Bratisl Lek Listy 2010; 111 (9)

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Indexed and abstracted in Science Citation Index Expanded and in Journal Citation Reports/Science Edition
TOPICAL REVIEW
Retinopathy oI prematurity epidemics, incidence, prevalence,
blindness
Gergely K
1
, Gerinec A
2
1
Faculty oI Medicine, Comenius University, Bratislava, Slovakia, and
2
Department oI Pediatric Ophthalmology, Children`s Teaching Hospi-
tal, Comenius University, Bratislava, Slovakia
Address for correspondence: K. Gergely, MD, Poste Restante, Posta 1,
Jindrisska 14, CZ-110 00 Praha 1, Czech Republic.
Facultv of Medicine, Comenius Universitv, Bratislava, Slovakia. kvetagergelyseznam.cz
Abstract: Currently, there are enough financial resources in industrial most developed countries to provide
quality health care to the risk population of premature children. Neonatological units are equipped with state-
of-the-art technological background, and highly qualified personnel are employed at the units. This as well
allows providing optimum care of extremely immature newborns. ROP prevalence in these countries reaches
approximately 58 %.
Today, a boom of surviving premature newborns can be seen in countries with medium-developed economy.
Nevertheless, limited financing resources do not allow for standard high-level care. In such countries, the
prevalence reaches up to 30 %. In this respect, the third ROP epidemic is mentioned. Birth weight and
gestational age parameters achieve significantly lower values in ROP-infants than in those not affected by the
disease.
Higher number of surviving immature newborns correlates with an increased risk of advanced ROP stages
occurrence, while the frequency and degree of the disease are of inverse nature to the gestational age and
birth weight (Tab. 1, Ref. 39). Full Text in free PDF www.bmj.sk.
Key words: retinopathy, quality health care, children.
Abbreviations: CRYO-ROP-Study Cryotherapy Ior the Treat-
ment oI Retinopathy oI Prematurity Study,ELBW-inIant/s Ex-
tremely low birth weight-inIant/s, ETROP-Study Early Treat-
ment Ior Retinopathy oI Prematurity Study, g Gram, HDI
The human development index, MBW Minimal birth weight,
ROP Retinopathy oI prematurity, UNDP The United Nations
Development Programme, VLBW-inIant/s Very low birth
weight inIant/s, WGA Weeks` gestational age, WHO World
Health Organization
ROP is a vasoproliIerative disease oI the eye, which aIIects
premature newborns (The Committee Ior the ClassiIication oI
Retinopathy oIPrematurity, 1984). The pathological process in-
cludes several Iactors that have an impact on each other: prema-
ture birth, immature pulmonary Iunction, development oI retinal
vessels, maturation oI retinal cells with subsequent growth oI
metabolic demands, activity oI various growth Iactors, eIIect oI
vasoactive substances, and condition oI the antioxidative system
(Reynolds, 2001).
Since 1984, six multicentric studies oI ROP have been con-
ducted:
Cryotherapy Ior the Treatment oI Retinopathy oI Prematurity
Supplemental Therapeutic Oxygen Ior Prethreshold Retino-
pathy oI Prematurity
Light Reduction in Retinopathy oI Prematurity
Early Treatment Ior Retinopathy oI Prematurity
Laser Therapy Ior Retinopathy oI Prematurity
Photographic Screening Ior Retinopathy oI Prematurity
Nevertheless, the exact causal Iactor oI this disease remains
unknown Ior the time being (Bashour, 2006).
Epidemics
Two ROP epidemics occurred in industrial developed coun-
tries during the past 60 years. The Iirst epidemic was diagnosed
in 19401950. In 1951, Campbell Iormulated the idea Ior the
Iirst time that ROP occurred in connection with the introduction
oI oxygen therapy in immature children (Saugstad, 2001). Ac-
cording to studies published between 19511956 it was assumed
that the cause oI this disease was due to hyperoxia in incubators.
Research conIirmed subsequently that high blood oxygen level
causes obliteration oI retinal vessels. AIter this Iinding had been
made, it was recommended to reduce the oxygen supply, and
subsequently, a dramatic decline was observed in ROP incidence.
On the other hand however, a distinctly increased death rate oI
premature children was connected with this phenomenon, namely
due to breathing diIIiculties and neurological changes. These
observations led to lower oxygen reduction, which however, in-
creased again the incidence oI the disease.
In spite oI careIul oxygen supply monitoring, in the course
oI 19701980, a second ROP epidemic was registered while it
was noted that a greater percentage oI ELBW-inIants survived
in industrial developed countries (Gilbert, 2005).
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Gergely K, Gerinec A. Retinopathy of prematurity
At present, we can witness a third ROP epidemic taking place
in industrial medium-developed countries (Gibson, 1989; Chen,
2006; Bouzas, 2007). There are several explanations oI its oc-
currence:
The ratio oI prematurely born children to all newborns is
higher.
The neonatal care level is likely to have decreased due to
insuIIicient Iinancial resources, while screening and therapeutic
programme are not applied at all at neonatological units oI many
cities, towns or countries, respectively. This leads to a higher
number oI advanced ROP stages not only in extremely immature
but also in rather mature children.
The personnel are undereducated and insuIIiciently compe-
tent (Gilbert, 2005).
Prematurely born individuals should be treated at special-
ized departments enabling to consider better the risks occurring
during neonatal care. Good cooperation between ophthalmolo-
gists and neonatologists, especially the elaborated screening,
should make it possible to perIorm timely examinations and pro-
vide all children at risk with optimal timing oI therapy aIter
achieving the required stage (Drack, 1998; Reynolds, 2001;
Wheatley, 2002).
Incidence
Together with the progress in neonatology, the survival oI
ELBW-inIants increased Irom 5 to 65 during the last 40
years, while in VLBW-inIants, it increased Irom 35 to 90 .
The latter increase in survival rates has provided a situation pro-
pitious to increasing the number oI diagnosed ROP cases (The
Royal College oI Ophthalmologists and British Association oI
Perinatal Medicine, 1995; Chen, 1998; Good, 2000; Gilbert,
2005).
CRYO-ROP-Study (I/1986 XI/1987) was the Iirst to deal
with the incidence oI the disease. The study examined this phe-
nomenon in a group oI premature newborns with birth weight
1251 g. Some ROP stage developed in 65.8 oI these new-
borns (Cryotherapy Ior Retinopathy oI Prematurity Cooperative
Group, 1990; Palmer, 1991; National Eye Institute, 2003).
ETROP-Study (X/2000 IX/2002) was a multicentric study
also Iocused on ROP incidence. The study observed a group oI
premature children with birth weight 1251 g. The incidence oI
any ROP stage reached 68 ,decreased sharply with the increas-
ing birth weight and gestational age, and it was lower at the ob-
served study centres compared to other Iacilities (Early Treat-
ment Ior Retinopathy oI Prematurity Cooperative Study Group,
2005).
ROP incidence in both multicentric studies was almost iden-
tical. We attach importance to the Iact that the data oI both stud-
ies can be compared (there was the same birth weight, namely
1,251 g). Despite the Iact that there are many other sophisticated
pieces oI works dealing with ROP incidence, we see a problem
in the Iact that their results cannot be compared since each oI
them used a slightly diIIerent set oI criteria (see examples in
Table 1).
We assume that it would be advisable to observe only stan-
dard weight categories in incidence research: ELBW (1000 g),
VLBW (1500 g), LBW (2500 g). We could thus compare ROP
incidence (and not only ROP incidence) on the worldwide basis,
similarly as in CRYO-ROP-Study and ETROP-Study.
We also think that another special category should be de-
Iined Ior children with birth weight 500 g. We propose to reIer
to this category as minimal birth weight (MBW). There are al-
ready many surviving children with this birth weight, yet their
Iindings do diIIer slightly Irom larger and more mature inIants.
Prevalence
Fielder and Reynolds (Fielder, 2001) dealt with details oI
ROP prevalence in 2001. The authors divided world countries
into categories according to economic indicators, and they used
the same division Ior guiding the prevalence:
Currently, there are enough Iinancial resources in industrial
most developed countries to provide quality health care to the
risk population oI premature children. Neonatological units are
equipped with state-oI-the-art technological background, and
highly qualiIied personnel are employed at the units. This as well
allows providing optimum care oI extremely immature newborns.
ROP prevalence in these countries reaches approximately 58
.
Today, a boom oI surviving premature newborns can be seen
in countries with medium-developed economy. Nevertheless, lim-
ited Iinancing resources do not allow Ior standard high-level care.
In such countries, the prevalence reaches up to 30. In this re-
spect, the 'third ROP epidemic is mentioned. Birth weight and
gestational age parameters achieve signiIicantly lower values in
ROP-inIants than in those not aIIected by the disease.
A very low number oI ROP cases or virtually none is regis-
tered in third-world countries or in countries with low gross do-
mestic product and high mortality oI children. The cause lies in
the absence oI neonatological intensive care units and low index
oI surviving premature newborns, especially ELBW-inIants. For
this reason, Iew premature inIants live up to the age when ROP
Author Age (WGA) Weight (g) Incidence (ROP)
Rehka, 1996 34 1500 46
Hussain, 1999 37 21.3
Larsson, 2002 1500 36.4
Al-Amro, 2003 2000 37.4
Phan, 2003 36 2000 45.8
1250 81.2
Martin Begue, 2003 1501 29.2
Gotz-Wieckowska, 2004 1250 32.6
Shah, 2005 1500 29.2
Good, 2005 1251 68
Fortes, 2007 1000 48.9
1500 18.2
Binkhathlan, 2008 36 2000 56
g Gram, ROP retinopathy oI prematurity, WGA weeks` gestational age
Tab. 1. Different criteria.
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development can occur (thereIore there is also a minimal num-
ber oI older children suIIering there Irom blindness due to ROP).
The ophthalmological specialists accepted the above-men-
tioned division and conIirmed it in their papers, e.g. Flynn (2002),
Lerman (2006), Sitorius (2006), etc. It is sad that in spite oI
eight years that have elapsed Irom publishing the Fielder and
Reynolds work, the situation in groups 2 and 3 has not changed
much, and the prospects Ior near Iuture do not show much hope
Ior an improvement in respect oI the current worldwide economic
problems.
Blindness
The blindness rate due to ROP varies signiIicantly among
individual countries; it depends on their level oI development
including the neonatal care availability and quality, presence oI
eIIicient ROP screening, and therapeutic programme (Lomickova,
1990).
Gilbert et al. (2005) divided the world countries into catego-
ries based on position in tables according to UNDP - HDI crite-
ria. They classiIied the countries as highly developed as long as
they rank top 30 in the UNDP - HDI list (developed industrial
countries). Here, ROP as the cause oI paediatric blindness ranges
Irom 3 to 11 . The population oI newborns endangered by
advanced ROP stages is extremely immature in such countries,
with birth weight almost always 1000 g (Wheatley, 2002).
Countries ranking Irom 31 to 100 according to UNDP HDI
criteria were marked as medium-developed by Gilbert et al.
(2005). In these countries, ROP with an incidence achieving 60
seems to be the most signiIicant cause oI blindness (Gilbert,
1997). These are especially the countries oI Latin America (about
2/3 oI blind children are blind due to ROP) and Iormer Eastern
Bloc countries (those showing medium level oI development).
In this respect, the 'third ROP epidemic is mentioned.
According to Gilbert et al. (2005), countries Iound beyond
the 101st position in the tables mentioned above Iall among low-
developed ones. These countries include the majority oI Sub-
Saharan AIrica and Asia countries. Blindness due to ROP is vir-
tually unknown here and represents no current problem. Care oI
immature inIants is not optimal in these regions, and premature
newborns oI the lowest weight categories do not live long enough
to show the development oI the disease (Wheatley, 2002). South
AIrica is an exception, where ROP-induced blindness is given in
about 11 (Varughese, 2008).
The population in which advanced ROP stages occur in highly
developed countries diIIers Irom that Iound in medium and low-
developed ones (more advanced ROP stages develop in more
mature children here). These Iacts conIirm not only the diIIerent
level oI care provided to premature inIants, but also the need to
adjust the screening criteria in medium and low-developed coun-
tries so that larger and more mature inIants are captured (Phan,
2003; Chen, 2006; Vedantham, 2007). The Ioundation on which
the guideline concerning examined immature newborns is built
in individual countries consists oI an accurate detailed image oI
this population (Ior example, there are screening criteria in US,
which are reviewed and adjusted constantly according to how
such data change) (Gilbert, 2005).
WHO summarized all knowledge mentioned above in a com-
munication according to which ROP is the leading cause oI vi-
sion damage in children in developed countries, while playing
an important role in others. There are three essential possibili-
ties oI prevention oI blindness caused by ROP, namely elimina-
tion oI premature births, changes in neonatal care, and improve-
ment in detection oI threatening ROP markers. In general, there
are approximately 70,000 children in the world, blind due to
ROP (Gilbert, 2008).
Conclusion
Higher number oI surviving immature newborns correlates
with an increased risk oI advanced ROP stages occurrence
(Giannantonio, 2008), while the Irequency and degree oI the dis-
ease are oI inverse nature to the gestational age and birth weight
(Kothari, 2006).
Thirty years ago, Houstk (1979) stated that 'in the human
foetus, the 28th WGA period is considered the lower limit for a
prematurelv born foetus to be able to become viable. We can
see that the survival limit has moved signiIicantly downward,
and thereIore we must be prepared to solve the complications
and problems related to this Iact.
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Received February 24, 2009.
Accepted June 26, 2010.