Clinical characteristics and ultrasound biomicroscopic evaluation of anterior segment dysgenesis: a retrospective cross-sectional study
Introduction
Anterior segment dysgenesis (ASD) encompasses a spectrum of disorders involving malformations in the anterior segment of the eye, including the cornea, iris, anterior chamber angle, lens, and ciliary body (1-3). The disrupted anatomical relationships in the structures of the anterior segment can alter the aqueous humor flow, resulting in elevated intraocular pressure and subsequent glaucoma, which can cause irreversible blindness if not appropriately managed (1-3). Patients with ASD have a high risk of developing glaucoma, often at a young age (4-6).
The phenotypes of ASD include primary congenital glaucoma (PCG), aniridia, Axenfeld-Rieger syndrome (ARS), Peters anomaly (PA), congenital ectropion uveae (CEU), persistent fetal vasculature (PFV), congenital fibrovascular pupillary membrane (CFPM), iris coloboma, microcornea, and other related conditions. The complex and overlapping nature of these phenotypes poses challenges in diagnosis and differentiation, particularly in cases where concurrent corneal opacity obscures the assessment of intraocular conditions (2,5,6). The clinical presentation of ASD is highly heterogeneous, ranging from subtle anomalies detectable only through advanced imaging techniques to severe, visually apparent defects present at birth.
Ultrasound biomicroscopy (UBM) stands as a pivotal and noninvasive modality, offering dynamic, high-resolution imaging of the anterior segment in vivo (7,8). This imaging tool is particularly valuable in patients with ASD who exhibit corneal opacity or anomalies situated posterior to the iris. The utilization of UBM in clinical work facilitates precise diagnosis, which is a critical factor in guiding appropriate treatment and ultimately preserving visual function.
Despite the significant clinical implications of ASD, existing research is predominantly focused on genetic variations (4,9,10). Reports with large sample sizes comparing clinical features between ASD subtypes are limited. The rarity of ASD makes it challenging to conduct studies that require a considerable number of cases. Accurate diagnosis of ASD, especially with its complex phenotypic presentations, is essential for timely and effective management to prevent severe visual impairment and blindness. The objective of this study is to describe and differentiate the clinical characteristics and UBM features of different ASD subtypes, in order to enhance diagnostic accuracy and guide appropriate interventions. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-24-875/rc).
Methods
This retrospective cross-sectional study reviewed the medical records of patients consecutively admitted to the Eye & ENT Hospital, Fudan University between January 2013 and December 2022. The diagnoses encompassed various subtypes of ASD, including PCG, aniridia, ARS, PA, CEU, PFV, CFPM, iris coloboma, and microcornea. Patients with dysgenesis of the anterior segment but not fitting into any of the categories mentioned above would be diagnosed with ASD-unknown. Patients with a history of trauma, uveitis, or previous ocular surgeries were excluded from the study. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and was approved by the Institutional Review Board of Eye & ENT Hospital of Fudan University (No. KJ2011-04) and the requirement for individual consent for this retrospective analysis was waived.
A comprehensive analysis was conducted, involving demographic profiles, clinical manifestations, and UBM images. Demographic data comprised age at diagnosis, gender, and any relevant family history. Visual acuity was assessed using Snellen’s test-chart, and in patients with very poor vision, visual acuity was categorized using a semiquantitative scale, including counting fingers (CF), hand motion (HM), light perception (LP), or no light perception (NLP). Ocular manifestations were thoroughly examined with a slit lamp microscope; children who were unable to cooperate were assessed under general anesthesia. The laterality, best-corrected visual acuity (BCVA), and ocular comorbidities were documented. UBM (MD-300L; MEDA Co., Ltd., Tianjin, China) with a 50 MHz resolution was performed.
Statistical analysis was conducted using the software SPSS 20.0 (IBM Corp, Armonk, NY, USA). The normality of continuous data distribution was assessed using the Shapiro-Wilk test. Continuous data were reported as mean and standard deviation for normally distributed data, or as median and interquartile range (IQR) for non-normally distributed data. Categorical data were displayed as counts and percentages.
Results
A total of 1,249 patients fitting the criteria for ASD were initially reviewed. Out of these, 218 patients were excluded due to a history of trauma, uveitis, or previous ocular surgeries. Consequently, we analyzed the medical records of 1,031 patients diagnosed with ASD. The specific diagnoses identified among these patients included: PCG (396 patients, 625 eyes), aniridia (61 patients, 122 eyes), ARS (28 patients, 56 eyes), PA (149 patients, 234 eyes), CEU (8 patients, 13 eyes), PFV (177 patients, 189 eyes), CFPM (15 patients, 16 eyes), iris coloboma (102 patients, 169 eyes), microcornea (93 patients, 155 eyes), and ASD-unknown (48 patients, 71 eyes) (Figure 1). A total of 46 patients carried 2 or more ASD-related diagnoses. A detailed summary of demographic and clinical characteristics for each condition is provided in Table 1.
Table 1
| Characteristic | PCG | Aniridia | ARS | PA | CEU | PFV | CFPM | Iris coloboma | Microcornea |
|---|---|---|---|---|---|---|---|---|---|
| Number (eyes/patients) | 625/396 | 122/61 | 56/28 | 234/149 | 13/8 | 189/177 | 16/15 | 169/102 | 155/93 |
| Age at diagnosis (years) | 0.9 [0.4–3] | 20 [5–34.5] | 10 [0.8–25.5] | 0.6 [0.5–0.9] | 6 [0.3–27.8] | 3 [0.7–6] | 0.4 [0.25–6] | 42.5 [26–51] | 35 [4.5–47] |
| Gender (male/female) | 260/136 | 37/24 | 20/8 | 77/72 | 3/5 | 91/86 | 8/7 | 43/59 | 41/52 |
| Laterality (unilateral/bilateral) | 167/229 | 0/61 | 0/28 | 64/85 | 3/5 | 165/12 | 14/1 | 35/67 | 31/62 |
| Family history | 20 (5.1) | 7 (11.5) | 9 (32.1) | 1 (0.7) | 0 | 0 | 0 | 0 | 0 |
| BCVA | 0.05 [HM–0.15] | 0.05 [CF–0.1] | 0.10 [CF–0.35] | CF [LP–0.04] | 0.8 [0.15–1.0] | 0.05 [CF–0.15] | NLP/0.5/0.5/0.8† | 0.01 [HM–0.08] | CF [HM–0.1] |
| Main complaint | |||||||||
| Corneal whitening | 87 (22.0) | 7 (11.5) | 4 (14.3) | 147 (98.7) | 1 (12.5) | 3 (1.7) | 4 (26.7) | 3 (2.9) | 10 (10.8) |
| Corneal enlargement | 133 (33.6) | 1 (1.6) | 2 (7.1) | 1 (0.7) | – | 1 (0.6) | 4 (26.7) | – | – |
| Photophobia | 207 (52.3) | 10 (16.4) | 7 (25.0) | 3 (2.0) | 3 (37.5) | 14 (7.9) | 2 (13.3) | 1 (1.0) | – |
| Tearing | 196 (49.5) | 6 (9.8) | 6 (21.4) | 4 (2.7) | 3 (37.5) | – | 2 (13.3) | – | – |
| Decreased vision | 20 (5.1) | 31 (50.8) | 11 (39.3) | 1 (0.7) | 3 (37.5) | 48 (27.1) | 1 (6.7) | 86 (84.3) | 63 (67.7) |
| Ocular pain | – | – | 2 (7.1) | – | 1 (12.5) | 8 (4.5) | – | 2 (2.0) | 1 (1.1) |
| Leukocoria | – | 10 (16.4) | – | – | – | 86 (48.6) | 4 (26.7) | 3 (2.9) | 12 (12.9) |
| Strabismus | – | – | – | – | – | 14 (7.9) | – | 5 (4.9) | 6 (6.5) |
| Exophthalmos | 6 (1.5) | – | – | – | – | – | – | – | – |
| Small eye | – | – | – | – | – | 3 (1.7) | – | 2 (2.0) | 1 (1.1) |
| Common ocular comorbidities | |||||||||
| Corneal opacification | 525 (84.0) | 48 (39.3) | 21 (37.5) | 234 (100.0) | 6 (46.2） | 22 (11.6) | 10 (62.5) | 6 (3.6) | 25 (16.1) |
| Cataract | 25 (4.0) | 98 (80.3) | 17 (30.4) | 27 (11.5) | 1 (7.7) | 181 (95.8) | 2 (12.5) | 150 (88.8) | 131 (84.5) |
| Lens dislocation | 2 (0.3) | 14 (11.5) | 1 (1.8) | 12 (5.1) | – | 4 (2.1) | – | 29 (17.2) | 23 (14.8) |
| Glaucoma | 625 (100.0) | 45 (36.9) | 50 (89.3) | 26 (11.1) | 13 (100.0) | 26 (13.8) | 10 (62.5) | 9 (5.3) | 21 (13.5) |
| Nystagmus | 18 (2.9) | 100 (82.0) | 2 (3.6) | 48 (20.5) | – | 23 (12.2) | 1 (6.3) | 92 (54.4) | 91 (58.7) |
| Strabismus | 9 (1.4) | 19 (15.6) | 1 (1.8) | 24 (10.3) | – | 45 (23.8) | 1 (6.3) | 37 (21.9) | 41 (26.5) |
| Ptosis | 2 (0.3) | 12 (9.8) | – | – | 2 (15.4) | – | – | – | 2 (1.3) |
| Microcornea | – | 2 (1.6) | 2 (3.6) | 1 (0.4) | – | 2 (1.1) | – | 60 (35.5) | 155 (100.0) |
| Microphthalmia | – | – | – | 5 (2.1) | – | 3 (1.6) | – | 15 (8.9) | 8 (5.2) |
| Iris coloboma | – | – | – | – | – | 1 (0.5) | – | 169 (100.0) | 60 (38.7) |
| Choroidal coloboma | 1 (0.2) | – | – | – | – | – | – | 124 (73.4) | 58 (37.4) |
| Lens coloboma | – | – | – | – | – | – | – | 1 (0.6) | – |
| Retinal detachment | – | – | – | – | – | 12 (6.3) | – | 31 (18.3) | 15 (9.7) |
| Persistent pupillary membrane | – | – | – | – | – | 6 (3.2) | – | 2 (1.2) | 5 (3.2) |
| Entropion and trichiasis | 58 (9.3) | – | – | – | – | – | – | – | – |
| Foveal hypoplasia | – | 34 (27.9) | – | – | – | – | – | – | – |
| Optic disc dysplasia | – | – | – | – | – | 2 (1.1) | – | – | – |
| Retinal dysplasia | – | – | – | – | – | – | – | 2 (1.2) | – |
| Microspherophakia | – | – | – | – | – | 1 (0.5) | – | – | 2 (1.3) |
Data are presented as number, median [IQR], or number (%). †, BCVA assessment was only conducted in 4 cooperative patients in the CFPM group. PCG, primary congenital glaucoma; ARS, Axenfeld-Rieger syndrome; PA, Peters anomaly; CEU, congenital ectropion uveae; PFV, persistent fetal vasculature; CFPM, congenital fibrovascular pupillary membrane; BCVA, best-corrected visual acuity; HM, hand motion; CF, counting finger; LP, light perception; NLP, no light perception; IQR, interquartile range.
PCG
PCG predominated among our patients, which comprised 396 patients with a median age of 0.9 years (IQR, 0.4–3 years). Males accounted for 65.7%, and 57.8% had bilateral involvement. Notably, 20 patients (5.1%) had a positive family history of PCG. The main symptoms were photophobia, tearing, corneal enlargement, and corneal whitening. Corneal involvement, including corneal opacity and Haab striae, was the most commonly observed sign in PCG eyes (525, 84.0%). Additional ocular comorbidities identified were entropion and trichiasis (58, 9.3%), and cataracts (25, 4.0%), among others.
UBM was performed on 262 patients, encompassing 420 PCG eyes and 104 contralateral eyes. In all eyes, the anterior chamber angle was open. Compared with contralateral eyes, PCG eyes exhibited a deeper anterior chamber, thinner iris, and elongated ciliary process. Abnormal tissue in the anterior chamber angle was found in 266 PCG eyes (63.3%), anterior insertion of iris root in 307 PCG eyes (73.1%), and shallow or obliterated ciliary sulcus in 133 PCG eyes (31.7%). Representative anterior segment photographs and UBM images of PCG are depicted in Figure 2.
Aniridia
Among the 61 aniridia patients (median age: 20 years), bilateral involvement was observed across the entire cohort, with 7 patients (11.5%) reporting a positive family history of aniridia. The median BCVA was 0.05 (IQR, from CF to 0.1). Main symptoms included decreased vision, leukocoria, photophobia, and corneal whitening. Aniridia manifested as a panocular disease affecting various ocular structures, including corneal opacification and vascularization (48, 39.3%), microcornea (2, 1.6%), cataracts (98, 80.3%), lens subluxation (11, 9.0%), lens luxation (3, 2.5%), foveal hypoplasia (34, 27.9%), and ptosis (12, 9.8%). Additionally, glaucoma was diagnosed in 45 eyes (36.9%), nystagmus in 100 eyes (82.0%), and strabismus in 19 eyes (15.6%).
UBM on 20 patients (40 eyes) showed that all eyes exhibited an iris stump and a small ciliary body. A total of 14 patients had open angles in both eyes, 5 patients had partially or completely closed angles in both eyes, and 1 patient had an open angle in 1 eye and a partially closed angle in the other eye. Among the 22 eyes affected by both aniridia and glaucoma, 15 eyes (68.2%) exhibited open angles, whereas 7 eyes (31.8%) had closed angles. Figure 3 shows the representative anterior segment photographs and UBM images of aniridia.
ARS
The 28 patients with ARS had a median age of 10 years (IQR, 0.8–25.5 years). Males were more frequently affected (20, 71.4%). A total of 9 patients (32.1%) had a family history of ARS. The primary symptoms included decreased vision, photophobia, tearing, and corneal whitening. Under slit lamp examination of the 56 eyes, notable ocular features were observed: posterior embryotoxon (24, 42.9%), iridocorneal adhesions (14, 25.0%), corectopia (16, 28.6%), polycoria (13, 23.2%), irregular pupil (7, 12.5%), and ectropion uvea (5, 8.9%). Common ocular comorbidities included corneal opacification (21, 37.5%), cataracts (17, 30.4%), and glaucoma (50, 89.3%).
UBM on 21 patients (42 eyes) revealed different degrees of iris hypoplasia. Posterior embryotoxon was noted in 12 eyes, iris process (peripheral iris strands extending to the protruding Schwalbe’s line) was observed in 6 eyes, and iridocorneal adhesions were noted in 12 eyes. Out of the 38 eyes with glaucoma, 17 eyes (44.7%) exhibited open angles, while 21 eyes (55.3%) had partially or completely closed angles. Figure 4 shows the representative anterior segment photographs and UBM images of ARS.
PA
Among the 149 PA patients with a median age of 0.6 years, 85 patients (57.0%) had bilateral PA. Only 1 patient reported a positive family history. The majority of our PA patients (98.7%) sought medical attention due to corneal whitening and were initially diagnosed in corneal clinics. Ocular comorbidities included corneal opacity (234, 100.0%), nystagmus (48, 20.5%), cataracts (27, 11.5%), glaucoma (26, 11.1%), strabismus (24, 10.3%), and lens dislocation (12, 5.1%), among others. Of these eyes, 197 were classified as PA type I (84.2%), and 37 were classified as PA type II (15.8%) (11).
UBM on 36 patients revealed a posterior corneal defect with iridocorneal adhesions in all 56 PA eyes. Lens opacity or keratolenticular adhesions were observed in 18 eyes, indicating PA type II. A total of 25 eyes had open angles, whereas 31 eyes had partially or completely closed angles. Out of the 16 eyes with glaucoma, 14 eyes (87.5%) exhibited closed angles, and 2 eyes (12.5%) had open angles. Figure 5 shows the representative anterior segment photograph and UBM images of PA.
CEU
CEU represented the rarest condition among our patients, with only 8 patients (13 eyes) diagnosed, who had a median age of 6 years (IQR, 0.3–27.8 years). Bilateral CEU was found in 5 patients (62.5%). The main complaints reported by patients included photophobia, tearing, decreased vision, corneal whitening, and ocular pain. Corneal edema was observed in 6 eyes (46.2%), glaucoma in 13 eyes (100.0%), ptosis in 2 eyes (15.4%), and cataract in 1 eye (7.7%). In the 3 patients with unilateral CEU, the contralateral eyes were all normal.
UBM imaging displayed a loss of normal iris configuration, specifically lacking iris crypts, in all 12 CEU eyes. Among these eyes (all having glaucoma), 2 (16.7%) had open angles, 4 (33.3%) had partially closed angles, whereas 6 (50.0%) had completely closed angles. Representative anterior segment photographs and UBM images of CEU are shown in Figure 6.
PFV
In the 177 PFV patients with a median age of 3 years, the majority (93.2%) presented with unilateral involvement. None of the patients had a positive family history of PFV. The primary complaints were leukocoria and decreased vision. Ocular features observed in these patients included cataracts (181, 95.8%), strabismus (45, 23.8%), glaucoma (26, 13.8%), nystagmus (23, 12.2%), corneal opacity (22, 11.6%), retinal detachment (12, 6.3%), persistent pupillary membrane (6, 3.2%), subluxation of lens (4, 2.1%), microphthalmia (3, 1.6%), microcornea (2, 1.1%), and optic disc dysplasia (2, 1.1%), among others.
UBM was performed on 31 patients (37 PFV eyes). Among these eyes, 23 had a shallow anterior chamber, and 4 had a disappearing anterior chamber. Increased echogenicity indicating fibroplasia in posterior lens, zonules, ciliary region, and peripheral vitreous body was observed in 23 eyes. A total of 14 eyes had open angles, whereas 23 had partially or completely closed angles. Out of the 20 eyes with glaucoma, all eyes (100.0%) exhibited completely closed angles. Representative anterior segment photograph, fundus photograph, and UBM images of PFV are shown in Figure 7.
CFPM
A total of 15 patients were diagnosed with CFPM, also referred to as “anterior-anterior PFV” in the literature (12). These patients had a median age of 0.4 years, ranging from 1 month to 13 years. Meanwhile, 14 patients (93.3%) presented with unilateral CFPM with normal contralateral eyes, whereas 1 patient (6.7%) presented with bilateral CFPM. None of the patients had a positive family history of CFPM. The main complaints reported included leukocoria, corneal whitening, and corneal enlargement. Under slit lamp examination, pupillary white membrane was observed in all 16 eyes (100.0%). Glaucoma was diagnosed in 10 eyes (62.5%), cataracts in 2 eyes (12.5%), nystagmus in 1 eye (6.3%), and strabismus in 1 eye (6.3%).
UBM was performed on 10 patients (11 CFPM eyes). Among these eyes, 2 had open angles and 9 had closed angles. In the 9 eyes with closed angles, 4 eyes exhibited complete pupillary obstruction due to a membrane and presented with iris bombé (‘U’ shape), 2 eyes had stretching of the iris towards the fibrotic membrane, accompanied by more severe iris bombé and anterior synechiae (‘Y’ shape), and 3 eyes showed complete contact between the iris and cornea, with the absence of the anterior chamber (‘I’ shape) (13,14). All 9 eyes (100%) with glaucoma exhibited completely closed angles, whereas 2 eyes without glaucoma had open angles. Figure 8 shows the representative anterior segment photograph and UBM images of CFPM.
Iris coloboma
Among the 102 patients (169 eyes) diagnosed with iris coloboma, the median age was 42.5 years. Roughly 2/3 of patients (67, 65.7%) were bilaterally affected and 1/3 of patients (35, 34.3%) were unilaterally affected. Most patients (84.3%) sought medical attention due to decreased vision. Common ocular comorbidities included cataracts (150, 88.8%), choroidal coloboma (124, 73.4%), nystagmus (92, 54.4%), microcornea (60, 35.5%), strabismus (37, 21.9%), retinal detachment (31, 18.3%), lens subluxation (21, 12.4%), microphthalmia (15, 8.9%), glaucoma (9, 5.3%), and lens luxation (8, 4.7%), among others. In the contralateral eyes without iris coloboma, 2 eyes exhibited anophthalmia. Other abnormalities included cataracts, corneal opacity, choroidal coloboma, lens luxation, microcornea, microphthalmia, and so on.
UBM was performed on 37 patients (63 iris coloboma eyes). The iris appeared short in the corresponding quadrant of coloboma. Lens dislocation due to zonular weakness or absence was observed in 39 eyes. Of the 6 eyes with glaucoma, 3 eyes (50.0%) exhibited open angles, and 3 eyes (50.0%) displayed partially or completely closed angles. Figure 9 shows the representative anterior segment photograph, fundus photograph, and UBM images of iris coloboma.
Microcornea
There were 93 patients diagnosed with microcornea, who had a median age of 35 years. Bilateral microcornea was observed in 62 patients (66.7%). The major symptom (67.7%) was decreased vision. Microcornea was commonly associated with other ASDs, particularly observed more frequently in coloboma cases. Ocular comorbidities in microcornea included cataracts (131, 84.5%), nystagmus (91, 58.7%), iris coloboma (60, 38.7%), choroidal coloboma (58, 37.4%), strabismus (41, 26.5%), corneal opacity (25, 16.1%), lens dislocation (23, 14.8%), glaucoma (21, 13.5%), retinal detachment (15, 9.7%), and microphthalmia (8, 5.2%), among others. In the contralateral eyes without microcornea, 2 eyes exhibited anophthalmia. Other abnormalities included nystagmus, cataracts, corneal opacity, coloboma, lens luxation, and so on.
UBM evaluation of 51 microcornea eyes revealed small and shallow anterior chambers. However, not all glaucomatous eyes presented closed angles. Among the 16 glaucomatous eyes, 4 (25%) showed open angles, whereas 12 (75%) exhibited partially or completely closed angles. Lens dislocation due to zonular weakness or absence was observed in 28 eyes. Representative anterior segment photographs and UBM images of microcornea are shown in Figure 10.
Discussion
ASD constitutes a range of congenital defects affecting various components of the eye’s anterior segment, which heightens the risk of glaucoma (1-3). The phenotypes of ASD are characterized by their complexity and overlap, and some ASDs have not been fully described yet. As a result, accurate diagnosis and differentiation of ASD can be challenging in clinical practice. In this study, we examined a large sample of patients from a Chinese tertiary hospital and analyzed the clinical characteristics of ASD and their UBM images of anterior segment structures. To the best of our knowledge, this is the most extensive single-center study describing ASD.
In our series, PCG emerged as the predominant condition among our patients, whereas CEU was the least common. The age at diagnosis varied across different ASDs: PCG, PA, and CFPM were diagnosed at a very young age, with a median age of less than 1 year, due to noticeable signs such as corneal whitening, corneal enlargement, photophobia, and tearing caused by congenital corneal defects or early-onset glaucoma. In contrast, iris coloboma and microcornea were diagnosed at older ages, with median ages of 42.5 and 35 years, respectively, likely because their signs are subtle at the beginning. These conditions often go unnoticed until decreased vision due to cataract formation later in life. Male predominance was observed in PCG and ARS, consistent with prior studies (15,16). Aniridia and ARS were bilateral ocular diseases, whereas PFV and CFPM mainly affected 1 eye. The other conditions could manifest as either unilateral or bilateral. The rates of family histories in PCG and aniridia were lower than those reported in the literature (17,18). Additionally, family histories were not noted in iris coloboma and microcornea. These might be possibly due to missing information in the medical records.
Ocular comorbidities were frequently observed in our ASD patients, which might offer valuable insights for clinical practice. For instance, entropion and trichiasis were relatively common in PCG patients, highlighting the importance of considering PCG in infants presenting with entropion. About 11.1% of our patients with PA developed glaucoma, a prevalence lower than reported in previous studies (16–52%) (19,20), which may be attributed to the notably young age of our patients. The majority of these patients were hospitalized due to corneal opacity and required keratoplasty; hence, glaucoma might not have manifested during the initial assessment, underscoring the importance of postoperative monitoring in PA patients following keratoplasty.
CFPM and PFV are postulated to belong to the same category of congenital abnormalities caused by hyaloid vascular system regression failure, with differing locations of fibrovascular remnants between the two conditions. CFPM primarily affects the lens anterior capsule, pupil, and iris, whereas PFV mainly involves the retrolental region, vitreous, and retina (12,21,22). Consistently, our CFPM patients exhibited anterior segment abnormalities, including pupillary white membrane and glaucoma resulting from pupillary block, whereas PFV patients displayed both anterior and posterior segment abnormalities, such as cataract, glaucoma, and retinal detachment, among others.
Iris coloboma and microcornea rarely occur in isolation and often manifest alongside other ocular abnormalities, such as lens and retinochoroidal colobomas, microphthalmia, cataract, glaucoma, and retinal detachment (23-25). In our case series, we observed a close association between iris coloboma and microcornea, with approximately a third of patients displaying both conditions. In addition to the ocular comorbidities mentioned above, corneal opacity, lens dislocation, nystagmus, and strabismus were also frequently noted among patients with iris coloboma and microcornea in our cohort.
ASD often develops in infants or children, who are unlikely to cooperate with inspection. Moreover, corneal opacity occurs frequently in ASD, which makes ophthalmic examinations even more challenging. The combination of these factors leads to the common occurrence of misdiagnosis and missed diagnoses in clinical practice. High-frequency UBM allows detailed examination of the anterior segment in vivo and is effective in guiding treatment decisions and surgical strategies (26,27). In the present study, we assessed the UBM images of patients with ASD, providing imaging evidence for differential diagnosis. PCG exhibited a deeper anterior chamber, thinner iris, elongated ciliary process, and an open angle with anterior insertion of iris root. Aniridia showed an iris stump and a small ciliary body. ARS presented with posterior embryotoxon, iris process, and iridocorneal adhesions. PA had a posterior corneal defect with iridocorneal adhesions or keratolenticular adhesions. CEU showed loss of normal iris configuration, with some cases having distinctive closed angles. PFV exhibited fibroplasia in the posterior lens, zonules, ciliary region, and peripheral vitreous body. CFPM demonstrated pupillary block due to a membrane, resulting in diverse morphologies of iris bombé. Iris coloboma showed a short iris in the corresponding quadrant, and some cases had zonular weakness or absence. Microcornea was characterized by a small cornea and shallow anterior chamber. Due to the early onset of ASD, the eyeball develops along with the development of the disease, which makes differential diagnosis more difficult. However, UBM is a powerful tool capable of unveiling subtle changes in the cornea, iris, anterior chamber angle, ciliary body, lens, and even the peripheral vitreous. For example, some ARS patients with very early-onset glaucoma may present with enlarged eyeballs and cloudy corneas in both eyes, which closely resemble the presentation of PCG. Yet, UBM can distinguish ARS from PCG by revealing posterior embryotoxon and iridocorneal adhesions. Similarly, the appearance of CFPM and PFV may be similar, but UBM can differentiate them by identifying lesion locations, with CFPM manifesting in the lens anterior region and PFV in the posterior region. PA is characterized by the observation of a posterior corneal defect, setting it apart from other diseases. The UBM image of open-angle CEU may resemble that of PCG, making it challenging to distinguish between the two in infantile glaucoma patients with corneal edema. However, differentiation becomes possible if UBM detects typical iris synechia with closure of the anterior chamber angle in CEU.
Additionally, we explored the relationship between anterior chamber angle status and the development of glaucoma in different subtypes of ASD. Our findings unveiled a diverse array of angle morphologies in glaucomatous eyes across various ASDs, including PCG, aniridia, ARS, PA, CEU, iris coloboma, and microcornea. Remarkably, a portion of glaucomatous eyes exhibited open angles across all quadrants, highlighting the significant involvement of trabeculodysgenesis (open yet dysplastic angle) in the pathogenesis of glaucoma in these conditions. Conversely, in PFV and CFPM eyes with glaucoma, all (100%) exhibited completely closed angles, suggesting that glaucoma in PFV and CFPM was mostly attributed to pupil block and iris bombé, leading to peripheral anterior synechia and consequently angle-closure.
Our study has several limitations, primarily owing to its retrospective nature. The BCVA assessments were not performed in young children, which could potentially impact the comprehensive evaluation of visual acuity across all age groups. Additionally, the collection of family history information, particularly concerning conditions such as iris coloboma and microcornea, might not have been exhaustive, leading to an absence of corresponding family history data. Furthermore, the lack of axial length measurements in certain cases might have resulted in underestimating the prevalence of microphthalmia within our dataset. Finally, our data was sourced from hospitalized patients; its generalizability to the broader population affected by these conditions may be restricted.
Conclusions
ASD manifest diverse clinical features and various degrees of associated glaucoma. This study presents the largest series of evidence to date on the diagnosis of these disorders. The description of clinical characteristics and UBM features for these cases offers valuable insights for the understanding and management of ASD.
Acknowledgments
Funding: This work was supported by
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-24-875/rc
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-875/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Review Board of Eye & ENT Hospital of Fudan University (No. KJ2011-04) and the requirement for individual consent for this retrospective analysis was waived.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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