What’s New in Pediatric Ophthalmology

Forrest J Ellis MD Northern Virginia Ophthalmology Associates

Falls Church, Fairfax, Alexandria (Milan, Paris, Singapore, London)

What’s New

• Myopia treatment • Retinopathy of Prematurity • Vision Screening • Genetics of Strabismus

Myopia

Myopia

• Most common eye problem worldwide – 20% of world population – 10% of US school age Children

• Asians> Hispanics> Caucasians and African Americans

– 77% of High school children in China

• 99% of current South Korean high school graduates

Why do we care?

• Lifetime increased risks – Cataract – Glaucoma – Retinal detachment – Macular degeneration

• Costs – $125 per myopic child per year direct costs – $90 per capita for all eye disease per year – US $10 billion per year on myopia

Myopia – risk factors

• Genetics • Environmental (no strong correlation)

– Near work – Computer games

• Environmental (positive correlation) – Urbanization – associated with increasing rates of

myopia – Higher IQ – Time spent indoors (not spent outdoors)

Myopia – Associated Disorders

Ocular Disease Congenital Glaucoma ROP RP Cataract CSNB Keratoconus Aland eye disease Gyrate Atropy Pseudomyopia Albinism

Multi-system disease Sticklers Syndrome Diabetes Mellitus (uncontrolled) Marfan Weill-Marchesani Knobloch Ehlers Danlos

Myopia - Treatment

• Glasses • Contact Lenses • Refractive Surgery

What if glasses invented after Lasik?

• “Amazing new device eliminates need for millions to undergo expensive eye procedure”

Myopia progression management

• Atropine topical eye drops • Orthokeratology • Bifocals • Specialty fit contact lenses

– Peripheral optical blur

Atropine Trials for Myopia control ATOM 1

• Atropine 1% ophthalmic – Nonspecific muscarinic acetylcholine receptor

antagonist – Atropine 1% each eye at bedtime

• ATOM 1 (1994-2004) – 77% REDUCTION IN PROGRESSION OF MYOPIA

• Significant rebound once treatment discontinued • Side effects

– Pupil dilation – Paralysis of near focus

ATOM 2

• Lower dose atropine (2 year study) – 0.5%, 0.1%, 0.01% – All clinically similar results – 0.01% atropine drop

• No pupil dilation • No near defocus • No rebound effect when discontinued • No cases of allergic or chemical conjunctivitis

• Atropine decreased myopic progression and axial length elongation by >50%

ATOM 1 and 2

Alternative treatments

• Orthokeratology (ortho-K) (CRT) – Contact lens worn at night to reshape cornea – Effect lasts about 3 days

• Ortho-K to prevent myopia progression – Limited long term studies – Similar results to treatment with glasses and

Atropine 0.01% – Risks include bacterial keratitis

Recommendations to prevent or slow down Myopia

• Increase time outdoors • Atropine 0.01% each eye at bedtime

– Probably can stop after puberty

• Full myopic power correction – No evidence that glasses or contacts increase rate

of myopia correction

• Bifocals – Small effect

Retinopathy of Prematurity

Retinopathy of Prematurity

• Disease of the retina of premature infants • Risk factors

– Lower birth weight – Lower gestational age – Many additional risk factors

• Caused by disorganized blood vessel growth in the developing infant eye.

ROP – laser treatment

ROP – Zone 1

Advanced ROP

Bevacizumab (Avastin) for ROP • BEAT ROP

– Bevacizumab (Avastin) vs Laser in ROP. – Prospective, controlled, randomized, stratified, multicenter

trial – Intravitreal bevacizumab monotherapy for zone I or zone II

posterior stage 3 ROP with plus disease. – Avastin showed a significant benefit for zone I but not zone

II disease. – Development of peripheral retinal vessels continued

(recurs) after treatment with intravitreal bevacizumab – Conventional laser therapy led to permanent destruction

of the peripheral retina. • Safety issues regarding Avastin in ROP not assessed.

Bevacizumab (Avastin) for ROP

• VEGF levels reduced in serum following VEGF intravitreal injection

• Neurodevelopmental Outcomes Following Bevacizumab Injections for Retinopathy of Prematurity. Pediatrics. 2016 Apr;137(4). pii: e20153218. doi: 10.1542/peds.2015-3218. Epub 2016 Mar 17. – Preterm infants treated with bevacizumab versus

laser had higher (3.1x) odds of severe neurodevelopmental disabilities.

Current Therapy of ROP at INOVA

• Laser Treatment for Zone 2 ROP – Zone II, stage 2-3 with plus disease

• Avastin for ROP in Zone 1 – Zone I, any stage with plus disease – Zone I, stage 3 without plus disease

• Rescue therapy with laser if ROP recurs following avastin treatment

Vision Screening

Vision Screening

• Emerging technologies – Instrument based visual screening

• Photo screening • Autorefraction • Birefringent retinal screening

Age Tests Referral Criteria Comments

Newborn to 12 months

•Ocular history •Vision assessment •External inspection of the eyes and lids •Ocular motility assessment •Pupil examination •Red reflex examination

•Refer infants who do not track well after 3 months of age. •Refer infants with an abnormal red reflex or history of retinoblastoma in a parent or sibling.

12 to 36 months

•Ocular history •Vision assessment •External inspection of the eyes and lids •Ocular motility assessment •Pupil examination •Red reflex examination •Visual acuity testing •Objective screening device “photoscreening” •Ophthalmoscopy

•Refer infants with strabismus •Refer infants with chronic tearing or discharge. •Refer children who fail photoscreening.

36 months to 5 years

•Ocular History •Vision assessment •External inspection of the eyes and lids •Ocular motility assessment •Pupil examination •Red reflex examination •Visual acuity testing (preferred) or photoscreening •Ophthalmoscopy

Visual acuity thresholds •Ages 36-47 months: Must correctly identify the majority of the optotypes on the 20/50 line to pass. •Ages 48-59 months: Must correctly identify the majority of the optotypes on the 20/40 line to pass. •Refer children who fail photoscreening.

5 years and older* *Repeat screening every 1-2 years after age 5.

•Ocular history •Vision assessment •External inspection of the eyes and lids •Ocular motility assessment •Pupil examination •Red reflex examination •Visual acuity testing •Ophthalmoscopy

•Refer children who cannot read at least 20/32 with either eye. Must be able to identify the majority of the optotypes on the 20/32 line. •Refer children not reading at grade level.

Related

Why screen?

• Amblyopia 2-4% of children • Etiology

– Unequal refractive error – Strabismus – Less common

• Cataract, corneal abnormalities, ptosis, etc

Vision screening

• Visual acuity testing in office difficult – Children less than 3 years – Developmental delays

• Important to detect amblyopia early • Assess amblyopia risk factors

Amblyopia risk factors

• Strabismus • Astigmatism • Unequal refractive errors • High hyperopia (bilateral) • High myopia (bilateral) • Media opacities

Instrument based vision screening

• AAPOS guidelines for referral for photoscreening should have a high specificity and sensitivity

• Depending on age – Astigmatism >1.5-2.0 diopters – Hyperopia >3.5-4.5 diopters – Myopia > 1.5- 3.5 diopters – Inter-eye difference (anisometropia) >1.5-3.5 diopters – Media opacity greater than 1mm – Strabismus (greater than 8 prism diopters)

Photoscreening devices

• Plusoptix

– Measures pupil size – Corneal reflexes – Refraction – 92% sensitivity – 88% specificity

Photoscreening devices

• Spot vision screener – Similar feel to camera – Refraction – Pupil size – Automated computer analysis

Photoscreening devices

• iScreen • Mobile apps

– GoCheck Kids • No upfront costs to

download app • In app pricing model • Similar to other devices in

accuracy

Retinal Scanning

• Rebiscan – Even minimal amblyopia results in micro-

strabismus – Measures exact foveal fixation using retinal

birefringence and laser scanning – Very high sensitivity and specificity – Recently obtained FDA approval – Not yet commercially available

Rebiscan

Rebiscan

Genetics of Strabismus

Mis-innervation / Dysinnervation

• Congenital fibrosis of the extraocular muscles – Types 1,2,3, and Tukel syndrome

• Duane syndrome • Moebius syndrome • Horizontal gaze palsy with progressive

scoliosis • Synergistic divergence

Mis-innervation / Dysinnervation

• Congenital ptosis • Jaw-wink ptosis • Congenital superior oblique paresis • Brown syndrome

Mis-innervation Mechanism

• What happens when the nerve fails to develop – The innervated muscle does not develop – The opposing extraocular muscles develop

unopposed and appear contractured and fibrotic

Congenital cranial dysinnervation disorders

• Known genetic abnormalities • Duane syndrome

– CHN1 gene • DURS2 locus (autosomal dominant)

– DURS1 locus (chromosome 8q13) • Simplex cases

• Horizontal gaze palsy with progressive scoliosis – ROBO3 gene

• Congenital ptosis – Locus on chromosome 1p

• Jaw –wink ptosis – A patient with Duane syndrome and Marcus Gunn Jaw-wink has been

reported – KIF21A mutation reported in a patient with MG ptosis and CFEOM

• Congenital fibrosis of the extraocular muscles

Duane syndrome • SALL4- related disorders

– Okihiro, Duane radial ray, acro-renal-ocular syndrome, IVAC syndrome – Unilateral or bilateral Duane syndrome with radial ray abnormalities

• SALL1-related disorders – Duane syndrome and renal anal, limb and ear deformities

• HoXA1 related syndromes – Duane syndrome and bilateral senorineural hearing loss and

craniofacial maldevelopment • Wildervank syndrome

– Duane syndrome, deafness, Klippel-Feil anomaly • Goldenhar syndrome

– Hemifacial microsomia. Oculoauriculovertebral, Duane syndrome

Duane syndrome

• What happens when the nerve fails to develop – In Duane syndrome the 6th nerve nucleus is

typically absent – However, a branch of the 3rd nerve innervates the

lateral rectus – As a result the lateral rectus develops as a normal

muscle, but just contracts at the wrong time

Unusual associations

Duane with severe leash?

Duane with severe leash? (or SR mis-innervation)

Congenital ptosis

• Congenital ptosis – Genetically identified abnormality (1p)

• PTOS1 locus

– Often associated with other syndromes or abnormalities of the EOMs

– Unilateral, bilateral, or asymmetric – Often a family history

Congenital ptosis

Unusual associations

• Left ptosis with Left infraduction deficit

Marcus Gunn jaw wink ptosis

• What happens when the nerve fails to develop – Marcus-Gunn Jaw-wink ptosis – The nerve to the levator palpebrae superioris fails to

develop – Unlike congenital ptosis, the levator muscle appears

fairly normal because it is innervated a branch of the trigeminal nerve (usually the branch to the lateral pterygoid muscle)

• Rare familial cases have been reported • KIF21A mutation reported in a patient with MG ptosis and

CFEOM

Marcus Gunn jaw wink ptosis

What about congenital superior oblique paresis

• MRI evidence of hypoplastic development or absence of the 4th nerve/nucleus

• Hypoplasia of the SO muscle • Occasionally familial

Congenital superior oblique paresis

• Left so paresis mom • Right SO paresis in daughter

Bilateral Brown syndrome

Left Duane syndrome

Left Duane syndrome

Unusual associations

Fresnel prism

• Film used to correct double vision • Kind of new

Fresnel prism

Fresnel prism

Thank You