RETINAL DISPLACEMENT AFTER IDIOPATHIC MACULAR HOLE SURGERY
Study Participants We retrospectively analyzed the records and OCT images of all patients operated with PPV and an inverted ILM flap for IMH by a single surgeon with postoperative follow-up longer than 6 months. All patients received surgery at the IRCCS Bietti Foundation between October 2022 and June 2023. Exclusion criteria were as follows: (1) concomitant history of ocular and specifically macular disorders including age-related macular degeneration, retinal vascular occlusions, retinal detachment, trauma, ametropias exceeding sf +1 and sf −3 diopters in spherical equivalent refraction, and uveitis; (2) history of systemic diseases, including hypertension and diabetes; (3) poor imaging quality due to media opacity; (4) incomplete medical records; and (5) diagnosis of macular hole (MH) for more than 6 months. All patients had at least three complete ophthalmic assessments after surgery, with manifest and corrected refraction, Best Corrected Visual Acuity (BCVA) using Early Treatment Diabetic Retinopathy Study acuity charts converted to the logarithm of Minimum Angle of Resolution units for statistical purposes. The degree of horizontal and vertical metamorphopsia was assessed through M-CHARTS (Inami, Co, Tokyo, Japan). All included patients had the above information available just before the intervention (T 0 ) and 1, 3, 6, months (±7 days) after surgery (hereafter indicated by T 1 , T 3 , and T 6 , respectively). Included patients had a full thickness MH, according to the international committed classification. All patients provided written informed consent; the study adhered to the tenets of the Declaration of Helsinki and received approval of the local Ethics Committee (ERMLAB01 N° 77/18/FB). Surgical Procedure All patients underwent a standard 25-gauge three-port PPV with combined uneventful phacoemulsification and intraocular lens placement in the capsular bag, if phakic (using BVI R-Evolution CR800; BVI Medical Waltham, MA). All patients underwent 360° ILM peeling and ILM inverted flap after a single Brilliant Blue G staining applied before attempting ILM peeling manoeuvres (Monoblue, BVI Medical Waltham, MA), aiming at creating a round 360° “classic” ILM flap spanning the vascular arcades. All patients have been left with air in the vitreous chamber at the end of the procedure, making sure that the ILM flap fell on the MH at the end of the fluid–air exchange. Optical Coherence Tomography Image Acquisition Spectral domain OCT (Optovue Solix; Optovue Inc - Fremont CA) images were acquired using a horizontal SD-OCT cross-sectional scanning protocol. Optical coherence tomography angiography images were also acquired at each visit and automatic segmentation for the choroidal, deep retinal, and superficial retinal plexi used. En-face OCT scans at the ILM level were also used to trace the ILM peeling border. Only patients whose scans were performed enabling the follow-up mode were included in the study to ensure repeatability. Coronal Displacement Measures Coronal displacement was measured by comparing the displacement occurring between two successive OCTA images, as previously described. This study compared the first month after surgery (T 0 –T 1 ), the following three months (T 1 –T 3 ) (post-operative) and the entire course of the follow-up (T 0 –T 6 ). Coronal displacement measures used OCTA images, 6.4 mm × 6.4 mm in size, obtained during each visit under follow-up mode. As described in detail elsewhere, the local anatomical structures visible on the digital images were compared to measure their displacements between the first and the second image using the Farneback motion estimation method. The algorithm approximates the images by means of polynomial functions and iteratively searches for the best displacement by minimizing the sum of squared differences between the predicted and actual local image intensities. In the first step, a rigid roto-translation minimizing the sum of the squared differences of the displacements yielded by the Farneback algorithm is subtracted to the second image at the aim of eliminating the unperfect alignment between the successive scans. In the successive step, the same algorithm was applied to the resulting images thus estimating the retinal deformation. As a result of the procedure, the two components ( Dx , horizontal, and Dy , vertical) of the displacement in the reference frame of the images were obtained in microns (as given by the OCT image scale) and mean values were computed using the magnitude of the local displacement vectors D = D x 2 + D y 2 included in the selected region of interest. Main Outcome Measures Main study outcome measures included BCVA, M-Chart grading, central minimum foveal thickness, and mean retinal displacement of OCTA images. Statistical Analysis Analysis of variance with t -test and t -test for repeated measures applied to numerical variables were used to assess changes at different time points. Bivariate Pearson r correlation coefficient was applied for continuous variables, while Spearman rho and Kendall Tau were used for the assessment of ordinal variables. The Shapiro-Wilk test was used to assess normality. In all cases, P values <0.05 were considered statistically significant.   We retrospectively analyzed the records and OCT images of all patients operated with PPV and an inverted ILM flap for IMH by a single surgeon with postoperative follow-up longer than 6 months. All patients received surgery at the IRCCS Bietti Foundation between October 2022 and June 2023. Exclusion criteria were as follows: (1) concomitant history of ocular and specifically macular disorders including age-related macular degeneration, retinal vascular occlusions, retinal detachment, trauma, ametropias exceeding sf +1 and sf −3 diopters in spherical equivalent refraction, and uveitis; (2) history of systemic diseases, including hypertension and diabetes; (3) poor imaging quality due to media opacity; (4) incomplete medical records; and (5) diagnosis of macular hole (MH) for more than 6 months. All patients had at least three complete ophthalmic assessments after surgery, with manifest and corrected refraction, Best Corrected Visual Acuity (BCVA) using Early Treatment Diabetic Retinopathy Study acuity charts converted to the logarithm of Minimum Angle of Resolution units for statistical purposes. The degree of horizontal and vertical metamorphopsia was assessed through M-CHARTS (Inami, Co, Tokyo, Japan). All included patients had the above information available just before the intervention (T 0 ) and 1, 3, 6, months (±7 days) after surgery (hereafter indicated by T 1 , T 3 , and T 6 , respectively). Included patients had a full thickness MH, according to the international committed classification. All patients provided written informed consent; the study adhered to the tenets of the Declaration of Helsinki and received approval of the local Ethics Committee (ERMLAB01 N° 77/18/FB).   All patients underwent a standard 25-gauge three-port PPV with combined uneventful phacoemulsification and intraocular lens placement in the capsular bag, if phakic (using BVI R-Evolution CR800; BVI Medical Waltham, MA). All patients underwent 360° ILM peeling and ILM inverted flap after a single Brilliant Blue G staining applied before attempting ILM peeling manoeuvres (Monoblue, BVI Medical Waltham, MA), aiming at creating a round 360° “classic” ILM flap spanning the vascular arcades. All patients have been left with air in the vitreous chamber at the end of the procedure, making sure that the ILM flap fell on the MH at the end of the fluid–air exchange.   Spectral domain OCT (Optovue Solix; Optovue Inc - Fremont CA) images were acquired using a horizontal SD-OCT cross-sectional scanning protocol. Optical coherence tomography angiography images were also acquired at each visit and automatic segmentation for the choroidal, deep retinal, and superficial retinal plexi used. En-face OCT scans at the ILM level were also used to trace the ILM peeling border. Only patients whose scans were performed enabling the follow-up mode were included in the study to ensure repeatability.   Coronal displacement was measured by comparing the displacement occurring between two successive OCTA images, as previously described. This study compared the first month after surgery (T 0 –T 1 ), the following three months (T 1 –T 3 ) (post-operative) and the entire course of the follow-up (T 0 –T 6 ). Coronal displacement measures used OCTA images, 6.4 mm × 6.4 mm in size, obtained during each visit under follow-up mode. As described in detail elsewhere, the local anatomical structures visible on the digital images were compared to measure their displacements between the first and the second image using the Farneback motion estimation method. The algorithm approximates the images by means of polynomial functions and iteratively searches for the best displacement by minimizing the sum of squared differences between the predicted and actual local image intensities. In the first step, a rigid roto-translation minimizing the sum of the squared differences of the displacements yielded by the Farneback algorithm is subtracted to the second image at the aim of eliminating the unperfect alignment between the successive scans. In the successive step, the same algorithm was applied to the resulting images thus estimating the retinal deformation. As a result of the procedure, the two components ( Dx , horizontal, and Dy , vertical) of the displacement in the reference frame of the images were obtained in microns (as given by the OCT image scale) and mean values were computed using the magnitude of the local displacement vectors D = D x 2 + D y 2 included in the selected region of interest.   Main study outcome measures included BCVA, M-Chart grading, central minimum foveal thickness, and mean retinal displacement of OCTA images.   Analysis of variance with t -test and t -test for repeated measures applied to numerical variables were used to assess changes at different time points. Bivariate Pearson r correlation coefficient was applied for continuous variables, while Spearman rho and Kendall Tau were used for the assessment of ordinal variables. The Shapiro-Wilk test was used to assess normality. In all cases, P values <0.05 were considered statistically significant.   Demographics, Visual Acuity, and Metamorphopsia Overall, 33 patients (11 men and 22 women) satisfied the inclusion criteria; mean age was 68.9 ± 10.2 years, with no significant difference among sexes: 68 ± 11 years for women and 69.4 ± 8.5 for men. Seven patients were pseudophakic at T 0 , the remaining were made pseudophakic at the time of surgery and underwent a combined PPV and uneventful phacoemulsification with intraocular lens implantation within the capsular bag. Macular hole diameter on presentation was less than 250 μ m in 6/33 eyes (18.1%), between 250 and 400 μ m in 8/33 (24.2%) eyes, and greater than 400 μ m in 19/33 (57.5%). The MH closed in 31 cases (93.9%) and BCVA significantly improved from T 0 to T 1 (0.50 ± 0.62 logarithm of Minimum Angle of Resolution [20/62 Snellen] to 0.23 ± 0.63 logarithm of Minimum Angle of Resolution [20/47 Snellen]; P = 0.0064)) and showed a further trend toward improvement, although not significant, up to 6 months post-op. The 2 MHs that did not close belonged (one each) to the intermediate and bigger diameter class and the closure rate among diameter classes did not vary significantly. Both vertical and horizontal metamorphopsia decreased significantly between T 0 and T 6 ( P = 0.0028) from 0.98 ± 0.68 to 0.51 ± 0.59° and 0.84 ± 0.63 to 0.29 ± 0.45° ( P < 0.001), respectively. There was no correlation between BCVA gain and metamorphopsia reduction. Coronal (En-Face) Retinal Displacement The average retinal displacement across the coronal plane throughout the 6 months follow-up is reported in Table for each considered layer. The choriocapillaris layer showed an average 60.9 ± 20.2 µ m displacement, mostly located within the central 0.5 mm and displaced significantly less than the deep (79.4 ± 45.7 µ m; P < 0.05) and superficial layers (81.2 ± 44.1 µ m; P < 0.05; see also Table and Figure ). There was no significant displacement difference between the deep and superficial layers for any considered region. The 2 MHs that did not close showed an average displacement of 40.82 ± 23.74 µ m over the entire 6.4 × 6.4 mm analyzed superficial plexus, 49.50 ± 30.99 µ m within the deep plexus, and 37.81 ± 29.03 µ m of the choriocapillaris (the difference compared with successfully closed MHs was not significant). Retinal displacement occurred mostly within the central circular region 0.5 mm in radius and was significantly greater than within the central region of 3-mm radius (see Table ; P < 0.05). The displacement behavior over time is shown in Figure : all layers and considered regions showed a significantly higher displacement within the first month ( P < 0.01 for all) compared with the following period. The supero-temporal deep and superficial retinal plexi quadrant displaced more than any other quadrant (Figure ; P < 0.05) within the central 1.5-mm radius , while the temporal choriocapillaris hemifield displaced more than all other choriocapillaris fields but less than the retinal plexi (Figure ; P < 0.05 in all cases). There was a significant correlation between MH size and retinal displacement across the different layers that have been reported in Table . There was no correlation between displacement at any level and metamorphopsia changes.   Overall, 33 patients (11 men and 22 women) satisfied the inclusion criteria; mean age was 68.9 ± 10.2 years, with no significant difference among sexes: 68 ± 11 years for women and 69.4 ± 8.5 for men. Seven patients were pseudophakic at T 0 , the remaining were made pseudophakic at the time of surgery and underwent a combined PPV and uneventful phacoemulsification with intraocular lens implantation within the capsular bag. Macular hole diameter on presentation was less than 250 μ m in 6/33 eyes (18.1%), between 250 and 400 μ m in 8/33 (24.2%) eyes, and greater than 400 μ m in 19/33 (57.5%). The MH closed in 31 cases (93.9%) and BCVA significantly improved from T 0 to T 1 (0.50 ± 0.62 logarithm of Minimum Angle of Resolution [20/62 Snellen] to 0.23 ± 0.63 logarithm of Minimum Angle of Resolution [20/47 Snellen]; P = 0.0064)) and showed a further trend toward improvement, although not significant, up to 6 months post-op. The 2 MHs that did not close belonged (one each) to the intermediate and bigger diameter class and the closure rate among diameter classes did not vary significantly. Both vertical and horizontal metamorphopsia decreased significantly between T 0 and T 6 ( P = 0.0028) from 0.98 ± 0.68 to 0.51 ± 0.59° and 0.84 ± 0.63 to 0.29 ± 0.45° ( P < 0.001), respectively. There was no correlation between BCVA gain and metamorphopsia reduction.   The average retinal displacement across the coronal plane throughout the 6 months follow-up is reported in Table for each considered layer. The choriocapillaris layer showed an average 60.9 ± 20.2 µ m displacement, mostly located within the central 0.5 mm and displaced significantly less than the deep (79.4 ± 45.7 µ m; P < 0.05) and superficial layers (81.2 ± 44.1 µ m; P < 0.05; see also Table and Figure ). There was no significant displacement difference between the deep and superficial layers for any considered region. The 2 MHs that did not close showed an average displacement of 40.82 ± 23.74 µ m over the entire 6.4 × 6.4 mm analyzed superficial plexus, 49.50 ± 30.99 µ m within the deep plexus, and 37.81 ± 29.03 µ m of the choriocapillaris (the difference compared with successfully closed MHs was not significant). Retinal displacement occurred mostly within the central circular region 0.5 mm in radius and was significantly greater than within the central region of 3-mm radius (see Table ; P < 0.05). The displacement behavior over time is shown in Figure : all layers and considered regions showed a significantly higher displacement within the first month ( P < 0.01 for all) compared with the following period. The supero-temporal deep and superficial retinal plexi quadrant displaced more than any other quadrant (Figure ; P < 0.05) within the central 1.5-mm radius , while the temporal choriocapillaris hemifield displaced more than all other choriocapillaris fields but less than the retinal plexi (Figure ; P < 0.05 in all cases). There was a significant correlation between MH size and retinal displacement across the different layers that have been reported in Table . There was no correlation between displacement at any level and metamorphopsia changes.   Macular hole closure is a well-documented spontaneous or iatrogenic event, characterized by the re-arrangement of retinal tissue across all retinal layers and associated with changes in the choriocapillaris. We used a method previously applied to retinal images 11 12 , capable of tracing retinal displacement, to analyze MHs pre- and postoperative OCTA images and monitor the displacement of the superficial and deep retinal vascular plexi and the choriocapillaris. The superficial plexus , in fact, is positioned within the Ganglion Cell Layer and the deep capillary plexus below the Inner Nuclear Layer, while the choriocapillaris does not belong to the retina and is located underneath the retinal pigment epithelium. The success rate, BCVA, and metamorphopsia improvement observed in this study was comparable to the existing literature, suggesting that this series does not differ from previously reported ones. Our data support the hypothesis that the entire 6.4 × 6.4-mm central retinal field and choriocapillaris contributed (or reacted) to MH closure, with an average displacement of about 75 µ m (see Table and Figure ). Both retinal plexi (superficial and deep) displaced significantly more than the choriocapillaris and most displacement occurred within the first month (Figure ) at all layers and tested eccentricity. Interestingly, the choriocapillaris displaced significantly within the central 0.5-mm radius area, a process suggestive of vascular remodeling secondary to the metabolic changes imposed by the overlying retinal shift ; despite from the “tectonic” point of view, there is no void to fill at this level. On the other hand, an increase of choriocapillaris vascular density after MH repair has been previously reported. Topographically, the supero-temporal and supero-nasal quadrants displaced more than the others, across the central deep and superficial retinal plexi , while the choriocapillaris behaved somehow differently, with the supero-temporal and infero-temporal central quadrants (0.5-mm radius; Figure ) exhibiting the maximum displacement. Consequently, the superior deep and superficial retinal hemifield shifted more intensely, while the temporal choriocapillaris hemifield displaced the most (Figure ). Takeyama et al also noticed a correlation between retinal displacement and inner nuclear layer thickness of the superior and temporal quadrants. Previous studies already focused on retinal tectonics after successful MH surgery: Ishida et al traced the linear distance between the optic nerve and vascular landmarks and noticed that the temporal retina displaced the most. In agreement with the present findings, they found a correlation between MH diameter and amount of displacement (Table ) and that it mostly occurred within the first 2 weeks. After surgery, the retina tends to displace in proportion to the MH size until the entire MH width is spanned. The exact signaling mechanism of this intriguing process remains matter of speculation. In addition, we noted that the two MHs that did not close showed less displacement compared with those that successfully closed, despite having similar MH size and areas of ILM peeling (Figure ). Although the difference was not statistically significant, that is likely due more to the small sample size rather than the extent of displacement. The reason why some MHs exhibit less displacement than others, following otherwise identical surgical procedures, remains uncertain. The pattern of maximum retinal displacement always occurred within the ILM peeling area (Figure , A–C) but rarely reached its boundaries, instead it seemed conditioned by the superficial plexus vessels path. It should be noted that the retina is a highly anisotropic and inhomogeneous structure, whose mechanical properties, are determined by its stiffer structures such as the retinal vessels, due to their muscular wall. It is therefore conceivable that peeling manoeuvres favor and/or initiate retinal displacement by disrupting the integrity of the ILM, which is a physical constraint, but then the larger vessels “guide” displacement extension and orientation. The displacement shown in Figure , A–C, skims the vascular arcade and does not go any further, despite the ILM peeling extends more peripherally, as if indeed the vascular backbone influenced its deployment and prevented further extension. It has been reported that ILM peeling greater dimension facilitates MH closure and seems also correlated with better visual outcome. It should be noted that the ILM is among the stiffest retinal layers, , a basement membrane without contractile capability per se , whose removal alters the balance of forces between other structures that do retain contractile properties, such as the vessels and the retinal nerve fiber layer, which is rich in microtubules and actin filaments. The retinal nerve fiber layer, and specifically the interpapillo-macular bundle, also seemed to shape the retinal displacement with limited motion on the nasal side of the MH, invariably oriented along the horizontal meridian, while on the MH temporal side, displacement occurred in a whirl fashion resembling the curving retinal nerve fiber layer path (Figure , A–C). Orientation of ILM peeling during surgery has previously reported to be nonrelevant to retinal displacement: Liu et al found no difference when performed clockwise or counterclockwise in agreement with present series where a single surgeon performed clockwise ILM peeling, with no significant difference in retinal shifting of the single quadrants when right and left eyes were analyzed separately. This finding suggests that the retinal anatomy more than surgeon's peeling direction influences displacement. Vascular displacement across different layers displayed varying patterns. In most cases (see Figure ), the deep vascular plexus mirrored the behavior of the overlying superficial plexus , with changes in the choriocapillaris confined to the fovea. However, in others (see Figure ), the displacement of the deep retina and choriocapillaris was widespread and multifocal. Previous studies noted an increase of choriocapillaris vascular density after MH repair and attributed it to the increased flow and osmolarity from the restored retina. While this explanation accounts for the vascular remodeling observed in the choriocapillaris beneath the MH (Figure ), it does not fully explain the extensive vascular changes observed in the deep plexus and the choriocapillaris present in many patients, as illustrated Figure . The present work suffers the limitations of a relatively small, single surgeon, retrospective series. Furthermore, the image analysis method has only been recently applied to retinal images, and the displacement recognition relies only on the features apparent on the images. On the other hand, the consistency of imaging and clinical data across the follow-up and the analytical measure of retinal shifting using a displacement algorithm through hundreds of points, compared with previous papers using a few anatomical landmarks, represent points of strength. In addition, it should be noted that OCTA images represent the projection of a sphere segment onto a plane, thus “flattening” retinal vessels in a “cartography”. This way, the vectorial component lying on the sagittal plane is missed together with the displacement along such plane; we excluded highly myopic eyes to reduce this effect that cannot be eliminated and, in any case, the displacement we measured, lying on the coronal plane, represents a slight underestimation of the 3D displacement. In summary, our study demonstrated that MH closure is linked to significant retinal displacement of all inquired retinal layers and to remodeling of the choriocapillaris. The surgical peeling removes the ILM constraint, disrupting the balance of forces between the contractile structures surrounding the macula, including the larger superficial retinal vessels and the densely packed interpapillo-macular bundle of the retinal nerve fiber layer. Notably, the displacement primarily affected the temporal retina and occurred mainly in the early postoperative phase. Further research is needed to clarify the molecular mechanism that triggers and regulate displacement in response to surgery.   