Retinopathy of prematurity, neonate, management

1. Retinopathy Of
Prematurity
Presented By : Dr. Sonali Mhatre

2. Introduction
• Retinopathy Of prematurity, is a disease of the developing
retinal vasculature resulting from the interruption of normal
progression of the newly forming retinal vessels.
• It is a multifactorial disorder with incidence increasing with
decreasing gestational age.
• It is one of the most common causes of blindness & other
visión errors in children.
• Earlier, it was known as Retrolental fibroplasia.

3. History of ROP
• 1940 – Retrolental Fibroplasia, first described by Terry.
• 1984 – Proved that RLF was associated with use of
oxygen in newborn infants.
• 1951 - Heath suggested term “Retinopathy of Prematurity”
• Campbell (1952): relationship of intensive oxygen therapy
& subsequent development of ROP.
• Kinsey: ROP was inversely proportional to birth weight.

4. Basic
structure of
the eye

5. Structure of
the Retina

6. Embryology
• Eye formation is first evident at the beginning of the 4th wk of gestation
with the appearance of the optic sulci.
• The Retina, Iris and the optic nerve develops from the neuroectoderm.
• The Retina develops from the walls of the Optic cup, which is an outgrowth
of the forebrain.
• During the embryologic and fetal periods, the two layers of the retina
(i.e.) the Retinal pigment layer and the Neural retina are seperated by an
Interretinal space.
• The photoreceptors – Rods & Cones, cell bodies of neurons are developed
from the neuroepithelium.

7. Retinal
Vasculature
Development

8. Pathogenesis
Stage 2 :
Neovascularisation

9. Pathogenesis (cont…)
Stage 1
Initial insults like hypoxia,
hypotension, hyperoxia
Vasoconstriction of retinal
vasculature
Arrest in vascular development.
Stage 2
Excess angiogenic factors cause
aberrant retinal vessel growth.
New vessels grow through the retina
to the vitreous.
Extensive & severe extraretinal
fibrovascular proliferation can cause
retinal detachment and abN retinal
function.

10. Pathogenesis (cont…)

11. Risk Factors
• Extreme Prematurity
• Apnea
• Sepsis
• Hypo/ hypercapnia
• Intraventricular hemorrhage
• Anaemia
• Lactic acidosis
• Exchange transfusión
• OXYGEN….!!!

12. Key Nomenclatures
• ICROP (1984 & 1987 )
– Zone, Stage, Extent, Plus
• ICROP revisited (2005)
– APROP
– Pre plus

13. International classification of
Retinopathy Of Prematurity
• Four features are evaluated:
– Location
– Severity
– Extent
– Presence or absence of plus disease

14. International classification of
Retinopathy Of Prematurity
• Four features are evaluated:
– Location
– Severity
– Extent
– Presence or absence of plus disease

15. Locations

16. ICROP ( locations)
Zone 1 :
Imaginary circle with
the optic nerve at the
centre & the radius of
twice the distance of
optic nerve to macula.

17. ICROP ( locations)
Zone 2 :
Extends from the
edge of zone 1 to the
ora serrata on the
nasal side of the eye
and approximately
half the distance to
the ora serrata on the
temporal side.

18. ICROP ( locations)
Zone 3 :
Consists of the
outer crescent
shaped área
extending from
zone 2 out to the
ora serrata
temporally.

19. International classification of
Retinopathy Of Prematurity
• Four features are evaluated:
– Location
– Severity
– Extent
– Presence or absence of plus disease

20. ICROP ( severity)
Stage 1 :
A demarcation line
appears as a thin
White line that
seperates the normal
retina from the
undeveloped
avascular retina.

21. ICROP ( severity)
Stage 2 :
A ridge of fibrovascular
tissue with height and
width replaces the line of
stage 1. It extends inward
from the plane of the
retina.

22. ICROP ( severity)
Stage 3 :
The ridge has extraretinal
fibrovascular proliferation.
Abnormal blood vessels
and fibrous tissue
develop on the edge of
the ridge and extends into
the vitreous.

23. ICROP ( severity)
Stage 4 :
Partial retinal
detachment.
Stage 4A : partial
detachment not involving
macula.
Stage 4B : Partial
detachment involving the
macula.

24. ICROP stages

25. International classification of
Retinopathy Of Prematurity
• Four features are evaluated:
– Location
– Severity
– Extent
– Presence or absence of plus disease

26. ICROP (extent)
• Extent refers
to the
circumferentia
l location of
the disease.
• It is reperted
as clock
hours in the
appropriate
zone.

27. International classification of
Retinopathy Of Prematurity
• Four features are evaluated:
– Location
– Severity
– Extent
– Presence or absence of plus disease

28. Plus disease
This refers to the presence
of vascular dilatation and
tortuosity of the posterior
retinal vessels in atleast 2
quadrants.
This indicates a more
severe degree of ROP &
may be associated with iris
vascular engorgement,
pupillary rigidity and
vitreous haze.

29. Pre - Plus disease
Vascular abnormalities of the posterior pole (mild venous dilatation or arterial
tortuosity) that are present but are insufficient for diagnosis of a PLUS
disease.
APROP
Aggressive Posterior ROP : uncommon, rapidly progressive, severe form of
ROP, characterised by posterior location., & prominence of plus disease out
of proportion to the peripheral retinopathy.
Threshhold ROP
If 5 or more contiguous or 8 cumulative clock hours(30 degree) of Stage 3
with plus disease in either zone 1 or 2 are present.
This is the level at which chances of blindness are atleast 50%.
Terminologies

30. Pre – threshhold ROP
1.) Type 1 pre-threshhold ROP:
a.) Zone 1, eyes with any ROP and plus disease or stage 3 with/without
plus disease.
b.) In zone2, stage 2 or 3 ROP with plus disease.
2.) Type 2 pre – threshhold ROP:
a.) In zone 1, stage 1 or 2 without plus disease.
b.) In zone 2, stage 3 without plus disease.
Terminologies (cont…..)

31. Pre – threshhold ROP
1.) Type 1 pre-threshhold ROP:
a.) Zone 1, eyes with any ROP and plus disease or stage 3 with/without
plus disease.
b.) In zone2, stage 2 or 3 ROP with plus disease.
2.) Type 2 pre – threshhold ROP:
a.) In zone 1, stage 1 or 2 without plus disease.
b.) In zone 2, stage 3 without plus disease.
Terminologies (cont…..)

32. • Screening of at risk babies
• Diagnosis
• Treatment
• Cryotherapy ( mostly outdated)
• Laser treatment (gold standard)
• Anti-VEGF (adjuvant) before laser and surgery
• Surgery
– Rx of ROP related complications
• Post treatment follow up
• Rehabilitation
Management

33. • Screening of at risk babies
• Diagnosis
• Treatment
• Cryotherapy ( mostly outdated)
• Laser treatment (gold standard)
• Anti-VEGF (adjuvant) before laser and surgery
• Surgery
– Rx of ROP related complications
• Post treatment follow up
• Rehabilitation
Management

34. Should be performed in all infants :
1.) weight <1500gm, <30 wks gestation.
2.) Weight >1500gm, with an unstable
clinical course.
Screening to be done starting at 4 – 6 wks
of age or 31-32 wks postmenstrual age.
Examination to be done every 2-3 wks till
maturity is reached, if no disease found.
Infants with ROP – to be examined every
1 – 2 wks untill vessels are mature or
disease threshhold has passed away.
Screening

36. • Screening of at risk babies
• Diagnosis
• Treatment
• Cryotherapy ( mostly outdated)
• Laser treatment (gold standard)
• Anti-VEGF (adjuvant) before laser and surgery
• Surgery
– Rx of ROP related complications
• Post treatment follow up
• Rehabilitation
Management

37. Opthalmologic examination by an experienced
examiner usually confirms diagnosis.
1.) Binocular indirect opthalmoscopy is
generally used.
Limitations- does not permit adequate
assessment of ROP in retinal periphery.
Appropriate pain relieving steps like local
anaesthetic eye drops and oral sucrose to be
employed.
2.) Retcam
Wide angle digital paediatric retinal imaging
system.
• Avoids stress & expertise of I/O examination &
indentation, but as specific and sensitive as I/O
• Useful for diagnosis, telemedicine &
documentation
Diagnosis

38. • Screening of at risk babies
• Diagnosis
• Treatment
• Cryotherapy ( mostly outdated)
• Laser treatment (gold standard)
• Anti-VEGF (adjuvant) before laser and surgery
• Surgery
– Rx of ROP related complications
• Post treatment follow up
• Rehabilitation
Management

39. Treatment of ROP

40. • Cryotherapy significantly improves
the outcome of severe ROP
• 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
Treatment - Cryotherapy

41. • Procedure of choice, being less
invasive, less traumatic and causes
less discomfort to the infant.
• 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.
Treatment – Laser therapy

42. Treatment – Anti VEGF therapy
• 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

43. Treatment – Surgery

44. 1.) Scleral buckling
1.
Treatment – surgery

45. 2.) Vitrectomy
1.
Treatment – surgery

46. • Screening of at risk babies
• Diagnosis
• Treatment
• Cryotherapy ( mostly outdated)
• Laser treatment (gold standard)
• Anti-VEGF (adjuvant) before laser and surgery
• Surgery
– Rx of ROP related complications
• Post treatment follow up
• Rehabilitation
Management

47. Prognosis
• 90% of stage 1,2 ROP – spontaneous regression.
• Approx 50% stage 3 –spontaneous regression.
• >stage3 : prognosis better with early laser
photocoagulation , cryopexy.
• Long term sequelae may require follow up.

48. Complications
• Blindness
• High myopia
• Other refractive errors
• Strabismus
• Amblyopia
• Astigmatism
• Late retinal detachment
• Glaucoma

49. Prevention
Interventions to prevent or limit the progression
of ROP have been unsuccessful, further
evaluation may be needed.
Experimental : Antioxidant therapies, such as
vitamin E, D-penicillamine are being tried
Restricted Supplemental oxygen therapy
Insulin-like growth factor-1(IGF-1)

50. Evidences
• CRYO-ROP (1980) - RCT
Peripheral Cryotherapy vs. Observation
Result : Cryotherapy superior to Observation.
• ET-ROP (2003) - RCT
Early peripheral laser vs conventional treatment
– Finding: Observation advised until Type 1 or Regression
Peripheral laser better than conventional treatment for Type 1.
• BEAT-ROP - “Bevacizumab Eliminates the Angiogenic Threat in ROP”
RCT . 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

51. Evidences (cont…)
• STOP-ROP (2000 ) ‘Supplemental Theraupetic Oxygen for Pretreshold
Retinopathy of Prematurity trial randomized infants with prethreshold ROP to low
(SpO 2 89–94%) or high (SpO 2 96–99%) oxygen targets.The high targets caused
more pulmonary complications but no significant difference in the rate of progression
to threshold ROP.
• BOOST 2 (2013) - In the Benefits of Oxygen SaturationTargeting trial, infants <30
weeks’ gestational age were randomized from 3 weeks or more after birth to target a
low SpO 2 (91–94%) or high SpO 2 (95–98%) until they breathed air. A high oxygen
saturation target increased the days of oxygen therapy and use of health care
resources
• A Meta-Analysis and Systematic Review of the Oxygen Saturation Target
Studies (2013) - RRs for mortality and necrotizing enterocolitis are significantly
increased and severe retinopathy of prematurity significantly reduced in low
compared to high oxygen saturation target infants. Until more studies have been
performed, it is suggested to target SpO 2 in these babies at between 90 and
95%.

52. Take home message
• Retinopathy of prematurity is an important cause of blindness in premature
infants.
• ROP is a disease of developing retinal vasculature.
• ROP development occurs in 2 stages – Vascular arrest f/b
neovascularization.
• High risk factors include – Extreme prematurity, Hypo/hyperoxia,
hypo/hypercapnia, sepsis, IVH, anaemia, apnea.
• ICROP (International classification of Retinopathy of prematurity ) classifies
ROP based on 4 parameters – Zone, Severity, Extent, Presence of plus
disease.

53. Take home message
• Screening plays a mojor role in ROP management.
Screening criteria :
1.) weight <1500gm, <30 wks gestation.
2.) Weight >1500gm, with an unstable clinical course.
ROP to be examined every 1 – 2 wks untill vessels are mature or disease
threshhold has passed away.
Treatment includes – Cryotherapy, Laser treatment (gold standard), Anti-VEGF
(adjuvant) before laser and surgery.
Until more studies have been performed, it is suggested to target SpO 2
in these babies at between 90 and 95%.