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Editorial

Expounding newer vistas in VEGF

Natarajan, Sundaram

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Indian Journal of Ophthalmology: January 2013 - Volume 61 - Issue 1 - p 1-2
doi: 10.4103/0301-4738.105047
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Dear Friends,

Year 2012 has been an eventful year for IJO with the introduction of several exciting features, the iPad app, the mobile downloads, author institute mapping and so on. Year 2013 promises to be even better as the Diamond Jubilee kicks off to a great start. Team IJO has several offerings for you starting with the monthly issues, a new look cover and an academic feast for your benefit.

As you can see, IJO has a brand new look for the Diamond Jubilee celebrations. I would like to invite you for a special session in APAO -AIOS 2013 in association with BJO and APJO to give insights into the world of research and publications. For the first time in the history of Ophthalmology, a special postage stamp is planned to be released by the IJO AIOS to commemorate 60 years of IJO! A truly magnificent feat indeed.

In this issue, I draw your attention to two diseases which are on the upswing in India and are threatening the health of the average Indian - Diabetes and Hypertension. An uninterrupted quest is on to delve deeper into the basic pathophysiology of these disorders and their complications. Evolving insight into the biochemical and molecular basis of these diseases is set to turn our present perception of diseases and their management upside down in coming years. This cannot be more obvious than in the management of retinal vascular diseases where the use of anti vascular endothelial growth factors (VEGFs) and interferons is now commonplace. This is a direct consequence of our better understanding of the biochemical mechanisms involved in these disorders.

Evolution of management of retinal venous occlusions (RVO) also reminds us of the importance of better understanding of the fine biochemical and molecular mechanisms which are at the core of every living system.

Once steroids were the only useful choice in the treatment of macular edema (ME) secondary to RVO, which was gradually replaced by anti-VEGF agents in a hope to address the underlying upregulation of VEGF's in retina and vitreous.[14]

However, newer insights into the biochemistry and molecular biology has again tilted the balance the other way and intravitreal steroids are now more preferred for the treatment of ME in RVO.

Though upregulation of VEGFs occur post venous occlusion, it is only a small piece in the big pathogenetic web of ME. Not only VEGF's but a number of cytokines and growth factors play their role in the breakdown of blood retinal barrier, evolution of ME and retinal neovascularization following retinal venous occlusions.[56] Presence of low grade inflammation in retina is also well documented in RVO.

Since anti-VEGF's target only VEGF isoforms, it could not be hailed as an appropriate treatment for ME following RVO. Also, VEGF's have been shown to have a protective role in retinal hemodynamics and have a neuroprotective role in hypoxic conditions. VEGF's also promote collateral vessels to overcome the effects of ischemic injuries and establish reperfusion of the retina. Anti-VEGF's are believed to induce vasoconstriction in macular capillary bed in hypoxic retina thereby perpetuating further hypoxic damage and macular ischemia.[710] Clinically anti-VEGF's are contraindicated in patients with macular or foveal ischemia. Shorter duration of stay of anti-VEGF's inside eyes may also necessitate repeated monthly injections of these agents.

It has been demonstrated that steroids are as effective in the management of ME by virtue of their broad spectrum anti-inflammatory property. Longer duration of action obviating the need for reinjection at short intervals is also a great advantage with intravitreal steroids.[11] Steroids also suppress VEGF's and in this way target a wider part of the pathophysiology involved in ME.

Intraocular pressure (IOP) rise following the injection of steroids may be a concern for some, although in a majority of patients rise is mild and easily controlled by topical antiglaucoma medications.[11]

Again, in this regard newer biochemical and molecular insights in the local regulation of glucocorticoid (GC) actions at the level of ocular tissues by 11 beta hydroxysteroid dehydrogenase 1 and 2 (11 beta HSD 1 and 2) and the role of GC in the regulation of aqueous formation and drainage through 11 beta HSD 1 (thus IOP regulation) offer fresh hope. This understanding might help us come up with novel steroid preparations which would be free of the IOP increasing property.[1214]

Intravitreal triamcinolone acetonide (IVTA) is the most commonly used intraocular steroid. Recently, sustained release intravitreal dexamethasone implants have been introduced. Incidence of ocular hypertension and cataract progression have been claimed to be lower than IVTA.[1516] Clinical studies are awaited for the further evaluation of the role of these newer modalities in retinal vascular disorders.

In this issue Senturk et al., has evaluated the role of IVTA on retinal sensitivity as evaluated by microperimetry, in cases of ME secondary to branch retinal vein occlusion (BRVO). This is definitely a better approach than only assessing visual acuity, which is a foveal function, to judge the effectiveness of a treatment in these cases. Authors approach will help in better assessment of the entire visual function, which is of more importance from the patient point of view, in response to the treatment. First time microperimetry of the macular area has been simultaneously used with objective assessment of morphological changes at macula by optical coherence tomography (OCT) in cases of ME associated with BRVO in this study.

I hope further advances anticipated in the understanding of biochemical and molecular processes of the living systems will help patients in a better way.

I will keep you updated on the upcoming events in this very special Diamond Jubilee year!

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    3. Tolentino MJ, Miller JW, Gragoudas ES, Jakobiec FA, Flynn E, Chatzistefanou K, et al Intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate Ophthalmology. 1996;103:1820–8
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      5. Shimura M, Nakazawa T, Yasuda K, Kunikata H, Shiono T, Nishida K. Visual prognosis and vitreous cytokine levels after arteriovenous sheathotomy in branch retinal vein occlusion associated with macular oedema Acta Ophthalmol. 2008;86:377–84
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          10. Papadopoulou DN, Mendrinos E, Mangioris G, Donati G, Pournaras CJ. Intravitreal ranibizumab may induce retinal arteriolar vasoconstriction in patients with age-related macular degeneration Ophthalmology. 2009;116:1755–61
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          12. Rauz S, Walker EA, Shackleton CH, Hewison M, Murray PI, Stewart PM. Expression and putative role of 11b-hydroxysteroid dehydrogenase isozymes within the human eye Invest Ophthalmol Vis Sci. 2001;42:2037–42
          13. Suzuki T, Sasano H, Kaneko C, Ogawa S, Darnel AD, Krozowski ZS. Immunohistochemical distribution of 11bhydroxysteroid dehydrogenase in human eye Mol Cell Endocrinol. 2001;173:121–5
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            15. Yeh W, Haller J, Lanzetta P, Kuppermann B, Wong T, Mitchell P. Effect of the duration of macular edema on clinical outcomes in retinal vein occlusion treated with dexamethasone intravitreal implant Ophthalmology. 2012;119:1190–8
            16. Haller JA, Bandello F, Belfort R Jr, Blumenkranz MS, Gillies M, Heier J, et alOzurdex GENEVA Study Group. Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion: twelve-month study results Ophthalmology. 2011;118:2453–60
            © 2013 Indian Journal of Ophthalmology | Published by Wolters Kluwer – Medknow