Big changes to affect small vessels.

Diabetes is known to have many complications associated with the disease. Among those are microvascular complications, such as diabetic retinopathy, neuropathy, nephropathy, and cardiovascular disease. While early diagnosis and treatment can lessen complications, timely control of glucose can potentially prevent these painful and disrupting problems from occurring. Previous studies concerning glucose control and prevention of diabetic complication have been individually insufficient to form treatment guidelines or guide clinical practitioners.

Due to lack of evidence, researchers from CONTROL (Collaborators on Trials of Glucose Lowering) analyzed the benefit of intensive glucose control versus less intensive control on the outcome of microvascular complications. Researchers performed a meta-analysis using data from four major trials: Action to Control Cardiovascular Risk in Diabetes (ACCORD), Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE), the UK Prospective Diabetes Study (UKPDS), and the Veterans Administration Diabetes Trial (VADT). These trials were picked due to their assessment of the effects of low versus high HbA1c, fasting glucose, and post-load glucose targets in patients with type 2 diabetes. The included trials also had an average of two years follow-up with approximately 1,000 patient-years follow-up in each randomized treatment group, used intention to treat analysis, were double blind or open label, used pre-specified outcomes, and had at least a 90% follow-up on patients’ vital status. Exclusion criteria included critical care patients, patients with type 1 diabetes or under the age of 16, treatment with multifactorial interventions where effects of glycemic control could not be assessed separately, or patients with acute myocardial infarction or acute myocardial syndromes receiving invasive management strategies. Primary outcomes were kidney events, eye events, and nerve events. Kidney events were defined as composite end stage renal disease, renal death, development of estimated glomerular filtration rate of less than 30 ml/min per 1.73 m2 , or development of overt diabetic nephropathy. Eye events were outlined as a patient need for retinal photocoagulation therapy or vitrectomy, development of proliferative retinopathy, fibrous proliferations on the disc, or progression of diabetic retinopathy. Nerve events included new loss of vibratory sensation, new loss of ankle reflexes, or new loss of light touch. Secondary events were stated as: individual factors of eye events, kidney events, and nerve events as well as the development of macular edema, diabetic related blindness, vision decline, cataract extraction, development/progression of albuminuria, or maintenance/regression of normoalbuminuria. Effects of randomized treatment on the primary outcomes were assessed using cox proportional hazards models and overall estimates of effect were calculated using a random-effects model.

The final evaluation included 27,049 adults with type 2 diabetes. Patients were treated with more intensive or less intensive glucose control and followed for a median of five years. A total of 1,626 kidney events, 795 eye events, and 7,598 nerve events occurred during the follow-up period. For the composite of primary events, more intense glucose control resulted in 20% relative risk reduction in kidney events (HR 0·80, 95% CI 0·72–0·88; p<0·0001), 13% relative risk reduction in eye outcomes (HR 0·87, 95% CI 0·76–1·00; p=0·042), and no relative risk reduction in nerve outcome (HR 0·98, 95% CI 0·87–1·09; p=0·68) compared to less intensive glucose control. More intensive glucose control resulted in difference in mean HbA1c of -0.90% (95% confidence interval (CI) -1.22 to -0.58) and mean difference in fasting plasma glucose of -1.69 mmol/L (95% CI -2.12 to -1.26) in pooled data in comparison to less intensive glucose control. The number needed to treat to prevent one kidney or eye event in a patient with type 2 diabetes was calculated to be 63-73 patients.

Intensive glucose control shows modest improvement in HbA1c, which leads to significant relative risk reduction in the occurrence of kidney and eye events. Since more people are being diagnosed with diabetes every year it is important to implement proper glucose control early to reduce the occurrence of harmful kidney and eye events. Weakness of the study include the low occurrence of more serious events such as end-stage renal disease (256 events) and renal death, small number of included trials, and application to patients who do not fall within the criteria of the study.

Practice Pearls:

• In this study, more intensive glucose control led to a 20% relative risk reduction in kidney events and 13% relative risk reduction in eye events when compared to less intensive glucose control.
• Intensive glucose control seems to have little benefit for prevention of neuropathy.
• Glucose lowering is pertinent for the prevention of long-term microvascular complications in adults with type 2 diabetes.

References:

“About diabetes.” WHO. World Health Organization, Web. 13 Apr. 2017.

Zoungas, Sophia, Hisatomi Arima, Hertzel C. Gerstein, Rury R. Holman, Mark Woodward, Peter Reaven, Rodney A. Hayward, Timothy Craven, Ruth L. Coleman, and John Chalmers. “Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomised controlled trials.” The Lancet Diabetes & Endocrinology (2017)

Priscilla Rettman, BS, PharmD Candidate 2017, Philadelphia College of Osteopathic Medicine- GA Campus

Race, socioeconomic status thought reasons behind lack of adherence to the recommendations.

As the youth population continues to experience an increased prevalence of obesity, the incidence of type 2 diabetes in children and adolescence is also on the rise, with roughly 45% of all new adolescent diagnoses consisting of T2D, where previously most cases of juvenile diabetes were type 1.

Estimates extrapolated from U.S. Census data suggest that by 2050, the rate of type 1 diabetes in youth will triple, and the rate of type 2 in the same population will quadruple.  Along with this unsettling picture, the associated risk of diabetic retinopathy is expected to rise as well. Because DR can lead to blindness, early screening for DR remains important. Screening guidelines are established for TD1 patients, generally supporting retinal exam at 5-6 years from initial diagnosis, while recommending initial screening takes place coincident with diagnosis of T2D.  Previous studies report that only 33% of youth with T1D and 50% with T2D obtained eye examinations according to guidelines.  This may reflect concerns about younger age, diagnosis of T2D versus T1D, and shorter duration of diabetes in this population. Not surprising is that most studies have been done in adults, and very few of the youth studies looked at other demographic factors that may contribute to the lack of adherence to the guideline recommendations.  In the recent issue of JAMA Ophthalmology, a study was presented looking at retinopathy screening rates in youth with diabetes.

Data from 5,453 youth with T1D and 7,233 with T2D were collected from a nationwide managed care network from January 2001 through December 2014. Inclusion criteria were uninterrupted enrollment in the medical plan for at least 3 years and at least 2 diagnoses of diabetes on separate dates. Children who had never filled a prescription for insulin or an oral hypoglycemic, and those with pre-existing diabetes (diagnosed prior to 12 months in the medical plan) were excluded. Those children whose data lacked socioeconomic information were also excluded. The primary outcome was documentation of an eye exam as defined by Current Procedural Terminology.  Timing from initial diagnosis to initial eye exam in both T1D and T2D were compared using the log-rank test.

Multivariable Cox proportional hazards regression were used to evaluate the effects of diabetes type and sociodemographic factors on the proportion of those screened.

In those with T1D, the median age at diagnosis was 11 year (interquartile range 8-15 years), while in T2D, the median was 19 years (IQR 16-22 years).  The median time in the medical plan for both types was 2.1 years.  In the T2D subset, most patients were female (83.5%).  Of the T1D patients, 82.6% were white, 8.2% were black, 7.2% Latino, and 2% were Asian, while T2D patients were 69.9% white, 14.6% Latino, 12.8% black, and 2.8% Asian. Survival analysis showed that by 6 years after initial diagnosis, patients with T1D had a higher rate of eye examination than did those with T2D (HR 2.14; 95% CI 1.97-2.33).  Whites and Asians had a higher rate of exam (54.7% and 57.3% respectively) than did blacks and Latinos (44.6% and 41.6%).  Economic data showed the likelihood of an eye exam increased as household income increased (net worth ≥ $500,000 vs < $25,000, HR 1.50; 95% CI 1.34-1.68). Stratified for type of diabetes, analysis showed that type 2 patients were less likely to be examined the farther they were from initial diagnosis, whereas type 1 patients were unaffected. Considering race, utilizing the prevalence of white patients who were screened as the reference point, blacks and Latinos were less likely to be screened (11%, p=0.04 and 18%, p<0.001) respectively, whereas Asians were 9% (NS) more likely to be screened.

Overall, 64.9% of T1D and 42.2% of T2D youths had received an eye examination within six years of their initial diagnosis. This study is considered to be the first to account for race and socioeconomic factors in the youth population, and suggests that existing barriers to DR screening may include lack of understanding on the parts of both the patient and the provider, patient financial barriers such as lack of health insurance, non-acceptance of the diagnosis, and even an aversion to pupillary dilation. While the study was strong in the number of patients analyzed, and available of records to confirm performance of eye exams (versus relying on patients self-reporting), the algorithm used to determine presence of diabetes may have allowed inclusion of misclassified diagnoses, such as use of metformin for prediabetes or insulin resistance. This may have led to underestimating the time of onset to first eye exam, and overestimation of the numbers who were actually screened within 6 years.  The general conclusion that youth with diabetes are considerably under-screened for retinopathy is supported, suggesting that practitioners revaluate their approach to screening in this population.

Practice Pearls:

• Diabetic retinopathy is a serious potential complication in the diabetes population, regardless of age.
• A remarkably high percentage of youth with diabetes are not screened for retinopathy as recommended by accepted guidelines.
• Potential barriers to screening may be predicted by factors such as race and socioeconomic status of the patients’ families.

References:

Wang SY, Andrews CA, Gardner TW, Wood M, Singer K, Stein JD. Ophthalmic Screening Patterns Among Youths With Diabetes Enrolled in a Large US Managed Care Network. JAMA Ophthalmol. 2017. Epub 2017/03/23. doi: 10.1001/jamaophthalmol.2017.0089. PubMed PMID: 28334336.

Mark T. Lawrence, RPh, PharmD Candidate, University of Colorado-Denver, School of Pharmacy NTPD

Improvements in assessment and treatment of diabetic retinopathy position statement

Diabetic retinopathy (DR) is a complication of diabetes that affects vision. High blood sugar levels can damage the blood vessels starving the retina of vital nutrients and oxygen resulting in blurry vision. Without appropriate treatment this condition may lead to complete vision loss. A recent update on diabetic retinopathy by American Diabetes Association (ADA) has considerably improved in terms of diagnosing and treating this complication since the 2002 ‘Position Statement.’

The statement was comprised of natural history of diabetic retinopathy with associated risk factors and different stages categorized by the growth of new blood vessels on the retina and posterior surface of the vitreous. The four stages ranged from mild non-proliferative diabetic retinopathy (NPDR) to moderate NPDR, to severe NPDR, to the most advanced stage – proliferative diabetic retinopathy (PDR). It evaluated the general acceptance of optical coherence tomography to assess retinal thickness, along with intraretinal pathology and wide-angle fundus photography to expose clinically silent microvascular lesions. Moreover, it summarized the recent data on screening and treatment with recommendations and discussed about cost-effectiveness.

DR is explicitly a neurovascular complication of both type 1 and type 2 diabetes and its rate of occurrence depends on the level of glycemic control and the duration of diabetes. Other risk factors associated with DR include hyperglycemia, nephropathy, hypertension, and dyslipidemia. Studies have proven that reduction in blood pressure (BP) decreases the progression of retinopathy in people with type 2 diabetes, but strict BP targets (systolic blood pressure of 120 mmHg vs. 140 mmHg) do not provide additional benefits. In another study, retinopathy progression was slowed in patients with dyslipidemia by adding fenofibrate, mainly in NPDR at baseline. In addition, several studies propose that pregnant patients with type 1 diabetes may exacerbate retinopathy with poor glycemic control during conception and may threaten their vision.

Optimization of blood glucose, blood pressure, and serum lipid levels in conjunction with appropriately scheduled dilated eye examinations can decrease the risk of vision loss from DR complications, but a substantial amount of those affected with diabetes develop diabetic macular edema (DME) or proliferative changes that require intervention. Large prospective randomized studies have shown that the use of intensive therapy could possibly prevent or delay DR with the goal of attaining near-normoglycemia. Although, intravitreal injection of anti–vascular endothelial growth factor agents may treat DME and PDR, it may threaten reading vision.

A meta-analysis study, conducted worldwide from 1980–2008 and consisting of 35 studies, predicted the global prevalence of DR to be 35.4% and PDR to be 7.5%. In developed countries, DR is mostly the cause of new cases of blindness among those 20 to 74 year old and eye disorders, such as glaucoma and cataracts, are frequently seen in diabetes patients. However, recent advancements in systemic therapy of diabetes have helped patients to improve their metabolic control. The statement incorporates these medical developments for the use of physicians and patients to aid in diagnosis and treatment of DR. It also provides an opportunity to improve glucose management and avoid or delay potential progression of the retinopathy.

The statement includes that screening recommendations for patients with diabetes depend on the rates of appearance and progression of DR and the associated risk factors. Ophthalmologist or optometrist examinations in patients with type 1 and 2 diabetes should be within 5 years after onset of diabetes and at the time of diabetes diagnosis, respectively. Women planning for pregnancy or who are pregnant with pre-existing diabetes should be examined before pregnancy or in the first trimester. In diabetes patients where no evidence of retinopathy is found, follow-up eye exams can be scheduled every two years. If any retinopathy is identified, then subsequent dilated-pupil retina exams are advised at least yearly, but more frequently if progressive retinopathy is diagnosed.

Fortunately, the cost-effectiveness of screening and traditional laser treatment for DR has been established with no more disputes. It is focused on telemedicine’s impact on the detection and eventual management of DR that appears to be most effective with lower ratio of providers to patients, with prohibitive distance to reach a provider, or when the alternative is no patient screening. The latest advancement in retinopathy treatment, anti-VEGF therapy has been taken into consideration, as they are more cost-effective than laser monotherapy for DME. Also, having retinopathy is not contraindicated with aspirin therapy for cardioprotection because studies suggest that aspirin does not increase the risk for retinal hemorrhage. Nonetheless, future studies are needed to determine the cost-effectiveness of anti-VEGF as a first-line treatment option for PDR.

Practice Pearls:

• Optimize glycemic control, blood pressure, and serum lipids to reduce the risk or slow the progression of diabetic retinopathy.
• Follow the screening recommendations for patients with diabetes for eye examination by ophthalmologist or optometrist.
• The presence of retinopathy is not a contraindication to aspirin therapy for cardioprotection because aspirin does not increase the risk of retinal hemorrhage.

Reference:

Javitt JC, Canner JK, Sommer A. Cost effectiveness of current approaches to the control of retinopathy in type I diabetics. Ophthalmology 1989;96:255–264 42

Pasquel FJ, Hendrick AM, Ryan M, Cason E, Ali MK, Narayan KMV. Cost-effectiveness of different diabetic retinopathy screening modalities. J Diabetes Sci Technol 2015;10:301–307

Solomon SD, Chew E, Duh EJ, Sobrin L, Sun JK, VanderBeek BL, Wykoff CC, and Gardner TW. Diabetic Retinopathy: A Position Statement by the American Diabetes Association. Diabetes Care. Mar 2017; 40(3): 412-418.https://doi.org/10.2337/dc16-2641

By Dr. Paul Chous

This represents the first such update by the American Diabetes Association since 2002, and is notable for inclusion of the latest evidence and recommendations with respect to appropriate eye examination intervals, referral criteria, prevention of incidence and progression of diabetic retinopathy (DR), and treatment strategies with respect to preventing vision loss from vision-threatening diabetes-related retinal disease –  proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME).

Diabetes remains the leading cause of severe vision loss and blindness in Americans of working age, and though improved metabolic control of diabetes and advances in therapy have significantly diminished the probability of poor vision outcomes for individual patients, the increased prevalence of diabetes (despite plateauing incidence) combined with improved longevity of patients serve to sustain the impact of DR on a population level. [1]

With respect to prevention of DR and vision loss, the Statement continues to emphasize the importance of good diabetes control (blood glucose, blood pressure and lipids), including the benefits of good, early glycemic control (protective metabolic memory) even in patients with T2DM (based on findings from ACCORD-Eye). It also emphasizes the emerging benefit of fenofibrate therapy to prevent progression of mild to moderate non-proliferative diabetic retinopathy (NPDR) in patients with T2DM (based on findings from two RCTs, FIELD and ACCORD-Eye). In fact, fenofibrate is approved as first-line therapy for adults with T2DM and NPDR in Australia; the number needed to treat to prevent one patient from requiring laser photocoagulation or intraocular injection of anti-vascular endothelial growth factor (anti-VEGF) agents is a mere fourteen (NNT =- 14) [2]. Trials are now underway to see if such preventative therapy is effective in patients with T1DM.

What is not discussed in the section, understandably because it is an enormous topic, is the importance of preventing diabetes in the first place. The fundamental impact of the Diabetes Prevention Program (DPP) and similar efforts to prevent insulin resistance and the development of T2DM through lifestyle modification and other therapies deserves at least some consideration, in my view. Put simply – patients won’t lose vision to diabetes-related eye disease if they don’t develop diabetes in the first place.

Eye examination frequency recommendations for people with diabetes are notable for the caveat that patients with no retinopathy and good metabolic control may be considered for dilated eye examinations every two years, rather than annually as has always been the US standard of care. This makes good economic sense, based on low probability of incidence and progression in such patients.

I believe this recommendation should be tempered based on patient history of compliance with recommended eye examination intervals as well as metabolic control – and the fact that emerging imaging modalities (adaptive optics, optical coherence tomography angiography) are showing that many patients with no apparent DR with normal examination techniques (dilated ophthalmoscopy and/or standard fundus photography) do indeed have structural abnormalities that likely increase the risk of vision loss (see figure 1). As use of these technologies becomes more widespread and evidence accumulates, we may very well find that the definition of DR and appropriate examination frequency and interventional targets will necessarily change.

The most significant change with respect to treatment is the recognition of anti-VEGF agents as the ‘gold standard’ for diabetic macular edema (DME), the leading cause of vision loss due to diabetes. A number of clinical trials have demonstrated that serial injection of these agents reduces swelling of the macula and preserves/improves visual acuity better than traditional focal laser therapy for patients with DME. Recent evidence (DRCR.net Protocol S) has shown that anti-VEGF therapy is non-inferior to panretinal photocoagulation for proliferative retinopathy (PDR), and also results in better visual function (night and peripheral vision).

My only caveat about anti-VEGF therapy is that these agents are known to increase the risk of thromboembolism when used systemically, and that even though they are quite safe and effective for DME, there is at least some evidence that patients at high cardiovascular risk (especially those with a prior history of MI or stroke) are at increased risk with higher cumulative exposure (i.e. more intraocular injections).

In conjunction with the emphasis on anti-VEGF therapy for ‘center-involved’ DME (i.e. involving the center of the macula, the fovea) is recognition that optical coherence tomography (OCT) has become the standard for assessing DME and response to therapy. In fact, OCT is the most sensitive tool for detecting DME, and although not all cases of DME identified by OCT require treatment, patients with subclinical DME are far more likely to develop more severe edema and require more careful follow-up. The bottom line for me is that patients with diabetes are best served by eye doctors who have and routinely use OCT.

The Position Statement ends with consideration of retinal telescreening to identify patients with DR and, most importantly, sight-threatening DR (STR). There is no doubt that such technology provides access to patients in remote areas without high quality eye care, and is becoming more critical for efficient use of resources as the Worldwide population of persons with diabetes and DR burgeons.

These benefits must be tempered with the reality that patients are often better-served by face to face contact with knowledgeable and experienced eye care providers, both optometrists and ophthalmologists. There is, I believe, an educative effect of receiving in-person examination and counsel from live health care providers who can answer questions, discuss preventative strategies and treatment options even and especially in patients who do not have STR. Moreover, patients with diabetes are at increased risk for ocular complications other than DR, including cataracts, glaucoma, dry eye disease, and significant changes in eyeglass prescription that often signal poor blood glucose control. There are many reasons for every American, especially those with or at-risk for diabetes (more than half the U.S. adult population per NHANES analysis) [3], to receive regular eye care distinct from detection of STR.

Overall, this new Position Statement does a wonderful job of succinctly summarizing the most important epidemiological and clinical studies regarding diabetic retinopathy and updates to ever-changing clinical practice recommendations. Hopefully, this will improve the quality and frequency of interactions amongst diabetes patients, eye care providers, and other members of the diabetes care team towards preventing catastrophic outcomes of this all-too-frequent complication.

(http://care.diabetesjournals.org/content/40/3/412)

[1] Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye and Vision. 2015;2:17.

[2] Wright AD, Dodson PM. Medical management of diabetic retinopathy: fenofibrate and ACCORD Eye studies. Eye. 2011;25(7):843-849.

[3]  Menke A, Casagrande S, Geiss L, Cowie CC. Prevalence of and Trends in Diabetes Among Adults in the United States, 1988-2012.JAMA. 2015 Sep 8;314(10):1021-9.

(Advisory Board Member) Dr. Paul Chous received his undergraduate education at Brown University and the University of California at Irvine, where he was elected to Phi Beta Kappa in 1985. He received his Master’s Degree in 1986 and his Doctorate of Optometry in 1991, both with highest honors from the University of California at Berkeley. Dr. Chous has practiced optometry with a special emphasis on diabetic eye disease and diabetes education for 20 years in the State of Washington, winning the American Diabetes Association’s Distinguished Public Service Award in 1998.  

Paul Chous, M.A., O.D.  See list of articles.

Studies suggest fenofibrate can prevent microvascular changes, decrease need for surgery.

Diabetic retinopathy is a one of the most common microvascular complications in patients with poorly controlled diabetes. The hypothesized mechanisms by which diabetic retinopathy occurs relies on oxidative stress, which can lead to neuronal accumulation, altered balance of neurotrophic factors, and loss of nuclear gene expressions. All of these mechanisms lead patients to experience clinical manifestations, such as electroretinography changes, perimeter vision change, dark adaption, contrast sensitivity, and changes in color vision. Hence, this is how improper glucose control has been linked to these pathophysiological mechanisms. The CDC estimates that 4.2 million adults have diabetic retinopathy and 655,000 suffer from life-threatening diabetic retinopathy. Thus, proper disease management is imperative to delay the progression of uncontrolled blood glucose to diabetic retinopathy or life-threatening diabetic retinopathy.

Consequently, with proper glucose control and proper blood pressure management, the retinal vasculature and neuronal tissue damage can be delayed in this patient population.

Various studies have focused on studying medications that can potentially help delay the progression of uncontrolled diabetes to retinopathy. The FIELD study and the ACCORD-eye studies have studied the use of fenofibrate in this patient population to understand its effect on diabetic retinopathy. Both studies saw a reduction in the need for laser surgery in those subjects receiving fenofibrate. Based on these studies, it was explained how activation of the nuclear transcription factor peroxisome proliferator-activated receptor alpha (PPARa) leads to anti-apoptosis signaling, inhibition of inflammatory factors and various antioxidant effects in the vasculature. It was also noted that these effects were independent of the lipid-lowering properties of fenofibrate.

In another study recently published, Marta Garcia-Ramirez and colleagues discovered other benefits of fenofibrate in retinopathy. In the retinal pigment epithelium of the eye, fenofibric acid, the active metabolite of fenofibrate, downregulates fibronectin and collagen in the basement membrane of the epithelium that leads to fluid accumulation, which impacts normal eye function. It also promotes downregulation of stress-mediated signaling pathways (i.e apoptosis, autophagy) and increases survival pathways. Inflammation in the eye vasculature is also reduced with the use of fenofibrate through downregulation of NF-kB. Thus, providing increased benefits in the management of diabetic retinopathy.

The profound effects of fenofibrate have not been evaluated in recent clinical studies. However, a study done in the Ukraine looked at the use of fenofibrate and statins in patients with type 2 diabetes patients. In this trial conducted by Yevgeniya Ilyina and colleagues, 47 patients with moderate non-proliferative diabetic retinopathy were enrolled to evaluate the effect of dual statin and fenofibrate therapy. Study subjects were separated into two groups, one control and with moderate non-proliferative diabetic retinopathy. All patients were followed for one year and changes in ophthalmological measurements were used as the primary endpoint of the study. Patients with moderate non-proliferative diabetic retinopathy were exposed to atorvastatin 20 mg daily and fibrates 250 mg daily (supplied as lipofen). All patients were assessed every 6 months for visual acuity, light sensitivity, and mean defect of the visual field. There was a significant difference in between mean defects visual fields, hence, those patients in the study group obtained a 22% reduction in mean defects of visual fields, whereas those patients in the control group obtained a 54% reduction (p<0.05). Meaning that the local defects in visual fields was progressively slower in the study population. The microvascular changes observed were more severe in the control group that in those patients exposed to the treatment regimen.

In conclusion, the use of fibrates and statins provided some visual field stabilization. This relationship has been observed independent of levels of A1c. This study further explores the potential of using fenofibrate and statin as a means of slowing the progression of diabetic retinopathy.  These findings support the findings obtained by the FIELD and ACCORD-eye studies. Therefore, with adequate glycemic control and use of other therapies, such as fenofibrate, microvascular complications like retinopathy, can be delayed. However, further studies are needed to translate these findings in patient populations with more advanced stages of diabetes.

Practice Pearls:

• Fenofibrate therapy can decrease the need for eye surgery in patients with diabetic retinopathy.
• The use of statins and fenofibrate can potentially slow local defects in visual field and prevent severe microvascular changes.
• Fenofibrate can decrease inflammation through downregulation of cytokines.

Researched and prepared by Pablo A. Marrero-Núñez – USF College of Pharmacy Student Delegate –  Doctor of Pharmacy Candidate 2017 – University of South Florida – College of Pharmacy

References:

Garcia-Ramírez, Marta, Cristina Hernández, Xavier Palomer, Manuel Vázquez-Carrera, and Rafael Simó. “Fenofibrate Prevents the Disruption of the Outer Blood Retinal Barrier through Downregulation of NF-κB Activity.” Acta Diabetol Acta Diabetologica 53.1 (2015): 109-18. Web.

Ilyina, Yevgeniya, Pavlo Bezditko, Ajaj Samer Mohamed, Olesya Zavoloka, and Darya Zubkova. “Statins and Fibrates as the Treatment of Nonproliferative Diabetic Retinopathy in Type 2 Diabetes Mellitus.” Spektrum Augenheilkd. Spektrum Der Augenheilkunde 30.3 (2016): 111-16. Web.

Moraes, Gabriela De, and Christopher J. Layton. “Therapeutic Targeting of Diabetic Retinal Neuropathy as a Strategy in Preventing Diabetic Retinopathy.” Clinical & Experimental Ophthalmology (2016): n. pag. Web.

Knickelbein, Jared E., Akshar B. Abbott, and Emily Y. Chew. “Fenofibrate and Diabetic Retinopathy.” Curr Diab Rep Current Diabetes Reports 16.10 (2016): n. pag. Web.