Retinopathy of prematurity:

Altered development
A disorder with a uniquely
American heritage

Early History
Silverman, WA. Retrolental Fibroplasia: A
Modern Parable. Monographs in
Neonatology. 1980
Dr. Stewart Clifford, Boston pediatrician
discovers first case -1941
Dr. Harry Messenger, Boston
ophthalmologist coined the term RLF

RLF National Cooperative Study

Group

Scarring
RLF

No
Scarring
RLF

Total

Routine

39

47

Curtailed

20

405

425

Total

28

444

472

Relative Risk = 3.6 ( 95% CI 1.7 7.75)

Normal oxygen values

Uterine
vein
(mom)

Umbilical Umbilical
artery
vein

P02

40

15

27

Hb sat
(%)

76

30

68

Oxygen
content

12.2

6.4

14.5

Hb g/dl

12

16

16

Avery et al. Neonatology: Pathophysiology and Management of the

Newborn, 4th ed. Pg 130, table 11-2.

Retinal vascular development

(ontogeny)
The choroidal vessels can supply the thin
retina via diffusion
The retinal nerve cells (photoreceptors)
develop from the optic nerve to the
periphery
Additional blood supply develops as the
retinal nerve cell layer becomes thicker

Ontogeny of the retinal vascular

bed
Inner vascular plexus
Within the nerve fiber layer
Capillaries appear around the 16th week of
gestation and reach the ora serrata at about
32 36 weeks gestation nasally and
temporally just before term
Vasculogenesis

The goal supply blood to the

maturing retina

http://www.tsbvi.edu/Outreach/seehear/winter98/ICROP.gif

Ontogeny of the retinal vascular

bed
Outer vascular plexuses
Develops later in gestation and continues to
develop postnatally
Capillaries arise as cellular buds from the
innermost vessels
Angiogenesis

When ROP develops

How bad is it ?
Stage One A line of demarcation
between the vascular and avascular retina
Stage Two The line comes a ridge
Stage Three The ridge is associated with
neonvascularization entering the vitreous

When ROP develops

How bad is it ?
Stage Four Subtotal detachment of the
retina
IV A is extrafoveal detachment
IV B the detachment includes the fovea

Stage Five Total Detachment

The old retrolental fibroplasia
An International Classification of Retinopathy of Prematurity. Arch Ophthalmol.
1987;105: 906-912.

When ROP develops

How bad is it ?
Plus Disease very tortuous vessels
implying high blood flow; bad
Rush Disease Plus disease in zone 1

Stage One

http://ropard.org/ The Association for Retinopathy of

Prematurity and Related Diseases

Stage Two

Stage Three

Stage Four

Stage Five

When ROP develops where is it?

ROP A disease that can regress

BW < 1250 gm

1981 -1985
n = 185

1985 1988
n = 226

Mild ROP

86 (46%)

118 (52%)

Moderate ROP

24 (13%)

35 (15%)

Severe ROP

10 (5%)

12(5%)

ROP A disease that can regress

Stage one Stage two

Stage three

Birth weight
< 750 gm

18%

34%

48%

750 999

30%

38%

31%

1000 - 1250

51%

31%

18%

Pediatrics. 2005;116:15 23.

Incidence inversely proportional to

gestational age at birth

Incidence inversely proportional to

gestational age at birth
ETROP

CRYO-ROP

< 27 wks

89%

83%

> 27- 31 wks

52%

55%

> 32 wks

14%

30%

Prevention of severe disease

Primary decrease the number of infants
born at the gestations with highest risk
Secondary
An agent that will prevent the retinal blood
vessel drop out after birth in very premature
infants
Limit the vasoproliferative phase
Safe oxygen administration

Prevention of severe disease

Cryotherapy and laser therapy limit the
vasoproliferative phase by destroying the
avascular retina once THRESHOLD has
been reached
Intravitreal bevacizumab (Avastin)
injection

Prevention of severe disease

Cyrotherapy outcome at 5 years
Treated Eye

Control Eye

Normal

103 (49%)

68 (33%)

Total retinal
detachment

46 (22%)

80 (39%)

Blind

70 (31%)

106 (48 %)

Arch Opthalmol. 1996;224:417-424

Earlier treatment of disease in Zone

One
Early Treatment Conventional
Treatment
Normal

213 (64%)

200 (62%)

Blind or Low
vision

33 (10%)

47 (15%)

Arch Opthalmol. 2003; 121:1684-96

Limit excessive oxygen exposure

Conclusion: Inappropriate oxygen use is a neonatal
health hazard associated with aging, DNA damage and
cancer, retinopathy of prematurity, injury to the
developing brain, infection and others. Neonatal
exposure to pure O2, even if brief, or to pulse oximetry
>95% when breathing supplemental O2 must be avoided
as much as possible

Sola, A, et al. Acta Paediatrica. 96(6):801-812,

June 2007.

Limit oxygen exposure

Chow et al. Pediatrics. 2003;111:339-45

Screen
All infants with birth weights less than
1500 grams or gestational age less than
32 weeks
Begin at 4 to 6 weeks
Continue until mature (vascularized to the
periphery)

Other ophthalmologic sequelae

Regressed
ROP

No ROP

Strabismus

31%

19%

Myopia > 3 D

16%

2%

Decreased
vision

31%

5%

Cats B. and Tan K. J Ped Opthamal & Strabismus. 1989:271-75

Myopia related to ROP

Quinn GE et al.Opthalmology 1998; 105:1292-1299

Myopia related to ROP

Quinn GE et al.Opthalmology 1998; 105:1292-1299