The Multifactorial Nature of Retinal Vascular Disease

Kleinman, Mark E.; Baffi, Judit; Ambati, Jayakrishna

doi:10.1159/000315152

Cited by 21 publications

(17 citation statements)

References 104 publications

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“…Macular oedema can occur at any stage of the disease and therefore may not always be driven by the same cytokines that drive retinopathy severity. This important disparity and the various morphological subtypes of macular oedema as defined by optical coherence tomography (OCT) have led researchers to lend importance to other insults such as inflammatory pathways . Several pro‐inflammatory pathways are being explored in diabetic retinopathy and diabetic macular oedema, but there are likely to be multiple inciting factors for inflammation.…”

Section: Pathogenesismentioning

confidence: 99%

Diabetic retinopathy: pathogenesis, clinical grading, management and future developments

et al. 2013

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Decades of research into the pathophysiology and management of diabetic retinopathy have revolutionized our understanding of the disease process. Diabetic retinopathy is now more accurately defined as a neurovascular rather than a microvascular disease as neurodegenerative disease precedes and coexists with microvascular changes. However, the complexities of the pathways involved in different stages of disease severity continue to remain a challenging issue for drug discovery. Currently, laser photocoagulation is the mainstay of treatment for proliferative diabetic retinopathy, but is gradually being superseded for diabetic macular oedema. However, it is destructive and at best results in a gradual but modest improvement in vision in the long term. So, diabetic retinopathy remains the most prevalent cause of visual impairment in the working-age population despite established screening programmes, early diagnosis and treatment of the condition. The recent discovery of inhibitors of vascular endothelial growth factor is revolutionizing the management of diabetic retinopathy, particularly diabetic macular oedema. However, not all patients respond to anti-vascular endothelial growth factor agents, reinforcing the fact that diabetic retinopathy is a multifactorial disease. Studies are still required to improve our understanding of how retinal structure correlates with visual function. It is hoped that these will lead to better characterization of the disease phenotype based on treatment responses to different agents and allow an algorithm to be developed that will guide the management of diabetic retinopathy and diabetic macular oedema at different stages of severity.

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Section: Pathogenesismentioning

confidence: 99%

Diabetic retinopathy: pathogenesis, clinical grading, management and future developments

et al. 2013

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“…Research into the pathophysiology of ME has led to a greater understanding of the underlying mechanisms and the role of inflammatory mediators that facilitate cellular damage, leading to accumulation of fluid within the retina. 1 , 2 The anti-inflammatory, antiangiogenic, and antipermeability effects of corticosteroids counteract three key pathologic processes involved in the development of ME. 2 , 3 However, the efficacy of corticosteroids is greatly affected by the route of administration.…”

Section: Introductionmentioning

confidence: 99%

Real-world assessment of intravitreal dexamethasone implant (0.7 mg) in patients with macular edema: the CHROME study

Lam¹,

Albiani²,

Yoganathan³

et al. 2015

OPTH

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BackgroundThe purpose of this study was to evaluate the real-world use, efficacy, and safety of one or more dexamethasone intravitreal implant(s) 0.7 mg (DEX implant) in patients with macular edema (ME).MethodsThis was a retrospective cohort study of patients with ME secondary to retinal disease treated at ten Canadian retina practices, including one uveitis center. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), intraocular pressure (IOP), glaucoma and cataract surgery, and safety data were collected from the medical charts of patients with ≥3 months of follow-up after the initial DEX implant.ResultsOne hundred and one patient charts yielded data on 120 study eyes, including diagnoses of diabetic ME (DME) (n=34), retinal vein occlusion (RVO, n=30; branch in 19 and central in 11), and uveitis (n=23). Patients had a mean age of 60.9 years, and 73.3% of the study eyes had ME for a duration of ≥12 months prior to DEX implant injection(s). Baseline mean (± standard error) BCVA was 0.63±0.03 logMAR (20/86 Snellen equivalents) and mean CRT was 474.4±18.2 μm. The mean number of DEX implant injections was 1.7±0.1 in all study eyes; 44.2% of eyes had repeat DEX implant injections (reinjection interval 2.3–4.9 months). The greatest mean peak changes in BCVA lines of vision occurred in study eyes with uveitis (3.3±0.6, P<0.0001), followed by RVO (1.3±0.5, P<0.01) and DME (0.7±0.5, P>0.05). Significant decreases in CRT were observed: −255.6±43.6 μm for uveitis, −190.9±23.5 μm for DME, and −160.7±39.6 μm for RVO (P<0.0001 for all cohorts). IOP increases of ≥10 mmHg occurred in 20.6%, 24.1%, and 22.7% of DME, RVO, and uveitis study eyes, respectively. IOP-lowering medication was initiated in 29.4%, 16.7%, and 8.7% of DME, RVO, and uveitis study eyes, respectively. Glaucoma surgery was performed in 1.7% of all study eyes and cataract surgery in 29.8% of all phakic study eyes receiving DEX implant(s).ConclusionDEX implant(s) alone or combined with other treatments and/or procedures resulted in functional and anatomic improvements in long-standing ME associated with retinal disease.

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“…126 It was further suggested that corticosteroids may inhibit PLA2 and downstream products, for example, prostaglandins and leukotrienes, as well as inhibit adhesion signalling pathway components, including ICAM-1, IL-6, VEGF-A, and stromal cell-derived factor-1, which are involved in vascular permeability and leucocytosis (inflammation). 127 Steroids may also inhibit TJ disassembly. Further elucidation of the cellular mechanisms underlying increased permeability in diabetes and hyperglycaemia, and the effects of different pharmacologic agents and their interactions is required.…”

Section: Scientific Basismentioning

confidence: 99%

A review of therapies for diabetic macular oedema and rationale for combination therapy

Amoaku

Saker

Stewart

2015

Eye

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Diabetic macular oedema (DMO) is responsible for significant visual impairment in diabetic patients. The primary cause of DMO is fluid leakage resulting from increased vascular permeability through contributory anatomical and biochemical changes. These include endothelial cell (EC) death or dysfunction, pericyte loss or dysfunction, thickened basement membrane, loss or dysfunction of glial cells, and loss/change of EC Glycocalyx. The molecular changes include increased reactive oxygen species, pro-inflammatory changes: advanced glycation end products, intracellular adhesion molecule-1, Complement 5-9 deposition and cytokines, which result in increased paracellular permeability, tight junction disruption, and increased transcellular permeability. Laser photocoagulation has been the mainstay of treatment until recently when pharmacological treatments were introduced. The current treatments for DMO target reducing vascular leak in the macula once it has occurred, they do not attempt to treat the underlying pathology. These pharmacological treatments are aimed at antagonising vascular endothelial growth factor (VEGF) or non-VEGF inflammatory pathways, and include intravitreal injections of anti-VEGFs (ranibizumab, aflibercept or bevacizumab) or steroids (fluocinolone, dexamethasone or triamcinolone) as single therapies. The available evidence suggests that each individual treatment modality in DMO does not result in a completely dry macula in most cases. The ideal treatment for DMO should improve vision and improve morphological changes in the macular (eg, reduce macular oedema) for a significant duration, reduced adverse events, reduced treatment burden and costs, and be well tolerated by patients. This review evaluates the individual treatments available as monotherapies, and discusses the rationale and potential for combination therapy in DMO.

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The Multifactorial Nature of Retinal Vascular Disease

Cited by 21 publications

References 104 publications

Diabetic retinopathy: pathogenesis, clinical grading, management and future developments

Diabetic retinopathy: pathogenesis, clinical grading, management and future developments

Real-world assessment of intravitreal dexamethasone implant (0.7 mg) in patients with macular edema: the CHROME study

A review of therapies for diabetic macular oedema and rationale for combination therapy

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The Multifactorial Nature of Retinal Vascular Disease

Cited by 21 publications

References 104 publications

Diabetic retinopathy: pathogenesis, clinical grading, management and future developments

Diabetic retinopathy: pathogenesis, clinical grading, management and future developments

Real-world assessment of intravitreal dexamethasone implant (0.7&nbsp;mg) in patients with macular edema: the CHROME study

A review of therapies for diabetic macular oedema and rationale for combination therapy

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Product

Resources

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Real-world assessment of intravitreal dexamethasone implant (0.7 mg) in patients with macular edema: the CHROME study