A TALK on Retinopathy of Prematurity (ROP) mainly for pediatricians THE POWERPOINT presentation describes the important diseaee ofROP KEEPING in view teh responsibilities of neonatologists and pediatricians. Which babies are to be screened and when should they be referred for ROP screening are described. It describes the criteria for screening for ROP, screening regimen, when to treat what are the complications, different methods of treatment an their rationale is described .

1. DR. VIVEK B WANI MS FRCSED
Consultant Vitreoretina surgeon
KLES Dr Prabhakar Kore Hospital & RC
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2. 1/6/2023 ROP FOR PEDIATRICIANS BY DR WANI 2
Who is this?

3. OBJECTIVES OF THIS TALK
Give an overview of ROP
Highlight the role of neonatologists
in management of ROP
 Which babies are for ROP screening
 How to arrange ROP screening
 How to manage discharged babies
 Medico-legal aspects of ROP
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4. Subheadings of the talk
 Overview of ROP
 Introduction
 Definition of ROP
 History and epidemiology
 Pathogenesis
 ROP clinical features and classification
 Risk factors for ROP
 Treatment guidelines and results
 Role -of neonatologists
 Screening protocol
 Whom, when, how, follow ups and medico-legal aspects
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5. Introduction
WHY SHOULD PEDIATRICIANS KNOW ABOUT
ROP?
 There are good reasons
 There are bad reasons
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6. Good reasons are
 By knowing about ROP- you refer at risk babies to
ophthalmologists in time and prevent blindness
 Blindness in babies is for life
 That is a noble service!
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7. Prompt reference, proper screening and laser treatment
done in BE 20 years ago -Now a graduate in US
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8. Bad reasons to know about ROP
1/6/2023 ROP FOR PEDIATRICIANS BY DR WANI 8
BE AWARE OF ALL PROTOCOLS AND
DO YOUR PART IN CARE OF ROP TO
AVOID SUCH MEDICOLEGAL cases

9. Definition of ROP?
ROP is a vaso-
proliferative
disorder of the
retina in
premature babies
with immature
retina - avascular
area
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10. History of ROP
1/6/2023 ROP FOR PEDIATRICIANS BY DR WANI 10
Terry 1942 -- two cases of white membranes behind the lenses in
premature babies and termed it as Retrolental Fibroplasia
(RLF)1
Campbell and Patz showed that premature babies receiving
higher oxygen supplementation developed RLF2,3
,
1.Terry TL. Am J Ophthalmol 1942;25:203-204
2. Campbell K. Med J Aust 1951;2:48–50
3. Patz et al Am J Ophthalmol 1952;35:1248–52

11. Knee jerk reaction-curtail oxygen
 Reducing oxygen led to reduction in RLF from 50% to
4%4
 BUT- a very high rate of mortality and morbidity due
to cerebral palsy 5
 It was estimated that by reducing oxygen-for every
baby they saved the sight- there were 16 babies who
either died or had cerebral palsy6
 So oxygen was restarted to be used
4. Hatfield EM. Sight Sav Rev 1972;42:69–89
5.. Avery ME, Oppenheimer EH. J Pediatr 1960;57:553–9.
6. Cross KW. Cost of preventing retrolental fibroplasia? Lancet. 1973;2:954–6
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12. Three Epidemics of ROP
 First epidemic of RLF or ROP was in 1940s-
50s –soon after oxygen was introduced for
premature babies- none knew about ROP
 Second epidemic started in 70s-80s
Due to liberal use of oxygen to prevent
cerebral palsy or death7
Due to increased survival of smaller babies8
7.Gibson DL et al Pediatrics 1989;83:486–92.
8.Valentine PH et al. Pediatrics 1989;84:442–5
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13. The third epidemic -1990s onwards
 Advances and expansion of neonatal services in
middle income countries like India, China, Mexico,
Brazil etc are occurring
 More premature babies are surviving
 So ROP is increasing in these countries -3RD WAVE
 It is still going on
 It is our duty to expand ROP services to cover every
neonate
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14. How big is ROP problem?
 13 million premature babies born every year in the world
 And severe ROP in more than 50 000 babies every year9
 One in 820 babies born premature may become blind due to
ROP10
 An estimated 32000 children went blind world wide in 2010
and 10% of them were in India11
 ROP is an important cause of blindness during childhood12
9. Blencowe H et al. Pediatr Res. 2013;74(Suppl 1):35-49
10. Lad et al Br J Ophthalmol 2008;92:320-325
11. Blencowe H et al Indiann Paediattrics 2016;53:supl 2
12. Steinkuller PG et al J AAPOS 1999;3:26 –32.
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15. How does fetal retinal vasculature develop?
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• At 12 weeks of gestation
mesenchymal cells grow out
from the disc
• They form capillaries, venules
and arterioles and then major
vessels
• The avascular retina produce
a cytokine vascular
endothelial growth factor –
VEGF-which promotes
vascularization of retina
• Vessels reach nasal periphery-
ora serrata- at 32 weeks of
gestation and temporal
periphery at term
• So by term, the retina is
fully vascularized LEFT EYE

16. So if a baby is born premature
 Some avascular retina will be
present -extent depends upon
prematurity
 In such babies
retinal vessels may grow
towards the ora to complete
vascularization of retina in a
normal fashion or
ROP may develop in some
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17. Pathogenesis
Pathogenesis of ROP occurs in two phases13-15
 Hyperoxic phase
 Hypoxic phase
13. Chen J, Smith LE. Angiogenesis. 2007;10:133-140.
14. Hartnett ME. Ophthalmology. 2015;122:200-210.
15. Mintz-Hitner HA et al N Engl J Med. 2011;364:603-615
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In utero baby lives in hypoxic environment -PaO2 of < 30 mm of Hg.
Hypoxia promotes normal VEGF expression which facilitates
vascularization of retina
If a baby is born premature it is exposed to higher PaO2 of 100 mm
of Hg in room air. Baby may also receive O2 treatment
High PaO2 –no hypoxia - VEGF expression suppressed –needed for
normal growth of blood vessels -so vessel growth stops –vaso-cessation
high PaO2 in blood -O2 radicals –death of endothelial cells of
growing retinal vessels –cause obliteration –vaso-obliteration
Vessels and capillaries stop growing to periphery
The peripheral retina remains avascular - becomes hypoxic -
hypoxia triggers next phase of pathogenesis-HYPOXIC PHASE
HYPEROXIC PHASE 22 to 30 weeks of PMA

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Phase 2 –HYPOXIC PHASE-31 to 44 weeks of PCA
Hypoxia causes up-regulation of VEGF and other
growth factors in retinal cells in avascular retina
High VEGF and other growth factors lead to
active ROP and abnormal vaso-proliferation
ROP develops at the junction between
vascularized and avascular retina
These cells now produce VEGF, EPO and IGF1
VEGF levels increase -130 times normal values

20. .
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16. Invest. Ophthalmol. Vis. Sci.. 2008;49(12):5177-5182

21. Classification of ROP
 International classification of ROP(ICROP) 17 issued
guidelines to uniformly describe ROP in 1984
 Further modifications for this have occurred
subsequently but basic aspects remain same
17. ICROP GROUP Arch Ophthalmol 1984;102:1130-1134
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22. ROP – ICROP17
1) Location
2) Staging
3) Extent
4) Plus disease
17. ICROP GROUP Arch Ophthalmol 1984;102:1130-1134
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23. 1) Location –Zone-
tells us where the disease is located
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26. 2) Stages of ROP
Stage 1-demarcation line
A simple flat line is seen at the edge of advancing vessels
separating avascular from vascular retina
Stage 2-Ridge
The demarcation line becomes thick and has volume
and height –then it is called as ridge-stage 2
It is pinkish or whitish
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28. Stage 3
 When new blood vessels called as extra-retinal
proliferations (ERP) develop in addition to the ridge
New vessels may grow
into vitreous or
back on the surface of vascularized retina from the
ridge area giving it ragged appearance
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30. Stage 3
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31. Do all babies who develop stage 1
or 2 progress to stage 3 ROP?
No
 Many babies who develop stage 1 or 2 show
spontaneous resolution of disease
 Retina may become fully vascularized
 Some cases of Stage 3 also show regression
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32. We should not see this stage
Stage 4-subtotal retinal detachment
When extensive ERP
contract they pull
retina TRD
Stage 4a
 Macula not involved
Stage 4b
 Macula is involved
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33. Stage 5- we should never see it
 Total retinal
detachment
 Results of surgery
very poor
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34. 3) ICROP- Extent of the disease
 We note how many clock
hours of disease is
present
 Report as so many clock
hours of the disease
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35. 4) ICROP- 4th component is plus disease MOST
IMPORTANT SIGN
 Dilatation and tortuosity of the posterior vessels in
zone 1
 Vitreous haze
 Pupil rigidity-does not dilate well
 Iris vessel engorgement, iris new vessels
PLUS disease is a very important sign and its presence
is usually an indication for treatment
Further classified as pre-plus or plus
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38. Tunica vasculosa lentis
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39. ZONE I stage 3 plus disease
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40. When do we treat ROP
 The purpose of screening is to catch ROP at treatable
stage and prevent stages 4 and 5
 The window of opportunity is small in ROP
 One missed appointment -baby may progress from stage 2
to stage 4 or stage 5
 So screening a timely protocol is very important
 RCTs have established guidelines for treatment
 We follow ETROP study guidelines for indications of
treatment 18
18. Early Treatment of Retinopathy of Prematurity Group. Arch Ophthalmol. 2003;121:1684-1694
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41. Type1 ROP (treatment is required)18
 Zone I-stage 1 OR 2 ROP with plus disease
 Zone I-stage 3 ROPeven without plus disease
 Zone II-stage 2 or 3 withplus disease
Treatment is
 Retinal ablation of all the avascular retina by laser is
established form of treatment
 However presently zone I ROP is treated by
intravitreal injection of anti VEGF
18.Early Treatment of Retinopathy of Prematurity Group. Arch Ophthalmol. 2003;121:1684-1694
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43. ROP that does not meet the criteria of type 1 ROP is
termed as Type 2 ROP
 Zone I, stage 1 or 2 ROP without plus disease
 Zone II, stage 2 or stage3 ROP without plus disease
 No treatment is required at that point of time
 But continued follow up is needed
 If progresses to type I treat the baby
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44. Aggressive ROP-AROP or APROP
 It is fulminant variant of ROP
 Seen usually in very small babies
 ROP is in the zone 1 or posterior zone 2
 Rapidly progresses to higher stages without starting
with stage 1 or 2
 Has disproportionate plus disease
 Neovascularization of retina may be intraretinal
 Treatment results are less satisfactory
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45. ZONE I DISEASE - APROP
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46. How do we treat
A) Laser –laser burns applied to all the avascular
retina which is hypoxic -is producing VEGF. Once is
‘destroyed’ VEGF comes down and
The ROP regresses
B) Anti VEGF injections–in eyes with zone I disease
or aggressive ROP(A-ROP)
 Anti VEGF – it neutralizes high levels of VEGF in the
eye and stops neovascularization
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47. Laser treatment
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51. What are the risk factors for ROP
 Lower Gestational age at birth-prematurity
 Lower Birth weight-prematurity
 Oxygen administration
 Need for ventilation
 HMD
 CLD
 Sepsis
 Intra-ventricular hemorrhage
 Need for blood transfusion
 Poor postnatal weight gain
 NEEC
 PDA
 Many other factors
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52. Oxygen spO2
 Keeping SpO2 83% and 93% from birth and during
transport virtually eliminated severe ROP
 Need for laser treatment was 4.5% for high SpO2
(90%–98%) versus 0% for low SpO2 (85%–93%)19
19.Chow LC, et al . Pediatrics. 2003;111:339–45.
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EVENT HIGHER
OXYGEN
91-95%
LOWER
OXYGEN
85-89%
RR LEVEL
P VALUE
MEANI
NG
PRIMARY
OUTCOME
51.6% 53.5% P=0.21 NS
DEATH 17.1% 19.9% P=0.01 S
ROP treatment
need
14.9% 10.9% P < .001 S
NEEC 6.9% 9.2% P = .003 S
NEOPROM STUDY20
20. Askie LM et al JAMA. 2018 Jun 5;319(21):2190-2201.

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21
21. Wani et al Indian J Ophhthlamol 2010;58: 204-208

55. 22. Middle East Afr J Ophthalmol.2013;20(1):66-71.
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56. Incidence of ROP and type I ROP-KLE experience 2019 one year
data
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Study and place of
study
Number of
infants
Inclusion criteria
GA* and BW†
Mean BW± SD in grams
GA± SD in weeks
Any ROP%
Type 1 ROP%
Quinn et al 6
USA
7483 GA≤30
BW<1500g
28 ± 3
1099± 259
43.1
6.9
Braimah et al7
Ghana
401 GA<37
BW<2000
32.2± 2.4
1600± 400
13.7
1.8
Bas et al 10
Turkey
6115 GA<32 W
BW <1500G
1457±479
28.9±6.3
27
6.7
Ahuja et al11
India
325 GA≤36 W
BW ≤1900G
1420±300
30.68±2.84
32.6
13.2
Vinekar et al 14
India
4167 GA<34
BW<2000G
1592.7
31.7
24.33
4.4
Castellon et al21
Mexico
132 GA≤34
BW <1700g
1594±96
32±3
56.1
28.8
ETROP study23
USA
6998 BW <1251g 907
27.4
68
36.9
Present study 263 GA<34
BW<2000G
1598.8 ±440.1
33± 2.8
24.3
5.7

57. Results of treatment of ROP till
2021 in KLE
 55 babies(KLE BORN AND OUTSIDE BORN)
 GA 30.1( 27-33)weeks
 BWT 1299.7( 718-2500)g
 PCA at treatment 35.9 weeks
 AROP in 6 babies
 20 treated by anti vegf injections
 None developed RD
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58. Role of Pediatricians in ROP
Which premature babies to screen?23
Following guidelines are from Govt. of India
 Birth weight(BW) less than or = 2000g
 Gestational age(GA) less than or =34 weeks
 GA 34-36 weeks n BW >2000G but has following
risk factors
a) Cardiopulmonary support b) Prolonged oxygen administration c)Respiratory
distress syndrome d) Chronic lung disease e)Fetal hemorrhage f)Blood transfusion
g)Neonatal infection h)Exchange transfusion i)Intraventricular hemorrhage j)Apneas
k)Poor postnatal weight gain
 Infants with unstable clinical course who are at
high risk (as determined by neonatologist)
23 https://nhm.gov.in/images/pdf/programmes/RBSK/Resource_Documents/Revised_ROP_Guidelines-Web_Optimized.pdf
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59. Who chooses the babies for
screening?
 The neonatologist will choose the babies
 All the names of eligible babies are entered in a
register by an assigned staff and date for first screening
to be entered in the register
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Rashtriya Bala Swasthya Karykrama
June 201723

61. When to perform the first ROP
screening?23
 Early screening for babies born with GA < 28 weeks
OR babies with BW<1200g
-first ROP screening at 2-3 weeks after birth (To detect
AROP)
 All other babies undergo the first ROP screening at
four weeks after birth
23. https://nhm.gov.in/images/pdf/programmes/RBSK/Resource_Documents/Revised_ROP_Guidelines-
Web_Optimized.pdf
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62. Sample register entry
Name
of
baby
IP
nu
mbe
r
DOB SE
X
GA
wk
s
BW
g
I ROP
screening
date
Mobile
of
parent
s
b/o
ABC I
twin
32**
****
01/01/2018 M 29 1150 14 or 21 of
January 2018
988****
***
b/o
ABC II
twin
32**
****
01/01/2018 M 29 1240 28TH JAN 2018 same
b/o
MNO
33**
****
25/01/2018 F 30 1400 25/2/2018 944****
***
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63. Baby unfit for eye examination
In case the baby is too sick to tolerate dilatation & ROP
screening is postponed
Neonatologist should
 Clearly write in the case sheet the reason for
cancellation of screening examination
 ROP screening at the earliest possible to be arranged
 Inform the parents
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64. Who performs the screening?
 It is an ophthalmologist who is experienced in ROP
examination and management
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65. Arrangement regarding visit of the Ophthalmologist to the
nursery
 Neonatology and Ophthalmologist should arrange
day/days to conduct ROP screening examination/s
 Usually a fixed day and timings are preferred to avoid
confusion except under special circumstances
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66. Arrangement regarding visit of the Ophthalmologist to the
nursery
 The staff of NICU should inform the timing of eye
examination to all the sections of the Neonatology
dept-NICU, WARDS, OPDs
 Babies for first time ROP screening and follow up
examinations are to be included (see later)
 Keep the pupils dilated of all the selected babies
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67. The method for dilatation of the pupils
1) 0.5% Tropicamide every 15 minutes for three times-0,15,30
minutes
OR
2) Cyclopentolate 0.5% eye drops (Cyclogyl) to be used every 15
minutes for three times 0, 15, 30 minutes
AND
3) At 45 minutes Tropicamide 0.5% with 2.5% phenylephrine
combination is instilled
If the above strengths are not available( TROPICACYL PLUS, I
TROP –need dilution) then commercially available drops should
be diluted with artificial eye drops and required strength of drops
prepared
 Difficult to dilate eyes could be harboring severe ROP
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68. The method for dilatation of the pupils
 Instill one drop only in the conjunctival sac after
pulling the lower lid
 Wipe out the excessive drops that spill out onto the
cheek to prevent systemic absorption through the thin
skin
 Monitor BP and HR, decreased bowel movements,
paralytic ileus and other side effects
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69. Systemic effects of dilating drops for
retinopathy of prematurity
Increase in BP, heart rate, renal failure,
acute gastric dilatation, paralytic ileus
have all been reported as side effects of
dilating drops24-26
24.Laws et al Br J Ophthalmol. 1996 ;80(5):425-8
25. Shinomiya K et al J Med Invest. 2003;50:203-6
26. Sarici SU et al Pediatr Radiol. 2001 Aug;31(8):581-3
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70. How to arrange screening
 Start dilating the eyes 1 ½ hour before arrival of
ophthalmologist
 Information leaflet to be given to parents and a
common consent taken for multiple ROP screenings
 ROP examination sheet for each baby should be filled
up and kept ready
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73. Aseptic techniques should be
followed for ROP examination
 Washing hands before and between cases
 Preferably wear sterile gloves for each baby
 Sterile instruments for each baby
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74. What is done after ROP
examination
 The findings are entered in the ROP sheet in triplicate
by the examining ophthalmologist
 Clear instructions
When is the follow up
Does the child need treatment for ROP or follow up
only?
 The babies in Nursery and OPD who are advised
follow up are to be entered in a separate registers for
follow up --date wise
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75. Guidelines for follow up intervals
 Follow up intervals depend upon
extent of retinal vascularization
stage of ROP and
presence or absence of pre plus disease
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76. Follow up intervals-
ophthalmologist decides it
1. More posterior the zone more often do we see the
baby
2. No ROP but retinal vessels in zone I still - every week
3. No ROP but retina vessels in zone II- every 2 weeks
4. Zone I ROP stage 1 or 2 with no plus disease –every
week or earlier
5. Zone II ROP stage 1 no plus disease every 2 weeks
6. Zone II ROP stage 2 or 3 no plus --every one week or
earlier if pre plus present
7. Zone III – No ROP every 2-3 weeks
8. Zone III- ROP stage 1-2 no plus every two weeks
9. Zone III-ROP stage 3 no plus every week
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77. Appointments on date 26-3-2018
Name of
baby
File
number
DOB Examine
d
BEFORE
S NO of
exam
FU
advice
Remarks
b/o xyz 43^^^^ 24-01-
2018
No 1 After one
week
b/o mnl 34**** 12-02-
2018
Yes 4th exam After 2
weeks
b/o abc 36**** 10-01-2018 Yes 5th exam After one
mo
Discharged
FU given for
OPD
ophthalm
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78. When should we stop ROP follow
up?
 To be decided by ophthalmologist and not you!
 Babies are to be followed till
a. Retina is fully vascularized both nasally and
temporally
b. If ROP stages were present they completely regress
and retinal vessels reach temporal ora serrata
c. Usually follow ups are needed up to 45-50 weeks of
PCA
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79. What happens when a baby that needs ROP screening is
discharged home
 See the recommendation of Ophthalmologist in the
last ROP screening
 Give verbal AND written instructions to the parents
regarding date and place of next ROP screening
 The parent’s signature should be taken in a register to
the effect that he/she has been informed about the
need of ROP screening, ITS IMPORTANCE and has
been given a referral letter with date and place of
referral
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80. What happens when a baby that needs ROP screening is referred
or transferred to another hospital for care
 The referral letter to that center should clearly
mention the scheduled date of ROP screening and
request that hospital to arrange for an ophthalmologist
for it
 Parents should be informed about it and signature
taken
 Documentation regarding these is very important to
avoid legal hassles
 These referrals are to be given by the
NEONATOLOGIST as they are the ones who discharge
or transfer the patient
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81. FOLLOW UP EXAMINATIONS
after ROP discharge
a. All premature babies with ROP are at high risk of
developing myopia and squint
b. More severe the ROP- greater the degree of myopia
c. ROP treated babies commonly develop high myopia
d. Premature babies even without ROP are at higher
risk of developing myopia AND strabismus
compared to FT babies
e. So these babies need annual examinations even if the
ROP has regressed completely or there was no ROP
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82. 270 eyes of 148 babies
treated by laser
between 1999 to 2003
20 eyes (7.6%)
Unfavorable
structural outcome
47% of eyes had
VA of <20/40
17% eyes had myopia of 5 D or more
Zone I disease
Was the risk factor
For structural,
refractive and
visual
Unfavorable
Outcomes
82
27. Wani et al Clinical Ophthalmology 2013
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83. 1/6/2023 ROP FOR PEDIATRICIANS BY DR WANI 83
28. Day et al Arch Ophthalmol 2009;127:794-798

84. Counseling the parents of babies
with Type I ROP-ophthalmologist
 Alert the parents of infants who are nearing Type I
status-pediatrician and ophthalmologist
 An informed consent for treatment for TYPE I
ROP is must
 The ophthalmologist will counsel the parents and
consent taken in the Neonatology
department/OPD
 Even with early treatment of eyes with type I ROP,
some eyes may still progress to an unfavorable
visual and/or structural outcome
 This is especially true for eyes with Zone I disease
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85. Guidelines for the treatment
 Written informed consent from parents
 Treatment -in operation theater or NICU
 Arrange OT
 Start dilate both eyes 1 ½ hour before timing of laser
 A neonatologist must accompany the child to the OT and
manage emergencies SOS
 IF no contraindication then baby may be given sedation as
appropriate
 Both laser treatment and anti VEGF inj are carried out
under topical anesthesia with infant being restrained by
staff nurse
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86. POST LASER ROP AFTER 10 YEARS
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Thanks for your kind attention