Enhancing Glaucoma Diagnosis in Myopia: Validating OCT-Based Prespecified Rules for Optic Neuropathy Detection

Highlight

• Diagnosing glaucoma in myopic eyes is challenged by overlapping anatomical features such as optic disc tilt and retinal nerve fiber layer (RNFL) shifts.
• This study validated five expert-prespecified OCT rules to differentiate glaucomatous optic neuropathy (GON) from nonpathologic myopia with high sensitivity and specificity.
• The temporal-superior-inferior-nasal-temporal (TSNIT) curve dip (rule A) demonstrated superior diagnostic performance across internal and international cohorts.
• Combining inferior peripapillary RNFL and inferotemporal macular ganglion cell-inner plexiform layer (mGC-IPL) thinning also achieved robust diagnostic accuracy.

Study Background

Glaucoma is a leading cause of irreversible blindness globally, with early detection critically impacting prognosis. Myopic eyes, especially moderate to high myopia without pathological lesions, display structural changes such as optic disc tilt, torsion, and shifts in retinal nerve fiber layer bundles. These glaucomatous-mimicking features confound the identification of glaucomatous optic neuropathy (GON), often leading to false-positive or false-negative diagnoses. Commercial diagnostic databases and algorithms frequently misclassify healthy myopic eyes as abnormal, limiting clinical confidence in OCT-based assessments.

Establishing standardized, objective diagnostic criteria that reliably distinguish GON in myopic eyes remains an unmet clinical need. Improving diagnostic performance across diverse populations and OCT devices would enhance patient care by enabling timely and accurate glaucoma detection.

Study Design

This multicenter diagnostic study incorporated a sequential two-phase design. Initially, a modified Delphi process among international glaucoma experts generated five prespecified OCT-based diagnostic rules addressing hallmark structural features relevant to GON in nonpathologic myopia. Subsequently, these rules underwent cross-sectional validation in two cohorts: an internal cohort from Zhongshan Ophthalmic Center, China, and an external international cohort including sites in Hong Kong, Taiwan, the United States, and India.

The study population comprised adults with nonpathologic moderate or high myopia, explicitly excluding eyes with pathologic myopia characterized by staphyloma or myopic maculopathy category ≥2. Data collection spanned from January 2019 through December 2024, with analysis performed between December 2024 and June 2025. OCT imaging focused on peripapillary RNFL and macular ganglion cell-inner plexiform layer (mGC-IPL) assessments.

Key Findings

A total of 943 adults contributed 1,525 eyes to the internal validation cohort. The mean participant age was 45.9 years with approximately 44% female representation. Of these eyes, 814 (53.4%) had clinically confirmed GON based on expert-masked reference diagnoses.

The diagnostic rules evaluated were:

• Rule A: Temporal-Superior-Inferior-Nasal-Temporal (TSNIT) curve dip or depression.
• Rule B: Inferior peripapillary RNFL thinning.
• Rule C: Inferotemporal mGC-IPL thinning.
• Rule D: Either Rule B or Rule C positive.
• Rule E: Both Rule B and Rule C positive.

Rule A exhibited the highest diagnostic utility:

• Internal cohort sensitivity was 96% (95% CI, 94-98%) with specificity of 95% (95% CI, 92-97%).
• External multiethnic cohort (684 eyes) maintained sensitivity of 93% (95% CI, 90-95%) and specificity of 93% (95% CI, 90-96%).

Rule D also demonstrated robust performance in external validation, with 90% sensitivity (95% CI, 87-93%) and 93% specificity (95% CI, 89-97%). The combination of inferior pRNFL and inferotemporal mGC-IPL thinning leveraged complementary structural changes, enhancing diagnostic confidence.

Rules B, C alone, and rule E showed relatively lower sensitivity, underscoring the diagnostic value of isolated and combined structural measurements in OCT analysis.

Expert Commentary

The study provides compelling evidence supporting the use of expert-prespecified OCT criteria tailored to the myopic population to reduce diagnostic ambiguity in glaucoma detection. The TSNIT curve analysis reflects comprehensive RNFL thickness profiling along the optic nerve head circumference, capturing subtle glaucomatous changes amidst myopia-associated alterations.

Integrating multiple OCT parameters also acknowledges the heterogeneity in glaucomatous damage patterns, especially in anatomically distorted myopic eyes. This enhances the ability to differentiate true optic neuropathy from myopia-related variations.

One limitation includes the exclusion of pathologic myopia, which limits generalizability to all myopic patients but focuses application on the more diagnostically challenging nonpathologic subgroup. Further studies might explore the utility of these rules in longitudinal progression detection and in varying myopic severities.

Conclusion

In conclusion, this multicenter study validates the diagnostic accuracy of prespecified OCT-based rules for identifying glaucomatous optic neuropathy in nonpathologic myopic eyes. The TSNIT curve dip criterion, alongside combined inferior peripapillary RNFL and inferotemporal mGC-IPL thinning rules, offer objective and generalizable decision support across diverse international populations and OCT platforms.

Implementing these criteria may enhance early glaucoma detection and reduce false positives in high-risk myopic patients, thereby improving clinical management and preserving visual function. Future work should integrate these rules into clinical algorithms and explore automated OCT interpretation tools to standardize glaucoma diagnosis in myopia.

Funding

The study was supported by collaborations across international academic ophthalmology institutions, including the Zhongshan Ophthalmic Center. Funding details and trial registration information were not provided in the primary source.

References

• Li F, Kong K, Jiang J, et al. Diagnostic Performance of Prespecified OCT Rules for Glaucomatous Optic Neuropathy in Nonpathologic Myopia. JAMA Ophthalmol. 2026; published online July 2. PMID: 42390850.
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• Wong TY, et al. Global Prevalence and Impact of Myopia. Ophthalmology. 2019;126(6):824-830.
• Ou Y, et al. Differentiation of Myopic and Glaucomatous Changes on OCT Imaging. Invest Ophthalmol Vis Sci. 2021;62(3):13.