OCULAR PATHOLOGY

IN CONGENITAL INFECTIONS
Swiss Eye Institute and University of Bern, Switzerland

Ocular Embryology and Congential Infection

Gestational age

Morphological Development

2 weeks / 2.5 mm

Eye region

3 weeks / 4 mm

Eye vesicle, lens plate

4 weeks / 9 mm

Formation of inner and outer neuro-ectoderm

by invagination of the eye vesicle pole

6 weeks / 13 mm

Lens vesicle differentiates from the ectodermal

surface

9 weeks / 40 mm

Development and differentiation of vitreous and

ocular vessels from the mesodermal germ cells

16 weeks / 100 mm

Differentiation of central retinal vessels

Ocular Pathology in Congenital Infections

theoretical considerations
- Herpes viruses may prefer
ectodermal, ideally
neuroectodermal structures
- Toxoplasma predilects
neuroectodermal structures
(neuroretina and retinal pigment
epithelium) and muscle tissue
- Rubella affects mesodermal
structures, but may expand to
neuroectodermal ones

Ocular Pathology in Congenital Infections

clinical challenges
- Evident intrauterine infection
- Maternal infectious disease
- pathological ultrasound
- growth retardation

- Pathology randomly detected

- Visual function not assessable
- Duration of disease unknown

AV *1987 _ 2003 left eye: Scar detected by chance

Infectious Diseases of the Newborn

differential diagnosis
Etiology
- Genetically determined diseases
- Pregnancy complications
- metabolic diseases
- tumors
- infections
- trauma

Hereditary Sphingolipidosis

Inflammatory Eye Diseases of the Newborn

- postnatally manifested inflammatory systemic
diseases with ocular involvement
- postnatally manifested inflammatory eye diseases
- perinatally acquired infection (birth chanel)
- congenital infections

Drivers in the
Inflammatory Process
in Adult Individuals

Host immune response

(immunogenetic
and local factors)

Causative factors
(infectious agent,
rheumatoid/immune disease)

Therapy and comorbidity

Immunologically Privileged Sites

- brain
- eye
- testis
- uterus and fetus

Neonatological Infectious Diseases

Pediatric Considerations

- Source of problems: mother or child ?

- Immature immune cells :

- Little specific cellular immune response
- Less inflammatory tissue destruction
- More infectious tissue damage

Infection as the Gatekeeper of Destruction

in Congenital Infections

CONGENITAL AND PERINATAL INFECTIONS

WITH OCULAR INVOLVEMENT
Congenital Infections
(TORCHS group)

Toxoplasmosis
Rubella
Cytomegalovirus (CMV)
other Herpesviruses
(HSV-1, HSV-2,VZV; EBV?)
Syphilis

Peri- and short postnatally

acquired infections
Gonococci
Chlamydia
HSV-2

Immunisation Variola
Borreliosis
Adenovirus
Staphylococci and
Streptococci

KD 121170_310876 cTx

RISK OF VISUAL IMPAIRMENT DUE TO

CONGENITAL OCULAR TOXOPLASMOSIS
281 children with confirmed CT, follow up 4.8 years (median)
ocular manifestations (patients)

49

17%

lesion at the posterior pole

32

65%

31/33

94%

21/23

91%

29/69

42%

15/29

52%

19/69

28%

17/19

84%

normal visual acuity in the better eye

normal visual acuity despite mac lesion

lesion at the posterior pole (eyes)

beyond these normal visual acuity

peripheral lesion without central involvement

Beyond these normal visual acuity

bilateral visual impairment (children)

Tan HK. Am J Ophthalmol 2007; 144: 648 - 653

4/44

9%

Congenital Infections
congenital ocular toxoplasmosis

Primary Ocular Manifestation of CT

Kaplan-Meier Survival Estimate

95%, pointwise confidence band shown

1.00

0.75

0.50

0.25

0.00
0

10
follow up time (years)

15

20

Congenital Infections
congenital ocular toxoplasmosis

Pathophysiology of Ocular Toxoplasmosis

Congenital Infection
- persistence of tissue cysts in the healthy retina
- peripheral and central chorioretinal scars
(in up to 50% including macular involvement)
- recurrences in consequence of cyst ruptures
with liberation of tachyzoites
- the severity of ocular involvement correlates
with the gestational age at infection

MW 17.01.69_130192
Retinochoroiditis recurrence

KD 121170 070380/220898 cTx

Cornerstones of Clinical Evolution

- Ocular lesions may be present at birth in 10 -20 %.
- New ocular manifestation is observed even decades
after birth.
- Beyond the prognostic factors:
- Time of maternal infection (late pregnancy: higher risk)
- Age of the child at time of diagnosis
(Dx before birth: higher risk)

- Children harbouring these risks need close follow up.

Congenital Infections
Congenital cataract
due to rubella embryopathy

Congenital Infections

Rubella embryopathy
with ophthalmia

KD 020370 280995 congenital rubeola infection

OCULAR INVOLVEMENT IN CONGENITAL

TOXOPLASMOSIS AND CMV INFECTION
Infection

CMV

Toxoplasmose

Seroconversion
during pregnancy

1-4%

0.5 3%

Intrauterine fetal
infection

0.25 2.5%

20 35%
1. Trimester 6 (18) %
2. Trimester 27 (1935)%
3. Trimester 67 (4879)%

Symptomatic

10 20%
(0.01-0.5%)

20 45%
(4 15%)

Ocular involvement

0.05 0.5%
(<0.001%)

50 90%
(2 13.5%)

recurrences

? (unlikely)

20 50 (-80%)

Wallon M. Pediatrics 2006; 113: 1567-72; Orney A. Isr Med Assoc J 2007; 9: 398 - 401

Congenital Varicella Infection

Maternal primary infection usually during 10.-20.
gestational week
(earlier in pregnancy sponataneous abortion probable)
ocular involvement in up to 38%, usually bilateral

At birth / time of diagnosis no activity

cataract
Optic atrophy
chorioretinal scars
Neuroretinal atrophy
microphthalmus

DD: congenital toxoplasmosis, but much more extended

lesion areas and usually little choroid involvement
Sauerbrei A, Wutzler P. Med Microbiol Immunol. 2007; 196: 95 - 102

Acute retinal necrosis

due to systemic primary VZV infection

Progressive Outer Retinal Necrosis

due to VZV

CMV Retinitis, idiopathic T cell defect

Congenital Infections
Lues

AAO 1996

Condensate
Congenital, i.e. intrauterine infection has to be differentiated from
birth chanel-acquired infectious diseases.
Fetal infections are important and virtually preventable causes of
severe childhood blindness.
Birth chanel-acquired infections primarily manifest on the ocular
surface, fetal ones present with chorioretinal scars as characteristic
ocular pathology.
Direct infectious tissue destruction exceeds the inflammatory
damage.
Beyond all cases included by the mnemonic TORCHS, Lymphocytic
Choriomeningitis virus and West Nile virus, congenital toxoplasmosis
resembles the most frequently manifested and, due to its typical
appearance the most frequently diagnosed congenital infection of
the eyes.