Reply to comment on: “Partial recovery of amblyopia following contralateral ischemic optic neuropathy”

We thank Dr. Örnek for his interest in our work on this important topic.

We agree that elimination of monocular inputs imparts a strong drive for neuroplastic expansion of cortical responsiveness to the unaffected eye that defies the traditional concept of the critical period. Since publishing this article, we have extended our examination of this phenomenon to all published cases to identify clinical factors that facilitate recovery from amblyopia¹. As Dr. Örnek points out, there are several potential mechanisms at play as we’ve outlined in a recent review². We are committed to elucidating these mechanisms which hold translational potential for visual recovery beyond amblyopia.

To address the question of visual acuity recovery in ischemic optic neuropathy (ION)-affected eyes and the potential influence on amblyopic eye visual acuity, we provide detailed information about the fellow eye best-corrected visual acuity (FEVA) across the post-ION follow-up period (Figure 1). The degree of FEVA vision loss, worsening over time, and recovery do not systematically influence the degree of amblyopic recovery. Among those showing improvement, there were 3/9 cases (5, 7, 12) that showed 1–2 lines of AEVA regression between the best AEVA and the final follow up visit (Figure 1; red), though with the caveats that case 5 had macular pathology in the amblyopic eye that may have progressed and the final examination was without glasses for case 12. Nevertheless, these cases do not consistently demonstrate prominent ION/FEVA recovery. Overall, the relatively small sample size precludes us from drawing definitive conclusions regarding this question.

Figure 1. Fellow eye best-corrected visual acuity (FEVA).

FEVA plotted for each relevant post-ION visit: Initial, Nadir (worst FEVA documented), Best amblyopic eye best-corrected visual acuity (AEVA), and the Final follow up visit. Cases are represented by symbols according to the category of AEVA recovery as indicated by legend (lines of AEVA improvement). Cases in red showed 1–2 lines of AEVA regression between the best-recorded timepoint and the final follow up visit.

In our meta-analysis of 101 reported cases with AEVA improvement after FE vision loss (which included this ION dataset), multiple regression analysis revealed that FEVA nadir was independently associated with greater grains AEVA¹. We did not examine durability of AEVA as follow-up duration is highly variable across the few reports that include this information. Data from animal models demonstrate that the functional and structural consequences of amblyopia can be reversed at older ages with temporary FE inactivation with durability even after FE responses have returned to baseline^3–5. Those longitudinal data do not demonstrate regression of AE gains as FE function recovers, and thus that AE gains are durable. Restoration of cortical activity driven through the AE (as enabled through metaplastic change) would confer a relatively high threshold for synaptic plasticity and maintain ocular dominance at that new baseline². Therefore, we would expect that the clinical gains in AEVA observed after temporary or partially reversible FE pathology would also be durable. Future clinical studies focused on completely reversible FE pathologies may be informative in this regard.