Challenges of managing HIV cytomegalovirus co-infection in the presence of pancytopenia

A 60-year-old male patient who presented with generalized weakness and low-grade fever was diagnosed to be human immunodeficiency virus (HIV) positive with a CD4 count of 17. Routine laboratory investigations revealed pancytopenia. Serum cytomegalovirus (CMV) DNA polymerase chain reaction (PCR) was positive and fundoscopy showed CMV retinitis in the right eye. The patient was started on tablet valganciclovir. After 2 weeks, the patient was brought back in an altered sensorium. He was found to have hyponatremia which was corrected. He was started on antiretroviral therapy and tablet valganciclovir was continued. The patient came back again after one and a half months with a urinary tract infection and fissure-in-ano. He was found to have severe neutropenia. Valganciclovir was stopped. He was started on injection granulocyte colony-stimulating factor. The patient clinically improved and his hematological parameters became normal. Patients having HIV and CMV co-infection with pre-existing pancytopenia have to be closely monitored as the medicines used for treatment can exacerbate the existing conditions.

Clinical characteristics in the misdiagnosis of cytomegalovirus retinitis: A retrospective analysis of eight patients

Purpose: To highlight characteristics in the misdiagnosis of cytomegalovirus retinitis (CMVR). Methods: Misdiagnosed cases related to CMVR were analyzed retrospectively at the Department of Ophthalmology, Beijing Youan Hospital, from July 2017 to October 2019. The medical records were reviewed by two independent senior ophthalmologists and the patients’ clinical characteristics were analyzed. Results: Eight patients (16 eyes) were identified with misdiagnoses related to CMVR. Six of the patients with CMVR were previously unaware of their human immunodeficiency virus (HIV) infection; one patient with CMVR concealed their history of HIV infection. The cases were initially misdiagnosed as diabetic retinopathy (1/7, 14.3%), branch retinal vein occlusion (1/7, 14.3%), ischemic optic neuropathy (1/7, 14.3%), Behçet’s disease (1/7, 14.3%), iridocyclitis (2/7, 28.6%), and progressive outer retinal necrosis (1/7, 14.3%). One patient with binocular renal retinopathy and chronic renal insufficiency was misdiagnosed with CMVR. Four eyes (4/16, 25%) presented with pan?retinal involvement. Fourteen eyes (14/16, 87.5%) had optic disc or macular area involvement. At the final diagnosis, one patient was blind, and two patients had low vision. Seven AIDS patients showed an extremely low level of CD4+ T lymphocytes (median of 5 cells/?l; range 1–9 cells/?l). Conclusion: CMVR may be misdiagnosed in the absence of known immune suppression. CMVR and HIV screening cannot be overlooked if a young male patient presents with yellowish?white retinal lesions. These misdiagnosed patients had severe retinitis associated with poor vision

Retinal toxicity study of different-dose intravitreal ganciclovir in albino rabbit / 中华眼底病杂志

Objective:To explore safe dosage of single intravitreal injection of ganciclovir (IVG) in healthy rabit eyes, and to explore retinal toxicity of different dosage of ganciclovir after continues intravitreal injection into the vitreous cavity of healthy albino rabbit eyes.Methods:Ten healthy New Zealand albino rabbits were divided into 5 groups with 2 rabbits in each group. Each group was injected with 1 mg/0.025 ml,2 mg/0.025 ml, 5 mg/0.025 ml, 10 mg/0.025 ml ganciclovir or 0.025 ml saline (control group). After 1 week of intervention, rabbits were examined by ultra-wide-angle fundus photography, optical coherence tomography (OCT) and full field electroretinogram (ERG). The maximum mixed response of rod and cone cells (Max-R) was measured under dark adaption conditions, cone response (Cone-R) and 30 Hz flicker response (30 Hz-R) were measured under light adaption conditions. Twenty-four healthy New Zealand albino rabbits were randomly divided into a low-dose experimental group, a low-dose control group, a high-dose experimental group, and a high-dose control group, with 6 rabbits in each group, with the right eye as the experimental eye. The rabbits in the high-dose experimental group were continuously injected with ganciclovir 2 mg/0.025 ml, once a week, for a total of 4 times. The rabbits in the low-dose experimental group were injected with 1 mg/0.025 ml ganciclovir, the induction period was 2 times/week, a total of 4 times; the maintenance period was 1 time/week, a total of 2 times. The rabbits in the high-dose control group and the low-dose control group were injected with 0.025 ml normal saline into the vitreous cavity respectively. Full-field ERG examination was performed 1 day before each injection and 1 week after the last injection. Max-R was measured under dark-adapted conditions, and Cone-R and 30 Hz-R were measured under light-adapted conditions. OCT was recorded before the first injection and one week after the last injection. One week after the last injection, the experimental rabbits in each group were sacrificed for hematoxylin-eosin staining, and the retinal structure was observed under a light microscope. The comparison of a-wave and b-wave amplitude of Max-R, Cone-R and 30 Hz-R amplitude at different time was performed by two independent sample nonparametric test.Results:There were no abnormal results of fundus photography, OCT and ERG after single intravitral injection of 1 mg or 2 mg ganciclovir. One week after single 5 mg IVG, fundus photography of rabbits showed vascular occlusion and preretinal hemorrhage and ERG showed slight decrease of amplitude of Max-R, Cone-R and 30 Hz-R. One week after single 10 mg IVG, retinal necrosis and exudative changes were also observed. OCT showed edema and unclear retinal structure in the necrotic area. ERG showed significant decrease of amplitude of Max-R, Cone-R and 30 Hz-R. After continuous IVG in high dose and low-dose experimental group, the amplitude of Max-R a wave ( Z=-0.160, 0.000) and b wave ( Z=-0.321, 0.000), Cone-R a wave ( Z=-0.641,-0.641) and b wave ( Z=-0.321, -0.160), and 30 Hz-R ( Z=-0.321,-0.160) showed no difference compared to control group. No histologic evidences of retinal microstructure abnormalities were found in both groups. OCT and fundus photography before and after the intervention did not show any difference, either. Conclusion:There was no retinal toxicity of continuous 1 mg or 2 mg IVG recorded in albino rabbits.

Clinical features of infant cytomegalovirus infection / 中华眼底病杂志

Objective:To observe the ocular clinical features of infantile cytomegalovirus (CMV) infection.Methods:A retrospective clinical study. From March 2019 to July 2021, 876 eyes of 438 children with CMV infection who visited Department of Ophthalmology of Henan Provincial Children's Hospital were included in the study. Among them, there were 254 males and 184 females; the age ranged from 3 days to 11 months; the gestational weeks were 28 to 42 weeks; the birth weight was 1 120 to 8 900 g. There were 384 and 54 full-term and premature infants, respectively. Fundus examination was performed in 385 cases (770 eyes) after medical consultation; 53 cases (106 eyes) of premature infants were routinely screened. CMV retinitis (CMVR) was divided into granular type and fulminant type. Patients with CMV-related diseases with moderate to severe symptoms were given intravenous drip and/or oral ganciclovir; patients with severe fundus vasculitis were combined with intravitreal injection of ganciclovir. The follow-up period was from 4 to 28 months, and the characteristics of eye lesions, systemic comorbid diseases and treatment outcomes were observed.Results:There were 516 eyes of 258 cases with normal fundus (58.9%, 258/438); 291 eyes of 180 cases with CMVR (41.1%, 180/438), of which binocular and monocular were 111 (61.7%, 111/180) and 69 (38.3%, 69/180) cases. Among the 291 eyes of CMVR, 281 eyes (96.6%, 281/291) of granular type; yellow-white point-like opacity and/or retinal hemorrhage; 10 eyes (3.4%, 10/291) of fulminant type; fundus Showed a typical "cheese ketchup-like" and vascular white sheath-like changes. Among the 180 children with CMVR, 72 patients (118 eyes) were given systemic intravenous drip and/or oral ganciclovir; 5 patients (10 eyes) were given intravitreal ganciclovir, all of which were fulminant CMVR. At the last follow-up, fundus lesions regressed significantly in 100 eyes of 61 cases; 18 eyes of 11 cases had old lesions or uneven retinal pigment; 108 cases were not treated.Conclusion:The most common fundus manifestation of CMV infection in infants is granular retinitis, and fulminant retinitis is more severe, and the lesions can be significantly regressed after timely antiviral treatment.

Changes of aqueous cytomegalovirus DNA in patients with cytomegalovirus retinitis after allogeneic bone marrow hematopoietic stem cell transplantation / 中华眼底病杂志

Objective:To observe aqueous cytomegalovirus (CMV) DNA load in patients with cytomegalovirus retinitis (CMVR) after allogeneic hematopoietic stem cell transplantation (Allo-HSCT), and to explore influencing factors for transient elevation of CMV-DNA load during the treatment.Methods:A retrospective study. From January 2016 to July 2020, 28 eyes of 19 patients with CMVR after Allo-HSCT diagnosed in the Department of Ophthalmology of Peking University People's Hospital were included in the study. Among them, there were 8 males with 12 eyes, 11 females with 16 eyes; the mean age was 28 years; 10 patients were unilateral and 9 patients were bilateral. During the course of treatment and follow-up, the blood CMV-DNA remained negative. All patients were treated with intravitreal injection of 60 mg/ml ganciclovir 0.05 ml (containing ganciclovir 3 mg), twice a week for two weeks in induction phase and weekly injection in maintenance phase. Aqueous humor sample was collected during injection of ganciclovir (IVG) and CMV-DNA load was determined by real-time quantitative polymerase chain reaction. Intravitreal treatment was terminated if aqueous CMV-DNA load turned negative after the fourth or later intravitreal injection. The patients were followed up every 2 weeks for at least 6 months. Serum CMV-DNA was negative in all patients during treatment and follow-up. All the eyes were divided into continuous decline group and non-continuous decline group depending on whether there was transient elevation of aqueous CMV-DNA load, and data between two groups were compared. Pearson linear regression analysis was used to analyze the correlation between aqueous CMV-DNA load and injection times or treatment duration.Results:At the end of treatment, the median number of IVG in the affected eye was 7 (4, 9). The results of correlation analysis showed that the aqueous humor CMV-DNA load of the affected eye was related to the number of treatments [ R2=0.385, P<0.000 1, B=-0.237 log 10 copies/(ml·time)], and the duration of treatment [ R2=0.394, P <0.000 1, B=-0.301 log 10 copies/(ml·week)] were negatively correlated. Among the 28 eyes, 13 eyes (46.4%, 13/28) in the continuous decline group and 15 eyes (53.6%, 15/28) in the non-sustained decline group. Baseline visual acuity ( t=-1.223), intraocular pressure ( t=1.538), aqueous humor CMV-DNA load ( t=-0.109), retinitis lesion area ( Z=-0.308) in the continuous decline group and the non-continuous decline group), the number of quadrants involved ( Z=-0.024) and whether the macula was involved ( Z=-1.826), combined with anterior segment inflammation ( Z =-0.499), combined with high intraocular pressure ( Z=-1.342), terminal visual acuity ( t =-0.845), intraocular pressure ( t=-0.068), total IVG times ( Z=0.907), age ( Z=-0.832), gender composition ( Z=-1.074), etc. The difference was not statistically significant ( P>0.05). Conclusion:The CMV-DNA load in aqueous humor decreases by about 50% every week during the treatment of CMVR eyes after Allo-HSCT; the transient increase in the CMV-DNA load in the aqueous humor during treatment does not affect the treatment process and clinical prognosis.

Clinical features of cytomegalovirus retinitis-associated uveitis in patients undergoing hematopoietic stem cell transplantation / 中华眼底病杂志

Objective:To observe the clinical features of cytomegalovirus (CMV) retinitis (CMVR)- related uveitis after hematopoietic stem cell transplantation (HSCT).Methods:A retrospective clinical study. From October 2015 to May 2020, 14 cases of 21 eyes of CMVR patients with CMVR after HSCT confirmed by the ophthalmological examination of The First Affiliated Hospital of Soochow University were included in the study. Among them, there were 5 males with 8 eyes and 9 females with 13 eyes. The average age was 35.12± 12.24 years old. All the affected eyes were examined by slit lamp microscope combined with front lens and fundus color photography. At the same time, fluorescein fundus angiography (FFA) was performed to examine 10 eyes of 5 cases; 3 cases of 3 eyes were examined for inflammatory cytokines in aqueous humor. All eyes received intravitreal injection of ganciclovir; patients with a history of systemic CMV infection received intravenous infusion of ganciclovir/foscarnet. The retinal lesions in the eye were completely resolved or the aqueous CMV-DNA was negative as a cure for CMVR. The uveitis symptoms, signs, FFA manifestations and the test results of inflammatory factors in aqueous humor before and after the CMVR cure was observed. The follow-up time after CMVR was cured was 3-42 months, and the average follow-up time was 14.28±13.12 months.Results:All eyes with CMVR were diagnosed with retrocorneal dust and/or stellate keratic precipitates (KP), anterior chamber flare and cells, and varying degrees of vitreous flocculent opacity; the retina was typical of a mixture of hemorrhage and yellow-white necrosis like "scrambled eggs with tomatoes". After CMVR was cured, there were 16 eyes (71.4%, 10/14) in 10 cases with KP, anterior chamber flare, cell and vitreous opacity. FFA examination revealed that the majority of retinal leakage during the active period of CMVR was necrotic foci and surrounding tissues; after CMVR was cured, the majority of retinal leakage was the retina and blood vessels in the non-necrotic area. The test results of inflammatory factors in aqueous humor showed that interleukin (IL)-6, IL-8, and vascular endothelial cell adhesion molecules were significantly increased in the active phase of CMVR; after 3 months of CMVR cured, inflammatory factors did not increase significantly.Conclusion:CMVR-associated uveitis after HSCT show as chronic panuveitis, with no obvious eye congestion, KP, anterior chamber flare, cell and vitreous opacity, and retinal vessel leakage which could exist for a long time (>3 months).

Clinical manifestations of the initial-stage cytomegalovirus retinitis in acquired immunodeficiency syndrome patients / 中华眼底病杂志

Objective:To investigate the clinical manifestations of acquired immunodeficiency syndrome(AIDS) patients with initial-stage cytomegalovirus (CMV) retinitis (CMVR).Methods:Retrospective case series study. From July 2017 to November 2019, 21 patients with 22 eyes of AIDS combined with CMVR in the initial stage of AIDS and CMVR diagnosed in the eye examination in the study. Among them, there were 19 males with 19 eyes and 2 females with 3 eyes; the average age was 34.3±9.6 years. The average CD4 + T lymphocyte count of patients was 26.1±23.2/μl. Routine fundus screening revealed 17 cases, and the contralateral eye disease was found in 4 cases. There were 13 cases of CMVR in both eyes (61.9%, 13/21). Among them, both eyes were in the initial stage of CMVR, and the contralateral eyes were in the early stage of CMVR in 12 cases. The contralateral eye included 2 cases of human immunodeficiency virus-related retinal microangiopathy, 1 case of optic disc edema, and 5 cases of no obvious abnormality on fundus examination. All patients underwent slit lamp microscopy and ultra-wide-angle fundus photography examination. At the same time, 18 eyes underwent optical coherence tomography (OCT). Blood CMV-DNA detection was performed in 17 cases within 1 week before the first diagnosis; aqueous CMV-DNA detection was performed in 7 eyes within 1 week after the first diagnosis. Within 1 week after the fundus examination, 8 eyes of 8 cases and 8 eyes of 7 cases were received and not received systemic anti-CMV treatment; the treatment status was unknown in 6 cases and 6 eyes. After treatment, 18 eyes of 17 cases were followed up. The follow-up time was 0.5-28 months. Results:There were no obvious abnormalities in the anterior segment examination of all the affected eyes; the vitreous body was transparent. The fundus lesions were less than 1 optic disc diameter (DD), and they were white granular, clustered, with blurred edges. Among them, there were granular satellite lesions around the lesion in 18 eyes (81.8%, 18/22). The lesions were located in 19 eyes (86.4%, 19/22) in zone 2, 1 eye in zone 1 and 2 (4.5%, 1/22), and 2 eyes in zone 3 (9.1%, 2/22). In 18 eyes that underwent OCT examination, 12 eyes failed to obtain image data because the lesion was not in the conventional scanning range; the other 6 eyes showed the inner or full retina thickened or atrophy depression, structural destruction, accompanied by local vitreous punctate strong reflection. Among the 17 patients who underwent blood CMV-DNA testing, 1 (5.9%, 1/17) and 16 (94.1%, 16/17) cases were CMV-DNA negative and positive, respectively. The 7 eyes that underwent the CMV-DNA test of aqueous humor were all negative. Among the 18 eyes who were followed up, the lesions did not expand, and gradually subsided and absorbed in 4 eyes (22.2%, 4/18); the varying degrees of lesion enlargement in 14 eyes (77.8%, 14/18).Conclusion:The patients with AIDS and CMVR at the initial stage have no obvious ocular symptoms; the fundus shows white granular lesions less than 1 DD with blurred edges.

Diagnostic analysis of Optos panoramic laser scanning ophthalmoscope and aqueous humor detection in patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis / 中华眼底病杂志

Objective:To observe and preliminarily explore the relationship between the area of active fundus lesions and aqueous cytomegalovirus (CMV)-DNA in patients with acquired immunodeficiency syndrome (AIDS) with cytomegalovirus retinitis (CMVR).Methods:A retrospective study. From November 2019 to December 2020, the study population consisted of 22 AIDS patients (31 eyes) with active CMVR at the Beijing Ditan Hospital, Capital Medical University. All the patients were male. The age of the patients was 38.0±8.7 years. In total, 13 patients accepted highly active antiretroviral therapy (HAART). The median duration of treatment was 4 months. There were 9 cases that did not receive HAART. Ultra-wide-angle fundus imaging examination was performed using Optos P200T laser scanning ophthalmoscope. The software was used that comes with the device to measure the area of active lesions. Anterior chamber puncture was performed in all the affected eyes, 100 μl of aqueous humor was extracted, and the CMV-DNA load was quantitatively detected by polymerase chain reaction. At the same time, 19 cases of peripheral blood CD4 +T lymphocytes and CMV-DNA load were tested; 17 cases of the human immunodeficiency virus (HIV)-RNA load were tested. The area of active lesions was used as the independent variable, and the CMV-DNA load of aqueous humor was used as the dependent variable to construct a linear regression function. Results:All eyes were active CMVR, with lesions ranging from 1 to 264 optic disc diameters, with a median of 43 optic disc diameters. Among 31 eyes, 30 eyes (96.8%, 30/31) had a median aqueous CMV-DNA load of 1.3×10 4 copies/ml, and one eye was negative for CMV-DNA in aqueous humor. In 19 patients who underwent peripheral blood CD4 +T lymphocyte detection, the median CD4 +T lymphocytes were 18 cells/μl; 4 cases (21.1%, 4/19) were detected with CMV-DNA load. In the 17 patients who underwent HIV-RNA load testing, the median HIV-RNA load was 4.1×10 4 copies/ml. The results of correlation analysis showed that the amount of CMV-DNA in aqueous humor was significantly correlated with the size of active fundus lesions ( r=0.601, P<0.001), and was correlated with CD4 + T lymphocytes, CMV-DNA load in blood, and HIV-RNA load. There was no significant correlation between the amounts ( r=0.125, 0.202, -0.096; P>0.05). The regression equation was CMV-DNA load in aqueous humor = 3.38 + 0.01 × active lesion area. Conclusion:The amount of CMV-DNA in the aqueous humor is significantly correlated with the area of fundus active lesions, which can reflect the activity of fundus lesions.

The image characteristics of optical coherence tomography in patients of acquired immunodeficiency syndrome with cytomegalovirus retinitis / 中华眼底病杂志

Objective To observe the image characteristics of OCT in patients of acquired immunodeficiency syndrome (AIDS) with cytomegalovirus retinitis (CMVR).Methods Thirty-nine eyes of 26 patients of AIDS with CMVR diagnosed in Department of ophthalmology of Beijing Ditan Hospital Capital Medical University from January 2015 to December 2017 were included in this study.All the patients were males,with the mean age of 33.12± 9.87 years.All the patients underwent the OCT examination by Spectralis HRA+OCT.The locations of scanning were macular,optical papilla and posterior pole of retina with retinitis.Typical images were saved and analyzed.Results The OCT pathological changes of CMVR included increase of retinal thickness and reflex of retina,indiscernible retinal layers,irregularity or absent external limiting membrane and/or ellipsoid zone,hyperreflective spots,vitreous cells.Among 39 eyes,there were 6 eyes with strong point-like reflection in the outer layer of retina around the lesion,31 eyes (79.49％) with strong point-like reflection in the full layer of retina,25 eyes (64.10％) with lesion involved macular area,34 eyes (87.17％) with vitreous cells.Conclusions OCT images of the eyes with AIDS with CMVR were characterized by lesions involving the whole retina.Absent ellipsoid zone or structural changes can be seen in the affected areas and peripheral areas of the lesion.

Regime for cytomegalovirus retinitis based on aqueous virology and inflammatory cytokine determination / 中华眼底病杂志

Objective To observe the safety and efficacy of regime that based on aqueous cytomegalovirus-DNA (CMV-DNA) load and IL-8 determination for therapeutic monitoring and local treatment cessation of cytomegalovirus retinitis (CMVR) patients after allogeneic hematopoietic stem cell transplantation (HSCT).Methods A prospective case series study.A total of 14 CMVR patients (22 eyes) after allogeneic HSCT diagnosed in Ophthalmology Department of Peking University People's Hospital between January 2016 and December 2018 were involved in this study.All patients were CMV-DNA seronegative at baseline and were treated with intravitreous injection of ganciclovir (IVG,3 mg in 0.05 ml) twice per week for 4 times in the induction stage and once a week in the maintenance stage.Aqueous humor sample was collected during the first time of IVG every week.CMV-DNA and the level of IL-8 were measured by real time quantitative PCR and ELISA,respectively.During follow-up,negative CMV-DNA (＜ 103/ml) or level of IL-8 ＜ 30 pg/ml in aqueous sample was set as local treatment cessation.Then patients were followed every 2 weeks for at least 6 months.BCVA,intraocular pressure and fundus examination were taken for each visit.The BCVA examination was performed using the international standard visual acuity chart,which was converted into logMAR visual acuity.BCVA and intraocular pressure at the baseline and the last follow-up were compared by the Student t matching test.Results Of the 14 CMVR patients (22 eyes) after allogeneic HSCT,8 patients (16 eyes) were bilateral,6 patients (6 eyes) were unilateral.At the baseline,the mean logMAR BCVA was 0.814 ± 0.563,the intraocular pressure was 17.2 ± 7.8 mmHg (1 mmHg=0.133 kPa),the mean aqueous CMV-DNA load was (3.43 ± 4.96)× 105/ml,the mean level of IL-8 was 518 ± 541 pg/ml.At cessation of local treatment,the median number of intravitreal injections was 5 times.Nine eyes showed negative CMV-DNA in aqueous humor,of which,7 eyes showed negative IL-8 in aqueous.CMV-DNA could still be detected in 13 eyes,while IL-8 was negative.Only one eye's retinal lesion was completely quiet.Six months after local treatment cessation,the mean logMAR B CVA was 0.812 ± 0.691,the intraocular pressure was 14.8± 5.4 mmHg;which was not significantly different from baseline (t=-0.107,1.517;P=0.916,0.137).Recurrence of CMVR happened in only 1 eye because of systemic EB virus infection.Retinal lesions progressively improved and became completely quiet in all the remaining 20 eyes.In 22 eyes,iatrogenic vitreous hemorrhage occurred due to low platelet count during treatment (＜ 30 × 109/ml) in 4 eyes.When the treatment was terminated for 6 months,the fundus of hematoma absorption was clearly visible.At the time of CMVR diagnosis,there were 2 eyes (9％) with posterior subcapsular opacity,which may be caused by systemic glucocorticoid therapy after allogeneic HSCT.Conclusion Aqueous CMV-DNA load and level of IL-8 could be used as quantitative variables for monitoring the therapeutic effect and determining time for local treatment cessation for CMVR after HSCT safely and efficiently.

A Case of Cytomegalovirus Retinitis Following Intravitreal Dexamethasone Implant in an Immunocompetent Patient with Uveitis

PURPOSE: We report a case of cytomegalovirus (CMV) retinitis following placement of an intravitreal dexamethasone implant in an immunocompetent patient diagnosed with non-infectious uveitis. CASE SUMMARY: A 60-year-old woman was referred to our hospital for recurrent anterior uveitis. Fundus examination and fluorescein angiography showed dense vitritis, but no definite retinal infiltration. After laboratory examinations, the patient was diagnosed with non-infectious panuveitis. Uveitis was much improved after the patient started taking oral steroid medication. However, the patient complained of systemic side effects from the oral steroids. Medication was stopped, and an intravitreal dexamethasone implant was fitted to address worsening inflammation. Two months later, perivascular retinal infiltration developed and vitritis recurred. Viral retinitis was suspected, and the patient underwent diagnostic vitrectomy adjunctive with intravitreal ganciclovir injection. Polymerase chain reaction of vitreous fluid confirmed the diagnosis of CMV retinitis. The patient has remained inflammation-free for more than 20 months after vitrectomy, single ganciclovir injection, and 2 months of oral valganciclovir medication. CONCLUSIONS: This is a case report of CMV retinitis following placement of an intravitreal dexamethasone implant in an immunocompetent patient without any risk factors or previous history of immunosuppression. Potential risk factors for CMV retinitis should be evaluated and careful follow-up should be performed when intravitreal dexamethasone injections are unavoidable for the treatment of non-infectious uveitis.

Macular cytomegalovirus retinitis following dexamethasone intravitreal implant combined with phacoemulsification

A 60-year-old diabetic patient, who had undergone a renal transplant 2 years earlier, presented with sudden decrease in vision in his left eye (LE). He had undergone phacoemulsification combined with intravitreal dexamethasone implant injection in his LE 2 months earlier, for coexistent cataract and diabetic macular edema. Examination revealed necrotizing retinitis with hemorrhages in the macula. A diagnosis of cytomegalovirus retinitis was made, which was confirmed on vitreous polymerase chain reaction. Intravitreal and systemic ganciclovir led to the resolution of retinitis and improvement of visual acuity over a follow-up of 9 months.

Retinite por citomegalovírus em paciente com Síndrome de Good / Cytomegalovirus retinitis in Good Syndrome

Resumo A Síndrome de Good é uma síndrome paraneoplásica caracterizada pela associação de timoma e hipogamaglobulinemia, cursando com imunossupressão. Relatamos um caso raro de retinite por citomegalovírus em paciente com esta síndrome.

Abstract Good syndrome is a paraneoplastic syndrome characterized by the association of thymoma and hypogammaglobulinemia, with immunosuppression. We report a rare case of cytomegalovirus retinitis in a patient with this syndrome.

Clinical characteristics and treatment of cytomegalovirus retinitis in leukemia / 中华眼底病杂志

Objective To observe the clinical characteristics and treatment of cytomegalovirus retinitis (CMVR) in leukemia patients.Methods This is a retrospective analysis. Seven leukemia patients (13 eyes) with CMVR were studied. All patients underwent examinations of visual acuity, slit lamp microscope, ophthalmoscope, color fundus photography, peripheral blood CD4+T cell count and serum/aqueous CMV-DNA test. All patients were treated with ganciclovir or zoledronic acid combined with intravitreal injection of ganciclovir. The follow-up period was 3-14 months.Results Six patients were treated with hematopoietic stem cell transplantation and 1 patient was with chronic leukemia. All patients were CMV-DNA positive for serum, and 18.5％ (2/7) for aqueous humor. CMVR in leukemia patients showed mild anterior segment inflammation, ocular fundus with irregular yellowish-white retinal necrosis and radial hemorrhage (7 eyes). Some (2 eyes) also shoed gray and white granular retinal infiltrates. Intravenous ganciclovir/zoledronic acid combined with intravitreal injection of high concentration ganciclovir was an effective treatment, while systemic corticosteroids were effective in reducing vitreous opacity.Conclusions CMVR is characterized by progressive necrotic retinitis with hemorrhage and vasculitis. Intravenous ganciclovir/zoledronic acid combined with intravitreal injection of ganciclovir is effective in the treatment of CMVR with leukemia.

Ocular Inflammation Associated with Systemic Infection / 한양의대학술지

Systemic infections that are caused by various types of pathogenic organisms can be spread to the eyes as well as to other solid organs. Bacteria, parasites, and viruses can invade the eyes via the bloodstream. Despite advances in the diagnosis and treatment of systemic infections, many patients still suffer from endogenous ocular infections; this is particularly due to an increase in the number of immunosuppressed patients such as those with human immunodeficiency virus infection, those who have had organ transplantations, and those being administered systemic chemotherapeutic and immunomodulating agents, which may increase the chance of ocular involvement. In this review, we clinically evaluated posterior segment manifestations in the eye caused by hematogenous penetration of systemic infections. We focused on the conditions that ophthalmologists encounter most often and that require cooperation with other medical specialists. Posterior segment manifestations and clinical characteristics of cytomegalovirus retinitis, endogenous endophthalmitis, toxoplasmosis, toxocariasis, and ocular syphilis are included in this brief review.

Safety and Efficacy of Intravitreal Ganciclovir Injections More than 10 Times for Cytomegalovirus Retinitis

PURPOSE: To study the treatment outcomes in patients who were administered multiple intravitreal ganciclovir injections more than 10 times alone without systemic anti-cytomegalovirus therapy for cytomegalovirus retinitis. CASE SUMMARY: A 64-year-old man who underwent immunosuppressive therapy after thymectomy due to an invasive thymoma and pure red-cell aplasia, a 60-year-old woman who underwent chemotherapy after diagnosis of diffuse large B-cell lymphoma, a 49-year-old man with a history of bone marrow transplantation due to acute myeloid leukemia, a 29-year-old woman with dermatomyositis treated with oral steroids and cyclosporine, and a 47-year-old woman who received intravitreal dexamethasone implant injections, intravitreal and subtenon steroid injections due to Behcet's disease were diagnosed with cytomegalovirus retinitis. All patients showed systemic complications such as pancytopenia after systemic anti-cytomegalovirus therapy, and therefore, they were administered multiple intravitreal ganciclovir injections alone. Best-corrected visual acuities improved in all patients, except in one case, where viral lesions were observed in the fovea. Retinal hemorrhaging and infiltrative lesions decreased in all patients. No severe complication was observed during the injection and in the follow-up period. CONCLUSIONS: Multiple intravitreal ganciclovir injections alone can be used as a treatment modality for cytomegalovirus retinitis to avoid the systemic side effects of systemic anti-cytomegalovirus therapy.

When Dermatomyositis Patient Has Blurring of Vision – What Goes Wrong?

Cytomegalovirus (CMV) retinitis occurs predominantly in Human Immunodeficiency Virus (HIV) -infected patients. It was also reported in HIV-seronegative patients with systemic autoimmune disorder requiring systemic immunosuppression, organ or bone marrow transplantation, haematological or breast malignancy receiving chemotherapy, ocular diseases following intraocular or periocular corticosteroid injection, diabetes mellitus and Good syndrome. However, CMV retinitis in patients with concurrent dermatomyositis and malignancy has not been previously reported. It has not been reported in cancer other than haematological or breast malignancy, or in cancer patient prior to chemotherapy. We report a case of 40-year-old HIV-seronegative woman with underlying dermatomyositis and lung malignancy who developed right CMV retinitis which relapsed after recommencement of immunosuppressant. Both episodes of CMV retinitis were successfully treated after taken her immunocompromised state into consideration.

Experimental autoimmune uveitis and other animal models of uveitis: An update.

Over the past several decades, animal models of autoimmune uveitis directed at eye‑specific antigens (Ags) have been developed. These have allowed researchers to understand the basic mechanisms that lead to these diseases and also recently helped the researchers in translational research for therapeutic interventions. Experimental autoimmune uveitis (EAU) is an animal disease model of human endogenous uveitis and can be induced in susceptible animals by immunization with retinal Ags. Ever since the first description of EAU in mice in 1988, several animal models of uveitis has been described by researchers. Disease‑specific model for cytomegalovirus retinitis and tubercular uveitis has evolved our understanding of these complex entities. Endotoxin induced uveitis is another useful model for anterior uveitis, which is not an autoimmune process and is triggered by injection of bacterial endotoxin (lipopolysaccharides) resulting in a rapid short lasting uveitis. The current article will give an insight into the various EAU animal models and their current implications in translational research. The article will also highlight the different grading systems for EAU in the animal model.

Human leucocyte antigen profile in patients with aids and cytomegalovirus retinitis with and without macular involvement

Cytomegalovirus retinitis is one of the ocular manifestations of AIDS. The objective of the present study was to determine possible associations of class I and II HLA antigens and alleles in patients with AIDS and cytomegalovirus retinitis (CMV-R) with and without macular involvement. Method: The study population consisted of 22 patients with AIDS and CMV-R with macular involvement (Group I), 19 patients with AIDS and CMV-R without macular involvement (Group II), and 202 individuals with negative serology for human immunodeficiency virus (Group III - control). Class I HLA antigens were typed by classical serology. Class II alleles were identified using sequence-specific oligonucleotide primers hybridized with amplified DNA. Results: HLA-DRB1*14 and HLA-DRB1*10 specificities were more frequent among patients with macular involvement, possibly indicating greater susceptibility to this condition. In contrast, the HLA-B35 antigen may be associated with protection against macular involvement since it was significantly more frequent among patients without this involvement. Conclusions: The HLA-DRB1*14 and HLA-DRB1*10 alleles may favor the development of CMV-R with macular involvement, whereas the HLA-B35 subtype may be associated with protection against macular involvement...

Hypertensive iridocyclitis associated with delayed onset biopsy proven Cytomegalovirus retinitis.

We describe a case of primary hypertensive iridocyclitis with biopsy-proven Cytomegaloviral retinitis. It is an observational case report of a 69-year-old diabetic gentleman on azathioprine for Crohn’s disease who presented with recurrent episodes of hypertensive iridocyclitis. On the 4th a􀄴 endance in 5 months, a granular white lesion was noted in the temporal periphery of the mid-peripheral fundus and a chorioretinal and vitreous biopsy performed. Vitreous PCR was positive for Cytomegalovirus (CMV). Hematoxylin and eosin staining revealed cytomegaliclike inclusions within necrotic neural retina. Transmission electron microscopy revealed herpes family virus particles and immunohistochemistry demonstrated CMV protein. This case provides further evidence implicating CMV infection in the etiology of hypertensive iridocyclitis. With hindsight, the cumulative eff ect of diabetes and azathioprine on the immune surveillance system proved sufficient to render the patient susceptible to CMV retinitis.