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

activity. An increased awareness of RVF among both residents and visitors to endemic areas is paramount to the future control and prevention of outbreaks. Education regarding modes of disease transmission and necessary precautions, especially protection against mosquito bites is vital.12

PROGNOSIS

Most cases of human RVF manifest as a mild selflimited influenza like illness.11 However, ocular involvement is frequently associated with permanent visual loss resulting from macular and paramacular scarring, vascular occlusion, and optic atrophy.

KEY POINTS

•RVF infection should be considered in the differential diagnosis of macular or paramacular retinitis in a patient living in or returning from a specific endemic area, especially during confirmed outbreaks of the disease.

•Prevention is the mainstay of RVF infection control. It principally relies on intensified mosquito control methods.

•The differential diagnosis for RVF retinitis includes other viral and nonviral entities.

•Treatment is entirely supportive.

•Although in most symptomatic cases of RVF infection recovery is uneventful and complications are exceptional, ocular involvement lead to profound visual loss in most cases.

REFERENCES

1.Ellis DS, Simpson DI, Stamford S, Abdel Wahab KS. Rift Valley fever virus: some ultrastructural observations on material from the outbreak in Egypt 1977. J Gen Virol 1979;42:329-37.

2.Daubney R, Hudson JR, Garnham PC. Enzootic hepatitis or Rift Valley fever: an undescribed virus disease of sheep, cattle and man from East Africa. J Pathol Bacteriol 1931;34:545-79.

3.Meegan JM, Watten RH, Laughlin LW. Clinical experience with Rift Valley fever in humans during the 1977 Egyptian epizootic. Contrib Epidemiol Biostatics 1981;3:114 -23.

4.Siam AL, Meegan JM, Gharbawi KF. Rift Valley fever ocular manifestations: observations during the 1977 epidemic in Egypt. Br J Ophthalmol 1980;64:366-74.

5.Elwan MS, Sharaf MH, Gameel K, et al. Rift Valley fever retinopathy: observations in a new outbreak. Ann Saudi Med 1997;17:377-80.

6.Mundel B, Gear J. Rift Valley fever: The occurrence of human cases in Johannesburg. S Afr Med J 1951;25:797-800.

7.Laughlin LW, Meegan JM, Strausbaugh LJ, et al. Epidemic Rift Valley fever in Egypt: observations of the spectrum of human illness. Trans R Soc Trop Med Hyg 1979;73:630-3.

8.Al-Hazmi A, Al-Rajhi AA, Abboud EB, et al. Ocular Complications of Rift Valley Fever Outbreak in Saudi Arabia. Ophthalmology 2005;112:313-8.

9.Olaleye OD, Tomori O, Ladipo MA, Schmitz AH. Rift Valley fever in Nigeria: infections in humans. Revue Scientifique et Technique 1996;15:923-35.

10.Garcia LL, Crance JM, Billecocq A, et al. Quantitative realtime PCR detection of Rift Valley fever virus and its application to evaluation of antiviral compounds. Journal of Clinical Microbiology 2001;39:4456-61.

11.Peters CJ. Bunyaviridae. In: Principles and practice of infectious disease, 5th ed. Philadelphia: Churchill Livingstone, 2000:1849-55.

12.Pollack RJ, Eiszewski AE, Spielman A. Repelling mosquitoes. New England Journal of Medicine 2002;347:2-3.

Amod Gupta, Vishali Gupta

Unlike uveitis in adults, uveitis in children poses challenges of a different kind for both the ophthalmologist as well the parents. Confronted with the prospect of their child becoming blind, the parents are highly anxious1 and the ophthalmologist will need to draw upon all his experience, time and patience to allay their fears besides making a diagnosis of uveitis and designing an effective management strategy. Moreover, uveitis in small children is often asymptomatic as they do not complain and the eye remains white. In the absence of history, duration of uveitis is not known. It may be detected either during the course of a routine eye checkup/screening in children with systemic inflammatory diseases or as is most common, parents detect the loss of vision when they find the child fumbling and striking against objects in her/his path at a time when the vision is already seriously compromised due to complications of uveitis.

Very small children need to be examined under general anaesthesia limiting the examination under microscope to evaluation only of adnexa, cornea, extent of synechiae, cataract, measurement of intraocular pressure and fundoscopy. However, one of the most important evaluations in uveitis i.e. the severity of inflammation cannot be done reliably as not many ophthalmologists have access to a microscope mounted slit lamp that is required for examination of a supine child under general anaesthesia.

Further, administration of eye drops or drugs in children is a daunting task and hence there are serious

concerns with compliance. All these factors lead to a high complication rate of uveitis in children and even in successfully treated children, development of amblyopia and its effective management remains a major issue.

DEMOGRAPHY OF UVEITIS IN CHILDREN

Uveitis in children is distinctly uncommon and may vary from 5 to 10 percent of all uveitis patients in large tertiary referral centres.2,3 Girls appear to develop uveitis slightly more frequently than boys.2 Anterior uveitis may account for 30-40 percent, posterior uveitis for 40-50 percent,intermediate uveitis for 10-20 percent and panuveitis for 5-10 percent.2The most common cause of anterior uveitis is juvenile idiopathic arthritis while the most frequent cause of posterior uveitis is toxoplasmic retinchoroditis. Most cases of intermediate uveitis and diffuse uveitis are bilateral, chronic and idiopathic.2

In a population based study in Finland, 4.9 percent of all uveitis were in children under 16 years. In this population 90.9 percent had anterior uveitis.4 In a large tertiary clinic in the US, of the 130 children with onset of uveitis before the age of 16 years, uveitis associated with juvenile rheumatoid arthritis was the largest group (41.5%) followed by idiopathic uveitis in 21.5 percent and pars planitis in 15.3 percent.3 In a later study from the same institute, 269 of the 1242 patients (21%) had childhood uveitis and 53.5 percent were

girls at a median age of 8 years. Anterior uveitis was present in 56.9 percent, intermediate uveitis in 20.8 percent, panuveitis in 16 percent and posterior in 6.3 percent. Uveitis was bilateral in 74.4 percent and nongranulmatous in 77.6 percent and non infectious in 85.7 percent. Diagnosis was established in 48 percent and remained idiopathic in 52 percent.No systemic associations were found in 58 percent of patients and JIA was responsible in 33 percent of cases.5 In our uveitis clinic in a tertiary care institute in India, ~5 percent of all uveitis patients belonged to the paediatric age group. In a group of 188 children with uveitis, who were followed up to 10 years with a mean follow up of 45 months and median follow up of 11 months, 100 were male and 88 female (unpublished data). However, ~90 percent of uveitis in pediatric age group was seen in children above the age of 5 years, with 25 percent in ages between 6-10 years and 65 percent in ages between 11-14 years. Only 16 children (8.5%) were aged <5 years. Uveitis was bilateral in 103 children (54.8%).

PRESENTING SYMPTOMS

In our experience, fifty eight children (31%) were symptomatic with pain, tearing and photophobia. In 30 children (16%), uveitis was detected during routine examination by the ophthalmologist. However, in 72 children (38%) there was already severe visual loss, strabismus in 12 (6%) and leucocoria in 16 (9%) when noticed by the parents.

ANATOMICAL AND ETIOLOGICAL DISTRIBUTION OF UVEITIS IN CHILDREN (TABLE 1)

In nearly two-third of children, uveitis was ascribed to a specific etiology.

ANTERIOR UVEITIS IN CHILDREN

Of 188 children with uveitis, 77 had anterior uveitis (40.95%), of whom 27 (35%) were due to unknown

Table 1: Anatomical and etiological distribution of uveitis in children

cause. In 50 children (65%) a specific diagnosis could be reached (Table 2).

Table 2: Etiology of anterior uveitis in children

JIA-Juvenile idiopathic arthritis; FU-Fuchs’ uveitis; HSV-Herpes Simplex Virus; VZV-Varicella-Zoster Virus.

POSTERIOR UVEITIS IN CHILDREN

Of 57 children (30.31%of all children with uveitis) seen by us with posterior uveitis specific diagnosis could be reached in 38 (66.6%) and is shown in Table 3.

Table 3: Etiology of posterior uveitis in children

VKH-Vogt- Koyanagi-Harada’s disease; APMPPE-Acute posterior multifocal placoid pigment epitheliopathy

PAN UVEITIS IN CHILDREN

In our experience of 38 children (20.74% of all children with uveits) with pan uveitis specific diagnosis could be reached in 28 (73.68%) and is shown in Table 3.

Table 4: Etiology of panuveitis in children

It is widely believed that it is difficult to accurately record visual acuity in children. In our experience, it was possible to record best corrected visual acuity in 177 of the 188 children (94%). Of the remaining 11 children, 4 were less than 5 years and only 7 children could not be persuaded to accurately read the chart.

SLITLAMP EXAMINATION

It was possible to examine 94 percent of the children on the slit lamp biomicroscope. Examination can be greatly facilitated by providing a wooden block of appropriate size so that child can stand erect .The chin rest should be adjusted to make the child comfortable. Slitlamp as it is moved forward to focus on the eye often hits the protruding abdomen especially in babies sitting in the lap of a parent resulting in a crying baby and examination failure. Both parent and baby should be comfortably seated to ensure a satisfactory examination.

Figure 2: Recording of intraocular pressure with a non contact tonometer in a small child.

POSTERIOR SEGMENT EXAMINATION

In our experience it is possible to examine posterior segment in all the children with uveitis provided the media permit, either using the +90D lens on the slit lamp biomicroscope or the binocular indirect ophthalmoscope.

FUNDUS FLUORESCEIN ANGIOGRAPHY

Figure 1: A 4 -year-old child undergoing +90 D lens examination standing comfortably on a wooden block

RECORDING OF INTRAOCULAR PRESSURE

In our experience, it was possible to record the intraocular pressure in ~90 percent of the children with uveitis (Figure 2) either with a Goldmann applanation tonometer (65%) or a non contact tonometer (25%).

Fundus fluorescein angiography was required as an ancillary investigation in nearly 55 percent of the children with uveitis and it could be done successfully in 80 percent of the patients. In the remaining 20 percent it could not be done because of poor media in 9 percent and lack of cooperation in 11 percent.

ULTRASONOGRAPHY

Ultrasonographic evaluation is essential in childhood uveitis since many of them have opaque media because of band shaped keratopathy, dense posterior synechiae or complicated cataract. It is possible to do this investigation in all children with uveitis. If the child is uncooperative it may have to be done under general anaesthesia for it yields very useful information on the status of the vitreous, choroidal detachment and tractional, exudative or rhegmatogenous retinal detachment. Very often long forgotten intraocular foreign bodies may masquerade as uveitis and in that sense all children with uveitis who have unclear media should undergo ultrasonogrphy.

ULTRASONGRAPHIC BIOMICROSCOPY (UBM) EXAMINATION

UBM is an important investigation in evaluation of uveitis in children since the visual outcome of chronic uveitis in these patients depends largely on the status of the ciliary processes including atrophy, tractional detachment or the formation of cyclitic membranes. Even in adults it requires a great deal of cooperation on the part of the patient. Of the 26 children where in we did this procedure, it could be successfully accomplished in 16 (61%). We believe that in children with chronic hypotony, UBM is one of the most critical evaluations before taking up the patient for pars plana lensectomy and vitrectomy and if need be, it should be done under general anaesthesia.

EXAMINATION UNDER GENERAL ANAESTHESIA

Under special circumstances when children are either very small or highly uncooperative, they may have to be examined under general anaesthesia especially for

recording of intraocular pressure, ultrasonography or the UBM examination. In very small children who may be suspected of masquerade syndrome, aqueous or vitreous tap may be required under general anaesthesia for reaching a conclusive diagnosis. If indicated general anaesthesia should be preferred in children for giving posterior subtenon injection of corticosteroids.

DIAGNOSTIC AND MANAGEMENT CHALLENGES IN CHILDHOOD UVEITIS

In extremes of ages, uveitis is distinctly uncommon and masquerades should be ruled out.

RETINOBLASTOMA

In children especially in the older age group, retinoblastoma may present as cellular reaction in the anterior chamber, vitreous infiltrates or lime white deposits in the anterior chamber (Figures 3A-F).In such unusual cases, diagnostic fine needle aspiration biopsies may become life saving by prompting institution of definitive therapy.

Figures 4A and B: A 7-year-old male child presented with acute uveitis with hypopyon (A). He was a known case of acute lymphoblastic leukemia in remission on chemotherapy. He posed a diagnostic dilemma as an opportunistic infective uveitis was seriously considered. An anterior chamber fine needle aspiration biopsy proved local recurrence of the leukemic infiltrates (B)

LEUKAEMIA

Besides retinoblastoma, children with acute lymphoblastic leukemia may present with signs of inflammation in the eye (Figures 4A and B). Iris infiltration, spontaneous hyphema and raised intraocular pressure are some other presentations. However, most of these patients are already known cases of leukemia. The leukemia relapse may be seen only in the anterior segment. Some of these children may have simultaneous relapse in the CNS or the bone marrow.6 Anterior chamber aspiration and/or iris biopsy are

essential procedures in their evaluation. Anterior segment relapse in these children is harbinger of poor survival.7

Hypopyon uveitis in children is distinctly uncommon and one should be aware of either an infective endophtalmitis from a trauma often not revealed to parents or the masquerade as discussed above. Ciliary granulomas may present as hypopyon uveitis (Figures 5A-E).

GRANULOMATOUS UVEITIS

Granulomatous uveitis is uncommon in children. In a large series, only 13.75 percent of uveitis in children was due to granulomatous uveitis.5 In children, Vogt- Koyanagi-Harada disease may present first as granulomatous uveitis since the children may not complain of the prodrome or the painless loss of vision that characterizes the stage of exudative retinal detachment (Figures 6-8).

MEDICAL MANAGEMENT

Use of frequently administered topical corticosteroids and short acting mydriatics and cycloplegics given 3-4 times a day are the mainstay of treatment in anterior uveitis. Use of atropine is reserved for severe cases. Uveitis in children often requires prolonged therapy. The drops need to be used frequently till the eyes become quiescent followed by slowly tapering. Even after stopping the treatment the child should be closely observed for a possible recurrence.

Posterior subtenon injections of depot steroids such as triamcinolone acetonide may be required in children with intermediate uveitis or chronic uveitis with hypotony. Occasionally, children who are intolerant of oral corticosteroids may also be given depot steroids. In our experience of 43 eyes requiring such injections, only one-third required general anaesthesia to facilitate the administration of the depot steroid. None of the eyes showed rise in intraocular pressure.

Effective management of childhood uveitis mandates a close cooperation and consultation between an experienced paediatric rheumatologist and the ophthalmologist with a common goal of bringing the inflammation under control at the earliest and at the same time preventing sight threatening complications. In our experience ~50 percent of children with

Figure 6: A 14-year-old girl presented with diminution of vision for one month. Her history was non contributory. She showed mutton fat keratic precipitates and granulomatous uveitis in both eyes

uveitis have required oral corticosteroids which was generally well tolerated. Major compliance issues were seen in 10 of the 83 (12%) patients who were treated on oral steroids. Wait gain was seen in 11 children while raised intraocular pressure developed in 3 patients. Corticosteroids however, can cause growth retardation, cushnoid habitus and osteoporosis, besides hypertension, psychosis, and hip necrosis.8 Juvenile idiopathic arthritis, the commonest cause of uveitis in children may require the use of immunosuppressive therapy for controlling the systemic inflammation. These drugs have potential for serious side effects including bone marrow suppression, alopecia, liver toxicity, infections and rarely malignancies.8 Of all the immunosuppressive agents, the most well tolerated in children is methotrexate given

weekly either orally or intramuscularly. Other alternative treatment regimens rarely may include use of azathioprine or intravenous once-a-month pulse therapy with cyclophosphamide in severe sight threatening uveitis. Cyclophosphamide is reserved for prepubertal children. Recent years have seen increasing use of immunoglobulins and TNF-á blocker drugs in children who are resistant to standard immunosuppressive therapy. Infliximab appears more effective in childhood uveitis than etanercept (98% versus 54%).9 Anaphylactic reactions were, however, a concern with infliximab therapy which have been addressed by the use of Adalimumab, a complete humanized anti TNF alpha antibody (Humira). In a

series of 18 children with refractory uveitis, adalimumab was effective in 88 percent of uveitis. Additional immunosuppressive therapy may be required in nearly half of the patients. Dosage and duration of treatment is still not very clear.10

COMPLICATIONS OF CHILDHOOD UVEITIS

Childhood uveitis is remarkable for the occurrence of a number of complications most of which are vision threatening. Onefourth to onethird of all children with uveitis have severe visual loss.2

Most believe that childhood uveitis has more complications than the adult uveitis. In a series of 148

childhood uveitis patients, 34 percent had one or more ocular complication at the time of diagnosis increasing to 61.6 percent by 3 months, 69.4 percent by 6 months, 75.2 percent by 1 year and 86.3 percent by 3 years of follow up.11Among the most common complications are band shaped keratopathy, complicated cataract, glaucoma and phthisis bulbi. In a series of patients, the rate for the band shaped keratopathy increased from 12.5 to 49.8 percent, cataract from 11.1 to 67.7 percent, posterior synechiae from 31.7 to 66.4 percent, glaucoma from 7.7 to 45.5 percent, cystoid macular edema from 10.4 to 48.8 percent and hypotony from 2.8 to 19.5 percent from 3 months to 10 years of follow up respectively.11

KEY POINTS

1.Uveitis in children is uncommon and only 5-10 percent of all the uveitis cases.

2.The diagnosis is often delayed as uveitis in children is asymptomatic and is seen in white eyes

3.The most common cause of uveitis in children is juvenile idiopathic arthritis.

4.Often children present with visual loss and complications such as cataract, band shaped keratopathy, glaucoma, hypotony and phthisis bulbi.

5.Though uncommon, masquerade need to be ruled out in very small children.

6.Corticosteroids may lead to growth retardation in children and all systemic treatment should be initiated in close consultation with a paediatric rheumatologist

7.Immunosuppressive drugs may be required and recent years have seen increasing use of anti TNF alpha blocker drugs especially in uveitis associated with juvenile idiopathic arthritis

REFERENCES

1.Samson CM, Ekong A, foster CS. Uveitis in children: Diagnosis and management. Intern Ophthalmol Clin 2001;41:199-216.

2.Cunningham ET Jr. Uveitis in children. Ocul Immunol Inflamm 2000;8:251-61.

3.Tugal-Tutkun I, Havrlikova K, Power WJ, Foster CS. Changing patterns in uveitis of childhood. Ophthalmology 1996;103:375-83.

4.Paivonsalo-Hietanen T, Tuominen J, Saari KM. Uveitis in children: Populationbased study in Finland. Acta Ophthalmol Scan 2002;78:84-8.

5.Kump LF, Cervantes-Castaneda RA, Androudi SN, Foster CS. Analysis of pediatric uveitis cases at a tertiary referral centre. Ophthalmology 2005;112:1287-92.

6.Novakovic P, Kellie SJ, Taylor D. Childhood leukaemia: relapse in the anterior segment of the eye. Br J Ophthalmol 1989;73:354-9.

7.Rennie I. Ophthalmic manifestations of childhood leukaemia. Br J Ophthalmol 1992;76:641.

8.Kotaniemi K, Savolainen A, Karma A, Aho K. Recent advances in uveitis of juvenile idiopathic arthritis. Surv Ophthalmol 2003;48:489-502.

9.Saurenmann RK, Levin AV, Rose JB, et al. Tumor necrosis factor á inhibitors in the treatment of childhood uveitis. Rheumatology 2006;45:982-9.

10.Biester S, Deuter C, Michels H, et al. Adalimumab in the therapy of uveitis in childhood. Br J Ophtalmol 2007;91: 319-24.

11.Rosenberg KD, Feuer WJ, Davis JL. Ocular complications of pediatric uveitis. Ophthalmology 2004;111:2299-2306.

Surjit Singh

Uveitis is not an uncommon accompaniment of several rheumatic diseases in children. However, the milder forms of the condition may often remain unrecognised if not looked for carefully by an ophthalmologist familiar with the clinical manifestations.

Common rheumatic disorders associated with uveitis in children include the following:

i. Juvenile rheumatoid arthritis

ii.Juvenile ankylosing spondylitis

iii.Kawasaki disease

iv.Psoriatic arthritis

v.Miscellaneous conditions, e.g. Arthropathy of inflammatory bowel disease, reactive arthritis, sarcoidosis, Vogt-Koyanagi-Harada syndrome, Behcet’s disease, CINCA (chronic infantile neurologic cutaneous and articular) syndrome.

Figure 1: Pauciarticular JRA Type I presenting as asymmetric knee joint involvement

JUVENILE RHEUMATOID ARTHRITIS (JRA)

CHARACTERISTICS OF ARTHRITIS

Uveitis is most commonly seen in children with Pauciarticular JRA Type I, which affects young girls (usually 3-5 years of age) and presents as an asymmetric lower limb arthritis (often involving the ankle or knee) (Figure 1). Joint swelling is the predominant feature rather than pain. Antinuclear antibodies (ANAs) are frequently present but antidouble stranded DNA (dsDNA) antibodies are always absent. This type of arthritis has recently been associated with soluble retinal antigen (S antigen); HLA associations – A2, DR5, DR1; of note is the fact that uveitis is very rare in children with Systemic JRA and Polyarticular JRA.1,2

CHARACTERISTICS OF UVEITIS

Asymptomatic, chronic, anterior, nongranulomatous uveitis; predominantly affects the iris and ciliary body and choroid rarely affected (Figures 2 and 3). The disease is bilateral in majority; onset is insidious; visual disturbances occur late and may be progressive. The diagnosis can only be made on careful slit lamp examination. Uveitis may precede onset of arthritis in 10 percent patients; at times, uveitis may first appear when arthritis has been in remission; other ocular manifestations include keratoconjunctivitis sicca; of note is the fact that scleritis and keratitis, (which are common findings in adults with rheumatoid arthritis), are seldom seen in children with JRA.1,3

Figure 2: Uveitis with posterior synechiae in a child with Pauciarticular JRA Type I

Figure 3: Keratic precipitates with cells in anterior chamber seen on slit lamp biomicroscopy in Pauciarticular JRA Type I

ROLE OF THE PAEDIATRICIAN

Parents need to be counselled regarding the necessity of regular (atleast 3 monthly) slit lamp examinations during the first 12-24 months of onset of the disease in children with Pauciarticular JRA Type I. Follow-up examinations may be carried out at 6 monthly intervals thereafter. In other forms of JRA the frequency of slit examinations may be less frequent; the paediatrician must be on the look out for the classic triad of anterior uveitis, band shaped keratopathy and secondary cataract. Band shaped keratopathy results from deposition of calcium in Bowman’s layer (Figures 4 and 5).