Anna Praidou

Angiogenic Growth Factors and their Inhibitors in Diabetic Retinopathy

Diabetic retinopathy is considered one of the vision-threatening diseases among working-age population. The pathogenesis of the disease is regarded multifactorial and complex: capillary basement membrane thickening, loss of pericytes, microaneuryms, loss of endothelial cells, blood retinal barrier breakdown and other anatomic lesions might contribute to macular edema and/or neovascularization the two major and sight threatening complications of diabetic retinopathy. A number of proangiogenic, angiogenic and antiangiogenic factors are involved in the pathogenesis and progression of diabetic retinal disease, Vascular Endothelial Growth Factor (VEGF) being one of the most important. Other growth factors, which are known to participate in the pathogenesis of the disease, are: Platelet Derived Growth Factor (PDGF), Fibroblast Growth Factor (FGF), Hepatocyte Growth Factor (HGF), Transforming Growth Factor (TGF), Placental Endothelial Cell Growth Factor (PlGF), Connective Tissue Growth Factor (CTGF). Other molecules that are involved in the disease mechanisms are: intergrins, angiopoietins, protein kinase C (PKC), ephrins, interleukins, leptin, angiotensin, monocyte chemotactic protein (MCP), vascular cell adhesion molecule (VCAM), tissue plasminogen activator (TPA), and extracellular matrix metalloproteinases (ECM-MMPs). However, the intraocular concentration of angiogenic factors is counterbalanced by the ocular synthesis of several antioangiogenic factors such as pigment epithelial derived factor (PEDF), angiostatin, endostatin, thrombospondin, steroids, atrial natriuretic peptide (ANP), inteferon, aptamer, monoclonal antibodies, VEGF receptor blocker, VEGF gene suppressors, intracellular signal transduction inhibitors, and extracellular matrix antagonists. Growth stimulation or inhibition by these factors depends on the state of development and differentiation of the target tissue. The mechanisms of angiogenesis factor action are very different and most factors are multipotential; they stimulate proliferation or differentiation of endothelial cells. This review attempts to briefly outline the knowledge about peptide growth factor involvement in diabetic retinopathy. Further ongoing research may provide better understanding of molecular mechanisms, disease pathogenesis and therapeutic interactions.

Vitreous and serum levels of vascular endothelial growth factor and platelet-derived growth factor and their correlation in patients with non-proliferative diabetic retinopathy and clinically significant macula oedema.

Purpose:  To investigate possible correlations between vitreous and/or serum levels of platelet‐derived growth factor isoforms (PDGF‐AA, ‐AB and ‐BB) with parameters associated with non‐proliferative diabetic retinopathy (NPDR) and clinically significant macula oedema (CSMO); to compare the results to relevant results regarding vascular endothelial growth factor (VEGF), which is an established growth factor affecting NPDR.

Vitreous and Serum Levels of Platelet-Derived Growth Factor and Their Correlation in Patients with Proliferative Diabetic Retinopathy

Purpose: We investigated possible correlations between vitreous and/or serum levels of platelet derived growth factor isoforms (PDGF-AA, -AB, -BB) with parameters associated with proliferative diabetic retinopathy (PDR), and compared the results to vascular endothelial growth factor (VEGF), which is an established growth factor affecting PDR. Methods: Thirty-one patients with PDR and 15 non-diabetic patients were included in the study. Vitreous and serum samples were obtained during vitrectomy. PDGF-AA, -AB, and -BB, as well as VEGF, were measured by enzyme-linked immunosorbent assay. Results: PDGF-AA, -AB, -BB, and VEGF were all expressed in serum and vitreous of controls and patients with PDR. The levels of all PDGF isoforms and VEGF in vitreous were significantly increased in the PDR group, as compared to controls. No such differences were evident in serum. PDGF-AA and PDGF-BB correlated significantly to the severity but not the activity of PDR. PDGF-AB and -BB were significantly lower in vitreous of patients with pre-performed complete panretinal photocoagulation (PRP) as compared to incomplete or without PRP. PDGF did not correlate significantly to fibrovascular tissue, on the disc or elsewhere, to long-standing vitreous hemorrhage, to tractional retinal detachment, or to posterior vitreous detachment. PDGF or VEGF in vitreous or serum of PDR patients did not correlate with the serum levels of HbA1C. There was no correlation between the vitreous and serum levels of VEGF or PDGF in patients with PDR. Conclusions: It appears that, in addition to VEGF, PDGF-AA, -AB, and -BB in the vitreous are also correlated with PDR.

Antivascular endothelial growth factor agents for neovascular age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of severe visual loss and blindness over the age of 50 in developed countries. Vascular endothelial growth factor (VEGF) is considered as a critical molecule in the pathogenesis of choroidal neovascularization (CNV), which characterizes the neovascular AMD. Anti-VEGF agents are considered the most promising way of effectively inhibition of the neovascular AMD process. VEGF is a heparin-binding glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells. Two anti-VEGF agents have been approved by the US Food and Drug Administration (FDA) for the treatment of neovascular AMD. Pegaptanib sodium, which is an aptamer and ranibizumab, which is a monoclonal antibody fragment. Another humanized monoclonal antibody is currently off-label used, bevacizumab. This paper aims to discuss in details the effectiveness, the efficacy and safety of these three anti-VEGF agents. New anti-VEGF compounds which are recently investigated for their clinical usage (VEGF-trap, small interfering RNA) are also discussed for their promising outcomes.

Retinal vasculitis in rheumatic diseases: an unseen burden

Retinal vascular inflammation, a potentially blinding condition (herein: retinal vasculitis (RV)) is commonly associated with a heterogeneous group of diseases characterized by systemic inflammatory cell infiltration and/or necrosis of blood vessel walls. RV may arise as an isolated ocular disorder, as part of systemic vasculitis (Wegener’s granulomatosis and Adamantiadis–Behcet Disease), or it can be secondary to an underlying connective tissue disease (systemic lupus erythematosus, sarcoidosis, and rheumatoid arthritis), systemic infection, or malignancy. Depending on the type of RV, it can be a potentially disabling condition, in the short or long term. Early diagnosis is the key to successful treatment and better prognosis. However, early diagnosis can be difficult, because these conditions usually present with nonspecific visual symptoms for a long period before diagnostic manifestations occur. The retina should be examined in warranted patients with verified rheumatic disease, since retinal vasculitis may be asymptomatic at the beginning (peripheral retinal disease). RV can be detected clinically (often accompanied by uveitis, scleritis, or macular edema) or revealed on fluorescein fundus angiography, even if minimal signs of retinal vessel inflammation are present. RV may also represent one of the possible extra-articular manifestations of the rheumatic disease. Rheumatologists should be familiar with the ocular manifestations of these disorders, since they may not only be sight-threatening, but more importantly, could be the presenting or even the very first manifestations of active, potentially lethal systemic disease in a patient with nonspecific rheumatologic presentation.

Safety and efficacy of small incision, sutureless pars plana vitrectomy for patients with posterior segment complications secondary to uveitis

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OCT-3 Study of Serous Retinal Detachment in a Preeclamptic Patient

We report optical coherence tomography-3 (OCT-3) of retinal disorders in acute preeclampsia. A 33-year-old woman developed mind hypertension (170/90 mm Hg) and proteinuria in the 28th week of pregnancy. The patient complained of sudden and severe visual acuity decrease. Fundus exam showed bilateral serous retinal detachment at the macula area. OCT-3 exam demonstrated subretinal and intraretinal fluid. Bilateral serous retinal detachment is an unusual finding of preeclampsia of unknown aetiology. Intense arteriolar vasospasm has been implicated in the pathogenesis of the serous retinal detachment. OCT-3 showed the presence of both subretinal and intraretinal fluid during the acute phase of preeclampsia.

Diabetic Retinopathy Treated with Laser Photocoagulation and the Indirect Effect on Glycaemic Control

Purpose. To identify any possible relation between glycaemic control and previous laser photocoagulation for diabetic retinopathy. Methods. Seventy-two patients with diabetes were included in the study and were separated into 2 groups according to previous treatment (group A) or not (group B) with argon laser photocoagulation. Glycaemic control was estimated by measuring blood levels of HbA1c in four consecutive measurements. Results. Blood levels of HbA1c in group A were significantly lower 3, 6, and 12 months after laser treatment as compared to blood levels of HbA1c before laser treatment (7.1 ± 0.4% versus 7.6 ± 0.9%, 7.2 ± 0.2% versus 7.6 ± 0.9%, and 7.1 ± 0.2% versus 7.6 ± 0.9%, resp., all P < 0.05). Blood levels of HbA1c in group B did not differ significantly in four consecutive measurements. Conclusion. Our results suggest that we should anticipate a better glycaemic control in cases of patients with diabetes previously treated with laser photocoagulation.

Bilateral herpes simplex keratitis presenting as peripheral ulcerative keratitis.

Purpose: To report a case of bilateral Herpes simplex keratitis (HSK) masquerading as peripheral ulcerative keratitis (PUK). Methods: A case of a 47-year-old female complaining of painful red eyes with a history of arthritis and anterior uveitis attacks with positive antinuclear antibodies (ANA). Biomicroscopy revealed PUK, stromal infiltrations and bilateral central corneal epithelial erosions. Slit-lamp examination disclosed +3 anterior chamber cells in both eyes. Results: Blood testing was positive for ANA. Herpes simplex virus (HSV) antigen was identified in both eyes using polymerase chain reaction (PCR). The management included topical prednisolone and acyclovir, as well as systemic valacyclovir. Improvement of epithelial corneal defects, PUK, and visual acuity was achieved gradually during the follow-up period. Conclusions: Bilateral herpetic keratitis presenting as PUK is an extremely rare manifestation of herpetic disease. PUK can pose a diagnostic dilemma in cases with immune system dysregulation. Excluding infectious agents is mandatory for appropriate treatment.

Early diagnosis of Stargardt disease with multifocal electroretinogram in children

To present two pediatric cases where multifocal electroretinogram (mfERG) was able to establish an earlier diagnosis compared to full field electroretinogram (ERG) Case 1: an 11-year-old boy with reduced visual acuity, pale discs, macular pigmentation with white dots bilaterally. Case 2: a 12-year-old girl with reduced vision in her right eye, slight pallor of the right optic disc, intense pigmentation at both maculae and scattered punctate lesions throughout the peripheral fundi. Both had been investigated with electrodiagnostic tests according to the International Society of Clinical Electrophysiology for Vision protocol. Full-field ERGs for both children showed normal responses. Case 1: mfERG revealed a severe reduction in function in the inner 20°. Case 2: mfERG showed attenuated responses in each eye. Clinical examination and mfERG were consistent with Stargardt disease. mfERG is applicable to children and is a sensitive tool for early diagnosis of retinal dystrophies.