Tiny Eyes, Big Responsibility The Fight Against ROP

Retinopathy of prematurity (ROP) is a proliferative disease of vessels of the retina primarily seen in the premature babies. It is one of the leading causes of preventable childhood blindness worldwide. With major improvements and advances in neonatal care and increased survival rates of preterm babies there is an increasing rate of retinopathy of prematurity. Increased survival of preterm babies has simultaneously increased the number of cases of retinopathy of prematurity.

Retinopathy of prematurity was first described in 1942. Following which three distinct global epidemics of ROP has been documented. The first one occurred in 1940s – 1950s in the high-income countries. This occurred due to unrestricted oxygen use and inadequate monitoring. Second epidemic (1960s-1970s) emerged in the industrialized countries. This occurred due to the advancement in neonatal intensive care where extremely premature infants with very low birth weight started surviving despite improvements in oxygen monitoring. The third epidemic started from 1990s till current date where low- and middle-income countries also started expanding neonatal services which improved neonatal survival rates. Even though the survival rates have improved in low and middle income countries insufficient neonatal care, improper oxygen saturation monitoring and inadequate manpower and resources to examine and treat babies at risk have increased the number of ROP cases in these regions.1 Various studies of Nepal have shown the prevalence rate of ROP to be between 25.3% – 29.5%.2,3

WHY DOES ROP OCCUR?
Development of normal retinal vascularization begins at around 16 weeks of gestation. The retinal vessels reach the nasal periphery at around 36 weeks of gestation and reaches the temporal retina at 40 weeks of gestation when the retinal vascularization is completed. Under normal circumstances the fetus is under a hypoxic state. This state of hypoxia is important to stimulate vascular endothelial growth factor (VEGF) production. VEGF is an important factor which stimulates the retinal vessel growth into the peripheral avascular retina. Preterm delivery exposes the baby to hyperoxia. This state of hyperoxia causes reduced production of VEGF and this halts the normal vessel growth into the avascular retina. The more preterm the baby the greater area of avascular retina. With time as the metabolic demand increased retinal hypoxia develops. This hypoxia now stimulates the production of VEGF. This upregulation of VEGF leads to the growth of abnormal retinal vessels and neovascularization at the junction of vascular and avascular retina. The disease progresses to fibrovascular proliferation, vitreoretinal traction, retinal detachment and irreversible blindness.

WHAT ARE THE RISK FACTORS OF ROP?
The most important risk factors for ROP is prematurity and low birth weight. Other risk factors of ROP are as follows

• Prolonged supplemental oxygen therapy
• Mechanical ventilation
• Sepsis
• Respiratory distress syndrome
• Bronchopulmonary dysplasia
• Intraventricular hemorrhage
• Blood transfusions
• Poor postnatal weight gain
• Necrotizing enterocolitis
• Multiple gestation

Supplemental oxygen has a very important role in development of ROP. It is important to maintain a good balance of supplemental oxygen since excessive oxygen can damage the eye while less oxygen can damage the lungs, brain and vital organs. Therefore, strict oxygen monitoring is an important measure, balancing both the prevention of ROP against the morbidity and mortality in neonates

HOW IS ROP CLASSIFIED?
ROP is classified on the basis of the International Classification of Retinopathy of Prematurity which is a consensus statement that creates a standard nomenclature for classification of ROP. Currently its third revision is followed. “ROP is divided into three zones. The most central zone which includes the optic nerve and macula is zone 1 and zone 2 and 3 extends towards the periphery of the retina. The more central the disease, the more severe it is.”

There are five stages of ROP. Stage I starts with a demarcation line at the vascular- avascular junction and as the disease progress can lead to retinal detachment leading to blindness. Treatment is required for more posterior disease, advanced stages of disease, plus and aggressive diseases

Plus disease is defined as the appearance of dilatation and tortuosity of retinal vessels and aggressive ROP is a rapid development of pathologic neovascularization and severe plus disease without progressing through the typical stages of ROP
Regression of the disease refers to the involution and resolution of disease and reactivation refers to recurrence of acute phase features. It is seen that 80-90% of stage 1 disease regresses on its own.

SCREENING RECOMMENDATIONS FOR ROP
The gestational age and birth weight of ROP screening criteria is lower in the developed world. However, in low- and middle-income countries like ours, criteria need to be broader in order to allow the variation of quality of neonatal care therefore gestational age and birth weight criteria of ROP screening is higher. Nepal lacks any formal comprehensive national guideline for retinopathy of prematurity. Due to the similar risk profiles and quality of care in India and Nepal, most of the institution in Nepal follows the Indian guideline for screening of ROP

The screening recommendations are as follows:1

1. All infants born at 34 weeks or less of gestational age
2. All infants weighing 2000 gm or less
3. All infants born at more than 34 weeks of gestational age with associated risk factors (cardiorespiratory support, prolonged oxygen requirement, respiratory distress syndrome, chronic lung di sease, fetal hemorrhage, blood transfusion, interventricular hemorrhage, apnea, poor post-natal weight gain or any other babies on the discretion of the pediatrician or neonatologist

WHEN TO SCREEN?
The first retinal examination is generally performed

• At 4 weeks after birth or 25-30 days of life1 or 31 weeks of life whichever is later

HOW DO WE SCREEN?
Screening is done either in the Neonatal intensive care unit if the baby is still admitted during the time of examination or it is done in the out patient department if the baby is discharged. The procedure is well explained to the parents or the guardians and pupillary dilatation is done using dilating drops 30 to 60 mins prior to the examination. Once the pupil is fully dilated, examination is done after instilling an anesthetic drop to numb the ocular surface and a lid speculum is used. Screening is usually done using a binocular indirect ophthalmoscope and using an indentor. Nowadays, wide angle fundus camera for ROP screening can also be used where the ophthalmologist reviews the fundus examination and decide for the management. The advantage of wide-angle fundus camera is the ophthalmologist can review the photo remotely and also plan for treatment.
Follow up examinations is recommended depending on the basis of retinal findings. In patients with no ROP and incomplete or immature vascularization the follow up is decided depending on the zone of vascularization and earlier follow ups are required for zone I or II vascularization. Also, in patients with ROP depending on the stage and zone involved the patient is kept in close follow up or treatment is given. Treatment requiring ROP is termed as Type 1 and ROP requiring close follow up/ observation is termed as Type 2 ROP.

Screening in preterm babies ends one full retinal vascularization is seen.

HOW IS ROP TREATED?
Treatment requiring ROP are also called Type 1 ROP. Treatment should be provided as early as possible. The various modalities of treatment include

1. Intravitreal Anti-Vascular Endothelial Growth Factor such as Bevacizumab is given for more posterior and aggressive ROP. Anti VEGF therapy helps to regress the neovascularization and allow peripheral retinal vascularization
2. Laser Photocoagulation helps in ablating the peripheral avascular retinal therefore reducing VEGF production and preventing further neovascularization
3. Surgical management is reserved for disease with retinal detachment and advanced disease. The outcome depends on the stage of the disease

WHAT ARE THE COMPLICATIONS OF ROP
Complications of ROP include

• Tractional and rhegmatogenous Retinal detachment
• Macular folds
• Myopia
• Strabismus
• Amblyopia
• Persistent avascular retina
• Macular abnormalities
• Glaucoma

To conclude, ROP is a preventable childhood blindness, it is important that at – risk infants are identified early by timely screening and also receive prompt and appropriate intervention. With a very short time frame for diagnosis and treatment for ROP it is very important that all at risk infants be screened within 4 weeks of life. Therefore, there is equal and important role of society and healthcare system to prevent ROP. It is important to create public awareness, educate parents of at-risk babies, adhere to the guideline, develop a robust referral network and train adequate manpower for screening and treating ROP. Therefore, with development of guidelines, timely screening, multidisciplinary collaboration and societal support we all can prevent blindness due to ROP so as to promote better and quality life of these precious babies.

References

Chiang MF, Quinn GE, Fielder AR, Ostmo SR, Chan RVP, Berrocal A, et al. International Classification of Retinopathy of Prematurity , Third Edition. Am Acad Ophthalmol. 2021;1–18.

Shukla R, Murthy GVS, Gilbert C, Vidyadhar B, Mukpalkar S. Operational guidelines for ROP in India: A Summary. Indian J Ophthalmol. 2020;68 Suppl:S108–14.

Adhikari S, Badhu BP, Bhatta NK, Rajbhandari RS, Kalakheti BK. Retinopathy of prematurity in a tertiary care hospital in eastern Nepal. J Nepal Med Assoc. 2008;47(169):24–7.

Shrestha JB, Bajimaya S, Sharma A, Shrestha J, Karmacharya P. Incidence of Retinopathy of Prematurity in a Neonatal Intensive Care Unit in Nepal. J Pediatr Ophthalmol Strabismus. 2009;477(5).