Phenotypic Spectrum of Early Onset Angle Closure Glaucoma in Young Indian Patients.

Early-onset angle-closure glaucoma (EOACG), defined as onset of angle-closure glaucoma (ACG) manifesting at or before 40 years of age, represents a distinct and understudied subset of angle-closure disease, with limited literature describing its clinical and demographic diversity [1, 2]. Unlike its late-onset counterpart, EOACG demonstrates considerable heterogeneity in clinical presentation and underlying mechanisms [1]. Against this backdrop, this observational study investigated the aetiopathogenic mechanisms and demographic profile of EOACG in a North Indian cohort. Among the enrolled 259 eyes (160 patients), 205 (79%) were categorised as EOPACG, 29 (11%) nanophthalmos, 21 (8%) RAM and 4 (2%) microspherophakia. The mean age of onset was highest in EOPACG (36.9 ± 3.6 years), followed by RAM (32.2 ± 4.2 years), nanophthalmos (29.8 ± 9.1 years) and microspherophakia (24 ± 1.1 years) (p < 0.001). A slight male predominance was observed (p = 0.8) (Table 1). Mechanistic evaluation revealed marked heterogeneity. PIC [4] and pseudo–PIC (PPIC) emerged as the most common mechanisms in EOPACG and RAM. PPIC refers to angle narrowing caused by iridociliary cysts that push the peripheral iris forward, creating a plateau-like appearance without the characteristic iris roll seen in PIC. UBM confirmed cyst-related anterior iris displacement as the underlying pathology [4]. Nanophthalmos was more commonly associated with mixed mechanisms, whereas microspherophakia demonstrated combined features of exaggerated lens vault (LV > ⅓ ACD) and pupillary block. The predominant mechanism was defined as the mechanism involving > 2 quadrants on gonioscopy or UBM. In microspherophakia, UBM revealed a small spherical lens (equatorial diameter, 5.12 ± 0.10 mm; LT, 5.34 ± 0.12 mm), lens vault (LV, 1.24 ± 0.13 mm), shallow ACD (1.65 ± 0.13 mm) and normal AL (22.14 ± 0.23 mm) (Table 2). RAM eyes exhibited the longest AL, whereas nanophthalmic eyes demonstrated the shortest, with EOPACG eyes having intermediate values (p < 0.001). ACD was comparable between eyes with RAM and EOPACG but significantly shallower in nanophthalmos (p < 0.001). LT and LV did not differ significantly across the phenotypes, suggesting LT alone does not drive angle crowding. Instead, rLP emerged as a key discriminator. A lower rLP value, reflecting a more anteriorly positioned lens, was most pronounced in RAM (p < 0.001), explaining the paradox of angle crowding despite longer axial dimensions. In nanophthalmos, globally reduced anterior segment dimensions were observed, exacerbated by significantly steeper corneas compared with EOPACG and RAM (K-mean: 46.8 ± 2.2 D vs. 44.0 ± 1.7 D and 43.6 ± 4.4 D, respectively; overall p < 0.001). In contrast, EOPACG and RAM showed comparable keratometry profiles (p = 0.9). Hence, in younger patients presenting with high intraocular pressure and angle-closure, EOPACG emerged as the predominant phenotype, with PIC and PPIC among the most frequent patho-mechanisms. However, a detailed anatomical evaluation is essential to distinguish EOPACG from other phenotypes, as standard gonioscopy alone is insufficient. Biometric assessments, including AL, ACD and corneal diameter, are critical to differentiate entities like RAM and nanophthalmos, as misclassification may lead to inappropriate treatment decisions. Microspherophakia, although uncommon, may clinically mimic EOACG and should be carefully excluded based on dilated slit-lamp examination, myopic refractive profile and supportive UBM findings. Importantly, its recognition has direct surgical implications, as lens extraction may be the preferred initial intervention [5]. Correct identification of phenotypes is therefore essential to ensure appropriate therapeutic decision-making. Although limited by its single-centre design, this study represents one of the largest EOACG cohorts, particularly for EOPACG, RAM and nanophthalmos. Broader, multicentre studies with longer follow-up are needed to validate these findings. To conclude, EOACG is not a monolithic entity but rather a spectrum of distinct phenotypes, each demanding a unique diagnostic and therapeutic strategy. Incorporating detailed imaging and quantitative parameters refines diagnosis, risk stratification and targeted therapy. The authors have nothing to report. The authors declare no conflicts of interest. This study was reviewed by the Institutional Ethics Committee of All India Institute of Medical Sciences, New Delhi and conducted in accordance with the Declaration of Helsinki. The requirement for individual informed consent was waived for this retrospective analysis. The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.