A slide show summarizing pertinent points of retinopathy of prematurity.

1. Retinopathy of
Prematurity
Dr Haitham Al-Mahrouqi
Oman Medical Specialty Board
September 2018

2. Resources
❖ AAO, BSCS books
❖ Ophthalmology by Yanoff
❖ Retina by Ryan

3. Definition
❖ Vasoproliferative retinal disorder of premature babies.

4. History
❖ It was first described in the 1950s when premature babies were
supplemented with high oxygen.

5. Embryology
❖ Retinal vasculature begins in
the 16th week.
❖ The vessels grow centrifugally
from the optic disc.
❖ The nasal ora is fully
vascularized by week 36.
❖ The temporal ora is fully
vascularized by week 40.

6. Angiogenesis
❖ De novo vessel formation, vasculogenesis, and for angiogenesis, the
formation of vessels from pre-existing vasculature

8. Simplified pathogenesis
❖ Immature retina is exposed to high oxygen environment
❖ Vaso-obliteratin ensues
❖ Child is returned to room level oxygen
❖ Ischaemic tissue produce VEGF leading to neovascularization

9. Classification
❖ Location (zone)
❖ Stage (severity)
❖ Extent (in clock hours)

10. Location (Zones)
❖ Zone I (posterior pole): With the
nasal edge of the optic disc at one
edge of the field of view with a 28D
lens, the limit of Zone I is at the
temporal field of view.
❖ Zone II: From zone I to the nasal ora
serrata; temporally equidistant from
the disc. NOTE: ROP should not be
considered zone III until one is sure
the nasal side is vascularized to the
ora serrata.
❖ Zone III: The remaining temporal
periphery.

11. Stage (severity)
❖ Stage 1: Flat demarcation line separating the vascular posterior retina from the
avascular peripheral retina
❖ Stage 2: Ridged demarcation line.
❖ Stage 3: Ridged demarcation line with fibrovascular proliferation or extra-retinal
neovascularization extending from the ridge into the vitreous
❖ Stage 4A: Extrafoveal partial retinal detachment.
❖ Stage 4B: Foveal partial retinal detachment.
❖ Stage 5: Total retinal detachment.

12. Stage I
❖ Demarcation line

13. Stage II
❖ Ridge

14. Stage III
❖ Ridge with tufts of NV

16. Stage IV
❖ Partial RD

18. Stage V
❖ Total RD

19. “Plus disease”
❖ At least two quadrants of engorged veins and tortuous arteries in the posterior pole.
❖ Other signs of plus disease: Iris vascular engorgement, pupillary rigidity, and vitreous haze.
❖ If plus disease is present, a “+” is placed after the stage (e.g., stage 3+).
❖ If vascular dilatation and tortuosity are present but inadequate to diagnose plus disease, it is
called “pre-plus” disease.
❖ Posterior ROP (usually Zone I) with plus disease out of proportion to the peripheral
retinopathy, or so-called “rush” disease (also known as aggressive posterior disease),
may progress rapidly to stage 5 ROP without passing through the other stages. This
aggressive ROP may also show hemorrhages at the junction between vascular and
avascular retina.

20. Plus disease

21. NOTE
Overall stage is determined by the most severe manifestation;
however, it is recommended to define each stage and extent.

22. Extent
❖ Simply in clock hours

23. Risk factors
❖ Gestational age
❖ Low birth weight
❖ High supplemental oxygen
❖ Therefore screening in (Wills Eye Manual):
❖ Birth weight ≤1,500 g.
❖ Gestational age ≤30 weeks.
❖ Selected infants with birth weight >1,500 g or gestational age ≥31 weeks with unstable clinical course thought to
be at high risk.
❖ Timing of first eye examination is based on postmenstrual (gestational age at birth plus chronologic age) and
postnatal (chronologic since birth) age. The first eye examination should start at 31 weeks postmenstrual age or
4 weeks postnatal age, whichever is later.

24. Treatment
❖ Cryotherapy (Study: Cryo-ROP)
❖ Laser photocoagulation (Study: ETROP)
❖ Anti-VEGF (Beat-ROP)

25. Cryotherapy
❖ Earliest treatment
❖ Effectiveness addressed by CRYO-ROP
study
❖ Defined threshold disease: stage 3+ ROP in
zones 1 or 2 occupying at least five
contiguous clock-hours or eight noncon-
tiguous clock-hours of retina.
❖ Severity of ROP where spontaneous
regression was equal to progression to
unfavourable outcome. Therefore, threshold
disease or worse was only treated.

26. Laser photocoagulation
❖ Roughly 44% of eyes with zone 2 ROP in
the CRYO-ROP had an unfavorable
outcome despite appropriate intervention.
Therefore ETROP was designed to test
earlier intervention and the use of laser
ablation.
❖ Treatment of Type I pre-threshold ROP
significantly decreases unfavorable visual
acuity outcomes (19.5% to 14.5%; p = 0.01)
and structural outcomes (15.6% to 9.1%; p
< 0.001).

27. Anti-VEGF
❖ BEAT-ROP study
❖ In the BEAT-ROP study,49
150 infants with bilateral stage 3+ ROP in zone 1 or posterior zone 2
were randomized to receive either intravitreal bevacizumab monotherapy (0.625 mg in 0.025
cc) or laser photocoagulation in each eye. The primary outcome measure was recurrence of
retinal neovascularization by 54 weeks postconceptional age, ascer- tained in 143 surviving
infants. In subjects with zone I ROP treated with bevacizumab, recurrence was significantly less
than in subjects treated with standard laser photocoagulation (6% compared with 42%, p=0.003).
In subjects with posterior zone II ROP, recurrence was lower in those treated with bevacizumab
(5% compared with 12%, p = 0.27), but not to a statistically significant degree. The timing of
recurrence was much later in subjects treated with bevacizumab (16 weeks com- pared to 6
weeks). No systemic safety signals were raised, but no systemic adverse events were defined a
priori as outcome measures.

28. Treatment summary
❖ Treatment should be initiated within 48-72 hrs
❖ Type 1 ROP needs treatment.
❖ Type 2 ROP should be followed closely.
❖ For stages 4 and 5: Surgical repair of retinal detachment by scleral buckling,
vitrectomy surgery, or both is recommended.

29. Follow-up
❖ A single ocular examination is sufficient only if it unequivocally shows full retinal vascularization in both
eyes.
❖ One week or less: immature vascularization, zone I, no ROP; immature retina localized to boundary of zone I and II;
zone I, stage 1 or 2; zone II, stage 3; or any concern for aggressive posterior ROP.
❖ One to 2 weeks: immature vascularization localized to posterior zone II; or zone II, stage 2; or zone I, regressing
ROP.
❖ Two weeks: immature vascularization localized to zone II, no ROP; zone II, stage 1; or zone II, regressing ROP.
❖ Two to 3 weeks: zone III, stage 1 or 2; or zone III, regressing ROP.
❖ Children who have had ROP have a higher incidence of myopia, strabismus, amblyopia, macular dragging,
cataracts, glaucoma, and retinal detachment. An untreated fully vascularized fundus needs examination at age 6
months to rule out these complications.
❖ Because of the possibility of late retinal detachments and other ocular complications, ROP patients should
be followed at yearly intervals for life.

30. When to stop screening?
Will’s eye manual
❖ Acute-phase ROP screening can be discontinued when any of the following signs is present, indicating
that the risk of visual loss from ROP is minimal or passed:
❖ Zone III retinal vascularization attained without previous zone I or II ROP. If there is doubt about the
zone or if the postmenstrual age is <35 weeks, confirmatory examinations may be warranted.
❖ Postmenstrual age of 50 weeks and no ROP disease equivalent to or worse than zone I, any stage or
zone II, stage 3.
❖ Full retinal vascularization in close proximity to the ora serrata (for cases treated with anti-VEGF
therapy).
❖ If treated with anti-VEGF, follow-up should be extended due to risk of ROP recurring after 45 weeks.

31. If you are stuck!
You need to do something within 48-72 hours if:
1) Plus disease and OR
2) Stage III and above

32. Thanks