ROP Classification Update: Pre-plus and Aggressive Posterior ROP
The incidence of ROP has remained unchanged in recent decades as neonatal survival has improved. Ophthalmologists are encountering profoundly premature infants and posterior ROP with greater frequency. In response to these issues, the ICROP classification was updated recently to refine the concept of pre-plus disease and to expand the understanding of aggressive posterior ROP (APROP).
Pre-plus disease: While useful as an indicator of disease activity, plus disease does not appear as an all-at-once phenomenon. Pre-plus disease is defined as increased dilation and/or tortuosity of retinal arteries and/or veins in at least two quadrants, of insufficient severity for the diagnosis of plus disease (Figure 5). These dilated and/or tortuous vessels are often present peripherally, initially near the ridge and progress posteriorly with increasing VEGF activity. Therefore, it is important to evaluate the vasculature near the ridge. The importance of recognizing pre-plus disease is that it may be a harbinger of more active disease. Simply evaluating the vasculature near the optic disc may miss early pre-plus clinical findings. Over time, the vessel abnormalities of pre-plus may progress to frank plus disease or revert to normal. Surveillance should be considered at a tempo of approximately one-half week in the presence of pre-plus disease.
Aggressive Posterior ROP: This is a once uncommon severe form of ROP, which presents earlier and progresses rapidly to stage 4 and 5 if left untreated. In APROP, the ROP is confined to zone 1 and posterior zone 2. Aggressive posterior ROP may differ from zone 2 ROP in appearance, progression, pace, treatment, and treatment response.
Appearance: APROP is characterized by neovascular fronds that lay flat on the retinal surface (Figs. 6A-6C). No ridge tissue is seen in these eyes, and yet the AV shunting, which occurs within the ridge tissue in more typical ROP, is seen throughout the posterior pole. Vessels are dilated and tortuous in a syncytial pattern.
Progression: APROP may progress directly from stage 1 to stage 3, without interval findings typical of stage 2 ROP. This is one of the most critical features of APROP. The findings of early posterior stage 3 ROP may be subtle. An inexperienced examiner may be lulled by the absence of a conventional ridge and extraretinal fibrovascular proliferation seen in zone 2 ROP only to find on a subsequent exam that the eye has moved rapidly to posterior stage 3 or 4 ROP.
Pace: APROP may progress considerably more rapidly than ROP located in zone 2, sometimes in a matter of days.
Treatment: The avascular retina beneath the flat posterior stage 3 ROP is difficult to treat at the initial laser session. Once flat stage 3 ROP regresses, the untreated avascular retina remains as a source of VEGF and can slowly continue to drive the ROP process. A second laser session may be necessary a week later, with application to the avascular retina now exposed by regression of the flat stage 3 ROP (Figure 7).
Treatment Response: Conventional zone 2 ROP typically regresses after a single treatment session. APROP may also regress post-laser but can reactivate. If reactivation occurs, it is characterized by the return of plus disease, progressive posterior hyaloidal contraction, and progression to traction posterior retinal detachment (Figure 8). Post-treatment vigilance is necessary so vitrectomy can be performed to interrupt the progression to advanced ROP.
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