CMV retinitis

Christopher J. Hoffmann, M.D., M.P.H., James P. Dunn, M.D.

PATHOGENS

Cytomegalovirus (CMV): ubiquitous beta-herpesvirus that reactivates with advanced HIV (CD4 < 50). Most HIV+ pts have latent infection (+ anti-CMV IgG).

CLINICAL

CMV retinitis (CMV-R) occurred in ~30% AIDS pts pre-HAART (with CD4 < 50 cells/mm³), now ~5% or less in HAART era.
Most common cause of visual loss in AIDS and most common ocular disease when CD4 < 50 cells/mm³. Retinitis comprises 80-90% of end-organ CMV disease.
Med. survival after Dx w/ CMV-R 8.5-12 mos in pre-HAART era.
Sx: (1) often none (15-50% asymptomatic); (2) floaters, photopsias, blind spots, distortion; (blind spots % distortion especially if macula involved); (3) no pain, redness, photophobia.
Bilateral involvement at time of Dx in 35%. 50% w/ unilateral retinitis develop contralateral involvement within 6 mos if untreated.
Causes of visual loss: central macular (foveal) necrosis (irreversible); optic neuritis (occasionally reversible); macular edema (occasionally reversible); retinal detachment (surgically treatable). Greater risk in eyes with larger lesions and with lesions involving vitreous base anteriorly. 50% will have detachment in ≥1 eye at 1 yr after Dx of CMV-R without immune recovery; 33% of eyes will suffer detachment. In HAART era, detachment rate has decreased, but remains similar among those with CD4 < 50.
Cataract and macular edema are most common causes of visual loss in patients with immune recovery uveitis.
Clinical course: relentless progression of retinitis in untreated pts: 24 microns/day (range 0-164).

DIAGNOSIS

Location of retinitis: Zone 1 (posterior, often visible with direct ophthalmoscopy) within 1500 mu (~1 disc diameter) of optic disc or 3000 mu of fovea; considered immediately vision-threatening. Zone 2 (peripheral to zone 1 but posterior to zone 3) not considered immediately vision-threatening; direct ophthalmoscopy in well-dilated pupil can image retina into mid-periphery of zone 2. Zone 3 (anterior to imaginary circle connecting ampulla of vortex veins).
Spectrum of clinical findings: (1) Fulminant/granular retinitis: hemorrhagic retinal necrosis, often with perivascular sheathing (may be present in retina away from area of necrosis); rarely mis-Dx’d; (2) Indolent/granular retinitis: minimal or no hemorrhage and no perivascular sheathing; more commonly misdiagnosed; (3) Mixed features can be present; (4) Dry, granular-appearing border characteristic; (5) Lesions may be single or multiple, unilateral or bilateral; (6) Full-thickness retinal necrosis with irreversible loss of function in affected tissue; (7) Mild anterior chamber and vitreous inflammatory reaction usually present; fine keratic precipitates typical; no posterior synechiae. Retinal detachment may occur in areas of necrosis.
CMV Immune reconstitution inflammatory reaction (IRIS): usually causes uveitis or vitritis with viral suppression after starting ART in patients with very low CD4 count. Risk greatest in patients with large areas of CMV retinitis.
DDx: acute retinal necrosis (HSV or VZV), progressive outer retinal necrosis (VZV), toxoplasmosis, syphilis, cotton-wool spots, metastatic Candida or other fungal endophthalmitis, intraocular lymphoma, tuberculosis
Dx: Dx made clinically, confirmatory tests rarely necessary. CMV PCR from vitreous, blood, other sources not in widespread clinical use, but vitreous PCR occasionally helpful in distinguishing CMV-R from necrotizing herpetic retinitis or toxoplasmosis. CMV viral load: not used, uncertain significance.
Sensitivity testing: not yet in widespread use; resistant CMV uncommon at time of Dx but reported to occur at rate of 0.25/person-year in pre-HAART era, similar for ganciclovir and foscarnet; rate is lower in era of HAART, perhaps due to more potent anti-CMV therapy.

TREATMENT

General principles

Induction-maintenance: induction: higher or more frequent doses of drug given initially with systemic therapy for 2-3 wks; maintenance (2^o prophylaxis): lower or less frequent chronic suppressive doses continued indefinitely to prevent relapse (or until retinitis is quiescent), treatment has been for >3 months, CD4 count is persistently >100 cells/mm³, and patient is on effective ART.
Choice of treatment based on location of retinitis, pt preference, overall general health.
Common approach to sight-threatening disease is systemic therapy with oral valganciclovir with intravitreal ganciclovir of foscarnet.
CMV retinitis that is not immediately sight-threatening may be treated with systemic therapy with valganciclovir.
IV Ganciclovir (GCV) and foscarnet (FOS) now rarely used because of need for permanent indwelling catheter and availability of safer options (e.g., valganciclovir).
Systemic GCV shown in randomized clinical trial to reduce risk of KS in patients with CMV-R. Systemic anti-CMV therapy in persistently immunocompromised patients increases survival.
Zone 1 lesions in eyes of pts without immune recovery are best candidates for GCV implant. Small Zone 2 or Zone 3 lesions may respond to HAART alone (see below), but concurrent valganciclovir therapy for up to 6 mos recommended.
Additional anti-CMV Rx may decrease risk of immune recovery uveitis (see below) and may have systemic benefits. Relapse after cessation of therapy is certain in pts not on HAART: average within 4 wks.
Clinical features of treated retinitis: sharp demarcation between necrotic and uninvolved retina; variable pigmentation of necrotic retina; lipid or calcification may be present and should not be confused with active retinitis.
CMV uveitis or vitritis: initial therapy is topical corticosteroids (systemic steroids may be considered).

Systemic therapy

IV GCV (FDA-approved): induction: 5 mg/kg twice-daily x 2 wks; maintenance: 5 mg/kg once-daily. Side effects: reversible bone marrow suppression (especially leukopenia & anemia), GI (nausea, diarrhea), requires indwelling central venous catheter for daily infusions.
Oral ganciclovir (GCV) (FDA-approved for maintenance therapy only after 3-wk IV induction therapy completed): 1 gm PO three times a day. Side effects: similar to IV GCV but no catheter-related complications. Due to large pill burden, use has been replaced by valganciclovir.
Valganciclovir (FDA-approved): valine ester (pro-drug) of GCV gives comparable serum levels to IV GCV. Induction: 900 mg PO twice-daily x 3 wks; maintenance: 900 mg orally PO once-daily. Side effects: similar to IV GCV but no catheter-related complications.
Foscarnet (FOS) (FDA-approved): induction 90 mg/kg IV q12h x 2 wks then maintenance 90-120 mg/kg IV once-daily. Efficacy similar to IV GCV. Side effects: reversible nephrotoxicity (dose adjustment required), nausea, hypocalcemia, genital ulcerations, catheter-related infections (including sepsis). Use of FOS now generally limited to pts with bone marrow suppression, unable to tolerate GCV implant surgery, and/or evidence of resistance to GCV. In pre-HAART era, survival in pts treated with FOS longer than with IV GCV (12.6 v. 8.5 mos), possibly due to weak antiretroviral effect of FOS. Probably no enhanced survival benefit of FOS vs. GCV in pts concurrently treated with HAART.
Cidofovir (CDV) (FDA-approved): induction: 5 mg/kg IV q wk x 2 wks then maintenance: 5 mg/kg IV q2wks. Avoids need for permanent IV catheter. Side effects: nephrotoxicity (drug given with probenecid and saline hydration before and after CDV infusion), which is usually but not always reversible, cessation of CDV usually required; probenecid toxicity (rash, malaise); uveitis - may be severe, with loss of vision due to ocular hypotony (more common with repeated infusions, usually responds to topical corticosteroids and cessation of cidofovir therapy). Efficacy: comparable to GCV implant in randomized clinical trial.

Local therapy

Intravitreous injections (non-FDA-approved): sometimes used to obtain rapid intraocular drug levels in eyes with Zone 1 disease prior to more definitive therapy. Should not be sole therapy as provides no protection against contralateral or extraocular CMV infection and is associated with higher morbidity than combined local and systemic therapy. May allow control of retinitis during times when pt unable to tolerate systemic therapy because of illness or toxicity. Dosages: GCV 2 mg/0.1 ml qweek; FOS 2.4 mg/0.1 ml 1-2 x/wk. Side effects: infection, retinal detachment, vitreous hemorrhage, cataract. Note: intravitreous CDV is toxic to the eye (inflammation and hypotony) and should not be used.

Selected Drug Comments

Drug	Recommendation
Valganciclovir	Preferred for most cases of CMV-R; efficacy comparable to IV forms of therapy with fewer side effects. Particularly effective when combined with ART. Should also be used as 2^o prophylaxis when GCV implant used to reduce risk of visceral CMV disease and decrease mortality.
Ganciclovir	Difficult to obtain in oral formulation with no benefit over valganciclovir. IV GCV can be substituted for valganciclovir in patients unable to tolerate oral anti-CMV therapy. GCV implant often the preferred therapy in pts with CMV-R threatening optic nerve or fovea, particularly in pts not taking or poorly responsive to HAART.
Foscarnet	IV FOS not used as primary therapy for CMV-R but may be useful in patients with GCV resistance or severe bone marrow suppression. Short half-life, nephrotoxicity, and limitation to IV form are major drawbacks. Intravitreal FOX can be useful as short-term therapy for lesions threatening optic nerve and macula.
Cidofovir	IV CDV has efficacy comparable to GCV implant plus oral therapy but usually less well tolerated because of nephrotoxicity, long duration of infusion, and side effects of probenecid that must be given with cidofovir to reduce risk of renal disease. May be useful in pts with GCV resistance. Intravitreous CDV should not be used.

FOLLOW UP

Relapse

Clinical features of relapse or progression: increased border opacification ("smoldering retinitis"); expansion of previously inactive border of retinitis; appearance of new lesions in same or fellow eye; progression may occur without visible border opacification.
Careful monitoring of retinitis with serial retinal photographs is most effective means of determining active vs. inactive disease.
Effect of progression on vision is function of location: small progression in zone 1 disease may cause severe visual loss; occurs within 48-121 days in pts not treated with HAART (depending on criteria used to define relapse).
Hemorrhage alone not an indication of relapse.
Causes: non-adherence to therapy; poor intraocular drug availability; antiviral resistance (occurred at a rate of ~0.25/person-year with systemic therapy in pre-HAART era, but much lower now).
Resistance: (1) UL97 mutations: low-grade GCV resistance, results in decreased phosphorylation of GCV (required for cellular antiviral effect uptake), may respond to GCV implant, usually responds to cidofovir or FOS (neither requires phosphorylation by viral enzymes); (2) UL54 mutations: high-grade GCV resistance, results in failure to impair CMV DNA polymerase, often causes resistance to GCV implant and cidofovir; (3) mutations causing FOS resistance less well studied and more difficult to identify

Treatment of relapse (or progression)

Options: Reinduction with same drug.
Higher dose of maintenance therapy (e.g., FOS 120 vs. 90 mg/kg/day) after reinduction.
Change to different drug (e.g., CDV instead of GCV; use of GCV implant)
Combination therapy (e.g., GCV + FOS); may be more effective but also more toxic.
Most effective means of treating or preventing relapse is immune recovery with ART.
Response to treatment: relapse-free intervals become progressively shorter.

Impact of HAART

Reduced incidence of CMV-R and other ocular infection: 75-85% reduction in incidence of CMV-R in several studies.
ART alone may control CMV-R: occasional finding of inactive or regressing CMV-R in pts treated with HAART but no specific anti-CMV therapy.
Not recommended as sole therapy due to: (1) risk of spread of retinitis to fovea or optic nerve before immune recovery occurs in pts with Zone 1 disease; (2) increased risk of immune recovery uveitis among pts with inadequate treatment of CMV-R then started on ART; (3) benefit of systemic anti-CMV therapy on survival among immunocompromised patients.
Use of HART associated with fewer ocular complications in patients with CMV-R and lower risks of retinal detachment and vision loss.
Immune recovery uveitis (IRU): syndrome of vitritis and other sequelae of increased intraocular inflammation (+/- cystoid macular edema [CME], epiretinal membranes) in pts with CMV-R who have been treated with ART. More common in eyes with larger area of retinal involvement, in less aggressively treated eyes, and in eyes of pts treated with IV cidofovir. Dx: clinical examination, fluorescein angiography, optical coherence tomography. Rx: 50% of pts with CME respond to oral or periocular corticosteroids . Relapse of retinitis in pts treated with corticosteroids rare. May respond to valganciclovir.
Cessation of anti-CMV therapy: chronic maintenance can be safely discontinued in pts with immune recovery (CD4 >100x ≥3-6 mos. Resume maintenance if CD4 declines to < 75. Best candidates are those who are ART-nave at time of Dx, show good immune recovery, and are adherent to ART regimen. Pts with immune recovery have relapse rate of 0.03/person-yr and require regular ophthalmic follow-up (recommended q 3 mos).

OTHER INFORMATION

Most newly Dx’d CMV-R now found in ART-experienced pts.
ART reduces ocular morbidity associated with CMV-R, especially in pts with immune recovery but to a lesser extent even in non-responders.
Progression of CMV-R can occur even in pts with excellent response to ART (0.03/person-yr), so regular ophthalmic monitoring is indicated.

Pathogen Specific Therapy

Pathogen	1st Line Agent	2nd Line Agent
CMV	Valganciclovir	Ganciclovir

Basis for recommendation

Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Accessed 4/11/2022. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportunis...
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References

Port AD, Alabi RO, Koenig L, et al. Cytomegalovirus retinitis in the post-cART era. Curr Ophthalmol Rep. 2018;6(2):133-144. [PMID:30886765]
Holland GN. AIDS and ophthalmology: the first quarter century. Am J Ophthalmol. 2008;145(3):397-408. [PMID:18282490]
Comment: This article reviews the evolution of CMV-R from a pre-terminal manifestation of AIDS to a chronic, manageable disease with numerous complications. Points of emphasis include retinal detachment, immune recovery uveitis, and visual disturbances (reduced contrast sensitivity, altered color vision, visual field abnormalities) that can occur in HIV+ pts even without infectious retinopathy.
Otiti-Sengeri J, Meenken C, van den Horn GJ, et al. Ocular immune reconstitution inflammatory syndromes. Curr Opin HIV AIDS. 2008;3(4):432-7. [PMID:19373002]
Comment: This review of immune recovery uveitis (IRU) summarizes risk factors (in addition to improved immunity itself, a low CD4 count at time of initiation of ART, and involvement of a larger proportion of retina), effect on vision and morbidity, and current treatment. A precise definition of IRU remains lacking.
Morrison VL, Kozak I, LaBree LD, et al. Intravitreal triamcinolone acetonide for the treatment of immune recovery uveitis macular edema. Ophthalmology. 2007;114(2):334-9. [PMID:17270681]
Comment: In a small, non-randomized, prospective, consecutive, interventional case series, intravitreal triamcinolone acetonide appeared to be more effective for treatment of macular edema caused by immune recovery uveitis than historical controls have shown with periocular corticosteroid injections.
Martin BK, Ricks MO, Forman MS, et al. Change over time in incidence of ganciclovir resistance in patients with cytomegalovirus retinitis. Clin Infect Dis. 2007;44(7):1001-8. [PMID:17342657]
Comment: In 10-yr prospective observational study from 1993-2003, 2-yr incidence of resistance was 28% among pts enrolled before 1996 and 9% among those enrolled in or after 1996 (P=.001). All cases of resistance occurred among pts with CD4 <50, and + CMV Cx results at baseline associated with approximately 4-fold increase in resistance. Better control of CMV replication may have contributed to this decrease.
Jabs DA, Van Natta ML, Holbrook JT, et al. Longitudinal study of the ocular complications of AIDS: 1. Ocular diagnoses at enrollment. Ophthalmology. 2007;114(4):780-6. [PMID:17258320]
Comment: In a large cohort study of patients with AIDS in the HAART era, there has been substantial decline in incidence of CMV retinitis from compared to pre-HAART era. Incidence of CMV retinitis estimated from retrospective data was 5.60/100 person-yrs. Of 360 patients with CMV-R, over 75% had pre-existing CMV-R. Nevertheless, new cases continue to occur, and there is population of patients with long-standing retinitis who will require management.
Jabs DA, Van Natta ML, Holbrook JT, et al. Longitudinal study of the ocular complications of AIDS: 2. Ocular examination results at enrollment. Ophthalmology. 2007;114(4):787-93. [PMID:17210182]
Comment: In the HAART era, CMV-R and other ocular opportunistic infections are associated with intraocular inflammation, structural ocular complications, and visual impairment. Patients with newly diagnosed CMV-R have eye examination findings similar to those seen in pre-HAART era.
Thorne JE, Jabs DA, Kempen JH, et al. Causes of visual acuity loss among patients with AIDS and cytomegalovirus retinitis in the era of highly active antiretroviral therapy. Ophthalmology. 2006;113(8):1441-5. [PMID:16781775]
Comment: In HAART era, zone 1 involvement and retinal detachment remain most common causes of visual acuity loss among patients with CMV-R. Immune recovery uveitis due to ART associated with vision loss from cataract and CME also are common causes of loss of visual acuity.
Kuo IC, Kempen JH, Dunn JP, et al. Clinical characteristics and outcomes of cytomegalovirus retinitis in persons without human immunodeficiency virus infection. Am J Ophthalmol. 2004;138(3):338-46. [PMID:15364214]
Comment: CMV-R in pts without HIV has clinical course similar to that in pts with AIDS treated with HAART, except incidence of retinal detachment lower for pts without AIDS. Cessation of anti-CMV therapy often possible in pts who discontinue or reduce their immunomodulatory therapy.
Jabs DA. AIDS and ophthalmology in 2004. Arch Ophthalmol. 2004;122(7):1040-2. [PMID:15249370]
Comment: Summary of trends in incidence of CMV-R and treatment recommendations for affected patients in era of HAART. Systemic therapy, with or without GCV implant, recommended for all pts with newly Dx'd CMV-R to increase survival and possibly decrease risk of immune recovery uveitis.
Dunn JP, Van Natta M, Foster G, et al. Complications of ganciclovir implant surgery in patients with cytomegalovirus retinitis: the Ganciclovir Cidofovir Cytomegalovirus Retinitis Trial. Retina. 2004;24(1):41-50. [PMID:15076943]
Comment: Patients with CMV-R randomized to treatment with GCV implant had low risk of serious complications in first 60 days after surgery. Vitreous hemorrhage was most commonly observed complication and resolved in all cases.
Jabs DA, Van Natta ML, Thorne JE, et al. Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: 2. Second eye involvement and retinal detachment. Ophthalmology. 2004;111(12):2232-9. [PMID:15582079]
Comment: Compared with rates reported in pre-HAART era of 2nd eye involvement (approximately 0.40/person-year) and retinal detachment (approximately 0.50/PY), rates of these events reduced among pts in the HAART era. However, among patients with CD4 <50, rates more similar to those from pre-HAART era.
Jabs DA, Van Natta ML, Thorne JE, et al. Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: 1. Retinitis progression. Ophthalmology. 2004;111(12):2224-31. [PMID:15582078]
Comment: Although retinitis progression in pts with CMV-R treated with anti-CMV therapy and HAART much less than in pre-HAART era, significant risk factors for retinitis progression included low CD4 count, positive CMV viral load, longer time from AIDS Dx and low Karnofsky score
Kempen JH, Jabs DA, Wilson LA, et al. Mortality risk for patients with cytomegalovirus retinitis and acquired immune deficiency syndrome. Clin Infect Dis. 2003;37(10):1365-73. [PMID:14583871]
Comment: Study of nearly 600 patients with CMV-R: use of HAART associated with 96% reduction in mortality in pts who developed immune recovery compared to 49% reduction in those who did not. In pts with profound immunodeficiency despite HAART, continued use of HAART and systemic anti-CMV therapy predicted to reduce risk of mortality by 65%, over and above benefits of PCP and MAC prophylaxis.
Kempen JH, Martin BK, Wu AW, et al. The effect of cytomegalovirus retinitis on the quality of life of patients with AIDS in the era of highly active antiretroviral therapy. Ophthalmology. 2003;110(5):987-95. [PMID:12750102]
Comment: In HAART era, CMV-R associated with reduced vision-related quality of life in pts both with newly Dx'd and long-standing disease.
Drew WL. Cytomegalovirus Disease in the Highly Active Antiretroviral Therapy Era. Curr Infect Dis Rep. 2003;5(3):257-265. [PMID:12760824]
Comment: In HAART era, pts still present with CMV disease, and resistance or intolerance to HAART does develop, which may give rise to resurgence of CMV syndromes in AIDS pts. Treatment should be based on both systemic health and local ocular factors.
Holbrook JT, Jabs DA, Weinberg DV, et al. Visual loss in patients with cytomegalovirus retinitis and acquired immunodeficiency syndrome before widespread availability of highly active antiretroviral therapy. Arch Ophthalmol. 2003;121(1):99-107. [PMID:12523893]
Comment: In 3 clinical trials of CMV-R conducted between 1990-96 (pre-HAART era), visual loss common, with major causes of visual loss in pts being retinal detachment and either optic nerve or macular involvement. However, visual outcomes better after 1992, even before availability of HAART.
Jabs DA, Martin BK, Forman MS, et al. Cytomegalovirus resistance to ganciclovir and clinical outcomes of patients with cytomegalovirus retinitis. Am J Ophthalmol. 2003;135(1):26-34. [PMID:12504693]
Comment: Detection of CMV resistant to GCV (IC50 > 6.0 micromol/l) in either the blood or urine of a pt with CMV-R associated with an increased risk of adverse ocular outcomes, including a roughly 5-fold increased risk in odds of progression.
Tanna AP, Kempen JH, Dunn JP, et al. Incidence and management of cataract after retinal detachment repair with silicone oil in immune compromised patients with cytomegalovirus retinitis. Am J Ophthalmol. 2003;136(6):1009-15. [PMID:14644210]
Comment: High incidence of cataract following repair of CMV-R-related retinal detachment surgery with silicone oil tamponade. Posterior capsule opacification occurs rapidly after cataract surgery in these patients.
Kempen JH, Jabs DA, Wilson LA, et al. Risk of vision loss in patients with cytomegalovirus retinitis and the acquired immunodeficiency syndrome. Arch Ophthalmol. 2003;121(4):466-76. [PMID:12695243]
Comment: In eyes with CMV-R, prevalence of a visual acuity measurement of 20/50 or worse or 20/200 or worse at time of CMV-R Dx was 33% and 17%, respectively. Incidence of vision loss did not differ based on type of anti-CMV therapy used, but pts receiving HAART had approximately 75% lower risk of visual impairment.
Jabs DA, Van Natta ML, Kempen JH, et al. Characteristics of patients with cytomegalovirus retinitis in the era of highly active antiretroviral therapy. Am J Ophthalmol. 2002;133(1):48-61. [PMID:11755839]
Comment: Multicenter study of pts with newly Dx'd (incident) or previously Dx'd (prevalent) CMV-R: nearly 2/3 of pts with prevalent disease had successfully discontinued anti-CMV therapy, immune recovery uveitis had been Dx'd in 16%, and incident cases more likely than prevalent cases to be female, African-American, and uninsured.
Hu H, Jabs DA, Forman MS, et al. Comparison of cytomegalovirus (CMV) UL97 gene sequences in the blood and vitreous of patients with acquired immunodeficiency syndrome and CMV retinitis. J Infect Dis. 2002;185(7):861-7. [PMID:11920309]
Comment: In study of 87 pts with CMV-R who had paired blood and vitreous specimens, 13 (15%) had either a GCV resistance-conferring mutation or a polymorphism in CMV UL97 gene. 11 of the 13 mutations or polymorphisms in vitreous also identified in blood
Martin DF, Sierra-Madero J, Walmsley S, et al. A controlled trial of valganciclovir as induction therapy for cytomegalovirus retinitis. N Engl J Med. 2002;346(15):1119-26. [PMID:11948271]
Comment: In this randomized clinical trial, PO valganciclovir as effective as IV GCV for induction treatment of CMV-R and was convenient and effective for long-term management of CMV-R in pts with AIDS. However, progression of retinitis occurred in 10% in both groups despite continued therapy.
Velez G, Roy CE, Whitcup SM, et al. High-dose intravitreal ganciclovir and foscarnet for cytomegalovirus retinitis. Am J Ophthalmol. 2001;131(3):396-7. [PMID:11239885]
Comment: Single case report describing successful control of CMV-R over 1 year with intravitreous injections up to twice weekly of high-dose GCV 3 mg/ml and FOS2.4 mg/ml.
Kempen JH, Jabs DA, Dunn JP, et al. Retinal detachment risk in cytomegalovirus retinitis related to the acquired immunodeficiency syndrome. Arch Ophthalmol. 2001;119(1):33-40. [PMID:11146724]
Comment: Use of HAART associated with 60% reduction in retinal detachment rate (P<.001), with greatest reduction in HAART responders. No significant difference in risk of retinal detachment in eyes treated with GCV implants vs. systemic anti-CMV therapy only.
Holbrook JT, Davis MD, Hubbard LD, et al. Risk factors for advancement of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome. Studies of Ocular Complications of AIDS Research Group. Arch Ophthalmol. 2000;118(9):1196-204. [PMID:10980764]
Comment: In pre-HAART study of CMV-R, risk factors at baseline for progression of retinitis while receiving treatment included smaller area involved, active margins, and posterior location. Risk factors for development of retinitis in uninvolved fellow eyes included blood and urine Cx positive for CMV and lower CD8 count.
Nguyen QD, Kempen JH, Bolton SG, et al. Immune recovery uveitis in patients with AIDS and cytomegalovirus retinitis after highly active antiretroviral therapy. Am J Ophthalmol. 2000;129(5):634-9. [PMID:10844056]
Comment: In this study of 33 pts with CMV-R and good response to HAART, incidence rate of immune recovery uveitis (IRU) was 0.109/person-year, lower than reported in some other studies, but decreased vision occurred in some pts due to macular edema, epiretinal membrane, or optic disc neovascularization.
Holland GN. New strategies for the management of AIDS-related CMV retinitis in the era of potent antiretroviral therapy. Ocul Immunol Inflamm. 1999;7(3-4):179-88. [PMID:10611726]
Comment: Summary of treatment options for CMV-R in HAART era. Previous short-term therapies are being adapted to long-term management of what has in many cases become a chronic disease.
Martin DF, Kuppermann BD, Wolitz RA, et al. Oral ganciclovir for patients with cytomegalovirus retinitis treated with a ganciclovir implant. Roche Ganciclovir Study Group. N Engl J Med. 1999;340(14):1063-70. [PMID:10194235]
Comment: In this randomized clinical trial in pts with AIDS and CMV-R, combination of oral GCV and GCV implant reduced incidence of new CMV disease and delayed progression of retinitis compared to implant + oral placebo. Treatment with oral or IV GCV also reduced the risk of KS.
Jabs DA, Bolton SG, Dunn JP, et al. Discontinuing anticytomegalovirus therapy in patients with immune reconstitution after combination antiretroviral therapy. Am J Ophthalmol. 1998;126(6):817-22. [PMID:9860006]
Comment: In this study of 15 pts with CMV-R and immune recovery from HAART (med. CD4 count 297), none had recurrence of retinitis after discontinuation of anti-CMV therapy for 3-16 mos (median 8 mos).
Martin DF, Ferris FL, Parks DJ, et al. Ganciclovir implant exchange. Timing, surgical procedure, and complications. Arch Ophthalmol. 1997;115(11):1389-94. [PMID:9366668]
Comment: In pts undergoing routine GCV implant exchange, initial exchange procedure well tolerated with continued long-term control of CMV-R. Multiple re-entries through same wound may be associated with increased risk for vitreous hemorrhage.
Mortality in patients with the acquired immunodeficiency syndrome treated with either foscarnet or ganciclovir for cytomegalovirus retinitis. Studies of Ocular Complications of AIDS Research Group, in collaboration with the AIDS Clinical Trials Group. N Engl J Med. 1992;326(4):213-20. [PMID:1345799]
Comment: In this randomized clinical trial of CMV-R in pre-HAART era, IVGCV and FOS were comparably effective for treatment of CMV-R, but retinitis recurred in almost all pts over time in both groups. Mortality significantly lower in FOS-treated group, possibly due to its weak antiretroviral effect.

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