Oculisti Associati Savoia

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.

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.

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.

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.

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.

A cura del dottor Emilio Simongini – Avastin, maculopatia, VEGF, neovascolarizzazone, corioretinopatia puntata

n questo studio prospettico si valuta l’efficacia del Bevacizumab (Avastin) nel trattamento di una forma particolare di degenerazione maculare, legata alla corioretinopatia puntata interna. Il trattamento si conferma efficace e sicuro anche in questo particolare condizione a distanza di 12 mesi dall’inizio della terapia.

INTRAVITREAL BEVACIZUMAB AS PRIMARY TREATMENT OF CHOROIDAL NEOVASCULARIZATION SECONDARY TO PUNCTATE INNER CHOROIDOPATHY: Results of a 1-year Prospective Trial

Zhang, Han MD, PhD; Liu, Zhe-Li MD, PhD; Sun, Peng MD, PhD; Gu, Feng MD

Retina:June 2012 – Volume 32 – Issue 6 – p 1106–1113

Methods: Twelve eyes of 12 patients with subfoveal or juxtafoveal choroidal neovascularization secondary to punctate inner choroidopathy received intravitreal bevacizumab injection (1.25 mg) in this prospective case series. Injection was repeated if persistent or recurrent activity of choroidal neovascularization was indicated by optical coherence tomography or fundus fluorescein angiography at 1-month intervals. Visual, clinical, angiographic, and anatomical changes were observed over a 12-month follow-up period.

Results: After 12 months of follow-up, mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.49 (20/62 in Snellen equivalent) at baseline to 0.23 (20/34 in Snellen equivalent; P < 0.001). Mean central retinal thickness determined by optical coherence tomography decreased from 333 μm to 241 μm (P < 0.001). All eyes (100%) had stable or improved vision, and 9 eyes (75%) showed an improvement of ≥2 lines. All lesions converted to the cicatricial phase after 12 months of follow-up. No drug-related systemic or ocular side effects were observed.

Conclusion: Intravitreal bevacizumab is well tolerated and improves best-corrected visual acuity in choroidal neovascularization secondary to punctate inner choroidopathy over a 12-month period.

A cura del dottor Emilio Simongini – intravitreali, maculopatia senile, AMD

In questo studio si è valutato quale effetto abbia sulla contaminazione del campo operatorio il fatto che il paziente o il chirurgo parlino durante l’intervento. È risultato un aumento significativo della contaminazione batterica, che si riduce se si indossa la mascherina chirurgica. La contaminazione batterica è aumentata dalla posizione sdraiata che si tiene sul lettino operatorio. Per ridurre il tanto temuto rischio di infezione, è decisamente meglio evitare di parlare durante i pochi minuti della procedura.

Bacterial Dispersal Associated With Speech in the Setting of Intravitreous Injections
Joanne C. Wen, MD; Colin A. McCannel, MD; A. Brian Mochon, PhD; Omai B. Garner, PhD
Arch Ophthalmol. 2011;129(12):1551-1554.

Methods  Fifteen volunteers were recruited. Each volunteer was positioned over an open blood agar plate and did the following: read a 5-minute script with a face mask, read a 5-minute script without a face mask, read a 5-minute script with the face turned away from the plate without a face mask, and stood in silence for 5 minutes. Each volunteer then read a 5-minute script while reclined in a standard ophthalmic examination chair with an open blood agar plate secured to the forehead to simulate bacterial dispersal associated with a talking patient. Total numbers of colony-forming bacteria per plate were counted, and the bacteria were identified.
Results  Significantly less bacterial growth occurred in the face mask and silence conditions compared with the no face mask condition (both P < .001). Bacterial growth was significantly greater in the reclined condition compared with the room control (P = .02). Oral streptococcal species represented 66.7% to 82.6% of bacterial colonies in the no face mask, face turned, and reclined conditions.
Conclusions  During simulated intravitreous injection, wearing a face mask or remaining silent significantly decreases culture plate contamination from talking. Talking from above and talking in the reclined position were associated with a significant increase in culture plate contamination. Physicians performing intravitreous injections should be aware of these patterns of bacterial contamination, should consider either wearing a face mask or minimizing speech, and should encourage patients to minimize speech during the procedure.

From Regeneron Pharmaceuticals, Inc. — 12/5/2011

Recensione e commento a cura del dottor Emilio Simongini – maculopatia

La Regeneron Pharmaceuticals, Inc. ha reso noti i risultati di due studi sul nuovo farmaco per la cura della maculopatia senile essudativa (forma umida), EYLEA (aflibercept).
Il farmaco viene iniettato in sede intraoculare come quelli attualmente disponibili (Lucentis, Avastin, Macugen).
Negli studi sono stati confrontati i risultati sui pazienti trattati con Eylea rispetto a quelli tattati con il Lucentis.
Il trattamento con Eylea 2 mg, iniettato ogni due mesi, è risultato equivalente aLucentis iniettato ogni mese, alla fine del primo anno di osservazione.
I risultati al secondo anno hanno mostrato che il proseguimento del regime terapeutico è risultato efficace nel garantire una conservazione della vista. Il numero delle iniezioni effettuate è risultato essere in media di una ogni tre mesi.
Sul fronte degli eventi avversi il nuovo farmaco ha mostrato un buon profilo di sicurezza, simile a quello del Lucentis. Tra gli eventi oculari sono stati riportati arrossamento oculare, dolore oculare, emorragie retiniche, e riduzione del visus. Tra gli effetti sistemici sono comparsi infarto del miocardio, fibrillazione atriale, polmonite e cadute. Tali eventi sono da mettere in relazione all’età avanzata della popolazione studiata, un campione esposto di per sé a tali eventi morbosi. In effetti l’incidenza complessiva di eventi cardiovascolari riscontrati è stata del 3,2% dei pazienti con Lucentis e 3,3% dei pazienti con Eyle.
In conclusione, il nuovo farmaco per il tattamento della maculopatia senile è in fase di arrivo tra l’armamentario terapeutico a nostra disposizione. Dal 18 novembre 2011 è in vendita nelle farmacie americane. La sua efficacia non sembra essere molto diversa rispetto a quella dei farmaci già disponibili ma i risultati sembrano mostrare che, a parità di efficacia e di effetti collaterali, il suo regime di somministrazione potrà essere molto ridotto, con iniezioni ogni due o tre mesi invece che ogni mese.