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BRIEF COMMUNICATION
Year : 2017  |  Volume : 24  |  Issue : 2  |  Page : 94-99  

Patterns of intermediate uveitis in children presenting at a tertiary eye care center in South India


1 Deparment of Uveitis and Ocular Inflammation, Sankara Nethralaya, Chennai, Tamil Nadu, India
2 Department of Uveitis and Ocular pathology, Sankara Nethralaya, Chennai, Tamil Nadu, India

Date of Web Publication7-Sep-2017

Correspondence Address:
Jyotirmay Biswas
Department of Ocular Pathology, Sankara Nethralaya, No 18, College Road, Nungambakkam, Chennai - 600 006, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/meajo.MEAJO_264_15

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   Abstract 

Purpose: To study the patterns of intermediate uveitis in the pediatric age group in a referral eye care center in South India.
Methods: This is a study of twenty consecutive patients under 16 years of age with intermediate uveitis, conducted at a tertiary referral center. Numerous variables were assessed, including age and gender distribution, laboratory data, the presence of systemic diseases, onset and course of ocular inflammation, clinical features, their complications, therapeutic strategies with their outcomes, remission, final visual acuity (VA), and characteristics associated with poor visual outcome.
Results: Bilateral involvement was observed in 80% of the patients. Remission was observed in five out of 7 patients (78%) with completed follow-up of 5 years. Final VA improved by at least two lines in 11 patients, remained stable in 6 patients, and worsened in 3 patients. The etiological diagnosis showed one patient with Bechet's disease, one with juvenile idiopathic arthritis, 1 with human leukocyte antigen B27 associated uveitis, 9 with laboratory proven tuberculosis, and 3 with sarcoidosis and 5 where it was idiopathic. The mean follow-up was 4.8 years (range 3–8 years). Cataract was the most frequent complication observed (40%). Glaucoma, choroidal neovascularization, and amblyopia accounted for worsening of vision in three patients.
Conclusion: Median time of development of complications is about 3 years based on our study. Intermediate uveitis of childhood might exhibit a self-limiting course after several years. Visual recovery is good in the majority, and visual loss is limited despite the high rate of ocular complications.

Keywords: Children, intermediate uveitis, pars planitis, snow banking, vitritis


How to cite this article:
Annamalai R, Biswas J. Patterns of intermediate uveitis in children presenting at a tertiary eye care center in South India. Middle East Afr J Ophthalmol 2017;24:94-9

How to cite this URL:
Annamalai R, Biswas J. Patterns of intermediate uveitis in children presenting at a tertiary eye care center in South India. Middle East Afr J Ophthalmol [serial online] 2017 [cited 2020 Oct 31];24:94-9. Available from: http://www.meajo.org/text.asp?2017/24/2/94/214176


   Introduction Top


Uveitis is more common among adults than children. Several studies[1] have shown that children constitute about 5%–10% of the total number of new uveitis patients. In the pediatric population, anterior uveitis accounts for 30%–40%, posterior uveitis 40%–50%, intermediate uveitis (IU) 10%–20% and panuveitis 5%–10%.[2] The unique problems in detection of intraocular inflammation in the pediatric age group may arise due to the inability of children to clearly articulate their ocular complaints, the absence of symptoms in certain diseases, such as sarcoidosis and juvenile rheumatoid arthritis, and the development of amblyopia if the vision is impaired. Children also exhibit a more exuberant inflammatory fibrovascular response another reason for loss of vision if diagnosis is delayed.

IU is a chronic intraocular inflammation, mainly affecting the anterior vitreous and the pars plana. The International Uveitis Study Group (IUSG) suggested the term IU to denote an inflammatory syndrome, mainly involving the anterior vitreous, peripheral retina, and the ciliary body with minimal or no anterior segment or chorioretinal signs.[3] Standardization of uveitis nomenclature (SUN) working group international workshop suggested that the term IU should be used for that subset of uveitis where the vitreous is the major site of inflammation, which may at times be associated with peripheral vascular sheathing and macular edema.[4] The diagnostic term pars planitis should be used only for that subset of IUwhere there is snow banking or snowball formation that occurs in the absence of an associated infection or systemic disease or when thought to be idiopathic. If there is an associated infection such as tuberculosis (TB) or Lyme disease or an underlying systemic disease such as sarcoidosis, then the term IU should be used.[5]

IU predominantly affects patients under 40 years of age and forms approximately 8%–22% of all uveitis in the general uveitic population.[6] The percentage of IU increases in the uveitis population aged <16 years (18%–33%).[7] The ocular inflammation in children is frequently discovered late in the disease process and the child might have already developed advanced signs and complications. The etiology of IU in adults is associated with sarcoidosis, multiple sclerosis (MS), or infectious diseases. In India, infections as a cause of IU seem to be more common than the autoimmune type. Besides, in the pediatric population, the causes, presentations, and prognosis of IU have not yet been studied. Our aim was to determine the presentation, course, treatment, and outcome of IU and pars planitis in children.


   Methods Top


In this study, we retrospectively reviewed case records of twenty children seen in a tertiary care referral eye institute and investigated the clinical manifestations, associated systemic diseases, the complication rate, therapy, remission rate, and the visual outcome of intermediate uveitis.

We analyzed the medical records of twenty consecutive children who had sought treatment at our outpatient department over a 1-year period from January 2012 to December 2012 were reviewed. Patients with IU above pediatric age group were excluded.

The collected data comprised details of ocular examination performed at each visit including those examined under anesthesia. All consecutive patients with clinical suspicion of IU and pars planitis were included in the study. Patients with vitreous activity due to anterior uveitis, posterior uveitis, or panuveitis were excluded from the study. After diagnosis, all patients were referred for an opinion from the pediatrician about coexisting systemic or infectious diseases. A diagnosis of pars planitis was made if snow ball opacities were observed in the pars plana region along with vitreous inflammation in the absence of an etiologic diagnosis.

Examination consisted of best-corrected visual acuity (VA), ocular motility, slit lamp biomicroscopy, tonometry, and indirect ophthalmoscopy. Details of presence and treatment of systemic disease and results of laboratory workup were collected and analyzed. The routine laboratory workup included complete blood count, erythrocyte sedimentation rate, urinalysis, purified protein derivative test, venereal disease research laboratory test, X-ray chest, high-resolution chest tomography (HRCT), QuantiFERON-TB Gold (QFT) for TB, and serum angiotensin enzyme for sarcoidosis. These tests were performed on all patients. Apart from the above investigations, tests such as antinuclear antibody, rheumatoid factor, and antineutrophilic antibody were performed based on history and clinical suspicion. Opinions were obtained from the rheumatologist and infectious disease specialist depending on the differential diagnosis.

The final diagnosis was based on chronological history, clinical manifestations, and the results of specific laboratory investigations. Immunosuppressive and corticosteroid therapy were started after concurrence with the pediatrician, and these patients were monitored every 2 weeks for side effects.

Immediately after treatment was started, all patients were seen every month. A complete ophthalmic evaluation was performed during each visit which included slit lamp biomicroscopy, best-corrected VA, indirect ophthalmoscopy, and tonometry. Fluorescein angiography (FFA) and optical coherence tomography (OCT) were performed when macular edema was confirmed. During each follow-up visit, complications were looked for and treated. The dose and mode of administration and the effectiveness and improvement with treatment were noted. Surgeries performed were lens extraction with implantation of intraocular lens, vitrectomy, strabismus surgery, and laser photocoagulation.

Remission of uveitis was defined as absence of inflammatory cells in aqueous humor and vitreous or resolution of signs such as snowballs or snow banking for at least 1 year without treatment. Indications for treatment were cystoid macular edema (CME), retinal neovascularization, or severe vitreous opacities causing VA <6/12. CME was treated with periocular corticosteroid injections or systemic corticosteroids. Immunosuppressive medication was given in those with steroid intolerance or as supplementation to steroids. Raised intraocular pressure (IOP) was managed with topical medication, tablet acetazolamide, and glaucoma filtration surgery.


   Results Top


Twenty patients with IU were identified from a total of 74 cases of childhood uveitis seen. Our series included 6 girls (30%) and 14 boys (70%). The uveitis was unilateral in four patients (20%) and bilateral in sixteen patients (80%), resulting in 36 affected eyes. Thirteen patients presented with diminution of vision (65%), nine patients complained of floaters (45%), three patients presented with redness (15%), and one with squint (5%). The presenting symptom in the majority of cases was a decreased VA, detected during visual screening at school or noticed by teachers or parents. In 2 children, there were complaints of floaters and pain. One child presented with intermittent convergent squint and diplopia. The mean follow-up was 4.8 years (range 3–8 years); 9 patients were followed for at least 3 years, 6 patients were followed for at least 5 years and 5 patients for at least 8 years. The mean age at onset of uveitis was 12.7 years (range 9–15 years). The uveitis had a chronic course in all cases. On clinical examination, snow ball opacities in a few [Figure 1] and vitreous opacities were noted in the majority [Figure 2].
Figure 1: Pars planitis with inferior snow ball opacities

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Figure 2: Dense vitreous strands in intermediate uveitis

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At diagnosis, the VA was 6/18 or better in 4 eyes (20%), between 6/18 and 6/60 in 11 eyes (55%), worse than 6/60 in 4 eyes (20%) and counting fingers close to face in one eye (5%). Biomicroscopy on the first visit revealed keratic precipitates (4 eyes), anterior chamber cells (4 eyes), cataract (2 eyes), posterior synechiae (4 eyes), vitreous cells in all cases, and vitreous opacities in 6 eyes. Binocular ophthalmoscopy revealed macular edema (3 eyes), periphlebitis (2 eyes) and the presence of snowballs and snowbanking (5 eyes). We did not note optic disc hyperemia or edema in any of our patients. Screening for etiological factors was negative, except for the patient who was human leukocyte antigen (HLA) B27 positive.

After a follow-up of 3 years, seven of the nine patients showed a complete remission. Complete remission of IU was noted in 3 out of 6 patients (78%) after follow-up of 5 years. Four patients showed remission at 8 years follow-up. Median time of the development of complications was 3 years. Survival analysis and depiction with Kaplan Meier plot could not be done for recurrences as the number of events is very small (only three).

Among the 20 patients studied, 5 patients had cataract. It was found to be the most frequent complication (25%). 2 patients developed glaucoma (10%), 1 patient had raised IOP at the first visit (5%), and 3 had CME (15%) [Figure 3]. Other complications included epiretinal membranes (1 of 20, 10%), vitreous hemorrhage (1 of 20, 5%), neovascularization (1 of 20, 5%), choroidal neovascular membrane (1 of 20, 5%), and amblyopia (1 of 20, 5%). A raised IOP of 30 mmHg ± 1.24 mmHg (range 27.3 to 32 mmHg) was noted in 3 eyes of 3 patients, of whom it was due to steroid response in one patient.
Figure 3: Optical coherence tomography showing cystoid macular edema in intermediate uveitis

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All patients had normal complete blood counts. Erythrocyte sedimentation rate (ESR) was raised in 10 patients (50%). Fifteen patients (75%) had a positive Mantoux (tuberculin skin test) test. High-resolution computed tomography was suggestive of TB in three patients (15%). QFT was positive in 7 patients (35%). Positive QFT was due to latent TB in 4 and active TB in 3 patients. Serum angiotensin converting enzyme was raised in 2 patients. No abnormalities were observed in serum lysozyme, antinuclear antibody, and rheumatoid factor. Other ancillary investigations such as OCT and fundus FFA were done during both the initial visit and review to identify activity of the disease and its complications. In all patients, an extensive workup based on clinical suspicion, showed a positive result from the first visit.

The etiological diagnosis showed one patient with Bechet's disease, one with juvenile idiopathic arthritis (JIA), 1 with HLA B27 associated uveitis, 9 with laboratory proven TB, 3 with sarcoidosis, and 5 idiopathic.

IU due to TB in our study population was found to be associated with anterior uveitis in the majority of patients. All had vitreous cells and haze but we did not note pars plana involvement in any of the patients. Progression was rapid and visual loss was due to CME in three of nine patients.

One patient who was positive for HLA B5 and HLA B51 with history of recurrent oral ulcers and a positive pathergy test was diagnosed as a Bechets disease. Another patient was diagnosed as a case of JIA based on history, clinical examination, ESR, and ANA and was treated in concurrence with a rheumatologist. The patient with JIA was a 12-year-old girl with inflammation of both her knee joints. An etiological diagnosis of JIA was made based on systemic features after obtaining an opinion from the rheumatologist along with a positive ANA and elevated ESR.

Pretreatment liver function tests and renal function tests were normal in all patients. Five patients had raised serum alkaline phosphatase while on treatment with methotrexate. The modified Kaplan approach was used in the treatment of patients. Thirteen out of 20 patients (65%) were treated with periocular corticosteroid injections, and the VA improved 3–6 months after injection. Posterior subtenon injections of triamcinolone acetonide were given under general anesthesia. Lack of response occurred in two eyes with long-standing CME. Three patients were already on systemic corticosteroid treatment for 2 months when they were first seen at our clinic as they did not note an improvement in their symptoms. Among the 20 patients studied, 3 of them were already on treatment with oral steroid tablets but were not improving. On investigation, we found that all had an idiopathic etiology. Two of them were started on tablet methotrexate and one on tablet azathioprine.

Immunosuppressive medication (azathioprine, methotrexate, cyclosporine, or mycophenolate mofetil) was added in five patients due to contraindications for corticosteroid treatment.[8] Methotrexate was stopped in of them due to lack of response and was substituted by mycophenolate mofetil. Five patients were given topical antiglaucoma medications for controlling IOP. Among those who received systemic corticosteroids, an additional posterior subtenon injection of triamcinolone acetonide was given in 2 patients. One patient was given intravenous methyl prednisolone in the dose of 1mg/kg bodyweight for nonresolving macular edema. Surgical intervention for complications of IU was performed in six patients (30%). Cataract surgery with intraocular lens implantation was done for four eyes of three patients after controlling the inflammation. In one of them, an anterior vitrectomy was required. One patient required strabismus surgery, and trabeculectomy was done in one patient (5%).

At initial presentation, 14 patients presented with VA of 6/36 or better and the remaining 6 patients had VA of 6/60 or worse. The final VA was 6/36 or better in 14 patients and 6/60 or worse in 6 patients. Final VA improved by at least two lines in 11 patients, remained stable in 6 patients and worsened in 3 patients. Glaucoma, choroidal neovascularization, and amblyopia accounted for the worsening of vision in these three patients. The child with amblyopia presented with squint, and surgery was planned after the inflammation settled.


   Discussion Top


IU with onset in childhood and early adulthood showed a similar course at intermediate follow-up. However, associated diseases and complication patterns differed between children and young adults in a study which compared juvenile and adult onset IU with regard to visual loss and complications.[9] Among those with IU due to TB, majority presented with vitritis. Snow banking with pars planitis was noted in one patient. The presence of pars plana exudates in TB is reported as rare in a patient by Babu and Bhat.[10]

In our study, based on etiological diagnosis, improvement in signs and resolution of IU was noted to occur earliest with TB after the patient was started on treatment with antitubercular treatment patients with noninfectious uveitis, treated with steroids, and immunosuppressive drugs started showing improvement later. Methotrexate is now used extensively as systemic immunosuppressive therapy to control disease progression in children as a steroid sparing agent in both IU and pars planitis. Other immunomodulatory drugs with variable success in treatment include cyclosporine, chlorambucil, azathioprine, tacrolimus, and tumor necrosis factor antagonists. Cyclophosphamide though known for its faster onset of action has significant side effects and hence not recommended in children.

This study demonstrates that spontaneous remission of IU might occur in pediatric patients with IU. We observed remission in 7 out of 9 patients with a minimum follow-up of 5 years. Our follow-up period was not uniform as some patients did not review after improvement in symptoms. An 8-year follow-up was restricted to only a portion of our patients and our patient population was relatively small. Hence, the exact remission rate in childhood IU could not be calculated from the present series. Although most of the patients with remissions were followed for several years after the onset of remission, the possibility that IU might recur in some of them at a later time cannot be excluded. IU is generally believed to be autoimmune in nature, and snow banking is not an important clinical sign of IU.[11]Involvement of the vitreous is prominent in these patients and is seen as vitreous cells, haze, and opacities.

The IUSG has described IU as an idiopathic inflammatory syndrome that primarily involves the anterior vitreous, peripheral retina, and ciliary body with mild or no anterior segment inflammation.[12] The SUN Working Group defined IU as a subset of uveitis with vitreous activity as the major sign, and peripheral vascular sheathing and macular edema may coexist. They defined “pars planitis” as a subset of IU which is seen to have snowball or snow bank formation in the absence of any systemic disease and hence is idiopathic in etiology.

The etiology of IU is known to be mostly due to autoimmune diseases and can be associated with systemic causes such as sarcoidosis, MS, and inflammatory bowel disease.[8] Infections such as toxocariasis, Lyme's disease,[13] and human T-cell leukemia virus have been reported to be other causes.

The course of IU is usually prolonged with remissions and exacerbations. A complete and extensive workup is required in the majority of patients to enable precise management, to reduce recurrences, and to prevent complications. The etiology itself can vary between different geographic locations and among various ethnic groups. In epidemiologic studies performed from referral institutes in India, IU has been reported as idiopathic in 77.5% in Northeast India,[14] 91.4% in North India,[15] and 81.6% in South India.[16]

IU needs to be differentiated from pars planitis. In pars planitis, the primary site of inflammation is the vitreous base, peripheral retina, and ciliary body, and the etiology is idiopathic. It can have cells and debris in the vitreous with periphlebitis and snowball formation over the pars plana and peripheral retina. Cyclitic membranes can cause tractional retinal detachment, and retinal vasculitis can result in neovascularization.[17]

In three studies reported from various parts of the world, all cases were reported to be idiopathic IU. This is in contrast to the South Indian population where infection was the most frequent etiology.[18] In our study, we noted a male preponderance. Bilateral involvement was seen in 80% patients, and chronicity of uveitis is 100%. Mean time to remission was 6.4 years. Common complications seen were disc edema, CME, cataract, and glaucoma.

An autoimmune pathogenesis of IU has also been suggested and furthermore, a familial predisposition has also been reported.[19] Malinowsky and associates reported that 15% of patients with pars planitis developed MS after 5 years of follow-up.[20] Since the etiology of IU remains elusive in most cases, therapy is mainly symptomatic. In our series, no differences between patients with disease onset before or after the age of 8 years were noted in the initial presentation, complications, and visual prognosis. Kaplan and associates recommended treatment in IU when the VA dropped below 20/40. Since CME is the major cause of visual loss or impairment of IU in children, early detection, and treatment of CME is crucial for the prevention of visual loss.


   Conclusion Top


Our study indicates that IU in children might resolve after several years and despite a high ocular complication rate, severe visual loss is uncommon. Children with pars planitis are more likely than adults to experience vitreous hemorrhage. Risk factors for IU in pediatric age group seem to differ from noninfectious uveitis in the same age. There appear to be racial differences in the outcomes of children with uveitis.[21] The variation in disease severity prompts the use of individually tailored immunosuppressive regimens.

The similarities in clinical findings, course of pars planitis, and outcome between the patients with no evidence of underlying systemic disease and the patients with proven or suspected underlying systemic disease of immunologic origin may represent indirect evidence for the existence of a common pathogenetic mechanism and common treatment needs. Our retrospective study comprised a small number of children who presented with similar signs but varying response to treatment and complications. The majority of our patients had resolution of the disease with the improvement of VA after completion of treatment. In conclusion, we reinforce the need for precise and early treatment and frequent follow-up because of the fluctuant activity and remissions and exacerbations associated with the disease.

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Conflicts of interest

There are no conflicts of interest.

 
   References Top

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Das D, Bhattacharjee H, Bhattacharya PK. Patterns of uveitis in North East India: A tertiary care center study. Indian J Ophthalmol 2009;57:144-6.  Back to cited text no. 14
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