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Retinopathy Of Prematurity

Disease Details

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Description: Retinopathy of prematurity (ROP) is a potentially blinding eye disorder primarily affecting premature infants, characterized by abnormal development of retinal blood vessels.
Type: Retinopathy of prematurity (ROP) is not primarily a genetic disease; it is a developmental disorder. It occurs in premature infants and is associated with abnormal development of retinal blood vessels. While genetic factors may influence susceptibility, ROP is chiefly related to prematurity and environmental factors, such as oxygen therapy. Therefore, it does not have a well-defined type of genetic transmission.
Signs And Symptoms: Signs and symptoms of retinopathy of prematurity (ROP) often include:

1. Abnormal eye movements
2. Crossed eyes (strabismus)
3. Severe myopia (nearsightedness)
4. White pupils (leukocoria)
5. Difficulty with visual fixation or following objects

In its early stages, ROP may not present any noticeable symptoms and requires an eye examination by a specialist for detection.
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 stage 3 ROP is present in either zone I or zone II, with at least five continuous or eight total clock hours of disease, and the presence of plus disease. Progression to stage 4 (partial retinal detachment), or to stage 5 (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
Onset: The onset of retinopathy of prematurity (ROP) typically occurs several weeks after birth, most commonly in premature infants born before 31 weeks of gestation or weighing less than 1,250 grams (about 2.75 pounds) at birth. The condition can begin to develop as these infants start to receive oxygen therapy and experience changes in their retinal blood vessels. The exact timing may vary, but initial signs usually appear between 4 to 10 weeks after birth.
Prevalence: Retinopathy of prematurity (ROP) primarily affects premature infants. The prevalence varies significantly based on the population and medical care practices. In high-income countries, approximately 10-20% of very low birth weight infants (those weighing less than 1,500 grams) develop some degree of ROP. The condition is more common and severe in infants with lower birth weights and earlier gestational ages. In low- and middle-income countries, the prevalence can be higher due to differences in neonatal care.
Epidemiology: ROP prevalence varies, from 5 to 8% in developed countries with adequate neonatological facilities, to up to 30% in middle-income developing countries.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 South East 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. In countries with high development indices and very low neonatal mortality rates (e.g. North America, Western Europe), severe ROP is generally limited to extremely preterm infants i.e. those weighing less than 1 kg (2.2 lbs) at birth. At the other end of the development spectrum, countries with very low development indices and very high neonatal mortality rates (e.g. much of subSaharan Africa) ROP is rare as most premature babies do not have access to neonatal intensive care and so do not survive. Countries with moderate development indices are improving access to neonatal intensive care, and in these settings bigger, more mature babies are also at risk of severe ROP as neonatal care may be suboptimal. These findings have two main implications: firstly, much can be done in countries with moderate development indices to improve neonatal care, to reduce the risk of severe ROP in bigger babies and increase survival of extremely preterm infants, and secondly, in these settings bigger more mature babies need to be included in ROP programs and examined regularly so as to detect those babies developing ROP requiring treatment.
In 2012, the World Health Organization published data on rates of preterm birth and the number of premature babies born in different regions of the world. 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.
Intractability: Retinopathy of Prematurity (ROP) is not necessarily intractable. It refers to a potentially blinding eye disorder that primarily affects premature infants. Early stages of ROP often regress without treatment; however, severe cases may require interventions such as laser therapy, cryotherapy, or intravitreal injections. Early detection and timely treatment are crucial for managing the disease and improving visual outcomes. Therefore, while it can be challenging to treat in severe cases, it is not considered intractable.
Disease Severity: Retinopathy of prematurity (ROP) can vary in severity and is classified into stages:

1. **Stage 1:** Mildly abnormal blood vessel growth. Usually resolves without treatment and has no long-term effects.
2. **Stage 2:** Moderately abnormal blood vessel growth. Often resolves without treatment but needs monitoring.
3. **Stage 3:** Severely abnormal blood vessel growth. May require treatment to prevent retinal detachment.
4. **Stage 4:** Partial retinal detachment. Requires immediate treatment to preserve vision.
5. **Stage 5:** Total retinal detachment. Can lead to severe vision loss or blindness, requiring surgical intervention.

In addition to these stages, ROP is also classified by the extent and location of the abnormal vessel growth. Early diagnosis and careful monitoring are crucial for preventing severe complications.
Healthcare Professionals: Disease Ontology ID - DOID:13025
Pathophysiology: During development, blood vessels grow from the central part of the retina outwards. This process is completed a few weeks before the normal time of delivery. However, in premature babies, the process has yet to be completed. If the vessels grow and branch abnormally, the baby becomes susceptible to developing ROP. These abnormal blood vessels may grow up from the plane of the retina and bleed inside the eye. When the blood and abnormal vessels are reabsorbed, it may give rise to multiple band-like membranes which can pull up the retina, causing detachment of the retina and eventually blindness before six months.Normally, maturation of the retina proceeds in utero, and at term, the medial portion (nasal retina) of the retina is fully vascularized, while the lateral portion (temporal retina) is only incompletely vascularized. The normal growth of the blood vessels is directed to relatively low-oxygen areas of the retina, but the vessels remain in the plane of the retina and do not grow into the vitreous humor. If excess oxygen is given, normal blood vessels degrade and cease to develop. When the excess oxygen environment is removed, the blood vessels rapidly begin forming again and grow into the vitreous humor of the eye from the retina.The key disease element in ROP is fibrovascular proliferation. This is growth of abnormal new vessels; this may regress, but frequently progresses. Associated with the growth of these new vessels is fibrous tissue (scar tissue) that may contract to cause retinal detachment. Multiple factors can determine whether the disease progresses, including overall health, birth weight, the stage of ROP at initial diagnosis, and the presence or absence of "plus disease". Supplemental oxygen exposure, while a risk factor, is not the main risk factor for development of this disease. Restricting supplemental oxygen use reduces the rate of ROP, but may raise the risk of other hypoxia-related systemic complications, including death.Patients with ROP, particularly those who have developed severe disease needing treatment are at greater risk for strabismus, glaucoma, cataracts and shortsightedness (myopia) later in life and should be examined yearly to help prevent or detect and treat these conditions.
Carrier Status: Retinopathy of Prematurity (ROP) is not typically associated with carrier status, as it is not a condition inherited in a carrier-dependent genetic manner. ROP is a disease that affects the eyes of premature infants, primarily caused by abnormal blood vessel development in the retina rather than inherited genetic mutations.
Mechanism: Retinopathy of prematurity (ROP) is a disease that affects the retina of preterm infants.

**Mechanism:**
ROP occurs primarily due to abnormal blood vessel development in the retina. In premature infants, the retinal blood vessels may stop growing normally, leading to incomplete vascularization. Upon exposure to higher oxygen levels outside the womb, the halted blood vessel growth can lead to subsequent hypoxia (deprivation of adequate oxygen supply) in the retina. This hypoxia stimulates the overproduction of vascular endothelial growth factor (VEGF) and other factors, causing abnormal and excessive blood vessel proliferation. These new vessels are often fragile and can leak, leading to fibrosis, scarring, and potentially retinal detachment.

**Molecular mechanisms:**
1. **Hypoxia and VEGF:** When premature infants are born, the sudden change from the intrauterine to the extrauterine environment triggers hypoxia in avascular regions of the retina. Hypoxia-inducible factors (HIF) then promote the expression of VEGF and other angiogenic factors. VEGF is critical for blood vessel formation but becomes pathologic in excess, contributing to aberrant neovascularization.

2. **Role of IGF-1:** Insulin-like growth factor 1 (IGF-1) is essential for normal vascular development, and preterm infants typically have lower levels of IGF-1. Deficiency in IGF-1 delays normal retinal vascularization, prolonging the period of hypoxia and further promoting aberrant VEGF expression.

3. **Oxygen Regulation:** Excessive supplemental oxygen given for neonatal care can disturb the natural oxygen gradient necessary for normal retinal vascular development. After a hyperoxic phase, the subsequent relative hypoxia triggers an overreaction leading to pathologic neovascularization.

4. **Inflammatory Pathways:** Inflammation in preterm infants due to infections or other insults can also modulate VEGF expression and aggravate the disease progression.

Effective management of ROP often involves carefully regulating oxygen exposure and, in severe cases, medical interventions such as laser therapy or anti-VEGF injections to curb abnormal blood vessel growth.
Treatment: 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 (stages 4 and 5) 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 zone I but not zone II disease when used to treat infants with stage 3+ 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 stage 3, 58% reduction for progression to stage 3 plus, and 100% reduction for progression to stage 4. 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.
Compassionate Use Treatment: For retinopathy of prematurity (ROP), compassionate use, off-label, or experimental treatments might be considered in severe cases or when standard treatments are not effective. Some of these treatments include:

1. **Bevacizumab (Avastin)**: This anti-VEGF (vascular endothelial growth factor) medication is typically used for cancer treatment but is sometimes used off-label as an intravitreal injection to inhibit abnormal blood vessel growth in the retina.

2. **Ranibizumab (Lucentis)**: Another anti-VEGF agent similar to bevacizumab, ranibizumab is also used off-label for ROP. Some studies suggest it may be safer due to its shorter systemic half-life.

3. **Aflibercept (Eylea)**: An anti-VEGF drug, currently less commonly used for ROP but is under investigation for potential benefits in preventing or treating the disease.

4. **Gene Therapy**: Still largely experimental, gene therapy approaches aim to correct or counteract the genetic and molecular pathways causing abnormal vascular development in the retina.

5. **Retinal Cytoprotection Drugs**: Research is ongoing into drugs that might protect retinal cells from damage or death caused by abnormal blood vessel growth.

6. **Pharmacological Treatments**: Other experimental drug treatments are in development and testing, targeting different mechanisms involved in the pathogenesis of ROP.

It's important to note that while these treatments show promise, their safety and efficacy profiles are still being studied, and they are not yet part of the standard care regimen for ROP. They are typically considered in settings where traditional treatments such as laser therapy or cryotherapy are not suitable or sufficient.
Lifestyle Recommendations: Retinopathy of prematurity (ROP) is a condition that affects the eyes of premature infants. While lifestyle recommendations are not directly applicable to prevent or manage ROP, ensuring proper prenatal and neonatal care can reduce its risk.

1. **Prenatal Care**: Adequate prenatal care can help prevent premature births, thus reducing the risk of ROP. Pregnant women should follow a healthy diet, avoid smoking and alcohol, and manage chronic health conditions under medical supervision.

2. **Neonatal Care**: After birth, premature infants should receive appropriate care in a neonatal intensive care unit (NICU). This includes:
- Monitoring and controlling oxygen levels carefully.
- Regular eye examinations by a pediatric ophthalmologist.
- Ensuring proper nutrition and avoiding infections.

These steps can help manage the risk and progression of ROP in premature infants.
Medication: Retinopathy of prematurity (ROP) primarily requires careful monitoring and interventions like laser therapy or cryotherapy for advanced stages. While there is no specific medication to treat ROP directly, certain measures can help manage its progression. For example, medications like bevacizumab (an anti-VEGF agent) may be injected into the eye in severe cases to inhibit abnormal blood vessel growth. Administering proper oxygen therapy and ensuring good overall neonatal care are also crucial in managing this condition.
Repurposable Drugs: Research into repurposable drugs for retinopathy of prematurity (ROP) is ongoing. Some potential repurposable drugs being studied include:

1. **Bevacizumab (Avastin)**: Originally used for treating certain cancers and age-related macular degeneration, this anti-VEGF (vascular endothelial growth factor) drug has shown promise in treating ROP by inhibiting abnormal blood vessel growth in the retina.
2. **Ranibizumab (Lucentis)**: Similar to Bevacizumab, this anti-VEGF drug has been used in eye conditions and is being investigated for potential use in ROP.
3. **Erythropoietin**: Known for its role in treating anemia, erythropoietin has neuroprotective properties and has been explored for its potential to protect retinal cells.

Please consult a healthcare professional or researcher for the most current treatment options and research updates.
Metabolites: Retinopathy of prematurity (ROP) is a potentially blinding eye disorder primarily affecting premature infants. The exact metabolites involved in ROP are not fully established, but abnormalities in oxygen levels and the resulting metabolic responses can play significant roles. Elevated or fluctuating oxygen levels can lead to oxidative stress and the production of reactive oxygen species (ROS).

These ROS can subsequently cause damage to retinal vessels. Also, metabolic pathways involving hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF) are crucial in the progression of ROP, as they influence the development and regression of retinal blood vessels.

Nanotechnology-based therapies, while still largely in the research phase, hold promise for the treatment or management of ROP. These approaches could potentially deliver drugs more directly and effectively to the retina, minimize side effects, and improve the outcomes of premature infants with this condition.
Nutraceuticals: There is currently no established evidence supporting the use of nutraceuticals for the treatment or prevention of retinopathy of prematurity (ROP). ROP is primarily managed through screening and timely medical or surgical interventions. Nutritional strategies, such as appropriate delivery of oxygen and overall nutritional support, are critical in the management of infants at risk, but specific nutraceutical interventions have not been proven effective.

If you need details on particular aspects such as medical interventions or prevention strategies, let me know!
Peptides: Retinopathy of prematurity (ROP) is a disease affecting the retinal blood vessels in premature infants. It is primarily treated through laser therapy, cryotherapy, or in severe cases, anti-VEGF (vascular endothelial growth factor) injections. Research into peptides and nanoparticles for ROP is still in early stages but shows potential for delivering more targeted therapies with fewer side effects. Peptides could be designed to interfere with abnormal blood vessel growth, while nanoparticles may offer precise delivery of drugs or genes to affected retinal areas.