This is a prospective study that included 60 patients who had LASIK eye surgery for correction of refractive errors. The procedure was performed by the same surgeon (Fouda S), and the flap was created using a Moria M2® microkeratome with 90 or 120 blades according to the measured pre-operative central corneal thickness. Laser treatment was done using an Excimer laser (192 nm UV laser) of a Schwind Amaris 500E® machine (Schwind eyetech solution, Germany). All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964, as revised in 2013. Informed consent was obtained from each patient before Botox injection and punctal plugs application. All procedures were performed between February 2015 and April 2016 in a private eye center in Egypt.
All patients received pre-operative full medical and ocular history taking, full ophthalmic examination, corneal imaging and tear secretion tests. Exclusion criteria were pre-operative dry eye, ocular surface irregularities, neuromuscular disorders prohibiting botulinum toxin injection, e.g. myaethenia gravis, or patients with known hypersensivity to botulinum toxin.
Dry eye was assessed by both subjective and objective methods. Eye discomfort was assessed using an ocular surface disease index (OSDI). An OSDI questionnaire was used to quantify the dry eye symptoms. Subjects were asked questions regarding the symptoms of dry eye that they had experienced during a 1-week recall period; the OSDI questions comprised three different subscales: ocular symptoms, vision-related functions, and environmental triggers and each answer was scored on a four-point scale ranging from zero (no problems) to four (significant problem). Responses to all of the questions were combined to generate an OSDI score that ranged from 0 to 100 using the OSDI formula: OSDI© = sum of scores × 25/number of questions answered. The OSDI scores and the level of ocular disability were categorized on a 4-class scale ranging from none (OSDI total score ≤12) to severe (OSDI total score ≥33) [14, 15]. Tear break-up time (TBUT) and the Schirmer tear secretion test were used to objectively evaluate the tear film before performing the refractive surgery and post-operatively in all follow-up visits.
The sample size was calculated through Epi-Info (Epidemiological Information Package) software version 6.1. The improvement rate for dry eyes was 83.3% with injection of botulinum toxin and the improvement rate for dry eyes in the punctual plugs group was 50.0% . So, at 95% confidence interval and power of study 80%, the sample size was calculated to be 60 patients.
Patients were randomly assigned to one of three methods of dry eye management; the first method was conventional medical treatment with preservative-free tear substitutes only (group A: 20 patients = 40 eyes); the second method was intraoperative injection of botulinum toxin A (BTA) in the orbicularis muscle below the lower punctum of both eyes (group B: 20 patients = 40 eyes) and the third method was intraoperative insertion of a temporary extended duration silicone punctal plug in the lower punctum of both eyes (group C: 20 patients = 40 eyes).
All patients were instructed to put preservative-free tear substitute eye drops (polyethylene glycol and propylene glycol) Systane ultra® (Alcon Laboratories, Inc., Fort Worth, TX, USA) as needed and the frequency was recorded in a special chart. Antibiotic eye drops of Ofloxacin 0.3% (Oflox®; Allergan corporation, Irvine, CA, USA) and anti-inflammatory eye drops in the form of fluorometholone (FML®; Alcon Laboratories, Inc, Fort Worth, TX, USA) were used in the first 2 weeks in all patients.
Group B patients were injected with 3.75 units (0.15 ml) of botulinum toxin at the end of the LASIK procedure using a 28-gauge insulin needle. The injection site was subcutaneous in the orbicularis muscle of the lower lid 2 mm below the lower punctum to induce punctal ectropion and thus interfering with the normal tear drainage pathway and improving dry eye manifestations. BTA (Botox®, Allergan® Corporation, Westport, Mayo, Ireland) comes in a vial containing 100 units of freeze-dried BTA. It was reconstituted and diluted with 4 ml of saline, resulting in a concentration of 25 units/ml (2.5 units/0.1 ml). Before starting the LASIK procedure, percutaneous anaesthesia was induced by applying a eutectic mixture of local anaesthetics (EMLA® cream) over the site of injection to avoid any undesired pain response that may unstabilize the LASIK flap. The site and dose of botulinum toxin injection were chosen based on the previous work of Salhin et al. .
Silicone punctal plugs (FCI Ophthalmics, Inc., Paris, France) were inserted in the lower punctum in both lower eyelids at the end of the LASIK procedure in group C patients.
The patients’ data were reported at 2 and 6 weeks and 3 and 6 months post-operatively. The main outcome measures included tear film stability as per the TBUT test, tear secretion per the Schirmer’s test and dry eye symptoms per the OSDI questionnaire and the tear substitute daily frequency by a simple daily chart. The TBUT test was considered positive for dry eye when the break in the pre-corneal tear film appeared within less than 10 s following fluorescein dye instillation, and a positive Schirmer’s test was considered when the amount of the Schirmer strip wetting was less than 5 mm after 5 min with pre-test instillation of one drop of benoxinate hydrochloride 0.4 mg (Benox®-Eipico, Egypt) as a local anaesthetic.
Data were checked and analyzed by using SPSS for Windows (version 16, SPSS, Chicago, IL, USA). We checked normality and for normally distributed data, we used the mean ± SD and the parametric ANOVA test, and for not normally distributed data, we used the median (range) and the non-parametric Kruskal–Wallis test. For all analyses, a P value of <0.05 was considered statistically significant.