LASER photocoagulation is considered the mainstay of treatment in pre-threshold type 1 ROP (Retinopathy of Prematurity). However Indian studies have shown that only 3.5% of the infants screened for ROP have any form of ROP and the proportion of treatable ROP in this group is even smaller. Needless to say, efforts are on to identify more specific screening protocols which would ensure that the efforts of the ophthalmologist are directed towards those babies who are truly at a higher risk of ROP.

Post-natal weight gain
WINROP (Weight, Insulin-like growth factor and neonatal ROP):

2-stage algorithm. In the first stage weekly post-natal body weight and Insulin-like Growth Factor 1(IGF-1) levels are measured. Any slowdown in these factors compared to similar neonates is identified, and an alarm is raised. Subsequently, in the next stage in eyes where an alarm is raised, the birth weight, gestational age, IGF-1 levels and IGF binding protein 3 levels are measured based on which the neonate is placed in high risk or low-risk alarm state. Analysis of this protocol showed that 100% of the cases needing ROP treatment were correctly identified to be in the high-risk alarm group. None of the cases in the normal group or the low-risk alarm group needed any kind of treatment for ROP. This protocol suggests that a more targeted screening of the at-risk infants for ROP can be done safely without missing out on any potential cases.

Moreover, all the babies developing ROP needing treatment were identified 3 weeks before the actual development of ROP and 4 weeks before the development of ROP, thus needing a LASER. This ensures that the ophthalmologist and the neonatologist are better prepared to alter the course of the disease by taking remedial measures.

A similar protocol has been assessed where only the post-natal weight gain was evaluated longitudinally, and at-risk babies were identified reliably and that too well in advance (median of 9 weeks).

In certain borderline cases, the weight at 6 weeks can be used to decide if a baby might eventually end up needing a LASER. If the baby gains more than 50% of the birth weight in the first 6 weeks, the chances of the baby needing LASER becomes minimal.

Serum markers: Serum levels of certain proteins can be reliably used to prognosticate the possibility of a neonate developing a severe ROP.

IGF-1: Poor IGF-1 levels at 3 weeks post-partum are a good predictor of the development of severe ROP.

Plasma soluble E selectin: Increase in levels by 10 ng/ml at 3 weeks postpartum increases the risk of severe ROP by 1.6 times.

Genetic markers: Mutation in NDP gene/ FZD4 gene increases the risk of developing severe ROP.

Image analysis techniques:

Retinal Image multiScale Analysis (RISA): This technique quantifies arterial tortuosity in ROP and shows that in infants with plus disease arteriolar and venous curvature, diameter and tortuosity index were increased in eyes with plus disease as against the normal eyes.

ROPtool: This was developed by Duke University, North Carolina and had 97% sensitivity in identifying tortuosity sufficient enough to identify plus disease.

Computer-Aided Image Analysis of Retina (CAIAR): This was developed from RISA for faster image analysis. It analyses the mean width and tortuosity of the three widest and most tortuous vessels and predicts the risk of progressing from pre-plus to plus disease.

Summary: A combination of weight gain and image analysis algorithms in conjunction with genetic and serum markers might be used to reliably eliminate 90% of premature infants who will never develop high-risk ROP. This will enable the ophthalmologists to concentrate on the remaining 10% of the neonates at risk for high-risk sight-threatening ROP.

Dr. Raja Rami Reddy P