Retinopathy of prematurity

The prevalence of ROP is evolving and varies, from 5 to 8% in developed countries with adequate neonatological facilities, to up to 30% in middle-income developing countries. The increasing prevalence is thought to be due to increased survival of premature infants. There is increasing evidence that ROP and blindness due to ROP are now public health problems in the middle income countries of Latin America, Eastern Europe and the more advanced economies in Southeast Asia and the Middle East region. In these countries ROP is often the most common cause of blindness in children. ROP is highly likely to become an increasing problem in India, China and other countries in Asia as these countries expand the provision of services for premature infants. There is also evidence that the population of premature infants at risk of severe ROP varies depending on the level of neonatal intensive care being provided. This report contained three main findings: • Premature birth has many different causes, and prevention is challenging, • Prematurity is the most common cause of neonatal death in many countries, totaling as many as 1 million infants annually due to complications of preterm birth, and • the number of preterm births is currently estimated to be 15 million, and increasing. ==Pathophysiology==

Retinal vascular development begins prior to 16 weeks gestation, growing from the optic nerve toward the ora serrata, and completing by term. ==Diagnosis==

The classification of ROP has been defined by the International Classification of Retinopathy of Prematurity (ICROP). There are four components in describing a child with ROP: zone, stage, plus, and clock hours. Zones The zones are centered on the optic nerve. The lower the zone number the more posterior the disease, and so the higher the risk of ROP. Familial exudative vitreoretinopathy (FEVR) is another retinal disease in similarly characterized by incomplete vascularization of the peripheral retina and vascular pathology at the interface between the vitreous and retina. Diseases on the differential diagnosis include: • FEVR • Persistent fetal vasculature that can cause a traction retinal detachment difficult to differentiate but typically unilateral. • Coats disease genetic disorder that may lead to retinal detachment, often affecting one eye of males. • Norrie disease • Incontinentia pigmenti • Cutis marmorata telangiectatica congenita ==Screening==

Almost all infants with ROP have a gestational age of 31 weeks or less (regardless of birth weight) or a birth weight of 1250 g (2.76 lbs) or less; these indications are generally used to decide whether a baby should be screened for ROP, but some centres, especially in developing countries, extend birth weight screening criteria to 1500 g (3.3 lbs). Any premature baby with severe illness in perinatal period (respiratory distress syndrome, sepsis, blood transfusion, intraventricular haemorrhage, apnoeic episodes, etc.) may also be offered ROP screening. Timing Retinal examination with scleral depression is generally recommended for patients born before 30–32 weeks gestation, or 4–6 weeks of life, whichever is later. It is then repeated every 1–3 weeks until vascularization is complete (or until disease progression mandates treatment). The 2016 screening guidelines offer a schedule which detects "prethreshold ROP" (defined by ETROP study) with 99% confidence, usually before any required treatment. without accounting for clinical judgement factors that might lead to more frequent screening (e.g., tempo [rate at which disease is progressing], presence of pre-plus, number of clock-hours involved). Plus disease and A-ROP are excluded because their presence is an indication for treatment. Termination of acute screening occurs when one of the following five criteria are met: Once the vessels have grown into zoneIII (see below) it is usually safe to discharge the child from further screening for ROP. The stage of ROP refers to the character of the leading edge of growing retinal blood vessels (at the vascular-avascular border). Monitoring In order to allow timely intervention, a system of monitoring is undertaken for infants at risk of developing ROP. These monitoring protocols differ geographically because the definition of high-risk is not uniform or perfectly defined. In the USA, the consensus statement of experts is informed by data derived by clinical trials and published in Pediatrics 2006. They included infants with birthweights under 1500 grams or under 30 weeks gestation in most cases. The first examination should take place within the first four weeks of birth, and regular, weekly examination is required until it is clear that the eyes are not going to develop disease needing treatment, or one or both eyes develop disease requiring treatment. Treatment should be administered within a 48 hours, as the condition can progress rapidly. ==Management==

Treatment , blue) is placed around the eye. This brings the wall of the eye into contact with the detached retina, allowing the retina to re-attach. • Peripheral retinal ablation is the mainstay of ROP treatment. The destruction of the avascular retina is performed with a solid state laser photocoagulation device, as these are easily portable to the operating room or neonatal ICU. Cryotherapy, an earlier technique in which regional retinal destruction was done using a probe to freeze the desired areas, has also been evaluated in multi-center clinical trials as an effective modality for prevention and treatment of ROP. However, when laser treatment is available, cryotherapy is no longer preferred for routine avascular retinal ablation in premature babies, due to the side effects of inflammation and lid swelling. Furthermore, recent trials have shown that treatment at an earlier stage of the disease gives better results. • Scleral buckling and/or vitrectomy surgery may be considered for severe ROP (stages4 and5) for eyes that progress to retinal detachment. Few centers in the world specialize in this surgery, because of its attendant surgical risks and generally poor outcomes. • Intravitreal injection of bevacizumab (Avastin) has been reported as a supportive measure in aggressive posterior retinopathy of prematurity. In a 2011 clinical trial comparing bevacizumab with conventional laser therapy, intravitreal bevacizumab monotherapy showed a significant benefit for zoneI but not zoneII disease when used to treat infants with stage3+ retinopathy of prematurity. Potential benefits of intravitreal Avastin injection over laser therapy include: reduction in level of anesthesia required, preservation of viable peripheral retina, and, possibly, reduced incidence of subsequent high refractive error. However, the safety of this new treatment has not yet been established in terms of ocular complications as well as systemic complications. The latter are theoretically possible, as the active ingredient of bevacizumab not only blocks the development of abnormal blood vessels in the eye but may also prevent the normal development ofother tissues such as the lung and kidney. A 2018 Cochrane review also examined the effectiveness of anti-vascular endothelial growth factor drugs and their use for ROP. • Oral propranolol is being evaluated for counteracting the progression of ROP, but safety is a concern. A prospective randomized trial in which pre-term newborns were randomized to receiving oral propranolol with standard treatment or standard treatment alone found that oral propranolol showed a 48% relative risk reduction for progression to stage3, 58% reduction for progression to stage3 plus, and 100% reduction for progression to stage4. Furthermore, there was a 52% relative risk reduction for the need for laser treatment or intravitreal bevacizumab. However 19% of the newborns experienced serious adverse effects including hypotension and bradycardia. A study in a mouse model of human ROP has shown that beta-blockade is protective against retinal angiogenesis and ameliorate blood-retinal barrier dysfunction. Follow-up • Once diagnosed with ROP lifelong follow-up (yearly) is performed in some centers. In others, only children treated for ROP are followed yearly. • Follow-up after laser or anti-VEGF treatment is individualized. • Follow-up of premature children (with or without ROP) is varying among centers and countries, mirroring the diverse states of health care system in different countries. ==Prognosis==

Stages 1 and 2 do not lead to blindness. However, they can progress to the more severe stages. Threshold disease is defined as disease that has a 50% likelihood of progressing to retinal detachment. Threshold disease is considered to be present when stage3 ROP is present in either zoneI or zoneII, with at least five continuous or eight total clock hours of disease, and the presence of plus disease. Progression to stage4 (partial retinal detachment), or to stage5 (total retinal detachment), will result in substantial or total loss of vision for the infant. • Refractive errors including myopia (most common) • Strabismus • Amblyopia • Retinal detachment, traction of the retina and blindness • Glaucoma • Impairments in visual acuity, contrast sensitivity, visual field, convergence, and accommodation ==History==

This disease was first described in a premature baby in 1942 as reported by Theodore L. Terry. Between 1941 and 1953, over 12,000 babies worldwide were affected by it. However, Kate Isabel Campbell (1899–1986), a specialist in children's diseases, was responsible in 1951 for proving the link between retrolental fibroplasia (a blindness in premature babies) and oxygen levels in humidicribs. Notable people diagnosed with the disease include soul musician Stevie Wonder, actor Tom Sullivan, pianist Derek Paravicini, jazz singer Diane Schuur, and singer Gilbert Montagné. The first case of the epidemic was seen on St. Valentine's Day in 1941 when a premature baby in Boston was diagnosed. Cases were then seen all over the world and the cause was, at that point, unknown. By 1951 a clear link between incidence and affluence became clear: many cases were seen in developed countries with organized and well-funded health care. Two British scientists suggested that it was oxygen toxicity that caused the disease. Babies born prematurely in such affluent areas were treated in incubators which had artificially high levels of oxygen. Studies on rats made this cause seem more likely, but the link was eventually confirmed by a controversial study undertaken by American pediatricians. The study involved two groups of babies. Some were given the usual oxygen concentrations in their incubators, while the other group had "curtailed" oxygen levels. The latter group was shown to have a lower incidence of the disease. As a result, oxygen levels in incubators were lowered and consequently, the epidemic was halted. == References ==