Obtained Mydriasis in Long-Term Type 2 Diabetic Patients

Abstract

Purpose:

The purpose of this study was to evaluate obtained mydriasis and prevalence of small pupil in long-term type 2 diabetic patients.

Methods:

A prospective observational cross-sectional study was carried out. We included 107 eyes from 107 patients (mean age: 60.8) with long-term (≥10 years) type 2 diabetes mellitus. Patients were divided into 2 groups: no apparent diabetic retinopathy (group 1, n=33) and diabetic retinopathy (group 2, n=74). Exclusion criteria were eyes with prior intraocular surgeries, presence of other ocular disorders that may affect iris, or any other condition that precludes the precise measurement of pupil size. Sixty eyes in 60 age-matched nondiabetic patients (mean age: 61.0) scheduled for routine fundoscopy exam were enrolled as control. We measured pupil diameter by pupil gauges at 40 min after instillation of eye drops (phenylephrine 10% and tropicamide 1%). Small pupil was defined as pupil diameter of 6 mm or less.

Results:

Mean pupil diameter was 8.07 mm [standard deviation (SD): 0.59 mm] in the control group, 7.46 mm (SD: 0.71 mm) in group 1, and 7.24 mm (SD: 0.83 mm) in group 2. Both group 1 (P<0.001) and group 2 (P<0.001) showed significant difference when compared with the control group. The incidences of small pupil were 1.9% in the control group, 6.1% in group 1, and 13.5% in group 2. When compared with control, group 2 showed significantly higher incidence of small pupil (P=0.023).

Conclusions:

Long-term diabetic patients showed poorer response to pharmacological mydriasis than nondiabetic patients. Higher prevalence of small pupil size was found in patients with diabetic retinopathy.

Introduction

Pharmacological mydriasis is important in both evaluation and management of patients with diabetes mellitus (DM). Some diabetic pupils may dilate poorly to mydriatic drugs.¹ Inadequate pupil size may preclude fundus examination and application of retinal laser photocoagulation.^2,3 Diabetic patients also have higher incidence of cataract and may require cataract surgery earlier than nondiabetic patients.^4,5 By compromising the visibility during cataract surgeries, poor dilated pupil significantly increases the risk of intraoperative complications, such as vitreous loss and capsular rupture.⁶ Thus, it is important to understand the incidence and risk factors of poor dilated pupil in diabetic patients.

The pupil reaction is controlled by the sphincter pupillae muscle, which is innervated by parasympathetic system, and the dilator pupillae muscle, which is innervated by the sympathetic system. Poor response to mydriatic drugs might implicate certain damages in autonomic nervous system after long duration of DM.⁷ Long-term diabetic patients were more intended to develop diabetic neuropathy.⁸ We proposed that long-term diabetic patients may have poorer response to mydriatic drugs. The purpose of this study was to compare the difference in obtained mydriasis between long-term type 2 diabetic patients and nondiabetic patients. We also evaluated the incidence of small pupil in these patients.

Methods

Subjects

A prospective collaborative study was conducted at the Department of Ophthalmology and Department of Internal Medicine (Division of Endocrinology and Metabolism), Chang Gung Memorial Hospital, Keelung, Taiwan, between August 2007 and December 2008. This study was performed in accordance with the Helsinki Declaration of 1975 (1983 revision). The institutional review boards of Chang Gung Memorial Hospital approved the protocol. All patients gave written informed consent before enrolment.

The patients who were being followed regularly in our hospital and met all the following criteria were invited to participate in this study. Enrollment criteria were (1) patients with type 2 DM who had been diagnosed for 10 years or more and (2) patients scheduled for dilated funduscopy exam in our vitreoretinal clinic. The exclusion criteria were (1) any prior intraocular surgeries such as cataract extraction or vitrectomy; (2) presence of other ocular disorders that may affect iris or pupils, such as ocular trauma, rubeosis iridis, glaucoma, pseudoexfoliation syndrome, uveitis, and so on; (3) use of topical pilocarpine; (4) presence of pupil synechiae; (5) use of tamsulosin; and (6) any condition that preclude the precise measurement of pupil size such as significant corneal opacity, hyphema, or poor patient cooperation. Totally, 107 patients [55 women and 52 men; mean age: 60.8 years; standard deviation (SD): 12.3 years] with long-term (≥10 years) type 2 DM were enrolled in this study. Only one eye of each patient was included. If both eyes were eligible, the eye with larger pupil diameter was selected. Pupil sizes of 60 eyes in 60 age-matched nondiabetic patients (31 women and 29 men; mean age: 61.0 years; SD: 14.0 years) scheduled for routine fundoscopy exam were used as control.

Clinical data collection

A standardized questionnaire was used to collect medical history. Data collection included the patient's age, gender, ocular history, duration of DM, recent HbA1C level, and any other significant medical history, such as hypertension, cardiovascular diseases, renal insufficiency, dyslipidemia, smoking, and so on.

Each patient in study group underwent a complete ocular examination on the day of enrollment. The ocular exams included best corrected visual acuity, intraocular pressure by noncontact tonometer, and dilated fundus exam with both slit-lamp biomicroscopy and indirect ophthalmoscopy. Best-corrected visual acuity was measured on the Snellen chart and converted to the logarithm of the minimum angle of resolution for calculation. The severity of diabetic retinopathy was graded by experienced ophthalmologists according to the International Clinical Diabetic Retinopathy Disease Severity Scale.⁹ Cataract status was evaluated by the lens opacities classification system III.¹⁰

One drop of phenylephrine 10% (Phenylephrine soln. 10%; Wu-Fu Laboratories Co. Ltd., Ilan, Taiwan) and one drop of tropicamide 1% (Mydriacyl; Alcon Laboratories, Inc., Puurs, Belgium) were administered for pupil dilation. Two drugs were applied with 5-min interval. Patients were instructed to close eyelids gently after instillation of each drop and to maintain eye closed for at least 10 min. The pupil sizes were measured by experienced technicians who were unaware of the patients' underline systemic diseases and ocular conditions. Pupil diameter was measured at 40 min after eye drops instillation by pupil gauges in 0.5 mm scales. In patient with oval-shaped pupil, the pupil diameter was determined by the average of maximum and minimum diameters in 2 right-angled meridians. Small pupil was defined as pupil diameter 6 mm or less.

Statistical analysis

For statistical analysis, diabetic patients were divided into 2 groups: group 1, no apparent diabetic retinopathy (33 eyes); and group 2, with diabetic retinopathy (74 eyes). Chi-square analysis was used for categorical data, and independent sample Student's t-test was used for continuous data to determine whether significant differences appeared between each group. The Fisher's exact test was used when one or more cells in the chi-square analysis had expected values below 5. Multivariate linear regression was performed to evaluate whether the factors correlated to pupil size. A 2-tailed P value of <0.05 was considered as statistically significant. All data were analyzed using SPSS Program Package Version 17.0 (SPSS, Inc., Chicago, IL).

Results

The demographic data of 107 long-term diabetic patients and 60 nondiabetic patients are summarized in Table 1. There were no significant differences between diabetic and nondiabetic patients in their age (P=0.905) and gender (P=0.974). Among diabetic patients, group 1 and group 2 were similar in duration of disease, recent HbA1C level, and rates of dyslipidemia, renal insufficiency, cigarette smoking, and using insulin. However, group 2 patient has higher rate of hypertension (P=0.027) than group 1.

Table 1.

Demographic Data of Patients

		Diabetic patients
	Control	Group 1	Group 2	Overall
No. of patients	n=60	n=33	n=74	n=107
Age (mean±SD)	61.0±14.0	59.2±14.4	61.5±11.3	60.8±12.3
Gender (F:M)	31:29	13:20	42:32	55:52
Systemic conditions
Duration of diagnosis of DM, years		15.2±6.3	15.1±5.5	15.1±5.7
Recent HbA1C, % (mean±SD)		7.8±1.8	8.5±1.8	8.2±1.8
Hypertension		19 (68%)	58 (78%)	77 (72%)
Dyslipidemia		18 (54%)	43 (58%)	61 (57%)
Renal insufficiency		0 (0%)	8 (11%)	8 (8%)
Cigarette smoking		6 (18%)	9 (12%)	15 (14%)
Using insulin		12 (36%)	40 (54%)	52 (49%)
Other ocular conditions
Corrected visual acuity, logMAR (mean±SD)		0.31±0.28	0.46±0.42	0.41±0.39
Spherical equivalent, D (mean±SD)		−0.64±2.08	0.26±1.65	−0.01±1.83
Cataract grading (mean±SD)
Nuclear opalescence		2.0±1.2	2.4±1.0	2.3±1.1
Cortical cataract		1.2±0.8	1.2±0.8	1.2±0.8
Posterior subcapsular cataract		0.4±0.6	0.4±0.7	0.4±0.7

SD, standard deviation; logMAR, logarithm of the minimum angle of resolution; DM, diabetes mellitus.

Mean pupil diameter was 8.07 mm (SD: 0.59 mm) in the control group, 7.46 mm (SD: 0.71 mm) in group 1, and 7.24 mm (SD: 0.83 mm) in group 2 (Table 2). Both group 1 (P<0.001) and group 2 (P<0.001) showed statistic difference when compared with the control group. There was also a trend that group 2 had smaller pupil diameter than group 1. However, the difference was not statistically significant (P=0.256). The incidences of small pupil were 1.9% in the control group, 6.1% in group 1, and 13.5% in group 2. When compared with control, group 2 showed significantly higher incidence of small pupil (P=0.023). In multivariate linear regression, age (P=0.211) and gender (P=0.904) were not correlated with pupil size. Diabetes (P<0.001) was correlated with pupil size after control for age and gender.

Table 2.

Obtained Mydriasis and Incidence of Small Pupil in Each Group

		Diabetic patients
	Control	Group 1	Group 2	Overall
Pupil diameter, mm (mean±SD)	8.07±0.59	7.46±0.71	7.24±0.83	7.30±0.80
P value^a		<0.001	<0.001	<0.001
Small pupil (≤6 mm)	1 (1.9%)	2 (6.1%)	10 (13.5%)	12 (11%)
P value^b		0.286	0.023	0.033

Compared with the control group, P values were calculated by independent sample t-test.

Compared with the control group, P values were calculated by Fisher's exact test.

Discussion

Our results show that long-term diabetic patients had poorer response to pharmacological mydriasis than nondiabetic patients (P<0.001). The difference was statistically significant in both patients without diabetic retinopathy and patients with diabetic retinopathy. Further, there was a trend that patients with diabetic retinopathy had smaller pupil diameter than patients without diabetic retinopathy, although the difference was statistically insignificant.

Coblentz et al. compared obtained mydriasis (with phenylephrine 10% and tropicamide 1%) in 40 type 2 diabetic patients and 60 nondiabetic patients.¹¹ They found no difference between these groups and concluded that diabetic patients can achieve mydriasis as satisfactory as nondiabetic patients when an appropriate drug combination is used. However, it is not uncommon in our daily clinical practice to have poor dilated pupil among diabetic patients. It is well known that the rate of diabetic complications increased with duration of the disease.^12,13 Patient with longer disease duration is more likely to develop diabetic neuropathy and damages in autonomic nervous system.^7,8 Chronic glycogen accumulation in iris stroma and iris muscles could be the reason for poor pupillary dilation in diabetic patients.^11,14 Thus, our result, different from prior study, is most likely due to the fact that we selectively included patient with DM for 10 years or more. The results of our study show that patients with long-term DM are more likely to have poorer response to mydriatic drugs.

In our study, long-term diabetic patients also had significantly higher rate of small pupil (pupil diameter 6 mm or less; P=0.033). Subgroup analysis showed that group 2 patients had higher incidence of small pupil than the control group (13.5% vs. 1.9%; P=0.023), but the difference is insignificant between group 1 patients and the control group (6.1% vs. 1.9%; P=0.286). Thus, despite most diabetic patients can achieve satisfactory pharmacologic mydriasis by using routine dilating agents, a significant number of patients with diabetic retinopathy may have inadequate pupil dilation. Poor dilated pupils in these patients not only cause difficulties in their fundus exam and application of retinal laser photocoagulation,^2,3,15 but also increase the complication rate in cataract surgery.^6,16 We suggested that cataract surgery should be more cautiously performed in this subgroup of patients. The potential complications caused by small pupil in cataract surgery should be considered in advance.

There are certain limitations in our study. We measured pupil size by pupil gauges but not by pupillometer. Each incremental scale for pupil gauges is 0.5 mm. So, minor measurement error may occur. Further, some diabetic pupils may dilate a little bit more after instillation of mydriatic drugs for multiple times and waiting for longer duration. However, to have better comparison in each different group, we performed measurement at 40 min after single instillation of drugs for all patients.

In conclusion, pupil response to mydriatic drugs was poorer in long-term diabetic patients than in nondiabetic patients. Between diabetic patients, those presenting diabetic retinopathy tend to have a higher rate of small pupil size.

Footnotes

Acknowledgment

This study was supported by Chang Gung Medical Research Foundation (CMRPG260391 and CMRPG260401).

Author Disclosure Statement

None of authors has financial interests/conflicts to disclose.

References

Ohrt

Diabetic iridopathy. Dan. Med. Bull., 15:244–248. 1968.

Huber

M.J.

, Smith

S.A.

, Smith

S.E.

Mydriatic drugs for diabetic patients. Br. J. Ophthalmol., 69:425–427. 1985.

Hayashi

, Ishikawa

Pharmacology of pupillary responses in diabetes—correlative study of the responses and grade of retinopathy. Jpn. J. Ophthalmol., 23:65–72. 1979.

Hiller

, Sperduto

R.D.

, Ederer

Epidemiologic associations with cataract in the 1971–1972 National Health and Nutrition Examination Survey. Am. J. Ophthalmol., 118:239–248. 1983.

Kreines

, Rowe

K.W.

Cataract and adult diabetes. Ohio Med. J., 75:782–786. 1979.

Guzek

J.P.

, Holm

, Cotter

J.B.

et al. Risk factors for intraoperative complications in 1000 extracapsular cataract cases. Ophthalmology, 94:461–466. 1987.

Cahill

, Eustace

, de Jesus

Pupillary autonomic denervation with increasing duration of diabetes mellitus. Br. J. Ophthalmol., 85:1225–1230. 2001.

Low

P.A.

Diabetic autonomic neuropathy. Sem. Neurol., 16:143–151. 1996.

Wilkinson

C.P.

, Ferris

F.L.

3rd. , Klein

R.E.

et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology, 110:1677–1682. 2003.

10.

Chylack

L.T.

Jr. , Wolfe

J.K.

, Singer

D.M.

et al. The lens opacities classification system III. The Longitudinal Study of Cataract Study Group. Arch. Ophthalmol., 111:831–836. 1993.

11.

Coblentz

, Motta

M.M.

, Fernandes

B.F.

, Burnier

M.N.

Jr. , Vianna

R.N.

Comparison between obtained mydriasis in type 2 diabetics and non-diabetic patients. Curr. Eye Res., 34:925–927. 2009.

12.

Nathan

D.M.

Long-term complications of diabetes mellitus. N. Engl. J. Med., 328:1676–1685. 1993.

13.

Hreidarsson

A.B.

Pupil size in insulin-dependent diabetes: relationship to duration, metabolic control, and long-term manifestations. Diabetes, 31:442–448. 1982.

14.

Fialho

S.A.

The iris in diabetes. Int. Ophthalmol. Clin., 3:609–616. 1963.

15.

Ghose

, Garodia

V.K.

, Sachdev

M.S.

et al. Evaluation of potentiating effect of a drop of lignocaine on tropicamide induced mydriasis. Invest. Ophthalmol. Vis. Sci., 42:1581–1585. 2001.

16.

Artzén

, Lundström

, Behndig

et al. Capsule complication during cataract surgery: case-control study of preoperative and intraoperative risk factors: Swedish Capsule Rupture Study Group report 2. J. Cataract. Refract. Surg., 35:1688–1693. 2009.