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Chronic multifocal retinal infiltrates in patients infected with human immunodeficiency virus [see comments] [Comment]

Levinson RD; Vann R; Davis JL; Friedberg DN; Tufail A; Terry BT; Lindley JI; Holland GN
PURPOSE: To describe the clinical features of a disorder characterized by chronic multifocal retinal infiltrates and uveitis in individuals with human immunodeficiency virus (HIV) disease. METHODS: We reviewed the medical records of HIV-infected patients with multifocal retinal infiltrates of unknown cause seen by investigators at four institutions. The following data were collected: demographic characteristics, presenting signs and symptoms, laboratory test results, and course of disease. RESULTS: We identified 26 HIV-infected patients (50 involved eyes) with this syndrome. Median CD4+ T-lymphocyte count at presentation was 272 per microl (range, 7 to 2,118 per microl). The most common presenting symptom was floaters. Median visual acuity of involved eyes at presentation was 20/20 (range, 20/15 to 20/100) and remained stable (median, 20/20; range, 20/15 to 20/70) after a median follow-up period of 9 months (range, 0 to 110 months). Typical retinal lesions were gray-white or yellow, irregular in shape, and less than 200 microm in greatest dimension. All were located in the midperiphery or anterior retina and enlarged slowly or remained static in size. Mild to moderate anterior chamber or vitreous humor inflammatory cells were present in 47 of 50 eyes (26 of 26 patients). Retinal lesions possibly responded to zidovudine but not to acyclovir or ganciclovir. Anterior chamber and vitreous humor inflammatory reactions responded to topical or periocular injections of corticosteroid. CONCLUSIONS: Uveitis with chronic multifocal retinal infiltrates is a distinct clinical entity of unknown cause that occurs in HIV-infected patients. Retinal lesions may respond to antiretroviral therapy. Visual prognosis is good
PMID: 9512148
ISSN: 0002-9394
CID: 7655

MSL-109 adjuvant therapy for cytomegalovirus retinitis in patients with acquired immunodeficiency in syndrome - The monoclonal antibody cytomegalovirus retinitis trial

Lewis, RA; CarrHolden, LM; Doyle, K; Fainstein, V; Gardner, N; Gross, R; OrengoNania, S; Patel, V; Samo, TC; Shigley, JW; Shawver, L; Spencer, SS; Weinert, M; Martin, DF; Gibbs, D; Jernigan, J; Dunn, JP; Bartlett, J; Becker, R; Jabs, DA; Johnson, DA; LaSalvia, S; Leslie, J; Maenza, J; Miller, T; Neisser, LG; Semba, RD; Tucker, P; Barron, B; Jarrott, C; Peyman, G; Swenie, D; Heinemann, MH; Janis, R; Polsky, B; Sepkowitz, K; Friedman, AH; Ginsburg, R; Severin, C; Teich, S; Wallach, F; Rescigno, R; PaezBoham, R; Buroff, E; Kloser, P; Wanner, M; Friedberg, DN; Addessi, A; Chachoua, A; Dieterich, D; Hill, J; Hutt, R; Kaul, A; Ligh, J; LorenzoLatkany, M; Pei, M; Powers, T; Weinberg, DV; Jampol, EM; Lyon, AT; Munana, A; Murphy, R; Palella, F; Richine, L; Strugala, Z; Valadez, G; Holland, GN; Carlson, ME; Chafey, SA; Hardy, WD; Johiro, AK; MacArthurChang, LJ; Martin, MA; Moe, AA; Strong, CA; Tufail, A; Ugalat, PS; Weisz, JM; Freeman, WR; ArevaloColina, JF; Clark, T; Jarman, CL; Meixner, L; Meng, TC; Spector, S; Taskintuna, I; Torriani, FJ; ODonnell, J; Alfred, P; Ballesteros, F; Clay, D; Coleman, R; Gordon, K; Gumbley, D; Hoffman, J; Irvine, A; Jacobson, M; Larson, M; Macalalag, L; Narahara, M; Payne, M; Seiff, S; Wilson, S; Woodring, H; Davis, J; Blenke, A; Madera, I; Mendez, P; Murray, T; vanderHorst, C; Kylstra, J; Wohl, D; Ziman, K; Pavan, PR; Grizzard, WS; Bergen, GA; Cohen, SM; Craig, JA; Dehler, RL; Elbert, E; Fox, RW; Hammer, ME; Hernandez, LS; Herrera, S; Holt, D; Kemp, S; Larkin, JA; Ledford, DK; Lockey, RF; Menosky, MM; Millard, S; Nadler, JP; Nelson, RP; Norris, D; Ormerod, LD; Pautler, SE; Poblete, SJ; Rodriguez, D; Rosenbach, KP; Seekins, DW; Toney, JR; Dodge, JM; Klemstine, JL; Schuerholtz, TA; Stevens, M; Meinert, CL; AmendLibercci, D; Coleson, L; Collins, KL; Collison, BJ; Dawson, C; Dodge, J; Donithan, M; Ewing, C; Fink, N; Gerczak, C; Harle, J; Holbrook, JT; Huffman, R; Isaacson, MR; Gilpin, AMK; Lane, M; Levine, CR; Martin, B; Meinert, J; Min, N; Nowakowski, DJ; Owens, RM; Oziemkowska, MJ; Piantadosi, B; Saah, A; Smith, M; Tonascia, J; VanNatta, ML; Davis, MD; Armstrong, J; Brickbauer, J; Brothers, R; Chop, M; Hubbard, L; Hurlburt, D; Kastorff, L; Neider, M; Onofrey, J; Stoppenbach, V; VanderhoofYoung, M; Walls, M; Hughes, R; Kurinij, N; Mowery, RL; Alston, B; Foulkes, M; Nadler, PI; Wood, DL; Bladet, M; Wu, N; Clark, T; Feinberg, J; Freeman, W; Holbrook, J; McArthurChang, L; Duncan, WR; Kessler, H; Lambert, AG; Powderly, W; Schnittman, S; Spector, S; Brown, BW; Conway, B; Grizzle, J; Nussenblatt, R; Phair, JP; Smith, H; Whitley, R; Cheng, B; Frost, K; Marco, M
Objective: To evaluate the the efficacy and safety of an intravenous human monoclonal antibody to cytomegalovirus (CMV), MSL-109, as adjuvant treatment for CMV retinitis. Methods: Two hundred nine patients with acquired immunodeficiency syndrome and active CMV retinitis were enrolled in a multicenter, phase 2/3, randomized, placebo-controlled clinical trial. Patients received adjuvant treatment with MSL-109, 60 mg intravenously every 2 weeks, or placebo. Randomization was stratified on the basis of whether patients had untreated or relapsed retinitis. Primary drug therapy for CMV retinitis was determined by the treating physician. Results: The rates of retinitis progression, as evaluated in a masked fashion, were 3.04/person-year in the MSL-109-treated group and 3.05/person-year in the placebo-treated group (P=.98; Wald test); the median times to progression were 67 days in the MSL-109-treated group and 65 days in the placebo-treated group. No differences between the 2 groups were noted in the rates of increase in retinal area involved by CMV, visual field loss, or visual acuity outcomes. The mortality rate in the MSL-109-treated group was 0.68/person-year, and in the placebo-treated group, 0.31/person-year (P=.01). The mortality difference was not explained by differences in baseline variables or in concurrent antiretroviral therapy. Among patients with newly diagnosed retinitis, mortality rates were similar (MSL-109, 0.41/person-year; placebo, 0.42/person-year; P=.95), whereas among patients with relapsed retinitis the MSL-109-treated group had a greater mortality rate (MSL-109, 0.83/person-year, placebo, 0.24/person-year; P=.003). However, the mortality rate in the placebo-treated patients with relapsed CMV retinitis was lower than that in the placebo-treated patients with newly diagnosed CMV retinitis and lower than that in other trials of patients with relapsed CMV retinitis. Conclusions: Intravenous MSL-109, 60 mg every 2 weeks, appeared to be ineffective adjuvant therapy for CMV retinitis. The mortality rate was higher in the MSL-109-treated group, but the reasons for this difference remain uncertain
ISI:A1997YK25100005
ISSN: 0003-9950
CID: 53126

Hypotony and visual loss with intravenous cidofovir treatment of cytomegalovirus retinitis [Letter]

Friedberg DN
PMID: 9194736
ISSN: 0003-9950
CID: 14730

Re-evaluation of time to progression of foscarnet salvage therapy for cytomegalovirus retinitis in AIDS patients clinically resistant to ganciclovir [Letter]

Mueller AJ; Jacobson MA; Hurwitz S; Chuang EL; Friedberg DN; Haidt SJ; Heinemann MH; Jabs DA; Kaplan HJ; Freeman WR
PMID: 9147441
ISSN: 0269-9370
CID: 14731

New Approaches to the Treatment of Cytomegalovirus Retinitis - Proceedings based on a Roundtable Meeting held in Washington, DC, January 26, 1996 - Open discussion [Meeting Abstract]

Whitley, RJ; Friedberg, DN; Kuppermann, BD; Lalezari, JP; Spector, SA; Hardy, WD
ISI:A1997WN35800008
ISSN: 1077-9450
CID: 53248

Parenteral cidofovir for cytomegalovirus retinitis in patients with AI

Lewis, RA; Carr, LM; Doyle, K; Fainstein, V; Gross, R; OrengoNania, S; Samo, TC; Shigley, JW; Spencer, SS; Weinert, M; Dunn, JP; Bartlett, J; Becker, R; Feinberg, J; Jabs, DA; Johnson, DA; LaSalvia, S; Miller, T; Neisser, LG; Semba, RD; TayKearney, ML; Tucker, P; Barron, B; Jarrott, C; Peyman, G; Swenie, D; Friedman, AH; Ginsburg, R; Sacks, H; Severin, C; Teich, S; Wallach, F; Rescigno, R; Cowan, J; Horan, C; Kloser, P; Wanner, M; Friedberg, DN; Addessi, A; Chachoua, A; Dieterich, D; Hill, J; Hutt, R; Ligh, J; LorenzoLatkany, M; Pei, M; Powers, T; Scoppe, C; Weinberg, DV; Jampol, LM; Lyon, AT; Munana, A; Murphy, R; Palella, F; Richine, L; Strugala, Z; Valadez, G; Holland, GN; Carlson, ME; Chafey, S; Hardy, WD; Johiro, AK; MacarthurChang, L; Martin, MA; Moe, AA; Strong, CA; Tufail, A; Ugalat, PS; Weisz, JM; Freeman, WR; ArevaloColina, JF; Clark, T; Jarman, CL; Meixner, L; Meng, TC; Spector, S; Taskintuna, I; Torriani, FJ; ODonnell, J; Alfred, P; Ballesteros, F; Clay, D; Coleman, R; Gumbley, D; Hoffman, J; Irvine, A; Jacobson, M; Larson, J; Macalalag, L; Narahara, M; Payne, M; Seiff, S; Wilson, S; Woodring, H; Davis, J; Mendez, P; Murray, T; Simmons, T; vanderHorst, C; Kylstra, J; Wohl, D; Ziman, K; Pavan, PR; Bergen, GA; Cohen, SM; Craig, JA; Dehler, RL; Elbert, E; Fox, RW; Grizzard, WS; Hammer, ME; Hernandez, LS; Herrera, S; Holt, D; Kemp, S; Larkin, JA; Ledford, DK; Lockey, RF; Menosky, MM; Millard, S; Nadler, JP; Nelson, RP; Norris, D; Ormerod, LD; Pautler, SE; Poblete, SJ; Rodriguez, D; Rosenbach, KP; Seekins, DW; Toney, JR; Dodge, JM; Klemstine, JL; Schuerholtz, TA; Stevens, M; Meinert, CL; AmendLibercci, D; Coleson, L; Collins, KL; Collison, BJ; Dawson, C; Dodge, J; Donithan, M; Ewing, C; Fink, N; Gerczak, C; Harle, J; Holbrook, JT; Huffman, R; Isaacson, MR; Gilpin, AMK; Lane, M; Levine, CR; Martin, B; Meinert, J; Nowakowski, DJ; Owens, RM; Piantadosi, B; Saah, A; Smith, M; Tonascia, J; VanNatta, ML; Davis, MD; Armstrong, J; Brickbauer, J; Brothers, R; Chop, M; Hubbard, L; Hurlburt, D; Kastorff, L; Magli, Y; Neider, M; Onofrey, J; Stoppenbach, V; VanderhoofYoung, M; Walls, M; Hughes, R; Kurinij, N; Mowery, RL; Alston, B; Foulkes, M; Freeman, W; Holbrook, J; Meinert, C; Mowery, R; Polsky, B; Duncan, WR; Kessler, H; Lambert, AG; Powderly, W; Schnittman, S; Spector, S; Brown, BW; Conway, B; Grizzle, J; Nussenblatt, R; Phair, JP; Smith, H; Whitley, R; Cheng, B; Frost, K; Marco, M
Background: Cytomegalovirus (CMV) retinitis is a common infection and a major cause of visual loss in patients with the acquired immunodeficiency syndrome (AIDS). Objective: To evaluate intravenous cidofovir as a treatment for CMV retinitis. Design: Two-stage, multicenter, phase II/III, randomized, controlled clinical trial. Setting: Ophthalmology and AIDS services at tertiary care medical centers. Patients: 64 patients with AIDS and previously untreated, small, peripheral CMV retinitis lesions (that is, patients at low risk for loss of visual acuity). Intervention: Patients were randomly assigned to one of three groups: the deferral group, in which treatment was deferred until retinitis progressed; the low-dose cidofovir group, which received cidofovir, 5 mg/kg of body weight once weekly for 2 weeks, then maintenance therapy with cidofovir, 3 mg/kg once every 2 weeks; or the high-dose cidofovir group, which received cidofovir, 5 mg/kg once weekly for 2 weeks, then maintenance therapy with cidofovir, 5 mg/kg once every 2 weeks. To minimize nephrotoxicity, cidofovir was administered with hydration and probenecid. Measurements: Progression of retinitis, evaluated in a masked manner by a fundus photograph reading center; the amount of retinal area involved by CMV; the loss of visual acuity; and morbidity. Results: Median time to progression was 64 days in the low-dose cidofovir group and 21 days in the deferral group (P = 0.052, log-rank test). The median time to progression was not reached in the high-dose cidofovir group but was 20 days in the deferral group (P = 0.009, log-rank test). Analysis of the rates of increase in the retinal area affected by CMV confirmed the data on time to progression. The three groups had similar rates of visual loss. Proteinuria of 2+ or more occurred at rates of 2.6 per person-year in the deferral group, 2.8 per person-year in the low-dose cidofovir group (P > 0.2), and 6.8 per person-year in the high-dose cidofovir group (P = 0.135). No patient developed 4+ proteinuria, but two cidofovir recipients developed persistent elevations of serum creatinine levels at more than 177 mu mol/L (2.0 mg/dL). Reactions to probenecid occurred at a rate of 0.70 per person-year. Conclusions: Intravenous cidofovir, high- or low-dose, effectively slowed the progression of CMV retinitis. Concomitant probenecid and hydration therapy, intermittent dosing, and monitoring for proteinuria seemed to minimize but not eliminate the risk for nephrotoxicity
ISI:A1997WH06800004
ISSN: 0003-4819
CID: 53289

Cytomegalovirus retinitis: diagnosis and status of systemic therapy

Friedberg DN
Cytomegalovirus (CMV) retinitis is a disease of advanced immunosuppression that occurs almost exclusively in patients with CD4+ counts of or =50 cells/mm3. Therefore, this disease usually presents in patients who have already been diagnosed with acquired immunodeficiency syndrome (AIDS). The rate of progression of untreated CMV retinitis is variable. Typical initial complaints of patients with CMV retinitis may include blurred or decreased vision, loss of peripheral or central vision, and multiple 'floaters.' The diagnosis of CMV retinitis requires ruling out a number of other ocular disorders that may be confused with CMV retinitis. This review discusses the different appearances of CMV retinitis at presentation and the possible retinal responses to therapy for CMV retinitis. An overview of intravenous (i.v.) ganciclovir or i.v. foscarnet as systemic therapy for treatment of CMV retinitis and their use in combination is also presented. Results indicate that combination therapy with both ganciclovir and foscarnet is more effective in controlling progression of CMV retinitis in relapsed patients than is monotherapy with either drug. However, combination systemic therapy is time-consuming, and this regimen has the greatest negative impact on quality of life. Treatment should involve a cooperative effort between the patient's ophthalmologist and the primary AIDS-treating physician. Both must be aware of the location and activity of the retinitis and of other medical conditions and concomitant medications
PMID: 9058611
ISSN: 1077-9450
CID: 14732

Cryptococcal choroiditis in a patient with AIDS: case report and review [Case Report]

Gandhi SA; McMeeking AA; Friedberg D; Holzman RS
PMID: 8922837
ISSN: 1058-4838
CID: 12495

Assessment of cytomegalovirus retinitis - Clinical evaluation vs centralized grading of fundus photographs

Lewis, RA; Clogston, P; Fainstein, V; Gross, R; Samo, TC; Tuttle, C; Jabs, DA; Apuzzo, L; Bartlett, J; Coleson, L; Dunn, JP; Eldred, L; Feinberg, J; Flynn, T; King, R; Leslie, J; Barron, B; Greenspan, D; Heinemann, MD; Polsky, B; Squires, K; WiseCampbell, S; Friedman, AH; Cheung, TW; Justin, N; Teich, S; Sacks, H; Severin, C; Friedberg, DN; Addessi, A; Dieterich, D; Frost, K; Weinberg, D; Jampol, L; Murphy, R; Naughton, K; Henderly, D; Holland, GN; Chafey, S; Fall, H; Hardy, WD; Kimbrell, C; McArthurChang, L; Freeman, WR; Meinert, L; Peterson, TJ; Quiceno, JI; Rickman, L; Simanello, MA; Spector, S; ODonnell, J; Hoffman, J; Irvine, A; Jacobson, M; Larson, J; Seiff, S; Wanner, M; Davis, J; Chuang, E; Espinal, M; Mendez, P; Vandenbroucke, R; Cheesman, SH; Gittinger, J; Haubrich, R; Kachadoorian, H; Tolson, K; Kline, JM; Klemm, AC; Stevens, M; Webb, R; BrownBellamy, J; Markowitz, JA; Brookmeyer, R; Collins, KB; Collison, BJ; Dodge, J; Donithan, M; Fink, N; Gilpin, AMK; Gerczak, C; Holbrook, JT; Isaacson, MR; Levine, CR; Martin, B; Min, YI; Owens, RM; Nowakowski, DJ; Saah, A; Singer, S; Smith, M; Sternberg, AL; Tonascia, J; VanNatta, ML; Davies, MD; AgresSegal, M; Armstrong, J; Brickbauer, J; Brothers, R; Freitag, G; Hubbard, L; Hurlburt, D; Jensen, K; Kastorff, L; King, B; Magli, Y; Messing, S; Miner, K; Neider, M; Onofrey, J; Stoppenbach, V; Thomas, S; VanderhoofYoung, M; Stewart, G; Hughes, R; Welch, L; Kurinij, N; Mowery, R; Ellenberg, S; Korvick, J; Davis, MD; Clark, T; Clogston, PS; Freeman, W; Kolvick, J; Mowery, R; Sattler, F; Brown, BW; Conway, B; Grizzle, J; Nussenblatt, R; Phair, J; Smith, H; Whitley, R; Bowers, M; Cheng, B; Lambert, AG; Link, D
Background: In the Foscarnet-Ganciclovir Cytomegalovirus (CMV) Retinitis Trial, time to first progression of newly diagnosed CMV retinitis was similar in the 2 treatment groups but was shorter when assessed by grading of fundus photographs at a central reading center than when assessed at the participating clinical centers. This report describes the extent and causes of this disagreement and considers the implications of the findings for clinical practice and future research. Methods: Clinical findings and photographic gradings were compared for extent and activity of retinitis at baseline and during follow-up. In selected cases of disagreement, the photographs and summaries of gradings and clinical findings were reviewed concurrently to determine the cause of disagreement. Results: Movement of the border of retinitis was observed sooner and activity of the border was considered to have increased more often at the reading center than at the clinical centers. Disagreements on time to first progression were more frequent when degree of border movement was small (odds ratios [ORs] for several comparisons ranged from 1.7 to 5.2), when border activity was judged to have decreased or remained the same since the preceding visit (OR, 2.0-193), and when retinitis at baseline did not involve zone 1 (the area within 1 disc diameter of the disc or within 2 disc diameters of the center of the macula [OR, 1.4-3.6]). There were 2 important causes of disagreement between clinical center and reading center. First, difficulty was encountered clinically in recognizing retinitis border movement in the absence of an obvious increase in border activity. Second, the reading center used a threshold for border movement small enough to be crossed by an initial expansion of retinitis borders occurring within 2 to 5 weeks of enrollment in some patients who were responding favorably to treatment (in that retinitis was becoming inactive and showed no further progression for many weeks). Conclusions: Comparisons of photographs from the current visit with those from several previous visits may increase clinicians' abilities to detect progression promptly. The use of additional outcome measures by reading centers, such as border movement of 1500 pm or more and change in area of retina involved by retinitis, may provide more accurate and useful comparisons of treatments. In making such comparisons, centralized photographic grading has the advantages of greater reproducibility and lesser risk of observer bias
ISI:A1996UX51500001
ISSN: 0003-9950
CID: 52858

Ocular complications of tuberculosis

Chapter by: Friedberg, Dorothy Nahm; Lorenzo-Latkany, Monica
in: Tuberculosis by Rom, William; Garay, Stuart M [Eds]
Boston : Little Brown, 1996
pp. ?-?
ISBN: 0316755745
CID: 4841