Spectral domain optical coherence tomography and fundus autofluorescence findings in cytomegalovirus retinitis in HIV-infected patients

Purpose

To assess the usefulness of spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) findings in cytomegalovirus (CMV) retinitis.

Study design

Observational case series.

Methods

Thirteen eyes of 11 human immunodeficiency virus (HIV)-positive patients with CMV retinitis underwent full ophthalmologic examinations, SD-OCT, and 4 eyes of 4 patients underwent FAF. FAF images included short-wavelength autofluorescence (SW-AF) and near-infrared autofluorescence (IR-AF). CMV retinitis was classified into proposed categories of acute, subacute, remission, and recurrent; the acute stage was further subdivided into initial, early, and late stages.

Results

In the initial stage, vertical structural disruption of all retinal layers was observed by SD-OCT, and FAF showed hyperautofluorescence on SW-AF and hypoautofluorescence on IR-AF. In the early stage, SD-OCT showed significant retinal thickening; cells and debris from the retinal surface to the vitreous; enlarged vessels with/without thickened vessel walls; and highly complicated serous retinal detachment. In the late to subacute stage, features observed included rhegmatogenous retinal detachment with shrinking posterior hyaloid membrane and waving from the ellipsoid zone to the retinal pigment epithelium. In remission, FAF findings were hypoautofluorescence on SW-AF and hyperautofluorescence on IR-AF.

Conclusion

Although the number of examined eyes was limited, SD-OCT and FAF provide new information in various stages of CMV retinitis in patients with HIV infection that is not obtainable by conventional examination and which may be of great benefit when screening for the initial stage of CMV retinitis.

     

Disc neovascularization in patients with AIDS and cytomegalovirus retinitis.

The authors report two patients with AIDS and cytomegalovirus retinitis who developed disc neovascularization. The disc neovascularization regressed spontaneously over several months and did not cause vitreous hemorrhage or visual loss.     

Subretinal hemorrhage in cytomegalovirus retinitis.

A case of subretinal hemorrhage associated with cytomegalovirus (CMV) retinitis in a human immunodeficiency virus-positive woman is described. The patient was found to have an exudative retinal detachment involving the fovea, subretinal hemorrhage, cotton wool spots, and active CMV retinitis temporal to the exudative detachment. No evidence of systemic coagulopathy was found. Although unusual, subretinal hemorrhage may be observed in association with CMV retinitis in the absence of a systemic coagulopathy.     

Zidovudine and cytomegalovirus retinitis.

A 38-year-old bisexual man with acquired immunodeficiency syndrome (AIDS) who was being treated with oral acyclovir for herpetic stomatitis had a history of blurred vision OS that was diagnosed as cytomegalovirus retinitis. The patient refused ganciclovir administration. Two additional lesions developed OS in the succeeding four months. All clinical evidence of active retinitis cleared after zidovudine was administered, and the patient has remained free of any clinically active retinal lesions for 28 months while continuing to receive acyclovir and zidovudine. Although ganciclovir and foscarnet are the drugs of choice to treat cytomegalovirus retinitis, this observation may be fortuitous for patients whose other AIDS manifestations suggest using zidovudine rather than ganciclovir or for patients whose cytomegalovirus retinitis appears to be resistant to agents currently used to treat this infection.     

Incidence of cytomegalovirus (CMV) retinitis in second eyes of patients with the acquired immune deficiency syndrome and unilateral CMV retinitis

PURPOSE: To evaluate the risk and risk factors for developing cytomegalovirus (CMV) retinitis in previously uninvolved second eyes among patients with unilateral CMV retinitis. DESIGN: Cohort study. METHODS: SETTINGS: Single-center academic AIDS ophthalmology practice. PATIENT POPULATION: Three hundred seventy-six consecutive patients with AIDS and unilateral CMV retinitis were followed from the time of CMV retinitis diagnosis for the development of second-eye retinitis. EXPERIMENTAL PROCEDURES: Demographic and clinical characteristics were noted at baseline. Use of highly active antiretroviral therapy (HAART) and immune recovery in response to HAART were noted prospectively. MAIN OUTCOME MEASURE: Development of CMV retinitis in a previously uninvolved eye. RESULTS: Ninety-one percent of subjects received systemic anti-CMV treatment. Second-eye retinitis occurred in 26.1%/person-year (19.6% within the first 6 months), less than half the rate previously reported in untreated groups. Initial CD4+ T cell count >12 cells/microl, use of HAART, and initial posterior pole involvement were associated with 64%, 46%, and 41% reductions in incidence vis-à-vis comparison groups. Benefit from HAART was limited to that subset who developed immune recovery of a degree expected to restore innate control of CMV (a rise in the CD4+ T cell count by >50 cells/microl to a level >100 cells/microl). CONCLUSIONS: The risk of second-eye retinitis is substantial in patients with unilateral CMV retinitis but appears to be reduced by anti-CMV therapy and by HAART-induced immune recovery. Patients are at highest risk when CD4+ T cell counts are very low and in the months immediately after CMV retinitis diagnosis.     

Retinal aneurysms in adult cytomegalovirus retinitis.

We observed aneurysms of the retinal arteries, capillaries, and venules occurring in a patient with cytomegalovirus retinitis. These aneurysms were caused by involvement of the retinal vascular endothelium resulting in focal weaknesses in the vascular walls. The clinical appearance of this retinitis superficially resembled retinal branch vein occlusion.     

Quantitative analyses of cytomegalovirus genome in aqueous humor of patients with cytomegalovirus retinitis

PURPOSE: To investigate copy numbers of cytomegalovirus (CMV) in CMV retinitis patients during ganciclovir treatment using real-time polymerase chain reaction (PCR). METHODS: Thirteen aqueous humor samples obtained from 6 patients with clinically diagnosed CMV retinitis were analyzed. As controls, aqueous humor samples were obtained at the time of surgery from patients with senile cataracts. RESULTS: The CMV genome was detected in the range from 10(1) to 10(4) copies/microL of aqueous humor before antiviral treatment. The samples obtained from retinitis patients showing widespread retinal changes contained much higher copy numbers than those from patients with focal lesions. After treatment, the copy number decreased to one hundredth of that observed prior to treatment, but the CMV genome was detectable for 4 to 8 weeks after ganciclovir administration to 4 patients. CONCLUSION: These results revealed the correlation between the copy numbers of the CMV genome and the extent of the area affected by CMV retinitis before antiviral treatment, and the prolonged retention of CMV genome after antiviral treatment. Quantitation of the viral genome after the start of therapy will be of value in determining whether to continue or intensify the dosage of antiviral agents.     

Anterior segment findings in AIDS patients with cytomegalovirus retinitis

Background: Anterior segment findings in AIDS patients presenting with cytomegalovirus (CMV) retinitis have not been specifically addressed in the American literature. Methods: Our study evaluated 21 AIDS patients with CMV retinitis. Results: Nineteen (90%) of these patients exhibited corneal endothelial deposits concurrent with CMV retinitis. The endothelial deposits were microscopic, opaque, linear flecks arranged in a reticular-like fashion. Of 42 eyes evaluated, 32 (76%) demonstrated active CMV retinitis. Corneal endothelial deposits were noted in 26 (81%) of the 32 eyes with retinitis. These corneal endothelial deposits were absent in the eyes which did not have CMV retinitis. Conclusion: Meticulous examination of the retina of an HIV-positive or AIDS patient who presents with reticularly arranged, linear, flecked corneal endothelial deposits should be performed to ensure that the diagnosis of CMV retinitis can be ruled out.     

Surgical repair of rhegmatogenous retinal detachment in immunosuppressed patients with cytomegalovirus retinitis.

The authors performed retinal reattachment surgery in 29 eyes of 24 patients with acquired immune deficiency syndrome virus with retinal detachment associated with cytomegalovirus (CMV) retinitis and documented the course of eight additional untreated eyes. Retinal detachment repair using vitrectomy, posterior hyaloid removal, and intraocular tamponade with silicone oil or SF-6 gas resulted in a total retinal reattachment rate of 76% and a macular attachment rate of 90% in one operation. The mean postoperative visual acuity (best corrected) was 20/60, but, in some patients, the visual acuity decreased because of progressive retinitis. Prophylactic laser photocoagulation of fellow eyes to surround CMV lesions did not appear to prevent retinal detachment. The mean postoperative survival was 37 weeks (range, 8 to 127 weeks). The surgical techniques used and pathophysiology of these retinal detachments are discussed.     

Cytomegalovirus retinitis in HIV-infected patients with and without highly active antiretroviral therapy.

PURPOSE: To assess the impact of highly active antiretroviral therapy on the epidemiology of cytomegalovirus retinitis in patients infected with the human immunodeficiency virus (HIV). METHODS: In a study performed in a single center for infectious diseases, we compared the data collected in 1995 (without highly active antiretroviral therapy) with 1997 data (with highly active antiretroviral therapy). RESULTS: In a comparison of 1997 with 1995 data, the mean CD4+ cell count of patients with cytomegalovirus (CMV) retinitis was higher (169 +/- 150 CD4/microl vs 15 +/- 47 CD4/microl) (P = .05), and the relapses of CMV retinitis were less frequent (17% vs 36%) (P = .02). Newly diagnosed CMV retinitis decreased from 6.1% (59 of 952 patients) in 1995 to 1.2% (nine of 726 patients) in 1997 (P < .0001). In 1997, patients with newly diagnosed or relapsing CMV retinitis had a lower mean CD4+ (37 +/- 42) cell count than patients with no relapsing CMV retinitis (197 +/- 160) (P = .01). CONCLUSION: The incidence and recurrences of CMV retinitis decreased from 1995 to 1997, probably as a result of restored immunity while the patients were undergoing highly active antiretroviral therapy; however, the increasing frequency of HIV resistance to highly active antiretroviral therapy justifies close ocular follow-up.     

Incidence and management of cataract after retinal detachment repair with silicone oil in immune compromised patients with cytomegalovirus retinitis

PURPOSE: To determine the incidence of and risk factors for cataract and to describe the visual outcomes of cataract surgery in eyes with cytomegalovirus-related retinal detachments repaired with silicone oil. STUDY DESIGN: Retrospective cohort study. METHODS: A prospectively generated database of all patients with cytomegalovirus retinitis examined at a single tertiary care institution was used to identify all cases of retinal detachment between October 1983 and August 1997. Data on retinal detachment repair, development of cataract, and outcomes of cataract surgery were obtained retrospectively. RESULTS: Among 904 eyes of 587 immune-compromised patients diagnosed with cytomegalovirus retinitis, 198 eyes of 155 patients developed retinal detachment. Among these, 106 eyes of 90 patients underwent retinal detachment repair with silicone oil. The Kaplan-Meier estimated median time to cataract was 1.8 months after surgery with silicone oil. The adjusted relative risk of cataract in eyes that underwent retinal detachment repair with silicone oil compared with eyes that did not was 6.74 (P <.0001). Eight of the eyes that developed cataract underwent uncomplicated cataract surgery by phacoemulsification and posterior chamber intraocular lens implantation. Among these, six eyes experienced >or=2 lines of improvement in visual acuity. All developed posterior capsule opacification a median of 7 days after cataract surgery. Four of five eyes that that underwent neodymium:yttrium-aluminum-garnet laser capsulotomy experienced >or=2 lines improvement in visual acuity. CONCLUSIONS: There is a high incidence of cataract after surgery with silicone oil tamponade for cytomegalovirus-related retinal detachment. Posterior capsule opacification occurs rapidly after cataract surgery in these patients.     

Histopathological findings in cytomegalovirus retinitis

PURPOSE: We examined eyeballs collected from autopsied acquired immunodeficiency syndrome patients with cytomegalovirus (CMV) retinitis, and analyzed the precise pathogenesis of CMV retinitis. MATERIAL AND METHODS: Eyeballs were fixed with 10% buffered formalin embedded in paraffin. CMV antigens were investigated by histopathological and immunohistochemical analyses. Histopathological findings were compared with funduscopic images. RESULTS: CMV antigens remained in the necrotic area of the retina and many CMV immediate early antigens existed in intact parts of the inner retina showing almost intact structure, and around retinal vessels. CONCLUSIONS: The results suggest that CMV infects the inner retina first via the retinal vessels, although funduscopic examination may appear normal. It extends through the neuronal cells and glial cells horizontally and Muller cells vertically. CMV severely damages the retinal structure.     

Rhegmatogenous retinal detachment complicating cytomegalovirus retinitis.

Six eyes in four patients with cytomegalovirus retinitis developed retinal holes and retinal detachment. Holes appeared in areas of necrosis and were typically large and round with shaggy edges. Differentiation from exudative detachment was sometimes difficult because of obscuration of the fundus by vitreous haze. Cryotherapy was successful in closing open breaks without detachment; cryotherapy and exoplant surgery were used effectively to treat the initial detachments. The occurrence of massive periretinal proliferation and late development of new areas of hole formation or retinitis complicated therapy for these detachments.     

High-dose (5000-microg) intravitreal ganciclovir combined with highly active antiretroviral therapy for cytomegalovirus retinitis in HIV-infected patients in Venezuela

PURPOSE: To describe the use of high doses of intravitreal ganciclovir combined with highly active antiretroviral therapy (HAART) for the treatment of cytomegalovirus (CMV) retinitis in human immunodeficiency virus (HIV)-infected patients. METHODS: Thirteen HIV-infected patients (18 eyes) with active CMV retinitis (83.3% in zone 1 and 38.4% resistant) participated in this prospective interventional case series. Patients were treated with high dose intravitreal ganciclovir (5.0 mg/0.1 mL once a week) in combination with HAART therapy. Intravitreal injections were discontinued once CMV retinitis healed if there was a significant increase in CD4+ count (any increase of > or 50 cells/microL to levels over 100 cells/microL sustained for at least 3 months). Mean follow-up was 15.6 months. Main outcome measures included assessment of visual acuity and retinal inflammation (CMV retinitis activity). A matched historical control group of 20 eyes (15 patients) with CMV retinitis treated with systemic ganciclovir (intravenous [induction] and oral [maintenance]) was included. RESULTS: Complete regression of the retinitis was obtained with high doses of intravitreal ganciclovir in 88.8% of eyes (two patients died during follow-up) at a mean of 4.5 weeks (2 to 8 weeks). Visual acuity improved two or more lines in 61.1% of eyes. No ganciclovir retinal toxicity was identified. Three eyes presented CMV retinitis reactivation at a mean of 25.6 days after their last injection. Complications (33.3%) included retinal detachment (RD; 3 eyes), immune recovery uveitis (IRU; 2 eyes), and endophthalmitis (1 eye). In our control group complete regression of the retinitis was obtained in 100% of eyes at a mean of 4 weeks (3 to 7 weeks). However, 12 eyes (60%) presented with CMV retinitis relapse at a mean of 29 days (21 to 32 days) after initiating oral ganciclovir (maintenance). Complications included RD (7 eyes, 35%) and IRU (3 eyes, 15%). Severe neutropenia occurred in 2 patients (13%). CONCLUSIONS: High doses of intravitreal ganciclovir (5.0 mg) once a week in combination with HAART therapy is effective to control CMV retinitis, and may be discontinued after CMV retinitis has healed if immune reconstitution with a significant increase in CD4+ count has occurred.