Download PDF
Semin Respir Crit Care Med 2020; 41(05): 673-688
DOI: 10.1055/s-0040-1710536
Review Article

Ocular Sarcoidosis

Pascal Sève
1   Department of Internal Medicine, Hopital de la Croix-Rousse, Université Claude Bernard Lyon I, Lyon, France
2   Hospices Civils de Lyon, Pôle IMER, Lyon, France
3   University Claude Bernard-Lyon 1, HESPER EA 7425, Univ. Lyon, Lyon, France
,
Yvan Jamilloux
1   Department of Internal Medicine, Hopital de la Croix-Rousse, Université Claude Bernard Lyon I, Lyon, France
,
Caroline Tilikete
1   Department of Internal Medicine, Hopital de la Croix-Rousse, Université Claude Bernard Lyon I, Lyon, France
,
Mathieu Gerfaud-Valentin
1   Department of Internal Medicine, Hopital de la Croix-Rousse, Université Claude Bernard Lyon I, Lyon, France
,
Laurent Kodjikian
4   Neurology D and Neuro-Ophthalmology Unit, Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Bron, France
5   Université de Lyon, Lyon 1 University, Lyon, France
6   Lyon Neuroscience Research Center, INSERM U1028 CNRS UMR5292, Team ImpAct, Bron, France
7   Department of Ophthalmology, Hopital de la Croix-Rousse, Université Claude Bernard Lyon I, Lyon, France
,
Thomas El Jammal
1   Department of Internal Medicine, Hopital de la Croix-Rousse, Université Claude Bernard Lyon I, Lyon, France
› Author Affiliations
› Further Information
    Permissions and Reprints

Abstract

Sarcoidosis is one of the leading causes of inflammatory eye disease. Any part of the eye and its adnexal tissues can be involved. Uveitis and optic neuropathy are the main manifestations, which may require systemic treatment. Two groups of patients with sarcoid uveitis can be distinguished: one of either sex and any ethnicity in which ophthalmological findings are various and another group of elderly Caucasian women with mostly chronic posterior uveitis. Clinically isolated uveitis revealing sarcoidosis remains a strictly ocular condition in a large majority of cases. Although it can be a serious condition involving functional prognosis, early recognition in addition to a growing therapeutic arsenal (including intravitreal implant) has improved the visual prognosis of the disease in recent years. Systemic corticosteroids are indicated when uveitis does not respond to topical corticosteroids or when there is bilateral posterior involvement, especially macular edema. In up to 30% of the cases that require an unacceptable dosage of corticosteroids to maintain remission, additional immunosuppression is used, especially methotrexate. As with other forms of severe noninfectious uveitis, monoclonal antibodies against tumor necrosis factor-α have been used. However, only very rarely does sarcoid uveitis fail to respond to combined corticosteroids and methotrexate therapy, a situation that should suggest either poor adherence or another granulomatous disease. Optic neuropathy often affects women of African and Caribbean origins. Some authors recommend that patients should be treated with high-dose of corticosteroids and concurrent immunosuppression from the onset of this manifestation, which is associated with a poorer outcome.

Keywords

sarcoidosis - uveitis - ocular sarcoidosis - 18-FDG PET - anti-TNF-α


Publication History

Article published online:
10 August 2020

© 2020. Thieme. All rights reserved.

Thieme Medical Publishers
333 Seventh Avenue, New York, NY 10001, USA.

 

  • References

  • 1 Jamilloux Y, Kodjikian L, Broussolle C, Sève P. Sarcoidosis and uveitis. Autoimmun Rev 2014; 13 (08) 840-849
    CrossrefPubMedGoogle Scholar
  • 2 Bodaghi B, Touitou V, Fardeau C, Chapelon C, LeHoang P. Ocular sarcoidosis. Presse Med 2012; 41 (6 Pt 2): e349-e354
    CrossrefPubMedGoogle Scholar
  • 3 Birnbaum AD, French DD, Mirsaeidi M, Wehrli S. Sarcoidosis in the national veteran population: association of ocular inflammation and mortality. Ophthalmology 2015; 122 (05) 934-938
    CrossrefPubMedGoogle Scholar
  • 4 Groen F, Rothova A. Ocular involvement in sarcoidosis. Semin Respir Crit Care Med 2017; 38 (04) 514-522
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Baughman RP, Teirstein AS, Judson MA. , et al; Case Control Etiologic Study of Sarcoidosis (ACCESS) research group. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 2001; 164 (10, Pt 1): 1885-1889
    CrossrefPubMedGoogle Scholar
  • 6 Pasadhika S, Rosenbaum JT. Ocular sarcoidosis. Clin Chest Med 2015; 36 (04) 669-683
    CrossrefPubMedGoogle Scholar
  • 7 Rothova A. Ocular involvement in sarcoidosis. Br J Ophthalmol 2000; 84 (01) 110-116
    CrossrefPubMedGoogle Scholar
  • 8 Koczman JJ, Rouleau J, Gaunt M, Kardon RH, Wall M, Lee AG. Neuro-ophthalmic sarcoidosis: the University of Iowa experience. Semin Ophthalmol 2008; 23 (03) 157-168
    CrossrefPubMedGoogle Scholar
  • 9 Prabhakaran VC, Saeed P, Esmaeli B. , et al. Orbital and adnexal sarcoidosis. Arch Ophthalmol 2007; 125 (12) 1657-1662
    CrossrefPubMedGoogle Scholar
  • 10 Braswell RA, Kline LB. Neuro-ophthalmologic manifestations of sarcoidosis. Int Ophthalmol Clin 2007; 47 (04) 67-77 , ix
    CrossrefPubMedGoogle Scholar
  • 11 Evans M, Sharma O, LaBree L, Smith RE, Rao NA. Differences in clinical findings between Caucasians and African Americans with biopsy-proven sarcoidosis. Ophthalmology 2007; 114 (02) 325-333
    CrossrefPubMedGoogle Scholar
  • 12 Birnbaum AD, Oh FS, Chakrabarti A, Tessler HH, Goldstein DA. Clinical features and diagnostic evaluation of biopsy-proven ocular sarcoidosis. Arch Ophthalmol 2011; 129 (04) 409-413
    CrossrefPubMedGoogle Scholar
  • 13 Grégoire M-A, Kodjikian L, Varron L, Grange J-D, Broussolle C, Seve P. Characteristics of uveitis presenting for the first time in the elderly: analysis of 91 patients in a tertiary center. Ocul Immunol Inflamm 2011; 19 (04) 219-226
    CrossrefPubMedGoogle Scholar
  • 14 Grumet P, Kerever S, Gilbert T. , et al. Clinical and etiologic characteristics of de novo uveitis in patients aged 60 years and above: experience of a French tertiary center. Graefes Arch Clin Exp Ophthalmol 2019; 257 (09) 1971-1979
    CrossrefPubMedGoogle Scholar
  • 15 Kitamei H, Kitaichi N, Namba K. , et al. Clinical features of intraocular inflammation in Hokkaido, Japan. Acta Ophthalmol 2009; 87 (04) 424-428
    CrossrefPubMedGoogle Scholar
  • 16 Ohguro N, Sonoda K-H, Takeuchi M, Matsumura M, Mochizuki M. The 2009 prospective multi-center epidemiologic survey of uveitis in Japan. Jpn J Ophthalmol 2012; 56 (05) 432-435
    CrossrefPubMedGoogle Scholar
  • 17 Goto H, Mochizuki M, Yamaki K, Kotake S, Usui M, Ohno S. Epidemiological survey of intraocular inflammation in Japan. Jpn J Ophthalmol 2007; 51 (01) 41-44
    CrossrefPubMedGoogle Scholar
  • 18 Bajwa A, Osmanzada D, Osmanzada S. , et al. Epidemiology of uveitis in the mid-Atlantic United States. Clin Ophthalmol 2015; 9: 889-901
    CrossrefPubMedGoogle Scholar
  • 19 Jakob E, Reuland MS, Mackensen F. , et al. Uveitis subtypes in a german interdisciplinary uveitis center--analysis of 1916 patients. J Rheumatol 2009; 36 (01) 127-136
    CrossrefPubMedGoogle Scholar
  • 20 Barisani-Asenbauer T, Maca SM, Mejdoubi L, Emminger W, Machold K, Auer H. Uveitis- a rare disease often associated with systemic diseases and infections- a systematic review of 2619 patients. Orphanet J Rare Dis 2012; 7: 57
    CrossrefPubMedGoogle Scholar
  • 21 Jones NP. The Manchester Uveitis Clinic: the first 3000 patients--epidemiology and casemix. Ocul Immunol Inflamm 2015; 23 (02) 118-126
    CrossrefPubMedGoogle Scholar
  • 22 Llorenç V, Mesquida M, Sainz de la Maza M. , et al. Epidemiology of uveitis in a Western urban multiethnic population. The challenge of globalization. Acta Ophthalmol 2015; 93 (06) 561-567
    CrossrefPubMedGoogle Scholar
  • 23 Luca C, Raffaella A, Sylvia M. , et al. Changes in patterns of uveitis at a tertiary referral center in Northern Italy: analysis of 990 consecutive cases. Int Ophthalmol 2018; 38 (01) 133-142
    PubMedGoogle Scholar
  • 24 Bro T, Tallstedt L. Epidemiology of uveitis in a region of southern Sweden. Acta Ophthalmol (Copenh) 2020; 98 (01) 32-35
    CrossrefPubMedGoogle Scholar
  • 25 Bertrand P-J, Jamilloux Y, Ecochard R. , et al. Uveitis: autoimmunity… and beyond. Autoimmun Rev 2019; 18 (09) 102351
    CrossrefPubMedGoogle Scholar
  • 26 Bodaghi B, Cassoux N, Wechsler B. , et al. Chronic severe uveitis: etiology and visual outcome in 927 patients from a single center. Medicine (Baltimore) 2001; 80 (04) 263-270
    CrossrefPubMedGoogle Scholar
  • 27 Abad S, Meyssonier V, Allali J. , et al. Association of peripheral multifocal choroiditis with sarcoidosis: a study of thirty-seven patients. Arthritis Rheum 2004; 51 (06) 974-982
    CrossrefPubMedGoogle Scholar
  • 28 Chung Y-M, Lin Y-C, Liu Y-T, Chang S-C, Liu H-N, Hsu W-H. Uveitis with biopsy-proven sarcoidosis in Chinese--a study of 60 patients in a uveitis clinic over a period of 20 years. J Chin Med Assoc 2007; 70 (11) 492-496
    CrossrefPubMedGoogle Scholar
  • 29 Khanna A, Sidhu U, Bajwa G, Malhotra V. Pattern of ocular manifestations in patients with sarcoidosis in developing countries. Acta Ophthalmol Scand 2007; 85 (06) 609-612
    CrossrefPubMedGoogle Scholar
  • 30 Lee SY, Lee HG, Kim DS, Kim J-G, Chung H, Yoon YH. Ocular sarcoidosis in a Korean population. J Korean Med Sci 2009; 24 (03) 413-419
    CrossrefPubMedGoogle Scholar
  • 31 Rothova A, Alberts C, Glasius E, Kijlstra A, Buitenhuis HJ, Breebaart AC. Risk factors for ocular sarcoidosis. Doc Ophthalmol 1989; 72 (3–4): 287-296
    CrossrefPubMedGoogle Scholar
  • 32 Matsou A, Tsaousis KT. Management of chronic ocular sarcoidosis: challenges and solutions. Clin Ophthalmol 2018; 12: 519-532
    CrossrefPubMedGoogle Scholar
  • 33 Rochepeau C, Jamilloux Y, Kerever S. , et al. Long-term visual and systemic prognoses of 83 cases of biopsy-proven sarcoid uveitis. Br J Ophthalmol 2017; 101 (07) 856-861
    CrossrefPubMedGoogle Scholar
  • 34 Ma SP, Rogers SL, Hall AJ. , et al. Sarcoidosis-related uveitis: clinical presentation, disease course, and rates of systemic disease progression after uveitis diagnosis. Am J Ophthalmol 2019; 198: 30-36
    CrossrefPubMedGoogle Scholar
  • 35 Febvay C, Kodjikian L, Maucort-Boulch D. , et al. Clinical features and diagnostic evaluation of 83 biopsy-proven sarcoid uveitis cases. Br J Ophthalmol 2015; 99 (10) 1372-1376
    CrossrefPubMedGoogle Scholar
  • 36 Coulon C, Kodjikian L, Rochepeau C. , et al. Ethnicity and association with ocular, systemic manifestations and prognosis in 194 patients with sarcoid uveitis. Graefes Arch Clin Exp Ophthalmol 2019; 257 (11) 2495-2503
    CrossrefPubMedGoogle Scholar
  • 37 Judson MA, Hirst K, Iyengar SK. , et al; SAGA Study Consortium. Comparison of sarcoidosis phenotypes among affected African-American siblings. Chest 2006; 130 (03) 855-862
    CrossrefPubMedGoogle Scholar
  • 38 Steele MP, Brown KK. Genetic predisposition to respiratory diseases: infiltrative lung diseases. Respiration 2007; 74 (06) 601-608
    CrossrefPubMedGoogle Scholar
  • 39 Rybicki BA, Iannuzzi MC, Frederick MM. , et al; ACCESS Research Group. Familial aggregation of sarcoidosis. A case-control etiologic study of sarcoidosis (ACCESS). Am J Respir Crit Care Med 2001; 164 (11) 2085-2091
    CrossrefPubMedGoogle Scholar
  • 40 Rossman MD, Thompson B, Frederick M. , et al; ACCESS Group. HLA-DRB1*1101: a significant risk factor for sarcoidosis in blacks and whites. Am J Hum Genet 2003; 73 (04) 720-735
    CrossrefPubMedGoogle Scholar
  • 41 Darlington P, Tallstedt L, Padyukov L. , et al. HLA-DRB1* alleles and symptoms associated with Heerfordt's syndrome in sarcoidosis. Eur Respir J 2011; 38 (05) 1151-1157
    CrossrefPubMedGoogle Scholar
  • 42 Sato H, Woodhead FA, Ahmad T. , et al. Sarcoidosis HLA class II genotyping distinguishes differences of clinical phenotype across ethnic groups. Hum Mol Genet 2010; 19 (20) 4100-4111
    CrossrefPubMedGoogle Scholar
  • 43 Suzuki H, Ota M, Meguro A. , et al. Genetic characterization and susceptibility for sarcoidosis in Japanese patients: risk factors of BTNL2 gene polymorphisms and HLA class II alleles. Invest Ophthalmol Vis Sci 2012; 53 (11) 7109-7115
    CrossrefPubMedGoogle Scholar
  • 44 Spagnolo P, Sato H, Marshall SE. , et al. Association between heat shock protein 70/Hom genetic polymorphisms and uveitis in patients with sarcoidosis. Invest Ophthalmol Vis Sci 2007; 48 (07) 3019-3025
    CrossrefPubMedGoogle Scholar
  • 45 Thompson IA, Liu B, Sen HN. , et al. Association of complement factor H tyrosine 402 histidine genotype with posterior involvement in sarcoid-related uveitis. Am J Ophthalmol 2013; 155 (06) 1068-1074.e1
    CrossrefPubMedGoogle Scholar
  • 46 Akahoshi M, Ishihara M, Namba K. , et al. Mutation screening of the CARD15 gene in sarcoidosis. Tissue Antigens 2008; 71 (06) 564-567
    CrossrefPubMedGoogle Scholar
  • 47 Asukata Y, Ota M, Meguro A. , et al. Lack of association between toll-like receptor 4 gene polymorphisms and sarcoidosis-related uveitis in Japan. Mol Vis 2009; 15: 2673-2682
    PubMedGoogle Scholar
  • 48 Kim HS, Choi D, Lim LL. , et al. Association of interleukin 23 receptor gene with sarcoidosis. Dis Markers 2011; 31 (01) 17-24
    CrossrefPubMedGoogle Scholar
  • 49 Kuroda H, Saijo Y, Fujiuchi S, Takeda H, Ohsaki Y, Hasebe N. Relationship between cytokine single nucleotide polymorphisms and sarcoidosis among Japanese subjects. Sarcoidosis Vasc Diffuse Lung Dis 2013; 30 (01) 36-42
    PubMedGoogle Scholar
  • 50 Martin TM, Doyle TM, Smith JR, Dinulescu D, Rust K, Rosenbaum JT. Uveitis in patients with sarcoidosis is not associated with mutations in NOD2 (CARD15). Am J Ophthalmol 2003; 136 (05) 933-935
    CrossrefPubMedGoogle Scholar
  • 51 Sakuyama K, Meguro A, Ota M. , et al. Lack of association between IL10 polymorphisms and sarcoidosis in Japanese patients. Mol Vis 2012; 18: 512-518
    PubMedGoogle Scholar
  • 52 Chaperon M, Pacheco Y, Maucort-Boulch D. , et al. BTNL2 gene polymorphism and sarcoid uveitis. Br J Ophthalmol 2019; 103 (12) 1690-1694
    PubMedGoogle Scholar
  • 53 Jabs DA, Nussenblatt RB, Rosenbaum JT. ; Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol 2005; 140 (03) 509-516
    CrossrefPubMedGoogle Scholar
  • 54 Zaidi AA, Ying G-S, Daniel E. , et al; Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Hypopyon in patients with uveitis. Ophthalmology 2010; 117 (02) 366-372
    CrossrefPubMedGoogle Scholar
  • 55 Sève P, Cacoub P, Bodaghi B. , et al. Uveitis: diagnostic work-up. A literature review and recommendations from an expert committee. Autoimmun Rev 2017; 16 (12) 1254-1264
    CrossrefPubMedGoogle Scholar
  • 56 Sève P, Kodjikian L, Adélaïde L, Jamilloux Y. Uveitis in adults: What do rheumatologists need to know?. Joint Bone Spine 2015; 82 (05) 308-314
    CrossrefPubMedGoogle Scholar
  • 57 Ness T, Boehringer D, Heinzelmann S. Intermediate uveitis: pattern of etiology, complications, treatment and outcome in a tertiary academic center. Orphanet J Rare Dis 2017; 12 (01) 81
    CrossrefPubMedGoogle Scholar
  • 58 Jones NP. Sarcoidosis and uveitis. Ophthalmol Clin North Am 2002; 15 (03) 319-326 , vi
    CrossrefPubMedGoogle Scholar
  • 59 Koop A, Ossewaarde A, Rothova A. Peripheral multifocal chorioretinitis: complications, prognosis and relation with sarcoidosis. Acta Ophthalmol 2013; 91 (06) 492-497
    CrossrefPubMedGoogle Scholar
  • 60 Herbort CP, Rao NA, Mochizuki M. ; members of Scientific Committee of First International Workshop on Ocular Sarcoidosis. International criteria for the diagnosis of ocular sarcoidosis: results of the first International Workshop On Ocular Sarcoidosis (IWOS). Ocul Immunol Inflamm 2009; 17 (03) 160-169
    CrossrefPubMedGoogle Scholar
  • 61 Stavrou P, Linton S, Young DW, Murray PI. Clinical diagnosis of ocular sarcoidosis. Eye (Lond) 1997; 11 (Pt 3): 365-370
    CrossrefPubMedGoogle Scholar
  • 62 Crick RP, Hoyle C, Smellie H. The eyes in sarcoidosis. Br J Ophthalmol 1961; 45 (07) 461-481
    CrossrefPubMedGoogle Scholar
  • 63 Uyama M. Uveitis in sarcoidosis. Int Ophthalmol Clin 2002; 42 (01) 143-150
    CrossrefPubMedGoogle Scholar
  • 64 Kluger N. Tattoo-associated uveitis with or without systemic sarcoidosis: a comparative review of the literature. J Eur Acad Dermatol Venereol 2018; 32 (11) 1852-1861
    CrossrefPubMedGoogle Scholar
  • 65 Sève P, Kodjikian L, Jamilloux Y. Ocular sarcoidosis: What the internist should know? [in French]. Rev Med Interne 2018; 39 (09) 728-737
    CrossrefPubMedGoogle Scholar
  • 66 Lobo A, Barton K, Minassian D, du Bois RM, Lightman S. Visual loss in sarcoid-related uveitis. Clin Exp Ophthalmol 2003; 31 (04) 310-316
    CrossrefPubMedGoogle Scholar
  • 67 Kirsch O, Frau E, Nodarian M, Labetoulle M, Offret H. Clinical course of ocular sarcoidosis in patients with histologically proven systemic sarcoidosis [in French]. J Fr Ophtalmol 2001; 24 (06) 623-627
    PubMedGoogle Scholar
  • 68 Paovic J, Paovic P, Sredovic V, Jovanovic S. Clinical manifestations, complications and treatment of ocular sarcoidosis: correlation between visual efficiency and macular edema as seen on optical coherence tomography. Semin Ophthalmol 2016; (September): 1-8
    CrossrefPubMedGoogle Scholar
  • 69 Miserocchi E, Modorati G, Di Matteo F, Galli L, Rama P, Bandello F. Visual outcome in ocular sarcoidosis: retrospective evaluation of risk factors. Eur J Ophthalmol 2011; 21 (06) 802-810
    CrossrefPubMedGoogle Scholar
  • 70 Dana MR, Merayo-Lloves J, Schaumberg DA, Foster CS. Prognosticators for visual outcome in sarcoid uveitis. Ophthalmology 1996; 103 (11) 1846-1853
    CrossrefPubMedGoogle Scholar
  • 71 Edelsten C, Pearson A, Joynes E, Stanford MR, Graham EM. The ocular and systemic prognosis of patients presenting with sarcoid uveitis. Eye (Lond) 1999; 13 (Pt 6): 748-753
    CrossrefPubMedGoogle Scholar
  • 72 Lardenoye CW, Van der Lelij A, de Loos WS, Treffers WF, Rothova A. Peripheral multifocal chorioretinitis: a distinct clinical entity?. Ophthalmology 1997; 104 (11) 1820-1826
    CrossrefPubMedGoogle Scholar
  • 73 Clement DS, Postma G, Rothova A, Grutters JC, Prokop M, de Jong PA. Intraocular sarcoidosis: association of clinical characteristics of uveitis with positive chest high-resolution computed tomography findings. Br J Ophthalmol 2010; 94 (02) 219-222
    CrossrefPubMedGoogle Scholar
  • 74 Takayama K, Harimoto K, Sato T. , et al. Age-related differences in the clinical features of ocular sarcoidosis. PLoS One 2018; 13 (08) e0202585
    CrossrefPubMedGoogle Scholar
  • 75 Grumet P, Kodjikian L, de Parisot A. , et al; ULISSE group. Contribution of diagnostic tests for the etiological assessment of uveitis, data from the ULISSE study (Uveitis: clinical and medicoeconomic evaluation of a standardized strategy of the etiological diagnosis). Autoimmun Rev 2018; 17 (04) 331-343
    CrossrefPubMedGoogle Scholar
  • 76 Niederer RL, Al-Janabi A, Lightman SL, Tomkins-Netzer O. Serum angiotensin-converting enzyme has a high negative predictive value in the investigation for systemic sarcoidosis. Am J Ophthalmol 2018; 194: 82-87
    CrossrefPubMedGoogle Scholar
  • 77 Sahin O, Ziaei A, Karaismailoğlu E, Taheri N. The serum angiotensin converting enzyme and lysozyme levels in patients with ocular involvement of autoimmune and infectious diseases. BMC Ophthalmol 2016; 16: 19
    CrossrefPubMedGoogle Scholar
  • 78 Gundlach E, Hoffmann MM, Prasse A, Heinzelmann S, Ness T. Interleukin-2 receptor and angiotensin-converting enzyme as markers for ocular Sarcoidosis. PLoS One 2016; 11 (01) e0147258
    CrossrefPubMedGoogle Scholar
  • 79 Groen-Hakan F, Eurelings L, ten Berge JC. , et al. Diagnostic value of serum-soluble interleukin 2 receptor levels vs angiotensin-converting enzyme in patients with sarcoidosis-associated uveitis. JAMA Ophthalmol 2017; 135 (12) 1352-1358
    CrossrefPubMedGoogle Scholar
  • 80 Jones NP, Tsierkezou L, Patton N. Lymphopenia as a predictor of sarcoidosis in patients with uveitis. Br J Ophthalmol 2016; 100 (10) 1393-1396
    CrossrefPubMedGoogle Scholar
  • 81 Groen-Hakan F, Eurelings L, Rothova A, van Laar J. Lymphopaenia as a predictor of sarcoidosis in patients with a first episode of uveitis. Br J Ophthalmol 2019; 103 (09) 1296-1300
    CrossrefPubMedGoogle Scholar
  • 82 Hadjadj J, Dechartres A, Chapron T. , et al. Relevance of diagnostic investigations in patients with uveitis: retrospective cohort study on 300 patients. Autoimmun Rev 2017; 16 (05) 504-511
    CrossrefPubMedGoogle Scholar
  • 83 Takahashi T, Azuma A, Abe S, Kawanami O, Ohara K, Kudoh S. Significance of lymphocytosis in bronchoalveolar lavage in suspected ocular sarcoidosis. Eur Respir J 2001; 18 (03) 515-521
    CrossrefPubMedGoogle Scholar
  • 84 Ohmichi M. Histologic diagnosis of sarcoidosis [in Japanese]. Nihon Rinsho 2002; 60 (09) 1759-1765
    PubMedGoogle Scholar
  • 85 Ohara K, Okubo A, Kamata K, Sasaki H, Kobayashi J, Kitamura S. Transbronchial lung biopsy in the diagnosis of suspected ocular sarcoidosis. Arch Ophthalmol 1993; 111 (05) 642-644
    CrossrefPubMedGoogle Scholar
  • 86 de Boer S, Milne DG, Zeng I, Wilsher ML. Does CT scanning predict the likelihood of a positive transbronchial biopsy in sarcoidosis?. Thorax 2009; 64 (05) 436-439
    CrossrefPubMedGoogle Scholar
  • 87 Khan F, Wessely Z, Chazin SR, Seriff NS. Conjunctival biopsy in sarcoidosis: a simple, safe, and specific diagnostic procedure. Ann Ophthalmol 1977; 9 (05) 671-676
    PubMedGoogle Scholar
  • 88 Spaide RF, Ward DL. Conjunctival biopsy in the diagnosis of sarcoidosis. Br J Ophthalmol 1990; 74 (08) 469-471
    CrossrefPubMedGoogle Scholar
  • 89 Chung Y-M, Lin Y-C, Huang D-F, Hwang D-K, Ho DM. Conjunctival biopsy in sarcoidosis. J Chin Med Assoc 2006; 69 (10) 472-477
    CrossrefPubMedGoogle Scholar
  • 90 Crick R, Hoyle C, Mather G. Conjunctival biopsy in sarcoidosis. BMJ 1955; 2 (4949): 1180-1181
    CrossrefPubMedGoogle Scholar
  • 91 James DG. Ocular sarcoidosis. Am J Med 1959; 26 (03) 331-339
    CrossrefPubMedGoogle Scholar
  • 92 Blaise P, Fardeau C, Chapelon C, Bodaghi B, Le Hoang P. Minor salivary gland biopsy in diagnosing ocular sarcoidosis. Br J Ophthalmol 2011; 95 (12) 1731-1734
    CrossrefPubMedGoogle Scholar
  • 93 Bernard C, Kodjikian L, Bancel B, Isaac S, Broussolle C, Seve P. Ocular sarcoidosis: when should labial salivary gland biopsy be performed?. Graefes Arch Clin Exp Ophthalmol 2013; 251 (03) 855-860
    CrossrefPubMedGoogle Scholar
  • 94 Delcey V, Morgand M, Lopes A. , et al. Prevalence of granulomatous lesions in minor salivary gland biopsy in a case series of 65 patients with tuberculosis [in French]. Rev Med Interne 2016; 37 (02) 80-83
    CrossrefPubMedGoogle Scholar
  • 95 Takase H, Shimizu K, Yamada Y, Hanada A, Takahashi H, Mochizuki M. Validation of international criteria for the diagnosis of ocular sarcoidosis proposed by the first international workshop on ocular sarcoidosis. Jpn J Ophthalmol 2010; 54 (06) 529-536
    CrossrefPubMedGoogle Scholar
  • 96 Fakin A, Terčelj M, Vidović Valentinčič N. Frequency of IWOS suggestive ocular Signs in Slovenian uveitis patients with confirmed pulmonary sarcoidosis. Ocul Immunol Inflamm 2016; 24 (06) 660-664
    CrossrefPubMedGoogle Scholar
  • 97 Agrawal R, Gonzalez-Lopez JJ, Meier F, Gupta B, Pavesio CE. Ocular and systemic features of sarcoidosis and correlation with the International Workshop for Ocular Sarcoidosis diagnostic criteria. Sarcoidosis Vasc Diffuse Lung Dis 2015; 32 (03) 237-245
    PubMedGoogle Scholar
  • 98 Acharya NR, Browne EN, Rao N, Mochizuki M. ; International Ocular Sarcoidosis Working Group. Distinguishing features of ocular sarcoidosis in an international cohort of uveitis patients. Ophthalmology 2018; 125 (01) 119-126
    CrossrefPubMedGoogle Scholar
  • 99 Mochizuki M, Smith JR, Takase H. , et al. Revised criteria of International Workshop on Ocular Sarcoidosis (IWOS) for the diagnosis of ocular sarcoidosis. Br J Ophthalmol 2019; 103 (10) 1418-1422
    CrossrefPubMedGoogle Scholar
  • 100 Scott AW, Mruthyunjaya P, McCallum RM, Jaffe GJ. Diagnostic yield of vitreous biopsy in presumed sarcoidosis-related posterior segment inflammation. Graefes Arch Clin Exp Ophthalmol 2012; 250 (09) 1379-1385
    CrossrefPubMedGoogle Scholar
  • 101 Kojima K, Maruyama K, Inaba T. , et al. The CD4/CD8 ratio in vitreous fluid is of high diagnostic value in sarcoidosis. Ophthalmology 2012; 119 (11) 2386-2392
    CrossrefPubMedGoogle Scholar
  • 102 Maruyama K, Inaba T, Tamada T, Nakazawa T. Vitreous lavage fluid and bronchoalveolar lavage fluid have equal diagnostic value in sarcoidosis. Medicine (Baltimore) 2016; 95 (49) e5531
    CrossrefPubMedGoogle Scholar
  • 103 Nishiyama Y, Yamamoto Y, Fukunaga K. , et al. Comparative evaluation of 18F-FDG PET and 67Ga scintigraphy in patients with sarcoidosis. J Nucl Med 2006; 47 (10) 1571-1576
    PubMedGoogle Scholar
  • 104 Rahmi A, Deshayes E, Maucort-Boulch D. , et al. Intraocular sarcoidosis: association of clinical characteristics of uveitis with findings from 18F-labelled fluorodeoxyglucose positron emission tomography. Br J Ophthalmol 2012; 96 (01) 99-103
    CrossrefPubMedGoogle Scholar
  • 105 Chauvelot P, Skanjeti A, Jamilloux Y. , et al. 18F-fluorodeoxyglucose positron emission tomography is useful for the diagnosis of intraocular sarcoidosis in patients with a normal CT scan. Br J Ophthalmol 2019; 103 (11) 1650-1655
    CrossrefPubMedGoogle Scholar
  • 106 de Parisot A, Kodjikian L, Errera M-H. , et al; ULISSE group. Randomized controlled trial evaluating a standardized strategy for uveitis etiologic diagnosis (ULISSE). Am J Ophthalmol 2017; 178: 176-185
    CrossrefPubMedGoogle Scholar
  • 107 Han YS, Rivera-Grana E, Salek S, Rosenbaum JT. Distinguishing uveitis secondary to sarcoidosis from idiopathic disease: cardiac implications. JAMA Ophthalmol 2018; 136 (02) 109-115
    CrossrefPubMedGoogle Scholar
  • 108 Rosenbaum JT, Bodaghi B, Couto C. , et al. New observations and emerging ideas in diagnosis and management of non-infectious uveitis: A review. Semin Arthritis Rheum 2019; 49 (03) 438-445
    CrossrefPubMedGoogle Scholar
  • 109 Bae JH, Lee CS, Lee SC. Efficacy and safety of intravitreal bevacizumab compared with intravitreal and posterior sub-tenon triamcinolone acetonide for treatment of uveitic cystoid macular edema. Retina 2011; 31 (01) 111-118
    CrossrefPubMedGoogle Scholar
  • 110 Weijtens O, Feron EJ, Schoemaker RC. , et al. High concentration of dexamethasone in aqueous and vitreous after subconjunctival injection. Am J Ophthalmol 1999; 128 (02) 192-197
    CrossrefPubMedGoogle Scholar
  • 111 Pearson PA, Comstock TL, Ip M. , et al. Fluocinolone acetonide intravitreal implant for diabetic macular edema: a 3-year multicenter, randomized, controlled clinical trial. Ophthalmology 2011; 118 (08) 1580-1587
    CrossrefPubMedGoogle Scholar
  • 112 Lowder C, Belfort Jr R, Lightman S. , et al; Ozurdex HURON Study Group. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol 2011; 129 (05) 545-553
    CrossrefPubMedGoogle Scholar
  • 113 Pohlmann D, Vom Brocke GA, Winterhalter S, Steurer T, Thees S, Pleyer U. Dexamethasone inserts in noninfectious uveitis: a single-center experience. Ophthalmology 2018; 125 (07) 1088-1099
    CrossrefPubMedGoogle Scholar
  • 114 Touhami S, Diwo E, Sève P. , et al. Expert opinion on the use of biological therapy in non-infectious uveitis. Expert Opin Biol Ther 2019; 19 (05) 477-490
    CrossrefPubMedGoogle Scholar
  • 115 Jabs DA, Rosenbaum JT, Foster CS. , et al. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol 2000; 130 (04) 492-513
    CrossrefPubMedGoogle Scholar
  • 116 Hoang-Xuan K, Bessell E, Bromberg J. , et al; European Association for Neuro-Oncology Task Force on Primary CNS Lymphoma. Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology. Lancet Oncol 2015; 16 (07) e322-e332
    CrossrefPubMedGoogle Scholar
  • 117 Dev S, McCallum RM, Jaffe GJ. Methotrexate treatment for sarcoid-associated panuveitis. Ophthalmology 1999; 106 (01) 111-118
    CrossrefPubMedGoogle Scholar
  • 118 Baughman RP, Lower EE. A clinical approach to the use of methotrexate for sarcoidosis. Thorax 1999; 54 (08) 742-746
    CrossrefPubMedGoogle Scholar
  • 119 Baughman RP, Lower EE, Ingledue R, Kaufman AH. Management of ocular sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2012; 29 (01) 26-33
    PubMedGoogle Scholar
  • 120 Baughman RP, Lower EE. Leflunomide for chronic sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2004; 21 (01) 43-48
    PubMedGoogle Scholar
  • 121 Bhat P, Cervantes-Castañeda RA, Doctor PP, Anzaar F, Foster CS. Mycophenolate mofetil therapy for sarcoidosis-associated uveitis. Ocul Immunol Inflamm 2009; 17 (03) 185-190
    CrossrefPubMedGoogle Scholar
  • 122 Cabahug VLO, Uy HS, Yu-Keh E, Sapno KJD. Outcomes of treatment with sirolimus for non-infectious uveitis: a meta-analysis and systematic review. Clin Ophthalmol 2019; 13: 649-669
    CrossrefPubMedGoogle Scholar
  • 123 Nguyen QD, Merrill PT, Clark WL. , et al; Sirolimus study Assessing double-masKed Uveitis tReAtment (SAKURA) Study Group. Intravitreal sirolimus for noninfectious uveitis: a phase III Sirolimus Study Assessing Double-masKed Uveitis TReAtment (SAKURA). Ophthalmology 2016; 123 (11) 2413-2423
    CrossrefPubMedGoogle Scholar
  • 124 Linke M, Pham HTT, Katholnig K. , et al. Chronic signaling via the metabolic checkpoint kinase mTORC1 induces macrophage granuloma formation and marks sarcoidosis progression. Nat Immunol 2017; 18 (03) 293-302
    CrossrefPubMedGoogle Scholar
  • 125 Jaffe GJ, Dick AD, Brézin AP. , et al. Adalimumab in patients with active noninfectious uveitis. N Engl J Med 2016; 375 (10) 932-943
    CrossrefPubMedGoogle Scholar
  • 126 Nguyen QD, Merrill PT, Jaffe GJ. , et al. Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial. Lancet 2016; 388 (10050): 1183-1192
    CrossrefPubMedGoogle Scholar
  • 127 Dick AD, Rosenbaum JT, Al-Dhibi HA. , et al; Fundamentals of Care for Uveitis International Consensus Group. Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative. Ophthalmology 2018; 125 (05) 757-773
    CrossrefPubMedGoogle Scholar
  • 128 Vallet H, Seve P, Biard L. , et al; French Uveitis Network. Infliximab versus adalimumab in the treatment of refractory inflammatory uveitis: a multicenter study from the french uveitis network. Arthritis Rheumatol 2016; 68 (06) 1522-1530
    CrossrefPubMedGoogle Scholar
  • 129 Jamilloux Y, Saadoun D, Sève P. Re: Dick et al.: Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative (Ophthalmology. 2018;125:757-773). Ophthalmology 2018; 125 (08) e53-e54
    CrossrefPubMedGoogle Scholar
  • 130 Adler BL, Wang CJ, Bui T-L, Schilperoort HM, Armstrong AW. Anti-tumor necrosis factor agents in sarcoidosis: A systematic review of efficacy and safety. Semin Arthritis Rheum 2019; 48 (06) 1093-1104
    CrossrefPubMedGoogle Scholar
  • 131 Baughman RP, Lower EE, Bradley DA, Raymond LA, Kaufman A. Etanercept for refractory ocular sarcoidosis: results of a double-blind randomized trial. Chest 2005; 128 (02) 1062-47
    CrossrefPubMedGoogle Scholar
  • 132 Maneiro JR, Salgado E, Gomez-Reino JJ, Carmona L. ; BIOBADASER Study Group. Efficacy and safety of TNF antagonists in sarcoidosis: data from the Spanish registry of biologics BIOBADASER and a systematic review. Semin Arthritis Rheum 2012; 42 (01) 89-103
    CrossrefPubMedGoogle Scholar
  • 133 Erckens RJ, Mostard RLM, Wijnen PA, Schouten JS, Drent M. Adalimumab successful in sarcoidosis patients with refractory chronic non-infectious uveitis. Graefes Arch Clin Exp Ophthalmol 2012; 250 (05) 713-720
    CrossrefPubMedGoogle Scholar
  • 134 Riancho-Zarrabeitia L, Calvo-Río V, Blanco R. , et al. Anti-TNF-α therapy in refractory uveitis associated with sarcoidosis: multicenter study of 17 patients. Semin Arthritis Rheum 2015; 45 (03) 361-368
    CrossrefPubMedGoogle Scholar
  • 135 Jamilloux Y, Cohen-Aubart F, Chapelon-Abric C. , et al; Groupe Sarcoïdose Francophone. Efficacy and safety of tumor necrosis factor antagonists in refractory sarcoidosis: a multicenter study of 132 patients. Semin Arthritis Rheum 2017; 47 (02) 288-294
    CrossrefPubMedGoogle Scholar
  • 136 Wartique L, Jamilloux Y, De Parisot De Bernecourt A. , et al. Development of vitreoretinal lymphoma in a patient with sarcoid uveitis. Ocul Immunol Inflamm 2019; (July): 1-4
    PubMedGoogle Scholar
  • 137 Bloem K, Hernández-Breijo B, Martínez-Feito A, Rispens T. Immunogenicity of therapeutic antibodies: monitoring antidrug antibodies in a clinical context. Ther Drug Monit 2017; 39 (04) 327-332
    CrossrefPubMedGoogle Scholar
  • 138 Vande Casteele N, Gils A, Singh S. , et al. Antibody response to infliximab and its impact on pharmacokinetics can be transient. Am J Gastroenterol 2013; 108 (06) 962-971
    CrossrefPubMedGoogle Scholar
  • 139 Burmester G-R, Kivitz AJ, Kupper H. , et al. Efficacy and safety of ascending methotrexate dose in combination with adalimumab: the randomised CONCERTO trial. Ann Rheum Dis 2015; 74 (06) 1037-1044
    CrossrefPubMedGoogle Scholar
  • 140 Crommelin HA, van der Burg LM, Vorselaars ADM. , et al. Efficacy of adalimumab in sarcoidosis patients who developed intolerance to infliximab. Respir Med 2016; 115: 72-77
    CrossrefPubMedGoogle Scholar
  • 141 Seve P, Varron L, Broussolle C, Denis P, Kodjikian L. Sarcoid-related uveitis occurring during adalimumab therapy. Ocul Immunol Inflamm 2012; 20 (01) 59-60
    CrossrefPubMedGoogle Scholar
  • 142 Daïen CI, Monnier A, Claudepierre P. , et al; Club Rhumatismes et Inflammation (CRI). Sarcoid-like granulomatosis in patients treated with tumor necrosis factor blockers: 10 cases. Rheumatology (Oxford) 2009; 48 (08) 883-886
    CrossrefPubMedGoogle Scholar
  • 143 Valeyre D, Jeny F, Nunes H. Current medical therapy for sarcoidosis. Semin Respir Crit Care Med 2017; 38 (04) 523-531
    Article in Thieme ConnectPubMedGoogle Scholar
  • 144 Beccastrini E, Vannozzi L, Bacherini D, Squatrito D, Emmi L. Successful treatment of ocular sarcoidosis with rituximab. Ocul Immunol Inflamm 2013; 21 (03) 244-246
    CrossrefPubMedGoogle Scholar
  • 145 Lower EE, Baughman RP, Kaufman AH. Rituximab for refractory granulomatous eye disease. Clin Ophthalmol 2012; 6: 1613-1618
    PubMedGoogle Scholar
  • 146 Heiligenhaus A, Minden K, Tappeiner C. , et al. Update of the evidence based, interdisciplinary guideline for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis. Semin Arthritis Rheum 2019; 49 (01) 43-55
    CrossrefPubMedGoogle Scholar
  • 147 Silpa-Archa S, Oray M, Preble JM, Foster CS. Outcome of tocilizumab treatment in refractory ocular inflammatory diseases. Acta Ophthalmol 2016; 94 (06) e400-e406
    CrossrefPubMedGoogle Scholar
  • 148 Sepah YJ, Sadiq MA, Chu DS. , et al. Primary (Month-6) outcomes of the STOP-uveitis study: evaluating the safety, tolerability, and efficacy of tocilizumab in patients with noninfectious uveitis. Am J Ophthalmol 2017; 183: 71-80
    CrossrefPubMedGoogle Scholar
  • 149 Vegas-Revenga N, Calvo-Río V, Mesquida M. , et al. Anti-IL6-receptor tocilizumab in refractory and noninfectious uveitic cystoid macular edema: multicenter study of 25 patients. Am J Ophthalmol 2019; 200: 85-94
    CrossrefPubMedGoogle Scholar
  • 150 Damsky W, Thakral D, Emeagwali N, Galan A, King B. Tofacitinib treatment and molecular analysis of cutaneous sarcoidosis. N Engl J Med 2018; 379 (26) 2540-2546
    CrossrefPubMedGoogle Scholar
  • 151 Rotenberg C, Besnard V, Brillet P-Y, Giraudier S, Nunes H, Valeyre D. Dramatic response of refractory sarcoidosis under ruxolitinib in a patient with associated JAK2-mutated polycythemia. Eur Respir J 2018; 52 (06) 1801482
    CrossrefPubMedGoogle Scholar
  • 152 Wei JJ, Kallenbach LR, Kreider M, Leung TH, Rosenbach M. Resolution of cutaneous sarcoidosis after Janus kinase inhibitor therapy for concomitant polycythemia vera. JAAD Case Rep 2019; 5 (04) 360-361
    CrossrefPubMedGoogle Scholar
  • 153 Levraut M, Martis N, Viau P, Suarez F, Queyrel V. Refractory sarcoidosis-like systemic granulomatosis responding to ruxolitinib. Ann Rheum Dis 2019; 78 (11) 1606-1607
    CrossrefPubMedGoogle Scholar
  • 154 Paley MA, Karacal H, Rao PK, Margolis TP, Miner JJ. Tofacitinib for refractory uveitis and scleritis. Am J Ophthalmol Case Rep 2018; 13: 53-55
    CrossrefPubMedGoogle Scholar
  • 155 Bauermann P, Heiligenhaus A, Heinz C. Effect of janus kinase inhibitor treatment on anterior uveitis and associated macular edema in an adult patient with juvenile idiopathic arthritis. Ocul Immunol Inflamm 2019; 27 (08) 1232-1234
    CrossrefPubMedGoogle Scholar
  • 156 Menezo V, Lobo A, Yeo TK, du Bois RM, Lightman S. Ocular features in neurosarcoidosis. Ocul Immunol Inflamm 2009; 17 (03) 170-178
    CrossrefPubMedGoogle Scholar
  • 157 Obenauf CD, Shaw HE, Sydnor CF, Klintworth GK. Sarcoidosis and its ophthalmic manifestations. Am J Ophthalmol 1978; 86 (05) 648-655
    CrossrefPubMedGoogle Scholar
  • 158 Kidd DP, Burton BJ, Graham EM, Plant GT. Optic neuropathy associated with systemic sarcoidosis. Neurol Neuroimmunol Neuroinflamm 2016; 3 (05) e270
    CrossrefPubMedGoogle Scholar
  • 159 Chen RC, McLeod JG. Neurological complications of sarcoidosis. Clin Exp Neurol 1989; 26: 99-112
    PubMedGoogle Scholar
  • 160 Graham EM, Ellis CJ, Sanders MD, McDonald WI. Optic neuropathy in sarcoidosis. J Neurol Neurosurg Psychiatry 1986; 49 (07) 756-763
    CrossrefPubMedGoogle Scholar
  • 161 Beardsley TL, Brown SV, Sydnor CF, Grimson BS, Klintworth GK. Eleven cases of sarcoidosis of the optic nerve. Am J Ophthalmol 1984; 97 (01) 62-77
    CrossrefPubMedGoogle Scholar
  • 162 Blain JG, Riley W, Logothetis J. Optic nerve manifestations of sarcoidosis. Arch Neurol 1965; 13 (03) 307-309
    CrossrefPubMedGoogle Scholar
  • 163 Gudeman SK, Selhorst JB, Susac JO, Waybright EA. Sarcoid optic neuropathy. Neurology 1982; 32 (06) 597-603
    CrossrefPubMedGoogle Scholar
  • 164 Kelley JS, Green WR. Sarcoidosis involving the optic nerve head. Arch Ophthalmol 1973; 89 (06) 486-488
    CrossrefPubMedGoogle Scholar
  • 165 Jabs DA, Johns CJ. Ocular involvement in chronic sarcoidosis. Am J Ophthalmol 1986; 102 (03) 297-301
    CrossrefPubMedGoogle Scholar
  • 166 Ing EB, Garrity JA, Cross SA, Ebersold MJ. Sarcoid masquerading as optic nerve sheath meningioma. Mayo Clin Proc 1997; 72 (01) 38-43
    CrossrefPubMedGoogle Scholar
  • 167 Delaney P. Neurologic manifestations in sarcoidosis: review of the literature, with a report of 23 cases. Ann Intern Med 1977; 87 (03) 336-345
    CrossrefPubMedGoogle Scholar
  • 168 Frohman LP, Guirgis M, Turbin RE, Bielory L. Sarcoidosis of the anterior visual pathway: 24 new cases. J Neuroophthalmol 2003; 23 (03) 190-197
    CrossrefPubMedGoogle Scholar
  • 169 Baughman RP, Weiss KL, Golnik KC. Neuro-ophthalmic sarcoidosis. Eye Brain 2012; 4: 13-25
    CrossrefPubMedGoogle Scholar
  • 170 Frohman LP. Treatment of neuro-ophthalmic sarcoidosis. J Neuroophthalmol 2015; 35 (01) 65-72
    CrossrefPubMedGoogle Scholar
  • 171 Cohen Aubart F, Bouvry D, Galanaud D. , et al. Long-term outcomes of refractory neurosarcoidosis treated with infliximab. J Neurol 2017; 264 (05) 891-897
    CrossrefPubMedGoogle Scholar