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IMPORTANCE: Acute anterior uveitis has been reported to be associated with Zika virus (ZIKV) infection in case reports and retrospective studies based on systemic clinical signs of ZIKV and positive serologic tests. OBJECTIVE: To describe the ophthalmic findings associated with systemic ZIKV infection during the 2016 ZIKV outbreak in Guadeloupe in the French West Indies. DESIGN, SETTING, AND PARTICIPANTS: This cohort study assessed adult patients with red eye and virologic or serologic confirmation of acute ZIKV infection who were admitted to the Pointe-à-Pitre University Hospital from January 1, 2016, to January 1, 2017, for a systematic ophthalmologic examination. All patients with anterior uveitis also underwent a complete uveitis workup to rule out other causes of uveitis. Patients were excluded from the study if they had active uveitis and a history of uveitis or positive serology for other infectious diseases including dengue fever virus and chikungunya virus. Data were analyzed from January 1, 2016, to January 1, 2017. EXPOSURES: Patients with confirmed ZIKV infection underwent full ophthalmic examination at study inception and 3, 6, and 12 months. MAIN OUTCOMES AND MEASURES: Description of the presenting ocular characteristics, management, and outcome. RESULTS: Of 62 total patients with a red eye, 32 (51.6%) had no uveitis (mean [SD] age, 27.8 [3.7] years; 26 women [81.3%]) and 30 (48.4%) had anterior uveitis (mean [SD] age, 27.5 [3.8] years; 26 women [86.7%]), which was bilateral in all cases. Acute anterior uveitis was nongranulomatous and without synechiae, exhibiting mild anterior chamber reaction with small keratic precipitates. Ocular hypertension occurred in 25 patients (83.3%) with uveitis at presentation and persisted in 15 patients (50%) at 1 year despite antiglaucoma therapy and control of uveitis. Uveitis responded to topical steroids in all cases. Intraocular pressure was within normal limits for all patients without uveitis throughout the follow-up period. CONCLUSIONS AND RELEVANCE: Anterior uveitis was present in almost half of patients with a red eye and acute systemic ZIKV infection; the uveitis was usually bilateral and often associated with increased intraocular pressure. These results suggest that ophthalmic evaluation should be performed in patients with red eye and acute ZIKV infection to potentially detect and manage hypertensive anterior uveitis.

This case series assesses the utility of metagenomic deep sequencing in identifying rubella virus infection in patients with uveitis., Key Points Question What are the ocular findings of patients with the rubella viral genome detected with metagenomic deep sequencing? Findings In this case series study, 6 patients with detectable rubella virus RNA in the intraocular compartment exhibited typical and atypical characteristics of Fuchs heterochromic iridocyclitis. Confocal imaging of the cornea revealed endothelial cell alterations in the affected eyes. Meanings These findings suggest that patients with persistent intraocular rubella virus infection can present with heterogeneous clinical findings, including endothelial cell damage., Importance Metagenomic deep sequencing (MDS) demonstrates that persistent and active rubella virus (RV) infection is associated with Fuchs heterochromic iridocyclitis (FHI). Objective To assess the utility of MDS in identifying RV infection in patients with uveitis. Design, Setting, and Participants This case series assessed 6 patients diagnosed by MDS with RV-associated uveitis at a tertiary uveitis referral center in the United States. Exposures Prior RV infection. Main Outcomes and Measures Clinical examination findings, slitlamp photography, corneal confocal imaging, and infectious pathogen genome obtained from RNA sequencing. Results Six white men (age range, 36-61 years) were diagnosed with RV-associated uveitis by MDS. Three patients exhibited iris heterochromia associated with their uveitis in classic FHI fashion. The other 3 patients had less classic FHI features and exhibited anterior vitritis. Three patients had in vivo corneal confocal microscopy, with 2 demonstrating stellate keratic precipitates in addition to endothelial infiltration, spotlike holes, and enlarged intercellular boundaries. Of these 3 patients, 1 patient exhibited polymorphism and polymegathism of the endothelial cells. Conclusions and Relevance These findings suggest that persistent RV infection is associated with recurrent or chronic anterior or anterior-intermediate uveitis as well as corneal endothelial cell damage. Ophthalmologists should consider RV infection as a potential cause of hypertensive anterior and intermediate uveitis.

A better pathophysiologic understanding of the neurodevelopmental abnormalities observed in neonates exposed in utero to Zika virus (ZIKV) is needed to develop treatments. The retina as an extension of the diencephalon accessible to in vivo microcopy with spectral-domain optical coherence tomography (SD-OCT) can provide an insight into the pathophysiology of congenital Zika syndrome (CZS).To quantify the microstructural changes of the retina in CZS and compare these changes with those of cobalamin C (cblC) deficiency, a disease with potential retinal maldevelopment.This case series included 8 infants with CZS and 8 individuals with cblC deficiency. All patients underwent ophthalmologic evaluation at 2 university teaching hospitals and SD-OCT imaging in at least 1 eye. Patients with cblC deficiency were homozygous or compound heterozygotes for mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Data were collected from January 1 to March 17, 2016, for patients with CZS and from May 4, 2015, to April 23, 2016, for patients with cblC deficiency.The SD-OCT cross-sections were segmented using automatic segmentation algorithms embedded in the SD-OCT systems. Each retinal layer thickness was measured at critical eccentricities using the position of the signal peaks and troughs on longitudinal reflectivity profiles.Eight infants with CZS (5 girls and 3 boys; age range, 3-5 months) and 8 patients with cblC deficiency (3 girls and 5 boys; age range, 4 months to 15 years) were included in the analysis. All 8 patients with CZS had foveal abnormalities in the analyzed eyes (8 eyes), including discontinuities of the ellipsoid zone, thinning of the central retina with increased backscatter, and severe structural disorganization, with 3 eyes showing macular pseudocolobomas. Pericentral retina with normal lamination showed a thinned (30% of normal thickness) ganglion cell layer (GCL) that colocalized in 7 of 8 eyes with a normal photoreceptor layer. The inner nuclear layer was normal or had borderline thinning. The central retinal degeneration was similar to that of cblC deficiency.Congenital Zika syndrome showed a central retinal degeneration with severe GCL loss, borderline inner nuclear layer thinning, and less prominent photoreceptor loss. The findings provide the first, to date, in vivo evidence in humans for possible retinal maldevelopment with a predilection for retinal GCL loss in CZS, consistent with a murine model of the disease and suggestive of in utero depletion of this neuronal population as a consequence of Zika virus infection.

Importance Zika virus has spread rapidly throughout the Americas since 2015. The public health implications of Zika virus infection lend special importance to identifying the virus in unsuspected hosts. Objective To describe relevant imaging studies and clinical features of chorioretinal lesions that are presumably associated with Zika virus and that share analogous features with chorioretinal lesions reported in cases of Dengue fever and West Nile virus. Design, Setting, and Participants This is a case report from an academic referral center in Miami, Florida, of a woman in her 60s from Guaynabo, Puerto Rico, who presented with reduced visual acuity and bilateral diffuse, subretinal, confluent, placoid, and multifocal chorioretinal lesions. The patient was observed over a 5-month period. Main Outcomes and Measures Visual acuity, clinical course, and multimodal imaging study results. Results Fluorescein angiography revealed early hypofluorescence and late staining of the chorioretinal lesions. Optical coherence tomography demonstrated outer retinal disruption in the placoid macular lesions. Zika RNA was detected in a plasma sample by real-time reverse transcription polymerase chain reaction testing and was suspected to be the cause of chorioretinal lesions after other viral and infectious causes were ruled out. Three weeks after the onset of symptoms, the patient’s visual acuity had improved to 20/60 OD and 20/25 OS, with intraocular pressures of 18 mm Hg OD and 19 mm Hg OS. In 6 weeks, the chorioretinal lesions had healed and visual acuity had improved to 20/25 OD and 20/20 OS. Follow-up optical coherence tomography demonstrated interval recovery of the outer retina and photoreceptors. Conclusions and Relevance Acute-onset, self-resolving, placoid, or multifocal nonnecrotizing chorioretinal lesions may be a feature of active Zika virus chorioretinitis, as reported in other Flavivirus infections in adults. Similar findings in potentially exposed adults suggest that clinicians should consider IgM antibody or polymerase chain reaction testing for Zika virus as well as diagnostic testing for Dengue fever and West Nile virus.

Importance The Zika virus (ZIKV) might cause microcephaly and ophthalmoscopic findings in infants of mothers infected during pregnancy. Objective To assess and identify possible risk factors for ophthalmoscopic findings in infants born with microcephaly and a presumed clinical diagnosis of ZIKV intrauterine infection. Design, Setting, and Participants We conducted a cross-sectional study at the Altino Ventura Foundation in Recife, Brazil, that included 40 infants with microcephaly born in Pernambuco state, Brazil, between May and December 2015. Toxoplasmosis, rubella, cytomegalovirus, syphilis, and human immunodeficiency virus were ruled out in all of them. Testing of cerebrospinal fluid for ZIKV using IgM antibody-capture enzyme-linked immunosorbent assay was performed in 24 of 40 infants (60.0%). The infants and mothers underwent ocular examinations. The infants were divided into 2 groups, those with and without ophthalmoscopic alterations, for comparison. Main Outcomes and Measures Identification of risk factors for ophthalmoscopic findings in infants born with microcephaly and ZIKV intrauterine infection. Results Among the 40 infants, the mean (SD) age was 2.2 (1.2) months (range, 0.1-7.3 months). Of the 24 infants tested, 100% had positive results for ZIKV infection: 14 of 22 infants (63.6%) from the group with ophthalmoscopic findings and 10 of 18 infants (55.6%) from the group without ophthalmoscopic findings. The major symptoms reported in both groups were rash by 26 mothers (65.0%), fever by 9 mothers (22.5%), headache by 9 mothers (22.5%), and arthralgia by 8 mothers (20.0%). No mothers reported conjunctivitis or other ocular symptoms during pregnancy or presented signs of uveitis at the time of examination. Thirty-seven eyes (46.3%) of 22 infants (55.0%) had ophthalmoscopic alterations. Ten mothers (71.4%) of infants with ocular findings reported symptoms during the first trimester (frequency, 0.48; 95% CI, 0.02-0.67; P = .04). A difference was also observed between the groups of infants with and without ocular findings regarding the cephalic perimeter: mean (SD) of 28.8 (1.7) and 30.3 (1.5), respectively (frequency, −1.50; 95% CI, −2.56 to −0.51; P = .004). Conclusions and Relevance Ocular involvement in infants with presumed ZIKV congenital infection were more often seen in infants with smaller cephalic diameter at birth and in infants whose mothers reported symptoms during the first trimester.

A 19-year-old womanwith a history of leukemia in remission after bone marrow transplant presented with a 2-week history of photophobia and decreased vision in the left eye. The right eye was normal. Vision in the affected left eye was 20/32 without an afferent pupillary defect and an intraocular pressure of 9mmHg. Anterior segment examination revealed mild cell and flare and moderate vitritis. Scattered retinal hemorrhages and circumferential retinal pallor were observed on fundus examination. Fluorescein angiography (Figure) revealed marked peripheral vascular occlusion, papillitis, and posterior vascular leakage in acute retinal necrosis due to herpes zoster virus. She was treated with intravitreous ganciclovir and intravenous acyclovir. Systemic prednisone was administered 3 days later, and she recovered. Final visual acuity at 6 months was 20/25 OS.

SELECTED CASES Case 1 A 58-YEAR-OLD bisexual man presented to the eye clinic of the National Institutes of Health, Clinical Center, Bethesda, Md, with a 2-day history of shadows in his left eye that had progressed to a more confluent clouding of his peripheral field. Visual acuity was 6/6 (20/20) in his right eye and 6/12 (20/40) in his left. Retinal examination revealed an area of hemorrhagic retinitis extending to within 2 disc diameters of his optic nerve. A white perivascular sheath was noted along major vessels beyond the area of involvement. A diagnosis of cytomegalovirus (CMV) retinitis was made and the patient was started on ganciclovir sodium (5 mg/kg intravenously, twice a day) with resolution of the retinitis. However, after 6 weeks on maintenance ganciclovir therapy (5 mg/kg, once a day), he noted further change in his vision and had funduscopic evidence of CMV reactivation. He was given another

A 10-year-old boy presented to a cornea subspecialty clinic with a 6-month history of intermittent redness, swelling, and itching of the right eye.Hehad seasonal allergies butwas otherwise healthy. He had not beenwearing his contact lenses since the episodes started. The patient’s symptoms persisted despite previous treatment regimenswith topical corticosteroids foratopicconjunctivitis andtopical antibiotics for staphylococcalblepharitis.Conjunctival cultures forbacteriaorviruses (includingadenovirusandherpessimplexvirus)were negative. The patient’s visual acuity with eyeglasses was 20/20OU. Findings from examination of the right eye were significant for lower eyelid follicles andmild conjunctival injection. A nontender preauricular lymph nodewas noted aswell as a raised erythematous papule on the patient’s upper cheek (Figure 1A). Findings fromexamination of the skin revealedmultiple raised papules on the right elbow and knee that were diagnosed as warts by the patient’s dermatologist (Figure 1B). Thesepapules hadbeenpresent for about6months and, despite the use of topical salicylic acid and cryotherapy, they continued to spread. A B

Amaninhis30s,whowasknowntobecoinfectedwithdenguehemorrhagic fever andmalaria for a duration of 20 days, presentedwith suddenonsetofdefectivevision inhis lefteyeforadurationof10days. Theresultsofserologictestingwerepositivefor IgMantibodiestodengue virus, andhis peripheral blood smear showedmalarial parasites. His visual acuity was handmotion in the left eye. Discussion Afundusphotographofthelefteyerevealedmultiple intraretinalhemorrhages, vascular sheathing typical of frosted branch angiitis, and macular edema (Figure). The patient received an intravitreal bevacizumab injection in the left eye for the management of macular edema. At the 4-month follow-up, his visual acuity improved to counting fingers (at 1 m) in the left eye, and a fundus examination of the left eye revealed the partial resolution of the hemorrhages, vascular sheathing typical of frosted branch angiitis, and the resolution of macular edema.

Importance Swimming pools can be a vector for transmission of adenovirus ocular infections. Polyhexamethylene biguanide (PHMB) is a disinfectant used in swimming pools and hot tubs. Objective To determine whether PHMB is an effective disinfectant against ocular adenovirus serotypes at a concentration used to disinfect swimming pools and hot tubs. Design In vitro laboratory study. Interventions The direct disinfecting activity of PHMB was determined in triplicate assays by incubating 9 human adenovirus types (1, 2, 3, 4, 5, 7a, 8, 19, and 37) with PHMB concentrations of 50 and 0 ppm (micrograms per milliliter) for 24 hours at room temperature to simulate swimming pool temperatures or 40 o C to simulate hot tub temperatures. Main Outcome Measures Plaque assays were performed to determine adenovirus titers after incubation. Titers were log 10 converted and mean (SD) log 10 reductions relative to controls were calculated. Virucidal (>99.9%) decreases in mean adenovirus titers after PHMB treatment were determined for each adenovirus type and temperature tested. Results At room temperature, 50 ppm of PHMB produced mean reductions in titers less than 1 log 10 for all adenovirus types tested. At 40°C, 50 ppm of PHMB produced mean reductions in titers less than 1 log 10 for 2 adenovirus types and greater than 1 but less than 3 log 10 for 7 of 9 adenovirus types. Conclusions and Relevance At a concentration of 50 ppm, PHMB was not virucidal against adenovirus at temperatures consistent with swimming pools or hot tubs. Recreational water maintained and sanitized with PHMB can serve as a vector for the transmission of ocular adenovirus infections.

OBJECTIVE To describe the clinical characteristics and prognosis of diverse variants of herpetic uveitis with posterior segment involvement. METHODS/DESIGN Retrospective observational study of clinical, imaging, and laboratory data. RESULTS Twenty-five patients were classified as having typical acute retinal necrosis (ARN) and 13 patients as not having ARN (non-ARN). Age at symptom onset, sex, bilateral involvement, and prevalence of viral species were not significantly different between patients in the ARN and non-ARN groups. All patients in the ARN group had necrotic retinal lesions that progressed quickly, whereas only 4 of 13 patients (31%) in the non-ARN group (P < .001) had necrotic retinal lesions that progressed slowly. Necrotizing variants were noted in 29 of 38 patients (76%), including 4 patients with slowly progressing lesions. Nine remaining patients in the non-ARN group had non-necrotizing posterior uveitis without retinal lesions; their cases were characterized by vitritis, vasculitis, and/or papillitis, or as panuveitis without any distinct features (5 patients [38.5%]). At 6 months' follow-up, visual acuity of less than 0.1 developed in 13 of 25 patients (52%) in the ARN group and in 4 of 13 patients (31%) in the non-ARN group (P = .30). CONCLUSIONS Herpes simplex and varicella zoster viruses can cause a wide spectrum of clinical manifestations ranging from severe ARN to slow-progressing necrotizing and non-necrotizing types of inflammation. The non-ARN variants are currently underdiagnosed. Patients with these variants could potentially benefit from earlier recognition and treatment.

To define optic neuritis associated with chikungunya virus (CHIKV) infection in a clinical setting.This observational case series includes 14 patients with clinical features of CHIKV infection and associated optic neuritis. Complete ophthalmic evaluations were performed, as well as other examinations, including Mantoux test, Widal test, blood profile, color vision, neuroimaging, visual fields, visual evoked potentials, VDRL test, and enzyme-linked immunosorbent assay for CHIKV-specific immunoglobulin. Relevant clinical findings of optic neuritis associated with seropositive CHIKV infection were recorded.Nineteen eyes (in 14 patients) had optic nerve involvement. The mean +/- SD patient age was 45.8 +/- 15.6 years. Eight eyes (42%) had papillitis, 4 eyes (21%) had retrobulbar neuritis, 4 eyes (21%) had retrochiasmal (optic tract) neuritis, and 3 eyes (16%) had neuroretinitis. Parenteral corticosteroids were administered in all patients. Color vision, visual fields, and best-corrected visual acuity of 6/12 (or 20/40 Snellen visual acuity) or better improved statistically significantly by the end of 3 weeks (P.001). Partial to complete recovery of visual function was seen in 10 patients (71%). Four patients had a poor visual outcome; 3 of them were initially seen 1 month after onset of ocular symptoms.Acute-onset visual loss due to optic neuritis may be associated with CHIKV infection. Visual recovery is good. Corticosteroids accelerated recovery when initiated at an early stage of the disease.

Objective To describe the clinical spectrum of fundus manifestations and angiographic and optical coherence tomographic features of dengue-associated maculopathy in a large series. Methods We reviewed clinical records of patients diagnosed as having dengue maculopathy at the Singapore National Eye Centre between January 1, 2002, and December 31, 2005. Results We identified 41 patients with serological evidence of dengue fever who had ocular signs and symptoms not attributable to other diseases within 1 month after onset of symptoms of dengue. Seventy-one eyes had maculopathy. Mean best-corrected visual acuity in the affected eye was 20/40 (range, hand motions to 20/20). Intraretinal hemorrhages were seen in 45% of eyes, usually in association with venous sheathing. Fundus fluorescein angiography demonstrated venular occlusion in 25% or arteriolar and/or venular leakage in 3% and 13%, respectively. Yellow subretinal dots were an unusual finding in 28%. Of these, 50% showed corresponding hypofluorescent spots on indocyanine green angiography. Central or paracentral scotomas were observed in 63%. Twenty-eight patients received steroid treatment. Mean visual acuity showed significant improvement between weeks 2 and 4, with an increasing proportion of eyes achieving a best-corrected visual acuity of 20/40 or better across time. Conclusion Fundus fluorescein and indocyanine green angiography, optical coherence tomography, and visual field testing are useful tools in the diagnosis of dengue maculopathy.

Objective: To describe the visual outcome, fundus appearance, and fluorescein angiographic findings of a patient diagnosed as having acute West Nile virus infection. Methods: We conducted comprehensive eye examinations, including visual acuity testing and slitlamp and fundus examinations, along with fluorescein angiography at the initial and follow-up visits. Results: A 62-year-old white woman had a 2-week history of floaters in her left eye along with symptoms of fatigue, a left-sided frontal headache, and a low-grade fever. She was found to have anterior uveitis, vitritis, and nonnecrotizing chorioretinitis in her left eye with similar but milder findings in the right eye. The anterior uveitis responded to topical steroids. Because of continued fevers and fatigue, a serologic test for West Nile virus immunoglobulin M was performed, and the results were found to be positive for this disease. Conclusion: These unique eye findings, along with associated systemic signs and symptoms, can potentially indicate infection with the West Nile virus.

Objective To validate a real-time polymerase chain reaction (PCR) assay allowing rapid and sensitive detection and quantitation of 4 common infectious posterior uveitis pathogens. Methods A real-time PCR assay using previously validated primer sets for cytomegalovirus, herpes simplex virus, varicella-zoster virus, and Toxoplasma gondii was developed. A standard curve for quantitation of pathogen load was generated for each pathogen using SYBR Green I fluorescence detection. Ocular samples from patients with posterior uveitis and from negative control samples were assayed and compared with standards to identify pathogens and quantify infectious load. Results Sensitivity for detection of purified pathogen DNA by PCR was not reduced by application of the real-time method. Standard curves for the quantitation of pathogen loads showed sensitivity to fewer than 10 organisms for all pathogens. The technique was applied to 2 clinical problems. First, sensitivities of existing monoplex and multiplex PCR were compared by real-time PCR. No significant difference in sensitivity was observed between multiplex and monoplex techniques. Second, pathogen loads of vitreous specimens from patients previously diagnosed as having infectious posterior uveitis were calculated. Pathogen loads were found to be generally higher for patients with disease caused by varicella-zoster virus than those caused by cytomegalovirus or herpes simplex virus. Conclusions Real-time PCR may be applied to infectious agents responsible for posterior uveitis. This technique will likely prove useful for the diagnosis of posterior uveitis as well as the linkage of pathogen to disease. Clinical Relevance Real-time PCR provides a rapid technique for quantitatively evaluating ocular samples for the presence of infectious pathogens.

Objective To evaluate the efficacy of 0.2% cidofovir eyedrops and 1% cyclosporine eyedrops administered 4 times daily (qid) to treat acute adenoviral keratoconjunctivitis. Methods A randomized, controlled, double-masked study was conducted on 39 patients with acute adenoviral keratoconjunctivitis of recent onset. Patients were divided into 4 treatment groups: (1) cidofovir qid, (2) cyclosporine qid,(3) cidofovir + cyclosporine qid, and (4) sodium chloride qid (control). The diagnosis was confirmed using adenoviral polymerase chain reaction from conjunctival swabs. Duration of treatment was 21 days. Main Outcome Measures Severity of conjunctival hyperemia, conjunctival chemosis, superficial punctate keratitis during treatment, and presence and severity of corneal subepithelial infiltrates were evaluated using a clinical score. Duration until subjective improvement of symptoms was recorded. Results Subjective improvement of local symptoms was accelerated in the cyclosporine group. All other clinically relevant variables showed no statistically significant difference among the 4 treatment groups. Particularly, we did not find a difference in the frequency of corneal subepithelial infiltrates at the end of treatment. Conclusions Use of cidofovir, cyclosporine, or both did not accelerate the improvement of clinical symptoms of acute adenoviral keratoconjunctivitis compared with the natural course of the infection as demonstrated by this pilot study. This might be because of the wide spectrum of the clinical course of the infection, low sensitivity to cidofovir, too low of a concentration of cidofovir, or early cessation of viral replication in the course of the infection. The effect of a higher concentration of topical cidofovir with and without cyclosporine requires investigation in a larger group of patients.

Objective To evaluate the antiviral activity of topical diclofenac sodium (Voltaren Ophthalmic) and ketorolac tromethamine (Acular) (2 nonsteroidal anti-inflammatory drugs [NSAIDs]) on adenoviral replication in vitro and in the adenovirus (Ad) 5 McEwen–New Zealand rabbit ocular model. Methods The 50% inhibitory concentration of ketorolac and diclofenac and their respective preservative components were determined for common ocular adenoviral serotypes (Ad8, Ad19, Ad1, and Ad5). In a series of experiments, Ad5 McEwen–inoculated New Zealand rabbit eyes were treated topically 4 times daily for 18 days with either ketorolac, diclofenac, prednisolone acetate (Pred Forte), or control vehicle (Comfort Tears). Main Outcome Measures Outcome measures included serial ocular tear film titers and the formation of subepithelial immune corneal infiltrates. Results In vitro, neither ketorolac nor diclofenac demonstrated significant inhibitory activity against Ad1, Ad5, Ad8, or Ad19. In the rabbit model, there were no statistically significant differences among ketorolac, diclofenac, and the control vehicle with respect to viral replication or the formation of subepithelial immune infiltrates. In contrast, 1% prednisolone prolonged viral shedding and inhibited immune infiltrates ( P Conclusions Our experimental study suggests that treatment of epidemic keratoconjunctivitis with topical NSAIDs may be a safer alternative than topical steroids. Only controlled clinical trials can determine whether topical NSAIDs can provide symptomatic relief and not interfere with normal viral clearance.

A 36-year-old patient with the acquired immunodeficiency syndrome sought care because of an upper eyelid lesion that dramatically increased in size. The histopathologic examination revealed a high-grade diffuse large cell non-Hodgkin lymphoma in continuity with a Kaposi sarcoma. In situ hybridization revealed Epstein-Barr virus in the large cell lymphoma and Kaposi sarcoma-associated herpesvirus in the Kaposi sarcoma lesion. This collision tumor is an unusual presentation of 2 malignant neoplasms in a patient with acquired immunodeficiency syndrome, with in situ hybridization evidence of Epstein-Barr virus and Kaposi sarcoma-associated herpesvirus in the lesion.

A man with acquired immunodeficiency syndrome developed a generalized rash and bilateral dendritic epithelial keratitis without retinitis. Cytologic examination of superficial corneal scrapings showed many megalosyncytial giant cells that were highly characteristic of cytomegalovirus (CMV) infection. Viral cultures yielded CMV from 2 separate specimens obtained by corneal epithelial debridement from both eyes. The slightly elevated, opaque, branching, nonulcerative epitheliopathy recurred after corneal scrapings and persisted despite oral and topical antiviral therapy. Stromal keratouveitis subsequently developed. This case report confirms that CMV can produce corneal involvement and suggests that CMV keratitis may be an emergent complication of acquired immunodeficiency syndrome.

Objective: To evaluate (s)-1-(3-hydroxy-2-phosphonyl methoxypropyl) cytosine (HPMPC), a potent antiherpes and anticytomegalovirus drug, as a long-term treatment of experimental retinitis in rabbits. Methods: The drug was first encapsulated into a liposome delivery system in three different concentrations and injected intravitreally. Sequentially, the highest concentration that was shown to be nontoxic to the retina was evaluated in a model of retinitis at 60, 90, 120, 170, and 240 days, after which herpes simplex virus type 1 was inoculated onto the retinal surface. Results: A dose of 1000 μg of HPMPC encapsulated in liposomes gives a protective effect for up to 8 months. Conclusions: Reduced toxic effects and longer-term efficacy compared with free drug was observed. Given the 50 times higher activity of HPMPC against human cytomegalovirus than herpes simplex virus type I, a single injection of 1000 μg of liposome-encapsulated HPMPC may have a very prolonged effect in the treatment of cytomegalovirus retinitis.

Cytomegalovirus (CMV) infection of the brain, optic nerves, and retinas from 47 consecutive autopsies of patients with acquired immunodeficiency syndrome (AIDS) were examined. Immunocytochemistry demonstrated CMV infection in 11 (23%) brains, two (2%) of 94 optic nerves, and 38 (40%) of 94 retinas. Ten (91%) of 11 patients with CMV encephalitis had concurrent retinitis. While 10 (42%) of 24 patients with CMV retinitis had CMV encephalitis, when the retinitis included the peripapillary region, 75% had encephalitis. Usually, the optic nerve parenchyma was not infected histologically despite extensive peripapillary retinitis. The strength of these associations suggests that CMV retinitis defines a group of patients with AIDS at risk for development of CMV encephalitis (relative risk, 9.5), particularly when the retinitis involves the peripapillary region (relative risk, 13). Furthermore, in patients with AIDS without CMV retinitis, central nervous system symptoms are unlikely to be attributable to CMV encephalitis.

Objective: To test the hypothesis that the iridocorneal endothelial (ICE) syndrome has a viral origin by comparing the incidence of viral DNA in corneal specimens from patients with the ICE syndrome and from controls. Design: Thirty-one corneas obtained from 25 patients with the ICE syndrome and six with chronic herpetic keratitis (n=31) were compared with 30 control specimens obtained from 15 healthy donors and from 15 patients with other, nonviral chronic corneal diseases. Methods: Primer pairs and polymerase chain reaction methods were used to identify and amplify either a segment of the DNA polymerase gene in the case of the herpes simplex and zoster viruses or a region of the nuclear antigen gene for the Epstein-Barr virus. The oligonucleotide amplified by polymerase chain reaction was fully characterized with the use of restriction enzyme, hybridization, and sequence analyses to determine that it contained the expected base pair sequence. Results: Sixteen of 25 ICE syndrome specimens and four of six herpetic keratitis specimens were positive for herpes simplex virus (HSV) DNA. All nine ICE syndrome specimens tested were negative for the presence of DNA from the herpes zoster or the Epstein-Barr viruses. Controls were uniformly negative for HSV DNA whether they were obtained from ostensibly normal corneas (n=15) or from corneas with interstitial keratitis, aphakic bullous keratopathy, or keratoconus (n=15). Tissue samples cut from positive ICE syndrome specimens yielded negative results when retested after the endothelial layer was removed. These findings indicate that localization of HSV DNA is within the endothelium, the tissue primarily involved in the pathogenesis of the ICE syndrome. Conclusions: Polymerase chain reaction evidence shows that HSV DNA is present in a substantial percentage of ICE syndrome corneal specimens and that HSV-DNA is absent in normal corneas and in corneas from patients with three other chronic corneal diseases. These results provide direct evidence to support our hypothesis that the ICE syndrome has a viral origin. We discussed clinical implications, including possible therapeutic interventions.

Human T-cell lymphotropic virus type I has been associated with a wide range of ocular conditions, including neoplastic, infectious, and inflammatory lesions. We studied a patient infected with human T-cell lymphotrophic virus type I who presented with deep retinal and subretinal infiltrates but without cells in the vitreous. The differential diagnosis included intraocular lymphoma and fungus infection. A chorioretinal biopsy specimen obtained for tissue diagnosis disclosed large atypical mononuclear cells located primarily at the level of the retinal pigment epithelium but focally involving overlying retina. Electron microscopy of this infiltrate showed features consistent with adult T-cell lymphoma/leukemia. Infection by human T-cell lymphotropic virus type I was verified by polymerase chain reaction studies conducted on peripheral-blood mononuclear cells. This case emphasizes the occurrence of intraocular lesions in adult T-cell lymphoma/leukemia that clinically show some features similar to those of the usual ocular lymphoma (reticulum cell sarcoma); diagnosis can be established by chorioretinal biopsy, thereby allowing appropriate therapy.

• A surgically implantable device for sustained intravitreal release of ganciclovir has been developed. The device delivers ganciclovir intraocularly over approximately 4 to 5 months. Eight patients with acquired immunodeficiency syndrome (AIDS) and associated cytomegalovirus (CMV) retinitis were recruited as part of a phase 1 study. Thirteen eyes with active CMV retinitis underwent surgical implantation of the ganciclovir device. All eyes showed resolution of the CMV retinitis; none showed progression. Visual acuity remained unchanged in three eyes, improved in six eyes, and decreased in four eyes. Surgical complications included mild vitreous hemorrhage, astigmatism, and suprachoroidal placement of the device. Retinal detachment occurred in three eyes as the retinitis resolved. This new intraocular drug delivery system offers many advantages compared with intravenous therapy or repeated intravitreal ganciclovir injections for the management of CMV retinitis in patients with AIDS.

Vaccination against smallpox with a live attenuated virus has resulted in a variety of statistically minor but clinically unusual complications including reported cases of encephalitis, acute renal failure, glomerulonephritis, thrombocytopenic purpura, and vaccinial keratitis. 1 The keratitis is considered a serious ocular complication 2 in spite of reports which allude to its benignity when treated with a number of therapeutic agents including cortisone. 3 Presented here is a single case of keratitis immediately associated with generalized vaccinia, thought to clinically represent vaccinial keratitis which was treated with 5-iodo-2′-deoxyuridine (IDU).* Realizing that a single case might stand as apocryphal concerning the efficacy of treatment, we still feel that the unusual circumstances of the corneal disease and the course of the illness after IDU treatment are of significant interest. Vaccinia is a laboratory virus evolved from cowpox or variola virus which is modified by animal passage through calves or rabbits and irreversibly