Multimodal imaging in infectious and noninfectious intermediate, posterior and panuveitis.

PURPOSE OF REVIEW: Given the heterogeneity of uveitis, markers of inflammation vary from patient to patient. Multimodal imaging has proven itself to be critical for accurate evaluation for disease activity and treatment response in uveitis. RECENT FINDINGS: Ultra-widefield (UWF) fluorescein angiography and autofluorescence (AF) as well as optical coherence tomography angiography (OCTA) have provided insights into disease pathogenesis and monitoring not previously appreciated. In addition to structural retinal imaging, OCT can be used to assess the choroid, the posterior cortical vitreous and the retinal vasculature in eyes with uveitis. SUMMARY: Multimodal ocular imaging in eyes with uveitis is critical for disease diagnosis and assessing response to treatment. UWF fluorescein angiography can detect retinal vasculitis even in the absence of overt vascular sheathing. UWF AF can help detect more chorioretinal lesions than clinically visible. OCT can be used to assess the posterior cortical vitreous, retina, large retinal vessels and choroid in uveitis. The use of multimodal imaging will likely be needed to determine clinical trial endpoints in studies evaluating therapeutics for uveitis.

Superficial and deep retinal foveal avascular zone OCTA findings of non-infectious anterior and posterior uveitis.

PURPOSE: To compare the superficial (FAZ-S) and deep foveal avascular zones (FAZ-D) of non-infectious anterior and posterior uveitis to healthy controls, using optical coherence tomography angiography (OCTA). METHODS: OCTA was performed on 74 eyes: 34 eyes with non-infectious posterior uveitis (with (post+CME) and without macular edema (post-CME)), 11 eyes with non-infectious anterior uveitis (with (ant+CME) and without macular edema (ant-CME)), and the control group which included 29 healthy eyes. RESULTS: Eyes suffering from non-infectious posterior uveitis presented with significantly larger FAZ-D when compared to healthy controls, both in the presence or in the absence of macular edema (p < 0.001). In the presence of macular edema, eyes presenting with anterior uveitis (ant+CME) also showed significantly larger FAZ-S (p = 0.03) and FAZ-D (p < 0.001), when compared to healthy controls. In the absence of macular edema, eyes with anterior uveitis cannot be distinguished from controls (p > 0.6). CONCLUSION: The deep retinal foveal avascular zone seems to be enlarged in eyes presenting with non-infectious posterior uveitis, both in the presence or absence of macular edema.

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.

Relationship between ultra-widefield optical coherence tomography and ophthalmoscopy for detecting posterior inflammation in posterior uveitis and panuveitis.

PURPOSE: To confirm the utility of ultra-widefield optical coherence tomography (W-OCT) for diagnosing uveitis. METHOD: We retrospectively studied patients who had been diagnosed with uveitis and had undergone W-OCT. All patients had visited at Osaka Metropolitan University between January 2019 and January 2022. On W-OCT, vitreous opacity ("W-OCT VO") and the presence of vitreous cells ("W-OCT Cells") were identified by three specialists. We compared findings from ophthalmoscopy ("Ophthalmoscopic findings") and fluorescein angiography ("FAG findings") with those from W-OCT. RESULTS: This study investigated 132 eyes from 68 patients (34 males, 34 females; mean age, 53.97±22.71 years). Vitreous cells in posterior uveitis and panuveitis differed significantly between "W-OCT Cells" and "Ophthalmoscopic findings" for all cases (P = 0.00014). Vitreous opacities in posterior uveitis and panuveitis did not differ significantly between "W-OCT VO" and "Ophthalmoscopic findings" (P = 0.144) for all cases. Compared to "Ophthalmoscopic findings", "W-OCT Cells" offered 51.1% sensitivity and 66.7% specificity for all cases (p<0.01). Compared to "Ophthalmoscopic findings", "W-OCT VO" offered 78.6% sensitivity and 30% specificity for all cases (p = 0.19). In addition, "W-OCT Cells" did not differ significantly from "FAG findings" for all cases (P = 0.424). CONCLUSION: W-OCT was shown to offer significantly greater sensitivity than ophthalmoscopy for detecting vitreous cells. The results of this study may add an option for the evaluation of uveitis.

Spectrally resolved autofluorescence imaging in posterior uveitis.

Clinical discrimination of posterior uveitis entities remains a challenge. This exploratory, cross-sectional study investigated the green (GEFC) and red emission fluorescent components (REFC) of retinal and choroidal lesions in posterior uveitis to facilitate discrimination of the different entities. Eyes were imaged by color fundus photography, spectrally resolved fundus autofluorescence (Color-FAF) and optical coherence tomography. Retinal/choroidal lesions' intensities of GEFC (500-560 nm) and REFC (560-700 nm) were determined, and intensity-normalized Color-FAF images were compared for birdshot chorioretinopathy, ocular sarcoidosis, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and punctate inner choroidopathy (PIC). Multivariable regression analyses were performed to reveal possible confounders. 76 eyes of 45 patients were included with a total of 845 lesions. Mean GEFC/REFC ratios were 0.82 ± 0.10, 0.92 ± 0.11, 0.86 ± 0.10, and 1.09 ± 0.19 for birdshot chorioretinopathy, sarcoidosis, APMPPE, and PIC lesions, respectively, and were significantly different in repeated measures ANOVA (p < 0.0001). Non-pigmented retinal/choroidal lesions, macular neovascularizations, and fundus areas of choroidal thinning featured predominantly GEFC, and pigmented retinal lesions predominantly REFC. Color-FAF imaging revealed involvement of both, short- and long-wavelength emission fluorophores in posterior uveitis. The GEFC/REFC ratio of retinal and choroidal lesions was significantly different between distinct subgroups. Hence, this novel imaging biomarker could aid diagnosis and differentiation of posterior uveitis entities.

Advances and potential new developments in imaging techniques for posterior uveitis Part 2: invasive imaging methods.

The aim of this review was to identify the imaging methods at our disposal to optimally manage posterior uveitis at the present time. The focus was put on methods that have become available since the 1990s, some 30 years after fluorescein angiography had revolutionised imaging of posterior uveitis in particular imaging of the retinal vascular structures in the 1960s. We have focussed our review on precise imaging methods that have been standardised and validated and can be used universally thanks to commercially produced and available instruments for the diagnosis and follow-up of posterior uveitis. The second part of this imaging review will deal with invasive imaging methods and in particular ocular angiography.

Role of Ocular Imaging in Diagnosis and Determining Response to Therapeutic Interventions in Posterior and Panuveitis.

ABSTRACT: This review provides a comprehensive description and careful interpretation of various ocular imaging techniques to visualize the different ocular structures in posterior and panuveitis. This can help in the diagnosis, follow-up, and monitoring the response to treatment in patients with different posterior and panuveitic entities.

Advances and potential new developments in imaging techniques for posterior uveitis. Part 1: noninvasive imaging methods.

The aim of this review was to identify the imaging methods at our disposal to optimally manage posterior uveitis at the present time. The focus was put on methods that have become available since the 1990s, some 30 years after fluorescein angiography had revolutionized imaging of posterior uveitis in particular imaging of the retinal vascular structures in the 1960s. We have focussed our review on precise imaging methods that have been standardized and validated and can be used universally thanks to commercially produced and available instruments for the diagnosis and follow-up of posterior uveitis. The first part of this imaging review will deal with noninvasive imaging methods, focusing on fundus autofluorescence and optical coherence tomography as well as recent developments in imaging of the posterior segment.

IMMUNE RECOVERY UVEITIS-LIKE SYNDROME MIMICKING RECURRENT T-CELL LYMPHOMA AFTER AUTOLOGOUS BONE MARROW TRANSPLANT.

PURPOSE: To report the multimodal imaging findings of immune recovery uveitis mimicking recurrent T-cell lymphoma after autologous bone marrow transplant therapy. METHODS: A 71-year-old man presented with posterior uveitis 6 weeks after chemotherapy and autologous bone marrow transplant for angioimmunoblastic T-cell lymphoma. Multimodal imaging included fluorescein angiography, fundus autofluorescence, and optical coherence tomography. Diagnostic testing included ocular polymerase chain reaction and diagnostic vitrectomy. RESULTS: Clinical examination demonstrated vitritis and perivascular deep retinal whitening. Imaging of the retinal whitening showed late hyperfluorescence on fluorescein angiography, hyperautofluorescence on fundus autofluorescence, and ellipsoid zone loss on optical coherence tomography without infiltrative lesions. Testing was negative for syphilis, herpes simplex virus, varicella-zoster virus, and cytomegalovirus. After no clinical improvement with valacyclovir and intravitreal foscarnet treatment, diagnostic vitrectomy was performed. Bacterial and fungal cultures were negative, and herpes simplex virus, varicella-zoster virus, and cytomegalovirus were not detected by polymerase chain reaction. Cytopathology showed mature small nonneoplastic lymphocytes, macrophages, and monocytes. Flow cytometry demonstrated a reactive T-cell population. The patient demonstrated clinical improvement over time with spontaneous resolution of all retinal findings. CONCLUSION: This case most likely represents immune recovery uveitis-like syndrome. Diagnostic vitrectomy is highly valuable when the differential includes inflammatory, infectious, and neoplastic processes.

High-Resolution Imaging of Retinal Vasculitis by Flood Illumination Adaptive Optics Ophthalmoscopy: A Follow-up Study.

Purpose: To monitor perivascular sheathing during the course of retinal vasculitis by flood illumination adaptive optics ophthalmoscopy (AOO). Methods: Perivenous sheathing and venous diameters were quantitatively analyzed by semi-automatic segmentation of AOO images in 12 eyes of treatment-naive patients with retinal vasculitis. Results: The width of venous sheathing ranged from 45 to 225 µm (mean 101.0 µm ± 54.3). In 10 cases, the underlying vein showed focal narrowing (mean ± SD 14% ± 10). Focal narrowing of arteries was also present in one eye. At presentation, width of sheathing and vessel diameters were not correlated with fluorescein leakage. During follow-up, 5 eyes showed an increase in vein diameter or resolution of narrowing and in 10 eyes a thinning of vascular sheathing was observed (p= .003). Conclusions: Perivenous sheathing may be quantitatively analyzed and monitored by AOO. AOO may therefore contribute to monitor vascular sheathing during posterior uveitis.

Optical coherence tomography angiography in comparison with other multimodal imaging techniques in punctate inner choroidopathy.

AIMS: To characterise punctate lesions and choroidal neovascularisation (CNV) in eyes with punctate inner choroidopathy (PIC) using current standard multimodal imaging techniques and optical coherence tomography angiography (OCTA). METHODS: In our prospective, single-centre study, 20 individuals with PIC underwent imaging with spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), indocyanine green angiography, fundus autofluorescence, fundus colour photography and OCTA. RESULTS: Thirty-two eyes of 20 patients were affected. Eight (20%) eyes revealed typical punctate lesions, while 24 (60%) eyes had confirmed CNV on SD-OCT and FA in addition to punctate lesions. Of these 24 eyes with CNV, a reoccurrence of active CNV was detected in 5 (21%) eyes, a residual fluid in 3 (13%) eyes, while 16 (67%) eyes were defined as being stable. On OCTA, CNV was classified as having 'lacy wheel', 'pruned large-trunk' and 'dead tree aspect' vessel shapes with or without areas of non-perfusion. The disease activity was dependent on several predictors in the regression analysis such as intraretinal fluid (p=0.0014), CNV type (p=0.0199), leakage (p<0.0001) and hypoperfusion/non-perfusion (p<0.0001) on OCTA. CONCLUSION: OCTA offers additional valuable insight into the current standard multimodal imaging techniques used for characterisation of PIC. This imaging technique can be a useful tool for analysis of disease activity.

Detection of mild papilloedema in posterior uveitis using spectral domain optical coherence tomography.

OBJECTIVE: To compare two methods for diagnosing mild papilloedema (PO) using peripapillary total retinal (PTR) and retinal nerve fibre layer (RNFL) thickness measurement by spectral domain optical coherence tomography (OCT) in patients suffering from posterior uveitis. METHODS: 17 eyes in 17 patients with PO caused by posterior uveitis, 15 eyes in 15 patients with uveitis but with no PO based on slit lamp analysis were studied. High-quality OCT fundus images were analysed and graded by three masked observers using the Modified Frisén Scale. Eyes with PO were divided into two subgroups: mild (n=15) and moderate-severe PO (n=2). Two measurement methods were evaluated and compared: RNFL and PTR thickness measurements centred on the optic disc. Thickness values were calculated overall and for each quadrant and compared between groups. The main outcome measures were RNFL and PTR thickness, and thickness variation between control and affected patients for both protocols. RESULTS: Average RNFL and PTR thickness in the moderate-severe PO, mild PO and control groups were 274.5±54.45 µm, 134±31.69 µm, 97.4±14.43 µm and 722.25±29.34 µm, 437.53±84.47 µm, 327.8±25.92 µm, respectively. Mild PO differed from the control groups according to both the RNLF (p=0.0006) and the PTR (p=0.0002) measurements. The average thickness variation between control and mild PO was significantly different between RNFL and PTR measurements: 36.6 µm vs 109.73 µm (p<0.0001), respectively. CONCLUSIONS: PTR thickness measurement increases the sensitivity of detection of mild PO and could be useful for diagnosing and monitoring papillitis. A new protocol should be developed to measure PTR in the same 3.5 mm disc as the RNFL measurement.

Role of Ultra-Wide Field Imaging in the Management of Tubercular Posterior Uveitis.

PURPOSE: To assess the utility of ultra-wide field (UWF) versus conventional fundus imaging in the management of tubercular (TB) posterior uveitis. METHODS: Twenty-two consecutive patients (33 eyes) diagnosed with TB posterior uveitis in a tertiary care center who underwent UWF fundus photography and fluorescein angiography (FA) between July 2014 and March 2015 were included. Complete clinical and imaging records of the patients were retrospectively reviewed. A circle simulating the central 75-degree field was drawn on UWF pseudocolor and fluorescein angiography images. Findings within the circle were compared with the information yielded by the complete image and its impact on patient management was noted. RESULTS: The clinical manifestations of posterior tubercular uveitis included retinal vasculitis (17 eyes), multifocal serpiginoid choroiditis (13 eyes), choroidal granulomas (2 eyes) and intermediate uveitis (1 eye). UWF imaging revealed additional capillary non-perfusion areas, neovascularization, active vasculitis, and peripheral choroiditis lesions in 30/33 eyes (90.9%), which influenced treatment decision in 15 eyes (45.5%). CONCLUSIONS: UWF imaging is useful in the detection of peripheral pathologies in tubercular posterior uveitis that may influence management decisions, such as addition of immunosuppressive therapy or scatter laser photocoagulation.

In-vivo immunofluorescent imaging in cases of posterior uveitis.

In-vitro immunofluorescent assays/imaging are routinely used methods of detecting antigens. The ability to perform ocular angiography to study the choroidal and retinal vasculature in real time provides us with a unique opportunity to perform real time in-vivo immunofluorescent imaging. This unique combination of in-vivo immunofluorescent imaging and live imaging of choroidal and retinal circulation can help detect antigens of infective organisms in-vivo to diagnose causative infective aetiology in cases of choroiditis/retinitis. The following paper describes the basic designing of such an imaging platform.

Gallium-67-citrate scanning in patients with sarcoid uveitis.

Gallium-67-citrate is useful for characterizing activity in patients with sarcoidosis. Gallium-67 uptake in bilateral symmetrical hilar lymphadenopathy and/or symmetrical salivary glands is typical of this clinical entity. Sarcoidosis is a systemic disease, and uveitis is considered the hallmark of ophthalmic sarcoidosis. We present two cases of ophthalmic sarcoidosis that shows uveal accumulation of 67Ga-citrate associated with clinical symptoms.

[Utility of ultrasonography in toxoplasmic uveitis]. / Utilidad de la ecografía en las uveítis por toxoplasmosis.

PURPOSE: To analyze the main indications and the most common ultrasonographic features observed in uveitis due to toxoplasmosis. MATERIAL AND METHODS: We carried out a retrospective, observational and descriptive study performed in 97 exams corresponding to 89 patients with uveitis during 7 consecutive years (1994-2000) using B-ultrasonography evaluation. RESULTS: The main ultrasonographic indication in toxoplasmosis was vitreous opacity. We observed that the most frequent findings were: a) intravitreous punctiform echoes, b) thickening of posterior hyaloid, c) partial or total posterior vitreous detachment and d) focal retinochoroidal thickening. This last finding should be highlighted due to its significant correlation (p<0.01) with toxoplasmosis. CONCLUSIONS: Our results suggest that ultrasonography plays an important role in the diagnosis and clinical follow-up of toxoplasmic uveitis.

[Leukokoria. Diagnosis and treatment]. / Leucocorie. Aspecte etiopatogenetice si terapeutice.

PURPOSE: Is to evaluate the importance of the imaging tests when the posterior segments of the eye cannot be visualized due the opaque ocular media. MATERIAL AND METHODS: The paper presents 50 patients with unilateral or bilateral leukokoria treated în the University Eye Hospital from Cluj-Napoca. The parameters who had been watched were: the visual acuity, ultrasonography of the eye, and the management of the lesions associated with leukokoria. The ultrasonography was indicated for the diagnosis of the conditions associated with leukokoria, using a transducer of 7.5 MHz. RESULTS: The conditions associated with leukokoria were: intraocular tumors în 8% of cases; congenital cataract în 24% of cases; persistent hyperplastic primary vitreous în 2% of cases; complicate or pathologic cataract în 27% of cases; retinopathy of prematurity în 6% of cases; vitreous opacities în 33% of cases. In 30% of cases ultrasonography of the eye was normal. Echography is also important for the differential diagnosis of secondary retinal detachment. We found exudative retinal detachment în 20% of cases; în 28% of cases there was a tumor retinal detachment, în 44% a tractional retinal detachment, and în 8% a posterior vitreous detachment. The performed management was represented by: enucleation în 12% of cases; EEC în 21% of cases; EEC + sinechiolisis în 11% of cases; sinechiolisis în 2% of cases; vitrectomy în 11% of cases; evisceration în 6% of cases; medical treatment în 20% of cases. CONCLUSIONS: Ultrasonography is an important imaging test for the diagnosis of the conditions associated with leukokoria. Taking into account echographic results the adequate treatment of the eye lesions can be established.

Reacción en cadena de la polimerasa en fluidos oculares en las formas atípicas de uveítis posterior / Polymerase chain reaction in ocular fluids in atypical forms of posterior uveitis

RESUMEN La toxoplasmosis ocular es la causa de uveítis posterior más frecuente en muchos países. El diagnóstico correcto se basa principalmente en las características clínicas de la enfermedad; pero en las formas de uveítis posterior atípicas se necesita el apoyo del laboratorio para confirmar el diagnóstico y no indicar tratamientos inapropiados. Se resalta el valor de la reacción en cadena de la polimerasa en fluidos oculares en pacientes con títulos serológicos en suero positivos para toxoplasma y presentaciones atípicas de uveítis posterior. Se presenta un caso clínico de una paciente con toxoplasmosis sistémica, confirmada con títulos serológicos en suero positivos, quien concomitó con uveítis posterior bilateral sin características típicas de toxoplasmosis ocular, en la cual la reacción en cadena de la polimerasa de fluidos oculares fue esencial en el diagnóstico. La reacción en cadena de la polimerasa en fluidos oculares constituye una herramienta inequívoca en el diagnóstico correcto de las formas atípicas de uveítis posteriores(AU)

ABSTRACT Ocular toxoplasmosis is the most frequent cause of posterior uveitis in many countries. Correct diagnosis is mainly based on the clinical characteristics of the disease, but in atypical forms of posterior uveitis laboratory support is required to confirm the diagnosis and not indicate inappropriate treatments. Evidence is provided of the usefulness of polymerase chain reaction in ocular fluids from patients with serum serological titers positive for toxoplasma and atypical presentations of posterior uveitis. A clinical case is presented of a female patient with systemic toxoplasmosis confirmed by positive serum serological titers and concomitant bilateral posterior uveitis without typical features of ocular toxoplasmosis, in which polymerase chain reaction in ocular fluids was essential for the diagnosis. Polymerase chain reaction in ocular fluids is an unequivocal tool for the correct diagnosis of atypical forms of posterior uveitis(AU)