Looking past the eye in paediatric noninfectious uveitis

Uveitis may have more extraocular effects than previously recognised, investigators explained. Image credit: ©nicoletaionescu – stock.adobe.com

The effects of noninfectious uveitis may not be limited to the eye but can affect the systemic microcirculation in children, and the manifested changes can vary depending on the uveitic subtype, according to data from a new study¹ published by Dutch researchers. Carlyn V. Kouwenberg, who is an MD PhD candidate from the Department of Ophthalmology, University Medical Center Utrecht, Utrecht, the Netherlands, and colleagues explained that uveitis may have more extraocular effects than previously recognised.

In paediatric patients, uveitis can develop in association with a systemic condition such as juvenile idiopathic arthritis. The investigators pointed out, however, “In up to 60% of cases, the etiology remains unknown, and these cases are considered an isolated idiopathic inflammatory eye condition^.2-6 Inflammatory involvement of the ocular vasculature is common in patients with intermediate uveitis or panuveitis and can include retinal vasculitis, diffuse retinal capillary leakage, and/or macular oedema.^7-10 However, whether changes in the extraocular vascular and/or microcirculation are involved in paediatric patients with uveitis is currently unknown.”

The authors investigated the systemic microcirculation in 119 children with noninfectious uveitis and 25 healthy children using nailfold capillaroscopy (NFC). This is a noninvasive diagnostic technique used to evaluate the microcirculation in the nailfold that is often performed in rheumatology and dermatology. NFC has been reported to identify various abnormal patterns associated with diseases such as systemic sclerosis and systemic lupus erythematosus.^11-14

NFC has been used to detect microvascular abnormalities in ocular diseases, especially in glaucoma^15–17 and in adults with uveitis,¹⁸ but the study under discussion is the first to use NFC in children with uveitis. The parameters evaluated included the number of capillaries/mm (density), dilated capillaries (apex > 20 m), avascular area, the presence of microhemorrhages and capillary morphology.

NFC procedure

During this procedure, investigators looked at the nailfold of all fingers except for the thumbs. They applied immersion oil on the nailfold bed to improve the resolution. The same clinician preformed all the NFC procedures. Initially, low magnification (50%) was used to determine the distribution of any obvious abnormalities and to obtain an overview of the nailfold area. Four images were obtained at 200 times magnification to assess the detailed morphology of the capillaries. Three other clinicians evaluated the images for the presence of hemorrhages and to determine the capillary morphology.

Group comparison using NFC

The mean age of the 119 patients was 13.7 years; 56% were female. Patients presented with the following uveitic types: anterior uveitis 46%, intermediate uveitis 18%, and panuveitis 36%; overall mean disease duration was 4.7 ± 4.0 years.

The investigators reported that when compared with the healthy control group, the patients with paediatric uveitis had a significantly higher number of dilated capillaries/mm and a higher prevalence of ramified capillaries. The patients with intermediate uveitis had a significantly higher number of dilated capillaries. In contrast, the patients with anterior uveitis had a lower capillary density and a higher prevalence of ramified capillaries.

In commenting on their findings, the investigators said, “Paediatric uveitis can present with changes in the systemic microcirculation, with specific differences based on the subtype of uveitis. Our results suggested that noninfectious paediatric uveitis is not always limited to intraocular inflammation but may also include systemic inflammation. The changes observed in the systemic microcirculation do not appear to be correlated with retinal vascular inflammation involvement in our clinically
heterogenous cohort.”

Investigators also believe that whether capillary changes reflect vascular involvement in specific uveitis subtypes warrants further investigation. However, they emphasised the value of their findings; “Our results may provide new insights into the pathogenesis of this potentially sight-threatening paediatric condition as well as new insights regarding the development and application of new diagnostic and/or prognostic biomarkers.”

References

1. Kouwenberg CV, Spierings J, de Groot EL, de Boer JH, Ayuso VK. Involvement of the systemic microcirculation in pediatric uveitis. Pediatr Rheumatol Online J. 2023;21(1):109. doi:10.1186/s12969-023-00896-7

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

3. Angeles-Han ST, Rabinovich CE. Uveitis in children. Curr Opin Rheumatol. 2016;28(5):544-549. doi:10.1097/BOR.0000000000000316

4. Tugal-Tutkun I. Pediatric uveitis. J Ophthalmic Vis Res. 2011;6(4):259-269.

5. Smith JA, Mackensen F, Sen HN, et al. Epidemiology and course of disease in childhood uveitis. Ophthalmology. 2009; 116(8):1544-1551.e1. doi:10.1016/j.ophtha.2009.05.002

6. Ferrara M, Eggenschwiler L, Stephenson A, et al. The challenge of pediatric uveitis: tertiary referral center experience in the United States. Ocul Immunol Inflamm. 2019; 27(3):410-417. doi:10.1080/09273948.2017.1420202

7. Lee RWJ, Dick AD. Current concepts and future directions in the patho-
genesis and treatment of non-infectious intraocular inflammation. Eye (Lond). 2012;26(1):17-28. doi:10.1038/eye.2011.255

8. Hoeve M, Ayuso VK, Schalij-Delfos NE, et al. The clinical course of juvenile idiopathic arthritis-associated uveitis in child- hood and puberty. Br J Ophthalmol. 2012;96(6):852-856. doi:10.1136/bjophthalmol-2011-301023

9. Kalinina Ayuso V, Makhotkina N, van Tent-Hoeve M, et al. Pathogenesis of juvenile idiopathic arthritis associated uveitis: the known and unknown. Surv Ophthalmol. 2014;59(5):517-531. doi:10.1016/j.survophthal.2014.03.002

10. Kalinina Ayuso V, Ten Cate HAT, Van Den Does P, Rothova A, De Boer JH. Young age as a risk factor for complicated course and visual outcome in intermediate uveitis in children. Br J Ophthalmol. 2011; 95(5):646-651. doi:10.1136/bjo.2010.184267

11. Smith V, Vanhaecke A, Herrick AL, et al. Fast track algorithm: how to differentiate a “scleroderma pattern” from a “non-scleroderma pattern.” Autoimmun Rev. 2019;18(11):102394. doi:10.1016/j.autrev.2019.102394.

12. Smith V, Herrick AL, Ingegnoli F, et al; EULAR Study Group on Microcirculation in Rheumatic Diseases and the Scleroderma Clinical Trials Consortium Group on Capillaroscopy. Standardisation of nailfold capillaroscopy for the assessment of patients with Raynaud’s phenomenon and systemic sclerosis.Autoim mun Rev. 2020;19(3):102458. doi:10.1016/j.autrev.2020.102458

13. Tavakol ME, Fatemi A, Karbalaie A, Emrani Z, Erlandsson BE. Nailfold capillaroscopy in rheumatic diseases: which parameters should be evaluated? Biomed Res Int. 2015;2015:974530. doi:10.1155/2015/974530

14. Melsens K, Cutolo M, Schonenberg-Meinema D, et al; EULAR Study Group on Microcirculation in Rheumatic Diseases. Standardized nailfold capillaroscopy in children with rheumatic diseases: a worldwide study. Rheumatology (Oxford). 2023;62(4):1605-1615. doi:10.1093/rheumatology/keac487

15. Philip S, Najafi A, Tantraworasin A, Pasquale LR, Ritch R. Nailfold capillaroscopy of resting peripheral blood flow in exfoliation glaucoma and primary open-angle glaucoma. JAMA Ophthalmol. 2019;137(6):618-625. doi:10.1001/jamaophthalmol.2019.0434

16. Cousins CC, Kang JH, Bovee C, et al. Nailfold capillary morphology in exfoliation syndrome. Eye (Lond). 2017;31(5):698-707. doi:10.1038/eye.2016.312

17. Erol MK, Balkarli A, Toslak D, et al. Evaluation of nailfold videocapillaroscopy in central serous chorioretinopathy. Graefes Arch Clin Exp Ophthalmol. 2016;254(10):1889-1896. doi:10.1007/s00417-016-3322-1

18. Chen X, Yao X, Chi Y, et al. A cross-sectional observational study of nailfold capillary morphology in uveitis. Curr Eye Res. 2018;43(11):1342-1350. doi:10.1080/02713683.2018.1496265

Carlyn V. Kouwenberg | E: C.V.Kouwenberg-3@umcutrecht.nl

Kouwenberg is an MD PhD candidate at the Department of Ophthalmology, University Medical Center Utrecht, Utrecht, The Netherlands, and has no financial interest in this subject matter.