Retinopathy of prematurity is a multifactorial

vasoproliferative retinal disorder that

Increases in incidences with decreasing gestational age .

Its a developmental vascular proliferative disorder

that occurs in the incompletely vascularized retina of

primarily premature infants.

• First described by TERRY in 1941

• Originally known as Retrolental fibroplasia

• Term RETINOPATY OF PREMATURITY was

coined by Health in 1951.

• Campbell suggested the relationship of

intensive oxygen therapy & subsequent

development of ROP.

• Kinsey: ROP was inversely proportional to

birth weight.

• Retina is a thin, semitransparent, multilayered sheet of neural tissue that lines the inner aspect of the posterior two-thirds of the wall of the globe.

• It is a thin delicate layer of nervous tissue of surface area 266mm2.

• It extends from optic disc to ora serrata

Retinal Vascularization begins at optic nerve head by 16 weeks of gestation, which migrate from the optic disc

at posterior pole and move towards periphery by 21-22 weeks of gestation.

Before the retinal vessels develops the avascular retina receives it oxygen supply by diffusion across the retina from choroidal vessels.

Choroidal Vascularization begins at 6th weeks of gestation and it is completed by 21 weeks

Retinal vessels grow out of the optic disc as a

wave of mesenchymal spindle cells.

Mesenchymal spindle cells lead the shunt,

endothelial proliferation and capillary

formation follow.

These new capillaries will form the mature

retinal vessels.

6 wks- The choroidal vessels supply the rest of

the avascularized retina.

32 Wks- The nasal portion of the retina is

completely vascularized to the ora serrata .

40-42 weeks - The larger temporal area usually

is completed

The onset of ROP progresses in two phases:

PHASE 1 : It involves an initial insult such as hyperoxia , hypoxia

or hypotension at a critical point in retinal vascularization. Which

causes vasoconstriction and decreased blood supply to the

developing retina with subsequent arrest in vascular

development.

The relative hyperoxia after birth is hypothesized to downregulate

the production of growth factor such as vascular endothelial

growth factor (VEGF)essential for normal development of Retinal

vessels.

PHASE 2: during the second phase Neovascularization

occurs. This abberant retinal vessel growth is thought to

be driven by excess angiogenic factors (VGEF) upregulated

by hypoxic avascular retina.

New vessels grow through the retina in to the vitreous .

These vessels are permeable , thus hemorrhage and edema

occurs.

Extensive and severe extraretinal fibrovascular proliferation

can lead to retinal detachment .

ROP pathogenesis and suggested treatments. (a) Retina vessels in the process of their

formation and progressive covering of the retina surface. (b) Hyperoxia at this formative

stage suppresses VEGF and, consequently, results in regression of newly formed

vessels. (c) Upon return to normal air, the ischemic retina upregulates VEGF to high

levels, causing excessive formation of leaky vessels. To antagonize VEGF at this stage

has been suggested as a strategy to reduce adverse vessel formation. (d) An alternative

strategy proposed by Shih et al. (2) is to protect retina vessels from oxygen-induced

obliteration through administration of PlGF-1.

• prematurity / low gestational age < 30 weeks

• Low birth weight

• Hyperoxia / Hypoxia

• High Light exposure

• Vitamin E deficiency

• Postnatal sepsis

• Mechanical ventilation

• Intraventricular haemorrhage

• Apneic attacks

• PDA

• Breast feeding is proctective against development of

ROP.

• Infant born to mother with pregnancy induced

hypertension have a reduced risk of developing ROP

due to accelerated fetal maturity of retinal vessels.

The International Classification of retinopathy of prematurity

(ICROP).

The classification consists of four components : Location

Severity

Extent

Plus Dieasese

Refers to how far the developing retinal vessels have

progressed . The retina is divided into three concentric circles or

zones :

Consist of an imaginary circle with optic

nerve at the centre and a radius is twice

the distance from optic nerve to the macula

.

Extents 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.

Consist of the outer cresent

shaped area extending from the

Zone 2 out to the ora serrata

temporally.

It refers to the stage of the diesease :

A demarcation line appears as a thin white line that

separates the normal retina from underdeveloped

avascular retina

A ridge of Fibrovascular tissue wight height and

width replaces the demarcation line . It extends

inwards from the plane of retina .

Ridge of fibrovascular tissue

Popcorn Isolated tufts of neovascular tissue

posterior to ridge at the level of retina

The ridge has extraretinal fibrovascular proliferation .

Abnormal blood vessels nd fibrous tissue develop on the

edge of the ridge and extend in to the vitreous.

Partial retinal detachment may result when the

scar tissue pulls on the retina.

-Tractional, as part of the change over from acute to cicatricial disease.

-Rhegmatogenous detachments, years later

STAGE 4 A

Macula Spared

STAGE 4 B

Macula involved

Complete retinal detachment occurs . The retina assmes a

funnel shaped appearance and is described as open or

narrow in the anterior and posterior zone .

REPORTED AS CLOCK HOURS IN THE APPROPRIATE ZONES

• Additional designation that refers to the presence of vascular dilation and arteriolar tortuosity of posterior retinal vessels at least 2 quadrants

• This indicates the severe form of the disease

• It may be associated with Iris vascular engorgement, pupillary rigidity, and vitreous haze.

It’s a vascular abnormalities of the posterior pole more than normal, less than PLUS

The newly accepted preplus serves as a warning

THRESHOLD ROP: • CRYO ROP study

• Zone I stage III with Plus

• Zone II Stage III with Plus

• ( 5 contigous or total 8 clock hours

• Risk of blindness is 50%

PRETHRESHOLD ROP :

• High risk Prethreshold

• Zone I Stage I, II, III with plus

• Stage III without plus

• Zone II Stage II and III with plus

WHOM TO SCREEN ?

• The recommendation is to screen all babies with

a Birth Weight < 1500gm

• Gestational age < 30 weeks

• Babies born after 30 weeks of gestation may be

considered for screening if they have been ill (

RDS, hypotension, surgery ) .

When to screen ?

• Babies born at < 26 of gestation area examined at

the at the postnatal age of 6 weeks .

• Babies born between 27 – 28 weeks of gestation are

examined at the postnatal age of 5 weeks .

• Babies born between 29 – 30 weeks of gestation are

examined at the postnatal age of 4 weeks.

• Babies of gestation >30 weeks are examined at the

postnatal age of 3 weeks.

• Patients are screened every 2 weeks until their

vessels have grown out to the ora Serrata and the

retina is considered mature.

• If ROP is diagnosed the frequency of the

examination depends on the severity and

rapidity of the progression of the disease.

How to screen ?

• The procedure is performed at in NICU by pediatric

opthalmologist , under thesupervision of neonatologist so that

complication can be handled.

• The pupil are dilated with a mixture of phenyl phrine 2.5% and

tropicamide or cyclopentolate 0.5% instilled 3times at 10min

intervals before the scheduled examination.

• Indirect opthalmoscopy is performed with 20D / 30D lens using

fresh sterile instruments.

• Scleral depression is done to stabalize the eye , rotate it , indent

it, and contrast retina.

• RETCAM can be used to provide real time video display of

images

• Tropical anesthetic should be used to reduce discomfort.

• Atleast two fundal examination should be performed after

dilatation

using binocolor indirect opthalmoscope.

• When ROP is diagnosed the frequency of examination depends

severity and rapidity of disease.

Wide angle digital paediatric retinal imaging system

Mobile, self contained system for use in nursery, ICU,

O.T

Easily used by technicians or nurses

Provide retinal images at 130 degree

Avoids stress & expertise of I/O examination &

indentation, but as specific and sensitive as I/O

Useful for diagnosis, telemedicine & documentation

When can the Retinal examination be

terminated ?

• COMPLETE VASCULARIZATION

• VASCULARIZATION in ZONE III (till 1 DD of temporal ora) – if no previous ROP in zone I & II

• REGRESSED ROP ( b/w 40 -44 weeks PCA)– no active disease left

• 45 weeks PCA with less than pre threshold disease

Cryotherapy ( mostly

outdated)

Laser treatment (gold

standard)

Anti-VEGF (adjuvant)

before laser and surgery

Surgery

Cryotherapy significantly improves the outcome of

severe ROP

Superceded by laser photocoagulation.

Cyroprobe is applied to the external surface of the

sclera and areas peripheral to the ridge are frozen

until in avascular retina has been treated.

The procedure is done general anesthesia.

End point of cryotherapy is the appearance of

mild whitening.

360 degrees circumference, under direct

visualization avoid the ridge.

multiple white cryo burns (black

arrows) in avascular retina

anterior to ridge (white arrow).

Complications of cryotherapy

Procedure of choice, being less invasive, less

traumatic and causes less discomfort to the

infant.

Laser treatment is delivered through an

indirect opthalmoscope .

It can be performed in NICU and under local

anesthesia

Easy to treat posterior located lesion.

Argon green and Diode red LASER has been

used

An average of 1000 to 2000 spots of 100 mm

size 1½ burn width apart can be placed in

each eye.

Entire avascular retina till ora, avoid the

ridge.

Fundus picture of RE showing

laser scars (black arrows)

Complications of laser therapy

Burns in cornea and iris. Other

complications include cataract, and

retinal and vitreous haemorrhage.

Development of cataracts and glaucoma

or anterior segment ischemia following

laser has been reported.

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

• Once the macula detaches in stage 4b or 5 ROP retinal

reattachment is done.

• It may include vitrectomy with or without lensectomy.

• Membrane peeling is done to remove the tractional force

causing the retinal detachment.

• A Scleral buckling procedure is useful for perpheral

detachments with drainageof subretinal fluid for effusional

detachment.

• Sucessful retinal reattachment outcome of the visual acuity

is in the range of the Legal blindness.

• Despite low vision outcome it is considered superior to

untreated stage 5 .

SCLERAL BUCKLE

It is done under GA

Peritomy

2.5 mm encircling band passed beneath 4 Recti

One anchoring mattress suture applied in all quadrants

Removal after 3-6 months

VITRECTOMY

Necessary in advanced cases

Lensectomy avoided

Peeling of membranes

Relieve of traction

No attempt to drain Sub Retinal Fluid

AIM : Ambulatory vision ie being able to see objects and move around a room without stumbling or bumping into obstacles.

Randomn Control Trial study , conducted on 172 preterm

infants

Peripheral Cryotherapy vs. Observation

“Threshold Disease”

Stage 3 (neovascularization)

5 contiguous, 8 noncontiguous clock hours

Zone I or II

Plus Disease

Cryotherapy superior to Observation:

Reduced unfavorable outcomes

Related improved visual acuity results

Randomn control trial study was conducted on

(n=317 bilateral; n=84 asymmetric unilateral infants)

Early peripheral laser vs conventional treatment

“High Risk Prethreshold” ROP disease – Type 1 or Type

2

Type 1 ROP

Zone I: Any Stage, plus / Stage 3, no plus

Zone II: Stage 2 or 3, plus

Finding: Early Peripheral laser superior to

conventional treatment .

• Type 2 ROP

Zone I: Stage 1 or 2, no plus

Zone II: Stage 3, no plus

Finding: Observation advised until Type 1 or

Regression

• Peripheral laser better than conventional

treatment for Type 1:

It concludes reduced unfavorable anatomic

outcome from 15.6% to 9.1% .

Reduced unfavorable visual acuity grating from

19.5% to 14.5%

Bevacizumab Eliminates the Angiogenic Threat in ROP”

Randomn Control Trial was conducted on 150 infants, 300

eyes

Stage 3, plus

Zone 1 and posterior Zone 2

Comparison : 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

• AVRY BOOK OF NEONATOLOGY

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