Development and preliminary evaluation of a novel preoperative index for quantitative analysis of photoreceptor loss in full-thickness macular holes

Abstract

Purpose: To identify novel quantitative parameters for evaluating photoreceptor loss in full-thickness macular holes (FTMH), exploring their potential clinical impact on postoperative functional and anatomical recovery.

Methods: This pilot study enrolled 38 eyes from 38 patients diagnosed with FTMH. Preoperatively, eyes underwent analysis and were subsequently followed for six months post-surgery. Best-corrected visual acuity (BCVA) was recorded, and cross-sectional images of FTMH were obtained using B-scan optical coherence tomography (OCT) and en-face OCT. Quantitative assessment of ellipsoid zone (EZ) and external limiting membrane (ELM) integrity changes was conducted and correlated with postoperative anatomical and functional recovery. The photoreceptor Integrity Index (PIIN), calculated as the ratio of photoreceptor area to lumen hole area measured at customized segmentation, was correlated with the minimum and base diameters of the hole, positive change in BCVA, preoperative EZ defect (EZd), preoperative ELM defect (ELMd), and changes in EZ and ELM over the six-month follow-up period (∆-EZ and ∆-ELM). The main outcome measures focused on evaluating the effectiveness of PIIN in predicting postoperative anatomical and functional changes.

Results: A higher PIIN correlated with a greater BCVA change over six months (p < 0.001). Univariate regression analysis using the PIIN as a predictor for positive change in BCVA (|∆-BCVA| [logMAR]) over time yielded significant results (p < 0.001). Additionally, the PIIN significantly correlated with EZd at baseline, ELM at baseline, and ELMd change over the six-month follow-up period.

Conclusion: The PIIN shows promise as a tool for evaluating photoreceptor loss in macular holes and estimating postoperative functional and anatomical recovery.

Key messages: What is known Previous studies have extensively used optical coherence tomography (OCT) to investigate various biomarkers for assessing patients with full-thickness macular hole (FTMH), without considering detailed MH ultrastructural features Existing indexes used to predict surgical outcomes for FTMH primarily depend on geometrical parameters and do not integrate detailed ultrastructural characteristics, such as cellular components. What is new A novel concept introduces the quantitative measurement of residual photoreceptors located at the edge of FTMH. The Photoreceptor Integrity Index (PIIN) integrates different ultrastructural components of macular holes, aiming to become a valuable clinical tool to predict both anatomical and functional recovery outcomes following surgical intervention for FTMH.

Keywords: Full-thickness macular hole; Macular hole borders; PIIN; Photoreceptors.

Fig. 1

Representative optical coherence tomography [OCT] of a 65-year-old woman left eye with full thickness macular hole. [Upper left] B-scan OCT showing macular hole with irregular border before surgery (A) and after surgery at 6 months (B). En face 3 x 3 mm scan at the ELM end over the border, obtained by segmentation performed on lower right scan (D). [Upper left] Corresponding En-face OCT scan showing the slab set to visualize the photoreceptors at the hole hedge (C)

Fig. 2

Representative En-face OCT scans with the proposed algorithm performed. Scan on the right shows boundary of the hole area (A), on the center boundary of lumen of the hole (B) and on the right the difference between the two (C), representing photoreceptors remnant area

Fig. 3

Box plots for EZ defect [μm], ELM defect [μm] and BCVA [logMAR] at Baseline [T0] and Follow-up [T1]. P-values derived from the Wilcoxon rank sum test

Fig. 4

Univariate regression analysis using the ''Photoreceptor Integrity Index'' [PIIN] as a predictor for positive change of BCVA [|∆-BCVA| [logMAR]] over time [follow-up vs baseline]. The performance is expressed by adjusting R2, and the p-value for the regression coefficient is reported

Fig. 5

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