Retinopathy of Prematurity : ROP

What is ROP?

Retinopathy of prematurity (ROP) is a disease that primarily occurs in premature babies. It causes abnormal blood
vessels to grow in the retina, the layer of nerve tissue in the eye that enables us to see. This growth can cause
the retina to detach from the back of the eye, leading to blindness.

Originally described as “retrolental fibroplasia” in the early 1940s, owing to (overly?) aggressive oxygen use.Nearly disappeared between 1954-1970, when oxygen use severely restricted. But now, has returned, secondary to improved neonatal practice of VLBW infants. Est. 400 infants blinded each yr; 4300 with serious retinal scars.

Epidemiology

• Incidence and severity correlates with LBW and early post-conceptual gestational age.
• Caucasians and Hispanics have ?aggressive ROP compared to African Americans.
• Mayet and Cockinos (CHBara) – There is a similar incidence of ROP in Africans compared to other races but with less  severity (3%).

Incidence-

• Related to gestational age (GA) and birth weight (bw).
• ROP rare in birth weight > 2000 grams.
• 70% ROP in birth weight  < 1250g and 7% develop threshold ROP.
• Threshold ROP very rare in bw > 1250g. (Mayet & Cockinos)
• 95% ROP begins at 32-34 weeks GA.
• Threshold disease at 36 weeks.
• Regression with spontaneous healing at 45-48 weeks GA.
• Long term ophthalmic follow up of formerly premature neonates who suffered severe ROP

Pathogenesis

ROP can occur when the retinal vessels have not yet completed their centrifugal growth from the optic disc to the
ora serratia. Primitive endothelial cells (“spindle cells”) form cords that canulize into capillaries and further differentiate  into arterioles and venules

16 weeks of gestation – primitive spindle cells gradually grow out over the surface of the retina.29 weeks -reached ora serrata. At this time these spindle cells start to form blood vessels.The vessels reach the anterior edge of the retina and stop their progression at about the time of birth. During vasculogenesis if exposed to toxic substance vasculogenesis is interrupted. (A sharp demarcation line).

After the “injury,” vessel growth can resume normally (no ROP), or (for unknown reasons), the primitive vessels
pile-up within the retina.The retina anterior to this line does not have an adequate oxygen supply, and probably exudes chemical signals that  stimulate new vessel growth. Arterio-venous shunts at the location of the barrier on the surface of the retina.This shunt gradually enlarges, becoming thicker and more elevated. The new vessels are accompanied by fibroblasts, which produce fibrous scar tissue.When this scar tissue contracts, it pulls on the retina and produces a traction retinal detachment. Highly vulnerable vasculogenesis occurs.

 

ROP Classification

1984 and 1987 International Classification of ROP:

1. 3 Zones (location)
2. Clock hours (extent)
3. Stages 1 through 5
4. Plus Disease

Stage 1. Demarcation line between the normal retina (left) and the non-vascularized
retina (right).

Stage 2 – ridge (R) of scar tissue and new vessels in place of the demarcation line.
Popcorn vessels

Stage3- Increased size of the vascular ridge (between the arrowheads), with growth of fibrovascular tissue.

Stage 4 – Partial retinal detachment.

• Stage 4A – Extrafoveal
• Stage 4B – Foveal

Stage 5 – Complete retinal detachment.

Plus disease –
Signs indicating severity. Venous dilatation or arteriolar tortuosity in at least two quadrants; vitreous haze;
poor pupil dilatation; vascular engorgement of the iris.
International Classification For Retinopathy of Prematurity (Archives Ophthalmol 2005)

 Pre-plus disease
 Aggressive Posterior (AP-ROP)
Terminologies-

Pre-threshold ROP –Increased likelihood of progression to retinal detachment if left untreated Zone I, any stage Zone II, “plus disease” with stage 1, 2

Threshold ROP- ROP with 50% likelihood of progression to retinal detachement if left untreated Stage 3 with 5 continuous clock  hours or 8 cumulative clock hours with plus disease

Risk Factors for ROP-

1. Gestational age and low birth weight
2. Supplemental oxygen
3. Vitamin E deficiency
4. Race (increased in Caucasians)
5. Surfactant
6. Light levels
7. Multiple births
8. Transport after delivery

OTHERS- Indomethacin, Elevated blood carbon dioxide levels, Anemia  Blood transfusions, IVH, RDS ,Chronic hypoxia in utero , Multiple spells of apnea or bradycardia,mechanical ventilation, Seizures
Systemic Findings (Prematurity)

• Respiratory Distress Syndrome
• Sepsis
• Cardiac Defects
• Anemia
• Intracranial Hemorrhage
• Developmental Delay
• Jaundice

Prognosis

• Onset in Zone 2, slower progression.
• Onset in Zone 3, good prognosis for full recovery.
• May take up to one year to stabilize, usually outcome
• apparent by 3 months of age.
• Mild ROP (Stage 1 or 2 without plus) and heals without a residual cicatrix (retinal scar)> may have higher
• incidence of myopia, strabismus, amblyopia
• Threshold ROP with residual cicatrix> severe myopia,
• strabismus, amblyopia, retinal detachments

 

MANAGEMENT

Prevention –

Prevent preterm labor.
(Optimal) minimum use of oxygen.
Prevention of complications

 

1. Infants with birth wt. < 1500g or GA < 30 weeks.

2. Examine 1 or 2 weekly depending on stage of  disease at initial visit.

3. Treat threshold disease.

4. Examine until 45 weeks GA without threshold disease  or till vascularisation reaches zone 3.

For threshold ROP (stage 3 in at least 5 clock hours with plus disease)
Procedure is painful and done under general anesthesia.
Complications: anesthesia problems; eyelid and conjunctivae edema

Laser photocoagulation:
the treatment of choice for treshold retinopathy of prematurity (ROP)
Laser photocoagulation is associated with a good anatomic outcome.

ROP more posterior is difficult to treat successfully with ablative therapy.

ROP: Laser Complications
 Anterior Segment Ischemia
 Cataracts
 Burns to Cornea, Iris and Tunica Vasculosa Lentis

• SCLERAL BUCKLE
• VITRECTOMY
• RETINAL REATTACHMENT
• HIGH MYOPIA
• ANISOMETROPIA
• STRABISMUS
• AMBLYOPIA
• LATE-ONSET RETINAL DETACHMENT
• GLAUCOMA

Every 1-2 years for infants with fully regressed ROP.
Every 6-12 months for those with cicatricial ROP.
Premature infants even in the absence ROP should have an eye examination by 6 months of age.

90% of stage 1 & 2 disease regress spontaneously.
About 50% of stage3+ disease regress spontaneously.
In stage4 macula sparing has better prognosis.
If retina is detached then prognosis is worst even with reattachment.
Prevention of premature births.
VEGF and IGF-1 may prevent progression.
Timely screening and determination of critical timing of treatment.
Digital fundus imaging.

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.

Author – Dr Shyam Kumar Gupta .

Resident Department of Neonatology ,

Dhaka, Bangladesh

Visit his Neonatology Experience Page