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Corresponding author. Department of Ophthalmology, Faculty of Medicine University of Indonesia, Cipto Mangukusumo National Hospital, Jl. Kimia, No. 8, Jakarta, Indonesia.
Anterior segment dysgenesis (ASD) is an ocular malformation that can lead to childhood blindness. Although ASD prevalence is rare, it is potentially devastating for children and caretakers. We aim to report the clinical features of ASD patients in a tertiary referral center in Indonesia.
Methods
We conducted a retrospective review of medical records of ASD patients in the Pediatric Ophthalmology clinic in Cipto Mangunkusumo National Central Public Hospital, Jakarta, Indonesia between January 1, 2018, and December 31, 2021.
Results
A total of 172 eyes of 107 children with ASD were included in this study. Most of the patients were male, aged 3.4 years ±5.0 SD at first examination, 67.3% patients came from outside Jakarta, and 75.6% of eyes had bilateral ASD. Most common clinical manifestations was congenital corneal opacities (CCO), microcornea, and congenital glaucoma. The most common visual acuity (VA) was fixation and following light/object. Intraocular pressure (IOP) increased in 41% eyes. The most common surgery performed was glaucoma surgery, which was performed in 6.4% of eyes in the study.
Conclusion
ASD has a devastating impact on children's VA, along with its poor prognosis despite surgery thus contributes largely to childhood blindness. ASD detection and management is highly challenging in children, and increased awareness on ASD is pivotal in earlier referral and treatment of ASD.
Anterior segment dysgenesis (ASD) is defined as failed development of the anterior segment of ocular tissues, this includes a wide spectrum of conditions involving the cornea, iris, anterior chamber angle, and lens.
ASD leads to anomalies in the structure of the anterior segment which can develop elevated intraocular pressure and is associated with an increased risk of glaucoma and corneal opacity.
As ASD could lead to permanent blindness in children, it is imperative to increase awareness of its manifestations, prognosis, and management. Despite its rarity, blindness, and visual impairment from ASD has a devastating impact for patients as well as their caretakers, leading to significant financial and social burden. Treatment of ASD is challenging, and ASD serves as a significant contributor towards the continuously high rates of childhood blindness.
Therefore, thorough understanding of ASD is essential. In this study, we aimed to provide a comprehensive illustration of the most recent data on ASD patients in a tertiary referral center in Indonesia in the years 2018–2021.
2. Methods
A retrospective review of medical records of pediatric patients with ASD was performed at the Pediatric Ophthalmology clinic at an Indonesian national referral hospital [institution masked for blinding] between January 1, 2018, and December 31, 2021. This study was granted ethical approval (Protocol Number: 22-10-1197) by the Health Research Ethics Committee of [institution masked for blinding], informed consent was obtained from all study subjects, and this study was conducted in accordance with the Declaration of Helsinki. The inclusion criteria of this study were medical records of children between 0 and 18 years of age with manifestation of ASD. Diagnosis of ASD was extracted from medical records and was established by one consultant pediatric ophthalmologist (DEY). Diagnosis was made based on AAO's diagnostic criteria, with microcornea defined as newborns with corneal diameter of <9 mm, and congenital glaucoma defined as IOP >21 mmHg with presence of Hauub striae, corneal edema, or increased corneal diameter. Congenital corneal opacities (CCO) was diagnosed using slit lamp examination. Due to limited resources, we were unable to specifically identify the specific types of corneal opacity as we lacked access to advanced anterior segment examinations such as ultrasound biomicroscopy (UBM) and anterior segment optical coherence tomography (AS-OCT) at our hospital. Incomplete medical records were excluded from this study. We recorded patients' demography (gender, age, domicile), laterality, delivery history, ocular manifestation, visual outcome, intraocular pressure (IOP), and surgical management from medical records. Visual outcome was ideally measured uniocularly and was conducted in most patients, and binocular measurement of visual outcome was done in patients who were not cooperative. Vision was assessed using either Snellen chart or LEA symbols chart, with the latter being preferred for those 5 years of age or below. As for patients who were unable to recognize letters or symbols, assessment was done by light object perception. IOP was measured before anesthesia was administered during evaluation under anesthesia (EUA).
Descriptive analysis was done on the characteristics of the subjects, and quantitative data was described as mean (SD) or median (min-max), depending on the normality of the given data. Categorical variables were presented in frequency and percentage, n (%). Data was managed and analyzed using Microsoft Excel v. 16.62.
3. Results
There was a total of 172 eyes of 107 children with ASD that were eligible for inclusion in our study. As shown in Table 1, most of the patients were male (59.8%) and were within 0 months–17 years of age (average 3.4 ± 5.0 years) at first examination. Most patients (67.3%) were based outside of Jakarta. Notably, only a minority of patients had pre-term births (13.1%) and had low birthweight (14%). The majority (75.6%) of eyes had bilateral ASD.
Patients presented with a variety of clinical manifestation of ASD, and this is shown in Table 2. The three most common clinical manifestations were corneal opacities with 55.8% (as shown in Fig. 1), followed by microcornea (33.1%), and congenital glaucoma (20.3%).
Table 2Clinical manifestation in patients, n = 172 eyes.
Visual acuity of these children was also recorded upon initial examination and presented in Table 3. Most patients presented with visual acuity of following light or object (39.5%), and this is followed by blink reflex (34.9%).
Table 3Distribution of Visual Outcome, n = 172 eyes.
In terms of elevated IOP, 55 eyes (41%) had elevated IOP above 21 mmHg, whereas 79 eyes (59%) had normal IOP (10–21 mmHg). Moreover, presence of elevated IOP was mostly found in patients with concurrent congenital glaucoma and corneal opacity.
Surgical management of the patients are shown in Table 4. Findings of elevated IOP in the patients is in line with the most commonly performed surgery on these patients, which was filtering surgery for primary congenital glaucoma including trabeculotomy and trabeculectomy which was performed in 6.4% of the eyes in this study.
This study provides a comprehensive understanding of the characteristics of ASD patients that present at an Indonesian tertiary referral center in the years 2018–2021. Although prevalence of ASD is considerably low, we included a relatively large sample size of patients in our study with a total of 172 eyes of 107 patients with ASD. Past studies on ASD typically included general ocular anomalies in their study population,
and a study in India by Tupe et al. showed that the number of children with congenital ocular anomalies was 0.53%, 82% of which were patients with anterior segment abnormality.
In a study in Egypt on 2500 cases with genetic disorders reported that 65% of their ocular cases were ASD, which accounted for 1.56% of all their enrolled cases.
With this, although the prevalence of ASD is relatively low, these ocular malformations are a lifelong vision-threatening disease, and it maintains important to understand the disease manifestation and its complications. Our study is one of the first to describe characteristics of ASD at a national referral hospital in Indonesia.
Our study found that more than half of ASD patients were male. Similarly, a study by Tomairek et al. reported that male to female ratio of children with ocular malformation was 1.7:1.
Our data showed similarity with Tomairek et al.‘s study in terms of males having slightly higher prevalence, although we only included ASD patients whereas the two studies measured all spectrum of congenital ocular anomalies. Majority of ASD patients were bilateral cases in our study, and this is similar to findings in Shigeyatsu et al.‘s study.
This can be explained as congenital anomalies typically present bilaterally.
Mean age of patients at initial examination was 3.4 ± 5 years in our study population. Patients presented to our hospital at an older age in comparison to a previous study by Shigeyasu et al., where the average age in their study was 1.2 years.
We postulate that this difference in terms of our patients presenting at an older age is due to the lack of early detection strategies in Indonesia, particularly because of limited access to healthcare outside the capital city of Jakarta. In addition, most patients in our study were noted to be from outside of Jakarta, and with this, some patients would have required air transportation due to the limited availability of specialized ophthalmology facilities in rural areas. This distance and financial barrier to access of care thus potentially leads to the patients’ later presentation to our hospital.
In terms of delivery history, 86.9% of patients were born full term and 86% of patients had normal birth weight in our study. This is in line with Tupe at al.‘s study that reported 96% of children with congenital anomalies were full term deliveries.
Nonetheless, Vogt et al. suggested birth characteristics might be associated with ocular abnormalities; they reported shorter mean gestational age and smaller mean birth weight in patients with ocular congenital abnormalities.
Our result differed with Vogt et al.‘s study because our study only focused on ASD patients instead of ocular congenital abnormalities.
None of the patients in our study had a history of consanguinity, whereas a study in Egypt reported 76.7% of ocular anomaly patients had history of consanguinity, suggesting high incidence of genetic disorders with an ocular component.
However, our study only included ASD cases, therefore explaining the possible cause of lack of consanguinity data, whereas other studies included all ocular malformation cases.
The most common clinical manifestation among ASD patients in our study was congenital corneal opacity or leucoma. Tupe et al. reported that among all congenital eye malformation, most cases were in the anterior segment, although congenital corneal opacity was only found in 0.02% of cases.
Shigeyasu et al.‘s study on clinical features of congenital corneal opacity in children reported that Peters anomaly was the most common manifestation.
From all patients with CCO in our study, 6.3% of eyes had sclerocornea and 10.4% of eyes had adherent leucoma, meanwhile the other entities of CCO cannot be defined specifically due to lack of advanced anterior segment examinations such as UBM and AS-OCT in our hospital. The UBM can visualize structures of the anterior segment of the eye,
however UBM is relatively uncomfortable and requires a highly skilled operator. Anterior segment optical coherence tomography in our hospital can provide more high-quality cross-sectional images compared to ultrasound biomicroscopy and it is not operator-dependent.
Malformations of the anterior segment of the eye is frequently accompanied by elevation of IOP. Unfortunately, we only had IOP data of 134 eyes in 85 cooperative children in this study. Elevated IOP was present in 41% of eyes, and most were diagnosed with primary congenital glaucoma and corneal leucoma with rates at 50.9% and 43.6%, respectively. Notably, primary congenital glaucoma was the third most common manifestation of ASD in our study.
The intraocular pressure values should be interpreted with caution, especially in corneal leucoma cases, due to the possibility of false positive elevated intraocular pressure. In our study, intraocular pressure measurement was conducted using iCare® rebound tonometer. Previous studies have suggested that intraocular pressure measurements using rebound tonometer may result in higher values in children with congenital corneal opacities because it is affected by thickened and stiffened cornea.
Better methods of intraocular pressure measurement that are not affected by corneal abnormalities should be developed and adopted into future clinical practice.
In our study, the most common visual acuity was fixation and following light or object at initial examination, with children on average being 3.4 years of age. Normally, children at this age should be able to recognize pictures or letters, however almost half of older children could not recognize this and therefore could be categorized as blind. This condition can be caused by the most common manifestation of ASD in our study, which was congenital corneal opacity. Congenital corneal opacity that covers the visual axis thus leads to severe visual impairment and potential blindness, and treatment of congenital corneal opacity is challenging with low success rates. Late presentation of these patients to our hospital could also contribute to difficulty of therapy. Shigeyasu et al. also reported the severity of visual acuity outcome in which 40%–50% of eyes in their population with ASD were stated as blind.
Keratoplasty surgery was considered in 8.3% of eyes with congenital corneal opacity, however, none of the patients underwent keratoplasty. The surgery itself is challenging and prognosis is poor, furthermore, etiology of congenital corneal opacity is difficult to determine due to the lack of advanced anterior segment diagnostic equipment in our hospital. Some studies indicated that the success rate of surgery depends on the etiology of congenital corneal opacity, for instance, sclerocornea had the poorest outcome among others.
Therefore, careful selection of cases that should undergo surgery is advisable. Kim et al. who studied keratoplasty in children with congenital corneal opacity showed the overall graft survival rate was 50%,
they stated that functional success may be limited due to the presence of high astigmatism and amblyopia. Similarly, a study by Lin et al. on keratoplasty in congenital corneal opacity patients reported 61.5% of eyes with high astigmatism did not achieve an ambulatory vision.
The most common type of surgery in our study was trabeculotomy and trabeculectomy that was performed in 11 eyes to lower intraocular pressure. Surgical outcome with trabeculectomy is worse in children due to healing response which can lead to scarring of the fistula or the conjunctiva. Antimetabolite agent such as mitomycin C (MMC) can be used to prevent scarring of the subconjunctival space.
In our study, MMC was given in five eyes that underwent trabeculectomy. In our study, 81.8% of eyes with primary congenital glaucoma who underwent filtering surgery had an intraocular pressure improvement in one year follow up whereas the rest were treated with glaucoma drainage devices and trans scleral photocoagulation. However, in our study, 60% of eyes were only treated with conventional glaucoma medication due to unwillingness of patients to undergo surgery.
Congenital cataracts sometimes present with concurrent ASD manifestations. In this study, 60% of eyes underwent cataract surgery, and 88.9% of eyes showed visual acuity improvement in one year follow-up after surgery. We postulated that children with poor vision following cataract surgery could be due to the fact that the cataracts manifested together with other anterior segment abnormalities. Kohli et al. reported poor functional outcome of cataract surgery were seen in eyes with microcornea and extensive chorioretinal coloboma.
Limbal dermoid has been associated with oculo-auriculo-vertebral dysplasia or known as Goldenhar syndrome. In our study, this was present in 2.3% of eyes, and 22% of eyes with limbal dermoid underwent excision surgery. Simple excision and conjunctivoplasty surgery is mainly performed for cosmetic reason and rarely for functional reason (ocular motility restriction, visual axis obstruction). Early intervention in the first year of life provide faster recovery and improved quality of life.
Childhood blindness is of major concern, and ASD serves as one of the etiologies of childhood blindness with little to no prevention available. Currently, there is no data on the nation-wide prevalence of childhood blindness in Indonesia. Previously published studies conducted in certain regions in Indonesia have reported that the estimated prevalence of blindness or severe vision loss was 0.25 per 1000 children in Sumba, Indonesia, and 0.23 per 1000 children in Yogyakarta, Indonesia, with nearly half (46%) of their study population having reported that blindness was present since birth, and 75.2% reported blindness or severe vision loss before five years of age. Furthermore, their study reported that a total of 22.1% of children were blind due to unavoidable causes, including 28% of which were congenital eye anomalies.
A past study conducted in blind schools in Indonesia reported that 32.7% of blind or severely visually impaired children were attributed to congenital ocular anomalies, this of which mainly included microphthalmos and ASD.
Limitations of our study include our inability to identify the specific phenotype of ASD due to limited resources and lack of access to advanced anterior segment examinations in our country. However, this study is important as it serves as one of the first studies to describe characteristics of ASD at a national referral hospital in Indonesia with a relatively large sample size considering the rarity of the disease.
In conclusion, ASD is an ocular malformation with devastating impact on children's visual acuity. Its poor prognosis despite surgery, along with the lack of advanced ocular diagnostic imaging examination especially for corneal opacity cases in children as the biggest manifestation of ASD in our study, thus contributes largely to childhood blindness. Childhood blindness impact the patients and the caretakers gravely as it negatively impacts quality of life, as well as increases financial and social burden drastically. ASD detection and management is highly challenging in children. Increased awareness on ASD is pivotal especially in fighting childhood blindness.
Sources of funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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