RETINOPATHY OF

PREMATURITYCommon cause of blinding disease

Also known as retrolental fibroplasia

Originally described by terry – 1940s

‘terry syndrome’

Affects immature vasculature in the eyes

of premature babies.

Retinopathy of prematurity

(ROP)

• Mild - no visual defects

• Aggressive - new blood vessel formation

(neovascularization) and progress to

retinal detachment and blindness.

embryology

• The retinal vasculature begins in the 16th week of gestation.

• Retinal vascularization originates from the center of optic disc and progresses radially outwards towards the ora seratta

• 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.

Schematic representation of IGF-I/VEGF control of blood vessel development in ROP. (A) In

utero, VEGF is found at the growing front of vessels.

Hellstrom A et al. PNAS 2001;98:5804-5808

©2001 by National Academy of Sciences

embryology

• 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

pathophysiology

• ROP progresses in two phases.

• The first phase - delayed retinal vascular

growth after birth and partial regression of

existing vessels due to hyperoxia.

• Second phase - hypoxia-induced

pathological vessel growth.

Kretzer and hittner

Extra uterine hyperoxia

Gap junctions in

mesenchymalspindle cells

Abnormal vacularisation

Ashton theory {bi-phasic model}

Risk factors

• Three 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.

SCREENING

• When to screen? When should a pediatrician refer to ophthalmologist for ROP screening?

– 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.

SCREENING

• Whom to screen?

• UK guidelines – GA £ 31 weeks or birth weight (BW) £ 1500 g.

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

• The Indian scenario – GA £ 35 weeks or having BW £ 1800 g should be

screened for ROP.

– babies that have a rough course in neonatal intensive care unit (NICU) “sickness criteria”.

HOW TO SCREEN?

• Indirect ophthalmoscope

– 28 D lens, scleral depressor (wire vectis) and alphonso speculum.

– 0.5% proparacaine drops- topical anesthesia

– Half strength tropicamide plus (0.4% tropicamide with 2.5% phenylephrine) -

pupillary dilatation.

• Disadvantage

– Examinations via binocular indirect ophthalmoscope for ROP are difficult

– Require doctors with specialized paediatric retina training.

– Hand drawn sketches are the only means of documentation for infant retina

RETCAM

– Retcam is a digital camera for imaging the retina of infants.

– Mobile self-contained system that can move easily around the hospital or office.

– provides retinal imaging (130 degrees).

– Instant accurate documentation, avoiding time-consuming retinal drawings

– In just a few minutes one can do an entire exam and the images are stored

permanently

– Easy accessible imaging even by non-ophthalmologists

– Allows the transmission of these digital images to centers where rop expertise is

available via telemedicine.

– serves as a good teaching tool for others

International Classification of

Retinopathy of Prematurity• Location of disease: Each eye is divided in three

zones to define the exact location.

– 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

EXTENT OF THE DISEASE

LINE OF DEMARCATION -

STAGE I

RIDGE – STAGE 2

Extraretinal fibrovascular

proliferation – STAGE 3

Partial retinal detachment - STAge

4

Total retinal detachment - Stage 5

AGGRESSIVE POSTERIOR

ROP

PLUS DISEASE

MANAGEMENT OF ROP

• Threshold disease: ( defined by the

CRYO-ROP study)

– Stage 2 in zone I or II involving > 5

contiguous or 8 cumulative clock hours with

plus disease.

– This was the previous “cut off” stage for

treatment.

• Prethreshold Disease: ( Early Treatment ROP (ETROP) study)

– High Risk Prethreshold or Type 1 ROP:• 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: These eyes should be considered for treatment only if they progress to type 2 or threshold ROP. It is defined as

• Zone 1 stage 1 or 2 without plus disease or

• Zone 2 stage 3 without plus disease.

TREATMENT

Principle :

Ablation of the ischemic peripheral retina stops release of angiogenicfactors.

Cryotherapy:

placing a very cool probe on the sclera and freezing, until an ice ball is formed on the retina inside.

Multiple applications are made to treat entire avascular retina anterior to the ridge.

Disadvantages.

requires general anesthesia,

local complications like severe lid edema

zone I cases, the cryo probe cannot reach posteriorlybecause of the restriction caused by the conjunctival fornix.

CRYOTHERAPY

multiple white cryo burns (black

arrows) in avascular retina anterior to

ridge (white arrow).

• Laser Photocoagulation:

• Direct treatment of retina from inside,

• Diode red (810 nm) is the laser of choice. However green laser (532 nm) laser can also be used.

• Advantages– can be performed under topical anesthesia,

– systemic and local complications are much less

– can be done as out patient procedure

– posterior retina in zone I cases can be treated easily.

LASER PHOTO COAGULATION

Fundus picture of RE

showing laser scars (black

arrows)

• Laser or cryotherapy can only be done till stage 3 ROP.

• Management of stages 4 and 5 is surgical and final outcome is very poor for these stages.

• Surgical treatment:– Surgery is advocated if laser or cryotherapy is unsuccessful in

preventing progression to stage 4 or 5.

• Surgical options – Scleral buckling

– Lens sparing vitrectomy for stage 4

– Lensectomy + vitrectomy

– Open sky vitrectomy for stage 5

Role of anti VEGF injections in

ROP• Very controversial

• For normal vascularization of the retina to be completed, VEGF is needed in these premature infants.

• 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 organs developing 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

Follow up

• ROP management doesn’t end with laser or surgery.

• Once treated, lifelong followup (yearly) is mandatory.

• All other premature infants irrespective of having ROP- yearly followup till the age of 5 years is advisable.

• To rule out - refractive errors (most common), squint and amblyopia.