Structural and Vascular Characteristics of PHOMS in Pediatric Pseudopapilledema  

Structural and Vascular Characteristics of PHOMS in Pediatric Pseudopapilledema | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Structural and Vascular Characteristics of PHOMS in Pediatric Pseudopapilledema Selda Celik Dulger, Fırat Uygur, Ismail Murat Seyhun This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9524903/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 18 You are reading this latest preprint version Abstract Purpose To evaluate the structural and vascular characteristics of peripapillary hyperreflective ovoid mass-like structures (PHOMS) in pediatric pseudopapilledema and to investigate their relationship with retinal nerve fiber layer (RNFL) thickness and optic nerve head parameters. Methods This retrospective study included 38 pediatric patients with pseudopapilledema (with or without optic disc drusen [ODD]) and 36 age- and sex-matched healthy controls. Structural optical coherence tomography (OCT) and OCT angiography (OCTA) parameters were analyzed, including global and sectoral RNFL thickness, ganglion cell complex (GCC) metrics, Bruch’s membrane opening (BMO) diameter, choroidal vascularity index (CVI), radial peripapillary capillary (RPC) density, and macular vascular parameters. In PHOMS-positive eyes, maximum PHOMS diameter was measured on enhanced depth imaging OCT. Group comparisons were performed using generalized estimating equations. Correlation and regression analyses were conducted to evaluate associations between PHOMS size and structural or vascular parameters. Results In single-eye analysis, PHOMS-positive eyes (n = 23) demonstrated significantly higher global RNFL thickness compared with controls (p = 0.018). No significant differences were observed in spherical equivalent, BMO diameter, optic disc area, GCC thickness, CVI, or OCTA-derived vascular parameters (all p > 0.05). Maximum PHOMS diameter showed a significant positive correlation with global RNFL thickness (r = 0.526, p = 0.010) and remained independently associated in multivariable regression analysis (β = 0.44, p = 0.044). In eye-level analyses including ODD-positive, ODD-negative, and healthy eyes, RNFL thickness differed significantly among groups (p < 0.001), whereas no consistent differences were observed in vascular or ganglion cell parameters. Conclusions In pediatric pseudopapilledema, PHOMS are associated with increased RNFL thickness, and PHOMS size independently predicts RNFL variation. The absence of consistent vascular or ganglion cell alterations suggests that PHOMS predominantly represent a structural optic nerve head phenotype rather than a generalized microvascular disorder. Recognition of this pattern may aid in differentiating benign structural variants from early optic neuropathy in children. Peripapillary hyperreflective ovoid mass-like structures Pediatric pseudopapilledema Retinal nerve fiber layer Optical coherence tomography angiography Optic disc drusen Key Message What is known • Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are increasingly recognized in association with optic disc drusen, myopia, and elevated intracranial pressure, but their structural and vascular characteristics in pediatric pseudopapilledema remain incompletely defined. What is new • In pediatric pseudopapilledema, PHOMS-positive eyes demonstrate significantly increased global RNFL thickness without consistent alterations in ganglion cell or OCTA-derived vascular parameters. • Maximum PHOMS diameter independently correlates with RNFL thickness, suggesting that PHOMS size reflects localized axonal crowding rather than disc size or microvascular changes. • In the absence of elevated intracranial pressure, PHOMS appear to behave as a stable structural optic nerve head phenotype rather than a primary microvascular disorder. Introduction Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are increasingly recognized on enhanced depth imaging optical coherence tomography (EDI-OCT) as peripapillary hyperreflective configurations located above the level of the Bruch’s membrane opening [ 1 , 2 ]. Initially considered a variant or precursor of optic disc drusen (ODD), PHOMS are now defined by the Optic Disc Drusen Studies (ODDS) Consortium as a distinct morphologic entity characterized by lateral displacement and herniation of prelaminar nerve fibers [ 2 ]. PHOMS have been reported across a broad spectrum of clinical conditions, including optic disc drusen, tilted discs, myopia, papilledema, idiopathic intracranial hypertension (IIH), and inflammatory optic neuropathies [ 1 , 3 , 4 ]. Population-based studies in children have demonstrated a prevalence of approximately 8–9% in otherwise healthy cohorts, with associations noted between PHOMS, axial elongation, and optic disc tilt [ 5 , 6 ]. In adult populations, PHOMS have also been identified in large epidemiologic studies, further supporting their non–disease-specific nature [ 7 ]. The relationship between PHOMS and ODD remains controversial. While some pediatric studies suggest that PHOMS frequently coexist with deep ODD and may represent an early stage in drusen evolution [ 8 ], other reports confirm the presence of isolated PHOMS in the absence of detectable drusen or raised intracranial pressure [ 9 ]. Multimodal imaging, including B-scan ultrasonography and fundus autofluorescence, has been emphasized as essential for differentiating PHOMS from buried drusen, particularly in children where drusen may be difficult to visualize clinically [ 10 ]. Beyond their association with structural disc anomalies, PHOMS have also been linked to elevated intracranial pressure. In children with syndromic craniosynostosis, PHOMS were found to correlate strongly with elevated intracranial pressure and concurrent papilledema, and resolution was observed following surgical decompression [ 11 , 12 ]. Similarly, studies in patients evaluated for suspected papilledema have demonstrated that PHOMS may occur in IIH but are not specific to this diagnosis [ 9 ]. These findings suggest that PHOMS may represent a common morphologic response to mechanical or axoplasmic stress at the optic nerve head rather than a disease entity per se. Despite growing recognition of PHOMS, their structural and vascular characteristics in pediatric pseudopapilledema remain incompletely understood. In particular, it is unclear whether PHOMS are associated with alterations in peripapillary retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) parameters, or optic nerve head microvasculature as assessed by optical coherence tomography angiography (OCTA). Clarifying these associations is clinically relevant to distinguish benign structural variants from early optic neuropathy. The aim of the present study was therefore to evaluate structural and vascular characteristics of PHOMS in a pediatric pseudopapilledema cohort, with particular emphasis on RNFL thickness, PHOMS size, Bruch’s membrane opening (BMO) diameter, and OCTA-derived vascular parameters. Materials and Methods Study Population This retrospective study included pediatric patients under 18 years of age who were followed in the Neuro-ophthalmology Unit between January 2023 and June 2025. Ethical approval was obtained from the Ankara Etlik City Hospital Ethics Committee. The study was conducted in accordance with the Declaration of Helsinki. Due to the retrospective design, the requirement for written informed consent was waived. A total of 38 patients with pseudopapilledema, with or without optic disc drusen (ODD), and 36 age- and sex-matched healthy controls were included. In the pseudopapilledema group, ODD was present in 36 eyes of 18 patients. PHOMS were detected in 23 of 40 eyes. For PHOMS-based analyses, in patients with bilateral PHOMS, the eye with the larger maximum PHOMS diameter was selected; in unilateral cases, the affected eye was analyzed. One eye per control subject was randomly selected. For ODD-based comparisons, analyses were performed at the eye level and included 36 eyes of 18 ODD patients, 40 eyes of 20 non-ODD pseudopapilledema patients, and 72 eyes of 36 healthy controls. ODD was diagnosed based on combined B-scan ultrasonography and OCT findings. Hyperreflective signals on B-scan were present in all ODD cases. Fundus autofluorescence was performed in selected cases to support the diagnosis. The pseudopapilledema group without ODD consisted of patients with stable optic nerve head appearance for at least 6 months, congenitally crowded discs, no evidence of ODD on imaging, normal cerebrospinal fluid opening pressure (< 250 mmH₂O), and, when clinically indicated, normal brain MRI findings. Healthy controls had BCVA ≥ 20/20, normal anterior and posterior segment findings, normal visual fields, structurally normal optic nerve heads, and no ocular, neurologic, or systemic disease. Exclusion criteria included age outside 5–18 years, incomplete data, significant media opacity, motion artifacts, refractive error > ± 6 diopters, prior intraocular surgery, or any ocular/systemic disease affecting retinal or optic nerve parameters. All participants underwent comprehensive ophthalmic examination including BCVA, refractive error, axial length (IOLMaster 500, Carl Zeiss Meditec, Jena, Germany), slit-lamp biomicroscopy, and dilated fundus examination. The following parameters were included in the analysis: best-corrected visual acuity (BCVA) and spherical equivalent (SE); structural OCT measurements including global and sectoral retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) thickness, focal loss volume (FLV), global loss volume (GLV), Bruch’s membrane opening (BMO) distance, and optic disc area; peripapillary choroidal thickness and choroidal vascularity index; and OCTA-derived vascular parameters. Macular OCTA parameters included vessel density measurements of the superficial and deep capillary plexuses (whole image, foveal, parafoveal, and perifoveal regions), foveal avascular zone (FAZ) area, flow density (FD), and flow area measurements. Peripapillary vascular density was assessed using radial peripapillary capillary (RPC) measurements in sectoral analyses. Image Acquisition All OCT examinations were performed after pupillary dilation and between 9:00 AM and 12:00 PM to minimize diurnal variation, particularly for choroidal measurements. [ 13 ] Peripapillary RNFL thickness was measured using SD-OCT (Cirrus HD-OCT 5000, Carl Zeiss Meditec, Dublin, CA, USA) with an optic disc-centered scan protocol. EDI-OCT and OCTA imaging were performed using the RTVue XR Avanti system (Optovue Inc., Fremont, CA, USA). Macular OCTA scans were obtained using a 6 × 6 mm cube centered on the fovea, and optic nerve head scans were obtained using a 4.5 × 4.5 mm cube centered on the disc. Superficial and deep capillary plexus vessel densities, radial peripapillary capillary density, foveal avascular zone area, and flow area parameters were automatically calculated using the device software. Only OCTA images with a signal strength index ≥ 7 were included in the analysis. Scans with motion artifacts, segmentation errors, or projection artifacts were carefully reviewed and excluded. Projection artifacts were minimized using the device’s built-in algorithm. The presence or absence of PHOMS was determined according to the Optic Disc Drusen Studies (ODDS) Consortium definition using optic disc–centered horizontal and vertical enhanced depth imaging (EDI) OCT scans.[ 2 ] PHOMS were defined as peripapillary hyperreflective ovoid mass-like structures located above the level of the Bruch’s membrane opening. For quantitative analysis, the horizontal and vertical diameters of each PHOMS were measured on EDI-OCT images. The larger of the horizontal and vertical diameters was defined as the maximum PHOMS diameter to represent PHOMS size. CVI was calculated on EDI-OCT images using Fiji software (ImageJ, NIH, Bethesda, MD, USA) following a previously described binarization method. [ 14 ] A standardized 1000-µm peripapillary choroidal region extending from the Bruch’s membrane opening was manually selected. Images were converted to 8-bit format and binarized using the Niblack auto-local threshold. CVI was defined as the ratio of luminal area to total choroidal area. Bruch’s membrane opening (BMO) distance was measured on the horizontal EDI-OCT B-scan passing through the center of the optic disc, as previously described in optic nerve head morphometric studies [ 15 ]. BMO distance was defined as the linear distance between the nasal and temporal edges of the Bruch’s membrane opening. In eyes with coexisting optic disc drusen (ODD), BMO measurements were not performed due to potential distortion of the Bruch’s membrane contour and difficulty in reliably identifying BMO margins. All measurements were performed by a single masked observer to ensure consistency. Statistical Analysis Statistical analyses were performed using IBM SPSS Statistics version 23 (IBM Corp., Armonk, NY, USA) and R software version 4.4.1 (R Foundation for Statistical Computing, Vienna, Austria). Normality of data distribution was assessed using the Shapiro–Wilk and Kolmogorov–Smirnov tests. Continuous variables with normal distribution were compared between two groups using the independent samples t-test, while non-normally distributed variables were compared using the Mann–Whitney U test. Correlations between normally distributed continuous variables were evaluated using Pearson’s correlation analysis, whereas Spearman’s rank correlation was used for non-normally distributed variables. Associations between categorical variables were analyzed using the chi-square test with Yates’ correction. Linear regression analysis was performed to evaluate the effects of independent variables on normally distributed dependent variables. For non-normally distributed dependent variables, robust regression analysis was conducted using the MASS package in R. To account for inter-eye correlation, generalized estimating equations (GEE) were used for group comparisons of quantitative variables at the eye level. Bonferroni correction was applied for multiple comparisons. Continuous variables are presented as mean ± standard deviation or median (minimum–maximum), as appropriate. Categorical variables are presented as frequency (percentage). A p-value < 0.05 was considered statistically significant. Results 1. Demographic Characteristics There was no significant difference between the groups in terms of sex distribution (female: 71.1% in the patient group vs. 69.4% in the control group, p = 1.000). The mean age was 12.8 ± 4.0 years in the patient group and 12.9 ± 3.8 years in the control group, with no statistically significant difference between the groups (p = 0.913). The demographic characteristics of the study population are summarized in Table 1 . Table 1 Demographic Characteristics of the Study Population Variable Patients (n = 38) Controls (n = 36) p value Sex, n (%) 1.000 Female 27 (71.1) 25 (69.4) Male 11 (28.9) 11 (30.6) Age (years) 12.82 ± 4.01 12.92 ± 3.87 0.913 Categorical variables were compared using the chi-square test with Yates correction. Continuous variables were compared using the independent samples t-test. Data are presented as mean ± standard deviation or frequency (%). 2. Single-Eye Analysis: PHOMS-Positive Eyes vs Controls A total of 23 PHOMS-positive eyes and 36 healthy control eyes were included in the single-eye analysis. Among all evaluated parameters, global RNFL thickness was significantly higher in PHOMS-positive eyes compared to controls (p = 0.018) (Table 2 ). Table 2 Comparison of Structural and OCTA-Derived Parameters Between PHOMS-Positive Eyes and Healthy Controls Parameter PHOMS-Positive Eyes (n = 23) Healthy Controls (n = 36) p value Structural parameters Spherical equivalent (D)† −1.25 (− 5.00 to 4.00) −0.13 (− 5.00 to 1.75) 0.171 BMO diameter (mm) 1.56 ± 0.35 1.41 ± 0.16 0.067 Optic disc area (mm²) 1.82 ± 0.33 1.85 ± 0.29 0.763 Global RNFL thickness (µm) 110.07 ± 22.51 97.73 ± 8.33 0.018 Average GCC thickness (µm)† 103.00 (96.00–121.00) 103.00 (95.00–116.00) 0.932 Choroidal vascularity index 0.69 ± 0.06 0.71 ± 0.04 0.177 OCTA-derived parameters SCP whole vessel density (%) 48.94 ± 1.63 49.61 ± 1.36 0.091 DCP whole vessel density (%)† 53.10 (48.40–55.00) 53.40 (47.90–54.90) 0.822 FAZ area (mm²)† 0.20 (0.05–0.31) 0.22 (0.07–0.51) 0.071 Radial peripapillary capillary density (%) 50.53 ± 1.70 51.32 ± 2.08 0.123 Data are presented as mean ± standard deviation or median (range). † Mann–Whitney U test; other comparisons performed using independent samples t-test. BMO: Bruch’s membrane opening; RNFL: retinal nerve fiber layer; GCC: ganglion cell complex; SCP: superficial capillary plexus; DCP: deep capillary plexus; FAZ: foveal avascular zone. No statistically significant differences were observed between groups regarding spherical equivalent, Bruch’s membrane opening (BMO) diameter, optic disc area, ganglion cell complex thickness, choroidal vascularity index (CVI), or OCTA-derived vascular parameters including radial peripapillary capillary density, superficial capillary plexus whole image vessel density, deep capillary plexus whole image vessel density, and foveal avascular zone area (all p > 0.05) (Table 2 ). 3. Correlation Analyses Correlation analyses were performed within the PHOMS-positive group (n = 23 eyes) to evaluate the associations between maximum PHOMS diameter, Bruch’s membrane opening (BMO) diameter, and structural and vascular parameters. Maximum PHOMS diameter demonstrated a significant positive correlation with global RNFL thickness (r = 0.526, p = 0.010). No significant correlations were observed between maximum PHOMS diameter and BMO diameter, ganglion cell complex thickness, mean choroidal vascularity index (CVI), or peripapillary radial capillary density (all p > 0.05) ( Table 3 ). Table 3 Correlation Between Maximum PHOMS Diameter and Ocular Parameters in PHOMS-Positive Eyes (n = 23) Parameter Correlation coefficient (r) p value BMO diameter −0.323 0.133 Choroidal vascularity index −0.153 0.518 Average GCC thickness 0.128 0.560 Radial peripapillary capillary density 0.266 0.232 Global RNFL thickness 0.526 0.010 Correlations were assessed using Spearman’s rank correlation coefficient. BMO: Bruch’s membrane opening; GCC: ganglion cell complex; RNFL: retinal nerve fiber layer. Within the PHOMS-positive group, BMO diameter was not significantly associated with optic disc area (r = 0.243, p = 0.348), RNFL thickness, maximum PHOMS diameter, or spherical equivalent (all p > 0.05). In contrast, in healthy control eyes, BMO diameter showed a significant positive correlation with optic disc area (r = 0.675, p 0.05) ( Supplementary Tables 1 and 2 ). 4. Regression Analyses A multivariable linear regression analysis was performed in PHOMS-positive eyes to evaluate the independent effects of maximum PHOMS diameter and BMO diameter on global RNFL thickness (Table 4 ). Table 4 Multivariable Linear Regression Analysis for Global RNFL Thickness and RPC density in PHOMS-Positive Eyes (n = 23) Dependent variable Independent variable B (95% CI) Standardized β p value Global RNFL thickness Maximum PHOMS diameter 0.055 (0.002 to 0.109) 0.437 0.044 BMO diameter 5.768 (− 21.237 to 32.774) 0.091 0.661 RPC density Maximum PHOMS diameter 0.003 (− 0.002 to 0.008) 0.321 0.218 Global RNFL thickness 0.002 (− 0.043 to 0.047) 0.023 0.928 Model statistics • Global RNFL thickness model : F(2,20) = 2.309; R² = 0.188; Adjusted R² = 0.107; Durbin–Watson = 1.747 • RPC density model : F(2,19) = 1.185; R² = 0.111 Although the overall model did not reach statistical significance (F(2,20) = 2.309, p = 0.125), maximum PHOMS diameter remained independently associated with RNFL thickness (β = 0.44, p = 0.044), whereas BMO diameter was not significantly associated with RNFL thickness (p > 0.05). In PHOMS-positive eyes, linear regression analysis demonstrated that neither maximum PHOMS diameter nor RNFL thickness was significantly associated with peripapillary radial capillary density (F(2.19) = 1.185, p = 0.327). Linear regression analysis showed that neither maximum PHOMS diameter nor RNFL thickness was significantly associated with peripapillary vessel density (F(2,19) = 1.185; p = 0.327). 5. Group Comparisons Using GEE Group comparisons were performed using generalized estimating equations (GEE) to account for inter-eye correlation (Table 5 ). Table 5 Group Comparisons Using Generalized Estimating Equations (GEE) Parameter ODD-Positive Eyes (n = 36) Non-ODD Pseudopapilledema (n = 40) Healthy Controls (n = 72) p value Global RNFL thickness (µm) 132.27 ± 30.36ᵃ 102.17 ± 16.08ᵇ 97.55 ± 8.54ᵇ < 0.001 Average GCC thickness (µm) 107.31 ± 7.44 104.54 ± 5.84 104.10 ± 5.93 0.682 Radial peripapillary capillary density (%) 50.75 ± 1.82 50.52 ± 2.03 51.15 ± 1.96 0.287 Choroidal vascularity index 0.69 ± 0.03 0.69 ± 0.08 0.70 ± 0.05 0.698 Footnote Group comparisons were performed using generalized estimating equations to account for inter-eye correlation. Bonferroni correction was applied for multiple comparisons. RNFL comparisons were adjusted for BMO diameter and spherical equivalent. GCC and RPC comparisons were adjusted for global RNFL thickness. Different superscript letters indicate statistically significant differences between groups. RNFL: retinal nerve fiber layer; GCC: ganglion cell complex. A significant difference was observed among the three groups only for global RNFL thickness (p < 0.001). RNFL thickness was significantly higher in the ODD group (132.27 ± 30.36 µm) compared with both the non-ODD pseudopapilledema group (102.17 ± 16.08 µm) and healthy controls (97.55 ± 8.54 µm). No significant difference was found between the non-ODD and healthy control groups. No statistically significant differences were observed among groups for mean CVI, average GCC thickness, or peripapillary radial capillary density (all p > 0.05). 6. Supplementary Analyses Additional structural and vascular parameters were analyzed using GEE with Bonferroni correction and are presented in Supplementary Table 3. Among structural parameters, BMO diameter differed significantly among groups (p < 0.001). FLV values were higher in the ODD group (p = 0.010), whereas GLV and average GCC thickness did not differ significantly. Among vascular parameters, most macular and peripapillary OCTA metrics did not differ significantly across groups. A sectoral difference was observed in nasal-inferior RPC (p = 0.006); however, no consistent vascular pattern was observed across sectors. Sectoral RNFL measurements were significantly higher in the ODD group across multiple quadrants (all p < 0.05). Discussion In this pediatric cohort, PHOMS-positive eyes demonstrated significantly increased global RNFL thickness compared with healthy controls. Maximum PHOMS diameter showed a positive correlation with RNFL thickness and remained significantly associated after adjustment for BMO diameter. In contrast, no consistent differences were observed in macular or peripapillary vascular parameters, CVI, or average GCC thickness. Similar findings were confirmed in eye-level GEE analyses, where RNFL thickness differed significantly among ODD-positive, non-ODD pseudopapilledema, and healthy eyes, whereas GCC, RPC density, and CVI showed no significant differences. The lack of association between PHOMS size and BMO diameter is noteworty, as BMO is considered a surrogate marker of scleral canal size and optic nerve head configuration. Our results indicate that PHOMS enlargement may occur independently of disc size, supports the concept that PHOMS represent localized axoplasmic stasis rather than a simple consequence of anatomical crowding at the level of the scleral canal. Interestingly, BMO diameter was correlated with optic disc area in healthy controls but not in PHOMS-positive eyes, which may indicate a disruption of the normal anatomical relationship between disc size and scleral canal dimensions in the presence of PHOMS. Furthermore, the absence of correlation between PHOMS diameter and peripapillary capillary density or choroidal vascularity index suggests that vascular alterations may not play a primary role in PHOMS development. Taken together, these findings highlight that PHOMS size is selectively associated with RNFL thickness, while remaining largely independent of optic disc morphology and vascular parameters. PHOMS were initially described as peripapillary hyperreflective configurations above the level of the Bruch’s membrane opening and are now recognized as a distinct morphologic entity separate from optic disc drusen (ODD) [ 1 , 2 ]. Importantly, PHOMS have been observed in both optic disc edema and pseudopapilledema, supporting the notion that they are not specific to a single underlying pathology [ 16 ]. However, their relationship with ODD remains debated. A recent pediatric study reported that PHOMS were consistently observed in conjunction with deep or superficial ODD and suggested that RNFL thickening may reflect early drusen stages, with subsequent thinning as drusen become superficial [ 8 ]. In contrast, PHOMS-positive eyes in our cohort did not show clinically detectable ODD, and RNFL thickening persisted independently of visible drusen. Furthermore, ultrasonographic differentiation studies emphasize that PHOMS and ODD represent structurally distinct entities, even when coexisting [ 4 ]. Together, these findings support the concept that PHOMS can occur as an isolated structural configuration rather than merely as a secondary manifestation of buried drusen. The association between PHOMS and RNFL thickness has been described in both pediatric and adult populations. Population-based studies in children have demonstrated PHOMS in otherwise healthy cohorts, often in association with myopia and disc morphology variations [ 5 , 6 ]. Similarly, in adult epidemiologic data, PHOMS were linked to optic disc configuration without clear evidence of neurodegeneration [ 7 ]. In highly myopic eyes, larger PHOMS area has been associated with increased RNFL thickness [ 10 ]. Our findings extend this body of evidence by demonstrating that PHOMS size itself, rather than BMO diameter, appears to be associated with RNFL thickness in pediatric pseudopapilledema. The vascular implications of PHOMS remain controversial. Some OCTA studies have suggested altered peripapillary vessel density in association with PHOMS [ 3 ], whereas others have demonstrated preserved or even increased radial peripapillary capillary signals [ 10 ]. Moreover, PHOMS have been described in diverse clinical settings including idiopathic intracranial hypertension (IIH), papilledema, and inflammatory optic neuropathies, reinforcing the concept that PHOMS are not disease-specific [ 1 , 9 ]. In children with syndromic craniosynostosis, PHOMS were strongly associated with elevated intracranial pressure and were shown to resolve following surgical decompression, suggesting a dynamic structural response to mechanical stress [ 11 , 12 ]. Kirik et al. evaluated peripapillary choroidal vascularity in myopic pediatric eyes with PHOMS and reported a tendency toward reduced choroidal area parameters with relatively higher CVI values. In contrast, our pseudopapilledema cohort did not demonstrate significant CVI differences, suggesting that peripapillary choroidal vascularity may not represent a consistent feature of PHOMS across different pediatric populations [ 17 ]. These heterogeneous observations suggest that PHOMS may represent a final common morphologic response to axoplasmic stasis or mechanical crowding at the optic nerve head. Clinically, the selective involvement of RNFL thickness without accompanying ganglion cell loss or diffuse vascular alteration is important. Recognition of this pattern may help differentiate benign structural PHOMS from early optic neuropathy and may reduce unnecessary diagnostic escalation in asymptomatic pediatric patients. This study is limited by its cross-sectional design and relatively small number of PHOMS-positive eyes. Although the sample size is modest, the use of GEE and consistent findings across analyses support robustness. BMO measurements were not performed in ODD-positive eyes due to potential distortion of Bruch’s membrane margins. In addition, the absence of longitudinal follow-up limits assessment of temporal changes in PHOMS morphology. Longitudinal studies are required to determine whether PHOMS-associated RNFL thickening remains stable over time or evolves with disc morphology changes. In conclusion, pediatric PHOMS are associated with increased RNFL thickness, and PHOMS size appears to be associated with RNFL variation. The absence of consistent vascular or ganglion cell alterations supports the interpretation of PHOMS as a structural optic nerve head phenotype whose clinical significance depends on the accompanying pathophysiologic context. Declarations Acknowledgement: None. Funding : This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Conflict of Interest : The authors declare that they have no conflicts of interest. Ethics approval and consent to participate: This study was approved by the Ethical Committee of Ankara Etlik City Hospital. Due to the retrospective design, the requirement for written informed consent was waived. The study was conducted in accordance with the principles of the Declaration of Helsinki. Availability of data and materials: The data that support the findings of this study are not publicly available due to patient privacy and ethical restrictions but are available from the corresponding author upon reasonable request and with appropriate ethical approval. Author Contributions SCD: Conceptualization, Methodology, Data curation, Formal analysis, Writing – original draft. SCD,FU, IMS: Data curation, Writing – review & editing. SCD, FU, IMS : Formal analysis, Supervision, Writing – review & editing. All authors approved the final version of the manuscript. References Xiao D, Lhamo T, Meng Y, Xu Y, Chen C. Peripapillary hyperreflective ovoid mass-like structures: multimodal imaging and associated diseases. Front Neurol. 2024;15:1379801. https://doi.org/10.3389/fneur.2024.1379801 . Malmqvist L, Bursztyn L, Costello F, Digre K, Fraser JA, Fraser C, et al. 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Diurnal variation in choroidal parameters among healthy subjects using wide-field swept-source optical coherence tomography angiography. Transl Vis Sci Technol. 2024;13:16. https://doi.org/10.1167/tvst.13.5.16 . Agrawal R, Gupta P, Tan KA, Cheung CMG, Wong TY, Cheng CY. Choroidal vascularity index as a measure of vascular status of the choroid: measurements in healthy eyes from a population-based study. Sci Rep. 2016;6:21090. https://doi.org/10.1038/srep21090 . Hosseini H, Nassiri N, Azarbod P, Giaconi J, Chou T, Caprioli J, et al. Measurement of the optic disc vertical tilt angle with spectral-domain optical coherence tomography and influencing factors. Am J Ophthalmol. 2013;156:737–44. https://doi.org/10.1016/j.ajo.2013.05.036 . Malmqvist L, Sibony PA, Fraser CL, Wegener M, Heegaard S, Skougaard M, et al. Peripapillary ovoid hyperreflectivity in optic disc edema and pseudopapilledema. Ophthalmology. 2018;125:1662–4. https://doi.org/10.1016/j.ophtha.2018.04.036 . Kirik F, Dizdar Yiğit D, Sevik MO, Ertürk KM, İskandarov F, Şahin Ö, Özdemir H. Peripapillary choroidal vascularity of paediatric myopic eyes with peripapillary hyperreflective ovoid mass-like structures. Acta Ophthalmol. 2024. https://doi.org/10.1111/aos.16761 . Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9524903","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":639665284,"identity":"a15d0623-8c86-4717-b6a3-8b452550dc37","order_by":0,"name":"Selda Celik Dulger","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYDCCAwyMB3gYLAz4QZyEAuK0MAC1SBhINoC0GJCixeAAiEeMFr7bxx8ceFMjYWx8fnXihwcGDPL8Ygfwa5E8l2NwcM4xCTOzG283SwAdZjhzdgJ+LQZneBgO8zZI2JjdOLsBpCXB4DZBLewPwFqMZ5zd/INILQwGIC1mBvy924izRfIMD9gvxhI3eLdZJBhIEPYL3xn2hw/e1NgY9vef3XzzR4WNPL80AS0IIAFWKUGschDgP0CK6lEwCkbBKBhJAAB8c0cBlYr/JgAAAABJRU5ErkJggg==","orcid":"","institution":"Ankara Etlik City Hospital","correspondingAuthor":true,"prefix":"","firstName":"Selda","middleName":"Celik","lastName":"Dulger","suffix":""},{"id":639665286,"identity":"55ddb57c-c146-4f95-94df-8f2bba2defe9","order_by":1,"name":"Fırat Uygur","email":"","orcid":"","institution":"Ankara Etlik City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Fırat","middleName":"","lastName":"Uygur","suffix":""},{"id":639665288,"identity":"926a1fe2-6dd7-40f9-9489-e80ec956c9af","order_by":2,"name":"Ismail Murat Seyhun","email":"","orcid":"","institution":"Ankara Etlik City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ismail","middleName":"Murat","lastName":"Seyhun","suffix":""}],"badges":[],"createdAt":"2026-04-25 10:39:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9524903/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9524903/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109259402,"identity":"499dc713-2633-490b-81d6-9f18238c1d94","added_by":"auto","created_at":"2026-05-14 11:00:17","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":13415,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarytable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-9524903/v1/5359728c77df5bfb80c12e46.docx"},{"id":109296223,"identity":"51088122-422f-4d65-847a-0ba372229e33","added_by":"auto","created_at":"2026-05-15 08:46:16","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":12731,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarytable2.docx","url":"https://assets-eu.researchsquare.com/files/rs-9524903/v1/b842ca2cb18af6f3d0870dfc.docx"},{"id":109259404,"identity":"38dadda0-e1ea-4f41-9c75-c2459df268b4","added_by":"auto","created_at":"2026-05-14 11:00:17","extension":"docx","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":17225,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarytable3.docx","url":"https://assets-eu.researchsquare.com/files/rs-9524903/v1/6b98a4f8b12db5826a4d4dbb.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Structural and Vascular Characteristics of PHOMS in Pediatric Pseudopapilledema ","fulltext":[{"header":"Key Message","content":"\u003cp\u003e\u003cstrong\u003eWhat is known\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026bull; Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are increasingly recognized in association with optic disc drusen, myopia, and elevated intracranial pressure, but their structural and vascular characteristics in pediatric pseudopapilledema remain incompletely defined.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is new\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026bull; In pediatric pseudopapilledema, PHOMS-positive eyes demonstrate significantly increased global RNFL thickness without consistent alterations in ganglion cell or OCTA-derived vascular parameters.\u003c/p\u003e\n\u003cp\u003e\u0026bull; Maximum PHOMS diameter independently correlates with RNFL thickness, suggesting that PHOMS size reflects localized axonal crowding rather than disc size or microvascular changes.\u003c/p\u003e\n\u003cp\u003e\u0026bull; In the absence of elevated intracranial pressure, PHOMS appear to behave as a stable structural optic nerve head phenotype rather than a primary microvascular disorder.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003ePeripapillary hyperreflective ovoid mass-like structures (PHOMS) are increasingly recognized on enhanced depth imaging optical coherence tomography (EDI-OCT) as peripapillary hyperreflective configurations located above the level of the Bruch\u0026rsquo;s membrane opening [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Initially considered a variant or precursor of optic disc drusen (ODD), PHOMS are now defined by the Optic Disc Drusen Studies (ODDS) Consortium as a distinct morphologic entity characterized by lateral displacement and herniation of prelaminar nerve fibers [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePHOMS have been reported across a broad spectrum of clinical conditions, including optic disc drusen, tilted discs, myopia, papilledema, idiopathic intracranial hypertension (IIH), and inflammatory optic neuropathies [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Population-based studies in children have demonstrated a prevalence of approximately 8\u0026ndash;9% in otherwise healthy cohorts, with associations noted between PHOMS, axial elongation, and optic disc tilt [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In adult populations, PHOMS have also been identified in large epidemiologic studies, further supporting their non\u0026ndash;disease-specific nature [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe relationship between PHOMS and ODD remains controversial. While some pediatric studies suggest that PHOMS frequently coexist with deep ODD and may represent an early stage in drusen evolution [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], other reports confirm the presence of isolated PHOMS in the absence of detectable drusen or raised intracranial pressure [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Multimodal imaging, including B-scan ultrasonography and fundus autofluorescence, has been emphasized as essential for differentiating PHOMS from buried drusen, particularly in children where drusen may be difficult to visualize clinically [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBeyond their association with structural disc anomalies, PHOMS have also been linked to elevated intracranial pressure. In children with syndromic craniosynostosis, PHOMS were found to correlate strongly with elevated intracranial pressure and concurrent papilledema, and resolution was observed following surgical decompression [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Similarly, studies in patients evaluated for suspected papilledema have demonstrated that PHOMS may occur in IIH but are not specific to this diagnosis [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. These findings suggest that PHOMS may represent a common morphologic response to mechanical or axoplasmic stress at the optic nerve head rather than a disease entity per se.\u003c/p\u003e \u003cp\u003eDespite growing recognition of PHOMS, their structural and vascular characteristics in pediatric pseudopapilledema remain incompletely understood. In particular, it is unclear whether PHOMS are associated with alterations in peripapillary retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) parameters, or optic nerve head microvasculature as assessed by optical coherence tomography angiography (OCTA). Clarifying these associations is clinically relevant to distinguish benign structural variants from early optic neuropathy.\u003c/p\u003e \u003cp\u003eThe aim of the present study was therefore to evaluate structural and vascular characteristics of PHOMS in a pediatric pseudopapilledema cohort, with particular emphasis on RNFL thickness, PHOMS size, Bruch\u0026rsquo;s membrane opening (BMO) diameter, and OCTA-derived vascular parameters.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003e This retrospective study included pediatric patients under 18 years of age who were followed in the Neuro-ophthalmology Unit between January 2023 and June 2025. Ethical approval was obtained from the Ankara Etlik City Hospital Ethics Committee. The study was conducted in accordance with the Declaration of Helsinki. Due to the retrospective design, the requirement for written informed consent was waived.\u003c/p\u003e \u003cp\u003eA total of 38 patients with pseudopapilledema, with or without optic disc drusen (ODD), and 36 age- and sex-matched healthy controls were included. In the pseudopapilledema group, ODD was present in 36 eyes of 18 patients. PHOMS were detected in 23 of 40 eyes.\u003c/p\u003e \u003cp\u003eFor PHOMS-based analyses, in patients with bilateral PHOMS, the eye with the larger maximum PHOMS diameter was selected; in unilateral cases, the affected eye was analyzed. One eye per control subject was randomly selected.\u003c/p\u003e \u003cp\u003eFor ODD-based comparisons, analyses were performed at the eye level and included 36 eyes of 18 ODD patients, 40 eyes of 20 non-ODD pseudopapilledema patients, and 72 eyes of 36 healthy controls.\u003c/p\u003e \u003cp\u003eODD was diagnosed based on combined B-scan ultrasonography and OCT findings. Hyperreflective signals on B-scan were present in all ODD cases. Fundus autofluorescence was performed in selected cases to support the diagnosis.\u003c/p\u003e \u003cp\u003eThe pseudopapilledema group without ODD consisted of patients with stable optic nerve head appearance for at least 6 months, congenitally crowded discs, no evidence of ODD on imaging, normal cerebrospinal fluid opening pressure (\u0026lt;\u0026thinsp;250 mmH₂O), and, when clinically indicated, normal brain MRI findings.\u003c/p\u003e \u003cp\u003eHealthy controls had BCVA\u0026thinsp;\u0026ge;\u0026thinsp;20/20, normal anterior and posterior segment findings, normal visual fields, structurally normal optic nerve heads, and no ocular, neurologic, or systemic disease.\u003c/p\u003e \u003cp\u003eExclusion criteria included age outside 5\u0026ndash;18 years, incomplete data, significant media opacity, motion artifacts, refractive error\u0026thinsp;\u0026gt;\u0026thinsp;\u0026plusmn;\u0026thinsp;6 diopters, prior intraocular surgery, or any ocular/systemic disease affecting retinal or optic nerve parameters.\u003c/p\u003e \u003cp\u003eAll participants underwent comprehensive ophthalmic examination including BCVA, refractive error, axial length (IOLMaster 500, Carl Zeiss Meditec, Jena, Germany), slit-lamp biomicroscopy, and dilated fundus examination.\u003c/p\u003e \u003cp\u003eThe following parameters were included in the analysis: best-corrected visual acuity (BCVA) and spherical equivalent (SE); structural OCT measurements including global and sectoral retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) thickness, focal loss volume (FLV), global loss volume (GLV), Bruch\u0026rsquo;s membrane opening (BMO) distance, and optic disc area; peripapillary choroidal thickness and choroidal vascularity index; and OCTA-derived vascular parameters.\u003c/p\u003e \u003cp\u003eMacular OCTA parameters included vessel density measurements of the superficial and deep capillary plexuses (whole image, foveal, parafoveal, and perifoveal regions), foveal avascular zone (FAZ) area, flow density (FD), and flow area measurements. Peripapillary vascular density was assessed using radial peripapillary capillary (RPC) measurements in sectoral analyses.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eImage Acquisition\u003c/h3\u003e\n\u003cp\u003eAll OCT examinations were performed after pupillary dilation and between 9:00 AM and 12:00 PM to minimize diurnal variation, particularly for choroidal measurements. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003cp\u003ePeripapillary RNFL thickness was measured using SD-OCT (Cirrus HD-OCT 5000, Carl Zeiss Meditec, Dublin, CA, USA) with an optic disc-centered scan protocol.\u003c/p\u003e \u003cp\u003eEDI-OCT and OCTA imaging were performed using the RTVue XR Avanti system (Optovue Inc., Fremont, CA, USA). Macular OCTA scans were obtained using a 6 \u0026times; 6 mm cube centered on the fovea, and optic nerve head scans were obtained using a 4.5 \u0026times; 4.5 mm cube centered on the disc. Superficial and deep capillary plexus vessel densities, radial peripapillary capillary density, foveal avascular zone area, and flow area parameters were automatically calculated using the device software. Only OCTA images with a signal strength index\u0026thinsp;\u0026ge;\u0026thinsp;7 were included in the analysis. Scans with motion artifacts, segmentation errors, or projection artifacts were carefully reviewed and excluded. Projection artifacts were minimized using the device\u0026rsquo;s built-in algorithm.\u003c/p\u003e \u003cp\u003eThe presence or absence of PHOMS was determined according to the Optic Disc Drusen Studies (ODDS) Consortium definition using optic disc\u0026ndash;centered horizontal and vertical enhanced depth imaging (EDI) OCT scans.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] PHOMS were defined as peripapillary hyperreflective ovoid mass-like structures located above the level of the Bruch\u0026rsquo;s membrane opening. For quantitative analysis, the horizontal and vertical diameters of each PHOMS were measured on EDI-OCT images. The larger of the horizontal and vertical diameters was defined as the maximum PHOMS diameter to represent PHOMS size.\u003c/p\u003e \u003cp\u003eCVI was calculated on EDI-OCT images using Fiji software (ImageJ, NIH, Bethesda, MD, USA) following a previously described binarization method. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] A standardized 1000-\u0026micro;m peripapillary choroidal region extending from the Bruch\u0026rsquo;s membrane opening was manually selected. Images were converted to 8-bit format and binarized using the Niblack auto-local threshold. CVI was defined as the ratio of luminal area to total choroidal area.\u003c/p\u003e \u003cp\u003eBruch\u0026rsquo;s membrane opening (BMO) distance was measured on the horizontal EDI-OCT B-scan passing through the center of the optic disc, as previously described in optic nerve head morphometric studies [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. BMO distance was defined as the linear distance between the nasal and temporal edges of the Bruch\u0026rsquo;s membrane opening. In eyes with coexisting optic disc drusen (ODD), BMO measurements were not performed due to potential distortion of the Bruch\u0026rsquo;s membrane contour and difficulty in reliably identifying BMO margins.\u003c/p\u003e \u003cp\u003eAll measurements were performed by a single masked observer to ensure consistency.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using IBM SPSS Statistics version 23 (IBM Corp., Armonk, NY, USA) and R software version 4.4.1 (R Foundation for Statistical Computing, Vienna, Austria).\u003c/p\u003e \u003cp\u003eNormality of data distribution was assessed using the Shapiro\u0026ndash;Wilk and Kolmogorov\u0026ndash;Smirnov tests. Continuous variables with normal distribution were compared between two groups using the independent samples t-test, while non-normally distributed variables were compared using the Mann\u0026ndash;Whitney U test.\u003c/p\u003e \u003cp\u003eCorrelations between normally distributed continuous variables were evaluated using Pearson\u0026rsquo;s correlation analysis, whereas Spearman\u0026rsquo;s rank correlation was used for non-normally distributed variables.\u003c/p\u003e \u003cp\u003eAssociations between categorical variables were analyzed using the chi-square test with Yates\u0026rsquo; correction.\u003c/p\u003e \u003cp\u003eLinear regression analysis was performed to evaluate the effects of independent variables on normally distributed dependent variables. For non-normally distributed dependent variables, robust regression analysis was conducted using the MASS package in R.\u003c/p\u003e \u003cp\u003eTo account for inter-eye correlation, generalized estimating equations (GEE) were used for group comparisons of quantitative variables at the eye level. Bonferroni correction was applied for multiple comparisons.\u003c/p\u003e \u003cp\u003eContinuous variables are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median (minimum\u0026ndash;maximum), as appropriate. Categorical variables are presented as frequency (percentage). A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cb\u003e1. Demographic Characteristics\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThere was no significant difference between the groups in terms of sex distribution (female: 71.1% in the patient group vs. 69.4% in the control group, p\u0026thinsp;=\u0026thinsp;1.000). The mean age was 12.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0 years in the patient group and 12.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8 years in the control group, with no statistically significant difference between the groups (p\u0026thinsp;=\u0026thinsp;0.913). The demographic characteristics of the study population are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic Characteristics of the Study Population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatients (n\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControls (n\u0026thinsp;=\u0026thinsp;36)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27 (71.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25 (69.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11 (28.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11 (30.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12.82\u0026thinsp;\u0026plusmn;\u0026thinsp;4.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12.92\u0026thinsp;\u0026plusmn;\u0026thinsp;3.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.913\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eCategorical variables were compared using the chi-square test with Yates correction. Continuous variables were compared using the independent samples t-test. Data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or frequency (%).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003e2. Single-Eye Analysis: PHOMS-Positive Eyes vs Controls\u003c/b\u003e \u003c/p\u003e \u003cp\u003eA total of 23 PHOMS-positive eyes and 36 healthy control eyes were included in the single-eye analysis.\u003c/p\u003e \u003cp\u003eAmong all evaluated parameters, global RNFL thickness was significantly higher in PHOMS-positive eyes compared to controls (p\u0026thinsp;=\u0026thinsp;0.018) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of Structural and OCTA-Derived Parameters Between PHOMS-Positive Eyes and Healthy Controls\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePHOMS-Positive Eyes (n\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHealthy Controls (n\u0026thinsp;=\u0026thinsp;36)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStructural parameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpherical equivalent (D)\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;1.25 (\u0026minus;\u0026thinsp;5.00 to 4.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;0.13 (\u0026minus;\u0026thinsp;5.00 to 1.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.171\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMO diameter (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.067\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOptic disc area (mm\u0026sup2;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.85\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.763\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlobal RNFL thickness (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e110.07\u0026thinsp;\u0026plusmn;\u0026thinsp;22.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97.73\u0026thinsp;\u0026plusmn;\u0026thinsp;8.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.018\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage GCC thickness (\u0026micro;m)\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e103.00 (96.00\u0026ndash;121.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103.00 (95.00\u0026ndash;116.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.932\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChoroidal vascularity index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.71\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.177\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOCTA-derived parameters\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSCP whole vessel density (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48.94\u0026thinsp;\u0026plusmn;\u0026thinsp;1.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.61\u0026thinsp;\u0026plusmn;\u0026thinsp;1.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.091\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDCP whole vessel density (%)\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53.10 (48.40\u0026ndash;55.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.40 (47.90\u0026ndash;54.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.822\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFAZ area (mm\u0026sup2;)\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.20 (0.05\u0026ndash;0.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.22 (0.07\u0026ndash;0.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.071\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadial peripapillary capillary density (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50.53\u0026thinsp;\u0026plusmn;\u0026thinsp;1.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.32\u0026thinsp;\u0026plusmn;\u0026thinsp;2.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.123\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median (range).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u0026dagger; Mann\u0026ndash;Whitney U test; other comparisons performed using independent samples t-test.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eBMO: Bruch\u0026rsquo;s membrane opening; RNFL: retinal nerve fiber layer; GCC: ganglion cell complex; SCP: superficial capillary plexus; DCP: deep capillary plexus; FAZ: foveal avascular zone.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNo statistically significant differences were observed between groups regarding spherical equivalent, Bruch\u0026rsquo;s membrane opening (BMO) diameter, optic disc area, ganglion cell complex thickness, choroidal vascularity index (CVI), or OCTA-derived vascular parameters including radial peripapillary capillary density, superficial capillary plexus whole image vessel density, deep capillary plexus whole image vessel density, and foveal avascular zone area (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cb\u003e3. Correlation Analyses\u003c/b\u003e \u003c/p\u003e \u003cp\u003eCorrelation analyses were performed within the PHOMS-positive group (n\u0026thinsp;=\u0026thinsp;23 eyes) to evaluate the associations between maximum PHOMS diameter, Bruch\u0026rsquo;s membrane opening (BMO) diameter, and structural and vascular parameters.\u003c/p\u003e \u003cp\u003eMaximum PHOMS diameter demonstrated a significant positive correlation with global RNFL thickness (r\u0026thinsp;=\u0026thinsp;0.526, p\u0026thinsp;=\u0026thinsp;0.010). No significant correlations were observed between maximum PHOMS diameter and BMO diameter, ganglion cell complex thickness, mean choroidal vascularity index (CVI), or peripapillary radial capillary density (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelation Between Maximum PHOMS Diameter and Ocular Parameters in PHOMS-Positive Eyes (n\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCorrelation coefficient (r)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMO diameter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;0.323\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.133\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChoroidal vascularity index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;0.153\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.518\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage GCC thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.560\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadial peripapillary capillary density\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.266\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.232\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlobal RNFL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.526\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.010\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eCorrelations were assessed using Spearman\u0026rsquo;s rank correlation coefficient.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eBMO: Bruch\u0026rsquo;s membrane opening; GCC: ganglion cell complex; RNFL: retinal nerve fiber layer.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWithin the PHOMS-positive group, BMO diameter was not significantly associated with optic disc area (r\u0026thinsp;=\u0026thinsp;0.243, p\u0026thinsp;=\u0026thinsp;0.348), RNFL thickness, maximum PHOMS diameter, or spherical equivalent (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In contrast, in healthy control eyes, BMO diameter showed a significant positive correlation with optic disc area (r\u0026thinsp;=\u0026thinsp;0.675, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), whereas no significant correlations were found with RNFL thickness or spherical equivalent (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) \u003cb\u003e(\u003c/b\u003eSupplementary Tables\u0026nbsp;1 and 2\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cb\u003e4. Regression Analyses\u003c/b\u003e \u003c/p\u003e \u003cp\u003eA multivariable linear regression analysis was performed in PHOMS-positive eyes to evaluate the independent effects of maximum PHOMS diameter and BMO diameter on global RNFL thickness (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariable Linear Regression Analysis for Global RNFL Thickness and RPC density in PHOMS-Positive Eyes (n\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDependent variable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndependent variable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eB (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStandardized β\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGlobal RNFL thickness\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMaximum PHOMS diameter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.055 (0.002 to 0.109)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.437\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBMO diameter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.768 (\u0026minus;\u0026thinsp;21.237 to 32.774)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.091\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.661\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRPC density\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMaximum PHOMS diameter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.003 (\u0026minus;\u0026thinsp;0.002 to 0.008)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.321\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.218\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGlobal RNFL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.002 (\u0026minus;\u0026thinsp;0.043 to 0.047)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.928\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cb\u003eModel statistics\u003c/b\u003e\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u0026bull; \u003cb\u003eGlobal RNFL thickness model\u003c/b\u003e: F(2,20)\u0026thinsp;=\u0026thinsp;2.309; R\u0026sup2; = 0.188; Adjusted R\u0026sup2; = 0.107; Durbin\u0026ndash;Watson\u0026thinsp;=\u0026thinsp;1.747\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u0026bull; \u003cb\u003eRPC density model\u003c/b\u003e: F(2,19)\u0026thinsp;=\u0026thinsp;1.185; R\u0026sup2; = 0.111\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAlthough the overall model did not reach statistical significance (F(2,20)\u0026thinsp;=\u0026thinsp;2.309, p\u0026thinsp;=\u0026thinsp;0.125), maximum PHOMS diameter remained independently associated with RNFL thickness (β\u0026thinsp;=\u0026thinsp;0.44, p\u0026thinsp;=\u0026thinsp;0.044), whereas BMO diameter was not significantly associated with RNFL thickness (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eIn PHOMS-positive eyes, linear regression analysis demonstrated that neither maximum PHOMS diameter nor RNFL thickness was significantly associated with peripapillary radial capillary density (F(2.19)\u0026thinsp;=\u0026thinsp;1.185, p\u0026thinsp;=\u0026thinsp;0.327). Linear regression analysis showed that neither maximum PHOMS diameter nor RNFL thickness was significantly associated with peripapillary vessel density (F(2,19)\u0026thinsp;=\u0026thinsp;1.185; p\u0026thinsp;=\u0026thinsp;0.327).\u003c/p\u003e \u003cp\u003e \u003cb\u003e5. Group Comparisons Using GEE\u003c/b\u003e \u003c/p\u003e \u003cp\u003eGroup comparisons were performed using generalized estimating equations (GEE) to account for inter-eye correlation (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eGroup Comparisons Using Generalized Estimating Equations (GEE)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eODD-Positive Eyes (n\u0026thinsp;=\u0026thinsp;36)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-ODD Pseudopapilledema (n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHealthy Controls (n\u0026thinsp;=\u0026thinsp;72)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlobal RNFL thickness (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e132.27\u0026thinsp;\u0026plusmn;\u0026thinsp;30.36ᵃ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e102.17\u0026thinsp;\u0026plusmn;\u0026thinsp;16.08ᵇ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e97.55\u0026thinsp;\u0026plusmn;\u0026thinsp;8.54ᵇ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage GCC thickness (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e107.31\u0026thinsp;\u0026plusmn;\u0026thinsp;7.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e104.54\u0026thinsp;\u0026plusmn;\u0026thinsp;5.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e104.10\u0026thinsp;\u0026plusmn;\u0026thinsp;5.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.682\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadial peripapillary capillary density (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e50.75\u0026thinsp;\u0026plusmn;\u0026thinsp;1.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e50.52\u0026thinsp;\u0026plusmn;\u0026thinsp;2.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e51.15\u0026thinsp;\u0026plusmn;\u0026thinsp;1.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.287\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChoroidal vascularity index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.698\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cb\u003eFootnote\u003c/b\u003e\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eGroup comparisons were performed using generalized estimating equations to account for inter-eye correlation.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eBonferroni correction was applied for multiple comparisons.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eRNFL comparisons were adjusted for BMO diameter and spherical equivalent.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eGCC and RPC comparisons were adjusted for global RNFL thickness.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eDifferent superscript letters indicate statistically significant differences between groups.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eRNFL: retinal nerve fiber layer; GCC: ganglion cell complex.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eA significant difference was observed among the three groups only for global RNFL thickness (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). RNFL thickness was significantly higher in the ODD group (132.27\u0026thinsp;\u0026plusmn;\u0026thinsp;30.36 \u0026micro;m) compared with both the non-ODD pseudopapilledema group (102.17\u0026thinsp;\u0026plusmn;\u0026thinsp;16.08 \u0026micro;m) and healthy controls (97.55\u0026thinsp;\u0026plusmn;\u0026thinsp;8.54 \u0026micro;m). No significant difference was found between the non-ODD and healthy control groups.\u003c/p\u003e \u003cp\u003eNo statistically significant differences were observed among groups for mean CVI, average GCC thickness, or peripapillary radial capillary density (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cb\u003e6. Supplementary Analyses\u003c/b\u003e \u003c/p\u003e \u003cp\u003eAdditional structural and vascular parameters were analyzed using GEE with Bonferroni correction and are presented in Supplementary Table\u0026nbsp;3.\u003c/p\u003e \u003cp\u003eAmong structural parameters, BMO diameter differed significantly among groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). FLV values were higher in the ODD group (p\u0026thinsp;=\u0026thinsp;0.010), whereas GLV and average GCC thickness did not differ significantly.\u003c/p\u003e \u003cp\u003eAmong vascular parameters, most macular and peripapillary OCTA metrics did not differ significantly across groups. A sectoral difference was observed in nasal-inferior RPC (p\u0026thinsp;=\u0026thinsp;0.006); however, no consistent vascular pattern was observed across sectors.\u003c/p\u003e \u003cp\u003eSectoral RNFL measurements were significantly higher in the ODD group across multiple quadrants (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this pediatric cohort, PHOMS-positive eyes demonstrated significantly increased global RNFL thickness compared with healthy controls. Maximum PHOMS diameter showed a positive correlation with RNFL thickness and remained significantly associated after adjustment for BMO diameter. In contrast, no consistent differences were observed in macular or peripapillary vascular parameters, CVI, or average GCC thickness.\u003c/p\u003e \u003cp\u003eSimilar findings were confirmed in eye-level GEE analyses, where RNFL thickness differed significantly among ODD-positive, non-ODD pseudopapilledema, and healthy eyes, whereas GCC, RPC density, and CVI showed no significant differences. The lack of association between PHOMS size and BMO diameter is noteworty, as BMO is considered a surrogate marker of scleral canal size and optic nerve head configuration. Our results indicate that PHOMS enlargement may occur independently of disc size, supports the concept that PHOMS represent localized axoplasmic stasis rather than a simple consequence of anatomical crowding at the level of the scleral canal.\u003c/p\u003e \u003cp\u003eInterestingly, BMO diameter was correlated with optic disc area in healthy controls but not in PHOMS-positive eyes, which may indicate a disruption of the normal anatomical relationship between disc size and scleral canal dimensions in the presence of PHOMS. Furthermore, the absence of correlation between PHOMS diameter and peripapillary capillary density or choroidal vascularity index suggests that vascular alterations may not play a primary role in PHOMS development.\u003c/p\u003e \u003cp\u003eTaken together, these findings highlight that PHOMS size is selectively associated with RNFL thickness, while remaining largely independent of optic disc morphology and vascular parameters.\u003c/p\u003e \u003cp\u003ePHOMS were initially described as peripapillary hyperreflective configurations above the level of the Bruch\u0026rsquo;s membrane opening and are now recognized as a distinct morphologic entity separate from optic disc drusen (ODD) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Importantly, PHOMS have been observed in both optic disc edema and pseudopapilledema, supporting the notion that they are not specific to a single underlying pathology [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, their relationship with ODD remains debated. A recent pediatric study reported that PHOMS were consistently observed in conjunction with deep or superficial ODD and suggested that RNFL thickening may reflect early drusen stages, with subsequent thinning as drusen become superficial [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In contrast, PHOMS-positive eyes in our cohort did not show clinically detectable ODD, and RNFL thickening persisted independently of visible drusen. Furthermore, ultrasonographic differentiation studies emphasize that PHOMS and ODD represent structurally distinct entities, even when coexisting [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Together, these findings support the concept that PHOMS can occur as an isolated structural configuration rather than merely as a secondary manifestation of buried drusen.\u003c/p\u003e \u003cp\u003eThe association between PHOMS and RNFL thickness has been described in both pediatric and adult populations. Population-based studies in children have demonstrated PHOMS in otherwise healthy cohorts, often in association with myopia and disc morphology variations [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Similarly, in adult epidemiologic data, PHOMS were linked to optic disc configuration without clear evidence of neurodegeneration [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In highly myopic eyes, larger PHOMS area has been associated with increased RNFL thickness [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Our findings extend this body of evidence by demonstrating that PHOMS size itself, rather than BMO diameter, appears to be associated with RNFL thickness in pediatric pseudopapilledema.\u003c/p\u003e \u003cp\u003eThe vascular implications of PHOMS remain controversial. Some OCTA studies have suggested altered peripapillary vessel density in association with PHOMS [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], whereas others have demonstrated preserved or even increased radial peripapillary capillary signals [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Moreover, PHOMS have been described in diverse clinical settings including idiopathic intracranial hypertension (IIH), papilledema, and inflammatory optic neuropathies, reinforcing the concept that PHOMS are not disease-specific [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In children with syndromic craniosynostosis, PHOMS were strongly associated with elevated intracranial pressure and were shown to resolve following surgical decompression, suggesting a dynamic structural response to mechanical stress [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Kirik et al. evaluated peripapillary choroidal vascularity in myopic pediatric eyes with PHOMS and reported a tendency toward reduced choroidal area parameters with relatively higher CVI values. In contrast, our pseudopapilledema cohort did not demonstrate significant CVI differences, suggesting that peripapillary choroidal vascularity may not represent a consistent feature of PHOMS across different pediatric populations [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. These heterogeneous observations suggest that PHOMS may represent a final common morphologic response to axoplasmic stasis or mechanical crowding at the optic nerve head.\u003c/p\u003e \u003cp\u003eClinically, the selective involvement of RNFL thickness without accompanying ganglion cell loss or diffuse vascular alteration is important. Recognition of this pattern may help differentiate benign structural PHOMS from early optic neuropathy and may reduce unnecessary diagnostic escalation in asymptomatic pediatric patients.\u003c/p\u003e \u003cp\u003eThis study is limited by its cross-sectional design and relatively small number of PHOMS-positive eyes. Although the sample size is modest, the use of GEE and consistent findings across analyses support robustness. BMO measurements were not performed in ODD-positive eyes due to potential distortion of Bruch\u0026rsquo;s membrane margins. In addition, the absence of longitudinal follow-up limits assessment of temporal changes in PHOMS morphology. Longitudinal studies are required to determine whether PHOMS-associated RNFL thickening remains stable over time or evolves with disc morphology changes.\u003c/p\u003e \u003cp\u003eIn conclusion, pediatric PHOMS are associated with increased RNFL thickness, and PHOMS size appears to be associated with RNFL variation. The absence of consistent vascular or ganglion cell alterations supports the interpretation of PHOMS as a structural optic nerve head phenotype whose clinical significance depends on the accompanying pathophysiologic context.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement:\u003c/strong\u003e None.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e: The authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e This study was approved by the Ethical Committee of Ankara Etlik City Hospital. Due to the retrospective design, the requirement for written informed consent was waived. The study was conducted in accordance with the principles of the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e The data that support the findings of this study are not publicly available due to patient privacy and ethical restrictions but are available from the corresponding author upon reasonable request and with appropriate ethical approval.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;SCD: Conceptualization, Methodology, Data curation, Formal analysis, Writing \u0026ndash; original draft.\u003cbr\u003e\u0026nbsp;SCD,FU, IMS: Data curation, Writing \u0026ndash; review \u0026amp; editing.\u003cbr\u003e\u0026nbsp;SCD, FU, IMS : Formal analysis, Supervision, Writing \u0026ndash; review \u0026amp; editing.\u003cbr\u003e\u0026nbsp;All authors approved the final version of the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eXiao D, Lhamo T, Meng Y, Xu Y, Chen C. 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Ophthalmology. 2025;132:1402\u0026ndash;10. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ophtha.2025.07.025\u003c/span\u003e\u003cspan address=\"10.1016/j.ophtha.2025.07.025\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJeon-Chapman JG, Estrela T, Zurakowski D, Chang YH, Dagi LR, Gise RA. Prevalence and clinical associations of peripapillary hyperreflective ovoid mass-like structures in craniosynostosis. J Neuroophthalmol. 2025;45:483\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/WNO.0000000000002315\u003c/span\u003e\u003cspan address=\"10.1097/WNO.0000000000002315\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHe G, Zhang X, Zhuang X, Zeng Y, Chen X, Gan Y, et al. 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Sci Rep. 2016;6:21090. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/srep21090\u003c/span\u003e\u003cspan address=\"10.1038/srep21090\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHosseini H, Nassiri N, Azarbod P, Giaconi J, Chou T, Caprioli J, et al. Measurement of the optic disc vertical tilt angle with spectral-domain optical coherence tomography and influencing factors. Am J Ophthalmol. 2013;156:737\u0026ndash;44. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ajo.2013.05.036\u003c/span\u003e\u003cspan address=\"10.1016/j.ajo.2013.05.036\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMalmqvist L, Sibony PA, Fraser CL, Wegener M, Heegaard S, Skougaard M, et al. Peripapillary ovoid hyperreflectivity in optic disc edema and pseudopapilledema. Ophthalmology. 2018;125:1662\u0026ndash;4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ophtha.2018.04.036\u003c/span\u003e\u003cspan address=\"10.1016/j.ophtha.2018.04.036\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKirik F, Dizdar Yiğit D, Sevik MO, Ert\u0026uuml;rk KM, İskandarov F, Şahin \u0026Ouml;, \u0026Ouml;zdemir H. Peripapillary choroidal vascularity of paediatric myopic eyes with peripapillary hyperreflective ovoid mass-like structures. Acta Ophthalmol. 2024. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/aos.16761\u003c/span\u003e\u003cspan address=\"10.1111/aos.16761\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":false,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Peripapillary hyperreflective ovoid mass-like structures, Pediatric pseudopapilledema, Retinal nerve fiber layer, Optical coherence tomography angiography, Optic disc drusen","lastPublishedDoi":"10.21203/rs.3.rs-9524903/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9524903/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e\u003cbr\u003e\nTo evaluate the structural and vascular characteristics of peripapillary hyperreflective ovoid mass-like structures (PHOMS) in pediatric pseudopapilledema and to investigate their relationship with retinal nerve fiber layer (RNFL) thickness and optic nerve head parameters.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003cbr\u003e\nThis retrospective study included 38 pediatric patients with pseudopapilledema (with or without optic disc drusen [ODD]) and 36 age- and sex-matched healthy controls. Structural optical coherence tomography (OCT) and OCT angiography (OCTA) parameters were analyzed, including global and sectoral RNFL thickness, ganglion cell complex (GCC) metrics, Bruch’s membrane opening (BMO) diameter, choroidal vascularity index (CVI), radial peripapillary capillary (RPC) density, and macular vascular parameters. In PHOMS-positive eyes, maximum PHOMS diameter was measured on enhanced depth imaging OCT. Group comparisons were performed using generalized estimating equations. Correlation and regression analyses were conducted to evaluate associations between PHOMS size and structural or vascular parameters.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003cbr\u003e\nIn single-eye analysis, PHOMS-positive eyes (n = 23) demonstrated significantly higher global RNFL thickness compared with controls (p = 0.018). No significant differences were observed in spherical equivalent, BMO diameter, optic disc area, GCC thickness, CVI, or OCTA-derived vascular parameters (all p \u0026gt; 0.05). Maximum PHOMS diameter showed a significant positive correlation with global RNFL thickness (r = 0.526, p = 0.010) and remained independently associated in multivariable regression analysis (β = 0.44, p = 0.044). In eye-level analyses including ODD-positive, ODD-negative, and healthy eyes, RNFL thickness differed significantly among groups (p \u0026lt; 0.001), whereas no consistent differences were observed in vascular or ganglion cell parameters.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003cbr\u003e\nIn pediatric pseudopapilledema, PHOMS are associated with increased RNFL thickness, and PHOMS size independently predicts RNFL variation. The absence of consistent vascular or ganglion cell alterations suggests that PHOMS predominantly represent a structural optic nerve head phenotype rather than a generalized microvascular disorder. Recognition of this pattern may aid in differentiating benign structural variants from early optic neuropathy in children.\u003c/p\u003e","manuscriptTitle":"Structural and Vascular Characteristics of PHOMS in Pediatric Pseudopapilledema ","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-14 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