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2. Strategy for the management of uncomplicated retinal detachments: the European vitreo-retinal society retinal detachment study report 1

Author

BENMERZOUGA N, METTI F, RAZZARI A, MIESBAUER P, SCHÖNHERR U, ZEYNALOVA Z, BASHIR SJ, JACOB J, KOCH P, LADHA R, SMETS E, STALMANS P, DARE A, DEVENYI R, LAM WC, SHAHEEDA M, POTAMITIS T, CHRISTENSEN SR, RAYES E, MORTADA H, SHOUMAN A, HOLM M, ALBINET P, AMAR JP, BECQUET F, BERROD JP, BOULZE M, BOSCHER C, COURJARET JC, DENION E, FOURMAUX, E, GUIGOU S, HAMON F, LAFONTAINE PO, LE ROUIC JF, LEYNAUD JL, NOCHEZ Y, PERONE JM, RYSANEK B, SOYEUR R, BOPP S, BRIX A, HÖHN F, KUSSEROW C, LUCKE K, MOHR A, SCHÜLER A, WEINBERGER A, GOTZARIDIS S, KARATZENIS D, STEFANIOTOU M, K. TSILIMBARIS MK, TSOURIS D, TSANG CW, GABOR R, SZIJARTO Z, BABU N, BANKER AS, BAPAYE M, KELKAR A, ENTEZARI, M, FATEH MOGHADAM HF, RAMEZANI A, SAFARPOUR LIMA B, OMER K, BOSCIA F, CHIARA FRENO M, CIAN R, DONVITO G, FACINO M, LESNONI G, LIUZZI, F, METE M, MININNI F, MOCHI B, PRIMAVERA V, PERTILE G, TURCO I, VASTARELLA P, FONG K, LEE M, VP LOO A, ARAGON HARRISON O, FLORES AGUILAR M, LOPEZ MONTERO LM, LOPEZCARASA HERNANDEZ G, VELASCO I, BOEYDEN V, BOSSCHA M, DE VRIES KNOPPERT W, LINDSTEDT, E. RENARDEL DE LAVALETTE VW, VAN DEN BIESEN PR, ALHASSAN M, BAERLAND TP, BOBER AM, FORSAA V, FOSSEN K, VARHAUG P, ATIENZA J.r. NF, CISIECKI S, FRYCZKOWSKI P, KOWAL LANGE A, MICHALEWSKA Z, MICHALEWSKI J, NAWROCKI J, NOWOSIELSKA A, ODROBINA D, PIETRAS TRZPIEL M, ZAKRZEWSKA A, MEIRELES A, TEIXEIRA S, ELSHAFEI M, DANIELESCU C, TALU S, ALTYNBAEV U, GORIN A, SEREJINE I, EL DEEB M, DAVIDOVIC S, IGNJATOVIC Z, STEFANICKOVA J, VENTER L, CHANG W, JO YL, KIM JY, LEE J, LIM ST, SAGONG M, ASCASO FJ, CASTRO J, CORDOVES L. DESCO ESTEBAN C, MORENO MANRESA J, VILAPLANA D, JANIEC S, TOMIC Z, BEN YAHIA S, ACAR N, GÜNGEL H, KAPRAN Z, OSMANBASOGLU O, OZDEK S, TOPBAS S, TOTAN Y, ÜNVER YB, CHICHUR D, DOBROVOLSKEY O, KOZLOVSKA I, LYTVYNCHUK L, PHYLYPCHUK O, POSTOLOVSKA A, SERGIIENKO A, SHEVCHYK V, WINDER S, CULOTTA J, KIM S, KING J, KURUP SK, LIN SJ, PACURARIU R, ROTH D, SINCLAIR S, WEBER P, DOAN H, TUNG T., ROMANO, MARIO, Benmerzouga, N, Metti, F, Razzari, A, Miesbauer, P, Schönherr, U, Zeynalova, Z, Bashir, Sj, Jacob, J, Koch, P, Ladha, R, Smets, E, Stalmans, P, Dare, A, Devenyi, R, Lam, Wc, Shaheeda, M, Potamitis, T, Christensen, Sr, Rayes, E, Mortada, H, Shouman, A, Holm, M, Albinet, P, Amar, Jp, Becquet, F, Berrod, Jp, Boulze, M, Boscher, C, Courjaret, Jc, Denion, E, Fourmaux, E, Guigou, S, Hamon, F, Lafontaine, Po, LE ROUIC, Jf, Leynaud, Jl, Nochez, Y, Perone, Jm, Rysanek, B, Soyeur, R, Bopp, S, Brix, A, Höhn, F, Kusserow, C, Lucke, K, Mohr, A, Schüler, A, Weinberger, A, Gotzaridis, S, Karatzenis, D, Stefaniotou, M, K., TSILIMBARIS MK, Tsouris, D, Tsang, Cw, Gabor, R, Szijarto, Z, Babu, N, Banker, A, Bapaye, M, Kelkar, A, Entezari, M, FATEH MOGHADAM, Hf, Ramezani, A, SAFARPOUR LIMA, B, Omer, K, Boscia, F, CHIARA FRENO, M, Cian, R, Donvito, G, Facino, M, Lesnoni, G, Liuzzi, F, Mete, M, Mininni, F, Mochi, B, Primavera, V, Romano, Mario, Pertile, G, Turco, I, Vastarella, P, Fong, K, Lee, M, VP LOO, A, ARAGON HARRISON, O, FLORES AGUILAR, M, LOPEZ MONTERO, Lm, LOPEZCARASA HERNANDEZ, G, Velasco, I, Boeyden, V, Bosscha, M, DE VRIES KNOPPERT, W, Lindstedt, E., RENARDEL DE LAVALETTE VW, VAN DEN BIESEN, Pr, Alhassan, M, Baerland, Tp, Bober, Am, Forsaa, V, Fossen, K, Varhaug, P, ATIENZA J. r., Nf, Cisiecki, S, Fryczkowski, P, KOWAL LANGE, A, Michalewska, Z, Michalewski, J, Nawrocki, J, Nowosielska, A, Odrobina, D, PIETRAS TRZPIEL, M, Zakrzewska, A, Meireles, A, Teixeira, S, Elshafei, M, Danielescu, C, Talu, S, Altynbaev, U, Gorin, A, Serejine, I, EL DEEB, M, Davidovic, S, Ignjatovic, Z, Stefanickova, J, Venter, L, Chang, W, Jo, Yl, Kim, Jy, Lee, J, Lim, St, Sagong, M, Ascaso, Fj, Castro, J, CORDOVES L., DESCO ESTEBAN C, MORENO MANRESA, J, Vilaplana, D, Janiec, S, Tomic, Z, BEN YAHIA, S, Acar, N, Güngel, H, Kapran, Z, Osmanbasoglu, O, Ozdek, S, Topbas, S, Totan, Y, Ünver, Yb, Chichur, D, Dobrovolskey, O, Kozlovska, I, Lytvynchuk, L, Phylypchuk, O, Postolovska, A, Sergiienko, A, Shevchyk, V, Winder, S, Culotta, J, Kim, S, King, J, Kurup, Sk, Lin, Sj, Pacurariu, R, Roth, D, Sinclair, S, Weber, P, Doan, H, and Tung, T.

Abstract

OBJECTIVE: To study success and failure in the treatment of uncomplicated rhegmatogenous retinal detachments (RRDs). DESIGN: Nonrandomized, multicenter retrospective study. PARTICIPANTS: One hundred seventy-six surgeons from 48 countries spanning 5 continents provided information on the primary procedures for 7678 cases of RRDs including 4179 patients with uncomplicated RRDs. METHODS: Reported data included specific clinical findings, the method of repair, and the outcome after intervention. MAIN OUTCOME MEASURES: Final failure of retinal detachment repair (level 1 failure rate), remaining silicone oil at the study's conclusion (level 2 failure rate), and need for additional procedures to repair the detachment (level 3 failure rate). RESULTS: Four thousand one hundred seventy-nine uncomplicated cases of RRD were included. Combining phakic, pseudophakic, and aphakic groups, those treated with scleral buckle alone (n = 1341) had a significantly lower final failure rate than those treated with vitrectomy, with or without a supplemental buckle (n = 2723; P = 0.04). In phakic patients, final failure rate was lower in the scleral buckle group compared with those who had vitrectomy, with or without a supplemental buckle (P = 0.028). In pseudophakic patients, the failure rate of the initial procedure was lower in the vitrectomy group compared with the scleral buckle group (P = 3×10(-8)). There was no statistically significant difference in failure rate between segmental (n = 721) and encircling (n = 351) buckles (P = 0.5). Those who underwent vitrectomy with a supplemental scleral buckle (n = 488) had an increased failure rate compared with those who underwent vitrectomy alone (n = 2235; P = 0.048). Pneumatic retinopexy was found to be comparable with scleral buckle when a retinal hole was present (P = 0.65), but not in cases with a flap tear (P = 0.034). CONCLUSIONS: In the treatment of uncomplicated phakic retinal detachments, repair using scleral buckle may be a good option. There was no significant difference between segmental versus 360-degree buckle. For pseudophakic uncomplicated retinal detachments, the surgeon should balance the risks and benefits of vitrectomy versus scleral buckle and keep in mind that the single-surgery reattachment rate may be higher with vitrectomy. However, if a vitrectomy is to be performed, these data suggest that a supplemental buckle is not helpful.

Published
2013

3. Strategy for the management of complex retinal detachments: the European vitreo-retinal society retinal detachment study report 2

Author

BENMERZOUGA N, METTI F, RAZZARI A, MIESBAUER P, SCHÖNHERR U, ZEYNALOVA Z, BASHIR SJ, JACOB J, KOCH P, LADHA R, SMETS E, STALMANS P, DARE A, DEVENYI R, LAM WC, SHAHEEDA M, POTAMITIS T, CHRISTENSEN SR, RAYES E, MORTADA H, SHOUMAN A, HOLM M, ALBINET P, AMAR JP, BECQUET F, BERROD JP, BOULZE M, BOSCHER C, COURJARET JC, DENION E, FOURMAUX, E, GUIGOU S, HAMON F, LAFONTAINE PO, LE ROUIC JF, LEYNAUD JL, NOCHEZ Y, PERONE JM, RYSANEK B, SOYEUR R, BOPP S, BRIX A, HÖHN F, KUSSEROW C, LUCKE K, MOHR A, SCHÜLER A, WEINBERGER A, GOTZARIDIS S, KARATZENIS D, STEFANIOTOU M, K. TSILIMBARIS MK, TSOURIS D, TSANG CW, GABOR R, SZIJARTO Z, BABU N, BANKER AS, BAPAYE M, KELKAR A, ENTEZARI, M, FATEH MOGHADAM HF, RAMEZANI A, SAFARPOUR LIMA B, OMER K, BOSCIA F, CHIARA FRENO M, CIAN R, DONVITO G, FACINO M, LESNONI G, LIUZZI, F, METE M, MININNI F, MOCHI B, PRIMAVERA V, PERTILE G, TURCO I, VASTARELLA P, FONG K, LEE M, VP LOO A, ARAGON HARRISON O, FLORES AGUILAR M, LOPEZ MONTERO LM, LOPEZCARASA HERNANDEZ G, VELASCO I, BOEYDEN V, BOSSCHA M, DE VRIES KNOPPERT W, LINDSTEDT, E. RENARDEL DE LAVALETTE VW, VAN DEN BIESEN PR, ALHASSAN M, BAERLAND TP, BOBER AM, FORSAA V, FOSSEN K, VARHAUG P, ATIENZA J.r. NF, CISIECKI S, FRYCZKOWSKI P, KOWAL LANGE A, MICHALEWSKA Z, MICHALEWSKI J, NAWROCKI J, NOWOSIELSKA A, ODROBINA D, PIETRAS TRZPIEL M, ZAKRZEWSKA A, MEIRELES A, TEIXEIRA S, ELSHAFEI M, DANIELESCU C, TALU S, ALTYNBAEV U, GORIN A, SEREJINE I, EL DEEB M, DAVIDOVIC S, IGNJATOVIC Z, STEFANICKOVA J, VENTER L, CHANG W, JO YL, KIM JY, LEE J, LIM ST, SAGONG M, ASCASO FJ, CASTRO J, CORDOVES L. DESCO ESTEBAN C, MORENO MANRESA J, VILAPLANA D, JANIEC S, TOMIC Z, BEN YAHIA S, ACAR N, GÜNGEL H, KAPRAN Z, OSMANBASOGLU O, OZDEK S, TOPBAS S, TOTAN Y, ÜNVER YB, CHICHUR D, DOBROVOLSKEY O, KOZLOVSKA I, LYTVYNCHUK L, PHYLYPCHUK O, POSTOLOVSKA A, SERGIIENKO A, SHEVCHYK V, WINDER S, CULOTTA J, KIM S, KING J, KURUP SK, LIN SJ, PACURARIU R, ROTH D, SINCLAIR S, WEBER P, DOAN H, TUNG T., ROMANO, MARIO, Benmerzouga, N, Metti, F, Razzari, A, Miesbauer, P, Schönherr, U, Zeynalova, Z, Bashir, Sj, Jacob, J, Koch, P, Ladha, R, Smets, E, Stalmans, P, Dare, A, Devenyi, R, Lam, Wc, Shaheeda, M, Potamitis, T, Christensen, Sr, Rayes, E, Mortada, H, Shouman, A, Holm, M, Albinet, P, Amar, Jp, Becquet, F, Berrod, Jp, Boulze, M, Boscher, C, Courjaret, Jc, Denion, E, Fourmaux, E, Guigou, S, Hamon, F, Lafontaine, Po, LE ROUIC, Jf, Leynaud, Jl, Nochez, Y, Perone, Jm, Rysanek, B, Soyeur, R, Bopp, S, Brix, A, Höhn, F, Kusserow, C, Lucke, K, Mohr, A, Schüler, A, Weinberger, A, Gotzaridis, S, Karatzenis, D, Stefaniotou, M, K., TSILIMBARIS MK, Tsouris, D, Tsang, Cw, Gabor, R, Szijarto, Z, Babu, N, Banker, A, Bapaye, M, Kelkar, A, Entezari, M, FATEH MOGHADAM, Hf, Ramezani, A, SAFARPOUR LIMA, B, Omer, K, Boscia, F, CHIARA FRENO, M, Cian, R, Donvito, G, Facino, M, Lesnoni, G, Liuzzi, F, Mete, M, Mininni, F, Mochi, B, Primavera, V, Romano, Mario, Pertile, G, Turco, I, Vastarella, P, Fong, K, Lee, M, VP LOO, A, ARAGON HARRISON, O, FLORES AGUILAR, M, LOPEZ MONTERO, Lm, LOPEZCARASA HERNANDEZ, G, Velasco, I, Boeyden, V, Bosscha, M, DE VRIES KNOPPERT, W, Lindstedt, E., RENARDEL DE LAVALETTE VW, VAN DEN BIESEN, Pr, Alhassan, M, Baerland, Tp, Bober, Am, Forsaa, V, Fossen, K, Varhaug, P, ATIENZA J. r., Nf, Cisiecki, S, Fryczkowski, P, KOWAL LANGE, A, Michalewska, Z, Michalewski, J, Nawrocki, J, Nowosielska, A, Odrobina, D, PIETRAS TRZPIEL, M, Zakrzewska, A, Meireles, A, Teixeira, S, Elshafei, M, Danielescu, C, Talu, S, Altynbaev, U, Gorin, A, Serejine, I, EL DEEB, M, Davidovic, S, Ignjatovic, Z, Stefanickova, J, Venter, L, Chang, W, Jo, Yl, Kim, Jy, Lee, J, Lim, St, Sagong, M, Ascaso, Fj, Castro, J, CORDOVES L., DESCO ESTEBAN C, MORENO MANRESA, J, Vilaplana, D, Janiec, S, Tomic, Z, BEN YAHIA, S, Acar, N, Güngel, H, Kapran, Z, Osmanbasoglu, O, Ozdek, S, Topbas, S, Totan, Y, Ünver, Yb, Chichur, D, Dobrovolskey, O, Kozlovska, I, Lytvynchuk, L, Phylypchuk, O, Postolovska, A, Sergiienko, A, Shevchyk, V, Winder, S, Culotta, J, Kim, S, King, J, Kurup, Sk, Lin, Sj, Pacurariu, R, Roth, D, Sinclair, S, Weber, P, Doan, H, and Tung, T.

Abstract

OBJECTIVE: To study the outcome of the treatment of complex rhegmatogenous retinal detachments (RRDs). DESIGN: Nonrandomized, multicenter, retrospective study. PARTICIPANTS: One hundred seventy-six surgeons from 48 countries spanning 5 continents reported primary procedures for 7678 RRDs. METHODS: Reported data included clinical manifestations, the method of repair, and the outcome. MAIN OUTCOME MEASURES: Failure of retinal detachment repair (level 1 failure rate), remaining silicone oil at the study's conclusion (level 2 failure rate), and need for additional procedures to repair the detachments (level 3 failure rate). RESULTS: The main categories of complex retinal detachments evaluated in this investigation were: (1) grade B proliferative vitreoretinopathy (PVR; n = 917), (2) grade C-1 PVR (n = 637), (3) choroidal detachment or significant hypotony (n = 578), (4) large or giant retinal tears (n = 1167), and (5) macular holes (n = 153). In grade B PVR, the level 1 failure rate was higher when treated with a scleral buckle alone versus vitrectomy (P = 0.0017). In grade C-1 PVR, there was no statistically significant difference in the level 1 failure rate between those treated with vitrectomy, with or without scleral buckle, and those treated with scleral buckle alone (P = 0.7). Vitrectomy with a supplemental buckle had an increased failure rate compared with those who did not receive a buckle (P = 0.007). There was no statistically significant difference in level 1 failure rate between tamponade with gas versus silicone oil in patients with grade B or C-1 PVR. Cases with choroidal detachment or hypotony treated with vitrectomy had a significantly lower failure rate versus treatment with scleral buckle alone (P = 0.0015). Large or giant retinal tears treated with vitrectomy also had a significantly lower failure rate versus treatment with scleral buckle (P = 7×10(-8)). CONCLUSIONS: In patients with retinal detachment, when choroidal detachment, hypotony, a large tear, or a giant tear is present, vitrectomy is the procedure of choice. In retinal detachments with PVR, tamponade with either gas or silicone oil can be considered. If a vitrectomy is to be performed, these data suggest that a supplemental buckle may not be helpful. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Published
2013

4. Dexamethasone Intravitreal Implant in Patients with Macular Edema Related to Branch or Central Retinal Vein Occlusion

Author

Haller, Ja, Bandello, F, Belfort R., Jr, Blumenkranz, M. S., Gillies, M, Heier, J, Loewenstein, A, Yoon, Yh, Jiao, J, Li, Xy, Whitcup, S. M., Aaberg, Tm, Abraham, P, Abujamra, S, Acton, J, Adamczyk Ludyga, A, Adenwalla, M, Agahigian, Dd, Agoas, V, Aguilar Mendoza, M, Aisenbrey, S, Alam, S, Albiani, D, Alexandrescu, B, Alfaiate, Mm, Allam, S, Almeida, Hp, Anagnoste, S, Anand, R, Anderson, N, Antoszyk, A, Armogan, N, Arnold, J, Ash, D, Atlas, Wg, Augustin, Ja, de Ávila MP, Awh, C, Azzolini, C, Babkova, B, Bakri, Sj, Banach, Mj, Barak, A, Barile, G, Barker, D, Barnard, T, Bartz Schmidt KU, Battaglia Parodi, M, Baumal, C, Bedrich, P, Beer, P, Belfort Mattos Junior, R, Bellini, L, Benner, J, Benson, W, Benz, M, Berger, B, Bergren, R, Bharadwaj, A, Bhavan, S, Bhavsar, A, Binder, S, Biondi, A, Bishop, F, Blair, N, Blinder, K, Blumenkranz, M, Bohm, A, Boldrey, Ee, Bornfeld, N, Borrillo, Jl, Boyer, D, Bradford, R, Bridges, W, Brigatti, L, Briggs, M, Brooks HL Jr, Brown, D, Browning, A, Browning, D, Brunner, S, Brunnerova, R, Bryan, Js, Brydak Godowska, J, Buettner, H, Burns, J, Burrows, Af, Busbee, B, Butner, R, Butter, J, Byrnes, G, Callahan, C, Campochiaro, P, Cano Hildalgo RA, Canziani, T, Capaccioli, K, Capone, A, Carmichael, T, Carnevale, K, Casella, Am, Casey, R, Castanheira Dinis, A, Celis, B, Chambers, R, Chang, S, Chang, Yh, Chechik, D, Chee, Sp, Chen, E, Chen, Jt, Chen, Sn, Chen, S, Cheng, B, Chiquet, C, Chong, K, Chong, Lp, Chong, V, Chou, T, Chow, V, Chrapek, O, Chu, T, Chua, J, Chun, D, Chung, Hw, Cialdini, Ap, Ciancas, E, Cihelkova, I, Cisiecki, S, Clark, W, Cleary, T, Coco, R, Codenotti, M, Cohen, Bz, Cohen, Ja, Cohen, J, Connolly, B, Conway, B, Cook, H, Cooper, B, Coors, L, Corwin, J, Costa, Jr, Cottrell, D, Couvillion, S, Craig, J, Cruess, A, Dabbs, T, Danesh, S, Davidorf, F, Davis, J, De Cilla, S, De Fazio, R, de la Fuente MA, de la Rua ER, De Mattia, M, Deen, A, Del Priore, L, Delyfer, Mn, Deuter, C, Devadason, Ds, Devenyi, R, D'Heurle, D, Dickinson, J, Doft, B, Dooner, J, Doubell, D, Downie, J, Drenser, K, Dreyer, R, D'Sousa, Y, Du, T, Duarte, L, Dubiner, Hb, Dubovy, S, Dubska, Z, Dugel, P, Dunn, W, Dusova, J, Dvorak, J, Dyer, D, Dziegielewska, K, Earl, M, Egan, C, Eichenbaum, D, Eifrig, C, Ells, A, El Shabrawi, Y, Elsherbiny, S, Engel, H, Engelbrecht, N, Ernest, J, Essex, R, Eter, N, Evans, R, Fakadej, A, Falcone, P, Fan, D, Fan, Jt, Eid Farah, M, Farah, S, Feiner, L, Feldman, Rm, Ferencz, J, Fernandez Vega Sanz, A, Ferreira, Jl, Figueira, J, Fineman, M, Fiser, I, Fish, G, Fish, Rh, Fishburne, B, Fisher, Sj, Fitzsimons, R, Flaxel, C, Fletcher, E, Flores Aguilar, M, Florez, S, Flynn, H, Fogarty, S, Folgado, A, Foster, Bs, Fox, Gm, Frambach, D, Framme, C, Fransen, S, Fraser Bell, S, Frederick, A, Freeman, W, Freisberg, L, Friedman, E, Friedman, L, Fucik, M, Fuller, Dg, Gaitan, J, Gallemore, R, Gallogly, P, Arumi, Jg, Garg, S, Garretson, B, Gastaud, P, Gaudric, A, Gawrilow, P, Gehlbach, Pl, Geyer, O, Ghuman, At, Giansanti, F, Luiz Gil, A, Gilbert, Hd, Girmens, Jf, Giubilato, A, Glacet Bernard, A, Glaser, D, Glatzer, R, Goldstein, D, Gomes, Am, Gon Yu, H, Gonçalves, Fp, Gonzales, C, Googe, J, Gopal, L, Gordon, A, Gous, P, Grand, M, Cristina, P, Magro, G, Granero Riano, M, Grassi, M, Green, J, Green, S, Gregor, Z, Gregori, N, Grizzard, Ws, Groenewald, C, Gross, Jg, Gross, Ne, Gruber, A, Grutow, G, Guillet, E, Gupta, A, Gyorgyova, D, Haas, A, Haas, K, Hadden, P, Hagemann, L, Hainsworth, D, Haivala, D, Haller, J, Halperin, L, Hamer, P, Hammer, M, Han, D, Handa, Jt, Handelman, I, Handza, J, Harder, B, Harding, S, Hariprasad, Sm, Hartley, K, Hartman, P, Hartnett, Me, Harvey, P, Hassan, T, Headon, M, Hejsek, L, Higgins, P, Hillenkamp, J, Ho, A, Ho, T, Holekamp, N, Holz, E, Holz, F, Hooper, P, Hopkins, Jj, Hoskin Mott, A, Hoskins, J, Hrisomalos, N, Hsu, J, 3rd, Hubbard B., Hudson, H, Hughes, E, Hunt, A, Hunyor, A, Hwang, T, Hwang, Jf, Ibarra, M, Incarnato, N, Inhetvin Hutter, C, Introini, U, Isaacs, T, Islam, N, Iyer, Mn, Jablonski, C, Jack, Rl, Jager, R, Jahn, C, Jao, C, Jehan, F, Jonas, J, Joseph, D, Joshi, M, Jost, B, Jurklies, B, Kaincova, I, Kaiser, P, Kaiser, R, Kalvodova, B, Kamppeter, B, Kanann, Nb, Kang, K, Katz, Rs, Kaushal, S, Kecik, D, Kellaway, J, Kelly, K, Kelly, S, Khan, J, Kherani, A, Kim, R, Kim, I, Kim, J, Kim, Jg, Kim, N, Kim, Tw, Kingsley, R, Klein, R, Klemperer, I, Kociecki, J, Korbasova, M, Korda, V, Korobelnik, Jf, Koshy, Z, Kostamaa, H, Kovach, J, Kozak, I, Kozousek, V, Krasny, J, Kreiger, A, Krivosic, V, Krug JV Jr, Kruger, L, Kunimoto, D, Kuppermann, Bd, Kurtz, R, Kuznik Borkowska, A, Lai, J, Lai, W, Lake, S, Lalwani, G, Lam, Wc, Lanning, Rc, Lanzetta, Paolo, Lara, W, Larrison, Wi, Lattanzio, R, Lavina, A, Lavinsky, J, Lazzaroni, F, Lee, E, Yong Lee, J, Lee, M, Young Lee, S, Lee, V, Leff, S, Lehr, J, Lenfesty, P, Leonard, R, Levine, A, Levitan, M, Lewis, H, Liew, S, Lim, J, Lim, R, Lin, R, Lip, Pl, Liu, J, Lobes, La, Loose, I, Lotery, A, Lottenberg, Cl, Loutchkina, D, Lu, Dw, Lubczynska, A, Lujan, B, Lyssek Boron, A, Ma, C, Ma, P, Maberley, D, Maccumber, M, Madhusudhana, Kc, Madreperla, S, Magee, M, Magolan, J, Maia Junior Ode, O, Maia, A, Majji, A, Malthieu, D, Mango, C, Marmor, M, Marques, L, Martin, D, Martinez, Ja, Massaoutis, P, Mathai, A, Mathur, R, Mattioli, S, Maturi, Rk, Mazur Michalek, I, Mcallister, I, Mccabe, F, Mccannel, Ca, Mcgimpsey, S, Mchugh, Jd, Mckibbin, M, McLean WC Jr, Mcmillan, T, Meireles, R, de Melo CS, Menchini, U, Meredith, T, Merrill, P, Mian, U, Michels, M, Midena, E, Mieler, Wf, Migliavacca, L, Miller, D, Miller, J, Mincey, G, Mitchell, P, Katsuki Mizubuti, S, Mohamed, S, Mohammed, M, Moinfar, N, Moisseiev, J, Mones, J, Montemayor Lobo, R, Montero, J, de Moraes NI, Moreira CA Jr, Morely, M, Moreno, Jm, Moron, Jt, Morrison, Vl, Morse, L, Moshfeghi, A, Moshfeghi, D, Muccioli, C, Munshi, V, Murthy, Rc, Naing, T, Nair, R, Nascimento, J, Nascimento, Vp, Nawrocka, Z, Nawrocki, J, Newell, C, Newsom, R, Nguyen, J, Nguyen, Q, Nguyen, Rl, Nichols, J, Nilanjana, D, Noguchi, B, Noorily, S, Novack, R, Novak, M, Novalis, G, O'Brien, D, Offermann, I, Oguido, Ap, Oh, K, Okruszko, A, de Oliveira TL, Oliver, S, Ong, S, Orellana, J, Orzalesi, N, O'Toole, L, Ovando, Y, Paccione, J, Pach, J, Packo, K, Packowska, Ma, Palmer, J, Palmer, H, Palombi, K, Papp, A, Paques, M, Paranhos A., Jr, Park, D, Park, Ri, Park, S, Parke, D, Parravano, M, Pastor Jimeno JC, Patel, S, Patra, S, Pavan, Pr, Pearce, I, Pecold, K, Pedio, M, Peh, Kk, Pelosini, L, Pendergast, S, Perez, Br, Perez Ortiz DJ, Perkins, S, Peters, M, Pheasant, T, Pilat, J, Pilotto, E, Piltz Seymour, J, Pirracchio, A, Pollack, A, Portella, E, Pracharova, Z, Prati, M, Prensky, Jg, Preston, R, Prieto, F, Puls, S, Purohit, Ar, Quintao, T, Rahhal, F, Rahman, W, Ramos, Ar, Ramsey, S, Rani, A, Rao, Pk, Rapizzi, E, Raskauskas, P, Ratiglia, R, Ratnakaram, R, Rauser, Me, Regillo, C, Rehak, J, Reichel, E, Reid, Da, Rejmont, L, Rougier, Mb, Ribon, Ri, Ricarova, R, Rich, R, Riley, A, Ripandelli, G, Rishi, E, Rivett, K, Rogers, A, Romanet, Jp, Rosa, Pj, Rosberger, D, Rose, S, Rosenfeld, P, Ross, Rr, Rotberg, M, Roth, Cb, Roth, D, Rubaltelli, D, Rubsamen, P, Ruby, A, Ruiz Moreno JM, Ruiz, R, Russell Gonder, J, Russell, M, Ryu, Jw, Sachs, H, Sadda, S, Safar, A, Salinas, C, Sall, K, Samad, A, Samkova, K, Sanders, J, Sandhu, R, Sandhu, Ss, Sandner, D, Sanislo, Sr, Sartani, G, Saviano, S, Savy, O, Schechter, Ba, Schenker, Hi, Schiff, W, Schlichtenbrede, F, Schneider, B, Schneider, L, Schneiderman, T, Schocket, L, Schoenherr, U, Schoenleber, D, Scholl, Hp, Schreiber, J, Schwartz, Sd, Sears, J, Sedlakova, J, Seery, C, Sell, C, Shah, G, Shapiro, M, Sharma, A, Sheidow, T, Sheu, Sj, Sheufele, T, Shukla, D, Siewec Proscinska, J, Silva, Er, Singer, M, Singer, S, Singerman, Lj, Singh, M, Siow, Yc, Sipperley, Jo, Sivaprasad, S, Sjaarda, R, Snyder, W, Sobrin, L, Sodi, A, Solomon, S, Sonkin, P, Soubrane, G, Soucek, P, Spirn, B, Srivastava, S, Stannard, K, Staurenghi, G, Steinmetz, R, Stepien, K, Stern, W, Stevenson, Od, Stewart, D, Stewart, J, Stolba, U, Stoller, G, Stone, C, Stout, Jt, Stringfellow, G, Studnicka, J, Suarez Figueroa, M, Sung, J, Susini, A, Syracuse, R, Szaflik, J, Tabandeh, H, Tadayoni, R, Takahashi, Wy, Taleb, Ac, Talks, Sj, Tamayo, L, Tan, M, Taney, B, Tarnawska, D, Tassinari, G, Taylor, J, Telander, D, Territo, C, Thomas, El, Thomas, M, Thompson, Jt, Thompson, Ws, Tiedeman, Js, Topping, T, Trese, M, Truong, S, Tsang, Cw, Tufail, A, Ufret Vincenty, R, Uhmannova, R, 2nd, Ulanski L., Ulinska, M, Urminsky, J, Uy, H, Vaishnav, H, Varano, M, Vavvas, D, Vega Sanz BF, Veloso, A, Vicha, I, Viola, F, Visser, L, Vlkova, E, Voelker, M, Volkert, D, Vossmerbaumer, U, Vu, C, Vyas, S, Wald, Kj, Walker, J, Walter, A, Wang, R, Wasiak, K, Watt, Dr, Weger, M, 3rd, Weidman F., Weinberger, D, Weisz, Jm, 3rd, Wells J., Wheatley, M, Wickremasingh, S, Wiegand, T, Wieland, M, Will, D, Williams, G, Williams, Rg, Wilson, D, Win, Ph, Wing, Gl, Wirostko, W, Wirthlin, R, Wong, Al, Wong, T, Woo, J, Wu, Tt, Wylegala, E, Yan, J, Yang, Ch, Yang, Cm, Yang, Y, Yang, Yc, Yarian, D, Yates, P, Yedavally, S, Yoken, J, Young, L, Young, S, Zago, Rj, Zakov, Z, Zaras, M, Zegarra, H, Ziemianski, M, Zimmer Galler, I, Zourdani, A, and Zur, C.

Published
2011

5. Randomized, Sham-Controlled Trial of Dexamethasone Intravitreal Implant in Patients with Macular Edema Due to Retinal Vein Occlusion

Author

Haller, Ja, Bandello, F, Belfort R., Jr, Blumenkranz, Ms, Gillies, M, Heier, J, Loewenstein, A, Yoon, Yh, Jacques, Ml, Jiao, J, Li, Xy, Whitcup, Sm, OZURDEX GENEVA Study Group, Aaberg, Tm, Abraham, P, Abujamra, S, Acton, J, Adamczyk Ludyga, A, Adenwalla, M, Agahigian, Dd, Agoas, V, Aguilar Mendoza, M, Aisenbrey, S, Alam, S, Albiani, D, Alexandrescu, B, Alfaiate, Mm, Allam, S, Almeida, Hp, Anagnoste, S, Anand, R, Anderson, N, Antoszyk, A, Armogan, N, Arnold, J, Ash, D, Atlas, Wg, Augustin, Ja, de Avila MP, Awh, C, Azzolini, C, Babkova, B, Bakri, Sj, Banach, Mj, Barak, A, Barile, G, Barker, D, Barnard, T, Bartz Schmidt KU, Parodi, Mb, Baumal, C, Bedrich, P, Beer, P, Mattos RB Jr, Bellini, L, Benner, J, Benson, W, Benz, M, Berger, B, Bergren, R, Bharadwaj, A, Bhavan, S, Bhavsar, A, Binder, S, Biondi, A, Bishop, F, Blair, N, Blinder, K, Blumenkranz, M, Bohm, A, Boldrey, Ee, Bornfeld, N, Borrillo, Jl, Boyer, D, Bradford, R, Bridges, W, Brigatti, L, Briggs, M, Brooks HL Jr, Brown, D, Browning, A, Browning, D, Brunner, S, Brunnerova, R, Renata, Js, Brydak Godowska, J, Buettner, H, Burns, J, Burrows, Af, Busbee, B, Butner, R, Butter, J, Byrnes, G, Callahan, C, Campochiaro, P, Cano Hildalgo RA, Canziani, T, Capone, A, Carmichael, T, Carnevale, K, Casella, Am, Casey, R, Castanheira Dinis, A, Celis, B, Chambers, R, Chang, S, Chang, Yh, Chechik, D, Chee, Sp, Chen, E, Chen, Jt, Chen, Sn, Chen, S, Cheng, B, Chiquet, C, Chong, K, Chong, Lp, Chong, V, Chou, T, Chow, V, Chrapek, O, Chu, T, Chua, J, Chun, D, Chung, Hw, Cialdini, Ap, Ciancas, E, Cihelkova, I, Cisiecki, S, Clark, W, Cleary, T, Coco, R, Codenotti, M, Cohen, Bz, Cohen, Ja, Cohen, J, Connolly, B, Conway, B, Cook, H, Cooper, B, Coors, L, Corwin, J, Costa, Jr, Cottrell, D, Couvillion, S, Craig, J, Cruess, A, Cupo, G, Dabbs, T, Danesh, S, Davidorf, F, Davis, J, De Cilla, S, De Fazio, R, de la Fuente MA, de la Rua ER, De Mattia, M, Deen, A, Del Priore, L, Delyfer, Mn, Deuter, C, Devadason, Ds, Devenyi, R, D'Heurle, D, Dickinson, J, Doft, B, Dooner, J, Doubell, D, Downie, J, Drenser, K, Dreyer, R, D'Sousa, Y, Du, T, Duarte, L, Dubiner, Hb, Dubovy, S, Dubska, Z, Dugel, P, Dunn, W, Dusova, J, Dvorak, J, Dyer, D, Dziegielewska, K, Earl, M, Egan, C, Eichenbaum, D, Eifrig, C, Ells, A, El Shabrawi, Y, Elsherbiny, S, Engel, H, Engelbrecht, N, Ernest, J, Essex, R, Eter, N, Evans, R, Fakadej, A, Falcone, P, Fan, D, Fan, Jt, Farah, Me, Farah, S, Feiner, L, Feldman, Rm, Ferencz, J, Fernandez Vega Sanz, A, Ferreira, Jl, Figueira, J, Fineman, M, Fiser, I, Fish, G, Fish, Rh, Fishburne, B, Fisher, Sj, Fitzsimons, R, Flaxel, C, Fletcher, E, Flores Aguilar, M, Florez, S, Flynn, H, Fogarty, S, Folgado, A, Foster, Bs, Fox, Gm, Frambach, D, Fransen, S, Fraser Bell, S, Frederick, A, Freeman, W, Freisberg, L, Friedman, E, Friedman, L, Fucik, M, Fuller, Dg, Gaitan, J, Gallemore, R, Gallogly, P, Garcia Arumi, J, Garg, S, Garretson, B, Gastaud, P, Gaudric, A, Gawrilow, P, Gehlbach, Pl, Geyer, O, Ghuman, At, Giansanti, F, Gil, Al, Gilbert, Hd, Girmens, Jf, Giubilato, A, Glacet Bernard, A, Glaser, D, Glatzer, R, Goldstein, D, Gomes, Am, Gon Yu, H, Gonçalves, Fp, Gonzales, C, Googe, J, Gopal, L, Gordon, A, Gous, P, Grand, M, Grandao Magro PC, Granero Riano, M, Grassi, M, Green, J, Green, S, Gregor, Z, Gregori, N, Grizzard, Ws, Groenewald, C, Gross, Jg, Gross, Ne, Gruber, A, Grutow, G, Guillet, E, Gyorgyova, D, Haas, A, Haas, K, Hadden, P, Hagemann, L, Hainsworth, D, Haivala, D, Haller, J, Halperin, L, Hamer, P, Hammer, M, Han, D, Handa, Jt, Handelman, I, Handza, J, Harder, B, Harding, S, Hariprasad, Sm, Hartley, K, Hartman, P, Hartnett, Me, Harvey, P, Hassan, T, Headon, M, Hejsek, L, Higgins, P, Hillenkamp, J, Ho, A, Ho, T, Holekamp, N, Holz, E, Holz, F, Hooper, P, Hopkins, Jj, Hoskin Mott, A, Hoskins, J, Hrisomalos, N, Hsu, J, 3rd, Hubbard B., Hudson, H, Hughes, E, Hunt, A, Hunyor, A, Hwang, T, Hwang, Jf, Ibarra, M, Incarnato, N, Inhetvin Hutter, C, Introini, U, Isaacs, T, Islam, N, Iyer, Mn, Jablonski, C, Jack, Rl, Jager, R, Jahn, C, Jao, C, Jehan, F, Jonas, J, Joseph, D, Joshi, M, Jost, B, Jurklies, B, Kaincova, I, Kaiser, P, Kaiser, R, Kalvodova, B, Kamppeter, B, Kanann, Nb, Kang, K, Katz, Rs, Kaushal, S, Kecik, D, Kellaway, J, Kelly, K, Kelly, S, Khan, J, Kherani, A, Kim, R, Kim, I, Kim, J, Kim, Jg, Kim, N, Kim, Tw, Kingsley, R, Klein, R, Klemperer, I, Kociecki, J, Korbasova, M, Korda, V, Korobelnik, Jf, Koshy, Z, Kostamaa, H, Kovach, J, Kozak, I, Kozousek, V, Krasny, J, Kreiger, A, Krivosic, V, Krug JV Jr, Kruger, L, Kunimoto, D, Kuppermann, Bd, Kurtz, R, Kuznik Borkowska, A, Lai, J, Lai, W, Lake, S, Lalwani, G, Lam, Wc, Lanning, Rc, Lanzetta, Paolo, Lara, W, Larrison, Wi, Lattanzio, R, Lavina, A, Lavinsky, J, Lazzaroni, F, Lee, E, Lee, Jy, Lee, M, Lee, Sy, Lee, V, Leff, S, Lehr, J, Lenfesty, P, Leonard, R, Levine, A, Levitan, M, Lewis, H, Liew, S, Lim, J, Lim, R, Lin, R, Lip, Pl, Liu, J, Lobes, La, Loose, I, Lottenberg, Cl, Loutchkina, D, Lu, Dw, Lubczynska, A, Lujan, B, Lyssek Boron, A, Ma, C, Ma, P, Maberley, D, Maccumber, M, Madhusudhana, Kc, Madreperla, S, Magee, M, Magolan, J, Maia Ode O., Jr, Maia, A, Majji, A, Malthieu, D, Mango, C, Marmor, M, Marques, L, Martin, D, Martinez, Ja, Massaoutis, P, Mathur, R, Mattioli, S, Maturi, Rk, Mazur Michalek, I, Mcallister, I, Mccabe, F, Mccannel, Ca, Mcgimpsey, S, Mchugh, Jd, Mckibbin, M, McLean WC Jr, Mcmillan, T, Meireles, R, de Melo CS, Menchini, U, Meredith, T, Merrill, P, Mian, U, Michels, M, Midena, E, Mieler, Wf, Migliavacca, L, Miller, D, Miller, J, Mincey, G, Mitchell, P, Mizubuti, Sk, Mohamed, S, Mohammed, M, Moinfar, N, Moisseiev, J, Mones, J, Montemayor Lobo, R, Montero, J, de Moraes NI, Moreira CA Jr, Morely, M, Moreno, Jm, Moron, Jt, Morrison, Vl, Morse, L, Moshfeghi, A, Moshfeghi, D, Muccioli, C, Munshi, V, Murthy, Rc, Naing, T, Nair, R, Nascimento, J, Nascimento, Vp, Nawrocka, Z, Nawrocki, J, Newell, C, Newsom, R, Nguyen, J, Nguyen, Q, Nguyen, Rl, Nichols, J, Nilanjana, D, Noguchi, B, Noorily, S, Novack, R, Novak, M, Novalis, G, O'Brien, D, Offermann, I, Oguido, Ap, Oh, K, Okruszko, A, de Oliveira TL, Oliver, S, Ong, S, Orellana, J, Orzalesi, N, O'Toole, L, Ovando, Y, Paccione, J, Pach, J, Packo, K, Packowska, Ma, Palmer, J, Palmer, H, Palombi, K, Papp, A, Paques, M, Paranhos A., Jr, Park, D, Park, Ri, Park, S, Parke, D, Pastor Jimeno JC, Patel, S, Patra, S, Pavan, Pr, Pearce, I, Pecold, K, Pedio, M, Peh, Kk, Pelosini, L, Pendergast, S, Perez, Br, Perez Ortiz DJ, Perkins, S, Peters, M, Pheasant, T, Pilat, J, Pilotto, E, Piltz Seymour, J, Pirracchio, A, Pollack, A, Portella, E, Pracharova, Z, Prati, M, Prensky, Jg, Preston, R, Prieto, F, Puls, S, Purohit, Ar, Quintao, T, Rahhal, F, Rahman, W, Ramos, Ar, Ramsey, S, Rani, A, Rao, Pk, Rapizzi, E, Raskauskas, P, Ratiglia, R, Ratnakaram, R, Rauser, Me, Regillo, C, Rehak, J, Reichel, E, Reid, Da, Rejmont, L, Renaud Rougier MB, Ribon, Ri, Ricarova, R, Rich, R, Riley, A, Ripandelli, G, Rishi, E, Rivett, K, Rogers, A, Romanet, Jp, Rosa, Pj, Rosberger, D, Rose, S, Rosenfeld, P, Ross, Rr, Rotberg, M, Roth, Cb, Roth, D, Rubaltelli, D, Rubsamen, P, Ruby, A, Ruiz Moreno JM, Ruiz, R, Russell Gonder, J, Russell, M, Ryu, Jw, Sachs, H, Sadda, S, Safar, A, Salinas, C, Sall, K, Samad, A, Samkova, K, Sanders, J, Sandhu, R, Sandhu, Ss, Sandner, D, Sanislo, Sr, Sartani, G, Saviano, S, Savy, O, Schechter, Ba, Schenker, Hi, Schiff, W, Schlichtenbrede, F, Schneider, B, Schneider, L, Schneiderman, T, Schocket, L, Schoenherr, Schoenleber, D, Scholl, Hp, Schreiber, J, Schwartz, Sd, Sears, J, Sedlakova, J, Seery, C, Sell, C, Shah, G, Shapiro, M, Sharma, A, Sheidow, T, Sheu, Sj, Sheufele, T, Shukla, D, Siewec Proscinska, J, Silva, E, Singer, M, Singer, S, Singerman, Lj, Singh, M, Siow, Yc, Sipperley, Jo, Sivaprasad, S, Sjaarda, R, Snyder, W, Sobrin, L, Sodi, A, Solomon, S, Sonkin, P, Soubrane, G, Gisèle, P, Spirn, B, Srivastava, S, Stannard, K, Staurenghi, G, Steinmetz, R, Stepien, K, Stern, W, Stevenson, Od, Stewart, D, Stolba, U, Stoller, G, Stone, C, Stout, Jt, Stringfellow, G, Studnicka, J, Suarez Figueroa, M, Sung, J, Susini, A, Syracuse, R, Szaflik, J, Szlechter, M, Tabandeh, H, Tadayoni, R, Takahashi, Wy, Taleb, Ac, Talks, Sj, Tamayo, L, Tan, M, Taney, B, Tarnawska, D, Tassinari, G, Taylor, J, Telander, D, Territo, C, Thomas, M, Thompson, Jt, Thompson, Ws, Tiedeman, Js, Topping, T, Trese, M, Truong, S, Tsang, Cw, Tufail, T, Ufret Vincenty, R, Uhmannova, R, 2nd, Ulanski L., Ulinska, M, Urminsky, J, Uy, H, Vaishnav, H, Varano, M, Vavvas, D, Vega Sanz BF, Veloso, A, Vicha, I, Viola, F, Visser, L, Vlkova, E, Voelker, M, Volkert, D, Vossmerbaumer, U, Vu, C, Vyas, S, Walker, J, Walter, A, Andreas, R, Wasiak, K, Watt, Dr, Weger, M, 3rd, Weidman F., Weinberger, D, Weisz, Jm, 3rd, Wells J., Wheatley, M, Wickremasingh, S, Wiegand, T, Wieland, M, Will, D, Williams, G, Williams, Rg, Wilson, D, Win, Ph, Wing, Gl, Wirostko, W, Wirthlin, R, Wong, Al, Wong, T, Woo, J, Wu, Tt, Wylegala, E, Yan, J, Yang, Ch, Yang, Cm, Yang, Y, Yang, Yc, Yarian, D, Yates, P, Yedavally, S, Yoken, J, Young, L, Young, S, Zago, Rj, Zakov, Z, Zaras, M, Zegarra, H, Ziemianski, M, Zimmer Galler, I, Zourdani, A, and Zur, C.

Published
2010

9. Absence of Infectious Retinitis after Injection of Human Cytomegalovirus into Rabbit Eyes

Author

Tatebayashi, M., primary, Neyts, J., additional, Besen, G., additional, Flores-Aguilar, M., additional, Smith, I. L., additional, Wiley, C. A., additional, Spector, S. A., additional, Lynn, G. B., additional, Maudgal, P. C., additional, Clercq, E. D., additional, Gangan, P. A., additional, Chavez, E., additional, Russack, V., additional, and Freeman, W. R., additional

Published
1995
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15. Evaluation of retinal toxicity and efficacy of anti-cytomegalovirus and anti-herpes simplex virus antiviral phosphorothioate oligonucleotides ISIS 2922 and ISIS 4015.

Author

Flores-Aguilar M, Besen G, Vuong C, Tatebayashi M, Munguia D, Gangan P, Wiley CA, and Freeman WR

Subjects
Animals, Antiviral Agents toxicity, Humans, Oligonucleotides, Antisense therapeutic use, Rabbits, Retinitis drug therapy, Swine, Thionucleotides therapeutic use, Thionucleotides toxicity, Antiviral Agents therapeutic use, Cytomegalovirus genetics, Herpesvirus 1, Human genetics, Oligonucleotides, Antisense toxicity, Retina drug effects, Retinitis prevention & control
Abstract

Retinal toxicity of ISIS 2922 and ISIS 4015, phosphorothioate oligonucleotides complementary to human cytomegalovirus (CMV) and herpes simplex virus (HSV) RNA, were evaluated. The intravitreal concentration of ISIS 2922 found not to cause permanent toxic changes in the rabbit retina was 10 microM and in the pig retina, 5 microM. The 3 microM concentration was associated with a transient inflammatory response, and 1 microM caused no retinal toxicity or inflammation. ISIS 4015 showed very mild toxicity with no permanent retinal changes and very mild inflammation at doses of 10 microM; this dose was effective in ameliorating or preventing HSV-1 retinitis when injected 1 day and 1 week prior to virus inoculation. These oligonucleotides have a low intraocular therapeutic index. Attempts to improve the therapeutic index of these compounds are indicated. Only a clinical trial can determine the toxicity profile of ISIS 2922 for the treatment of CMV retinitis.

Published
1997
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16. Evaluation of a novel lipid prodrug for intraocular drug delivery: effect of acyclovir diphosphate dimyristoylglycerol in a rabbit model with herpes simplex virus-1 retinitis.

Author

Taskintuna I, Banker AS, Flores-Aguilar M, Bergeron-Lynn G, Aldern KA, Hostetler KY, and Freeman WR

Subjects
Acyclovir therapeutic use, Animals, Disease Models, Animal, Ganciclovir therapeutic use, Herpes Simplex virology, Liposomes, Rabbits, Retinitis virology, Virus Replication, Acyclovir analogs & derivatives, Antiviral Agents therapeutic use, Herpes Simplex drug therapy, Phosphatidylglycerols therapeutic use, Prodrugs therapeutic use, Retinitis drug therapy, Simplexvirus physiology
Abstract

Background: Acyclovir diphosphate dimyristoylglycerol is a lipid prodrug of acyclovir that forms liposomes and provides substantial activity against herpes simplex virus, acyclovir-resistant strains of herpes simplex virus, and human cytomegalovirus. We therefore tested this promising new drug in a rabbit model of herpes simplex retinitis., Methods: A total of 22 pigmented rabbits were pretreated with either acyclovir diphosphate dimyristoylglycerol, ganciclovir, acyclovir, or buffer. Retinae then were inoculated with herpes simplex virus-1 or buffer 1 week after the injection of drug. In another experiment we compared the effects of acyclovir diphosphate dimyristoylglycerol and acyclovir diphosphate dioleoylglycerol on the optical clarity of vitreous., Results: Animals injected intravitreally with acyclovir diphosphate dimyristoylglycerol showed retinitis that was less severe than that in animals injected with ganciclovir, acyclovir, and buffer; differences in grading scores of the retinitis between animals injected with acyclovir diphosphate dimyristoylglycerol and those injected with buffer were statistically significant (P = 0.0015). Vitreous and optical media became clear 4 days after acyclovir diphosphate dioleoylglycerol injection compared with 10 days after with acyclovir diphosphate dimyristoylglycerol injections., Conclusion: Acyclovir diphosphate dimyristoylglycerol had prolonged antiviral activity against herpes simplex virus-1 retinitis in a rabbit model. This drug delivery system, modified to improve optical clarity, may allow long-acting intravitreal treatment of cytomegalovirus retinitis and other retinal diseases.

Published
1997
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17. Use of perflubron as a new temporary vitreous substitute and manipulation agent for vitreoretinal surgery. Wills Eye Hospital Perflubron Study Group.

Author

Banker AS, Freeman WR, Vander JF, Flores-Aguilar M, and Munguia D

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Fluorocarbons adverse effects, Foreign-Body Migration physiopathology, Humans, Hydrocarbons, Brominated, Intraoperative Period, Lens Subluxation physiopathology, Male, Middle Aged, Prospective Studies, Retinal Perforations physiopathology, Visual Acuity, Vitrectomy methods, Vitreoretinopathy, Proliferative physiopathology, Vitreous Body, Fluorocarbons therapeutic use, Foreign-Body Migration surgery, Lens Subluxation surgery, Lenses, Intraocular, Retinal Perforations surgery, Vitreoretinopathy, Proliferative surgery
Abstract

Purpose: The authors determine the intraocular tolerance of a new widely used liquid perfluorocarbon, perfluoroctylbromide (perflubron)., Methods: Pars plana vitrectomy was performed on 54 eyes of 54 patients with vitreoretinal disorders at three centers. Diagnoses included giant retinal tears, proliferative vitreoretinopathy, and dislocated intraocular and crystalline lenses. At the conclusion of the vitrectomy, perflubron was removed., Results: Perflubron was efficacious for vitreoretinal manipulation. Of the 45 eyes with retinal detachment, 23 (51.1%) of the retinas were reattached after a single surgery; redetachment occurred in 22 (48.9%) after the initial procedure, and further surgery was necessary to reattach the retina. Final retinal reattachment was achieved in 40 (88.9%) eyes. Mean visual acuity improvement was six lines (P < 0.0019). Visualization of the water/perfluorocarbon interface was good. There was no evidence of adverse effects from perflubron on the retina, lens, or anterior segment., Conclusion: Findings indicate that perflubron is safe for temporary intraoperative use intravitreally. The absence of adverse effects is consistent with the properties of perflubron that our group has studied in the eyes of animals and in other uses in human patients.

Published
1996
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18. Clinical versus fundus photographic evaluation of the status of cytomegalovirus retinitis in AIDS patients.

Author

Flores-Aguilar M, Munguia D, Besen G, Gangan P, Arevalo JF, and Freeman WR

Subjects
AIDS-Related Opportunistic Infections drug therapy, AIDS-Related Opportunistic Infections physiopathology, Antiviral Agents therapeutic use, Cytomegalovirus Retinitis drug therapy, Cytomegalovirus Retinitis physiopathology, Fluorescein Angiography, Fundus Oculi, Humans, Ophthalmoscopy, Prospective Studies, Reproducibility of Results, Retina pathology, Sensitivity and Specificity, Visual Acuity, AIDS-Related Opportunistic Infections diagnosis, Cytomegalovirus Retinitis diagnosis, Photography methods
Abstract

Purpose: To evaluate the accuracy of clinical examinations and serial fundus photographic readings in determining the response of cytomegalovirus retinitis to antiviral therapy in patients with acquired immune deficiency syndrome., Methods: Fifty two consecutive patients with cytomegalovirus retinitis who were prospectively evaluated over a 30-month period for a minimum of 6 months (or until death) were included in this study. There was a total of 708 patients visits. The clinical evaluations included indirect ophthalmoscopy, fundus drawings, 60 degrees fundus photographs, and a comparison of the photographs with those of the previous visit. The fundus photographs were reevaluated in a blinded fashion. Cytomegalovirus retinitis was classified as active (progression of border since last examination) intermediate (border activity without progression), healed (no activity since last visit), or normal (no retinitis)., Results: Using the photographic data as the measure of cytomegalovirus retinitis activity, the sensitivity and specificity of clinical assessments were determined. The sensitivity and specificity of clinical versus photographic evaluations varied with retinitis status. In healed retinitis the sensitivity of the clinical examination was 98%, and the specificity was 83%. In cases of border opacification without progression the sensitivity was 80%, and the specificity was 96%. In cases of clinically active retinitis the sensitivity was 63% with a specificity of 100%. Clinical detection of active retinitis and border opacification without progression was reduced when potential problems were present that made visualization of the retinitis border difficult, such as smoldering retinitis, progressive retinal destruction without border opacification, poor media, or fundus pigmentation., Conclusions: Progressive retinal destruction and visual loss can occur in patients with cytomegalovirus retinitis despite antiviral therapy. Examining the patient through indirect ophthalmoscopy only can result in failure to detect subtle changes.

Published
1996
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19. Clinically resistant cytomegalovirus retinitis.

Author

Flores-Aguilar M

Subjects
AIDS-Related Opportunistic Infections etiology, Antiviral Agents pharmacology, Cytomegalovirus Retinitis etiology, Drug Resistance, Microbial, Drug Therapy, Combination, Foscarnet pharmacology, Foscarnet therapeutic use, Fundus Oculi, Ganciclovir pharmacology, Ganciclovir therapeutic use, Humans, AIDS-Related Opportunistic Infections drug therapy, Antiviral Agents therapeutic use, Cytomegalovirus drug effects, Cytomegalovirus Retinitis drug therapy
Published
1995
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20. Long-term therapy for herpes retinitis in an animal model with high-concentrated liposome-encapsulated HPMPC.

Author

Besen G, Flores-Aguilar M, Assil KK, Kupperman BD, Gangan P, Pursley M, Munguia D, Vuong C, De Clercq E, and Bergeron-Lynn G

Subjects
Animals, Antiviral Agents pharmacokinetics, Antiviral Agents toxicity, Cidofovir, Cytosine administration & dosage, Cytosine pharmacokinetics, Cytosine toxicity, Disease Models, Animal, Electroretinography, Eye Infections, Viral pathology, Fundus Oculi, Herpes Simplex pathology, Liposomes, Longitudinal Studies, Organophosphorus Compounds pharmacokinetics, Organophosphorus Compounds toxicity, Rabbits, Retinitis pathology, Retinitis virology, Antiviral Agents administration & dosage, Cytosine analogs & derivatives, Eye Infections, Viral drug therapy, Herpes Simplex drug therapy, Organophosphonates, Organophosphorus Compounds administration & dosage, Retinitis drug therapy
Abstract

Objective: To evaluate(s)-1-(3-hydroxy-2-phosphonyl methoxypropyl) cytosine (HPMPC), a potent antiherpes and anticytomegalovirus drug, as a long-term treatment of experimental retinitis in rabbits., Methods: The drug was first encapsulated into a liposome delivery system in three different concentrations and injected intravitreally. Sequentially, the highest concentration that was shown to be nontoxic to the retina was evaluated in a model of retinitis at 60, 90, 120, 170, and 240 days, after which herpes simplex virus type 1 was inoculated onto the retinal surface., Results: A dose of 1000 micrograms of HPMPC encapsulated in liposomes gives a protective effect for up to 8 months., Conclusions: Reduced toxic effects and longer-term efficacy compared with free drug was observed. Given the 50 times higher activity of HPMPC against human cytomegalovirus than herpes simplex virus type 1, a single injection of 1000 micrograms of liposome-encapsulated HPMPC may have a very prolonged effect in the treatment of cytomegalovirus retinitis.

Published
1995
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21. Results of rhegmatogenous retinal detachment repair in cytomegalovirus retinitis with and without scleral buckling.

Author

García RF, Flores-Aguilar M, Quiceno JI, Capparelli EV, Munguia D, Kuppermann BD, Arevalo F, and Freeman WR

Subjects
Adult, Fundus Oculi, Humans, Laser Therapy, Middle Aged, Retinal Detachment etiology, Retinal Detachment pathology, Silicone Oils administration & dosage, Treatment Outcome, Visual Acuity, Vitrectomy, AIDS-Related Opportunistic Infections complications, Cytomegalovirus Retinitis complications, Eye Infections, Viral complications, Retinal Detachment surgery, Scleral Buckling
Abstract

Purpose: To determine if scleral buckling is of any benefit in surgical repair of cytomegalovirus (CMV)-associated retinal detachment if combined with vitrectomy, silicone oil, and inferior midperipheral endolaser., Materials and Methods: Twenty-two consecutive eyes with CMV-associated retinal detachments were repaired with vitrectomy and endolaser to all breaks and to the inferior midperipheral retina using silicone oil without scleral buckling (group 1, control group) between July 1987 and May 1992. Results were compared with another series of 56 consecutive eyes undergoing vitrectomy, silicone oil injection, endolaser to all breaks, and 360 degrees encircling scleral buckling (group 2, study group) between June 1992 and July 1993., Results: Total retinal reattachment rates were 84% for group 1 and 86% for group 2. Rates of macular reattachment were 91% for group 1 and 91% for group 2. Mean best postoperative refracted visual acuity was 20/66 for group 1 and 20/67 for group 2. Median best postoperative refracted visual acuity was 20/74 for group 1 and 20/80 for group 2. These differences in results between the two groups were not statistically significant. Mean postoperative refractive error was +3.95 for group 1 and +4.92 for group 2. Patients who underwent surgery with the macula attached had a better postoperative visual outcome., Conclusion: Scleral buckling may not be necessary in CMV-related retinal detachment if repaired with vitrectomy, silicone oil, and inferior midperipheral endolaser. Elimination of scleral buckling may reduce intraoperative time, patient morbidity, and the risk of an accidental needle stick. Patients with macula-on retinal detachments also should be considered for surgery before macular detachment.

Published
1995
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22. Evaluation of retinal toxicity of acetylcholine in rabbit eyes.

Author

Ahn DS, Flores-Aguilar M, Kirsch L, Munguia D, Gangan P, and Freeman WR

Subjects
Animals, Drug Evaluation, Electroretinography, Injections, Ophthalmoscopy, Rabbits, Retina physiology, Retina ultrastructure, Sulfur Hexafluoride, Vitrectomy, Vitreous Body, Acetylcholine toxicity, Retina drug effects
Abstract

Purpose: In vitreoretinal surgery, pupillary constriction may be required at the termination of a procedure especially if mechanical pupillary dilation was used in eyes filled with gas or silicone oil. A miotic agent instilled into the anterior chamber will sink and come into direct contact with retina in the aphakic or pseudophakic vitrectomized eye. Therefore, the retinal toxicity of acetylcholine, a miotic used for pupillary constriction, was studied., Methods: Eight Dutch pigmented rabbit eyes were vitrectomized, had air-fluid exchange, and were injected with a 20% mixture of SF6. Subsequently eyes were randomly selected to have injections of 0.75 ml of 10 mg/ml acetylcholine (Miochol, Iolab Corp., Claremont CA) versus 0.75 ml of lactated Ringer's solution. Short-term (2 weeks) and long-term (6 weeks) retinal toxicity was assessed by ophthalmoscopy, electroretinogram, and histology by light and electron microscopy at both times., Results: Ophthalmoscopy, electroretinographic tracings, histology, and electron microscopy disclosed no significant abnormalities., Conclusions: Acetylcholine does not appear to have significant retinal toxicity even when undiluted solutions are in direct contact with the retina. We therefore postulate that intraoperative use of acetylcholine in previously vitrectomized eyes filled with gas or silicone is safe.

Published
1995
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23. Intraocular tolerance of perfluorooctylbromide (perflubron)

Author

Flores-Aguilar M, Munguia D, Loeb E, Crapotta JA, Vuong C, Shakiba S, Bergeron-Lynn G, Wiley CA, Weers J, and Freeman WR

Subjects
Animals, Cataract chemically induced, Cataract pathology, Drug Tolerance, Electroretinography, Emulsions, Hydrocarbons, Brominated, Lens, Crystalline drug effects, Lens, Crystalline pathology, Longitudinal Studies, Rabbits, Retina physiology, Retina ultrastructure, Swine, Swine, Miniature, Vitreous Body drug effects, Fluorocarbons toxicity, Retina drug effects, Vitrectomy
Abstract

Purpose: To determine the intraocular tolerance of perfluorooctylbromide (perflubron) in vitrectomized rabbit and pig eyes and evaluated its use as a vitreous substitute in virteoretinal surgery., Methods: Pars plana vitrectomy was performed on 33 Dutch pigmented rabbits and 11 micro mini pigs. After vitrectomy the eyes were filled with perflubron for 2 hours, 1 week, 2 weeks, 1 month, and up to 6 months., Results: No clinical, electroretinographic, or light and electron microscopic evidence of adverse effects on the retina and lens were observed. Perflubron emulsified and dispersed into small bubbles after 2-3 weeks. The lens showed mild posterior subcapsular cataracts in pig eyes after long-term retention of perflubron., Conclusion: These findings indicate that perflubron is safe for intraoperative and for long-term use intravitreally. However, emulsification and the breakdown into small bubbles limits the view of the retina when perflubron is used as a long-term tamponade.

Published
1995

24. Long-acting therapy of viral retinitis with (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine.

Author

Flores-Aguilar M, Huang JS, Wiley CA, De Clercq E, Vuong C, Bergeron-Lynn G, Chandler B, Munguia D, and Freeman WR

Subjects
Animals, Antiviral Agents toxicity, Cidofovir, Cytosine therapeutic use, Cytosine toxicity, Drug Therapy, Combination, Ganciclovir therapeutic use, Herpesvirus 1, Human, Organophosphorus Compounds toxicity, Rabbits, Retinitis microbiology, Time Factors, Antiviral Agents therapeutic use, Cytosine analogs & derivatives, Herpes Simplex drug therapy, Organophosphonates, Organophosphorus Compounds therapeutic use, Retinitis drug therapy
Abstract

(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), a high-potency antiherpes and anticytomegalovirus (CMV) drug was evaluated in the treatment of experimental retinitis caused by preretinal herpes simplex virus (HSV-1) injection in rabbits. HPMPC (100 micrograms/0.1 mL) was intravitreally injected 10, 15, 21, 30, or 46 days before, concurrently, or 3, 5, or 7 days after viral inoculation. Ganciclovir (200 micrograms/0.1 mL) was intravitreally injected 3, 7, or 10 days before HSV-1 inoculation, concurrent with viral inoculation, or 3, 5, or 7 days after viral inoculation. Eyes pretreated with HPMPC were protected from retinitis for 15-21 days. Ganciclovir did not protect completely even if administered 3 days before inoculation. Early treatment of established retinitis with HPMPC markedly delayed the progression of the infection. However, with ganciclovir there was delayed progression only in rabbits treated 3 days after viral inoculation. HPMPC had a remarkably potent and prolonged (< or = 1 month) antiviral effect in this retinitis model and may prove more useful than ganciclovir in local treatment of CMV retinitis.

Published
1994
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25. A masked prospective evaluation of outcome parameters for cytomegalovirus-related retinal detachment surgery in patients with acquired immune deficiency syndrome.

Author

Kuppermann BD, Flores-Aguilar M, Quiceno JI, Capparelli EV, Levi L, Munguia D, and Freeman WR

Subjects
AIDS-Related Opportunistic Infections pathology, Adult, Cytomegalovirus Retinitis pathology, Evaluation Studies as Topic, Follow-Up Studies, Humans, Incidence, Middle Aged, Optic Disk pathology, Prospective Studies, Retinal Detachment etiology, Retinal Detachment pathology, Survival Rate, Treatment Outcome, Visual Acuity, AIDS-Related Opportunistic Infections complications, Cytomegalovirus Retinitis complications, Retinal Detachment surgery
Abstract

Purpose: The management of cytomegalovirus (CMV)-related rhegmatogenous retinal detachments in patients with acquired immune deficiency syndrome (AIDS) has been the subject of recent attention and controversy because of the high degree of variability in visual outcome, as well as significant differences in the reported incidence of profound postoperative optic atrophy. This study was designed to evaluate the various parameters affecting postoperative visual outcome, and to quantitate the degree of postoperative optic disc pallor., Methods: The results of 65 consecutive surgeries for CMV-related retinal detachments in 51 patients with AIDS were prospectively studied. Postoperative vision, survival, optic disc pallor, and retinitis extent were analyzed. Serial photographs of optic discs underwent masked evaluation., Results: Mean postoperative survival was 30 weeks (range, 2-146 weeks). Mean best postoperative visual acuity was 20/66 (range, 20/20-2/200) and mean final postoperative visual acuity was 20/100 (range, 20/25-no light perception). Analysis of visual outcome for eyes with no macular or papillo-macular retinitis showed a best postoperative visual acuity of 20/60 (range, 20/25-2/200) and mean final postoperative visual acuity of 20/80 (range, 20/25-no light perception). Postoperative vision was not affected by the presence of a preoperative macular detachment, with both groups (macula on or off detachments), achieving a best postoperative visual acuity of 20/60 in the absence of macular retinitis. Mild postoperative optic disc pallor was observed in 30% of surgical eyes at the final postoperative visit, and moderate pallor was noted in 13%. The mean degree of optic disc pallor was not different from the degree of optic disc pallor seen in fellow, nonsurgical eyes with CMV retinitis (surgical versus fellow nonsurgical eyes, 29% +/- 23% versus 26% +/- 30%; P = 0.64)., Conclusion: In this largest reported series of reattachment surgery for CMV-related retinal detachments, patients are experiencing increased postoperative survival, good vision, and relative optic nerve health.

Published
1994
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26. Intravitreal ganciclovir concentration after intravenous administration in AIDS patients with cytomegalovirus retinitis: implications for therapy.

Author

Kuppermann BD, Quiceno JI, Flores-Aguilar M, Connor JD, Capparelli EV, Sherwood CH, and Freeman WR

Subjects
Adult, Chromatography, High Pressure Liquid, Cytomegalovirus Retinitis complications, Female, Ganciclovir administration & dosage, Ganciclovir therapeutic use, Humans, Injections, Intravenous, Male, Middle Aged, Regression Analysis, Retinal Detachment metabolism, Retinal Detachment surgery, AIDS-Related Opportunistic Infections drug therapy, Cytomegalovirus Retinitis drug therapy, Ganciclovir pharmacokinetics, Vitreous Body metabolism
Abstract

To determine whether therapeutic intravitreal concentrations of ganciclovir are achieved after intravenous administration, vitreous samples were obtained intraoperatively from 23 eyes of 22 AIDS patients with retinal detachments associated with cytomegalovirus (CMV) retinitis. The mean intravitreal ganciclovir concentration of all samples was 0.93 +/- 0.39 microgram/mL (3.6 +/- 1.5 microM). This level is near the published trough serum concentrations obtained with every-12-h intravenous dosing and well below the peak. It is significantly below the concentration of ganciclovir required to achieve 50% of viral plaque formation for many human CMV strains. Only a small decrease in vitreous drug levels was observed as a function of time after last dose. Intravenous administration of ganciclovir results in near-steady-state subtherapeutic intravitreal ganciclovir concentrations for many CMV isolates. This may explain the difficulty of long-term complete suppression of CMV retinitis.

Published
1993
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27. Combination ganciclovir and foscarnet in the treatment of clinically resistant cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome.

Author

Kuppermann BD, Flores-Aguilar M, Quiceno JI, Rickman LS, and Freeman WR

Subjects
Adult, Drug Resistance, Microbial, Drug Therapy, Combination, Female, Foscarnet adverse effects, Ganciclovir adverse effects, Humans, Infusions, Intravenous, Male, Middle Aged, AIDS-Related Opportunistic Infections drug therapy, Cytomegalovirus Retinitis drug therapy, Foscarnet therapeutic use, Ganciclovir therapeutic use
Abstract

Objective: To assess the clinical response and patient tolerance to daily infusions of both ganciclovir sodium and foscarnet sodium for the treatment of clinically resistant cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome., Design and Patients: Nine patients with clinically resistant cytomegalovirus retinitis who had shown progression of retinitis despite extended intravenous induction single-drug therapy or alternating therapy with induction doses of ganciclovir or foscarnet at 6 weeks were subsequently treated with a combination of ganciclovir and foscarnet. The dosing regimen for induction combination therapy was ganciclovir at 5 mg/kg every 12 hours and foscarnet at 60 mg/kg every 8 hours. Maintenance combination therapy was ganciclovir at 5 mg/kg every 12 to 24 hours and foscarnet at 90 to 120 mg/kg every day. Patients were observed closely for signs of a toxic effect or intolerance to the drug regimen., Results: All patients exhibited a favorable response to combination therapy, with complete healing of retinitis in 12 of 14 eyes and partial healing of retinitis with decreased border activity and a cessation of border advancement in two of 14 eyes. Two of the nine patients stopped receiving combination therapy before completion of the study owing to their dissatisfaction with the time commitment. The regimen was otherwise well tolerated, with no significant medical toxic effects attributable to the drugs requiring cessation of therapy., Conclusions: Combination anticytomegalovirus therapy should be considered in those patients who have shown a poor clinical response to sustained single-drug induction therapy and alternating drug therapy. As survival time for patients with cytomegalovirus retinitis continues to improve, clinical resistance may become more common. Further work to delineate the optimal dosing and indications for combination therapy will be important.

Published
1993
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28. Evaluation of retinal toxicity and liposome encapsulation of the anti-CMV drug 2'-nor-cyclic GMP.

Author

Shakiba S, Assil KK, Listhaus AD, Munguia D, Flores-Aguilar M, Vuong C, Wiley CA, Tolman RL, Karkas JD, and Bergeron-Lynn G

Subjects
Animals, Antiviral Agents pharmacokinetics, Cytomegalovirus drug effects, Drug Carriers, Drug Evaluation, Electroretinography drug effects, Guanine pharmacokinetics, Guanine toxicity, Half-Life, Liposomes, Organophosphorus Compounds pharmacokinetics, Pigment Epithelium of Eye drug effects, Rabbits, Retina ultrastructure, Rod Cell Outer Segment drug effects, Antiviral Agents toxicity, Guanine analogs & derivatives, Organophosphorus Compounds toxicity, Retina drug effects
Abstract

Purpose: Human cytomegalovirus (HCMV) is an important pathogen in the immunocompromised patient. CMV retinitis is a leading cause of blindness in patients with AIDS. Ganciclovir and foscarnet are currently the treatments being used for this retinitis, but they both have major toxicities when used systemically. Intravitreal therapy with ganciclovir has been used in some patients who cannot tolerate systemic treatment. The major problem with this modality is the necessity for administration of between 1 and 3 intravitreal injections per eye per week. 2'-nor-cyclic GMP is a nucleotide analog, a cyclic phosphate derivative of ganciclovir. Neutral salts of the compound are extremely water soluble, and the charged phosphate group at neutral pH make it an ideal candidate for encapsulation into a multivesicular liposome system., Methods: The authors evaluated the retinal toxicity of the diethanolammonium salt 2'-nor-cyclic GMP by using electroretinographic, morphologic, and ophthalmoscopic techniques after intravitreal injections in rabbit eye., Results: The intraocular therapeutic index for 2'-nor-cyclic GMP is 20. At the 10 micrograms dose, electroretinogram, ophthalmoscopic examination, and both light and electron microscopy revealed no abnormalities. Toxicity was evident at 50 micrograms and higher doses with ERG changes (loss of amplitude) and retinal pathology that varied from vacuolization of the retinal pigment epithelium and loss of height of the outer photoreceptor segment to loss of the entire outer retina. In addition, an in vitro drug release half-life of 1,000 hours (more than 75 times that of ganciclovir) was found for 2'-nor-cyclic GMP in liposome, which may be able to be exploited in the therapy of patients with CMV retinitis unable to tolerate toxic systemic therapy., Conclusion: The anti-CMV drug, 2'-nor-cyclic GMP, may be promising for intravitreal injection, particularly if encapsulated into liposomes.

Published
1993

29. Pathophysiology and treatment of clinically resistant cytomegalovirus retinitis.

Author

Flores-Aguilar M, Kuppermann BD, Quiceno JI, Dankner WM, Wolf DG, Capparelli EV, Connor JD, Sherwood CH, Fullerton S, and Gambertoglio JG

Subjects
AIDS-Related Opportunistic Infections physiopathology, Adult, Cytomegalovirus drug effects, Cytomegalovirus Infections physiopathology, Drug Resistance, Microbial, Drug Therapy, Combination, Eye Infections, Viral physiopathology, Female, Foscarnet pharmacokinetics, Foscarnet therapeutic use, Fundus Oculi, Ganciclovir pharmacokinetics, Humans, Male, Microbial Sensitivity Tests, Prospective Studies, Retinitis microbiology, Retinitis physiopathology, Survival Rate, Visual Acuity, AIDS-Related Opportunistic Infections drug therapy, Cytomegalovirus Infections drug therapy, Eye Infections, Viral drug therapy, Ganciclovir therapeutic use, Retinitis drug therapy
Abstract

Purpose: To determine the incidence, pathophysiology, clinical outcome, and survival in patients with clinically resistant retinitis., Methods: Cytomegalovirus (CMV) retinitis was prospectively studied in 100 patients with acquired immune deficiency syndrome (AIDS). In 11 of these patients, clinically resistant retinitis developed, defined as new activity or progression, despite at least 8 consecutive weeks of induction doses of either foscarnet or ganciclovir. Fundus photography, pharmacokinetics, CMV cultures and sensitivities, and survival analyses were studied. The therapeutic interventions attempted after clinically resistant retinitis was identified included continuing a high dose (induction level) of the same antiviral drug, changing the antiviral drug, and combining antiviral therapy with foscarnet and ganciclovir., Results: Clinically resistant retinitis occurred in 11 (11%) of 100 patients with CMV retinitis and appeared to be a manifestation of acquired CMV antiviral drug resistance. Drug metabolism and pharmacokinetics in these patients were normal. The use of combination therapy with foscarnet and ganciclovir was effective in halting the progression of retinitis in three (75%) of four patients (6 of 7 eyes able to be evaluated) receiving combination therapy., Conclusion: Clinically resistant retinitis is a manifestation of infection by CMV that has acquired drug resistance. In these patients, combination antiviral drug treatment should be considered. It is likely that clinically resistant retinitis will become more frequent as patients with CMV retinitis and AIDS survive longer.

Published
1993
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30. Evaluation of cytologic specimens obtained during experimental vitreous biopsy.

Author

Huang JS, Russack V, Flores-Aguilar M, Gharib M, and Freeman WR

Subjects
Animals, Evaluation Studies as Topic, Eye Infections, Viral pathology, Herpesviridae Infections pathology, Humans, Inhalation, Rabbits, Retinitis microbiology, Retinitis pathology, Viscosity, Vitrectomy, Vitreous Body microbiology, Vitreous Body physiology, Biopsy methods, Vitreous Body pathology
Abstract

Vitreous specimens can be useful for diagnosis of intraocular infection, inflammation, and neoplasms. Concern has been raised that obtaining vitreous specimens through a guillotine cutter might result in suboptimal cytologic changes. To determine if aspiration yields better cytologic information than vitrectomy, the authors performed experimental vitreous biopsies on rabbit eyes with vitritis to compare specimens taken by aspiration or vitrectomy with cutting rates of 100, 300, 600 per minute. The specimens were processed by cytospin preparations and stained with Papanicolaou and May-Grünwald-Giemsa stain. There was no difference in the adequacy of the specimens. Cell loss or damage to cell morphologic features when obtaining specimens through aspiration or vitrectomy at different cutting rates could not be differentiated by a blinded cytologic evaluation. A theoretical model of shear stress on cells passing through a guillotine cutter was also developed. The experimental and theoretical data show that vitrectomy with a cutting rate as fast as 600 per minute yields an adequate specimens with a sufficient number of well preserved cells to make definite cytologic interpretations, and that vitreous aspiration is not necessary.

Published
1993
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