This study used en-face OCT images to characterize photoreceptors observed at the edge of idiopathic MHs. We propose the Photoreceptor Integrity Index (PIIN), an index reflecting the residual preoperative photoreceptor cells on the hole hedge, which could be used to predict postoperative visual outcomes.

As the distance of the MH borders from the RPE increases due to alterations of the vitreoretinal interface, there may be a decrease in the oxygen supply to the photoreceptors and a reduction in the availability of nutrients.

Moreover, compared to the base of the hole, the retina at the MH's edge is likely more prone to increased wall shear stress supported by vitreous dynamics from eye movement [14].

The PIIN considers the photoreceptors at the highest edge of the hole, i.e. the highest point of ELM, where the oxygen deprivation is more severe [10], as illustrated in Figure 5. The index is obtained by dividing the photoreceptor area calculated by means of the en-face scan by the luminal area of the hole, providing a standardized measure applicable for different MH sizes. To the best of our knowledge, this is the first index described in the literature that considers a cellular component to predict changes in postoperative BCVA. Previous works explored the possibility of considering macular deformation parameters to predict postoperative functional outcomes. The macular hole index proposed by Kusuhara et al. [8] consists of the ratio between hole height and basal diameter. Also, Ruiz-Moreno et al. [2] proposed additional indexes, such as tractional hole index and diameter hole index obtained from B-scan OCT, relying on macular deformation and accounting for tangential and anteroposterior forces in macular hole development. All these indexes were based on MH structural macroscopical characteristics, without considering a cellular component. In addition, OCT B-scan indexes based on linear metrics can estimate tangential and tractional components involved in MH formation but do not consider quantitative photoreceptor disruption and loss. From a pure mathematical standpoint, an index oscillates between 0 and 1 values where the higher the index, the better. Our index is different from the well-known previous indexes since it introduces normalized measures.

Cartoonized representation of the macular hole from a bird-eye view and comparison with en-face OCT scan show densely packed photoreceptors at the border of the hole, with disrupted ones that fall off the border and lie over the retinal pigmented epithelium [RPE] as remnants. Considering the oxygen’s role in photoreceptors nutrition through choroid, at the maximum height of neurosensory detachment and by focusing at the end of the external limiting membrane, the hypoxic phenomenon may be exacerbated due to the distance from the first oxygen and nutrients source

Recently, Spaide proposed that MH healing reflects the foveation process, with an outward migration of the inner retinal layer and inward migration of the photoreceptor, with associated improvement in visual acuity over time [15]. This potential could be higher if the residual photoreceptors and retinal layers are more preserved, leading to optimal visual acuity. Beyond foveation theory in restoring visual function, the contracting scar tissue from macular hole closure allows residual packaging of photoreceptors to self-organize to compensate for the lack of effective replication of the macula's highly specialized postmitotic photoreceptor cells. Our study confirms this potential, as the PIIN significantly correlates with postoperative EZd, where the higher the PIIN, the smaller the EZ residual defect will be. A higher PIIN may suggest a higher probability to have a better visual outcome due to higher availability of photoreceptors in external bands reconstruction. It is well known that post-operative EZ correlates with final BCVA. In our study PIIN correlates with both, so the higher the PIIN the higher BCVA recovery from baseline.

The novel index may impact surgical prognosis, starting from the idea that our work demonstrates and quantifies photoreceptor disruption at the borders of FTMHs.

Our work may have some implications in clinical practice. Currently, no parameters quantify the number of photoreceptors lost in the macular hole. In addition, this novel finding may suggest a proper timing for surgery, but probably after a large prospective study that could validate our index.

The novel index might help to understand when the damage to photoreceptors becomes irreversible, confirming Govetto's findings [9].

The present study has several limitations. First, the absence of small MHs makes the index questionable in these cases. Second, data regarding the duration of symptoms could pose challenges when considering the number of cells at the border, as many patients cannot distinguish the exact time of vision drop. Third, the sample size was relatively small, necessitating further validation of the index in a larger population. Metamorphopsia improvements were qualitatively evaluated with the Amsler test, lacking a quantitative test such as M-Chart. However, because the study aimed to demonstrate a photoreceptor loss, this data was considered additional support for a good visual prognosis.

The seven cases that failed to close were excluded from the final analysis because the study's focus was on understanding how photoreceptor integrity, as assessed by the PIIN, relates to successful postoperative outcomes. The PIIN is particularly relevant in cases where the hole has closed, as it is designed to evaluate the contribution of surviving photoreceptors at the hole edge to visual recovery. Further studies with larger samples are needed to understand the PIIN’s role in evaluating surgical failure and its effectiveness across different MH dimensions. Moreover, although any potential interactions between phacoemulsification and functional outcomes in patients with were previously excluded [16], further studies should evaluate possible associations with quantitative measures. In conclusion, the preoperative PIIN appears to be a reliable index representing the preoperative macular photoreceptor at the hole hedge, with a potential for visual outcomes in eyes with full-thickness idiopathic macular holes. Further studies comparing different indexes are warranted to validate their strength.