The Differential Diagnosis of Functional Vs. Pathological Vision Loss

THE DIFFERENTIAL DIAGNOSIS OF FUNCTIONAL VS. PATHOLOGICAL VISION LOSS

Sherry J. Bass, OD, FAAO, FCOVD

Distinguished Teaching Professor

SUNY State College of Optometry

New York, NY

I. Amblyopia

A. Accepted Definitions of Amblyopia

All assume an absence of underlying structural or pathological anomaly:

1. A difference in best corrected visual acuity between the two eyes of two lines or more of Snellen acuity

2. An absolute reduction in Snellen acuity in either eye (accounts for bilateral loss)

3. VA poorer than 20/20 in the absence of underlying structural or pathological anomalies, but with at least one of its causes occurring by the age of 6-8 years

B. The Cost of Misdiagnosis of Amblyopia

1. Cost To The Patient

a. Blindness

b Death

c. Quadriplegia

d. Financial

1. Cost To The Doctor

a.Largest single category of malpractice cases

b.Large jury awards

1. 6-7 figures

c. Loss of career/reputation

II. Possible Causes of Amblyopia

A. Significant anisometropia

1. greater than 1D difference for hyperopia, 3D for myopia and 1.50D for astigmatism

B. Significant unilateral or bilateral uncorrected isometropia

1. Greater than 5D of hyperopia, 8D of myopia and 2.50D of astigmatism

C. Constant unilateral strabismus

1. Esotropia, except alternating

2. Rare in exotropia -most can alternate

3. Image degradation-deprivation amblyopia

a. Cornea

b. Lens

III Standard Examination Techniques to Rule Out Disease

A. Pupils: usually normal in amblyopia

B. Slit Lamp Exam

1. Cornea

a. Keratoconus

i. >Fleischer’s Ring, Scissors Reflex on Retinoscopy

ii. >Confirm with Keratometry/Corneal Topography

b. Central Corneal Opacities

Corneal dystrophies: inherited corneal diseases causing central corneal opacities and reduced acuity in some cases

2. Careful Lens Evaluation through Dilated Pupil

a. R/O Central nuclear cataract-suspect in young patient with h/o trauma

b. R/O small posterior subcapsular cataracts

C. Keratometry/Corneal Topography

a. R/O High cylinders, oblique axes, corneal distortion

b. Use a RGP contact lens to see if VA improves

D. Ophthalmoscopy

1. Indirect with headset and 20D lens

2. Indirect with slit lamp and 78D, 90D lens

a. Detailed inspection of optic nerve head and macula

E. Chairside Tests Supporting Diagnosis of Amblyopia

1. Neutral density filter in front of amblyopic eye:

a. VA remains the same, slightly decreases or mildly improves in

amblyopia; VA will often be markedly reduced in organic disease

2. Color Vision

a. Normal in amblyopia, may not be in optic nerve disease and some

Retinal diseases

3. Stereopsis

a. Abnormal findings support binocular functional problem

IV. Additional Tests to Rule Out Disease

A. Chairside Tests

1. Color Vision

2. Light Brightness Comparison

3. Photostress Tests

4. Red Desaturation

5. Gross confrontations with small red targets

B. Optical Coherence Tomography (OCT)

1. In vivo cross-sectional imaging of the retina and optic nerve

2. Images posterior pole abnormalities not evident on ophthalmoscopy

3. Images the photoreceptor integrity line which is disrupted in hereditary retinal disease

4. Quantifies retinal thickness

5. Quantifies RNFL thickness (as does Scanning Laser Polarimtery-GDx)

a. Useful for ruling out glaucoma

b. Useful for ruling out RNFL loss secondary to optic disc hypoplasia and tilted discs

5. The OCT examination is normal in amblyopia

C. Visual Fields

1. Are usually normal in amblyopia

2. Amblyopic eye may demonstrate relative desensitivity centrally and increase in fixation losses

3. Exception is in constant, large angle ET

a. May get nasal field loss in affected eye

4. Amblyopia affects form sense, not light sense

D. Fundus Autofluorescence Imaging-FAF

1. Imaging technology using the principle of autofluorescence of the retina when stimulated using certain filters

2. Useful for imaging abnormalities of the outer retina and RPE

E. Fluorescein Angiography

1. Useful for detection of fundus abnormalities not visible with ophthalmoscopy

a. RPE defects

b. Vascular anomalies

B. Visual Evoked Potentials in Amblyopia

1. Decreased amplitude in amblyopic eye(s), especially to smaller size checks, can be delayed

2. Normal non-patterned (flash) responses

a. In some cases, even supernormal responses

3. If you get no response to a flash stimulus, be very suspicious of visual pathway disease

C. Electroretinography (ERG)

1. Standard full-field ERG tests overall retinal function

2. Order if patient has nyctalopia

3. Order if patient presents with nystagmus

4. Order if patient has abnormal color vision with reduced VA

D. Neuroimaging

1. Order if visual field defects are suggestive of visual pathway disease

a. Bitemporal field defects

b. Congruous field defects

c. Central field defect in one eye with normal fluorescein result

2. Order if VEP is flat to non-patterned flash stimulation

V. Diseases Misdiagnosed As Amblyopia and Functional Problems

1. Presumed Ocular Histoplasmosis Syndrome

a. Chorioretinitis caused by histoplasm capsulatum spores

b. Seen in patients living around chicken farms and river valleys

c. Signs

a. Peripapillary atrophy

b. Chorioretinal punched out lesions, “histo spots”

c. Macular CNV lesions-affect VA

2. Early Stargardt Disease

a. Autosomal recessive disease affecting central retina

b. Maculopathy

a. Not always apparent in teenage years

b. Progresses to a “beaten-bronze” appearance

c. May also be associated with “fundus flavimaculatus”

a. Fish-tail flecks made of lipofuscin

d. Gradual loss of vision (20/100-20/200)

e. Diagnostic tests

a. Visual fields: Superior paracentral scotomas

b. Electroretinography: Normal responses

c. Fluorescein angiography: “Dark” or “silent” choroid during early choroidal flush stage

f. Caused by mutations in the ABCA4 gene on chromosome 1

3. Cone and Cone/Rod Dystrophy

a. Autosomal dominant or recessive

b. Reduced central vision early in life

c. Abnormal color vision

e. Photophobia

f. Signs-Supported by FAF

a. Granular macular appearance

b. Bull’s Eye macular appearance

g. ERG

a. abnormal photopic response

b. scotopic (rod) response normal in cone dystrophy

h.. If disease progresses to involve the rods

a. night vision will be affected

b. arterioles will be attenuated

c. ERG scotopic (rod) response will become more reduced

i. Mutations in 12 genes have been identified

4. X-Linked Juvenile Retinoschisis

a. Reduced vision from or shortly after birth

b. Sex-linked: Males affected

c. Foveal schisis

i. Retina is split at the nerve fiber layer

ii. Cystic macula on OCT

d. About 50% have associated inferotemporal schisis

5. Coat’s Disease

a. Unilateral retinal disease

b. Mostly males under 20 years

c. No hereditary pattern or associated systemic disease

d. Signs

a. Irregular dilatation (aneurysms) of retinal vessels (telangiectasia)

e. May progress to intraretinal and subretinal exudation

f. If untreated, may progress to retinal neovascularization and vitreal hemorrhage

g. If macula is affected, VA will be reduced

6. Drug-induced maculopathies-get a good history!

a. Mellaril and psychotropic drugs

1. high daily dose can cause damage years after discontinuation of the drug

2. poorly excreted

b. Chloroquine

1. can cause damage years after discontinuation of the drug

c. Tamoxifen

7. Solar retinopathy

a. Mildly reduced central VA

1. causes a foveal “burn” or RPE defects

c. Unilateral or bilateral

d. Diagnostic test: Fluorescein angiography

1. hyperfluorescent window defects 2* RPE breaks

8. Ocular Albinism and Foveal Hypoplasia

a. Reduced VA from birth

b. Nystagmus

c. Foveal hypoplasia

d. Diagnostic tests

1. iris transillumination

2. VEP abnormalities

a. abnormal decussation of temporal fibers in chiasm

i. high incidence of strabismus

9. Rod Monochromatism (Achromatopsia)

a. Reduced VA from birth

i. Worse VAS than cone dystrophy

b. Nystagmus

c. Autosomal recessive

d. Poor color vision

e. Photophobia

f. Signs

i. Macular granularity

ii. Fundus can look normal!

g. Diagnostic test

i. ERG: abnormal photopic or cone response

ii. Normal scotopic or rod response

10. Resolved Central Serous Choroidopathy

a. Macular or paramacular RPE defects

b. Orange glow in indirect illumination demonstrates RPE defects

c. U-shaped RPE defect from old CSC “drip”

d. Decreased BCVA in affected eye(s)

11. Congenital Combined Hamartoma of the Retina and RPE

a. Rare Congenital tumor of the retina and RPE

b. Reduced VA from birth

B. Optic Nerve and Visual Pathway Disease

1. Congenital Optic Atrophy

a. Autosomal dominant or recessive

b. Congenital or Juvenile onset

2. Congenital Optic Nerve Head Anomalies

a. Tilted discs

1. can be associated with mildly reduced VA

b. Hypoplastic disc

1. small vs. hypoplastic ONH

c. Coloboma

1. associated with retinal detachment (RD)

d. Optic Pit

1. incomplete coloboma

2. associated with RNFL defects

a. paramacular VF loss

3. associated with macula serous RD

a. decreased VA

e.. Morning Glory Syndrome

1. funnel-shaped ONH

2. peripapillary changes

3. stick-like emerging blood vessels

4. unilateral or bilateral

a. unilateral cases -decreased VA b. bilateral cases- normal VA,

3. Visual Pathway Lesions That Can Affect Visual Acuity

need to be > 1cm in size to affect visual pathways and visual fields

a.. Craniopharynigioma

1. most common intracranial mass in children

2. are slow-growing

b. Glioma

1. are associated with neurofibromatosis

a. Café-au-lait spots (>5)

b. Lisch nodules on the iris

c. Type II-associated with acoustic neuroma

d. autusomal dominant

4. Congenital Glaucoma and Juvenile Glaucoma

a. Congenital glaucoma

Large (“marble”) eyes

Megalocornea

b. Juvenile Glaucoma

Easier to miss

VI. Exemplary Case Presentations

Case 1- VEP Sounds the Alert

a. 11 year-old female c/o decreased VA

b. Health history: stiff neck with normal X-ray, losing weight, passive behavior, poor appetitie

c. Normal pupils, normal fundus, VA=20/400 OD and OS

d. Dx: Bilateral amblyopia

e. +3.00 prescribed OU-no help

f. School suggests psychological counseling

g. 2nd eye exam-all normal, no explanation for reduced VA

h. Referred for VEP-r/o malingering

i. Flat VEP to pattern and flash

j. MRI reveals glioma

Case 2- “I Don’t Like the Way I See Out of My New Glasses”

a. 21 yo black female c/o blurred vision

b. BCVA 20/30 OD and OS

c. Dx: Bilateral amblyopia-Rx given

d. Gets 2nd opinion: doesn’t like the way she sees out of her new glasses

e. Health history: has been gaining weight, walks with a wide gait

f. Presents with elevated IOPs and blurred optic discs

g. VF: altitudinal field loss OU

h. MRI reveals cerebellar mass

Case 3 Amblyopia Due To “Farsightedness”

a. 10 yo boy c/o decreasing vision OD

b. BCVA: OD +1.50 20/100, OS + 1.25-0.75X180 20/60

c. Fundus normal

d. Dx: “Amblyopia due to farsightedness”

e. 9 mos later, pt returns, VA in OD “can’t be measured”

f. Pt told to return in one year-VA is recorded as “no response right eye”

g. Family went for a 2nd opinion to another doctor, who referred pt. to an ophthalmologist

h. MRI: Craniopharyngioma

Case 4 “Get Used To Your Glasses”

a. 20 y-o female c/o blurry vision OD

b. BCVA OD 20/30 +050,OS 20/20, +1.00 Add

c. Normal fundus and slit lamp

d. Dx: Amblyopia OD

e. Gave Rx +1.50 OD near use

f. Rx no help-told to try to “get used to the glasses”

g. 3 wks later VA OD=20/100-went to another doctor

h. Dx: POHS

Case 5 “Eyes Not Straight All the Time”

a. 11 yo female cc: “eyes not straight all the time”

b. BCVA OD -0.75-0.75 X 90 20/70 OS -0.50 20/20

c. Cover test: Right XT at distance, exophoria at near

d. Keystone skills: “dog over pig”, 3 balls D/N, near phoria-exo’

e. Checklist used: Disc, macula, IOP “checked off”

f. Dx: Amblyopia 2* rt exotropia at distance; VT suggested

g. Pt returns 2 years OD= 20/400, VA OS=20/20

h. Optic nerve: OD “extreme cupping”, OS “moderate cupping”

i. NCT: OD=51 OS= 49

j. Dx: Advanced glaucoma OD>OS

Case 6 “Amblyopia 2* 0.50D Anisometropia”

a. 7 yo female routine exam

b. BCVA OD +0.25-0.25X 120 20/20, OS +0.75-0.75X180 20/30

c. CVF: Normal, Ophthal: Normal-(could not legally dilate)

d. Dx: Amblyopia OS 2* 0.50D anisometropia in sph and cyl

e. 2 yrs later gets hit in OD (the better eye). Sees an MD

f. Vitreous hemorrhage and exudates in temporal retina OS

g. Dx: Coat’s Disease

Case 7: Case of the Shrinking Eye

a. 7 yo female

b. BCVA=20/60 OD (+6.00D) 20/20 OS (Plano)

c. OD Pupil: not reactive to light or accomodation; irregular

d. No strabismus, +fusion at near, but suppressed OD at distance

e.IOPs: OD=10mm OS: 16mm

f. SLE: Old KPs, OD and 1+ cells/flare

Pred forte BID OD

g. Patching trial for 2 hours each day for anisometropic amblyopia, OD;1 mo. f/u tapered PF to QD

h. 2 mos later, uveitis recurred

i.VA OD: 20/70 (+7.00D)

j.2+ a/c cells and 2+ vitritis

k. IOPs: OD=4mm (was 10mm)

l. Macular folds on DFE

m. PF increased to TID OD

n. VA decreased to 20/150 OD with a +9.00-0.75 X 110

o. Stable fundus exam

p. Hertel exophthalmometry:

OD=5mm OS= 11mm (84 base)

r.Why is the OD “shrinking”?

s: Dx: Parry-Romberg Syndrome