Retinopathy of Prematurity: Laser,
Anti-VEGF,Surgery & Others
Dr. Mangat R. Dogra
Professor of Ophthalmology
Advanced Eye Centre
PGIMER, Chandigarh
No financial disclosure
Introduction

Retinopathy of prematurity (ROP) is the leading cause of
childhood blindness worldwide.

Becoming a major public health concern in developing
countries like India. (New and emerging cause of blindness)

Blindness due to ROP is potentially preventable.

A large number of babies in our country are
presenting late with bilateral, irreversible
blindness due to absence or delayed screening.
Predicting ROP blindness according to Infant mortality rates.
Gilbert C. Early Hum Dev 2008;84 (2):77-82.
ROP in India

Incidence of ROP: 38% – 47. 3 % in low birth weight
infants.
–
–




Charan R, Dogra MR, Gupta A, Narang A. Indian J Ophthalmol 1995; 43:123-26.
Gopal L et al. Indian J Ophthalmol 1995; 43:50-61.
Live births: 26 million /year
Incidence of Low birth weight (< 2000g)- 8.7%
2 million newborns are at risk for developing ROP.
National Neonatalogy Forum of India. National Neonatal Perinatal Database. Report
New Delhi 2005
Indian scenario of ROP

1995 : Charan R ,Dogra MR et al IJO 43:123-126;1995 first
prospective study
(<1700g)
incidence of
47.27%
 1995 : Gopal etal ;
(<2000g) 38%
 1996 : Rekha etal ;
(<1500g) 47.3%
 1996 : Maheshwari etal; (<1500g)
20%
 2001 : Varughese etal; (<1500g)
51.89%
 2009 : Chaudhari etal;
(<1500g) 22.30%
 2012 : Hungi B etal;
(<2000g) 41.5%
Implications for screening

The American screening guidelines

Babies ≤ 1500 g birth weight or
≤ 30 weeks gestational age

Selected infants with a birth
weight 1500 -2000 g or
gestational age > 30 weeks be
screened at the discretion of the
attending neonatologist.

Pediatrics 2013;131(2)

Indian Screening guidelines

Infants weighing < 1750 grams or
< 34 weeks of gestation.

Heavier (1750-2000g) or older babies
(34-36 weeks) may be screened
depending upon the attending risk
factors like mechanical ventilation,
prolonged oxygen therapy,
hemodynamic instability or adverse
respiratory or cardiac disease profile.
National neonatology forum. Clinical practice
guidelines 2010.
Why screen for ROP

Premature child is not born with ROP
 Screening aims to identify treatable stage
 Narrow window for screening and treatment
 Delay cause blindness or visual impairment
 Medico-legal implications
 Economic and social burden of childhood
blindness is immense
Aggressive Posterior ROP



The keys to diagnosis:
Identification of plus
disease
Location in zone 1 or
posterior zone 2
Subtle neovascular
findings at the junction
without any stages of
ROP
These cases progress
rapidly and directly to
retinal detachment .
ICROP revisited:
Arch Ophthalmol.2005;1239:991-99
Sanghi G, Dogra MR et al
.Aggressive posterior retinopathy of prematurity in Asian Indian
babies:Spectrum of Disease and Outcome After Laser
Treatment. Retina 2009:29;1335-39
Jalali S, Kesarwani S, Hussain A.
Outcomes of a protocol-based management for zone 1 retinopathy
of prematurity: the Indian Twin Cities ROP Screening Program
report number 2.
Am J Ophthalmol. 2011 Apr;151(4):719-724
Shah PK, Narendran V, Kalpana N Aggressive posterior
retinopathy of prematurity in large preterm babies in South
India.
Arch Dis Child Fetal Neonatal Ed. 2012 Sep;97(5):F371-5.
The mean birth weight and
gestational age in APROP
Author
year
Country
Mean Birth
weight (g)
Mean gestational
age (wk)
Jalali et al
2011
India
1228
29.63
Drenser et al
2010
USA
627
24.3
Sanghi et al
2009
India
1259
29.75
Azuma et al
2006
Japan
773
25
Shah et al
2012
India
1572
31.7
Current treatments of ROP

Peripheral retinal ablation with laser delivered
through laser indirect ophthalmoscope (LIO)
is a gold standard in ROP treatment
 Anti-VEGF is emerging therapy for selective
cases of ROP
 Vitreoretinal surgery is required in stage 4 and
5 ROP
Rationale for laser treatment

VEGF is stimulus for
abnormal vessels
which comes from
avascular retina
 Ablate the avascular
retina between ora
and ridge to reduce
VEGF
Laser Treatment of ROP
Laser treatment earlier than threshold
ROP has shown better results & outcome
after ETROP Study
Arch Ophthalmol.121:1684-1696; 2003
ETROP Recommendations
Arch Ophthalmol. 121:1684-96;2003
Z
o
n
e
No Plus
1
Plus
Z
o
n
e
No Plus
2
Plus
Stage 1
Follow
Stage 2
Follow
Stage 3
Treat
Stage 1
Treat
Stage 2
Treat
Stage 3
Treat
Stage 1
Follow
Stage 2
Follow
Stage 3
Follow
Stage 1
Follow
Stage 2
Treat
Stage 3
Treat
Plus disease

If pupil does not dilate
suspect tunica vasculosa
lentils and plus disease.
Plus disease

Plus disease
means at least 2
quadrants of
dilation and
tortuosity of the
posterior retinal
blood vessels
Preplus & Plus disease
Laser treatment

Delivered in
confluent pattern
(less than half burn
width apart)
 Around 90% attain
favourable outcome
Laser treatment for ROP: evolution in treatment technique over
15years Hurley et al. Retina 26: S16-7; 2006
Laser treatment
Possible inside the
incubator through
the slopping
transparent wall in
extremely unstable
premature infants
Dogra etal Ophthalmic Surg Lasers Imaging 39:350-352;2008
Frequency doubled Nd: YAG
(532 nm green) versus diode laser (810
nm) in treatment of ROP

Favorable outcome in 97% with 532 nm laser
versus 96.9% in diode laser group.
 Treatment possible in eyes with TVL, vitreous or
preretinal hemorrhage and without inducing any
cataract, anterior segment ischemia or hyphema .
Sanghi G, Dogra MR, Vinekar A,Gupta A. Frequency doubled
Nd: YAG (532 nm green) vs diode laser(810 nm ) in treatment
of retinopathy of prematurity
Br J Ophthalmol 94;1265-1265 : 2010
Laser treatment
of APROP

Delivered through LIO in
confluent pattern (less
than half burn width
apart) with in 24-48
hours of diagnosis
 Around 55% to 84%
attain favourable
outcome in reported
series
Sanghi G, Dogra M R et al. Aggressive posterior retinopathy of prematurity in Asian
Indian babies:Spectrum of Disease and Outcome After Laser Treatment.
Retina 2009:29;1335-39
APROP in posterior zone 1 with mat like
proliferation
Unfavourable outcome
after laser
Risk factors for RD after laser
treatment of APROP

Gestational age less than 29 weeks
 Posterior zone 1 APROP
 Pre-retinal hemorrhages
 Need for repeat laser treatment
 New onset fibrovascular proliferation after
laser treatment
Sanghi G, Dogra M R et al.Aggressive posterior retinopathy of
prematurity: risk factors for RD despite confluent laser photocoagulation.
Am J Ophthalmol. 2013: Jan;155(1):159-164
Indications for ROP surgery


Progression despite laser treatment
Delayed or no screening
 Stage 4A, 4b and stage 5 ROP
 Bilateral cases
Current surgical
approaches in ROP

Scleral buckle is rarely performed
 Lens sparing vitrectomy
 Lensectomy & vitrectomy
Management of stage 4A and
4B ROP

? Observation if < 4
clock hrs of elevation
 Lens sparing
vitrectomy has shown
reattachment in 60 %
to 85% eyes
Bende P, Gopal L et al. Indian J Ophthalmol 57:267-271;2009
Lakhanpal et al. Arch Ophthalmol 124: 675-679;2006
Capone A Jr, Trese MT. Ophthalmology 108:2068-2070;2001
Lens sparing vitrectomy
(LSV)

Most important recent innovation
 Ideal for stage 4A and 4B ROP
 Both 2 or 3 port LSV is possible
 23G and 25G LSV are preferred at present
ROP stage 5 :
Total retinal detachment
Management of stage 5 ROP



Lensectomy and vitrectomy in these cases
Reattachment in some eyes (< 1/3)
Functional results extremly poor and dismal
ETROP Study results: Arch Ophthalmol 124;24-30:2006
Arch Ophthalmol 129;1175-1179:2011
Shah et al. Eye 23;176-180:2009
Gopal et al. IJO 48:101-106; 2000
Bevacizumab monotherapy
 Avastin
monotherapy showed a
significant benefit for zone 1 but not for
zone 2 ROP as compared to conventional
laser therapy.
 Trial was too small to assess safety issue.
Mintz-Hittner et al. N Engl J Med 2011; 364:603-15
Avastin in ROP
 Caution
is warranted for routine use at this
time due to safety issues.
 0.625mg in 0.025ml of intravitreal avastin
is usually given.
 Mostly used as rescue therapy in zone 1
ROP along with laser
Increasing ROP blindness in
India

High rate of preterm birth
 Neonatal care not optimal
 ROP screening and treatment programs not
in place
 Inadequate treatment and follow up
 Increasing numbers of NICUs and SNCUs
SNCUs

Sick Newborn Care Units
 District level
 Provide newborn care to decrease mortality
 Potential sources for ROP in the coming
years
ROP Stage 5
86.4% of infants presenting with stage 5 ROP were never
screened
 74.2% were picked up by the parents when they noticed that
child is not seeing.
 Pediatricians referred none
 25.8% referred by an ophthalmologist.

–
Sanghi G, Dogra MR, Katoch D, Gupta A. Demographic profile of infants with stage 5 retinopathy
of prematurity in North India: implications for screening. Ophthalmic Epidemiol 2011;18(2):72-4.

Prevailing clinical practices among pediatricians
Only 14.5% were following the recommendations
ROP referral.
–
for
Patwardhan SD, Azad R, Gogia V, Chandra P, Gupta S. Prevailing clinical practices regarding screening for retinopathy of prematurity
among pediatricians in India: a pilot survey. Indian J Ophthalmol 2011;59(6):427-30.
Role of neonatologist and / or
pediatrician

Prevention of ROP
 ROP screening
 During ROP treatment / surgery
 Follow up of cases
Prevention of ROP

Prevention of prematurity
 Good antenatal and obstetrics care
1.Use of antenatal steroids
2.Trained personal in delivery room to avoid asphyxia

Judicious use of oxygen therapy and
ventilation
 Reduce morbidity of premature infants
ROP screening

Single nodal person to be identified
 Communicate with parents and ophthalmologist
 Identify babies and decide time for screening
 Combine ROP screening visit with follow up for
neonatal problems
 Record keeping is most important
During laser therapy

Monitoring during therapy
 Counseling
 Resuscitation
What should be done

Wall chart regarding whom to screen, when
to screen and how to dilate should be pasted
in NICU and Nursery
What should be done

Any one weighing the new born infant
should paste a bold sticker on card / file for
ROP screening in babies < 1750gms at birth
in 3 to 4 weeks.
 Responsibility is of Obstetrician /
Pediatrician / nurses to get ROP screening
done from Ophthalmologist at appropriate
time
A novel, low-cost method of enrolling infants at risk
for Retinopathy of Prematurity in centers with no
screening program: the REDROP study.
Vinekar A, Avadhani K, Dogra M, Sharma P, Gilbert
C, Braganza S, Shetty B.
Ophthalmic Epidemiol. 2012 Oct;19(5):317-21
Goals of an ROP workshop

Define criteria for identification of babies at
risk with birth weight and gestational age
 Develop programs for prevention, detection
and treatment of ROP
 Develop teams at NICUs with no program
 Prepare action plan for prevention of ROP
 Stimulate government participation
Conclusions

Lack of awareness about ROP in India
 Neonatal care and screening program are
variable not optimal
 More mature and higher birth weight babies are
developing ROP
 Delayed or no screening responsible for
increasing rates of childhood blindness due to
ROP in India
Conclusions

Treat ROP as per ETROP Study
recommendations & with APROP promptly with
confluent laser
 Use anti-VEGF as rescue therapy.
 Lens sparing vitrectomy is the most important
recent exciting innovation for stage 4A and 4B.
 Lensectomy and vitrectomy in complex cases
usually results in poor outcome.
 ROP prevention, screening and management is a
team effort
India
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