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Editors Selection IGR 26-1

Progression / Prognostic Factors: Longitudinal lens changes predict angle closure progression risk

Comment by Sunee Chansangpetch & Shan Lin on:

127611 Short-Term Ocular Biometric Changes as Predictors of Long-Term Angle Closure Progression, Hong KL; Xu BY; Wang W et al., JAMA ophthalmology, 2025; 143: 543-551

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The Zhongshan Angle-Closure Prevention (ZAP) Trial has demonstrated a low 6-year risk of progression from untreated primary angle closure suspect (PACS) to primary angle closure (PAC) (<1% per eye year). Although laser peripheral iridotomy (LPI) reduced the risk of progression by 47% over 6 years (and 69% over 14 years), the number needed to treat with LPI to prevent a progression was high—44 at six years and 12 at 14 years—and widespread prophylactic treatment is generally not recommended.1, 2 This leaves an important gap in clinical management– how to identify the subset of PACS individuals who are at high risk of progression and would benefit most from intervention. Previous studies found that static baseline biometric measurements were only moderately predictive of outcomes, with concordance indexes ranging from 0.48 to 0.68, necessitating the identification of additional risk factors.3

This retrospective cohort study from Hong and colleagues investigated whether short-term (18-month) anatomical changes could predict long-term (36-72 month) progression to PAC. The study analyzed serial anterior segment optical coherence tomography (AS-OCT) images of the 785 untreated PACS eyes in the ZAP trial. According to the study, between 36 and 72 months, 26 eyes (3.3%) progressed. The study found that while static baseline measurements are moderately predictive of outcomes, longitudinal monitoring provides independent information regarding a patient's risk. Specifically, an increase in lens vault (ΔLV) and a decrease in angle width (ΔTISA750) over the initial 18 months were significantly associated with long-term progression. The addition of 18-month change data improved the predictive model's concordance index from 0.69 to 0.73. The study also developed multivariable models using categorical data, which provided a risk stratification based on specific biometric thresholds. The best model showed that baseline TISA500 and ΔLV independently conferred the greatest risk of progression: patients identified with high-risk features—specifically a narrow TISA500 at baseline (lowest quartile, <0.031 mm², hazard ratio 2.65) combined with rapid increase in lens vault (highest quartile, >0.663 mm, hazard ratio 2.70)—faced a progression risk of 4.4% per eye-year, more than triple the 1.3% risk seen in eyes of same baseline angle width with stable LV. Although the predictive performance was moderate and has not yet undergone formal external validation, the findings highlight the value of incorporating serial measurements and suggest that longitudinal lens changes may contribute to PAC development. The study has limited generalizability to non-Chinese populations. It is also important to note that the AS-OCT data used in the study were derived from a single horizontal time-domain OCT scan. Modern AS-OCT technology now allows three-dimensional volumetric angle imaging with a higher resolution, which could provide more comprehensive information about anterior segment anatomy.4 Additionally, individual variability in dynamic pupillary responses may play a role in progression and warrants further investigation. Lastly, while anatomical parameters are essential for risk assessment, other clinical factors—such as family history of angle closure and the need for repeated dilation—should also be considered. Overall, this study represents an important early step toward individualized care, supporting the development of a comprehensive risk score to identify PACS patients at higher risk of progression.

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