Injection Of Ganciclovir Research Articles

Typical cytomegalovirus retinitis in non-human immunodeficiency virus partially immunosuppressed patients: A case series

Purpose: The purpose of the study was to analyze the occurrence of severe, typical cytomegalovirus (CMV) retinitis (CMVR) in human immunodeficiency virus (HIV) negative, partially immunosuppressed patients, emphasizing inconsistency in the clinical presentation of CMVR and to evaluate the role of combined anti-CMV therapy in the management of such patients. Materials and Methods: This study was a retrospective, observational, noncomparative case series. We examined and treated consecutive HIV-negative adult patients of CMVR. Blood-based polymerase chain reaction analysis of the CMV genome was done pre- and posttreatment. Details of underlying systemic conditions were collected. Patients were treated with simultaneous administration of intravitreal and intravenous (IV) anti-CMV therapy. Follow-up was for 1 year. All outcomes were determined retrospectively. Results: A total of 6 eyes of 4 consecutive patients were diagnosed with CMVR in HIV-negative patients. Patients were only partially immunosuppressed but revealed typical severe fulminant CMVR. Patients received a total of 2 intravitreal ganciclovir injections, and IV ganciclovir/oral valganciclovir was given. All patients achieved complete healing within the treatment period. Conclusion: As opposed to the general perception, typical, fulminant, severe CMVR may occur in patients with limited immune dysfunction. Our report underlines this inconsistency in the clinical presentation of CMVR in partially immunosuppressed patients. The immune status of the patients seems a significant factor in determining the clinical phenotypes of CMVR. Combined intravitreal and IV ganciclovir/oral valganciclovir therapy was successful in treating this group of CMVR patients.

Presumed macular toxicity of high-dose intravitreal ganciclovir

Abstract: A 56-year-old male with bilateral cytomegalovirus retinitis was initiated on oral valganciclovir and intravitreal ganciclovir injection twice a week in first 2 weeks and once a week in subsequent weeks. An intravitreal dose of 2 mg/0.08 mL was administered in the 1st week. Considering the suboptimal response, the dose of intravitreal ganciclovir was increased to 4 mg/0.08 mL. After 4 weeks of therapy (four doses of 4-mg ganciclovir), the patient complained of worsening of vision. Fundus examination showed resolving retinitis, but the optical coherence tomography (OCT) showed neurosensory detachment (NSD) at the fovea in both eyes with inner retinal hyperreflectivity in the right eye. Considering the possibility of retinitis involving fovea, a higher dose of intravitreal ganciclovir (6 mg/0.08 mL) was administered. The patient reported further worsening of vision immediately after removing the eye patch 2 hr following the injection. OCT showed a full-thickness hyperreflective vertical band with ellipsoid zone disruption at the fovea and inner retinal hyperreflectivity in the right eye. Hyperreflective vertical band with NSD was seen in the left eye. A possibility of macular toxicity due to intravitreal ganciclovir was considered. Intravitreal therapy was stopped and oral valganciclovir was continued. At 1-month follow-up, the patient reported improvement in vision. The hyperreflectivity and NSD were resolved at month follow-up. Although higher doses of ganciclovir up to 6 mg have been used in the past, it would be better to avoid higher doses considering the development of presumed drug toxicity in our case following the use of 4 mg and 6 mg.

Retinitis after haematopoietic stem cell transplantation with multiple intraocular viral infections (cytomegalovirus, Epstein‒Barr virus and herpes simplex virus)- a case report

BackgroundTo report a case of retinitis with multiple intraocular viral infections after second haematopoietic stem cell transplantation.Case presentationA 39-year-old female patient developed retinitis after a second haematopoietic stem cell transplant. Right eye was tested for three viral infections– cytomegalovirus, Epstein‒Barr virus and herpes simplex virus, while left was infected with cytomegalovirus. The patient was subsequently treated with vitreous cavity ganciclovir injections, and 1 week later both eyes tested negative for aqueous humour viruses.Discussion and conclusionCMV, EBV and HSV belong to the herpes virus family. They are all commonly observed in the body and represent opportunity infectious viruses. The retinitis they cause have different characteristics. But simultaneous infection of the eye by multiple viruses is quite rare. In this case, three viruses were detected in the patient’s eye, but whether the retina was caused by all three viruses at the same time could not be determined. A satisfactory outcome was achieved after treatment with vitreous cavity ganciclovir injection.

Clinical pattern and outcomes of acute retinal necrosis in a referral Center in Tunisia, North Africa: A 17‐year retrospective study

Aims/Purpose: To describe the pattern of acute retinal necrosis (ARN) in a referral centre in Tunisia, North Africa.Methods: The charts of 22 patients diagnosed with ARN from January 2006 to January 2023 were retrospectively reviewed.Results: The mean age at presentation was 39.2 (range, 12–70) years, sex ratio was 1.75. The mean diagnostic delay was 17.9 days (range 1–60). The mean visual acuity at presentation was 20/400. All patients presented with a mild to moderate anterior uveitis (100%) with granulomatous keratic precipitates in 18 eyes (81%) and ocular hypertension in 4 eyes (18%). Necrotizing retinitis involved >50% of the retina in 36.5%of eyes. Polymerase chain reaction on aqueous humour sample identified varicella zoster virus in 10 eyes (45%), herpes simplex virus‐1 in 4 eyes (18%) and was negative in 8 eyes (22%). All patients received intravenous acyclovir, followed by oral antivirals. Intravitreal injections of ganciclovir were administered in 12 eyes (54.5%). Follow‐up ranged from 1 month to 48 months. The mean final visual acuity was 20/200. Complications included retinal detachment (RD) (31.8%), macular oedema (18%), macular atrophy (22%), epimacular membrane (22%), cataract (27%), optic nerve atrophy (18%) and central retinal artery occlusion (4%). No patient developed bilateral ARN. Prophylactic laser was performed in 7 eyes (32%). RD was treated with pars plana vitrectomy and silicone oil injection in 7 eyes.Conclusions: ARN syndrome in Tunisia is most commonly caused by VZV.

Cytomegalovirus Reactivation in Postrenal Transplant Patients Immediately in Association with Coronavirus Disease 2019 (COVID-19) Infection: A Case Report of 2 Patients and a Brief Review of the Literature

Introduction: The coronavirus disease 2019 (COVID-19) infection has been associated with multiple opportunistic infections, including secondary cytomegalovirus (CMV) reactivation. Several cases of CMV syndrome and invasive CMV infection have been reported following severe COVID-19 infection worldwide during the COVID-19 pandemic in both immunocompetent and immunosuppressed patients. A case-control study conducted in India showed that during the first and second waves, CMV was the most common co-infection among fatal cases of severe COVID-19 lung infection in Indian renal transplant recipients. Case Presentation: We present 2 cases of CMV disease in postrenal transplant patients who developed clinical manifestations of CMV co-infection after mild COVID-19 infection during the fourth wave of COVID-19 infection in India. In both cases, CMV infection was treated by discontinuing mycophenolate mofetil and administering ganciclovir injections. However, the treatment resulted in 2 contrasting clinical outcomes: Cure and death. Conclusions: We reviewed the recent literature on the increased incidence of CMV reactivation after both COVID-19 infection and vaccination in immunocompetent and immunocompromised populations. Subsequently, we discussed some clinical questions relevant to the population of postrenal transplant recipients after the detection of mild COVID-19 infection.

Dexamethasone intravitreal implant for macular edema and some other rare indications in uveitis.

In the present study, 110 eyes of 81 patients with uveitis who underwent intravitreal dexamethasone implant (IDI) injection and had a follow-up of at least 6 months between January, 2012 and September, 2022, were retrospectively analyzed. A total of 298 IDI injections were administered (mean, 2.71±2.37; range, 1-12). The mean age of the patients was 49.44±16.67 years (range, 15-86 years). The mean follow-up time after the first IDI was 34.31±26.53 months (range, 6-115 months). In total, 77 (95.1%) patients had non-infectious uveitis, while 4 patients (4.9%) received IDI for uveitic macular edema in association with infectious uveitis (1 patient with acute retinal necrosis and 3 patients with systemic tuberculosis). IDI was injected under the umbrella of intravitreal ganciclovir injection in the patient with healed acute retinal necrosis for the associated pseudophakic cystoid macular edema. A total of 6 patients (7.4%) received IDI prior to phacoemulsification surgery to control the possible post-operative macular edema. In addition, 3 patients (3.7%) with Vogt-Koyanagi-Harada disease received bilateral IDI as the systemic therapy could not be administered due to side-effects of the systemic treatment. In total, 1 patient (1.2%) with idiopathic retinal vasculitis, aneurysms and neuroretinitis was treated with IDI injections in both eyes in addition to systemic therapy to reduce the ongoing inflammation. Of note, two eyes (1.8%) received simultaneous single IDI and anti-vascular endothelial growth factor administration for the treatment of unilateral extrafoveal macular neovascularization (one with active serpiginous choroiditis and one with sympathetic ophthalmia). IDI was administered for the treatment of uveitic macular edema in 68 patients (83.9%). Best-corrected visual acuity improved from 0.69±0.64 to 0.60±0.76 logMAR at the final visit (P=0.008). Baseline mean central macular thickness (CMT) was 499.74±229.60 µm (range, 187-1,187 µm) and the mean final CMT was 296.60±152.02 µm (range, 126-848 µm). Intraocular pressure elevation requiring topical antiglaucomatous eye drops occurred in 28 eyes (25.5%). During the follow-up period, bilateral glaucoma surgery was required in 1 patient (1.2%) and 25 of 65 phakic eyes (38.4%) underwent phacoemulsification. Retinal detachment occurred in one eye (0.9%), endophthalmitis in one eye (0.9%), and transient intravitreal hemorrhage occurred in three eyes (2.7%) after the IDI injections. On the whole, the present study demonstrates that although IDI is mostly employed in non-infectious uveitic eyes with macular edema, it can also be administered in cases with systemic therapy intolerance, pseudophakic macular edema prophylaxis, and with great caution, in selected cases involving infectious uveitis and macular edema.

CMV retinitis and subsequent acute cystoid macular oedema after treatment with vitreous ganciclovir injection: a case report

BackgroundTo report a very rare acute cystoid macular oedema following ganciclovir injection in patients receiving allogeneic haematopoietic stem cell transplantation.Case presentationA 44-year-old male patient experienced vision loss in his left eye eight months after allogeneic stem cell transplantation. Ophthalmologic examination showed posterior retinopathy with retinal haemorrhage, a yellow necrotic border, and a vascular white sheath involved in the superior temporal retina but not the posterior pole. Cytomegalovirus DNA results in both plasma and ocular fluid were positive. All tests combined with the patient’s medical history suggested that his ocular disease was cytomegalovirus retinitis. Consequently, he received a weekly ganciclovir vitreous injection. The disease was visibly controlled, and the fundus condition improved after the first three treatments. However, the patient had severe vision loss in his left eye and acute cystic oedema in the macula, while the original lesion was stable two hours after the fourth treatment. The macular oedema subsided significantly on the first day. Over the next week, daily OCT findings indicated that the patient's macular oedema gradually subsided and resolved completely by the second week, and his left eye vision partially improved.ConclusionMacular oedema may occur in patients with cytomegalovirus retinitis, but it rarely occurs during treatment. In this case, the patient's macular oedema appeared and resolved quickly. Macular oedema in patients with cytomegalovirus retinitis receiving vitreous cavity injections of ganciclovir needs to be further studied and discussed.

Cytomegalovirus Retinitis in a Child with Acute Lymphoblastic Leukemia

BACKGROUND: Due to the reduced immune response following chemotherapy, cytomegalovirus (CMV) retinitis is the most prevalent opportunistic intraocular infection in HIV-infected adults. It can also affect children with acute lymphoblastic leukemia (ALL). CASE PRESENTATION: We describe an 11.5-year-old female who is undergoing maintenance chemotherapy for B-lineage ALL. She had vision loss in her right eye and began to have hazy vision in her left eye. Bilateral active retinitis lesions were discovered during the retinal examination. The diagnosis of bilateral CMVR was made based on clinical symptoms, retinal examination findings, and a blood sample for CMV DNA detection using the polymerase chain reaction (PCR) technique. She was given ganciclovir intravenously and intravitreally, followed by oral valganciclovir prophylaxis. Patients who received a solid organ or hematopoietic stem cell transplant were infected with CMVR, although patients with ALL who received less immunosuppressive chemotherapy were also affected (maintenance phase therapy). Intravenous and intravitreal ganciclovir injections are effective treatments, the patient had significant clinical improvement. CMV retinitis is frequent in children with ALL who are in the maintenance phase of the treatment. CONCLUSION: The importance of early detection and treatment cannot be overstated. CMV retinitis: Key prognostic variables. CMV retinitis should be considered as cause of blurred vision in patients with ALL.

Treatment for Epstein-Barr Virus-associated uveitis confirmed by polymerase chain reaction: Efficacy of Anti-Viral Agents and a literature review.

There are still many research challenges and unanswered questions in relation to Epstein-Barr virus-associated uveitis. These include the presence of Epstein-Barr virus (EBV) DNA in asymptomatic patients, its pathogenicity in the uveitis eye, and the role of antiviral therapy for EBV-associated intraocular inflammation. This was a retrospective review of prospectively collected data from the Ophthalmology Department, Rajavithi Hospital between 2015 and 2020. A qualitative assay using multiplex real-time PCR was performed to detect pathogen genes from specimens obtained from a total of 344 patients. The main outcome measure was treatment success defined by clinical improvement and absence of viral DNA confirmed by PCR. Of the 35 cases, 24 with complete data were enrolled in the study, including 22 with post-treatment PCR results. Sixty-seven percent were HIV-infected, and other plausible causes or coinfection with other pathogens were found in 75% of patients. Cytomegalovirus (38%) was the most common co-infecting pathogen. The most commonly employed regimen was a combination of systemic acyclovir and intravitreal ganciclovir injection (58%). Of the 22 cases who had post-treatment PCR results, absence of detection of the virus by PCR in the intraocular fluid after treatment was demonstrated in 73% of patients. Patients with EBV infection can be simultaneously co-infected with other pathogens. Systemic acyclovir and ganciclovir achieved clinical improvement in most cases, and EBV infection was cured in the majority of patients.

Treatment of noninfectious uveitis.

Uveitis is a broad term that refers to a large group of eye disorders categorized by intraocular inflammation, a leading cause of visual impairment. Historically, treatment of noninfectious uveitis has depended on corticosteroid drugs. Owing to the myriad of side effects caused by corticosteroids, immunomodulatory therapy has become the preferred treatment for chronic noninfectious intraocular inflammation. Recently, biological response modifiers have established a new era in uveitis therapy, with the range of targets continuing to expand. In this review, we aimed to convey up-to-date information on the treatment of noninfectious uveitis to the general ophthalmologist.

Comparative Effects of Valganciclovir and Ganciclovir on the Congenital Cytomegalovirus Infection and Hearing Loss: A Randomized Controlled Trial

Background: Cytomegalovirus (CMV) is a highly specific herpes virus spreading only from person to person. Valganciclovir (VGCV) and ganciclovir (GCV) are effective in the treatment of neonatal congenital CMV infection. Objectives: This study aimed to compare the curative effects of VGCV and GCV among neonates with CMV infection and evaluate their effects on hearing. Methods: A total of 48 neonates with congenital CMV infection admitted to Huaian Maternal and Child Health Care Hospital, China, were selected from January 2016 to December 2019 and randomly divided into two equal groups of intervention and group (n = 24 each). While the control group received intravenous injection of GCV, the intervention group received oral VGCV. After a 6-week course of treatment, polymerase chain reaction (PCR) was applied to detect the CMV load in both urine and blood. We used the ELISA method to detect the serum CMV-IgM expression level before and after treatment. Moreover, we compared the positive rates of CMV-DNA and CMV-IgM, hyperbilirubinemia, retinitis, hepatosplenomegaly, thrombocytopenia, neutropenia, as well as the results of hearing screening and brainstem auditory evoked potentials (BAEP). Results: Before treatment, there was no statistical difference in blood/urine CMV-DNA expression level and positive expression rates of blood/urine CMV-DNA and CMV-IgM between the groups (P > 0.05). After treatment, blood/urine CMV-DNA expression and the positive expression rates of blood/urine CMV-DNA and CMV-IgM significantly decreased in both groups compared to before treatment (P < 0.05), but there was no statistical significance between the two groups (P > 0.05). Before treatment, there was no significant difference in hearing abnormality rates between the control (50%) and intervention (62.5%) groups (P > 0.05). After treatment, both the control (20.83%) and intervention (29.17%) groups had significantly decreased hearing abnormality rates, and the difference was statistically significant compared with before treatment (P < 0.05), but the difference between the two groups was not statistically significant (P > 0.05). After treatment, the results of comparing BAEP showed that both groups had no statistically significant differences in the number of neonates with normal hearing, mild hearing loss, moderate to severe hearing loss, severe hearing loss, and extremely severe hearing loss (P > 0.05). Before treatment, both groups had no statistically significant differences in the number of neonates with hyperbilirubinemia, retinitis, hepatosplenomegaly, thrombocytopenia, and neutropenia (P > 0.05). After treatment, while the number of neonates with hyperbilirubinemia, retinitis, hepatosplenomegaly, and thrombocytopenia decreased, neutropenia cases increased, and the difference before and after treatment was statistically significant (P < 0.05); however, the difference between the two groups was not statistically significant (P > 0.05). Conclusions: VGCV is similar to GCV in the treatment of neonatal congenital CMV infection, but the oral route of administration of VGCV is more acceptable among neonates.

Continuous High-Dose (6 mg) vs. Low-Dose (3 mg) Intravitreal Ganciclovir for Cytomegalovirus Retinitis After Haploidentical Hematopoietic Stem Cell Transplantation: A Randomized Controlled Study.

Purpose: To evaluate the safety and efficacy of continuous high-dose (6 mg) intravitreal ganciclovir injections (IVG) for cytomegalovirus (CMV) retinitis (CMVR) after haploidentical hematopoietic stem cell transplantation (Haplo-HSCT), and to explore factors that may influence the treatment procedure.Design: Prospective, randomized, single-blinded, positive-controlled, interventional, comparative study.Methods: A total of 22 patients with CMVR (32 eyes) were randomized to either high-dose group (IVG 6 mg weekly) or low-dose group (IVG 3 mg given twice weekly for 2 weeks as induction phase and weekly thereafter as maintenance phase). Patients who were recorded any positive CMV DNAemia or other active CMV diseases and needed systemic anti-CMV treatment during the study period were excluded. The vision outcome, variables of the treatment procedure, and incidence of complication and CMVR recurrence were analyzed and compared. Logistic regression was applied to determine the factors that may have an impact on the treatment process at baseline.Results: Compared to the low-dose group, the high-dose group resulted in a median of two less intravitreal injections (4 vs. 6 times, respectively, P = 0.016), while the rate of vision stability or improvement (81.2 vs. 87.5%), the incidence of complication (6.2 vs. 18.8%), and CMVR recurrence (12.5% vs. 6.2%) were similar (all P > 0.05). No drug-related toxicity was observed. Initial aqueous CMV-DNA load (OR: 6.872, 95% CI: 1.335–35.377, P = 0.021) and extension of lesion (OR: 0.942, 95% CI: 0.897 to .991, P = 0.020), but not dosing regimen (P = 0.162), were predictors of the treatment duration.Conclusions: Continuous high-dose regimen was well tolerated and resulted in less intravitreal injections, with similar vision outcomes and safety profiles. The clinical course of CMVR after Haplo-HSCT was determined by its own nature at baseline and could not be modified by treatment protocols under consistent immune background.

924. Cytomegalovirus (CMV) Retinitis during Maintenance Chemotherapy for Acute Lymphoblastic Leukemia

Abstract Background Acute leukemia patients are at risk for cytomegalovirus (CMV) retinitis following hematopoietic stem cell transplantation, though the disease can also occur in non-transplant adult leukemia patients. Emerging data suggest a shift to pediatric-inspired chemotherapy regimens in adults with acute lymphoblastic leukemia (ALL) can lead to increasing cytopenias and impaired functional immunity, placing these patients at risk for this opportunistic infection. Here we describe a case of CMV retinitis in an ALL patient following a lower-intensity regimen during maintenance chemotherapy. Methods Chart review. Results A 55-year-old male with ALL presented to his optometrist with complaints of visual changes including “fogginess” and “floaters”. The patient had completed 8 cycles of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) and achieved complete remission. He had been on maintenance chemotherapy with 6-mercaptopurine, vincristine, methotrexate, and prednisone (POMP) for 2 months at the time of symptom onset. He was referred to his local ophthalmologist who had concerns for bilateral, zone 1 CMV retinitis based on fundoscopic exam (Figure 1). Vitreous aspiration was performed and CMV DNA PCR returned positive at 1.6 million IUs/ml. Peripheral blood CMV DNA PCR was also positive at 1133 IU/ml. He was started on combination therapy with intravitreal ganciclovir injections and oral valganciclovir 900 mg twice daily (Figure 2). The patient received 14 intravitreal injections with resultant stability of his eye exam, though he remained on induction valganciclovir for 5 months due to persistent blood CMV DNAemia. Letermovir was added to help suppress his peripheral CMV DNAemia and he attained partial vision recovery. Figure 1. Fundoscopic images Conclusion CMV retinitis is an uncommon and highly morbid infection that can occur during maintenance chemotherapy in adult non-transplant ALL patients. Early identification of the disease is imperative as delay can result in blindness or further systemic CMV disease. Treatment is challenging, involving systemic and intravitreal antiviral therapy, serial ophthalmologic exams, serum CMV monitoring, and close coordination with the treating hematologist. Disclosures Michael Boeckh, MD PhD, AlloVir (Consultant)Ansun Biopharma (Grant/Research Support)Astellas (Grant/Research Support)EvrysBio (Consultant, Other Financial or Material Support, Options to acquire equity, but have not exercised them)Gilead Sciences (Consultant, Grant/Research Support)GlaxoSmithKline (Consultant)Helocyte (Consultant, Other Financial or Material Support, Options to acquire equity, but have not exercised them)Janssen (Grant/Research Support)Kyorin (Consultant)Merck (Consultant, Grant/Research Support)Moderna (Consultant)Symbio (Consultant)Takeda (formerly known as Shire) (Consultant, Grant/Research Support)VirBio (Consultant, Grant/Research Support) Ryan Cassaday, MD, Amgen (Grant/Research Support, Advisor or Review Panel member)Kite/Gilead (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support)Pfizer (Grant/Research Support, Advisor or Review Panel member)Seagen (Other Financial or Material Support, Spouse is employee and hold stock)Vanda Pharmaceuticals (Grant/Research Support)

Macular dual retinitis with Herpes simplex and Cytomegalovirus following periocular corticosteroid in a patient of Pemphigus Vulgaris.

Cytomegalovirus (CMV) retinitis may occur in non-HIV individuals following systemic immunosuppressive treatment or periocular corticosteroid administration. However, simultaneous multiple viral retinitis is rare in HIV-negative individuals. We report a case of dual viral retinitis in a non-HIV female on systemic immunosuppressive for pemphigus vulgaris who was administered a periocular corticosteroid injection. A 32-year-old female on double immunosuppressive therapy (prednisolone and cyclophosphamide) for pemphigus vulgaris, presented with gradual painless diminution of vision in the right eye for one month. She was initially diagnosed to have possible autoimmune neuroretinitis by the referring ophthalmologist and received a single injection of posterior subtenon triamcinolone acetonide for the same. Her vision however deteriorated further and she received an intravitreal ganciclovir injection with a revised diagnosis of CMV retinitis. Due to suboptimal response she was referred to us. Aqueous Polymerase chain reaction (PCR) revealed dual positivity for CMV and Herpes simplex virus. She was successfully managed with intravitreal ganciclovir injections, systemic acyclovir and tapering of systemic immunosuppressive drugs. The retinitis lesions resolved gradually leaving behind a pale optic disc and foveal atrophy at 12 weeks follow-up. Infective etiology must be ruled out in immunosuppressed patients before considering periocular corticosteroids. Dual viral involvement, although rare, may cause fulminant retinitis in predisposed individuals. High index of suspicion and PCR from ocular fluids should be performed at the earliest in patients with atypical or poorly responding retinitis lesions.

Acute Retinal Necrosis in an Immunocompetent Patient Treated With Intravitreal Ganciclovir

Acute retinal necrosis (ARN) is an inflammatory syndrome of high clinical concern; untreated or misdiagnosed cases may progress to optic neuropathy or retinal detachment, leading to irreversible blindness. ARN affects men and women equally and is often seen in immunocompromised patients but is also known to present in immunocompetent patients. It is usually due to systemic viral infection with secondary vitreoretinal inflammation. Most commonly, the first-line management of ARN is oral or intravenous antiviral therapy. Here, we report the case of an immunocompetent patient presenting with necrotizing retinopathy secondary to ARN. This patient was treated with oral valacyclovir and then intravenous acyclovir with no improvement. However, intravitreal injection of ganciclovir successfully halted the progression of ARN and led to the preservation of vision in the patient.

Does ganciclovir exert retinal toxicity after multiple continuous intravitreal injections?

BackgroundThe objective of this study is to report a case of acute retinal necrosis in which abnormalities in visual function did not correspond to retinal anatomical outcomes.Case presentationA 39-year-old female diagnosed with acute retinal necrosis underwent repeated (nine rounds) intravitreal ganciclovir injection (3 mg/0.1 ml) into the left eye, one injection every 2 weeks. During the therapy, the patient noticed her visual acuity declining gradually. The best corrected visual acuity in the left eye was 20/33. The visual field showed massive visual damage. There was no posterior necrotizing involvement, no macular edema or exudation, and only slight abnormity of the interdigitation zone in the fovea area was visible on OCT. Angio-OCT revealed normal capillary density of three retinal capillary and choriocapillaris layers. The visually evoked potential was normal. The photopic single-flash response showed a declined amplitude of a-wave and b-wave. The amplitudes of photopic 30 Hz flicker were decreased. Multifocal electroretinography revealed macular dysfunction.ConclusionGanciclovir-associated photoreceptor damage may induce abnormalities in retinal function in response to multiple continuous intravitreal ganciclovir injections at a relatively high dosage (3 mg/0.1 ml).

Clinical Characteristics Associated with the Development of Cystoid Macular Edema in Patients with Cytomegalovirus Retinitis.

We evaluated the incidence and characteristics of eyes with cytomegalovirus (CMV) retinitis according to the occurrence of cystoid macular edema (CME) and identified the risk factors of its occurrence. Patients diagnosed with CMV retinitis and examined using optical coherence tomography were classified according to the development of CME. The CME group was further divided according to the presence of active retinitis at the time of CME development. The demographics, serologic findings, ophthalmic presentations, ocular treatments, and visual prognosis were compared. CME was identified in 25 eyes (17 eyes with active retinitis and 8 eyes with inactive retinitis) out of the 67 eyes with CMV retinitis. Visual acuity was worse in the CME group than in the non-CME group. The CME group had longer CMV viremia duration, zone 1 involvement, and larger extent of CMV retinitis. While CME with concurrent active retinitis developed in eyes with direct foveal involvement of retinitis in the acute phase and required more ganciclovir injections after CME development, CME without active retinitis developed in eyes with larger extents of involvement and more intravitreal ganciclovir injections before CME development. Zone 1 involvement and longer CMV viremia duration were independently associated with the occurrence of CME. CME, which caused visual deterioration, developed in considerable patients with CMV retinitis and had different characteristics according to the presence of active retinitis.

Flow cytometric analysis of T lymphocytes and cytokines in aqueous humor of patients with varicella zoster virus-mediated acute retinal necrosis

BackgroundThe purpose of this study is to investigate the aqueous humor (AH) T lymphocyte subsets and cytokines of acute retinal necrosis (ARN) to elucidate the immunologic inflammatory features of this disorder.MethodsThree patients with ARN infected with varicella zoster virus (VZV) who underwent multiple intravitreal injections of ganciclovir were enrolled in this study. The control group consisted of four non-infectious patients with acute anterior uveitis (AAU). Flow cytometric analysis was performed on the lymphocyte subsets from the AH and peripheral blood (PB) samples during the active phase of intraocular inflammation. Five inflammatory cytokines were measured in each AH sample and various clinical characteristics were also assessed.ResultsVZV deoxyribonucleic acid (DNA) was detected by real-time polymerase chain reaction (PCR) in AH from all the ARN patients, who showed higher CD8+ T lymphocytes population in AH than the AAU patients (p = 0.006). CD4/CD8 ratios of T lymphocytes and the percentage of CD8 + CD25+ T lymphocytes in AH were significantly lower in ARN than in AAU (p = 0.006; p = 0.012). In the ARN patients, the percentages of CD4+ and CD8+ T lymphocytes in AH were higher than those found in PB. The percentage of CD4 + CD25+ T lymphocytes in AH was significantly higher than the proportion in PB in the AAU patients (p = 0.001). Immunoregulatory cytokine Interleukin-10 in AH was significantly elevated in the ARN patients in comparison with the case of the AAU patients (p = 0.036). In ARN, the copy number of VZV DNA in AH positively correlated with the percentage of CD8+ T lymphocytes in AH and negatively correlated with the CD4/CD8 ratio in AH during the course of disease treatment (p = 0.009, r = 0.92; p = 0.039, r = − 0.834).ConclusionThe ARN patients caused by VZV had different intraocular T lymphocyte subsets and cytokines profile than those of the non-infectious patients. High percentages of CD8+ T lymphocytes and low CD4/CD8 T cell ratios may be a potential biomarker for diagnosis of viral-infectious uveitis. T lymphocytes examination at the inflammatory sites has the potential to become a useful research tool for differentiating viral and non-viral uveitis.

Treatment of cytomegalovirus anterior segment infection with intravitreal injection of ganciclovir in adjunction with or without oral valganciclovir: a long-term results

We evaluated the therapeutic outcome of intravitreal injection (IVI) of ganciclovir with/without oral valganciclovir for cytomegalovirus (CMV) anterior segment infection. We enrolled 61 patients (61 eyes) with PCR-proven CMV anterior segment infection. IVI of ganciclovir (2 mg/0.05 mL) was given as a loading dose; subsequent use of oral valganciclovir (900 mg twice daily) was determined according to the severity of anterior chamber inflammation after injection. All eyes had IVI of ganciclovir, and 53 patients received oral valganciclovir as adjunctive therapy with a mean duration of 1.9 months to achieve disease remission. Repeated diagnostic aqueous taps were performed in 37 eyes with suspected recurrence, and CMV DNA was positive in 24 eyes. This therapeutic strategy afforded a median 50% recurrence-free survival time of 47.0 ± 8.12 months. The patients’ mean best corrected visual acuity, intraocular pressure and corneal endothelial cell counts stabilized or improved. Corneal transplantation before CMV infection diagnosis was identified as an independent risk factor for recurrence (hazard ratio 6.81, 95% confidence interval 1.21–38.23, P = 0.029). In patients with CMV anterior segment infection, the relative short-term therapeutic strategy, IVI of ganciclovir in adjunction with/without oral valganciclovir, effectively achieved a median recurrence-free survival time of nearly 4 years.

Iron Oxide Nanoparticles Promote Cx43-Overexpression of Mesenchymal Stem Cells for Efficient Suicide Gene Therapy during Glioma Treatment.

Background: Mesenchymal stem cells (MSCs) have been applied as a promising vehicle for tumour-targeted delivery of suicide genes in the herpes simplex virus thymidine kinase (HSV-tk)/ganciclovir (GCV) suicide gene therapy against malignant gliomas. The efficiency of this strategy is largely dependent on the bystander effect, which relies on high suicide gene expression levels and efficient transportation of activated GCV towards glioma cells. However, up to now, the methods to enhance the bystander effect of this strategy in an efficient and safe way are still lacking and new approaches to improve this therapeutic strategy are required.Methods: In this study, MSCs were gene transfected using magnetosome-like ferrimagnetic iron oxide nanochains (MFIONs) to highly express HSV-tk. Both the suicide and bystander effects of HSV-tk expressed MSCs (MSCs-tk) were quantitatively evaluated. Connexin 43 (Cx43) expression by MSCs and glioma cells was measured under different treatments. Intercellular communication between MSCs and C6 glioma cells was examined using a dye transfer assay. Glioma tropism and the bio-distribution of MSCs-tk were observed. Anti-tumour activity was investigated in the orthotopic glioma of rats after intravenous administration of MSCs-tk followed by intraperitoneal injection of GCV.Results: Gene transfection using MFIONs achieved sufficient expression of HSV-tk and triggered Cx43 overexpression in MSCs. These Cx43 overexpressing MSCs promoted gap junction intercellular communication (GJIC) between MSCs and glioma cells, resulting in significantly inhibited growth of glioma through an improved bystander effect. Outstanding tumour targeting and significantly prolonged survival with decreased tumour size were observed after the treatment using MFION-transfected MSCs in glioma model rats.Conclusion: Our results show that iron oxide nanoparticles have the potential to improve the suicide gene expression levels of transfected MSCs, while promoting the GJIC formation between MSCs and tumour cells, which enhances the sensitivity of glioma cells to HSV-tk/GCV suicide gene therapy.