What Does Plus Disease Mean in Retinopathy of Prematurity?

Plus disease is a term eye doctors use when the blood vessels in the light-sensing layer of the eye (the retina) have become abnormally dilated (thick and swollen) and tortuous (twisted) ^{[1] [2]}.

When a doctor diagnoses plus disease, it means the Retinopathy of Prematurity (ROP) is severe and active, carrying a high risk of progressing to vision-threatening disease ^{[3] [4]}.

Hearing this terminology can be frightening, but it is important to know that plus disease does not mean your baby has already lost vision or has a retinal detachment. However, it is a major clinical warning sign that usually requires prompt assessment and management by an ROP specialist ^[5].

What Exactly Is Happening in the Eye?

In normal eye development, blood vessels grow smoothly from the optic nerve to the edges of the retina. In ROP, this growth is interrupted. When the condition becomes severe, the abnormal blood vessels undergo two distinct changes:

• Venous dilation: The veins (vessels carrying blood back to the heart) become abnormally thick and swollen ^[2].
• Arteriolar tortuosity: The arteries (vessels carrying oxygen-rich blood) become highly twisted, wavy, and crooked ^[1].

Doctors compare what they see in your baby’s eye against standard reference photographs to diagnose plus disease ^[1].

Because these vessel changes happen on a continuous spectrum, doctors sometimes use the term pre-plus disease ^[6]. Pre-plus means the blood vessels are beginning to look abnormal, but have not reached the severity of full plus disease ^[7]. Pre-plus is an early warning sign that the eyes require closer follow-up to monitor for progression ^[8].

How “Plus” Fits Into the Diagnosis

To fully understand how severe the ROP is, doctors assess three distinct factors for each eye:

1. Zone: The location of the abnormal growth in the eye.
2. Stage: How severe the abnormal tissue looks.
3. Plus Status: Whether the eye has plus disease, pre-plus, or neither ^[6].

Plus disease is a key piece of the puzzle, but it is not the only factor that determines whether your baby needs treatment ^[9].

The Trigger for Prompt Treatment

Many mild cases of ROP heal completely on their own. However, the presence of plus disease significantly lowers the likelihood of spontaneous healing—one study found it resolved without treatment in only about 13% of cases ^[4]. If severe ROP is left untreated, the abnormal tissue can eventually contract and pull the retina away from the back of the eye (tractional retinal detachment), causing permanent vision loss ^[9].

Plus disease is a major factor in identifying Type 1 ROP, which is the specific threshold where medical guidelines recommend prompt treatment ^{[10] [11]}. A baby has Type 1 ROP if they meet any of these criteria:

• ROP in Zone I at any stage, with plus disease
• ROP in Zone I at Stage 3, without plus disease
• ROP in Zone II at Stage 2 or 3, with plus disease

Notice that plus disease does not automatically make every case Type 1 ROP, and some cases qualify for treatment even without plus disease ^[10]. However, when plus is present in the critical zones, it typically acts as the tipping point for intervention ^[11].

Treatment Options and What to Expect

If your baby meets the criteria for treatment, the specialist will recommend a prompt intervention. While treatment significantly reduces the risk of severe structural damage and vision loss, it does not guarantee perfect vision ^[5]. The two main options are:

• Laser therapy: Uses targeted light to stop the abnormal vessel growth.
• Anti-VEGF injections: Medication injected into the eye to block the signals causing the abnormal growth (this may be an off-label use for premature infants, depending on the medication and jurisdiction) ^[12].

The specialist will recommend the best option based on the exact zone and stage of the disease, as well as your baby’s overall health ^[12].

Crucial Note on Follow-Up: Treatment does not end the ROP journey. Particularly after anti-VEGF injections, ROP can sometimes reactivate weeks or even months later ^[13]. Strict attendance at all follow-up appointments is absolutely essential to protect your baby’s vision, even if their eyes look perfectly fine from the outside ^[13]. Over the long term, children with treated ROP will also need ongoing ophthalmic monitoring for issues like the need for glasses, amblyopia (lazy eye), and strabismus (crossed eyes).