Zika and the Eye: Pieces of a Puzzle

Zika virus (ZIKV) is an arbovirus mainly transmitted to humans by mosquitoes from Aedes genus. Other ways of transmission include the perinatal and sexual routes, blood transfusion, and laboratory exposure. Although the first human cases were registered in 1952 in African countries, outbreaks were only reported since 2007, when entire Pacific islands were affected. In March 2015, the first cases of ZIKV acute infection were notified in Brazil and, to date, 48 countries and territories in the Americas have confirmed local mosquito-borne transmission of ZIKV. Until 2015, ZIKV infection was thought to only cause asymptomatic or mild exanthematous febrile infections. However, after explosive ZIKV outbreaks in Polynesia and Latin American countries, it was confirmed that ZIKV could also lead to Guillain-Barré syndrome and congenital birth abnormalities. These abnormalities, which can include neurologic, ophthalmologic, audiologic, and skeletal findings, are now considered congenital Zika syndrome (CZS). Brain abnormalities in CZS include cerebral calcifications, malformations of cortical development, ventriculomegaly, lissencephaly, hypoplasia of the cerebellum and brainstem. The ocular findings, which are present in up to 70% of infants with CZS, include iris coloboma, lens subluxation, cataract, congenital glaucoma, and especially posterior segment findings. Loss of retinal pigment epithelium, the presence of a thin choroid, a perivascular choroidal inflammatory infiltrate, and atrophic changes within the optic nerve were seen in histologic analyses of eyes from deceased fetuses. To date, there is no ZIKV licensed vaccines or antiviral therapies are available for treatment. Preventive measures include individual protection from mosquito bites, control of mosquito populations and the use of barriers measures such as condoms during sexual intercourse or sexual abstinence for couples either at risk or after confirmed infection. A literature review based on studies that analyzed ocular findings in mothers and infants with CZS, with or without microcephaly, was conducted and a theoretical pathophysiologic explanation for ZIKV-ocular abnormalities was formulated.     

Ophthalmologic findings in children with congenital cytomegalovirus infection.

BACKGROUND: Cytomegalovirus (CMV) infection is the most common congenital viral infection in the United States, affecting 0.5% to 2% of live births. Approximately 90% of infected infants are asymptomatic at birth. We undertook this study to determine the incidence and etiology of visual impairment and other ophthalmologic abnormalities in children with congenital CMV infection. METHODS: We prospectively evaluated 42 symptomatic and 83 asymptomatic children with congenital CMV infection, along with 21 control patients. One or more comprehensive ophthalmologic examinations were performed on each patient. The frequency and etiology of visual impairment and other ophthalmologic problems were tabulated for each patient. RESULTS: Nine of 42 (22%) patients in the symptomatic group had moderate to severe visual impairment in 16 eyes. Visual impairment was primarily due to optic atrophy in 6 of 16 (37%) eyes, macular scars in 2 of 16 (13%) eyes, and cortical visual impairment in 8 of 16 (50%) eyes. In comparison, none of 83 asymptomatic patients had severe visual impairment (P <.001). One asymptomatic patient had mild unilateral visual impairment caused by a macular scar. Strabismus developed in 12 of 42 (29%) symptomatic patients compared with 1 of 83 (1.2%) asymptomatic patients (P <.001). CONCLUSIONS: Visual impairment and strabismus are common in patients with symptomatic congenital CMV infection and rare in patients with asymptomatic congenital CMV infection. Visual impairment may be caused by cortical, optic nerve, and/or retinal abnormalities. Infants with symptomatic congenital CMV infection should undergo careful ophthalmologic screening and follow-up examinations.     

Toxoplasmic chorioretinitis: positive PCR on vitreous with negative serology for Toxoplasma gondii

Ocular recurrences of congenital toxoplasmosis usually occur during the first and second decades of life. At that time, serum levels of IgG against toxoplasmosis are almost always detectable because of the very high sensitivity of the test. The diagnosis is mainly supported by the ophthalmological examination and the good clinical response to treatment. In atypical cases, the Goldman-Witmer coefficient (GWC) on aqueous and polymerase chain reaction (PCR) on aqueous or vitreous is usually performed to substantiate the diagnosis. We report a case of recurrent macular chorioretinitis in a 13-year-old immunocompetent patient with a history of congenital toxoplasmosis whose repeated serologies remained negative or uncertain. However, the diagnosis of toxoplasmic chorioretinitis was supported by the detection of Toxoplasma gondii DNA by PCR analysis in a vitreous sample. Although the sensitivity of serology is very high, it is not perfect and there are false-negative results. In case of high clinical presumption in spite of a negative serology, PCR could be a helpful contribution to the diagnosis.     

Presumed ocular histoplasmosis syndrome

Presumed ocular histoplasmosis syndrome (POHS) is a commonly observed fungal infection. Ocular findings include peripapillary atrophy, peripheral punched-out lesions, and a macular subretinal neovascular membrane. Laser photocoagulation can be beneficial in reducing visual loss from macular scarring due to subretinal neovascular membranes. Herein we describe a patient with POHS in which laser treatment regressed a parafoveal subretinal neovascular membrane. Her vision improved from 20/70 to 20/20 in the treated eye.     

Autosomal dominantly inherited macular dystrophy with preferential short-wavelength sensitive cone involvement

We found an apparently inherited tritan-like color vision defect in five members of a family, spanning three generations. The defect was associated with mild macular pigmentary changes, poor foveolar reflexes, or slightly reduced visual acuity in four of the affected individuals. The inheritance pattern appeared to be autosomal dominant. Results of various color vision tests indicated preferential involvement of the short-wavelength sensitive cone system, with relative preservation of the middle- and long-wavelength sensitive cone systems. Both anomaloscope testing with larger (8-degree) fields and short-wavelength sensitive electroretinography indicated some short-wavelength sensitive cone system involvement beyond the central macula in the three affected individuals on whom testing was performed. The condition appeared to be a familial macular dystrophy with preferential short-wavelength sensitive cone involvement. The abnormal macular findings and mild reduction in visual acuity distinguish this condition from congenital tritanopia; the normal optic disks distinguish it from autosomal dominant optic atrophy.     

Epidemiology of ocular toxoplasmosis

Retinal infection with Toxoplasma gondii is the most important cause of posterior uveitis, whereby prevalence and incidence of ocular symptoms after infection depend on socio-economic factors and the circulating parasite genotypes. Ocular toxoplasmosis is more common in South America, Central America, and the Caribbean and parts of tropical Africa as compared to Europe and Northern America, and is quite rare in China. Ocular disease in South America is more severe than in other continents due to the presence of extremely virulent genotypes of the parasite. Drinking untreated water is considered the major source of Toxoplasma infection in developing countries, whereas in the Western world the consumption of raw or undercooked meat (products) is the most important cause. Since acquired infection with T. gondii is currently a more important cause of ocular toxoplasmosis compared to congenital infection, prevention should be directed not only toward pregnant women but toward the general population.     

Long-term results of treatment of macular complications in eyes with immune recovery uveitis using a graded treatment approach

PURPOSE: To evaluate the results of a graded treatment approach in a cohort of eyes with macular complications of immune recovery uveitis. METHODS: A cohort of 18 eyes of 13 patients representing all eyes with these complications at the University of California, San Diego AIDS Ocular Treatment Unit was studied. Eyes were classified into three groups and treated according to a graded protocol. RESULTS: Eyes with mild disease (macular edema and vision of 20/30 or better) were observed. These six eyes maintained good vision with only one dropping to 20/40. In eyes with worse macular edema and vision of 20/30 or worse (10 eyes of 9 patients), repository sub-Tenon steroid injections were used repeatedly. There were no complications of steroid use but visual improvement occurred in only 40% of eyes. Macular edema persisted. In eyes with structural macular changes, such as epiretinal membrane, vitrectomy resulted in vision improvement in three of four eyes. The cystoid macular edema persisted despite surgery. CONCLUSION: Mild cases of immune recovery uveitis and macular edema may be observed. In eyes with reduction of vision due to cystoid macular edema, there was only a modest treatment effect using repository corticosteroids. Eyes with immune recovery uveitis that develop epiretinal membrane undergo some visual improvement after removal of the membrane. The macular edema of immune recovery uveitis is resistant to corticosteroid treatment.     

Two discrete uveal melanomas in a child with ocular melanocytosis

OBJECTIVE: To describe a case of two uveal melanomas in a child with mild ocular melanocytosis. METHODS: A 6-year-old girl was followed for 5 years with an ill-defined, slowly enlarging presumed choroidal nevus in the postequatorial fundus. Ocular oncology evaluation revealed mild sectorial scleral and uveal melanocytosis and an episcleral sentinel vessel superotemporally. Two discrete uveal melanomas were present. In the circumpapillary and macular region, tumor 1 was diffuse at 9.0 mm in base and 4.1 mm in thickness and with overlying subretinal fluid. In the ciliary body, tumor 2 was discovered by transillumination and was 6.0 mm in base and 2.2 mm in thickness. Enucleation was performed. RESULTS: Histopathologic analysis disclosed two discrete uveal melanomas in a bed of diffuse mild uveal melanocytosis. Tumor 1 was a mixed, predominantly epithelioid cell melanoma with active mitotic figures, and tumor 2 was a mixed, predominantly spindle cell melanoma. The choroid between the melanomas showed only benign, dendritic melanocytes consistent with melanocytosis. There was no extrascleral extension. CONCLUSIONS: Ocular melanocytosis can predispose to one or multiple uveal melanomas. Lifetime ophthalmic monitoring of affected patients is warranted.     

Bartonella henselae infection presenting as a unilateral acute maculopathy

BACKGROUND: The purpose of this article is to report an unusual ocular manifestation of cat scratch disease (CSD) presenting as a unilateral acute maculopathy (UAM). We describe and review the clinical, laboratory, fluorescein angiography (FA), indocyanine green angiography (ICG) and optical coherence tomography (OCT) records of a patient with CSD. HISTORY AND SIGNS: A 30-year-old Chinese woman presented with a painless progressive visual loss affecting her left eye. Fundus examination of the left eye disclosed rare vitreous cells and a deep-creamy choroidal macular lesion with satellite foci of choroiditis. THERAPY AND OUTCOME: FA revealed an early hypofluorescence of the lesion, becoming progressively hyperfluorescent with a leakage on the late phase. The ICG disclosed an early hypofluorescence of the macular lesion with a mild staining of its periphery on the late frames. Hypofluorescent satellite lesions were visible both on the early and late frames. The OCT disclosed a serous retinal detachment at the level of the whitish lesion. Serologies for Bartonella henselae (BH) became positive (IgG 1: 512, IgM < 1:20) confirming an active or recent infection. CONCLUSIONS: Ocular manifestations of CSD can appear as a UAM with satellite lesions. CSD should be ruled out in patients manifesting such clinical features.     

Paramacular coloboma.

BACKGROUND: Paramacular coloboma (plural: colobomata) is a solitary oval football or torpedo-shaped chorioretinal lesion located temporal to the fovea in one or both eyes. Previous case reports have speculated varying etiology, but few have justified its pathognomonic shape and location. We believe it to be congenital in nature and caused by incomplete differentiation of the arcuate bundles along the horizontal raphe in development of the macular architecture. Associated ocular findings may include blepharophimosis, situs inversus, or other anomalous retinal vascular patterns. CASE REPORTS: Three cases of asymptomatic unilateral paramacular colobomata are presented. In each case, a single oval chorioretinal lesion temporal to the macula was found during routine examination. Visual acuity and Humphrey threshold visual field testing were normal with no other associated congenital, systemic, or ocular abnormalities. Because the lesion is nonprogressive, these patients can be followed on an annual basis. CONCLUSION: Due to their anatomical origin, paramacular colobomata are always located temporal to the macula and have an oval football-shaped appearance. Visual acuity and visual field testing are usually normal, although highly observant patients may be aware of a mild scotoma. Differential diagnosis is important because the clinical appearance can be similar to acquired conditions, most notably age-related macular degeneration and presumed ocular histoplasmosis syndrome.     

Disease of the Year 2019: Ocular Toxoplasmosis in HIV-infected Patients

ABSTRACT

Ocular toxoplasmosis (OT) may be an initial manifestation of acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus (HIV)-infected patients. OT has different clinical manifestations and can mimic other intraocular infections. Clinical findings may show single or multifocal retinochoroidal lesions or panuveitis. Atypical presentations are associated with extensive uni- or bilateral areas of retinal necrosis. OT lesions not associated with preexisting retinochoroidal scars are usually due to acquired rather than congenital infection. When CD4+ T cell counts are <100 c/uL, vitritis is frequently mild. Isolated anterior uveitis has been reported in single cases. Positive immunoglobulin M (IgM) antibodies are rare but their presence can support the diagnosis. As atypical presentations of OT are common, anterior chamber puncture for multiplex polymerase chain reaction amplification of infectious DNA should be considered, as early diagnosis and treatment can prevent massive tissue destruction and preserve vision. This review provides an overview of OT in HIV–infected patients.     

Rift Valley fever ocular manifestations: observations during the 1977 epidemic in Egypt.

Ocular manifestations resulting from Rift Valley fever (RVF) virus infection were studied during an extensive RVF epidemic in Egypt during 1977. Colour photography and fluorescein angiography of 7 serologically diagnosed patients showed the commonest manifestations to be macular, paramacular, and/or extramacular retinal lesions, often occurring bilaterally. Haemorrhage and oedema were frequently associated with the lesions, and vasculitis, retinitis, and vascular occlusion were also observed. Patients were monitored during a 6-month convalescence, and, though resorption of the lesions occurred, approximately half the patients experienced permanent loss of visual acuity. Ocular disease was one form of the clinical spectrum of RVF; acute febrile, encephalitic, and fatal haemorrhagic RVF illnesses were also observed during the epidemic.     

Epidemiology of Ocular Toxoplasmosis

Retinal infection with Toxoplasma gondii is the most important cause of posterior uveitis, whereby prevalence and incidence of ocular symptoms after infection depend on socio-economic factors and the circulating parasite genotypes. Ocular toxoplasmosis is more common in South America, Central America, and the Caribbean and parts of tropical Africa as compared to Europe and Northern America, and is quite rare in China. Ocular disease in South America is more severe than in other continents due to the presence of extremely virulent genotypes of the parasite. Drinking untreated water is considered the major source of Toxoplasma infection in developing countries, whereas in the Western world the consumption of raw or undercooked meat (products) is the most important cause. Since acquired infection with T. gondii is currently a more important cause of ocular toxoplasmosis compared to congenital infection, prevention should be directed not only toward pregnant women but toward the general population.     

Bilateral macular dysplasia (''colobomata'') and congenital retinal dystrophy.

Three unrelated patients with bilateral macular dysplasia ('colobomata') with no relevant family history were found to have absent or substantially abnormal electroretinograms, implying that there was an associated retinal dystrophy. This may suggest that the macular lesions are associated with a global failure of retinal development, with a regional preponderance rather than a purely localised cause such as an intrauterine infection. It is important to distinguish between congenital infections such as toxoplasmosis and developmental macular colobomata, which have a somewhat similar ophthalmoscopic appearance as a cause of bilateral macular abnormalities seen in young children, since they have different implications for genetic advice and future ophthalmic care.     

Macular coloboma type Leber's congenital amaurosis

Three brothers, with the macular coloboma type Leber's congenital amaurosis aged 10, 8, and 6 years respectively, are described in this report. Only the two elder brothers were symptomatic while the third patient had no complaint at the time of diagnosis. The patients had no associated systemic or ocular disorders, including nystagmus. They had mild myopic astigmatism. All three had a relatively well-circumscribed bilateral macular atrophy with a seemingly normal peripheral retina. The electroretinogram was non recordable but the visualy evoked potential responses were within normal limits. During three years of follow-up, the macular lesions did not progress and the visual acuity did not deteriorate further. Our experience with these three familial cases supports the general view that the macular coloboma variant does not necessarily have the typical signs and symptoms and perhaps also the dismal prognosis of classic Leber's congenital amaurosis, and as such should stand as a distinct subtype of the disease.     

Atypical macular coloboma: a case report

CLINICAL CASE: This was a 15-month-old boy who had macular retinochoroidal lesions in both eyes following maternal varicella during pregnancy. DISCUSSION: The scars were suggestive of congenital chorioretinal infection, but because of negative serology and the clinical picture, we believe the problems are atypical macular colobomata.     

Ocular toxoplasmosis I: parasitology,epidemiology and public health

Ocular toxoplasmosis results from retinal infection with the protozoan, Toxoplasma gondii. This parasite, which exists as multiple clonal subpopulations and in three stages, is capable of replication in any nucleated cell of its primary feline or multiple paratenic hosts. Human seroprevalence of toxoplasmosis is high across the globe, but with geographic variation. While prevalence of ocular toxoplasmosis is not well documented, toxoplasmic retinochoroiditis is the commonest form of posterior uveitis in many countries. Correlation of parasite genotype with disease is an important area of new research. Ocular infection with T. gondii often follows ingestion of bradyzoites in undercooked infected meat. Oocysts may survive for an extended period in the environment, and water contaminated with oocysts is an important source in toxoplasmosis epidemics. Ocular toxoplasmosis is preventable by a combination of community activities and personal measures. Public health action is well justified by the considerable burden of congenital and postnatal infections.     

Characterization of optical coherence topography findings in Kenny-Caffey syndrome.

An unusual congenital syndrome was first reported in 1966 by Kenny and Linarelli, who described two patients with dwarfism, cortical thickening of the long bones, transient hypocalcemia, and normal intelligence,(1) the radiological features in the condition being reported by Caffey.(2) The constellation of dwarfism, medullary stenosis, transient hypocalcemia, and ophthalmologic abnormalities has been classically recognized as Kenny-Caffey syndrome with additional manifestations ranging from hypoplastic nails, persistent neutropenia, abnormal T-cell function, and neonatal liver disease.(3) Ocular findings range from uncomplicated nanophthalmos with hypermetropia to extreme pseudopapilloedema, vascular tortuosity, and macular crowding. Other reported ophthalmic findings include bilateral band keratopathy,(4) bilateral optic atrophy,(5) and myelinated nerve fibers.(6) We report two cases of Kenny-Caffey syndrome with an ellipsoid macular fold orientated horizontally involving the fovea and document this unusual feature with optical coherence topography (OCT).     

Bilateral congenital glaucoma in a child with cutis marmorata telangiectatica congenita: a case report

BACKGROUND: Cutis marmorata telangiectatica congenita is a rare, cutaneous and vascular anomaly characterised by congenital cutis marmorata, telangiectasis, and phlebectasia. Systemic abnormalities are frequently associated with this condition, although they may be highly variable. Ocular abnormalities are quite rare and include retinal detachment and congenital glaucoma. If glaucoma is present it is unilateral in most cases. CASE REPORT: A case of bilateral congenital glaucoma associated with cutis marmorata telangiectatica congenita in a 4-month-old girl is presented. Follow-up and treatment over a four-year period are reported. CONCLUSION: Congenital glaucoma is a rare ophthalmic condition encountered in patients with cutis marmorata telangiectatica congenita. If glaucoma is present it is most likely unilateral, although cases of bilateral glaucoma in these patients occur. Regular ophthalmological examinations are recommended for children with cutis marmorata telangiectatica congenita--especially if characteristic skin changes are present in the face.     

Bilateral Full Thickness Macular Holes in Association With Serpiginous Choroiditis

Purpose: To report serpiginous choroiditis associated with full thickness macular holes (FTMH).

Design: Interventional case report.

Methods: A 58-year-old female with bilateral serpiginous choroiditis developed right-sided blurred vision and metamorphopsia. Ocular assessment, FFA, OCT, and right macular hole surgery were performed.

Results: Preoperative visual acuity was 6/36 right, 6/9 left. Fundus assessment found bilateral geographic chorioretinal scarring, epiretinal membranes, right FTMH, and mild vitritis. OCT revealed bilateral FTMHs. Pars plana vitrectomy, membrane peel, and gas tamponade resulted in right macular hole closure, visual acuity improvement (6/18) and resolution of metamorphopsia.

Conclusions: Macular hole may be another posterior segment complication of serpiginous choroiditis.