RETINOPATH OF PREMATURITY

Afsaneh Naderi Beni, MD

Glaucoma Fellowship

I am not just a “Small” baby… I am a “Preterm”

baby….

I am a “Unique Baby”… with “Unique

Problems”!!

Retinopathy of Prematurity (ROP)

What is ROP?

Retinopathy Of prematurity, is a disease of the developing retinal vasculature resulting from the interruption of normal progression of the newly forming retinal vessels.

It is a multifactorial disorder with incidence increasing with decreasing gestational age.

It is one of the most common causes of blindness & other visión errors in children.

• Earlier, it was known as Retrolental fibroplasia.

History of ROP

• 1940 – Retrolental Fibroplasia, first described by Terry.

• 1984 – Proved that RLF was associated with use of oxygen in newborn infants.

• 1951 - Heath suggested term “Retinopathy of Prematurity”

• Campbell (1952): relationship of intensive oxygen therapy & subsequent development of ROP.

• Kinsey: ROP was inversely proportional to birth weight.

ROP Blindness Risk and Infant Mortality

Rates

ROP in IRAN

Iran scenario of ROP

Why screen for ROP

Premature child is not born with ROP

Screening aims to identify treatable stage

Narrow window for screening and treatment

Delay cause blindness or visual impairment

Medico-legal implications

Economic and social burden of childhood blindness is immense

Basic structure of the eye

Structure of the Retina

Embryology

Eye formation is first evident at the beginning of the 4th wk of gestation with the appearance of the optic sulci.

The Retina, Iris and the optic nerve develops from the neuroectoderm.

The Retina develops from the walls of the Optic cup, which is an outgrowth of the forebrain.

During the embryologic and fetal periods, the two layers of the retina (i.e.) the Retinal pigment layer and the Neural retina are seperated by an Interretinal space.

The photoreceptors – Rods & Cones, cell bodies of neurons are developed from the neuroepithelium.

Retinal Vasculature development

Timing of vascularization of the peripheral retina

FULL TERM EYE, RETINA FULLY

DEVELOPED

PREMATURE EYE WITH

DEVELOPED RETINA

Pathogenesis

Pathogenesis

Pathogenesis of ROP

Hypotension, hypoxia, or hyperoxia, with free radical formation, injures newly developing blood vessels and disrupts normal angiogenesis neovascularization retinal edema, hemorrhage and abnormal fibrovascular tissue development.

Risk factors

Three crucial risk factors:

Birth weight

Gestational age

Number of days oxygen administered

No consensus is present on which of these criteria should be used, either alone or in combination for screening of ROP.

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

Key Nomenclatures

• The International Classification of Retinopathy of Prematurity ICROP (1984 & 1987 )

– Zone, Stage, Extent, Plus

• The International Classification of Retinopathy of Prematurity ICROP revisited (2005)

–aggressive posterior retinopathy of prematurity (APROP) – Pre plus

International classification of Retinopathy Of

Prematurity

Four features are evaluated:

– Location

– Severity

– Extent

– Presence or absence of plus disease

Location

ICROP Locations

ICROP locations

ICROP (locations)

International Classification – Zones

Zones: Zone 1 is posterior, Zone 2 is equatorial and Zone 3 is anterior.

Zone 1 – High Risk

Zone 2 – Intermediate Risk

Zone 3 – Low Risk

ICROP (severity)

ICROP (severity)

ICROP (severity)

ICROP (severity)

ICROP (stages)

ICROP(extend)

Extend refers to the circumferential location of disease.

It is reperted as clock hours in the appropriate zone.

Plus disease

Pre - Plus disease :Vascular abnormalities of the posterior pole (mild venous dilatation or arterial tortuosity) that are present but are insufficient for diagnosis of a PLUS disease.

APROP Aggressive Posterior ROP : uncommon, rapidly progressive, severe form of ROP, characterised by posterior location., & prominence of plus disease out of proportion to the peripheral retinopathy.

Threshhold ROP If 5 or more contiguous or 8 cumulative clock hours(30 degree) of Stage 3 with plus disease in either zone 1 or 2 are present. This is the level at which chances of blindness are at least 50%.

Pre – threshhold ROP 1.)

Type 1 pre-threshhold ROP: a.) Zone 1, eyes with any ROP and plus disease or stage 3 with/without plus disease. b.) In zone2, stage 2 or 3 ROP with plus disease. 2.)

Type 2 pre – threshhold ROP: a.) In zone 1, stage 1 or 2 without plus disease. b.) In zone 2, stage 3 without plus disease. Terminologies (cont…..)

ROP - Management

PREVENTION -

Prevent preterm labor.

(Optimal) minimum use of oxygen.

Prevention of complications.

Screening

When to screen? When should a pediatrician refer to ophthalmologist for ROP screening? Ideally babies are to be screened at 31 weeks post conceptional age (gestational age + post natal age) or 4 weeks after birth, whichever is later.

first retinal examination should be done by first month of life.

Whom to screen?

UK guidelines state that babies with gestational age (GA) £ 32 weeks or birth weight (BW) £ 1500 g should be screened for ROP.

USA guidelines are GA £ 30 weeks or BW £ 1500 g.

for the Iranian scenario all babies having GA £ 32weeks or having BW £ 1750 g should be screened for ROP.

Apart from this, babies that fall outside the screening guidelines but have a rough course in neonatal intensive care unit (NICU) should also be screened at the pediatrician’s discretion. This is called “sickness criteria”

How to screen?

A retina specialist or a pediatric ophthalmologist does screening.

Limitations- does not permit adequate assessment of ROP in retinal periphery. Appropriate pain relieving steps like local anaesthetic eye drops and oral sucrose to be employed.

Examination technique

The examination technique traditionally involves two steps

dilatation of pupil

indirect ophthalmoscopy preferably with a 28D lens.

dilatation of pupil

pupillary dilatation 45 min prior to commencement of the screening.

Dilating drops mixture of cyclopentolate (0.5%) and phenylephrine (2.5%) drops to be applied two to three times about 10-15 min apart.

tropicamide (0.4%) and phenylephrine (2.5%) drops . Use of atropine is to be avoided.

The neonatal nurse should be instructed to wife any excess drops from the eye lid to prevent systemic absorption and complications like tachycardia and hyperthermia. If the pupil is resistant to dilatation, it may indicate presence of persistent iris vessels (tunica vasculosa lentis) and must be confirmed by the ophthalmologist before applying more drops.

It is done with the help of indirect ophthalmoscope, 28 D lens, scleral depressor (wire vectis) and alphonso speculum.

Examinations via binocular indirect ophthalmoscope for ROP are difficult and require doctors with specialized paediatric retina training. Moreover hand drawn sketches are the only means of documentation for infant retina, which has its own disadvantages.

Recently, a new digital camera, Retcam, is available for screening but is a very expensive tool.

It is the duty of the pediatrician to call these trained ophthalmologists to their NICU or they should refer the children to them at end of first month. ROP screening should be included as a part of neonatal care.

The RetCam is the emerging standard

for screening and early detection of

Pediatric eye diseases

http://www.intechopen.com/source/html/47005/media/image3.jpeg

RetCam is a digital camera for imaging the retina of infants.

It is a mobile self-contained system

provides wide field pediatric retinal imaging (130 degrees).

instant & accurate documentation,

avoiding time-consuming retinal drawing

few minutes one can do an entire exam

images are stored permanently on a 9.4 GB DVD.

It allows easy accessible imaging even by non-ophthalmologists (NICU nurses)

allows the transmission of these digital images to centers where ROP expertise is available via telemedicine.

It provides 24-bit color, mega-pixel digital images, presented on a 17- inch computer monitor available for printout or electronic transmission.

Is a good teaching tool for others.

Comprehensive database keeps track of each image, session and patient allowing for later side-by-side comparison of the case images.

Retcam shuttle is laptop based.

http://www.intechopen.com/source/html/47005/media/image5.png

Disadvantages of Retcam :

Imaging of infant retina till ora in not possible without scleral depression

it is a very expensive tool.

ETROP Recommendations

Stage 1 Follow twice weekly

Stage 2 Follow twice weekly

Stage 3 Treat <48hr

Stage 1 Treat <48hr

Stage 2 Treat <48hr

Stage 3 Treat <48hr

Stage 1 Follow No Change

Stage 2 Follow weekly

Stage 3 Follow twice weekly

Stage 1 Follow No Change

Stage 2 Treat <48hr

Stage 3 Treat <48hr

Z

on

e

1

Z

o

n

e

2

No Plus

Plus

No Plus

Plus

Treatment of ROP

The first stage of ROP is when the blood vessels stop growing and form a line that separates normal from premature retina.

In the second stage, the line of separation takes on substance as an elevated ridge of tissue.

As the ROP advances fragile new abnormal blood vessels grow toward the center of the eye (Stage 3). At this point, the eye is still capable of repairing itself.

As Stage 3 advances the normal vessels dilate, indicating that the ROP may not go away on its own. This is known as "plus disease."

If enough retina has Stage 3 and so-called "plus disease," then treatment is indicated. Laser treatment using light energy is shown. Eyes can also be treated with cryo-therapy (freezing).

In favorable cases, treatment results in disappearance of the abnormal vessels with potentially good vision.

In some cases, the ROP continues to progress and the retina detaches. A partial detachment is Stage 4A. If the center of vision is involved, it is 4B.

Left untreated, the retina can become totally detached, Stage 5. These eyes have very poor visual outcomes.

Removal of the vitreous tissue that fills the eye can relieve the traction which pulls the retina away from the wall of the eye.

Treatment Options

Cryotherapy

Laser photocoagulation – standard treatment

Surgical interventions

Scleral buckling

Vitrectomy

New treatment options for ROP

Avastin alone for ROP stage 3 may become primary treatment replacing LASER therapy (Helen et al.,2009).

Recently ,chen et al., report in a retrospective study effective outcomes using trans-scleral diode laser instead of transpupillary laser treatment for threshold ROP(Chen et al.,2011)

Prognosis

90% of stage 1,2 ROP – spontaneous regression.

Approx 50% stage 3 –spontaneous regression.

>stage3 : prognosis better with early laser photocoagulation , cryopexy.

Long term sequelae may require follow up.

Complications

• Blindness

High myopia Strabismus

• Other refractive errors

• Strabismus

• Amblyopia

• Astigmatism

• Late retinal detachment

• Glaucoma

Prevention :Interventions to prevent or limit the progression of ROP have been unsuccessful, further evaluation may be needed.

Experimental : Antioxidant therapies, such as vitamin E, D-penicillamine are being tried ,Restricted Supplemental oxygen therapy ,Insulin-like growth factor-1(IGF-1)

Conclusion

Ultimate prevention = prevent premature

births.

ROP is a lifelong disease with sequelae

manifesting into the 2nd

decade.

Surgical intervention preserves vision in ROP-

related retinal detachment esp. before macular

detachment.

THANK YOU