Ординатура / Офтальмология / Учебные материалы / Uveitis Text and Imaging Text and Imaging Text and Imaging 2009

lesion at the centre of the fovea is best imaged with the OCT, as FFA only rarely may demonstrate early foveal hyperfluorescence. OCT is able to image a corresponding area of focal outer neurosensory retinaRPE thickening at the foveal centre (Figure 5). It is also useful for monitoring clinical progress.9

OCT is also useful for assessing the severity and monitoring the progress of neurosensory retinal detachment (Figure 3) in 15% of eyes with retinal vascular leakage. Macular cystic spaces were starkly absent in macula oedema associated with dengue maculopathy. 9

TREATMENT

It is unclear if treatment is beneficial nor what is the optimal modality of treatment, as the disease may be self-limiting and there have been no prospective randomised trials on therapy to date. Immunosuppression with topical, periocular, oral, intravenous steroids and immune globulins has been attempted with variable success.9

KEY POINTS

1.Three commonest fundal manifestations are retinal haemorrhage, venular sheathing and yellow subretinal dots.

2.Most common findings on fluorescein angiogram are: blocked fluorescence (retinal haemorrhage), venular occlusion and leakage.

3.Indocyanine green angiography in the mid to late phases may manifest hypofluorescent dark dots corresponding

to the yellow subretinal lesions, suggesting involvement of the choriocapillaries. More hypofluorescent dots may be seen on ICG than those that are clinically evident.

4.Indocyanine green angiography may show the presence of large choroidal vasculopathy.

5.Optical coherence tomogram is indispensable in detecting and monitoring the progress of foveolitis, seen clinically as a round yellowish lesion at the fovea.

6.Optical coherence tomogram is also useful for assessing the severity and charting the progress of exudative retinal detachment.

REFERENCES

1.World Health Organization. Dengue Hemorrhagic Fever: Diagnosis, Treatment and Control (2nd edn), Geneva, Switzerland: WHO; 1997.

2.Ministry of Health, Singapore. Communicable diseases surveillance in Singapore 2003. Ministry of Health, Singapore. 2004:105. Available at: http://www. moh.gov.sg/corp/publications/CDS2003. Accessed March 2, 2007.

3.Wen KH, Sheu MM, Chung CB, Wang HZ, Chen CW. [In Chinese] The ocular fundus findings in dengue fever. Gaoxiong Yi Xue Ke Xue Za Zhi 1989;5:24-30.

4.Haritoglou C, Scholz F, Bialaslewicz A, Klauss V. Ocular manifestations in dengue fever. [In German] Ophthalmologe 2000;97:433-6.

5.Haritoglou C, Dotse SD, Rudolph G, Stephan CM, Thurau SR, Klauss V. A tourist with dengue fever and visual loss. Lancet 2002;360:1070.

6.Lim WK, Mathur R, Koh A, Yeoh R, Chee SP. Ocular manifestations of dengue fever. Ophthalmology 2004;111: 2057-64.

7.Chlebicki MP, Ang B, Barkham T, Laude A. Retinal haemorrhages in 4 patients with dengue fever. Emerg Infect Dis [serial on the Internet] 2005 May Available at http://www.cdc.gov/ncidod/EID/vol11/n005/040992.htm

8.The Eye Institute Dengue-related Ophthalmic Complications Workgroup. Ophthalmic complications of dengue. Emerg Infect Dis [serial on the Internet]. 2006 Feb Available at http://www.cdc.gov.ncidod/EID/vol12no02/050274.htm

9.Bacsal K, Chee SP, Cheng CL, Flores JVPG. Dengue-asso- ciated maculopathy. Arch Ophthalmol 2007;125:501-10.

10.Kapoor HK, Bhai S, John M, Xavier J. Ocular manifestations of dengue fever in an East Indian epidemic. Can J Ophthalmol 2006;41:741-6.

11.Mehta S. Ocular lesions in severe dengue hemorrhagic fever (DHF). J Assoc Physicians India 2005;53:656-7.

12.Cruz-Villegas V, Berrocal AM, Davis JL. Bilateral choroidal effusions associated with dengue fever. Retina 2003;23: 576-8.

13.Siqueira RC, Vitral NP, Campos WR, Orefice F, de Moraes Figueiredo LT. Ocular manifestations in dengue fever. Ocul Immunol Inflamm 2004;12:323-7.

14.Su DHW, Bacsal K, Chee SP, et al. Prevalence of dengue maculopathy in patients hospitalized for dengue fever. Ophthalmology 2007;114:1743-7.

15.Chia A, Luu CD, Mathur R, Cheng B, Chee SP. Electrophysiological findings in patients with dengue-related maculopathy. Arch Ophthalmol 2006;124:1421-6.

Padmamalini Mahendradas

INTRODUCTION

Chikungunya virus is a single-stranded RNA virus of the genus Alphavirus in the family Togaviridae. It is transmitted to humans by the bite of infected mosquitoes, primarily Aedes aegypti,1 and sometimes by Aedes albopictus. Chikungunya fever is a debilitating viral infection caused by chikungunya virus, first described by Robinson2 and Lumsden3 in 1955. Its name is derived from Makonade word meaning “that which bends up,” in reference to the stooped posture developed as a result of arthritis.

Epidemic of chikungunya fever has been reported in the past from different parts of the world.4 Although the virus had been passive for quite sometime, recent reports of outbreaks of chikungunya fever in several parts of southern India have confirmed the reemergence of the virus.5

SYSTEMIC MANIFESTATIONS

Chikungunya virus was recognised to cause illness that was self limiting and characterised by sudden onset of fever with chills, headache, malaise, arthralgia

or arthritis, vomiting, myalgia, skin rash and low back pain. Incubation period is about 2-4 days. Although chikungunya fever typically lasts for 3-7 days and recovery is usually the outcome, yet certain patients experienced persistent joint symptoms for weeks or months and occasionally years after the initial onset of illness. Neurological complications such as meningoencephalitis have been reported during the first Indian outbreak as well as the recent French Reunion island’s outbreak.7 Mother-to-child transmission of chikungunya virus was a new observation recorded during the recent outbreak in the French Reunion island.

Many complications including death have been reported in the current outbreak. The increased virulence

has been attributed to absence of the herd immunity as well as the possible emergence of a new strain.6,7

OCULAR MANIFESTATIONS

Ocular manifestations associated with Chikungunya can be present at the time of systemic illness or after resolution of systemic disease. Ocular involvement can be unilateral or bilateral. Ocular symptoms include redness, blurred vision, floaters, pain, watering, photophobia, irritation and diplopia.

Numerous ocular features have been described, including conjunctivitis,8 iridocyclitis,9,11,13 episcleritis,9 scleritis, keratitis,11 retinitis,9 choroiditis,10 neuroretinitis,11 panuveitis,11 optic neuritis,11,12 central retinal

artery occlusion,11 exudative retinal detachment,11 secondary glaucoma,9,13 cranial nerve palsies,11 and lagophthalmos. Iridocyclitis and retinitis are the most common manifestations of chikungunya, with a typically benign clinical course. Iridocyclitis can have a nongranulomatous or granulomatous presentation which can be associated with increased intraocular pressure (Figures 1A-D). Chikungunya retinitis occurs several weeks after the primary illness, which is similar

to herpetic retinitis in immunocompetent individuals, the former is characterised by minimal vitritis, retinitis and retinal edema (Figures 2 and 3). The retinal vessel involvement in the posterior pole may be associated with haemorrhage, whereas in acute retinal necrosis multifocal retinitis lesions with severe vitritis are seen primarily in the retinal periphery (Figures 2A-D). Chikungunya retinitis should also be differentiated from cytomegalovirus retinitis, which occurs in

immunodeficient individuals. Although chikungunya retinitis may morphologically mimic the herpetic viral retinitis, the history of fever, joint pains and skin rash prior to the onset of the visual symptoms are helpful in the clinical diagnosis, particularly in the endemic regions. Chikungunya retinitis may also mimic rickettsiosis retinitis, which is typically associated with a history of high fever and skin rash.

Chikungunya clinically resembles dengue, and hence should be differentiated from dengue fever, by absence of dengue IgM and IgG antibodies in the serum and also by platelet count.

PATHOGENESIS

The systemic manifestation of the fever may be related to viraemia, and in the case of joints involvement it is believed to be immune mediated from the viral antigen and antibody reactions.

Exact mechanism of ocular involvement following chikungunya infection remains unknown. Simultaneous occurrence of systemic and ocular disease suggests the possibility of direct viral involvement of ocular structures. Late involvement of ocular tissue suggests a delayed immune response. Antigenic mimicry between the stimulating virus derived antigens and normal or altered host tissue proteins, immediate hypersensitivity reactions and stimulation of a pathogenic lymphocytic reaction may be responsible for this delayed immune response.14

However, further studies are required to address the exact pathogenesis of the ocular changes.

DIAGNOSIS

Confirmation of chikungunya virus infection can be performed by reverse transcriptase-polymerase chain reaction or by virus isolation.15 These are rapid confirmatory tests of choice if the illness is of less than four days duration. Beyond four days diagnosis is possible only with the detection of chikungunya specific IgM in the serum.16 Syphilis, tuberculosis, sarcoidosis, rickettsiosis, dengue, herpes, cytomegalovirus and human immunodeficiency virus infections are to be ruled out.

The temporal association between the systemic manifestations, the ocular changes and the positive IgM serology will help us to make a diagnosis of chikungunya associated ocular changes.

MANAGEMENT

Chikungunya fever is managed by the use of nonaspirin analgesics and antipyretics. Chloroquine phosphate is used for joint pains.17 Topical steroids and cycloplegic agents are used for anterior uveitis.

Associated ocular hypertension is managed with topical beta blockers and oral or topical carbonic anhydrase inhibitors. Systemic steroids are used to control the inflammation in posterior uveitis, panuveitis, and optic neuritis. No specific antiviral therapy is available for chikungunya. However few cases have been empirically treated with acyclovir, along with systemic steroids9 (Figures 3A-I). The efficacy of acyclovir against chikungunya is doubtful, and further studies are needed to address this issue.

PREVENTION

There is no vaccine that protects one against chikungunya virus. Prevention and control depend on surveillance, early identification of outbreak, vector control and by use of protective measures to prevent being bitten by an infected mosquito.

Ocular manifestations of chikungunya virus infection are likely to be encountered during an epidemic. Ophthalmologists should be aware of the ocular manifestations of chikungunya infection, which can result in permanent visual impairment.

KEY POINTS

1.Chikungunya fever is a debilitating viral infection caused by a single stranded RNA virus of the genus Alphavirus.

2.Chikungunya virus infects human following bite of an infected Aedes aegypti and to lesser extent Aedes albopictus.

3.Incubation period is about 2-4 days. Systemic features include sudden onset of fever with chills, headache, malaise, arthralgia or arthritis, myalgia, vomiting and skin rash.

4.Ocular features can be present at the time of fever or can manifest after many weeks or months with conjunctivitis, episcleritis, keratitis, iridocyclitis, retinitis,

choroiditis, neuroretinitis, panuveitis, optic neuritis, central retinal artery occlusion, exudative retinal detachment, lagophthalmos, cranial nerve palsies and secondary glaucoma. Iridocyclitis and retinitis are the most common ocular manifestations of Chikungunya.

5.Diagnosis of Chikungunya can be made by demonstration of Chikungunya IgM antibody in the serum and also by reverse-transcriptase-polymerase chain reaction (RT-PCR) analysis.

6.In absence of specific antiviral regimen, the treatment of systemic or ocular disease is supportive. Topical and systemic steroids are used for intraocular inflammation.

7.Prevention using protective measures against mosquito bite is the mainstay for control of Chikungunya disease. No vaccine is available at present.

REFERENCES

1.Calisher CH, Shope RE, Brandt W, et al. Proposed antigenic classification of registered arboviruses I (Togaviridae, Alphavirus). Intervirology 1980;14:229-32.

2.Robinson MC. An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952-53. I. Clinical features. Trans R Soc Trop Med Hyg 1955;49:28-32.

3.Lumsden WH. “An Epidemic of Virus Disease in Southern Province, Tanganyika Territory, in 1952-53; II. General Description and Epidemiology”. Trans Royal Society Trop Med Hyg 1955;49:33-57.

4.WHO. Disease outbreak news: Chikungunya and Dengue in the south west Indian Ocean. 17 March, 2006;http:// www.who.int/csr/don/2006_03_17/en. (Accessed 10 January 2008).

5.WHO. Disease outbreak news: Chikungunya in India. 17 October, 2006: www.who.int/csr/don/2006_10_17/ en.(accessed 10 January 2008).

6.Mourya DT, Mishra AC. Chikungunya fever. Lancet 2006; 368:186-7.

7.Schuffenecker I, Iteman I, Michault A, Murri S, Frangeul L, Vaney MC, et al. Genome microevolution of chikungunya viruses causing the Indian Ocean outbreak. PLoS Med 2006;3: e263.

8.Parola P, Lamballerie X, Jourdan J, et al. Novel chikungunya virus variant in travelers returning from Indian Ocean islands. Emerg Infect Dis Volume 12, Number 10 2006 Oct. http://www.cdc.gov/ncidod/EID/vol12no10/ 06-0610.htm Accessed December 15th 2006

9.Mahendradas P, Ranganna SK, Shetty R, Balu R, Narayana KM, Babu RB, Shetty BK. Ocular manifestations associated with chikungunya. Ophthalmology 2008;115:287-91.

10.Chanana B, Azad RV, Nair S. Bilateral macular choroiditis following chikungunya virus infection. Eye 2007;21(7): 1020-1.

11.Lalitha P, Rathinam S, Banushree K, Maheshkumar S, Vijayakumar R, Sathe P. Ocular involvement associated with an epidemic outbreak of chikungunya virus infection. Am J Ophthalmol 2007;144(4): 552-6.

12.Mittal A, Mittal S, Bharati MJ, Ramakrishnan R, Saravanan S, Sathe PS. Optic neuritis associated with Chikungunya virus infection in South India. Arch Ophthalmol 2007;125(10):1381-6.

13.Mittal A, Mittal S, Bharathi JM, Ramakrishnan R, Sathe PS. Uveitis during outbreak of chikungunya fever. Ophthalmology 2007;114(9):1798.

14.Mahalingam S, Meanger J, Foster PS, Lidbury BA. The viral manipulation of the host cellular and immune

environments to enhance propagation and survival: a focus on RNA viruses. J Leukoc Biol 2002;72:429-39.

15.Rohani A, Yulfi H, Zamree I, Lee HL. Rapid detection of chikungunya virus in laboratory infected Aedes aegypti by reverse-transcriptase-polymerase chain reaction (RTPCR). Trop Biomed 2005;22(2):149-54.

16.Kumarasamy V, Prathapa S, Zuridah H, Chem YK, Norizah I, Chua KB. Re-emergence of chikungunya virus in Malaysia. Med J Malaysia 2006;61(2):221-5.

17.Brighton SW. Chloroquine phosphate treatment of chronic chikungunya arthritis. An open pilot study. S Afr Med J 1984;66:217-8.

DEFINITION

Rift Valley fever (RVF) is an arthropod-borne viral disease caused by Bunyaviridae, primarily affecting domesticated cattle. It is transmitted to humans through a bite by infected mosquitoes or through direct contact with infected animals.1 The disease was first described in the Rift Valley of Kenya in 1930.2 Since, several outbreaks have been reported in subSaharan and North Africa, and more recently in Arabian Peninsula.

SYSTEMIC MANIFESTATIONS

Human exposure to the virus is often occupational, either through handling infected livestock or their products or by breathing in aerosols released at slaughter. Mosquito bites and the consumption of raw milk have been documented as routes of exposure. The incubation period in humans is generally from 3 to 7 days, followed by one of 3 clinical syndromes.

The most common clinical syndrome is an uncomplicated, febrile, influenza like illness. The main symptoms are fever with biphasic temperature curve, headache, arthralgias, myalgias, and gastrointestinal disturbances.3 The fever subsides in 12 to 36 hours, and the other symptoms are relieved within four days. Other clinical presentations include a haemorrhagic fever with liver involvement, thrombocytopenia, icterus and bleeding tendencies; and a neurologic involvement with encephalitis following a febrile episode with confusion and coma. Death is infrequent but there may be some residual damage.

OCULAR MANIFESTATIONS

Ocular involvement has been reported to occur in 1 to 20% of RVF infections.2-8 Al-Hazmi et al8 recently

reported the largest series (30 hospitalised patients and 113 outpatients) of serologically proven RVF with ocular manifestations during an outbreak in Saudi Arabia. The mean interval between the onset of RVF and visual symptoms ranged from 4 to 15 days. Macular or paramacular retinitis was identified in all the affected eyes at the time of initial assessment (Figures 1A and 2A). Other lesions included retinal haemorrhages (40%), vitreous reactions (26%), optic disc oedema (15%), and retinal vasculitis (7%). Anterior uveitis was present in 31% of outpatients. Fluorescein angiography of the retinitis showed early hypofluorescence with late staining of retinal lesions and blood vessels. Symptoms resolved spontaneously within 2 to 3 weeks from the onset of systemic symptoms and did not result in complications such as glaucoma, posterior synechiae, or cataract. Initial visual acuity was less than 20/200 in 80% of eyes in the outpatient group. Vision remained the same or deteriorated in 87% of eyes. Evaluation at the last follow-up showed macular (60%) or paramacular (9%) scarring, vascular occlusion (23%), and optic atrophy (20%) in the outpatient group (Figures 1B and 2B).

DIAGNOSIS

Once an outbreak is recognised and early cases are proven, it becomes much easier to diagnose further cases of RVF. The most popular method of laboratory diagnosis uses serology to detect antibodies, either IgM antibodies in a single serum sample, or by detecting a rising titre of IgG antibody in acute and convalescent serum samples.9 In patients with encephalitis, cerebrospinal fluid may be tested for locally produced IgM. With the presence of equipped virological laboratories, RVF virus can be isolated from blood in

the acute phase of illness. Finally, PCR detects the viral nucleic acid sequence of the RVF virus both in serum and tissue.10

The differential diagnosis for RVF retinitis includes other viral entities such as measles, rubella, influenza, dengue fever, and West Nile virus infection. These diseases can be differentiated from RVF by clinical history and serologic testing. Other haemorrhagic fever viruses have been reported to have ocular involvement such as Hantaavirus, Puumala, Marburg, and Ebola viruses.11

Some bacterial infections have been reported to cause retinitis. These mainly include rickettsial

infection, Lyme disease, and cat scratch disease. These diseases can be ruled out with serologic testing.

TREATMENT

Treatment is entirely supportive. For mild to moderate cases of RVF simple analgesia and fluids can be administered. For patients who develop severe disease, including encephalitis, and haemorrhage, early recognition and aggressive critical care, including assisted ventilation and blood product transfusion is essential, for any hope of survival.11

Intensified mosquito control methods must be implemented in areas of epizootic and human RVF