Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Macular edema, a condition usually associated with an underlying disease process, is a common cause of severe visual loss. There have been a variety of approaches to the treatment of macular edema; within the past few years, however, intravitreal corticosteroid treatments have emerged as an increasingly used treatment option for patients with macular edema. Intravitreal delivery allows the steroid to bypass the blood-retinal barrier, leading to a more concentrated dose of steroid for a prolonged period of time. Corticosteroids have likely been successful in the treatment of various forms of macular edema, due to their known anti-angiogenic, anti-edematous, anti-inflammatory, anti-apoptotic, and anti-proliferative effects. Intravitreal triamcinolone acetonide has been repeatedly successful in reducing macular edema and improving visual acuity, although the duration of action is typically short-term. Due to the recurrent and chronic nature of macular edema, biodegradable implants may be the future of intravitreal steroids. Intravitreal corticosteroids are not without risks. Steroid-related side effects include cataract formation and elevated intraocular pressure. Injection-related side effects include retinal detachment, vitreous hemorrhage, bacterial endophthalmitis, and sterile endophthalmitis. This article reviews the evolving role of intravitreal corticosteroids in the treatment of macular edema secondary to uveitis, diabetes, and retinal vascular disorders.
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PMID:Intravitreal steroids for macular edema: the past, the present, and the future. 1942 73

Diabetes Mellitus (DM) is a serious medical problem that causes long-term systemic complications and considerable associated morbidity. DM can cause retinopathy (DRP), maculopathy, cataract, optic neuropathy, defects of eye muscles. DM is a risk factor for acute infectious conjunctivitis, bacterial keratitis, herpes virus infections and endophtalmitis. Elevated blood glucose induces structural, physiological and hormonal changes which affect retinal capillaries. DRP is recognized by loss of pericyte function and capillary occlusions together leading to breakdown of blood-retinal barrier, edematous changes and proliferation of vessels and fibrous tissue. Depending on stage of DRP, there are different preferable therapeutic approaches applied. In the case of ETDRS, in the area of leakage focal treatment should be performed, while panretinal photocoagulation is applied towards ischemic areas or beginning proliferations. Vitreal haemorrhage followed by fibroproliferative changes or tractional retinal detachment is treated by vitrectomy alone or in combination with ILM peeling. In pathogenesis of DRP, Insulin Growth Factor (IGF-1) can play an important role in production of VEGF (Vascular Endothelial Growth Factor). Hypoxia can up-regulate VEGF expression levels leading to pathologic ocular neovascularisation. An application of intravitreal corticosteroid treatment modulates vascular permeability by suppressing the production of VEGF, reducing both extracellular matrix metalloproteinase activity and basic fibroblast growth factor, decreasing major histocompatibility complex 2 Ag expression levels, and inhibiting activity of inflammatory cells. Clinical effects of treatment using intravitreal corticosteroids are evaluated by reduction of macular thickness and visual improvement. Intravitreal use of Anti-VEGF drugs, Pegaptanib, Ranibizumab and Bevacizumab can modify vasoproliferation, trigger macular edema, and, therefore, influence a prognosis for visual loss.
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PMID:Eye disorders in diabetes: potential drug targets. 1853 2

By means of highly sensitive radioimmunoassays, the levels of substance P (SP) and secretoneurin (SN) were detected in vitreous aspirates of patients with macular holes which served as controls, in patients with nonproliferative diabetic retinopathy (DR), active proliferative diabetic retinopathy (active PDR), inactive PDR, rhegmatogenous retinal detachment and proliferative vitreoretinopathy (PVR). Furthermore, SN-like immunoreactivities were characterized by reversed phase-HPLC. The concentration of SN was more than 20-fold higher in macular holes when compared with SP and reversed phase HPLC revealed evidence that the vitreous levels of SN represent authentic SN. SN was significantly decreased in patients with nonproliferative DR, active PDR and inactive PDR by more than 70% which seems to result from a reduced expression and/or secretion from the cilary epithelium and a reduced release from the retina both due to diabetes mellitus. By contrast SP was increased in rhegmatogenous retinal detachment most obviously due to an enhanced outflow of the peptide through retinal breaks. Despite their proangiogenic activities, SP and SN are unlikely to be involved in the pathogenesis of neovascularizations in DR because of their unchanged and reduced levels, respectively, but the low levels of both peptides may facilitate the regression of vasoproliferations following laser photocoagulation.
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PMID:Substance P and secretoneurin in vitreous aspirates of patients with various vitreoretinal diseases. 1855 Feb 23

Anti-VEGF drugs may be employed in the surgical treatment of diabetic retinopathy: 1. Prior to surgery. The intravitreal injection of anti-VEGF drugs leads to a significant reduction of neovascularization, with a reduction in the adherence of the fibrovascular complex to the retina. This simplifies viscodelamination and reduces intraoperative bleeding during delamination and segmentation. To minimize the risk of tractional retinal detachment due to the contraction of fibrovascular tissue, vitrectomy must be performed within one week after the injection. 2. To decrease the risk of postoperative bleeding. Recurrent vitreous hemorrhages after vitrectomy are often due to small bleeding from persistent neovascularization. The injection of anti-VEGF drugs at the end of vitrectomy could prevent bleeding from these vessels by blocking the pro-inflammatory stimulus of the surgical procedure. 3. To treat postoperative vitreous hemorrhage. The intravitreal injection of anti-VEGF drugs in patients with postoperative bleeding leads to resolution of the hemorrhage. 4. To treat rubeosis iridis. In eyes with complete panretinal photocoagulation, the combination of cryotherapy and intravitreal anti-VEGF injection in the same surgical procedure produces a disappearance of iris neovascularization together with a long term effect with no recurrences. In neovascular glaucoma, anti-VEGF drugs can also facilitate filtrating surgery.
Curr Diabetes Rev 2009 Feb
PMID:Anti-angiogenic drugs as an adjunctive therapy in the surgical treatment of diabetic retinopathy. 1919 99

This paper reviews the current experience and trends in 23-gauge transconjunctival sutureless vitrectomy for diabetic retinopathy in those patients that need a surgical intervention for either vitreous hemorrhage, fibrovascular proliferation with traction retinal detachment affecting or threatening the macula, traction-rhegmatogenous retinal detachment, or refractory macular edema with taut posterior hyaloid. Since the instruments in 23-gauge vitrectomy are less flexible and perform in a more similar way to 20-gauge instruments, the vitrectomy is more thorough and for more complex manoeuvres can be done. The 23-gauge transconjuntival sutureless vitrectomy avoids some of the shortcomings of the 25-gauge systems.
Curr Diabetes Rev 2009 Feb
PMID:Transconjunctival sutureless 23-gauge vitrectomy for diabetic retinopathy. Review. 1919 1

Despite considerable recent advances in vitreoretinal surgery, generally performed in more advanced stages of diabetic vitreoretinopathy (DVR), a satisfying visual acuity cannot always be achieved. Even in the early DVR stages that might be detected by routine eye exams, management of general factors, such as blood glucose concentration and blood pressure, currently constitutes the only proven preventive measures. New approaches for amelioration and treatment of DVR are needed. The Hisayama study, an ongoing prospective cohort study of cardiovascular disease and its risk factors in a community in Hisayama Town adjoining Fukuoka City, revealed that the cut-off point for diagnostic fasting glucose level is lower (116 mg/dl) than that of the current diagnostic criteria (126 mg/ dl), indicating that more rigid diagnostic criteria might reduce the incidence of DVR in the Japanese population. In early stages of DVR, leukocyte adhesion in the retinal microvasuculature substantially contributes to DVR. We investigated the involvement of the Rho/ ROCK pathway in diabetic microvasculopathy and the therapeutic potential of fasudil, a selective ROCK inhibitor, and demonstrated that the Rho/ROCK pathway plays a critical role in leukocyte adhesion in diabetic retinal microvasculature and endothelial damage. Fasudil protects the vascular endothelium at least in part by inhibiting neutrophil adhesion and reducing neutrophil-induced endothelial injury via endothelial nitric oxide. In later stages of DVR, namely proliferative diabetic retinopathy, tractional retinal detachment associated with a cicatrical contraction of proliferative membranes can cause severe vision loss. We demonstrated the possible involvement of hyalocytes in proliferative membrane formation and its contraction mainly mediated through the function of TGF-beta 2 resulting in myofibroblastic transdifferentiation and phosphorylation of the myosin light chain, a downstream mediator of ROCK. ROCK inhibition by fasudil or statins successfully inhibited cicatrical contraction of the proliferative membranes both in vitro and in vivo. Further studies for direct evidence demonstrating whether altered diagnostic criteria of diabetes may lead to a lower incidence of DVR and determination of the therapeutic potential of ROCK inhibition in the clinic could provide new avenues of intervention for inhibiting DVR.
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PMID:[Preventive strategy for the treatment of diabetic vitreoretinopathy]. 1934 84

Spontaneously Diabetic Torii (SDT) rat shows severe ocular complications such as tractional retinal detachment. In the present study, effect of protein kinase C beta (PKCbeta) inhibitor JTT-010 was evaluated to clarify the involvement of PKCbeta in complications of SDT rat. SDT rats were administered JTT-010 (10 or 50 mg/kg/day) for 48 weeks. SDT rats showed delayed oscillatory potentials in electroretinogram. Delayed motor nerve conduction velocity, decreased coefficients of variation of R-R intervals in electrocardiogram and thermal hypoalgesia were also observed. These functional disorders were prevented by administration of JTT-010. Abnormal retinal vascular was formed and the optic disc was protruded in SDT rat; however, JTT-010 did not prevent these hyperglycaemia-induced retinal abnormalities. These findings indicate that PKCbeta is intimately involved in diabetic complications; however, it seems that other factor(s) are primary contributors to histopathological abnormalities in retina. Therefore, PKCbeta inhibitors require concurrent administration of antihyperglycaemic drugs to achieve maximum effect on diabetic complications.
Diabetes Obes Metab 2009 Nov
PMID:Protein kinase C beta inhibitor prevents diabetic peripheral neuropathy, but not histopathological abnormalities of retina in Spontaneously Diabetic Torii rat. 1961 49

The volume of cells that a length of capillary supplies with O(2) is called a Krogh cylinder. This geometric 'tissue unit' was named after the Danish zoophysiologist and Nobel laureate August Krogh who made important discoveries in the fields of external and internal respiration in the first half of the last century. Krogh's ideas concerning tissue O(2) distribution can be extrapolated to retinal oxygenation by larger vessels (including arterioles, arteries and even veins) and by vessel groups within higher-order 'microvascular units' (including the choroid). During retinal development, for example, the difference in pO(2) levels within arteries and capillaries determines Krogh cylinders of different radius and establishes the periarterial capillary-free zone of His. The O(2) supply to the venous end of a tissue unit may be compromised during periods of reduced perfusion, increased O(2) consumption or hypoxaemia, resulting in an 'anoxic corner' of the Krogh cylinder. A funnel of hypometabolic (and therefore hypoxia-tolerant) cells will likely intervene between the necrotic cells and unaffected cells located closer to the O(2) source. Macular perivenular whitening heralds anoxic corners and/or hypoxic funnels owing to hypoperfusion within second-order microvascular units. In eyes with extensive retinal capillary closure from diabetes, Krogh cylinders surround the medium-sized arteries and veins that form arteriovenous shunts while traversing the midperipheral retina. These isolated tissue units incorporate an outer sheath of hypoxic cells within which vascular endothelial growth factor is upregulated. This 'angiogenic sheath' expands following retinal detachment; it corresponds to the hypoxia-tolerant funnel within capillary-based tissue units and to the cerebral penumbra after stroke.
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PMID:Krogh cylinders in retinal development, panretinal hypoperfusion and diabetic retinopathy. 2006 21

The association between serous retinal detachment of macula (SRD) in hypertensive retinopathy (HTR) and malignant hypertension has been reported. This cross-sectional study included 14 consecutive patients on treatment for hypertension, who were referred for ophthalmic evaluation and were found to have macular SRD, documented by optical coherence tomography. All underwent systemic evaluation for hypertensive status and to rule out other associated/similar diseases such as diabetes, coagulopathies, lupus etc. The mean age of the patients was 44.35 +/- 15.5 years; the mean best-corrected visual acuity was 6/12. All had grade 3-4 HTR; 10 patients had bilaterally symmetrical retinopathy (grade 3 or 4); 4 had asymmetric fundus changes. Systemically, every patient was found to have malignant hypertension. The mean systolic and diastolic pressures were 208.57 +/- 32.78 and 117.86 +/- 14.2 mm Hg, respectively. SRD predicted malignant hypertension more consistently than papilledema (P = .0132). The presence of macular SRD in a hypertensive patient may serve as an indicator of malignant hypertension.
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PMID:Localized Serous Retinal Detachment of Macula as a Marker of Malignant Hypertension. 2033 99

Retinal vein occlusion (RVO) is the most common retinal vascular disease after diabetic retinopathy. Owing to its multifactorial nature, however, management of this condition remains a challenge. Of the two main types of RVO, branch retinal vein occlusion (BRVO) is more prevalent than central retinal vein occlusion (CRVO). Most patients develop the disease at an elderly age, and more than half of them have associated systemic disorders (e.g. hypertension, hyperlipidemia and/or diabetes mellitus). There is no evidence to suggest routine testing for heritable thrombophilias in patients with RVO. The main cause of the visual impairment is macular edema, while neovascularization of the retina and optic disc are the most serious complications leading to vitreous hemorrhage, retinal detachment and neovascular glaucoma. Macular grid laser photocoagulation is an effective treatment for macular edema in patients with BRVO and a visual acuity of 20/40 or less. Other treatment options for reducing the edema are intravitreal steroids, anti-VEGF drugs and vitrectomy. The recently introduced intravitreal application of steroids and anti-VEGF drugs may prove to be a better approach for improving visual acuity. Finally, scatter panretinal laserphotocoagulation can effectively treat neovascularization and its secondary complications.
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PMID:Retinal vein thrombosis: pathogenesis and management. 2195 4


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