Although less common than adult glaucoma, childhood glaucoma can have a large impact on childhood visual development. According to the World Health Organization VISION 2020 program, childhood glaucoma is the third most common cause of severe visual impairment and blindness in childhood in low- and middle-income countries1 and accounts for 5% of childhood blindness globally.2 Patients with childhood glaucoma are treated with both medication and surgery. Medication is used as the first-line treatment, but is generally not effective in controlling increased intraocular pressure (IOP) in the long term.3 Glaucoma surgery is generally unavoidable and considered a mainstay in childhood glaucoma cases.4 However, glaucoma surgery in children has a lower success rate than that in adults.
Two main outcomes regarding glaucoma treatment are surgical and visual outcomes. Literature findings on the success of childhood glaucoma treatment mostly focus on surgical outcome with IOP control as a predictor.5–10 However, in patients with childhood glaucoma whose IOP is controlled, the final visual outcome still may not be favorable.11–13 Prognostic factors associated with poor visual acuity have also been studied.13–15 However, other clinical characteristics (eg, interval time between onset and surgery) that may affect the final visual outcome have not been assessed. The aim of the current study was to analyze the relationship between clinical characteristics and visual acuity in childhood glaucoma. Such knowledge can contribute to planning of patient care and parental advice.
Patients and Methods
The study protocol was approved by the Human Research Ethics Committee of the Faculty of Medicine, Prince of Songkhla University. The medical records of all patients with childhood glaucoma aged 4 years or younger who received surgical intervention at Songklanagarind Hospital, Hatyai, Thailand, from 2002 to 2019 were reviewed. Childhood glaucoma was defined and classified as primary congenital glaucoma and secondary childhood glaucoma according to the Childhood Glaucoma Research Network.16 Cases were excluded from this study if they initially had medical and surgical treatment from other hospitals and inadequate follow-up time (less than 6 months).
The collected variables were type of glaucoma and associated ocular and systemic conditions such as family history of congenital glaucoma. At the initial visit, we recorded the gender, laterality, age at onset and initial presentation, presenting symptom, signs including Haab's striae, and degree of corneal haze (defined below). At every visit, we recorded the IOP, corneal diameter, cup-to-disc ratio, axial length, number of glaucoma medications, and number and types of glaucoma surgeries. At the final visit, best corrected visual acuity (BCVA) and cause of visual impairment (if BCVA was worse than 20/50) were determined.
Corneal haze degree was graded as mild, moderate, or severe based on the visibility of the anterior segment structure at the initial visit. Mild degree was defined when the iris and pupil were clearly seen. Moderate degree was defined when the iris was not clearly seen but the pupil detail could still be outlined. Severe degree was defined when the iris and pupil detail were totally obscured.17
The IOP was measured by pneumatonometry (Tono-Pen; Reichert Technologies), rebound tonometry (iCare), or applanation tonometry (Goldmann and Perkins). For gold standard assessment of IOP, we used a Goldmann tonometer in the outpatient department and a Perkins tonometer for patients under general anesthesia. At follow-up visits, we used Goldmann tonometry in cooperative patients and the Tono-Pen and iCare mainly in uncooperative patients.
At the final visit, BCVA was determined with the best optical correction according to the patient's developmental ability. For preschool children, preferential looking visual acuity including Cardiff and Teller grating acuity was evaluated as normal and subnormal according to an age-matched population. For older children, Snellen acuity was recorded and categorized according to the World Health Organization classification: good (20/50 or better), fair (worse than 20/50 to 20/200), and poor (worse than 20/200). For statistical analysis, Snellen visual acuity was converted to logarithm of the minimum angle of resolution (logMAR) units. Non-optotype visual acuities were converted to logMAR units as follows: 1.9 for counting fingers, 2.3 for hand motions, 2.5 for light projection, 2.7 for light perception, and 3 for no light perception.18
For patients with a final BCVA of worse than 20/50, the primary cause of visual impairment was identified by examining physicians, including amblyopia (deprivation, anisometropic, and strabismic), glaucoma, and others. If there were several possible causes, the most important underlying cause would be determined individually based on the patient's history, eye examination, and investigation results (if available). Because amblyopia and glaucoma are interlinked and it is hard to differentiate between the two based on clinical examination findings alone, optical coherence tomography (OCT) measurements demonstrating greater reduction in retinal nerve fiber layer could be one surrogate measure for glaucoma. However, retrospectively reviewed, OCT results were not available in our patients.
The glaucoma operations conducted in this study could be broadly divided into enhancing innate outflow procedure (goniotomy and trabeculotomy), creating external aqueous drainage (trabeculectomy and glaucoma drainage device), and reducing aqueous production (cyclodestruction).4
The age at onset was defined as age when the parents first noticed the abnormalities. The age at diagnosis was defined as age when the patient was first diagnosed as having glaucoma. Interval to surgery was defined as the time in calendar months from glaucoma onset to the first glaucoma surgery. If the onset could not be identified, time at diagnosis was used instead.
Statistical analysis was performed using R version 3.6.1 software (The R Foundation). Continuous data were presented using the mean and standard deviation or median and interquartile range as appropriate. Categorical data were presented using frequency and percentage and analyzed using the Pearson chi-square test. Risk factors associated with poor vision at final visit were analyzed by univariate analysis. The generalized estimating equation method for dichotomous outcomes was used to control the correlation of visual outcome within the same patient. A P value of less than .05 was considered significant.
Baseline characteristics are shown in Table 1. Two patients had missing data on family history of glaucoma. Of 45 eyes, 15 (33.3%) had primary childhood glaucoma and 30 (66.7%) had secondary glaucoma. Among those with secondary glaucoma, most (53.4%) had glaucoma associated with non-acquired ocular anomalies. The distribution of associated non-acquired systemic diseases, ocular anomalies, acquired conditions, and those following cataract surgeries are shown in Table 2.
Baseline Characteristics of 31 Patients With Childhood Glaucoma (45 Eyes)
Types of Childhood Glaucoma (31 Patients, 45 Eyes)
The distribution of glaucoma surgeries according to age and final visual outcomes for each eye is shown in Figure 1.
Distribution of glaucoma operations for each eye according to age. Each line represents the timeline of one of the enrolled eyes. The bold line represents the right eye. The dashed line represents the left eye. The black dot represents age at diagnosis. The solid triangles represent major glaucoma surgeries, including goniotomy, trabeculotomy, trabeculectomy, combined trabeculotomy-trabeculectomy, combined goniotomy-trabeculectomy, glaucoma drainage device (GDD), and cyclodestructive procedure. The hollow triangles represent other surgeries, such as needling with mitomycin C, repositioning GDD, and enucleation. At the end of each line, the squares represent visual outcome at the final visit; empty squares for good, crossed squares for fair, bold squares for poor, and no squares for undetermined visual outcome.
At the initial visit, 41 of 46 eyes received glaucoma medication, and the mean number of medications was 1.25. At the final visit, 26 eyes received glaucoma medication and 19 did not, of which 2 were enucleated and 4 had phthisis. Among the 26 eyes that received medication, the mean number of medications received at the final visit was 1.20. The most commonly performed initial glaucoma operation was trabeculectomy (17 eyes, 37.8%), followed by goniotomy (11 eyes, 24.4%) (Table 3). The mean number of glaucoma operations was 2.7 per eye. Approximately 48.9% of patients required further surgical intervention.
Management of Childhood Glaucoma (45 Eyes)
At the final visit, the visual acuity of 44 eyes was evaluated for visual outcome. One eye was excluded because the final visual acuity could not be compared with age-matched visual acuity due to delayed development. The patient had one eye diagnosed as having secondary glaucoma due to Sturge-Weber syndrome. His final visual acuity in both eyes at the age of 10 years was 20/80 by Cardiff cards at 50 cm.
Of 44 eyes, 11 eyes belonged to children younger than 4 years at the final visit, so Snellen acuity could not be determined. The final visual acuity was evaluated according to the patient's age and developmental ability (Table 4). All were done by an experienced optometrist in cooperative patients as noted in the medical records. Three eyes of patients 1 and 3 with Teller grating acuity were considered as good final visual acuity. Others were considered as poor final visual acuity.
Visual Acuity of Patients Younger Than 4 Years at the Final Visit (11 Eyes)
Good final visual acuity was achieved in 9 eyes (20.5%), whereas 7 eyes (15.9%) had fair and 28 eyes (63.6%) had poor visual acuity. Among 36 eyes with visual impairment (fair and poor visual acuity), the major cause was deprivation amblyopia (Table 5). Of 20 eyes with deprivation amblyopia, corneal haze was the major cause.
Final Visual Outcomes in Childhood Glaucoma (44 Eyes)
Among 15 eyes with primary glaucoma, 7 (46.7%) had good final visual acuity. The percentage of eyes that were visually impaired with secondary glaucoma (86.2%) was higher compared to eyes with primary glaucoma (53.3%). The most common cause of visual impairment in both groups was deprivation amblyopia.
Risk factors associated with poor visual acuity at the final visit (visual acuity worse than 20/200) from univariate analysis are shown in Table 6. Poor final visual acuity was significant in patients with unilateral and secondary glaucoma.
Univariate Analysis of Risk Factors Associated With Poor Visual Acuity at Final Visit (44 Eyes)
Results of the logistic regression analysis are shown in Table 7. Risk factors associated with poor visual acuity at the final visit were type of glaucoma, age at diagnosis, and interval to the first glaucoma surgery. Eyes with secondary glaucoma and interval to surgery of 3 or more months were 9 and 20 times more likely to have poor final vision, respectively. In contrast, children who, at diagnosis, were aged 3 months or older were less likely to have poor final visual acuity (P = .003).
Analysis of Risk Factors Associated With Poor Visual Acuity at the Final Visit
IOP was recorded at 1,331 of 1,474 follow-up visits. The mean IOP was 21.24 ± 10 mm Hg. The IOP trends after the first glaucoma surgery were compared between the two groups as shown in Figure 2. Eyes with a final visual acuity of 20/200 or better had lower mean IOP preoperatively (28.2 vs 34.4 mm Hg) and postoperatively compared to the other group. Likewise, IOP at every follow-up visit was also lower, as shown in Figure 3.
Box plot showing the distribution of intraocular pressure (y-axis) and preoperative and postoperative time (x-axis) of the first glaucoma surgery.
Trends in intraocular pressure at every follow-up visit between the two groups.
This study gave a perspective of childhood glaucoma, especially in the Asian context. In surgically treated childhood glaucoma, two-thirds of eyes had poor final vision. The prognostic factors for poor visual outcome were secondary glaucoma, age at diagnosis of younger than 3 months, and interval to surgery of more than 3 months.
The epidemiology of childhood glaucoma has been widely studied in Western countries and Asia. Our study found that secondary glaucoma, especially glaucoma associated with non-acquired ocular anomalies, occupied the majority. Other studies in Pittsburgh15 and Philadelphia13 also found that secondary glaucoma was the major cause, especially syndrome-associated and aphakic glaucoma, respectively. In contrast, studies from Canada,19 United Kingdom,3 India,20 Saudi Arabia,17 and China21 revealed that primary congenital glaucoma was the most common cause.
Patients with secondary glaucoma had a worse visual prognosis than those with primary glaucoma. Similarly, other studies13–15 concluded that secondary glaucoma associated with aniridia, Peters anomaly, Axenfeld-Reiger syndrome, Sturge-Weber syndrome, uveitis, and congenital cataract had worse visual prognosis than primary congenital glaucoma. This might be because secondary glaucoma had associated ocular anomalies that caused poor visual outcome besides glaucoma. Our study also found that good final visual acuity of 0.4 or better was achieved in only 8 eyes (18.2%). Our result exhibited a lower proportion of eyes with good final visual acuity compared to previous studies. Alsheikheh et al22 reported a final visual acuity of 0.3 or better in 35 of 66 eyes (53%). This could be because their study consisted of primary congenital glaucoma (83.7%), which conveyed a better prognosis, as the majority of the cases. Another study from Kargi et al,15 in which secondary glaucoma was predominant, showed that 29% of the eyes (60 of 204) achieved final visual acuity of 0.3 or better. This could be because the latter included both medically and surgically treated patients and the medically treated patients might have less severity and better prognosis. Shaffer23 also reported a final visual acuity of 0.3 or better in 54% of eyes with developmental glaucoma (28 of 52); however, there was a high rate of loss to follow-up in the study (80%). Considering only patients with primary congenital glaucoma, our study reported only 40% achieved good final visual acuity, whereas other studies13,15,24,25 reported percentages of 46% to 79%.
Eyes of children diagnosed at younger than 3 months of age were more likely to have poor final visual acuity (worse than 20/200). Similar to a study from Australia,26 eyes with primary congenital glaucoma detected at younger than 3 months of life were associated with a final visual acuity of worse than 20/200 even with controlled IOP. This might be because the earlier the diagnosis was made, the less developed the eye became. This resulted in more severe disease and consequently poor visual outcome. Another possible explanation was that early diagnosis reflected faster progression of the disease. The finding emphasized the need to detect the condition as early as possible. However, another study13 found that age at diagnosis had no association with final visual acuity of worse than 20/200. The disparity in the result could be related to different inclusion criteria. The latter included patients aged up to 14 years old. The visual prognosis of childhood glaucoma in older children might be better because the eye is more developed at the time of diagnosis.
We found that the interval of more than 3 months was associated with poor visual outcome in childhood glaucoma. The longer interval to surgery might reflect the longer uncontrolled disease period and more severity at the time of operation. Hence, early detection and treatment were crucial steps in managing these patients.
Similar to other studies,13,15 most unilateral childhood glaucoma was secondary. Unilaterality was also associated with poor visual outcome from univariate analysis. A similar result was shown in a study by Khitri et al13 on childhood glaucoma. The reason was that consequent deprivation amblyopia, which contributed as the main cause of visual impairment, occurred more frequently in unilateral disease. However, this effect was not shown in the multivariate analysis.
Zagora et al26 found that, unlike adult glaucoma, good IOP control in children with primary congenital glaucoma did not determine good visual outcome. Perhaps young children's eyes were more susceptible to increased IOP, resulting in permanent damage. However, the study only correlated the final IOP and visual outcome. The control of IOP at each visit was not taken into consideration. Kargi et al15 studied IOP control at each visit in 204 eyes with childhood glaucoma. The authors found that control of IOP of 19 mm Hg or less on 80% of visits was associated with stable cup-to-disc ratio and visual fields, but the percentage of IOP control had weak correlation with final visual acuity. We could not identify the significance of initial IOP on the final visual outcome. However, the mean IOP was lower preoperatively and tended to decrease postoperatively and every visit afterward in eyes with a final visual acuity of 20/200 or better. This suggested that good IOP control played a role in good final visual outcome. As discussed above, deprivation amblyopia played a major role in visual impairment, so the treatment should not be focused only on IOP control; amblyopia treatment also had to be taken into consideration for the best treatment outcome.
There are several limitations in our study, including small sample size, retrospective design, and short follow-up period (at least 6 months). Because our patients were children, the IOP assessment was done by different methods, and no ancillary tests (fundus photographs, OCT, and visual fields) could be obtained. Also, we only recorded visual acuity at the final visit because of the difficulty of measuring visual acuity in young children at earlier visits. Finally, our data only represented clinical characteristics of Asian eyes.
Our study highlights that, even after surgical treatment, two-thirds of eyes with childhood glaucoma ended up with poor final vision. The risk factors were secondary glaucoma, age at diagnosis of younger than 3 months, and interval to surgery of more than 3 months. Hence, early surgery to control IOP and amblyopia treatment are recommended to prevent poor visual outcome.