Zone II is an annulus with the inner border defined by zone I and the outer border defined by the radius defined as the distance from the optic nerve to the nasal ora serrata. Zone III is the residual temporal crescent of the retina. The circumferential extent of the disease is described in segments as if the top of the eye were 12 on the face of an analog clock, e.g. stage 1 from 4:00 to 7:00. (The extent is a bit less important since the treatment indications from the Early Treatment for ROP. )The Stages describe the ophthalmoscopic findings at the junction between the vascularized and avascular retina. Stage 1 is a faint demarcation line. Stage 2 is an elevated ridge. Stage 3 is extraretinal fibrovascular tissue. Stage 4 is sub-total retinal detachment. Stage 5 is total retinal detachment. Plus disease
Plus disease can be present as a major complicating factor at any stage. It is characterised by:

Significant level of vascular dilation and tortuosity observed at the posterior retinal arterioles. This reflects the increase of blood flow through the retina. Vitreous haze and anterior chamber haze
Iris vascular engorgement
Persistent tunica vasculosa lentis or immature blood vessels growing over the lens which also restrict the dilatation of the pupils. Differential diagnosis
The most difficult aspect of the differential diagnosis may arise from the similarity of two other diseases:

Familial exudative vitreoretinopathy which is a genetic disorder that also disrupts the retinal vascularization in full-term infants.
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.