Comparison of Deep Optic Nerve Head Structures and Optic Disc Morphology in Unilateral Peripapillary Intrachoroidal Cavitation

Abstract

Purpose

To compare background characteristics, deep optic nerve head (ONH) structures, and optic disc morphology in participants with unilateral peripapillary intrachoroidal cavitation (PICC).

Design

Retrospective cross-sectional study.

Participants

One hundred six eyes of 53 participants with unilateral PICC determined on OCT.

Methods

Twelve ONH-centered OCT radial slices were used to manually measure Bruch membrane opening (BMO) area, BMO ovality, scleral flange opening (SFO) area, SFO ovality, and SFO/BMO offset magnitude which represents the degree of SFO/BMO centroid displacement and clinically corresponds to the peripapillary atrophy–gamma and delta zones. Optic disc tilt, rotation, area, and longest and shortest diameters were measured from line scanning laser ophthalmoscopy images.

Main Outcome Measures

Paired t tests and Wilcoxon signed-rank tests were used to compare background characteristics and obtained parameters between PICC eyes and their contralateral eyes. False discovery rate was controlled using the Benjamini–Hochberg method to account for multiple comparisons.

Results

Peripapillary intrachoroidal cavitation eyes showed significantly larger BMO area (P < 0.001) and its ovality (P = 0.020), larger SFO area (P = 0.003), larger SFO/BMO offset magnitude (P = 0.007), greater optic disc tilt (P < 0.001), and smaller optic disc shortest diameter (P = 0.010). There was no significant difference in axial length (AL) (P = 0.081) and optic disc rotation (P = 0.067).

Conclusions

Although AL was similar between PICC eyes and their contralateral eyes, significant intereye differences in deep ONH structures and optic disc morphology were observed. Peripapillary intrachoroidal cavitation eyes exhibited a more elliptically expanded BMO, larger SFO, greater SFO/BMO misalignment, and greater optic disc tilt, which are structural changes associated with border tissue elongation. Our findings indicate a strong association between the presence of PICC and myopia-related characteristic deep ONH remodeling, providing a foundation for understanding structural abnormalities in myopic eyes.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Peripapillary intrachoroidal cavitation (PICC) is an ophthalmic finding characterized by an intrachoroidal hyporeflective lesion observed on OCT and a yellow-orange lesion adjacent to the optic nerve head (ONH).1, 2, 3 Peripapillary intrachoroidal cavitation has been commonly associated with high myopia (HM)4, 5, 6, 7, 8 and suggested as a potential contributor to myopia-related visual field (VF) defects which can resemble glaucomatous VF abnormalities.^6,7,9, 10, 11, 12, 13, 14, 15 Given that HM is a major risk factor for open-angle glaucoma,^16,17 differentiating between glaucomatous VF defect and myopia-related glaucoma-like VF defect remains a significant clinical challenge. A deeper understanding of the structural basis and clinical implications of PICC is essential for elucidating the mechanisms underlying myopia-related functional abnormalities.

Recent studies have reported that 29.1% to 35.7% of PICC eyes were non-HM eyes with axial length (AL) <26.5 mm,^6,15,18 and PICC has also been reported in hyperopic eyes with AL <24 mm,^15,19 suggesting that PICC development is not solely dependent on AL elongation. In addition to AL, myopia-related ONH structural changes, such as peripapillary atrophy (PPA) optic disc tilt and rotation, have been associated with PICC formation.^3,5,7,20 Yet, the relationships between these myopia-related deep ONH structural changes and PICC have not been fully investigated.

Recent advancements in OCT technology have enabled detailed visualization of deep ONH structures and quantitative assessment of their myopic changes.^21,22 We hypothesized that these OCT-based structural changes are associated with PICC formation. Because PICC does not develop in all HM eyes and can occur unilaterally despite similar genetic and environmental exposures, comparing PICC eyes with their contralateral eyes in unilateral PICC participants offers an opportunity to identify the characteristic features of PICC eyes while minimizing interindividual variability. To further reduce confounding factors, we excluded eyes with pathological myopia (PM), which can induce a broad range of structural deformations that may obscure factors specifically related to PICC. In this study, we aimed to investigate OCT-based ONH structural factors associated with PICC by comparing PICC eyes and their contralateral eyes in unilateral non-PM PICC participants.

Methods

Participants

Protocols for this observational study were approved by the Research Ethics Committee of the Graduate School of Medicine and Faculty of Medicine at The University of Tokyo and adhered to the tenets of the Declaration of Helsinki. Patients gave written informed consent for participation in this study.

Participants for this study included patients with unilateral PICC who visited Yotsuya Shirato Eye Clinic (Tokyo, Japan) between July 2020 and September 2020 and the University of Tokyo Hospital (Tokyo, Japan) between January 2024 and December 2024 for regular eye examinations. All participants underwent the following ocular examinations: refraction and corneal curvature radius measurements, best-corrected visual acuity measurements with the Landolt chart (converted to the logarithm of the minimum angle of resolution values for statistical analysis), AL measurements (IOL master, Carl Zeiss Meditec), slit lamp examination, intraocular pressure (IOP) measurements with Goldmann applanation tonometry, gonioscopy, fundus examination under pupillary dilation including stereoscopic assessment of ONH using indirect ophthalmoscopy with a 90D lens, fundus photography (TRC-NW8F, Topcon), OCT imaging (Cirrus HD-6000, Carl Zeiss Meditec), and HFA (Carl Zeiss Meditec) measurements with the 24-2 Swedish Interactive Threshold Algorithm standard strategy within 3 months of the OCT scanning. All examinations were conducted by clinically qualified ophthalmologists or certified orthoptists as part of routine clinical care at each facility. Unreliable VF measurements (≥15% false negative errors or ≥15% false positive errors) were excluded from the analysis of VF parameters. Fixation loss was not used as a criterion for excluding VF tests, as previous evidence suggests it has little impact on VF reliability or mean deviation.²³

The presence of PICC was confirmed as hyporeflective areas and posterior bowing of the peripapillary sclera on OCT images (200 × 200 ONH cube scans and 12 ONH-centered 6.0 mm radial scans after pupillary dilation) using the Cirrus HD-6000 OCT (Carl Zeiss Meditec) (Fig 1).^1,3,6 Tubelike hyporeflective areas without scleral bowing corresponding to choroidal vessels on fundus photographs were considered to be large choroidal vessels and excluded from the analysis. Peripapillary intrachoroidal cavitation identification was independently conducted by 2 experienced examiners (K.A. and H.S.) with any disagreements resolved by a third adjudicator (S.A.). The PICC location was determined according to Garway-Heath sectors²⁴ as previously reported.¹⁵ The inclusion criterion for this study was confirmation of unilateral PICC on ≥2 consecutive ONH-centered OCT radial slices with a PICC depth of ≥50 μm. Peripapillary intrachoroidal cavitation depth was calculated as the distance from Bruch membrane opening (BMO) to the sclera subtracted from the circumpapillary choroidal thickness (cpChT) of the corresponding region (Fig S2, available at www.ophthalmologyscience.org). Although some previous reports defined the presence of PICC based on a BMO-sclera distance of ≥200 μm,^5,18,20 this measurement is directly influenced by cpChT. Therefore, we evaluated PICC depth with adjustment for choroidal thickness.

Figure 1.

A, D Fundus photographs of a participant with unilateral PICC. The black arrow on the line scanning laser ophthalmoscopy image in (B), (E) shows the orientation of OCT B-scan of (C), (F), respectively. Peripapillary intrachoroidal cavitation was observed only in the left eye, as a yellow-orange lesion at the edge of peripapillary atrophy (D, white arrowhead) and hyporeflective lesion with posterior scleral bowing on OCT B-scans (F, yellow arrowhead). PICC = peripapillary intrachoroidal cavitation.

Participants who have any history of intraocular surgery (except for uncomplicated cataract surgery), corneal opacity, clinically significant cataract causing noticeable degradation in image quality or segmentation errors on OCT or fundus photography, retinal disease, and nonglaucomatous optic neuropathy in either eye were excluded from this study. Eyes with PM (diffuse chorioretinal atrophy, patchy chorioretinal atrophy, macular atrophy, lacquer cracks, myopic choroidal neovascularization, Fuchs’ spot, and posterior staphyloma)²⁵ and cases with poor quality OCT scans (signal strength indices <8) with artifacts or segmentation errors were also excluded.²⁶

Deep ONH Structure Parameters

Twelve ONH-centered radial slices, spaced 15° apart, were exported from the device and imported into Fiji ImageJ 1.54f (Java 1.8.0_322 64 bit, National Institutes of Health). Bruch membrane opening and scleral flange opening (SFO) points were manually determined on both sides of the radial B-scans by 2 experienced examiners (K.A. and H.S.) (Fig 3).

Figure 3.

Identification of deep optic nerve head structures. Bruch membrane opening (orange dots) and SFO (blue dots) were determined upon 12 radial OCT B-scans (A). In slices where a scleral flange was not present, SFO was assumed to match anterior scleral canal opening. Bruch membrane opening and SFO points are overlayed upon the line scanning laser ophthalmoscopy image (B). The temporal area between BMO and SFO contains peripapillary zone without Bruch membrane and a region of exposed scleral flange (B, yellow area). Scleral flange opening/BMO offset magnitude was defined as the distance between BMO centroid and SFO centroid projected onto the BMO plane (C, red line). BMO = Bruch membrane opening; SFO = scleral flange opening.

Scleral flange opening, a recently proposed landmark representing the neural canal opening, is identified on OCT images as the transition between the anterior laminar surface and the anterior surface of scleral flange, when present.^22,27,28 In regions where an exposed scleral flange was not present, SFO was assumed to match anterior scleral canal opening in accordance with previous reports.²² The BMO and SFO coordinates were imported into R software version 4.4.1 (R Foundation for Statistical Computing), and a plane minimizing the mean squared axial error was fitted to the 24 BMO and SFO points, respectively. The coordinates were projected onto their respective planes, and a best-fit ellipse was applied to determine their centroids, areas, and longest and shortest diameters. Bruch membrane opening and SFO ovality were defined as the ratio between longest and shortest diameters of BMO and SFO ellipse, respectively. Scleral flange opening/BMO offset magnitude, representing the degree of SFO/BMO displacement, was defined as the distance between the BMO centroid and the SFO centroid projected onto the BMO plane (Fig 3).²⁹ We used SFO instead of anterior scleral canal opening to represent the neural canal opening because anterior scleral canal opening (defined as the intersection between the anterior scleral surface and border tissues [BTs]²⁷) was indeterminable in PICC regions with disrupted BTs. The temporal region between BMO and SFO contains PPA-gamma and delta. Peripapillary atrophy–gamma is defined by the absence of Bruch membrane and PPA-delta zone is characterized by an extended and thinned peripapillary scleral flange without choroidal layers.³⁰ Scleral flange opening/BMO offset magnitude enlargement corresponds to the expansion of this combined region of PPA-gamma and delta (Fig 3B).²²

Excellent intraobserver (K.A.) and interobserver (K.A. and H.S.) reproducibility of BMO and SFO related parameters were previously reported, ranging from 0.966 to 0.994.¹⁵

Optic Disc Tilt and Rotation

Clinical disc margin was determined upon line scanning laser ophthalmoscopy images obtained by 200 × 200 macular cube OCT scanning using Fiji ImageJ. A best-fit ellipse was applied to determine optic disc centroids, areas, and longest and shortest diameters. Optic disc tilt was defined as the ratio of the longest to shortest diameters of optic disc (ovality index). Optic disc rotation was defined as the angular deviation of the longest optic disc diameter from the vertical meridian, where the vertical meridian was set perpendicular to the line connecting fovea and optic disc centroid (Fig 4). Positive disc rotation values indicated inferotemporal rotation and negative values indicated supernasal rotation.

Figure 4.

Evaluation of optic disc morphology. The optic disc centroid (yellow cross), longest and shortest diameters (yellow lines) were determined from the clinical disc margin on the line scanning laser ophthalmoscopy image. Optic disc rotation was defined as the deviation of the longest optic disc diameter from the vertical meridian. The white lines represent the reference axes: the line connecting the fovea (white cross) and the optic disc centroid, and the vertical meridian perpendicular to this line.

Circumpapillary Retinal Nerve Fiber Layer Thickness and Choroidal Thickness

Global and 6 Garway-Heath sectoral²⁴ circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and cpChT were measured on 3.46-mm and 4.5-mm diameter BMO-centered measurement circles, respectively. Global and sectoral cpRNFLT values were calculated from exported ONH cube scan data automatically segmented by custom Zeiss software. Circumpapillary choroidal thickness was manually measured on each radial slice using Fiji ImageJ.

Magnification Correction

All planar measurements (BMO area, SFO area, optic disc area, and diameters) and measurement circle diameters for cpRNFLT, cpChT were corrected for magnification error using the modified Littmann formula.^31,32

Statistical Analysis

All data are reported as mean ± standard deviation unless otherwise specified. Background parameters, deep ONH structure, and optic disc morphology parameters were compared between PICC eyes and their contralateral eyes. Normality of the paired differences for each parameter was assessed using the Shapiro–Wilk test. Based on the results, paired t tests were applied to normally distributed variables, while Wilcoxon signed-rank tests were used for non-normally distributed variables. To address the issue of multiple comparisons, the false discovery rate was controlled using the Benjamini–Hochberg method for the statistical analyses of ONH structural parameters. Statistical analyses were performed with R software version 4.4.1.

Results

One hundred sixty-four eyes of 82 unilateral PICC participants met the inclusion criteria. After excluding 29 participants (15 participants for history of glaucoma surgery, 5 participants for retinal disease, 2 participants for PM or its suspects, and 7 participants for insufficient quality of OCT scans), 106 eyes of 53 unilateral PICC participants were enrolled in the current study. Fifty of 53 included participants had reliable VF results. Peripapillary intrachoroidal cavitation was detected among 104 sectors of 53 eyes and most frequently observed in the inferior temporal sector (46 sectors, 44%), followed by the inferior nasal sector (35 sectors, 34%), temporal sector (12 sectors, 12%), nasal sector (5 sectors, 5%), superior temporal sector (4 sectors, 4%), and superior nasal sector (2 sectors, 2%). Table 1 presents background data of the study participants and intraindividual comparison of deep ONH structure and optic disc morphology parameters between PICC eyes and their contralateral eyes. There was no significant difference in AL, visual acuity, mean spherical equivalent refraction, IOP, 24-2 VF mean deviation, and pattern standard deviation between PICC eyes and their contralateral eyes. Global and sectoral cpRNFLT showed no significant differences, but global, inferior temporal, and inferior nasal cpChT were significantly thicker in PICC eyes (P = 0.037, P = 0.001, P < 0.001, respectively) (Table 1, Table S2, available at www.ophthalmologyscience.org). Table 3 presents deep ONH structure and optic disc morphology parameters between PICC eyes and their contralateral eyes. Bruch membrane opening area (P < 0.001) and its ovality (P = 0.020), SFO area (P = 0.003), and SFO/BMO offset magnitude (P = 0.007) were significantly larger in PICC eyes (Fig 5). Optic disc tilt was significantly greater (P < 0.001) and optic disc short diameter was significantly shorter (P = 0.010) in PICC eyes. Optic disc rotation was greater in the inferotemporal direction of PICC eyes but did not reach statistical significance (P = 0.067) (Fig 6).

Table 1.

Background Characteristics of Participants with Unilateral Peripapillary Intrachoroidal Cavitation

	PICC Eyes	Contralateral Eyes	P Value
Age (yrs old)	56.6 ± 11.5
Sex (male and female)	23/30
Right eye and left eye	14/39	39/14
AL (mm) (range)	27.01 ± 1.44 (24.87 to 31.28)	26.85 ± 1.55 (23.10 to 30.13)	0.081†
Visual acuity (logMAR)	–0.021 ± 0.120	–0.045 ± 0.077	0.315†
Mean spherical equivalent refraction (diopter)	–7.74 ± 2.66	–7.30 ± 3.23	0.062†
IOP (mmHg)	13.3 ± 1.9	13.5 ± 2.2	0.284†
Mean deviation of 24-2 (dB)‡	–5.64 ± 5.40	–5.44 ± 6.41	0.380†
Pattern standard deviation of 24-2 (dB)‡	6.72 ± 4.27	6.10 ± 4.68	0.616∗
Global cpRNFLT (μm)	82.0 ± 11.9	81.5 ± 14.8	0.754∗
Global cpChT (μm)	103.0 ± 30.2	95.0 ± 30.8	0.037∗
PICC depth (μm)	155.6 ± 71.4

AL = axial length; cpChT = circumpapillary choroidal thickness; cpRNFLT = circumpapillary retinal nerve fiber layer thickness; dB = decibel; IOP = intraocular pressure; logMAR = logarithm of the minimum angle of resolution; PICC = peripapillary intrachoroidal cavitation.

^∗Paired t-test.

^†Wilcoxon signed-rank test.

^‡Analyzed in 50 participants whose visual field tests met the reliability criteria. Significant values are shown in bold.

Table 3.

Comparison of Deep Optic Nerve Head Structures and Optic Disc Morphology Parameters

	PICC Eyes	Contralateral Eyes	P Value
BMO area (mm2)	3.77 ± 1.24	3.33 ± 1.21	<0.001∗
BMO ovality	1.16 ± 0.10	1.12 ± 0.07	0.020†
SFO area (mm2)	3.04 ± 0.63	2.85 ± 0.64	0.003†
SFO ovality	1.23 ± 0.12	1.20 ± 0.11	0.115∗
SFO/BMO offset magnitude (μm)	651.41 ± 196.83	549.25 ± 204.75	0.007∗
Optic disc longest diameters (mm)	1.92 ± 0.36	1.87 ± 0.32	0.132†
Optic disc shortest diameters (mm)	1.36 ± 0.31	1.44 ± 0.28	0.010∗
Optic disc area (mm2)	2.11 ± 0.80	2.16 ± 0.75	0.506∗
Optic disc tilt	1.44 ± 0.24	1.32 ± 0.19	<0.001∗
Optic disc rotation (degree)	17.26 ± 19.61	11.49 ± 16.17	0.067∗

BMO = Bruch membrane opening; PICC = peripapillary intrachoroidal cavitation; SFO = scleral flange opening.

^∗Paired t-test.

^†Wilcoxon signed-rank test. Statistically significant P values after the Benjamini–Hochberg procedure are shown in bold.

Figure 5.

Fundus photographs of a unilateral PICC participant (A, B) and deep ONH structures overlaid on line scanning laser ophthalmoscopy images (C, D). Peripapillary intrachoroidal cavitation was observed in the right eye (A, arrowheads). Bruch membrane opening is elliptically enlarged in the PICC eye (C, orange area). Misalignment of BMO (C, D, orange dots) and SFO (C,D, blue dots) is larger in the PICC eye (C, red line). BMO = Bruch membrane opening; ONH = optic nerve head; PICC = peripapillary intrachoroidal cavitation; SFO = scleral flange opening

Figure 6.

Box plots of SFO and BMO offset magnitude, optic disc tilt, and optic disc rotation in eyes with PICC and their contralateral eyes. BMO = Bruch membrane opening; PICC = peripapillary intrachoroidal cavitation; SFO = scleral flange opening.

Discussion

In this study of unilateral PICC participants, we identified significant differences in deep ONH structures and optic disc morphology between PICC eyes and their contralateral eyes. Peripapillary intrachoroidal cavitation eyes exhibited a more elliptically expanded BMO, larger SFO, greater SFO/BMO misalignment, and greater optic disc tilt, despite the absence of significant intraindividual difference in AL. Our findings provide new insights into the structural factors that may contribute to PICC formation.

Although the association of PICC and HM is well documented,^4,5 recent reports of PICC in non-HM suggest that factors other than AL elongation may also be involved in its pathogenesis.^15,19 Moreover, studies on PM have indicated that structural deformations accompanying AL elongation, such as optic disc tilt and posterior staphyloma, may play a more critical role in PICC formation than AL itself.^5,20

We observed a larger SFO/BMO offset magnitude in PICC eyes, which clinically corresponds to an enlargement of the combined PPA-gamma and delta area. A previous study by Dai et al²⁰ on unilateral PICC found no significant difference in the combined PPA-beta and gamma area between PICC eyes and their contralateral eyes. While PPA-beta is associated with both myopia and glaucoma, PPA-gamma is more closely linked with AL elongation and is primarily a myopic change rather than a glaucomatous one.^33,34 The enlargement of the PPA-gamma and delta regions results from the spatial offset between the BMO and SFO, accompanied by elongation of the BT (Fig 7). By focusing on the PPA-gamma and delta regions which is more strongly associated with the elongation of AL and BT, we were able to highlight the role of deep ONH structural remodeling in PICC formation.

Figure 7.

Consecutive OCT radial slices of eyes with PICC. The BT of Jacoby and Elschnig is between the BMO (orange dots) and SFO (blue dots). The BT is maintained in (A). The BT becomes elongated with discontinuity as the misalignment of BMO and SFO increases in (B, yellow arrowhead). The BT is disrupted in (C, red arrowhead) and posterior peripapillary scleral bowing is observed (C, white arrowhead). BMO = Bruch membrane opening; BT = border tissue; PICC = peripapillary intrachoroidal cavitation; SFO = scleral flange opening.

We also found that PICC eyes exhibited a more spindle-like optic disc configuration with smaller shortest diameters, consistent with a previous report.²⁰ This morphological change represents pronounced optic disc tilt around the vertical and horizontal axes. Optic disc tilt is a well-known feature of myopic eyes and considered to result from the nasal displacement of the lamina cribrosa (LC) during AL elongation.³⁵ Kim et al provided further insight into morphological change by suggesting that LC does not simply shift nasally parallel to the BMO plane with AL elongation. Instead, the nasal neural canal becomes more constricted and the nasal peripapillary tissue becomes elevated, resulting in a tilted appearance of the optic disc.³⁶ The larger SFO area in our PICC eyes further supports this, suggesting that the neural canal itself was not constricted but rather appeared smaller in shortest diameter due to its tilted orientation.

We observed a tendency for greater optic disc rotation in PICC eyes in agreement with Dai et al²⁰ although the difference did not reach statistical significance (P = 0.067). A post hoc power analysis yielded a power of 0.45, suggesting that the current sample size may have been insufficient to detect a statistically significant difference. Optic disc rotation is an indicator of rotation around the sagittal axis and may induce tangential strain on the BT,³⁷ while optic disc tilt is more closely related to BT elongation in the z-axis direction. The association of optic disc tilt and rotation and enlargement of PPA-gamma and delta with PICC may be explained by their contribution to the elongation of BT, although these myopia-related structural changes influence BT elongation along different vectors.

Border tissue of Jacoby and Elschnig are continuous structures connecting the BMO and LC and thought to play a biomechanically important role in LC stabilization.^30,38 Previous studies have proposed that BT rupture is a key factor in PICC formation.^3,39 Enlargement of the PPA-gamma and delta regions, and optic disc tilt and rotation, may lead to BT disruption by compromising its structural stability (Fig 7). Tensile testing on porcine Bruch membrane-choroid complex have demonstrated that it can withstand IOP of up to 82 mmHg before rupture,⁴⁰ indicating that rupture is unlikely to occur under normal IOP conditions. However, a recent finite element analysis study predicted that horizontal eye movement–related mechanical forces can generate ONH strain exceeding that induced by IOP of 50 mmHg,⁴¹ and this mechanical strain has been reported to be greater in HM eyes.⁴² Given the background that BT tends to be elongated in the temporal to the inferior region as part of myopic ONH remodeling,²² such mechanical stress may be one possible mechanism for BT rupture in PICC eyes.

Another hypothesis for the etiology of PICC has been the vitreous fluid inflow into the choroid,^6,9 which may be a result from BT disruption. Furthermore, Spaide et al³ suggested a relationship between posterior bowing of the peripapillary sclera and PICC formation. Border tissue disruption could alter the biomechanics around ONH,³⁰ potentially making the sclera more directly susceptible to IOP stress, leading to posterior peripapillary scleral bowing. Alternatively, posterior peripapillary scleral bowing could precede BT elongation and rupture.

In our sectoral analysis, there was no significant difference in cpRNFLT between PICC eyes and their contralateral eyes, either globally or within any specific sector. In contrast, cpChT was significantly greater in the inferior temporal and inferior nasal sectors of PICC eyes, corresponding to the regions where PICC was most frequently observed. This localized increase in cpChT likely reflects regional expansion of the choroidal space associated with PICC. These findings further underscore the presence of region-specific ONH structural alterations in PICC eyes.

In the current study, 42 (79%) PICC eyes met the Anderson–Patella criteria⁴³ for abnormal VF. However, whether these defects represent glaucomatous damage or reflect structural alterations associated with PICC remains unclear and warrants further investigation. We recently investigated factors associated with VF abnormalities corresponding to PICC location. Our findings indicated that the presence of a PICC itself was not directly associated with a reduction in VF sensitivity. Instead, thinning of the cpRNFL and disruption of the overlying retina—often accompanying BT rupture—was identified as key contributors to localized sensitivity loss at the PICC site.¹⁵ In the present study, disruption of the overlying retina was observed in 4 PICC eyes, whereas none were found in their contralateral non-PICC eyes. Notably, even in the absence of full thickness retinal defects, localized retinal thinning near the SFO¹⁵ was frequently observed, suggesting the presence of subclinical structural compromise in these regions. The characteristic ONH structural changes associated with BT elongation in PICC eyes in the present study provide a foundation for understanding the underlying structural changes that lead to VF impairment that differ from those of typical glaucoma. These alterations may also contribute to the differences in the biomechanics of the LC between eyes with and without PICC, potentially leading to structural vulnerability of ONH.

There are some limitations to our study. First, its cross-sectional design limited our ability to determine whether the ONH structural changes associated with PICC are a cause or a consequence of its development. Future longitudinal studies are needed to address the temporal relationship between these structural changes and PICC formation. Second, this study exclusively enrolled participants with unilateral PICC. In our previous investigation of consecutive PICC cases, 36 of 93 patients (38%) exhibited bilateral PICC.¹⁵ While restricting the study to unilateral cases may introduce selection bias, our current approach reduces interparticipant variability and enables a characterization of structural features specifically associated with PICC. Finally, although our cases showed no significant difference in AL between PICC eyes and their contralateral eyes, post hoc power analysis indicated the statistical power of 0.38, suggesting that our study may have been underpowered to detect small differences in AL. Nonetheless, significant differences were observed in other parameters more directly associated with PICC, which highlights the structural characteristics relevant to PICC.

In conclusion, despite having similar AL, PICC eyes exhibited a more elliptically expanded BMO, larger SFO, greater SFO/BMO misalignment, and greater optic disc tilt in comparison with their contralateral eyes in unilateral non-PM PICC participants. These findings indicate a strong association between PICC and myopia-related characteristic deep ONH remodeling, particularly BT elongation. Improved understanding of these structural features provides a foundation for characterizing structural abnormalities in myopic eyes and may contribute to their future differentiation from glaucomatous damage.

Manuscript no. XOPS-D-25-00399.