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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 31  |  Issue : 1  |  Page : 262-266

Theassociationof hypolipidemic agents with macular edema in diabetic maculopathy


1 Department of Ophthalmology, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
2 Department of Ophthalmology, OphthalmologyHospital, Kafr El Sheikh, Egypt

Date of Submission17-Nov-2017
Date of Acceptance25-Feb-2017
Date of Web Publication14-Jun-2018

Correspondence Address:
Heba A Abd El-Fatah
Ophthalmology Hospital, Kafr El Sheikh
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_535_16

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  Abstract 


Objective
Theaimof this study was to assess the effect of lipid-lowering agents on macular edema in patients with diabetic maculopathy guided by optical coherence tomography and fundus fluorescein angiography.
Backgrounds
The most threatening complication of diabetic retinopathy(DR) is diabetic macular edema.The risk factors for diabetic macular edema are largely similar to those for DR, but dyslipidemia appears to play a more significant role. Serum lipid level has a direct role in the development of macular edema. Lowering of serum lipids has shown a benefit on both proliferative disease and maculopathy besides their lipid-lowering effect. Independentof accompanying macular edema, the severity of retinal hard exudates at baseline was associated with decreased visual acuity.
Patients and methods
The study included 80patients with DR and hyperlipidemia; 50% of were undergoing treatment with antihyperlipidemic drugs(group I) and other 50% did not receive treatment(group II) (control group) at the Ophthalmology Clinic at the Menoufia University Hospital.
Results
In patients with DR and dyslipidemia, lowering of serum lipids has shown a benefit on both proliferative disease and maculopathy. Besides their lipid-lowering effect, there was a significant decrease in macular thickness measured using optical coherence tomography after 9 months of treatment with antihyperlipidemic drugs.
Conclusion
Dyslipidemia appears to play a direct role in the development of clinically significant macular edema. Lowering of serum lipids has shown a benefit on both proliferative DR and maculopathy, besides their lipid-lowering effect.

Keywords: diabetic retinopathy, macular edema, optical coherence tomography, serum lipid-lowering agents


How to cite this article:
El-Lakwa AF, El-Sawya MF, Abd El-Fatah HA. Theassociationof hypolipidemic agents with macular edema in diabetic maculopathy. Menoufia Med J 2018;31:262-6

How to cite this URL:
El-Lakwa AF, El-Sawya MF, Abd El-Fatah HA. Theassociationof hypolipidemic agents with macular edema in diabetic maculopathy. Menoufia Med J [serial online] 2018 [cited 2019 Aug 19];31:262-6. Available from: http://www.mmj.eg.net/text.asp?2018/31/1/262/234224




  Introduction Top


Diabetes mellitus(DM) is a very dangerous health problem [1]. Diabetic retinopathy(DR) is one of the important complications of diabetes [2]. It was considered one of the principle causes of vision impairment in the world [3].

Globally, it has been estimated that up to 100 million people have DR and that more than 20 million will have vision-threatening retinopathy [4].

The risk factors for DR are degree of glycemic and blood pressure control, duration of diabetes, presence of nephropathy, and raised serum lipids. Elevated lipid concentrations may be an additional risk factor for diabetic macular edema(DME), particularly the deposition of hard exudates in the retina [5].

Patients with DM are known to have severe lipid abnormalities–namely, hypercholesterolemia and elevated serum triglycerides [6],[7].

The most threatening complication of DR is DME [8].

The risk factors for DME are largely similar to those for DR, but dyslipidemia appears to play a more significant role. Serum lipid level has a direct role in the development of macular edema [9].

Elevated low density lipoprotein(LDL) was associated with an increased risk for macular edema and elevated serum triglycerides levels were also associated with a great risk of developing high-risk proliferative DR [10].

Visual loss from DR may be secondary to macular edema, hemorrhage from new vessels, retinal detachment, or neovascular glaucoma [1].

Lowering of serum lipids has shown a benefit on both proliferative disease and maculopathy besides their lipid lowering effect [10].

Early detection of DR and DME through screening programs and appropriate referral for therapy is important to preserve vision in diabetic patients [6].

Aim

The aim of this study was to investigate the effect of lipid-lowering agents on macular edema in patients with diabetic maculopathy guided by ocular computed tomography and fundus fluorescein angiography.


  Patients and Methods Top


This was a prospective case–control study conducted at the Ophthalmology Clinic at the Menoufia University Hospital. Thisstudy was conducted on 80patients with type II diabetes for more than 5years.

The study included 80patients with diabetic maculopathy and hyperlipidemia; 50% of them were undergoing treatment with antihyperlipiemic drugs and the other 50% did not receive treatment.

Inclusion criteria were as follows: patients with more than 5years of diagnosed diabetes with hyperlipidemia and macular edema.

Exclusion criteria were as follows:

  • A history of less than 5years of diagnosed diabetes
  • History of ocular surgery of less than 6 months
  • Pregnancy, accelerated hypertension, active ocular infection, and coexisting ocular disorders such as uveitis and opaque or hazy media
  • Retinal disorders such as retinal vein or artery occlusions or retinitis pigmentosa
  • Vitreoretinal degenerations and dystrophies, high myopia, glaucoma, and cataract.


Examination

All patients were subjected to the following:

  • History as regards the onset, duration, and type of diabetes
  • Visual acuity and best-corrected visual acuity
  • Intraocular pressure measurement
  • Slit lamp biomicroscopy to examine the anterior segment of the eye and the pupil to note any abnormalities
  • Fundus examination: dilated fundus examination with indirectophthalmoscope (Volk Optical Inc., Mumbai, India)and Volk 90 D lens
  • Fundus colored photography
  • Optical coherence tomography(OCT)
  • Fundus fluorescein angiography
  • Lipid profile: serum lipid measurements were carried out using fasting samples
  • Fasting and postprandial blood sugar
  • Hemoglobin A1c.


Patients underwent antilipidemic therapy according to the type of lipid elevated by medical specialist as follows. Simvastatin 20 mg tablet was given daily after dinner for 2weeks to patients with high total cholesterol or high cholesterol components, LDL, and very LDL. Ezetimibe 10 mg once daily may be added to simvastatins to inhibit cholesterol absorption in some resistant cases.

Fenofibrate 300 mg tablet(lipase stimulant drug) was given once daily with or after meal for 3weeks to patients with high triglyceride levels. Patients with high total cholesterol or its components, LDL, and very LDL together with triglycerides were given Simvastatin 20 mg tablet daily after dinner with fenofibrate 300 mg tablet once daily with or after meal for 1 month. All doses were repeated until normal levels were gained. Ophthalmological examinations and follow-up were carried out every 45days.

After 9 months, the investigations were repeated again to see the effect of treatment with proper dietary control.

Fluorescein angiography

Fundus fluorescein angiography was performed on patients who were clinically suspected of having retinopathy

Optical coherence tomography measurement:

OCT scans were performed using the Spectralis HRA+OCT(Heidelberg Engineering GmbH, Heidelberg, Germany), which is a high-resolution spectral domain-OCT that can simultaneously perform scanning laser ophthalmoscopy.

The central macular thickness was the average thickness calculated from different readings obtained from a 1.0 mm diameter circular macular area. The outer two circles are divided into sectors with a diameter of 2.22 mm for the second middle circle and 3.45 mm for the third outer circle.

A cutoff value of 250 μm for central subfield thickness was taken as 'normal' as has been determined by previous studies [9], above which the macula was taken as thickened.

Cystoid macular edema was accredited to patients with central macular thickness of greater than 250 μm and characterized by intraretinal cystoid spaces.

Subretinal fluid detachment was accredited to patients with central macular thickness greater than 250 μm and subretinal fluid accumulation with a distinct outer border of the detached retina.

Some cases showed a combination of the above morphological forms. In those situations, the morphological typing was given to the graver diagnosis(i.e.,in the presence of cystoid macular edema and serous retinal detachment, the morphological subtype was defined as serous retinal detachment).

Written informed consent was obtained from all patients before the procedure. All patients' names were replaced by a code number to maintain confidentiality of the patient; the data had been resolved in a conventional manner.

Statistical analysis

The data collected were tabulated and analyzed using statistical package for the social science software. Quantitative data were expressed as mean±SD and analyzed by applying Student's t-test for comparison of three groups. Qualitative data were expressed as number and percentage and analyzed.


  Results Top


This study included 80patients with DR and hyperlipidemia. Their ages ranged between 42 and 81years, with a mean±SD of 60.55±8.96 in group I and 57.65±6.19 in group II. As regards the duration of DM, the mean±SD DM duration was 19.85±6.03 in group I and 18.35±5.09 in group II[Table1]. There was no significant difference between groups I and II as regards macular thickness measured using OCT before treatment with antihyperlipidemic drugs (P=0.480; [Table2]). However, there was a significant difference between groups I and II with respect to macular thickness measured using OCT after 9 months of treatment with antihyperlipidemic drugs (P=0.001; [Table3]).
Table 1: Relationship between groups I and II according to duration of diabetes mellitus

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Table 2: Relationship between groups I and II according to optical coherence topography before treatment with antihyperlipidemic drugs

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Table 3: Relationship between groups I and II according to optical coherence topography after 9 months of treatment with antihyperlipidemic drugs

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As regards the relationship between groups I and II in terms of cholesterol level before treatment with antihyperlipidemic drugs, there was no significant difference between the two groups(P=0.654; [Table4]). However, there was a significant difference between groups I and II after 9 months of treatment with antihyperlipidemic drugs(P=0.005; [Table5]).
Table 4: Relationship between groups I and II according to mean cholesterol level before treatment with antihyperlipidemic drugs

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Table 5: Relationship between groups I and II according to mean cholesterol level after 9 months of treatment with antihyperlipidemic drugs

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There was no significant relationship between groups I and II with respect to high density lipoprotein before treatment with antihyperlipidemic drugs (P=0.493; [Table6]). However, there was a significant relationship between groups I and II with respect to high density lipoprotein after 9 months of treatment with antihyperlipidemic drugs(P=0.033; [Table7]).
Table 6: Relationship between groups I and II according to high density lipoprotein before treatment with antihyperlipidemic drugs

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Table 7: Relationship between groups I and II according to high density lipoprotein after treatment with antihyperlipidemic drugs

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  Discussion Top


DR is one of the important complications of diabetes [2]. The most threatening complication of DR is DME. The risk factors for DME are similar to those for DR, but dyslipidemia appears to play a more significant role. Serum lipid level has a direct role in the development of macular edema. Patients with DM are known to have severe lipid abnormalities–namely, hypercholesterolemia and elevated serum triglycerides.

In our study, we found that oral antihyperlipidemic drugs such as oral atorvastatin could be an important adjunct in the management of clinically significant macular edema(CSME). This result is similar to that of Gupta etal. [11], who studied 30patients, 21 men and nine women, with noninsulin-dependent DM. There was no difference between the two groups as regards age, sex, and duration of diabetes as found in our study. Moreover, there was a significant reduction in total cholesterol concentration, LDL, and triglyceride concentration after atorvastatin therapy in group I, whereas there was no significant reduction found in group II, which did not undergo treatment with atorvastatin; this is similar to ourresults.

In this study, we found that lowering of serum lipids has shown a benefit on both proliferative disease and maculopathy besides their lipid-lowering effect. Independent of accompanying macular edema, the severity of retinal hard exudates at baseline was associated with decreased visual acuity. Similar results were seen in early treatment diabetic retinopathy study(ETDRS) and Wisconsin Epidemiology Study of Diabetic Retinopathy studies [10]. Decreasing dietary polyunsaturated fats may have an association with shrinkage of exudates and a treatment that lowers plasma lipid levels reduced the risk size of perimacular hard exudates. It has also been shown that in type2 diabetic patients there was an increase in the lipid peroxidation in plasma and this is accentuated in patients with diabetic complications [12].

The other significant finding in diabetic patients was that DME also showed a strong correlation with high LDL levels in the same study [13].

In a study of the risk factors associated with development of subretinal fibrosis in ETDRS patients with DME, the presence of severe hard exudates was the strongest risk factor. Elevated serum triglyceride levels were also associated with a greater risk of developing high-risk proliferative DR in the ETDRS.

Currently, the hypothesis that treatment of dyslipidemia is very important in the role of progression of DR is currently evaluated in the Actions to Control Cardiovascular Risk in Diabetes trial. Some recent studies have shown lipid-lowering drugs to significantly cause regression of hard exudate deposits and improvement in vision [14].


  Conclusion Top


Dyslipidemia appears to play a direct role in the development of CSME.

Lowering of serum lipids has shown a benefit on both proliferative DR and maculopathy besides their lipid-lowering effect. Some lipid-lowering agents such as fibrates and statins have been extensively tested for diabetic patients with retinopathy and proven a good efficacy. Preservation of good vision and healthy cardiovascular system may be a motivating factor for lowering serum lipids.

Oral atorvastatin therapy in patients with type2 diabetes with dyslipidemia reduces the severity of hard exudates and subfoveal lipid migration in CSME and could be an important adjunct in the management of CSME.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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2.
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Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, etal. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 2012; 35:556–564.  Back to cited text no. 4
    
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Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, etal. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. NEngl J Med 1994; 331:1480–1487.  Back to cited text no. 5
    
6.
Dornan TL, Carter RD, Bron A. Low density lipoprotein cholesterol: an association with the severity of diabetic retinopathy. Diabetologia 1982; 22:167–170.  Back to cited text no. 6
    
7.
Larsson LI, Alm A, Lithner F, Dahlen G, Bergstrom R. The association of hyperlipidemia with retinopathy indiabetic patients aged 15–50years in the county of Umea. Acta Ophthalmol Scand 1999; 77:585–591.  Back to cited text no. 7
    
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Ding J, Wong TY. Current epidemiology of diabetic retinopathy and diabetic macular edema. Curr Diab Rep 2012; 12:346–354.  Back to cited text no. 8
    
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Sachdev N, Sahni A. Association of systemic risk factors with the severity of retinal hard exudates in a north Indian population with type2 diabetes. JPostgrad Med 2010; 56:3–6.  Back to cited text no. 9
    
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[No authors listed]. Early treatment diabetic retinopathy study design and baseline patient characteristics. ETDRS report number 7. Ophthalmology 1991; 98(Suppl):741–756.  Back to cited text no. 10
    
11.
Gupta A, Gupta V, Thapar S, Bhansali A. Lipid-lowering drug atorvastatin as an adjunct in the management of diabetic macular edema. Am J Ophthalmol 2004; 137:675–682.  Back to cited text no. 11
    
12.
Sundaram RK, Bhaskar A, Vijayalingam S, Viswanathan, Rema M, Shanmugasundram KR. Antioxidant status and lipid peroxidation in type II diabetes mellitus with and without complications. Clin Sci 1996; 90:255–260.  Back to cited text no. 12
    
13.
Rema M, Srivastava BK, Anitha B, Deepa R, Mohan V. Association of serum lipids with diabetic retinopathy in urban south Indians–the Chennai Urban Rural Epidemiology Study(CURES) Eye Study-2. Diabet Med 2005; 23:1029–1036.  Back to cited text no. 13
    
14.
Gordon B, Chang S, Kavanagh M, Berrocal M, Yannuzzi L, Robertson C, etal. The effects of lipid lowering on diabetic retinopathy. Am J Ophthalmol 1991; 112:385–391.  Back to cited text no. 14
    



 
 
    Tables

  [Table1], [Table2], [Table3], [Table4], [Table5], [Table6], [Table7]



 

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