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Changing Pattern of Retinopathy of Prematurity: A 37-Year Clinic Experience


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of Retinopathy



A 37-Year



A. H. Hoon,

MD, J. E. Jan, MD, M. F. Whitfield,


A. 0. McCormick,

MD, CM, D. P. Richards,



G. C. Robinson,


From the Department of Paediatrics, University of British Columbia, Visually Impaired Program, and Neonatal Follow-up Program, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada

ABSTRACT. A retrospective analysis was done of

multi-disciplinary neurodevelopmental assessments in 70

chil-then who were legally blind because of cicatricial

retinop-athy of prematurity. The subjects lived in British

Colum-bia and were born during a 37-year period between 1951

and 1987. The purpose of the study was to investigate changes in the perinatal characteristics and to evaluate

the associated handicaps. All patients were assessed at

least once in the Visually Impaired Program, British Columbia Children’s Hospital. In the majority, the visual

loss was profound. Since 1951, blinding retinopathy of

prematurity has become a disease ofprogressively smaller

and less mature infants. Since 1981, it has been almost

entirely confined to infants of birth weight less than

1,000 g in British Columbia. The diagnosis of mild spastic

diplegia was made more commonly in patients born after

1980 but, despite the progressive reduction in birth weight

and gestational age during the study period, the number

of patients without other associated handicaps remained

constant (approximately 30%) during each successive

decade. Pediatrics 1988;82:344-349; retinopathy of

pre-maturity, blindness, handicap, very low birth weight.

Despite 40 years of medical progress, netrolental

fibroplasia, or retinopathy of prematurity, as it is

now called, continues to be a handicap among the

intensive cane nursery graduates.1 Silverman and

Flynn2 estimated that there were 10,000 cases

worldwide during the years 1943 to 1953 when

retinopathy of prematurity was seen in epidemic

proportions. With restrictions in the use of

supple-mentany oxygen, the prevalence of retinopathy of

prematurity decreased. It is again increasing despite

Received for publication Dec 27, 1987; accepted March 8, 1988.

Reprint requests to (J.E.J.) Visually Impaired Program, British

Columbia Children’s Hospital, 4480 Oak St, Vancouver,

British Columbia V6H 3V4 Canada.

PEDIATRICS (ISSN 0031 4005). Copyright © 1988 by the

American Academy of Pediatrics.

wide availability and use of better techniques for

surveillance of PA02.3’4 Phelps5 estimated that in

the United States in 1979 there were 546 infants

blinded from retinopathy ofprematunity in addition

to those affected by cicatnicial sequelae. Robinson

et al6 showed a slight increase in birth prevalence

rates for blinding retinopathy of prematurity in

British Columbia since the mid-1970s, although the

rates are well less than the epidemic numbers of

the 1950s.

There has been speculation concerning the

pos-sible risk factors related to the acute stages of the

disease.79 A few articles were written concerning

the neurodevelopmental outcome of infants with

blinding retinopathy of prematurity, but long-term

studies of trends have not been published


The purpose of this retrospective study was to

investigate changes in the characteristics of

new-horns blinded by retinopathy of prematurity and in

the pattern and severity of associated handicaps of

children who were examined in the Visually

Im-paired Program of the British Columbia Children’s

Hospital since 1970.


The Visually Impaired Program was established

in 1970 as a provincial assessment facility for blind

children in British Columbia. In 1985, the program

served a population of 2.7 million people, with a

delivery rate of 43,000 pen year, with one provincial

tertiary perinatal center at Grace and Children’s


Within the Visually Impaired Program,

multidis-ciplinany patient assessments are done. The team

includes a pediatric neurologist (J.E.J.), an


psy-1951-1960 1961-1970 1971-1980 1981-1987

(n = 11) (n = 19) (n = 17) (n = 23)

Gender (No.)

Male 4 9 11 10

Female 7 10 6 13

Birth place (No.)

British Columbia 8 11 15 21

Other 3 8 2 2

Birth wt (g)

Mean 1,279 1,197 957 795

Range 737-1,644 850-1,616 580-1,134 580-1,200

Gestational age (wk)

Mean 29.7 29.5 28.1 25.6

Range 26-34 26-34 24-34 22-28

Last assessment (age in yr)

Mean 17.1 10.3 6.6 2.0

Range 13-22 3.5-17.5 3.5-10 0.3-5

chologist, a speech pathologist, a physiotherapist,

and an audiologist. Other specialties are involved

in individual cases. The referral of patients to the

Visually Impaired Program and the integration of

services received by the visually impaired are

facil-itated by the Canadian National Institute for the

Blind. Recently, coordinated assessments of new

infant patients with retinopathy of prematurity

have also been made with the Neonatal Follow-up

Program, British Columbia Children’s Hospital (M.F.W., A.H.H.).

A total of 70 patients with retinopathy of

pre-maturity (34 boys and 36 girls) were studied; they

had visual acuity of 20/200 or less in the better eye

with connection. Of these, 55 patients were born in

British Columbia and 15 patients were born

else-where. Single-occasion assessment was made of 42

patients; 28 were assessed more than once. In

pa-tients seen several times, the most recent

evalua-tion was used in determining neunodevelopmental

outcome. Of the 70 patients, 11 wene bonn between

1951 and 1960, 19 between 1961 and 1970, 17

be-tween 1971 and 1980, and 23 in the 7-year period

from 1980 to 1987. Although the majority were

assessed during childhood, some of those born

be-fore 1960 were seen as young adults. Results of

neunodevelopmental assessments of patients born

after 1981 may not yet reflect ultimate outcome,

because many of these patients were less than 3

years of age.

A battery of standardized, age-appropriate

psy-chologic tests suitable for visually impaired children

were administered by the developmental

psycholo-gist, who had extensive experience in testing

visu-ally impaired children. A description of the

psy-chologic assessment of blind children as it is done

in our clinic has been published elsewhere.”

Although the patient population represents

nearly all infants with blinding retinopathy of

pre-TABLE 1. Demographic Data

Demographic Data

maturity bonn in British Columbia during the last

17 years, the ascertainment prior to this period is

less complete. The influence of emigration,

decreas-ing neonatal and postnatal mortality, the changing

practice of institutionalizing severely handicapped

infants, and other epidemiologic factors were not

considered. Therefore, this is not an accurate study

of incidence or prevalence in a geographically

con-fined area but a profile of clinic population

through-out a prolonged period of time. Nevertheless, we

believe that the data are valuable and that they

merit publication.


Details of the study population by decade of birth

are given in Table 1. There was a progressive

de-crease in birth weight and gestational age from the

1950s to the 1980s. Only two infants of 22 born

after 1980 had a birth weight greater than 1,000 g.

Growth failure in weight, length, and head

circum-ference was a common finding (Table 2).

Hydro-cephalus developed in one child from the 1971 to

1980 and two patients from the 1981 to 1987

pe-nods. Head growth appears to have been more

appropriate in those born in the 1980s, but a greaten

proportion of infants were underweight and of short

stature. These findings parallel the growth

prog-nosis of sighted infants born in the same decade

and within the same birth weight cohort (MF

Whit-field Neonatal Follow-up Program, British

Colum-bia Children’s Hospital, Vancouver, Canada, 1987).

In Table 3, details of visual function are shown.

There was a progressive reduction in the proportion

of patients who had light perception only on no

vision. Some of these children were young, however,

and may yet develop later cicatnicial sequelae


TABLE 2. Growth Failure in Weight, Height, and Head Circumference*

Characteristics 1951-1960

(n = 11)


(n = 19)


(n = 17)


(n = 23)

Wt 1 3 6 5

Height 1 2 7 6

Microcephaly 2 4 3 2

* Results are given in numbers of patients. Measurements of weight and length were

compared to National Center for Health Statistics percentiles!5 Growth failure in weight

and length was defined as a measure less than the fifth percentile. Microcephaly was

defined as a head circumference more than 2 SD less than the mean for sex and age.

TABLE 3. Residual Vision*

Vision 1951-1960

(n = 11)


(n = 19)


(n = 17)


(n = 23)

20/200-20/400 1 3 7 4

20/400 to perception 1 2 1 9

of hand movement

Light perception 4 8 9 9

None 5 6 0 1

* Results are given in num

hers of patients.

the children of school age were Braille- rather than


The results of the neurologic examination are

given in Table 4 and results of developmental and

psychologic assessments are presented in Table 5.

The overall incidence of mental retardation was

34%. These results also show that from 1951 to

1980 there was no change in the proportion of

children who were mentally retarded. However,

Sufficient data are not yet available regarding the

new survivors of ultraintensive neonatal care (born

after 1980) to provide a clean prediction of their

later functioning. Speech and language problems,

learning difficulties, and psychiatric problems are

detailed in Table 6. A total of 19 (26%) patients

had severe behavioral problems. Seven were

re-ferned to psychiatric and five to special treatment

facilities. Many of these children exhibited marked

autistic-like behavior. The overall spectrum of

handicaps present in addition to visual impairment

is given in Table 7. A total of 26% of patients had

cerebral palsy. Seven infants born prior to 1980 and

seven born after 1980 had spastic diplegia. Three

children had other types of cerebral palsy and one

child bonn between 1960 and 1970 acquired his

hemiplegia secondary to severe dehydration at 4

years of age. The majority of children with spastic

diplegia were mildly affected. Seizures, hearing loss,

learning disabilities, and speech and language

dis-orders are included as other disorders.

A seizure disorder was present in 14 (20%)

chil-dren, four of whom had seizures confined to the

newborn period. As part of another study,16 26

EEGs were obtained in 20 children with

retinopa-thy of prematurity. These records were located and

reassessed. Fourteen records showed either

occipi-tal #{244}-waves or spikes, which were associated in 12

patients with CT evidence of peniventniculan


Of the 62 children who had hearing assessments,

seven (11%) patients had sensonineunal hearing

loss. In two patients the bilateral hearing loss was

profound and in two others it was mild. Three

children had mild unilateral hearing loss. The cause

was unclear in all. There was no change in the

incidence of permanent hearing impairment with

time throughout the study period. The proportion

of children free of additional handicaps remained

approximately 30% throughout the study (Table 7).

The 15 patients who were not bonn in British

Columbia but were evaluated in the Visually

Im-paired Program received their peninatal care in

various North American centers. Three children of

11 had no additional handicaps.


This study provides a unique panorama of

changes occuning in patients with blinding

retinop-athy of prematurity during a 37-year period. The

study period spans the era of liberal, uncontrolled

oxygen use (early 1950s), drastic curtailment of

oxygen use after the first cooperative study (early

1960s in Vancouver)’7 leading to availability of

methods for measuring arterial partial pressure of

oxygen in small blood samples, and arterial

cathe-tenization in the later 1960s and early 19705.18 It

also includes the introduction and subsequently

ready availability of tertiary negionalized perinatal

care in the 1970s and 1980s, supported by major

technologic advances such as continuous oxygen


TABLE 6. Speech, Language, and Psychiatric Disorders*

1951-1960 1961-1970

(n=11) (n=19)

1971-1980 1981-1987

(n = 17) (n = 23)t

Speech and language 1 0 3

Learning 2 3 5

Psychiatric 4 3 8

0 0 4

* Results are given as numbers of patients.

t Of these, 12 children were too young for accurate evaluation.

TABLE 7. Overview of Associated Handicaps*

1951-1960 1961-1970 1971-1980 1981-1987

(n = 11) (n = 19) (n = 17) (n = 23)

Handicap (No. of children)

Mental retardation 4 4 6 5

Cerebral palsy 3 5 2 8

Psychiatric 4 3 8 4

Other 5 12 11 10

No.(%)ofhandicapped 8(73) 12(67) 12(71) 11/15t(73)


fully assessed for

TABLE 4. Neurologic Examination*




(n = 11)t


(n = 19)


(n = 17)


(n = 23)

Normal 3 6 3 8

Borderline 3 4 9 4

Abnormal 4 91: 5 11

* Results are given as numbers of patients. Borderline abnormal results included mild

hypotonia and impaired coordination. Abnormal findings were most commonly, but not

always, due to spastic diplegic cerebral palsy.

t In one child, the examination was not done by a neurologist.


Includes one child who at 4 years of age became hemiplegic.

TABLE 5. Developmental Delay and Psychologic Assessment*


Psychologic Assessment


(n = 11)


(n = 19)


(n = 17)


(n = 23)

Early developmental delay 8 12 10 10

Formal IQ testing

Above average 0 1 2 0

Average 7 14 9 3

Mental retardation 4 4t 6 5

* Results are given as numbers of patients. For analysis purposes, above-average

intelli-gence was defined as a global IQ greater than 110 and mental retardation as an IQ of 70

or less. Developmental delay was noted in children younger than 2#{189}years and too young

for formal psychologic assessment who were slower than average in reaching childhood


t One child, in whom brain damage was apparent at 4 years of age, was included.


Of these, 15 children were too young to have formal psychologic testing.


* Some children had more than one handicap.

t Eight children were 13 months of age or younger and could not be

mental retardation and learning disabilities.

oximeten) and major improvements in ventilator In each of the four decades, approximately 30%

and incubator design and reliability. of the patients had no additional handicaps. The

One of the most striking findings in this study remaining 70% had a wide spectrum of disabilities

was a confirmation that the birth weight of the including cerebral palsy, mental retardation,

deaf-study children with retinopathy of prematurity has ness, and learning and psychiatric difficulties. In a

progressively decreased during the study period. survey of all causes of congenital blindness

includ-Clearly, most premature infants who developed net- ing retinopathy of prematurity in British Columbia

inopathy of prematurity in recent years would have from 1945 to 1984, Robinson et al6 reported that


handi-caps. Since 1960 however, the proportion of

chil-dren without additional handicaps has increased to

5o%#{149}6When searching for neurologic handicaps, it

is important to assess children beyond infancy.

Indeed, Gillman and Goddard’9 noted an increasing

number of additional handicaps in 77 legally blind

children as they grew toward maturity.

The overall incidence of mental retardation

(30%) in our clinic population is similar to that

reported by other authors.”9’2#{176} It is well recognized

that retinopathy of prematurity itself does not lead

to mental retardation; many of the patients in this,

and in other studies, have normal or superior


The percentage of patients with abnormal

neu-rologic findings did not change during the study

period, but the incidence of spastic diplegia

in-creased. The diplegia was usually mild, affecting

the legs mainly, but permitted ambulation. The

increase in spastic diplegia correlated with the

pro-gressive reduction in birth weight of the infants

blinded by retinopathy of prematurity.2’

During the last two decades, there have been

more children in the retinopathy of prematurity

study with residual vision than before, but these

younger subjects remain at risk for late

complica-tions such as retinal detachment or glaucoma.22 The

severity of visual loss in patients with retinopathy

ofprematunity reflects the inability of modern

med-icine to control the progression of this ocular

dis-order that can be readily diagnosed in the acute

stage. The incidence of sensonineural hearing loss

among graduates of the neonatal intensive care unit

whose birth weight was less than 1,500 g is reported

to be between 2% and 10%, but in most cases there

is no clear causitive factor.23 Unilateral on bilateral

sensonineural hearing loss was present in 7 (11%)

of the children in our study, two of whom were

classified as deaf-blind.

More than one quarter of the patients exhibited

severe behavioral problems. The association of

au-tistic behavior and children with retinopathy of

prematurity is well documented in the literature.24

This is thought to be related to CNS injury rather

than to environmental deprivation, and it is not as

prominent in children with most other ocular

le-sions.24 The numbers in this report and the young

age of the most recent patients do not permit any

comment about trends.

The EEGs of children with retinopathy of

pre-maturity have been studied.25’26 The records of these

individuals frequently show posterior #{244}-activity

with or without occipital spikes. The presence of

peniventnicular leukomalacia appears to explain

these changes.’6 The records ofblind children

with-out any additional neurologic deficits do not show

these abnormalities, and the generation of

a-rhythm is affected only when the visual loss is severe, at the level of finger counting on less.’6

Large-trend studies of children with blinding

ret-inopathy of prematurity such as ours have not been

published before. It has repeatedly been emphasized

in the literature that the results of follow-up studies

concerning very low birth weight infants cannot be

accurately compared. Important variables include

the time of publication, duration of follow-up,

pre-natal care, prematurity and birth weight of the

infants, birthplace (ie, whether newborn was born

in or transported to the peninatal center), and social

and economic factors. Nevertheless, although by

selection all of our patients were blind, only 30%

were free from additional neurologic handicaps. In

contrast, in follow-up studies of very low birth

weight, sighted infants, fewer than one third had

one or more additional neunologic handicaps.273’

This clearly suggests that the majority of infants

with blinding retinopathy of prematurity are

ex-posed to more severe neurologic insults than their

sighted contemporaries.

In summary, this retrospective analysis confirms

that, because of modern intensive care techniques,

blinding retinopathy of prematurity has become a

disease primarily affecting infants smaller than

1,000 g. The study clearly shows that despite the

downward change in birth weight and gestational

age, the number of survivors without associated

handicaps has remained constant (approximately

30%) throughout nearly four decades. However,

mild spastic diplegia has increased as a result of

lower birth weight and shorter gestational age of

affected patients. Finally, the visual loss is profound in the majority of patients with severe retinopathy of prematurity.

In the 1980s, the increasing survival of infants of

less than 1,000-g birth weight may cause a

signifi-cant increase in the absolute numbers of very low

birth weight infants blinded by retinopathy of

pre-maturity. By the end of the decade, this will further

strain the services that support visually impaired

and handicapped individuals.


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A. H. Hoon, J. E. Jan, M. F. Whitfield, A. Q. McCormick, D. P. Richards and G. C.

Changing Pattern of Retinopathy of Prematurity: A 37-Year Clinic Experience


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