Automated quantification of uveitic keratic precipitates by use of anterior segment optical coherence tomography.

BACKGROUND: Evaluation of ocular inflammation via common imaging modalities like optical coherence tomography (OCT) has emphasised cell visualisation, but automated detection of uveitic keratic precipitates (KPs) remains unexplored. METHODS: Anterior segment (AS)-OCT dense volumes of the corneas of patients with uveitic KPs were collected at three timepoints: with active (T0), clinically improving (T1), and resolved (T2) inflammation. At each visit, visual acuity and clinical grading of the anterior chamber cells were assessed. A bespoke algorithm was used to create an en face rendering of the KPs and to calculate their volume and a ratio of the volume of precipitates over the analysed area. The variation of AS-OCT-derived measurements over time was assessed, and compared with clinical grading. RESULTS: Twenty eyes from 20 patients (13 females, mean age 39 years) were studied. At T0, the mean volume of the corneal KPs was 0.1727 mm3 , and it significantly reduced to 0.1111 mm3 (p = 0.03) only at T2. The ratio between the volume of the KPs and the corneal area decreased from T0 (0.007) to T1 (0.006; p = 0.2) and T2 (0.004; p = 0.009). There was a statistically significant correlation between the AC cell count and the AS-OCT volume measurements of the KPs at the three time points. CONCLUSIONS: AS-OCT can image uveitic KPs and through a bespoke algorithm we were able to create an en face rendering allowing us to extrapolate their volume. We found that objective quantification of KPs correlated with inflammatory cell counts in the anterior chamber.

Iridian anterior segment OCT in rubella uveitis syndrome and cytomegalovirus anterior uveitis: a comparative study.

PURPOSE: To compare iris affectation in cytomegalovirus anterior uveitis (CMVAU), rubella virus-associated uveitis (RVU), and healthy contralateral eyes, using swept-source anterior segment optical coherence tomography (SS-AS-OCT). MATERIALS AND METHODS: A comparative, transversal, retrospective study examining 60 eyes from 30 patients-18 eyes (17 patients) with CMVAU, 14 eyes (13 patients) with RVU, and 28 healthy eyes-was performed. Six-millimeter cross-sectional SS-AS-OCT B-scans were obtained in each iris quadrant. Images were exported to ImageJ®. Qualitative and quantitative analyses were done: stromal thickness (ST), smooth index (SI), and optical density (OD) of pigment epithelium. Comparisons between measurements and clinical-demographic parameters were performed using SPSS®. RESULTS: Qualitative analysis showed extensive damage in iris stroma but was unable to differentiate between both uveitis. RVU eyes had a lower mean ST (315.72 µm ± 42.4) compared to those with CMVAU (348.6 µm ± 46) (p = 0.047) and a lower ST in the upper (338.9 µm ± 38.52)/(386.25 µm ± 47.2) (p = 0.005) and temporal (281.5 µm ± 57.3)/(326.43 µm ± 62.3) (p = 0.016) quadrants. Mean (0.94 ± 0.02)/(0.9 ± 0.03) (p = 0.001), temporal (0.94 ± 0.02)/(0.89 ± 0.03) (p < 0.001), and nasal SI (0.094 ± 0.02)/(0.9 ± 0.04) (p = 0.005) were higher in RVU. OD was similar in both uveitis. In healthy eyes, mean ST (376.8 µm ± 39.7) was higher and mean SI was lower (0.87 ± 0.04) than in RVU (p < 0.001) and CMVAU eyes (p = 0.032). Mean OD was higher in healthy eyes (911 ± 130) than in CMVAU eyes (800 ± 200) (p = 0.037). CONCLUSIONS: The quantitative analysis of the SS-AS-OCT iris images allows for the differentiation between healthy eyes and those with CMVAU and RVU, as well as between both uveitis.

Assessment of Anterior Uveitis Through Anterior-Segment Optical Coherence Tomography and Artificial Intelligence-Based Image Analyses.

Purpose: The purpose of this study was to develop an automated artificial intelligence (AI) based method to quantify inflammation in the anterior chamber (AC) using anterior-segment optical coherence tomography (AS-OCT) and to explore the correlation between AI assisted AS-OCT based inflammation analyses and clinical grading of anterior uveitis by Standardization of Uveitis Nomenclature (SUN). Methods: A prospective double blinded study of AS-OCT images of 32 eyes of 19 patients acquired by Tomey CASIA-II. OCT images were analyzed with proprietary AI-based software. Anatomic boundaries of the AC were segmented automatically by the AI software and Spearman's rank correlation between parameters related to AC cellular inflammation were calculated. Results: No significant (p = 0.6602) differences were found between the analyzed AC areas between samples of the different SUN grading, suggesting accurate and unbiased border detection/AC segmentation. Segmented AC areas were processed by the AI software and particles within the borders of AC were automatically counted by the software. Statistical analysis found significant (p < 0.001) correlation between clinical SUN grading and AI software detected particle count (Spearman ρ = 0.7077) and particle density (Spearman ρ = 0.7035). Significant (p < 0.001) correlation (Pearson's r = 0.9948) between manually and AI detected particles was found. No significant (p = 0.8080) difference was found between the sizes of the AI detected particles for all studies. Conclusions: AI-based image analysis of AS-OCT slides show significant and independent correlation with clinical SUN assessment. Translational Relevance: Automated AI-based AS-OCT image analysis suggests a noninvasive and quantitative assessment of AC inflammation with clear potential application in early detection and management of anterior uveitis.

Grading Anterior Chamber Inflammation with Anterior Segment Optical Coherence Tomography: An Overview.

The objective grading of anterior chamber inflammation (ACI) has remained a challenge in the field of uveitis. While the grading criteria produced by the Standardization of Uveitis Nomenclature (SUN) International Workshop have been widely adopted, limitations exist including interobserver variability and grading confined to discrete categories rather than a continuous measurement. Since the earliest iterations of optical coherence tomography (OCT), ACI has been assessed using anterior segment OCT and shown to correlate with slit-lamp findings. However, widespread use of this approach has not been adopted. Barriers to standardization include variability in OCT devices across clinical settings, lack of standardization of image acquisition protocols, varying quantification methods, and the difficulty of distinguishing inflammatory cells from other cell types. Modern OCT devices and techniques in artificial intelligence show promise in expanding the clinical applicability of anterior segment OCT for the grading of ACI.

The feasibility of clinical evaluation for anterior uveitis through spectral-domain optical coherence tomography in dogs.

OBJECTIVE: To evaluate the clinical application of spectral-domain optical coherence tomography (SD-OCT) for anterior uveitis in dogs. Animals and procedures Client-owned dogs presenting with anterior uveitis and clinically healthy dogs were enrolled in this study. Included eyes were divided into 5 groups by flare grade and 3 groups by cell grade through slit-lamp biomicroscopy. Each eye was examined using SD-OCT following slit-lamp biomicroscopy. The ratio of aqueous signal intensity to air signal intensity, which is called the aqueous-to-air relative intensity (ARI) index, was used to evaluate the flare grade. Cell number, central corneal thickness (CCT), and the presence of keratic precipitates (KPs) were analyzed on SD-OCT. The OCT parameters, including ARI index, cell number, and CCT, were compared to the slit-lamp clinical flare and cell grade. RESULTS: Thirty-six eyes with anterior uveitis and 27 healthy eyes were enrolled. The ARI index showed a significant correlation with clinical flare grade (rs  = 0.811, p < .001). In multiple regression analysis, the ARI index and CCT showed a significant negative correlation (r = -0.258, p = .044). The number of cells on SD-OCT significantly increased with cell grade on slit-lamp biomicroscopy (rs  = 0.653, p < .001). The clinical flare grade and CCT were significantly correlated in the partial correlation analysis after controlling for age (partial correlation coefficient = 0.471, p = .002). KPs were observed in 61% of the eyes with flare using SD-OCT (22/36 eyes). CONCLUSIONS: Spectral-domain optical coherence tomography could provide quantitative information, including the ARI index, cell counts, and CCT in dogs. SD-OCT is an auxiliary modality for slit-lamp biomicroscopy when evaluating anterior uveitis in dogs.

Peripapillary retinal nerve fiber layer and ganglion cell-inner plexiform layer changes on optical coherence tomography in patients with unilateral hypertensive cytomegalovirus anterior uveitis.

PURPOSE: To investigate whether peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thinning are present in patients with unilateral hypertensive Cytomegalovirus anterior uveitis (hCMV AU). METHODS: We included 19 eyes with unilateral hCMV AU and their unaffected fellow eyes as the control group in this study. Peripapillary RNFL and macular GCIPL changes were determined using spectral-domain (SD) - optical coherence tomography (OCT). RESULTS: The overall calculated mean pRNFL thickness was significantly lower in the effected eyes with hCMV AU than in the uneffected fellow eyes (p = 0.012). The mean macular GCIPL thickness in the affected eyes was also significantly lower than in the normal eyes (p < 0.001). CONCLUSION: Measurement of pRNFL and macular GCIPL thickness with OCT may detect signs of damage before the visual field changes in patients with hypertensive CMV AU. Early aggressive treatment in these patients may prevent further glaucomatous damage.

Retinal Microcirculation Defects on OCTA Correlate with Active Inflammation and Vision in Vogt-Koyanagi-Harada Disease.

Purpose: To analyze quantitative OCT-angiography (OCTA) measurements of Vogt-Koyanagi-Harada (VKH) disease at different disease stages.Methods: OCTA scans of 110 VKH patients in acute uveitic, convalescent and chronic recurrent stage were reviewed; posterior uveitis recurrent cases were excluded. Superficial and deep capillary plexus (SCP and DCP) vascular densities (VD) and subfoveal choroidal thickness (SFCT) were compared.Results: DCP VD was significantly lower and SFCT higher in VKH than normal controls (NC) in all 3 stages (all p < .001). Anterior uveitis recurrent patients had lower SCP and DCP VDs and thicker SFCT than convalescent patients (p = .001, p < .001, and p = .003, respectively). DCP VD was significantly correlated with visual acuity (p < .05). Patients with history of anterior recurrence had lower retinal VDs in the convalescent stage than those without (p < .001).Conclusion: Retinal microcirculation is impaired in VKH. DCP VD might be a sensitive indicator of inflammatory status and appeared to be well associated with visual outcome.

Evaluation of changes in choroidal vascularity during acute anterior uveitis attack in patients with ankylosing spondylitis by using binarization of EDI-optical coherence tomography images.

BACKGROUND: To evaluate the effect of the first acute anterior uveitis (AAU) attack on the choroid by using an image binarization tool on images from enhanced depth imaging (EDI)-optical coherence tomography (OCT) scans in patients with ankylosing spondylitis (AS). METHODS: In this study, three groups were formed: uveitic eyes (UE; n = 20) of patients with AS, the non-uveitic eyes (NUE; n = 20) of these patients, and the eyes of healthy controls (n = 20). EDI-OCT images were obtained during the first AAU attack and at three months after treatment in patients with AS. An image binarization tool (ImageJ software; Bethesda, MD USA) was used on EDI-OCT images to determine choroidal structures. Choroidal vascularity index (CVI) was defined as the ratio of luminal area to total subfoveal choroidal area. RESULTS: Compared to the convalescent period, CVI was found to be significantly increased in UE (63.2 ± 2.87 vs. 60.9 ± 5.2 %, p = 0.045) and NUE (63.8 ± 5.67 vs. 61.5 ± 4.3 %, p = 0.039), while stromal area (SA) was found to be significantly reduced only in UE (0.487 ± 0.19 vs. 0.569 ± 0.18, p = 0.012) in the attack period. CONCLUSIONS: Changes in the CVI values of UE and NUE groups in the first AAU attack shows that there is underlying choroidal inflammation in patients with AS. It also seems that SA is the most affected choroidal structure in eyes suffering from an attack. The present study revealed that CVI measurements can be used for follow-up and the determination of treatment response in AS patients with AAU attack.

Quantitative Analysis of Anterior Chamber Inflammation Using the Novel CASIA2 Optical Coherence Tomography.

PURPOSE: We evaluated the clinical utility of a novel anterior segment optical coherence tomography (AS-OCT) device, CASIA2, to evaluate parameters indicative of anterior chamber (AC) inflammation severity in uveitis, including AC cell number, flare, and keratic precipitates (KPs). DESIGN: Prospective evaluation of a diagnostic device. METHODS: Uveitis eyes were classified into active and inactive groups. The number of hyperreflective dots representing AC cells and optical density ratio (aqueous-to-air relative intensity [ARI] index) for flare qualification were calculated from AS-OCT images. In addition, a program was designed to quantify the posterior corneal surface smoothness (PCSS) of each image for KPs evaluation. The maximum, minimum, and average PCSS values were calculated from 128 images per eye and compared among active uveitis, inactive uveitis, and control eyes. Correlations between Standardization of Uveitis Nomenclature grade and both hyperreflective dot number and ARI index were evaluated. Receiver operating characteristic (ROC) curves were constructed to test the values of these indicators for uveitis diagnosis. RESULTS: AC hyperreflective dot count, ARI index, and maximum and average PCSS values were all significantly higher in the active uveitis group than in the inactive and control groups. Hyperreflective dot count and ARI index were associated with Standardization of Uveitis Nomenclature cell and flare grade. According to ROC curve analysis, maximum PCSS was the best indicator for the diagnosis of uveitis involving the anterior segment, meanwhile the hyperreflective dot number was the best to identify active AC inflammation from the inactive. CONCLUSIONS: Quantification of AC cell number, flare, and KPs using the CASIA2 device is a promising strategy for the objective assessment of AC inflammation.

Anterior Uveitis with Negative Work-up: Giant Cell Arteritis Remains the Pet Peeve.

BACKGROUND: Giant Cell Arteritis (GCA), is the most common primary vasculitis. It affects large vessels such as the aorta and its branches. According to Chapel Hill Consensus, GCA is one of the larger vessel vasculitis. The underlying mechanism involves inflammation of the large arteries. The most frequent presentation consists of headache, polymyalgia, and jaw claudication. GCA can put the visual prognosis at risk, and rapid diagnosis is compulsory. Cotton wool spots, due to focal inner retinal ischemia, are an early diagnostic ophthalmological sign. The most frequent presentation is a rapid, partial or complete blindness. However, atypical presentations, such as uveitis, especially in the anterior chamber, can delay diagnosis. CASE REPORT: We report a 75-year-old woman with GCA who initially presented with anterior uveitis and without any other clinical sign. At the beginning, there was the only ophthalmic sign and systemic inflammation, the all exhaustive work-up including positron emission tomography (PET) scan was negative. The biology was fully normal without auto-immune profile (Angiotensin converting enzyme level, Interferon Gamma Release Assay, Syphilis serology, antinuclear antibody titer, Rheumatoid factor, CCP antibodies, and chest x-ray were normal. HLA B27 was negative). In the following weeks, she subsequently developed large vessel vasculitis with headache and more typical sign. She developed cotton wool spots linked to retinal arteriolar hypoperfusion. Anterior uveitis has been reported rarely in GCA and moreover, it is very uncommon at the early stages of GCA. Our case stresses that uveitis onset can precede large vessels vasculitis and typical symptoms of GCA. PET-scan is a useful tool for atypical GCA, but its sensitivity is not perfect, and its repetition can be helpful in selected cases such as that of this patient.

Transscleral cyclophotocoagulation as primary management in a nanophthalmic eye with anterior uveitis and secondary mixed mechanism glaucoma.

A 36-year-old woman presented with eye pain and blurring of vision in her right eye. On eye examination, it was noted that there were angle-closure glaucoma and anterior uveitis in both eyes. Ocular ultrasound showed short axial lengths as well as a choroidal thickening in both eyes, confirming the diagnosis of nanophthalmos. Nanophthalmos is a condition where the eye is abnormally short, resulting in axial hyperopia and predisposing it to angle-closure glaucoma. The patient was initially managed medically, but the glaucoma was intractable. The patient underwent repeated sessions of transscleral cyclophotocoagulation which eventually lowered the intraocular pressure. The management of nanophthalmic eyes can be quite challenging due to the risk of inciting uveal effusion syndrome with any form of intraocular surgery. Controlled and repeated sessions of transscleral cyclophotocoagulation may be considered as a viable management option in these cases.

Bilateral acute anterior uveitis: a rare ocular side effect of erlotinib.

Erlotinib used in the treatment of advanced non-small cell lung cancer (NSCLC) is a first-generation small-molecule tyrosine kinase inhibitor which reversibly inhibits the kinase domain of epithelial growth factor receptor (EGFR). The incidence of ocular toxicities as adverse effects (AE) of erlotinib is relatively common. However, post-marketing, acute anterior uveitis (AAU) has been reported in a small number of cases as a putative AE resulting from erlotinib therapy. We present a case of a 67-year-old, Caucasian woman, lifelong non-smoker with stage IV NSCLC who presents with decreased visual acuity and 'floaters' 6 weeks after commencing erlotinib. She was later diagnosed with erlotinib-associated bilateral AAU. This is the fifth documented case of erlotinib-associated bilateral AAU since 2010, highlighting the rarity of this AE. Thus, the possibility of AAU should always be considered in patients on EGFR-blocking therapies as significant ocular damage can occur if ophthalmic complaints are not triaged and assessed quickly.

Instrument-based tests for quantifying aqueous humour protein levels in uveitis: a systematic review protocol.

BACKGROUND: Inflammation in anterior uveitis is characterised by breakdown of the blood-ocular barrier, which allows leakage of blood constituents of higher molecular weight into the aqueous humour. In routine clinical care, increase in aqueous protein levels can be observed at the slit lamp as 'flare' and the severity can be graded using various clinical grading systems, of which the Standardization of Uveitis Nomenclature (SUN) grading system is most commonly used. Alternative instrument-based technologies are available, which can detect aqueous protein levels in an objective and quantifiable way. This review will identify instruments capable of measuring anterior chamber inflammation in this way, their level of reliability, and how well the measurements correlate with clinical grading and/or actual aqueous protein concentration. METHODS: Standard systematic review methodology will be used to identify, select and extract data from studies that report the use of any instrument-based technology in the assessment of aqueous protein levels. Searches will be conducted through bibliographic databases (MEDLINE, EMBASE and Cochrane Library), clinical trial registries and the grey literature. No restrictions will be placed on language or year of publication. The outcomes of interest are the level of correlation between identified instrument-based test measurements, clinical grading and/or actual aqueous protein concentration, as well as the reliability of each index test identified. Study quality assessment will be based on QUADAS2. Correlation and reliability outcomes will be pooled and meta-analysed if appropriate. DISCUSSION: The assessment of inflammation in anterior chamber protein levels currently relies on crude and subjective clinical examination. The findings of this review will identify non-invasive technologies which show good correlation with actual protein concentration, which could be used in routine clinical practice for objective monitoring of AC inflammation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017084167. Study screening stage has just been completed.

Estudio del ángulo iridocorneal mediante OCT Swept-Source en paciente con uveítis anterior granulomatosa / Iridocorneal angle assessment using Swept-Source OCT in a patient with anterior granulomatous uveítis

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In vivo confocal microscopy of the inflamed anterior segment: A review of clinical and research applications.

In vivo confocal microscopy (IVCM) allows non-invasive imaging of the living human cornea, specifically enabling the detection of immune cells in the healthy and diseased ocular anterior segment. Studies using IVCM have provided insight into the effects of contact lens wear on corneal Langerhans cell density and morphology, and the effects of eye drops on conjunctiva-associated lymphoid tissue. IVCM has also been shown to be a useful adjunctive diagnostic tool in distinguishing infective and non-infective uveitis and in diagnosing atypical infective keratitis. In the research setting, this technology has enhanced our understanding of the role of inflammatory cells in corneal neuropathy and angiogenesis. In vivo-ex vivo correlation using animal models has helped overcome some of the difficulties in identifying cell type on IVCM images. As highlighted in this review, currently there are multiple established, and emerging, clinical and research applications for IVCM in the inflamed anterior segment.

Idiopathic Central Nervous System Inflammatory Disease in the Setting of HLA-B27 Uveitis.

Purpose: The purpose of the article is to describe a novel case of idiopathic central nervous system inflammatory disease with bilateral human leukocyte antigen (HLA)-B27-positive anterior uveitis. Methods/Results: A 15-year-old African American boy with bilateral HLA-B27-positive anterior uveitis controlled with topical and oral steroids for 8 months acutely developed headaches, left eyelid ptosis, and binocular diplopia. Imaging showed lesions in the right midbrain, superior colliculus, cerebellar peduncles, and cerebellar vermis and leptomeningeal enhancement along the vermian foliae. Cerebral spinal fluid tests showed mild lymphohistiocytic pleocytosis with negative cytology; inflammatory and infectious workup were negative. He received intravenous methylprednisolone without initial symptomatic improvement; repeat magnetic resonance imaging (MRI) showed reduced lesion burden. Oral steroids were continued; his symptoms resolved in 1 month. Repeat MRI 2 months after presentation showed almost complete lesion resolution. Conclusions: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) was diagnosed. HLA-B27 positivity may represent a novel association with CLIPPERS.

Uveítis anterior aguda hipertensiva granulomatosa bilateral como efecto adverso a brimonidina tópica / Hypertensive acute granulomatous anterior uveitis as a side effect of topical brimonidine

CASO CLÍNICO: Mujer de 81 años en tratamiento con una combinación fija de timolol y brimonidina en colirio que fue diagnosticada en urgencias de uveítis anterior aguda hipertensiva granulomatosa. La paciente respondió favorablemente a la retirada del colirio sin mostrar recaída posterior. DISCUSIÓN: La uveítis por brimonidina es un efecto adverso raro, pero que debe ser conocido. Una vez se llega al diagnóstico de sospecha, el tratamiento efectivo es la retirada del colirio de brimonidina, con adición o no de corticoides tópicos para controlar la inflamación según la gravedad del cuadro. Se trata de un proceso con un pronóstico excelente

CLINICAL CASE: The case concerns an 81-year-old woman on treatment with a topical fixed combination of timolol and brimonidine who was diagnosed in the Emergency Department with acute anterior granulomatous hypertensive uveitis. The patient responded favourably to the withdrawal of the eye drops without showing any subsequent relapse. DISCUSSION: Uveitis due to brimonidine is a rare adverse effect, but it must be known. Once the diagnosis is suspected, the effective treatment is the withdrawal of brimonidine, with or without the addition of topical corticosteroids to control inflammation depending on the severity of the condition. It is a process with an excellent prognosis

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.