• Are associated with vascular or systemic disease

Treatment

There is no treatment for the myelination itself.

Management is directed toward associated visual problems.

Refractive Correction

Significant refractive error should be corrected as early as possible.

This is particularly important in children with:

• High myopia
• Anisometropia
• Astigmatism

Amblyopia Therapy

Amblyopia should be treated when present.

Treatment may include:

• Full optical correction
• Patching
• Penalization

Historically, amblyopia associated with extensive myelinated nerve fibers and high myopia was believed to respond poorly.

However, some patients can achieve meaningful improvement with appropriately timed amblyopia therapy.

Strabismus

Strabismus should be managed according to:

• Visual potential
• Angle of deviation
• Binocular function
• Cosmetic considerations

Surgery may be considered when indicated.

Referral

Referral may be appropriate to:

• Pediatric ophthalmology for amblyopia or strabismus
• Medical genetics if a syndromic association is suspected
• Dermatology if findings suggest Gorlin syndrome

Ongoing Care

Follow-Up

Follow-up is usually determined by associated problems rather than the myelinated fibers themselves.

Children should be monitored for:

• Refractive change
• Amblyopia
• Strabismus
• Visual development

Patient Education

Patients and families should understand that:

• Myelinated nerve fibers are usually benign
• The retinal appearance itself generally does not require treatment
• Vision problems are usually due to associated:
• Myopia
• Anisometropia
• Amblyopia
• Strabismus

Early treatment of amblyopia is important.

Prognosis

The retinal myelination itself is generally stable and benign.

Visual prognosis depends mainly on associated:

• High myopia
• Amblyopia
• Strabismus
• Other ocular abnormalities

Some patients with substantial myelination and severe anisometropic myopia may have limited visual potential.

Regression or Disappearance

Rarely, previously visible myelinated nerve fibers have been reported to diminish or disappear after severe damage to retinal ganglion cell axons or the optic nerve.

Reported settings include:

• Optic atrophy
• Glaucoma
• Central retinal artery occlusion
• Optic neuritis
• Compressive optic neuropathy

Loss of the white myelinated appearance in these settings reflects axonal loss rather than improvement.

Complications

Potential associated complications include:

• Amblyopia
• High myopia
• Anisometropia
• Strabismus
• Reduced visual acuity

Ophthalmology Pearls

• Myelinated retinal nerve fibers appear as white, feathery, striated patches following the retinal nerve fiber layer.
• They commonly arise adjacent to the optic disc and can partially obscure retinal vessels.
• The condition is usually congenital and benign.
• Think of the classic association: myelinated nerve fibers + high myopia + amblyopia.
• The lesion itself requires no treatment.
• In children, the priority is early detection and treatment of refractive error and amblyopia.
• OCT may show a thick, highly reflective retinal nerve fiber layer with posterior shadowing.
• Do not confuse stable congenital myelination with acquired cotton-wool spots.
• Rare disappearance of myelination can occur after severe optic nerve or retinal ganglion cell injury.

Ophthalmology – Myasthenia Gravis

Basics

Description

Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction characterized by painless, fluctuating, fatigable skeletal-muscle weakness.

The most commonly affected muscles are the extraocular and eyelid muscles, so ophthalmic manifestations are frequently the first sign of disease.

Typical manifestations include:

• Ptosis
• Diplopia
• Variable ophthalmoplegia
• Orbicularis weakness
• Bulbar weakness
• Limb weakness
• Respiratory muscle weakness in severe disease

A characteristic feature is that weakness:

• Worsens with repeated or prolonged muscle use
• Often worsens later in the day
• Improves after rest
• Can vary considerably from one examination to another

Sensation and pupillary function remain normal.

⸻

Clinical Forms

Ocular Myasthenia Gravis

In ocular MG, weakness remains limited to:

• Eyelids
• Extraocular muscles

Patients typically develop:

• Ptosis
• Diplopia
• Variable ocular misalignment

⸻

Generalized Myasthenia Gravis

Generalized disease can involve:

• Ocular muscles
• Bulbar muscles
• Facial muscles
• Neck muscles
• Limb muscles
• Respiratory muscles

Ocular manifestations often precede generalized disease.

⸻

Serologic Forms

MG can also be categorized according to circulating antibodies.

AChR-Antibody Positive MG

Antibodies are directed against the acetylcholine receptor (AChR) on the postsynaptic membrane.

This is the most common form.

MuSK-Antibody Positive MG

Antibodies are directed against muscle-specific receptor tyrosine kinase (MuSK).

These patients are more likely to have prominent:

• Bulbar weakness
• Facial weakness
• Neck weakness
• Respiratory involvement

Pure ocular presentations are uncommon.

Seronegative MG

Some patients have no detectable conventional AChR or MuSK antibodies despite a compatible clinical syndrome.

Additional antibodies such as LRP4 may be detectable in a subset.

⸻

Epidemiology

MG may occur at any age.

A broadly bimodal pattern is recognized.

Earlier-Onset Disease

Usually affects younger adults and is more common in women.

Later-Onset Disease

Usually affects older adults and has a greater male predominance.

The prevalence has increased over time, probably because of:

• Better recognition
• Improved diagnostic testing
• Greater survival

⸻

Risk Factors and Exacerbating Factors

Factors that can worsen myasthenic weakness include:

• Infection
• Fever
• Emotional or physical stress
• Heat
• Sleep deprivation
• Pregnancy
• Menstruation
• Thyroid dysfunction
• Certain medications

Patients should be reviewed carefully for drugs capable of worsening neuromuscular transmission.

⸻

Genetics

MG is not usually inherited in a simple Mendelian fashion.

However:

• Autoimmune susceptibility may cluster in families.
• Relatives of affected individuals have an increased risk of autoimmune disease and MG.
• Congenital myasthenic syndromes are distinct inherited disorders and should not be confused with autoimmune MG.

⸻

Neonatal Myasthenia

Approximately a minority of infants born to mothers with autoimmune MG may develop transient neonatal myasthenia due to transplacental passage of maternal antibodies.

Symptoms may include:

• Poor suck
• Weak cry
• Generalized hypotonia
• Respiratory weakness

The condition usually resolves as maternal antibodies disappear.

⸻

General Prevention

There is no proven method to prevent autoimmune MG.

However, exacerbations may sometimes be reduced by:

• Prompt treatment of infection
• Avoidance of medications known to impair neuromuscular transmission
• Maintaining appropriate vaccinations
• Careful perioperative planning
• Appropriate management during pregnancy

⸻

Drugs That May Worsen MG

Important medications that can exacerbate weakness include selected:

• Aminoglycoside antibiotics
• Fluoroquinolones
• Macrolides
• Magnesium
• Neuromuscular blocking agents
• Beta-blockers
• Some antiarrhythmics

Penicillamine can induce an MG-like autoimmune syndrome.

Medication risks are not absolute in every patient, but potentially aggravating agents should be used carefully.

⸻

Pathophysiology

Normal neuromuscular transmission depends on acetylcholine released from the presynaptic nerve terminal binding to acetylcholine receptors on the postsynaptic muscle membrane.

In autoimmune MG, antibodies interfere with this process.

⸻

AChR Antibodies

Anti-AChR antibodies cause:

• Functional blockade of acetylcholine receptors
• Receptor internalization and degradation
• Complement-mediated postsynaptic membrane injury

This causes simplification of the postsynaptic folds and reduces the safety margin of neuromuscular transmission.

With repetitive stimulation, transmission increasingly fails, producing fatigable weakness.

⸻

MuSK Antibodies

MuSK is important in organizing and maintaining acetylcholine receptors at the neuromuscular junction.

MuSK autoantibodies disrupt receptor clustering and neuromuscular transmission.

⸻

Thymus and Myasthenia Gravis

The thymus plays an important role, particularly in AChR-antibody positive MG.

Abnormalities include:

• Thymic lymphoid hyperplasia
• Germinal-center formation
• Thymoma

Approximately 10–15% of MG patients have a thymoma.

Conversely, a significant proportion of patients with thymoma develop MG.

⸻

Associated Conditions

MG is associated with other autoimmune disorders, particularly:

• Autoimmune thyroid disease
• Rheumatoid disease
• Systemic lupus erythematosus
• Pernicious anemia

Thyroid disease is especially relevant in patients with ocular symptoms because thyroid eye disease can mimic ocular MG.

⸻

Diagnosis

History

Typical complaints include:

• Drooping eyelid
• Intermittent diplopia
• Worsening symptoms late in the day
• Increasing symptoms after reading or prolonged visual effort
• Difficulty chewing
• Difficulty swallowing
• Nasal or weak voice
• Choking during meals
• Liquids regurgitating through the nose
• Limb weakness
• Neck weakness

Respiratory weakness can occur and represents a potentially life-threatening complication.

Sensory symptoms are not characteristic of MG.

⸻

Ophthalmic Examination

Ptosis

Ptosis may be:

• Unilateral
• Bilateral
• Asymmetric
• Alternating
• Highly variable

Fatigability may be demonstrated by asking the patient to maintain prolonged upgaze.

The eyelid may gradually descend.

⸻

Cogan Lid Twitch

After sustained downgaze, the patient rapidly returns the eyes to primary gaze.

The upper lid may:

1. Overshoot upward
2. Briefly retract
3. Then fall into ptosis

This is called Cogan’s lid twitch and supports the diagnosis of ocular MG.

⸻

Frontalis Compensation

Patients may compensate for ptosis by:

• Raising the eyebrows
• Contracting the frontalis
• Adopting a chin-up posture

⸻

Ice-Pack Test

Cooling improves neuromuscular transmission.

For ptosis:

• Ice is placed over the closed eyelid for several minutes.
• Improvement in ptosis supports MG.

An improvement of approximately 2 mm or more is generally considered strongly suggestive in the appropriate clinical context.

The test is particularly useful because it is:

• Rapid
• Noninvasive
• Inexpensive

⸻

Ocular Motility Findings

MG can mimic almost any ocular motility disorder.

Findings may include:

• Variable ophthalmoparesis
• Changing patterns of strabismus
• Horizontal diplopia
• Vertical diplopia
• Oblique diplopia
• Isolated-appearing muscle weakness
• Apparent cranial nerve palsies

A major clue is variability.

⸻

Pseudo-Internuclear Ophthalmoplegia

Medial rectus weakness can produce an apparent internuclear ophthalmoplegia-like pattern.

Unlike a true brainstem INO:

• The lesion is at the neuromuscular junction rather than the MLF.
• Other variable muscle weakness may be present.
• Ptosis frequently supports MG.
• Pupils remain normal.

⸻

Pupils

The pupils are not affected in myasthenia gravis.

Pupillary abnormalities should suggest another diagnosis.

This is an important examination pearl.

⸻

Orbicularis Oculi Weakness

The examiner may be able to open the patient’s forcibly closed eyelids relatively easily.

A peek sign may occur:

• The patient initially closes the eyes completely.
• The eyelids then slowly separate because of orbicularis weakness.

⸻

Other Examination Findings

Generalized MG may produce weakness of:

• Facial muscles
• Jaw closure
• Palatal muscles
• Tongue
• Neck flexors
• Proximal limb muscles

Deep tendon reflexes and sensation are generally preserved.

⸻

Diagnostic Tests

Acetylcholine Receptor Antibodies

Testing commonly includes:

• AChR-binding antibodies
• AChR-blocking antibodies
• AChR-modulating antibodies

Binding antibody testing is usually the initial test.

Sensitivity is substantially higher in generalized MG than in purely ocular MG.

A positive result is highly supportive of the diagnosis.

⸻

MuSK Antibodies

MuSK antibody testing is particularly useful when:

• Generalized MG is suspected
• AChR antibodies are negative
• Bulbar or respiratory weakness is prominent

MuSK-positive disease is uncommon in isolated ocular MG.

⸻

Additional Antibody Testing

In appropriate seronegative patients, additional testing may include antibodies against:

• LRP4
• Other neuromuscular-junction targets

Availability varies.

⸻

Thyroid Testing

Because autoimmune thyroid disease can coexist with MG and thyroid eye disease can mimic ocular MG, testing may include:

• TSH
• Free T4
• Thyroid antibodies when indicated

⸻

Imaging

Chest CT or MRI

Patients with confirmed MG should generally be evaluated for thymoma using imaging of the anterior mediastinum.

CT is commonly used.

⸻

Neurophysiologic Testing

Repetitive Nerve Stimulation

Repetitive nerve stimulation may demonstrate a decremental response.

It is more useful in generalized disease than isolated ocular disease.

⸻

Single-Fiber EMG

Single-fiber electromyography is highly sensitive for abnormal neuromuscular transmission.

It may be especially useful when:

• Antibody testing is negative
• Clinical suspicion remains high

It is sensitive but not completely specific for MG.

⸻

Edrophonium Testing

Historically, intravenous edrophonium (Tensilon) was used to demonstrate transient improvement of ptosis or ophthalmoplegia.

Because of:

• Bradycardia
• Syncope
• Bronchospasm
• Other cholinergic adverse effects

and the availability of safer antibody and electrophysiologic testing, it is now rarely used.

⸻

Differential Diagnosis

Ocular MG Mimics

Important differential diagnoses include:

• Thyroid eye disease
• Cranial nerve III palsy
• Cranial nerve IV palsy
• Cranial nerve VI palsy
• Internuclear ophthalmoplegia
• Chronic progressive external ophthalmoplegia
• Mitochondrial myopathy
• Myotonic dystrophy
• Fisher syndrome
• Orbital disease
• Decompensated strabismus

⸻

Generalized MG Mimics

Consider:

• Lambert–Eaton myasthenic syndrome
• Botulism
• Amyotrophic lateral sclerosis
• Motor neuropathies
• Inflammatory myopathies
• Congenital myasthenic syndromes

⸻

Myasthenia vs Lambert–Eaton Syndrome

MG typically causes:

• Ocular and bulbar weakness
• Worsening with repetitive activity
• Normal or preserved reflexes

Lambert–Eaton syndrome more commonly causes:

• Proximal limb weakness
• Autonomic symptoms
• Reduced reflexes
• Strength that may transiently improve with activity

⸻

Treatment

Treatment depends on:

• Ocular versus generalized disease
• Degree of functional impairment
• Antibody status
• Bulbar or respiratory involvement
• Presence of thymoma
• Patient age
• Associated illnesses

⸻

Medication

Acetylcholinesterase Inhibitors

Pyridostigmine

Pyridostigmine (Mestinon) is the principal symptomatic treatment.

It increases the amount of acetylcholine available at the neuromuscular junction.

It may improve:

• Ptosis
• General muscle strength
• Bulbar symptoms

Its effect on ophthalmoplegia can be less reliable.

Common cholinergic adverse effects include:

• Abdominal cramping
• Diarrhea
• Excessive salivation
• Sweating
• Lacrimation

Dose is individualized according to response and adverse effects.

⸻

Corticosteroids

Corticosteroids may be used when symptomatic treatment is inadequate.

They are particularly useful for:

• Persistent ptosis
• Ophthalmoplegia
• Generalized disease

Prednisone is commonly used.

Treatment usually requires:

• Gradual titration
• Close monitoring
• Slow tapering once disease is controlled

Higher initial doses can occasionally transiently worsen weakness, so treatment strategy should be individualized by a clinician experienced in MG.

⸻

Steroid-Sparing Immunotherapy

When prolonged immunosuppression is required, options may include:

• Azathioprine
• Mycophenolate mofetil
• Tacrolimus
• Cyclosporine
• Methotrexate in selected cases

Monitoring depends on the medication and may include:

• CBC
• Liver function
• Renal function

⸻

Biologic and Targeted Therapy

For selected generalized or refractory MG, modern therapies can include targeted immunologic agents directed against:

• B cells
• Complement
• Neonatal Fc receptor pathways

These are generally managed by neuromuscular specialists.

⸻

Ophthalmic Symptomatic Treatment

Diplopia

Temporary measures include:

• Occlusion of one eye
• Translucent tape over one spectacle lens
• Eye patch

Prisms can help when deviation becomes sufficiently stable, but MG-related ocular misalignment is often too variable for prism correction to remain effective.

⸻

Ptosis

Mechanical ptosis crutches are occasionally used but are often poorly tolerated.

Definitive eyelid surgery should generally be avoided until:

• Disease is stable
• The degree of ptosis has remained consistent
• Medical treatment has been optimized

⸻

Thymectomy

Thymoma

A thymoma generally requires surgical management, usually with:

• Thymectomy
• Additional oncologic treatment when indicated

⸻

MG Without Thymoma

Thymectomy can benefit selected patients with generalized AChR-antibody positive MG, particularly younger adults.

It can reduce:

• Disease severity
• Steroid requirements
• Exacerbations

Its role in purely ocular MG is much less established.

⸻

Myasthenic Crisis

Alert

Difficulty breathing or swallowing in a patient with MG is a medical emergency.

A myasthenic crisis is severe worsening resulting in:

• Respiratory insufficiency
• Bulbar failure
• Inability to protect the airway

Patients may require:

• Intensive care
• Respiratory monitoring
• Mechanical ventilation

⸻

Acute Immunomodulatory Treatment

For severe exacerbations or myasthenic crisis:

• Intravenous immunoglobulin (IVIG)
• Plasma exchange

can produce relatively rapid improvement.

These are also used before surgery or during severe deterioration in selected patients.

⸻

Cholinergic Crisis

Excessive acetylcholinesterase inhibitor use can rarely produce excessive cholinergic activity.

Features may include:

• Weakness
• Salivation
• Diarrhea
• Sweating
• Miosis
• Bradycardia

It should be distinguished from worsening MG.

⸻

In-Patient Considerations

Admission may be required for:

• Myasthenic crisis
• Significant dysphagia
• Respiratory weakness
• Severe infection
• Rapidly progressive generalized weakness
• Plasma exchange
• IVIG

Respiratory parameters should be monitored carefully in patients with generalized deterioration.

⸻

Anesthetic Considerations

Patients with MG may be extremely sensitive to neuromuscular blocking medications.

Anesthesiologists must be informed of the diagnosis before surgery.

Perioperative medication management requires individualized planning.

⸻

Issues for Referral

Patients with confirmed or strongly suspected MG should be managed jointly with a:

Neurologist or neuromuscular specialist

because:

• Ocular disease can generalize
• Respiratory complications can occur
• Immunosuppressive therapy requires monitoring
• Thymic evaluation may be necessary

Neuro-ophthalmology referral is useful for complex ocular presentations.

⸻

Ongoing Care

Follow-Up

Patients should be monitored for:

• Change in ptosis
• Ocular motility
• Diplopia
• Development of bulbar symptoms
• Limb weakness
• Breathing difficulty
• Medication adverse effects

Patients initially presenting with ocular disease should be asked specifically about emerging systemic symptoms.

⸻

Prognosis

The course is variable.

Many patients initially present with ocular symptoms.

When ocular MG generalizes, this most commonly occurs during the first few years after onset, especially early in the disease course.

With modern therapy:

• Most patients achieve substantial disease control.
• Permanent remission without treatment is uncommon.
• Mortality is low when respiratory crises are rapidly recognized and appropriately managed.

⸻

Complications

The most important complication is:

Myasthenic Crisis

This is a neurologic emergency characterized by severe respiratory and/or bulbar weakness.

Management may require:

• ICU admission
• Airway support
• Mechanical ventilation
• IVIG
• Plasma exchange
• Treatment of precipitating infection or other trigger

Other complications arise from:

• Aspiration
• Infection
• Long-term corticosteroid treatment
• Chronic immunosuppression
• Thymoma

⸻

Ophthalmology Pearls

• Fluctuating ptosis + variable diplopia + normal pupils = think myasthenia gravis.
• MG can imitate almost any pattern of ocular motor palsy.
• Ocular findings may change during the same examination.
• Sustained upgaze can bring out fatigable ptosis.
• Cogan lid twitch is a useful bedside clue.
• The ice-pack test is a simple, useful test for myasthenic ptosis.
• Pupils are spared—pupillary involvement points away from MG.
• Medial rectus weakness can mimic an INO, producing a pseudo-INO.
• Orbicularis weakness and the peek sign are helpful supportive findings.
• AChR antibodies are less sensitive in isolated ocular MG than in generalized MG.
• Single-fiber EMG can help when antibody studies are negative.
• Evaluate confirmed MG for thymoma.
• New dysphagia, choking, weak cough, or dyspnea may represent impending myasthenic crisis and requires urgent assessment.

Ophthalmology – Multifocal Choroiditis / Punctate Inner Choroiditis

Basics

Description

Multifocal choroiditis (MFC) and punctate inner choroiditis (PIC) are inflammatory disorders affecting the choroid and outer retina.

Multifocal choroiditis with panuveitis is characterized by:

• Multiple active choroidal or chorioretinal lesions
• Vitreitis
• Frequently anterior uveitis
• Recurrent episodes of intraocular inflammation
• Risk of choroidal neovascularization and permanent chorioretinal scarring

Punctate inner choroiditis is closely related but typically:

• Occurs in young myopic women
• Produces small inflammatory lesions predominantly in the posterior pole
• Has little or no anterior chamber inflammation or vitreitis
• Frequently causes photopsias and central/paracentral scotomas

A related severe phenotype is diffuse subretinal fibrosis (DSF), in which inflammatory lesions coalesce and produce extensive subretinal fibrosis.

Etiology

The exact cause of MFC and PIC remains unknown.

They are believed to represent immune-mediated inflammatory chorioretinal disorders.

Possible mechanisms include:

• Abnormal autoimmune response against ocular antigens
• Molecular mimicry after exposure to an infectious or viral antigen
• Genetic susceptibility combined with an environmental trigger

MFC, PIC, and diffuse subretinal fibrosis may represent different manifestations along a common inflammatory disease spectrum.

Epidemiology

Multifocal Choroiditis

Typically affects:

• Young to middle-aged adults
• Women more often than men
• Commonly patients in the third to fourth decades of life

Punctate Inner Choroiditis

Classically occurs in:

• Young women
• Frequently myopic patients
• Otherwise healthy individuals

Both disorders may be bilateral, although disease activity may be markedly asymmetric.

History

Patients with MFC are usually otherwise healthy.

Some report a preceding:

• Viral-like illness
• Upper respiratory infection
• Nonspecific systemic prodrome

Common ocular complaints include:

• Blurred or decreased vision
• Floaters
• Photopsias
• Scotomas
• Peripheral visual field loss
• Metamorphopsia
• Distorted central vision

Symptoms may develop gradually.

Although patients may notice symptoms in only one eye initially, bilateral involvement is common.

Punctate Inner Choroiditis Symptoms

Patients with PIC commonly report:

• Photopsias
• Central or paracentral scotomas
• Metamorphopsia
• Blurred central vision

Because PIC often lacks significant anterior chamber or vitreous inflammation, the eye may appear externally quiet.

Physical Examination

Multifocal Choroiditis

Typical examination findings include:

• Vitreitis in most patients
• Anterior chamber inflammation in approximately half of cases
• Multiple yellow-white choroidal or chorioretinal lesions
• Pigmented borders around older lesions
• Chorioretinal scars in healed disease

The lesions:

• Are usually approximately 50–300 μm
• May occur throughout the posterior pole and peripheral fundus
• Represent focal inflammatory involvement of the choroid and outer retina

Older lesions often become:

• Punched-out
• Atrophic
• Pigmented

Punctate Inner Choroiditis

PIC lesions are generally:

• Small
• Yellow-white
• Located at the posterior pole
• Often at the level of the inner choroid/RPE/outer retina

Unlike classic MFC:

• Vitreitis is typically absent or minimal
• Anterior uveitis is generally absent

This distinction is clinically useful.

Diffuse Subretinal Fibrosis

In severe disease, multiple inflammatory lesions may coalesce, producing:

• Broad zones of subretinal fibrosis
• Macular distortion
• Extensive photoreceptor and RPE damage
• Severe irreversible visual loss

This phenotype is referred to as diffuse subretinal fibrosis syndrome.

Diagnostic Tests & Interpretation

Laboratory Evaluation

There is no specific laboratory test that confirms MFC or PIC.

Testing is primarily directed at excluding infectious and systemic inflammatory mimickers.

Depending on history, examination, and geographic exposure, investigations may include:

• Syphilis serology
• Tuberculosis testing
• Sarcoidosis evaluation
• Toxoplasmosis testing
• Lyme disease testing when epidemiologically appropriate

Before initiating systemic immunosuppression, baseline investigations commonly include:

• Complete blood count
• Liver function tests
• Renal function tests
• Screening for latent infection according to the proposed immunomodulatory agent

Imaging

Fundus Photography

Color and red-free fundus photography are useful for:

• Baseline documentation
• Assessing lesion distribution
• Comparing active versus healed lesions
• Monitoring progression or recurrence
• Documenting scar formation

Fluorescein Angiography

Fluorescein angiography (FA) is useful for identifying:

• Clinically inapparent lesions
• Active inflammatory lesions
• Choroidal neovascularization
• Cystoid macular edema
• Vascular leakage

Active lesions

Typically demonstrate:

• Early hypofluorescence from blockage
• Progressive hyperfluorescence or staining in later phases

Inactive lesions

May demonstrate:

• Window defects from RPE atrophy
• Late staining
• Persistent hypofluorescence if choriocapillaris loss is severe

Optical Coherence Tomography

OCT is essential for evaluating the macula.

It can demonstrate:

• Disruption of the outer retinal layers
• Photoreceptor loss
• RPE changes
• Subretinal fluid
• Intraretinal fluid
• Cystoid macular edema
• Choroidal neovascular membrane
• Fibrotic scar formation

Serial OCT is extremely useful for monitoring:

• Disease activity
• Treatment response
• Development of CNV
• Resolution of macular edema

OCT in PIC

Modern spectral-domain OCT may demonstrate focal abnormalities involving:

• RPE
• Ellipsoid zone
• Outer nuclear layer
• Choroid

Active lesions may protrude through or disrupt the RPE and outer retina before evolving into atrophic scars.

Indocyanine Green Angiography

Indocyanine green angiography may demonstrate more extensive choroidal involvement than is clinically visible.

It can show:

• Multiple hypofluorescent choroidal spots
• Areas of occult inflammatory activity

It may be particularly useful when the clinical diagnosis is uncertain.

Fundus Autofluorescence

Fundus autofluorescence can assist in demonstrating:

• Active RPE stress
• Areas of RPE loss
• Subclinical lesions
• Progression of chorioretinal atrophy

Hyperautofluorescent borders may indicate active or stressed RPE, whereas established atrophy generally becomes hypoautofluorescent.

Visual Field Testing

Visual field testing may show:

• Paracentral scotomas
• Peripheral field defects
• Enlarged blind spot

Visual field defects do not always correspond directly to currently active choroidal lesions.

Follow-Up During Active Disease

During active inflammation, patients may require examination every:

1–4 weeks

depending on:

• Severity
• Macular involvement
• Degree of vitreous inflammation
• Presence of CNV
• Treatment being used

Choroidal Neovascularization

One of the most important complications of both MFC and PIC is:

Choroidal neovascularization (CNV)

It may develop:

• Beneath the macula
• Adjacent to active inflammatory lesions
• In old scars
• In the peripapillary region
• Even after active inflammation has subsided

Patients should be educated to recognize:

• New metamorphopsia
• New central scotoma
• Sudden reduction in central vision

Amsler Grid

Home Amsler grid monitoring may help identify:

• New distortion
• New central scotoma
• Blurring
• Possible development of CNV

Any new change warrants prompt examination.

Differential Diagnosis

Important differential diagnoses include:

• Ocular syphilis
• Tuberculosis
• Toxoplasmosis
• Presumed ocular histoplasmosis syndrome
• Sarcoidosis
• Central serous chorioretinopathy
• Age-related macular degeneration
• Choroidal neovascularization from other causes
• Ocular trauma
• Acute posterior multifocal placoid pigment epitheliopathy
• Multiple evanescent white dot syndrome
• Birdshot chorioretinopathy
• Vogt–Koyanagi–Harada disease
• Intraocular lymphoma in atypical cases

Treatment

Treatment is determined by:

• Degree of active inflammation
• Laterality
• Macular involvement
• Presence of CNV
• Recurrence frequency
• Degree of structural damage

Medication

First Line

For significant posterior inflammation, topical corticosteroids alone are generally inadequate.

Treatment may include:

• Systemic corticosteroids
• Periocular corticosteroid injection
• Intravitreal corticosteroid therapy in selected cases

Topical corticosteroids may still be useful when there is significant anterior uveitis.

Important Precaution

Infectious causes must be excluded before starting corticosteroids or systemic immunosuppressive therapy.

Immunosuppression of an undiagnosed infectious posterior uveitis may result in severe disease progression.

Systemic Corticosteroids

Oral corticosteroids may be useful for:

• Bilateral disease
• Severe posterior inflammation
• Vision-threatening macular involvement
• Extensive active lesions

Long-term systemic corticosteroid therapy should generally be avoided when a steroid-sparing treatment strategy is appropriate.

Second-Line Therapy

Systemic immunomodulatory therapy may be indicated when:

• Disease is recurrent
• Inflammation is chronic
• Corticosteroid dependence develops
• Disease is bilateral and vision-threatening
• Corticosteroid toxicity is problematic

Potential steroid-sparing agents include, depending on the patient:

• Methotrexate
• Mycophenolate mofetil
• Azathioprine
• Cyclosporine
• Tacrolimus
• Selected biologic agents in refractory disease

These treatments require appropriate systemic monitoring.

Pregnancy Considerations

Many immunomodulatory drugs may:

• Be teratogenic
• Affect fetal development
• Require discontinuation before conception

Treatment in pregnancy should therefore be coordinated with:

• Uveitis specialist
• Obstetrician
• Rheumatologist or other prescribing specialist

Choroidal Neovascularization Treatment

Modern treatment for inflammatory CNV generally centers on:

Intravitreal anti-VEGF therapy

Examples include:

• Bevacizumab
• Ranibizumab
• Aflibercept

Treatment of underlying inflammatory activity may also be necessary.

Historically used treatments include:

• Photodynamic therapy
• Thermal laser photocoagulation in selected extrafoveal lesions

These are used much less commonly than anti-VEGF therapy for macular CNV.

Cystoid Macular Edema

CME may respond to:

• Periocular corticosteroid
• Intravitreal corticosteroid
• Systemic anti-inflammatory therapy

Anti-VEGF treatment may occasionally be used depending on the mechanism and associated pathology.

Issues for Referral

Because posterior uveitis has numerous infectious and inflammatory mimickers and can cause permanent vision loss, patients should generally be managed by or referred to a:

Uveitis specialist

Additional referral may be needed to:

• Retina specialist for CNV, macular edema, or structural complications
• Rheumatology for systemic immunomodulatory therapy
• Infectious disease when an infectious cause is suspected

Surgery / Other Procedures

Cataract Surgery

Chronic inflammation and corticosteroid treatment may cause cataract.

Cataract surgery can be considered when:

• Cataract is visually significant
• Inflammation has been well controlled
• The eye has been appropriately quiet before surgery

Perioperative anti-inflammatory therapy is often required.

Steroid Implants

Sustained-release intraocular corticosteroid implants may be considered in selected cases of:

• Chronic posterior uveitis
• Recurrent disease
• Inadequate response to other therapy

Potential complications include:

• Cataract
• Ocular hypertension
• Glaucoma

Vitrectomy

Pars plana vitrectomy may be considered for:

• Visually significant vitreous opacities
• Diagnostic uncertainty
• Suspected intraocular lymphoma or infection
• Selected structural complications

Diagnostic vitreous sampling may be particularly important in atypical presentations.

Ongoing Care

Long-term follow-up is important because disease may recur after prolonged periods of inactivity.

Monitoring should include:

• Visual acuity
• Slit-lamp examination
• Vitreous inflammation
• Dilated fundus examination
• OCT
• Assessment for CNV
• Intraocular pressure
• Cataract development

Patient Education

Patients should be advised to seek prompt review for:

• New photopsias
• New floaters
• New scotoma
• Metamorphopsia
• Sudden or progressive central visual loss

Home Amsler grid monitoring can be useful.

Prognosis

MFC and PIC often follow a chronic or relapsing course lasting months to years.

Visual prognosis depends primarily on:

• Macular involvement
• Recurrent inflammation
• Development of CNV
• Cystoid macular edema
• Photoreceptor loss
• Extent of chorioretinal scarring
• Diffuse subretinal fibrosis

Patients without foveal involvement may maintain good central vision.

Repeated macular inflammation, CNV, or extensive fibrosis can result in severe permanent visual impairment.

Complications

Important complications include:

• Choroidal neovascularization
• Cystoid macular edema
• Subretinal fibrosis
• Chorioretinal atrophy
• Photoreceptor loss
• Cataract
• Ocular hypertension
• Glaucoma
• Steroid-related complications
• Permanent central visual loss

CNV may occur even when there is no clinically active inflammation, making long-term surveillance essential.

Ophthalmology Pearls

• MFC = multifocal choroidal lesions + vitreitis ± anterior uveitis.
• PIC = young myopic women + posterior pole punctate lesions + little or no vitreitis.
• The two disorders likely belong to a related inflammatory spectrum.
• CNV is one of the most important causes of visual loss and may develop even after inflammation appears inactive.
• OCT is indispensable for distinguishing inflammatory damage from treatable complications such as CNV, CME, or subretinal fluid.
• Before immunosuppression, exclude important infectious mimickers—particularly syphilis and tuberculosis.
• Anti-VEGF therapy is the main contemporary treatment for inflammatory CNV.
• Recurrent disease can lead to extensive subretinal fibrosis and irreversible visual loss.
• Long-term, often lifelong ophthalmic surveillance is appropriate because recurrence and CNV can occur after apparently quiet intervals.

Ophthalmology – Morning Glory Syndrome

Basics

Description

Morning glory syndrome, also called morning glory disc anomaly (MGDA), is a rare congenital malformation characterized by a distinctive funnel-shaped excavation of the optic disc and surrounding posterior fundus.

Its name comes from the resemblance of the anomalous optic nerve head to a morning glory flower.

MGDA is usually:

• Unilateral
• Congenital
• Associated with reduced vision
• Occasionally associated with serious neurologic, cerebrovascular, craniofacial, pituitary, and retinal abnormalities

Because of these systemic associations, recognition of MGDA should prompt evaluation beyond the eye.

Epidemiology

Incidence

MGDA is very rare.

An estimated incidence of approximately:

1 per 1,000,000 live births

has been reported.

Pathophysiology

MGDA is thought to result from abnormal development of the optic nerve and surrounding posterior sclera during embryogenesis.

Typical developmental abnormalities include:

• Funnel-shaped excavation of the optic nerve head
• Abnormal surrounding scleral and peripapillary tissue
• Persistent glial tissue centrally
• Abnormal retinal vascular emergence

A characteristic central glial tuft often remains over the optic disc.

Some authors have proposed that the anomaly represents a form of mesenchymal or mesodermal dysgenesis.

Myocontractile tissue has occasionally been identified histologically, and rare contractile movements of the anomalous disc region have been described clinically.

Commonly Associated Conditions

Retinal Detachment

Retinal detachment occurs in a substantial proportion of patients, historically reported in approximately one-third.

The mechanism is variable and incompletely understood.

Proposed mechanisms include:

• Peripapillary retinal breaks
• Retinoschisis-like communications
• Abnormal communication between:
• The subarachnoid space
• The anomalous optic nerve
• The subretinal space
• Vitreoretinal traction

Detachment may be:

• Localized to the macula
• Shallow and chronic
• Bullous
• Total

Rare spontaneous resolution has been reported.

Cerebrovascular Abnormalities

MGDA has important associations with abnormalities of the intracranial circulation.

These may include:

• Internal carotid artery stenosis
• Carotid hypoplasia
• Carotid aplasia
• Abnormal Circle of Willis
• Cerebral arterial stenosis

These abnormalities may predispose to:

• Stroke
• Transient ischemic events
• Seizures

Moyamoya Disease

MGDA is associated with moyamoya arteriopathy.

Moyamoya is characterized by:

• Progressive stenosis of major intracranial arteries
• Development of abnormal collateral vessels
• Increased risk of:
• Cerebral ischemia
• Infarction
• Intracranial hemorrhage

The abnormal collateral network produces the classic angiographic appearance described as a “puff of smoke.”

Because of this association, cerebral vascular imaging is an important component of evaluation in MGDA.

Midline Cranial Abnormalities

MGDA may occur with congenital midline abnormalities such as:

• Basal encephalocele
• Absent or abnormal septum pellucidum
• Corpus callosal abnormalities
• Pituitary abnormalities
• Other midline craniofacial defects

Pituitary Dysfunction

Pituitary abnormalities can be:

• Structural
• Functional
• Both

Possible manifestations include:

• Growth hormone deficiency
• Growth retardation
• Hypothyroidism
• Other pituitary hormone deficiencies

Children with MGDA should therefore have growth and endocrine development assessed carefully.

Other Associations

Less commonly reported associations include:

• Retinal arteriovenous malformations
• Renal abnormalities
• Papillorenal-spectrum disorders
• Persistent fetal vasculature
• Craniofacial abnormalities

Scattered reports have also linked MGDA with other neurodevelopmental syndromes.

Diagnosis

Diagnosis is primarily based on the characteristic funduscopic appearance of the optic nerve head.

History

Patients may present with:

• Poor vision
• Strabismus
• Failed vision screening
• Leukocoria
• Abnormal pupillary reflex
• Acute visual decline

Acute visual decline should raise concern for:

Retinal detachment

Systemic History

Ask about manifestations suggesting associated neurologic or endocrine disease.

Possible Pituitary Dysfunction

• Poor growth
• Short stature
• Delayed development
• Symptoms of hypothyroidism

Possible Cerebrovascular Disease

• Seizures
• Transient weakness
• Stroke-like episodes
• Developmental regression
• Headaches
• Syncope

Physical Examination

Visual Acuity

Visual acuity is highly variable.

It may range from:

• Nearly normal vision
• Mild visual impairment
• Severe visual impairment
• No light perception

Visual potential depends on:

• Degree of optic nerve malformation
• Macular involvement
• Presence of retinal detachment
• Refractive error
• Amblyopia

Refraction

Myopia is common.

Significant refractive error should be corrected promptly, particularly in children.

Strabismus

Strabismus is common because of unilateral visual impairment.

Most commonly:

• Esotropia
• Exotropia

may occur depending on visual function and age.

Pupillary Examination

A unilateral case may show a:

Relative afferent pupillary defect

if optic nerve dysfunction is sufficiently asymmetric.

Color Vision

Color discrimination may be reduced in the affected eye.

Characteristic Fundus Appearance

The classic features of morning glory disc anomaly include:

• Large optic disc
• Funnel-shaped excavation of the optic nerve head and surrounding posterior sclera
• Central white glial tuft
• Radial arrangement of retinal vessels
• Vessels emerging abnormally from the peripheral edge of the excavation
• Peripapillary pigmentary disturbance
• Circumferential annular ring of pigmented chorioretinal tissue

The vessels may be:

• Numerous
• Narrow
• Radially oriented

and often lack the normal central emergence pattern.

Laterality

MGDA is usually:

Unilateral

Bilateral disease is uncommon.

Retinal Examination

Carefully inspect for:

• Shallow retinal detachment
• Macular detachment
• Retinoschisis
• Peripheral retinal abnormalities

Detachment can occasionally be subtle.

Systemic Examination

Children should have:

• Height measurement
• Weight measurement
• Growth chart assessment
• Complete neurologic assessment
• Developmental assessment

Diagnostic Tests

Laboratory Evaluation

Because of the association with pituitary dysfunction, selected endocrine testing may include:

• TSH
• Free T4
• Growth hormone axis testing
• IGF-1
• Additional pituitary hormones as clinically indicated

Endocrine testing should be guided by clinical findings and pediatric/endocrinology evaluation.

Renal Evaluation

When clinically indicated:

• Serum electrolytes
• Creatinine
• Basic metabolic panel
• Urinalysis

may be obtained.

Routine renal investigations are not necessary in every patient unless the phenotype suggests a syndromic association.

Neuroimaging

A patient with MGDA should be considered for brain and cerebrovascular imaging because of the potentially serious associated abnormalities.

In children, preferred evaluation often includes:

• MRI brain
• MRA head and neck

These avoid ionizing radiation.

Imaging should carefully evaluate:

• Internal carotid arteries
• Circle of Willis
• Intracranial arterial circulation
• Midline brain structures
• Pituitary gland
• Skull base

CT / CTA

CT or CTA may be considered when:

• MRI is unavailable
• Bony anatomy needs detailed assessment
• Basal encephalocele is suspected
• Rapid vascular imaging is clinically necessary

Fundus Photography

Fundus photography is useful for:

• Baseline documentation
• Long-term comparison
• Recording optic disc morphology
• Monitoring associated retinal changes

Optical Coherence Tomography

OCT is especially useful for evaluating:

• Peripapillary architecture
• Macular anatomy
• Intraretinal splitting
• Retinoschisis-like changes
• Subretinal fluid
• Retinal detachment

OCT may help demonstrate a potential communication between abnormal peripapillary structures and the subretinal space.

Fluorescein Angiography

Fluorescein angiography may help evaluate:

• Abnormal retinal vascular anatomy
• Retinal perfusion
• Associated vascular malformations
• Areas of leakage

It is not always required for diagnosis.

Differential Diagnosis

Important differential diagnoses include:

• Optic disc coloboma
• Peripapillary staphyloma
• Posterior staphyloma
• Optic nerve coloboma
• Microphthalmia with cyst
• Congenital optic nerve excavation

Morning Glory Disc vs Optic Disc Coloboma

MGDA typically shows:

• Central glial tuft
• Radial retinal vessels
• Annular peripapillary pigmentation
• Funnel-shaped excavation

Optic disc coloboma more often shows:

• Inferior excavation
• Sharply demarcated congenital defect
• Association with other colobomatous abnormalities

Treatment

There is no treatment that can correct the congenital optic nerve anomaly itself.

Management focuses on:

• Maximizing useful vision
• Treating amblyopia
• Correcting refractive error
• Managing retinal detachment
• Detecting systemic associations
• Protecting the better eye

Refractive Correction

Correct significant:

• Myopia
• Astigmatism
• Anisometropia

as early as possible in children.

Amblyopia Therapy

Amblyopia treatment may be appropriate when useful visual potential exists.

Options include:

• Full optical correction
• Patching of the better eye
• Penalization in selected cases

However, treatment should be pursued cautiously, because the affected eye may have limited structural visual potential.

Excessive occlusion of the better eye should be avoided.

Retinal Detachment Treatment

Retinal detachment associated with MGDA is often difficult to manage.

Treatment may include:

• Pars plana vitrectomy
• Removal of vitreoretinal traction
• Internal drainage when appropriate
• Laser photocoagulation
• Long-acting gas tamponade
• Silicone oil in selected complex cases

The optimal technique depends on:

• Retinal configuration
• Presence of retinal breaks
• Macular involvement
• Vitreous traction
• Patient age

Medical Treatment

There is no specific ophthalmic medication for MGDA itself.

Systemic therapy depends on associated abnormalities.

Examples include:

• Hormonal replacement for pituitary deficiencies
• Antithrombotic or cerebrovascular management as directed by neurology/neurosurgery

Issues for Referral

Pediatric Ophthalmology

Recommended for:

• Refraction
• Amblyopia management
• Strabismus assessment
• Long-term visual development monitoring

Retina Specialist

Indicated when there is:

• Retinal detachment
• Retinoschisis
• Subretinal fluid
• Sudden visual decline

Neurology

Neurologic evaluation is appropriate because of the association with:

• Seizures
• Stroke
• Cerebral arterial abnormalities
• Moyamoya disease

Neurosurgery / Neurovascular Specialist

Referral is important if imaging demonstrates:

• Moyamoya arteriopathy
• Severe carotid stenosis
• Intracranial arterial abnormalities
• Basal encephalocele

Endocrinology

Endocrine referral is appropriate for:

• Growth retardation
• Abnormal pituitary imaging
• Growth hormone deficiency
• Hypothyroidism
• Other pituitary hormone abnormalities

Additional Therapy

Monocular Precautions

When one eye has poor vision, the better eye should be protected.

Recommend:

Polycarbonate protective spectacles

especially for:

• Children
• Sports
• Occupational activities
• Any activity with potential eye trauma

Ongoing Care

Follow-Up Recommendations

Children with MGDA generally require regular lifelong ophthalmic surveillance.

At minimum:

• Annual ophthalmic examination

More frequent follow-up is appropriate when there is:

• Amblyopia
• Significant refractive error
• Strabismus
• Retinal detachment
• Progressive retinal changes

Patient Monitoring

Parents should monitor for:

• Sudden reduction in vision
• New strabismus
• Behavioral evidence of visual loss
• New visual field complaints
• Metamorphopsia
• Micropsia

Neurologic symptoms should also prompt urgent medical assessment.

Retinal Detachment Warning Symptoms

Patients and families should be educated about:

• New flashes
• New floaters
• Curtain or shadow in vision
• Sudden visual loss

In MGDA, a shallow macular detachment may produce more subtle symptoms such as:

• Metamorphopsia
• Micropsia
• Blurred central vision

Prognosis

Visual prognosis is highly variable but is often limited because of the underlying optic nerve malformation.

Vision depends on:

• Degree of optic nerve dysplasia
• Macular involvement
• Refractive error
• Amblyopia
• Retinal detachment

Patients presenting with relatively good stable vision and no retinal detachment may retain useful vision long term.

Complications

Important complications include:

• Retinal detachment
• Retinoschisis
• Amblyopia
• Strabismus
• Severe visual impairment
• Cerebral ischemia or stroke from associated vascular abnormalities
• Seizures
• Pituitary hormone deficiency

Ophthalmology Pearls

• Morning glory disc anomaly = funnel-shaped congenital optic disc excavation with a central glial tuft and radially arranged retinal vessels.
• It is usually unilateral.
• Always think beyond the eye: MGDA can be associated with carotid abnormalities, moyamoya disease, basal encephalocele, and pituitary dysfunction.
• MRI/MRA of the brain and cerebral circulation should be strongly considered, particularly in children.
• Approximately one-third of patients have historically been reported to develop retinal detachment.
• Acute deterioration in vision in a patient with MGDA should prompt urgent evaluation for retinal detachment.
• A child with poor unilateral vision requires careful refractive and amblyopia management, but aggressive patching may be inappropriate when structural visual potential is severely limited.
• Protect the better eye with polycarbonate spectacles when visual function is markedly asymmetric.

Ophthalmology – Moebius Syndrome

Basics

Description

Moebius syndrome is a congenital, usually nonprogressive disorder characterized primarily by:

• Unilateral or bilateral facial weakness
• Impaired ocular abduction
• Variable involvement of other cranial nerves
• Possible craniofacial and limb anomalies

The disorder is considered part of the spectrum of congenital cranial dysinnervation disorders (CCDDs).

Epidemiology

Incidence

Approximately 0.0002–0.002% of live births.

Prevalence

Estimated historical figures include:

• About 2,000 affected individuals worldwide
• About 800 affected individuals in the United States

Because the syndrome is rare and variably expressed, its true prevalence is uncertain.

Risk Factors

Possible risk factors include:

• Family history of Moebius syndrome
• Family history of another congenital cranial dysinnervation disorder
• In-utero exposure to certain proposed teratogens or vascular-disruptive events

Reported associations include:

• Maternal hyperthermia
• Chorionic villus sampling
• Electric shock
• Benzodiazepine abuse
• Alcohol
• Cocaine
• Thalidomide
• Misoprostol

Not every exposed pregnancy develops Moebius syndrome, and many cases occur without an identifiable exposure.

Genetics

Most cases are sporadic, but several inheritance patterns have been reported:

• Autosomal dominant
• Autosomal recessive
• X-linked recessive

Expression and penetrance may vary.

Reported loci have included:

• MBS1: 13q12.2–q13
• Proposed MBS2: 3q21–q22
• Proposed MBS3: 10q21.3–q22.1

Multiple chromosomal abnormalities have also been associated with a Moebius-like phenotype.

General Prevention

There is no specific preventive treatment.

General measures include:

• Avoidance of known or suspected teratogens during pregnancy
• Genetic counseling when there is:
• A family history
• A syndromic phenotype
• A known chromosomal abnormality

Pathophysiology

The exact mechanism is incompletely understood.

Moebius syndrome is thought to result from abnormal development of the rhombencephalon/brainstem, affecting predominantly:

• Cranial motor nuclei
• Cranial nerve axons
• Their long central pathways

Developmental disruption is thought to occur very early in embryogenesis, approximately during the 3rd to 5th weeks of gestation.

The classic neurologic involvement affects:

• CN VI — abducens nerve
• CN VII — facial nerve

Other cranial nerves may also be involved.

Etiology

Possible etiologies include:

• Genetic or inherited developmental abnormalities
• Chromosomal abnormalities
• Teratogenic exposure
• Embryonic vascular disruption

In many patients, no single cause is identified.

Commonly Associated Conditions

Cranial Nerve Abnormalities

Other cranial nerve abnormalities may occur.

CN XII Involvement

Hypoglossal nerve involvement may cause:

• Tongue hypoplasia
• Abnormal lateral tongue grooves or crenulations

Craniofacial Abnormalities

Reported features include:

• Epicanthal folds
• Flat nasal bridge
• Micrognathia
• High-arched palate
• External ear abnormalities
• Dental abnormalities
• Hypertelorism

Limb Abnormalities

Extremity malformations are common and may include:

• Syndactyly
• Brachydactyly
• Limb reduction defects
• Clubfoot
• Arthrogryposis

Feeding and Swallowing Problems

These are common and may result from:

• Cranial nerve dysfunction
• Poor oral motor coordination
• Weak facial musculature
• Tongue dysfunction

Other Ocular Motility Disorders

Duane retraction syndrome may coexist.

Poland Syndrome

Some patients have associated Poland syndrome, characterized by:

• Hypoplasia or absence of the pectoral muscle
• Ipsilateral upper-limb abnormalities

Rare Associations

Reported uncommon associations include:

• Congenital heart defects
• Dextrocardia
• Arthrogryposis multiplex congenita
• Urinary tract abnormalities
• Anosmia
• Hypogonadotropic hypogonadism

Diagnosis

Diagnosis is primarily clinical.

The classic combination is:

• Congenital facial weakness
• Congenital limitation of ocular abduction

Other cranial nerve, limb, and craniofacial abnormalities support the diagnosis.

History

Important points include:

• Family history
• Maternal medication or drug exposure
• Possible teratogenic exposure during pregnancy
• Feeding difficulties
• Swallowing difficulties
• Speech delay
• Abnormal facial movement since birth
• Eye movement abnormalities since birth
• Exposure symptoms such as:
• Tearing
• Irritation
• Redness
• Photophobia

Physical Examination

Ocular Examination

A complete ophthalmic examination should include:

• Visual acuity
• Refraction
• Pupils
• Ocular motility
• Alignment
• Anterior segment examination
• Corneal surface assessment
• Fundus examination

Ocular Motility

The most characteristic abnormality is limited abduction due to CN VI dysfunction.

Patients may have:

• Bilateral abduction limitation
• Unilateral abduction limitation
• Esotropia
• Variable primary-position alignment

Some patients may be approximately orthophoric in primary gaze despite significant abduction limitation.

Facial Weakness

CN VII dysfunction may cause:

• Reduced facial expression
• Inability to smile normally
• Weak orbicularis oculi
• Poor eyelid closure
• Lagophthalmos

The characteristic “mask-like” facial appearance is due to congenital facial nerve weakness rather than lack of emotional expression.

Ocular Surface Examination

Because orbicularis weakness may impair blinking and closure, evaluate carefully for:

• Lagophthalmos
• Exposure keratopathy
• Superficial punctate keratitis
• Corneal epithelial defects
• Corneal ulceration

Visual Function

Assess for:

• Refractive error
• Strabismic amblyopia
• Anisometropic amblyopia
• Reduced visual acuity from corneal exposure

Children require particular attention because amblyopia can become permanent.

External Examination

Look for:

• Facial asymmetry
• Mask-like facial appearance
• Micrognathia
• Ear abnormalities
• Dental abnormalities
• Palatal abnormalities
• Limb defects

Systemic Examination

Patients should be evaluated for:

• Limb abnormalities
• Feeding dysfunction
• Swallowing dysfunction
• Speech abnormalities
• Hearing problems
• Respiratory compromise
• Developmental concerns

Diagnostic Tests

Laboratory Testing

Routine laboratory testing is generally unnecessary.

When the phenotype is atypical or no clear environmental cause is identified, consider:

• Chromosomal microarray
• Karyotype in selected patients
• Targeted genetic testing when another congenital cranial dysinnervation disorder is suspected

There is no single universally diagnostic genetic test for classic Moebius syndrome.

Imaging

Routine imaging is not always necessary.

MRI Brain and Brainstem

MRI may be performed to assess:

• Brainstem anatomy
• Cranial nerve nuclei
• Cranial nerve pathways
• Associated central nervous system abnormalities

Imaging findings may be normal despite clinically definite disease.

Special Considerations

If the history of congenital disease is uncertain and ophthalmoplegia is progressive rather than static, consider alternative diagnoses such as:

• Mitochondrial disorders
• Chronic progressive external ophthalmoplegia
• Kearns–Sayre syndrome

A progressive course is not typical of Moebius syndrome.

Differential Diagnosis

Important differential diagnoses include:

• Isolated CN VI palsy
• Congenital esotropia with pseudo-abduction deficit
• Duane retraction syndrome
• Other congenital cranial dysinnervation disorders
• Hanhart syndrome
• Hypoglossia-hypodactyly syndrome
• Oromandibular limb hypogenesis syndromes
• Chronic progressive external ophthalmoplegia
• Mitochondrial disorders
• Thyroid eye disease
• Brainstem lesions

Internuclear ophthalmoplegia is fundamentally different because it is a central supranuclear/internuclear disorder rather than a congenital bilateral abduction deficit.

Treatment

There is no medication that corrects the underlying congenital cranial dysinnervation.

Management focuses on:

• Protecting the cornea
• Treating strabismus
• Preventing amblyopia
• Supporting feeding, speech, and development
• Correcting associated craniofacial or limb abnormalities when appropriate

Ocular Surface Treatment

Lubrication

For ocular surface dryness or exposure:

• Preservative-free artificial tears
• Lubricating gel
• Ophthalmic ointment at bedtime

Eyelid Protection

If lagophthalmos is significant:

• Tape eyelids closed at night
• Use moisture chambers when appropriate
• Increase lubrication

Bandage Contact Lens

A bandage contact lens may be considered for severe exposure-related epithelial disease.

Close monitoring is essential because contact lenses can increase the risk of infectious keratitis.

Amblyopia Treatment

Treat amblyopia when present using:

• Full refractive correction
• Patching of the better eye
• Penalization when appropriate

Early childhood treatment is especially important.

Strabismus Management

Strabismus surgery may be considered when clinically significant esotropia or another alignment abnormality is present.

Goals include:

• Improving primary-position alignment
• Improving binocular function where possible
• Improving abnormal head posture
• Cosmetic improvement

Because the underlying disorder is dysinnervational, normal abduction usually cannot be restored completely.

Exposure Keratopathy Surgery

Tarsorrhaphy

Temporary or permanent tarsorrhaphy may be needed for severe:

• Lagophthalmos
• Exposure keratopathy
• Recurrent epithelial breakdown
• Corneal ulceration

Multidisciplinary Management

Moebius syndrome frequently requires care from multiple specialties.

Possible referrals include:

• Pediatric ophthalmology
• Strabismus specialist
• Oculoplastic specialist
• Clinical genetics
• Pediatrics
• Neurology
• ENT
• Dentistry
• Orthopedics
• Plastic/craniofacial surgery
• Speech-language pathology
• Occupational therapy
• Physical therapy
• Nutrition
• Psychology or neuropsychology

Feeding and Swallowing

Feeding difficulties may require:

• Feeding therapy
• Occupational therapy
• Speech-language pathology
• Nutritional support

Severe bulbar dysfunction may rarely necessitate more intensive airway or feeding support.

Speech

Facial, lingual, and palatal weakness can cause dysarthria.

Speech therapy may improve:

• Articulation
• Oral motor control
• Communication strategies

Complementary and Alternative Therapy

No complementary treatment has been proven to reverse the underlying neurologic abnormalities.

Ongoing Care

Follow-Up Recommendations

Follow-up frequency depends on ocular complications.

Patients with exposure keratopathy may require frequent review.

Children require ongoing surveillance for:

• Refractive error
• Amblyopia
• Strabismus
• Corneal exposure

Patient Monitoring

Monitor:

• Visual acuity
• Refraction
• Ocular alignment
• Corneal integrity
• Lid closure
• Amblyopia treatment response
• School performance
• Feeding and speech development
• Overall developmental progress

Diet

There is no specific Moebius syndrome diet.

Dietary modifications may be needed when swallowing or chewing difficulties are present.

A nutritionist or feeding team may help determine:

• Food consistency
• Caloric requirements
• Aspiration precautions

Patient and Family Education

Families should understand that:

• Moebius syndrome is congenital
• It is generally nonprogressive
• Facial immobility does not indicate lack of emotion or cognitive impairment
• Corneal protection is important
• Amblyopia treatment must be performed early
• Multidisciplinary support may substantially improve function

Genetic counseling should be offered when appropriate.

The Moebius Syndrome Foundation can provide patient and family support.

Prognosis

Moebius syndrome is generally a nonprogressive congenital condition.

With appropriate supportive care:

• Life expectancy is usually normal
• Vision can remain good if:
• Exposure keratopathy is prevented
• Amblyopia is treated
• Significant strabismus is managed

Functional outcome depends largely on the extent of associated cranial nerve and systemic abnormalities.

Complications

Important ophthalmic complications include:

• Exposure keratopathy
• Corneal epithelial breakdown
• Corneal ulceration
• Corneal scarring
• Rare corneal perforation
• Amblyopia
• Strabismus-related visual dysfunction

Other important complications may include:

• Feeding difficulty
• Aspiration
• Speech impairment
• Dental problems
• Psychosocial difficulties related to facial immobility

Ophthalmology Pearls

• The classic Moebius phenotype combines CN VI and CN VII dysfunction.
• Think abduction deficit + congenital facial weakness.
• The ocular motility disorder is developmental and typically nonprogressive.
• Facial weakness can cause lagophthalmos and exposure keratopathy, making corneal protection a major ophthalmic priority.
• Strabismus and refractive error can produce amblyopia, so early pediatric ophthalmic surveillance is important.
• Progressive ophthalmoplegia should prompt reconsideration of the diagnosis and investigation for mitochondrial or acquired neurologic disease.
• A child with Moebius syndrome may appear expressionless, but facial immobility should not be interpreted as impaired emotion or intelligence.

Toxicology – Button Battery Ingestion

Sources

Button or coin batteries are commonly found in:

• Toys
• Watches
• Hearing aids
• Remote controls
• Small electronic devices

Young children are at greatest risk because the batteries are small, shiny, and easy to swallow.

Typical Presentation

A toddler may swallow a button battery and initially appear completely well.

The most dangerous situation is when the battery becomes lodged in the esophagus.

Clinical Features

Symptoms may include:

• Drooling
• Coughing
• Vomiting
• Dysphagia
• Chest discomfort
• Refusal to eat

However, some children with an esophageal battery may initially have few or no symptoms.

Serious complications include:

• Deep esophageal burns
• Perforation
• Tracheoesophageal fistula
• Injury to major blood vessels
• Mediastinitis

Batteries lodged in the nose or ear can also cause rapid local tissue injury.

Mechanism of Action

The main injury is caused by an electrical current that generates hydroxide ions at the battery surface.

This creates a strongly alkaline environment and causes liquefactive necrosis.

Severe tissue injury can begin within only a few hours.

Diagnosis

Plain radiographs are used to determine:

• Whether a battery is present
• Its location
• Whether it is still in the esophagus

Button batteries can usually be distinguished radiographically from coins by their characteristic layered appearance.

Management

An esophageal button battery is an emergency and requires prompt endoscopic removal.

Important principles include:

• Rapid localization with imaging
• Immediate specialty consultation
• Urgent removal if lodged in the esophagus
• Monitoring for delayed complications after significant esophageal injury

Batteries that have already passed into the stomach or intestine often pass spontaneously, but management depends on factors such as symptoms, battery size, age, location, and evidence of GI injury.

Key Points

• Esophageal impaction is the major emergency.
• Serious tissue injury can occur rapidly, sometimes within about 2 hours.
• A child may appear well despite significant internal injury.
• Large lithium coin cells are especially concerning.
• Batteries beyond the esophagus are often managed expectantly if the patient is asymptomatic and the battery continues to progress.
• Button batteries in the ear or nose also require prompt removal because they can cause rapid liquefactive tissue damage.