Retinopathy of Prematurity

Sasha Mansukhani
Algorithm Of Screening And Management (11,19, 23, 24)


The three important questions are whom to screen, when to screen and till when to continue screening.
Whom to screen:
According to the Indian guidelines set forth by the National Neonatology Forum (NNF) Guidelines(24)
1. All Preterms babies born at <34 wks gestational age
2. All preterm babies with birth weight <1750 Kgs
3. All preterm babies born at 34-36 wks gestational age or 1750-2000 Kgs at birth if:-
• Stormy neonatal course
• Prolonged oxygen delivered
• Oxygen fluctuations
• Sepsis
• Any major surgery
• Severe anemia
That is any preterm baby whom the neonatologist feels is at risk for retinopathy of prematurity.
4. All babies whose gestational age is not known.

The last point is especially important in our country as on several occasions one has only a rough estimate from ultrasonographic age.

In the United States, only the preterm babies less than 30 weeks by age or less than 1500Kgs are screened(23). However the Indian guidelines are different from the American Academy of Ophthalmology guidelines as it is found that in developing countries bigger and older babies are getting the disease, and therefore each country has been urged to make their own guidelines.

When to screen?
According to NNF guidelines(24):-
• For neonates >28wks gestational age: Screen at 4 weeks chronological age.
For neonate <28 wks gestational age or <1200 Kgs: Early screening at 2-3 weeks is recommended as these children are more prone to develop Aggressive posterior ROP which requires urgent treatment.

Follow examinations depend upon the fundus findings. An easy algorithm to follow is as given below(11):-

No ROP Every two weeks
ROP Weekly
Prethreshold ROP Daily

When to stop screening?
Screening can be stopped when :-
1. The retina is completely vascularised. This usually happens at 40-45 weeks post menstrual age (Gestational + Chronological Age) (24).
2. The disease has completely regressed(24).

Role of Retcam and Telemedicine
The Retcam or retinal camera is a wide angle (130°) digital camera that can be operated by technicians to take good quality fundus images. The Retcam can be used for professional record keeping. More importantly is the role in telemedicine where in a technician in the peripheral ICUs can image the fundus and transfer the images to the experts at the tertiary care centers. Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) telemedicine initiative found that Telemedicine had 100% sensitivity, 99.8% specificity, 93.7% positive predictive value and 100% negative predictive value for detection of treatment warranted ROP(25). Similarly the telemedicine ROP model developed in Karnataka called KIDROP model has shown promise in delivering services of the specialists in underserved areas (26).

Treatment of threshold & prethreshold ROP
The principle of treatment is to ablate the hypoxic retina either with laser ablation or with cryotherapy. Thus the hypoxic retina is converted to anoxic retina, which no longer produces VEGF, thus ending the tendency for vascular proliferation.

While the CRYO ROP trial treated all babies with threshold ROP, the ETROP trial found that treating babies with high risk prethreshold ROP also has benefit.

Laser Ablation
It is the mainstay of treatment at present(27). The structural and functional visual outcomes obtained with laser are superior to those with cryotherapy(28,29).

Diode red laser (810nm) delivered by laser indirect ophthalmoscopy is used. The procedure is done under topical anaesthesia and the neonate is well fed and burped 30-60 minutes prior. The parameters used are 250 mW power, 150ms duration with repeat mode interval of 300ms(27). The avascular retina is lasered to produce ‘greyish’ burns which are confluent. The power may be varied to ensure the right degree of burn, with lower energy for anterior and superior retina. Excessive energy to the retina can result in exudative retinal detachment. No skip areas are left.
In a single session, around 3000-4000 burns are required to cover the entire avascular region in zone I disease or APROP. For zone II threshold or prethreshold disease and non APROP eyes, around 1000-2000 spots are usually required(27).

There are many advantages of laser over cryotherapy as shown in the table (11,28,29).

  Cryotherapy Laser Ablation
Anaesthesia General Anaesthesia Can be done safely under Topical Anaesthesia
Bradycardia Higher chance Lower chance
Post procedure discomfort More Less
Lid edema and chemosis More Less
Post procedure Exudative Retinal Detachment Higher chance Lower chance
Ability to treat posterior disease No Yes
Can perform through small pupil Yes No
Can perform through hazy media Yes No

The Cryotherapy for Retinopathy of Prematurity (CRYOROP) trial showed the usefulness of cryotherapy in treating infants with threshold disease(30). When the laser indirect ophthalmoscopy became available, it soon gained acceptance over cryotherapy. This is because cryotherapy is more painful and requires general anaesthesia. Also zone I & II are difficult to reach with the cryo probe. However, cryotherapy still has a role to play as it is cheaper, can be done in non dilating pupils, hazy media and where laser delivery systems are not still available(11).

Management of advanced disease
Stage 5 of ROP and most often stage 4 also, require surgical management, in order to preserve some visual function. The options for retinal detachment surgery include, scleral buckling and pars plicata vitrectomy which could be lens sparing or with lensectomy.
A simplified algorithm for management of advanced disease(11,31),

Scleral buckling
It works on the principle that external indentation on the sclera, relieves the traction, thereby allowing the retina to reattach. Although scleral buckling has the advantages of being an external surgery, the problems are induced myopia and thereby amblyopia due to the buckle and the necessity for secondary surgery to remove the buckle. Also anatomical success rates are better vitrectomy, thus vitrectomy is generally considered superior to buckling(32). However scleral buckling still has a role to play in stage 4a disease with traction anterior to the equator(31).

In subtotal detachment involving the macula and in total retinal detachments, closed globe vitrectomy is performed. 3 ports are made through the pars plicata, a vitrectomy is performed, and a careful dissection is performed to release the sites of traction. This is followed by an air fluid exchange with the placement of an air bubble, or a viscoelastic agent(11).
If there is no retrolenticular space due to extensive detachment, a lensectomy is done prior to the vitrectomy to allow more anterior dissection(31).
In Stage 4 disease, even though retina gets reattached in an acceptable number of neonates (80-90%), functional outcome has been poor(31). In stage 5 disease however, results have been poor both anatomically as well as surgically(33). Recently adjuncts to vitrectomy surgery, like intravitreal triamcinolone(34), plasmin(35), and bevacizumab(36) have shown improved results.

Role of Bevacizumab
Bevacizumab is a humanized anti-VEGF monoclonal antibody, which has been given intravitreal as monotherapy as well as an adjunct(36). However there is still a lot of uncertainty surrounding its use, and currently it is being used only in selected cases of ROP for example infants with small pupils and dense vitreous hemorrhage.

Retinopathy of Prematurity Retinopathy of Prematurity 11/05/2014
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