This document provides an overview of retinopathy of prematurity (ROP), including: 1) ROP is a proliferative retinopathy affecting premature infants that can cause lifelong visual impairment. 2) The development of the retinal vasculature is disrupted in premature infants due to their early exposure to a hyperoxic extra-uterine environment. 3) Laser photocoagulation treatment is recommended for high-risk pre-threshold and threshold ROP to ablate the peripheral avascular retina and prevent retinal detachment and blindness.

1. RETINOPATHY OF PREMATURITY

2. Introduction & Definition
• Retinopathy of prematurity (ROP) is a proliferative retinopathy affecting
premature infants of low birth weight and young gestational age.
• ROP remains a leading cause of life long visual impairment among children
• Earlier this disease was known as Retrolental fibroplasia.

3. Development of retinal vasculature
• During normal retinal development , vasculogenesis transforms precursor
mesenchymal cells into capillary networks beginning at about 16 weeks of
gestation.
• Mature vessels differentiate from these networks and reach-
– Nasal ora serrata at about 36 weeks
– Temporal ora serrata at about 39 to 41 weeks

4. • Full retinal vascular development is mostly accomplished in utero, where
the fetus is:
1. In a relatively hypoxic environment ( average PaO2 is 25-35)
2. Exposed to the placental and maternal cytokines and growth factors

5. Risk factors for ROP
• Primary risk factors:
– Low gestation age, especially <32 weeks
– Low birth weight (<1500g, especially <1250g)
– Supplemental oxygen therapy

6. Other risk factors
• Light
• Vitamin E deficiency
• Respiratory distress syndrome
• Asphyxia
• Shock and acidosis

7. Pathogenesis
• Pathogenesis of ROP is multifactorial – influenced by developmental,
genetic and environmental factors
• Premature birth exposes the fetus to ex-utero hyperoxic environment and
disrupts several pivotal cell-signalling pathways and growth factors
involved in retinal vasculogenesis.
• High oxygen administration at birth was among the first factors to be
found critical to the pathogenesis of ROP.

8. Two phase hypothesis for ROP
• FIRST PHASE
– There is a delay or halting in physiological retinal vascular
development due to:
• Prematurity
• Hyperoxia induced endothelial cell damage
• Subsequent vasoattenuation

9. Second phase
• Peripheral avascular retina continues to develop in the
absence of a developing vascular bed
• Becomes relatively hypoxic and secretes pro-angiogenic
factors
• Promote retinal neovascularization and abnormal
vasoproliferation in the vitreous

10. Clinical features and classification
• The international classification of retinopathy of prematurity
(ICROP) was instrumental in establishing the standards and
nomenclature for the clinical assessment of ROP based on:
– Anatomical location (zone) and
– Severity (stage) of disease

13. Extent of involvement

14. Stages
• Stage 1: demarcation line
• Stage 2: ridge
• Stage 3: extra retinal fibrovascular proliferation
• Stage 4: Partial retinal detachment (extrafoveal/ foveal)
• Stage 5: total retinal detachment

17. Stage 2- ridge
• Demarcation line develops into a pink or white elevation
(ridge) of thickened tissue
• Small tufts of vessels may be seen posterior to the ridge

20. Stage 3 – Extraretinal fibrovascular
proliferation
• Vessel growth into and above the ridge (extraretinal
fibrovascular proliferation)
• This fibrovascular proliferation may extend into the overlying
vitreous and cause prereinal or vitreous hemorrhage

23. Stage 4- Partial detachment
• Contraction of fibrovascular proliferation exerts traction on
the retina, leading to partial retinal detachment
– Stage 4A: without foveal involvement
– Stage 4B: with foveal involvement

27. Stage 5- Total retinal detachment
• Detachments are funnel shaped and described as open or closed
anteriorly and open or closed posteriorly
• Retrolental fibroplasia: refers to what we know today as stage 5

28. ROP stage 5

30. Differential diagnosis
• Active ROP needs to be differentiated from:
– Familial exudative vitreoretinopathy (FEVR)
– Incontinentia pigmenti in girls
– Persistent fetal vasculture
• Advanced retrolental fibroplasia: the presenting fiding in this may be leukocoria and
hence needs to be differentiated from other causes of leukocoria like:
– Retinoblastoma
– Exudative Retinal detachment- commonly from Coat’s disease
– Coloboma optic disc or choroid
– Toxoplasmosis/ Toxocariasis
– Cataract
– Genetic syndromes like trisomy 13, Norrie’s disease etc

31. Diagnosis and screening
• Early diagnosis and treatment is essential to prevent blindness in high risk
cases.
• Therefore, a regular screening and timely intervention is recommended.
• Screening of ROP should be performed in all premature infants born :
– Less than or equal to 32 weeks of gestational age ( for Indian scenario < 35
weeks)
– Those weighing 1500g or less ( for Indian scenario <2800gm )

32. Screening procedure
• Initial examination of the anterior segment is performed with specific
attention to the iris vessels, lens, and tunica vasculosa lentis
• After pupillary dilation, fundus examination is performed with an indirect
ophthalmoscope and a 20 D lens
• The posterior pole is examined without depression for plus disease
• Scleral depression is then used to examine the temporal retina, followed
by thenasal retina, to establish the proximity of retinal vessels to the ora
serrata

33. First examination
• Should be performed between 4 and 6 weeks of chronological (postnatal) age
or between 31 & 33 weeks of postmenstrual age, whichever is later.
• Further line of action will depend upon the status of retina
• Immature retina is labelled when the vessels are short of one disc diameter of
the nasal or temporal ora serrata but ROP is not developed yet.
• ROP, when present should be classified as its stage, zone, and extent of
involvement.

34. Subsequent follow-ups
• Examination at 2 week intervals - Infants with immature
retinas (no ROP) vascularized into zone II or III
• Examination weekly or twice a week may be required in
infants with type 2 pre-threshold disease (low risk)
• Peripheral laser ablation - is required for infants with type1
prethreshold disease (high risk).

35. Retcam
• Delivers objective, interpretable detail
• Allows image comparison over time
• Enables remote consultations and facilitates
a convenient method for second opinions
• Serves as an effective educational
tool for staff and parents which may help with
compliance
• Provides reliable, defensible medico-legal
documentation

38. Management
• Treatment of well-established disease is unsatisfactory
• Thus prophylaxis is very important
• To reduce high-risk ROP:- premature newborns should not be placed in
incubator with an 02 concentration of more than 30%.
• Efforts should be made to avoid infections or attacks of apnoea.

39. Ablation of peripheral avascular retina
• Can be done by:
– Cryotherapy (or)
– Laser photocoagulation
• ETROP group has recommended use of laser over the cryotherapy
• Advantages of laser photocoagulation over cryotherapy include ease of
treatment, portability, and fewer systemic complications.

40. • Laser photocoagulation is done usingLIO
(Laser indirect ophthalmoscope)with
– Diode laser 810 nm (or)
– Frequency doubled Nd: YAG (532nm)
• Laser photocoagulation should be carried
out in all patients with high-risk pre-
threshold, threshold, and aggressive
posterior ROP

41. Post laser follow-ups
• Post-laser treatment follow-up should be done weekly for 3
weeks
• Persistent plus disease or fibrovascular proliferation are
indications for additional re-treatment
• Subsequent follow-up examination should be continued at 3,
6 and12 weeks after treatment.

42. • Complications of laser photocoagulation
– Anterior segment ischemia
– Cataract
– High myopia
– Burns of the cornea, iris, or tunica vasculosa lentis.

43. Pharmacological blockade of VEGF
• Intravitreal Bevacizumab & Ranibizumab (Anti-VEGF) has been
used for the treatment of ROP, but an optimal regimen is yet
to be established
– Zone I disease is more likely to respond than zone II
– Potential advantage is it allows retinal development to proceed
normally without destruction, which is integral to laser treatment
– However, systemic complications an long-term effects in this age
group are undetermined.

44. Surgery in ROP
• Although retinal ablation is effective in a majority of cases of ROP, some eyes will
progress to retinal detachment (RD)- Stages 4A, 4B and 5
• RD in ROP is most commonly tractional type originating at the ridge.
• The surgical goal is interrupting the traction resulting from fibrous proliferation
and several tractional vectors
• Patients with stage 4A, 4B and 5 require surgery
– Lens sparing vitrectomy
– Endolaser photocoagulation
– Retinal reattachment measures

45. THANK YOU