Inactive 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.

Development and Validation of a Deep Learning –Based  System for Detection of AIDS- Related  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.

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.

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.

The prevalence and incidence of epiretinal membranes in eyes with inactive extramacular CMV retinitis.

To determine the prevalence and incidence of epiretinal membranes (ERM) in eyes with inactive extramacular cytomegalovirus (CMV) retinitis in patients with acquired immune deficiency syndrome (AIDS). A case-control report from a longitudinal multicenter observational study by the Studies of the Ocular Complications of AIDS (SOCA) Research Group. A total of 357 eyes of 270 patients with inactive CMV retinitis and 1084 eyes of 552 patients with no ocular opportunistic infection (OOI) were studied. Stereoscopic views of the posterior pole from fundus photographs were assessed at baseline and year 5 visits for the presence of macular ERM. Generalized estimating equations (GEE) logistic regression was used to compare the prevalence and 5-year incidence of ERM in eyes with and without CMV retinitis at enrollment. Crude and adjusted logistic regression was performed adjusting for possible confounders. Main outcome measures included the prevalence, incidence, estimated prevalence, and incidence odds ratios. The prevalence of ERM at enrollment was 14.8% (53/357) in eyes with CMV retinitis versus 1.8% (19/1084) in eyes with no OOI. The incidence of ERM at 5 years was 18.6% (16/86) in eyes with CMV retinitis versus 2.4% (6/253) in eyes with no OOI. The crude odds ratio (OR) (95% confidence interval, CI) for prevalence was 9.8 (5.5-17.5) (P < 0.01). The crude OR (95% CI) for incidence was 9.4 (3.2-27.9) (P < 0.01). A history of extramacular CMV retinitis is associated with increased prevalence and incidence of ERM formation compared to what is seen in eyes without ocular opportunistic infections in AIDS patients.

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.

VITREORETINAL INTERFACE ABNORMALITIES IN HEALED CYTOMEGALOVIRUS RETINITIS

The purpose of this study was to use spectral domain-optical coherence tomography in imaging retina and vitreoretinal relationship in healed cytomegalovirus (CMV) retinitis. Patients with a history of confirmed CMV retinitis and a healed CMV scar on clinical examination underwent spectral domain-optical coherence tomography examinations using a Spectralis Heidelberg retinal angiograph/optical coherence tomography instrument (Heidelberg Engineering, Heidelberg, Germany). Horizontal and vertical cross-sectional B-scans 6 mm x 6 mm passing through the center and margins of healed CMV scars and adjacent retina were obtained. We analyzed the integrity of retinal layers in the area of the CMV scar, integrity of retinal layers at the margins of the CMV scar, margins of the scar and adjacent nonaffected retina, and any structural alterations in the retina or vitreous. Eleven eyes (50%) had vitreous detached, and 11 eyes attached over the area of healed retinitis. Nineteen eyes (86%) had an epiretinal membrane, and 12 eyes (54%) had vitreoretinal gliosis present over the healed retinitis or in its vicinity. The epiretinal membrane and vitreoretinal gliosis occurred concomitantly in 10 eyes and could be well differentiated on scans. None of these were found in control eyes. This first in vivo study of vitreoretinal interface in inactive CMV retinitis shows that the vitreoretinal interface in healed CMV is pathologically changed. The presence of epiretinal membranes, vitreoretinal gliosis, and traction may help explain the higher incidence of retinal elevation, retinal breaks, and retinal detachment in these eyes.

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.

Cytomegalovirus Retinitis and Immune Recovery Uveitis in AIDS Patients Treated with Highly Active Antiretroviral Therapy in Taiwanese

Purpose: To determine the characteristics of cytomegalovirus (CMV) retinitis and immune recovery uveitis (IRU) in the era of highly active antiretroviral therapy (HAART). Methods: We reviewed data from 47 of 79 consecutive patients with acquired immunodeficiency syndrome (AIDS) and CMV retinitis. Results: The incidence of CMV retinitis in AIDS patients has markedly decreased over the recent 10 years. The characteristics of CMV retinitis have changed. Development of IRU occurred in 24.4%. Conclusions: Symptomatic IRU develops in a significant number of patients with inactive CMV retinitis following successful HAART. Eyes with IRU respond favorably to antiinflammatory therapy without reactivation of retinitis.

Immune recovery uveitis in an HIV‐negative individual†

Immune recovery uveitis (IRU) is an intraocular inflammatory disorder originally described in individuals with human immunodeficiency virus (HIV) and inactive cytomegalovirus retinitis following highly active antiretroviral therapy. Although relatively common in individuals with acquired immune deficiency syndrome in the United States it is an extremely uncommon presentation in Australia. IRU also occurs in iatrogenically immunosuppressed individuals with a similar incidence to HIV-infected individuals. We report one case of IRU in an HIV-negative individual following a volunteer unrelated donor allogeneic stem cell transplant for non-Hodgkin's lymphoma. In the context of tapering the immunosuppression the patient developed bilateral IRU, consisting of panuveitis and macular oedema. The visual acuity (VA) at presentation of IRU was limited to counting fingers bilaterally. The IRU resolved with the re-intensification of the immunosuppression. VA restored to right 6/18 and left 6/12.

Immune recovery vitritis

Immune recovery vitritis (IRV) is symptomatic vitritis of > 1 + severity associated with inactive cytomegalovirus (CMV) retinitis. It is an opportunistic infection of the eye, in the patients who suffer from AIDS, and is treated with a highly active antiretroviral therapy (HAART). As a result of this therapy, there is an immune reconstitution in the body and inflammation of the vitreous body. The aim of the study was to show the incidence of IRV in patients treated with HAART. A retrospective study was conducted in patients who suffered from CMV retinitis. Twenty-one were treated with HAART and had the diagnosis of CMV retinitis, as well. All of them were examined by the same ophthalmologist who peformed slit lamp examination with mydriasis and indirect ophthalmoscopy. Nine of 21 patients developed IRV as a complication of HAART, two had cystoid macular oedema (CMO). CMV retinitis develops when the number of CD4+ T lymphocytes drops below 50/mm3. This results in necrotic retinitis which, if untreated, leads to complete loss of vision. With the introduction of HAART, we learned that the reconstitution of immune status was achieved as well as life expectancy, but there was a dramatic decline in the opportunistic infection, including CMV retinitis, as well. With the immune reconstitution, the inflammation develops in the eye, known as IRV. Sometimes, it is neccessary to treat this condition, but in the case of our patients, the inflammation was mild, and no treatment was neccessary.

The Safety of Discontinuation of Maintenance Therapy for Cytomegalovirus (CMV) Retinitis and Incidence of Immune Recovery Uveitis Following Potent Antiretroviral Therapy

Background: Reconstitution of immune function during potent antiretroviral therapy can prompt discontinuation of maintenance cytomegalovirus (CMV) therapy but has also been associated with sight-threatening inflammatory conditions including immune recovery uveitis (IRU). Method: Patients with inactive CMV retinitis and a CD4+ cell count above 100/mm3, receiving CMV therapy and stable combination antiretroviral therapy, were assigned to one of two groups based on willingness to discontinue CMV therapy. Results: Thirty-eight participants were enrolled: 28 discontinued anti-CMV therapy (Group 1) and 10 continued CMV treatment (Group 2). Median on-study follow-up was 16 months. One Group 1 participant who experienced an increase in plasma HIV viral load and a decline in CD4+ cell count developed confirmed progression of CMV retinitis. Progression or reactivation CMV retinitis was not observed among Group 2. IRU was present at study entry in 3 participants. Six participants in Group 1 and 3 participants in Group 2 developed IRU on-study. CMV viremia was not detected in any participants, and urinary shedding of CMV was intermittent. Conclusion: Recurrence of CMV retinitis following discontinuation of anti-CMV therapy among patients with antiretroviral-induced increases in CD4+ cell count was rare. However, IRU was common in both those who maintained and discontinued anti-CMV therapy.

Immune recovery uveitis in AIDS patients with cytomegalovirus retinitis treated with highly active antiretroviral therapy in Venezuela.

To determine the characteristics of immune recovery uveitis (IRU) in acquired immunodeficiency syndrome (AIDS) patients with inactive cytomegalovirus (CMV) retinitis who responded to highly active antiretroviral therapy (HAART) in a Venezuelan population. We examined 34 patients (50 eyes) with AIDS (HAART responders) and healed CMV retinitis. Patients were observed for a median of 19.3 months following an increase in the CD4 cell count. Ten eyes were treated with sub-Tenon space corticosteroid injections. An age-matched control group of patients with healed CMV retinitis who did not have IRU (30 eyes of 20 patients) was included to compare CMV surface area and complications. We found that 12 (37.5%) of 32 HAART responders developed IRU (18 eyes). The clinical findings of these 18 eyes with IRU are presented. The clinical spectrum of inflammation included vitritis, macular edema, epiretinal membranes, anterior uveitis, macular hole, retinal detachment with proliferative vitreoretinopathy, and cataract. Eyes with IRU had a mean CMV surface area of 31.7%. However, eyes without IRU (control group) had a mean CMV surface area of 35% (P = 0.41). Periocular treatment resulted in vision improvement (in 90% of eyes) without reactivation of retinitis. Symptomatic IRU developed in a significant number of patients with CMV retinitis following successful HAART in a Venezuelan population. CMV surface area does not seem to be a risk factor for the development of IRU. Eyes with IRU respond favorably to antiinflammatory therapy without reactivation of retinitis.

Detection of CMV DNA in the Aqueous Humor of AIDS Patients with CMV Retinitis by AMPLICOR CMV Test

The present study was performed to detect the cytomegalovirus (CMV) DNA in the aqueous humor from the eyes of acquired immunodeficiency syndrome (AIDS) patients with CMV retinitis. Detection of CMV DNA in the aqueous humor in the eyes with active CMV retinitis was compared with detection of CMV DNA in inactive retinitis. CMV DNA in the aqueous humor was evaluated before and after treatment with intravitreal injection of ganciclovir. CMV DNA in the aqueous humor was measured by AMPLICOR CMV test. Forty-two eyes of 35 AIDS patients were diagnosed ophthalmoscopically as having CMV retinitis that was subclassified as either active or inactive. The active and inactive CMV retinitis cases were distinguished based on clinical evaluations and fundus photographs. The results showed that 37 of the 42 eyes (88.1%) were positive for CMV DNA prior to treatment, while in 29 of these 37 eyes (78.4%), the aqueous humor became CMV DNA-negative after the treatment. Successful treatment with the intravitreal injection of ganciclovir was associated with a reduction in the detection of CMV DNA in the aqueous humor. CMV DNA was not detected in the aqueous humor of patients with quies cent CMV retinitis. In conclusion, the AMPLICOR CMV test was found to be a reliable tool for differentiating active and inactive CMV retinitis, and is useful for helping to select the optimal treatment regimen. The intravitreal injection of ganciclovir is highly effective in reducing detectable CMV DNA in the aqueous humor.

Uveitic Angle Closure Glaucoma in a Patient With Inactive Cytomegalovirus Retinitis and Immune Recovery Uveitis

We report a case of uveitic acute angle closure glaucoma in a patient with acquired immunodeficiency syndrome (AIDS) associated with inactive cytomegalovirus retinitis and immune recovery vitritis. We conducted a long-term, follow-up examination of a 47-year-old male with AIDS and inactive cytomegalovirus retinitis caused by immune recovery on highly active antiretroviral therapy (HAART). We found vitritis and ultimate development of uveitic glaucoma in the postoperative periods following repair of retinal detachment and extracapsular cataract extraction with intraocular lens implant. An episode of acute angle closure secondary to posterior synechiae and iris bombé subsequently developed, requiring peripheral laser iridotomy. Immune recovery in the setting of inactive cytomegalovirus retinitis can result in intraocular inflammation severe enough to cause angle closure glaucoma and profound ocular morbidity.

Ischemic maculopathy in patients with acquired immunodeficiency syndrome

PURPOSE: To describe the characteristics of ischemic maculopathy in patients with human immunodeficiency virus (HIV) infection, as a means of understanding this uncommon disorder more fully. METHODS: This is a multicenter, retrospective review of clinical data available for five HIV-infected patients who were given the diagnosis of ischemic maculopathy. RESULTS: All cases had been diagnosed on the basis of fluorescein angiograms obtained after patients complained of vision loss. Four of the five patients had bilateral macular disease. Visual acuity at presentation in the nine affected eyes ranged from 20/20 to count fingers. Vision loss was gradual in both eyes of one patient and was abrupt in onset in seven eyes. Each of the seven eyes with abrupt vision loss had opacification of the superficial retina and/or intraretinal hemorrhages near the fovea. Fluorescein angiography revealed enlargement of the foveal avascular zone and mild staining of the juxtafoveal vessels in affected eyes. Six eyes had active or clinically inactive cytomegalovirus retinitis at presentation, and a seventh eye developed cytomegalovirus retinitis 2 weeks later. All patients were receiving anticytomegalovirus drugs when they developed visual symptoms. Visual acuity remained stable in five eyes, became worse in two eyes, and improved in two eyes; final visual acuity ranged from 20/25 to count fingers. CONCLUSIONS: Ischemic maculopathy may cause profound and permanent vision loss in HIV-infected individuals. Fluorescein angiography should be considered in all HIV-infected patients with unexplained loss of vision. The pathogenesis of ischemic maculopathy remains unknown.

Cytomegalovirus infection: the point in 2001.

The incidence of cytomegalovirus (CMV) disease, one of the most prevalent opportunistic infections in HIV-infected persons in the early 1990s, has decreased by more than 80% since the introduction of highly active antiretroviral therapy (HAART). The rare cases of CMV disease still observed in Western countries occur mainly in profoundly immunosuppressed patients who have failed to respond to HAART. A new finding is the occasional occurrence of inflammatory retinitis in some patients on HAART with a history of healed retinitis. New tools for CMV detection have become available recently, including use of polymerase chain reaction (PCR) to detect CMV DNA from plasma. It has been possible to redefine, in the HAART period, patients at risk for CMV disease as those who have a low CD4 cell count as well as a blood marker of CMV blood dissemination (plasma CMV DNAaemia or high pp65 antigenaemia). Besides the classical therapeutic approach using ganciclovir (GCV), foscarnet and cidofovir, development of valganciclovir (VGCV), an orally administered prodrug of GCV, appears promising. There is evidence to suggest that it is as effective as intravenous GCV for the treatment of CMV retinitis, and it is currently being studied as a pre-emptive therapy in patients at high risk for CMV disease. Finally, patients with inactive CMV retinitis receiving HAART and with stable immune reconstitution may be able to discontinue maintenance therapy provided a regular ophthalmological and virological surveillance is maintained.

Immune recovery vitritis and uveitis in AIDS: clinical predictors, sequelae, and treatment outcomes.

To determine 1) clinical predictors of an inflammatory syndrome associated with cytomegalovirus (CMV) retinitis (immune recovery vitritis or uveitis [IRV or IRU]); 2) clinical sequelae of IRV; and 3) the effect of corticosteroid treatment on visual acuity. A cohort study from the AIDS Ocular Research Unit of the University of California, San Diego, and a case series from the Cleveland Clinic consisted of patients who had acquired immunodeficiency syndrome and inactive CMV retinitis who responded to highly active antiretroviral therapy (HAART) with CD4 T-lymphocyte levels >60 cells/mm3. The cohort was followed for a median of 13.5 months following increase in CD4 count. The authors studied the occurrence of IRV, defined as symptomatic (vision decrease and/or floaters) vitritis of 1+ or greater severity associated with inactive CMV retinitis. Macular edema or epiretinal membrane formation was determined by clinical examination and fluorescein angiography. Five eyes were treated with sub-Tenon corticosteroid injections. In the cohort study, 19 (63%) of 30 HAART responders developed IRV (26 eyes). The clinical spectrum of inflammation included vitritis, papillitis, macular edema, and epiretinal membranes. Eyes with CMV surface area >30% of the retina were at the highest risk (relative risk = 4.5) of developing IRV (P = 0.03). During follow-up, inflammation persisted without treatment for a median of 20 weeks and 14 patients (16 eyes) developed macular changes. Treatment resulted in vision improvement without reactivation of retinitis. Histology and immunohistochemistry of associated epiretinal membranes showed evidence of chronic inflammation with a predominant T-lymphocyte cell population. In the case series, 3 (38%) of 8 HAART responders developed IRV (4 eyes). All four eyes were treated and resulted in visual acuity improvement of one line. Symptomatic IRV or IRU develops in a significant number of patients with CMV retinitis following successful HAART. Eyes with CMV surface area >30% of the retina are at the greatest risk. Eyes with IRV respond favorably to antiinflammatory therapy without reactivation of retinitis. Immune recovery vitritis may be the result of an immunologic reaction to latent CMV antigens in the eye in which T-lymphocytes play a role.

Apoptosis in cytomegalovirus retinitis associated with AIDS

To determine the role of apoptosis in the pathogenesis of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. Forty-three eyes from patients with cytomegalovirus retinitis treated before the introduction of highly active anti-retroviral therapy were examined by routine histopathology and in situ techniques to detect apoptosis (TUNEL assay). Apoptosis was graded on a scale from 0 to 3+ by quantitating the number of TUNEL positive cells per case using a standard grading procedure. Statistical analysis describing the association between apoptosis grade and the proportions of eyes with active CMV infection, with choroidal inflammation and treated with the sustained-release intravitreal ganciclovir implant was performed using the Armitage procedure. Apoptosis in both CMV infected and uninfected retinal cells was detected in 28 of 41 eyes (68%); 13 (45%) with active and 15 (55%) with inactive cytomegalovirus retinitis. The degree of apoptosis was mild (1+) in 14 eyes, moderate (2+) in 6 eyes and severe (3+) in 8 eyes. Apoptosis was not identified in two eyes without CMVR. An increase in apoptosis grade was positively associated with active CMVR (p = 0.014). There was no significant association between apoptosis and choroidal inflammation. The presence and the severity of apoptosis was less in eyes treated with the sustained-release intravitreal ganciclovir implant compared to those treated with systemic anti-viral therapy, however, the difference was not statistically significant. Apoptosis contributes to retinal cell loss in eyes with cytomegalovirus retinitis associated with AIDS but did not correlate with the progressive loss of retinal cell function in patients with treated, inactive CMVR.

Stopping secondary prevention in AIDS patients with inactive CMV retinitis treated with HAART (highly active antiretroviral therapy)

Immune recovery of AIDS patients with cytomegalovirus (CMV) retinitis treated and healed by highly active antiretroviral therapy (HAART) is reflected by increased CD4 cell count and decreased virus load. Due to partial reconstitution of the immune status the risk of opportunistic infections decreases, as well as the risk of reactivating inactive CMV retinitis. It may therefore be possible to stop anti-CMV maintenance therapy may after HAART-induced immune recovery. We present six patients (nine eyes) with a follow-up of 9.5 months (range 7-12 months) after cessation of the CMV-specific maintenance therapy (five orally, one intravenously). There was no reactivation of retinal CMV infection during the follow-up period. The virus load (< 50 Eq/ml; a single value of one patient was 2047 Eq/ml) and CD4 cell counts (range 207-454/microliter; mean: 313/microliter) remained stable during the follow-up period, reflecting immune recovery. Our findings confirm the expected low risk of retinal CMV reactivation after immune recovery in AIDS patients receiving HAART without secondary prophylaxis with an anti-CMV maintenance therapy. Regular ophthalmic and medical follow-up is mandatory in these patients. Cessation of maintenance therapy represents a major improvement in quality of live in AIDS patients.