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      Longitudinal Changes in Retinal Nerve Fiber Layer Thickness after Intravitreal Anti-vascular Endothelial Growth Factor Therapy

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          Abstract

          Purpose

          To determine the effects of intravitreal anti-vascular endothelial growth factor (VEGF) on thickness of the retinal nerve fiber layer (RNFL) in patients with age-related macular degeneration.

          Methods

          Twenty eyes of 20 patients diagnosed with age-related macular degeneration who underwent intravitreal anti-VEGF injection were studied. Postinjection RNFL thickness was measured using optical coherence tomography. Average thickness, four-quadrant RNFL thicknesses, and intraocular pressure (IOP) in affected eyes were measured before and 6 and 12 months after anti-VEGF injection for comparison. RNFL thickness and IOP in affected and normal fellow eyes were also compared. Given that macular lesions can affect RNFL thickness, the changes in thickness were evaluated by dividing the 12 clock-hour RNFL into the pathologic areas adjacent to the lesion and the non-pathologic area.

          Results

          The mean clock-hour segment in the pathologic area was 4.8 hours. A significantly thicker RNFL was exhibited in temporal quadrants and pathologic areas ( p = 0.043 and 0.048, respectively) in affected eyes before injection compared to the baseline RNFL thickness in normal eyes. No significant differences were found in RNFL thickness or IOP between affected and normal eyes after injection. The changes over time in the temporal and pathologic areas were statistically significant at 6 and 12 months after injection compared to baseline data ( p < 0.05). No significant differences were displayed in RNFL thickness in the other three quadrants or in non-pathologic areas in either affected or normal eyes. Sequential changes in RNFL thickness in affected eyes were not significant.

          Conclusions

          Repeat intravitreal anti-VEGF treatment did not have a significant effect on RNFL thickness. RNFL thickness significantly decreased with time in the pathologic areas and in the temporal segment adjacent to exudative macular lesions. The reduction in RNFL thickness was most likely associated with changes in the macular lesion rather than with anti-VEGF injection.

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          Most cited references18

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          Neuroprotective Role of Vascular Endothelial Growth Factor: Signalling Mechanisms, Biological Function, and Therapeutic Potential

          Vascular endothelial growth factor (VEGF or VEGF-A) and its receptors play essential roles in the formation of blood vessels during embryogenesis and in disease. Most biological effects of VEGF are mediated via two receptor tyrosine kinases, VEGFR1 and VEGFR2, but specific VEGF isoforms also bind neuropilins (NP) 1 and 2, non-tyrosine kinase receptors originally identified as receptors for semaphorins, polypeptides with essential roles in neuronal patterning. There is abundant evidence that VEGF-A has neurotrophic and neuroprotective effects on neuronal and glial cells in culture and in vivo, and can stimulate the proliferation and survival of neural stem cells. VEGFR2 and NP1 are the major VEGF receptors expressed on neuronal cells and, while the mechanisms mediating neuroprotective effects of VEGF are not fully understood, VEGF stimulates several signalling events in neuronal cell types, including activation of phospholipase C-γ, Akt and ERK. Findings in diverse models of nerve damage and disease suggest that VEGF has therapeutic potential as a neuroprotective factor. VEGF is a key mediator of the angiogenic response to cerebral and peripheral ischaemia, and promotes nerve repair following traumatic spinal injury. Recent work has revealed a role for reduced VEGF expression in the pathogenesis of amyotrophic lateral sclerosis, a rare neurodegenerative disease caused by selective loss of motor neurons. In many instances, the neuroprotective effects of VEGF appear to result from a combination of the indirect consequences of increased angiogenesis, and the direct stimulation of neuronal function. However, more work is required to determine the specific functional role of direct neuronal effects of VEGF.
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            Short-term intraocular pressure changes immediately after intravitreal injections of anti-vascular endothelial growth factor agents.

            To assess short-term trends and the need to monitor intraocular pressure (IOP) changes immediately after intravitreal injections of ranibizumab, bevacizumab, pegaptanib, and triamcinolone acetonide. Retrospective, interventional case series. Charts of 213 consecutive injections to 120 eyes of 112 patients were reviewed. Pressures were measured before injection, immediately after injection (T0), and at five-minute intervals until IOP was less than 30 mm Hg. Optic nerve perfusion was assessed by testing for hand movement vision and by indirect ophthalmoscopic examination. Kaplan-Meier and Chi-square analyses of IOP after injections and correlation of IOP spikes to drug, needle bore size, injection volume, and history of glaucoma were performed. Mean preinjection IOP was 14 mm Hg (range, 7 to 22 mm Hg). Mean IOP at T0 was 44 mm Hg (range, 4 to 87 mm Hg). All but one eye had at least hand movement vision and a perfused optic nerve at T0. IOP was reduced to less than 30 mm Hg in 96% of injections by 15 minutes and in 100% by 30 minutes. Eyes with a history of glaucoma took longer to normalize the IOP (P = .002). Statistically significant IOP spikes were observed with a smaller needle bore size (P < .0001) and in eyes with a history of glaucoma (P = .001). Elevations in IOP immediately after intravitreal injections are common, but are transient. Prolonged monitoring of IOP may not be necessary on the day of injection in most cases if hand movement vision, optic nerve perfusion, and lack of intraocular complications have been verified. However, cautious monitoring should be considered in select cases.
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              Complications of intravitreal injections.

              Over the past few years, the results of many studies have highlighted the risks and benefits of intravitreal injection of a number of medications, the most common being triamcinolone, antivascular endothelial growth factor (VEGF) agents, antibiotics, antivirals, antifungals, and methotrexate. The purpose of this review is to highlight the complications associated with these injections. Elevated intraocular pressure and glaucoma are the most common complications of intraocular triamcinolone. There is also an increased incidence of cataract formation/progression over time. The immunosuppressive effect of triamcinolone does not appear to increase the risk of endophthalmitis. Recent reports suggest that intravitreal anti-VEGF injections have a low complication rate. Similarly, antimicrobials also have low rates of injection-associated complications. Intravitreal injections play a critical role in daily ophthalmic practice. The overall risk of endophthalmitis and retinal detachment appears to be low and most of the commonly used drugs are well tolerated, even with repeat injection. Further long-term studies need to be performed to elucidate ways of increasing the safety of these procedures and medications.
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                Author and article information

                Journal
                Korean J Ophthalmol
                Korean J Ophthalmol
                KJO
                Korean Journal of Ophthalmology : KJO
                The Korean Ophthalmological Society
                1011-8942
                April 2016
                25 March 2016
                : 30
                : 2
                : 114-120
                Affiliations
                [1 ]Department of Ophthalmology, Chungnam National University College of Medicine, Daejeon, Korea.
                [2 ]Research Institute for Medical Science, Chungnam National University College of Medicine, Daejeon, Korea.
                Author notes
                Corresponding Author: Jung-Yeul Kim, MD. Department of Ophthalmology, Chungnam National University Hospital, #282 Munhwa-ro, Jung-gu, Daejeon 35015, Korea. Tel: 82-42-280-8433, Fax: 82-42-255-3745, kimjy@ 123456cnu.ac.kr
                Article
                10.3341/kjo.2016.30.2.114
                4820521
                27051259
                d681de49-77f6-46b5-a6c7-a48ca60637e3
                © 2016 The Korean Ophthalmological Society

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 May 2015
                : 13 July 2015
                Categories
                Original Article

                Ophthalmology & Optometry
                anti-vascular endothelial growth factor,optical coherence tomography,retinal nerve fiber layer

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