Creative Commons License and Financial Disclaimer

This podcast is licensed under a Creative Commons, attribution, non-commercial, no-derivatives license. This means you can use it, copy it, and share it, but you can’t modify or sell it, in whole or in

part, without the express written consent of Dr. Kundart. The Powerpoint presentation on which this podcast is based is the intellectual property of Pacific University College of Optometry.

I’ve made every attempt to provide the most up-to-date and accurate information available. Forward questions or comments about this

presentation to: James Kundart OD MEd FAAO FCOVD-A

(kundart@pacificu.edu) Nadine Girgis Hanna, OD, FAAO, NOVA Southeasern University

The authors have no financial interest in products herein.

James Kundart OD MEd FAAO FCOVD-A Associate Professor

Pacific University College of Optometry Nadine Girgis Hanna, OD, FAAO

Assistant Professor NOVA Southeastern University

The Whiter, Brighter Pupil: Leukocoria in Children

http://avserver.lib.uthsc.edu:8080/Medicine/eye_exam/leukocoriaRB.htm

Focus Questions 1.  Which is the minimum number of tumors per eye

are seen to prove a case of genetic retinoblastoma? 2.  What is the treatment of choice for retinoblastoma

in recent years? 3.  What is “trilateral” retinoblastoma? Where is the

third tumor found in these cases? 4.  Which cause of leukocoria is affected by diet? 5.  Which cause of leukocoria is genetic and inherited

less than 10% of the time?

What Causes White Pupils? !  We all know that optically

empty space normally extends to posterior pole, leaving the red reflex of the choroidal vasculature visible on retro- illumination

!  Asymmetry in this reflex can be caused by: !  Anisometropia and refractive

asymmetry, as seen here in the Bruckner test

!  Misalignment of the visual axes

!  Media opacities and retinal disease, our topics for today

http://www.ojoonline.org/article.asp?issn=0974-620X;year=2010;volume=3;issue=3;spage=131;epage=135;aulast=Amitava

Pathological Causes of Leukocoria 1.  Retinoblastoma 2.  Congenital

Cataract 3.  Coats’ Disease 4.  Persistent

Hyperplastic Primary Vitreous

http://www.clearviewsouthbay.com/tmp/pseudo-leukocoria

Leukocoria Cause #1:

Retinoblastoma

http://www.kellogg.umich.edu/theeyeshaveit/non-trauma/retinoblastoma.html

Retinblastoma: Definitions !  The NEI defines

retinoblastoma as a cancer that forms in the tissues of the retina

!  It usually occurs in children younger than 5 years

!  It may be hereditary (<10%) or nonhereditary

!  ~25% are new mutations, and ~65% metastatic

http://www.hinsdale86.org/staff/kgabric/Disease09/Retinoblastoma/Retinoblastoma%20Help%20and%20Prevention.htm

Epidemiology of Retinoblastoma !  Retinoblastoma has been

described as “the most common intraocular tumor of childhood”

!  Incidence is 1 in 15-20K births, most under ages 5-6, peaking between ages 1-2 years (toddlers)

!  Retinoblastoma is bilateral in one-third of the cases

!  It’s called trilateral if the pineal gland is also affected

http://en.wikipedia.org/wiki/Retinoblastoma

The Causes of Retinoblastoma !  Retinoblastoma arises from

neural retina and typically grows into the vitreous

!  About 60% of cases are detected because of leukocoria

!  Another 25% of cases are found due to strabismus

!  The remaining ~15% aren’t discovered until they cause a child to fail a vision screening, develop a red eye due to glaucoma, or proptosis

!  Sometimes there are anterior segment signs

http://en.wikipedia.org/wiki/File:Retinoblastooma.jpg

Types of Retinoblastoma ! Anterior Segment ! Extraocular

Retinoblastoma ! Posterior Segment ! Sporadic

Nonhereditary ! Multifocal

Hereditary http://www.willseye.org/health-library/retinoblastoma

Retinoblastoma in the Anterior and Posterior Segments

http://www.thirdeyehealth.com/retinoblastoma.html

Source:: National Eye Institute, National Institutes of Health

Extraocular Retinoblastoma

Wright 2, Figure 9-8

Sporadic, Nonhereditary Retinoblastoma

!  Fundus photograph of typical endophytic retinoblastoma

!  Right eye of an 18-month-old child who presented with a 2-month history of an “unusual glint or reflex” in the right pupil

!  There is no tumor in the left eye, and the family history is entirely negative for evidence of retinoblastoma or other childhood cancers

Wright 2, Figure 9-2

Multifocal Hereditary Retinoblastoma

!  Fundus photograph of a child with multifocal, bilateral retinoblastoma

!  With the exception of one reported case, tumor has not been documented to spread from one eye to the other; these tumors have all arisen independently of each other

!  The findings in this child would be statistically impossible unless he is genetically predisposed to develop the tumor

Wright, Figure 9-10

Genetic Testing for Retinoblastoma

http://www.thirdeyehealth.com/retinoblastoma.html

Source: National Eye Institute, National Institutes of Health

!  Blood tests are positive for the RB1 gene in family members of bilateral retinoblastoma patients and a minority (one-seventh, or 15%) of unilateral cases

!  Mothers of RB1 positive unborn children may be induced early to receive treatment for better outcomes

Aggressive Metastasis in Retinoblastoma

!  Retinoblastoma can break through its smooth surface and spread tumor cells into the vitreous

!  Not infrequently, the early stages of vitreous “seeding” is a localized event, occurring just over the surface of an individual tumor

!  In this figure, the localized vitreous seeding is arising from a candy kiss-like structure on the surface of a previously smooth tumor mass

Wright 2, Figure 9-11

Case #1: Teasing out Retinoblastoma with Oral Steroids in a 7 YOM

Wright 2, Figure 9-6

Case #1 DDx: Toxocariasis

Pacific University Ocular Disease Digital Collection

!  Ocular larva migrans (OLM) comprises 10% of all toxocariasis cases, and 1% of all uveitis cases

!  Retinal inflammation occurs in response to the to the death of toxocariasis larvae

!  Signs and symptoms include: !  Blurred vision !  Floaters !  Mild pain !  Mild photophobia

Case #2: 4-month-old: Should You Ennucleate?

Wright 2, Figure 9-4

Case #3: 12 YOF with Prosthesis OD, Proptosis OS: Chronic Viral Syndrome?

Wright 2, Figure 9-13

Case #4: Retinoblastoma in 7 YOM?

Wright 2, Figure 9-9 A & B

Regressive Retinocytoma in 10 YOM

Wright 2, Figure 9-9 C & D

Case #4 DDx: Astrocytoma

http://www.nature.com/eye/journal/v20/n12/fig_tab/6702365f1.html

http://shop.onjoph.com/catalog/product_info.php?products_id=6159

Treating Retinoblastoma

Treatment options include: !  Chemotherapy

(treatment of choice) !  Cryotherapy !  Radioactive seeding !  Laser therapy !  Focal radiation therapy !  Ennucleation (last resort)

http://neuropathology-web.org/chapter7/chapter7aTumorsgeneral.html

Outcomes in Retinoblastoma !  “In the developed world,

retinblastoma has one of the best cure rates of all childhood cancers (95-98%)

!  More than nine out of every ten sufferers survive into adulthood.”

!  Early detection is the key, and digital photos with flash may be our best screening tool

http://en.wikipedia.org/wiki/Retinoblastoma

Leukocoria Cause #2:

Congenital Cataract

Bilateral cataracts in an infant due to congenital rubella syndrome

Adult vs. Pediatric Lens Anatomy

http://flylib.com/books/en/3.283.1.8/1/

Congenital Polar Cataract ! Congenital polar

cataracts are opacities on the anterior OR posterior lens capsule and cortex

!  Some are idiopathic, but others are genetic

!  In myotonic dystrophy, they are autosomal dominant and result in cystine deposition (Christmas Tree cataract, shown here)

http://www.flickr.com/photos/mieruzena/6255918232/

Congenital Nuclear Cataract ! Congenital nuclear

cataracts are most often bilateral

! Notice the Y-sutres can sometimes be seen

! They are associated with microphthalmos and microcornea, and their common causes

! This includes fetal alcohol spectrum disorders (FASD)

http://www.flickr.com/photos/communityeyehealth/5599871815/

Blue-Dot Opacities (Cerulean Cataract)

http://lessons4medicos.blogspot.com/2009/02/cataracts-few-interesting-types.html

! Focal blue dot opacities are frequently bilateral

!  There is a genetic connection to Down syndrome, as well as some unaffected families

! They may not progress to operable until adulthood, so the patient may be unaware

Congenital Zonular Cataract ! Zonular-lamellar

cataracts often have systemic associations

! Some are idiopathic, but others are genetic ! In galactosemia, they

are autosomal recessive, and happen with exposure to galactose in dairy products, but are reversible! http://lessons4medicos.blogspot.com/2009/02/

cataracts-few-interesting-types.html

Other Types of Congenital Cataract ! Posterior lenticonus is

protrusion in posterior lens capsule

! A similar cataract is seen here in congenital rubella

! Note this TORCH disease can liquify the lens with live virus!

! This is a problem for the surgeons, not us

http://www.images.missionforvisionusa.org/anatomy/2007/06/congenital-rubella-cataract.html

Treatment for Congenital Cataract !  Lensectomy and, often,

vitrectomy are necessary for sight-affecting cataracts – why?

!  They may require removal of the anterior and posterior capsule

!  Removal is also important to IOP, as juvenile glaucoma occurs in 20% of these eyes

http://en.wikipedia.org/wiki/Congenital_cataract

When Should Kids Get IOLs? !  In the US, surgeons are

reluctant to use an IOL before age 3 or so

!  Spectacles with double-digit plus power can be lower maintenance and sometimes, less expensive

!  Contact lenses are a better solution, especially if there is unilateral aphakia, in order to diminish significant aniseikonia

http://www.flickr.com/photos/prk2065/3049341752/

Contact Lenses for Pediatric Aphakia SilSoft Super Plus - pediatric lenses!!  Pros: Easy to fit, hyper Dk of

340, doesn’t absorb fluorescein due to 0.2% water content

!  Cons: Expensive, no UV protection

Base Curves: 7.5, 7.7, 7.9 mm Diameter: 11.3 mm

Powers: +23.00D to +32.00D (1.00D steps)

Optical Zone: 7.0mm

Center Thickness: 0.51mm - 0.71mm

Leukocoria Cause #3:

Coats’ Disease

http://savingryanseye.blogspot.com/2009/04/ryans-battle-with-coats-disease-brian.html

Leukocoria in Coats’ Disease

http://www.mrcophth.com/ophthalmologyhalloffame/coats.html

!  In a 1908 paper, Scottish ophthalmologist George Coats described “forms of retinal disease with massive exudation”

!  Seen 3:1 in males, what is now known as Coats’ disease affects 80% of patients unilaterally, and is not genetic

!  There are both juvenile and adult forms of Coats, and it has been identified as late as the seventh decade of life

Fundus Appearance in Coats’ Disease !  This 11 YOM patient was

asymptomatic until the prior week when he failed a school vision screening for football

!  VA OS 20/300 PH NI with >1.8 log unit RAPD OS

!  Note the resemblance to cotton-wool spots and the whitish to yellow color of the cholesterol deposits

http://webeye.ophth.uiowa.edu/eyeforum/cases/100-Coats-Disease.htm

Fluorescein Angiogram (FA) of Coats’ Disease

http://webeye.ophth.uiowa.edu/eyeforum/cases/100-Coats-Disease.htm

!  In Coats’ disease, expect the FA in one eye to appear unremarkable, while the other will show vessel anomalies

!  Note the hypofluorescence at the macula, and the lack of leakage in this early-stage FA in the same patient as the last slide

!  Later stages will show light bulb aneurysms and dilated telangiectatic vessels

Dilated Vessel Telangiectasia and Light Bulb Aneurysms in 11 YO with Coats’

http://webeye.ophth.uiowa.edu/eyeforum/cases/100-Coats-Disease.htm

Using FA to Diagnose Coats’ ! Fluorescein

angiogram of the periphery in a girl with Coats’ disease

! Note the bulblike telangiectasias and the avascular area beyond the tortuosity

Wright 2, Figure 13-3

Stages of Coats’ Disease

http://www.aapos.org/terms/conditions/34

!  Stage 1: abnormal dilation of retinal blood vessels Vision loss is usually reversible. However, Coats Disease is infrequently diagnosed at Stage 1 because patients are often too young to articulate their symptoms.

!  Stage 2: both telangiectasia and exudation. Visual prognosis is contingent upon the degree of involvement of the fovea

!  Stage 3: Exudative retinal detachment (seen here)

!  There are stages 4 and 5 also

Pseudoretinoblastoma in Coats’ Disease

!  Neovascular glaucoma has been seen in Coats’ disease, as in this 4 YOF patient

!  IOP 35 mm Hg OD, 14 OS !  OD was NLP and had

“total retinal detachment with heterogeneous subretinal fluid” on CT scan

!  This Stage 4 case required ennucleation and a prosthesis

http://www.diagnosticpathology.org/content/1/1/24

Retinal Hemorrhage in Coats’ Disease !  “The development of preretinal

neovascularisation in the temporal periphery is unusual

!  When it occurs, it could be secondary to retinal ischemia or a break in Bruch’s membrane after laser photocoagulation

!  Scattered laser photocoagulation is expected to result in reduction in microvascular telangiectatic changes and lipid exudates, similar to what has been described in diabetic retinopathy” (Ciardella et. al.)

http://bjo.bmj.com/content/88/7/970.full

Coats’ DDx: Toxocariasis !  25-50% of patients present with

posterior pole granuloma ! Hazy, ill-defined white lesion

with an overlying vitritis !  Inflammation resolves, the

lesion becomes well-demarcated, elevated white mass ranging in size

! Retinal folds extend from lesion, while granulomas on ONH cause severe vision loss and APD

http://cdm15925.contentdm.oclc.org/cdm/singleitem/collection/p15925coll4/id/444/rec/3

Treating Coats’ Disease

http://bjo.bmj.com/content/88/7/970.full

!  Stage 1: Cryotherapy !  Stage 2: Laser

photocoagulation, similar to PRP in diabetics

!  VEGF inhibitors like Avastin and Lucentis are adjunct Tx

!  This 14 YOF patient had been an absolute vegetarian from birth; her cholesterol level was 116, and her triglyceride level was 83, which may have helped to mitigate the retinal damage

Leukocoria Cause #4:

Persistent Hyperplastic Primary Vitreous

http://www.prenatalpartnersforlife.org/Stories/OtherGabriella.htm

PHPV Definition !  First described in 1955,

PHPV consists of a congenital malformation of the vitreous with a retrolental white plaque of fibrovascular tissue, visible through the pupil

!  The failure of the hyaloid artery to regress by birth is the cause of this rare condition unilaterally

http://webeye.ophth.uiowa.edu/eyeforum/atlas/pages/persistent-hyperplastic-primary-vitreous-PHPV.html

Retrolentar Fibrovascular Plaque in PHPV

http://health-7.com/Atlas%20of%20Pediatric%20Physical%20Diagnosis/Retina

!  In cases with anterior PHPV, the ciliary processes are drawn inward by their attachment to the fibrotic tissue, often lying against the posterior lens

!  In cases with posterior PHPV, strands of glial tissue extend from the retina into the vitreous

Posterior PHPV May Resemble ROP !  In posterior PHPV, ”the optic

disc contains dense, white fibrous tissue extending towards  the ora serrata (usually inferiorly)

!  Also, the retinal vessels are distorted as they emerge from the optic disc

!  Posterior PHPV may resemble ROP with dragged disc

!  The posterior PHPV patient may have microphthalmos and/or esotropia”

http://www.mrcophth.com/opticdisccases/phpv.html

Walker-Warburg and Anterior PHPV

http://www.retinaatlas.com/systemic-disorders/walker-warburg-syndrome/walker-warburg-4/

!  All patients who have this cerebellar syndrome also have muscular dystrophy

!  Like Arnold-Chiari and Dandy-Walker, you can expect cerebellar malformation and hydrocephalus with Walker-Warburg

!  Sadly, life expectancy with this is often < 3 years

!  Ophthalmically, you can expect retinal dysplasia, coloboma, and microophthalmos in addition to bilateral PHPV

Walker-Warburg and Posterior PHPV

http://www.retinaatlas.com/systemic-disorders/walker-warburg-syndrome/walker-warburg-7/

http://www.retinaatlas.com/systemic-disorders/walker-warburg-syndrome/walker-warburg-5/

Aphakia and PHPV

http://www.thetelegram.com/Arts%20-%20Life/2011-01-31/

article-2184910/Babies-parents-fight-rare-disease/1

http://www.eyesite.ca/7modules/Module5/html/fr_Mod5Sec1DiffD3.html

DDx: Is This PHPV or Retinoblastoma? !  Eye of a 3-year-old child who

presented with an intraocular mass OD

!  There was concern about the possibility of an intraocular ocular malignancy

!  The cornea in the right eye was 1 mm smaller than in the left eye. Slit lamp exam showed a vascularized membrane with anterior synechia

!  Ultrasound showed a stalk going from the back of the lens to the nerve head, and a diagnosis of PHPV was made

Wright 2, Figure 9-3

Last DDx: PHPV or Toxocariasis? !  50% of toxocariasis

patients have acute peripheral granuloma ! Appears as a hazy,

white mass in the peripheral fundus

! Over time, lesion becomes a peripheral, elevated mass ! Often with posteriorly

extending retinal folds http://www.medsci.org/v06p0129.htm `

Leukocoria Summary !  Some cases of white pupil are

due to media opacity (congenital cataract, PHPV)

!  Some are caused by vascular conditions (Coats’ disease)

!  Some are due to retinal lesions (retinoblastoma, astrocytoma)

!  But most are simply due to refractive error or strabismus

http://savingryanseye.blogspot.com/2009/04/ryans-battle-with-coats-disease-brian.html

Review Capsule 1.  Which brand of aphakic contact lenses comes in the

highest powers? What do they cost? 2.  Which systemic disease, a syndrome, causes PHPV? 3.  Astrocytoma is a differential diagnosis for which

cause of leukocoria? 4.  Which DDx in leukocoria causes vitritis at least

25% of the time? 5.  Which cause of leukocoria might be mistaken for

retinopathy of prematurity (ROP)?

Acknowledgements !  James Kundart OD MEd

FAAO FCOVD-A Associate Professor Pacific University

kundart@pacificu.edu

!  Nadine Girgis Hanna OD FAAO, Assistant Professor

NOVA Southeastern University

ngirgis@nova.edu

References !  “Clinical Ophthalmology”, Kanski, Jack J, 4th edition, Elsevier. !  “The Wills Eye Manual, Office and Emergency Diagnosis and Treatment of Eye Disease”, 3rd

Edition, Lippincott, Williams, Wilkins. !  Section on Ophthalmology American Academy of Pediatrics, American Academy of

Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus. Screening examination of premature infants for retinopathy of prematurity. Pediatrics. 2006 Feb;117(2):572-6.

!  International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol. 2005 Jul;123(7):991-9.

!  Tasman W. Retinopathy of Prematurity: the life of a lifetime disease. Am J Ophthalmol. Jan 2006; 141(1): 167-74.

!  Chen ML, Guo L, Smith LE, Dammann CE, Dammann O. High or low oxygen saturation and severe retinopathy of prematurity: a meta-analysis. Pediatrics. 2010 Jun;125(6):e1483-92.

!  Ellsbury DL, Ursprung R. Comprehensive Oxygen Management for the Prevention of Retinopathy of Prematurity: the pediatrix experience. Clin Perinatol. 2010 Mar;37(1):203-15.

!  “Toxocariasis” www.wikipedia.org, 12 Oct 2012