2.1 Study design
This is a retrospective observational multicenter cohort study based on the data from two Italian ocular centers: the Ophthalmology Unit of the Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy and the Ophthalmology Department of Bambino Gesù IRCCS Pediatric Hospital, Rome.
The study included the medical records of all patients (age 6-16 years) with coexisting ocular motility disorders, comitant and incomitant strabismus, ptosis and eyelid dynamic disorders either in primary or in other gaze positions, who have never been previously surgically treated, afferent at the two tertiary referral centers from January 1, 2017 through December 31, 2019.
All patients with iatrogenic and traumatic eyelid and ocular motility disorders and patients previously surgically treated on eyelids or extraocular muscles were excluded.
Data from ocular and orthoptic examination, including eye motility, cycloplegic refraction, best-corrected visual acuity (BCVA) measurement, upper margin reflex distance (MRD) and levator function (LF) were collected.
MRD and LF were measured for each patient while the patient looked at an examination torch held about half a meter away. A ruler was held against the upper eyelid and the distance between the light reflex and superior eyelid margin was measured in primary position (MRD). When patients failed to show a visible light reflex, as their upper lid covered the pupil foramen, either negative or 0 values were assigned for analytical purposes. When the value was 0, the upper lid margin covered the center of the pupil; when the value was -1, it outstripped the inferior pupil margin. The
LF was evaluated by measuring the excursion in millimeters of the upper eyelid between upgaze and downgaze, fixing the eyebrow.
The categories of the analyzed association were classified as “congenital isolated” and “others”, and included: congenital cranial dysinnervation disorders, genetic diseases, CNS disorders and neurologic diseases, ocular syndromes and orbital diseases. The prevalence of polymalformative syndromes was further assessed. Ptosis features were classified either as bilateral and unilateral ptosis or eyelid asymmetry, whereas strabismus as esotropia, exotropia, vertical squint, and either comitant or incomitant.
Ocular alignment was assessed using prism cover-uncover tests. Cover tests were performed with fixation targets at both distance (6 m) and near (33 cm). The refractive status of all patients was evaluated both before and after cycloplegia using retinoscopy. Refractive status type (Myopia, Hyperopia, and Astigmatism: with the rule and against the rule) and size (diopters) were recorded. Spherical equivalent (SEq) was calculated as the sum of the spherical plus half of the cylindrical power. Myopia, hyperopia and astigmatism were defined as SEq<0.5 diopters (D), SEq> 0.5 D and cylindrical error >1.0 D, respectively. Best Correct Visual Acuity (BCVA) was assessed for right and left eye, when possible, using Lea Symbols charts [7, 8], or using ETDRS charts [9]. During visual acuity testing, all subjects wore spectacles containing the best correction.
Amblyopia was evaluated according to Pediatric Eye Disease Investigator Group (PEDIG) as mild (20/25 to < 20/40), moderate (20/40 to 20/80) and severe (20/100 to 20/400) [10]. Family history for eyelid abnormalities, oculomotor disorders and systemic/ocular diseases were also recorded.
The study was carried out with the approval from the Fondazione Policlinico Universitario A. Gemelli IRCCS Ethics Committee (Protocol ID number 0039303/20, ID:3396) and in accordance with 1976 Declaration of Helsinki and its later amendments. A written informed consent for data collection and analysis of collected data from their medical records was obtained from all patients. Photographs were obtained in selected cases with patients’ permission.
2.2 Statistical Analysis
All variables included in the study were summarized by descriptive statistics techniques. In depth, qualitative variables were expressed as absolute and percentage frequency. As for quantitative variables, we performed the Shapiro-Wilk test to assess their distribution. Then, whether normally distributed, they were described as mean and standard deviation (SD), otherwise as median and interquartile range (IQR).
Between groups differences for each parameter considered (strabismus type, categories, refractive error, amblyopia, ptosis features) were assessed, as for qualitative variables, either by the Fisher Exact test or the Chi square test, with Yates correction, as appropriate. Quantitative variables were instead assessed either by one-way ANOVA or Student t test, if normally distributed, otherwise either Mann Whitney U test or Kruskal-Wallis test were applied. A p value <0.05 was considered as statistically significant. All analyses were conducted with STATA software, version 16 (StataCorp. College Station, TX: StataCorp LLC.