retinopathy of prematurity

1. Presented by
Dr Rohit Rao

2. 1.
Hs Niranjan & Et Al,Retinopathy Of Prematurity –Promising Newer
Modalities Of Treatment, Indian Pediatrics 139 Volume 49,February 16,
2012.
2.
Clinical Practice Guidelines Of Retinopathy Of Prematurity, December
2005 Moh/P/Pak103.05 (Gu)
3.
AIOS CME series on Retinopathy Of Prematurity no. 12.
4.
Ranjan Kumar Pejaver & et al Retinopathy of Prematurity, NNF Clinical
Practice Guidelines Page | 253
5.
Deepak Chawla & et al, Retinopathy of prematurity, AIIMS- NICU
protocols 2010
6.
Retinopathy of Prematurity by Tapas Ranjan Padhi

3.  1942-
Terry first identified ROP as ‘retro
lental fibroplasia” in 6 month premature
infant.
 1951 - Heath suggested term “Retinopathy of
Prematurity”
 Campbell: relationship of intensive oxygen
therapy & subsequent development of ROP.
 Kinsey: ROP was inversely proportional to
birth weight.

4.  It
is a developmental vascular proliferative
disorder that occurs in the incompletely
vascularized retina of primarily premature
infants.
 ROP is one of the most common causes of
blindness in children

5. 





Choroid vascularises at 6 weeks
Retinal vascularisation starts at optic nerve
head at 16 weeks gestation
Proceeds outward to the periphery
Vascularisation is almost complete by term
Vasculogenesis: primitive plexus formed from precursor cells, not
VEGF dependant
Angiogenesis: new vessels from pre existing vasculature, VEGF
dependant

6.  Classical
theory
Arthon & Patz
 O2
 Vasoconstriction-vasoocclusion-endothelial cell
proliferation-neovascularization

 Spindle


cell theory
Kretzer
Spindle cell exposure to hyperoxic environmentspindle cell insult- spindle cell stops to migration
& canalization

7. Premature delivery interrupts normal vascular growth
 Phase 1 : delayed retinal vascularisation (birth31/32 weeks)
Developing retina exposed to hyperoxic environment
(ambient and supplemental)
 Reduces angiogenic factors delaying retinal vascularisation


Phase 2 : neovascularisation

Neuroretina continues to develop causing hypoxia with
overproduction of angiogenic factors especially VEGF

Causes uncontrolled retinal blood vessel growth

8. Hypotension, hypoxia, or hyperoxia, with free radical formation, injures
newly developing blood vessels and disrupts normal angiogenesis 
neovascularization retinal edema, hemorrhage and abnormal
fibrovascular tissue development.

9.  ICROP

Zone, Stage, Extent, Plus
 ICROP



(1984 & 1987 )
revisited
APROP
Pre plus
Practical clinical tool for extent of Zone I

10.  Four




features are evaluated:
Zone (1-3)
Extent
Stage (1-5)
Presence or absence of plus disease

11.  Zone
I: retinal area within a circle centered
on the disk and with a radius of twice the
estimated disk-foveal distance
 Zone
II: retinal area extending from the edge
of zone I to a circle with a radius from the
disk to the nasal ora serrata
 Zone
III: a crescent-shaped retinal area
extending beyond zone II to the temporal ora
serrata

12.  The
extent of disease is described by dividing the
retinal surface into 30º sectors, similar to the
hours of a clock.
 As many as 12 clock hours can be affected, and
the stage of retinopathy can vary among sectors.

14.  Four




features are evaluated:
Zone (1-3)
Stage (1-5)
Extent
Presence or absence of plus disease

23.  Stage
5: Total tractional funnel shaped RD of
one of the 4 different configurations




Anterior Open, Posterior Open
Anterior Open, Posterior Narrow
Anterior Narrow Posterior open
Anterior Narrow posterior narrow

26.  Four




features are evaluated:
Zone (1-3)
Stage (1-5)
Extent
Presence or absence of plus disease

27.  Plus
disease:
Presence of dilated and tortuous vessels of the
posterior pole present in two or more quadrants

28.  Preplus
disease:
Abnormal vascular dilation and tortuosity
that is insufficient for diagnosis of plus
disease present in two or more quadrants

29. Aggressive posterior ROP recognized by:
1. marked dilation and tortuosity of posterior
pole vessels
2. difficulty in documenting the stage of ROP
at junction between vascularized and
avascular retina
3. occurs in zone I or zone II

31. ROP is defined as five contiguous clock hours
or eight total clock hours of stage 3 and plus
disease in zone 1 or 2.

32. Defined as one of the following:
 ROP at any stage less than threshold in zone 1
 Stage 2 and plus disease in zone 2
 Stage 3 without plus disease in zone 2
 Stage 3 with plus disease in zone 2 but with
fewer clock hours of stage 3 than required to
meet threshold

34.  Grade
0 None visible
 Grade 1 Minimal to mild (view of underlying
retina not significantly reduced)
 Grade 2 Moderate to marked (view of
underlying retina significantly obscured)

35. The most important risk factor for developing
ROP is prematurity.
 More than 50 separate risk factors have been
identified.
 On multivariate analysis, low birth weight, low
gestational age, assisted ventilation for longer
than one week, surfactant therapy, high blood
transfusion volume, and cumulative illness
severity were independently associated with
higher rates of ROP


36.  Myopia
occurs in about 80% of infants with
ROP
 Strabismus and amblyopia are also common
residual findings.

23% to 47% in infants with ROP
 RD

seen in 22% patients.
Can occur as early as 6 months up to 31 years
from the time of diagnosis
 Acute
angle closure glaucoma can be seen in
cicatricial ROP

37. 



Screening of at risk babies
Diagnosis
Decision to treat or not
Treatment

Tt. of ROP itself ...




Cryotherapy ( mostly outdated)
Laser treatment (gold standard)
Anti-VEGF (adjuvant) before laser and surgery
Surgery
Correction of systemic factors
 Rx of ROP related complications



Post treatment follow up
Rehabilitation

38. 
Should be performed in all preterm neonates
who are
< 34 weeks gestation and / or < 1750 grams birth
weight.
 34 to 36 weeks gestational age or a birth weight
between 1750 and 2000 grams with risk factors.

First screen should be performed not later than
4 weeks of age or 30 days of life in infants ≥ 28
weeks of gestational age.
 Infants <28 weeks or <1200 grams birth weight
should be screened early at 2-3 weeks of age, for
early diagnosis of AP-ROP.


42.  Retinal


examinations may be terminated if
Full retinal vascularization; occurs at 40th week
of postmenstrual age and completes by 45th
week
Regression of ROP noted

43.  To
dilate pupil: 2.5%Phenylepherine +1%
Tropicamide, twice, 10 minutes apart.

Watch the pulse and respiration.
 Screening
& Tt. can be done in minor
OR/OPD/NICU.
 Under topical anesthesia without any
sedation
 Indirect ophthalmoscope and a 20 D or 28 D
lens.
 Record the findings

44.  Wide
angle digital paediatric retinal imaging
system
 Mobile, self contained system for use in
nursery, ICU, O.T
 Easily used by technicians or nurses
 Avoids stress & expertise of I/O examination
& indentation, but as specific and sensitive
as I/O
 Useful for diagnosis, telemedicine &
documentation

45. RETCAM FOR ROP
DOCUMENTATION

46.  Mature

Vessels reached with in 1DD of both nasal and
temporal ora
 Immature


Vessels not reached with in 1DD of nasal or
temporal ora
Immature I,II,III(depending on zones)
 ROP

47.  Cryotherapy
( mostly outdated)
 Laser treatment (gold standard)
 Anti-VEGF (adjuvant) before laser and
surgery
 Surgery

48.  Based
on results of ETROP two new
terminologies have been suggested:
 Type 1 ROP:
Zone I, any stage ROP with plus disease
 Zone I, stage 3 ROP with or without plus disease
 Zone II, stage 2 or 3 ROP with plus disease

 Type
2 ROP:
Zone I, stage 1 or 2 ROP without plus disease
 Zone II, stage 3 ROP without plus disease

 Peripheral
retinal ablation should be carried
out for all cases with type 1 ROP and
continued serial examinations are advised for
type 2 ROP

51. 
Cryotherapy significantly improves the outcome of severe ROP

Superceded by laser photocoagulation

Cryotherapy applications are applied contiguously.
Probe placed trans-sclerally anterior to ridge in avascular zone.
End point of cryotherapy is the appearance of mild whitening.
360 degrees circumference, under direct visualization avoid the
ridge.




Complications of cryotherapy

Eyelid edema, laceration of the conjunctiva, and pre-retinal and
vitreous haemorrhage as well as systemic complications like
bradycardia, cyanosis and respiratory depression

52. Procedure of choice, being less invasive, less
traumatic and causes less discomfort to the
infant.
 Easy to treat posterior located lesion.
 Argon green and Diode red
 1500 to 1800 spots, 100 mm size 1½ burn width
apart.
 Entire avascular retina till ora, avoid the ridge.
 Complications of laser therapy


Burns in cornea and iris. Other complications include
cataract, and retinal and vitreous haemorrhage.

54. 
Monotherapy
Single injections
 Multiple injections for recurrence
 Less desirable if periphery not perfused


Adjunctive therapy

Injections to allow regression beyond Zone 1




Laser for recurrent ROP
Anti-VEGF as a Bridge to laser peripherally
Treatment after laser / cryotherapy failure
Perioperative therapy before surgery



Reduce bleeding
Promote regression of neovascularization
Vitrectomy and scleral buckles

56. Interventions to prevent or limit the progression of
ROP have been unsuccessful, further evaluation
may be needed.
Antioxidant therapies, such as
vitamin E
D-penicillamine
limited exposure to light, have been tested.
Supplemental oxygen therapy
Insulin-like growth factor-1(IGF-1)

58. RCT (172 infants)
 Peripheral Cryotherapy vs. Observation
 “Threshold Disease”


Stage 3 (neovascularization)

5 contiguous, 8 noncontiguous clock hours
Zone I or II
 Plus Disease


Cryotherapy superior to Observation:
Reduced unfavorable outcomes
 Related improved visual acuity results


59. 
RCT (n=317 bilateral; n=84 asymmetric unilateral infants)

Early peripheral laser vs conventional treatment

“High Risk Prethreshold” ROP disease – Type 1 or Type 2

Type 1 ROP


Zone II: Stage 2 or 3, plus


Zone I: Any Stage, plus / Stage 3, no plus
Finding: Early Peripheral laser superior to conventional treatment
Type 2 ROP


Zone II: Stage 3, no plus


Zone I: Stage 1 or 2, no plus
Finding: Observation advised until Type 1 or Regression
Peripheral laser better than conventional treatment for Type 1:

Reduced unfavorable anatomic outcome from 15.6% to 9.1%

Reduced unfavorable visual acuity grating from 19.5% to 14.5%

60. 





“Bevacizumab Eliminates the Angiogenic Threat in
ROP”
RCT (150 infants, 300 eyes)
Stage 3, plus
Zone 1 and posterior Zone 2
Comparison : Intravitreal Bevacizumab v/s Peripheral
Laser (ETROP)
Summary



Bevacizumab reduced recurrence of ROP
Bevacizumab benefit over laser in Zone 1
Bevacizumab allowed continued peripheral
vascularization into avascular retina

61. 
152 eyes with Zone 1, posterior Zone 2 ROP Stage 3,
plus disease

Group 1 (68 eyes)



Group 2 (84 eyes)




Pegaptanib (0.3 mg) with laser
Follow up 19.3 months
Laser / cryotherapy
Follow up 21.5 months
Primary Outcome: absence of recurrent Stage 3+ ROP
Results


Group 1 89.7% regression; 85.4% no recurrence
Group 2 60.8% regression; 50% no recurrence

62. Thanks

63. GET THE HELL
OUT OF HERE
ROP!!
h!!
Ahhh