Ocular Complications Of Diabetes Mellitus Research Articles

Prevention of ocular complications of diabetes mellitus

Diabetes mellitus, a chronic metabolic disease associated with abnormally high levels of the blood glucose over a prolonged period, can cause damage to the eyes, which can lead to poor vision, or even blindness. The ocular complications of diabetes mellitus are numerous and include diabetic retinopathy, cataract, diabetic macular edema and glaucoma, and these complications may be prevented by rigorous glycemic control.

Influence of diabetes mellitus on anterior segment of the eye.

Diabetes mellitus (DM) has been emerging as one of the most serious health problems worldwide. Ocular complications of DM are currently one of the major causes of blindness in developed countries, among which diabetic retinopathy is relatively well studied and understood. However, although ocular surface complications of DM are common, diabetic complications of anterior segment of the eye, such as, cornea, conjunctiva, and lacrimal glands, are often overlooked. DM is associated with progressive damage to corneal nerves and epithelial cells, which increases the risk of anterior segment disorders including dry eye disease, corneal erosion, persistent epithelial defects, and even sight-threatening corneal ulcer. In this review, the authors will discuss the association of DM with disorders of anterior segment of the eye. Studies indicating the value of corneal nerve assessment as a sensitive, noninvasive, and repeatable biomarker for diabetic neuropathy will also be introduced. In addition, treatment modalities of anterior segment disorders associated with DM is discussed. The studies introduced in this review suggest that early and periodic screening of the anterior segment of the eye, as well as the retina, is important for the optimal treatment of DM.

Association between endoplasmic reticulum stress and risk factors of diabetic retinopathy.

Diabetic retinopathy (DR) is one of the most common and challenging ocular complications of diabetes mellitus. As a chronic, progressive ocular disease that poses a serious threat to vision, DR has gradually become a leading cause of blindness worldwide. Emerging evidence points to an important role of endoplasmic reticulum (ER) stress in not only maintaining the steady-state equilibrium in the body, but also in intracellular synthesis, protein folding, and other essential functions. Recent studies have demonstrated clear associations between ER stress-related physiological functions and the pathogenesis of DR. When cells are stimulated by external stimuli, UPR pathway is activated firstly to protect it. However, long-term harmful factors can induce ER stress. which interferes with the physiological metabolism of retinal cells and participates in the occurrence of DR via the ATF6 pathway, PERK pathway and IRE1 pathway. At present, ER stress blocker is expected to become a new anti-DR therapy. Thus, understanding the relationship between ER stress and DR will help to develop new effective preventative treatments. In this review, we summarize the risk factors of DR pathogenesis induced by ER stress toward revealing potentially new therapeutic targets.

Diabetic eye

Diabetes mellitus is a chronic metabolic disease associated with abnormally high levels of the blood glucose over a prolonged period. The ocular complications of diabetes mellitus are numerous and include retinopathy, cataract, uveitis and neurophthalmic disorders.

Intravitreal Anti-VEGF Therapy in the Management of Diabetic Macular Edema

Diabetic macular edema (DME), an ocular complication of diabetes mellitus, can potentially lead to devastating visual outcomes. Traditionally, laser photocoagulation has been the gold standard in the management of this condition. Over the recent years, however, several landmark clinical trials have shown beneficial effects of anti-VEGF agents over both sham injections and laser photocoagulation. These results have led to the wide adoption of intravitreal anti-VEGF therapy in DME treatment. Currently, two anti-VEGF agents, ranibizumab and aflibercept, are FDA approved in the United States for the management of DME. Recently, the Diabetic Retinopathy Clinical Research Network released its protocol T results showing that compared to bevacizumab and ranibizumab, aflibercept yielded significantly better outcomes in patients with visual acuity (VA) of 20/50 or worse at baseline. Among patients with baseline VA better than 20/50, however, all three anti-VEGF drugs had comparable results.

Effects of activation of Src-family tyrosine kinases on human LECs apoptosis and EMT under the high glucose environment

Background Diabetic cataract is one of the major ocular complications in diabetes mellitus, including cortical cataract, nuclear cataract, subcapsular cataract and mixed cataract, and different cataractogenesis may be associated with lens epithelial cells (LECs). Subcapsular cataract is one of diabetic cataracts.Studying the biological behavior of LECs in subcapsular cataract is crucial for prevention and treatment. Objective This study was to investigate the effects of Src-family tyrosine kinases (SFKs) on apoptosis and epithelial-mesenchymal transition (EMT) of human LECs cultured by high glucose. Methods Human LECs (HLE-B3) were cultured for 24 hours with DMEM containing 5.5 mmol/L glucose (normal control group), DMEM containing 35.5 mmol/L glucose (high glucose group) and DMEM containing 35.5 mmol/L glucose + 10 μmol/L PP1, a specific inhibitor of SFKs (PP1 group). In 3, 6, 12 and 24 hours after culture, the apoptosis of human LECs was detected by flow cytometry assay; morphological change of human LECs was observed under the inverted microscope, and the expressions of the markers of EMT, E-cadherin and α-smooth muscle actin (α-SMA), in the cells were detected by immnofluorescence staining.In addition, the alternations of p-Src418 (active c-Src), bcl-xl, survivin, caspase-3, E-cadherin and α-SMA proteins were assayed by Western blot analysis. Results An elevated expression level of p-Src418 was found in LECs in the high glucose group and peaked 6 hours after cultured.The expressions of p-Src418 (grey levels) were 0.125±0.036 in the high glucose group, and which was significantly higher than 0.042±0.011 in the normal control group and 0.035±0.018 in the PP1 group, respectively (both at P 0.05). The apoptotic rates of human LECs were(6.433±2.084)%, (10.333±2.610)% and (8.033±2.967)% in the PP1 group, which were higher than (3.233±1.320)%, (3.533±1.159)%, (5.733±0.230)% in the high glucose group and (3.133±1.170)%, (2.833±0.751)%, (3.333±1.201)% in the normal control group (all at P 0.05). In 6 hours and 12 hours after cell culture, the expression levels of bcl-xl and survivin (grey values) in human LECs were significantly declined, but the expression of caspase-3 was increased in the PP1 group compared with the the high glucose group and the normal control group (all at P<0.05). The LECs showed slender in shape 24 hours after culture in the high glucose group, but the cell shape was close to the normal in the PP1 group.Western blot and immunofluorescence assay revealed that the expression of E-cadherin in human LECs was significantly reduced and that of α-SMA was significantly increased 6 hours after culture in the high glucose group compared with the PP1 group and the normal control group (all at P<0.05). Conclusions High glucose activates c-Src kinase of LECs in high glucose environment and therefore induces EMT and inhibits apoptosis.However, PP1 impedes the biological process of EMT and apoptosis of LECs to maintain the epithelial characteristics even under the stress of high glucose. Key words: Glucose; Human; Epithelial cell, Lens; Apoptosis; Src-family tyrosine kinases; Epithelial-mesenchymal transition; Signaling pathway

Ocular complications of diabetes mellitus.

Diabetes mellitus (DM) is a important health problem that induces ernestful complications and it causes significant morbidity owing to specific microvascular complications such as, retinopathy, nephropathy and neuropathy, and macrovascular complications such as, ischaemic heart disease, and peripheral vasculopathy. It can affect children, young people and adults and is becoming more common. Ocular complications associated with DM are progressive and rapidly becoming the world's most significant cause of morbidity and are preventable with early detection and timely treatment. This review provides an overview of five main ocular complications associated with DM, diabetic retinopathy and papillopathy, cataract, glaucoma, and ocular surface diseases.

TNF-related apoptosis inducing ligand in ocular cancers and ocular diabetic complications.

TNF-related apoptosis inducing ligand (TRAIL) is an intensively studied cytokine, in particular for its anticancer activity. The discovery that conjunctival sac fluid contains extremely high levels of soluble TRAIL as compared to other body fluids suggested important implications in the context of the immunological surveillance of the eye, in particular of the anterior surface. In this review, we discuss the potential physiopathologic and therapeutic role of the TRAIL/TRAIL receptor system in a variety of ocular cancers. Moreover, since an increasing amount of data has indicated the important biological activities of the TRAIL/TRAIL receptor systems also in a completely different pathologic context such as diabetes mellitus, in the second part of this review we summarize the currently available data on the involvement of TRAIL in the ocular complications of diabetes mellitus as modulator of the inflammatory and angiogenic response in the eye.

Awareness of Ocular Complications of Diabetes Among Diabetic Patients In A Tertiary Hospital In Western, Nigeria

Background:- Diabetes is no longer a disease of affluent and industrialized countries. It affects virtually all ocular structures and can lead to blindness. Routine eye examination is necessary for early detection of ocular involvement and prevention of blindness. Only few diabetics have regular eye examination. Aim:- To study the awareness of ocular complications of diabetes among diabetic patients Methodology:- A cross-sectional prospective study of 148 randomly selected diabetic patients was done. A semi structured questionnaire was administered to these patients by an interviewer who is medical personnel, not below the level of a house-officer. Informed consent was obtained from the patients before filling the questionnaires. The information obtained include the biodata, educational level, duration of diabetes, whether they were aware that diabetes can affect other parts of the body, if yes which parts, which parts of the eye can it affect, how can it affect the eye, whether or not routine eye examination is necessary in diabetics, if yes how often, how did they learn about diabetes and how they think awareness of diabetic complications can be improved. The results were collated and analyzed using SPSS version 13, with chi square done where necessary. Results:- A total of 148 patients were studied. Their ages range between 21years and 82years, with a mean of 58.53 +10.4years. Majority were between 36-60yearrs of age. Eighty-three (56.1%) had educational level within secondary level 40(27 %) tertiary education while 25(16.9 %)) do not have formal education. Most common co morbid factor was hypertension, found in 44.6%. One hundred and twenty three (83.1%) were aware that diabetes could affect other parts of the body, 41% were aware of brain affectation, 54% were aware that it can affect the kidneys, 77.7% were aware that it can affect the eyes, 39.2% blood vessels, 66.2% the legs, 40.5% the skin and 41.9% were aware that it can affect the genitals. Of the 77.7% who were aware that it can affect the eyes, more than half (58.8%) did not know the part of the eye that can be affected. 20.3% knew that it can affect the crystalline lens,4.1% external eye, 13.5% the retina and 3.4% thought it can affect the combination of external eye, lens and the retina. Forty nine respondents (33.1%) did not know that routine eye examination is necessary in diabetics, 16.2% says eye examination should be once, 18.2% twice, 18.9% thrice and 26.4% none. Only 18 (12.2%) respondents got their information of eye complication from eye specialists. Sixty- one respondents (41.2%) do not know how diabetes can affect the eye, 29.7% knew that poor control is the problem, 8.8% think it is due to long duration, 7.4% believe it was a combination of poor control and long duration, 2% claim it is due to infection, 8.8% combination of infection, poor control and long duration and 0.7% erroneously believe thinking too much of DM can result in eye complication. Patients who have been diabetic for more than 10years are more aware that diabetes can affect the eye than those below 5years (92.3% vs. 7.2%, p=0.001). Awareness of diabetic complication is better in those with tertiary education than others (p=0.001). Conclusion:- We conclude that though awareness of ocular complication of diabetes mellitus is high, the level of knowledge is low. Health Practitioners especially eye care specialist need to intensify health education through media, regular health talks in clinics to increase knowledge and increase health seeking behaviours of diabetics in the.

A decrease in VEGF and inflammatory markers is associated with diabetic proliferative retinopathy

Diabetic retinopathy is the most severe ocular complication of diabetes mellitus (DM), is associated with micro-vascular damage. The more advanced stage, proliferative diabetic retinopathy, has been linked to an increased risk of cardiovascular morbidity and mortality. Our hypothesis was that inflammatory and angiogenic markers will detect the different stages of type 2 diabetes, and may predict development of micro-vascular damage. Methods. Seventy three type II diabetic patients were randomly assigned to three groups (A - 25 patients {12 males], no diabetic retinopathy; B - 25 patients {19 males], non-proliferative retinopathy; and C - 23 patients {13 males], proliferative retinopathy),when they came for a routine follow-up visit in the ophthalmologic outpatient clinic. Twenty-three healthy subjects (14 males) served as controls. High-sensitivity C reactive protein (hs-CRP), soluble vascular cell adhesion molecule 1(sVCAM-1) and vascular endothelial growth factor (VEGF) were studied. Results. The duration of type II diabetes differed between group A (9 ± 6 years) and B (17 ± 9 years) patients (p = 0.001). No such difference was revealed between groups B and C (19 ± 6 years) (p = 0.30). A difference in hemoglobin A1C (HBgA1C) levels was detected between groups A (7.1 ± 2.7%) and B (8.5 ± 1.5%) (p = 0.02), but none was found between groups B and C (8.5 ± 1.6%) (p = 0.98). Only six patients (out of 23) used insulin treatment in group A, compared with 16 in group B (out of 25) and 17 in group C (out of 25) (p = 0.004). All three groups of diabetic patients were older (62.8 ± 10.8, 61.9 ± 9.4, 59.2 ± 10.3 years, respectively) than the controls(44.3 ± 11.6 years) (p≤0.001). Hs-CRP levels were higher in diabetic patients (4,391 ± 4,175, 4,109 ± 4,533, 3,005 ± 3,842ng/mL, respectively) than in controls (1,659 ± 1,866ng/mL); however, only the levels in patients of groups A (p = 0.01) and B (p = 0.03) were significantly different from those of the controls, in contrast to group C, which did not differ (p = 0.180). Similar findings were observed for sVCAM-1 (706 ± 347, 746 ± 328, 638 ± 208ng/mL, respectively, vs. controls {552 ± 143ng/mL]); sVCAM-1 levels of groups A and B, but not C, differed from the controls (p = 0.05, p = 0.01 and p = 0.125, respectively). With the exception of group B (p = 0.03), soluble VEGF DM type II levels (493 ± 353, 625 ± 342, 368 ± 223pg/mL, respectively) did not vary from those of the controls (392 ± 355pg/mL, p≥0.05). However, as the disease progressed, there was a significant decrease in VEGF levels, accompanied by a significant difference between groups B and C (p = 0.006). Conclusions. Patients with diabetes type 2with no-retinopathy and with non-proliferative retinopathy had high levels of inflammatory and angiogenic markers, which decreased in patients with diabetic proliferative retinopathy. Biomarkers of inflammation and angiogenesis may detect the progression of diabetic vascular disease and may lead towards earlier interventions that would prevent systemic complications.

Significance of Ultrasonography in Evaluation of Vitreo-retinal Pathologies

To assess the diagnostic value of ultrasonography in the detection of vitreo-retinal pathologies. This prospective study included all patients from retina department in Eye Clinic University Clinical Center Tuzla first time referred and examined by a single experienced vitreo-retinal surgeon in period from January 2011 to January 2012. Complete ophthalmic examination and ultrasonography-standardized echography were performed to all patients for detection and confirmation of vitreo-retinal pathology. Study included 146 eyes from 122 patients. 58 (39.7%) eyes had poor posterior segment visualization, 21 (14.4%) eyes due to dense cataracts and 37 (25.3%) eyes due to different vitreous opacities. 88 (60.3%) eyes had good or partial posterior eye segment visualization, where 67 (45.9%) eyes had proliferative vitreo-retinopathy and 55 (37.7%) eyes had tractional retinal detachment. Most common causes for referral to vitreo-retinal surgeon were ocular complications of diabetes mellitus 94 (64.4%), ocular trauma 18 (12.3%), rhegmatogenous retinal detachment 16 (10.9%) and intraocular inflammation 9 (6.2%). Ultrasonography confirmed suspected diagnosis and operative management plan in 120 (82.2%) eyes, sublassified previously established diagnosis in 19 (13%) eyes and helped further operative planning and established completely new diagnosis and changed initial management plan in 7 (4.8%) eyes. The final clinical diagnosis confirmed the ultrasonography findings in 142 from 146 (97.3%) eyes. Ultrasonography is useful part of ophthalmic examination for detection, evaluation and follow up of different vitreo-retinal pathologies.

Prevalence and Severity of Diabetic Retinopathy in Northwest Cameroon as Identified by Teleophthalmology

Diabetic retinopathy is a common ocular complication of diabetes mellitus, which can lead to significant visual impairment. The present study is the first to characterize the prevalence and severity of diabetic retinopathy and other ocular pathologies in a population of patients with diabetes who live in Northwest Cameroon using teleophthalmology. A retrospective review of the electronic charts of patients at the Banso Baptist Hospital and in neighboring communities between July 1, 2007 and June 30, 2008 was completed. The eyes of 253 consecutive patients with diabetes mellitus who attended mobile teleophthalmology clinics in Northwest Cameroon were included in the study. Eyes were graded for diabetic retinopathy using stereoscopic seven-field digital retinal images obtained by a mobile team in Cameroon and graded by ophthalmologists in Canada utilizing Early Treatment Diabetic Retinopathy Study criteria. Diabetic retinopathy was identified in 20.6% of eyes (18.2% nonproliferative, 2.4% proliferative) and in 24.3% of patients. About 8.0% of eyes demonstrated evidence of macular edema. Additional nondiabetes-related ocular pathologies were identified in 14.6% of eyes. Diabetic retinopathy was found to be common in people with diabetes who attended teleophthalmology clinics in Northwest Cameroon. The prevalence of treatable disease including macular edema and retinal neovascularization suggests that improved patient access to laser photocoagulation and vitreoretinal surgery would be beneficial in reducing vision loss in this vulnerable population. As the prevalence of diabetes increases across sub-Saharan Africa, the challenge of diagnosing and managing the complications of diabetes will increase.

Prevention of Proliferative Diabetic Retinopathy and Cataract in SDT Rats with Aminoguanidine, an Anti-Advanced Glycation End Product Agent

Advanced glycation end products (AGEs) play important roles in the development of ocular complications in diabetes mellitus. Spontaneously Diabetic Torii (SDT) rats have marked hyperglycemia and severe ocular complications. We evaluated the effect of anti-AGE agents, aminoguanidine and pyridoxamine, and an antioxidant, probucol, on the development of diabetic retinopathy (DR) and cataract in SDT rats. Experiment 1 included five SDT rats treated with aminoguanidine, four SDT rats treated with probucol, and four untreated control SDT rats. After age 55 weeks, we evaluated DR by fluorescein angiomicroscopy and pathological study and cataract by biomicroscopy. Experiment 2 included six SDT rats treated with pyridoxamine, and six SDT rats and 10 non-diabetic normal Sprague-Dawley (SD) rats not treated with pyridoxamine. Retinopathy and cataract were evaluated as in experiment 1. Urinary pentosidine and Maillard reaction product X (MRX) levels were measured for 40 weeks in each group. Experiment 1: Mature cataracts and DR developed in all untreated SDT rats; aminoguanidine prevented cataracts and DR (p<0.05, vs untreated SDT rats). Probucol had no effect. Experiment 2: Mature cataracts developed in all untreated SDT rats (p<0.001 vs normal SD rats [0/10]) and DR developed in 67% (p<0.01, vs normal SD rats [0/10, 0%]). Pyridoxamine did not prevent cataracts (6/6, 100􀀃) or DR (4/6, 37%) (nonsignificant vs untreated SDT rats) in SDT rats. Urinary pentosidine levels were higher in untreated (0.12±0.07 μg/mg􀀂Cre) and pyridoxamine-treated (0.12±0.05 μg/mg􀀂Cre) SDT rats than normal SD rats (0.069±0.019 μg/mg􀀂Cre), but not significantly so. Urinary MRX levels were significantly (p<0.01) lower in normal SD rats (17.5±9.6 μg/mg􀀂Cre) compared with untreated SDT rats (163.0±107.0 μg/mg􀀂Cre); pyridoxamine had no effect (149.0±66.5 μg/mg􀀂Cre) (nonsignificant vs untreated SDT rats). Aminoguanidine but not pyridoxamine and probucol prevents DR and cataracts in SDT rats.

ROCK as a Therapeutic Target of Diabetic Retinopathy

The increasing global prevalence of diabetes is a critical problem for public health. In particular, diabetic retinopathy, a prevalent ocular complication of diabetes mellitus, causes severe vision loss in working population. A better understanding of the pathogenesis and the development of new pharmacologic treatments are needed. This paper describes the relevance between Rho/ROCK pathway and the pathogenesis of diabetic retinopathy from its early to late stages. Moreover, the therapeutic potential of ROCK inhibitor in the total management of diabetic retinopathy is discussed.

Diabetic Retinopathy: Current Management and Experimental Therapeutic Targets

Diabetic retinopathy, a devastating ocular complication of diabetes mellitus, is the leading cause of blindness among working-age adults in the United States and is a serious public health problem throughout the world. Standard treatment is retinal laser photocoagulation, which is an invasive procedure with considerable limitations and adverse effects. Understanding the biochemical changes and molecular events that occur with diabetes as well as with retinopathy could lead to new and effective treatments. Research indicates an association between oxidative stress and the development of complications from diabetes, including retinopathy. Thus, many sites and sources of oxidative stress that may be involved in the development of diabetic retinopathy have been studied. However, in clinical trials, classic antioxidants have not been beneficial for patients with diabetes. Additional studies are needed to identify treatments that selectively target oxidative stress-mediated protein modification and thus prevent or at least delay diabetic retinopathy.

Efficacy and safety of one intravitreal injection of bevacizumab in diabetic macular oedema

To assess the efficacy, duration of effect and safety of one intravitreal injection of bevacizumab in diabetic macular oedema (DMO). Bevacizumab (1 mg/0.04 ml) was injected intravitreally into eyes with DMO (29 with and nine without previous treatments). Best corrected visual acuity (BCVA), intraocular pressure and central retinal thickness (CRT) were measured; slit-lamp examination, macular biomicroscopy, optical coherence tomography and fluorescein angiography were performed before and at 2-4, 8 and 12 weeks post-injection. Best corrected VA and CRT were analysed in both groups. In the non-pretreated group, mean BCVA improved from 0.76 +/- 0.33 (baseline) to 0.57 +/- 0.30 and 0.54 +/- 0.27 at 2-4 weeks and 8 weeks post-injection, respectively (p = 0.02, p = 0.014, paired t-test). Mean CRT decreased from 632.4 +/- 196.0 microm (baseline) to 392.3 +/- 113.6 microm and 370.4 +/- 141.7 microm at the same time-points, respectively (p = 0.01, p = 0.01). There was no difference in BCVA or CRT at 12 weeks. In the pretreated group, mean BCVA improved from 0.62 +/- 0.30 (baseline) to 0.53 +/- 0.33 at 2-4 weeks post-injection (p = 0.01), and mean CRT decreased from 583.9 +/- 180.7 microm (baseline) to 404.1 +/- 197.9 microm at 2-4 weeks post-injection (p < 0.001). Mean BCVA was unchanged at 8 weeks and 12 weeks post-injection, although mean CRT remained lower at 8 weeks (p = 0.004). No ocular or systemic side-effects developed during follow-up. One intravitreal injection of bevacizumab for DMO seems to be effective and safe in both eyes that have been treated previously and eyes that have not. The therapeutic effect is temporary and repeat treatment may be needed.

Interdisciplinary Management of Diabetic Eye Disease: A Global Approach to Care

Diabetic eye disease is a leading cause of acquired blindness in the United States. Most cases of blindness secondary to diabetes mellitus are preventable. In addition to exercise, proper diet, and aggressive glycemic control, patients with diabetes mellitus should be educated to adhere to established guidelines for an annual dilated retinal evaluation. The ideal model of care for patients with diabetic eye disease is an interdisciplinary, team-oriented approach with the patient as the central member of the healthcare team. The primary purpose of this paper is to present an interdisciplinary approach to management of the ocular complications of diabetes mellitus and to educate clinicians about diabetic eye disease.

Distinct Effects of High-Glucose Conditions on Endothelial Cells of Macrovascular and Microvascular Origins

Recent studies implicate hyperglycemia as an important cause of macrovascular and ocular complications in diabetes mellitus. In this study, the authors examined the effect of high glucose on macrovascular and microvascular endothelial cell viability and apoptosis in culture. Human aortic endothelial cells (HAECs) and human retinal endothelial cells (HRECs) were exposed to normal-glucose conditions (NG) and high-glucose conditions (NG supplemented with 25 mM D-glucose) for 72 h in vitro. D-Mannitol was used as an osmotic control. Cell viability was assessed by methlythiazolydiphenyltetrazolium bromide (MTT) assay, and induction of apoptosis was assessed by Hoechst staining. Statistics were analyzed by paired t tests. In HAECs, cell viability was decreased by 12.9% in high-glucose conditions, and apoptotic cells were significantly increased by 77%. However, in HRECs, cell viability was increased by 14.9% in high-glucose conditions, and apoptotic cells were significantly decreased by 33.3%. Mannitol did not show any effect on cell survival or apoptosis ruling out an osmotic effect. High-glucose conditions reduce cell viability and induce apoptosis in HAECs, which may contribute to macrovascular complications associated with diabetes. In contrast, high-glucose increases viability in HRECs and inhibits apoptosis, which may contribute to the development of diabetic retinopathy.

The Potential Role of Octreotide in the Treatment of Diabetic Retinopathy

Proliferative diabetic retinopathy is the main cause of vision loss in young and middle-aged adults. There is no accepted pharmaceutical therapy for this disease, although analogs of the naturally occurring growth hormone inhibitor, somatostatin, have been considered leading candidates for developing such therapies. This review examines the history of somatostatin analogs, especially octreotide, in the treatment of ocular complications of diabetes mellitus. The historical observations that indicated a role for somatostatin in retinopathy are discussed from an endocrinology perspective. The molecular mechanisms by which somatostatin may exert its anti-angiogenic effects, both indirect (through antagonism of the growth hormone axis) and direct (through direct antiproliferative and apoptotic effects on endothelial cells mediated by specific receptor subtypes) are described. Animal models that were used to demonstrate an anti-angiogenic effect of octreotide are detailed, as are the results of numerous clinical trials that used octreotide and other somatostatin analogs to treat diabetic retinopathy. The mixed results of these clinical results are examined along with possible explanations as to why these analogs both have and have not shown efficacy in limited clinical settings. Even with these mixed results, somatostatin analogs remain the only therapeutic alternative to patients with proliferative diabetic retinopathy who have failed to respond to panretinal photocoagulation.

Diabetic Retinopathy

Retinopathy is the most common and vision threatening ocular complication of diabetes mellitus. Epidemiologic studies have described the natural history of diabetic retinopathy, and several well-designed clinical studies have demonstrated the benefits of laser photocoagulation, vitrectomy and tight metabolic control. New therapeutic trials are in progress. But it is one of the major causes of blindness in the adult population, which suggest the importance of early diagnosis and careful follow up examination as well as proper treatment in time.