Retinopathy Of Prematurity: Symptoms, Types, Causes and Treatment

Retinopathy of prematurity (ROP) is a potentially blinding eye disorder that affects premature infants. As neonatal care advances and more preterm babies survive, understanding ROP—its symptoms, types, causes, and treatments—has become essential for parents, caregivers, and healthcare providers. In this comprehensive article, we’ll explore the key features of ROP in an approachable, evidence-based manner, synthesizing the latest research to help you understand this important condition.

Symptoms of Retinopathy Of Prematurity

ROP often develops silently in the early stages, making awareness of its symptoms and subtle signs crucial for early detection and effective management. While premature infants may not show obvious symptoms initially, regular screening is vital for identifying the disease before it leads to vision loss.

Symptom	Description	Detection Method	Source(s)
No symptoms	Most infants asymptomatic early	Screening exam	2 6 7
Abnormal retina	Abnormal blood vessel growth	Eye exam/fundoscopy	1 4 6
White pupils	Leukocoria in late stages	Clinical observation	4 6
Strabismus	Misalignment of the eyes	Clinical observation	3 4 6

Table 1: Key Symptoms

Early Course: Why Symptoms Are Often Missed

• Asymptomatic Nature: ROP typically does not cause pain or visible signs in its early stages. Infants cannot communicate vision problems, and parents rarely notice symptoms until advanced stages or complications arise 2 6.
• Detection Through Screening: The main method for identifying ROP is a systematic dilated eye examination by a pediatric ophthalmologist. Screening is recommended for infants below a certain birth weight or gestational age 2 7.

Recognizing Advanced ROP

• Leukocoria: A white reflection from the pupil (leukocoria) may be visible in severe cases, often indicating retinal detachment.
• Strabismus: Some infants develop misalignment of the eyes or abnormal eye movements if vision is compromised 3 4.
• Other Signs: In rare, advanced cases, infants may show nystagmus (uncontrolled eye movements) or decreased visual responsiveness.

Long-Term Visual Impact

Even after apparent resolution, some children with a history of ROP experience:

• Persistent visual disturbances
• Refractive errors (e.g., nearsightedness)
• Amblyopia (lazy eye) 3
• Impaired peripheral vision

Key Takeaway: Since early ROP is usually asymptomatic, adherence to screening protocols is the best way to ensure timely diagnosis and intervention.

Types of Retinopathy Of Prematurity

ROP isn’t a single disease but a spectrum, with various types and stages reflecting the location, severity, and progression of abnormal retinal blood vessel growth. Understanding these types is vital for both prognosis and treatment decisions.

Type/Stage	Defining Feature	Risk Level	Source(s)
Mild ROP	Minimal vessel changes	Low, often regresses	2 4 11
Type 2 ROP	Moderate changes, no plus disease	Moderate, needs monitoring	2 11
Type 1 ROP	Severe, with “plus disease”	High, needs treatment	2 4 11 14
Aggressive ROP	Rapid, severe progression	Very high, urgent treatment	4 11

Table 2: Main Types of ROP

International Classification: Zones and Stages

ROP classification is based on:

• Zones (Location):
  • Zone I: Center-most retina (highest risk)
  • Zone II: Mid-periphery
  • Zone III: Outermost retina (least risk) 4
• Stages (Severity):
  1. Stage 1: Demarcation line
  2. Stage 2: Ridge formation
  3. Stage 3: Extraretinal fibrovascular proliferation
  4. Stage 4: Partial retinal detachment
  5. Stage 5: Total retinal detachment 4

Plus Disease and Aggressive ROP

• Plus Disease: Defined by dilation and tortuosity of posterior retinal blood vessels, “plus disease” indicates a higher risk for progression and is a key criterion for treatment 4.
• Aggressive ROP: Previously called “aggressive posterior ROP,” this form progresses rapidly and may occur outside the classic posterior zones, especially in resource-limited settings 4 11. It requires urgent intervention.

Regression and Reactivation

• Regression: With or without treatment, many cases of mild ROP regress spontaneously.
• Reactivation: After anti-VEGF therapy, there is a risk of disease “reactivating,” necessitating extended follow-up 4 10 12.

Long-Term Sequelae

• Even after successful regression, some infants are left with abnormal retinal structure or function, impacting vision in later childhood 3 4.

Causes of Retinopathy Of Prematurity

The development of ROP is complex, involving a mix of biological, environmental, and medical factors. Not all at-risk infants develop ROP, and the interplay of causes helps explain its variable severity.

Cause	Mechanism/Effect	Associated Risk	Source(s)
Prematurity	Immature retinal blood vessels	Highest	1 2 6 7 8
Low birth weight	Correlates with severity	High	2 5 7 8
Oxygen therapy	Disrupts vessel growth phases	High	1 6 8 9
Systemic illness	Inflammation, poor growth	Moderate-High	5 7 8 9

Table 3: Main Causes of ROP

Pathophysiology: Two Phases

• Phase 1 (Vascular Arrest): After premature birth, exposure to high oxygen levels (relative to the womb) suppresses growth factors like VEGF, halting normal vessel growth 1 6.
• Phase 2 (Vasoproliferation): As the retina matures and becomes metabolically active, low oxygen (hypoxia) triggers a surge in VEGF, leading to abnormal vessel growth and possible scarring or detachment 1 6.

Key Risk Factors

1. Gestational Age and Birth Weight

• The most premature and smallest infants are at highest risk. Nearly all severe ROP occurs in infants <1251 grams 2 8.
• Extremely low gestational age (<25 weeks) or birth weight (<1000 grams) dramatically increases risk and severity 8.

2. Oxygen Therapy and Fluctuations

• Oxygen supplementation is necessary for survival but must be carefully controlled. Both excessive and fluctuating oxygen levels can trigger or worsen ROP 1 6 8 9.
• Prolonged oxygen therapy increases risk, especially when combined with other complications 8 9.

3. Systemic and Neonatal Illnesses

• Mechanical ventilation, sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and persistent ductus arteriosus are all linked with increased ROP risk and progression 5 7 8 9.

4. Other Contributing Factors

• Maternal health, poor postnatal growth, nutrition (low IGF-1, omega-3 fatty acids), genetic predisposition, and inflammation can also play roles 1 5 6 7.

Why Not All Preterm Infants Develop ROP

• The risk is multifactorial, and individual susceptibility varies. Some preterm infants with similar gestational ages or weights may not develop ROP, highlighting the roles of genetics, clinical course, and care practices 7 9.

Treatment of Retinopathy Of Prematurity

Timely treatment is critical for preventing permanent vision loss in infants with severe ROP. The approach has evolved significantly, with new therapies and ongoing research shaping the future of care.

Treatment	Main Technique/Goal	Key Considerations	Source(s)
Laser therapy	Ablates avascular retina	Gold standard, effective	10 11 13 14
Anti-VEGF drugs	Inhibit abnormal vessel growth	Recurrence risk, systemic effects	1 10 11 12 13
Surgery	Repairs retinal detachment	For advanced cases only	11 14
Supportive care	Optimize oxygen, nutrition	Prevention, adjunctive	6 13

Table 4: Main Treatments for ROP

Standard Treatments

1. Laser Photocoagulation

• How it works: Destroys peripheral avascular retina to reduce VEGF production and stop abnormal vessel growth.
• Effectiveness: Remains the gold standard for most cases of Type 1 ROP and is proven to reduce progression to blindness 10 11 14.
• Considerations: Requires anesthesia; some risk of peripheral visual field loss.

2. Anti-VEGF Therapy (e.g., Bevacizumab)

• How it works: Intravitreal injection of anti-VEGF agents blocks VEGF-driven abnormal vessel growth 1 10 12 13.
• Advantages: Particularly useful for posterior (Zone I) or aggressive ROP, where laser is less effective; less destructive to peripheral retina.
• Risks: Higher recurrence rate, need for prolonged follow-up due to possible disease reactivation; concerns over systemic VEGF suppression and unknown long-term effects on organ development 10 12 13.
• Trends: Use is increasing, but always with careful weighing of benefits and risks 11 13.

3. Surgical Intervention

• For advanced ROP (Stages 4 and 5): Scleral buckling or vitrectomy may be attempted to reattach the retina, but outcomes are often poor if detachment is total 11 14.

Prevention and Supportive Care

• Oxygen Management: Careful titration of oxygen to avoid both hypoxia and hyperoxia 6 13.
• Nutrition: Optimizing growth, especially with proper levels of IGF-1 and omega-3 fatty acids, may reduce risk 6.
• Infection Control: Preventing and treating systemic illness lowers ROP risk 6 8.

Emerging and Future Therapies

• Targeted anti-VEGF strategies: Ongoing research aims to refine dosing and minimize systemic exposure 1 12 13.
• Telemedicine & AI: Improving ROP screening in resource-limited areas 13.
• Non-invasive management: Light-based therapies and neuroprotective strategies are being explored 3 13.

Follow-Up and Long-Term Care

• Monitoring: All treated infants require extended follow-up to detect recurrences or late complications 10 12.
• Vision Rehabilitation: Children with vision loss benefit from early intervention and support services.

Conclusion

Retinopathy of prematurity is a complex, multifaceted disease that demands vigilance, timely intervention, and ongoing research. Here’s what you need to remember:

• ROP is most common in premature, low-birth-weight infants and is usually asymptomatic early—screening is essential 2 6.
• Types of ROP range from mild to aggressive, and classification guides management 4 11.
• Causes are multifactorial, with prematurity, oxygen therapy, and systemic illness being major contributors 1 6 7 8.
• Treatment has advanced from destructive therapies to targeted drugs, but each option has risks and benefits—long-term follow-up is crucial 10 11 12 13 14.

In summary:

• Early detection through screening saves sight.
• Treatment is most effective when tailored to disease severity and type.
• Prevention efforts focus on optimizing neonatal care.
• Ongoing research is key to improving outcomes for vulnerable infants.

By understanding the symptoms, types, causes, and treatments of ROP, families and healthcare teams can work together to minimize the risk of vision loss and give every premature infant the best possible start.