---
title: "Macular OCTA Signal and Lens Dislocation: Exploratory Comparison with Archived FBN1 Reports"
id: "plos-one-11-lens-dislocation-octa-and-archived-fbn1-reports-an-exploratory-study"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-11-lens-dislocation-octa-and-archived-fbn1-reports-an-exploratory-study"
content_type: "clinical_feed_article"
specialty: "General"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361193"
published_at: "2026-10-23T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Macular OCTA Signal and Lens Dislocation: Exploratory Comparison with Archived FBN1 Reports
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-one-11-lens-dislocation-octa-and-archived-fbn1-reports-an-exploratory-study
- **Specialty:** [General](https://medichelpline.com/clinical-feed/general.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361193)
- **Published At:** 2026-10-23T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- Retrospective, availability-based cohort of 16 participants classified by lifetime lens-dislocation status (7 LD+, 9 LD−); macular **OCTA** imaging from routine care formed the analytic basis. - Imaging used a 6 × 6-mm macular scan on an Optovue RTVue XR Avanti; analyses restricted to the manufacturer-defined superficial capillary plexus (SCP). - Five OCTA endpoints compared at participant level: whole-image, foveal, parafoveal, perifoveal SCP vessel density, and right-eye foveal avascular zone (FAZ) area. - Quality control: scans required SSI ≥50, adequate centration, preserved automated segmentation, vascular continuity, and absence of major motion artifact; 29 eyes from 15 participants met criteria for quantitative analysis. - Primary unadjusted finding: lower median foveal SCP vessel density in LD+ (19.38% vs 30.20%; p = 0.036). - Multiplicity sensitivity analysis using Benjamini–Hochberg q values attenuated that result (q = 0.180); other vessel-density endpoints and OD FAZ area were not statistically significant (all reported p and q values transcribed from source). - Archived clinical genetic reports were available for seven LD+ participants; six reported an **FBN1** variant and one report was negative within its assay scope. - Between-group differences in spherical equivalent and axial length were substantial and statistically significant (median SE −7.75 D vs −1.50 D; p = 0.001; median AL 25.25 mm vs 23.65 mm; p < 0.001), representing important potential confounders. - No genotype–OCTA association testing was performed; variants were not reclassified and genetic testing was not undertaken as part of the study. - Authors characterized findings as hypothesis-generating and emphasized small sample size, heterogeneous routine-care genetic reports, and biometric differences as limits to interpretation.
## Clinical Analysis & Structured Key Points
Lens dislocation, OCTA, and archived FBN1 reports: An exploratory study | PLOS One Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click here . Article Authors Metrics Comments Media Coverage Reader Comments Figures Figures Abstract Purpose Lens dislocation (ectopia lentis) is a recognized anterior-segment manifestation of fibrillinopathy. This exploratory phenotype-first study compared macular optical coherence tomography angiography (OCTA) parameters between participants with and without documented lens dislocation and descriptively reviewed available archived clinical FBN1 reports. Methods This retrospective, availability-based study included 16 participants classified by verified current or historical lens-dislocation status. Participant-level superficial capillary plexus (SCP) vessel density was calculated by averaging valid bilateral measurements or using the single valid eye. Five OCTA endpoints were compared using two-sided Mann–Whitney U tests; Benjamini–Hochberg q values were used as a multiplicity sensitivity analysis. Seven archived clinical FBN1 reports from lens-dislocation-positive (LD+) participants were summarized without variant reclassification. No genotype–OCTA association was assessed. Results The cohort comprised 7 LD+ and 9 lens-dislocation-negative (LD−) participants; 15 participants (6 LD+ and 9 LD−) contributed quantitative OCTA data. Foveal SCP vessel density was lower in LD+ participants (median [IQR], 19.38% [18.68–20.04] vs 30.20% [29.20–31.85]; p = 0.036), but the finding was not retained after multiplicity sensitivity analysis (q = 0.180). Whole-image, parafoveal, and perifoveal vessel-density comparisons were not significant (p = 0.328, 0.272, and 0.238; q = 0.410 each), and OD-only foveal avascular zone area did not differ (n = 14; p = 0.606; q = 0.606). Six of seven archived reports documented an FBN1 variant; one was negative within its assay scope. Conclusions The unadjusted foveal signal was not robust to multiplicity analysis, and other OCTA endpoints did not differ significantly. Marked between-group differences in spherical equivalent and axial length, the small sample, and heterogeneous routine-care genetic reports limit interpretation. These findings are hypothesis-generating and do not establish OCTA as a diagnostic or prognostic test or demonstrate an individual-level genotype–OCTA association. Citation: Çevik MÖ, Simsek M, Cevik SG, Perente I (2026) Lens dislocation, OCTA, and archived FBN1 reports: An exploratory study. PLoS One 21(10): e0361193. https://doi.org/10.1371/journal.pone.0361193 Editor: Neelam Pawar, Aravind Eye Care System, INDIA Received: May 2, 2026; Accepted: October 7, 2026; Published: October 23, 2026 Copyright: © 2026 Çevik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The participant-level analytical dataset cannot be made publicly available because it combines ophthalmic, biometric, phenotypic, and archived genetic-report variables from a small rare-disease cohort that includes related participants. Even after removal of direct identifiers, combinations of these variables may permit indirect identification of participants or family members. This restriction has been confirmed by the Bursa Yüksek İhtisas Training and Research Hospital Clinical Research Ethics Committee, Bursa, Türkiye. Researchers may request access to the minimum de-identified dataset necessary to reproduce the reported findings by contacting the Bursa Yüksek İhtisas Training and Research Hospital Clinical Research Ethics Committee, Bursa, Türkiye, at bursayuksekihtisaseah@saglik.gov.tr . Requests should specify the research purpose, requested variables, proposed analysis, data-security measures, and intended duration of use. Requests will be reviewed in accordance with applicable ethical, privacy, and data-protection requirements. Approved access may require a data-use agreement, and only the minimum data necessary for the approved purpose will be provided. The authors will not serve as the sole decision-makers or access contacts. The public data dictionary, aggregate results underlying Tables 1–3 , analysis code, and supporting-file documentation are provided as Supporting Information ( S1 – S4 Files ). These materials contain no participant-level values. The archived genetic reports and other potentially identifying source records are not publicly available. Funding: The author(s) received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. Introduction Lens dislocation (ectopia lentis) is a readily recognizable and clinically actionable anterior segment sign which may provide the presenting clue to an underlying systemic connective tissue disorder. The ophthalmologist might be the first clinician to suspect the disorder and initiate systemic and genetic evaluation, as it can be detected prior to molecular confirmation [ 1 ]. Such a sequence is especially important in pediatric and young adult eye care, where a striking anterior segment finding may lead to targeted genetic testing before a clear diagnosis of a syndrome is made [ 2 , 3 ]. FBN1 encodes fibrillin-1, a major microfibrillar component of the ciliary zonule and extracellular matrix [ 4 – 7 ]. Pathogenic FBN1 variation can cause Marfan syndrome and related fibrillinopathies, including presentations dominated by ectopia lentis [ 8 – 10 ]. Fibrillin-rich microfibrils also contribute to extracellular-matrix organization and latent TGF-β complex sequestration, providing biological context for systemic vascular manifestations [ 5 , 6 , 11 , 12 ]. Optical coherence tomography angiography (OCTA) is a non-invasive, dye-free modality that provides depth-resolved visualization of the retinal microvasculature and quantitative measures including vessel density and foveal avascular zone area [ 13 ]. Layer-specific OCTA measurements can be used to investigate subclinical microvascular variation, although they are influenced by device, image quality, segmentation, refractive status, and ocular biometry [ 14 – 19 ]. Prior studies in genetically confirmed Marfan syndrome reported differences in retinal vessel-density measures, but their reproducibility and diagnostic relevance in phenotype-first cohorts remain uncertain [ 3 , 20 , 21 ]. Recognizing ectopia lentis as an actionable clue to systemic connective-tissue disease, this exploratory, availability-based retrospective study compared macular OCTA parameters between groups defined by lens-dislocation status. Archived clinical genetic reports, when available, were reviewed descriptively for FBN1 findings. The OCTA and genetic components were interpreted in parallel, yielding complementary, hypothesis-generating observations to inform future prospective studies of combined ophthalmic and molecular assessment. Methods Study design, setting, and ethics This exploratory, availability-based retrospective cross-sectional study used clinical records and macular optical coherence tomography angiography (OCTA) images acquired during routine care at the Department of Ophthalmology Retina Unit of Bursa Yüksek İhtisas Training and Research Hospital, Bursa, Türkiye, between 1 January 2016 and 31 December 2020. The primary analysis compared participants according to documented lifetime lens-dislocation status, irrespective of molecular confirmation of Marfan syndrome or another fibrillinopathy. The study was approved by the Bursa Yüksek İhtisas Training and Research Hospital Clinical Research Ethics Committee (approval no. 2011-KAEK-25 2021/08–25; 11 August 2021) and was conducted in accordance with the Declaration of Helsinki. The ethics committee waived the requirement for informed consent because the study used existing clinical records and imaging data. Records and images were accessed for research purposes between 01/09/2021 and 01/12/2021 and were coded and de-identified before analysis. Participants and data structure Potentially eligible participants were identified from the retina unit’s existing clinical files in which lens-dislocation status had been evaluated or documented. These records were cross-referenced with archived 6 × 6-mm macular OCTA examinations obtained during routine care. Eligibility required verifiable current or historical lens-dislocation status and at least one available macular OCTA record. Availability or content of genetic reports did not influence participant identification, eligibility, or lens-dislocation classification. Eligibility was not restricted to participants with a molecularly confirmed diagnosis, and no additional diagnosis-based exclusion criterion was applied during retrospective selection. Because a complete screening denominator and contemporaneous screening or exclusion log were unavailable, sampling was availability-based rather than consecutive; denominator-level exclusion counts were therefore not inferred. No a priori sample-size calculation was performed because the study used the complete availability-based cohort meeting the retrospective eligibility criteria. Sixteen participants met the eligibility criteria and formed the imaging cohort. Image quality was evaluated separately for each eye, whereas quantitative comparisons were conducted at the participant level to avoid treating two eyes from the same participant as independent observations. Lens-dislocation phenotype and clinical variables Participants were classified as lens-dislocation positive (LD+) if current or previously documented crystalline lens dislocation was present and as lens-dislocation negative (LD−) if no current or historical lens dislocation was documented. Classification was adjudicated through review of available ophthalmology and clinical records, including lifetime lens-dislocation history, laterality, current lens status, and previous lens surgery. Previous lens surgery and current lens status were recorded separately and did not replace the lifetime phenotype definition. Seven participants were classified as LD+ and nine as LD − . Refraction and axial length were recorded separately for the right (OD) and left (OS) eyes. Objective refraction was measured using a Canon RK-F2 autorefractor/keratometer (Canon Inc., Tokyo, Japan), and spherical equivalent was calculated as sphere plus one-half cylinder. Axial length was measured using a NIDEK AL-Scan optical biometer (NIDEK Co., Ltd., Gamagori, Japan). For participant-level summaries, valid bilateral values were averaged; a unilateral value was used when the fellow-eye value was unavailable. Source-verified spherical-equivalent and axial-length measurements were available for all 16 participants. OCTA acquisition and quality control Macular OCTA imaging was performed using a spectral-domain RTVue XR Avanti system with AngioVue/AngioAnalytics software (Optovue Inc., Fremont, CA, USA; software version/build 2017.1.0.151). A 6 × 6-mm macular scan centered on the fovea was acquired for each eye. Flow was detected using split-spectrum amplitude-decorrelation angiography. Quantitative analyses were restricted to the manufacturer-defined superficial capillary plexus; deep capillary plexus and choriocapillaris measurements were not analyzed. All scans underwent eye-level quality assessment before quantitative extraction. Foveal centration, automated segmentation boundaries, vascular continuity, motion artifact, and overall signal quality were assessed by a single experienced retina specialist (I.P.) who was masked to lens-dislocation classification. No manual segmentation correction was performed. Scans were eligible for the primary analysis if they had an SSI of at least 50, adequate foveal centration, acceptable automated segmentation, preserved vascular continuity, and no substantial motion or other image artifact. Scans failing any of these criteria were excluded. Under this quality rule, 29 eyes from 15 participants contributed quantitative vessel-density measurements; one participant remained in the imaging cohort but had no eye meeting the quantitative-analysis criteria. Vessel density was calculated automatically by AngioAnalytics as the percentage of the analyzed area occupied by flow-positive vascular pixels. Whole-image, foveal, parafoveal, and perifoveal superficial capillary plexus vessel-density values were transcribed from device-generated reports. FAZ area was measured in square millimetres using the AngioVue semiautomatic non-flow measurement tool. For participant-level vessel-density analyses, valid OD and OS measurements were averaged when both eyes were analyzable; when only one eye was analyzable, the valid unilateral measurement was used. FAZ analysis was restricted to available OD measurements because the retained analytical export contained no OS FAZ values. Missing OS FAZ values were not inferred or imputed. Genetic report review Genetic testing was not performed as part of the research protocol. Archived clinical FBN1 reports issued during routine care by the hospital’s accredited medical genetics laboratory were reviewed retrospectively. Testing strategies reflected the original clinical indication and included broader FBN1 next-generation sequencing in some participants and family-specific targeted testing in others. Reported regions, coverage, and assay limitations were retained on a report-specific basis. A report-negative result was therefore interpreted only within the assay scope stated by the laboratory and was not considered equivalent to a uniform comprehensive negative result. Variant nomenclature, zygosity, and laboratory interpretation were transcribed as reported. Variants were not independently reconstructed from raw sequence data or reclassified under ACMG/AMP criteria or subsequent FBN1 -specific ClinGen specifications. Broader reports cited the FBN1 reference transcript NM_000138 without a version suffix, whereas targeted familial reports did not specify a transcript. The source-report descriptions c.4349G > C (p.Cys1450Ser) and c.5368C > T (p.Arg1790*) were consequently retained without author-generated transcript conversion or reinterpretation. Seven archived genetic reports were retained, all corresponding to unique participants in the LD+ subgroup. The reports were linked to coded participants through a confidential identity crosswalk and constituted an ancillary descriptive series nested within the imaging cohort. Because no corresponding report series was available for the LD− group, genetic findings were not compared by lens-dislocation status. Individual-level genotype–OCTA association analysis was not undertaken because the report series was small, included related participants, and comprised non-uniform testing strategies. Statistical analysis Statistical analyses were performed using Python 3.12.13 with NumPy 2.3.5, pandas 2.2.3, and SciPy 1.17.0. Because of the small sample and the exploratory design, continuous variables were summarized as median and interquartile range and compared using two-sided Mann–Whitney U tests without relying on preliminary normality testing. Categorical variables were summarized as n (%) and analyzed using two-sided Fisher’s exact tests for 2 × 2 comparisons. The participant was the unit of analysis. Valid bilateral OCTA measurements were averaged, and a valid unilateral measurement was used when only one eye was analyzable. FAZ analyses were restricted to available OD measurements. Missing values were not imputed. No observations were excluded as statistical outliers; exclusions were based only on the prespecified OCTA image-quality criteria. Effect sizes for continuous comparisons were expressed as rank-biserial correlations with percentile-bootstrap 95% confidence intervals based on 100,000 resamples performed within the lens-dislocation groups (seed 20260807). Negative values indicate lower measurements in LD+ participants. The five OCTA endpoints—whole-image, foveal, parafoveal and perifoveal vessel density, and FAZ area—were treated as exploratory. Unadjusted p values were reported as the primary results, and Benjamini–Hochberg q values across the five endpoints were calculated as a multiplicity sensitivity analysis. A two-sided p < 0.05 was considered the nominal threshold for the unadjusted exploratory analyses; Benjamini–Hochberg q values were interpreted as a multiplicity sensitivity analysis. No multivariable model was fitted because the sample size was insufficient for stable adjusted estimation. Analyses were conducted using the locked, de-identified dataset and finalized on 7 August 2026. Use of artificial intelligence tools OpenAI ChatGPT and Microsoft Powerpoint were used to assist with the conceptual organization and layout planning of Fig 1 ; the scientific content and final figure were reviewed and approved by the authors. All interpretations, conclusions, limitations, and scientific claims represent the authors’ own assessment and responsibility. Download: PNG larger image TIFF original image Fig 1. Three-tier evidence framework for ectopia lentis and retinal OCTA observations. Tier 1 summarizes the established structural role of fibrillin-1 in ciliary-zonule integrity [ 6 , 7 , 34 ]. Tier 2 summarizes context-dependent systemic and aortic evidence involving fibrillin-rich extracellular matrix and TGF-β regulation [ 5 , 6 , 34 – 38 ]. Tier 3 presents experimental retinal evidence and the unverified bridge to human optical coherence tomography angiography measurements [ 3 , 20 , 21 , 39 , 40 ]. The present study retrospectively compared OCTA parameters by lens-dislocation status and descriptively reviewed archived FBN1 reports in the LD+ subgroup; it did not test the depicted pathways or individual-level genotype–OCTA associations. https://doi.org/10.1371/journal.pone.0361193.g001 Results The imaging cohort included 16 participants: 7 LD+ and 9 LD − . Median age was 11.0 years (IQR, 8.0–14.0) in LD+ and 14.0 years (IQR, 14.0–16.0) in LD− (p = 0.111). Females comprised 2/7 (28.6%) of LD+ and 5/9 (55.6%) of LD− participants (p = 0.358). Median SE was −7.75 D (IQR, −8.25 to −6.75) in LD+ and −1.50 D (IQR, −1.75 to −1.38) in LD− (p = 0.001); median AL was 25.25 mm (IQR, 24.80–25.60) and 23.65 mm (IQR, 23.55–23.65), respectively (p < 0.001). All participants were bilaterally phakic, and none had undergone previous lens surgery. Six of seven LD+ participants and all nine LD− participants contributed analyzable OCTA data. One LD+ participant contributed OS only because the OD scan had an SSI of 32, and one LD+ participant contributed no quantitative OCTA data because both eyes were below the prespecified SSI threshold. Baseline characteristics are shown in Table 1 . Download: PNG larger image TIFF original image Table 1. Baseline clinical and imaging characteristics by lens-dislocation status. https://doi.org/10.1371/journal.pone.0361193.t001 Participant-level SCP vessel-density medians were lower in LD+ than in LD− for all four regions ( Table 2 ). Whole-image values were 45.48% (IQR, 44.31–49.45) versus 49.25% (IQR, 47.85–52.50; p = 0.328; q = 0.410). Foveal values were 19.38% (IQR, 18.68–20.04) versus 30.20% (IQR, 29.20–31.85; p = 0.036; q = 0.180). Although the foveal comparison met the conventional 0.05 threshold in the unadjusted exploratory analysis, it was not retained in the multiplicity sensitivity analysis. Parafoveal values were 48.35% (IQR, 47.02–53.88) versus 51.65% (IQR, 50.70–55.10; p = 0.272; q = 0.410), and perifoveal values were 45.20% (IQR, 43.56–50.44) versus 51.50% (IQR, 48.35–55.10; p = 0.238; q = 0.410). OD-only FAZ area was 0.148 mm 2 (IQR, 0.145–0.432; n = 5) in LD+ and 0.272 mm 2 (IQR, 0.252–0.312; n = 9) in LD− (p = 0.606; q = 0
## Related Clinical Research

- [Correction Notice: Photovoice-Greenspaces Health Protocol Republished After Error](https://medichelpline.com/clinical-feed/plos-one-3-correction-a-scoping-review-of-photovoice-studies-concerning-greenspaces-and.md)
- [Stride-length alters energy flow through the upper extremity in baseball pitching](https://medichelpline.com/clinical-feed/plos-one-19-the-composition-of-energy-flow-in-the-upper-extremity-under-different-lower.md)
- [How to define outcomes completely in clinical trials: six-element guidance](https://medichelpline.com/clinical-feed/plos-medicine-1-guidance-for-defining-outcomes-in-clinical-trials.md)
- [Major employers commit to faster, electronic prior authorizations for self-funded plans](https://medichelpline.com/clinical-feed/healthcare-dive-0-five-major-companies-pledge-faster-electronic-prior-authorizations.md)
- [Medicaid work requirements spark legal fights and implementation anxiety](https://medichelpline.com/clinical-feed/stat-news-5-anxiety-builds-over-medicaid-work-requirements.md)

## Navigation
- [← Back to General Feed](https://medichelpline.com/clinical-feed/general.md)
- [← All Clinical Specialties](https://medichelpline.com/clinical-feed.md)
## Medical & Regulatory Disclaimer

> [!CAUTION]
> MedicHelpline content is structured for research, educational, and professional discovery purposes. It does not constitute individual medical advice, clinical diagnosis, or treatment recommendations.
> Always verify dosing, contraindications, and regulatory alerts against official product labeling and primary regulatory sources before clinical decision-making.