Active Cytomegalovirus Retinitis Research Articles

Deep learning system for screening AIDS-related cytomegalovirus retinitis with ultra-wide-field fundus images

BackgroundOphthalmological screening for cytomegalovirus retinitis (CMVR) for HIV/AIDS patients is important to prevent lifelong blindness. Previous studies have shown good properties of automated CMVR screening using digital fundus images. However, the application of a deep learning (DL) system to CMVR with ultra-wide-field (UWF) fundus images has not been studied, and the feasibility and efficiency of this method are uncertain. MethodsIn this study, we developed, internally validated, externally validated, and prospectively validated a DL system to detect AIDS-related from UWF fundus images from different clinical datasets. We independently used the InceptionResnetV2 network to develop and internally validate a DL system for identifying active CMVR, inactive CMVR, and non-CMVR in 6960 UWF fundus images from 862 AIDS patients and validated the system in a prospective and an external validation data set using the area under the curve (AUC), accuracy, sensitivity, and specificity. A heat map identified the most important area (lesions) used by the DL system for differentiating CMVR. ResultsThe DL system showed AUCs of 0.945 (95 % confidence interval [CI]: 0.929, 0.962), 0.964 (95 % CI: 0.870, 0.999) and 0.968 (95 % CI: 0.860, 1.000) for detecting active CMVR from non-CMVR and 0.923 (95 % CI: 0.908, 0.938), 0.902 (0.857, 0.948) and 0.884 (0.851, 0.917) for detecting active CMVR from non-CMVR in the internal cross-validation, external validation, and prospective validation, respectively. Deep learning performed promisingly in screening CMVR. It also showed the ability to differentiate active CMVR from non-CMVR and inactive CMVR as well as to identify active CMVR and inactive CMVR from non-CMVR (all AUCs in the three independent data sets >0.900). The heat maps successfully highlighted lesion locations. ConclusionsOur UWF fundus image-based DL system showed reliable performance for screening AIDS-related CMVR showing its potential for screening CMVR in HIV/AIDS patients, especially in the absence of ophthalmic resources.

Relationship between opacity of cytomegalovirus retinitis lesion borders and aqueous viral load among patients after allogeneic hematopoietic stem cell transplantation

Objective: To evaluate the relationship between lesion features of cytomegalovirus (CMV) retinitis, including lesion size and degree of opacity of lesion borders, and aqueous CMV-DNA load in patients after allogeneic hematopoietic stem cell transplantation. Methods: It was a retrospective case series study. Data of patients diagnosed as CMV retinitis after allogeneic hematopoietic stem cell transplantation at the Department of Ophthalmology, Peking University Third Hospital from January 2018 to October 2020 were reviewed. Lesion size was detected by ultra-wide-field fundus image and measured by ImageJ, an image processing and analysis software. Opacity of lesion borders was evaluated by a masked reader. The CMV retinitis lesions were divided into 3 types according to the opacity degree of the border of the lesions: suspected active lesion mildly to moderately opacified lesion and severely opacified lesion. All eyes were diagnosed as active cytomegalovirus retinitis. CMV-DNA in aqueous humor was detected at the first visit and at the end of the induction period of antiviral drugs. CMV-DNA load was quantitatively detected by polymerase chain reaction after 100 μl of aqueous humor was extracted, and were converted to common logarithmic representations. Pearson correlation analysis was used to analyze the correlation between lesion area, opacity degree of lesion border and aqueous humor CMV-DNA load. Results: A total of 71 eyes from 46 patients were included and 26 was male and 20 was female. The age of the patients was 27(13, 33)years. The active lesion size of CMV retinitis was 40(12, 65) disc areas. Eight eyes (11.3%) had a suspected active lesion, 51 eyes (71.8%) had a mildly to moderately opacified lesion border, and 12 eyes (16.9%) had a severely opacified border. At the first visit, 67 eyes (94.4%) were CMV-positive, and the CMV-DNA load was 2.04×104 (6.24× 102, 1.48 ×105) copies/ml. After 2 weeks of induction therapy, the viral load was 2.47×102 (1.08× 10, 6.87 ×103) copies/ml. The correlation analysis showed that the CMV-DNA load in aqueous humor was significantly correlated with the lesion border opacity both at presentation and 2 weeks after intravitreal antiviral treatment (r=0.765, P<0.001; r=0.761, P<0.001), but was not related with the size of active fundus lesions (r=0.209, P=0.095; r=0.220, P=0.078). Conclusion: Degrees of lesion border opacity can reflect levels of aqueous viral load of CMV retinitis in patients after allogeneic hematopoietic stem cell transplantation and can become a useful measurement for investigation of CMV retinitis activity.

Cytomegalovirus retinitis in hospitalized people living with HIV in the late antiretroviral therapy era in São Paulo, Brazil.

There is scarce information on AIDS-related cytomegalovirus (CMV) retinitis in middle-income countries. The objectives of this study were to identify the prevalence of active CMV retinitis in severely immunosuppressed people living with HIV (PLWHIV) and to describe its main features. This retrospective cohort study was carried out at a tertiary center in São Paulo, Brazil. We included hospitalized adults PLWHIV with CD4 count ≤100 cells/μL, ≥ one quantitation of CMV DNA in plasma, and indirect ophthalmoscopy evaluation. Thirty-eight (21.6%) of 176 participants had at least an ophthalmoscopy diagnosis and only 3 (1.7%) individuals presented active CMV retinitis. All these participants were male, and retinitis was asymptomatic in 2 cases. Two participants had extraocular end-organ CMV disease and detectable CMV DNA in plasma. These results show a low prevalence of active CMV retinitis in the evaluated population. However, 2 of 3 participants had asymptomatic active CMV retinitis and a fifth of participants had at least one ophthalmoscopy diagnosis, suggesting the need for routine ophthalmologic evaluation in hospitalized severely immunosuppressed PLWHIV. The profile of participants with active CMV retinitis was similar to that described in the pre-ART era and quantitation of CMV DNA in plasma was variable.

Ocular Outcomes after Treatment of Cytomegalovirus Retinitis Using Adoptive Immunotherapy with Cytomegalovirus-Specific Cytotoxic T Lymphocytes

To describe ocular outcomes in eyes with cytomegalovirus (CMV) retinitis treated with adoptive immunotherapy using systemic administration of CMV-specific cytotoxic Tlymphocytes (CMV-specific CTLs). Retrospective cohort study. Patients with active CMV retinitis evaluated at a tertiary care academic center. Treatment of CMV retinitis with standard-of-care therapy (systemic or intravitreal antivirals) or CMV-specific CTLs (with or without concurrent standard-of-care therapies). The electronic medical record was reviewed to determine baseline characteristics, treatment course, and ocular outcomes, including best-corrected visual acuity (BCVA), treatments administered (CMV-specific CTLs, systemic antivirals, intravitreal antivirals), resolution of CMV retinitis, any occurrence of immune recovery uveitis, cystoid macular edema, retinal detachment, or a combination thereof. Seven patients (3 of whom had bilateral disease [n= 10 eyes]) were treated with CMV-specific CTLs, whereas 20 patients (6 of whom had bilateral disease [n= 26 eyes]) received standard-of-care treatment. Indications for CMV-specific CTL therapy included persistent or progressive CMV retinitis (71.4% of patients); CMV UL54 or UL97 antiviral resistance mutations (42.9%); side effects or toxicity from antiviral agents (57.1%); patient intolerance to longstanding, frequent antiviral therapy for persistent retinitis (28.6%); or a combination thereof. Two patients (28.6%; 4 eyes [40%]) received CMV-specific CTL therapy without concurrent systemic or intravitreal antiviral therapy for active CMV retinitis, whereas 5 patients (71.4%; 6 eyes [60%]) continued to receive concurrent antiviral therapies. Resolution of CMV retinitis was achieved in 9 eyes (90%) treated with CMV-specific CTLs, with BCVA stabilizing (4 eyes [40%]) or improving (4 eyes [40%]) in 80% of eyes over an average follow-up of 33.4 months. Rates of immune recovery uveitis, new-onset cystoid macular edema, and retinal detachment were 0%, 10% (1 eye), and 20% (2 eyes), respectively. These outcomes compared favorably with a nonrandomized cohort of eyes treated with standard-of-care therapy alone, despite potentially worse baseline characteristics. CMV-specific CTL therapy may represent a novel monotherapy or adjunctive therapy, or both, for CMV retinitis, especially in eyes that are resistant, refractory, or intolerant of standard-of-care antiviral therapies. More generally, adoptive cell transfer and adoptive immunotherapy may have a role in refractory CMV retinitis. Larger prospective, randomized trials are necessary.

Development and Validation of a Deep Learning –Based &amp;nbsp;System for Detection of AIDS- Related &amp;nbsp;Cytomegalovirus Retinitis in Ultra-Wide-Field Fundus Images

Background: Ophthalmological screening for cytomegalovirus retinitis (CMVR) for HIV/AIDS patients is important. The application of a deep learning (DL) system to AIDS-related CMVR with ultra-wide-field (UWF) fundus images is promising, but the feasibility and efficiency of this method have not been studied. Methods: We independently developed and internally validated a DL system for identifying active CMVR, inactive CMVR and non-CMVR in 6960 UWF fundus images from 862 AIDS patients and validated the system in a prospective and an external validation data set using area under curve (AUC), accuracy, sensitivity, and specificity. A heat map identified the most important area (lesions) used by the DL system for differentiating CMVR. This trial is registered with ClinicalTrials.gov, number NCT04831333. Findings The DL system showed AUCs of 0·945 (95% confidence interval [CI]: 0·929, 0·962), 0·964 (95% CI: 0·870, 0·999) and 0·968 (95% CI: 0·860, 1·000) for detecting active CMVR from non-CMVR and 0·923 (95% CI: 0·908, 0·938), 0·902 (0·857, 0·948) and 0·884 (0·851, 0·917) for detecting active CMVR from non-CMVR in the internal cross-validation, external validation, and prospective validation, respectively. It also showed the ability to differentiate active CMVR from non-CMVR and inactive CMVR as well as to identify active CMVR and inactive CMVR from non-CMVR (all AUCs in the three independent data sets >0·900). The heat maps successfully highlighted lesion locations. Interpretation: Our system showed reliable performance for detecting AIDS-rated CMVR. DL technology is promising for screening and differentiating CMVR in AIDS patients. Clinical Trial: This trial is registered with ClinicalTrials.gov, number NCT04831333. Funding: Scientific Research Project of Beijing Youan Hospital, CCMU, 2018 (YNKTQN20180201); Capital Health Research and Development of Special (2020-1-2052); Science & Technology Project of Beijing Municipal Science & Technology Commission (Z181100001818003); Beijing Municipal Administration of Hospitals’ Ascent Plan (DFL20150201). Declaration of Interest: The authors have no conflicts of interest to declare. Ethical Approval: This study was conducted in accordance with the Declaration of Helsinki. Both the Ethics Committee of Beijing YouAn Hospital (LL-2018-150-K) and the Ethics Committee of Beijing Tongren Hospital (TRECKY2018-056) approved the study. Written informed consent was obtained from each subject.

Spectral-domain optical coherence tomography finding in cytomegalovirus retinitis in AIDS patients.

To observe the findings of spectral domain optical coherence tomography (SD-OCT) scan in cytomegalovirus retinitis (CMVR). Forty-six eyes of 33 patients with acquired immunodeficiency syndrome and CMVR were enrolled in the study. Complete ophthalmologic examinations, color fundus photography, SD-OCT and fundus autofluorescence (FAF) were performed for all patients at the first visit and each follow-up visit. Retinal necrosis in CMVR was analyzed on SD-OCT and classified into two types, the typical type and the atypical type. Forty-one eyes of active CMVR and 4 eyes of recurrent CMVR were classified into typical type, and 4 eyes with graying retinal lesion without hemorrhage or only punctate hemorrhage were classified into atypical type. In active stage of CMVR, the retina in typical type was significant thickened with hyperreflective lesion and full-thickness disruption of retinal architecture with enlarged vessel; while in atypical type, the retina was also destroyed in all layers but without thickening or slightly thinned. The choroid, vitreous and retinal vessels were not significantly involved. In healed stage, the retina was thin with destroyed layers in both types. In typical type, FAF showed mottled hypofluorescence mixed with punctuate hyperfluorescence. In atypical type, the retina showed some "cavity" in outer nuclear layer, and FAF showed mild hyperfluorescence. SD-OCT show different changes in the retina in typical type and atypical type of CMVR, which should be useful in assisting diagnosis and follow-up management of the disease.

Immune recovery uveitis associated with active cytomegalovirus retinitis: A rare presentation

Immune recovery uveitis (IRU) is the ocular manifestation of immune reconstitution inflammatory syndrome in human immunodeficiency virus (HIV)-infected patients with cytomegalovirus (CMV) retinitis receiving highly active antiretroviral therapy (HAART). Here, we report the case of a 48-year-old HIV-infected patient, with poor adherence to HAART, who presented with gradual diminution of vision and pain in the left eye for 2 months. HAART was restarted along with anti-tubercular treatment for central nervous system tuberculosis 6 months ago. Clinical examination revealed the features of uveitis and active CMV retinitis. Laboratory investigations showed increased CD4+ T-lymphocyte count. We diagnosed the case as IRU associated with active CMV retinitis. The patient recovered with topical steroid and oral anti-CMV therapy. Although IRU is commonly seen in patients with inactive CMV retinitis, rarely this may be seen in association with active CMV retinitis, particularly when HAART therapy is initiated without treating CMV retinitis.

Ultra-Widefield Fundus Autofluorescence in Cytomegalovirus Retinitis

ABSTRACTPurpose: To study the role of ultra-wide field (UWF) fundus autofluorescence (FAF) in the management of CMV (cytomegalovirus) retinitis.Material and methods: In this prospective, observational, non-randomized study, we followed up patients with active CMV retinitis on UWF fundus photograph (FP) and UWF-FAF.Results: A total of 16 patients (24 eyes) were studied. There were 13 males and mean age of patients was 37 (range 9–56) years. On UWF FP, out of 24 eyes, 13 (54.2%) had granular lesions, 3 (12.5%) had necrotizing pattern, 1 (4.1%) had a frosted branch angiitis (FBA), and 7 (29.2%) had a mixed pattern. UWF-FAF showed better delineation of borders of lesions in 7 eyes (29.1%), larger area of involvement in 8 eyes (33.3%), picked up 7 of 9 (77.77%) eyes of recurrence and helped differentiate cotton wool spots from retinitis lesion in one eye.Conclusion: UWF-FAF is useful in the management of CMV retinitis.

Active cytomegalovirus retinitis after the start of antiretroviral therapy

Patients with AIDS-related cytomegalovirus (CMV) retinitis receiving combined antiretroviral therapy (cART), but not specific anti-CMV therapy, consistently showed active retinitis for several months. Delayed diagnosis and treatment of CMV retinitis...

OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN CYTOMEGALOVIRUS RETINITIS

To evaluate the vitreal, retinal, and choroidal features using spectral domain optical coherence tomography (SD-OCT) in eyes affected by cytomegalovirus (CMV) retinitis. Patients diagnosed with either active or inactive CMV retinitis were included in the study. Complete ophthalmic examination, serial color fundus photography, and SD-OCT (with and without enhanced depth imaging function) were performed for all the subjects at baseline and follow-up visits. The SD-OCT images were analyzed by two independent graders to evaluate the structural changes in areas of CMV retinitis. Prevalence data for vitreal, retinal, and choroidal SD-OCT features were collected. Twelve eyes from 9 patients (6 males, mean age: 52.7 ± 10.3 years) were enrolled. Nine eyes were diagnosed with active CMV retinitis at baseline. Active disease SD-OCT characteristic findings included nebulous vitritis (100%), posterior hyaloid thickening (83.3%), epiretinal membrane (100%), and retinal swelling (100%). Two distinct patterns of chorioretinal involvement were observed in active retinitis: 1) full-thickness retinitis (Full thickness retinitis) (n = 7 eyes) with choriocapillaris alterations and retinal pigment epithelial thickening and 2) cavernous retinitis (n = 3 eyes) characterized by inner retinal hyperreflectivity, large empty spaces in outer nuclear layer, and bridges of retinal tissue but retinal pigment epithelium and choriocapillaris sparing. Patients with cavernous retinitis develop retinal detachment during follow-up. Eyes with Full thickness retinitis developed choriocapillaris atrophy and choroidal thinning and retinal scars as the lesions healed. There are two distinct patterns of chorioretinal involvement in CMV retinitis. SD-OCT is a useful tool in the diagnosis, management, and prediction of the outcome of CMV retinitis.

Cytomegalovirus Retinitis Outcomes in HIV-Infected and Non–HIV Patients at a Tertiary Care Center

Purpose: To describe cytomegalovirus (CMV) retinitis outcomes in HIV-infected and non–HIV patients at a tertiary care center. Participants: Twenty-six eyes from 20 patients with active CMV retinitis were included in this study. Patients were immunocompromised due to HIV or secondary to immunosuppressive therapy for malignancy and organ transplantation. Methods: This is a retrospective, observational study of patients with newly diagnosed active CMV retinitis. The main outcomes included the incidence of visual acuity loss, the loss of visual acuity to 20/200 or worse, and the loss of 3 lines of vision or more. Secondary outcomes included the identification of risk factors for these visual results and the development of various complications such as retinal detachment (RD) and cataract formation. Results: In all, 51.9% (n = 14) of eyes lost vision from baseline at most recent follow-up and 34.6% (n = 9) lost 3 lines or more of vision, 34.6% (n = 9) of the eyes lost significant vision at most recent follow-up and had a final vision of 20/200 or worse, and 22.73% of phakic eyes underwent cataract surgery, whereas 23.1% (n = 6) of eyes developed RD. Patients presenting with a CD4+ T-cell count &lt;100 cells/µL were more likely to lose vision when compared to those presenting with a count &gt;100 cells/µL ( P = .0440). Although not statistically significant, patients who were immunocompromised due to HIV were less likely to lose 3 or more lines of vision ( P = .1881) and less likely to have a final visual acuity of 20/200 or worse ( P = .1881), when compared to patients who were immunocompromised due to other reasons. There was also a nonsignificant trend for eyes affected by a larger area of CMV retinitis at baseline (&gt;25%) to have a final visual acuity of 20/200 or worse when compared to eyes with CMV retinitis involving &lt;25% of the total retina ( P = .089). We did not detect trends or associations between any other risk factors tested and visual outcomes. We did not identify an association between HIV status and baseline area or zone affected by CMV retinitis. Conclusions: Our cohort demonstrated that CMV retinitis remains a vision-threatening problem among patients who are immunocompromised due to HIV or other conditions. Immunocompromised patients are still at a significant risk of vision loss and complications from CMV retinitis and should be managed by a multidisciplinary team of physicians. In the immediate future, improved therapies are necessary to achieve immune recovery in patients, particularly for those remaining chronically immunosuppressed.

Cytomegalovirus Identification and Quantification from the Saliva of Human Immunodeficiency Virus Seropositive and Seronegative Patients Using Real Time Polymerase Chain Reaction

Cytomegalovirus Identification and Quantification from the Saliva of Human Immunodeficiency Virus Seropositive and Seronegative Patients Using Real Time Polymerase Chain Reaction

Proposed clinical case definition for cytomegalovirus-immune recovery retinitis.

Cytomegalovirus (CMV) retinitis has been extensively described in patients with advanced or late human immunodeficiency virus (HIV) disease under ineffective treatment of opportunistic infection and antiretroviral therapy (ART) failure. However, there is limited information about patients who develop active cytomegalovirus retinitis as an immune reconstitution inflammatory syndrome (IRIS) after successful initiation of ART. Therefore, a case definition of cytomegalovirus-immune recovery retinitis (CMV-IRR) is proposed here. We reviewed medical records of 116 HIV-infected patients with CMV retinitis attending our institution during January 2003-June 2012. We retrospectively studied HIV-infected patients who had CMV retinitis on ART initiation or during the subsequent 6 months. Clinical and immunological characteristics of patients with active CMV retinitis were described. Of the 75 patients under successful ART included in the study, 20 had improvement of CMV retinitis. The remaining 55 patients experienced CMV-IRR; 35 of those developed CMV-IRR after ART initiation (unmasking CMV-IRR) and 20 experienced paradoxical clinical worsening of retinitis (paradoxical CMV-IRR). Nineteen patients with CMV-IRR had a CD4 count of ≥50 cells/µL. Six patients with CMV-IRR subsequently developed immune recovery uveitis. There is no case definition for CMV-IRR, although this condition is likely to occur after successful initiation of ART, even in patients with high CD4 T-cell counts. By consequence, we propose the case definitions for paradoxical and unmasking CMV-IRR. We recommend close follow-up of HIV-infected patients following ART initiation.

Bilateral intraocular calcification in necrotizing cytomegalovirus retinitis

We report a unique case of bilateral intraocular calcification due to necrotizing cytomegalovirus (CMV) retinitis associated with congenital CMV infection. A 7-month-old boy with a history of congenital CMV infection showed bilateral intraocular calcific plaques on computed tomography (CT) and ultrasonography. We reviewed the patient's medical files for the purpose of this report. The patient had a prior medical history of hospitalization for fever and swelling in the neck at 3 months of age. Systemic findings (anemia, neutropenia, hepatosplenomegaly, and reactive lymphadenomegaly) in association with a low CD4 count, high blood CMV viral load, and positivity for urine CMV DNA by polymerase chain reaction led to the diagnosis of bone marrow suppression and congenital CMV infection. At 7 months, he developed horizontal nystagmus and bilateral leukocoria over 20 days. Cranial CT and ultrasonography revealed bilateral intraocular calcific plaques and the patient was referred to rule out retinoblastoma. Fundoscopy was consistent with bilateral hemorrhagic, necrotizing CMV retinitis. Significant resolution of the retinal infiltrations occurred 2 weeks after initiation of systemic treatment with ganciclovir. Intraocular calcification may be a sign of active CMV retinitis. To our knowledge this is the first report of bilateral intraocular calcification serving as the presenting clinical manifestation of necrotizing CMV retinitis.

Immune recovery uveitis masked as an endogenous endophthalmitis in a patient with active CMV retinitis.

Cytomegalovirus (CMV) retinitis may occur in profoundly immunocompromised patients and be the initial AIDS-defining infection. The incidence and prevalence of CMV retinitis has declined substantially in the era of highly active antiretroviral therapy (HAART); nevertheless, it remains a leading cause of ocular morbility. We report the case of a 40-year-old man with blurred vision and pain in the right eye, three weeks after the initiation of effective HAART treatment. Ocular examination revealed a panuveitis causing an anterior chamber reaction with hypopyon and a dense vitreous haze. An endogenous endophthalmitis was suspected and treatment was ensued, without improvement. A vitreous tap was performed, and a positive polymerase chain reaction for CMV was found. A diagnosis of immune recovery uveitis (IRU) was made, and the patient responded to treatment with valganciclovir and dexamethasone. IRU is an intraocular inflammation that develops in patients with HAART-induced immune recovery and inactive CMV retinitis, although cases of active CMV retinitis have been described. Presentation with panuveitis and hypopion is rare and may be misleading regarding diagnosis and management.

Role of human cytomegalovirus genotype polymorphisms in AIDS patients with cytomegalovirus retinitis

Although several host factors have been identified to influence the course of HCMV infection, it still remains unclear why in AIDS patients without highly active antiretroviral therapy human cytomegalovirus (HCMV) retinitis is one of the most common opportunistic infections, whereas in other immunosuppressed individuals it has a low incidence. It was suggested that HCMV glycoprotein B strains may be suitable as marker for virulence and HCMV retinitis. Moreover, UL144 ORF, a member of the TNF-α receptor superfamily, may play a crucial role in innate defences and adaptive immune response of HCMV infection. Furthermore, sequence analyses of HCMV genes UL128, UL130, and UL131A as major determinants of virus entry and replication in epithelial and other cell types were performed. To evaluate the association of sequence variability of depicted viral genes with HCMV retinitis and in vitro growth properties in retinal pigment epithelial cells (RPE) and human foreskin fibroblasts (HFF), we compared 14 HCMV isolates obtained from vitreous fluid and urine of AIDS patients with clinically proven HCMV retinitis. Isolates were analyzed by PCR cycle sequencing and phylogenetic analysis. In addition, sequences of HCMV strains AF1, U8, U11, VR1814, and its cell culture adapted derivates were included. Sequence analysis of gB yielded three genetic subtypes (gB type 1 (5 isolates), gB type 2 (12 isolates), and gB type 3 (5 Isolates)), whereas sequence analysis of UL144 showed a greater diversity (7 isolates type 1A, 2 isolates type 1C, 7 isolates type 2, and 3 isolates type 3). In contrast, the UL128, UL130, and UL131A genes of all low-passage isolates were highly conserved and showed no preferential clustering. Moreover, in HFF and RPE cells, all of our HCMV isolates replicated efficiently independently of their genetic subtype. In conclusion, beside a possible link between the gB subtype 2 and HCMV retinitis, our study found no direct evidence for a connection between UL144/UL128/UL130/UL131A genotypes and the incidence of HCMV retinitis in AIDS patients.

Visual Field Loss in Patients with Cytomegalovirus Retinitis

To describe visual field (VF) loss among patients with cytomegalovirus (CMV) retinitis and the risk factors for such loss. Multicenter, prospective, observational study. A total of 476 patients with AIDS and CMV retinitis, and VF data. Follow-up every 3 months with medical history, ophthalmologic examination, Goldmann visual fields, and laboratory testing. Incidence of VF loss in eyes affected with CMV retinitis and characteristics associated with such VF loss. Over a median follow-up of 4 years (range, 0.5-9 years), the incidence rates of VF loss to 75% and 50% of normal were 0.22/eye-year (EY, 95% confidence interval [CI], 0.20-0.25) and 0.08/EY (95% CI, 0.06-0.10), respectively. The observed rates were 6- to 7-fold less than those observed rates of VF loss in the era before highly active antiretroviral therapy (HAART). Decreased CD4+ T-cell count, whether measured at enrollment or over follow-up time, was associated with increased rates of VF loss for all VF outcomes in a dose-dependent fashion. Risk factors for VF loss included lower CD4+ T-cell count, CMV lesion size >25% of the total retinal area, and active CMV retinitis after controlling for potential confounding. Highly active antiretroviral therapy use and immune recovery (CD4+ T-cell count >100 cells/μL) were associated with reduced risk of VF loss in multiple regression models. Immune recovery was statistically significantly associated with a lower risk of VF loss to 75% of normal (relative risk [RR] = 0.63; 95% CI, 0.49-0.86; P = 0.003) and to 50% of normal (RR = 0.60; 95% CI, 0.44-0.82; P = 0.001) after controlling for demographic characteristics, HIV viral load, HAART use, CMV lesion location and size, and retinitis activity. Cytomegalovirus retinitis was associated with a substantial risk of incident VF loss, but the incidence is approximately 6-fold lower than that observed in the pre-HAART era. Those who have HAART-induced immune recovery have approximately 40% lower risk of VF loss for both outcomes after controlling for confounding.

Clinical features and outcomes of AIDS-related cytomegalovirus retinitis in the era of highly active antiretroviral therapy

To describe the features and outcomes of patients with AIDS-related cytomegalovirus retinitis after highly active antiretroviral therapy availability. Retrospective chart review of 30 consecutive patients (44 eyes) with AIDS and newly diagnosed, active AIDS-related cytomegalovirus retinitis, examined from January 2005 to December 2007. The mean age was 34.8 years, 18 patients (60.0%) were male and median duration of AIDS was 90 months. Nineteen patients (63.3%) had evidence of highly active antiretroviral therapy failure and median CD4+ lymphocyte count was 12.5 cells/microl. Visual acuity at presentation was 20/40 or better in 27 eyes (61.4%). Retinitis involved Zone 1 in 13 eyes (39.5%). Despite specific anti-AIDS-related cytomegalovirus therapy, 16 eyes (36.4%) presented relapse of retinitis and 10 eyes (22.7%) lost at least three lines of vision. When compared to highly active antiretroviral therapy responsive patients, eyes of highly active antiretroviral therapy failure patients were more likely to develop relapse of retinitis (p=0.03) and loss of at least three lines of vision (p=0.03). The patients in this series are essentially young men with longstanding AIDS, non-responsive to highly active antiretroviral therapy and with a similar immunological profile as noted before highly active antiretroviral therapy era. These findings have implications for the management of the disease and confirm the magnitude of rational periodic screening after diagnosis of AIDS.

FUNDUS AUTOFLUORESCENCE CHANGES IN CYTOMEGALOVIRUS RETINITIS

The purpose of this study was to describe fundus autofluorescence imaging features of cytomegalovirus (CMV) retinitis and to correlate fundus autofluorescence features with clinical activity. A retrospective case series was undertaken to evaluate nine eyes of six patients with active CMV retinitis. Patients were evaluated with a comprehensive ophthalmic examination, fundus autofluorescence imaging, and fundus photography. Oral valganciclovir, intravitreal ganciclovir, intravitreal foscarnet, or an ganciclovir implant was administered as clinically indicated. In all nine eyes with active CMV retinitis, a hyperautofluorescent signal on fundus autofluorescence imaging was correlated spatially with the border of advancing CMV retinitis. Stippled areas of alternating hyperautofluorescence and hypoautofluorescence were observed in regions of retinal pigment epithelium atrophy from prior CMV retinitis. In three eyes with subtle CMV reactivation, a hyperautofluorescent border was helpful in the detection and localization of active CMV retinitis. In another patient, diffuse, punctate hyperautofluorescence after intravitreal ganciclovir and foscarnet was a concern for medication-related toxicity. Fundus autofluorescence imaging was valuable in highlighting areas of active CMV retinitis in all patients in this series, including two patients with subtle clinical features. Fundus autofluorescence may be useful as an adjunctive imaging modality for the detection of CMV activity and aid in our understanding of the structural changes during episodes of CMV retinitis.

Poor Predictive Value of Cytomegalovirus (CMV)-- Specific T Cell Assays for the Development of CMV Retinitis in Patients with AIDS

We examined the potential clinical utility of using a cytomegalovirus (CMV)-specific T cell immunoassay to determine the risk of developing new-onset CMV retinitis (CMVR) in patients with acquired immunodeficiency syndrome (AIDS). CMV-specific T cell assays were performed by multiparameter flow cytometry using stored peripheral blood mononuclear cells that had been obtained in an observational study 2-6 months before new-onset CMVR was diagnosed in case patients (at a study visit during which a dilated ophthalmologic examination revealed no evidence of CMVR) and at the same study visit in control subjects (matched by absolute CD4(+) T cell count at entry) who did not subsequently develop retinitis during 1-6 years of study follow-up. There were no significant differences in CMV-specific CD4(+) or CD8(+) T cell interferon-gamma or interleukin-2 expression in peripheral blood mononuclear cells from case patients and control subjects. Although there were trends toward lower percentages and absolute numbers of CMV-specific, cytokine-expressing CD8(+) T cells with a "late memory" phenotype (CD27(-)CD28(-)) as well as with an "early memory" phenotype (CD27(+)CD28(+)CD45RA(+)) in case patients than in control subjects, these differences were not statistically significant. Many studies have reported that CMV-specific CD4(+) and CD8(+) T cell responses distinguish patients with active CMVR (i.e., who lack CMV-protective immunity) from those with inactive CMVR after immune restoration by antiretroviral treatment (i.e., who have CMV-protective immunity). However, the multiple CMV-specific immune responses we measured do not appear to have clinical utility for predicting the risk for patients with AIDS of developing new-onset CMVR with sufficient accuracy to be used in guiding therapeutic management.