Aggressive Posterior Retinopathy of Prematurity (APROP)

Abstract

APROP is an uncommon form of ROP. Untreated, eyes with APROP rapidly progress to retinal detachment and blindness. However, early recognition and prompt treatment often allow for effective management. This chapter updates the category of APROP with a more complete discussion including a detailed description of the features, a range of photographic examples, a discussion of more types of APROP, a treatment of diagnostic challenges, and recognition of earlier APROP in order to increase the opportunities for successful treatment. We also discuss the challenges and the alternatives for its practical treatment in order to improve outcomes.

Appendix: Additional Aspects in the Development of APROP

With detection of early stages of APROP, there are new questions about it natural history. In the era between CRYO-ROP and ETROP, we routinely counted stage 3 clock hours in order to determine presence of threshold ROP. While counting clock hours we also examined eyes at very high risk twice weekly. At that time, the only treatment was laser and eyes without macular development did not undergo subsequent development when it was spared. Initially, we watched a few cases hoping that the fovea would vascularize but it did not. The fastest progression that we observed in APROP neovascular proliferation was about 1 clock hour daily and my sense was that after a 2-week delay APROP was moderate. The neovascularization thickened but remained at the same distance from the optic nerve (Fig. 6.12). Therefore, our opinion based on anecdotal experience with a small number of observed cases, is that there is no ocular advantage in delay of treatment beyond the usual 48 h. We hope for better data in the future. However, we now have a nondestructive alternative to laser treatment. We have seen macular vascularization after treatment with bevacizumab (Fig. 6.14).

Occasionally, there are reports about posterior demarcation lines (stage 1) in APROP [52]. Since we have not seen photographs or an eye with this finding in APROP, it is unclear if this demarcation line is the same or different from the line in ICROP. This finding is not part of R-ICROP as we have understood it. However, in fact if CROP stage 1 is present but stage 2 and 3 do not develop then it meets the R-ICROP “does not progress through the classic stages 1 to 3”. This difference points to another area of definitional confusion in APROP, and, therefore, will need to be studied and clarified for the next review of APROP. In any case, the ICROP definition of stage 1 requires more than a halo in order to be called a demarcation line. In ICROP the “line is a thin but definite structure that separates the avascular retina anteriorly from the vascularized retina posteriorly.”

Although I have not seen the demarcation line discussed within APROP literature, I assume that my colleagues are reporting a classic stage 1 line. Nonetheless, it is important to be sure this is not a posterior halo, since color contrast is not sufficient to diagnose the presence of a line. Since the perceive color change may reflect a very interesting visual illusion identified by Ernst Mach. This produces an illusion of a line at the border of two shades of gray or color because of the center surround lateral inhibition in the retina. Mach bands are known as a cause for mistaken diagnosis in radiology [53]. This can be true in ROP at the vascular–avascular junction. Many photographs of APROP show a halo at the posterior edge of the avascular retina. Sometimes this changes with reduction of illumination and angle. To add to the confusion of terms in the literature, occasionally the term “demarcation” was used as a noun synonymously for the term “junction” (of the vascularized and avascular retina) [25] (Figs. 6.5, 6.9). Finally, we also wonder if there is yet another halo or demarcation line that may be the result of interstitial fibrous opacification or an edge reflecting marking changes in the choroidal development. Since the posterior retina is very difficult to depress and stereoscopic viewing through small pupil may be limited, the thickness of the stage 1 demarcation line structure cannot always be determined. Finally, we have the impression that the current Japanese ROP literature equates APROP with Japanese type 2 ROP (described and established before R-ICROP) and the two terminologies have evolved in a slightly different manner with communication outcomes that are occasionally at cross purposes (Fig. 6.3).