maculopatia

Studio randomizzato sull’uso del pazopanib in collirio per la maculopatia essudativa.

Posted by Emilio Simongini on April 08, 2014
maculopatia essudativa, maculopatie / No Comments

A cura del dottor Emilio Simongini

Questo studio valuta l’efficacia di un farmaco inibitore del VEGF utilizzato per via topica nel trattamento della maculopatia essudativa.
I risultati preliminari mostrano una sua efficacia sia nei confronti dello spessore retinico sia nel migliorare l’acuità visiva dopo un mese di terapia topica. Non si sono registrati eventi avversi significativi, per cui le sperimentazioni di tale via di somministrazione potranno proseguire.
La particolarità evidenziata dallo studio è che l’efficacia terapeutica differisce molto a seconda dell’assetto genetico dei pazienti e, in particolare, rispetto alla presenza dell’allele CFH Y402H TT.
Lo spessore retinico, infatti, non si riduceva in tutti i pazienti ma solo nei portatori del CFH TT.
L’acuità visiva migliorava in tutti, ma in maniera diversificata: di 4.3 lettere nella media, di 6.9 lettere nei portatori di CFH TT e di 4.1 lettere nei portatori di CFH CT.
Ancora una volta viene confermata l’importanza di una correlazione tra assetto genetico e sensibilità alle terapie biologiche di ultima generazione.

Pazopanib eye drops: a randomised trial in neovascular age-related macular degeneration
Ronald Danis, Megan M McLaughlin, Michael Tolentino, Giovanni Staurenghi, Li Ye, Chun-Fang Xu, Robert Y Kim, Mark W Johnson
Br J Ophthalmol 2014;98:172-178 doi:10.1136/bjophthalmol-2013-303117

Methods 70 patients with minimally classic or occult subfoveal choroidal neovascularisation were randomly assigned to 5 mg/mL TID, 2 mg/mL TID, and 5 mg/mL QD pazopanib eye drops for 28 days in a multicentre, double-masked trial with an optional safety extension for up to 5 additional months. The primary outcomes were central retinal thickness (CRT) and best-corrected visual acuity (BCVA) at Day 29.
Results No significant decrease from baseline in CRT was observed overall; however, an exploratory analysis showed improvement in CRT (mean decrease of 89 μm) in patients with the CFH TT genotype who received 5 mg/mL TID (p=0.01, n=5). Mean increases in BCVA were observed in the 5 mg/mL TID overall (4.32 letters (p=0.002, n=26)) and in those that with CFH Y402H TT (6.96 letters (p=0.02, n=5)) and CT (4.09 letters (p=0.05, n=9)) genotypes. No safety signals that precluded continued investigation were detected.
Conclusions 5 mg/mL pazopanib eye drops resulted in mean improvement in BCVA at Day 29 and improvements in vision. However, improvement in macular oedema for age-related macular degeneration was found only in the subset of subjects with the CFH Y402H TT genotype, warranting further investigation.

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La prognosi visiva nella maculopatia essudativa è influenzata dalla rapidità di intervento.

Posted by Emilio Simongini on April 08, 2014
maculopatia essudativa, maculopatie / No Comments

A cura del dottor Emilio Simongini

In questo studio si è valutato l’impatto prognostico del ritardato trattamento con iniezioni intravitreali della maculopatia essudativa al suo esordio.
Si è verificato che il tempo trascorso dalla comparsa dei sintomi alla prima iniezione influenza la prognosi e la possibilità di conservare l’acuità visiva, indipendentemente da sesso, età e acuità visiva di base. Ritardare la prima iniezione di più di 21 settimane aumenta di 2.6 volte il rischio di cattivi esiti visivi rispetto ad un ritardo inferiore di 7 settimane o meno.
Lo studio conferma che l’efficacia delle terapie intravitreali è legata alla precocità della diagnosi e alla tempestività dell’intervento.

Delay to Treatment and Visual Outcomes in Patients Treated With Anti-Vascular Endothelial Growth Factor for Age-Related Macular Degeneration
Jonathan H. Lim Sanjeewa S. Wickremasinghe Jing Xie, Devinder S. Chauhan, Paul N. Baird, Luba D. Robman, Gregory Hageman, Robyn H. Guymer
American Journal of Ophthalmology, April 2012

Purpose To investigate the potential influences that affect visual acuity (VA) outcome in a clinic-based cohort of age-related macular degeneration (AMD) patients undergoing anti–vascular endothelial growth factor (anti-VEGF) treatment for choroidal neovascularization.
Design Prospective interventional case series.
Methods Patients with subfoveal choroidal neovascularization (CNV) secondary to AMD were prospectively recruited. A detailed questionnaire was given to patients at time of enrollment, to collect information relating to demographics, history of visual symptoms, visual acuity (VA), and treatment scheduling. Delay from symptoms to treatment (“Treatment delay”) was measured in terms of weeks and analyzed in tertiles. Information pertaining to treatment outcomes was collected over a 6-month period.
Results One hundred eighty-five eyes of 185 patients were recruited into the study. Longer delay from first symptoms suggestive of CNV to first injection was a significant predictor (P = .015) of poorer treatment outcome, when controlling for age, sex, and baseline VA. Patients with a delay in treatment of 21 weeks or more compared to a delay of 7 weeks or less had an odds ratio of 2.62 (1.20, 5.68) for worsening vision after treatment.
Conclusions Patients experiencing a longer delay between their first symptoms of CNV and their first anti-VEGF treatment have a significantly lower chance of improving vision at 6 months following anti-VEGF therapy. It is critical that this information reach those at potential vision loss from AMD, in order that prompt treatment may be instituted, to maximize the benefits of anti-VEGF treatment.

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Aumento della pressione oculare in seguito a numerose iniezioni intravitreali.

Posted by Emilio Simongini on April 08, 2014
glaucoma, maculopatia essudativa, maculopatie / No Comments

A cura del dottor Emilio Simongini

Usualmente le iniezioni intravitreali non comportano un aumento patologico del tono oculare. Gli autori dello studio mettono in guardia che è sempre possibile che tale condizione si verifichi con il proseguire delle iniezioni. Riportano una casistica di 25 occhi che dopo una media di 20 iniezioni manifestano toni molto elevati (anche 35 mm Hg). Pertanto l’insorgenza del glaucoma, in questi occhi, deve essere sempre temuta e un regolare monitoraggio della pressione intraoculare è indicato anche per quegli occhi che non hanno mai manifestato precedenti innalzamenti.

Sustained Increased Intraocular Pressure Related to Intravitreal Antivascular Endothelial Growth Factor Therapy for Neovascular Age-related Macular Degeneration
Tseng, Joseph J. MD*,†,‡; Vance, Sushma K. MD*,†,§; Della Torre, Kara E. MD*,†,§; Mendonca, Luis S. MD*,†; Cooney, Michael J. MD, MBA*,†,§; Klancnik, James M. MD*,†,§; Sorenson, John A. MD*,†,§; Freund, K. Bailey MD*,†,‡,§
Journal of Glaucoma: April/May 2012 – Volume 21 – Issue 4 – p 241–247

Abstract
Purpose: To describe a series of previously normotensive eyes experiencing sustained elevated intraocular pressure (IOP) associated with long-term intravitreal antivascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (AMD).
Patients and Methods: Clinical data were reviewed for 25 eyes of 23 patients with neovascular AMD who had increased IOP while receiving interval doses of intravitreal ranibizumab and/or bevacizumab. All eyes had tolerated multiple anti-VEGF injections in the past without IOP elevations.
Results: After a mean of 20.0 anti-VEGF injections (range, 8-40 injections), the mean IOP was 29.8 mm Hg (range, 22-58 mm Hg), compared with a baseline of 16.9 mm Hg (range, 14-21 mm Hg). The mean highest IOP while receiving intravitreal anti-VEGF therapy was 35.8 mm Hg (range, 23-58 mm Hg). Overall, 23 of 25 cases required IOP management. In the remaining 2 cases, anti-VEGF dosing was switched from regular interval dosing to an optical coherence tomography-guided variable regimen, with subsequent improvement in IOP without antiglaucoma treatment.
Conclusions: Serial injections of anti-VEGF agents may lead to persistent IOP elevations that require glaucoma therapy. The clinician should recognize this phenomenon, as it can occur even if the patient has tolerated multiple prior injections without IOP elevation. Further exploration of the relationship between anti-VEGF therapy and IOP is needed.

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Efficacia del farmaco Eylea nei casi resistenti al trattamento con Lucentis o Avastin.

Posted by Emilio Simongini on April 08, 2014
maculopatia essudativa, maculopatie / No Comments

A cura del dottor Emilio Simongini

In questo studio occhi affetti da maculopatia essudativa, già trattati con iniezioni intratìvitreali di Lucentis o Avastin, che mostravano una persistenza del quadro essudativo, sono stati trattati con il nuovo farmaco Eylea. I risultati mostrano una significativa risposta con il nuovo trattamento, che riguarda soprattutto l’aspetto anatomico e la scomparsa di fluido all’esame OCT, mentre vantaggi meno netti si sono avuti sotto il profilo del miglioramento visivo.

L’Eylea si conferma un prezioso strumento terapeutico nel trattamento della maculopatia senile essudativa, in particolar modo nei casi aggressivi e resistenti alle altre terapie oggi disponibili.

Aflibercept for exudative AMD with persistent fluid on ranibizumab and/or bevacizumab
Hyung Cho, Chirag P Shah, Marissa Weber, Jeffrey S Heier
Br J Ophthalmol 2013;97:1032-1035 doi:10.1136/bjophthalmol-2013-303344

Abstract
Objective To investigate the effect of aflibercept 2.0 mg in cases resistant to ranibizumab 0.5 mg and/or bevacizumab 1.25 mg treatment.
Purpose To evaluate the anatomic and visual effect of intravitreal aflibercept 2.0 mg in cases of exudative age-related macular degeneration (AMD) with persistent fluid on optical coherence tomography (OCT) despite regular ranibizumab 0.5 mg and/or bevacizumab 1.25 mg treatment at 1 and 6 months.
Methods Retrospective review at Ophthalmic Consultants of Boston, Boston, Massachusetts, USA of exudative AMD cases with persistent fluid on regular ranibizumab 0.5 mg and/or bevacizumab 1.25 mg treatment switched to intravitreal aflibercept 2.0 mg treatment and followed for 6 months. Tabulated data included details of prior treatments, best available visual acuity, central subfoveal thickness on registered spectral domain OCT before and after aflibercept injection centred on the anatomic fovea and macular description before and after aflibercept injection.
Results A total of 353 eyes with exudative AMD were switched to aflibercept during the study period. Of these, 28 eyes in 28 patients had persistent fluid after an average of 20 regular ranibizumab/bevacizumab injections (range 7–37). At 1 month, 89% (25 eyes) showed anatomic improvement and 18% (five eyes) were dry after a single aflibercept injection. Central subfoveal thickness improved from 295 to 272 microns (p<0.001) after one aflibercept injection. After an average of 4.4 aflibercept injections (range 3–6) over 6 months, the central subfoveal thickness remained improved (274 microns, p=0.008); 64% (18 eyes) showed anatomic improvement and a quarter of eyes (25%, seven eyes) were dry. Visual acuity did not improve at 1 month (logarithm of minimum angle of resolution (logMAR) 0.54, Snellen 20/69, p=0.64) or 6 months (logMAR 0.57, Snellen 20/76, p=0.49). Treatment was well tolerated with no adverse events reported.
Conclusions A significant proportion of exudative AMD cases with persistent fluid on OCT despite regular ranibizumab 0.5 mg and/or bevacizumab 1.25 mg treatment respond anatomically to aflibercept 2.0 mg. Visual acuity did not improve. Aflibercept may be beneficial anatomically in cases of exudative AMD treated with persistent fluid on ranibizumab and/or bevacizumab.

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Efficacia dell’Eylea nei casi di maculopatia essudativa resistenti al Lucentis.

Posted by Emilio Simongini on April 08, 2014
maculopatia essudativa, maculopatie / No Comments

A cura del dottor Emilio Simongini

Un ulteriore studio conferma l’efficacia dell’Aflibercept (Eylea) nel trattamento della maculopatia essudativa, anche dei casi resistenti al trattamento con Lucentis. Gli autori hanno riscontrato miglioramenti nell’essudazione, nel sollevamento dell’epitelio pigmentato (PED) e nell’acuità visiva passando dal Ranizumab (Lucentis) all’Aflibercept (Eylea).

Visual and Anatomical Outcomes of Intravitreal Aflibercept in Eyes With Persistent Subfoveal Fluid Despite Previous Treatments With Ranibizumab in Patients With Neovascular Age-Related Macular Degeneration
Kumar, Nishant FRCOphth*,†; Marsiglia, Marcela MD, PhD*,‡,§; Mrejen, Sarah MD*; Fung, Adrian Tien-chin MBBS, MMed*; Slakter, Jason MD*,‡; Sorenson, John MD*,‡; Freund, K. Bailey MD*,‡,§
Retina: September 2013 – Volume 33 – Issue 8 – p 1605-1612

Abstract
Purpose: To assess the efficacy of intravitreal aflibercept (2.0 mg) in patients with treatment-resistant neovascular age-related macular degeneration.
Methods: Retrospective analysis of eyes treated with aflibercept with persistent subretinal and/or intraretinal fluid despite previous treatments with intravitreal ranibizumab (0.5 mg). All patients were switched to intravitreal aflibercept (2.0 mg) and analyzed after 3 consecutive injections and after 6 months of treatment. Main outcome measures included change in visual acuity, central foveal thickness, and the height and diameter of the pigment epithelial detachment on the subfoveal scan on optical coherence tomography.
Results: Thirty-four eyes of 33 patients were analyzed. Mean duration of symptoms and average number of previous injections with anti–vascular endothelial growth factor agents was 44.7 ± 29.8 months (interquartile range [IQR] 24–76 months) and 28.6 ± 20.1 (IQR 10–47), respectively. At the 6-month follow-up, mean visual acuity and central foveal thickness improved significantly from 20/75 (logarithm of minimum angle of resolution 0.57 ± 0.36; IQR 0.30–1.0) and 416 ± 217 μm (IQR 263–487 μm) at baseline to 20/60 (logarithm of minimum angle of resolution 0.47 ± 0.32; IQR 0.30–0.60) (P = 0.004) and 248 ± 171 μm (IQR 235–419 μm) (P < 0.001), respectively. Maximum pigment epithelial detachment height improved significantly from 260 ± 162 μm (IQR 129–368 μm) to 214 ± 142 μm (IQR 111–305 μm) (P < 0.001) and PED diameter decreased significantly from 3,265 ± 1,622 μm (IQR 2,353–4,555 μm) to 2,949 ± 1,653 μm (IQR 1,721–4,484 μm) (P = 0.04).
Conclusion: Intravitreal injections of aflibercept resulted in a significant improvement in visual and anatomical outcomes in eyes with persistent subfoveal fluid despite previous treatment with ranibizumab.

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Prevenzione della maculopatia attraverso un’azione sul colesterolo.

Posted by Emilio Simongini on May 08, 2013
maculopatie / No Comments
Abstract a cura del dottor Emilio Simongini – maculopatia, prevenzione, colesterolo

In questa ricerca vengono dimostrati i meccanismi biochimici e genetici per i quali il metabolismo alterato del colesterolo determina il danno alla base della degenerazione maculare. In questo processo patologico sono coinvolte le cellule macrofagi che, la cui capacità di eliminare i depositi di colesterolo dai tessuti risulta alterata.

Impaired Cholesterol Efflux in Senescent Macrophages Promotes Age-Related Macular Degeneration
Cell Metabolism, Volume 17 , Issue 4, 549-561, 2 April 2013
Copyright © 2013 Elsevier Inc. All rights reserved.
Abdoulaye Sene, Aslam A. Khan, Douglas Cox, Rei E.I. Nakamura, Andrea Santeford, Bryan M. Kim, Rohini Sidhu, Michael D. Onken, J. William Harbour, Shira Hagbi-Levi, Itay Chowers, Peter A. Edwards, Angel Baldan, John S. Parks, Daniel S. Ory, Rajendra S. Apte

Summary
Pathologic angiogenesis mediated by abnormally polarized macrophages plays a central role in common age-associated diseases such as atherosclerosis, cancer, and macular degeneration. Here we demonstrate that abnormal polarization in older macrophages is caused by programmatic changes that lead to reduced expression of ATP binding cassette transporter ABCA1. Downregulation of ABCA1 by microRNA-33 impairs the ability of macrophages to effectively efflux intracellular cholesterol, which in turn leads to higher levels of free cholesterol within senescent macrophages. Elevated intracellular lipid polarizes older macrophages to an abnormal, alternatively activated phenotype that promotes pathologic vascular proliferation. Mice deficient for Abca1, but not Abcg1, demonstrate an accelerated aging phenotype, whereas restoration of cholesterol efflux using LXR agonists or miR-33 inhibitors reverses it. Monocytes from older humans with age-related macular degeneration showed similar changes. These findings provide an avenue for therapeutic modulation of macrophage function in common age-related diseases.
Prevenzione della maculopatia attraverso un’azione sul colesterolo.

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Trattamento della neovascolarizzazone coroideale idiopatica dei giovani adulti con iniezione intravitreale di Avastin

Posted by Emilio Simongini on June 13, 2012
maculopatie / No Comments
A cura del dottor Emilio Simongini – Bevacizumab, Avastin, intravitreale, maculopatia, maculopatia idiopatica giovanile

In questo studio si dimostra l’efficacia e la sicurezza dell’avastin nel trattamento delle forme idiopatiche giovanili di maculopatia con neovascolarizzazione. In 12 mesi la media delle somministrazioni era di 3.95 e tutti gli occhi stuidiati (20) hanno ottenuto una stabilizzazione o un miglioramento della visione.

Functional Recovery After Intravitreal Bevacizumab Treatments for Idiopathic Choroidal Neovascularization in Young Adults

Wang, Fenghua MD, PhD; Wang, Wenqiu MD; Yu, Suqin MD; Wang, Weijun MD; Lu, Fengqing MD; Xu, Feiping MD; Hu, Weiting MD; Jiang, Yuan MD; Wu, Ying BA; Wang, Hong MD; Xu, Xun MD; Sun, Xiaodong MD, PhD

Retina: April 2012 – Volume 32 – Issue 4 – p 679–686

Methods: For this interventional case series, 20 eyes of 19 patients with idiopathic choroidal neovascularization were treated with multiple intravitreal injections of bevacizumab. Changes in best-corrected visual acuity before the treatment and at follow-up visits were recorded. Structural changes were evaluated using optical coherence tomography and functional changes were assessed using microperimetry.

Results: Twenty eyes were followed for 12 months after their first injection. The eyes underwent an average of 3.95 injections. All eyes had a stable or an improved vision. The mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.43 to 0.06 (Wilcoxon signed-ranks test, P < 0.005). Improvement in macular function was detected as early as 1 month after the treatment and lasted for at least 6 months. Microperimetry demonstrated that mean retinal sensitivities within the central 10° field (10.29 ± 5.12 dB) at baseline improved to 13.98 ± 3.96 dB at the last visit. Dense scotomas were found in 13 of the 20 eyes at baseline and 5 of the 20 eyes at the last visit. Stable fixation (6 of 20 at baseline) was found in 17 of the 20 eyes at the last visit. Twelve of the 14 eyes with either a predominantly eccentric or poor central fixation at baseline established central fixation at 12 months. No serious local or systemic complications were encountered.

Conclusion: In young adults with idiopathic choroidal neovascularization, an improvement in visual acuity and macular function was detected after intravitreal injections of bevacizumab.

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Trattamento delle teleangiectasie perrifoveali con Ranizumab

Posted by Emilio Simongini on June 13, 2012
maculopatie / No Comments
A cura del dottor Emilio Simongini – Lucentis, intravitreali, maculopatia, teleangiectasie perifoveali

In questo lavoro viene confermata la difficoltà nell’ottenere buoni risultati terapeutici in questa particolare forma di maculopatia su base vascolare. A distanza di 12 mesi, nonostante un misurabile effetto positivo sullo stato anatomico della retina, non si è riuscito ad ottenere un miglioramento visivo significativo in questa serie di pazienti trattati con Ranizumab (Lucentis) intravitreale.

TREATMENT OF NONNEOVASCULAR IDIOPATHIC MACULAR TELANGIECTASIA TYPE 2 WITH INTRAVITREAL RANIBIZUMAB: Results of a Phase II Clinical Trial

Toy, Brian C. BS*; Koo, Euna MD*; Cukras, Catherine MD, PhD*; Meyerle, Catherine B. MD*; Chew, Emily Y. MD*; Wong, Wai T. MD, PhD†

Retina: May 2012 – Volume 32 – Issue 5 – p 996–1006

Methods: Single-center, open-label Phase II clinical trial enrolling five participants with bilateral nonneovascular idiopathic macular telangiectasia Type 2. Intravitreal ranibizumab (0.5 mg) was administered every 4 weeks in the study eye for 12 months with the contralateral eye observed. Outcome measures included changes in best-corrected visual acuity, area of late-phase leakage on fluorescein angiography, and retinal thickness on optical coherence tomography.

Results: The study treatment was well tolerated and associated with few adverse events. Change in best-corrected visual acuity at 12 months was not significantly different between treated study eyes (0.0 ± 7.5 letters) and control fellow eyes (+2.2 ± 1.9 letters). However, decreases in the area of late-phase fluorescein angiography leakage (−33 ± 20% for study eyes, +1 ± 8% for fellow eyes) and in optical coherence tomography central subfield retinal thickness (−11.7 ± 7.0% for study eyes and −2.9 ± 3.5% for fellow eyes) were greater in study eyes compared with fellow eyes.

Conclusion: Despite significant anatomical responses to treatment, functional improvement in visual acuity was not detected. Intravitreal ranibizumab administered monthly over a time course of 12 months is unlikely to provide a general and significant benefit to patients with nonneovascular idiopathic macular telangiectasia Type 2.

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Effetti dell’iniezione intravitreale di Avastin sull’emodinamica oculare

Posted by Emilio Simongini on June 13, 2012
maculopatie / No Comments
A cura del dottor Emilio Simongini – maculopatia, Avastin, Bevacizumab, neovascolarizzazione, intravitreali, maculopatia degenerativa

In questo lavoro i ricercatori hanno misurato l’effetto dell’iniezione intravitreale di Avastin sull’emodinamica oculare mediante l’ultrasonografia color Doppler. E’ stata confrontata l’emodinamica dell’occhio che riceveva l’iniezione e dell’occhio adelfo.

È risultata un effetto significativo sull’emodinamica oculare con riduzione della velocità sistolica di picco ed aumento degli indici di resistenza a carico dell’arteria centrale della retina e delle arterie ciliari posteriori brevi. Anche nell’occhio controlaterale si è registrata una riduzione della velocità sistolica di picco ma non un aumento delle resistenze.

Questi dati sono importanti per comprendere l’effetto bilaterale della singola iniezione e valutare con maggiore prudenza la condizione di occhi con preesistenti difficoltà di perfusione.

Effect of Intravitreal Bevacizumab on Retrobulbar Blood Flow in Injected and Uninjected Fellow Eyes of Patients With Neovascular Age-Related Macular Degeneration

Hosseini, Hamid MD*; Lotfi, Mehrzad MD†; Esfahani, Mina Heidari MD†; Nassiri, Nariman MD‡; Khalili, Mohammad Reza MD*; Razeghinejad, Mohammad Reza MD*; Nouri-Mahdavi, Kouros MD, Msc§

Retina:May 2012 – Volume 32 – Issue 5

Methods: In this prospective study, the retrobulbar hemodynamics of 43 patients with neovascular age-related macular degeneration was examined by color Doppler ultrasonography. Peak systolic velocity, end-diastolic velocity, and resistive index values in the central retinal artery and short posterior ciliary artery in both injected and uninjected fellow eyes were measured at baseline and 7 days after a single intravitreal injection of bevacizumab.

Results: At baseline, the peak systolic velocity, end-diastolic velocity, and the resistive index in the central retinal artery and short posterior ciliary artery of the injected eye were not significantly different compared with the fellow uninjected eye (P > 0.05 for all). However, intravitreal bevacizumab induced a significant reduction in the peak systolic velocity and end-diastolic velocity and a significant rise in the resistive index of the central retinal artery and short posterior ciliary artery of the injected eyeP ≤ 0.006 for all). Peak systolic velocity and end-diastolic velocity decreased in the central retinal artery (P = 0.023 and P = 0.030) and the short posterior ciliary artery (P = 0.001 and P < 0.000) in the uninjected eye while the resistive index did not significantly change in central retinal artery (P = 0.114) and short posterior ciliary artery (P = 0.082) of the fellow eyes.

Conclusion: Intravitreal injection of bevacizumab significantly affects ocular hemodynamic parameters of both the injected and the uninjected fellow eyes with neovascular age-related macular degeneration.

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Effetto della nicotina sulle terapie per la maculopatia degenerativa

Posted by Emilio Simongini on June 13, 2012
maculopatia senile, maculopatie / No Comments
A cura del dottor Emilio Simongini – maculopatia, nicotina, fumo, neovascolarizzazione, maculopatia degenerativa, maculopatia senile, VEGF, Avastin, Lucentis.

Il fumo di sigaretta rappresenta un fattore di rischio molto importante per lo sviluppo della maculopatia degenerativa.
Questo studio sperimentale, effettuato su animali di laboratorio, stabilisce che l’esposizione alla nicotina esercita un’azione negativa anche sull’evoluzione della malattia e sulla risposta alle terapie con inibitori del VEGF (Avastin, Lucentis). Nelle cavie esposte alla nicotina, la terapia con antiVEGF non riusciva a ridurre le dimensioni delle lesione neovascolare, mentre negli animali non esposti alla nicotina la lesione risultava ridotta, in seguito a terapia, del 61-86%. I ricercatori hanno anche rilevato che il fattore di crescita vascolare (VEGF) tornava ad essere presente in concentrazioni più elevate negli occhi delle cavie esposte alla nicotina 14 giorni dopo il trattamento.

Questo lavoro consente di comprendere l’importanza dell’esposizione alla nicotina nell’evoluzione della maculopatia degenerativa e la sua influenza nell’ottenere una migliore risposta alle terapie. E’ importante, quindi, cessare l’abitudine del fumo, non solo a scopo preventivo, ma anche una volta che la malattia si è presentata in fase essudativa.

The Effect of Nicotine on Anti–Vascular Endothelial Growth Factor Therapy in A Mouse Model of Neovascular Age-Related Macular Degeneration

Davis, Stephen J. MD; Lyzogubov, Valeriy V. PhD; Tytarenko, Ruslana G. MS; Safar, Ammar N. MD; Bora, Nalini S. PhD; Bora, Puran S. PhD

Retina:June 2012 – Volume 32 – Issue 6 – p 1171–1180

Purpose: The purpose of this article is to evaluate the effect of nicotine on anti–vascular endothelial growth factor therapy in the treatment of neovascular age-related macular degeneration.

Methods: One group of mice received nicotine in drinking water and the other group received water only. Choroidal neovascularization (CNV) was induced with a laser. Nicotinic acetylcholine receptor-α7 (nAChRα7) expression was evaluated by immunohistochemistry. Bevacizumab or adiponectin peptide II (APNpII) was injected intravitreally on Day 7 postlaser, and the effects were evaluated on Days 14 and 21. α-Bungarotoxin was injected intraperitoneally on Days 2 to 5, and its effect was evaluated on Day 14.

Results: Expression of nAChRα7 was 2 to 7 times higher between Days 3 and 7 postlaser compared with naive mice. In water-fed mice, APNpII, bevacizumab, and α-bungarotoxin significantly reduced CNV size. In nicotine-fed mice, treatment with APNpII or bevacizumab did not significantly reduce CNV size, whereas α-bungarotoxin did have an effect. Comparing water- and nicotine-fed mice, CNV size was 61% to 86% smaller in water-fed mice except for the α-bungarotoxin group, where there was no difference. Platelet-derived growth factor and vascular endothelial growth factor expression was 1.5- to 2.5-fold higher at Day 14 in nicotine-treated mice.

Conclusion: Nicotine significantly blocks the effect of anti–vascular endothelial growth factor therapy in the treatment of laser-induced neovascular age-related macular degeneration. nAChRα7 is significantly upregulated during the formation of CNV, and treatment with an nAChRα7 antagonist decreases CNV size irrespective of nicotine administration.

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