Background/aims To assess the prevalence, clinical features and risk factors of lower lid epiblepharon among patients with congenital glaucoma.
Methods Cross-sectional, observational, case–control study. Patients diagnosed with congenital glaucoma between August 1999 and November 2014 were included. Demographic and clinical characteristic data were collected. Age-matched normal controls were recruited form general population. Main outcome measures were the prevalence, laterality and factors associated with epiblepharon in patients with congenital glaucoma.
Results The prevalence of lower lid epiblepharon was higher in patients with congenital glaucoma compared with control group (40.7% vs 13.3%, p<0.001). Unilateral epiblepharon was only shown in patients with congenital glaucoma (47.8% vs 0.0%, p<0.001). Multivariate analysis revealed that high intraocular pressure (IOP) at glaucoma diagnosis (OR=1.122), presence of corneal erosion (OR=82.664) and presence of buphthalmos (OR=12.600) were significantly associated with the presence of lower lid epiblepharon. In addition, unilateral epiblepharon was associated with unilateral buphthalmos and unilateral glaucoma (OR of 49.849 and 7.338, respectively).
Conclusions The prevalence of epiblepharon was higher in patients with congenital glaucoma compared with age-matched general population. In patients with congenital glaucoma, epiblepharon was associated with corneal erosions. In addition, buphthalmos and initial high IOP were associated with the development of lower lid epiblepharon. More importantly, unilateral buphthalmos was also significantly associated with unilateral epiblepharon. Therefore, in patients with congenital glaucoma, presence of epiblepharon should be evaluated especially in patients accompanying buphthalmos or corneal erosion.
- congenital glaucoma
- corneal erosion
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Epiblepharon is a congenital eyelid anomaly, in which a fold of skin underlying the orbicularis muscle tilts the lashes, pushing them against the globe.1 2 Epiblepharon may cause keratopathy and astigmatism, and surgical corrections are recommended.3 4 Congenital glaucoma develops in the first few years of life and may cause megalocornea, corneal oedema or buphthalmos.5–9 Based on our experience, patients with congenital glaucoma occasionally present with lower lid epiblepharon and frequently require early surgical correction of epiblepharon due to severe keratopathy.
To the best of our knowledge, there is no case report of patients with congenital glaucoma with lower lid epiblepharon. Only a few cases of congenital glaucoma accompanying lower lid malposition were reported; Mandal et al 10 reported a case of unilateral congenital glaucoma associated with asymmetric congenital lower lid entropion in a 2-year-old girl. In addition, no study had evaluated the prevalence or clinical features of epiblepharon in patients with congenital glaucoma in a large scale. We investigated the prevalence of lower lid epiblepharon among patients with congenital glaucoma and evaluated its clinical features.
Patients with congenital glaucoma, including primary congenital glaucoma and congenital glaucoma associated with other ocular and systemic conditions were included. The medical records of patients with congenital glaucoma, who visited the ophthalmology clinics of Seoul National University Hospital, Seoul National University Bundang Hospital, and Seoul Municipal Government-Seoul National University Boramae Medical Center between August 1999 and November 2014, were reviewed. Patients who had undergone glaucoma surgery and had maintained their postoperative intraocular pressure (IOP) less than 21 mm Hg for at least 1 year were included. Patients diagnosed with acquired glaucoma due to trauma, surgery or steroid eye drops were excluded. Patients whose medical records lacked important relevant information, such as initial IOP or corneal status, were excluded from the study. We also selected an age-matched control group from patients who did not have congenital glaucoma and were diagnosed with congenital nasolacrimal duct obstruction, refractive error, pseudoesotropia or accommodative esotropia at the outpatient clinics of Seoul National University Hospital and Seoul National University Bundang Hospital. We randomly selected subjects matched in terms of age and outpatient clinic visit date (within a 6-month range). The study was approved by the Institutional Review Board of Seoul Municipal Government-Seoul National University Boramae Medical Center and adheres to the tenets of the Declaration of Helsinki.
Data were collected on demographics and clinical characteristics, including glaucoma diagnosis, duration of symptoms, IOP at diagnosis, corneal diameter, buphthalmos, number of glaucoma surgeries, age at glaucoma surgeries, the presence of epiblepharon, and presence and degree of corneal erosions. The presence of lower lid epiblepharon was identified from medical records and medical photographs. Details of surgical history, follow-up period and epiblepharon recurrence among patients who had undergone surgical correction of epiblepharon were collected. If both eyes of a patient met the study eligibility criteria, one eye was randomly selected for analysis.
Statistical analysis was performed using SPSS V.21.0 software and the SAS V.9.4 software. Demographic data (eg, gender and age) were compared between patients with and without lower lid epiblepharon. Differences between congenital glaucoma and control eyes, as well as differences between each type of congenital glaucoma, were assessed using the unpaired t-test or Pearson correlation test for continuous variable and χ2 test or Fisher’s exact test for categorical variable, as applicable. A p value of <0.05 was considered statistically significant. Bivariate logistic regression was performed with presence of lower lid epiblepharon as the dependent variable to evaluate the relationship between related variables. When a variable in either case or control group was 0, Firth’s method of bias correction was used. Predictors with a p value of 0.10 or less in the univariate analysis were included as candidate variables in the stepwise analysis. A backward elimination process was used to develop the final multivariate model. Data are presented as adjusted OR with 95% CI.
One hundred and thirteen patients with congenital glaucoma and 113 age-matched control patients were evaluated. The mean ages were not significantly different (3.40±2.95 vs 4.03±2.96 years old, p=0.226). Among the 113 patients with congenital glaucoma, 49 (43.4%) had unilateral congenital glaucoma. With regard to glaucoma diagnosis, 75 had primary congenital glaucoma and 37 had congenital glaucoma associated with other anomalies; associated anomalies were Sturge-Weber syndrome (n=20), aniridia (n=5), neurofibromatosis (n=4), Axenfeld-Reiger syndrome (n=3), Peter’s anomaly (n=2), anterior segment dysgenesis syndrome (n=1), morning glory anomaly (n=1) and persistent hyperplastic primary vitreous (n=1). The mean age at diagnosis was not significantly different between the two groups (1.03±1.65 and 0.75±1.64 years old, p=0.415). In control group, if myopia is defined as spherical equivalent of less than −0.5 diopters, 30 patients (28%) had myopia in at least one eye. Regarding high myopia which is generally defined as more than −6.0 diopters of spherical equivalent, two patients (1.9%) were categorised as having high myopia. These findings have been described in the Results section.
Comparison of patients with congenital glaucoma and age-matched controls
Patients with congenital glaucoma had a higher prevalence of lower lid epiblepharon compared with control group patients (40.7% vs 13.3%, p<0.001). Asymmetric lower lid epiblepharon was more frequent in patients with congenital glaucoma (24.8% vs 0.9%, p<0.001), and among 28 patients with asymmetric epiblepharon, most (22/28) of epiblepharon was confined to the unilateral. In contrast, no unilateral epiblepharon was found in control group (table 1).
The characteristics of patients with congenital glaucoma according to the presence or absence of lower lid epiblepharon are summarised in table 2. Among the 113 patients with congenital glaucoma, 46 had lower lid epiblepharon. The ages when glaucoma was diagnosed and surgery was performed were younger in group with epiblepharon than those in group without epiblepharon (6.9±8.4 vs 14.3±24.3 months; p=0.023) (8.3±8.4 vs 23.4±41.6; p=0.005). The IOP at diagnosis was significantly higher in group with epiblepharon than that in groups without epiblepharon (31.6±8.4 vs 27.2±7.2 mmHg; p=0.004). Corneal erosions were frequently found in group with epiblepharon (23/46, 50%) and rarely found in group without epiblepharon (1/67, 1.5%), suggesting that most of corneal erosions were caused by epiblepharon, not by congenital glaucoma. The buphthalmos was more frequently found in group with epiblepharon (20/46, 43.5%) than in group without epiblepharon (8/67, 11.9%) (p<0.001) (online supplementary table 1).
Figure 1 shows the representative cases of asymmetric unilateral epiblepharon in patients with unilateral congenital glaucoma (figure 1A-C) and symmetric bilateral epiblepharon in an age-matched control patients (figure 1D-F). Comparison of patients with congenital glaucoma with and without epiblepharon.
Among the 46 patients with congenital glaucoma and also diagnosed with epiblepharon, 22 (47.8%) were unilateral. Comparing patients with unilateral epiblepharon with those with bilateral epiblepharon, congenital glaucoma was frequently confined to unilateral eye (14/22, 63.6%) in patients with unilateral epiblepharon, in contrast to patients with bilateral epiblepharon whose glaucoma was mostly bilateral (21/24, 87.5%, p<0.001). Regarding buphthalmos, unilateral buphthalmos was found only in those with unilateral epiblepharon (13/22, 59.1%), and not found in patients with bilateral epiblepharon (p<0.001) (online supplementary table 2). On the other hand, among 28 patients with buphthalmos, epiblepharon was found in 20 (71.4%). Among 20 buphthalmic patients with epiblepharon, all the 13 unilaterally buphthalmic had unilateral epiblepharon and, in fact, on the side of the buphthalmic eye. In all the seven bilaterally buphthalmic patients, epiblepharon was also bilateral.
In the multivariate logistic regression models in which no significant effects were eliminated, the higher IOP at diagnosis of congenital glaucoma, corneal erosion and buphthalmos was significantly associated with the lower lid epiblepharon (binary logistic regression model, OR=1.122, CI 1.041 to 1.209, p=0.003; OR=82.664, CI 9.084 to 752.255, p<0.001; OR=12.600, CI 2.961 to 53.606, p<0.001, respectively) (table 2). Regarding unilateral epiblepharon, unilateral glaucoma and unilateral buphthalmos were significantly associated with the presence of unilateral epiblepharon (binary logistic regression model, OR=49.849, CI 2.497 to 996.252, p=0.001; OR=7.338, CI 1.370 to 39.292, p=0.020, respectively) (table 3).
Surgical outcomes of lower lid epiblepharon in patients with congenital glaucoma
Among the 46 patients with congenital glaucoma who were also diagnosed with lower lid epiblepharon, 14 underwent surgical correction of epiblepharon. The mean age at surgery was 5.0±2.7 years old (range 2–11). The rotating tarsal fixation suture technique, which was described in our previous study, was used to correct epiblepharon,11 and this procedure effectively corrected lower lid epiblepharon. All patients showed favourable results during the average 11 months of follow-up and there were no recurrences.
We found that almost 40% of patients with congenital glaucoma also had lower lid epiblepharon, and half of them were unilateral epiblepharon, which was significantly frequent compared with normal age-matched controls. This is the first study to assess the prevalence of lower lid epiblepharon in patients with congenital glaucoma. We also found that buphthalmos, corneal erosion and initial high IOP were associated with the presence of lower lid epiblepharon, and unilateral congenital glaucoma tends to develop unilateral epiblepharon.
Epiblepharon is a common congenital eyelid abnormality in Asian children.2 3 Noda et al 12 reported that the incidence of lower lid epiblepharon decreased with age in Japanese children; 24% at age 1, 20% at age 2, and 17% at ages 3–4. Similar results were obtained in our age-matched control (13% at mean age 4.03). On the contrary, patients with congenital glaucoma showed significantly higher prevalence in our cohort (43% at mean age 3.9). This discrepancy suggests that there might be other ocular abnormalities that affect the occurrence in lower lid epiblepharon in patients with congenital glaucoma.
Several studies have reported various conditions that can cause epiblepharon.13 14 Por and Fong13 reported a 33-year-old Chinese patient with lower lid epiblepharon who was eventually diagnosed as having a spontaneous dural carotid cavernous fistula. Subsequent embolisation of the fistula led to the resolution of the exophthalmos and the epiblepharon, suggesting that the cause of epiblepharon was exophthalmos. Our study has shown that buphthalmos and higher IOP at diagnosis are associated with the development of lower lid epiblepharon, and based on this finding and previous reports, epiblepharon in congenital glaucoma appears to be associated with exophthalmos caused by buphthalmos. High IOP causes buphthalmos and this condition usually persists even after the IOP has lowered, because the sclera loses its elasticity and does not readily contract.15 The buphthalmos pushes the lower lid downward and alters the balance of forces between the anterior and posterior lamella. This imbalance might lead to epiblepharon. The high prevalence of epiblehparon has also been reported in thyroid-associated orbitopathy (TAO).16 However, in patients with TAO, exophthalmos was not significantly different according to the epiblepharon type. In patients with TAO, lid retraction was thought to be the mechanism that induced epiblepharon, which differs from congenital glaucoma. Thus, the mechanism of lower eyelid epiblepharon may vary according to each diagnosis. In addition, this phenomenon seems to be unique to Asian eyes. The vulnerability of Asian patients to epiblepharon could be explained by anatomical characteristics of the lower eyelid; between the capsulopalpebral fascia and the orbital septum beneath the inferior tarsal border, there was no consistent fusion.17
Our study revealed that unilateral glaucoma and unilateral buphthalmos are strongly associated with the development of unilateral epiblepharon. This finding is very interesting because most epiblepharon in the general population is bilateral and symmetric, and unilateral epiblepharon is very rare.2 There has been no case report discussing the unilateral lower lid epiblepharon accompanying congenital glaucoma. Mandal et al 10 reported a case of unilateral congenital glaucoma associated with asymmetric congenital lower lid entropion in a 2-year-old girl. The horizontal corneal diameter was 14 mm on the right eye which reveals the possibility of buphthalmos on that eye. Our patients were differentiated with this case because they did not have an eyelid inversion as confirmed by slit lamp examination. However, it seems to be a similar example to support the assumption that unilateral buphthalmos can cause eyelid deformity on the same eye.
In our study, corneal erosion was associated with the presence of epiblepharon. We also found that the severe corneal erosion in epiblepharon was more frequent in patients with congenital glaucoma than in age-matched epiblepharon controls. As shown in the article of Noda et al,12 most cases of congenital epiblepharon in general population had mild complaints and did not always cause superficial keratitis. The frequent and severe corneal erosion observed in patients with epiblepharon and also with congenital glaucoma can be attributed to their increased susceptibility to corneal keratopathy.6 In addition, long-term use of topical antiglaucoma agents with 0.02% benzalkonium chloride, which is a common preservative for glaucoma eye drops, can cause epithelial fragility.8
Our study has a limitation. A selection bias may be present, as this study is of retrospective cross-sectional design. A prospective study with a long-term follow-up is warranted to elucidate the incidence, risk factors and natural course of epiblepharon in congenital glaucoma.
In conclusion, we report high prevalence (40.7%) of lower lid epiblepharon in 113 patients with congenital glaucoma. Buphthalmos, initial high IOP and presence of corneal erosion are associated with presence of lower lid epiblepharon. Unilateral epiblepharon was significantly related with unilateral glaucoma and unilateral buphthalmos. These findings suggest that lower lid epiblepharon should be evaluated in patients with congenital glaucoma and with corneal erosion or buphthalmos. In patients with unilateral buphthalmos, particular attention is needed on the examination of the ipsilateral lower lid. In addition, the surgeon should be aware of variations in epiblepharon for operative planning to relieve mechanical corneal irritation.
The authors thank the Medical Research Collaborating Center at Seoul National University Bundang Hospital for help with statistical analyses.
Contributors Conceptualisation: NK, H-KC. Methodology: NK, H-KC. Formal analysis: NK, YJY. Investigation: NK, YJY. Writing (original draft preparation): NK, YJY. Writing (review and editing): H-KC, SIK. Supervision: SIK. All authors have read and approved the final manuscript. NK and YJY contributed equally, and are the co-first authors for this paper.
Competing interests None declared.
Ethics approval Institutional Review Board of Seoul Municipal Government-Seoul National University Boramae Medical Center.
Provenance and peer review Not commissioned; internally peer reviewed.