Purpose: To investigate the clinical implications of lacquer cracks as precursors to idiopathic multifocal choroiditis/punctate inner choroidopathy (iMFC/PIC) and their role in disease progression, visual outcomes, and risk stratification in both affected and fellow eyes of iMFC/PIC patients. Design: Retrospective observational cohort study. Subjects: A total of 185 eyes from 142 patients with iMFC/PIC examined between 2005 and 2025. Methods: Multimodal imaging was performed on study and fellow eyes. Infrared images obtained at the time of iMFC/PIC lesion regression and patchy chorioretinal atrophy formation were contrast-enhanced, binarized, and segmented. Cartesian lesion coordinates were analyzed for spatial distribution, with K-means clustering estimating the number of clusters per eye. A second-degree polynomial regression model determined whether lesions followed a structured curvilinear pattern. Eyes were categorized as lacquer iMFC/PIC (≥1 structured lesion cluster) or nonlacquer iMFC/PIC (random lesion distribution). Main Outcome Measures: Clinical and demographic comparisons between groups conducted using linear mixed-effects models. Temporal relationship between lacquer cracks and iMFC/PIC onset in initially healthy fellow eyes assessed using Kaplan–Meier survival analysis and log-rank test comparisons. Results: A structured, lacquer crack-aligned lesion distribution was observed in 139 eyes (75%), classified as lacquer iMFC/PIC. These eyes had higher myopic refractive error (–11.1 D vs –5.25 D, P < .001), a greater prevalence of lacquer cracks on multimodal imaging (89% vs 39%, P < .001) and more atrophic lesions (median: 24 [interquartile range: 15-54] vs median: 2 [interquartile range: 1-9], P < .001). Higher lesion burden correlated with greater myopia (r = –0.24, P = .002) and more frequent inflammatory recurrences (r = 0.13, P = .07). Among 83 initially healthy fellow eyes, 15 (18%) developed lacquer iMFC/PIC. Lacquer cracks always preceded iMFC/PIC onset. Log-rank analysis showed no difference between the timing of lacquer crack formation and iMFC/PIC onset (P = .5), suggesting that both processes develop in parallel rather than as independent events. Conclusions: Our findings suggest that iMFC/PIC associated with lacquer cracks may not represent a purely idiopathic inflammatory disorder but rather could be related to mechanical outer retinal disruption in highly myopic eyes. The temporal association between lacquer cracks and iMFC/PIC onset in fellow eyes indicates that these processes likely develop in close relationship, although causality cannot be established. Early identification of lacquer cracks and careful monitoring of at-risk myopic patients may help in anticipating disease onset and limiting progression toward irreversible macular atrophy.

Idiopathic Multifocal Choroiditis/Punctate Inner Choroidopathy as a Secondary Inflammatory Reaction to Lacquer Cracks: A Structural and Temporal Analysis / Cicinelli, M. V.; Del Fabbro, S.; Ramtohul, P.; Maiucci, G.; Martino, G.; Bianco, L.; Introini, U.; Battaglia Parodi, M.; Bandello, F.; Miserocchi, E.. - In: AMERICAN JOURNAL OF OPHTHALMOLOGY. - ISSN 0002-9394. - 282:(2026), pp. 263-276. [10.1016/j.ajo.2025.11.019]

Idiopathic Multifocal Choroiditis/Punctate Inner Choroidopathy as a Secondary Inflammatory Reaction to Lacquer Cracks: A Structural and Temporal Analysis

Cicinelli M. V.;Del Fabbro S.;Bianco L.;Battaglia Parodi M.;Bandello F.;Miserocchi E.
2026-01-01

Abstract

Purpose: To investigate the clinical implications of lacquer cracks as precursors to idiopathic multifocal choroiditis/punctate inner choroidopathy (iMFC/PIC) and their role in disease progression, visual outcomes, and risk stratification in both affected and fellow eyes of iMFC/PIC patients. Design: Retrospective observational cohort study. Subjects: A total of 185 eyes from 142 patients with iMFC/PIC examined between 2005 and 2025. Methods: Multimodal imaging was performed on study and fellow eyes. Infrared images obtained at the time of iMFC/PIC lesion regression and patchy chorioretinal atrophy formation were contrast-enhanced, binarized, and segmented. Cartesian lesion coordinates were analyzed for spatial distribution, with K-means clustering estimating the number of clusters per eye. A second-degree polynomial regression model determined whether lesions followed a structured curvilinear pattern. Eyes were categorized as lacquer iMFC/PIC (≥1 structured lesion cluster) or nonlacquer iMFC/PIC (random lesion distribution). Main Outcome Measures: Clinical and demographic comparisons between groups conducted using linear mixed-effects models. Temporal relationship between lacquer cracks and iMFC/PIC onset in initially healthy fellow eyes assessed using Kaplan–Meier survival analysis and log-rank test comparisons. Results: A structured, lacquer crack-aligned lesion distribution was observed in 139 eyes (75%), classified as lacquer iMFC/PIC. These eyes had higher myopic refractive error (–11.1 D vs –5.25 D, P < .001), a greater prevalence of lacquer cracks on multimodal imaging (89% vs 39%, P < .001) and more atrophic lesions (median: 24 [interquartile range: 15-54] vs median: 2 [interquartile range: 1-9], P < .001). Higher lesion burden correlated with greater myopia (r = –0.24, P = .002) and more frequent inflammatory recurrences (r = 0.13, P = .07). Among 83 initially healthy fellow eyes, 15 (18%) developed lacquer iMFC/PIC. Lacquer cracks always preceded iMFC/PIC onset. Log-rank analysis showed no difference between the timing of lacquer crack formation and iMFC/PIC onset (P = .5), suggesting that both processes develop in parallel rather than as independent events. Conclusions: Our findings suggest that iMFC/PIC associated with lacquer cracks may not represent a purely idiopathic inflammatory disorder but rather could be related to mechanical outer retinal disruption in highly myopic eyes. The temporal association between lacquer cracks and iMFC/PIC onset in fellow eyes indicates that these processes likely develop in close relationship, although causality cannot be established. Early identification of lacquer cracks and careful monitoring of at-risk myopic patients may help in anticipating disease onset and limiting progression toward irreversible macular atrophy.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/201686
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