Retinopathy of Prematurity

Pathogenesis
• In the normal foetus, vascular development of
the retina occurs in two phases.
– Fase 1 : True vasculogenesis : 8-21 weeks of foetal
development
– Fase 2 : Angiogenesis : 22 to 40 weeks of
development : VEGF dependant
• Physiologic angiogenesis
• Pathologic angiogenesis (ROP pathogenesis)
 Risk Factors
• Crucial risk factors :
– Birth weight
– Gestational age
– Number of days oxygen administered
• Other risk factors :
– Multiple births
– Blood transfusions
– Respiratory Distress Syndrome (RDS)
– Sepsis
– Intra Ventricular Hemorrhage (IVH)
– Intra Uterine Growth Retardation (IUGR)
– Vit E deficiency
– Anemia
– Seizures.
 ROP Screening in Indonesia
• 1st Indonesia
National Workshop
in ROP (2009-
Jakarta)
• 2nd Indonesia
National Workshop
in ROP (2010-
Surabaya)
 Screening criteria in Indonesia

• BW < 1500 gr or GA < 34 minggu

• Pemeriksaan pada bayi dengan berat lahir lebih
atau usia gestasi lebih dapat diminta oleh
neonatologis atau dokter anak tergantung
keparahan faktor risiko seperti tingginya saturasi
O2 selama lebih dari 1 minggu, transfusi berulang
• Bayi dengan usia gestasi 37 mgg atau lebih tidak
perlu pemeriksaan ROP
 When to screen ??

• Jika usia gestasi > 30 mgg, diperiksa 2-4 mgg

setelah kelahiran
• Jika usia gestasi kurang atau sama dengan 30
mgg, diperiksa 4 mgg setelah kelahiran
• Setidaknya satu kali pemeriksaan sebelum
pulang dari rumah sakit
 How to examine ??
• Tropicamide 0.5%
• Phenylephrine hcl 2.5%
• Pantocain
• Topical antibiotic
• Indentator
• Eyelid speculum
 International Classification of ROP
(ICROP)
• Location
– A-P zone
• Severity
– Stage 1-5
– Aggressive Posterior ROP (AP-ROP)
– Plus (+) disease
• Extent
– Sectors
 Location of diseases
• Zone I - circle, the radius of which extends
from the disc to twice the distance from the
disc to the fovea.
• Zone II – extends from the edge of zone I
peripherally to ora serrata nasal and
equivalent area near the temporal equator
• Zone III – residual crescent of retina anterior
to zone II temporally
Zone and extent of ROP
 Stage of Retinopathy
• Immature – no ROP
• Stage 1 – Demarcation line
• Stage 2 – Ridge
• Stage 3 – Extraretinal neovascularization from
area of ridge
• Stage 4 – Partial retinal detachment
– 4a : Fovea not involve
– 4b : Fovea (+)
• Stage 5 : Total retinal detachment
Stage 1 : Demarcation line
Stage 1 : Demarcation line
Stage 2 : Ridge
Stage 2 : Ridge
Stage 3 : Extraretinal fibrovascular
proliferation
Stage 3 : Extraretinal fibrovascular
proliferation
Stage 3 : Extraretinal fibrovascular
proliferation
Stage 4 : Partial retinal detachment
Stage 4 : Partial retinal detachment
Stage 5 : Total retinal detachment
 Plus Disease
• At least two quadrants of sufficient vascular
abnormality required

• Other frequent associated findings :

– Iris vascular engorgement
– Poor pupillary dilation (rigid pupil)
– Vitreous haze
Plus Disease
Plus Disease
 Pre-Plus Disease
• Abnormal dilation and tortuosity of posterior
pole insufficient for the diagnosis of plus
disease
• Over time, pre-plus may progress to plus
disease
Aggressive Posterior – ROP (AP-ROP)
Aggressive Posterior – ROP (AP-ROP)
 Threshold Disease
• It was defined by the CRYO-ROP study,5 as
– Stage 2 in zone I or II involving > 5 contiguous
clock hours with plus disease.
– or Stage 2 in zone I or II involving 8 cumulative
clock hours with plus disease.

• This was the previous “cut off” stage for

treatment.
 Prethreshold disease
• Early Treatment ROP (ETROP) study has
revised the treatment guidelines. This study
proved that earlier treatment (Pre Threshold
stage) has a better outcome.
– High Risk Prethreshold or Type 1 ROP
– Low Risk Prethreshold Disease or Type 2 ROP
 High Risk Prethreshold or Type 1 ROP

• This is the new “cut off” for treatment

• It should be treated immediately
• Type 1 :
• Zone 1 any stage with plus disease or
• Zone 1 stage 3 without plus disease or
• Zone 2 stage 2 or 3 with plus disease.
Low Risk Prethreshold Disease or Type 2 ROP

• considered for treatment only if they progress

to type 1 or threshold ROP

• Type 2 ROP :
• Zone 1 stage 1 or 2 without plus disease or
• Zone 2 stage 3 without plus disease.
 Detection of serious acute phase ROP
relies on good understanding of ICROP
• Zone : 1, 2 or 3
• Severity :
– Stage 1 – 5
– PLUS disease, preplus disease
– AP-ROP
• Extent
– Not so important with current treatment
indications
– Sectors or hours
 Basic Principle of ICROP

The more posterior the disease and the

greater the amount of involved retina,
the more serious the disease
 How to treat ?
• Principle is ablation of the ischemic peripheral
retina stops release of angiogenic factors
• Cryotherapy
• Laser photocoagulation
• Surgical treatment
– Scleral buckling
– Lens sparing vitrectomy for stage 4
– Lensectomy + vitrectomy
– Open sky vitrectomy for stage 5
Cryotherapy
Laser Photocoagulation
Lens sparing vitrectomy
 Role of anti VEGF injections in ROP

• Very controversial
• In premature infants VEGF is needed for normal
vascularization to be completed.
• Thus anti VEGF injections will stop growth of not only
abnormal new vessels but also the normal ones.
• Also systemic absorption may cause vascular
development delay in other developing organs also.
• Currently anti-VEGF injections are used in ROP only
when the standard treatment (which is laser) fails and
the disease progresses. It is not recommended as the
first line of management till the results of randomized
trials are out.
Thank You