Retinal Microvascular and RNFL Changes After Bilateral Congenital Cataract Surgery: Preliminary Results from an Exploratory OCT/OCTA Analysis

Retinal Microvascular and RNFL Changes After Bilateral Congenital Cataract Surgery: Preliminary Results from an Exploratory OCT/OCTA Analysis | 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 Retinal Microvascular and RNFL Changes After Bilateral Congenital Cataract Surgery: Preliminary Results from an Exploratory OCT/OCTA Analysis Mehmet Omer Kiristioglu, Ahmet Tuncer Ozmen, Meral Yildiz, Ahmet Akcan, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9044196/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background Early visual deprivation and subsequent surgical rehabilitation in congenital cataracts may induce long-term structural retinal changes. This study aimed to investigate retinal microvascular and retinal nerve fiber layer (RNFL) alterations in children after bilateral congenital cataract extraction followed by secondary intraocular lens (IOL) implantation, using optical coherence tomography angiography (OCTA) combined with an OCTAVA-based quantitative analysis. Methods This retrospective, cross-sectional exploratory study included children who underwent bilateral congenital cataract extraction before one year of age with subsequent secondary IOL implantation. Age-matched healthy children served as controls. All participants underwent standardized ophthalmic examinations, spectral-domain OCT, and 6×6 mm macular and peripapillary OCTA imaging. Quantitative vascular metrics included mean vessel diameter, branchpoint density, and tortuosity. RNFL thickness was assessed in all quadrants. To account for significant baseline differences, imaging metrics were corrected for magnification effects, and between-group comparisons were adjusted for age, axial length (AL), and spherical equivalent (SE) using generalized estimating equations (GEE). Results Eighteen pseudophakic patients (36 eyes; median age 8 years) and 17 controls (34 eyes; median age 9 years) were included. Pseudophakic eyes were significantly more myopic and had longer AL than controls (p < 0.05). In GEE-adjusted models, OCTA demonstrated increased mean vessel diameter (p = 0.001), higher tortuosity (p < 0.001), and reduced branchpoint density (p = 0.004) in the study group. No significant group differences were observed for choroidal thickness, choroidal vascularity index, or foveal avascular zone. Adjusted RNFL thickness was significantly greater in the temporal (p = 0.006) and inferotemporal (p = 0.023) sectors of the study group, while global RNFL thickness did not differ. Conclusions Children undergoing bilateral congenital cataract surgery with secondary IOL implantation exhibit persistent microvascular remodeling—characterized by dilated, more tortuous vessels with reduced branching—and localized temporal RNFL thickening despite visual rehabilitation. These findings provide preliminary evidence of distinct structural alterations that warrant confirmation in larger longitudinal studies. Congenital cataract Optical coherence tomography angiography Retinal microvasculature Amblyopia Retinal nerve fiber layer Figures Figure 1 Figure 2 Figure 3 Introduction Congenital or infantile cataracts—lens opacities present within the first year of life—are uncommon but remain a major cause of childhood blindness worldwide ( 1 , 2 ). Because the first years of life are critical for visual development, lens opacity during this period can disrupt normal visual input, leading to permanent changes in ocular growth and neural visual pathways if left untreated ( 3 , 4 ). Early cataract removal, followed by optical correction and amblyopia therapy, is essential to optimize visual potential, with secondary intraocular lens (IOL) implantation commonly performed once the eye has grown sufficiently to ensure refractive stability ( 5 ). While structural outcomes after pediatric cataract surgery have been examined in unilateral and bilateral cases, most imaging studies have focused on macular thickness or retinal nerve fiber layer (RNFL) profiles, with limited attention to the retinal microvasculature—particularly in bilaterally operated children. Amblyopia-related macular changes have been reported in both anisometropic and strabismic cases, but these findings may not fully represent the unique effects of bilateral visual deprivation caused by congenital cataracts ( 6 , 7 ). Fourier-domain optical coherence tomography (OCT) has revealed that even when macular architecture appears grossly normal after surgery, subtle postoperative thickening can persist ( 8 ). Optical coherence tomography angiography (OCTA) extends this structural assessment by visualizing the retinal and peripapillary microvasculature in a depth-resolved, non-invasive manner. Although OCTA has been utilized in pediatric conditions such as anisometropic amblyopia, retinopathy of prematurity, and uveitis, to our knowledge, it has not been systematically applied to evaluate eyes following bilateral congenital cataract extraction and secondary IOL implantation. This study addresses this gap by combining OCTA with the OCTAVA platform to perform a comprehensive, quantitative analysis of vascular network morphology. By measuring these specific OCTA parameters alongside RNFL thickness, we aimed to detect subtle microvascular and structural alterations that may persist despite successful surgical and visual rehabilitation—changes that might remain undetected using conventional OCT metrics alone. Materials and Methods Study Design and Ethics This retrospective, cross-sectional and comparative study included pediatric patients who had undergone bilateral congenital cataract extraction followed by secondary IOL implantation. In this retrospective study, imaging and clinical data were retrieved from postoperative visits conducted between January 2024 and February 2025 at Bursa Uludağ University Faculty of Medicine, with all included examinations performed ≥ 12 months after surgery. The study was approved by the Institutional Review Board of Bursa Uludağ University Faculty of Medicine (Ethics approval no: 2025/8–17; Decision no: 621-8/17, dated 30 April 2025) and conducted in accordance with the Declaration of Helsinki. Participants Eligible patients met several criteria: a confirmed diagnosis of bilateral congenital cataract, birth after 37 weeks’ gestation, primary bilateral cataract extraction before 1 year of age, subsequent secondary IOL implantation (typically around 3 years of age), and at least one year of postoperative follow-up after the IOL implantation. All imaging was obtained at ages 4–16 years, and best-corrected visual acuity had to be at least 20/400 in each operated eye. Initially, a total of 42 patients were recruited (21 in the study group and 21 in the control group); however, due to insufficient OCTA image quality, poor cooperation, and missing data, 3 patients from the study group and 4 patients from the control group were excluded, leaving 18 and 17 patients, respectively, for the final analysis. Healthy, age-matched children without any known systemic or ocular diseases were recruited as controls. In addition to being free of ocular/systemic pathology, the same exclusion criteria applied to the study group were also applied to the controls to ensure comparability. Between-group differences in axial length (AL) and refractive status were modeled in all GEE analyses (covariates: age, AL, SE). For both study and control groups, exclusion criteria were summarized in Table 1. No patient with these conditions was present in the included cohort. Table 1. Exclusion criterias Anterior segment abnormalities (other than pseudophakia) Corneal pathology (e.g., edema) Ocular trauma (excluding cataract surgery) Aphakic glaucoma (past or present) Retinal or optic nerve pathology (e.g., dystrophies, atrophy, coloboma, tilted disc, myopic crescent, visible optic disc drusen) History of pars plana vitrectomy or glaucoma surgery History of premature retinopathy Severe amblyopia, nystagmus, or manifest strabismus High refractive errors (spherical equivalent 2 mm Surgical Technique All cataract extractions were performed under general anesthesia by the same surgical team of experienced pediatric and anterior segment surgeons using a standardized technique. Limbal incisions were made, the anterior capsule was stained with trypan blue, and a 5-mm continuous curvilinear capsulorrhexis was created. Lens aspiration was performed using bimanual irrigation/aspiration. Posterior capsulorrhexis and limited anterior vitrectomy were conducted with triamcinolone-assisted vitreous visualization. Secondary IOL implantation (Alcon SN60AT) was performed at approximately age 3 in the ciliary sulcus with optic capture. Postoperative management included optical correction with spectacles or contact lenses and alternating occlusion therapy of the fellow eye for half of waking hours. Prescriptions were updated if the refractive error changed > 1.00 D during 3-month follow-up visits. Ophthalmic Examination All participants underwent a standardized ophthalmic evaluation, which included best-corrected visual acuity measurement, intraocular pressure assessment, slit-lamp biomicroscopy, tear film evaluation, dilated fundus examination, and ocular biometry using the Lenstar 500 (Haag-Streit AG, Köniz, Switzerland). Imaging Protocol Retinal and optic nerve head microvasculature were imaged with the DRI OCT Triton (Topcon, Tokyo, Japan). Each eye underwent both a 6×6 mm macular scan and a 6×6 mm optic nerve head scan. Only scans with IQS > 40 were analyzed. The refractive error was entered into the device software prior to acquisition to minimize optical aberrations. All imaging was performed between 12:00 and 16:00 by the same examiner to reduce diurnal variation effects. OCTA image processing, slab definitions, and scaling. Because only refractive error (not AL) was entered into IMAGEnet at acquisition, device-level lateral scaling was not applied. Therefore, metrics derived from physical dimensions were corrected offline using Bennett–Littmann scaling with a unity reference axial length AL reference = 23.82 mm. Length-type metrics (e.g., MD, MED, TVL) were multiplied by (AL-1.82)/(AL reference -1.82) area-type metrics by its square. Percentage area measures (e.g., VAD %) were not altered. To avoid double-correction, exported metadata were inspected; when pixel size did not vary across eyes, external scaling was applied. As a sensitivity analysis, models were repeated without magnification correction; inferences were unchanged. We repeated all analyses with magnification-corrected values. Analyses were performed exclusively on the superficial capillary plexus (SCP). The SCP slab was defined per device default from the internal limiting membrane (ILM) to the IPL/INL boundary, and SCP en face angiograms were generated using maximum-intensity projection within the slab. For peripapillary analyses, the radial peripapillary capillaries (RPC) slab was used (from the ILM to the lower boundary of the RNFL). The deep capillary plexus (DCP) and choriocapillaris were excluded from the analysis, as the deeper layers in pediatric patients are highly susceptible to projection artifacts from the superficial vessels and motion artifacts caused by fixation difficulties ( 9 ). All automatic segmentations were reviewed by a grader masked to group allocation; minor boundary misalignments were manually corrected. Scans with uncorrectable segmentation errors were planned to be excluded from the analysis; however, all 70 scans (36 in the study group and 34 in the control group) that passed the initial image quality criteria had correctable segmentations and were successfully included in the final quantitative analysis. Optical Coherence Tomography Assessments Peripapillary retinal nerve fiber layer (RNFL) thickness and choroidal assessments were performed using the Heidelberg Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany). For RNFL evaluation, a standard peripapillary circular scan (3.4 mm diameter) centered on the optic disc was obtained. Global and sectoral RNFL thicknesses were calculated automatically by the device's software. All RNFL segmentations were meticulously reviewed and, if necessary, manually corrected by an experienced ophthalmologist blinded to the participants' clinical status. Subfoveal choroidal thickness (CT) was measured perpendicularly from the retinal pigment epithelium to the sclerochoroidal junction in four quadrants (0.5 mm and 1.5 mm from the fovea) using enhanced depth imaging (EDI) mode with a 9.0 mm seven-line scan centered on the foveola. The auto-rescan function was used for consistency. Choroidal vascularity index (CVI) was calculated from a 1.5 mm wide subfoveal region of interest using ImageJ software (v2.0.0, NIH, Bethesda, MD, USA). Three large choroidal vessels (> 100 µm) were sampled to determine average reflectivity, after which images were binarized using Niblack’s thresholding method, converted to RGB, and the luminal area was segmented with the Threshold tool. CVI was computed as the ratio of luminal to total choroidal area, following previously described protocols ( 10 , 11 ). All choroidal thickness and CVI measurements were performed by a masked, experienced ophthalmologist blinded to group allocation. OCTA Quantitative Analysis Motion and projection artifacts were suppressed using the device’s built-in software, which incorporates active eye tracking and projection-artifact removal. For each scan, an image quality score (IQS; 0–100) was generated by the system, and scans with an IQS < 40 were excluded. To account for magnification effects, images were adjusted using Littmann's method and the Bennett formula ( 12 ). OCTA scans were then exported from the DRI OCT Triton using IMAGEnet 6 software (v1.23; Topcon Healthcare) and analyzed with MATLAB (MathWorks, Natick, MA, USA) integrated with the OCTAVA platform. Binarization and skeletonization were applied to each image before quantitative measurement. Vessel diameters were calculated from the distance transform of the binarized image, branchpoints were detected automatically and verified manually, tortuosity was calculated for each segment and averaged, and fractal dimension (FD) was computed via box-counting analysis. All OCTA analyses were performed by an observer masked to the participants’ clinical status. (A detailed description and the potential biological relevance of each evaluated metric are summarized in Table 2 ). Table 2 Adapted Summary of Quantitative Metrics for Microvascular Network Architecture in OCTA (Adapted from Untracht et al., 2021 [( 40 )]). Metric Unit Description Potential Biological Relevance Vessel area density (VAD) % Ratio of perfused blood vessel area (from binarized OCTA MIP image) to total image area Reflects microvessel utilization; higher values suggest angiogenesis Vessel length density (VLD) % Total vessel centerline length (from skeletonized OCTA MIP image) per total image area Indicates possible dysfunction in oxygen/nutrient delivery; associated with angiogenesis Vessel diameter (average/distrib.) µm Vessel diameters estimated via local thickness algorithm on binarized OCTA MIP Provides insight into vascular dilation/regression; diameter distribution reflects perfusion changes Vessel length (average/distrib.) mm Length of vessel segments along the centerline from skeletonized OCTA MIP Indicates network interconnectivity and branching, reflecting tissue perfusion capabilities Tortuosity (average/distrib.) 1 Ratio of centerline segment length to straight-line (chord) length for each vessel Higher tortuosity suggests pathological remodeling or ischemia Branchpoint density nodes/mm Number of branch nodes per unit vessel length Reflects vascular network complexity and resistance to flow disturbances Fractal dimension 1 Measurement of spatial complexity using box-counting method Reflects network branching and remodeling characteristics Abbreviations: OCTA: Optical coherence tomography angiography, MIP: Maximum intensity projection, µm: Micrometer, mm: Millimeter. Primary endpoints were macular mean vessel diameter (MD), mean tortuosity (MT), branchpoint density (BD), and temporal RNFL thickness, which were prespecified to test a microvascular remodeling hypothesis. All other OCTA and RNFL metrics were considered exploratory; their p-values are descriptive and should be interpreted alongside effect sizes and 95% confidence intervals. The foveal avascular zone (FAZ) area was measured using the KSM program, an automated ImageJ macro developed for FAZ extraction ( 13 ). This method compensates for disruptions in the perifoveal capillary ring to achieve accurate delineation of the FAZ. Briefly, en face OCTA images from the superficial capillary plexus slab were downsized to 800 × 800 pixels to smooth boundary detection, followed by image binarization and skeletonization. Among various binarization algorithms, the Li method was applied. Capillary ring discontinuities were corrected by iterative dilation and erosion, optimized through preliminary trials. Finally, the images were restored to their original resolution, and the FAZ area was extracted with a 2-pixel enlargement to ensure boundary accuracy. All images were processed using the same ImageJ macro in a blinded fashion to maintain objectivity and consistency. Statistical Analysis Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 28.0 for Mac (SPSS Inc., Chicago, IL, USA). A p-value of < 0.05 was considered statistically significant. The normality of the data distribution was assessed using the Shapiro–Wilk test (p < 0.05 indicating non-normal distribution). For parameters that did not follow a Gaussian distribution, comparisons between the study and control groups were conducted using the Mann-Whitney U test. Primary endpoints were modeled with generalized estimating equations (GEE), adjusted for age, AL, and SE; results are reported as β (95% CI), p. Secondary metrics are exploratory and presented with effect sizes and 95% CIs without multiplicity correction. GEE with an exchangeable correlation structure were used to compare OCTA parameters between groups while accounting for inter-eye correlation. Multivariable models included age, AL, and spherical equivalent as covariates. Inter-eye agreement in the control group was assessed using the Intraclass Correlation Coefficient (ICC) based on a two-way mixed-effects model with absolute agreement. Results A total of 18 patients (8 girls, 10 boys) were included in the study group and 17 patients (8 girls, 9 boys) in the control group. The median age was 8 years (range: 5–16) in the study group and 9 years (range: 6–16) in the control group. All operated children had undergone cataract extraction before one year of age. The median BCVA in pseudophakic eyes was 0.6 in both the right and left eyes (range: 0.1–1.0), significantly lower than in controls, where BCVA was 1.0 in both eyes (range: 0.6–1.0 OD, 0.4–1.0 OS) (p < 0.05 for both comparisons). Refractive assessment revealed a more myopic profile in the study group. The median SE was − 2.625 D (range: −6.12 to 0.5) in the right eye and − 2.75 D (range: −5.88 to − 2.38) in the left eye. In contrast, control eyes showed a hyperopic tendency with median SE values of + 0.935 D (range: −0.68 to + 4.62) and + 1.245 D (range: 0 to + 6) in the right and left eyes, respectively (p < 0.05 for both). The median AL was significantly greater in the pseudophakic group [OD: 21.805 (range: 19.10 to 23.84) mm, OS: 21.655 (range: 19.44 to 23.82) mm] compared to controls [OD: 20.44 (range: 19.02 to 22.47) mm, OS: 20.48 (range: 19.04 to 22.15) mm] (p = 0.009 for right eye and p = 0.021 for the left eye). There were no statistically significant differences between groups in subfoveal choroidal thickness (OD: 384.5 µm vs. 373 µm, p = 0.264; OS: 373 µm vs. 363 µm, p = 0.052) or choroidal vascularity index (OD: 37.725% vs. 32.68%, p = 0.055; OS: 35.795% vs. 34.93%, p = 0.71). OCTA analysis showed significant microvascular differences in pseudophakic eyes. Mean vessel diameter (MD) was higher in the study group in both eyes (OD: 116 vs 107 µm, p = 0.049; OS: 112 vs 110 µm, p = 0.044). Mean tortuosity (MT) was higher in the study group in the right eye but lower in the left eye (OD: 1.16 vs 1.15, p = 0.036; OS: 1.14 vs 1.19, p = 0.047). Conversely, branchpoint density (BD) was reduced (OD: 1.0294 vs. 1.29, p = 0.018; OS: 1.033 vs. 1.11, p = 0.036), suggesting diminished microvascular branching (Fig. 1 ). Exploratory metrics (VAD, VLD, TVL, FD) showed no significant group differences; effect sizes and 95% CIs are provided for transparency. VAD in the right eye was not statistically significant (p = 0.052). Peripapillary disc OCTA metrics were also comparable between groups (p > 0.05) except MT (p = 0.036 in the right eye and p = 0.047 in the left eye), see Table 3 . Table 3 Comparison of Macular and Peripapillary OCTA Metrics Between Study and Control Groups in Right and Left Eyes Region Parameter (Units) Right Eye Left Eye Study Group Control Group P value Study Group Control Group P Value Macula VAD (%) 33.24 (29.53–39.65) 35.87 (33.45–36.33) 0,052 33.45 (27.59–35.98) 33.91 (32.0–35.33) 0,739 VLD (%) 4.3 (3.22–4.64) 4.66 (2.22–5.08) 0,506 4.17 (2.93–4.9) 4.08 (4.0–4.93) 0,925 TVL (mm) 68.78 (51.47–74.19) 74.54 (35.55–81.26) 0,87 63.72 (46.82–74.54) 65.27 (64.07–78.87) 0,79 MD (µm) 116.0 (95.0–124.0) 107.0 (101.0–129.0) 0,049 112.0 (101.0–137.0) 110.0 (102.0–131.0) 0,044 MED (µm) 97.0 (10.0–122.0) 94.0 (86.0–117.0) 0,29 104.0 (77.0–111.0) 95.0 (90.0–131.0) 0,22 BD (nodes/mm) 1.0294 (0.6–1.17) 1.29 (0.39–1.36) 0,018 1.033 (0.72–1.15) 1.11 (0.84–1.15) 0,036 FD (no unit) 1.86 (1.85–1.86) 1.86 (1.85–1.86) 0,532 1.84 (1.79–1.86) 1.86 (1.85–1.86) 0,251 MT (no unit) 1.15 (1.11–1.28) 1.14 (1.13–1.27) 0,126 1.15 (1.12–1.19) 1.12 (1.11–1.13) 0,048 Disc VAD (%) 33.6 (31.09–35.97) 32.87 (30.12–34.8) 0,217 31.2 (23.7–35.4) 33.0 (32.5–35.1) 0,167 VLD (%) 4.43 (3.96–4.81) 4.33 (3.5–4.57) 0,215 4.0 (2.42–4.63) 4.11 (3.9–5.1) 0,15 TVL (mm) 70.92 (63.4–76.94) 69.25 (55.94–73.12) 0,229 64.07 (52.54–67.0) 65.7 (62.38–81.64) 0,228 MD (µm) 116.0 (107.0–130.0) 115.0 (112.0–125.0) 0,797 120.0 (105.0–132.0) 118.0 (110.0–130.0) 0,691 MED (µm) 110.0 (94.0–128.0) 105.0 (102.0–119.0) 0,438 112.0 (97.0–131.0) 111.0 (103.0–133.0) 0,608 BD (nodes/mm) 1.01 (0.87–1.38) 0.99 (0.86–1.16) 0,652 0.991 (0.65–1.16) 0.99 (0.88–1.03) 0,277 FD (no unit) 1.86 (1.85–1.86) 1.86 (1.86–1.86) 0,23 1.86 (1.85–1.86) 1.86 (1.85–1.86) 0,776 MT (no unit) 1.16 (1.14–1.18) 1.15 (1.11–1.16) 0,036 1.14 (1.11–1.21) 1.19 (1.14–1.26) 0,047 Abbreviations: BD: Branchpoint Density, FD: Fractal Dimension, MD: Mean Diameter, MED: Median Diameter, MT: Mean Tortuosity, TVL: Total Vessel Length, VAD: Vessel Area Density, VLD: Vessel Length Density The median FAZ area in the right eye (OD) was lower in the study group (2398.5 µm², IQR: 1061.7) compared with the control group (3025.7 µm², IQR: 2203.9). In the left eye (OS), the study group also showed smaller values (2546.7 µm², IQR: 2616.0) than the control group (3045.4 µm², IQR: 1144.7). However, these differences were not statistically significant (OD: U = 46.0, p = 0.21; OS: U = 59.0, p = 0.48) (Fig. 2 ). Furthermore, the image quality score (IQS) of the analyzed OCTA scans did not differ significantly between the study and control groups (p = 0.254). Sectoral analysis of the RNFL revealed localized thickening in specific quadrants. In the study group, RNFL thickness was significantly higher in the temporal and superonasal quadrants of the right eye (p = 0.029 and p = 0.026, respectively), and in the temporal and inferotemporal quadrants of the left eye (p = 0.021 and p = 0.044, respectively). Total RNFL thickness and other quadrants did not differ significantly between groups (Fig. 3 ). Bilateral symmetry in controls: Inter-eye agreement in the healthy control group was assessed using the intraclass correlation coefficient (ICC). Inter-eye consistency was excellent for inferotemporal RNFL thickness (ICC = 0.97) and good for MD (ICC = 0.78), but poor for temporal RNFL thickness (ICC = 0.33) and BD (ICC = 0.32). The mean tortuosity (MT) demonstrated an ICC of -0.09, indicating substantial natural inter-eye variability for this microvascular metric rather than a direct negative correlation. GEE adjusting for age, AL, and SE confirmed the significance of OCTA and RNFL findings. MD (p = 0.001), MT (p < 0.001), and BD (p = 0.004) remained significantly different between groups. RNFL thickness also remained significantly increased in the temporal (p = 0.006) and inferotemporal (p = 0.023) sectors in the study group after adjustment. Discussion In this cohort of children who underwent bilateral congenital cataract surgery with secondary IOL implantation, our preliminary findings suggest the presence of distinctive alterations in retinal microvascular morphology and RNFL thickness compared with age-matched controls. To our knowledge, this is the first study to apply OCTA in eyes after bilateral congenital cataract surgery, and the first to perform a detailed quantitative vascular network analysis using OCTAVA in this population. While OCTA has been widely used in other ocular diseases, its application here provides new insight into the potential structural consequences of early visual deprivation and surgical rehabilitation. In the context of deprivation amblyopia and congenital cataract, most histologic and clinical studies have suggested that optic nerve development is compromised, with RNFL thinning expected as a consequence of reduced visual input during early life ( 14 , 15 ). Indeed, several clinical reports have described RNFL thinning in amblyopic eyes, particularly in unilateral cases or specific quadrants ( 16 ). By contrast, in our cohort we observed an apparent temporal RNFL thickening in pseudophakic eyes compared with controls. This is noteworthy, particularly given the well-established negative correlation between RNFL thickness and axial length, as our study group had significantly longer eyes ( 17 ). One explanation could be an amblyopia-related effect, as previous studies have reported thicker RNFL in anisometropic or strabismic amblyopia, and Yen et al. similarly documented higher RNFL values in refractive amblyopia ( 6 , 18 – 21 ). However, temporal thickening in our patients cannot be fully explained by amblyopia alone, especially given the mixed effects reported across different subtypes. Another possibility is a surgical effect. Dada et al. described postoperative RNFL thickening after adult cataract surgery, although this was measured using scanning laser ophthalmoscopy at week 4, representing a transient early postoperative phenomenon. In contrast, our patients were imaged years after surgery using spectral-domain OCT, making a direct parallel less likely ( 22 ). Cataractous eyes may also yield underestimated RNFL measurements, but this cannot account for our results, since the control group had clear lenses ( 23 ). The discrepancies between our findings and prior reports likely reflect a combination of factors, including amblyopia subtype (strabismic, anisometropic, deprivation), laterality (unilateral vs bilateral), age at imaging, axial length distribution, and differences in OCT technology (time-domain vs spectral-domain). Interestingly, our study indicates a trend that appears opposite to the thinning predicted by deprivation models, suggesting that the structural response of the optic nerve in bilaterally operated congenital cataract patients might be distinct. Because the RNFL consists of ganglion cell axons, changes in the ganglion cell layer (GCL) may also influence its thickness. Park et al. showed that several retinal layers were thicker in amblyopic eyes, supporting the hypothesis that amblyopia can affect multiple structures (24). In our cohort, amblyopia, congenital cataract, surgery, and occlusion therapy may all have contributed. RNFL thickening might also represent a compensatory response after deprivation is removed, though this remains speculative and difficult to verify in young children. Discrepancies with earlier studies may stem from differences in amblyopia type, laterality, patient age, axial length, and OCT methodology. While deprivation models generally predict RNFL thinning, we instead found temporal thickening, pointing to a potentially distinct structural response after bilateral congenital cataract surgery. Whether this reflects developmental alteration, compensation, or combined surgical and optical influences remains uncertain. Reliable RNFL measurements are rarely feasible in the early postoperative period of infancy, limiting insight into the initial course of these changes. Longitudinal studies with pre- and postoperative imaging are needed to clarify their trajectory and mechanism. Peripapillary OCTA metrics did not significantly differ between groups. Only MT values reached statistical significance; however, as this parameter did not follow a normal distribution and showed inconsistent patterns between fellow eyes, the finding was considered likely attributable to the small sample size. In the literature, findings regarding the FAZ in amblyopia are inconsistent; however, most studies have reported no significant differences in FAZ size in either strabismic or anisometropic amblyopia ( 25 – 27 ). Some reports, however, have demonstrated a smaller FAZ in amblyopic eyes, particularly in the superficial capillary plexus ( 28 ). To date, no study has specifically investigated FAZ morphology in congenital cataract. In our study, although this was not a primary endpoint, exploratory analyses likewise revealed no statistically significant differences between pseudophakic and control eyes. Our OCTAVA-based analysis highlighted a potentially unique microvascular profile: postoperative eyes tended to display larger vessel diameters and greater tortuosity, yet reduced BD. This configuration suggests a sparser but more dilated and sinuous network. Reduced capillary density has been reported in amblyopia, but our study is, to our knowledge, the first to characterize the superficial plexus en-face morphology in this setting, an approach with distinct quantitative advantages ( 27 , 29 , 30 ). Lower BD might imply reduced vascular interconnectedness, potentially limiting perfusion reserve, as observed in glaucoma ( 31 ). The absence of significant vessel area density differences between groups may reflect partial reversibility of deprivation-induced vascular changes following amblyopia treatment ( 32 ). No significant differences were detected in CT or CVI. The literature on amblyopia and CT is inconsistent: some studies report increased thickness, others no change, and some a reduction in congenital cataract eyes ( 33 – 37 ). Variations in AL correction, surgery timing, and treatment history may explain these discrepancies. In our cross-sectional design, postoperative optical correction and occlusion therapy—together with AL differences between groups— may have attenuated potential CVI differences ( 38 ). Our study has several limitations. This retrospective study was constrained by the size of the eligible population; analyses were exploratory and hypothesis-generating. The small sample size reduces statistical power and limits subgroup analyses, while the cross-sectional design precludes determining whether the observed changes predated surgery or developed during follow-up. Pediatric OCTA carries technical challenges; although we adjusted for AL, residual magnification effects remain possible ( 39 ). Given the exploratory aims and correlated vascular metrics, we did not adjust for multiple comparisons; findings should be interpreted with appropriate caution. We assessed only the superficial vasculature and peripapillary RNFL; the deeper capillary plexus was not analyzed to avoid the high susceptibility to projection and motion artifacts common in pediatric imaging. Although we excluded patients with obvious nystagmus or inability to fixate (given OCTA’s dependence on eye tracking), subclinical nystagmus in amblyopic patients could still have influenced results. Moreover, optic disc drusen were not specifically screened, and subclinical cases could not be excluded. Furthermore, we analyzed the entire superficial network without masking large vessels to capture global network alterations. Consequently, our morphometric metrics reflect both macro- and micro-vessel geometry. Future studies utilizing automated large-vessel masking are needed to isolate capillary-specific remodeling. Finally, the use of exclusively bilateral cases meant no internal control eyes were available, and although age-matching and statistical adjustments were applied, external control reliance carries a risk of unmeasured confounding. Magnification correction used an AL ref assumed from device documentation; although standard, this introduces minor uncertainty. Also, OCTA lateral scaling constants vary across platforms; therefore, cross-device quantitative comparisons should be made with caution. To our knowledge, this is the first study to combine pediatric post-cataract OCTA with quantitative network morphology (OCTAVA), suggesting a potential pattern of reduced branching with dilated, more tortuous vessels alongside sectoral temporal RNFL thickening—a phenotype not captured by conventional thickness metrics alone. The observed alterations, although analyzed after excluding major ocular or systemic comorbidities, may still be influenced by amblyopia and axial length differences. Future longitudinal work, ideally with pre- and postoperative imaging, is needed to clarify the temporal course of these findings and to determine their functional relevance for visual acuity, stereopsis, and contrast sensitivity. Declarations Financial Disclosures: The authors have no financial or proprietary interests in any material or method mentioned. Ethics approval and consent to participate This study was approved by the Institutional Review Board of Bursa Uludağ University Faculty of Medicine (Ethics approval no: 2025/8-17; Decision no: 621-8/17, dated 30 April 2025) and conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from the parents or legal guardians of all participating children prior to their inclusion in the study. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding The authors declare that no funding was received for this study. Authors' contributions MOK conceptualized and designed the study, analyzed and interpreted the OCTA data, and drafted the manuscript. AA contributed to data collection, clinical examinations, and data entry. MY and ESS assisted in data interpretation and critical revision of the manuscript. ATO and MB provided senior supervision, contributed to the surgical and clinical framework of the study, and critically reviewed the manuscript for important intellectual content. All authors read and approved the final manuscript. Acknowledgements Not applicable. Authors' information Not applicable. Declaration of generative AI and AI-assisted technologies in the manuscript preparation process. During the preparation of this work the author(s) used various AI tools in order to grammar editing. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the published article. References Gilbert C, Foster A. Childhood blindness in the context of VISION 2020–the right to sight. Bull World Health Organ. 2001;79(3):227–32. Sheeladevi S, Lawrenson JG, Fielder AR, Suttle CM. Global prevalence of childhood cataract: a systematic review. Eye (Lond). 2016;30(9):1160–9. Rabin J, Van Sluyters RC, Malach R. Emmetropization: a vision-dependent phenomenon. Invest Ophthalmol Vis Sci. 1981;20(4):561–4. Wallman J, Winawer J. Homeostasis of eye growth and the question of myopia. Neuron. 2004;43(4):447–68. Birch EE, Stager DR. The critical period for surgical treatment of dense congenital unilateral cataract. Invest Ophthalmol Vis Sci. 1996;37(8):1532–8. Huynh SC, Samarawickrama C, Wang XY, Rochtchina E, Wong TY, Gole GA, et al. Macular and nerve fiber layer thickness in amblyopia: the Sydney Childhood Eye Study. Ophthalmology. 2009;116(9):1604–9. Al-Haddad CE, El Mollayess GM, Mahfoud ZR, Jaafar DF, Bashshur ZF. Macular ultrastructural features in amblyopia using high-definition optical coherence tomography. Br J Ophthalmol. 2013;97(3):318–22. Wang J, Smith HA, Donaldson DL, Haider KM, Roberts GJ, Sprunger DT, et al. Macular structural characteristics in children with congenital and developmental cataracts. J AAPOS. 2014;18(5):417–22. Diao K, Huang X, Yao M, Li J, Fan F, Pan H, et al. Inter-examiner and intra-examiner reliability of optical coherence tomography angiography in vascular density measurement of retinal and choriocapillaris plexuses in healthy children aged 6–15 years. Front Med (Lausanne). 2023;10:1161942. Sonoda S, Sakamoto T, Yamashita T, Uchino E, Kawano H, Yoshihara N, et al. Luminal and stromal areas of choroid determined by binarization method of optical coherence tomographic images. Am J Ophthalmol. 2015;159(6):1123–e311. Zhu Q, Zhao Q. Short-term effect of orthokeratology lens wear on choroidal blood flow in children with low and moderate myopia. Sci Rep. 2022;12(1):17653. Bennett AG, Rudnicka AR, Edgar DF. Improvements on Littmann's method of determining the size of retinal features by fundus photography. Graefes Arch Clin Exp Ophthalmol. 1994;232(6):361–7. Ishii H, Shoji T, Yoshikawa Y, Kanno J, Ibuki H, Shinoda K. Automated Measurement of the Foveal Avascular Zone in Swept-Source Optical Coherence Tomography Angiography Images. Transl Vis Sci Technol. 2019;8(3):28. Maguire GW, Smith EL 3rd, Harwerth RS, Crawford ML. Optically induced anisometropia in kittens. Invest Ophthalmol Vis Sci. 1982;23(2):253–64. von Noorden GK, Crawford ML, Levacy RA. The lateral geniculate nucleus in human anisometropic amblyopia. Invest Ophthalmol Vis Sci. 1983;24(6):788–90. Bansal P, Ram J, Sukhija J, Singh R, Gupta A. Retinal Nerve Fiber Layer and Macular Thickness Measurements in Children After Cataract Surgery Compared With Age-Matched Controls. Am J Ophthalmol. 2016;166:126–32. Savini G, Barboni P, Parisi V, Carbonelli M. The influence of axial length on retinal nerve fibre layer thickness and optic-disc size measurements by spectral-domain OCT. Br J Ophthalmol. 2012;96(1):57–61. Baddini-Caramelli C, Hatanaka M, Polati M, Umino AT, Susanna R. Jr. Thickness of the retinal nerve fiber layer in amblyopic and normal eyes: a scanning laser polarimetry study. J AAPOS. 2001;5(2):82–4. Altintas O, Yuksel N, Ozkan B, Caglar Y. Thickness of the retinal nerve fiber layer, macular thickness, and macular volume in patients with strabismic amblyopia. J Pediatr Ophthalmol Strabismus. 2005;42(4):216–21. Repka MX, Kraker RT, Tamkins SM, Suh DW, Sala NA, Beck RW, et al. Retinal nerve fiber layer thickness in amblyopic eyes. Am J Ophthalmol. 2009;148(1):143–7. Yen MY, Cheng CY, Wang AG. Retinal nerve fiber layer thickness in unilateral amblyopia. Invest Ophthalmol Vis Sci. 2004;45(7):2224–30. Dada T, Behera G, Agarwal A, Kumar S, Sihota R, Panda A. Effect of cataract surgery on retinal nerve fiber layer thickness parameters using scanning laser polarimetry (GDxVCC). Indian J Ophthalmol. 2010;58(5):389–94. Kim NR, Lee H, Lee ES, Kim JH, Hong S, Je Seong G, et al. Influence of cataract on time domain and spectral domain optical coherence tomography retinal nerve fiber layer measurements. J Glaucoma. 2012;21(2):116–22. Park KA, Park DY, Oh SY. Analysis of spectral-domain optical coherence tomography measurements in amblyopia: a pilot study. Br J Ophthalmol. 2011;95(12):1700–6. Demirayak B, Vural A, Onur IU, Kaya FS, Yigit FU. Analysis of Macular Vessel Density and Foveal Avascular Zone Using Spectral-Domain Optical Coherence Tomography Angiography in Children With Amblyopia. J Pediatr Ophthalmol Strabismus. 2019;56(1):55–9. Lonngi M, Velez FG, Tsui I, Davila JP, Rahimi M, Chan C, et al. Spectral-Domain Optical Coherence Tomographic Angiography in Children With Amblyopia. JAMA Ophthalmol. 2017;135(10):1086–91. Yilmaz I, Ocak OB, Yilmaz BS, Inal A, Gokyigit B, Taskapili M. Comparison of quantitative measurement of foveal avascular zone and macular vessel density in eyes of children with amblyopia and healthy controls: an optical coherence tomography angiography study. J AAPOS. 2017;21(3):224–8. Araki S, Miki A, Goto K, Yamashita T, Yoneda T, Haruishi K, et al. Foveal avascular zone and macular vessel density after correction for magnification error in unilateral amblyopia using optical coherence tomography angiography. BMC Ophthalmol. 2019;19(1):171. Hormel TT, Wang J, Bailey ST, Hwang TS, Huang D, Jia Y. Maximum value projection produces better en face OCT angiograms than mean value projection. Biomed Opt Express. 2018;9(12):6412–24. Huang L, Ding L, Zheng W. Microvascular assessment of macula, choroid, and optic disk in children with unilateral amblyopia using OCT angiography. Int Ophthalmol. 2022;42(12):3923–31. Richter GM, Sylvester B, Chu Z, Burkemper B, Madi I, Chang R, et al. Peripapillary microvasculature in the retinal nerve fiber layer in glaucoma by optical coherence tomography angiography: focal structural and functional correlations and diagnostic performance. Clin Ophthalmol. 2018;12:2285–96. Kim JG, Lee SY, Lee DC. Short-term effects of occlusion therapy and optical correction on microvasculature in monocular amblyopia: a retrospective case-control study. Sci Rep. 2023;13(1):12191. Daniel MC, Dubis AM, MacPhee B, Ibanez P, Adams G, Brookes J, et al. Optical Coherence Tomography Findings After Childhood Lensectomy. Invest Ophthalmol Vis Sci. 2019;60(13):4388–96. Liu Y, Dong Y, Zhao K. A Meta-Analysis of Choroidal Thickness Changes in Unilateral Amblyopia. J Ophthalmol. 2017;2017:2915261. Baek J, Lee A, Chu M, Kang NY. Analysis of Choroidal Vascularity in Children with Unilateral Hyperopic Amblyopia. Sci Rep. 2019;9(1):12143. Kurt RA, Bayar SA, Ercan ZE, Yaman Pinarci E, Tekindal MA, Oto S. Choroidal and Macular Thickness in Eyes with Amblyopia. Beyoglu Eye J. 2021;6(4):320–7. Zhou Y, Wang J, Jin L, Chen W, Wang Q, Chen H, et al. Morphological characteristics of the subfoveal choroid and their association with visual acuity in postoperative patients with unilateral congenital cataracts. Ann Transl Med. 2022;10(13):726. Hui W, Xiaofeng H, Hua X, Yihan D, Yong T. Assessment of choroidal vascularity and choriocapillaris blood perfusion in Chinese preschool-age anisometropic hyperopic amblyopia children. Front Pediatr. 2022;10:1056888. Youssef MM, Sadek SH, Hatata RM. Macular and Optic Nerve Microvascular Alteration in Relation to Axial Length, by Optical Coherence Tomography Angiography (OCTA). Clin Ophthalmol. 2022;16:885–92. Untracht GR, Matos RS, Dikaios N, Bapir M, Durrani AK, Butsabong T, et al. OCTAVA: An open-source toolbox for quantitative analysis of optical coherence tomography angiography images. PLoS ONE. 2021;16(12):e0261052. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 24 Apr, 2026 Reviewers agreed at journal 24 Apr, 2026 Reviewers invited by journal 25 Mar, 2026 Editor invited by journal 10 Mar, 2026 Editor assigned by journal 09 Mar, 2026 Submission checks completed at journal 09 Mar, 2026 First submitted to journal 05 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-9044196","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":612314693,"identity":"e940248a-9b81-41f0-b378-1bcc0e920ea0","order_by":0,"name":"Mehmet Omer Kiristioglu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFklEQVRIie3RsUrEMBjA8a8U0iU91xyo9wRC4KAIfZkU4bLccJN0OEqmdBJf4PAlBOeUQLtkcLyxIojDDXVxEjHhTs+h9hwF8x+SEPKDkAD4fH8yBAqomyBQkMMxAHPb4UFCLLELA3hP0M/ERdygAvkLclbKTOeLohhF5b2ObzSmzcXjM+RpJiZXbR9JTK0qQzVB2Cx0fGeJeUrOwfBMoIj2kjUXlaCKIDJnW7JmCQ2ktqT/ZjtS7MjKEf5Kg/chMlOWhJZwpWPhyHzaBmKAmJpZoscSG6hWNcdjs7kEVvOpRLN+0sjpi3grjiZl+dBulunpqOG3XbdMT67Dupd8C3+9DyIMBn5yX9R+rsLu8Gmfz+f7R30AQelmUW/WWDEAAAAASUVORK5CYII=","orcid":"","institution":"Bursa Uludağ University","correspondingAuthor":true,"prefix":"","firstName":"Mehmet","middleName":"Omer","lastName":"Kiristioglu","suffix":""},{"id":612314698,"identity":"9c55f1a0-77e0-4077-b03d-29fe02c0ffa1","order_by":1,"name":"Ahmet Tuncer Ozmen","email":"","orcid":"","institution":"Private Practice","correspondingAuthor":false,"prefix":"","firstName":"Ahmet","middleName":"Tuncer","lastName":"Ozmen","suffix":""},{"id":612314701,"identity":"e0b4b527-7d2c-4b12-a67a-17a304cd0118","order_by":2,"name":"Meral Yildiz","email":"","orcid":"","institution":"Bursa Uludağ University","correspondingAuthor":false,"prefix":"","firstName":"Meral","middleName":"","lastName":"Yildiz","suffix":""},{"id":612314703,"identity":"a7ee5fd9-dd87-4706-8319-56097c77bf84","order_by":3,"name":"Ahmet Akcan","email":"","orcid":"","institution":"Bursa Uludağ University","correspondingAuthor":false,"prefix":"","firstName":"Ahmet","middleName":"","lastName":"Akcan","suffix":""},{"id":612314704,"identity":"ca6acc47-2133-45ac-84bb-750727eaad30","order_by":4,"name":"Esin Sogutlu Sari","email":"","orcid":"","institution":"Bursa Uludağ University","correspondingAuthor":false,"prefix":"","firstName":"Esin","middleName":"Sogutlu","lastName":"Sari","suffix":""},{"id":612314705,"identity":"370fb809-bb43-4269-9bc3-64de12b3bb37","order_by":5,"name":"Mehmet Baykara","email":"","orcid":"","institution":"Bursa Uludağ University","correspondingAuthor":false,"prefix":"","firstName":"Mehmet","middleName":"","lastName":"Baykara","suffix":""}],"badges":[],"createdAt":"2026-03-05 21:38:32","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9044196/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9044196/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105575290,"identity":"fd7270d0-dc19-4966-a88f-ad864d0a3d18","added_by":"auto","created_at":"2026-03-27 13:37:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2497849,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentative OCTA images from the superficial capillary plexus.\u003cbr\u003e\n(a) Age-matched control eye showing normal vessel caliber, branching, and tortuosity.\u003cbr\u003e\n(b) Pseudophakic eye after bilateral congenital cataract extraction with secondary IOL implantation, demonstrating larger vessel caliber and reduced branching.\u003c/p\u003e","description":"","filename":"Figure1son.png","url":"https://assets-eu.researchsquare.com/files/rs-9044196/v1/d14c5f308c74ea9591501f52.png"},{"id":105576028,"identity":"34d2f9bb-6ec2-4178-bdbe-3d8f5eee7609","added_by":"auto","created_at":"2026-03-27 13:42:36","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1369069,"visible":true,"origin":"","legend":"\u003cp\u003eFoveal avascular zone (FAZ) area in pseudophakic (study) and control eyes. (A) Right eye. (B) Left eye. Data are shown as median with interquartile range (µm²). Although FAZ tended to be smaller in the study group compared with controls, differences did not reach statistical significance.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-9044196/v1/245365330e59543d8faccfab.png"},{"id":105575373,"identity":"300e35be-fdc8-4355-a3c0-1fe0954368f1","added_by":"auto","created_at":"2026-03-27 13:38:38","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":493750,"visible":true,"origin":"","legend":"\u003cp\u003eSectoral retinal nerve fiber layer (RNFL) thickness in pseudophakic (study) and control eyes. (A) Right eyes. (B) Left eyes. Polar plots demonstrate median values across standard sectors. Study eyes exhibited significant thickening in the temporal, superonasal (A), and temporal and inferotemporal (B) sectors compared with controls (p \u0026lt; 0.05).\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-9044196/v1/058e768f1d083e6ef42fa57d.png"},{"id":105576441,"identity":"6f529be8-2c3b-44a9-83ca-5e46eab48042","added_by":"auto","created_at":"2026-03-27 13:44:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5651825,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9044196/v1/17d6efa4-c678-45ee-bb63-8c6328a7c7af.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Retinal Microvascular and RNFL Changes After Bilateral Congenital Cataract Surgery: Preliminary Results from an Exploratory OCT/OCTA Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCongenital or infantile cataracts\u0026mdash;lens opacities present within the first year of life\u0026mdash;are uncommon but remain a major cause of childhood blindness worldwide (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Because the first years of life are critical for visual development, lens opacity during this period can disrupt normal visual input, leading to permanent changes in ocular growth and neural visual pathways if left untreated (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Early cataract removal, followed by optical correction and amblyopia therapy, is essential to optimize visual potential, with secondary intraocular lens (IOL) implantation commonly performed once the eye has grown sufficiently to ensure refractive stability (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWhile structural outcomes after pediatric cataract surgery have been examined in unilateral and bilateral cases, most imaging studies have focused on macular thickness or retinal nerve fiber layer (RNFL) profiles, with limited attention to the retinal microvasculature\u0026mdash;particularly in bilaterally operated children. Amblyopia-related macular changes have been reported in both anisometropic and strabismic cases, but these findings may not fully represent the unique effects of bilateral visual deprivation caused by congenital cataracts (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFourier-domain optical coherence tomography (OCT) has revealed that even when macular architecture appears grossly normal after surgery, subtle postoperative thickening can persist (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Optical coherence tomography angiography (OCTA) extends this structural assessment by visualizing the retinal and peripapillary microvasculature in a depth-resolved, non-invasive manner. Although OCTA has been utilized in pediatric conditions such as anisometropic amblyopia, retinopathy of prematurity, and uveitis, to our knowledge, it has not been systematically applied to evaluate eyes following bilateral congenital cataract extraction and secondary IOL implantation.\u003c/p\u003e \u003cp\u003eThis study addresses this gap by combining OCTA with the OCTAVA platform to perform a comprehensive, quantitative analysis of vascular network morphology. By measuring these specific OCTA parameters alongside RNFL thickness, we aimed to detect subtle microvascular and structural alterations that may persist despite successful surgical and visual rehabilitation\u0026mdash;changes that might remain undetected using conventional OCT metrics alone.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Ethics\u003c/h2\u003e \u003cp\u003eThis retrospective, cross-sectional and comparative study included pediatric patients who had undergone bilateral congenital cataract extraction followed by secondary IOL implantation. In this retrospective study, imaging and clinical data were retrieved from postoperative visits conducted between January 2024 and February 2025 at Bursa Uludağ University Faculty of Medicine, with all included examinations performed\u0026thinsp;\u0026ge;\u0026thinsp;12 months after surgery. The study was approved by the Institutional Review Board of Bursa Uludağ University Faculty of Medicine (Ethics approval no: 2025/8\u0026ndash;17; Decision no: 621-8/17, dated 30 April 2025) and conducted in accordance with the Declaration of Helsinki.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eParticipants\u003c/h3\u003e\n\u003cp\u003eEligible patients met several criteria: a confirmed diagnosis of bilateral congenital cataract, birth after 37 weeks\u0026rsquo; gestation, primary bilateral cataract extraction before 1 year of age, subsequent secondary IOL implantation (typically around 3 years of age), and at least one year of postoperative follow-up after the IOL implantation. All imaging was obtained at ages 4\u0026ndash;16 years, and best-corrected visual acuity had to be at least 20/400 in each operated eye. Initially, a total of 42 patients were recruited (21 in the study group and 21 in the control group); however, due to insufficient OCTA image quality, poor cooperation, and missing data, 3 patients from the study group and 4 patients from the control group were excluded, leaving 18 and 17 patients, respectively, for the final analysis.\u003c/p\u003e \u003cp\u003eHealthy, age-matched children without any known systemic or ocular diseases were recruited as controls. In addition to being free of ocular/systemic pathology, the same exclusion criteria applied to the study group were also applied to the controls to ensure comparability. Between-group differences in axial length (AL) and refractive status were modeled in all GEE analyses (covariates: age, AL, SE).\u003c/p\u003e \u003cp\u003eFor both study and control groups, exclusion criteria were summarized in Table\u0026nbsp;1. No patient with these conditions was present in the included cohort.\u003c/p\u003e \u003cp\u003e \u003cb\u003eTable\u0026nbsp;1. Exclusion criterias\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eAnterior segment abnormalities (other than pseudophakia)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eCorneal pathology (e.g., edema)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eOcular trauma (excluding cataract surgery)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAphakic glaucoma (past or present)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eRetinal or optic nerve pathology (e.g., dystrophies, atrophy, coloboma, tilted disc, myopic crescent, visible optic disc drusen)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eHistory of pars plana vitrectomy or glaucoma surgery\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eHistory of premature retinopathy\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eSevere amblyopia, nystagmus, or manifest strabismus\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eHigh refractive errors (spherical equivalent\u0026thinsp;\u0026lt;\u0026thinsp;\u0026plusmn;\u0026thinsp;6 Diopter) or AL outside 19\u0026ndash;24 mm)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eSystemic or metabolic diseases affecting ocular development\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePoor-quality OCTA and motion artifacts\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eInterocular AL difference\u0026thinsp;\u0026gt;\u0026thinsp;2 mm\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e\n\u003ch3\u003eSurgical Technique\u003c/h3\u003e\n\u003cp\u003eAll cataract extractions were performed under general anesthesia by the same surgical team of experienced pediatric and anterior segment surgeons using a standardized technique. Limbal incisions were made, the anterior capsule was stained with trypan blue, and a 5-mm continuous curvilinear capsulorrhexis was created. Lens aspiration was performed using bimanual irrigation/aspiration. Posterior capsulorrhexis and limited anterior vitrectomy were conducted with triamcinolone-assisted vitreous visualization.\u003c/p\u003e \u003cp\u003eSecondary IOL implantation (Alcon SN60AT) was performed at approximately age 3 in the ciliary sulcus with optic capture. Postoperative management included optical correction with spectacles or contact lenses and alternating occlusion therapy of the fellow eye for half of waking hours. Prescriptions were updated if the refractive error changed\u0026thinsp;\u0026gt;\u0026thinsp;1.00 D during 3-month follow-up visits.\u003c/p\u003e\n\u003ch3\u003eOphthalmic Examination\u003c/h3\u003e\n\u003cp\u003eAll participants underwent a standardized ophthalmic evaluation, which included best-corrected visual acuity measurement, intraocular pressure assessment, slit-lamp biomicroscopy, tear film evaluation, dilated fundus examination, and ocular biometry using the Lenstar 500 (Haag-Streit AG, K\u0026ouml;niz, Switzerland).\u003c/p\u003e\n\u003ch3\u003eImaging Protocol\u003c/h3\u003e\n\u003cp\u003eRetinal and optic nerve head microvasculature were imaged with the DRI OCT Triton (Topcon, Tokyo, Japan). Each eye underwent both a 6\u0026times;6 mm macular scan and a 6\u0026times;6 mm optic nerve head scan. Only scans with IQS\u0026thinsp;\u0026gt;\u0026thinsp;40 were analyzed. The refractive error was entered into the device software prior to acquisition to minimize optical aberrations. All imaging was performed between 12:00 and 16:00 by the same examiner to reduce diurnal variation effects. OCTA image processing, slab definitions, and scaling.\u003c/p\u003e \u003cp\u003eBecause only refractive error (not AL) was entered into IMAGEnet at acquisition, device-level lateral scaling was not applied. Therefore, metrics derived from physical dimensions were corrected offline using Bennett\u0026ndash;Littmann scaling with a unity reference axial length AL\u003csub\u003ereference\u003c/sub\u003e = 23.82 mm. Length-type metrics (e.g., MD, MED, TVL) were multiplied by (AL-1.82)/(AL\u003csub\u003ereference\u003c/sub\u003e-1.82) area-type metrics by its square. Percentage area measures (e.g., VAD %) were not altered. To avoid double-correction, exported metadata were inspected; when pixel size did not vary across eyes, external scaling was applied. As a sensitivity analysis, models were repeated without magnification correction; inferences were unchanged. We repeated all analyses with magnification-corrected values.\u003c/p\u003e \u003cp\u003eAnalyses were performed exclusively on the superficial capillary plexus (SCP). The SCP slab was defined per device default from the internal limiting membrane (ILM) to the IPL/INL boundary, and SCP en face angiograms were generated using maximum-intensity projection within the slab. For peripapillary analyses, the radial peripapillary capillaries (RPC) slab was used (from the ILM to the lower boundary of the RNFL). The deep capillary plexus (DCP) and choriocapillaris were excluded from the analysis, as the deeper layers in pediatric patients are highly susceptible to projection artifacts from the superficial vessels and motion artifacts caused by fixation difficulties (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e All automatic segmentations were reviewed by a grader masked to group allocation; minor boundary misalignments were manually corrected. Scans with uncorrectable segmentation errors were planned to be excluded from the analysis; however, all 70 scans (36 in the study group and 34 in the control group) that passed the initial image quality criteria had correctable segmentations and were successfully included in the final quantitative analysis.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eOptical Coherence Tomography Assessments\u003c/h2\u003e \u003cp\u003ePeripapillary retinal nerve fiber layer (RNFL) thickness and choroidal assessments were performed using the Heidelberg Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany). For RNFL evaluation, a standard peripapillary circular scan (3.4 mm diameter) centered on the optic disc was obtained. Global and sectoral RNFL thicknesses were calculated automatically by the device's software. All RNFL segmentations were meticulously reviewed and, if necessary, manually corrected by an experienced ophthalmologist blinded to the participants' clinical status.\u003c/p\u003e \u003cp\u003eSubfoveal choroidal thickness (CT) was measured perpendicularly from the retinal pigment epithelium to the sclerochoroidal junction in four quadrants (0.5 mm and 1.5 mm from the fovea) using enhanced depth imaging (EDI) mode with a 9.0 mm seven-line scan centered on the foveola. The auto-rescan function was used for consistency.\u003c/p\u003e \u003cp\u003eChoroidal vascularity index (CVI) was calculated from a 1.5 mm wide subfoveal region of interest using ImageJ software (v2.0.0, NIH, Bethesda, MD, USA). Three large choroidal vessels (\u0026gt;\u0026thinsp;100 \u0026micro;m) were sampled to determine average reflectivity, after which images were binarized using Niblack\u0026rsquo;s thresholding method, converted to RGB, and the luminal area was segmented with the Threshold tool. CVI was computed as the ratio of luminal to total choroidal area, following previously described protocols (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). All choroidal thickness and CVI measurements were performed by a masked, experienced ophthalmologist blinded to group allocation.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eOCTA Quantitative Analysis\u003c/h3\u003e\n\u003cp\u003eMotion and projection artifacts were suppressed using the device\u0026rsquo;s built-in software, which incorporates active eye tracking and projection-artifact removal. For each scan, an image quality score (IQS; 0\u0026ndash;100) was generated by the system, and scans with an IQS\u0026thinsp;\u0026lt;\u0026thinsp;40 were excluded. To account for magnification effects, images were adjusted using Littmann's method and the Bennett formula (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). OCTA scans were then exported from the DRI OCT Triton using IMAGEnet 6 software (v1.23; Topcon Healthcare) and analyzed with MATLAB (MathWorks, Natick, MA, USA) integrated with the OCTAVA platform.\u003c/p\u003e \u003cp\u003eBinarization and skeletonization were applied to each image before quantitative measurement. Vessel diameters were calculated from the distance transform of the binarized image, branchpoints were detected automatically and verified manually, tortuosity was calculated for each segment and averaged, and fractal dimension (FD) was computed via box-counting analysis. All OCTA analyses were performed by an observer masked to the participants\u0026rsquo; clinical status. (A detailed description and the potential biological relevance of each evaluated metric are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e2\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 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAdapted Summary of Quantitative Metrics for Microvascular Network Architecture in OCTA\u003c/p\u003e \u003cdiv class=\"Credit\"\u003e\u003cp\u003e\u003cem\u003e(Adapted from Untracht et al., 2021\u003c/em\u003e [(\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e)]).\u003c/p\u003e\u003c/div\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMetric\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnit\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDescription\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePotential Biological Relevance\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVessel area density (VAD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRatio of perfused blood vessel area (from binarized OCTA MIP image) to total image area\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReflects microvessel utilization; higher values suggest angiogenesis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVessel length density (VLD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTotal vessel centerline length (from skeletonized OCTA MIP image) per total image area\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIndicates possible dysfunction in oxygen/nutrient delivery; associated with angiogenesis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVessel diameter (average/distrib.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026micro;m\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVessel diameters estimated via local thickness algorithm on binarized OCTA MIP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eProvides insight into vascular dilation/regression; diameter distribution reflects perfusion changes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVessel length (average/distrib.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003emm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLength of vessel segments along the centerline from skeletonized OCTA MIP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIndicates network interconnectivity and branching, reflecting tissue perfusion capabilities\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTortuosity (average/distrib.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRatio of centerline segment length to straight-line (chord) length for each vessel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigher tortuosity suggests pathological remodeling or ischemia\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBranchpoint density\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003enodes/mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNumber of branch nodes per unit vessel length\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReflects vascular network complexity and resistance to flow disturbances\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFractal dimension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMeasurement of spatial complexity using box-counting method\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReflects network branching and remodeling characteristics\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eAbbreviations: OCTA: Optical coherence tomography angiography, MIP: Maximum intensity projection, \u0026micro;m: Micrometer, mm: Millimeter.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePrimary endpoints were macular mean vessel diameter (MD), mean tortuosity (MT), branchpoint density (BD), and temporal RNFL thickness, which were prespecified to test a microvascular remodeling hypothesis. All other OCTA and RNFL metrics were considered exploratory; their p-values are descriptive and should be interpreted alongside effect sizes and 95% confidence intervals.\u003c/p\u003e \u003cp\u003eThe foveal avascular zone (FAZ) area was measured using the KSM program, an automated ImageJ macro developed for FAZ extraction (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). This method compensates for disruptions in the perifoveal capillary ring to achieve accurate delineation of the FAZ. Briefly, en face OCTA images from the superficial capillary plexus slab were downsized to 800 \u0026times; 800 pixels to smooth boundary detection, followed by image binarization and skeletonization. Among various binarization algorithms, the Li method was applied. Capillary ring discontinuities were corrected by iterative dilation and erosion, optimized through preliminary trials. Finally, the images were restored to their original resolution, and the FAZ area was extracted with a 2-pixel enlargement to ensure boundary accuracy. All images were processed using the same ImageJ macro in a blinded fashion to maintain objectivity and consistency.\u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 28.0 for Mac (SPSS Inc., Chicago, IL, USA). A p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant. The normality of the data distribution was assessed using the Shapiro\u0026ndash;Wilk test (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicating non-normal distribution). For parameters that did not follow a Gaussian distribution, comparisons between the study and control groups were conducted using the Mann-Whitney U test.\u003c/p\u003e \u003cp\u003ePrimary endpoints were modeled with generalized estimating equations (GEE), adjusted for age, AL, and SE; results are reported as β (95% CI), p. Secondary metrics are exploratory and presented with effect sizes and 95% CIs without multiplicity correction. GEE with an exchangeable correlation structure were used to compare OCTA parameters between groups while accounting for inter-eye correlation. Multivariable models included age, AL, and spherical equivalent as covariates. Inter-eye agreement in the control group was assessed using the Intraclass Correlation Coefficient (ICC) based on a two-way mixed-effects model with absolute agreement.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 18 patients (8 girls, 10 boys) were included in the study group and 17 patients (8 girls, 9 boys) in the control group. The median age was 8 years (range: 5\u0026ndash;16) in the study group and 9 years (range: 6\u0026ndash;16) in the control group. All operated children had undergone cataract extraction before one year of age.\u003c/p\u003e \u003cp\u003eThe median BCVA in pseudophakic eyes was 0.6 in both the right and left eyes (range: 0.1\u0026ndash;1.0), significantly lower than in controls, where BCVA was 1.0 in both eyes (range: 0.6\u0026ndash;1.0 OD, 0.4\u0026ndash;1.0 OS) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 for both comparisons).\u003c/p\u003e \u003cp\u003eRefractive assessment revealed a more myopic profile in the study group. The median SE was \u0026minus;\u0026thinsp;2.625 D (range: \u0026minus;6.12 to 0.5) in the right eye and \u0026minus;\u0026thinsp;2.75 D (range: \u0026minus;5.88 to \u0026minus;\u0026thinsp;2.38) in the left eye. In contrast, control eyes showed a hyperopic tendency with median SE values of +\u0026thinsp;0.935 D (range: \u0026minus;0.68 to +\u0026thinsp;4.62) and +\u0026thinsp;1.245 D (range: 0 to +\u0026thinsp;6) in the right and left eyes, respectively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 for both). The median AL was significantly greater in the pseudophakic group [OD: 21.805 (range: 19.10 to 23.84) mm, OS: 21.655 (range: 19.44 to 23.82) mm] compared to controls [OD: 20.44 (range: 19.02 to 22.47) mm, OS: 20.48 (range: 19.04 to 22.15) mm] (p\u0026thinsp;=\u0026thinsp;0.009 for right eye and p\u0026thinsp;=\u0026thinsp;0.021 for the left eye).\u003c/p\u003e \u003cp\u003eThere were no statistically significant differences between groups in subfoveal choroidal thickness (OD: 384.5 \u0026micro;m vs. 373 \u0026micro;m, p\u0026thinsp;=\u0026thinsp;0.264; OS: 373 \u0026micro;m vs. 363 \u0026micro;m, p\u0026thinsp;=\u0026thinsp;0.052) or choroidal vascularity index (OD: 37.725% vs. 32.68%, p\u0026thinsp;=\u0026thinsp;0.055; OS: 35.795% vs. 34.93%, p\u0026thinsp;=\u0026thinsp;0.71).\u003c/p\u003e \u003cp\u003eOCTA analysis showed significant microvascular differences in pseudophakic eyes. Mean vessel diameter (MD) was higher in the study group in both eyes (OD: 116 vs 107 \u0026micro;m, p\u0026thinsp;=\u0026thinsp;0.049; OS: 112 vs 110 \u0026micro;m, p\u0026thinsp;=\u0026thinsp;0.044). Mean tortuosity (MT) was higher in the study group in the right eye but lower in the left eye (OD: 1.16 vs 1.15, p\u0026thinsp;=\u0026thinsp;0.036; OS: 1.14 vs 1.19, p\u0026thinsp;=\u0026thinsp;0.047). Conversely, branchpoint density (BD) was reduced (OD: 1.0294 vs. 1.29, p\u0026thinsp;=\u0026thinsp;0.018; OS: 1.033 vs. 1.11, p\u0026thinsp;=\u0026thinsp;0.036), suggesting diminished microvascular branching (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Exploratory metrics (VAD, VLD, TVL, FD) showed no significant group differences; effect sizes and 95% CIs are provided for transparency. VAD in the right eye was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.052). Peripapillary disc OCTA metrics were also comparable between groups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) except MT (p\u0026thinsp;=\u0026thinsp;0.036 in the right eye and p\u0026thinsp;=\u0026thinsp;0.047 in the left eye), see Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\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 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of Macular and Peripapillary OCTA Metrics Between Study and Control Groups in Right and Left Eyes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameter (Units)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eRight Eye\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eLeft Eye\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=\"c3\"\u003e \u003cp\u003eStudy Group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eControl Group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eStudy Group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eControl Group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003e\u003cb\u003eMacula\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eVAD (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.24 (29.53\u0026ndash;39.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35.87 (33.45\u0026ndash;36.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,052\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e33.45 (27.59\u0026ndash;35.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e33.91 (32.0\u0026ndash;35.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0,739\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eVLD (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.3 (3.22\u0026ndash;4.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.66 (2.22\u0026ndash;5.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,506\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.17 (2.93\u0026ndash;4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.08 (4.0\u0026ndash;4.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0,925\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eTVL (mm)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.78 (51.47\u0026ndash;74.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74.54 (35.55\u0026ndash;81.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e63.72 (46.82\u0026ndash;74.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e65.27 (64.07\u0026ndash;78.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0,79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMD (\u0026micro;m)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e116.0 (95.0\u0026ndash;124.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e107.0 (101.0\u0026ndash;129.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,049\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e112.0 (101.0\u0026ndash;137.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e110.0 (102.0\u0026ndash;131.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0,044\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMED (\u0026micro;m)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97.0 (10.0\u0026ndash;122.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e94.0 (86.0\u0026ndash;117.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e104.0 (77.0\u0026ndash;111.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e95.0 (90.0\u0026ndash;131.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0,22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eBD (nodes/mm)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0294 (0.6\u0026ndash;1.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.29 (0.39\u0026ndash;1.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0,018\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.033 (0.72\u0026ndash;1.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.11 (0.84\u0026ndash;1.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0,036\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eFD (no unit)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.86 (1.85\u0026ndash;1.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.86 (1.85\u0026ndash;1.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,532\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.84 (1.79\u0026ndash;1.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.86 (1.85\u0026ndash;1.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0,251\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMT (no unit)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.15 (1.11\u0026ndash;1.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.14 (1.13\u0026ndash;1.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,126\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.15 (1.12\u0026ndash;1.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.12 (1.11\u0026ndash;1.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0,048\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003e\u003cb\u003eDisc\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eVAD (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.6 (31.09\u0026ndash;35.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.87 (30.12\u0026ndash;34.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,217\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31.2 (23.7\u0026ndash;35.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e33.0 (32.5\u0026ndash;35.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0,167\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eVLD (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.43 (3.96\u0026ndash;4.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.33 (3.5\u0026ndash;4.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,215\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.0 (2.42\u0026ndash;4.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.11 (3.9\u0026ndash;5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0,15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eTVL (mm)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.92 (63.4\u0026ndash;76.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e69.25 (55.94\u0026ndash;73.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,229\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e64.07 (52.54\u0026ndash;67.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e65.7 (62.38\u0026ndash;81.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0,228\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMD (\u0026micro;m)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e116.0 (107.0\u0026ndash;130.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e115.0 (112.0\u0026ndash;125.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,797\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e120.0 (105.0\u0026ndash;132.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e118.0 (110.0\u0026ndash;130.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0,691\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMED (\u0026micro;m)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110.0 (94.0\u0026ndash;128.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e105.0 (102.0\u0026ndash;119.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,438\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e112.0 (97.0\u0026ndash;131.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e111.0 (103.0\u0026ndash;133.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0,608\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eBD (nodes/mm)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.01 (0.87\u0026ndash;1.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.99 (0.86\u0026ndash;1.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,652\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.991 (0.65\u0026ndash;1.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.99 (0.88\u0026ndash;1.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0,277\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eFD (no unit)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.86 (1.85\u0026ndash;1.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.86 (1.86\u0026ndash;1.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.86 (1.85\u0026ndash;1.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.86 (1.85\u0026ndash;1.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0,776\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMT (no unit)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.16 (1.14\u0026ndash;1.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.15 (1.11\u0026ndash;1.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0,036\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.14 (1.11\u0026ndash;1.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.19 (1.14\u0026ndash;1.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0,047\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003cem\u003eAbbreviations: BD: Branchpoint Density, FD: Fractal Dimension, MD: Mean Diameter, MED: Median Diameter, MT: Mean Tortuosity, TVL: Total Vessel Length, VAD: Vessel Area Density, VLD: Vessel Length Density\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe median FAZ area in the right eye (OD) was lower in the study group (2398.5 \u0026micro;m\u0026sup2;, IQR: 1061.7) compared with the control group (3025.7 \u0026micro;m\u0026sup2;, IQR: 2203.9). In the left eye (OS), the study group also showed smaller values (2546.7 \u0026micro;m\u0026sup2;, IQR: 2616.0) than the control group (3045.4 \u0026micro;m\u0026sup2;, IQR: 1144.7). However, these differences were not statistically significant (OD: U\u0026thinsp;=\u0026thinsp;46.0, p\u0026thinsp;=\u0026thinsp;0.21; OS: U\u0026thinsp;=\u0026thinsp;59.0, p\u0026thinsp;=\u0026thinsp;0.48) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Furthermore, the image quality score (IQS) of the analyzed OCTA scans did not differ significantly between the study and control groups (p\u0026thinsp;=\u0026thinsp;0.254).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e Sectoral analysis of the RNFL revealed localized thickening in specific quadrants. In the study group, RNFL thickness was significantly higher in the temporal and superonasal quadrants of the right eye (p\u0026thinsp;=\u0026thinsp;0.029 and p\u0026thinsp;=\u0026thinsp;0.026, respectively), and in the temporal and inferotemporal quadrants of the left eye (p\u0026thinsp;=\u0026thinsp;0.021 and p\u0026thinsp;=\u0026thinsp;0.044, respectively). Total RNFL thickness and other quadrants did not differ significantly between groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBilateral symmetry in controls: Inter-eye agreement in the healthy control group was assessed using the intraclass correlation coefficient (ICC). Inter-eye consistency was excellent for inferotemporal RNFL thickness (ICC\u0026thinsp;=\u0026thinsp;0.97) and good for MD (ICC\u0026thinsp;=\u0026thinsp;0.78), but poor for temporal RNFL thickness (ICC\u0026thinsp;=\u0026thinsp;0.33) and BD (ICC\u0026thinsp;=\u0026thinsp;0.32). The mean tortuosity (MT) demonstrated an ICC of -0.09, indicating substantial natural inter-eye variability for this microvascular metric rather than a direct negative correlation.\u003c/p\u003e \u003cp\u003eGEE adjusting for age, AL, and SE confirmed the significance of OCTA and RNFL findings. MD (p\u0026thinsp;=\u0026thinsp;0.001), MT (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and BD (p\u0026thinsp;=\u0026thinsp;0.004) remained significantly different between groups. RNFL thickness also remained significantly increased in the temporal (p\u0026thinsp;=\u0026thinsp;0.006) and inferotemporal (p\u0026thinsp;=\u0026thinsp;0.023) sectors in the study group after adjustment.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this cohort of children who underwent bilateral congenital cataract surgery with secondary IOL implantation, our preliminary findings suggest the presence of distinctive alterations in retinal microvascular morphology and RNFL thickness compared with age-matched controls. To our knowledge, this is the first study to apply OCTA in eyes after bilateral congenital cataract surgery, and the first to perform a detailed quantitative vascular network analysis using OCTAVA in this population. While OCTA has been widely used in other ocular diseases, its application here provides new insight into the potential structural consequences of early visual deprivation and surgical rehabilitation.\u003c/p\u003e \u003cp\u003eIn the context of deprivation amblyopia and congenital cataract, most histologic and clinical studies have suggested that optic nerve development is compromised, with RNFL thinning expected as a consequence of reduced visual input during early life (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Indeed, several clinical reports have described RNFL thinning in amblyopic eyes, particularly in unilateral cases or specific quadrants (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBy contrast, in our cohort we observed an apparent temporal RNFL thickening in pseudophakic eyes compared with controls. This is noteworthy, particularly given the well-established negative correlation between RNFL thickness and axial length, as our study group had significantly longer eyes (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). One explanation could be an amblyopia-related effect, as previous studies have reported thicker RNFL in anisometropic or strabismic amblyopia, and Yen et al. similarly documented higher RNFL values in refractive amblyopia (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). However, temporal thickening in our patients cannot be fully explained by amblyopia alone, especially given the mixed effects reported across different subtypes.\u003c/p\u003e \u003cp\u003eAnother possibility is a surgical effect. Dada et al. described postoperative RNFL thickening after adult cataract surgery, although this was measured using scanning laser ophthalmoscopy at week 4, representing a transient early postoperative phenomenon. In contrast, our patients were imaged years after surgery using spectral-domain OCT, making a direct parallel less likely (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Cataractous eyes may also yield underestimated RNFL measurements, but this cannot account for our results, since the control group had clear lenses (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe discrepancies between our findings and prior reports likely reflect a combination of factors, including amblyopia subtype (strabismic, anisometropic, deprivation), laterality (unilateral vs bilateral), age at imaging, axial length distribution, and differences in OCT technology (time-domain vs spectral-domain). Interestingly, our study indicates a trend that appears opposite to the thinning predicted by deprivation models, suggesting that the structural response of the optic nerve in bilaterally operated congenital cataract patients might be distinct.\u003c/p\u003e \u003cp\u003eBecause the RNFL consists of ganglion cell axons, changes in the ganglion cell layer (GCL) may also influence its thickness. Park et al. showed that several retinal layers were thicker in amblyopic eyes, supporting the hypothesis that amblyopia can affect multiple structures (24). In our cohort, amblyopia, congenital cataract, surgery, and occlusion therapy may all have contributed. RNFL thickening might also represent a compensatory response after deprivation is removed, though this remains speculative and difficult to verify in young children.\u003c/p\u003e \u003cp\u003eDiscrepancies with earlier studies may stem from differences in amblyopia type, laterality, patient age, axial length, and OCT methodology. While deprivation models generally predict RNFL thinning, we instead found temporal thickening, pointing to a potentially distinct structural response after bilateral congenital cataract surgery. Whether this reflects developmental alteration, compensation, or combined surgical and optical influences remains uncertain. Reliable RNFL measurements are rarely feasible in the early postoperative period of infancy, limiting insight into the initial course of these changes. Longitudinal studies with pre- and postoperative imaging are needed to clarify their trajectory and mechanism.\u003c/p\u003e \u003cp\u003ePeripapillary OCTA metrics did not significantly differ between groups. Only MT values reached statistical significance; however, as this parameter did not follow a normal distribution and showed inconsistent patterns between fellow eyes, the finding was considered likely attributable to the small sample size.\u003c/p\u003e \u003cp\u003eIn the literature, findings regarding the FAZ in amblyopia are inconsistent; however, most studies have reported no significant differences in FAZ size in either strabismic or anisometropic amblyopia (\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Some reports, however, have demonstrated a smaller FAZ in amblyopic eyes, particularly in the superficial capillary plexus (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). To date, no study has specifically investigated FAZ morphology in congenital cataract. In our study, although this was not a primary endpoint, exploratory analyses likewise revealed no statistically significant differences between pseudophakic and control eyes.\u003c/p\u003e \u003cp\u003eOur OCTAVA-based analysis highlighted a potentially unique microvascular profile: postoperative eyes tended to display larger vessel diameters and greater tortuosity, yet reduced BD. This configuration suggests a sparser but more dilated and sinuous network. Reduced capillary density has been reported in amblyopia, but our study is, to our knowledge, the first to characterize the superficial plexus en-face morphology in this setting, an approach with distinct quantitative advantages (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Lower BD might imply reduced vascular interconnectedness, potentially limiting perfusion reserve, as observed in glaucoma (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). The absence of significant vessel area density differences between groups may reflect partial reversibility of deprivation-induced vascular changes following amblyopia treatment (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eNo significant differences were detected in CT or CVI. The literature on amblyopia and CT is inconsistent: some studies report increased thickness, others no change, and some a reduction in congenital cataract eyes (\u003cspan additionalcitationids=\"CR34 CR35 CR36\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). Variations in AL correction, surgery timing, and treatment history may explain these discrepancies. In our cross-sectional design, postoperative optical correction and occlusion therapy\u0026mdash;together with AL differences between groups\u0026mdash; may have attenuated potential CVI differences (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur study has several limitations. This retrospective study was constrained by the size of the eligible population; analyses were exploratory and hypothesis-generating. The small sample size reduces statistical power and limits subgroup analyses, while the cross-sectional design precludes determining whether the observed changes predated surgery or developed during follow-up. Pediatric OCTA carries technical challenges; although we adjusted for AL, residual magnification effects remain possible (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). Given the exploratory aims and correlated vascular metrics, we did not adjust for multiple comparisons; findings should be interpreted with appropriate caution. We assessed only the superficial vasculature and peripapillary RNFL; the deeper capillary plexus was not analyzed to avoid the high susceptibility to projection and motion artifacts common in pediatric imaging. Although we excluded patients with obvious nystagmus or inability to fixate (given OCTA\u0026rsquo;s dependence on eye tracking), subclinical nystagmus in amblyopic patients could still have influenced results. Moreover, optic disc drusen were not specifically screened, and subclinical cases could not be excluded. Furthermore, we analyzed the entire superficial network without masking large vessels to capture global network alterations. Consequently, our morphometric metrics reflect both macro- and micro-vessel geometry. Future studies utilizing automated large-vessel masking are needed to isolate capillary-specific remodeling. Finally, the use of exclusively bilateral cases meant no internal control eyes were available, and although age-matching and statistical adjustments were applied, external control reliance carries a risk of unmeasured confounding. Magnification correction used an AL\u003csub\u003eref\u003c/sub\u003e assumed from device documentation; although standard, this introduces minor uncertainty. Also, OCTA lateral scaling constants vary across platforms; therefore, cross-device quantitative comparisons should be made with caution.\u003c/p\u003e \u003cp\u003eTo our knowledge, this is the first study to combine pediatric post-cataract OCTA with quantitative network morphology (OCTAVA), suggesting a potential pattern of reduced branching with dilated, more tortuous vessels alongside sectoral temporal RNFL thickening\u0026mdash;a phenotype not captured by conventional thickness metrics alone. The observed alterations, although analyzed after excluding major ocular or systemic comorbidities, may still be influenced by amblyopia and axial length differences. Future longitudinal work, ideally with pre- and postoperative imaging, is needed to clarify the temporal course of these findings and to determine their functional relevance for visual acuity, stereopsis, and contrast sensitivity.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFinancial Disclosures:\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The authors have no financial or proprietary interests in any material or method mentioned.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Review Board of Bursa Uludağ University Faculty of Medicine (Ethics approval no: 2025/8-17; Decision no: 621-8/17, dated 30 April 2025) and conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from the parents or legal guardians of all participating children prior to their inclusion in the study.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funding was received for this study.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthors\u0026apos; contributions\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eMOK conceptualized and designed the study, analyzed and interpreted the OCTA data, and drafted the manuscript. AA contributed to data collection, clinical examinations, and data entry. MY and ESS assisted in data interpretation and critical revision of the manuscript. ATO and MB provided senior supervision, contributed to the surgical and clinical framework of the study, and critically reviewed the manuscript for important intellectual content. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthors\u0026apos; information\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDeclaration of generative AI and AI-assisted technologies in the manuscript preparation process.\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDuring the preparation of this work the author(s) used various AI tools in order to grammar editing. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the published article.\u0026nbsp;\u003cbr clear=\"all\"\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGilbert C, Foster A. Childhood blindness in the context of VISION 2020\u0026ndash;the right to sight. Bull World Health Organ. 2001;79(3):227\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSheeladevi S, Lawrenson JG, Fielder AR, Suttle CM. Global prevalence of childhood cataract: a systematic review. Eye (Lond). 2016;30(9):1160\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRabin J, Van Sluyters RC, Malach R. Emmetropization: a vision-dependent phenomenon. Invest Ophthalmol Vis Sci. 1981;20(4):561\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWallman J, Winawer J. 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J Pediatr Ophthalmol Strabismus. 2019;56(1):55\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLonngi M, Velez FG, Tsui I, Davila JP, Rahimi M, Chan C, et al. Spectral-Domain Optical Coherence Tomographic Angiography in Children With Amblyopia. JAMA Ophthalmol. 2017;135(10):1086\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYilmaz I, Ocak OB, Yilmaz BS, Inal A, Gokyigit B, Taskapili M. Comparison of quantitative measurement of foveal avascular zone and macular vessel density in eyes of children with amblyopia and healthy controls: an optical coherence tomography angiography study. J AAPOS. 2017;21(3):224\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAraki S, Miki A, Goto K, Yamashita T, Yoneda T, Haruishi K, et al. Foveal avascular zone and macular vessel density after correction for magnification error in unilateral amblyopia using optical coherence tomography angiography. BMC Ophthalmol. 2019;19(1):171.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHormel TT, Wang J, Bailey ST, Hwang TS, Huang D, Jia Y. Maximum value projection produces better en face OCT angiograms than mean value projection. Biomed Opt Express. 2018;9(12):6412\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang L, Ding L, Zheng W. Microvascular assessment of macula, choroid, and optic disk in children with unilateral amblyopia using OCT angiography. Int Ophthalmol. 2022;42(12):3923\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRichter GM, Sylvester B, Chu Z, Burkemper B, Madi I, Chang R, et al. Peripapillary microvasculature in the retinal nerve fiber layer in glaucoma by optical coherence tomography angiography: focal structural and functional correlations and diagnostic performance. Clin Ophthalmol. 2018;12:2285\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim JG, Lee SY, Lee DC. Short-term effects of occlusion therapy and optical correction on microvasculature in monocular amblyopia: a retrospective case-control study. Sci Rep. 2023;13(1):12191.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDaniel MC, Dubis AM, MacPhee B, Ibanez P, Adams G, Brookes J, et al. Optical Coherence Tomography Findings After Childhood Lensectomy. Invest Ophthalmol Vis Sci. 2019;60(13):4388\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu Y, Dong Y, Zhao K. A Meta-Analysis of Choroidal Thickness Changes in Unilateral Amblyopia. J Ophthalmol. 2017;2017:2915261.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaek J, Lee A, Chu M, Kang NY. Analysis of Choroidal Vascularity in Children with Unilateral Hyperopic Amblyopia. Sci Rep. 2019;9(1):12143.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKurt RA, Bayar SA, Ercan ZE, Yaman Pinarci E, Tekindal MA, Oto S. Choroidal and Macular Thickness in Eyes with Amblyopia. Beyoglu Eye J. 2021;6(4):320\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou Y, Wang J, Jin L, Chen W, Wang Q, Chen H, et al. Morphological characteristics of the subfoveal choroid and their association with visual acuity in postoperative patients with unilateral congenital cataracts. Ann Transl Med. 2022;10(13):726.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHui W, Xiaofeng H, Hua X, Yihan D, Yong T. Assessment of choroidal vascularity and choriocapillaris blood perfusion in Chinese preschool-age anisometropic hyperopic amblyopia children. Front Pediatr. 2022;10:1056888.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoussef MM, Sadek SH, Hatata RM. Macular and Optic Nerve Microvascular Alteration in Relation to Axial Length, by Optical Coherence Tomography Angiography (OCTA). Clin Ophthalmol. 2022;16:885\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUntracht GR, Matos RS, Dikaios N, Bapir M, Durrani AK, Butsabong T, et al. OCTAVA: An open-source toolbox for quantitative analysis of optical coherence tomography angiography images. PLoS ONE. 2021;16(12):e0261052.\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":true,"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":"Congenital cataract, Optical coherence tomography angiography, Retinal microvasculature, Amblyopia, Retinal nerve fiber layer","lastPublishedDoi":"10.21203/rs.3.rs-9044196/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9044196/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cb\u003eBackground\u003c/b\u003e \u003c/p\u003e \u003cp\u003eEarly visual deprivation and subsequent surgical rehabilitation in congenital cataracts may induce long-term structural retinal changes. This study aimed to investigate retinal microvascular and retinal nerve fiber layer (RNFL) alterations in children after bilateral congenital cataract extraction followed by secondary intraocular lens (IOL) implantation, using optical coherence tomography angiography (OCTA) combined with an OCTAVA-based quantitative analysis.\u003c/p\u003e \u003cp\u003e \u003cb\u003eMethods\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThis retrospective, cross-sectional exploratory study included children who underwent bilateral congenital cataract extraction before one year of age with subsequent secondary IOL implantation. Age-matched healthy children served as controls. All participants underwent standardized ophthalmic examinations, spectral-domain OCT, and 6\u0026times;6 mm macular and peripapillary OCTA imaging. Quantitative vascular metrics included mean vessel diameter, branchpoint density, and tortuosity. RNFL thickness was assessed in all quadrants. To account for significant baseline differences, imaging metrics were corrected for magnification effects, and between-group comparisons were adjusted for age, axial length (AL), and spherical equivalent (SE) using generalized estimating equations (GEE).\u003c/p\u003e \u003cp\u003e \u003cb\u003eResults\u003c/b\u003e \u003c/p\u003e \u003cp\u003eEighteen pseudophakic patients (36 eyes; median age 8 years) and 17 controls (34 eyes; median age 9 years) were included. Pseudophakic eyes were significantly more myopic and had longer AL than controls (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In GEE-adjusted models, OCTA demonstrated increased mean vessel diameter (p\u0026thinsp;=\u0026thinsp;0.001), higher tortuosity (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and reduced branchpoint density (p\u0026thinsp;=\u0026thinsp;0.004) in the study group. No significant group differences were observed for choroidal thickness, choroidal vascularity index, or foveal avascular zone. Adjusted RNFL thickness was significantly greater in the temporal (p\u0026thinsp;=\u0026thinsp;0.006) and inferotemporal (p\u0026thinsp;=\u0026thinsp;0.023) sectors of the study group, while global RNFL thickness did not differ.\u003c/p\u003e \u003cp\u003e \u003cb\u003eConclusions\u003c/b\u003e \u003c/p\u003e \u003cp\u003eChildren undergoing bilateral congenital cataract surgery with secondary IOL implantation exhibit persistent microvascular remodeling\u0026mdash;characterized by dilated, more tortuous vessels with reduced branching\u0026mdash;and localized temporal RNFL thickening despite visual rehabilitation. These findings provide preliminary evidence of distinct structural alterations that warrant confirmation in larger longitudinal studies.\u003c/p\u003e","manuscriptTitle":"Retinal Microvascular and RNFL Changes After Bilateral Congenital Cataract Surgery: Preliminary Results from an Exploratory OCT/OCTA Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-27 13:25:27","doi":"10.21203/rs.3.rs-9044196/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-24T13:38:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"239940616062583072389915269586187086507","date":"2026-04-24T09:32:05+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-25T13:02:08+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-10T09:56:36+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-09T08:19:14+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-09T08:19:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2026-03-05T21:24:02+00:00","index":"","fulltext":""}],"status":"published","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}}],"origin":"","ownerIdentity":"e372fb8b-d7b0-4a77-824a-196df819f125","owner":[],"postedDate":"March 27th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-27T13:25:29+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-27 13:25:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9044196","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9044196","identity":"rs-9044196","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}