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Retinopathy of Prematurity

By Dr. Namrata Todurkar

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Prematurity and intensive care influence the structure and function of the eyes in many different ways. Preterm birth can also affect the development of brain structures that are involved in post-retinal processing of visual information such as the optic nerves, optic radiations and the areas of the brain responsible for processing normal vision. The problems noted in kids born preterm include reduced visual acuity, higher rates of strabismus, presence of high refractive errors (myopia), lowered stereoacuity, and loss of peripheral vision.

Damage to the retina from Retinopathy of Prematurity (ROP) is a common condition in babies born very early. The consequences if ROP are long lasting and not entirely preventable. However, the incidence of severe ROP has drastically reduced with better understanding of neonatal physiology and outstanding research.

Development of the eye:

The appearance of optic grooves from the developing brain marks the first sign of eye development at week three of gestation. At four weeks, the retina is formed. Development of the choroid, a vascular layer that supplies the outer retina, begins during the 6-7 weeks. At week 12, capillaries are visible tracing the retinal and by week 22, arteries and veins resembling the adult eye are apparent. The peripheral retina gets its blood supply only near full term; therefore, when an infant is born preterm, areas of the peripheral retina do not have blood supply. In the first 2 months of life, the visual acuity is no better than 20/400 (can see an object at 20 feet while other people can see it at 400 feet) in term babies. Both monocular and binocular visual acuities are worse in premature infants than in full-term infants at the same age.

Retinopathy of Prematurity (ROP):

By far, the most common disease affecting the preterm eye is ROP. With the advancement of medical technology, more and more lives are being saved and very tiny babies now survive. However, they are very sick and require supplemental oxygen, ventilator support, antibiotic coverage for infections, parenteral nutrition, placement of various devices like central lines, arterial lines etc; and they spend a considerable amount of time in the NICU before they are ready for discharge. Thus, the screening, diagnosis and treatment of ROP starts in the NICU and is continued after discharge.

Large natural history studies have shown that, in most cases, ROP begins at 31 to 33 weeks of corrected age, with progression during the next 2 to 5 weeks. Overall, approximately 65% of infants weighing <1251 g develop some form of ROP. The process of development of ROP is complicated. As described earlier, the peripheral retina is devoid of blood vessels until term. After birth, the baby is exposed to a relatively high oxygenated environment compared to in utero and this decreases the production of a chemical factor responsible for growth of blood vessels (vascular endothelial growth factor-VEGF) and halts the growth of the blood vessels in the peripheral retina. As the retina becomes more metabolically active after around 31 weeks of corrected gestational age, the existing blood vessels cannot meet the oxygen demands. This upregulates VEGF production in the retina, resulting in uncontrolled proliferation of blood vessels. A series of changes result in fine blood vessels extending into the vitreous, fluid collection in retina, retinal haemorrhages, fibrosis, and traction on, and eventual detachment of, the retina. Advanced stages may lead to blindness.

According to the 2013 joint statement by the American Academy of Ophthalmology, infants weighing ≤1500 g or ≤30 weeks’ gestation and those weighing >1500 g or >30 weeks’ gestation with an unstable clinical course should have dilated eye examinations starting at 4 to 6 weeks of age or 31 to 33 weeks’ postmenstrual age. Examinations should continue every 2 to 3 weeks until retinal vascular maturity is reached, if no disease is present. Infants with retinopathy of prematurity or very immature vessels should be examined every 1 to 2 weeks until vessels are mature or the risk of disease requiring treatment has passed. Those at greatest risk should be examined every week.

These eye examinations can be stressful and sometimes painful for a new born as ROP examinations often necessitate the use of an eyelid speculum to retract the eyelids and pressure application on sclera (the white portion of the eye) to visualize the peripheral retina. Hence it is important to keep the baby under observation, during and after the eye examination.

Treatment: Ninety percent of cases of early disease regress spontaneously. In most centres, laser photocoagulation is preferred because of its advantages over cryotherapy, including less discomfort intraoperatively and postoperatively, less pigmentation resulting from the therapy, and direct visualization of the area during treatment. Laser ablation of the peripheral retina can prevent progression to blinding disease in patients with severe ROP and is currently the standard of care for treatment. With laser surgery, small scars are created on the retina which helps control the growth of new blood vessels and reduce the risk of retinal detachment.

Another treatment available for severe ROP is injection Bevacizumab, sold under the brand name Avastin, into the eye. This drug works by blocking the production of a chemical factor responsible for growth of blood vessels called VEGF. The BEAT-ROP trial used Bevacizumab, which has not yet been FDA approved for the treatment of ROP. Therefore, its use is considered as ‘off-label’ and more studies are necessary to determine short term and long term safety. However, research shows that injecting Bevacizumab into the eyes of premature babies with severe ROP may be even more effective than laser surgery. The drug remains for four to six weeks and appears to allow normal blood vessel growth in the eye. Because the dose used in premature infants is very tiny, the drug is barely detectable in blood after injection, and thus the risk of complications is low.

Advanced ROP has been treated surgically with vitrectomy and scleral buckle (retinal reattachment) with some anatomic success, but treatment is in general less successful.

Follow-up eye examinations: Sequelae of regressed disease such as myopia, strabismus, amblyopia, glaucoma, and late detachment require regular follow-up. Detailed eye examination is recommended every 1 to 2 years for infants with fully regressed ROP and every 6 to 12 months for those with scarring ROP. As early as 4 to 6 months after birth, most functions of the eye are permanently imprinted in the brain, and if impaired, cannot be fully restored to normalcy. It is therefore essential to identify the babies at risk so that timely examinations can be performed to prevent blindness or at least decrease its incidence. Premature infants are at risk for myopia even in the absence of ROP and should have an eye examination by 6 months of age. As babies may not be able to communicate about their problems in vision, the only way to diagnose them is by screening and examination early in life. Thus, one can find eye exam being an integral part of any neonatal follow up program because the team would like to make sure that those little eyes can actually see this world as it is.

Dr. Namrata Todurkar, MBBS, MD (Pediatrics), DNB (Pediatrics). Fellowship in Neonatology from National Neonatology Forum India. Fellow in Neonatal-Perinatal Medicine in University of British Columbia. Areas of interest: Neonatal nutrition, Fluid and Electrolyte Management, Inborn Errors, Neurodevelopmental follow-up of preterm infants. Dr. Todurkar is a volunteer blogger at CPBF.

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