Dorothy N Friedberg, M.D., Ph.D.

Risk of immune recovery uveitis in patients with AIDS and cytomegalovirus retinitis
Kempen, John H; Min, Yuan-I; Freeman, William R; Holland, Gary N; Friedberg, Dorothy N; Dieterich, Douglas T; Jabs, Douglas A
2006 Apr;113(4):684-694, Ophthalmology
OBJECTIVE: To evaluate the prevalence of and risk factors for immune recovery uveitis (IRU) in eyes of patients with AIDS and cytomegalovirus (CMV) retinitis. DESIGN: Enrollment data from a 19-clinical center cohort study. PARTICIPANTS: Three hundred seventy-four patients with AIDS and CMV retinitis affecting 539 eyes. METHODS: Patients with AIDS were enrolled at 19 United States AIDS ophthalmology clinics. Data were collected by interview, review of medical records, ophthalmic examination, and phlebotomy. MAIN OUTCOME MEASURE: Immune recovery uveitis. RESULTS: Thirty-six patients (9.6%) were diagnosed with IRU involving 50 eyes. The CD4+ T-cell count of 31 of these had risen by > or =50 cells per microliter above nadir to a level > or = 100 cells per microliter (immune recovery), making up 17.6% of the patients known to have immune recovery after diagnosis of CMV retinitis (95% confidence interval, 12.3%-24.1%). No patients with IRU were observed to have active retinitis or detectable CMV DNA in peripheral blood (P<0.001 and P<0.001 with respect to patients without IRU). Other factors associated with IRU were > or =25% retinal area (odds ratio [OR], 2.72; P = 0.014) or posterior pole involvement with CMV retinitis (odds ratio, 0.43; P = 0.039), treatment with intravitreous injection of cidofovir (OR, 10.6 with respect to eyes never exposed to intravitreous or IV cidofovir; P<0.001), and male gender (OR, 0.26; P = 0.012). More eyes with IRU had visual acuity (VA) of 20/50 or worse (38.0% vs. 26.3%, P = 0.077) relative to eyes without IRU, but the proportions with VA of 20/200 or worse were similar (14.0% vs. 13.8%, P = 0.96). Eyes with IRU more commonly had cystoid macular edema (CME) (45.5% vs. 3.7%, P<0.001) and epiretinal membrane (48.9% vs. 13.3%, P<0.001) than eyes without IRU. CONCLUSIONS: Among eyes of patients with immune recovery, the prevalence of IRU is substantial. Eyes with IRU have a high risk of additional morbidity over and above that seen with CMV retinitis, with several-fold higher risk of CME and epiretinal membrane. Large CMV lesions and use of intravitreous cidofovir are risk factors for IRU
— id: 96106, year: 2006, vol: 113, page: 684, stat: Journal Article,

Ocular complications
Friedberg DN; Lorenzo-Latkany M
Tuberculosis Philadelphia : Lippincott Williams & Wilkins, 2004,
— id: 3971, year: 2004, vol: , page: 465, stat: Chapter,

A safety study of oral valganciclovir maintenance treatment of cytomegalovirus retinitis
Lalezari, J; Lindley, J; Walmsley, S; Kuppermann, B; Fisher, M; Friedberg, D; Lalonde, R; Matheron, S; Nieto, L; Torriani, FJ; Van Syoc, R; Sutton, MA; Buhles, W; Stempien, MJ
2002 AUG 1 ;30(4):392-400, Journal of acquired immune deficiency syndromes. JAIDS
Valganciclovir, an oral prodrug of the anti-cytomegalovirus (CMV) agent ganciclovir, was evaluated in a single-arm open-label safety study. AIDS patients (median CD4 lymphocyte count of 140 cells/muL) with treated CMV retinitis (N = 212) received 900-mg once-daily valganciclovir maintenance therapy with courses of 900-mg twice-daily valganciclovir induction therapy as needed to treat progression. After a median treatment duration of 372 days, the adverse event profile was similar to that reported for intravenous (IV) and oral ganciclovir. Adverse event rates of note were diarrhea (35%), nausea (23%), fever (18%), neutropenia (absolute neutrophil count <500 cells/muL) (10%), and anemia (hemoglobin <8.0 g/dL) (12%). Consistent with prior treatment studies of oral ganciclovir, IV catheter-related adverse events were uncommon (6%) and lower than previously reported for IV ganciclovir. The mortality rate was 0.072 deaths per patient-year. Progression of CMV retinitis occurred in 17% of patients during the study treatment period, usually in association with a low CD4 cell count. Other than a higher than expected frequency of oral candidiasis (17%), no clinical toxicities or laboratory abnormalities occurred during treatment with valganciclovir that have not been observed during treatment with ganciclovir
— id: 98249, year: 2002, vol: 30, page: 392, stat: Journal Article,

High dose oral ganciclovir treatment for cytomegalovirus retinitis
Lalezari, Jacob P; Friedberg, Dorothy N; Bissett, Jack; Giordano, Michael F; Hardy, W David; Drew, W Lawrence; Hubbard, Larry D; Buhles, William C; Stempien, Mary Jean; Georgiou, Panos; Jung, Donald T; Robinson, Charles A
2002 Feb;24(1-2):67-77, Journal of clinical virology
BACKGROUND: The oral formulation of ganciclovir is approved at a dose of 3.0 g/day for maintenance treatment of cytomegalovirus (CMV) retinitis following an initial induction course of intravenous (IV) anti-CMV therapy. Median time to progression of CMV retinitis is 12-20 days shorter with oral compared to IV ganciclovir maintenance, likely due to the limited oral bioavailability of ganciclovir. OBJECTIVES: We hypothesized that higher systemic drug exposures associated with increased doses of oral ganciclovir would be associated with increased efficacy. STUDY DESIGN: Maintenance treatment of CMV retinitis with higher than standard doses of oral ganciclovir (>3.0 g/day) was studied in 281 AIDS patients with previously treated, stable retinitis randomized to 3.0, 4.5 or 6.0 g/day oral, or 5 m/kg/day IV ganciclovir. Graders unaware of treatment assignments determined retinitis progression using fundus photographs. Vision, other ophthalmic measures and safety were assessed open-label. RESULTS: Median days to photographic progression were 41, 50, 57 and 70, respectively (P=0.052; 3.0 g vs. IV). Hazard ratios for progression relative to IV were 1.66, 1.28 and 1.19 (P=0.016 for 3.0 g). NONMEM-modeled estimates of average serum ganciclovir concentration area under the curve (AUC(0-24)) correlated best with time to progression (P=0.0019). Six grams per day oral ganciclovir was most similar in efficacy to IV, although broad confidence intervals prevented a conclusive comparison. Patients receiving oral ganciclovir had a lower frequency of sepsis and IV catheter events. CONCLUSIONS: This study suggests that the efficacy of ganciclovir for the maintenance treatment of CMV retinitis improves with increasing total drug exposure (measured as average serum concentration AUC(0-24)). All four regimens of ganciclovir were reasonably well tolerated, with safety profiles similar to what has been reported in prior work
— id: 96107, year: 2002, vol: 24, page: 67, stat: Journal Article,

Long-term follow-up of patients with AIDS treated with parenteral cidofovir for cytomegalovirus retinitis: the HPMPC Peripheral Cytomegalovirus Retinitis Trial - The Studies of Ocular Complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group
Lewis, RA; Carr, LM; Doyle, K; Fainstein, V; Gross, R; Orengo-Nania, 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; Tay-Kearney, 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; Lorenzo-Latkany, 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; MacArthur-Chang, LJ; Martin, MA; Moe, AA; Strong, CA; Tufail, A; Ugalat, PS; Weisz, JM; Freeman, WR; Arevalo-Colina, JF; Clark, T; Jarman, CL; Meixner, L; Meng, TC; Spector, S; Taskintuna, I; Torriani, FJ; O'Donnell, J; Alfred, P; Ballesteros, F; Clay, D; Coleman, R; Gordon, K; 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; van der Horst, 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; Jabs, DA; Dodge, JM; Klemstine, JL; Schuerholtz, TA; Stevens, M; Meinert, CL; Amend-Libercci, 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; Van Natta, 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; Vanderhoof-Young, M; Walls, M; Hughes, R; Kurinij, N; Mowery, RL; Alston, B; Foulkes, M; Jabs, DA; Davis, MD; Kurinij, N; Meinert, CL; Mowery, RL; Jabs, DA; Addessi, A; Alston, B; Clark, T; Davis, MD; Feinberg, J; Freeman, W; Holbrook, J; Holland, GN; Hubbard, L; Jacobson, M; Kurinij, N; Lewis, RA; McArthur-Chang, L; Meinert, C; Mowery, R; Murphy, R; Polsky, B; Tonascia, J; Jabs, DA; Davis, MD; Duncan, WR; Feinberg, J; Kessler, H; Kurinij, N; Lambert, AG; Meinert, CL; Mowery, RL; Powderly, W; Schnittman, S; Spector, S; Tonascia, J; Brown, BW; Conway, B; Grizzle, J; Nussenblatt, R; Phair, JP; Smith, H; Whitley, R; Alston, B; Davis, MD; Foulkes, M; Jabs, DA; Kurinij, N; Meinert, CL; Mowery, RL; Tonascia, J; Jabs, DA; Freeman, WR; Jacobson, M; Murphy, R; Van Natta, ML; Meinert, CL; Cheng, B; Frost, K; Lambert, AG; Marco, M
2000 JUL 28 ;14(11):1571-1581, AIDS
Objective: To evaluate patients with cytomegalovirus (CMV) retinitis treated with intravenous cidofovir for long-term outcomes. Design: Patients with CMV retinitis enrolled in a randomized, controlled clinical trial of intravenous cidofovir as treatment for retinitis were followed for long-term outcomes, including 21 patients initially enrolled in the deferral group who received cidofovir therapy after progression of retinitis. Setting: Thirteen tertiary care clinics specializing in AIDS care and ophthalmology. Participants: Fifty-eight patients with AIDS and small peripheral CMV retinitis lesions. Interventions: Cidofovir 5 mg/kg once weekly for 2 weeks followed by low-dose maintenance cidofovir therapy (3 mg/kg) in 35 patients or high-dose maintenance (5 mg/kg) in 23 patients. Main outcome measures: Time to progression of retinitis, drug toxicities. Results: Median time to progression of retinitis was 2.5 months. Median time to discontinuation of cidofovir because of intolerance was 6.6 months, and did not differ significantly between the two maintenance doses. Median time to discontinuation of cidofovir for intolerance other than probenecid reaction was 16.3 months for patients treated with low-dose maintenance and 5.0 months for patients treated with high-dose maintenance (P = 0.021). Proteinuria of 2+ or more occurred at a rate of 1.22/person year. In patients with sufficient follow-up to determine resolution of proteinuria, 89.9% of episodes resolved, and the median time to resolution was 20 days. Rates of probenecid intolerance and of cidofovir-associated uveitis were 0.35/person-year, and 0.20/person-year, respectively
— id: 54539, year: 2000, vol: 14, page: 1571, stat: Journal Article,

Blurred vision during sexual arousal associated with narrow-angle glaucoma
Friedberg DN; Fox LE
1999 Nov;128(5):647-648, American journal of ophthalmology
PURPOSE: To describe three women with narrow-angle glaucoma who had transient blurred vision during sexual arousal. METHOD: Case reports. RESULTS: Three women, aged 37, 45, and 55 years, were seen with bilateral narrow-angle glaucoma and were treated with bilateral laser iridotomy. In each patient, additional surgery was required to control the glaucoma. After establishing a rapport with her physician, each patient described transient blurred vision, from a few minutes to several hours in duration, which began during sexual arousal. This symptom resolved after peripheral iridotomy and, in one patient, after laser iridoplasty. CONCLUSION: The association of transient blurred vision with sexual activity may delay presentation of patients with symptomatic narrow-angle glaucoma
— id: 6245, year: 1999, vol: 128, page: 647, stat: Journal Article,

Use of the ganciclovir implant for the treatment of cytomegalovirus retinitis in the era of potent antiretroviral therapy: recommendations of the International AIDS Society-USA panel [see comments]
Martin DF; Dunn JP; Davis JL; Duker JS; Engstrom RE Jr; Friedberg DN; Jaffe GJ; Kuppermann BD; Polis MA; Whitley RJ; Wolitz RA; Benson CA
1999 Mar;127(3):329-339, American journal of ophthalmology
PURPOSE: To describe the risks, benefits, and recommended use of the ganciclovir implant for the treatment of human immunodeficiency virus-related cytomegalovirus (CMV) retinitis in the era of potent antiretroviral therapy. METHODS: A panel of physicians with expertise in the use of the ganciclovir implant and in the management of CMV retinitis was convened by the International AIDS Society-USA. The panel reviewed and discussed available data, and developed recommendations for the use of the ganciclovir implant, the surgical technique, and related management issues. Recommendations were rated according to the strength and quality of the supporting evidence. RESULTS: The effect of potent antiretroviral therapy on the immunologic status of patients with human immunodeficiency virus disease has changed the manifestation and course of CMV retinitis in many patients. The clinical management of CMV retinitis and the role of the ganciclovir implant are thus changing. Factors in the decision to choose the ganciclovir implant include the patient's potential for immunologic improvement, location and severity of CMV retinitis, and the risks and costs associated with implantation and concomitant oral ganciclovir therapy. CONCLUSIONS: The ganciclovir implant is safe and effective for the treatment of CMV retinitis. The indications for its use should be modified to account for increased patient survival and the potential for CMV retinitis to be controlled by effective antiretroviral therapy. Optimal use of the ganciclovir implant and discontinuation of therapy in selected patients with improvement in immunity may result in better long-term visual outcomes
— id: 7402, year: 1999, vol: 127, page: 329, stat: Journal Article,

Chronic multifocal retinal infiltrates in patients infected with human immunodeficiency virus [see comments]
Levinson RD; Vann R; Davis JL; Friedberg DN; Tufail A; Terry BT; Lindley JI; Holland GN
1998 Mar;125(3):312-324, American journal of ophthalmology
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
— id: 7655, year: 1998, vol: 125, page: 312, stat: Journal Article,

Virus infections of the eye
Ritterband DC; Friedberg DN
1998 Oct;8(4):187-201, Reviews in medical virology
In reviewing the clinical features, diagnostic evaluations and therapies of the most common ocular viral infections we attempt to whet your appetite for attacking the numerous challenges in diagnosis and treatment of viral eye disease. The herpes viruses, HSV, VZV and CMV are the cause of significant ocular morbidity. HSV most commonly affects the cornea producing keratitis that can be recurrent and may lead to corneal clouding and neovascularisation. Manifestations can be purely infectious or immunological and treatment options must be tailored to the underlying pathophysiology. Herpes zoster ophthalmicus, caused by VZV infection of the first branch of the trigeminal nerve, produces a characteristic rash and can progress to keratitis and uveitis. HSV and VZV can cause retinitis in both immunocompetent and immunocompromised individuals. There has been a significant increase in the incidence of CMV retinitis since the beginning of the AIDS epidemic. We review the numerous new treatments, diagnostic tests and treatment strategies which have been developed in response to this potentially blinding retinal infection. Adenovirus produces an epidemic conjunctivitis and epidemic keratoconjunctivitis which are severe and extremely contagious conjunctival infections. HIV, molluscum contagiosum, EBV and rubeola also cause ocular diseases which are described.Copyright 1998 John Wiley & Sons, Ltd
— id: 14729, year: 1998, vol: 8, page: 187, stat: Journal Article,

Uveitis associated with human immunodeficiency virus infection [see comments]
Rosberger DF; Heinemann MH; Friedberg DN; Holland GN
1998 Mar;125(3):301-305, American journal of ophthalmology
PURPOSE: To report uveitis associated with human immunodeficiency virus (HIV) infection and to suggest guidelines for treatment. METHODS: Six HIV-seropositive patients (10 eyes) with anterior or posterior uveitis or both were evaluated. After ineffective prolonged treatment with systemic and topical corticosteroids, specific systemic antiretroviral therapy with zidovudine was initiated in all patients. Aqueous humor was cultured in three eyes of three patients, and vitreous humor was cultured in one eye of one patient. RESULTS: In all 10 eyes of six patients, there was resolution of inflammation in 10 to 42 days after commencement of treatment with zidovudine (600 to 800 mg/day), despite no or minimal response to corticosteroids. Cultures of aqueous humor from three eyes of three patients and culture of vitreous humor from one eye of one patient were positive for HIV; no other organism was isolated. Systemic evaluation disclosed no other identifiable cause for the uveitis in any patient. CONCLUSIONS: Infection with HIV appears to be a cause of uveitis. A trial of zidovudine may be warranted in HIV-seropositive patients with uveitis that is poorly responsive to corticosteroid treatment when no other cause is identified. The efficacy of other retroviral agents was not determined
— id: 7767, year: 1998, vol: 125, page: 301, stat: Journal Article,

Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in the era of potent antiretroviral therapy: recommendations of an international panel. International AIDS Society-USA
Whitley RJ; Jacobson MA; Friedberg DN; Holland GN; Jabs DA; Dieterich DT; Hardy WD; Polis MA; Deutsch TA; Feinberg J; Spector SA; Walmsley S; Drew WL; Powderly WG; Griffiths PD; Benson CA; Kessler HA
1998 May 11;158(9):957-969, Archives of internal medicine
OBJECTIVE: To provide recommendations for the treatment of acquired immunodeficiency syndrome-related cytomegalovirus (CMV) end-organ diseases, including retinitis, colitis, pneumonitis, and neurologic diseases. PARTICIPANTS: A 17-member panel of physicians with expertise in clinical and virological research and inpatient care in the field of CMV diseases. EVIDENCE: Available clinical and virological study results. Recommendations are rated according to the quality and strength of available evidence. Recommendations were limited to the treatment of CMV diseases; prophylaxis recommendations are not included. PROCESS: The panel was convened in February 1997 and met regularly through November 1997. Subgroups of the panel summarized and presented available information on specific topics to the full panel; recommendations and ratings were determined by group consensus. CONCLUSIONS: Although the epidemiological features of CMV diseases are changing in the setting of potent, combination antiretroviral therapy, continued attention must be paid to CMV diseases in patients infected with the human immunodeficiency virus to prevent irreversible endorgan dysfunction. The initial and maintenance treatment of CMV retinitis must be individualized based on the characteristics of the lesions, including location and extent, specific patient factors, and characteristics of available therapies among others. Management of relapse or refractory retinitis must be likewise individualized. Ophthalmologic screening for patients at high risk for retinitis or who have a prior diagnosis of extraretinal disease is recommended. Recommendations for gastrointestinal, pulmonary, and neurologic manifestations are included
— id: 7850, year: 1998, vol: 158, page: 957, stat: Journal Article,

Cytomegalovirus retinitis: diagnosis and status of systemic therapy
Friedberg DN
1997 ;14 Suppl 1:S1-S6, Journal of acquired immune deficiency syndromes & human retrovirology
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
— id: 14732, year: 1997, vol: 14 Suppl 1, page: S1, stat: Journal Article,

Hypotony and visual loss with intravenous cidofovir treatment of cytomegalovirus retinitis
Friedberg DN
1997 Jun;115(6):801-802, Archives of ophthalmology
— id: 14730, year: 1997, vol: 115, page: 801, stat: Journal Article,

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
1997 FEB 15 ;126(4):264-&, Annals of internal medicine
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
— id: 53289, year: 1997, vol: 126, page: 264, stat: Journal Article,

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
1997 DEC ;115(12):1528-1536, Archives of ophthalmology
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
— id: 53126, year: 1997, vol: 115, page: 1528, stat: Journal Article,

Re-evaluation of time to progression of foscarnet salvage therapy for cytomegalovirus retinitis in AIDS patients clinically resistant to ganciclovir
Mueller AJ; Jacobson MA; Hurwitz S; Chuang EL; Friedberg DN; Haidt SJ; Heinemann MH; Jabs DA; Kaplan HJ; Freeman WR
1997 Mar;11(3):397-399, AIDS
— id: 14731, year: 1997, vol: 11, page: 397, stat: Journal Article,

New Approaches to the Treatment of Cytomegalovirus Retinitis - Proceedings based on a Roundtable Meeting held in Washington, DC, January 26, 1996 - Open discussion
Whitley, RJ; Friedberg, DN; Kuppermann, BD; Lalezari, JP; Spector, SA; Hardy, WD
1997 MAR ;14(3):S36-S38, Journal of acquired immune deficiency syndromes & human retrovirology
— id: 53248, year: 1997, vol: 14, page: S36, stat: Journal Article,

Ocular complications of tuberculosis
Friedberg, Dorothy Nahm; Lorenzo-Latkany, Monica
Tuberculosis Boston : Little Brown, 1996,
— id: 4841, year: 1996, vol: , page: ?, stat: Chapter,

Cryptococcal choroiditis in a patient with AIDS: case report and review
Gandhi SA; McMeeking AA; Friedberg D; Holzman RS
1996 Nov;23(5):1193-1194, Clinical infectious diseases
— id: 12495, year: 1996, vol: 23, page: 1193, stat: Journal Article,

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
1996 JUL ;114(7):791-805, Archives of ophthalmology
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
— id: 52858, year: 1996, vol: 114, page: 791, stat: Journal Article,

Oral ganciclovir as maintenance treatment for cytomegalovirus retinitis in patients with AIDS. Syntex Cooperative Oral Ganciclovir Study Group [see comments]
Drew WL; Ives D; Lalezari JP; Crumpacker C; Follansbee SE; Spector SA; Benson CA; Friedberg DN; Hubbard L; Stempien MJ; et al
1995 Sep 7;333(10):615-620, New England journal of medicine
BACKGROUND. Cytomegalovirus retinitis, a sight-threatening infection associated with the acquired immunodeficiency syndrome (AIDS), currently requires lifelong intravenous treatment. An effective oral treatment would be an important advance. METHODS. We compared oral with intravenous ganciclovir in an open-label, randomized study in patients with AIDS and newly diagnosed, stable cytomegalovirus retinitis (the disease was stabilized by three weeks of treatment with intravenous ganciclovir). Sixty subjects were randomly assigned to maintenance therapy with intravenous ganciclovir at a dose of 5 mg per kilogram of body weight daily, and 63 to maintenance therapy with oral ganciclovir at a dose of 3000 mg daily. The subjects were followed for up to 20 weeks, with photography of the fundi conducted every other week. The photographs were evaluated at the completion of the study by an experienced grader who was unaware of the subjects' treatment assignments. RESULTS. Efficacy could be evaluated in 117 subjects; photographs were ungradable for 2 of the 117. On the basis of the masked assessment of photographs from 115 subjects, the mean time to the progression of retinitis was 62 days in those given intravenous ganciclovir and 57 days in those given oral ganciclovir (P = 0.63; relative risk [oral vs. intravenous], 1.08; 95 percent confidence interval for the difference in means, -22 to +12 days). On the basis of funduscopy by ophthalmologists who were aware of the subjects' treatment assignments, the mean time to progression was 96 days in subjects given intravenous ganciclovir and 68 days in subjects given oral ganciclovir (P = 0.03; relative risk [oral vs. intravenous], 1.68; 95 percent confidence interval for the difference in means, -45 to -11 days). Survival, changes in visual acuity, the incidence of viral shedding, and the incidence of adverse gastrointestinal events were similar in the two groups. Neutropenia, anemia, intravenous-catheter-related adverse events, and sepsis were more common in the group given intravenous ganciclovir. CONCLUSIONS. Oral ganciclovir is safe and effective as maintenance therapy for cytomegalovirus retinitis and is more convenient for patients to take than intravenous ganciclovir
— id: 14734, year: 1995, vol: 333, page: 615, stat: Journal Article,

Treatment of cytomegalovirus retinitis with intraocular sustained-release ganciclovir implant
Friedberg DN
1995 Nov;113(11):1354-1355, Archives of ophthalmology
— id: 14733, year: 1995, vol: 113, page: 1354, stat: Journal Article,

AIDS and the eye
Friedberg, Dorothy Nahm; Stenson, Susan M
New Orleans, LA : Contact Lens Association of Ophthalmologists, c1995,
— id: 503, year: 1995, vol: , page: , stat: ,

MORBIDITY AND TOXIC EFFECTS ASSOCIATED WITH GANCICLOVIR OR FOSCARNET THERAPY IN A RANDOMIZED CYTOMEGALOVIRUS RETINITIS TRIAL
LEWIS, RA; CLOGSTON, P; FAINSTEIN, V; GROSS, R; SAMO, T; 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; LECOUNT, C; PEYMAN, G; FRANKLIN, R; HEINEMANN, MH; 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; MACARTHUR, LJ; FREEMAN, WR; MEIXNERT, 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; CHEESEMAN, SH; GITTINGER, J; HAUBRICH, R; KACHADOORIAN, H; TOLSON, K; KLINE, JM; KLEMM, AC; STEVENS, M; WEBB, R; BROWNBELLAMY, J; MARKOWITZ, JA; MEINERT, CL; BINDER, KL; BROOKMEYER, R; BROWN, VE; COLLISON, BJ; DODGE, J; DONITHAN, M; FINK, N; GERCZAK, C; HOLBROOK, JT; ISAACSON, MR; JONES, CP; LEVINE, CR; MIN, YI; MEINERT, JL; OWENS, RM; NOWAKOWSKI, DJ; SAAH, A; SANDFORD, GR; SINGER, S; SMITH, M; STERNBERG, AL; TONASCIA, J; VANNATTA, ML; DAVID, MD; AGRESSEGAL, M; ARMSTRONG, J; BROTHERS, R; FREITAG, G; HUBBARD, L; HURLBURT, D; KASTORFF, L; MAGLI, Y; MINER, K; THOMAS, S; VANDERHOOFYOUNG, M; STEWART, G; HUGHES, R; WELCH, L; MOWERY, R; ELLENBERG, S; KORVICK, J; DAVIS, MD; CLARK, T; CLOGSTON, PS; FREEMAN, W; SATTLER, F; JORDAN, C; MILLS, J; BROWN, BW; CONWAY, B; GRIZZLE, J; NUSSENBLATT, R; PHAIR, J; SMITH, H
1995 JAN 9 ;155(1):65-74, Archives of internal medicine
Background: The Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial compared the use of either ganciclovir or foscarnet for the initial treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. We previously reported that patients treated with foscarnet lived longer but were more likely to have their treatment switched, the latter suggesting foscarnet may not have been as well tolerated as ganciclovir. This study compared the morbidity and toxic reactions reported during the trial. Methods: Two hundred thirty-four patients with the acquired immunodeficiency syndrome and preciously untreated cytomegalovirus retinitis at 11 university centers were randomly assigned to receive intravenously either foscarnet (n = 107) or ganciclovir (n = 127). Medical histories, laboratory tests, and drug treatment histories during the first 6 months of treatment were analyzed. Results: Neutropenia was more common in patients assigned to ganciclovir than to foscarnet (34% vs 14%; P = .001). Patients assigned to foscarnet reported more infusion-related symptoms (58% vs 24%; P < .001) and, in male patients, more genitourinary symptoms (36% vs 16%; P > .001); they also experienced a trend toward more nephrotoxic effects (13% vs 6%; P = .082) and electrolyte abnormalities. The incidence of seizures was similar in both groups (foscarnet, 12%; ganciclovir, 9%; P = .511). Patients assigned to foscarnet were more likely to be switched to the alternative treatment (foscarnet to ganciclovir, 46%; ganciclovir to foscarnet, 11%, P < .001), and most of this excess was attributable to toxic reactions. In 88% of cases in which treatment was snitched as a result of toxic reactions and in which follow-up data were available, the toxic reaction resolved after the switch. No permanent disability or death resulted from toxic reactions. Conclusions: Compared with ganciclovir, the use of foscarnet was more frequently limited by the occurrence of toxic reactions. However, these toxic reactions rarely had long-term sequelae. In light of the previously reported survival benefit seen in patients treated with foscarnet, these data support the use of foscarnet for the initial treatment of cytomegalovirus retinitis
— id: 87463, year: 1995, vol: 155, page: 65, stat: Journal Article,

INTRAOCULAR PRESSURES IN HIV-INFECTED PATIENTS
LORENZOLATKANY, M; LATKANY, P; FRIEDBERG, DN
1995 MAR 15 ;36(4):S316-S316, Investigative ophthalmology & visual science. IOVS
— id: 87334, year: 1995, vol: 36, page: S316, stat: Journal Article,

ANTIVIRAL EFFECTS OF FOSCARNET AND GANCICLOVIR THERAPY ON HUMAN-IMMUNODEFICIENCY-VIRUS P24 ANTIGEN IN PATIENTS WITH AIDS AND CYTOMEGALOVIRUS RETINITIS
QUINN, TC; JABS, DA; HOLBROOK, JT; HARDY, WD; POLSKY, B; LEWIS, RA; CLOGSTON, P; FAINSTEIN, V; GROSS, R; SAMO, T; TUTTLE, C; APUZZO, L; BARTLETT, J; DUNN, JP; ELDRED, L; FEINBERG, J; FLYNN, T; KING, R; BARRON, B; GREENSPAN, D; LECOUNT, C; PEYMAN, G; FRANKLIN, R; HEINEMANN, M; SQUIRES, K; WISECAMPBELL, S; FRIEDMAN, AH; CHEUNG, TW; JUSTIN, N; TEICH, SA; SACKS, H; SEVERIN, C; FRIEDBERG, DN; ADDESSI, A; DIETERICH, D; LAFLEUR, F; WEINBERG, D; JAMPOL, L; MURPHY, R; NAUGHTON, K; HENDERLY, D; HOLLAND, GN; CHAFEY, S; FALL, H; KIMBRELL, C; MACARTHUR, LJ; FREEMAN, WR; MEIXNERT, L; PETERSON, TJ; QUICENO, JI; RICKMAN, L; SIMANELLO, MA; SPECTOR, S; ODONNELL, J; HOFFMAN, J; IRVINE, A; JACOBSON, M; LARSON, J; SEIFF, S; WARNER, L; DAVIS, J; CHUANG, E; ESPINAL, M; MENDEZ, P; CHEESEMAN, SH; GITTINGER, J; HAUBRICH, R; KACHADOORIAN, H; TOLSON, K; BROWNBELLAMY, J; KLEMM, AC; MARKOWITZ, JA; MEINERT, CL; AMENDLIBERCCI, A; COLESON, L; COLLINS, KL; COLLISON, BJ; DODGE, J; DONITHAN, M; EWING, C; FINK, N; GERCZAK, C; ISAACSON, MR; KAPLANGILIPIN, A; HUFFMAN, R; LEVINE, CR; NOWAKOWSKI, DJ; SMITH, M; TONASCIA, J; VANNATTA, ML; AGRESSEGAL, M; ARMSTRONG, J; BROTHERS, R; HUBBARD, L; HURLBURT, D; MAGLI, Y; MINER, K; THOMAS, S; VANDERHOOFYOUNG, M; STEWART, G; HUGHES, R; LEEF, J; PALMER, S; MOWERY, R; ELLENBERG, S; KORVICK, J; DAVIS, MD; CLARK, T; MERIN, L; SATTLER, F; JORDAN, C; MILLS, J; BROWN, BW; CONWAY, B; GRIZZLE, J; NUSSENBLATT, R; PHAIR, J; SMITH, H; KLINE, R; MOSS, M; CARELLA, A
1995 SEP ;172(3):613-621, Journal of infectious diseases
To examine whether the prolonged survival seen in patients treated with foscarnet compared with those treated with ganciclovir was due to a direct effect on human immunodeficiency virus (HIV) replication, HIV p24 antigen was measured. Of 71 receiving foscarnet, 54% were p24 antigen-positive at enrollment (vs. 44% of 79 receiving ganciclovir). By immune complex-dissociated (ICD) p24 antigen analysis, 87% and 78%, respectively, were positive. After 1 month of treatment, there was a significant decline in standard (mean decline, 10.1 pg/mL) and ICD (mean, 39.6 pg/mL) p24 antigen in both groups (P = .0001). Mortality was greater in those who were ICD p24 antigen-positive than in those -negative at baseline (P = .03) and in subjects with an increase in ICD p24 antigen than in those with a decline (P = .09). Thus, each drug had a suppressive effect on circulating p24 antigen, which was predictive of improved survival. The inhibitory effect on CMV replication may have a beneficial effect on limiting HIV replication
— id: 86764, year: 1995, vol: 172, page: 613, stat: Journal Article,

LABORATORY DIAGNOSIS OF MICROSPORIDIAL KERATITIS
STENSON, SM; DIDIER, ES; FRIEDBERG, DN
1995 MAR 15 ;36(4):S316-S316, Investigative ophthalmology & visual science. IOVS
— id: 87333, year: 1995, vol: 36, page: S316, stat: Journal Article,

HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) ASSOCIATED UVEITIS
HEINEMANN, MH; ROSBERGER, DF; FRIEDBERG, DN; HOLLAND, GN
1994 MAR 15 ;35(4):1306-1306, Investigative ophthalmology & visual science. IOVS
— id: 52540, year: 1994, vol: 35, page: 1306, stat: Journal Article,

PHASE-II DOSE-RANGING TRIAL OF FOSCARNET SALVAGE THERAPY FOR CYTOMEGALOVIRUS RETINITIS IN AIDS PATIENTS INTOLERANT OF OR RESISTANT TO GANCICLOVIR (ACTG PROTOCOL 093)
JACOBSON, MA; WULFSOHN, M; FEINBERG, JE; DAVIS, R; POWER, M; OWENS, S; CAUSEY, D; HEATHCHIOZZI, ME; MURPHY, RL; CHEUNG, TW; DIETERICH, DT; SPECTOR, SA; MCKINLEY, GF; PARENTI, DM; CRUMPACKER, C; NISHIMOTO, B; LEEDOM, JM; KRAMER, F; COHEN, C; LOFTUS, J; KESSLER, HA; POTTAGE, JC; BENSON, CA; PHAIR, JP; GERITS, P; CHUSID, E; SACKS, HS; FRIEDBERG, D; CURRANKRIKORIAN, K; VALENTINE, FT; MENG, TC; FREEMAN, WR; MEIXNER, L; RICHMAN, D; ODONNELL, JJ; KIMBRELL, C; BOGGIO, K; LARSON, J; WHITMORE, PV; SIMON, GL; LELACHEUR, S; FIFE, K; ZWICKL, B; RELUE, J; STEIGBIGEL, RT; FUHRER, J; DONLON, W; BURK, RA; PORTMORE, AC; WEISSBACH, NE; HOOTON, TM; HOLZWORTH, P; DAVISON, S; COLLIER, AC; POWDERLY, WG; KLEBERT, M; ROYAL, M; SEYFRIED, W; SQUIRES, KC; WEISS, W; BARBACCI, M; BECKER, RL; JABS, D; BARTLETT, JG; PARA, MF; JONES, M; NEIDIG, JL; FASS, RJ; VANDERHORST, C; KYLSTRA, J; RAASCH, R; BLOODGOOD, K; WOLITZ, R; KIRK, S; ROLFE, L; PATRONEREESE, J; BARTLETT, JA; WASKIN, HA; WILLIAMS, DK; SHIP, KW; KAHL, P; ASSAYKEEN, T; KAROL, C; MARTINMUNLEY, S; SUMNER, P
1994 APR ;8(4):451-459, AIDS
Objective: To document response to foscarnet salvage therapy in patients with cytomegalovirus (CMV) retinitis who are intolerant of or resistant to ganciclovir. Methods: Patients with AIDS and CMV retinitis who had documented hematologic intolerance or resistance to ganciclovir therapy received an induction course of foscarnet, 60 mg/kg every 8h for 14 days, and subsequent chronic maintenance foscarnet therapy at a daily dose of 60, 90 or 120 mg/kg/day. The first 87 patients were randomly assigned to receive maintenance foscarnet at a dose of 60 or 90 mg/kg/day; all subsequent patients were assigned a maintenance dose of 120 mg/kg/day. Results: A total of 156 evaluable patients were enrolled. Median time to retinitis progression and survival did not differ significantly among groups assigned to different maintenance foscarnet doses. Among patients with retinitis progression documented ophthalmologically occuring at less-than-or-equal-to 2 week intervals, despite optimal doses of ganciclovir, time to progression on foscarnet therapy was a median 8 weeks at all doses studied. By dose assignment, there were no significant differences in serious drug-associated toxicity, although trends toward increased renal and hypocalcemic adverse events were observed at higher maintenance doses. Conclusion: in patients intolerant of ganciclovir, salvage foscarnet therapy resulted in a longer time to retinitis progression than reported previously in historic controls who terminated ganciclovir therapy. In patients who exhibited clinical resistance to ganciclovir, foscarnet appeared to have efficacy in controlling retinitis. No significant differences in either efficacy or toxicity were observed in the range of foscarnet maintenance doses studied
— id: 52528, year: 1994, vol: 8, page: 451, stat: Journal Article,

rhM-CSF for adult soft tissue sarcoma (ASTS)
Blum RH; Powers TV; Downey AM; Prasad N; Oratz R; Friedberg DN; Kuca BX; Kaye JA
1993 ;12:A1655-A1655, Proceedings (American Society of Clinical Oncology)
Our goal was to test the hypothesis that M-CSF would induce objective responses in ASTS. M-CSF is a recombinant glycoprotein produced in Chinese hamster ovarian cells by Genetics Institute, Cambridge, MA. We performed a phase II study of M-CSF in adults with measurable metastatic soft-tissue sarcomas. 14 patients (pts) were entered in a 4-mo period. Pt characteristics were 8 females, 6 males, 10 leiomyo, 2 lipo, 1 each rhabdomyo and Schwannoma; 5 pts had primary tumor in the peritoneal cavity, 4 uterus, 3 stomach, and 1 extremity. Six pts had radiation, including 1 who had pelvic radiation. 11 pts had been previously treated with a doxorubicin-containing combination. Three pts had not had prior therapy. Ten pts had a ECOG performance status (PS) of 1 and 4 had a PS of 0. Sites of measurable disease were abdominal cavity 5, liver 3, lung and soft tissue 2 each. Pts were given a course of continuous infusion of M-CSF for 7 days, every 14 days, at a dose of 80 ug/kg/day. Six pts have gone off study after 4 courses, 2 pts after 2 courses, 2 pts after 1 course. Four pts remain on study with, to date, 2 pts at 3 courses, and 1 pt each at 4 courses and 6 courses. M-CSF at this dose and schedule was well tolerated. No pt went off study because of toxicity. No delays in treatment occurred. The most significant toxicity was thrombocytopenia: grade 3, 4 pts; grade 2, 7 pts; grade 0, 3 pts. The platelet counts recovered within days of stopping the M-CSF. The other toxicities were grade 1 flu-like symptoms in 11 pts, which was self-limited and resulted in no change in PS. Grade 1 nausea was seen in 6 pts. Grade 1 itching of the eyes occurred in 3 pts. So far, no objective responses have been observed in this population on this dose and schedule. Seven pts had progressive disease. (C) American Society of Clinical Oncology 1997
— id: 6014, year: 1993, vol: 12, page: A1655, stat: Journal Article,

Concurrent use of ganciclovir and foscarnet to treat cytomegalovirus infection in AIDS patients
Dieterich DT; Poles MA; Lew EA; Mendez PE; Murphy R; Addessi A; Holbrook JT; Naughton K; Friedberg DN
1993 May;167(5):1184-1188, Journal of infectious diseases
Ten patients with AIDS and progressive cytomegalovirus disease were treated with ganciclovir and foscarnet concurrently. The patients had received ganciclovir and foscarnet monotherapy a median of 330 days before receiving combination therapy for a median of 80 days. Nine of the 10 patients responded to the combination. No electrolyte abnormalities were noted during combination therapy, but rates of neutropenia (relative rate, combination vs. ganciclovir, 1.99; P = .229) and thrombocytopenia (relative rate, combination vs. ganciclovir, 1.53; P = .616) were higher with combination therapy than with either drug alone. The relative rate of anemia was significantly increased with combination therapy compared with monotherapy (relative rate, combination vs. ganciclovir, 2.69; P = .025). These data suggest that combination ganciclovir and foscarnet therapy after failure of either alone appears to be as effective as standard therapy with single agents. The rate of anemia with combination therapy was significantly greater than either agent alone, but no significant difference was noted among the other parameters of toxicity studied
— id: 8401, year: 1993, vol: 167, page: 1184, stat: Journal Article,

Risk factors for development of rhegmatogenous retinal detachment in patients with cytomegalovirus retinitis [see comments]
Freeman WR; Friedberg DN; Berry C; Quiceno JI; Behette M; Fullerton SC; Munguia D
1993 Dec 15;116(6):713-720, American journal of ophthalmology
We studied 259 patients to determine the time-dependent risk and risk factors for the development of retinal detachment in patients with cytomegalovirus retinitis. The six-month and one-year retinal detachment rates (by eye) were 11% and 24%, respectively. Increasing retinal surface involvement outside of the posterior pole and the presence of retinitis activity were found to be the two covariates that best predicted retinal detachment. Eyes with peripheral involvement greater than 25% had a fivefold risk for detachment, compared to eyes with 10% involvement. If there was retinitis activity and more than 25% peripheral (external to major vascular arcades) involvement, the risk increased to 24-fold. The presence of a fellow eye with retinal detachment was not an independent risk factor. These observations should help in the design of a prophylactic trial intended to prevent retinal detachment and should also help ophthalmologists counsel patients with cytomegalovirus retinitis
— id: 14735, year: 1993, vol: 116, page: 713, stat: Journal Article,

Microsporidal keratoconjunctivitis
Friedberg DN; Didier ES; Yee RW
1993 Sep 15;116(3):380-381, American journal of ophthalmology
— id: 14736, year: 1993, vol: 116, page: 380, stat: Journal Article,

Epibulbar molluscum contagiosum in acquired immune deficiency syndrome. Case report and review of the literature
Charles NC; Friedberg DN
1992 Jul;99(7):1123-1126, Ophthalmology
BACKGROUND: While molluscum contagiosum of the eyelid skin is commonly complicated by conjunctivitis, primary involvement of the conjunctiva or cornea by molluscum lesions is exceedingly rare. The authors studied a 34-year-old man with acquired immune deficiency syndrome (AIDS) in whom multiple molluscum lesions of the lids and a single nodule of the limbus developed. METHODS: The nodular lesion was excised from the limbus and processed for histologic examination by light microscopy. Pertinent literature concerning epibulbar molluscum contagiosum was reviewed. RESULTS: Histopathology of the excised lesion showed molluscum bodies within the acanthotic, hyperkeratotic conjunctival epithelium with surrounding chronic, nongranulomatous inflammation. Only 10 previous cases of conjunctival or corneal primary lesions have been reported, half of which showed associated cutaneous involvement. Lesions tended to be single, noninflamed, dome-shaped, and umbilicated, often with a yellowish central core. Patients were otherwise well and ranged in age from 3 to 55 years. Simple excision was effective in eradicating the lesions. CONCLUSION: Primary epibulbar molluscum contagiosum is rare. Although cutaneous molluscum is common in AIDS, this report is the first to document conjunctival molluscum in a patient with AIDS
— id: 13543, year: 1992, vol: 99, page: 1123, stat: Journal Article,

Pneumocystis carinii of the orbit
Friedberg DN; Warren FA; Lee MH; Vallejo C; Melton RC
1992 May 15;113(5):595-596, American journal of ophthalmology
— id: 14737, year: 1992, vol: 113, page: 595, stat: Journal Article,

Isolation and characterization of a new human microsporidian, Encephalitozoon hellem (n. sp.), from three AIDS patients with keratoconjunctivitis
Didier ES; Didier PJ; Friedberg DN; Stenson SM; Orenstein JM; Yee RW; Tio FO; Davis RM; Vossbrinck C; Millichamp N; et al
1991 Mar;163(3):617-621, Journal of infectious diseases
A new human microsporidian was isolated from cultures of Madin-Darby canine kidney cells incubated with conjunctival scrapings or corneal tissues from three AIDS patients with keratoconjunctivitis. The three isolates were morphologically similar to Encephalitozoon cuniculi. The spores averaged 1 x 1.5-2.0 microns, had six to eight polar filament coils, displayed monokaryotic nuclei, and possessed relatively thick endospores with irregularly shaped exospores. Organisms developed within a parasitophorous vacuole. By SDS-PAGE analysis, the three isolates appeared to be identical but were different from E. cuniculi. Identical banding patterns on Western blots of the three isolates were expressed by each patient's serum. By Western immunoblotting, murine antisera to E. cuniculi reacted to several antigens of the new AIDS-related microsporidian, whereas murine antisera bound weakly to Nosema corneum. The name Encephalitozoon hellem (n. sp.) is proposed to identify this new human microsporidian
— id: 14738, year: 1991, vol: 163, page: 617, stat: Journal Article,

DOT-ELISA AND WESTERN-BLOT IMMUNOASSAY IN OCULAR MICROSPORIDIOSIS
DIDIER, ES; DAVIS, R; FRIEDBERG, D; LEMBACH, R; MEISLER, D; ORENSTEIN, J; YEE, R; SHADDUCK, JA
1991 MAR 19 ;5(6):A1626-A1626, FASEB journal
— id: 51652, year: 1991, vol: 5, page: A1626, stat: Journal Article,

A MULTICENTER STUDY OF PNEUMOCYSTIS CHOROIDOPATHY
Shami, MJ; Freeman, W; Friedberg, D; Siderides, E; Listhaus, A; Ai, E
1991 Jul 15;112(1):15-22, American journal of ophthalmology
We studied 21 patients with the acquired immunodeficiency syndrome and presumed Pneumocystis carinii choroidopathy. The lesions were characteristically yellow to pale yellow in color, appeared at the level of the choroid, and were found in the posterior pole. They varied in size from 300 to 3,000-mu-m, initially increasing in number before treatment and eventually resolving after systemic antimicrobial therapy. Of the 21 patients, 18 (86%) had received inhaled pentamidine as prophylaxis against Pneumocystis pneumonia. Visual acuity and visual field testing showed little evidence of retinal destruction. Survival after the diagnosis of the choroidopathy ranged from two to 36 weeks. Pneumocystis choroidopathy offers an easily accessible clue to disseminated Pneumocystis infection. When comparing drugs for Pneumocystis prophylaxis, careful ocular examination can provide one indicator of the relative efficacy of protection against extrapulmonary disease
— id: 32167, year: 1991, vol: 112, page: 15, stat: Journal Article,

Clofazamine-induced generalized retinal degeneration
Cunningham CA; Friedberg DN; Carr RE
1990 ;10(2):131-134, Retina
Clofazamine is an iminophenazine dye with antimycobacterial activity which has recently been used to treat mycobacterium avium complex infections in patients with acquired immunodeficiency syndrome. The authors present the second report of a presumed clofazamine-induced bull's-eye maculopathy and generalized retinal degeneration in a patient with AIDS. The importance of closely following patients on clofazamine, especially those with AIDS who may be particularly susceptible to developing this toxicity, is stressed
— id: 14741, year: 1990, vol: 10, page: 131, stat: Journal Article,

Asymptomatic disseminated Pneumocystis carinii infection detected by ophthalmoscopy
Friedberg DN; Greene JB; Brook DL
1990 Nov 17;336(8725):1256-1257, Lancet
— id: 14739, year: 1990, vol: 336, page: 1256, stat: Journal Article,

Microsporidial keratoconjunctivitis in acquired immunodeficiency syndrome
Friedberg DN; Stenson SM; Orenstein JM; Tierno PM; Charles NC
1990 Apr;108(4):504-508, Archives of ophthalmology
We describe three patients with acquired immunodeficiency syndrome who presented with a bilateral coarse superficial epithelial keratitis due to infection with the protozoal parasite Microspora, Encephalitozoon cuniculi. Despite the extent of the corneal surface disease, conjunctival inflammation was minimal. Visual acuity ranged from 20/20 to 20/200. In one patient, the keratitis was complicated by the development of a surface defect with secondary Pseudomonas species infection. All patients had a history of exposure to household pets. Standard cultures were negative. Diagnosis was established in two of the three cases based on characteristic appearance of the protozoan in conjunctival scrapings. Electron microscopy of a conjunctival biopsy specimen in one patient confirmed the species. No recognized effective treatment is available for this infection
— id: 14740, year: 1990, vol: 108, page: 504, stat: Journal Article,

Transient open-angle glaucoma associated with sickle cell trait: report of 4 cases
Friedman AH; Halpern BL; Friedberg DN; Wang FM; Podos SM
1979 Dec;63(12):832-836, British journal of ophthalmology
Four black patients, all with sickle trait (SA), developed transient open-angle glaucoma with blood in Schlemm's canal. In 3 patients the condition followed blunt trauma, while in the fourth no antecedent trauma was described. The intraocular pressure became normal in all 4 cases with the resolution of the haemorrhage from the trabecular meshwork and Schlemm's canal
— id: 14742, year: 1979, vol: 63, page: 832, stat: Journal Article,

Tosyl lysine chloromethyl ketone inhibition of the initiation of hemoglobin synthesis
Freedman, M L; Friedberg, D; Mucha, J; Troll, W
1973 Oct 1;22(19):2441-2451, Biochemical pharmacology
— id: 108492, year: 1973, vol: 22, page: 2441, stat: Journal Article,