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15 million preterm birth, India, china, Nigeria, rate of pre-term birth – 5 to 18% .Updated analysis -Sustainable dev. Goals 2016
4 mnths grow from disc, reach ora serrata 8 mnths & ora temporally after birth,
Still no trials for determining the best level for targeted saturation.
Temporal retina is susceptible to ROP. Oxygen exerts an important effect on the remodeling of the original primitive capillary network that develops in the retina
Showed vasoconstriction followed by vascular occlusion.
New vessels are formed from these cells..
Neovsculrstn posterior to ciliary closure-long arrow,short-lens cpsule. 2) neovsculristn in surface of disc.
FA of young kitten with o2 induced nv. Midtrnst phase & late phase of angiogram.
Specimen from 29 week old infnt. Thickened VNGURD---vasodilatation RERGUARD..
Similarly, role of Nitric oxide (Brooks and ass.) and decreased production of VEGF (Alon et al) , overall results in vasoattenuation. Mesenchyml shunt are found suggestive of pathognomic of ROP.
, where retinal findings are stable. --ie, endothelial proliferation and erupt through ILM growing anteriorly .---else leads to Tractional RD.
Inner zone : radius is twice the distance from disc to macul.2Peripheral of Zone I and encircles tangential to ora serrata.--Remaining temporal crest anterior to Zone II. Farthest and last zone to localize. As per 30 degree sector involvement.
These extra-retinal vascularization can be : placoid, polypoid or pedunculated.Placoid being the most common. Significant synchysis and condensation of vitreous over the ridge due to depolymerisation of hyaluronic acid and collapse of collagen framework.
pupil difficult to dilate because of adhesions to the anterior lens capsule and persistence of the pupillary membrane with retention of its vascular network.
Posterior synechiae, iris atrophy, ectropion uveae are common formations…
As defined by Cryo-ROP 1986-2003…
In 2010, the Canadian Paediatric Society suggested by the Royal College of Paediatrics and Child Health, and the Royal College of Ophthalmologists-found that the risk for severe ROP was greatest in infants ≤28 weeks’ GA or weighing <1000 g at birth.
ROP takes longest to develop in very immature infants
Fierson WM, American Academy of Pediatrics, Section on Ophthalmology. American Academy of Ophthalmology. American Association for Pediatric Ophthalmology and Strabismus. American Association of Certified Orthoptists Screening examination of premature infants for retinopathy of prematurity. Pediatrics. 2013;131(1):189–95.
Leads to maturation of spindle cells which decreases gap junction between adjacent cells , decreases cytoplasmic volume of RER and thus cessation of synthesis of angiogenic factors
peripheral ablation of the avascular retina for type 1 prethreshold ROP. monitored closely for regression of plus disease, neovascularization and ridge elevation. Lens sparing vitrectomy-ridge elevation (particularly six clock-hours or more), persistent plus disease or vitreous haze
regulating VEGF signaling through VEGF receptors can restore physiologic homeostasis and permit ordered developmental intraretinal angiogenesis thereby reducing hypoxic peripheral avascular retina, which drives disordered angiogenesis.later recurrence, myopia, longer f/u
essential for vascular growth through regulation of VEGF signalling…promoter of red blood cell formation, used to treat anemia in some premature infants
Late-onset retinal detachment and cataracts also require aggressive management. Individuals with ROP must be followed for eye disease throughout their lives.
Retinopathy of prematurity
• Retinopathy of prematurity (ROP) is a
proliferative retinopathy affecting premature
infants of very low birth weight, who have
often been exposed to high ambient oxygen
• Identified by Terry in 1942 , where he first told
regarding retrolental fibroplasia.
• Later Owens and Owens found out that hyaloid
system are normal at the time of birth and
retrolental fibroplasia developed post-natally.
• Term coined by Heath in 1951.
• In late 60s and 70s, ABG analysis came into use, this
evolved the paediatrician to titrate the incubator
Role of Oxygen
• In 1950s, confirmation were brought regarding
oxygen being the major cause.
• Later on, on different experimental findings :
― factors associated with very low birth weight (Lucey
―Cyanotic heart disease and ROP (Kalina et al and
Johns et al)
• Supplemental Therapeutic Oxygen for Prethreshold
ROP (STOP-ROP) trial.
Mechanism of Oxygen’s effect in immature
Primary Stage : Retinal vasoconstriction and
• Vascular caliber decreases by 50% but may rebound to its
• May be sustained vasoconstriction if there’s elevated arterial
• Local vascular obliteration is completed by 2-3 days of
sustained hyperoxic environment.
Secondary stage :Retinal neovascularization
• Marked endothelial proliferation from residual vascular
complexes, immediately adjacent to ablated retinal capillaries
• New vessels are formed & erupt from Internal Limiting
• Newly formed angioblastic mass called as popcorn formation,
mature into neovascular formation which are filled with
• Remodelling : regress from areas of higher oxygen and grows
towards area of lower oxygen.
• Mesenchyme, blood vessel precursor, grows from optic disc
through nerve fiber of retina. On posterior edge of advancing
mesenchyme, a “chicken wire” meshwork of capillaries
develops to produce mature arteries and veins. (Ashton)
• Similarly Vascular endothelial growth factor (VEGF)key factor
for vessels growth was stated as Factor X. (Michaelson)
• According to Foos, he divided into Vanguard and Rearguard.
Vanguard –anterior compartment containing spindle cells
(progenitors)- Garner for nourishment.
Rearguard contains primitive endothelial cells which aggregates
into cords for neovascularization.
Flynn and co-workers
1. Injury occurs where it has differentiated from mesenchyme
to form primitive capillary meshwork.
2. After injury, mature vessels merge and survive via few
vascular channels and forms mesenchymal AV shunts that
replaces destroyed capillary bed.
3. Shunt (AP-AV) consists of a nest of primitive mesenchymal &
maturing endothelial cells ,fed by mature arteries and veins.
Flynn also stated :-
• Retina will remain in dormant period after injury for
days to months
• Fate of the eye is decided as the tissue thickens and
changes its colour.
Grey white > pink > salmon > red.
• In Progressive disease, primitive cells proliferate.
• Normally, these cells divide and differentiate to form
normal capillary endothelium.
• The International Classification of ROP (ICROP)
that was published in 1984 standardized the
terminology used to describe ROP .In 2005, a
second committee for the classification of ROP
revised the original ICROP.
Staging of ROP
• 5 stages :
1. Demarcation line
3. Ridge with extraretinal fibrovascular proliferation
4. Subtotal Retinal Detachment (RD)
―4a : Extrafoveal RD
―4b : Partial RD with fovea
5. Total RD
Stage 1 : Demarcation Line
• Line separating Ant. &
• Usually white & flat ,
lies within plane of
• Due to abnormal
branching or arcading
Stage 2 : Ridge
• Grown demarcation line
• Has height & width &
• Extends centripetally
within the globe
• Small tufts of new
vessels (“popcorn “
lesion) seen posterior
but not attached to
Stage 3:Ridge with extraretinal
• Localised continuous
with posterior & inferior
aspect, causing ragged
appearance of ridge as
• Presence of increased
retinal vessels coursing
from retinal surface ,not
only constitute RD but
also signify Vitreous
Stage 4a : Subtotal Retinal Detachment
• concave, tractional type
• Occurs in periphery
without central macula
• Located at proliferative
• May extend 360
• Prognosis : good if
Stage 5 : Total Retinal Detachment
• Usually funnel shaped
as seen in USG.
• Involves both anterior
and posterior part.
• Concave configuration
and extends upto optic
• More florid form of ROP
• Increased dilatation &
tortuosity of retinal
• Iris vascular
• Pupillary rigidity
• Vitreous haze
• + : key sign of worst
Preplus disease/(‘rush’) disease
• Uncommon but if
untreated reaches to
stage 5 within few days
• Posterior location
• Prominence of plus
• Ill-defined nature of
1. Appearance of retrolenticular space
2. Peripheral trough : presence of peripheral
red reflex in combination with apparent
narrow funnel shows avascular peripheral
retina. ( stage 5)
3. Anterior segment abnormalities ( stage 4 or
Prethreshold and threshold disease
• Prethreshold ROP, Type 1.
› Zone I, any stage with plus disease;
› zone I, stage 3 without plus disease;
› zone II, stage 2 or 3 with plus disease.
• Prethreshold ROP, Type 2.
› Zone I, stage 1 or 2 without plus disease;
› zone II, stage 3 without plus disease.
• Threshold ROP.
› Zone I or II, stage 3 (five contiguous or eight total
clock hours with plus disease).
Involution of ROP
• Typically at 38-39 weeks post-conceptual or
• Downgrading of staging &/or growth of
retinal vessels into more peripheral zone
• Present in 70-80 % .
• About 20% of infants with active ROP may
develop this complication.
• More general and more advanced or more
posterior the proliferation , worse the
• Temporal vitreoretinal fibrosis and
straightening of vascular arcades with
‘dragging’ of macula and disc .
Cicatricial disease (continue)
• Progress to retrolental fibrovascular tissue
lead to falciform retinal fold formation and to
retinal detachment, sometimes total and
called as retrolental fibroplasia.
• Secondary glaucoma (angle closure) : major
• every infant ≤306/7 weeks’ GA regardless of
birth weight, as well as any infant with a birth
weight ≤1250 g were screened.
• In 2014, an updated (2009 to 2014) literature
search was conducted.
• 1st examination should be considered 4-6
weeks from birth i.e., 31 to 33 weeks post-
• Prior to 4 weeks are not considered necessary.
Techniques of eye examination
• Effective dilatation (
and phenylephrine 1%)
twice 1 to 5 minutes
• Lid speculum :
• N-P cultural swab
• Scleral depression
Prophylaxis & Therapy
1. Vitamin E : Recognized antioxidant of choice .
shouldn’t exceed 3 mg/dl.
(hittner et al and kretzer et al).
Role of Light
• On various researches and trials, no effective
results have been found.
• Neither the American Academy of
Ophthalmology nor the American Academy of
Pediatrics have made any recommendations
about restricting ambient light from the eyes
of premature infants.
• Laser > cryotherapy : easier
and few post-op sequalae.
• Diode laser (810 nm) is
better than argon laser (488-
532 nm ).
• Photocoagulation burns are
distributed 0.5-1 burn width
• 600-1000 laser spots.
• Power : 0.15 watts
• Pulse duration : 0.3-0.4
• Chest & CVS
• Swaddled in blanket
with mydriatics &
• In case of GA, perform
laser in both the eyes.
Intravitreal anti- VEGF agents
• More precedence in
• Look after systemic
complications and long
• The Bevacizumab Eliminates the
Angiogenic Threat of Retinopathy
of Prematurity (BEAT-ROP) Study
• Can be performed for stage 4a , where success
rate is 90 % .
Early treatment of ROP (ETROP) Trial
Type 1 ROP
• ZONE II : plus disease with
stage 2 or 3.
• ZONE I :Plus disease with stage
1, 2 or 3.
• Stage 3 without Plus disease.
• Treatment : Peripheral laser
• Plus disease: involve at least 2
quadrants of fundus with
Type 2 ROP
• Zone II : Stage 3 without
• Zone I : Stage 1 or 2 without
• Treatment : Wait and watch
Other recent studies
• IGF-1 pathway & dietary supplementation
with omega-3 polyunsaturated fatty acids
• Recombinant Erythropoeitin (Epo)
• Digital photographic retinal images that are
captured and sent for remote interpretation is
a developing approach to ROP screening
Evaluating Acute-phase ROP (e-ROP) study
1. Retina , 4th edition , Stephen J. Ryan
2. Kanski’s clinical ophthalmology , 8th edition,
3. Jefferies, A. L., & Canadian Paediatric Society,
Fetus and Newborn Committee. (2016).
Retinopathy of prematurity: An update on
screening and management. Paediatrics &
Child Health, 21(2), 101–104.