Polymerase Chain Reaction–Based Ganciclovir Resistance Testing of Ocular Fluids for Cytomegalovirus Retinitis

Clinical and Virological Characteristics and Prognostic Factors in Viral Necrotizing Retinitis

“…HSV2 necrotizing retinitis occurs in younger patients than VZV or CMV VNR, in agreement with our findings [12]. The immunosuppressed status found in all patients with CMV retinitis was congruent with the literature [9,11] as were the baseline visual acuity [9,[13][14][15][16][17][18][19], baseline vitritis grade [9] and number of retinal quadrants initially involved [9,13,14,20,21]. Immunodepressed patients with CMV retinitis were rarely affected by HIV (only 4 of 13 patients), which shows that CMV retinitis in this cohort cannot be considered as an AIDS-defining disease.…”

“…Reasonable implications of this would be to propose systematic sequential intraocular fluid sampling to all patients with VNR (at least during the first three weeks of treatment). In slow responders, escalating therapy might be proposed, including more frequent intravitreal injections or use of different antivirals and testing for resistance when the clinical situation does not improve [15]. In this study, we however could not find any clear cut-off in viral load that could be used to choose the most appropriate timing for the switch to prophylactic antiviral doses (data not shown).…”

Clinical and Virological Characteristics and Prognostic Factors in Viral Necrotizing Retinitis

“…HSV2 necrotizing retinitis occurs in younger patients than VZV or CMV VNR, in agreement with our findings [12]. The immunosuppressed status found in all patients with CMV retinitis was congruent with the literature [9,11] as were the baseline visual acuity [9,[13][14][15][16][17][18][19], baseline vitritis grade [9] and number of retinal quadrants initially involved [9,13,14,20,21]. Immunodepressed patients with CMV retinitis were rarely affected by HIV (only 4 of 13 patients), which shows that CMV retinitis in this cohort cannot be considered as an AIDS-defining disease.…”

“…Reasonable implications of this would be to propose systematic sequential intraocular fluid sampling to all patients with VNR (at least during the first three weeks of treatment). In slow responders, escalating therapy might be proposed, including more frequent intravitreal injections or use of different antivirals and testing for resistance when the clinical situation does not improve [15]. In this study, we however could not find any clear cut-off in viral load that could be used to choose the most appropriate timing for the switch to prophylactic antiviral doses (data not shown).…”

Case report: CMV retinitis following local and systemic immunosuppression

“…In these patients, administering prophylactic valganciclovir, intravenous ganciclovir, or valacyclovir is recommended ( 19 ). However, antiviral drug resistance mutations may develop in patients treated with long-term prophylactic valganciclovir and may be detected through aqueous humor samples ( 20 ).…”

“…The most common mutations are of the UL97 gene, which codes for a kinase that phosphorylates ganciclovir, or the UL54 gene, which codes for viral DNA polymerase. Screening for CMV resistance should be considered in select populations, especially those on chronic valganciclovir therapy or refractory CMV retinitis cases ( 20 ).…”

Rapid Detection of Human Cytomegalovirus UL97 and UL54 Mutations Directly from Patient Samples

“…If a drug-resistant variant is identified in the UL97 gene, subsequent UL54 gene sequencing is recommended (19). Many cases of resistance have been documented, both as case reports (6,(20)(21)(22)(23)(24)(25)(26) and cohort studies (5,15,27). Most of these cases report resistance arising from canonical UL97 ganciclovir resistance mutations.…”

Clinical and Virological Characteristics and Prognostic Factors in Viral Necrotizing Retinitis

“…HSV2 necrotizing retinitis occurs in younger patients than VZV or CMV VNR, in agreement with our findings [12]. The immunosuppressed status found in all patients with CMV retinitis was congruent with the literature [9,11] as were the baseline visual acuity [9,[13][14][15][16][17][18][19], baseline vitritis grade [9] and number of retinal quadrants initially involved [9,13,14,20,21]. Immunodepressed patients with CMV retinitis were rarely affected by HIV (only 4 of 13 patients), which shows that CMV retinitis in this cohort cannot be considered as an AIDS-defining disease.…”

“…Reasonable implications of this would be to propose systematic sequential intraocular fluid sampling to all patients with VNR (at least during the first three weeks of treatment). In slow responders, escalating therapy might be proposed, including more frequent intravitreal injections or use of different antivirals and testing for resistance when the clinical situation does not improve [15]. In this study, we however could not find any clear cut-off in viral load that could be used to choose the most appropriate timing for the switch to prophylactic antiviral doses (data not shown).…”

Case report: CMV retinitis following local and systemic immunosuppression

“…In these patients, administering prophylactic valganciclovir, intravenous ganciclovir, or valacyclovir is recommended ( 19 ). However, antiviral drug resistance mutations may develop in patients treated with long-term prophylactic valganciclovir and may be detected through aqueous humor samples ( 20 ).…”

“…The most common mutations are of the UL97 gene, which codes for a kinase that phosphorylates ganciclovir, or the UL54 gene, which codes for viral DNA polymerase. Screening for CMV resistance should be considered in select populations, especially those on chronic valganciclovir therapy or refractory CMV retinitis cases ( 20 ).…”

Rapid Detection of Human Cytomegalovirus UL97 and UL54 Mutations Directly from Patient Samples

“…If a drug-resistant variant is identified in the UL97 gene, subsequent UL54 gene sequencing is recommended (19). Many cases of resistance have been documented, both as case reports (6,(20)(21)(22)(23)(24)(25)(26) and cohort studies (5,15,27). Most of these cases report resistance arising from canonical UL97 ganciclovir resistance mutations.…”

Clinical and Virological Characteristics and Prognostic Factors in Viral Necrotizing Retinitis

“…HSV2 necrotizing retinitis occurs in younger patients than VZV or CMV VNR, in agreement with our findings [12]. The immunosuppressed status found in all patients with CMV retinitis was congruent with the literature [9,11] as were the baseline visual acuity [9,[13][14][15][16][17][18][19], baseline vitritis grade [9] and number of retinal quadrants initially involved [9,13,14,20,21]. Immunodepressed patients with CMV retinitis were rarely affected by HIV (only 4 of 13 patients), which shows that CMV retinitis in this cohort cannot be considered as an AIDS-defining disease.…”

“…Reasonable implications of this would be to propose systematic sequential intraocular fluid sampling to all patients with VNR (at least during the first three weeks of treatment). In slow responders, escalating therapy might be proposed, including more frequent intravitreal injections or use of different antivirals and testing for resistance when the clinical situation does not improve [15]. In this study, we however could not find any clear cut-off in viral load that could be used to choose the most appropriate timing for the switch to prophylactic antiviral doses (data not shown).…”

Case report: CMV retinitis following local and systemic immunosuppression

“…In these patients, administering prophylactic valganciclovir, intravenous ganciclovir, or valacyclovir is recommended ( 19 ). However, antiviral drug resistance mutations may develop in patients treated with long-term prophylactic valganciclovir and may be detected through aqueous humor samples ( 20 ).…”

“…The most common mutations are of the UL97 gene, which codes for a kinase that phosphorylates ganciclovir, or the UL54 gene, which codes for viral DNA polymerase. Screening for CMV resistance should be considered in select populations, especially those on chronic valganciclovir therapy or refractory CMV retinitis cases ( 20 ).…”

Rapid Detection of Human Cytomegalovirus UL97 and UL54 Mutations Directly from Patient Samples

“…If a drug-resistant variant is identified in the UL97 gene, subsequent UL54 gene sequencing is recommended (19). Many cases of resistance have been documented, both as case reports (6,(20)(21)(22)(23)(24)(25)(26) and cohort studies (5,15,27). Most of these cases report resistance arising from canonical UL97 ganciclovir resistance mutations.…”