Retinopathy of Prematurity : Causes, Symptoms, Treatment, and Prevention

1. Introduction

   1. Definition of Retinopathy of Prematurity

      Retinopathy of prematurity (ROP) is a disease of the eye that can happen in premature babies. This condition occurs in premature babies who receive neonatal intensive care, in which oxygen therapy is used.⁽¹⁾ ROP causes abnormal blood vessels to grow in the retina, which can lead to blindness.

   2. Historical background of Retinopathy of Prematurity

      In the 1940s, Retinopathy of prematurity (ROP) was called ‘Retrolental Fibroplasia (RLF)’ and RLF was termed first in 1942 by Terry.⁽²⁾ When it was first described, Retinopathy of prematurity was not seen commonly and thus had little interest. However, ten years later, it become a severe problem, and many ophthalmologists and pediatricians started seeing patients with ROP. Now, it affects thousands of children globally.⁽³⁾

   3. Prevalence of Retinopathy of Prematurity

      The incidence of Retinopathy of Prematurity varies with birth weight. However, it is reported to be approximately 50% to 70% in newborns who take birth with a weight of less than 1250 grams.⁽⁴⁾

      In the U.S. from 3.9 million infants that are born each year, about 14,000 children get Retinopathy of prematurity, and about 90% of those with the disease are of mild case.

2. Causes and Risk Factors of Retinopathy of Prematurity

   1. Prematurity and Low Birth Weight

      Low birth weight and premature birth or gestational age are the two major risk factors for retinopathy of prematurity. Babies are likely to get ROP if they are born with a birth weight of 1, 500 grams (3.3 pounds) or less, and also if they are born at a gestational age of 30 weeks or less.

      A baby’s eyes usually develop around the 16th week of pregnancy. However, in the case of premature babies, this process is cut short and the blood vessels in their eyes do not get enough time to develop. Thus, they grow where they are not supposed to, or they become so fragile that they start leaking or bleeding.

   2. Oxygen Therapy and Other Medical Interventions

      Prematurely born babies who receive neonatal intensive care, in which oxygen therapy is used, generally get Retinopathy of prematurity.⁽¹⁾ Supplemental oxygen exposure is a risk factor, however, not the main risk factor for getting this disease. Restricting the use of supplemental oxygen reduces the rate of Retinopathy of prematurity, however, can increase the risk of other hypoxia-related systemic complications, which can also include death.⁽⁵⁾

   3. Other Risk Factors

      Some other risk factors for the disease could be anemia, infection, transfusion, breathing difficulties, and heart disease.

      Ethnicity could also be one possible risk factor for ROP (It occurs slightly more often in Caucasian children)

3. Symptoms and Diagnosis of Retinopathy of Prematurity

   1. Stages of Retinopathy of Prematurity

      Retinopathy of prematurity develops through five different stages. Generally, doctors use these stages to track how serious the condition is.

      Stage 1 is the mildest form of Retinopathy of prematurity, and babies with stage 1 or even stage 2 do not require any treatment in general and will also have normal vision. Babies with

      stage 3 of the disease have more abnormal blood vessels, which means the retina might begin to come loose.

      The retina in infants with stage 4 ROP starts to move from its normal position. In the case of stage 5, the retina has come off, and the babies experience severe vision problems, including blindness.

   2. Screening and Diagnostic Methods

      The ophthalmologist uses a special instrument to look inside the affected eye at the retina and will grade the results of the examination on a standard of five stages, based on the severity of the disease.

      The first stage will be seen as a line on the retina, the second stage is seen as a ridge appearing on the retina, and in the case of the third stage there is a growth of fragile new abnormal blood vessels on the retina. As the disease gets worse, the blood vessels in the retina can turn wavy and thick. The fifth stage is the most severe one.

   3. Other Ocular Symptoms and Complications

      Sometimes mild cases of Retinopathy of prematurity might go on their own as the infant grows. However, they should be examined by an ophthalmologist regularly, as they grow. Some of the major ocular symptoms of this disease include vision loss and even blindness.

      However, some other possible symptoms could be bleeding inside the eye (vitreous hemorrhage), retinal detachment, cataracts, scarring of the retina, and also other eye problems (seen later in life) like strabismus (crossed eyes), glaucoma, amblyopia (lazy eye), and myopia (nearsightedness).

4. Management and Treatment of Retinopathy of Prematurity

   1. Watchful Waiting and Monitoring

      At first, an ophthalmologist will monitor Retinopathy of prematurity to see if the disease goes away on its own. If after watchful waiting and monitoring, the abnormal blood vessels continue to grow, the baby’s eyes should be treated using any of the treatment means, including laser therapy, cryotherapy, or medication eye injections.

   2. Laser Therapy and Other Surgical Interventions

      Retinopathy of prematurity can be treated in the following ways.

      Laser Therapy: This is the treatment method where the doctor uses a laser to burn the edge of the retina. This can stop abnormal blood vessel growth.

      Cryotherapy: It is the freezing treatment, where the surgeon uses a freeing cold instrument for destroying a part of the retina to stop the abnormal growth of blood vessels.

      Anti-VEGF Medications: These medications are injected into the eye to prevent or stop unwanted growth of the blood vessel. This treatment method has been quite promising for treating the third stage of ROP.⁽⁶⁾

      Scleral Buckling: The abnormal blood vessels in the eye and scar tissue pulls the retina away from the inside surface of the eyeball and damages it. This is known as retinal detachment and can result in vision loss. Scleral buckling can be used to reduce the tension on the retina, where an elastic band is placed around the eyeball, and it pushes the inside surface of the eye against the retina. This elastic band is removed when the retina gets reattached to the inside surface of the eye.

   3. Prognosis and Long-Term Outcomes

      In the small number of babies who need treatment for the disease, the treatments generally work well at preventing vision loss. The most important thing that parents should do to help get the best treatments for their children is to keep all scheduled doctor’s appointments and also follow expert medical advice after the treatments.

5. Prevention and Risk Reduction of Retinopathy of Prematurity

   1. Strategies To Reduce The Risk Of Retinopathy Of Prematurity

      A steroid course is given to mothers likely to give birth prematurely, which improves survival and also reduces the complications of prematurity, including retinopathy of prematurity.

      Many other low-cost, effective strategies and medical practices can reduce the risk of Retinopathy of prematurity.

   2. Role of Neonatal Care and Management

      Several neonatal care practices help in reducing the risk of severe ROP and also prevent blindness due to the condition. Neonatal care during the first few hours and weeks of life determines a premature baby’s chances of avoiding ROP and its complications.

      Routinely implementing standard interventions that can prevent retinopathy of prematurity will improve outcomes.

   3. Other Preventive Measures and Interventions

      Another way to prevent the disease is to closely mimic the intrauterine environment after premature birth. This would prevent the toxic post birth influences and also provide the intrauterine factors (like insulin growth factor 1), and also possibly reduce other complications of premature birth along with Retinopathy of prematurity.⁽⁷⁾

6. Research and Current Developments for Treating Retinopathy of Prematurity

   1. Advances in Understanding The Pathogenesis of Retinopathy of Prematurity

      During development, blood vessels grow outwards from the center of the retina and this process gets completed in a few weeks before delivery time. However, in preterm babies, the process remains incomplete. Retinopathy of prematurity does not occur if blood vessels grow normally. However, if the blood vessels grow abnormally then the baby develops the disease.

      The primary disease element in Retinopathy of prematurity is fibrovascular proliferation, which is the growth of abnormal new vessels. Fibrous tissue or scar tissue is associated with the growth of the new abnormal vessels that may contract and result in retinal detachment, which can cause blindness.

   2. Future Directions For Research and Treatment

      Since the introduction of VEGF or Anti-vascular endothelial growth factor therapy, the treatment of retinopathy of prematurity has gained a new height.⁽⁸⁾

      There is so much research on several topics to understand better ways of examining, screening, and also treating Retinopathy of prematurity. Some research topics are:

      • Links between various growth factor levels in the blood and retinopathy of prematurity.
      • Oxygen supplementation and Retinopathy of prematurity.
      • Long-term safety of ROP injection medications.

7. Living with Retinopathy of Prematurity

   1. Coping Strategies For Patients and Families

      In the case of extremely low-birthweight infants, an oxygen saturation target range of 90% to 95% is used, which might be a contributing factor to the growing incidence of Retinopathy of prematurity. To reduce this increasing incidence of ROP, it has been suggested to gradually increase oxygen saturation by targeting premature babies.⁽⁹⁾

      Screening and treatment interventions include regular retinal examinations of preterm babies who are at risk of developing retinopathy of prematurity and visual rehabilitation.^{(10, 11)}

   2. Support Groups and Resources

      Several groups provide help and support for children with retinopathy of prematurity and their families. Some of these support groups are:

      • The Association for Retinopathy of Prematurity and Related Diseases (ROPARD)
      • National Eye Instiute (NEI)

   3. Impact on Quality of Life

      Infants who are treated with Retinopathy of prematurity are at higher risk of developing long-term sequelae, which include amblyopia, anisometropia, cataract, squint, retinal detachment, and glaucoma.

      Moreover, this eye-related problem, which develops during childhood can have serious consequences on the mental, physical, and social well-being of the affected children and their parents. The knowledge of the quality of life in children with ROP and their families is desirable as such children might need prolonged care in their neonatal period and even after that.⁽¹²⁾

8. Conclusion

   Retinopathy of prematurity is an eye disease that is experienced in premature and low-birthweight babies. The condition is categorized into five different stages based on their severity. Though mild cases do not require any treatment, severe cases of ROP require different medical procedures to prevent vision loss. So, early detection and prompt treatment or management of the condition is highly essential.

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