Phenylephrine 10 % mydriatic effect : comparison between self instillation of eye drop in open eyes and spray in closed eyes

Objective: To compare the effectiveness of phenylephrine 10% applied by a spray onto the eye closed over drop instillation onto an open eye on patients who will perform ophthalmoscopy and assess the level of difficulty and technical adequacy of the administration methods. Methods: The study was a clinical trial, controlled, randomized and paired, performed in 2014, involving 100 eyes of 50 patients in the Polyclinic Ronaldo Gazolla RJ, with no ocular or systemic diseases that compromised the pupillary dilation. Patients underwent 10% phenylephrine eye drop instillation onto one open eye and spray application onto the other eye, which was closed. Pupillary diameter was measured before application and 10, 20, 30 minutes after. The process of instillation or vaporization was observed for its technical correctness by one of the authors. A questionnaire was asked to the patient about the difficulty of both methods after topical administration. Results: The average mydriasis difference between the eye groups assessed at a given time was at most 0.3 mm, which was not clinically or statistically significant (ANOVA: F = 1.97 and p = 0.163609). However, over time, the difference between the average pupil diameter before application and after 30 minutes was 1.15 mm to vaporized eyes and to 1.58 mm in eyes instilled with drops (ANOVA: F = 129, 22 and p ≤ 0.0001). Sixty per cent of patients touched the tip of the eye drop bottle onto the eye, while 12% touched the tip of the vaporizer with their fingers (p <0.000001). Seventy two percent (72%) considered the drops instillation easy or very easy, while 62% considered vaporization in a closed eye easy or very easy (p = 0.238). Conclusion: The instillation of drops phenylephrine 10% in open eyes and the vaporization onto closed eyes showed similar clinical efficacy. Vaporization was safer and a little more difficult than instillation, despite the patients being experienced for instilling drops and inexperienced to vaporize the medication in a closed eye.


S
praying is a therapeutic route often used in medicine for the prevention and treatment of various diseases.Antihistamine medications, steroids, mast cell membrane stabilizers, anticholinergics, among others are released by nasal spray in order to treat allergies or congestion due to rhinitis or sinusitis (1,2) .Agents for sun photoprotection or temporary skin substitutes that form impermeable dressings may also be applied by spraying on the skin. (3,4)n ophthalmology, there are lubricating sprays commercially available in several countries, for application both with eyes open or closed.There are few studies demonstrating the efficacy of medications when topically sprayed in the eye.The droplets of the ophthalmic solution are placed under pressure between the eyelashes and when the patient opens the eyes, they blend into the tear chamber. (5) recent study found that the fluorescein released by ocular vaporization reaches concentrations in the anterior chamber, but in a lower amount than would be reached by the instillation of drops (6) .Portes et al. reported in 2012 that the mydriasis produced by drops of tropicamide 1% was similar to that from spraying the same substance into the eyes.However, the amount of tropicamide released at each spray was twice that found in 1 drop of this said substance. (7)he use of the medication applied at a distance by spray it with the eyes previously closed can facilitate the treatment in adult or elderly patients with: high ametropia (which make it difficult to see the bottle of eye drops properly); blepharohematoma (which makes palpebral opening difficult and makes the touch of the fingers sensitive to the skin of the eyelids); in elderly patients with motor coordination difficulties and in patients presenting with emotional discomfort at instillation. (7)fter extensive literature review in databases like Scielo, LILACS and MEDLINE, the authors have not found studies on the mydriatic effectiveness of phenylephrine 10% by spraying in eyes closed.
The objectives of the present study were: a) to evaluate by serial measurements by pupilometry the mydriasis produced by the topical application of phenylephrine 10% by spray in the closed eye or instillation of drops in the open eye.
b) to make a comparative evaluation with a questionnaire about which topical application was more difficult.c) to evaluate by observation of self-instillation which method was best suited

METHODS
The survey was carried out from September to November 2014 at the Ophthalmology service of Policlínica Ronaldo Gazolla, Universidade Estácio de Sá, Campus Arcos da Lapa -RJ.A controlled, randomized clinical trial was conducted in a series of 50 patients to which phenylephrine 10% was instilled as drops in one eye, while the other was sprayed in the eyelid with the eye closed.
Patients were invited to participate in the study at their arrival for the ophthalmoscopy exam in the ophthalmology ambulatory at clinic of Policlínica Ronaldo Gazolla on Thursdays.
The eyes were chosen for the administration of eye drops or spray according to a pseudorandom number Excel table prior to application.The pupillary diameter was measured before the instillation and 190, 20 and 30 minutes after it in both eyes with a manual pupilometer "PD-meter".
A bottle of eye drop of a mydriatic ocular solution of phenylephrine 10% and a vial coupled to a vaporizer were used.
All patients had no ocular or systemic diseases that could affect the pupillary diameter.
Exclusion criteria: 1) Anisocoriasis and/or any change of pupillary diameter 2) Presence of any systemic disease affecting the autonomic nervous system.

5) Presence of ocular disease preventing the measurement of the pupillary diameter
Methods of application: all patients remained seated during the study and were requested to look forward.
The eye drop was applied in one of the eyes, always in the same way and as follows: The patient was requested to direct the head backwards, extending the neck and looking up.The lower Portes AJF, Fonseca ACS, Ruliere CM, Ferreira LFL, Souza NM eyelid was slightly drawn to expose the inferior conjunctival sac fundus.Then 01 drop of eye drops was self-instilled at the inferior sac fundus.
The spray was made in the eye where the eye drop was not applied, as follows: the patient was requested to remain seated, looking foward, and then to position the bottle so that the hole in the sprayer was in front of the eyelashes approximately 2 cm away from the eye of the patient, and the drug was sprayed only once with the lids closed.This whole process was done with dexterity and speed.The patients were requested to keep the sprayed eye closed for up to 10 seconds after instillation of the drop or spray.The bottle used was plastic, 7 cm high and 2 cm wide, with a volume of 7 ml.Each spray released an averaged 0.1 ml of ophthalmic solution, which corresponded to approximately 2 drops of eye drops in a circular dispersion area of 5.5 cm in diameter (measures taken on filter paper).This bottle vial was not available for commercial use with medications, so it was sterilized in ethylene oxide prior to the study, and then phenylephrine 10% was introduced into this bottle in sterile form.
After 30 minutes of the last pupillary diameter measurement, if the patient complained of ocular discomfort he underwent biomicroscopic examination to discard any corneal alteration, and the eyelids were also ectoscopically examined to rule out any sensitivity in the area of dispersion of the sprayer.
The instillation process or spray was followed by one of the authors.
After the process, the patient answered pre-formulated questions about the practicality of both methods.Administrationrelated aspects were observed and classified by the authors (Annex 1).
The database was created using the program Epi info 7. The test of "Wilcoxon signed rank" was applied to questions 4 and 5 of the questionnaire.Student's t-test for 2 paired samples was applied to questions 11 and 15, and the binomial test for two proportions of questions 8, 9, 10, 12, 13, 14.The ANOVA test for two factors with replicated measurements compared the results of mydriasis between the eyes in the several times after instillation.Statistical calculations were made by calculators from the website: "vassarstats.net".
This research was submitted to and approved by the Research Ethics Committee of Universidade Estácio de Sá (CAAE: 29365414.2.0000.5284).All participants signed an informed consent form.

RESULTS
The average age of the patients was 64.4 years with a standard deviation of 12.38.Sixteen (32%) patients were men and 34 (68%) were women.56% of patients were referred to ESF-Lapa/RJ, and the others were private or had health insurance.
Table 1 shows the mean mydriasis of each eye at corresponding time intervals from the beginning of instillation.It can be observed that the mean pupillary diameter and the standard deviation are very similar for each group.There were no clinically significant differences in the measurements (Table 1).
The analysis of variance (ANOVA) with two factors for repeated measurements showed F = 1.97 and p = 0.163609 when comparing the measurements between the groups of spray and drops.However, when we compared the groups in relation to time, F = 129.22 and p d" 0.0001.Therefore, the difference of the measures between the groups of spray and drops at each time was not statistically significant, but the difference of mydriasis of the groups between different times showed statistical significance.
The mean mydriasis difference between the groups of eyes evaluated at a given time was at most 0.3 mm, which is not clinically significant.However, over time, the difference between the diameter of the pupil in the initial time and the time of 30 minutes was at least 1.15 mm (clinically significant).
Seventy-two percent (72%) considered the instillation of drops easy or very easy, whereas 62% considered the spray in closed eye easy or very easy.The difference between the groups was not statistically significant (p = 0.238) according to the "Wilcoxon signed rank" test.
Three (6%) of the patients reported that they had difficulty in target the bottle of eye drops so that the drop hit the eye, and one (2%) always blinked during instillation.Nine (18%) patients said they had difficulty in targeting the sprayer to reach the eyelid margin, 5 (10%) that it was hard to squeeze the sprayer, and 2 (4%) that it was hard work with one eye closed.Forty-five patients (90%) did not report any particular difficulty to instill eye drops, and 32 (64%) to spray the eyes.
In 92% of individuals, the drop instilled fell in the eyes.In 90% of patients, the spray fell on the eyelid margin.Twenty-six percent repeated the drop instillation, whereas 40% repeated the spray.There was no statistically significant difference between the number of repetitions of drops in relation to the spray according to the binomial test (p = 0.0425).
The average drops applied by eye was 1.5, and the average was of sprays was 1.46 (p = 0.8036).Sixty percent of patients touched the tip of the bottle of eye drops in the eye, whereas 12% touched the tip of the sprayer with the fingers (p < 0.000001).The difference between the touch of eye drops in the eye tissues and the exit hole of the sprayer with the fingers was statistically significant.

DISCUSSION
The efficacy of phenylephrine 10% was clinically similar to the two routes of topical administration tested.According to the ophthalmic literature, the maximum mydriasis caused by the substance tested occurs between 20 and 30 minutes of initial topical administration.The eyes tested showed the biggest mydriasis 30 minutes after vaporization or instillation. (8)he average pupil dilatation was 1.15 mm for the eyes sprayed, and 1.78 mm for the eyes instilled with drops of phenylephrine 10%.Portes et al. (7) found average pupil dilatation of 2.35 mm for the eyes sprayed, and 2.48 mm for the eyes instilled