Background: Retinopathy of prematurity (ROP) is a serious complication of prematurity treatment and can lead to blindnessunless recognized and treated early. Objectives: The objectives were to estimate the prevalence of ROP in preterm infants in theneonatal intensive care unit (NICU), to identify the risk factors which predispose to ROP, and to assess the outcome of these cases.Methodology: A retrospective screening survey was performed enrolling all premature neonates admitted to the NICU betweenJanuary and December 2016, with a gestational age of 32 weeks or less at birth and a birth weight of 1500 g or less. Infants whosegestational age was &gt;32 weeks or birth weight was &gt;1500 g were included if they were exposed to oxygen therapy for more than7 days. A total of 344 neonates had a retinal evaluation by indirect ophthalmoscopy from the fourth postnatal week and followedup periodically. Perinatal risk factors for ROP were assessed using univariate and multivariate analysis. Infants who progressedto Stage 3 ROP were given laser therapy. Results: Out of the studied 344 neonates, 66 (19.2%) developed ROP in one or botheyes; 36 (54.5%) cases had Stage 1, 18 (27.3%) cases Stage 2, and 12 (18.2%) cases had Stage 3 ROP. None had Stages 4 and5 ROP. The 12 cases diagnosed as ROP Stage 3 underwent LASER therapy. Univariate analysis showed a significant relationshipbetween the occurrence of ROP and gestational age (p=0.001), sepsis (p=0.004), oxygen therapy (p=0.018), and frequent bloodtransfusions (p=0.030). However, an insignificant relationship was found between the occurrence of ROP and factors such asgender, mode of delivery, birth weight, respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage,hypotension, phototherapy, and duration of oxygen therapy, mechanical ventilation, and continuous positive airway pressure.Gestational age, sepsis, oxygen therapy, and frequent blood transfusions remained significant variables after logistic regressionanalysis. Conclusion: The prevalence of ROP in this study was 19.2%; low gestational age, sepsis, oxygen therapy, and frequentblood transfusions were significant risk factors for ROP. LASER was effective in the treatment and decreasing the progression ofROP

Kamalarathnam1, C N

Kumar, K Lathiesh

Seeralar, A T Arasar

English

Atharva Scientific Publications (E-Jounals)

Vol 4 | Issue 3 | Jul - Sep 2017 Indian J Child Health 390
Original Article
Retinopathy of prematurity in a tertiary care center: A study of prevalence, risk 
factors, and outcomes
K Lathiesh Kumar1, A T Arasar Seeralar2, C N Kamalarathnam1
From Department of Neonatology, 1Institute of Child Health and Hospital for Children, 2Institute of Obstetrics and Gynecology and Government 
Hospital for Women and Children, Madras Medical College, Chennai, Tamil Nadu, India
Correspondence to: K Lathiesh Kumar, Department of Neonatology, Institute of Child Health and Hospital for Children, Madras 
Medical College, Chennai, Tamil Nadu, India. E-mail: dr.lathiesh@gmail.com
Received - 10 March 2017 Initial Review - 14 April 2017 Published Online - 18 May 2017
Retinopathy of prematurity (ROP) is a disease that can cause blindness in very low birth weight (VLBW) infants. The incidence of ROP is closely correlated 
with the weight and the gestational age at birth. Despite current 
therapies, ROP continues to be a highly debilitating disease. Our 
advancing knowledge of the pathogenesis of ROP has encouraged 
investigations into new anti-vasculogenic therapies. ROP is an 
important cause of preventable blindness in children [1].
In developed countries, its incidence continues to increase 
with the improvement in the survival of extremely premature 
infants [2,3]. Until recently, the survival rates of VLBW neonates 
in India were relatively low and therefore, ROP was considered to 
be rare. With improving outcomes of the “at-risk” preterm infants 
at several newborn care centers, ROP is likely to emerge as a 
major problem in India. We assessed the prevalence of ROP in our 
setting and evaluated its association with a number of neonatal 
risk factors retrospectively.
METHODOLOGY
After obtaining approval from the ethics committee of the 
university, this study was pursued. A retrospective study was 
conducted in the neonatal intensive care unit (NICU) of the Madras 
Medical College, Chennai. The study population consisted of 
344 neonates who were screened for ROP, between January and 
December 2016. Neonates who satisfied the following criteria 
were included in the study: (i) Gestational age of 32 weeks or less 
at birth and a birth weight of 1500 g or less, (ii) infants whose 
gestational age was >32 weeks or birth weight was >1500 g if 
they were exposed to oxygen therapy for more than 7 days, and 
ABSTRACT
Background: Retinopathy of prematurity (ROP) is a serious complication of prematurity treatment and can lead to blindness 
unless recognized and treated early. Objectives: The objectives were to estimate the prevalence of ROP in preterm infants in the 
neonatal intensive care unit (NICU), to identify the risk factors which predispose to ROP, and to assess the outcome of these cases. 
Methodology: A retrospective screening survey was performed enrolling all premature neonates admitted to the NICU between 
January and December 2016, with a gestational age of 32 weeks or less at birth and a birth weight of 1500 g or less. Infants whose 
gestational age was >32 weeks or birth weight was >1500 g were included if they were exposed to oxygen therapy for more than 
7 days. A total of 344 neonates had a retinal evaluation by indirect ophthalmoscopy from the fourth postnatal week and followed 
up periodically. Perinatal risk factors for ROP were assessed using univariate and multivariate analysis. Infants who progressed 
to Stage 3 ROP were given laser therapy. Results: Out of the studied 344 neonates, 66 (19.2%) developed ROP in one or both 
eyes; 36 (54.5%) cases had Stage 1, 18 (27.3%) cases Stage 2, and 12 (18.2%) cases had Stage 3 ROP. None had Stages 4 and 
5 ROP. The 12 cases diagnosed as ROP Stage 3 underwent LASER therapy. Univariate analysis showed a significant relationship 
between the occurrence of ROP and gestational age (p=0.001), sepsis (p=0.004), oxygen therapy (p=0.018), and frequent blood 
transfusions (p=0.030). However, an insignificant relationship was found between the occurrence of ROP and factors such as 
gender, mode of delivery, birth weight, respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage, 
hypotension, phototherapy, and duration of oxygen therapy, mechanical ventilation, and continuous positive airway pressure. 
Gestational age, sepsis, oxygen therapy, and frequent blood transfusions remained significant variables after logistic regression 
analysis. Conclusion: The prevalence of ROP in this study was 19.2%; low gestational age, sepsis, oxygen therapy, and frequent 
blood transfusions were significant risk factors for ROP. LASER was effective in the treatment and decreasing the progression of 
ROP.
Key words: Oxygen therapy, Prematurity, Risk factors, Retinopathy of prematurity
Vol 4 | Issue 3 | Jul - Sep 2017 Indian J Child Health 391
Lathiesh et al. Retinopathy of prematurity
(iii) neonates between 32 and 34 weeks with a course of instability 
(such as sepsis, asphyxia, or ventilation). Neonates who died 
before the first ophthalmologic examination were excluded. 
Infants with congenital anomalies, chromosomal abnormalities, 
and inborn errors of metabolism were also excluded from the 
study. Risk factors of ROP, perinatal, intrapartum, and postnatal 
were noted in the history.
Findings of local eye examination were noted. In our 
institute, indirect ophthalmoscopy with a 28 diopter lens was 
performed. All infants were being examined regularly by the 
ophthalmologist at 1-2-week intervals from the 4th postnatal 
week onward and were repeated weekly or biweekly, using the 
schedule for follow-up recommended by AAP, AAO, and AAPO, 
until full vascularization of the retina reached zone 3 (the most 
peripheral temporal retinal zone), or until full remission of ROP 
after treatment. The eyes were dilated with a combination of 
cyclopentolate 0.1%, and phenylephrine 0.1% eye drops applied 
one hour before the examination. We followed the criteria 
established by the International Committee for Classification 
of ROP [4]. ROP was defined as the incomplete or abnormal 
vascular proliferation of the retina. The ROP was classified by 
location on the retina (Zone 1-3), and severity (Stage 1-5). All 
the patients diagnosed with Stage 3 ROP were treated with laser 
photocoagulation.
We considered a list of suspected pre and postnatal risk factors 
for ROP to identify independent risk factors associated with the 
development of mild and severe forms of this disease in our 
NICU conditions. The prenatal variables were gestational age, 
birth weight, sex, and mode of delivery. The post-natal variables 
were respiratory distress syndrome (RDS), oxygen therapy, and 
phototherapy for jaundice, frequency of blood transfusions, 
sepsis, hypotension, intraventricular hemorrhage (IVH), and 
patent ductus arteriosus (PDA).
Data were analyzed by the Statistical Package for the Social 
Sciences (SPSS for Windows, version 13.0). Descriptive statistics 
included the mean and standard deviation for numerical variables, 
and the percentage of different categories for categorical variables. 
The prevalence rate of ROP was described in simple proportion. 
Group comparisons were done by the Chi-square test or Fisher’s 
exact test for categorical variables. A logistic regression model 
was performed, and the adjusted odds ratio (95% confidence 
interval) was obtained for the risk factors which had been 
shown to be significant in the univariate analysis. A p<0.05 was 
considered statistically significant.
RESULTS
Of the 344 neonates, 168 (48.8%) were males and 176 (51.2%) 
were females. The mean gestational age was 33.02±1.72 weeks, 
48 were ≤32 weeks, and 296 were >32 weeks. The majority (176) 
weighed between 1000 and 1500 g. A total of 144 cases (41.9%) 
were delivered vaginally, and 200 (58.1%) cases were delivered 
by cesarean section (Table 1). Out of the 344 neonates, 66 (19.2%) 
cases developed ROP in one or both eyes classified as 36 (54.5%) 
cases Stage 1, 18 (27.3%) cases Stage 2, and 12 (18.2%) cases 
Stage 3. None of the studied neonates presented ROP at Stages 4 
or 5. The 12 cases diagnosed as ROP Stage 3 underwent LASER 
therapy.
Table 2 shows the relationship between ROP and risk factors. 
There was a significant relationship between the occurrence of 
ROP and gestational age (p=0.001), sepsis (p=0.004), oxygen 
therapy (p=0.018), and frequency of blood transfusions (p=0.030). 
On the other hand, there was no significant relationship between 
the occurrence of ROP and sex, mode of delivery, birth weight, 
RDS, PDA, IVH, hypotension, phototherapy, and duration 
of oxygen therapy, mechanical ventilation, and continuous 
positive airway pressure (CPAP) (all p>0.05). Table 3 shows the 
relationship between gestational age and stages of ROP. There 
was no significant relationship between the gestational age and 
stages of ROP (p=0.325). Table 4 shows the relationship between 
oxygen therapy and stages of ROP. Those variables that were 
statistically significant after univariate analysis were analyzed 
using logistic regression analysis. Gestational age, sepsis, oxygen 
therapy, and frequency of blood transfusions remained significant 
variables (Table 5).
DISCUSSION
The study showed the prevalence of ROP of 19.2% which was 
similar to that seen in a study by Hakeem et al. [5], but was 
less than most of the other studies such as 29.2% in a study 
by Shah et al. [6] and 32.4% in a study by Taqui et al. [7]. 
The possible reason for this high prevalence could be that 
these studies involved only VLBW infants. Our study found 
low-gestational-age, sepsis, oxygen therapy, and frequency 
of blood transfusions to be independent risk factors for the 
development of ROP. Whereas most of the studies showed low 
gestational age along with low birth weight, to be risk factors 
of ROP [8-10]. The other variables which proved to be non-
significant risk factors in our study (by univariate analysis) 
included sex, mode of delivery, birth weight, RDS, PDA, 
IVH, hypotension, phototherapy, duration of oxygen therapy, 
mechanical ventilation, and CPAP.
However, when we looked at the association of low 
gestational age with the risk of ROP, we found it to be a very 
strong and significant risk factor for ROP, and this finding was 
Table 1: Demographic data of the studied cases (n=344)
Data n (%) or mean±SD
Sex
Male 168 (48.8)
Female 176 (51.2)
Mode of delivery
Vaginal delivery 144 (41.9)
Cesarean section 200 (58.1)
Gestational age (weeks) 33.02±1.72
Birthweight (g) 1510±245
SD: Standard deviation
Vol 4 | Issue 3 | Jul - Sep 2017 Indian J Child Health 392
Lathiesh et al. Retinopathy of prematurity
in agreement with the results of studies done by Shah et al. [6], 
Karna et al. [11], and Fortes et al. [12]. The likely explanation for 
this could be the immaturity of vascularization that induces an 
increased susceptibility of the retina to oxidative damage and to 
a number of perinatal factors which include hyper and hypoxia, 
blood transfusions, and sepsis. Although many studies [6-12] 
found a significant relationship between the gestational age and 
the severity of ROP, our study did not find any such significant 
association. This could be attributed to the reason that we did not 
include more preterm babies in our study.
There was no significant relationship between low birth 
weight and the development of ROP in our study, which was 
controversial to the findings in many other studies [6,12,13]. 
Sepsis was found to have a significant role in the development of 
ROP in our study which was in agreement with Shah et al. [6] and 
Vinekar et al. [14], which could be due to the effect of endotoxins 
on retinal blood vessels.
Table 2: Relationship between retinopathy of prematurity and risk factors
Data Cases with ROP (n=66) (%) Cases without ROP (n=278) (%) p value
Sex
Male (n=168) 34 (51.5) 134 (48.2) 0.732
Female (n=176) 32 (48.5) 144 (51.8)
Mode of delivery
Vaginal delivery (n=144) 34 (51.5) 110 (39.6) 0.211
Cesarean section (n=200) 32 (48.5) 168 (60.4)
Gestational age (weeks)
≤32 (n=48) 22 (33.3) 26 (9.4) 0.0001*
>32 (n=296) 44 (66.7) 252 (90.6)
Birthweight (g)
<1000 (n=6) 4 (6) 2 (0.7) 0.109
1000-1500 (n=174) 32 (48.5) 142 (51.1)
>1500 (n=164) 30 (45.5) 134 (48.2)
RDS (n=120) 28 (42.4) 92 (33.1) 0.312
Sepsis (n=230) 58 (87.9) 172 (61.9) 0.004*
PDA (n=6) 2 (3) 4 (1.4) 0.530
IVH (n=18) 4 (6) 14 (5) 0.812
Hypotension (n=92) 20 (30.3) 72 (25.9) 0.607
Phototherapy (n=312) 60 (90.9) 252 (90.6) 0.963
Oxygen therapy (n=166) 44 (66.7) 122 (43.9) 0.018*
Duration of oxygen therapy
≤1 week (n=94) 30 (45.5) 64 (23) 0.202
>1 week (n=72) 14 (21.2) 58 (20.9)
Mechanical ventilation (n=44) 14 (21.2) 30 (10.8) 0.107
CPAP (n=54) 16 (24.2) 38 (13.7) 0.133
Frequency of blood transfusions
Once (n=50) 6 (9.1) 44 (15.8)
More than once (n=92) 18 (27.3) 28 (10.1)
*p<0.05 is significant, ROP: Retinopathy of prematurity, RDS: Respiratory distress syndrome, IVH: Intraventricular hemorrhage, PDA: Patent ductus arteriosus, 
CPAP: Continuous positive airway pressure
Table 3: Relationship between gestational age and stages of ROP
Stages of ROP Patients with ROP
≤32 weeks,  
(n=22) (%)
>32 weeks, 
(n=44) (%)
p value
Stage 1 ROP (n=36) 8 (36.4) 28 (63.6) 0.325
Stage 2 ROP (n=18) 8 (36.4) 10 (22.7)
Stage 3 ROP (n=12) 6 (27.2) 6 (13.7)
ROP: Retinopathy of prematurity
Table 4: Relationship between oxygen therapy and stages of ROP
Stages of ROP Cases required 
oxygen therapy 
(n=44) (%)
Cases without 
oxygen therapy 
(n=22) (%)
p value
Stage 1 ROP (n=36) 26 (59.1) 10 (45.5) 0.687
Stage 2 ROP (n=18) 10 (22.7) 8 (36.3)
Stage 3 ROP (n=12) 8 (18.2) 4 (18.2)
ROP: Retinopathy of prematurity
Table 5: Logistic regression analysis
Risk factors OR 95% CI p value
Gestational age 3.868 1.656-9.033 0.0001*
Sepsis 1.251 1.082-1.458 0.003*
Oxygen therapy 1.005 1.001-1.009 0.003*
Frequency of blood transfusions 2.483 1.182-5.222 0.016*
*p<0.05 is statistically significant. OR: Odds ratio, CI: Confidence interval
Vol 4 | Issue 3 | Jul - Sep 2017 Indian J Child Health 393
Lathiesh et al. Retinopathy of prematurity
Our study found oxygen therapy to have a significant 
relationship with the occurrence of ROP, which was similar to 
the results of several other studies [6,15,16]. Shah et al. and Ikeda 
et al. [6,16] reported that a duration of oxygen therapy more than 
7 days was a significant risk factor for the development of ROP, 
which was contrary to the results of our study. Both mechanical 
ventilation and CPAP were non-significant risk factors for ROP 
according to our study. Frequent blood transfusions were found 
to be an independent risk factor for the development of ROP, and 
this finding was in agreement with results of a study by Deepak 
et al. [17]. This can be explained by the fact that adult red blood 
cells are rich in 2,3-DPG and adult hemoglobin binds less firmly 
to oxygen, thus releasing excess oxygen to the retinal tissue.
Gender, mode of delivery, RDS, PDA, IVH, hypotension, 
and phototherapy showed an insignificant relationship with 
the occurrence of ROP in our study. The significance of the 
association between risk factors such as low gestational age, 
sepsis, oxygen therapy, and frequent blood transfusions and the 
development of ROP was established in multivariate analysis 
after logistic regression analysis.
Laser photocoagulation is now the preferred mode since the 
most severe forms of the disease are more easily treated with laser 
than with cryotherapy [18]. Laser was found to be very effective 
in regressing ROP. All the 12 cases of Stage 3 ROP were treated 
with Laser and showed improvement with regression of ROP on 
follow-up and this was similar to the findings by Coats et al. [1]. 
The limitations of our study are that it is a retrospective study and 
we did not include many preterm neonates (>32 weeks).
CONCLUSION
We found a 19.2% prevalence of ROP, with low gestational age, 
sepsis, oxygen therapy, and frequent blood transfusions being the 
most significant independent risk factors in the development of 
ROP.
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Funding: None; Conflict of Interest: None Stated.
How to cite this article: Lathiesh KK, Seeralar ATA, Kamalarathnam CN. 
Retinopathy of prematurity in a tertiary care center: A study of prevalence, 
risk factors, and outcomes. Indian J Child Health. 2017; 2017; 4(3):390-393.


Retinopathy of prematurity in a tertiary care center: A study of prevalence, risk factors, and outcomes

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Retinopathy of prematurity in a tertiary care center: A study of prevalence, risk factors, and outcomes

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