Retrolental Fibroplasia: Symptoms, Types, Causes and Treatment

Retrolental fibroplasia (RLF), also known today as retinopathy of prematurity (ROP), is a sight-threatening eye disease that primarily affects premature infants. Since its first description in the 1940s, RLF has become a leading cause of childhood blindness in many countries. Understanding its symptoms, types, causes, and available treatments is essential for parents, healthcare professionals, and anyone involved in neonatal care. In this article, we explore these aspects comprehensively, drawing on historical and current research.

Symptoms of Retrolental Fibroplasia

Retrolental fibroplasia often develops silently in the early stages, making early detection a challenge. As the disease progresses, several characteristic symptoms and signs emerge, many of which can have a profound impact on vision and eye structure.

Symptom	Description	Typical Age of Onset	Source(s)
Vascularized Membrane	Membrane forms behind the lens, often with blood vessels	1–5 months	1 2 6
Microphthalmia	Abnormally small eye	Early infancy	2 4 6
Retinal Detachment	Retina detaches from its normal position	Progresses in months	1 3 6 9
Visual Impairment	Reduced vision up to complete blindness	By preschool age	4 6 16

Table 1: Key Symptoms

Early and Late Symptoms

Early Symptoms:
In its earliest stages, RLF is often asymptomatic and only detectable by specialist eye examination. The first observable sign is a dilation of the retinal vessels, followed by an exudative retinitis—an inflammatory process with leakage of fluid from retinal vessels 1 3.

Late Symptoms:
As the disease advances, more obvious signs develop:

• A white, vascularized membrane forms behind the lens (the hallmark of RLF) 1 2.
• Microphthalmia, where the affected eye is noticeably smaller than normal 2 4.
• Shallow anterior chamber of the eye.
• Retinal detachment, which can progress to total retinal separation 1 3 6 9.
• Secondary complications such as glaucoma (increased intraocular pressure), corneal opacities, synechiae (adhesion of iris to lens or cornea), and iritis (inflammation of the iris) may also appear 1 4.

Functional Symptoms:

• Visual impairment is common and can range from mild reduction in acuity to total blindness, especially in severe or untreated cases 4 16.
• Nystagmus (involuntary eye movements) and photophobia (light sensitivity) may be observed in infants who retain some vision 2.

Clinical Course and Impact

RLF typically develops in infants born prematurely, with symptoms becoming apparent within the first 1–5 months of life, not at birth 1 6. The most severe visual outcomes—such as legal blindness—tend to occur in infants with the greatest prematurity and lowest birth weights 4 16. The disease can affect one or both eyes but is most often bilateral, further compounding its impact on early childhood development.

Types of Retrolental Fibroplasia

Understanding the types and stages of RLF is crucial, as they inform both prognosis and the urgency of intervention. The classification of RLF has evolved, but certain patterns and stages are consistently recognized in the literature.

Type/Stage	Key Features	Severity/Progression	Source(s)
Acute	Active vascular proliferation, exudates	Early, potentially reversible	13 15 16
Cicatricial	Fibrosis, membrane formation, retinal detachment	Late, often irreversible	4 6 9
Mild	Minimal vascular changes, spontaneous resolution	Least severe	16
Severe	Extensive retinal changes, high risk of blindness	Most severe	4 16

Table 2: Types and Stages

Acute vs. Cicatricial RLF

Acute RLF:
This is the early, active phase characterized by abnormal growth of retinal blood vessels (neovascularization). The vessels may become tortuous, dilated, and proliferate abnormally, leading to exudates and possible retinal edema. If identified here, there is potential for spontaneous resolution or successful intervention 13 15 16.

Cicatricial RLF:
If the acute phase does not resolve, scar tissue forms, resulting in the cicatricial (scarring) stage. This is marked by the formation of a fibrovascular membrane behind the lens, traction on the retina, and often retinal detachment. This stage is generally irreversible and associated with permanent vision loss 4 6 9.

Mild vs. Severe Forms

• Mild RLF:
  Most cases, especially in infants with higher birth weights, are mild and resolve without intervention. These may show only minimal vascular changes 16.
• Severe RLF:
  Severe cases are typically seen in the smallest and most premature infants. These cases progress to retinal detachment, extensive fibrosis, and profound vision impairment or blindness 4 16.

Historical and Modern Classifications

While modern ophthalmology uses detailed staging systems, the core clinical types remain: an early, potentially reversible phase and a late, fibrotic, vision-threatening stage 6 9. Recognizing progression from acute to cicatricial is key to intervention.

Causes of Retrolental Fibroplasia

The origins of RLF are complex, involving multiple interrelated risk factors. While oxygen therapy has historically been implicated, a growing body of research recognizes the multifactorial nature of the disease.

Cause/Risk Factor	Description	Role/Impact	Source(s)
Prematurity	Birth before 37 weeks, especially <30 weeks	Highest risk factor	1 4 5 12 16
Low Birth Weight	<1500 g (3.3 lbs)	Major risk	4 5 12 16
Oxygen Therapy	High/concentrated oxygen exposure after birth	Contributory, but not sole cause	8 10
Fluctuating Oxygenation	Both excessive and insufficient oxygen	Damages retinal vessels	8 10
Blood Transfusions	Large transfusions in neonatal period	Associated risk	12
Infection/Sepsis	Systemic infection in neonatal period	Increases risk	8 12 14
Genetic/Other Factors	Genetic, dietary, metabolic, and prenatal complications	Potential contributors	8 12

Table 3: Principal Causes and Risk Factors

Prematurity and Low Birth Weight

The single most significant risk factor for RLF is prematurity—specifically, birth before 30 weeks gestation—and low birth weight (under 1500 grams). The more premature the infant, the less developed the retinal blood vessels, rendering them highly susceptible to damage and abnormal growth 1 4 5 12 16.

Oxygen Therapy: Historical and Current Perspectives

Historically, RLF was closely linked to the administration of high concentrations of supplemental oxygen to premature infants. Early studies demonstrated a strong correlation, and animal experiments replicated similar retinal changes with oxygen exposure 10. However, more recent research suggests that oxygen is not the sole cause. Instead, the fluctuation in oxygen levels—both hyperoxia and hypoxia—can disrupt normal retinal vessel development 8 10.

Key points:

• Excessive oxygen can suppress normal vessel growth.
• Rapid reduction from high oxygen to normal air may trigger abnormal vessel proliferation (relative anoxia) 8 10.
• Not all infants exposed to supplemental oxygen develop RLF, and some cases occur without oxygen therapy 8 10.

Additional Contributing Factors

• Blood Transfusions: Large or repeated transfusions, especially during periods of fluid and electrolyte imbalance, have been linked to higher RLF risk 12.
• Sepsis and Infection: Systemic infection in premature newborns increases vulnerability 8 12 14.
• Genetics and Other Neonatal Complications: Factors such as genetic predisposition, prenatal complications, apnea, intraventricular hemorrhage, and metabolic disturbances can also contribute 8 12 14.

Why Is RLF Difficult to Prevent?

Because RLF arises from a complex interplay of prematurity, oxygen fluctuations, and systemic illness, it is challenging to fully prevent—even with current neonatal care standards 8 10 12 14.

Treatment of Retrolental Fibroplasia

The management of RLF has evolved greatly, from early attempts at medical therapy to modern interventions aimed at preserving vision. Timely treatment, especially during the acute phase, is crucial.

Treatment	Approach/Method	Effectiveness	Source(s)
Observation	Monitoring mild or early cases	Most cases resolve spontaneously	15 16
Cryotherapy	Freezing peripheral retina to halt abnormal vessels	Reduces progression, preserves vision	13 15 16
Laser Therapy	Photocoagulation to ablate avascular retina	Effective in select cases	16
Vitamin E	High-dose supplementation in preterm infants	Reduces incidence/severity	14
ACTH/Corticosteroids	Hormonal therapy to reduce inflammation	Largely ineffective	12 17
Surgery	Correction of retinal detachment or complications	Limited success in late stages	6 15

Table 4: Treatment Approaches

Observation and Natural Course

Most mild or early-stage cases of RLF resolve without intervention, especially if risk factors are controlled. Careful ophthalmologic monitoring is essential to detect progression 15 16.

Cryotherapy and Laser Therapy

Cryotherapy:
Applying freezing treatment to the peripheral (nonvascularized) retina has been shown to halt the progression of abnormal blood vessel growth and prevent retinal detachment in many cases. Several studies report that timely cryopexy can preserve useful vision and drastically reduce the risk of blindness without significant complications 13 16. However, some reports note variable effectiveness, and not all infants benefit equally 15.

Laser Photocoagulation:
More recently, laser treatment has replaced cryotherapy in many centers. Laser photocoagulation targets the same areas and is effective in preventing disease progression when applied at the right stage 16.

Medical Treatments

Vitamin E Supplementation:
High-dose Vitamin E has been shown in controlled trials to significantly reduce the incidence and severity of RLF, especially in high-risk preterm infants 14.

ACTH and Corticosteroids:
Early hopes that hormonal therapies like ACTH could reverse or halt RLF progression have not been realized. These treatments are now largely considered ineffective 12 17.

Surgical Interventions

In advanced, cicatricial-stage RLF with established retinal detachment, surgery may be attempted to reattach the retina or address complications. However, the success rate is limited, and most vision loss at this stage is irreversible 6 15.

Prevention and Supportive Care

• Careful Oxygen Management: Avoiding unnecessary fluctuations in oxygen levels remains a cornerstone of prevention 8 10.
• Minimizing Blood Transfusions and Infections: Judicious use of transfusions and prompt infection control can help reduce risk 12.
• Regular Screening: All at-risk preterm infants should undergo regular eye exams to detect RLF early and allow for timely intervention 15 16.

Conclusion

Retrolental fibroplasia, or retinopathy of prematurity, remains a significant challenge in neonatal care. Its complex interplay of risk factors, subtle early symptoms, and potential for permanent blindness require a multidisciplinary approach. Early recognition, careful monitoring, and advances in treatment offer hope for preserving vision in many affected infants.

Key Takeaways:

• Symptoms often begin silently but progress to include a vascularized membrane behind the lens, microphthalmia, retinal detachment, and severe visual impairment 1 2 3 4.
• Types include acute (potentially reversible) and cicatricial (scarring, often irreversible) stages, with severity linked to degree of prematurity 4 6 9 16.
• Causes are multifactorial, with prematurity, low birth weight, oxygen therapy, blood transfusions, infections, and genetic factors all contributing 4 5 8 10 12 14 16.
• Treatment ranges from observation and supportive care to cryotherapy, laser therapy, and vitamin E supplementation. Most mild cases resolve, but severe or late-stage disease can lead to permanent blindness 13 14 15 16 17.

By staying vigilant and advancing neonatal care, the incidence and impact of RLF can continue to decrease, offering improved outcomes for the most vulnerable infants.