Abstract

INTRODUCTION

Allergic diseases are among the most common disorders in children, and ocular allergy represents one of the most common ocular conditions encountered in clinical practice. The prevalence of allergic diseases in children aged 6 to 14 years varies significantly from 0.3% to 20.5%, and is gradually increasing.¹ This increase may be due to genetics, air pollution in urban areas, pets, and early childhood exposure.¹ The most common form of ocular allergy is seasonal allergic conjunctivitis (SAC), accounting for 90% of cases. The most prevalent allergens in SAC are grass, tree, and weed pollen and outdoor molds.^2,3 Although the signs and symptoms of SAC usually are mild, it may hinder school performance, work productivity, everyday tasks, such as reading resulting in an overall reduction in the quality of life.

Recently, more attention is being paid to dry eye, and the number of symptomatic patients has been increasing. Dry eye syndrome (DES) is caused by a heterogeneous group of diseases which share a functional tear deficit due to reduced production or excessive evaporation, associated with ocular discomfort symptoms which could limit the daily activities of affected patients.⁴ Traditionally, DES and AC are regarded as two different diseases. However, recent literature has shown both conditions share similar characteristics, including several signs and symptoms.⁵ Pflugfelder et al.⁶ suggested that activated T-cells and an increase in inflammatory cytokines such as epidermal growth factor, interleukin-1 (IL-1), and IL-8, damage goblet cells and conjunctival epithelial, which account for a reduction of mucin production and subsequent decrease of tear film break-up time (BUT). Many reports have shown an instability of mucins and decreased BUT in AC and suggested that up-regulation of inflammation affects the tear balance.^7,8 Corneal mechanical changes, related with the complex allergic process, may lead to stromal thinning, and may increase the corneal curvature.

In this study, we evaluated tear dynamics and keratometry (K1, K2) in patients with SAC, to determine whether clinically diagnosed patients have concomitant DES and changes in corneal curvature.

MATERIALS AND METHODS

Sixty children were examined for this study, but 11 children were excluded because they were uncooperative during the examination. Hence, 25 children with clinically diagnosed AC (AC group) and 24 age-matched healthy children (control group) were enrolled in this study. The patients were seen from May 2014 to June 2014 which is allergy season in our region. AC was diagnosed according to past history, clinical symptoms such as ocular itching, redness, tearing, or ocular pain, and slit-lamp examinations showing filamentous (mucous) discharge, chemosis, hyperemia, or papillae of the palpebral conjunctiva. Patients excluded from the study were those who had systemic and ocular diseases, which required any kind of medical or surgical treatment with an adverse effect on the tests for dry eye during examinations. This study received ethical approval from Erzincan University Research Ethics Committee. The research complies with the declaration of Helsinki of the World Medical Association, and informed consent was obtained from each subject and their parents after a full explanation of the procedures. We examined the ocular discomfort using the validated ocular surface disease index (OSDI) developed by Schiffman et al.⁹ which comprises 12 questions on ocular irritation symptoms related to dry eye disease and its impact on visual function. The survey was administered to all patients (we request parents to help us) by the same researcher in simple and easily understandable terms so that all the patients were able to score the intensity of their symptoms. After the OSDI questionnaire was completed, autokeratometry was performed with a tabletop autorefractometer (Canon RK-F1™).

The patients were explored in a softly lit room with a temperature of 25°C (77°F) and a humidity of 40%. Dry eye was confirmed by means of a set of tests performed in successive manner: Tear film BUT, tear meniscus height reflex (TMH-R) measurement and the Schirmer test. The conjunctiva and cornea were examined using a slit-lamp. A fluorescein strip (fluorescein, Haag-Streit International Co., Ltd, Koeniz, Switzerland) was moistened with a saline solution and touched the inferior fornix. The patients were instructed to blink, and the pre-corneal tear film was examined under blue-light illumination. The time in seconds between the last blink and the appearance of a random dry spot was recorded by a stopwatch as the BUT¹⁰ and 10 s or less was considered abnormal.

The tear meniscus, which is formed between the lid surface and the bulbar conjunctiva, is present along the inferior lid margin. Assessment of the TMH is used universally by eye care practitioners as part of routine ocular assessments.¹¹ Of the TMH parameters studied, central TMH-R seems to be the most useful, due to its relationship with subjective assessment while presenting an easy endpoint for the clinician. TMH-R was measured at the 6 o’clock position as the distance between the darker edge of the lower eyelid and the upper limit of the brightest reflex of the meniscus, with the observation and illumination systems set at 0°, without tilting the illumination column. TMH-R values <0.1 mm were considered abnormal.¹²

The Schirmer tear test is the most common and easily performed test for the evaluation of DES. The Schirmer I test (without anesthesia) measures both basal and reflex tearing, and the Schirmer II test (with anesthesia) measures only the basal secretion of tearing with topical anesthesia. Schirmer with anesthesia test for basal secretion was applied with a filter strip (SNO* Strips, Lab Chauvin, Aubenas, France) located inferotemporally without touching the cornea and is considered abnormal if wetting of the strip was 5 mm or less in 5 min.

Patients having at least severe to very severe grades from the OSDI questionnaire and two positive results for the clinical tests for dry eye in both eyes were considered dry eye positive.

All statistical analyses were performed with SPSS/PC 21.0 (IBM Corp., Armonk, NY, USA). The mean, median, and standard deviation from each data set were calculated for general statistical reporting. The Mann–Whitney U-test and independent sample t-test were used. To determine the correlation between the objective tests and the papillary reaction, OSDI Spearman's correlation analysis was used as appropriate. A P < 0.05 was considered statistically significant.

RESULTS

In this study, patients ranged in age from 6 to 18 years (mean ± SD of age for all subjects. The mean was 11.79 ± 3.7 years for both groups combined and 11.18 ± 2.5 years for the AC group and 10.94 ± 4.3 years for the control group. Twenty-three (46.9%) children were male, and 26 (53.1%) were female. There was no statistically significant difference between groups for age and gender (P > 0.05, both comparisons).

The results referring to clinical disease severity criteria are presented in Table 1. Most of AC group were classified as OSDI moderate and severe, followed by very severe [Table 2].

Table 1

Ocular surface disease severity according to OSDI scores

Open in a separate window

Table 2

Distribution of 25 patients based on ocular surface disease severity

Open in a separate window

All the patients in the AC group had itchy and red eyes. The papillary reaction was severe in 10% (5 of 50 of eyes) in the AC group. The Schirmer test was abnormal in 10% (5 of 50 of eyes) in the AC group, BUT was <10 s in 40% (20 of 50 eyes) of the AC group. TMH-R was 0.1 ± 0.05 in the AC group and 0.25 ± 0.16 in the control group. TMH-R was abnormal in 36% (18 of 50 eyes) of the AC group. The prevalence of dry eye in the AC group was 24% (6 of 25 patients). The odds ratios for Schirmer test, BUT, and TMH-R were 5.18, 15.3 and 6.7, respectively (the 95% confidence intervals were: 1.59–16.91, 3.3–70.43, and 2.09–21.77, respectively). The present study found no statistically significant differences between groups for the K1, K2 values and spherical equivalent (SE) (P = 0.052, 0.1, 0.549, respectively). K values were higher in the AC group compared to the control group [Table 3].

Table 3

Statistical findings of pediatric patients with and without dry eye symptoms

Open in a separate window

There were statistically significant difference between groups for the Schirmer test, BUT, and TMH-R (P < 0.001 for all comparisons). The Schirmer test, BUT, and TMH-R values were lower in the AC group compared to the control group. No statistically significant correlations were found in the height of the lacrimal meniscus and Schirmer II test with the OSDI values (ρ = 0.186, 0.267, and P = 0.256, 0.586, respectively). In what concerns clinical disease severity criteria, only BUT exhibited a statistically significant negative correlation with the OSDI values (ρ = −0.567; P = 0.004).

Statistically significant negative moderate correlation was found between papillary reaction and the Schirmer test, BUT, TMH-R (ρ = −0.454, −0.412, −0.419 and P = 0.001, 0.003, 0.002, respectively). The negative ρ values indicate that there is a linear relation between papillary reaction and dry eye tests, but the opposite relation remains untrue. Hence, the patients with papillary reaction had lower values for Schirmer test, BUT, and TMH-R.

DISCUSSION

The results of the study revealed that AC in the pediatric population may cause tear film dysfunction. AC was diagnosed based on past history, and clinical symptoms.

The diagnosis of ocular surface disease begins with a patient history and the large variety of symptoms related to the disease. Pediatric patients with DES tend to complain less about their symptoms than adult patients hence, DES is commonly overlooked in children. We chose the OSDI questionnaire for collecting data from children because it is a only survey that can evaluate the frequency of symptoms and their impact on the visual function.⁹ The questions were divided into three subscales: Symptoms (three questions); environmental triggers (three questions) and; vision-related function (six questions). Although, patient symptom-based surveys in adults are useful to study a disease and as a follow-up tool, objective tests can offer greater precise to determine lacrimal production (Schirmer test) and ocular surface alterations (tear film alterations with vital stains).¹³ Further studies are required to validate the questionnaire in children.

The effects of conjunctivitis on the ocular surface and tear balance have been discussed in many reports.^8,14 Increased inflammatory cytokines are associated with goblet cell loss and tear volume insufficiency. Current classification systems divide DES into two major categories: Aqueous deficient (tear volume insufficiency) and; evaporative dry eye (meibomian gland dysfunction and posterior blepharitis).¹⁵ The discussion so far generally refers to an aqueous deficient dry eye.

There are many instances in the literature connecting tear film dysfunction with AC. One study theorizes that tear film dysfunction is a possible complication of the ocular allergic disease.¹⁴ Our study concurs with previous reports that AC is the initial condition and predisposes to DES.^16,17 Closer evaluation of ocular allergy indicated it may be more common in the pediatric population whereas DES is uncommon. Studies support the observation that AC establishes an environment that generates a dry ocular surface.¹⁷ The present study found 6 children with dry eye, accounting for 24% of children with AC. This rate for a dry eye was lower than previous studies¹⁸ and could be related to the diagnostic criteria for DES or the pediatric population in our study.

We performed Schirmer II test, tear film BUT, and TMH-R as objective tests. Schirmer II after topical anesthesia with 0.5% proparacaine hydrochloride eye drops is objective and has greater reliability than without anesthesia in reflecting the status of the dry eye. Additionally, the diagnostic value in patients with aqueous deficient DES was even higher, providing meaningful evidence for the diagnosis and treatment of dry eye.¹⁹ The Schirmer test was abnormal in 10% (5 of 50 eyes) of the AC group. In dry eye patients, lower tear volume, and reduced tear secretion were well-documented.^11,13,15 We evaluated TMH-R to determine the deficiency of tear volume in children with AC. We found statistically significant differences for the Schirmer test, BUT, and TMH-R between groups. Clinical practice has not shown a correlation between the subjective symptoms and objective findings in assessing the dry eye patient. However, regardless of the poor association between symptoms and the traditional objective clinical measures, we have observed that tear film BUT was closely correlated with patient perception of the severity of the disease. Our study indicated a negative moderate correlation between papillary reaction caused by AC and objective tests.

Some studies reported that the complex allergic process involving biochemical (enzymes and enzymatic inhibitors) and cellular (apoptosis) disturbance leads to stromal thinning, causing an increase in corneal curvature and consequently myopic astigmatism.²⁰ In susceptible individuals, a long-term allergic disease with a chronic traumatic factor on the corneal epithelium could be related to keratoconus. For example, Kim et al.²¹ found that persistent and chronic corneal trauma on the corneal epithelium (in this particular situation, itching or chronic trauma provoked by giant papillae), induces a “silent” and chronic inflammatory process, leading to progressive loss of stromal mass and consequently to less biomechanical resistance, and thus to anterior corneal steepening, decreasing the optical competence of the anterior corneal surface. Scientific data support the observation that chronic AC may be a risk factor for myopic refractive error. We found that there was no statistically significant difference for K1, K2, and SE values between groups. However mean keratometry for the AC group was higher than the control group. Conjunctivitis in this study was not severe, and its duration may have been short because most cases were SAC. Hence, the conjunctivitis may not cause any cytological damage to the ocular surface.

The main limitation of our study was the small sample size of the study group. Additionally, this study was performed in a small district of the country, by the same examiner. In the pediatric population, confirmation of DES with these tests was troublesome. We examined 60 children during the study but for accurate analysis of data we excluded the uncooperative cases. Another limitation of our study was a lack of allergy testing (e.g., skin prick tests, etc.) on the clinically diagnosed patients with AC. Allergists can perform skin testing for specific allergens by scratch tests or intradermal injections of the allergen. In vitro tests for immunoglobulin E antibodies to specific allergens are widely used. Allergic tests would aid in differentiating intrinsic and extrinsic forms and therefore, be helpful for treatment. However, the diagnosis of ocular allergy is primarily clinical,²² so our results should be valid.

CONCLUSION

AC could be complicated by DES in the pediatric population. In such cases, artificial tears may improve the conditions of the ocular anterior segment. The present study is valuable for assessing the relationship between DES and AC in the pediatric population. Our results merit attention because there are little data on the prevalence of dry eye in this age group with AC.

REFERENCES