Klin Monbl Augenheilkd 2018; 235(04): 424-435
DOI: 10.1055/s-0043-124966
Klinische Studie
Georg Thieme Verlag KG Stuttgart · New York

Need for Quantitative Measurement Methods for Posterior Uveitis: Comparison of Dual FA/ICGA Angiography, EDI-OCT Choroidal Thickness and SUN Vitreous Haze Evaluation in Stromal Choroiditis

Bedürfnis für quantitative Messungsmethoden der Entzündung bei Uveitis posterior: FA/ICGA versus SUN-Glaskörpertrübungsmessung in stromalen Choroiditiden
Filippo Fabro
Ophthalmology, Retinal and Inflammatory Eye Diseases, Centre for Ophthalmic Specialized Care (COS), Clinic Montchoisi Teaching Centre, Lausanne, Switzerland
,
Carl P. Herbort
Ophthalmology, Retinal and Inflammatory Eye Diseases, Centre for Ophthalmic Specialized Care (COS), Clinic Montchoisi Teaching Centre, Lausanne, Switzerland
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Publikationsverlauf

received 20. September 2017

accepted 08. Dezember 2017

Publikationsdatum:
18. April 2018 (online)

Abstract

Background/Purpose Quantitative methods for posterior uveitis are necessary for precise appraisal and follow-up of inflammation in practice and in clinical trials. The aim of this study was to assess fluorescein angiography (FA), indocanine green angiography (ICGA), and enhanced depth imaging optical coherence tomography choroidal thickness (EDI-OCT CT) in two stromal choroiditis entities, birdshot retinochoroiditis (BRC), and Vogt-Koyanagi-Harada disease (VKH), as well as to determine (1) disease patterns, (2) respective response to therapy, and (3) their potential utility in clinical trials in comparison to vitreous haze, the present standard outcome used in clinical trials.

Methods This retrospective study included newly diagnosed patients with BRC and VKH, seen at the Centre for Ophthalmic Specialized Care, Lausanne, Switzerland. Angiographic signs were quantified using an established dual FA/ICGA scoring system for uveitis at presentation and on follow-up. FA/ICGA score ratios were compared between diseases to determine disease patterns. EDI-OCT CT was determined using a spectral domain instrument. Vitreous haze was determined using the SUN (Standardization of Uveitis Nomenclature) method.

Results Among 1872 uveitis patients seen from 1995 to 2016, 8 newly diagnosed BRC patients (16 eyes) and 6 newly diagnosed VKH patients (12 eyes) had sufficient data for study inclusion. Patients with BRC and VKH at initial onset had mean FA scores of 16.1 ± 7.0 vs. 4.6 ± 2.1 (p < 0.0001), respectively, while mean ICGA scores were similarly high in the two diseases, 18.9 ± 3.6 (BRC) vs. 20.8 ± 7.5 (VKH). After therapy, FA and ICGA scores decreased significantly for both entities (− 60% of FA score and 55% of ICGA score in BRC vs. − 72% of FA score and − 87% for ICGA score in VKH). EDI-OCT CT decreased significantly in the two entities. Vitreous haze was almost absent in VKH and low in BRC.

Conclusion Dual FA/ICGA scoring showed the diverse disease patterns of BRC and VKH; both the retina and choroid were involved at onset in BRC, whereas VKH was a pure choroidal disease with later spillover into the retina. Dual FA/ICGA allowed for the precise measurement of inflammation at onset and upon follow-up. EDI-OCT CT responded to therapy in both diseases but was found to be of limited use in this early/subacute disease phase because it lacked sensitivity to detect subclinical recurrences and was therefore only useful for long-term follow-up. Vitreous haze was low in both entities and thus useless as an inflammatory parameter.

Zusammenfassung

Hintergrund Quantitative Messungsmethoden sind unbedingt notwendig für eine präzise Einschätzung des Entzündungsgrads der Uveitis posterior. Ziel war es hier, Fluoreszenzangiografie (FA), Indocyaningrünangiografie (ICGA) und EDI-OCT (Enhanced Depth Imaging optical Coherence Tomography choroidal Thickness) bei 2 stromalen Choroiditiden, Birdshot-Retinochoroiditis (BRC) und Morbus Vogt-Koyanagi-Harada (VKH) abzuwägen und deren Nützlichkeit mit dem zurzeit gebrauchten Standard „SUN vitreous Haze“ (SUN: Standardization of Uveitis Nomenclature) im täglichen Gebrauch und in klinischen Studien zu vergleichen.

Patienten und Methoden Diese retrospektive Studie betrifft Patienten mit den Diagnosen BRC und VKH, die in unserem Zentrum bei Neudiagnose untersucht wurden. Angiografische Zeichen wurden durch ein etabliertes FA/ICGA-Scoring-System für Uveitis bei Eintritt und in Verlaufskontrollen ausgewertet und wurden zwischen beiden Krankheiten verglichen. Die Aderhautdicke wurde mit der EDI-OCT-Methode gemessen und die Glaskörperinfiltration wurde mit der „SUN vitreous Haze“-Methode beurteilt.

Resultate Acht neu diagnostizierte BRC-Patienten und 6 VKH-Patienten hatten genug Daten und konnten in die Studie aufgenommen werden. Der FA-Wert war hoch bei BRC (16,1 ± 7,0) und tief bei VKH (4,6 ± 2,1) (p < 0,0001), wobei die ICGA-Werte bei beiden Gruppen hoch waren (18,9 ± 3,6 [BRC] vs. 20,8 ± 7,5 [VKH]). Der Effekt der Therapie konnte exakt gemessen werden. FA- sowie ICGA-Werte wurden durch die Therapie in verschiedenen Proportionen signifikant herabgesetzt. Die FA-Werte bei BRC zeigten eine relative Resistenz zur Therapie. Die Glaskörperinfiltration war bei beiden Krankheiten gering und konnte kaum gemessen werden.

Schlussfolgerungen Das duale FA/ICGA-Scoring-System erlaubte es, verschiedene Krankheitsbilder bei BRC und VKH zu bestimmen. VKH ist eine pure Aderhautkrankheit, die sekundär auf die Retina übergreift. Bei BRC gibt von Anfang an eine duale retinale und choroidale Entzündung. Duales FA/ICGA Scoring erlaubte es, präzise beide Kompartimente zu verfolgen, und ist bestimmt das angebrachteste Mittel im Alltag und in Studien, um die Entzündung des hinteren Segments zu verfolgen. Die SUN-Glaskörperinfiltration erwies sich als unnütz zur Ermittlung des Entzündungsgrads bei Uveitis posterior und ist nicht mehr gerechtfertigt, um als Parameter gebraucht zu werden.

 
  • References

  • 1 Herbort jr. CP, Tugal-Tutkun I. The importance of quantitative measurement methods for uveitis, laser flare photometry endorsed in Europe while neglected in Japan where the technology measuring quantitatively intraocular inflammation was developed. Int Ophthalmol 2017; 37: 469-473
  • 2 Tugal-Tutkun I, Herbort CP. Laser flare photometry: a noninvasive, objective and quantitative method to measure intraocular inflammation. Int Ophthalmol 2010; 30: 453-464
  • 3 Herbort CP, Guex-Crosier Y, de Ancos E. et al. Use of laser flare photometry (LFP) to assess and monitor inflammation in uveitis. Ophthalmology 1997; 104: 64-72
  • 4 Guex-Crosier Y, Pittet N, Herbort CP. Evaluation of laser flare-cell photometry in the appraisal and management of intraocular inflammation in uveitis. Ophthalmology 1994; 101: 728-735
  • 5 Herbort CP, Tugal-Tutkun I. Laser flare (cell) photometry: 20 years already. Int Ophthalmol 2010; 30: 445-447
  • 6 Papadia M, Jeannin B, Herbort CP. OCT findings in birdshot chorioretinitis: a glimpse into retinal disease evolution. Ophthalmic Surg Lasers Imaging 2012; 43 (Suppl.) 25-31
  • 7 Onal S, Tugal-Tutkun I, Neri P. et al. Optical tomography imaging in uveitis. Int Ophthalmol 2014; 34: 401-435
  • 8 Herbort jr. CP, Tugal-Tutkun I, Neri P. et al. Failure to integrate quantitative measurement methods of ocular inflammation hampers clinical practice and trials on new therapies for posterior uveitis. J Ocul Pharmacol Ther 2017; 33: 263
  • 9 Herbort CP, LeHoang P, Guec-Crosier Y. Schematic interpretation of indocyanine angiography in posterior uveitis using a standard angiographic protocol. Ophthalmology 1998; 105: 432-440
  • 10 Herbort CP. Posterior uveitis: new insights given by indocyanine green angiography. Eye (Lond) 1998; 12: 757-759
  • 11 Herbort CP, Mantovani A, Papadia M. Use of indocyanine green angiography in uveitis. Int Ophthalmol Clin 2012; 52: 13-31
  • 12 Bouchenaki N, Herbort CP. The contribution of indocyanine green angiography to the appraisal and management of Vogt-Koyanagi-Harada disease. Ophthalmology 2001; 108: 54-64
  • 13 Fardeau C, Herbort CP, Kullman N. et al. Indocyanine green angiography in birdshot chorioretinopathy. Ophthalmology 1999; 106: 1928-1934
  • 14 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: 509-516
  • 15 Tugal-Tutkun I, Herbort CP, Khairallah M. The Angiography Scoring for Uveitis Group (ASUWOG). Scoring of dual fluorescein and ICG inflammatory angiographic signs for the grading of posterior inflammation (dual fluorescein and ICG angiographic scoring system for uveitis). Int Ophthalmol 2010; 30: 539-552
  • 16 Tugal-Tutkun I, Herbort CP, Khairallah M. et al. Interobserver agreement in scoring of dual fluorescein and ICG inflammatory angiographic signs for the grading of posterior segment inflammation. Ocul Immunol Inflamm 2010; 18: 385-389
  • 17 Spaide RF, Koisumi H, Posonni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol 2008; 146: 496-500
  • 18 Nakai K, Gomi F, Ikuno Y. et al. Choroidal observation in Vogt-Koyanagi-Harada disease using high penetration optical coherence tomography. Graefes Arch Clin Exp Ophthalmol 2012; 250: 1089-1095
  • 19 Skvortsova N, Gasc A, Jeannin B. et al. Evolution of choroidal thickness over time and effect of early and sustained therapy in birdshot retinochoroiditis. Eye (Lond) 2017;
  • 20 Herbort jr. CP, Pavésio C, LeHoang P. et al. Why birdshot retinochoroiditis should rather be called “HLA-A29 uveitis”. Br J Ophthalmol 2017; 101: 851-855 doi:10.1136/bjophthalmol-2016-309764
  • 21 Papadia M, Herbort CP. Reappraisal of birdshot retinochoroiditis (BRC): a global approach. Graefes Arch Clin Exp Ophthalmol 2013; 251: 861-869
  • 22 Abu El-Asrar AM, Hemachandran S, Al-Mezaine HS. et al. The outcomes of mycophenolate mofetil therapy combined with systemic corticosteroids in acute uveitis associated with Vogt-Koyanagi-Harada disease. Acta Ophthalmol 2012; 90: e603-e608
  • 23 Herbort jr. CP, Abu El Asrar AM, Yamamoto JH. Reappraisal of management of Vogt- Koyanagi-Harada disease: sunset glow fundus is no more a fatality. Int Ophthalmol 2016; 37: 1383-1395
  • 24 Ryan SJ, Maumenee AE. Birdshot retinochoroidopathy. Am J Ophthalmol 1980; 89: 31-45
  • 25 Gass JDM. Vitiliginous chorioretinitis. Arch Ophthalmol 1981; 99: 1778-1787
  • 26 Knecht PB, Papadia M, Herbort CP. Granulomatous keratic precipitates in birdshot retinochoroiditis. Int Ophthalmol 2013; 33: 133-137
  • 27 Balci O, Gasc A, Jeannin B. et al. Enhanced depth imaging is less suited than indocyanine green angiography for close monitoring of primary stromal choroiditis: a pilot report. Int Ophthalmol 2017; 37: 737-748 doi:10.1007/s10792-016-0303-7
  • 28 Herbort CP, Probst K, Cimino L. et al. Differential inflammatory involvement in retina and choroid in birdshot chorioretinopathy. Klin Monatsbl Augenheilkd 2004; 221: 351-356
  • 29 Abu El Asrar AM, Dosari M, Hemachandran S. et al. Mycophenolate mofetil combined with systemic corticosteroids prevents progression to chronic recurrent inflammation and development of ʼsunset glow fundusʼ in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada disease. Acta Ophthalmol 2017; 95: 85-90 doi:10.1111/aos.13189
  • 30 Kawaguchi T, Horie S, Bouchenaki N. et al. Suboptimal therapy controls clinically apparent disease but not subclinical progression of Vogt-Koyanagi-Harada disease. Int Ophthalmol 2010; 30: 41-50
  • 31 Bouchenaki N, Herbort CP. Indocyanine green angiography guided management of Vogt-Koyanagi-Harada disease. J Ophthalmic Vis Res 2011; 6: 241-248
  • 32 Bouchenaki N, Herbort CP. Stromal Choroiditis. In: Pleyer U, Mondino B. eds. Essentials in Ophthalmology: Uveitis and Immunological Disorders. Berlin, Heidelberg, New York: Springer; 2004: 234-253
  • 33 Miyanaga M, Kawaguchi T, Miyata K. et al. Indocyanine green angiography findings in initial acute pre-treatment Vogt-Koyanagi-Harada disease in Japanese patients. Jp J Ophthalmol 2010; 54: 377-382
  • 34 Abouammoh MA, Gupta V, Hemachandran S. et al. Indocyanine green angiography in initial-onset acute Vogt-Koyanagi-Harada disease. Acta Ophthalmol 2016. doi:101111/aos 12974.