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.

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.

Multimodal imaging of the disease progression of birdshot chorioretinopathy.

PURPOSE: To study outer retinal deterioration in relation to clinical disease activity in patients with birdshot chorioretinopathy using fundus autofluorescence and spectral-domain optical coherence tomography (OCT). METHODS: A single-centre retrospective cohort study was carried out on 42 eyes of 21 patients with birdshot disease, using a multimodal imaging approach including fundus autofluorescence, OCT, fluorescein angiography and indocyanine green angiography in combination with a patient chart review. The patients' overall clinical activity of retinal vasculitis during the follow-up period was determined by periods of clinical activity as indicated by fluorescein angiography and associated treatment decisions. Image analysis was performed to examine the spatial correspondence between autofluorescence changes and disruption of the photoreceptor inner segment ellipsoid zone on OCT. RESULTS: Three common types of outer retinal lesions were observed in fovea-centred images of 43% of patients: circular patches of chorioretinal atrophy, ellipsoid zone disruption on OCT, and outer retinal atrophy on autofluorescence and OCT. There was good spatial correspondence between ellipsoid zone disruption and areas of diffuse hyper-autofluorescence outside the fovea. Interestingly, the ellipsoid zone disruption recovered in four out of seven patients upon intensified therapeutic immunosuppression. CONCLUSION: Most patients only developed peripapillary atrophy and occasional perivascular hypo-autofluorescence. A multimodal imaging approach with autofluorescence imaging and OCT may help to detect ellipsoid zone disruption in the central retina of patients with birdshot disease. Our results suggest that ellipsoid zone disruption may be related to both the activity and duration of retinal vasculitis, and could help to determine therapeutic success in birdshot disease.

Relevance of wide-field autofluorescence imaging in Birdshot retinochoroidopathy: descriptive analysis of 76 eyes.

PURPOSE: To study and classify retinal lesions in patients with birdshot disease using wide-field autofluorescence imaging and correlate them according to patients' visual status. METHODS: A multicentre study was carried out on 76 eyes of 39 patients with birdshot disease, analysing colour images and under autofluorescence using the wide-field Optomap(®) imaging system. This was combined with a complete clinical exam and analysis of the macula with OCT. RESULTS: In over 80% of the eyes, a chorioretinal lesion has been observed under autofluorescence with a direct correlation between the extent of the lesion and visual status. The presence of macular hypo-autofluorescence was correlated with a decreased visual acuity, due to the presence of a macular oedema, active clinical inflammation or an epiretinal membrane. The hypo-autofluorescence observed correlated with the duration of the disease and the degree of inflammation in the affected eye, indicating a secondary lesion in the pigment epithelium in relation to the choroid. The pigment epithelium was affected in a diffuse manner, as in almost 50% of the eyes the wider peripheral retina was affected. CONCLUSION: Wide-field autofluorescence imaging could appear to be a useful examination when monitoring patients, to look for areas of macular hypo-autofluorescence responsible for an irreversible loss of vision.

Spectral-domain optical coherence tomographic findings at each stage of punctate inner choroidopathy.

PURPOSE: To describe the natural course of punctate inner choroidopathy (PIC) using spectral-domain optical coherence tomography (SD-OCT). DESIGN: Prospective observational case series. PARTICIPANTS: Forty-two consecutive patients (60 eyes) with PIC with at least 3 months of follow-up. METHODS: Serial SD-OCT images were obtained from both eyes of each participant at each visit. MAIN OUTCOME MEASURES: The morphologic characteristics of each stage of PIC lesions observed by SD-OCT. RESULTS: Continued stage progression of PIC lesions was observed in 27 eyes (45%), among which choroidal thickness changes were observed in 8 eyes (30%). Stage I lesion showed a normal appearance or slight irregularities in the outer nuclear layer. Stage II lesion appeared as a focal elevation of the retinal pigment epithelium (RPE) with corresponding disruption of the inner and outer segments of the photoreceptor interface. Stage III lesion broke through the RPE, forming a hump-shaped chorioretinal nodule with moderate reflectivity beneath the outer plexiform layer (OPL), generally with subsequent disruption of Bruch's membrane. Nodules occasionally invaded the inner retina, causing segmental retinal phlebitis in 2 eyes. Stage IV lesion regressed in a retrograde manner with tissue loss from the photoreceptor layer and inner choroid, finally leaving a V-shaped hernia of the OPL and inner retina into the choroid. Stage V lesion gradually eliminated the photoreceptors around the lesion; this process was accompanied by RPE proliferation at multiple levels, which reduced retinal herniation. Parafoveal stage V lesions caused late occult macular atrophy in 4 eyes. Choroidal thickness increased throughout the active phase and reached a peak at stage III; this parameter then significantly decreased at stage IV and gradually reached a minimum that was lower than the initial value at stage I. CONCLUSIONS: Punctate inner choroidopathy is a chorioretinitis rather than an inner choroidopathy. Spectral-domain OCT characterized a 5-stage evolution of PIC lesions: choroidal infiltration, formation of sub-RPE nodules, and then chorioretinal nodules, regression, and retinal herniation.

Differential inflammatory involvement in retina and choroïd in birdshot chorioretinopathy.

BACKGROUND: Birdshot chorioretinopathy is characterised by dual unrelated inflammatory involvement of the retina and the choroid. Indocyanine green angiography made it possible to assess and follow choroidal disease with the same precision as retinal involvement was followed so far. The aim of this study was to analyse the severity, progression and response to therapy of both retinal involvement using fluorescein angiography and choroidal involvement using indocyanine green angiography. PATIENTS AND METHODS: Patients with birdshot retinochoroidopathy followed at La Source Eye Centre in Lausanne, Switzerland from January 1995 to December 2002 were subdivided into three subgroups according to the duration of evolution of the disease: untreated patients with no more than one year duration of the disease (group 1, n = 6); treated patients with disease duration of 1 - 7 years duration (group 2, n = 5) and patients with disease lasting for more than 7 years (group 3, n = 4). Fluorescein and indocyanine green angiographic signs (angiographic scores given by a masked observer) were analysed in the 3 groups and compared to the "cream-coloured" fundus lesions. RESULTS: Fifteen out of the 742 patients (2.0 %) seen at La Source Eye Centre during the time period considered presented BC and were included in the study. In the "early disease group" fluorescein and ICG angiography showed more severe choroidal than retinal involvement with respective scores of 3 +/- 0.79 (ICG) and 2 +/- 1.17 (FA) while there were few depigmented fundus lesions to be seen (score 1 +/- 0.27). The choroidal involvement responded well to systemic corticosteroids +/- immunosuppressive therapy (scores in groups 2 and 3 = 1.2 and 0.75), while retinal disease was stabilised at best (scores in groups 2 and 3 = 2.2. and 2.4) and depigmented fundus lesions increased (scores in groups 2 and 3 = 2.8 and 3). CONCLUSION: The evolution and response to therapy of retinal and choroidal disease in birdshot chorioretinopathy have a different course with choroidal disease responding well to therapy while retinal disease is more resistant, possibly explaining the slow deterioration of functional parameters despite therapy. The increase of "cream-coloured" fundus lesions despite good choroidal response to therapy could be explained by depigmentation left behind after resolution of choroidal stromal granulomas, a hypothesis recently confirmed by an autopsy case of birdshot chorioretinopathy.

[Acute zonal occult outer retinopathy (AZOOR)]. / Akute zonale okkulte äussere Retinopathie (AZOOR).

BACKGROUND: The "white dot syndromes" are a clinically heterogeneous group of inflammatory chorioretinopathies with an inconsistent classification. It is not yet clear if they represent distinct entities or if they are only different forms of the same basic disease. CASE REPORT: A 53-year-old female patient presented with unilateral photopsia and reduced vision in the left eye. Funduscopy of the left eye showed peripapillary confluent whitish infiltrates in the deep retinal layers with corresponding enlargement of the blind spot. Slow progression of the lesions was observed followed by the development of subretinal fibrosis in the macula. The ERG was reduced in the left eye. In both eyes there were small round, partly confluent areas of RPE atrophy in the lower fundus periphery without inflammatory reaction in the vitreous body or anterior chamber. CONCLUSION: The presented case shows overlapping features of acute zonal occult outer retinopathy (AZOOR), multifocal choroiditis and diffuse subretinal fibrosis and uveitis. This case and other previously described cases with overlaps between different clinical entities support the theory that clinically different inflammatory chorioretinal diseases may represent parts of a spectrum of one common disease.

White spots syndromes.

The different types of white spots occurring in the fundus are analysed. A. Acute white spots, vanishing later on. 1. Multiple Evanescent White Dot Syndrome. 2. Cat scratch disease. 3. AIDS microangiopathy. 4. Cotton-wool spots. 5. Acute vitelliform maculopathy. B. Acute white spots with coalescence and diffuse scarring. 1. Acute posterior multifocal placoid pigment epitheliopathy. 2. Serpiginous choroïditis (geographic choroïditis). 3. Herpes retinitis. C. Acute white spots becoming white scars with variable pigmentation. 1. Multifocal choroiditis--classical form. 1a. Punctate inner choroidopathy. 1b. Diffuse subretinal fibrosis. 2. Toxoplasmic retinochoroiditis. 3. Tuberculous chorioretinitis. 4. Syphilitic chorioretinitis. 5. Lyme disease. 6. Sarcoidosis. 7. Sympathetic ophthalmia. 8. Vogt-Koyanagi-Harada disease. 9. Bacterial retinochoroiditis. 10. Fungal retinochoroiditis--Candida. 11. Pneumocystis carinii choroiditis. D. Late white spots with or without initial white-orange spots. Birdshot chorioretinitis.

Relentless placoid chorioretinitis: A new entity or an unusual variant of serpiginous chorioretinitis?

OBJECTIVE: To characterize an unusual clinical entity resembling acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and serpiginous choroiditis but with an atypical clinical course. PATIENTS: We describe 6 patients, aged 17 through 51 years, exhibiting this unusual entity who were seen at 6 different centers from 1984 to 1997. RESULTS: The acute retinal lesions in this series were similar to those of APMPPE or serpiginous choroiditis, both clinically and on fluorescein and indocyanine green angiography. However, the clinical course, number of lesions, and location of these lesions were atypical. These patients had evidence of numerous posterior and peripheral retinal lesions predating or occurring simultaneously with macular involvement. Older, healing pigmented lesions were often accompanied by the appearance of new active white placoid lesions. Additionally, these cases all demonstrated prolonged periods of activity resulting in the appearance of more than 50 and sometimes hundreds of lesions scattered throughout the fundus. Growth of subacute lesions and the appearance of new lesions continued for 5 to 24 months after initial examination, and relapses were common. CONCLUSIONS: This entity has clinical features similar to APMPPE and serpiginous choroiditis but has a prolonged progressive clinical course and widespread distribution of lesions. It may represent a variant of serpiginous choroiditis or may be a new entity. We call it relentless placoid chorioretinitis. Arch Ophthalmol. 2000;118:931-938

[Central serous chorioretinitis. Therapy experience over 20 years with and without laser coagulation]. / Chorioretinitis centralis serosa. Therapieerfahrung über 20 Jahre mit und ohne Laserkoagulation.

Since 1969, 1,179 eyes with central serous chorioretinopathy have been examined with fluorescein fundus angiography. The classic form with fluorescein leakage (type I) decreased in incidence from 86.4% to 55.4%, while an atypical form with frequent serous pigment epithelial detachment (type II) increased from 12.6% to 33.0%, and the mixed form (type I + II) increased from 1 to 11.6%. In type I with delayed healing laser coagulation of the leakage was performed, which improved the visual acuity from 0.64 to 0.92 an average (n = 122), while in cases without laser coagulation the percentage improved only from 0.66 to 0.84 on average (n = 34) with a statistically significant difference (t = 2.64, P < 0.01). Laser coagulation was especially beneficial in the mixed form (n = 16), in which the visual acuity improved from 0.42 to 0.86 on average. The proportion of women increased from 10.7 to 17.9%. The patient age tended to be higher in women more than in men.

[Clinical chorioretinal aspects in systemic immune vasculitis. II]. / Aspecte clinice corioretiniene în vasculitate imune sistemice. Partea a II-a.

Systemic immune vascular pathology raises very often diagnosis and differential diagnosis difficulties generated by the multitude and polymorphism of its clinical symptomatology. Chorioretinal modifications, sometimes particular, may complete the general clinical picture of the systemic immune vasculitis, favouring a correct clinical diagnosis. At the same time, a better knowledge of the clinical picture of some general systemic affections may lead to a correct diagnostic interpretation of these chorioretinal modifications. The paper presents the author's own classification of the main systemic immune vasculitis and also several rare affections (with immunologic implications) with emphasis on the vascular chorioretinal syndrome and on the clinical general one.

[Clinical chorioretinal aspects of systemic immune vasculitis. I. General aspects]. / Aspecte clinice corioretiniene în vasculitele imune sistemice. Partea I--generalitati.

The eye, due to its rich vascularity, is frequently involved, directly or not, in the systemic immune vascular pathology. For a better understanding of the ocular clinical syndrome, the paper discusses the etiologic and pathogenic factors, and their influence on the characteristics of chorioretinal changes. The etiologic factors are classified according to the predominance of the lesions of the choroidal or retinal vessels. The pathogeny of the chorioretinal changes is correlated with the histopathologic lesion (fibrinoid necrosis) and its involvement in the "choriocapillaris complex-brush membrane-EPR". Clinical chorioretinal syndrome, irrespective of its etiology, induces several retinal and choroidal changes having varied as a function of the evolution stage.