Retinopathy of Prematurity (ROP) is an eye disorder affecting premature infants whose retinas have not fully developed. The condition involves the abnormal growth of blood vessels in the retina, the light-sensitive tissue at the back of the eye. As the disease progresses, these disorganized vessels can cause scarring and retinal damage, potentially leading to severe, permanent vision impairment. Understanding the five stages of ROP is necessary to appreciate the potential for both spontaneous resolution and severe vision loss.
The Basis of Retinopathy of Prematurity
ROP occurs when premature birth interrupts the normal development of the eye’s blood vessels. Retinal vascularization, which is the process of blood vessel growth, starts around the 16th week of gestation and usually finishes near the full-term date of 40 weeks. Infants born early, especially before 31 weeks gestation or under 3.3 pounds, have an unvascularized peripheral retina. This developing tissue is then exposed to the relatively higher oxygen levels of the external environment, which is significantly different from the low-oxygen environment of the womb.
This exposure suppresses normal vessel growth, a process called hyperoxia-vasocessation. The incompletely vascularized retina becomes metabolically demanding, leading to oxygen deprivation (hypoxia) in the peripheral tissue. In response to this lack of oxygen, the body overproduces growth factors, such as Vascular Endothelial Growth Factor (VEGF). This overproduction stimulates the growth of new, abnormal, and disorganized blood vessels, which defines the pathology of ROP.
Detailed Progression of ROP: Stages 1 through 3
ROP severity is classified into five progressive stages, with the first three stages being milder. Stage 1 is defined by a thin, flat demarcation line marking the boundary between the vascularized and unvascularized peripheral retina. Vessel growth is mildly abnormal, and the condition often resolves on its own without intervention or long-term visual consequences. Infants diagnosed with Stage 1 ROP require close monitoring to ensure the condition does not worsen.
In Stage 2, the demarcation line develops into an elevated, three-dimensional ridge of abnormal fibrovascular tissue. Although vessel growth is more pronounced, a large percentage of cases still regress spontaneously as the retina continues to develop naturally. If the condition resolves, the visual impact is minimal, but the increased severity requires closer observation by an ophthalmologist. Stage 3 involves new, fragile, and disorganized blood vessels growing out from the ridge and into the vitreous, the gel-like substance filling the eye.
This growth of vessels into the vitreous is called extraretinal neovascularization and signals a potential vision-threatening disease. Stage 3 is often associated with “Plus Disease,” which signals a rapidly worsening condition. Plus Disease is defined by the engorgement and abnormal twisting (tortuosity) of the blood vessels in the posterior pole of the retina. Stage 3 ROP, especially when combined with Plus Disease, indicates a high risk of progression to retinal detachment and requires immediate treatment to preserve vision.
Advanced ROP and Severe Vision Loss (Stages 4 and 5)
When ROP progresses beyond Stage 3, it enters advanced stages defined by structural damage and a high risk of permanent vision impairment. Stage 4 ROP occurs when the abnormal, scar-like fibrovascular tissue in the vitreous contracts and pulls the retina away from the underlying tissue. This pulling action results in a partial retinal detachment, categorized into two types.
Stage 4A involves a partial detachment that does not affect the macula, the central part of the retina responsible for sharp vision. Stage 4B describes a partial detachment that includes the macula, directly impacting functional central vision. Surgical intervention is required at this stage to halt the progression of traction and prevent further vision loss.
Stage 5 ROP is the most severe form, characterized by a complete detachment of the retina. The extensive contraction of the abnormal tissue pulls the entire light-sensitive layer away from the back of the eye. Stage 5 often results in profound and irreversible vision loss or blindness, even after complex surgical treatments. The anatomical success rate for reattaching the retina in Stage 5 is significantly lower than in earlier stages.
Monitoring, Diagnosis, and Treatment Approaches
Early detection of ROP is important for preventing permanent vision loss in at-risk infants. Screening guidelines recommend routine eye examinations for premature babies, specifically those born at 30 weeks gestational age or less, or with a birth weight of 1,500 grams or less. An ophthalmologist performs these exams, usually starting four to six weeks after birth, using a technique called indirect ophthalmoscopy to view the retina after pupil dilation.
Treatment begins when ROP is considered vision-threatening, such as high-risk Stage 3 disease with Plus Disease. Interventions aim to destroy the unvascularized peripheral retina to reduce metabolic demand and suppress growth factor overproduction. Laser photocoagulation is a common approach that uses a laser to create tiny burns on the outer edges of the retina. This stops the abnormal blood vessels from growing further and successfully treats ROP in a large majority of cases.
Another element is anti-VEGF therapy, which involves injecting a medication directly into the eye to block the activity of Vascular Endothelial Growth Factor. This approach chemically inhibits the neovascularization and is particularly effective in the most posterior forms of the disease. If ROP progresses to Stage 4 or Stage 5, treatment shifts to complex surgical procedures performed by a retinal specialist. These surgeries may include a vitrectomy, which removes the contracting scar tissue and vitreous gel, or a scleral buckle, which involves placing a band around the outside of the eye to gently push the wall inward, helping the retina reattach.