The Effect of Topical Anesthesia on Pharmacological Mydriasis in Diabetic Patients Depends on the Presence of Retinopathy

Special Article - Diabetic Retinopathy: Clinical Cases and Images

Austin J Clin Ophthalmol. 2015; 2(4): 1056.

The Effect of Topical Anesthesia on Pharmacological Mydriasis in Diabetic Patients Depends on the Presence of Retinopathy

Clausen S, Jørgensen CM and Bek T*

Department of Ophthalmology, Aarhus University Hospital, Denmark

*Corresponding author: Bek T, Department of Ophthalmology, Aarhus University Hospital, DK-8000 Aarhus C, Denmark

Received: July 23, 2015; Accepted: September 10, 2015; Published: September 21, 2015

Abstract

Purpose: Instillation of topical anesthetics with or without preservatives in normal persons has been shown to enhance the effect of mydriatic eye drops. The purpose of the present investigation was to study whether a similar effect can be observed in diabetic patients screened for retinopathy and whether the effect depends on the presence of retinopathy.

Methods: Thirty-six patients attending a screening programme for diabetic retinopathy were randomized to receive local anesthetic eye drops on one eye, followed by instillation of both a sympathomimetic and a parasympatholytic eye drop in both eyes, which was repeated after 20 minutes. The pupil diameter in both eyes was measured with 5 minutes intervals until 35 minutes after the first application of mydriatics, and the responses in the two eyes were compared.

Results: The pupil diameter increased significantly throughout the observarion period in both eyes (p<0.0001), and after 10 minutes the effect was significantly higher in the patients who had received topical anesthesia. The increase in the pupil diameter in this group was significantly higher from 5-10 minutes after the first (p<0.003) and from 0-5 minutes after the second (p<0.01) application of mydriatic eye drops. The patients with retinopathy had significantly (p<0.05) smaller baseline pupil diameter than the patients with no retinopathy, and this difference persisted throughout the experiment.

Conclusions: Topical anesthesia enhances pharmacological mydriasis in patients during screening for diabetic retinopathy, but pupil size before and after the intervention depends on the presence of retinopathy.

Keywords: Topical anesthesia; Mydriasis; Screening; Diabetic retinopathy

Introduction

Screening for diabetic retinopathy requires pharmacological mydriasis for the retina to be studied in detail and documented by fundus photography [1]. The mydriatic effect can be achieved by topical application of parasympatholytic and/or sympatomimetic drugs with the side effect of inducing a short-lived smarting or burning sensation. In normal persons it has been shown that instillation of topical anesthetics with or without preservatives prior to the mydriatic eye drops can reduce the irritation induced by the mydriatic eye drops [2-4], and may increase corneal permeability to allow a faster onset and a more pronounced mydriatic effect [5-7].

It is likely that the influence of topical anesthesia on the effect of mydriatic compounds may be different in diabetic patients because pupil motility and corneal sensitivity are reduced due to autonomic neuropathy [2,8], and because the effect of topical anesthesia on corneal epithelial barrier permeability in diabetic patients differs from that of normal persons [9]. However, the effect of topical anesthesia on pharmacological mydriasis has not been studied in diabetic patients.

Therefore, 36 non-selected patients attending a screening programme for diabetic retinopathy were randomized for local anesthetic eye drops on one eye, followed by the routinely used instillation of both a sympathomimetic and a parasympatholytic compound on both eyes which was repeated after 20 minutes. The pupil diameter in both eyes was measured with 5 minutes intervals until 35 minutes after the first application of mydriatics, and the response was compared between the intervention eye and the control eye.

Materials and Methods

Design

Prospective randomized interventional study of the mydriatic effect of metaoxedrin and phenylephrin preceded by topical application of oxybuprocain with benzalkonium chloride preservative in one eye and in patients participating in a screening programme for diabetic retinopathy.

Patients

Thirty-six patients (twenty men and sixteen women) scheduled for examination in the screening clinic for diabetic retinopathy at the Department of Ophthalmology, Aarhus University Hospital, were studied. This clinic performs approximately 4,000 screening examinations for diabetic retinopathy annually, which corresponds to approximately twenty examinations each working day with no preferences for booking of particular patient types on specific times of the day. The patients were recruited prospectively among the two first patients scheduled in the programme on 2-3 days each week over a period of six months. Exclusion criteria were: Pregnant and lactating women and patients with any known previous or present ocular disease apart from diabetic retinopathy.

Written information about the study was sent by ordinary mail to the patients at least three weeks before the examination and included an e-mail address and a phone number to indicate an interest for participation in the study. One hundred and fourteen patients from 77 examination days were considered for an invitation of which six patients were excluded due to systemic conditions (2), previous ocular surgery (3) or acute conjunctivitis (1). Among the remaining 108 patients 38 reported that they were willing to participate. At the day of the examination one patient was excluded because of reminding of previous operation for cataract and another patient because of accidental deviation from the examination protocol, which resulted in the inclusion of 36 patients. These patients consisted of twelve patients with type 1 diabetes mellitus defined as onset of diabetes before the age of 40 and a need for treatment with insulin within one year after the diagnosis, and 24 patients defined as having type 2 diabetes mellitus. The iris colour was blue in 34 patients and brown in two patients. Twenty of the patients had no retinopathy, whereas the remaining sixteen patients had retinopathy.

A preliminary power analysis had shown that with an accuracy of 0.2 mm in the measurement of the pupil diameter, 31 patients would have to be included in order to detect a difference between the two eyes, assuming a power of 0.8 and p<0.05.

The study was approved by the Regional Committee for Scientific Ethics, The Danish Medicines Agency, The Danish Data Protection Agency and was monitored by the GCP unit at Aarhus University Hospital.

Ophthalmological examination

The patients who were interested in participating were further informed about the practical procedures, followed by the signing of a written consent. Subsequently, the patient was asked about the time of onset of diabetes mellitus, previous and current general and ophthalmological diseases, possible visual problems and current treatment of diabetes mellitus, and the patient record was updated if relevant. Finally, best corrected visual acuity was measured using ETDRS visual acuity charts. The diameter of the pupil was measured using an autorefractor (Nidek Tonoref II, Maehama, Hiroishicho, Gamagori, Aichi, Japan). Measurements of refraction by this apparatus includes photography of the iris plane under mesopic conditions in order to measure the pupil diameter to estimate the size of the optical zone. The image of the pupil is shown on a computer screen, and two vertical bars are moved manually until they align with respectively the nasal and the temporal edges of the pupil. When the examiner presses a button the horizontal distance between the two bars is displayed on the screen with a precision of 0.1 mm. This distance and the precision has been shown to be comparable with that obtained with Colvard’s electrical pupillometer [10].

Eye drops

Oxybuprocain 0.8 mg/ml containing benzalkonium chloride 0.01 mg/ml, borate acide 1.59 mg/ml and disodium EDTA 0.05 mg/ml, purchased from the hospital pharmacy at Aarhus University Hospital. Metaoxedrin 10 % containing benzalkonium chloride 0.1 mg/ml and disodium EDTA 0.5 mg/ml was purchased from the hospital pharmacy, Skanderborg, Denmark. Mydriacyl 1 % containing benzalkoniumchloride 0.1mg/ml (50% solution), disodium EDTA 0.1 mg/ml and sodium chloride 7.0 mg/ml was purchased from Alcon, Puurs, Belgium.

Procedure

The experimental protocol is shown in Figure 1. The right eye was selected as the test eye and the left eye as the control eye in the first included patient, which was subsequently alternated for each successively included patient. The instillation of mydriatic eye drops and the measurement of pupil diameter were in all patients performed initially in the right eye, immediately followed by instillation in the left eye. The sequence of events in the examination was as follows: