Retinopathy of Prematurity

Retinopathy of Prematurity (ROP) is a bilateral proliferative retinopathy, occurring in premature infants with low birth weight who often have been exposed to high concentration of oxygen. Earlier this disease was known as retrolental fibroplasia.

Etiopathogenesis

Usually, Primary risk factors include:

Low gestation age, especially <32 weeks
Low birth weight (<1500 g, especially <1250 g),
Supplemental oxygen therapy, and
Other risk factors reported include light, vitamin E deficiency, respiratory distress syndrome, asphyxia, shock, and acidosis.

Pathogenesis

In the normal development of retina, the vessels reach the nasal periphery after 8 months of gestation and temporal periphery about 1 month after delivery, by the effect of VEGF.

In premature birth, the production of VEGF is downregulated and vessel migration is halted. However, with growing age, because of increased metabolic demands, the oxygen regulated vasculo endothelial growth factors (VEGFs) and non-oxygen regulated insulin like growth factors (IGF-1) are produced in excess resulting in neovascularization and fibrous proliferation progressively resulting in different stages of retinopathy of prematurity described below.

Clinical features

The condition has been divided into active ROP and cicatricial ROP. International classification of ROP (ICROP) is based on the stage, zone and extent of ROP.

Staging of ROP

Clinically, the evolution of ROP has been divided into five stages:

Stage 1. Demarcation line formation at the edge of vessels, dividing the vascular from the avascular retina.
Stage 2. The line structure of stage 1 acquires a volume to form a ridge with height and width.
Stage 3. Ridge with extraretinal fibrovascular proliferation into the vitreous. This stage is further subdivided into mild, moderate and severe, depending on the amount of fibrovascular proliferation.
Stage la. Subtotal retinal detachment not involving the macula is a feature of this stage. It occurs as a result of exudation from incompetent blood vessels or traction from the fibrous (cicatricial) tissue.
Stage 4b. Subtotal retinal detachment involving the macula occur in this stage.
Stage 5. Total retinal detachment which is always funnel-shaped.

Zones of ROP

The retina is divided into three zones. The centre of the retinal map for ROP is the optic disc not the macula as in other retinal charts.

Diseases of the retina

Zone I

A circle drawn on the posterior pole, with the optic disc as the centre and twice the distance from the centre of disc to fovea as the radius, constitutes zone I. Any ROP in this zone is usually very severe because of a large peripheral area of avascular retina.

Zone II

A circle is drawn with the optic disc as the centre and the distance from the centre of disc to nasal oral serrata as the radius. The area between zone I and this boundary constitutes zone II.

Zone III

The temporal arc of retina left beyond the radius of zone II is zone III.

Extent of involvement

Extent of involvement is denoted by the clock hours of retinal involvement in the particular zone.

Other features

Plus disease

It refers to presence of engorged veins and tortuous arteries in at least two quadrants at posterior pole with any stage of ROP.

Associated with it is the engorgment and dilatation of iris vessels, which result in poor pharmacological dilatation of pupil. Plus diseases signifies a tendency to progression and is notated by adding plus sign (+) after the number of stage of ROP (e.g., stage 2+)

Pre-plus disease

It is labelled when venous dilation and arterial tortuosity is more than normal but insufficient to be defined as plus disease.

Aggressive posterior ROP (AP-ROP)

It is also called Rush disease, refers to the ROP located in zone I with plus disease out of proportion to the peripheral retinopathy or ROP in posterior zone II with severe plus disease. APROP requires immediate treatment. It may progress rapidly to stage 5 ROP without passing through the other stages.

Threshold disease

It refers to stage 3 +ROP with plus disease located in zone I or II and involving 5 continuous or 8 discontinuous clock hours. This stage needs laser therapy in less than 72 hours.

Prethreshold disease

Early treatment of retinopathy of prematurity (ETROP) group has classified prethreshold disease into two types:

Type I or high-risk prethreshold disease, which needs y laser photocoagulation. It includes:

Zone I Plus disease, any stage,
Zone I: Non-plus disease, stage 3,
And Zone II: Plus disease, stage 2, and 3.

Type 2 or low-risk prethreshold disease which requires weekly follow-up. It includes:

Zone I: Non-plus disease, stage 1, and 2, and
Zone II: Non-plus disease stage 3.

Differential diagnosis

Active ROP needs to be differentiated from familial exudative vitreoretinopathy (FEVR) and incontinentia pigmenti in girls and persistent fetal vasculature.
Advanced retrolental fibroplasia needs to be differentiated from other causes of leukocoria.

Management

Treatment of well-established disease is unsatisf actory. Prophylaxis is thus very important. To reduce high-risk ROP, the premature newborns should not be placed in incubator with an O, concentration of more than 30% and efforts should be made to avoid infections and attacks of apnoea. Early diagnosis and treatment is essential to prevent blindness in high risk cases. Therefore, a regular screening and timely intervention is recommended.

Screening protocol

All premature babies born at less than or equal to 32 weeks of gestational age and those weighing 1500 g or less (for Indian scenario <35 weeks and < 2800 g) should be screened for ROP.

First examination by indirect ophthalmosocpy should be done between 4 to 6 weeks postnatal age or 34 weeks postconceptual age (whichever is earlier). Further line of action will depend upon the status of retina.irst examination by indirect ophthalmosocpy should be done between 4 to 6 weeks postnatal age or 34 weeks postconceptual age (whichever is earlier). Further line of action will depend upon the status of retina.
Immature retina is labelled when the vessels are short of one disc diameter of the nasal or temporal ora but ROP is not developed yet.
ROP, when present should be classified as its stage, zone, and extent of involvement.

Subsequent follow up examination

Spontaneous regression of disease occurs in about 80% of the cases. So following patients should be examined as below till regression occurs or disease reaches treatment stage:

Immature retina but no ROP-bi-weekly
Stage 1 & 2 (Zone I & II ROP), weekly and
Stage 3 (Zone II ROP) also weekly.

Treatment protocol

Treatment options include laser therapy or cryotherapy. ETROP group has recommended use of laser over the cryotherapy.

Laser treatment

Laser photocoagulation using diode laser 810 nm or frequency doubled Nd:YAG (532 nm) with LIO (laser indirect ophthalmoscope) delivery should be carried out in all patients with high-risk pre threshold, threshold, and aggressive posterior ROP.

Post-laser treatment and follow-up

Antibiotic and steroid eye drops should be prescribed for a week. Post-laser treatment follow-up should be done weekly for 3 weeks and if required retreatment should be done. Subsequent follow-up examination should be continued at 3, 6 and 12 weeks after treatment. Long-term follow-up is must for timely management of complications if any.